Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good m...Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.展开更多
The umbilical,a key component in offshore energy extraction,plays a vital role in ensuring the stable operation of the entire production system.The extensive variety of cross-sectional components creates highly comple...The umbilical,a key component in offshore energy extraction,plays a vital role in ensuring the stable operation of the entire production system.The extensive variety of cross-sectional components creates highly complex layout combinations.Furthermore,due to constraints in component quantity and geometry within the cross-sectional layout,filler bodies must be incorporated to maintain cross-section performance.Conventional design approaches based on manual experience suffer from inefficiency,high variability,and difficulties in quantification.This paper presents a multi-level automatic filling optimization design method for umbilical cross-sectional layouts to address these limitations.Initially,the research establishes a multi-objective optimization model that considers compactness,balance,and wear resistance of the cross-section,employing an enhanced genetic algorithm to achieve a near-optimal layout.Subsequently,the study implements an image processing-based vacancy detection technique to accurately identify cross-sectional gaps.To manage the variability and diversity of these vacant regions,the research introduces a multi-level filling method that strategically selects and places filler bodies of varying dimensions,overcoming the constraints of uniform-size fillers.Additionally,the method incorporates a hierarchical strategy that subdivides the complex cross-section into multiple layers,enabling layer-by-layer optimization and filling.This approach reduces manufac-turing equipment requirements while ensuring practical production process feasibility.The methodology is validated through a specific umbilical case study.The results demonstrate improvements in compactness,balance,and wear resistance compared with the initial cross-section,offering novel insights and valuable references for filler design in umbilical cross-sections.展开更多
BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA ...BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA treatments,their use is limited by the condition itself,and understanding of the underlying mechanisms of OA is lacking.AIM To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.METHODS Sodium iodoacetate was injected into rat articulations to construct an animal model of OA.Interleukin(IL)-1βwas used to induce human chondrocytes(CHON-001)to construct an OA chondrocyte model.Exosomes in hUC-MSCs were isolated using Ribo™Exosome Isolation Reagent.Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins,and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay,terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho-sphate-nick end labelling staining and hematoxylin and eosin staining.RESULTS hUC-MSC-derived exosomes(hUC-MSC-Exos)inhibited the expression of IL-1β-induced inflammatory cytokines,namely,IL-6,IL-8 and tumor necrosis factor-α.hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells,improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo.Mechanistically,hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p,thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway,alleviating IL-1β-induced chondrocyte inflammation and apoptosis,and ultimately improving the development of OA.CONCLUSION hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway.The present findings suggest that miR-199a-3p delivery by hUC-MSCExos may be a novel strategy for the treatment of OA.展开更多
BACKGROUND The reference ranges for biochemical parameters can fluctuate due to factors like altitude,age,gender,and socioeconomic conditions.These values are crucial for interpreting laboratory data and guide clinica...BACKGROUND The reference ranges for biochemical parameters can fluctuate due to factors like altitude,age,gender,and socioeconomic conditions.These values are crucial for interpreting laboratory data and guide clinical treatment decisions.Currently,there is no established set of reference intervals for cord blood biochemical parameters of newborns in India,particularly in Mumbai.AIM To create cord blood biochemical parameters reference intervals specifically for Mumbai,India.METHODS A cross-sectional study was conducted in an Indian tertiary care hospital.This study focused on healthy newborns with normal birth weight,born to pregnant mothers without health issues.Cord blood samples,approximately 2-3 mL in volume,were collected from 210 term neonates.These samples were divided into fluoride(glucose)and clot activator(serum)tubes and were subsequently analyzed in the institute's biochemical laboratory.The data obtained from the analysis was then subjected to statistical analysis.The result of the Shapiro-Wilk test suggested non-normality in the data distribution.Consequently,nonparametric statistics were utilized for analysis.The Mann-Whitney U test was utilized to compare parameter distributions among different factors,including the infant’s sex,delivery method,maternal age,and obstetric history.A significance level of P<0.05 was considered to indicate statistical significance.RESULTS The following represent the median figures and central 95 percentile reference intervals for biochemical parameters in umbilical cord blood of newborns:Serum direct bilirubin=(0.1-0.55)mg/dL,indirect bilirubin=(0.64-2.26)mg/dL,total bilirubin=(0.62-3.14)mg/dL,creatinine=(0.27-0.76)mg/dL,sodium=(128.19-143.26)mmol/L,chloride=(100.19-111.68)mmol/L,potassium=(1.62-9.98)mmol/L and plasma glucose=(24.75-94.23)mg/dL.Statistically significant differences were observed in serum sodium,potassium,and plasma glucose levels when comparing delivery modes.CONCLUSION This is the pioneering study in which first time,the biochemical reference intervals in cord blood for newborns are established in western India.The values are applicable for newborns from this area.Larger study throughout the country is required.展开更多
BACKGROUND Cancer-induced incomplete bowel obstruction presents numerous clinical cha-llenges,notably pain management and inflammation control.Conventional thera-pies provide limited relief,prompting investigation int...BACKGROUND Cancer-induced incomplete bowel obstruction presents numerous clinical cha-llenges,notably pain management and inflammation control.Conventional thera-pies provide limited relief,prompting investigation into complementary approa-ches.This study compares the efficacy of bottle gourd moxibustion combined with umbilical therapy(BGM-UT)plus standard palliative care vs standard Wes-tern palliative care alone in symptom alleviation and inflammation reduction.AIM To compare the efficacy of BGM-UT plus standard palliative care vs standard pa-lliative care alone in reducing inflammatory cytokine levels,alleviating symp-toms,and improving gastrointestinal recovery in cancer-induced incomplete bowel obstruction.METHODS A retrospective analysis was conducted on 109 patients aged 18-75 years with cancer-induced incomplete bowel obstruction treated at the Foshan Hospital of Traditional Chinese Medicine between October 2023 and September 2024.The participants were categorized into two groups:(1)Regular group receiving stan-dard palliative care;and(2)BGM-UT group receiving additional moxibustion therapy.The inclusion criteria included ongoing opioid use and a Karnofsky per-formance status score below 60.The treatments were evaluated for 3 weeks in terms of opioid consumption,gastrointestinal function recovery,brief pain inven-tory scores,traditional Chinese medicine symptom scores,and inflammatory cytokine levels.RESULTS Initially,the groups were demographically and clinically comparable.Post-treatment,the BGM-UT group showed significant reductions in opioid intake(P=0.027),improved gastrointestinal recovery times,and enhanced pain management as reflected by their lower brief pain inventory scores(P<0.05).Similarly,the improvement in traditional Chinese medicine scores was greater in the BGM-UT group than in the regular group(P<0.05).Inflam-matory markers including interleukin-6,tumor necrosis factor-α,and C-reactive protein decreased significantly in the BGM-UT group,indicating the superior anti-inflammatory effects of this treatment(P<0.05).CONCLUSION The addition of BGM-UT to standard palliative care enhances pain relief,accelerates gastrointestinal recovery,and effectively reduces inflammatory cytokine levels in patients with cancer-induced incomplete bowel obstruction.This combination therapy offers a promising complementary approach to managing this challenging condition.Further prospective studies are warranted to validate these findings and explore underlying mechanisms.展开更多
BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilit...BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities.However,limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells(HUC-MSCs)on established airway remodeling in experimental asthma.AIM To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin(OVA)-induced asthma.METHODS BALB/c mice underwent sensitization and were challenged using OVA.Control animals were administered a saline solution following the same protocol.HUC-MSCs were identified using flow cytometry.HUC-MSCs at incremental dosages(1×105,2×105,4×105)were injected via tail veins on day 30(the second after the final stimulation).After comparing each group and determining the optimal dose,supplement the optimal dose twice on day 30 and day 33(the second and fifth day after the final stimulation).Bronchoalveolar lavage fluid(BALF)and serum were harvested for analysis of concentrations of interleukin-4(IL-4),IL-13,immunoglobulin E and interferon-gamma(IFN-γ)by enzyme-linked immunosorbent assay.Pharmacology of airways and lung functions were also evaluated to identify the optimal group.RESULTS The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models.This effect is associated with decreased Th2 cytokines IL-4 and IL-13,and increased Th1 cytokine IFN-γ.The optimal dose of 2×105 cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4,IL-13,and IFN-γin serum and BALF compared to other single doses of HUC-MSC.Multiple treatments with the medium dose(2×105 cells)of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes.However,double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γproduction in serum or BALF more effectively than a single medium dose.CONCLUSION HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF,modulating airway remodeling and lung function.In this acute mouse asthma model,a single dosage of 2×105 is optimal,with more significant effects of decreasing airway obstruction requiring repeated administration.展开更多
Endometrial injury caused by repeated uterine procedures,infections,inflammation,or uterine artery dysfunction can deplete endometrial stem/progenitor cells and impair regeneration,thereby diminishing endometrial rece...Endometrial injury caused by repeated uterine procedures,infections,inflammation,or uterine artery dysfunction can deplete endometrial stem/progenitor cells and impair regeneration,thereby diminishing endometrial receptivity and evidently lowering the live birth,clinical pregnancy,and embryo implantation rates.Currently,safe and effective clinical treatment methods or gene-targeted therapies are unavailable,especially for severe endometrial injury.Umbilical cord mesenchymal stem cells and their extracellular vesicles are characterized by their simple collection,rapid proliferation,low immunogenicity,and tumorigenicity,along with their involvement in regulating angiogenesis,immune response,cell apoptosis and proliferation,inflammatory response,and fibrosis,Therefore,these cells and vesicles hold broad potential for application in endometrial repair.This article reviewed recent research on human umbilical cord mesenchymal stem cells as well as their extracellular vesicles in repairing endometrial injury.展开更多
Buckling failure in submarine cables presents a prevalent challenge in ocean engineering.This work aims to explore the buckling behavior of umbilical cables with damaged sheaths subjected to compression and bending cy...Buckling failure in submarine cables presents a prevalent challenge in ocean engineering.This work aims to explore the buckling behavior of umbilical cables with damaged sheaths subjected to compression and bending cyclic loads.A finite element model is devised,incorporating a singular armor wire,a rigid core,and a damaged sheath.To scrutinize the buckling progression and corresponding deformation,axial compression and bending cyclic loads are introduced.The observations reveal that a reduction in axial compression results in a larger number of cycles before buckling ensues and progressively shifts the buckling position toward the extrados and fixed end.Decreasing the bending radius precipitates a reduction in the buckling cycle number and minimizes the deformation in the armor wire.Furthermore,an empirical model is presented to predict the occurrence of birdcage buckling,providing a means to anticipate buckling events and to estimate the requisite number of cycles leading to buckling.展开更多
BACKGROUND Diabetes mellitus(DM)and metabolic-associated fatty liver disease(MAFLD)are common metabolic disorders,and their coexistence can exacerbate the progression of either disease.Human umbilical cord mesenchymal...BACKGROUND Diabetes mellitus(DM)and metabolic-associated fatty liver disease(MAFLD)are common metabolic disorders,and their coexistence can exacerbate the progression of either disease.Human umbilical cord mesenchymal stem cell(hUCMSC)therapy has shown promising potential in the treatment of several metabolic diseases.AIM To investigate how hUC-MSCs affect liver metabolism in diabetic rats with MAFLD and assess their therapeutic potential and underlying mechanisms.METHODS A streptozotocin-induced rat model of DM with MAFLD was established,and hUC-MSCs were administered via tail vein injection.Changes in body weight,fasting blood glucose(FBG),and serum triglyceride(TG),alanine aminotransferase,aspartate aminotransferase levels,and pathological changes of liver were evaluated.Receiver operating characteristic analysis was used to assess the diagnostic value of differential metabolites and their ability to predict the therapeutic effects of hUC-MSCs.Spearman correlation was employed to analyze the relationships between liver metabolites and key biochemical markers.RESULTS hUC-MSC treatment significantly reduced FBG and TG levels in diabetic rats with MAFLD and improved histological steatosis and injury in the liver.Metabolomic analysis indicated that hUC-MSCs significantly ameliorated liver metabolic disturbances via their regulatory effect on several key metabolic pathways related to carbohydrate,amino acid,and lipid metabolism.Receiver operating characteristic curve analysis revealed that 70 differential metabolites had good diagnostic value for DM with MAFLD and could effectively predict the therapeutic effect of hUC-MSCs.Moreover,Spearman correlation analysis confirmed that significant correlations existed between differential liver metabolites and the concentrations of biochemical markers(FBG,TG,alanine aminotransferase,aspartate aminotransferase).CONCLUSION hUC-MSCs alleviate liver metabolic disturbances in diabetic rats with MAFLD,thereby mitigating the pathological state of DM and slowing the progression of MAFLD.展开更多
BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transpl...BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.展开更多
Acute liver failure(ALF),a severe clinical syndrome marked by high mortality rates and limited conventional treatments,urgently requires innovative therapeutic strategies.In recent years,human umbilical cord mesenchym...Acute liver failure(ALF),a severe clinical syndrome marked by high mortality rates and limited conventional treatments,urgently requires innovative therapeutic strategies.In recent years,human umbilical cord mesenchymal stem cells(hUC-MSCs)have emerged as a research hotspot due to their unique differentiation potential,remarkable regenerative capacity,and significant immune regulatory properties.Studies demonstrate that it can improve liver function through multiple mechanisms,promote hepatocyte regeneration,and reduce hepatic injury.Additionally,their role in regulating inflammatory responses provides new therapeutic approaches for ALF.This review systematically examines the latest research progress on hUC-MSCs in ALF treatment,focusing on their mechanisms of action,therapeutic efficacy,and clinical application prospects,aiming to provide valuable references for future research and clinical practice.展开更多
