Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments h...Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments have been extensively explored,limited research has addressed how thermal treatment alone alters the surface properties and reinforcing behavior of SCB fibers.This study aims to fill that gap by investigating the effects of heat treatment on SCB fiber structure and its performance in starch/poly(vinyl alcohol)(PVA)composites.Characterization techniques including Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and scanning electron microscopy(SEM)were employed to analyze changes in fiber morphology,surface chemistry,and crystallinity.Mechanical properties were assessed via tensile,flexural,and impact testing,and moisture absorption was also evaluated.Composites reinforced with SCB fibers treated at 200○C exhibited significantly superior mechanical properties compared to those prepared with untreated or differently treated fibers.The tensile,flexural,and impact performance of the composites were 15.13,19.37 MPa,and 7.28 J/m,respectively.Composites treated at this temperature also retained better mechanical properties after exposure to humidity.These findings demonstrate that heat treatment is a simple and sustainable method to improve the durability and mechanical performance of nature fiber-reinforced composites,expanding their potential for environmentally friendly material applications.展开更多
Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)...Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)K and at ambient pressure(81.5 kPa).From the experimental data,excess molar volume(V_(m)~E),thermal expansion coefficients(α),deviations in isentropic compressibility(Δκ_(S)),viscosity(Δ_η),and refractive index(Δn_(D))were calculated.These values were then correlated using the Redlich-Kister polynomial equation,with fitting coefficients and standard deviations determined.Additionally,the Prigogine-Flory-Patterson(PFP)theory and the Extended Real Associated Solution(ERAS)model were employed to correlate the excess molar volume,while the Perturbed Chain Statistical Associating Fluid Theory(PC-SAFT)was used to predict the density of mixtures.展开更多
BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
In this review,we explore the application of next-generation sequencing in liver cancer research,highlighting its potential in modern oncology.Liver cancer,particularly hepatocellular carcinoma,is driven by a complex ...In this review,we explore the application of next-generation sequencing in liver cancer research,highlighting its potential in modern oncology.Liver cancer,particularly hepatocellular carcinoma,is driven by a complex interplay of genetic,epigenetic,and environmental factors.Key genetic alterations,such as mutations in TERT,TP53,and CTNNB1,alongside epigenetic modifications such as DNA methylation and histone remodeling,disrupt regulatory pathways and promote tumorigenesis.Environmental factors,including viral infections,alcohol consum-ption,and metabolic disorders such as nonalcoholic fatty liver disease,enhance hepatocarcinogenesis.The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance,with immune cell infiltration,fibrosis,and angiogenesis supporting cancer cell survival.Advances in immune check-point inhibitors and chimeric antigen receptor T-cell therapies have shown po-tential,but the unique immunosuppressive milieu in liver cancer presents challenges.Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies.Next-generation sequencing is accele-rating the identification of genetic and epigenetic alterations,enabling more precise diagnosis and personalized treatment plans.A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.展开更多
BACKGROUND Treatment response to direct-acting antivirals(DAAs)is a challenging issue and the identification of non-responders patients is very important.AIM To evaluate the relation between baseline serum levels of h...BACKGROUND Treatment response to direct-acting antivirals(DAAs)is a challenging issue and the identification of non-responders patients is very important.AIM To evaluate the relation between baseline serum levels of hyaluronic acid(HA)and type III procollagen N-peptide(PIIINP)with direct-acting antivirals treatment failure in Egyptian patients with chronic hepatitis C.METHODS Hepatitis C patients(responders and non-responders to sofosbuvir/daclatasvir)were tested for HA and PIIINP using sensitive chemiluminescent immunoassay.RESULTS There were distinctly higher PIIINP(P=0.0003)and HA(P<0.0001)levels in non-responders than responders patients with a good ability for distinguishing non-responders from patients with sustained virological response(area under the curve=0.766 for HA and 0.684 for PIIINP).Logistic regression analysis revealed that the HA×PIIINP is the model with the highest predictive ability(area under the curve=0.809).Diagnostic performances were superior to each marker alone with good sensitivity(74.7%),specificity(74%),positive predictive(68.3%),negative predictive values(79.6%)and accuracy(74.3%).The multiplication of HA×PIIINP is correlated significantly(P<0.05)with elevated liver enzymes(r=0.212),decreased albumin(r=-0.26),elevated aspartate aminotransferase-platelet ratio index(r=0.223)and elevated fibrosis-4 score(r=0.216)scores.CONCLUSION These findings suggested the remarkable role of fibrogensis markers HA and PIIINP in the prediction of hepatitis C virus DAAs treatment response.Multiplying HA with PIIINP values increase the sensitivity to detect treatment success and thus may aim to improve treatment duration and the disease control.展开更多
Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met th...Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.展开更多
Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional ...Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.展开更多
This article seeks to emphasize a simplified approach to phylogeny research using complete mitochondrial genomes alone, while touching upon a number of technological perspectives, such as algorithmic selection, which ...This article seeks to emphasize a simplified approach to phylogeny research using complete mitochondrial genomes alone, while touching upon a number of technological perspectives, such as algorithmic selection, which can help improve accuracy and performance in comparative analysis. My results will show that reliable estimations can be obtained by using mitochondrial markers, even among time-extended taxonomical rankings. Six distinct mammalian groups of taxa were selected for comparison. In all cases, mtDNA models generated reliable phylogeny approximations when compared against other independent data, while rendering exceptional computational performance.展开更多
Background: Pregnant women and newborns are highly susceptible to Covid-19, manifesting as multisystem inflammatory syndrome-New-born (MISC-N) in many babies born to Covid positive mothers. The relationship between Co...Background: Pregnant women and newborns are highly susceptible to Covid-19, manifesting as multisystem inflammatory syndrome-New-born (MISC-N) in many babies born to Covid positive mothers. The relationship between Covid-19 infection during pregnancy and neonatal neurodevelopmental outcome, if any, is unclear necessitating a follow-up study in this aspect. Methods: 16 babies with MIS-N, born to symptomatic Covid antibody positive mothers were enrolled. Demographic profile, treatment details and biochemical parameters were analyzed with neurodevelopmental follow-up. Results: 25% mothers received 2 doses of Covid vaccine;50% had oligohydramnios and 75% received antenatal steroids. 87.5% were preterm of which 62.5% required surfactant with ventilator support and 75% required ionotropic support. Significant association was found between the antibody level and D-dimer levels with the ferritin and LDH levels of the baby (p 0.05);gestational age with LDH and D-dimer levels (p 0.05) and Covid antibody level of the baby vs the duration of ventilator requirement (P-value-0.0009). D-dimer values of babies were positively associated with both maternal antibody and D-dimer levels. Neurodevelopmental follow-up done at 6 months of corrected gestational age showed 37.5% were normal, 37.5% hypertonic and 25% hypotonic. HINE score was below 60 in 62.5%. Development assessment using Bayley-III showed a delay in the motor domain (62.5%), cognitive domain (56.25%) and language domain (62.5%). Conclusion: Neurodevelopmental problems occur in babies born to Covid positive mothers and should be stratified as “high risk”. Anticipatory guidance to prospective mothers for preterm care should be given. Covid antibody titre and D-dimer levels may help to predict the NICU stay, ventilator requirement and the adverse neurodevelopmental outcomes in these babies.展开更多
The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup p...The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup physico-chemical evaluation such as pH, density, identification of polysaccharide, tanning agents, ascorbic acid and shelf life was complied. The TLC and quantitative determination of alkaloid were quantified. Determination of biomarker has been validated for the analysis of vasicine. The study result revealed that Linkus syrup formulation was well standardized at different levels such as physic-chemical consistency and assay of bio marker compound.展开更多
The increasing integration of new technologies is driving a fundamental revolution in the healthcare sector.Developments in artificial intelligence(AI),machine learning,and big data analytics have completely transform...The increasing integration of new technologies is driving a fundamental revolution in the healthcare sector.Developments in artificial intelligence(AI),machine learning,and big data analytics have completely transformed the diagnosis,treatment,and care of patients.AI-powered solutions are enhancing the efficiency and accuracy of healthcare delivery by demonstrating exceptional skills in personalized medicine,early disease detection,and predictive analytics.Furthermore,telemedicine and remote patient monitoring systems have overcome geographical constraints,offering easy and accessible healthcare services,particularly in underserved areas.Wearable technology,the Internet of Medical Things,and sensor technologies have empowered individuals to take an active role in tracking and managing their health.These devices facilitate real-time data collection,enabling preventive and personalized care.Additionally,the development of 3D printing technology has