Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.展开更多
The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review ar...The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review article,Triggering sarcomerogenesis:Examining key stimuli and the role attributed to eccentric training—Historical,systematic,and meta-analytic review,Blazevich et al.3 provide a commendable overview of the history behind this area of research from the 1600s to present.展开更多
Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection ...Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection challenging,they are linked to problems.Diagnostic methods like imaging and tissue biopsy are only effective when the tumor has reached a size that can be identified.The liquid biopsy technique,the least intrusive and most convenient diagnostic method,is the subject of this review.It focuses on the significance of single cell analysis in examining uncommon cancer types.The many biomarkers found in bodily fluids and the cancer types they are linked to in children have been assessed,as has the potential route towards early detection and cancer recurrence forecasting.Combining the single cell liquid biopsy with the newest technologies,such as computational and multi-omics approaches,which have improved the efficiency of processing massive and unique genetic data,appears promising.This article discusses on a number of case reports for uncommon pediatric malignancies,such as Neuroblastoma,Medulloblastoma,Wilms Tumor,Rhabdomyosarcoma,Ewing Sarcoma,and Retinoblastoma,as well as their liquid biopsy profiles.Furthermore,the findings raise ethical questions regarding the therapeutic application of the technology as well as possible difficulties related to clinical translation.The likelihood that this single cell liquid biopsy will be clinically validated and eventually used as a routine diagnostic tool for uncommon pediatric cancers will rise with the realistic approach to sensitivity monitoring,specificity upgrading,and optimization.展开更多
Background:The mobility of people in rural areas may lead to more and more left-behind children(LBC)appearing,and being an LBC brings a lot of risks to mental health,which could greatly hinder children’s development ...Background:The mobility of people in rural areas may lead to more and more left-behind children(LBC)appearing,and being an LBC brings a lot of risks to mental health,which could greatly hinder children’s development and undermine their happiness and safety in life.Previous scholars have conducted plenty of studies that focused on Chinese rural LBCs’mental health issues,such as what they exactly look like and some potential factors,but there remains a paucity of reviews about the relationship among certain mental health issues.We will try to figure out how the most common mental health issues of LBC in China’s rural areas correlate with each other,as well as their related factors.Methods:In this study,we used a systematic review approach to analyze 35 publications from Web of Science and EBSCO(to August 2025),followed by the sorting standards of Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020.Results:By mainly using quantitative techniques,we found that Chinese rural LBC are more likely to have mental health issues than children who have no experience of being left behind,and they often suffer from depression,social anxiety,internet addiction,and suicidal ideation.These four mental health issues share influencing factors and positively correlate with each other.We also found that Chinese rural LBCs are somewhat resilient towards the risk factors of mental health issues,and national or social policies and interventions can really help them a lot.Conclusion:For Chinese rural LBC,there are important relationships among the common psychological disorders they often suffer,along with multiple factors that affect their mental health,which can help related scholars and practitioners pay attention to such mechanisms and think more comprehensively when they try to help the children who are left behind.展开更多
Malignant melanoma(MM)is a highly aggressive skin cancer known for its rapid progression,potential for metastasis,and resistance to treatment.Despite advances in targeted therapies and immunotherapy,the prognosis for ...Malignant melanoma(MM)is a highly aggressive skin cancer known for its rapid progression,potential for metastasis,and resistance to treatment.Despite advances in targeted therapies and immunotherapy,the prognosis for metastatic melanoma remains unfavorable.Recent research has shed light on the significance of epigenetic modifications in the pathogenesis of melanoma,revealing critical mechanisms of melanoma development and progression.Epigenetic modifications,including DNA and RNA modifications,histone modifications,chromatin remodeling,and non-coding RNA regulation,disrupt normal gene expression without modifying the DNA sequence,leading to cellular