Pulmonary fibrosis,a chronic,fatal lung disease affecting millions worldwide,urgently needs more effective treatments.This article comments on the study by Wang et al,which proposed that human umbilical cord mesenchym...Pulmonary fibrosis,a chronic,fatal lung disease affecting millions worldwide,urgently needs more effective treatments.This article comments on the study by Wang et al,which proposed that human umbilical cord mesenchymal stromal cellderived exosomes alleviate rats radiation induced pulmonary fibrosis.The study demonstrated that these exosomes suppressed inflammation,extracellular matrix deposition,and epithelial-mesenchymal transition by inhibition of AKT signaling in radiation-exposed alveolar epithelial cells.Despite these observations,aspects of the study merit further discussion.Most importantly,further confirmation is needed to prove that the therapeutic effect is exerted through the AKT signaling pathway.Moreover,the definitions of both mesenchymal stem cell and exosomes require further refinement,more rigorous terms should be mesenchymal stromal cell and extracellular vesicles.It seems apparent that this therapy will develop into one of great clinical value.展开更多
BACKGROUND Delayed umbilical cord separation(UCS)defined as failure of umbilical cord fall beyond 3 weeks is seen in up to 10%of newborns.Since delayed UCS can be associated with leukocyte adhesion deficiency(LAD)or c...BACKGROUND Delayed umbilical cord separation(UCS)defined as failure of umbilical cord fall beyond 3 weeks is seen in up to 10%of newborns.Since delayed UCS can be associated with leukocyte adhesion deficiency(LAD)or coagulation factorⅩⅢdeficiency,these children are commonly referred to hematology/oncology for further investigation.Although the incidence of urachal remnants(UR);also associated with delayed UCS,is more common(1.16%)than LAD(1:1000000 births),and coagulation factorⅩⅢdeficiency(1:5000000 births)it’s less commonly investigated.CASE SUMMARY Two otherwise healthy infants,a 6-week-old female and a 4-week-old male were seen at our hematology/oncology clinic for delayed UCS.In both cases the umbilical cords looked healthy,with no signs of infection or pus,but appeared to show small Umbilical Granulomas.They were both investigated for LAD type I and one was investigated forⅩⅢdeficiency,but both tests were negative.These infants however,were investigated via abdominal ultrasound which showed UR in both cases.These infants required no intervention.CONCLUSION This report demonstrates an often overlooked association between delayed UCS and UR and suggests abdominal ultrasound if necessary for diagnosis.展开更多
BACKGROUND Large number of decompensated liver cirrhosis patients in China have been diagnosed with hepatitis B virus(HBV).Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)can possibly cure decompensated l...BACKGROUND Large number of decompensated liver cirrhosis patients in China have been diagnosed with hepatitis B virus(HBV).Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)can possibly cure decompensated liver cirrhosis because of their self-renewal and multidirectional differentiation potential.AIM To explore the safety and effect of treating liver cirrhosis with HBV by hUC-MSCs.METHODS Twenty-four participants were recruited,divided into 3 groups,and injected with different amounts of hUC-MSCs via the peripheral vein.Therapy was administered 3 times.A 24-week follow-up examination of each patient’s liver function,coagulation function,general condition,and immune system was performed.Adverse events were also recorded.A 2-year survival assessment was subsequently performed.RESULTS Infusion therapy rapidly improved liver function.Serum albumin transiently increased on days 57 and 85 but returned to baseline by day 169,while prothrombin time activity demonstrated sustained improvement from day 29 through day 169.Interleukin-8 levels decreased persistently throughout treatment.All dosage groups achieved 100%6-month survival;2-year survival rates were 66.7%(low-dose),100%(medium-dose),and 87.5%(high-dose).The interaction between dosage and efficacy was weak.Notably,the improvement in liver function was statistically significant and sustained for almost 3 months,suggesting clinically meaningful therapeutic durability.CONCLUSION hUC-MSCs can be considered a safe treatment for patients with decompensated liver cirrhosis associated with HBV.However,larger-scale randomized controlled trials are needed to prove its therapeutic effect.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In Chin...BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In China,5.6%-11.5%of the population has IBS,with diarrheal IBS(IBS-D)comprising about 31.5%of the total.AIM To investigate how human umbilical cord mesenchymal stem cells(hUC-MSCs)can alleviate the symptoms with the help of an IBS-D rat model.METHODS Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups:Control group,model group,and three hUC-MSC groups with different doses.The model group was induced using a combination of acetic acid and binding stress.We determined the body weight of the mice;analyzed their fecal characteristics,inflammatory factors,and intestinal tissue damage;and conducted intestinal flora analyses.RESULTS The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent.In addition,hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue.In addition,hUC-MSCs were able to maintain the abundance and diversity of gut flora.CONCLUSION Thus,hUC-MSCs can reduce the expression of inflammatory factors,improve the expression of intestinal barrier functional proteins,and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.展开更多
One of the most prevalent long-term effects of diabetes is diabetic kidney disease(DKD),which is linked to problems with the metabolism of amino acids,fats,and carbohydrates.The fundamental pathogenic mechanisms of DK...One of the most prevalent long-term effects of diabetes is diabetic kidney disease(DKD),which is linked to problems with the metabolism of amino acids,fats,and carbohydrates.The fundamental pathogenic mechanisms of DKD cannot be adequately treated by current clinical medicines;they can only slow the illness’s progression to end-stage renal disease.We will concentrate on integrating human umbilical cord mesenchymal stem cell(hUC-MSC)-related mechanisms and potential applications into the therapy of DKD,as this work shows that hUCMSCs can be used to treat metabolic liver obesity associated with diabetes.Future studies on the connection between hUC-MSCs and related illnesses ought to be promoted.展开更多
Rationale:Abdominal pain is a common complaint with a broad differential diagnosis,including both intra-abdominal and abdominal wall pathologies.While visceral causes are frequently considered,abdominal wall condition...Rationale:Abdominal pain is a common complaint with a broad differential diagnosis,including both intra-abdominal and abdominal wall pathologies.While visceral causes are frequently considered,abdominal wall conditions are often overlooked,leading to diagnostic delays.Among them,umbilical abscesses are rare but require distinction from urachal abscesses due to differences in management.Patient’s concern:A 46-year-old woman presented with a one-week history of periumbilical pain unresponsive to analgesics.Diagnosis:Physical examination revealed localized tenderness and a positive Carnett’s sign.Computed tomographic images identified an umbilical abscess without evidence of urachal remnants,ruling out a urachal abscess.Interventions:The patient underwent abscess drainage and received cefalexin(1500 mg/day)for 28 days.Outcomes:The abscess resolved completely without recurrence.Lessons:Umbilical abscesses are rare and may be mistaken for urachal abscesses.A thorough clinical evaluation,including Carnett’s sign and imaging studies,is crucial for accurate diagnosis.Prompt differentiation facilitates appropriate management and prevents unnecessary interventions.展开更多
