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
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
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
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 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
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
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
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
Heart failure(HF)is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood.Currently,HF remains a leading cause of morbidity and mortality worldwide,imposing a substant...Heart failure(HF)is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood.Currently,HF remains a leading cause of morbidity and mortality worldwide,imposing a substantial burden on global healthcare systems.Recent advancements have highlighted the therapeutic potential of mesenchymal stromal cells(MSCs)in managing HF.Notably,umbilical cord-derived MSCs(UC-MSCs)have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs;this is evident in their non-invasive collection process,higher proliferation efficacy,and lower immunogenicity and tumorigenicity,as substantiated by preclinical studies.Although the feasibility and safety of UC-MSCs have been tested in animal models,the application of UC-MSCs in HF treatment remains challenged by issues such as inaccurate targeted migration and low survival rates of UC-MSCs.Therefore,further research and clinical trials are imperative to advance the clinical application of UC-MSCs.展开更多
Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,w...Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.展开更多
BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium...BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium.METHODS RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs(miRNAs)in human umbilical cord mesenchymal stem cell(hucMSC)treated with exosomes enriched with endometrial cell-derived components.Additionally,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways,molecular functions,and cellular components.Transwell and wound healing assays were performed to assess migratory potential,and western blotting was detected protein level.RESULTS A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components,comprising 27 upregulated and 26 downregulated miRNAs,which includes miR-137-3p.Enhanced migratory potential was observed in the Transwell and wound healing assays,and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3.These effects were attributed to the upregulation of miR-137-3p.CONCLUSION miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway,enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.展开更多
BACKGROUND We investigated the efficacy of intra-articular injection of human umbilical cord mesenchymal stem cells(hUC-MSCs)for the treatment of osteoarthritis(OA)progression in the knee joint.Although many experimen...BACKGROUND We investigated the efficacy of intra-articular injection of human umbilical cord mesenchymal stem cells(hUC-MSCs)for the treatment of osteoarthritis(OA)progression in the knee joint.Although many experimental studies of hUC-MSCs have been published,these studies have mainly used fetal bovine serumcontaining cultures of hUC-MSCs;serum-free cultures generally avoid the shortcomings of serum-containing cultures and are not subject to ethical limitations,have a wide range of prospects for clinical application,and provide a basis or animal experimentation for clinical experiments.AIM To study the therapeutic effects of serum-free hUC-MSCs(N-hUCMSCs)in a mouse model of knee OA.METHODS Fifty-five male C57BL/6 mice were randomly divided into six groups:The blank control group,model control group,serum-containing hUC-MSCs(S-hUCMSC)group,N-hUCMSC group and hyaluronic acid(HA)group.After 9 weeks of modeling,the serum levels of interleukin(IL)-1β and IL-1 were determined.Hematoxylin-eosin staining was used to observe the cartilage tissue,and the Mankin score was determined.Immunohistochemistry and western blotting were used to determine the expression of collagen type II,matrix metalloproteinase(MMP)-1 and MMP-13.RESULTS The Mankin score and serum IL-1 and IL-1β and cartilage tissue MMP-1 and MMP-13 expression were significantly greater in the experimental group than in the blank control group(P<0.05).Collagen II expression in the experimental group was significantly lower than that in the blank control group(P<0.05).The Mankin score and serum IL-1 and IL-1β and cartilage tissue MMP-1 and MMP-13 levels the experimental group were lower than those in the model control group(P<0.05).Collagen II expression in the experimental group was significantly greater than that in the model control group(P<0.05).CONCLUSION N-hUCMSC treatment significantly alleviate the pathological damage caused by OA.The treatment effects of the ShUCMSC group and HA group were similar.展开更多
BACKGROUND Umbilical artery thrombosis(UAT)is extremely uncommon and leads to adverse perinatal outcomes.Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT.Ultrasound is an effect...BACKGROUND Umbilical artery thrombosis(UAT)is extremely uncommon and leads to adverse perinatal outcomes.Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT.Ultrasound is an effective way to detect thrombosis.The mother can monitor her own fetal health using ultrasound,which enables her to take preventative action in case of emergency.AIM To investigate ultrasonic blood signal after UAT in the umbilical artery,and evaluate the relationship between hypercoagulability and UAT.METHODS We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow,and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital.Patients’information was collected from medical archives,including maternal clinical data,neonatal outcomes,pathological findings and ultrasonic indices of umbilical artery blood flow,such as systolic-diastolic duration ratio(S/D),resistance index(RI),pulsatility index(PI)and peak systolic velocity(PSV).Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R(version 4.2.1)including car(version 3.1-0)and stats(version 4.2.1),and visualized by ggplot2 package(version 3.3.6).RESULTS A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow(within 2.5th of reference ranges)in a short period of time.Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D,RI,and PI and increase of PSV during the disease process was greater than that of non-UAT.All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery,most of which(16/18)showed umbilical cord abnormalities,with 15 umbilical cord torsion and 1 pseudoknot.Coagulation parameters were not significantly changed in UAT patients compared with normal pregnancy women.CONCLUSION Significant changes in ultrasound indicators after UAT were demonstrated.PSV can play important roles in the diagnosis of UAT.Hypercoagulability alone is not sufficient for the occurrence of UAT.展开更多
Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regu...Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.展开更多
BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that t...BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that timely interventions can be implemented to safeguard the health and safety of the fetus.AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress.METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups(n=50 each),according to the presence or absence of intrauterine distress.The ultrasound hemodynamic parameters of the uterine artery(UtA),fetal middle cerebral artery(MCA),and umbilical artery(UmA)were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups.RESULTS Comparison of ultrasonic hemodynamic parameters,resistance index(RI),pulsatility index(PI),and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity(S/D),revealed higher values of fetal MCA,PI,and S/D of UmA in pregnant women with UtA compared to controls(P<0.05),while there was no difference between the two groups in terms of RI(P<0.05)The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group(66.7%)than in the control group(90.0%),and neonatal weight(2675.5±27.6 g)was lower than in the control group(3117.5±31.2 g).Further,cesarean section rate was higher in the observation group(70.0%)than in the control group(11.7%),and preterm labor rate was higher in the observation group(40.0%)than in the control group(10.0%).The incidence of fetal distress,neonatal growth restriction and neonatal asphyxia were also higher in the observation group(all P<0.05).CONCLUSION Fetal MCA,UmA,and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy,which suggests that clinical attention should be paid to them,and monitoring should be strengthened to provide guidance for clinical intervention.展开更多
Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechan...Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.展开更多
BACKGROUND Pelvic organ prolapse(POP)involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity,and vaginal structure is an essential factor.In POP,the vaginal walls exhibit abnormal collagen d...BACKGROUND Pelvic organ prolapse(POP)involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity,and vaginal structure is an essential factor.In POP,the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions.The intricate etiology of POP and the prohibition of trans-vaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development.Human umbilical cord mesenchymal stromal cells(hucMSCs)present limitations,but their exosomes(hucMSC-Exo)are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.suppressed inflammation in POP group fibroblasts,stimulated primary fibroblast growth,and elevated collagen I(Col1)production in vitro.High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11(MMP11)expression.CONCLUSION HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro.Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression.HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.展开更多
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.
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 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.
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.
文摘Heart failure(HF)is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood.Currently,HF remains a leading cause of morbidity and mortality worldwide,imposing a substantial burden on global healthcare systems.Recent advancements have highlighted the therapeutic potential of mesenchymal stromal cells(MSCs)in managing HF.Notably,umbilical cord-derived MSCs(UC-MSCs)have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs;this is evident in their non-invasive collection process,higher proliferation efficacy,and lower immunogenicity and tumorigenicity,as substantiated by preclinical studies.Although the feasibility and safety of UC-MSCs have been tested in animal models,the application of UC-MSCs in HF treatment remains challenged by issues such as inaccurate targeted migration and low survival rates of UC-MSCs.Therefore,further research and clinical trials are imperative to advance the clinical application of UC-MSCs.
基金the National Natural Science Foundation of China,No.82170406 and No.81970238the Royal Society United Kingdom,No.IEC\NSFC\201094.
文摘Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-080 and No.2022-PUMCH-C-064.
文摘BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium.METHODS RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs(miRNAs)in human umbilical cord mesenchymal stem cell(hucMSC)treated with exosomes enriched with endometrial cell-derived components.Additionally,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways,molecular functions,and cellular components.Transwell and wound healing assays were performed to assess migratory potential,and western blotting was detected protein level.RESULTS A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components,comprising 27 upregulated and 26 downregulated miRNAs,which includes miR-137-3p.Enhanced migratory potential was observed in the Transwell and wound healing assays,and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3.These effects were attributed to the upregulation of miR-137-3p.CONCLUSION miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway,enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.
基金Supported by the Cultivated by Outstanding Young Scientific and Technological Innovation and Entrepreneurship Talents in Nanning City,China,No.RC20210107and Self-Funded Research Project by Guangxi Health Commission,China,No.Z20191090.
文摘BACKGROUND We investigated the efficacy of intra-articular injection of human umbilical cord mesenchymal stem cells(hUC-MSCs)for the treatment of osteoarthritis(OA)progression in the knee joint.Although many experimental studies of hUC-MSCs have been published,these studies have mainly used fetal bovine serumcontaining cultures of hUC-MSCs;serum-free cultures generally avoid the shortcomings of serum-containing cultures and are not subject to ethical limitations,have a wide range of prospects for clinical application,and provide a basis or animal experimentation for clinical experiments.AIM To study the therapeutic effects of serum-free hUC-MSCs(N-hUCMSCs)in a mouse model of knee OA.METHODS Fifty-five male C57BL/6 mice were randomly divided into six groups:The blank control group,model control group,serum-containing hUC-MSCs(S-hUCMSC)group,N-hUCMSC group and hyaluronic acid(HA)group.After 9 weeks of modeling,the serum levels of interleukin(IL)-1β and IL-1 were determined.Hematoxylin-eosin staining was used to observe the cartilage tissue,and the Mankin score was determined.Immunohistochemistry and western blotting were used to determine the expression of collagen type II,matrix metalloproteinase(MMP)-1 and MMP-13.RESULTS The Mankin score and serum IL-1 and IL-1β and cartilage tissue MMP-1 and MMP-13 expression were significantly greater in the experimental group than in the blank control group(P<0.05).Collagen II expression in the experimental group was significantly lower than that in the blank control group(P<0.05).The Mankin score and serum IL-1 and IL-1β and cartilage tissue MMP-1 and MMP-13 levels the experimental group were lower than those in the model control group(P<0.05).Collagen II expression in the experimental group was significantly greater than that in the model control group(P<0.05).CONCLUSION N-hUCMSC treatment significantly alleviate the pathological damage caused by OA.The treatment effects of the ShUCMSC group and HA group were similar.