transformation,invasion,immune evasion,and therapeutic resistance.The reversible nature of epigenetic modifications opens up new opportunities for melanoma recognition and classification,as well as therapeutic applications,including the development of diagnostic and prognostic biomarkers and innovative targeted therapies aimed at restoring normal gene function and enhancing the efficacy of existing treatments.This review will focus on the multifaceted role of epigenetic dysregulation in melanoma.The future integration of epigenetic data and genomic profiling with clinical outcomes,likely facilitated by artificial intelligence(AI)algorithms,holds promise for personalized treatment strategies that are informed by precise and combinatorial diagnostic tools,ultimately improving melanoma care.The study aims to deliver a comprehensive overview of the current state of epigenetics in melanoma.展开更多
The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities...The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities and obstacles.The huge and diversified nature of these datasets cannot always be managed using traditional data analysis methods.As a consequence,deep learning has emerged as a strong tool for analysing numerous omics data due to its ability to handle complex and non-linear relationships.This paper explores the fundamental concepts of deep learning and how they are used in multi-omics medical data mining.We demonstrate how autoencoders,variational autoencoders,multimodal models,attention mechanisms,transformers,and graph neural networks enable pattern analysis and recognition across all omics data.Deep learning has been found to be effective in illness classification,biomarker identification,gene network learning,and therapeutic efficacy prediction.We also consider critical problems like as data quality,model explainability,whether findings can be repeated,and computational power requirements.We now consider future elements of combining omics with clinical and imaging data,explainable AI,federated learning,and real-time diagnostics.Overall,this study emphasises the need of collaborating across disciplines to advance deep learning-based multi-omics research for precision medicine and comprehending complicated disorders.展开更多
Background:The mechanisms underlying the beneficial effects of exercise on the human placenta are poorly understood.The objective of the current study was to ascertain the influence of a supervised concurrent exercise...Background:The mechanisms underlying the beneficial effects of exercise on the human placenta are poorly understood.The objective of the current study was to ascertain the influence of a supervised concurrent exercise intervention from gestational Week 17 until birth on key cytokines involved in placental development and function.Secondary aims were to explore:(a)the moderating effects of fetal sex and maternal weight status;and(b)whether gestational weight gain,lifestyle behaviors(diet,sleep patterns,and physical activity),and physical fitness(strength and cardiorespiratory fitness)mediated the effects of exercise on placental cytokines.Methods:Seventy-six pregnant women(33±4 years,mean±SD),divided into exercise(n=40)and control(n=36)groups,participated in this study.The exercise group followed a 60-min,3 days/week(aerobic+resistance)training program of moderate-to-vigorous intensity.Placental cytokines—including granulocyte-macrophage colony-stimulating factor(GM-CSF),granulocyte colony-stimulating factor(G-CSF),plateletderived growth factor AA(PDGF-AA),epidermal growth factor(EGF),monocyte chemoattractant protein-1(MCP-1),fractalkine,interleukin(IL)-8,IL-6,IL-1β,interleukin 1-receptor antagonist(IL-1ra),IL-10,tumor necrosis factor alpha(TNF-a),and interferon gamma(IFN-γ)were analyzed using Luminex multi-analyte profiling(x MAP)technology.Results:The exercise group presented higher placental levels of G-CSF and lower concentrations of EGF and IL-1ra than the control group(p<0.05).Significant effects of exercise on placental G-CSF and TNF-a(p<0.05)and a trend toward lower IL-6(p=0.08)were observed only in female placentas.Additionally,a reduction in weight gain partially mediated the effects of exercise on G-CSF(p<0.05).Conclusion:Maternal exercise during pregnancy is related to increased placental levels of G-CSF and lower EGF and IL-1ra levels.Some exercise-induced effects are observed exclusively in female placentas,including increased G-CSF and lower TNF-a and IL-6 concentrations.Notably,the increased levels of G-CSF observed with exercise might be due to a more adequate gestational weight gain.展开更多