revolutionized the medical field by enabling the production of customized prosthetics,implants,and anatomical models,significantly impacting surgical planning and treatment strategies.Accepting these advancements holds the potential to create a more patient-centered,efficient healthcare system that emphasizes individualized care,preventive care,and better overall health outcomes.This review's novelty lies in exploring how these technologies are radically transforming the healthcare industry,paving the way for a more personalized and effective healthcare for all.It highlights the capacity of modern technology to revolutionize healthcare delivery by addressing long-standing challenges and improving health outcomes.Although the approval and use of digital technology and advanced data analysis face scientific and regulatory obstacles,they have the potential for transforming translational research.as these technologies continue to evolve,they are poised to significantly alter the healthcare environment,offering a more sustainable,efficient,and accessible healthcare ecosystem for future generations.Innovation across multiple fronts will shape the future of advanced healthcare technology,revolutionizing the provision of healthcare,enhancing patient outcomes,and equipping both patients and healthcare professionals with the tools to make better decisions and receive personalized treatment.As these technologies continue to develop and become integrated into standard healthcare practices,the future of healthcare will probably be more accessible,effective,and efficient than ever before.展开更多
Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoi...Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.展开更多
Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fastin...Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.展开更多
Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cea...Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.展开更多
One major problem that humanity has been confronting recently is water quality. Just 2.5 percent of the water resources on Earth are freshwater resources. Water is an indispensable resource for all living things, and ...One major problem that humanity has been confronting recently is water quality. Just 2.5 percent of the water resources on Earth are freshwater resources. Water is an indispensable resource for all living things, and it is a vital value. Pollution of limited freshwater resources causes further pressure on freshwater resources. Humans play a major role in the waste and pollution of this essential natural resource. This research project focused on the impacts of water pollution and its effects on agriculture, land and aquatic systems, a case study which was conducted in River Njoro, in Nakuru County. With the aid of questioners for information acquisition, the study determined different pollutants and their impact on agriculture. Results indicated that there is a dire need for conservation efforts in the area. Humanity should receive education awareness-capacity building regarding water contamination in order to mitigate the issues to some extent. By doing so, the world we live in becomes a better place for all.展开更多
DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expressi...DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).展开更多
BACKGROUND Mesenchymal stromal cells(MSCs)are renowned for their immunosuppressive properties,which make them widely used in managing excessive inflammation.Although CD146+and CD146-MSCs exhibit similar morphological ...BACKGROUND Mesenchymal stromal cells(MSCs)are renowned for their immunosuppressive properties,which make them widely used in managing excessive inflammation.Although CD146+and CD146-MSCs exhibit similar morphological traits and surface marker expression levels,the specific characteristics and differential regulatory mechanisms of these two subtypes remain poorly understood.This knowledge gap has limited the precise application of MSCs in targeted thera-peutic strategies.AIM To compare the functional differences between CD146+and CD146-MSCs and investigate the underlying mechanisms.METHODS In this study,magnetic beads were used to sort umbilical cord-derived MSCs into CD146+and CD146-subsets.The pro-angiogenic factors(hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,angiopoietin-1)production and immunomodulatory effects on T lymphocyte subsets were evaluated in vitro.The therapeutic efficacy was assessed in an acute respiratory distress syndrome(ARDS)mouse model via tail vein injection.RESULTS Cytokine secretion and angiogenesis:CD146+MSCs significantly increased the production of hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,and angiopoietin-1 and exhibited increased pro-angiogenic activity in vitro.Immunomodulatory effects:CD146+MSCs potently inhibited the differentiation and proliferation of pro-inflammatory T helper type 1/T helper type 17 cells while promoting the expansion of regulatory T cells during T lymphocyte activation.ARDS therapy:In a mouse ARDS model,compared with CD146-MSCs,CD146+MSCs demonstrated superior therapeutic efficacy,as evidenced by improved clinical scores.Mechanistically,CD146+MSCs activated the nuclear factor kappa B pathway,upregulated cyclooxygenase 2 expression,and facilitated damaged epithelial cell repair.CONCLUSION CD146+MSCs show stronger ARDS therapeutic potential than CD146-MSCs via pro-angiogenic/immunomodulatory traits.Nuclear factor kappa B/cyclooxygenase 2 activation aids epithelial repair,highlighting CD146+MSCs as promising targets.