基金Natural Science Foundation of Xiamen,No.3502Z202373120and National Key R&D Program of China,No.2022YFF0606301.
文摘BACKGROUND Umbilical artery thrombosis(UAT)is extremely uncommon and leads to adverse perinatal outcomes.Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT.Ultrasound is an effective way to detect thrombosis.The mother can monitor her own fetal health using ultrasound,which enables her to take preventative action in case of emergency.AIM To investigate ultrasonic blood signal after UAT in the umbilical artery,and evaluate the relationship between hypercoagulability and UAT.METHODS We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow,and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital.Patients’information was collected from medical archives,including maternal clinical data,neonatal outcomes,pathological findings and ultrasonic indices of umbilical artery blood flow,such as systolic-diastolic duration ratio(S/D),resistance index(RI),pulsatility index(PI)and peak systolic velocity(PSV).Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R(version 4.2.1)including car(version 3.1-0)and stats(version 4.2.1),and visualized by ggplot2 package(version 3.3.6).RESULTS A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow(within 2.5th of reference ranges)in a short period of time.Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D,RI,and PI and increase of PSV during the disease process was greater than that of non-UAT.All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery,most of which(16/18)showed umbilical cord abnormalities,with 15 umbilical cord torsion and 1 pseudoknot.Coagulation parameters were not significantly changed in UAT patients compared with normal pregnancy women.CONCLUSION Significant changes in ultrasound indicators after UAT were demonstrated.PSV can play important roles in the diagnosis of UAT.Hypercoagulability alone is not sufficient for the occurrence of UAT.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)the National Natural Science Foundation of China No.81930070(to SF)+1 种基金Multi-fund Investment Key Projects,No.21JCZDJC01100(to ZW)the Tianjin Science and Technology Planning Project,No.22JRRCRC00010(to SF)。
文摘Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.
文摘BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that timely interventions can be implemented to safeguard the health and safety of the fetus.AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress.METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups(n=50 each),according to the presence or absence of intrauterine distress.The ultrasound hemodynamic parameters of the uterine artery(UtA),fetal middle cerebral artery(MCA),and umbilical artery(UmA)were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups.RESULTS Comparison of ultrasonic hemodynamic parameters,resistance index(RI),pulsatility index(PI),and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity(S/D),revealed higher values of fetal MCA,PI,and S/D of UmA in pregnant women with UtA compared to controls(P<0.05),while there was no difference between the two groups in terms of RI(P<0.05)The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group(66.7%)than in the control group(90.0%),and neonatal weight(2675.5±27.6 g)was lower than in the control group(3117.5±31.2 g).Further,cesarean section rate was higher in the observation group(70.0%)than in the control group(11.7%),and preterm labor rate was higher in the observation group(40.0%)than in the control group(10.0%).The incidence of fetal distress,neonatal growth restriction and neonatal asphyxia were also higher in the observation group(all P<0.05).CONCLUSION Fetal MCA,UmA,and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy,which suggests that clinical attention should be paid to them,and monitoring should be strengthened to provide guidance for clinical intervention.
基金supported by the tenth batch of"3221"industrial innovation and scientific research projects in Bengbu City(beng talent[2020]No.8)the 2021 Bengbu Medical College Science and Technology Project[Natural Science,Project Number:2021byzd217].
文摘Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.
基金Supported by the National Natural Science Foundation of China,No.81671439the Science and Technology Commission of Shanghai Municipality,No.21Y11906700 and No.20Y11907300the Medical Innovation Research Project of the Science and Technology Commission of Shanghai Municipality,No.22Y11906500。
文摘BACKGROUND Pelvic organ prolapse(POP)involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity,and vaginal structure is an essential factor.In POP,the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions.The intricate etiology of POP and the prohibition of trans-vaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development.Human umbilical cord mesenchymal stromal cells(hucMSCs)present limitations,but their exosomes(hucMSC-Exo)are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.suppressed inflammation in POP group fibroblasts,stimulated primary fibroblast growth,and elevated collagen I(Col1)production in vitro.High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11(MMP11)expression.CONCLUSION HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro.Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression.HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