In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis...In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cell on the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cell suspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 x 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after cell transplantation, more than 80% of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improvements were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electrophysiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After cell transplantation, no immunological rejections were observed. These findings suggest that human umbilical cord mesenchymal stem cell-loaded amniotic membrane can be used for the repair of radial nerve injury.展开更多
MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, t...MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.展开更多
OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic as...OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS： Effects of ASHMI and its components aqueous extracts of Lingzhi （Ganoderma lucidum）, Kushen （Sophora flavescens） and Gancao （Glycyrrhiza uralensis）, on Th2 cytokine secretion by murine memory Th2 cells （D10.G4.1） and eotaxin-1 secretion by human lung fibroblast （HLF-1） cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS： Individual Lingzhi, Kushen and Gancao extracts and ASHMI （the combination of individual extracts） inhibited production of interleukin （IL）-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration （IC2s） values （mg/mL） forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values （mg/mL） for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION： By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.展开更多
The arrangement of various biological structures should generally ensure the safety of crucial structures and increase their working efficiency; however, other principles governing the relative positions of structures...The arrangement of various biological structures should generally ensure the safety of crucial structures and increase their working efficiency; however, other principles governing the relative positions of structures in humans have not been reported. The present study therefore investigated other principles using nerves and their companion vessels in the human body as an example. Nerves and blood vessels usually travel together and in the most direct way towards their targets. Human embryology, histology, and gross anatomy suggest that there are many possible positions for these structures during development. However, for mechanical reasons, tougher or stronger structures should take priority. Nerves are tougher than most other structures, followed by arteries, veins, and lymphatic vessels. Nerves should therefore follow the most direct route, and be followed by the arteries, veins, and lymphatic vessels. This general principle should be applicable to all living things.展开更多
The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a...The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.展开更多
An overview of a long-gap peripheral nerve therapy： A long- gap peripheral nerve transection injury is an irreparable injury to the living body, and mostly leads to permanent loss of re- lated motor and sensory funct...An overview of a long-gap peripheral nerve therapy： A long- gap peripheral nerve transection injury is an irreparable injury to the living body, and mostly leads to permanent loss of re- lated motor and sensory functions. In such long gap injuries, nerve end-to-end suture is physically impossible. Therefore, bridging a long nerve-gap is critical to re-establish adequate mechanical support for separated nerve ends, and prevent the diffusion of neurotrophic and neurotropic factors secreted by transected stumps （Deumens et al., 2010）.展开更多
Objective:The antimicrobial activity of the ethanol extract of the Auklandia(Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.Methods:The antimicrobial a...Objective:The antimicrobial activity of the ethanol extract of the Auklandia(Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.Methods:The antimicrobial activity of the ethanol extract was tested against clinical isolates ofsome multidrug-resistant bacteria using the agar well diffusion method.Commercial antibioticswere used as positive reference standards to determine the sensitivity of the clinical isolates.Results:The extracts showed significant inhibitory activity against clinical isolates of methicillinresistantStaphylococcus aureus,Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumonia,Extended Spectrum Beta-Lactemase,Acinetobacter baumannii.The minimum inhibitory concentration values obtained using the agar dilution test ranged from 2.0μg/μL-12.0μg/μL.In the contrary the water extract showed no activity at all against the tested isolates.Furthermore,theresults obtained by examining anti-resistant activity of the plant ethanolic extract showed thatat higher concentration of the plant extract(12μg)all tested bacteria isolates were inhibited with variable inhibition zones similar to those obtained when we applied lower extract concentrationusing the well diffusion assay.Conclusion:The results demonstrated that the crude ethanolicextract of the Auklandia(Saussurea lappa)root plant has a wide spectrum of activity suggestingthat it may be useful in the treatment of infections caused by the above clinical isolates(humanpathogens).展开更多