Objective This study aimed to evaluate the potential of a collagen-coated,3D-printed tracheal scaffold(3D-TechTra)integrated with human umbilical cord mesenchymal stem cells(hUC-MSCs)for tracheal tissue regeneration.M...Objective This study aimed to evaluate the potential of a collagen-coated,3D-printed tracheal scaffold(3D-TechTra)integrated with human umbilical cord mesenchymal stem cells(hUC-MSCs)for tracheal tissue regeneration.Methods The thermoplastic polyurethane/polylactic acid(TPU/PLA)scaffold was engineered to optimize mechanical properties and biocompatibility,with the goal of mimicking the structural and tensile characteristics of native tracheal tissue.Subsequently,preclinical experiments were conducted using rabbit models:the performance of the collagen-coated TPU/PLA scaffold with hUC-MSCs was compared with that of uncoated scaffolds and collagen-only scaffolds.In vitro tests were also performed to assess the adhesion,proliferation,and differentiation of hUC-MSCs on the scaffold.For in vivo evaluation,multiple analytical methods were employed,including immunohistological analysis(to detect glycosaminoglycan deposition and extracellular matrix remodeling),radiographic and endoscopic evaluations(to assess tracheal contour and airway obstruction),and survival analysis(to monitor animal outcomes and systemic toxicity).Results In vitro,hUC-MSCs successfully adhered to and proliferated on the TPU/PLA scaffold,and differentiated into adipogenic,osteogenic,and chondrogenic lineages,which supported the potential for tissue-specific regeneration;in vivo,compared with uncoated or collagen-only scaffolds,the collagen-coated TPU/PLA scaffold integrated with hUC-MSCs exhibited enhanced integration with host tissues,superior biocompatibility,and reduced tracheal stenosis,while also preserving airway patency,alleviating inflammation,and facilitating epithelial regeneration,smooth muscle formation,and vascularization.Immunohistological analysis further revealed significant glycosaminoglycan deposition and extracellular matrix remodeling in the hUC-MSC-treated group,and radiographic and endoscopic evaluations confirmed preserved tracheal contour and reduced airway obstruction;additionally,survival analysis showed significantly improved outcomes in animals treated with the collagen-coated TPU/PLA scaffold containing hUC-MSCs,with no systemic toxicity observed.Conclusions This study demonstrated the synergistic potential of TPU/PLA scaffolds,collagen coatings,and hUC-MSCs,providing valuable evidence for advancing the application of these components in tracheal tissue engineering.展开更多
BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),off...BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),offer promise due to their osteogenic and immunomodulatory potential.Sclerostin(SOST)inhibits bone formation,so we developed a multi-target gene silencing strategy against SOST using RNA interference.We created hUCMSCs with SOST-silenced(sh-hUCMSCs)and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice.This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.AIM To assess the effects of sh-hUCMSCs on bone metabolism in SANFH.METHODS hUCMSCs were isolated from placental tissue and transfected with SOST-targeting short hairpin RNA plasmids.A SANFH mouse model was established through intraperitoneal injection of lipopolysaccharide(20μg/kg)followed by intramuscular methylprednisolone administration(40 mg/kg).Mice were randomized into four experimental groups(n=10/group):Sham control,SANFH(untreated),hUCMSCs-treated,and sh-hUCMSCs-treated.Micro-computed tomography was used to measure bone volume(BV),bone surface area,bone surface/BV ratio,tra-becular number,trabecular thickness,and trabecular separation.Quantification of adipocyte area by hematoxylin and eosin staining.Collagen fiber volume was assessed by Masson’s trichrome staining.Serum levels of osteopro-tegerin(OPG),receptor activator of nuclear factor kappa B(RANK),RANK ligand(RANKL),tartrate-resistant acid phosphatase,and the OPG/RANKL ratio were measured by enzyme-linked immunosorbent assay.The expression levels of alkaline phosphatase,OPG,SOST,β-catenin,peroxisome proliferator-activated receptor gamma,and CCAAT/enhancer-binding protein in bone tissue were determined by western blot analysis.RESULTS hUCMSCs and sh-hUCMSCs exhibited typical fibroblast-like morphology and high expression of MSC surface markers(CD90,CD73,CD105>98%).These cells demonstrated tri-lineage differentiation potential,confirmed by positive Alizarin Red S,Oil Red O,and Alcian Blue staining,and upregulation of lineage-specific genes.After SOST-RNA interference modification,sh-hUCMSCs showed enhanced inhibition of adipogenesis and improved bone formation in a rat model of SANFH.Histological analysis revealed reduced lipid infiltration and empty lacunae in the femoral head of the sh-hUCMSC group.Western blot showed decreased CCAAT/enhancer-binding protein and peroxisome proliferator-activated receptor gamma expression(P<0.05).Masson staining and micro-computed tomography analysis confirmed significantly increased BV,trabecular number,trabecular thickness,and reduced trabecular separation in the sh-hUCMSC group compared to unmodified MSCs and SANFH groups(P<0.05).Serum enzyme-linked immunosorbent assay showed higher OPG and lower RANK,RANKL,and tartrate-resistant acid phosphatase levels in the sh-hUCMSCs group.Western blot further confirmed upregulated alkaline phosphatase,OPG,β-catenin,and downregulated SOST expression in sh-hUCMSCs compared to controls(P<0.05).These results suggest that SOST inhibition enhances the osteogenic potential and therapeutic efficacy of hUCMSCs in SANFH.CONCLUSION sh-hUCMSCs alleviate SANFH by activating the Wnt/β-catenin signaling pathway,thereby promoting osteogenic differentiation and suppressing adipogenesis to restore bone metabolic balance.展开更多
Stem cell treatment may enhance erectile dysfunction(ED)in individuals with cavernous nerve injury(CNI).Nevertheless,no investigations have directly ascertained the implications of varying amounts of human umbilical c...Stem cell treatment may enhance erectile dysfunction(ED)in individuals with cavernous nerve injury(CNI).Nevertheless,no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)on ED.We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED.Sprague–Dawley rats(total=175)were randomly allocated into five groups.A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs(1×106 cells,5×106 cells,and 1×107 cells in 0.1 ml,respectively).Penile tissues were harvested for histological analysis on 1 day,3 days,7 days,14 days,28 days,60 days,and 90 days postsurgery.It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED.Moreover,there was no significant disparity in the effectiveness of various dosages of HUC-MSCs.However,the expression of endothelial markers(rat endothelial cell antigen-1[RECA-1]and endothelial nitric oxide synthase[eNOS]),smooth muscle markers(alpha smooth muscle actin[α-SMA]and desmin),and neural markers(neurofilament[RECA-1]and neurogenic nitric oxide synthase[nNOS])increased significantly with prolonged treatment time.Masson’s staining demonstrated an increased in the smooth muscle cell(SMC)/collagen ratio.Significant changes were detected in the microstructures of various types of cells.In vivo imaging system(IVIS)analysis showed that at the 1st day,the HUC-MSCs implanted moved to the site of damage.Additionally,the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.展开更多
基金supported by the Medicine-Engineering Interdisciplinary Project of Sun Yat-sen Memorial Hospital,China,No.YXYGRH202203(to YW)Key-Area Research and Development Program of Guangdong Province,China,No.2023B1111050003(to HC)Guangzhou Science and Technology Talent Project of China,No.201909020006(to HC).