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a prom...BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a promising therapeutic option for DFUs because of their angiogenic,immunomodulatory,and regenerative properties.However,studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.AIM To investigate the dose-response relationship,the optimal administration route,persistence,and molecular mechanisms of ADSCs in DFU healing.METHODS In this study,human ADSCs were isolated and cultured,and their differentiation potential was characterized.A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly.Wound closure rate,angiogenesis,inflammation,and collagen deposition were assessed in the ADSC-treated and model groups.Additionally,in vitro experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.RESULTS ADSC treatment significantly enhanced wound closure,promoted angiogenesis,modulated inflammatory responses,and accelerated tissue regeneration in the DFU model.Notably,the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route,with subcutaneous injection of 5×105 ADSCs yielding the most favorable outcomes,particularly when injected into the feet,which resulted in prolonged retention.In vitro experiments further revealed that ADSCs exert their therapeutic effects via multiple mechanisms,including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion,thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.CONCLUSION ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds.These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.展开更多
Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force t...Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force to catalyze the reaction that produces ATP.Deuterons disrupt the pumps,inducing excessive reactive oxygen species and decreased ATP synthesis.The aim of this review is to develop a theory that mitochondrial dysfunction due to deuterium overload,systemically,is a primary cause of Parkinson’s disease(PD).The gut microbes supply deuterium-depleted short chain fatty acids(SCFAs)to the colonocytes,particularly butyrate,and an insufficient supply of butyrate may be a primary driver behind mitochondrial dysfunction in the gut,an early factor in PD.Indeed,low gut butyrate is a characteristic feature of PD.Mitochondrial dysfunction is a factor in many diseases,including all neurodegenerative diseases.Biological organisms have devised sophisticated strategies for protecting the ATPase pumps from deuterium overload.One such strategy may involve capturing deuterons in bis-allylic carbon atoms present in polyunsaturated fatty acids(PUFAs)in cardiolipin.Cardiolipin uniquely localizes to the inner membrane of the intermembrane space,tightly integrated into ATPase proteins.Bis-allylic carbon atoms can capture and retain deuterium,and,interestingly,deuterium doping in PUFAs can quench the chain reaction that causes massive damage upon lipid peroxidation.Neuronal cardiolipin is especially rich in docosahexaenoic acid(DHA),a PUFA with five bisallylic carbon atoms.Upon excessive oxidative stress,cardiolipin migrates to the outer membrane,where it interacts withα-synuclein(α-syn),the amyloidogenic protein that accumulates as fibrils in Lewy bodies in association with PD.Such interaction leads to pore formation and the launch of an apoptotic cascade.α-syn misfolding likely begins in the gut,and misfoldedα-syn travels along nerve fibers,particularly the vagus nerve,to reach the brainstem nuclei,where it can seed misfolding ofα-syn molecules already present there.Mitochondrial dysfunction in the gut may be a primary factor in PD,and low-deuterium nutrients may be therapeutic.展开更多
文摘Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments have been extensively explored,limited research has addressed how thermal treatment alone alters the surface properties and reinforcing behavior of SCB fibers.This study aims to fill that gap by investigating the effects of heat treatment on SCB fiber structure and its performance in starch/poly(vinyl alcohol)(PVA)composites.Characterization techniques including Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and scanning electron microscopy(SEM)were employed to analyze changes in fiber morphology,surface chemistry,and crystallinity.Mechanical properties were assessed via tensile,flexural,and impact testing,and moisture absorption was also evaluated.Composites reinforced with SCB fibers treated at 200○C exhibited significantly superior mechanical properties compared to those prepared with untreated or differently treated fibers.The tensile,flexural,and impact performance of the composites were 15.13,19.37 MPa,and 7.28 J/m,respectively.Composites treated at this temperature also retained better mechanical properties after exposure to humidity.These findings demonstrate that heat treatment is a simple and sustainable method to improve the durability and mechanical performance of nature fiber-reinforced composites,expanding their potential for environmentally friendly material applications.