A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NM...A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NMR and GC-MS after a semi-preparative HPLC separation. Under optimized conditions, donepezil was derivatized by 9-fluorenylmethyl chloroformate in chloroform and carbonate buffer at pH 9.5 in the presence of NaI after solid-phase extraction from a plasma sample. The reaction product was quantified on a reversed-phase TRACER EXCEL ODS-A, 5 μm column using a mixture of acetonitrile–10 mM acetate buffer(pH 6.0)–THF(60:35:5, v/v/v) as the mobile phase with fluorescence detection at 264 nm(ex) and 313 nm(em). Fluoxetine was used as the internal standard. The total run-time of the analysis was about 10 min, and a clean chromatogram was obtained. The developed method was linear over the range of 1–100 ng/mL in 500 μL of plasma samples(r2>0.998). The intra-day and inter-day precision values were in the range of 2.6%–11.6%. The limit of quantification was 1 ng/mL.展开更多
C-type natriuretic peptide （CNP） is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B （NPR-B）. Recent studi...C-type natriuretic peptide （CNP） is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B （NPR-B）. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods （such as immunolocalization, real time polymerase chain reaction and Western Blot）, and then to evaluate the influence of CNP on sperm function in vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.展开更多
In this study, we developed a simple and sensitive HPLC method for the determination of lisinopril in human plasma. The sample clean-up was carried out by solid-phase extraction(SPE) using a cation-exchange(Strata-SCX...In this study, we developed a simple and sensitive HPLC method for the determination of lisinopril in human plasma. The sample clean-up was carried out by solid-phase extraction(SPE) using a cation-exchange(Strata-SCX~?) extraction cartridge. After a pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, the reaction mixture was analyzed on an Agilent Zorbax SB~?-C_(18)(150 mm×4.6 mm, 5 μm). The flow rate was set at 1.0 mL/min. Fluorescence detection was performed at an excitation wavelength of 470 nm and an emission wavelength of 530 nm. The mobile phase consisted of a mixture of methanol and 0.02 M sodium dihydrogen phosphate(pH = 3.0, 60:40, v/v). The average extraction recovery of lisinopril and fluvoxamine(internal standard) was >85%. The method exhibited a linear calibration curve over the concentration range of 1–1000 ng/mL with a correlation coefficient(r^2) of ≥0.98 and a limit of quantification(LOQ) equal to 2 ng/mL. The within-run and between-run precisions were satisfactory with an RSD of 3.8%–13.7%(accuracy: from 95.0% to 96.4%) and 4.273%–14.3%(accuracy: from 94.4% to 98.5%), respectively.展开更多
BACKGROUND： Cell culture in vitro trials have demonstrated that neurotrophin-3 （NT-3） can enhance the survival of sensory neurons and sympathetic neurons, and can also support embryo-derived motor neurons. This eff...BACKGROUND： Cell culture in vitro trials have demonstrated that neurotrophin-3 （NT-3） can enhance the survival of sensory neurons and sympathetic neurons, and can also support embryo-derived motor neurons. This effect is dependent on nerve growth factor on the surface of cells. Understanding the role of NT-3 and its receptor in the early development of human embryonic brains will help to investigate the correlation between early survival of nerve cells and the microenvironment of neural regeneration. OBJECTIVE： To observe the proliferation of cerebral neurons in the development of human embryonic brain, and to investigate the location, expression and distribution of NT-3 and its receptor TrkC during human brain development. DESIGN, TIME AND SETTING： An observation study on cells was performed in the Department of ttuman Anatomy, Histology and Embryology, Chengdu Medical College in September 2007. MATERIALS： Fifteen specimens of flesh human embryo, aged 6 weeks, were used in this study. METHODS： The proliferation of cerebral neurons was detected using proliferating cell nuclear antigen, and the immunocytochemistry ABC technique was applied to observe the location, expression and distribution of NT-3 and its receptor TrkC in the brain of the human embryo. MAIN OUTCOME MEASURES： Location, expression and distribution of NT-3 and its receptor in the brain of the human embryo. RESULTS： In the early period （aged 6 weeks） of human embryonic development, proliferating cell nuclear antigen-positive reactive substances were mainly observed in the nucleus of the forebrain ventricular zone and subventricular zone, and the intensity was stronger in the subventricular zone than the forebrain ventricle. NT-3 positive reactive substance was mainly distributed in the cytoblastema of the forebrain neuroepithelial layer and nerve cell process, while TrkC was mainly distributed in the cell membrane of the forebrain ventricular zone and subventricular zone. During embryonic development, NT-3 and TrkC showed a positive immune reaction to a greater or lesser extent in ependymal epithelium. CONCLUSION： During early human embryonic development, cerebral nerve cells proliferate in the ventricular zone and subventricular zone, and NT-3 is expressed in the neural axon. The results show that the highly expressed NT-3 could promote the proliferation of neural axons and maintain the neuron body＇s survival.展开更多