文摘Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.
基金financially supported by Guangdong Province Basic and Applied Basic Research Fund Project(Grant No.2022B1515250009)Liaoning Provincial Natural Science Foundation-Doctoral Research Start-up Fund Project(Grant No.2024-BSBA-05)+1 种基金Major Science and Technology Innovation Project in Shandong Province(Grant No.2024CXGC010803)the National Natural Science Foundation of China(Grant Nos.52271269 and 12302147).
文摘The umbilical,a key component in offshore energy extraction,plays a vital role in ensuring the stable operation of the entire production system.The extensive variety of cross-sectional components creates highly complex layout combinations.Furthermore,due to constraints in component quantity and geometry within the cross-sectional layout,filler bodies must be incorporated to maintain cross-section performance.Conventional design approaches based on manual experience suffer from inefficiency,high variability,and difficulties in quantification.This paper presents a multi-level automatic filling optimization design method for umbilical cross-sectional layouts to address these limitations.Initially,the research establishes a multi-objective optimization model that considers compactness,balance,and wear resistance of the cross-section,employing an enhanced genetic algorithm to achieve a near-optimal layout.Subsequently,the study implements an image processing-based vacancy detection technique to accurately identify cross-sectional gaps.To manage the variability and diversity of these vacant regions,the research introduces a multi-level filling method that strategically selects and places filler bodies of varying dimensions,overcoming the constraints of uniform-size fillers.Additionally,the method incorporates a hierarchical strategy that subdivides the complex cross-section into multiple layers,enabling layer-by-layer optimization and filling.This approach reduces manufac-turing equipment requirements while ensuring practical production process feasibility.The methodology is validated through a specific umbilical case study.The results demonstrate improvements in compactness,balance,and wear resistance compared with the initial cross-section,offering novel insights and valuable references for filler design in umbilical cross-sections.
基金Supported by Basic Research Plan of Yunnan Province,No.202201AT070059National Natural Science Foundation of China,No.81760407Science and Technology Talent and Platform Plan of Yunnan Provincial Department of Science and Technology,No.202205AC160066.
文摘BACKGROUND There is currently no effective treatment for osteoarthritis(OA),which is the most common joint disorder leading to disability.Although human umbilical cord mesenchymal stem cells(hUC-MSCs)are promising OA treatments,their use is limited by the condition itself,and understanding of the underlying mechanisms of OA is lacking.AIM To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.METHODS Sodium iodoacetate was injected into rat articulations to construct an animal model of OA.Interleukin(IL)-1βwas used to induce human chondrocytes(CHON-001)to construct an OA chondrocyte model.Exosomes in hUC-MSCs were isolated using Ribo™Exosome Isolation Reagent.Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins,and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay,terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho-sphate-nick end labelling staining and hematoxylin and eosin staining.RESULTS hUC-MSC-derived exosomes(hUC-MSC-Exos)inhibited the expression of IL-1β-induced inflammatory cytokines,namely,IL-6,IL-8 and tumor necrosis factor-α.hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells,improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo.Mechanistically,hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p,thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway,alleviating IL-1β-induced chondrocyte inflammation and apoptosis,and ultimately improving the development of OA.CONCLUSION hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway.The present findings suggest that miR-199a-3p delivery by hUC-MSCExos may be a novel strategy for the treatment of OA.
文摘BACKGROUND The reference ranges for biochemical parameters can fluctuate due to factors like altitude,age,gender,and socioeconomic conditions.These values are crucial for interpreting laboratory data and guide clinical treatment decisions.Currently,there is no established set of reference intervals for cord blood biochemical parameters of newborns in India,particularly in Mumbai.AIM To create cord blood biochemical parameters reference intervals specifically for Mumbai,India.METHODS A cross-sectional study was conducted in an Indian tertiary care hospital.This study focused on healthy newborns with normal birth weight,born to pregnant mothers without health issues.Cord blood samples,approximately 2-3 mL in volume,were collected from 210 term neonates.These samples were divided into fluoride(glucose)and clot activator(serum)tubes and were subsequently analyzed in the institute's biochemical laboratory.The data obtained from the analysis was then subjected to statistical analysis.The result of the Shapiro-Wilk test suggested non-normality in the data distribution.Consequently,nonparametric statistics were utilized for analysis.The Mann-Whitney U test was utilized to compare parameter distributions among different factors,including the infant’s sex,delivery method,maternal age,and obstetric history.A significance level of P<0.05 was considered to indicate statistical significance.RESULTS The following represent the median figures and central 95 percentile reference intervals for biochemical parameters in umbilical cord blood of newborns:Serum direct bilirubin=(0.1-0.55)mg/dL,indirect bilirubin=(0.64-2.26)mg/dL,total bilirubin=(0.62-3.14)mg/dL,creatinine=(0.27-0.76)mg/dL,sodium=(128.19-143.26)mmol/L,chloride=(100.19-111.68)mmol/L,potassium=(1.62-9.98)mmol/L and plasma glucose=(24.75-94.23)mg/dL.Statistically significant differences were observed in serum sodium,potassium,and plasma glucose levels when comparing delivery modes.CONCLUSION This is the pioneering study in which first time,the biochemical reference intervals in cord blood for newborns are established in western India.The values are applicable for newborns from this area.Larger study throughout the country is required.
基金Supported by Medical Research Project of Foshan Health Bureau in 2024,No.20240243.
文摘BACKGROUND Cancer-induced incomplete bowel obstruction presents numerous clinical cha-llenges,notably pain management and inflammation control.Conventional thera-pies provide limited relief,prompting investigation into complementary approa-ches.This study compares the efficacy of bottle gourd moxibustion combined with umbilical therapy(BGM-UT)plus standard palliative care vs standard Wes-tern palliative care alone in symptom alleviation and inflammation reduction.AIM To compare the efficacy of BGM-UT plus standard palliative care vs standard pa-lliative care alone in reducing inflammatory cytokine levels,alleviating symp-toms,and improving gastrointestinal recovery in cancer-induced incomplete bowel obstruction.METHODS A retrospective analysis was conducted on 109 patients aged 18-75 years with cancer-induced incomplete bowel obstruction treated at the Foshan Hospital of Traditional Chinese Medicine between October 2023 and September 2024.The participants were categorized into two groups:(1)Regular group receiving stan-dard palliative care;and(2)BGM-UT group receiving additional moxibustion therapy.The inclusion criteria included ongoing opioid use and a Karnofsky per-formance status score below 60.The treatments were evaluated for 3 weeks in terms of opioid consumption,gastrointestinal function recovery,brief pain inven-tory scores,traditional Chinese medicine symptom scores,and inflammatory cytokine levels.RESULTS Initially,the groups were demographically and clinically comparable.Post-treatment,the BGM-UT group showed significant reductions in opioid intake(P=0.027),improved gastrointestinal recovery times,and enhanced pain management as reflected by their lower brief pain inventory scores(P<0.05).Similarly,the improvement in traditional Chinese medicine scores was greater in the BGM-UT group than in the regular group(P<0.05).Inflam-matory markers including interleukin-6,tumor necrosis factor-α,and C-reactive protein decreased significantly in the BGM-UT group,indicating the superior anti-inflammatory effects of this treatment(P<0.05).CONCLUSION The addition of BGM-UT to standard palliative care enhances pain relief,accelerates gastrointestinal recovery,and effectively reduces inflammatory cytokine levels in patients with cancer-induced incomplete bowel obstruction.This combination therapy offers a promising complementary approach to managing this challenging condition.Further prospective studies are warranted to validate these findings and explore underlying mechanisms.