基金Bu-Ali Sina University for providing financial support for conducting this study。
文摘Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)K and at ambient pressure(81.5 kPa).From the experimental data,excess molar volume(V_(m)~E),thermal expansion coefficients(α),deviations in isentropic compressibility(Δκ_(S)),viscosity(Δ_η),and refractive index(Δn_(D))were calculated.These values were then correlated using the Redlich-Kister polynomial equation,with fitting coefficients and standard deviations determined.Additionally,the Prigogine-Flory-Patterson(PFP)theory and the Extended Real Associated Solution(ERAS)model were employed to correlate the excess molar volume,while the Perturbed Chain Statistical Associating Fluid Theory(PC-SAFT)was used to predict the density of mixtures.
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
文摘In this review,we explore the application of next-generation sequencing in liver cancer research,highlighting its potential in modern oncology.Liver cancer,particularly hepatocellular carcinoma,is driven by a complex interplay of genetic,epigenetic,and environmental factors.Key genetic alterations,such as mutations in TERT,TP53,and CTNNB1,alongside epigenetic modifications such as DNA methylation and histone remodeling,disrupt regulatory pathways and promote tumorigenesis.Environmental factors,including viral infections,alcohol consum-ption,and metabolic disorders such as nonalcoholic fatty liver disease,enhance hepatocarcinogenesis.The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance,with immune cell infiltration,fibrosis,and angiogenesis supporting cancer cell survival.Advances in immune check-point inhibitors and chimeric antigen receptor T-cell therapies have shown po-tential,but the unique immunosuppressive milieu in liver cancer presents challenges.Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies.Next-generation sequencing is accele-rating the identification of genetic and epigenetic alterations,enabling more precise diagnosis and personalized treatment plans.A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.
文摘BACKGROUND Treatment response to direct-acting antivirals(DAAs)is a challenging issue and the identification of non-responders patients is very important.AIM To evaluate the relation between baseline serum levels of hyaluronic acid(HA)and type III procollagen N-peptide(PIIINP)with direct-acting antivirals treatment failure in Egyptian patients with chronic hepatitis C.METHODS Hepatitis C patients(responders and non-responders to sofosbuvir/daclatasvir)were tested for HA and PIIINP using sensitive chemiluminescent immunoassay.RESULTS There were distinctly higher PIIINP(P=0.0003)and HA(P<0.0001)levels in non-responders than responders patients with a good ability for distinguishing non-responders from patients with sustained virological response(area under the curve=0.766 for HA and 0.684 for PIIINP).Logistic regression analysis revealed that the HA×PIIINP is the model with the highest predictive ability(area under the curve=0.809).Diagnostic performances were superior to each marker alone with good sensitivity(74.7%),specificity(74%),positive predictive(68.3%),negative predictive values(79.6%)and accuracy(74.3%).The multiplication of HA×PIIINP is correlated significantly(P<0.05)with elevated liver enzymes(r=0.212),decreased albumin(r=-0.26),elevated aspartate aminotransferase-platelet ratio index(r=0.223)and elevated fibrosis-4 score(r=0.216)scores.CONCLUSION These findings suggested the remarkable role of fibrogensis markers HA and PIIINP in the prediction of hepatitis C virus DAAs treatment response.Multiplying HA with PIIINP values increase the sensitivity to detect treatment success and thus may aim to improve treatment duration and the disease control.
基金supported by the Razi Vaccine and Serum Research Institute(RVSRI)Karaj,Iran,(No.17-18-18-063-01047-011130).
文摘Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.
基金partially supported by the National Natural Science Foundation of China(No.82473256)the Jiangxi Provincial Natural Science Foundation,China(No.20242BAB25521)+7 种基金Ganpo Promising Talents Supporting Plan—Talent Development Project of Leading Academic and Technological Researchers in Key Disciplines(No.20243BCE51060)the Anhui Province Higher Education Scientific Research Project,China(No.2024AH050818)the Anhui Provincial Natural Science Foundation,China(No.2208085MH251)the Fundamental Research Funds for the Anhui Medical University,China(No.2021xkj131)the Research Fund of Anhui Institute of Translational Medicine,China(No.2023zhyx-C19)the Health Research Program of Anhui,China(No.AHWJ2023A30007)the Anhui Provincial Department of Education,Provincial Quality Engineering Project for Higher Education(Nos.2022jyxm761 and 2023jyxm1106)the Basic and Clinical Cooperative Research and Promotion Program of the Anhui Medical University,China(No.2022xkj T024)。
文摘Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.
文摘This article seeks to emphasize a simplified approach to phylogeny research using complete mitochondrial genomes alone, while touching upon a number of technological perspectives, such as algorithmic selection, which can help improve accuracy and performance in comparative analysis. My results will show that reliable estimations can be obtained by using mitochondrial markers, even among time-extended taxonomical rankings. Six distinct mammalian groups of taxa were selected for comparison. In all cases, mtDNA models generated reliable phylogeny approximations when compared against other independent data, while rendering exceptional computational performance.
文摘Background: Pregnant women and newborns are highly susceptible to Covid-19, manifesting as multisystem inflammatory syndrome-New-born (MISC-N) in many babies born to Covid positive mothers. The relationship between Covid-19 infection during pregnancy and neonatal neurodevelopmental outcome, if any, is unclear necessitating a follow-up study in this aspect. Methods: 16 babies with MIS-N, born to symptomatic Covid antibody positive mothers were enrolled. Demographic profile, treatment details and biochemical parameters were analyzed with neurodevelopmental follow-up. Results: 25% mothers received 2 doses of Covid vaccine;50% had oligohydramnios and 75% received antenatal steroids. 87.5% were preterm of which 62.5% required surfactant with ventilator support and 75% required ionotropic support. Significant association was found between the antibody level and D-dimer levels with the ferritin and LDH levels of the baby (p 0.05);gestational age with LDH and D-dimer levels (p 0.05) and Covid antibody level of the baby vs the duration of ventilator requirement (P-value-0.0009). D-dimer values of babies were positively associated with both maternal antibody and D-dimer levels. Neurodevelopmental follow-up done at 6 months of corrected gestational age showed 37.5% were normal, 37.5% hypertonic and 25% hypotonic. HINE score was below 60 in 62.5%. Development assessment using Bayley-III showed a delay in the motor domain (62.5%), cognitive domain (56.25%) and language domain (62.5%). Conclusion: Neurodevelopmental problems occur in babies born to Covid positive mothers and should be stratified as “high risk”. Anticipatory guidance to prospective mothers for preterm care should be given. Covid antibody titre and D-dimer levels may help to predict the NICU stay, ventilator requirement and the adverse neurodevelopmental outcomes in these babies.
文摘The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup physico-chemical evaluation such as pH, density, identification of polysaccharide, tanning agents, ascorbic acid and shelf life was complied. The TLC and quantitative determination of alkaloid were quantified. Determination of biomarker has been validated for the analysis of vasicine. The study result revealed that Linkus syrup formulation was well standardized at different levels such as physic-chemical consistency and assay of bio marker compound.