基金Supported by the Joint Innovation Project Funds of Huaqiao University,No.2022YX001。
文摘BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities.However,limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells(HUC-MSCs)on established airway remodeling in experimental asthma.AIM To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin(OVA)-induced asthma.METHODS BALB/c mice underwent sensitization and were challenged using OVA.Control animals were administered a saline solution following the same protocol.HUC-MSCs were identified using flow cytometry.HUC-MSCs at incremental dosages(1×105,2×105,4×105)were injected via tail veins on day 30(the second after the final stimulation).After comparing each group and determining the optimal dose,supplement the optimal dose twice on day 30 and day 33(the second and fifth day after the final stimulation).Bronchoalveolar lavage fluid(BALF)and serum were harvested for analysis of concentrations of interleukin-4(IL-4),IL-13,immunoglobulin E and interferon-gamma(IFN-γ)by enzyme-linked immunosorbent assay.Pharmacology of airways and lung functions were also evaluated to identify the optimal group.RESULTS The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models.This effect is associated with decreased Th2 cytokines IL-4 and IL-13,and increased Th1 cytokine IFN-γ.The optimal dose of 2×105 cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4,IL-13,and IFN-γin serum and BALF compared to other single doses of HUC-MSC.Multiple treatments with the medium dose(2×105 cells)of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes.However,double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γproduction in serum or BALF more effectively than a single medium dose.CONCLUSION HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF,modulating airway remodeling and lung function.In this acute mouse asthma model,a single dosage of 2×105 is optimal,with more significant effects of decreasing airway obstruction requiring repeated administration.
文摘Endometrial injury caused by repeated uterine procedures,infections,inflammation,or uterine artery dysfunction can deplete endometrial stem/progenitor cells and impair regeneration,thereby diminishing endometrial receptivity and evidently lowering the live birth,clinical pregnancy,and embryo implantation rates.Currently,safe and effective clinical treatment methods or gene-targeted therapies are unavailable,especially for severe endometrial injury.Umbilical cord mesenchymal stem cells and their extracellular vesicles are characterized by their simple collection,rapid proliferation,low immunogenicity,and tumorigenicity,along with their involvement in regulating angiogenesis,immune response,cell apoptosis and proliferation,inflammatory response,and fibrosis,Therefore,these cells and vesicles hold broad potential for application in endometrial repair.This article reviewed recent research on human umbilical cord mesenchymal stem cells as well as their extracellular vesicles in repairing endometrial injury.
基金financially supported by the National Natural Science Foundation of China(Grant No.52471301)the Fujian Province Transportation Science and Technology Project(Grant No.JC202302)the Zhejiang Provincial Natural Science Foundation of China(Grant No.LY24E090003).
文摘Buckling failure in submarine cables presents a prevalent challenge in ocean engineering.This work aims to explore the buckling behavior of umbilical cables with damaged sheaths subjected to compression and bending cyclic loads.A finite element model is devised,incorporating a singular armor wire,a rigid core,and a damaged sheath.To scrutinize the buckling progression and corresponding deformation,axial compression and bending cyclic loads are introduced.The observations reveal that a reduction in axial compression results in a larger number of cycles before buckling ensues and progressively shifts the buckling position toward the extrados and fixed end.Decreasing the bending radius precipitates a reduction in the buckling cycle number and minimizes the deformation in the armor wire.Furthermore,an empirical model is presented to predict the occurrence of birdcage buckling,providing a means to anticipate buckling events and to estimate the requisite number of cycles leading to buckling.
基金Supported by the National Key Specialty Major Scientific Research Project of the Hunan Provincial Health Commission,No.Z2023158.
文摘BACKGROUND Diabetes mellitus(DM)and metabolic-associated fatty liver disease(MAFLD)are common metabolic disorders,and their coexistence can exacerbate the progression of either disease.Human umbilical cord mesenchymal stem cell(hUCMSC)therapy has shown promising potential in the treatment of several metabolic diseases.AIM To investigate how hUC-MSCs affect liver metabolism in diabetic rats with MAFLD and assess their therapeutic potential and underlying mechanisms.METHODS A streptozotocin-induced rat model of DM with MAFLD was established,and hUC-MSCs were administered via tail vein injection.Changes in body weight,fasting blood glucose(FBG),and serum triglyceride(TG),alanine aminotransferase,aspartate aminotransferase levels,and pathological changes of liver were evaluated.Receiver operating characteristic analysis was used to assess the diagnostic value of differential metabolites and their ability to predict the therapeutic effects of hUC-MSCs.Spearman correlation was employed to analyze the relationships between liver metabolites and key biochemical markers.RESULTS hUC-MSC treatment significantly reduced FBG and TG levels in diabetic rats with MAFLD and improved histological steatosis and injury in the liver.Metabolomic analysis indicated that hUC-MSCs significantly ameliorated liver metabolic disturbances via their regulatory effect on several key metabolic pathways related to carbohydrate,amino acid,and lipid metabolism.Receiver operating characteristic curve analysis revealed that 70 differential metabolites had good diagnostic value for DM with MAFLD and could effectively predict the therapeutic effect of hUC-MSCs.Moreover,Spearman correlation analysis confirmed that significant correlations existed between differential liver metabolites and the concentrations of biochemical markers(FBG,TG,alanine aminotransferase,aspartate aminotransferase).CONCLUSION hUC-MSCs alleviate liver metabolic disturbances in diabetic rats with MAFLD,thereby mitigating the pathological state of DM and slowing the progression of MAFLD.
基金Supported by the Major Science and Technology Project of Gansu Province-Social Development Field,No.25ZDFA007Health Industry Research Funding Project of Gansu Province,No.GSWSKY2024-54+3 种基金Youth Science and Technology Fund Program of Gansu Province,No.21JR11RA014National Natural Science Foundation of China,No.81273568Health Industry Research Funding Project of Gansu Province,No.GSWSKY2022-03Logistics Scientific Research Independent Project of the PLA.
文摘BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.
基金Key Project of the Hunan Provincial Department of Education(Project No.:21A0024):Effect of Exosomes Derived from Umbilical Cord Blood MSCs Transfected with VEGF165 Gene on Inflammatory Apoptosis of Hepatocytes in Rats with Acute Liver Failure.