文摘The increasing integration of new technologies is driving a fundamental revolution in the healthcare sector.Developments in artificial intelligence(AI),machine learning,and big data analytics have completely transformed the diagnosis,treatment,and care of patients.AI-powered solutions are enhancing the efficiency and accuracy of healthcare delivery by demonstrating exceptional skills in personalized medicine,early disease detection,and predictive analytics.Furthermore,telemedicine and remote patient monitoring systems have overcome geographical constraints,offering easy and accessible healthcare services,particularly in underserved areas.Wearable technology,the Internet of Medical Things,and sensor technologies have empowered individuals to take an active role in tracking and managing their health.These devices facilitate real-time data collection,enabling preventive and personalized care.Additionally,the development of 3D printing technology has revolutionized the medical field by enabling the production of customized prosthetics,implants,and anatomical models,significantly impacting surgical planning and treatment strategies.Accepting these advancements holds the potential to create a more patient-centered,efficient healthcare system that emphasizes individualized care,preventive care,and better overall health outcomes.This review's novelty lies in exploring how these technologies are radically transforming the healthcare industry,paving the way for a more personalized and effective healthcare for all.It highlights the capacity of modern technology to revolutionize healthcare delivery by addressing long-standing challenges and improving health outcomes.Although the approval and use of digital technology and advanced data analysis face scientific and regulatory obstacles,they have the potential for transforming translational research.as these technologies continue to evolve,they are poised to significantly alter the healthcare environment,offering a more sustainable,efficient,and accessible healthcare ecosystem for future generations.Innovation across multiple fronts will shape the future of advanced healthcare technology,revolutionizing the provision of healthcare,enhancing patient outcomes,and equipping both patients and healthcare professionals with the tools to make better decisions and receive personalized treatment.As these technologies continue to develop and become integrated into standard healthcare practices,the future of healthcare will probably be more accessible,effective,and efficient than ever before.
基金Foundation of Henan Educational Committee,Grant Number 22A310024Natural Science Foundation for Young Teachers’Basic Research of Zhengzhou University,Grant Number JC202035025.
文摘Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.
文摘Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.
文摘Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.
文摘One major problem that humanity has been confronting recently is water quality. Just 2.5 percent of the water resources on Earth are freshwater resources. Water is an indispensable resource for all living things, and it is a vital value. Pollution of limited freshwater resources causes further pressure on freshwater resources. Humans play a major role in the waste and pollution of this essential natural resource. This research project focused on the impacts of water pollution and its effects on agriculture, land and aquatic systems, a case study which was conducted in River Njoro, in Nakuru County. With the aid of questioners for information acquisition, the study determined different pollutants and their impact on agriculture. Results indicated that there is a dire need for conservation efforts in the area. Humanity should receive education awareness-capacity building regarding water contamination in order to mitigate the issues to some extent. By doing so, the world we live in becomes a better place for all.
文摘DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).
基金Supported by the Science and Technology SMEs Innovation Capacity Improvement Project of Shandong Province,No.2022TSGC1004National Key R&D Program of China,No.2021YFA1101502。
文摘BACKGROUND Mesenchymal stromal cells(MSCs)are renowned for their immunosuppressive properties,which make them widely used in managing excessive inflammation.Although CD146+and CD146-MSCs exhibit similar morphological traits and surface marker expression levels,the specific characteristics and differential regulatory mechanisms of these two subtypes remain poorly understood.This knowledge gap has limited the precise application of MSCs in targeted thera-peutic strategies.AIM To compare the functional differences between CD146+and CD146-MSCs and investigate the underlying mechanisms.METHODS In this study,magnetic beads were used to sort umbilical cord-derived MSCs into CD146+and CD146-subsets.The pro-angiogenic factors(hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,angiopoietin-1)production and immunomodulatory effects on T lymphocyte subsets were evaluated in vitro.The therapeutic efficacy was assessed in an acute respiratory distress syndrome(ARDS)mouse model via tail vein injection.RESULTS Cytokine secretion and angiogenesis:CD146+MSCs significantly increased the production of hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,and angiopoietin-1 and exhibited increased pro-angiogenic activity in vitro.Immunomodulatory effects:CD146+MSCs potently inhibited the differentiation and proliferation of pro-inflammatory T helper type 1/T helper type 17 cells while promoting the expansion of regulatory T cells during T lymphocyte activation.ARDS therapy:In a mouse ARDS model,compared with CD146-MSCs,CD146+MSCs demonstrated superior therapeutic efficacy,as evidenced by improved clinical scores.Mechanistically,CD146+MSCs activated the nuclear factor kappa B pathway,upregulated cyclooxygenase 2 expression,and facilitated damaged epithelial cell repair.CONCLUSION CD146+MSCs show stronger ARDS therapeutic potential than CD146-MSCs via pro-angiogenic/immunomodulatory traits.Nuclear factor kappa B/cyclooxygenase 2 activation aids epithelial repair,highlighting CD146+MSCs as promising targets.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金Supported by The Zhongguancun National Independent Innovation Demonstration Zone Industrial Ecosystem Cultivation Project,No.20220468089.
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a promising therapeutic option for DFUs because of their angiogenic,immunomodulatory,and regenerative properties.However,studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.AIM To investigate the dose-response relationship,the optimal administration route,persistence,and molecular mechanisms of ADSCs in DFU healing.METHODS In this study,human ADSCs were isolated and cultured,and their differentiation potential was characterized.A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly.Wound closure rate,angiogenesis,inflammation,and collagen deposition were assessed in the ADSC-treated and model groups.Additionally,in vitro experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.RESULTS ADSC treatment significantly enhanced wound closure,promoted angiogenesis,modulated inflammatory responses,and accelerated tissue regeneration in the DFU model.Notably,the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route,with subcutaneous injection of 5×105 ADSCs yielding the most favorable outcomes,particularly when injected into the feet,which resulted in prolonged retention.In vitro experiments further revealed that ADSCs exert their therapeutic effects via multiple mechanisms,including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion,thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.CONCLUSION ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds.These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.
基金funded in part by Quanta Computer,Inc.,in Tanyuan,Taiwan,under contract number 6950759,as part of the AIR project.
文摘Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force to catalyze the reaction that produces ATP.Deuterons disrupt the pumps,inducing excessive reactive oxygen species and decreased ATP synthesis.The aim of this review is to develop a theory that mitochondrial dysfunction due to deuterium overload,systemically,is a primary cause of Parkinson’s disease(PD).The gut microbes supply deuterium-depleted short chain fatty acids(SCFAs)to the colonocytes,particularly butyrate,and an insufficient supply of butyrate may be a primary driver behind mitochondrial dysfunction in the gut,an early factor in PD.Indeed,low gut butyrate is a characteristic feature of PD.Mitochondrial dysfunction is a factor in many diseases,including all neurodegenerative diseases.Biological organisms have devised sophisticated strategies for protecting the ATPase pumps from deuterium overload.One such strategy may involve capturing deuterons in bis-allylic carbon atoms present in polyunsaturated fatty acids(PUFAs)in cardiolipin.Cardiolipin uniquely localizes to the inner membrane of the intermembrane space,tightly integrated into ATPase proteins.Bis-allylic carbon atoms can capture and retain deuterium,and,interestingly,deuterium doping in PUFAs can quench the chain reaction that causes massive damage upon lipid peroxidation.Neuronal cardiolipin is especially rich in docosahexaenoic acid(DHA),a PUFA with five bisallylic carbon atoms.Upon excessive oxidative stress,cardiolipin migrates to the outer membrane,where it interacts withα-synuclein(α-syn),the amyloidogenic protein that accumulates as fibrils in Lewy bodies in association with PD.Such interaction leads to pore formation and the launch of an apoptotic cascade.α-syn misfolding likely begins in the gut,and misfoldedα-syn travels along nerve fibers,particularly the vagus nerve,to reach the brainstem nuclei,where it can seed misfolding ofα-syn molecules already present there.Mitochondrial dysfunction in the gut may be a primary factor in PD,and low-deuterium nutrients may be therapeutic.