文摘Acute liver failure(ALF),a severe clinical syndrome marked by high mortality rates and limited conventional treatments,urgently requires innovative therapeutic strategies.In recent years,human umbilical cord mesenchymal stem cells(hUC-MSCs)have emerged as a research hotspot due to their unique differentiation potential,remarkable regenerative capacity,and significant immune regulatory properties.Studies demonstrate that it can improve liver function through multiple mechanisms,promote hepatocyte regeneration,and reduce hepatic injury.Additionally,their role in regulating inflammatory responses provides new therapeutic approaches for ALF.This review systematically examines the latest research progress on hUC-MSCs in ALF treatment,focusing on their mechanisms of action,therapeutic efficacy,and clinical application prospects,aiming to provide valuable references for future research and clinical practice.
文摘Pulmonary fibrosis,a chronic,fatal lung disease affecting millions worldwide,urgently needs more effective treatments.This article comments on the study by Wang et al,which proposed that human umbilical cord mesenchymal stromal cellderived exosomes alleviate rats radiation induced pulmonary fibrosis.The study demonstrated that these exosomes suppressed inflammation,extracellular matrix deposition,and epithelial-mesenchymal transition by inhibition of AKT signaling in radiation-exposed alveolar epithelial cells.Despite these observations,aspects of the study merit further discussion.Most importantly,further confirmation is needed to prove that the therapeutic effect is exerted through the AKT signaling pathway.Moreover,the definitions of both mesenchymal stem cell and exosomes require further refinement,more rigorous terms should be mesenchymal stromal cell and extracellular vesicles.It seems apparent that this therapy will develop into one of great clinical value.
文摘BACKGROUND Delayed umbilical cord separation(UCS)defined as failure of umbilical cord fall beyond 3 weeks is seen in up to 10%of newborns.Since delayed UCS can be associated with leukocyte adhesion deficiency(LAD)or coagulation factorⅩⅢdeficiency,these children are commonly referred to hematology/oncology for further investigation.Although the incidence of urachal remnants(UR);also associated with delayed UCS,is more common(1.16%)than LAD(1:1000000 births),and coagulation factorⅩⅢdeficiency(1:5000000 births)it’s less commonly investigated.CASE SUMMARY Two otherwise healthy infants,a 6-week-old female and a 4-week-old male were seen at our hematology/oncology clinic for delayed UCS.In both cases the umbilical cords looked healthy,with no signs of infection or pus,but appeared to show small Umbilical Granulomas.They were both investigated for LAD type I and one was investigated forⅩⅢdeficiency,but both tests were negative.These infants however,were investigated via abdominal ultrasound which showed UR in both cases.These infants required no intervention.CONCLUSION This report demonstrates an often overlooked association between delayed UCS and UR and suggests abdominal ultrasound if necessary for diagnosis.
基金Supported by the Foundation of Health Commission of Hubei Province,No.WJ2019H053Natural Science Foundation of Hubei Province,No.2023AFB169+1 种基金Foundation of Health Commission of Hubei Province,No.ZY2021Q019Open Fund Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells,Taihe Hospital,No.2024SCOF008.
文摘BACKGROUND Large number of decompensated liver cirrhosis patients in China have been diagnosed with hepatitis B virus(HBV).Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)can possibly cure decompensated liver cirrhosis because of their self-renewal and multidirectional differentiation potential.AIM To explore the safety and effect of treating liver cirrhosis with HBV by hUC-MSCs.METHODS Twenty-four participants were recruited,divided into 3 groups,and injected with different amounts of hUC-MSCs via the peripheral vein.Therapy was administered 3 times.A 24-week follow-up examination of each patient’s liver function,coagulation function,general condition,and immune system was performed.Adverse events were also recorded.A 2-year survival assessment was subsequently performed.RESULTS Infusion therapy rapidly improved liver function.Serum albumin transiently increased on days 57 and 85 but returned to baseline by day 169,while prothrombin time activity demonstrated sustained improvement from day 29 through day 169.Interleukin-8 levels decreased persistently throughout treatment.All dosage groups achieved 100%6-month survival;2-year survival rates were 66.7%(low-dose),100%(medium-dose),and 87.5%(high-dose).The interaction between dosage and efficacy was weak.Notably,the improvement in liver function was statistically significant and sustained for almost 3 months,suggesting clinically meaningful therapeutic durability.CONCLUSION hUC-MSCs can be considered a safe treatment for patients with decompensated liver cirrhosis associated with HBV.However,larger-scale randomized controlled trials are needed to prove its therapeutic effect.
基金approved by the Institutional Animal Care and Use Committee of Cloud-Clone Corp Wuhan(protocol No.IACU23-1252,on November 29,2023).
文摘BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In China,5.6%-11.5%of the population has IBS,with diarrheal IBS(IBS-D)comprising about 31.5%of the total.AIM To investigate how human umbilical cord mesenchymal stem cells(hUC-MSCs)can alleviate the symptoms with the help of an IBS-D rat model.METHODS Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups:Control group,model group,and three hUC-MSC groups with different doses.The model group was induced using a combination of acetic acid and binding stress.We determined the body weight of the mice;analyzed their fecal characteristics,inflammatory factors,and intestinal tissue damage;and conducted intestinal flora analyses.RESULTS The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent.In addition,hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue.In addition,hUC-MSCs were able to maintain the abundance and diversity of gut flora.CONCLUSION Thus,hUC-MSCs can reduce the expression of inflammatory factors,improve the expression of intestinal barrier functional proteins,and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.
文摘One of the most prevalent long-term effects of diabetes is diabetic kidney disease(DKD),which is linked to problems with the metabolism of amino acids,fats,and carbohydrates.The fundamental pathogenic mechanisms of DKD cannot be adequately treated by current clinical medicines;they can only slow the illness’s progression to end-stage renal disease.We will concentrate on integrating human umbilical cord mesenchymal stem cell(hUC-MSC)-related mechanisms and potential applications into the therapy of DKD,as this work shows that hUCMSCs can be used to treat metabolic liver obesity associated with diabetes.Future studies on the connection between hUC-MSCs and related illnesses ought to be promoted.
文摘Rationale:Abdominal pain is a common complaint with a broad differential diagnosis,including both intra-abdominal and abdominal wall pathologies.While visceral causes are frequently considered,abdominal wall conditions are often overlooked,leading to diagnostic delays.Among them,umbilical abscesses are rare but require distinction from urachal abscesses due to differences in management.Patient’s concern:A 46-year-old woman presented with a one-week history of periumbilical pain unresponsive to analgesics.Diagnosis:Physical examination revealed localized tenderness and a positive Carnett’s sign.Computed tomographic images identified an umbilical abscess without evidence of urachal remnants,ruling out a urachal abscess.Interventions:The patient underwent abscess drainage and received cefalexin(1500 mg/day)for 28 days.Outcomes:The abscess resolved completely without recurrence.Lessons:Umbilical abscesses are rare and may be mistaken for urachal abscesses.A thorough clinical evaluation,including Carnett’s sign and imaging studies,is crucial for accurate diagnosis.Prompt differentiation facilitates appropriate management and prevents unnecessary interventions.
基金funded by the Ministry of Higher Education Malaysia for the Prototype Research Grant Scheme(PRGS)with Project Code PRGS/1/2021/SKK07/USM/02/1.
文摘Objective This study aimed to evaluate the potential of a collagen-coated,3D-printed tracheal scaffold(3D-TechTra)integrated with human umbilical cord mesenchymal stem cells(hUC-MSCs)for tracheal tissue regeneration.Methods The thermoplastic polyurethane/polylactic acid(TPU/PLA)scaffold was engineered to optimize mechanical properties and biocompatibility,with the goal of mimicking the structural and tensile characteristics of native tracheal tissue.Subsequently,preclinical experiments were conducted using rabbit models:the performance of the collagen-coated TPU/PLA scaffold with hUC-MSCs was compared with that of uncoated scaffolds and collagen-only scaffolds.In vitro tests were also performed to assess the adhesion,proliferation,and differentiation of hUC-MSCs on the scaffold.For in vivo evaluation,multiple analytical methods were employed,including immunohistological analysis(to detect glycosaminoglycan deposition and extracellular matrix remodeling),radiographic and endoscopic evaluations(to assess tracheal contour and airway obstruction),and survival analysis(to monitor animal outcomes and systemic toxicity).Results In vitro,hUC-MSCs successfully adhered to and proliferated on the TPU/PLA scaffold,and differentiated into adipogenic,osteogenic,and chondrogenic lineages,which supported the potential for tissue-specific regeneration;in vivo,compared with uncoated or collagen-only scaffolds,the collagen-coated TPU/PLA scaffold integrated with hUC-MSCs exhibited enhanced integration with host tissues,superior biocompatibility,and reduced tracheal stenosis,while also preserving airway patency,alleviating inflammation,and facilitating epithelial regeneration,smooth muscle formation,and vascularization.Immunohistological analysis further revealed significant glycosaminoglycan deposition and extracellular matrix remodeling in the hUC-MSC-treated group,and radiographic and endoscopic evaluations confirmed preserved tracheal contour and reduced airway obstruction;additionally,survival analysis showed significantly improved outcomes in animals treated with the collagen-coated TPU/PLA scaffold containing hUC-MSCs,with no systemic toxicity observed.Conclusions This study demonstrated the synergistic potential of TPU/PLA scaffolds,collagen coatings,and hUC-MSCs,providing valuable evidence for advancing the application of these components in tracheal tissue engineering.
基金Supported by the National Natural Science Foundation of China,No.82260944the Key Research and Development Programs of Guangxi,No.2021AB09011。
文摘BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),offer promise due to their osteogenic and immunomodulatory potential.Sclerostin(SOST)inhibits bone formation,so we developed a multi-target gene silencing strategy against SOST using RNA interference.We created hUCMSCs with SOST-silenced(sh-hUCMSCs)and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice.This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.AIM To assess the effects of sh-hUCMSCs on bone metabolism in SANFH.METHODS hUCMSCs were isolated from placental tissue and transfected with SOST-targeting short hairpin RNA plasmids.A SANFH mouse model was established through intraperitoneal injection of lipopolysaccharide(20μg/kg)followed by intramuscular methylprednisolone administration(40 mg/kg).Mice were randomized into four experimental groups(n=10/group):Sham control,SANFH(untreated),hUCMSCs-treated,and sh-hUCMSCs-treated.Micro-computed tomography was used to measure bone volume(BV),bone surface area,bone surface/BV ratio,tra-becular number,trabecular thickness,and trabecular separation.Quantification of adipocyte area by hematoxylin and eosin staining.Collagen fiber volume was assessed by Masson’s trichrome staining.Serum levels of osteopro-tegerin(OPG),receptor activator of nuclear factor kappa B(RANK),RANK ligand(RANKL),tartrate-resistant acid phosphatase,and the OPG/RANKL ratio were measured by enzyme-linked immunosorbent assay.The expression levels of alkaline phosphatase,OPG,SOST,β-catenin,peroxisome proliferator-activated receptor gamma,and CCAAT/enhancer-binding protein in bone tissue were determined by western blot analysis.RESULTS hUCMSCs and sh-hUCMSCs exhibited typical fibroblast-like morphology and high expression of MSC surface markers(CD90,CD73,CD105>98%).These cells demonstrated tri-lineage differentiation potential,confirmed by positive Alizarin Red S,Oil Red O,and Alcian Blue staining,and upregulation of lineage-specific genes.After SOST-RNA interference modification,sh-hUCMSCs showed enhanced inhibition of adipogenesis and improved bone formation in a rat model of SANFH.Histological analysis revealed reduced lipid infiltration and empty lacunae in the femoral head of the sh-hUCMSC group.Western blot showed decreased CCAAT/enhancer-binding protein and peroxisome proliferator-activated receptor gamma expression(P<0.05).Masson staining and micro-computed tomography analysis confirmed significantly increased BV,trabecular number,trabecular thickness,and reduced trabecular separation in the sh-hUCMSC group compared to unmodified MSCs and SANFH groups(P<0.05).Serum enzyme-linked immunosorbent assay showed higher OPG and lower RANK,RANKL,and tartrate-resistant acid phosphatase levels in the sh-hUCMSCs group.Western blot further confirmed upregulated alkaline phosphatase,OPG,β-catenin,and downregulated SOST expression in sh-hUCMSCs compared to controls(P<0.05).These results suggest that SOST inhibition enhances the osteogenic potential and therapeutic efficacy of hUCMSCs in SANFH.CONCLUSION sh-hUCMSCs alleviate SANFH by activating the Wnt/β-catenin signaling pathway,thereby promoting osteogenic differentiation and suppressing adipogenesis to restore bone metabolic balance.
基金supported by the Xuzhou City 2022 Special Program for Promoting Science and Technology Innovation(grant No.KC22096)Shandong Provincial Hospital Research Incubation Fund(No.2022FY063).
文摘Stem cell treatment may enhance erectile dysfunction(ED)in individuals with cavernous nerve injury(CNI).Nevertheless,no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)on ED.We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED.Sprague–Dawley rats(total=175)were randomly allocated into five groups.A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs(1×106 cells,5×106 cells,and 1×107 cells in 0.1 ml,respectively).Penile tissues were harvested for histological analysis on 1 day,3 days,7 days,14 days,28 days,60 days,and 90 days postsurgery.It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED.Moreover,there was no significant disparity in the effectiveness of various dosages of HUC-MSCs.However,the expression of endothelial markers(rat endothelial cell antigen-1[RECA-1]and endothelial nitric oxide synthase[eNOS]),smooth muscle markers(alpha smooth muscle actin[α-SMA]and desmin),and neural markers(neurofilament[RECA-1]and neurogenic nitric oxide synthase[nNOS])increased significantly with prolonged treatment time.Masson’s staining demonstrated an increased in the smooth muscle cell(SMC)/collagen ratio.Significant changes were detected in the microstructures of various types of cells.In vivo imaging system(IVIS)analysis showed that at the 1st day,the HUC-MSCs implanted moved to the site of damage.Additionally,the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