Dear Editor Research on neurodegenerative diseases is a hot topic worldwide[1],and MRI,genetics and epigenetics,and animal models have been commonly used.Considering species differences,research on human brain samples...Dear Editor Research on neurodegenerative diseases is a hot topic worldwide[1],and MRI,genetics and epigenetics,and animal models have been commonly used.Considering species differences,research on human brain samples is irreplaceable(2)Many countries and regions have built brain banks to collect and store brain tissue from donors.Samples provided by a brain bank can be used to study synaptic structure,protein,DNA,RNA[3,4],and lipids to illuminate the pathological mechanisms underlying neurodegenerative diseases.When brain tissue is used for gene expression research,the quantitative real-time polymerase chain reaction(RT-qPCR)is an accurate method,which simultaneously amplifies and quantifies the expression of target genes by measuring the intensity of fluorescence in each PCR cycle.展开更多
Agrizim and bayleton,two commonly usedagricultural fungicides in India,wereinvestigated for their genotoxicpotentialities on cultured humanlymphocytes by studying chromosomalaberrations and sister chromatid exchangesi...Agrizim and bayleton,two commonly usedagricultural fungicides in India,wereinvestigated for their genotoxicpotentialities on cultured humanlymphocytes by studying chromosomalaberrations and sister chromatid exchangesin the presence and absence of展开更多
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
文摘The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review article,Triggering sarcomerogenesis:Examining key stimuli and the role attributed to eccentric training—Historical,systematic,and meta-analytic review,Blazevich et al.3 provide a commendable overview of the history behind this area of research from the 1600s to present.
文摘Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection challenging,they are linked to problems.Diagnostic methods like imaging and tissue biopsy are only effective when the tumor has reached a size that can be identified.The liquid biopsy technique,the least intrusive and most convenient diagnostic method,is the subject of this review.It focuses on the significance of single cell analysis in examining uncommon cancer types.The many biomarkers found in bodily fluids and the cancer types they are linked to in children have been assessed,as has the potential route towards early detection and cancer recurrence forecasting.Combining the single cell liquid biopsy with the newest technologies,such as computational and multi-omics approaches,which have improved the efficiency of processing massive and unique genetic data,appears promising.This article discusses on a number of case reports for uncommon pediatric malignancies,such as Neuroblastoma,Medulloblastoma,Wilms Tumor,Rhabdomyosarcoma,Ewing Sarcoma,and Retinoblastoma,as well as their liquid biopsy profiles.Furthermore,the findings raise ethical questions regarding the therapeutic application of the technology as well as possible difficulties related to clinical translation.The likelihood that this single cell liquid biopsy will be clinically validated and eventually used as a routine diagnostic tool for uncommon pediatric cancers will rise with the realistic approach to sensitivity monitoring,specificity upgrading,and optimization.
基金funded by the Fundamental Research Funds for the Central Universities(No.1233300002).
文摘Background:The mobility of people in rural areas may lead to more and more left-behind children(LBC)appearing,and being an LBC brings a lot of risks to mental health,which could greatly hinder children’s development and undermine their happiness and safety in life.Previous scholars have conducted plenty of studies that focused on Chinese rural LBCs’mental health issues,such as what they exactly look like and some potential factors,but there remains a paucity of reviews about the relationship among certain mental health issues.We will try to figure out how the most common mental health issues of LBC in China’s rural areas correlate with each other,as well as their related factors.Methods:In this study,we used a systematic review approach to analyze 35 publications from Web of Science and EBSCO(to August 2025),followed by the sorting standards of Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020.Results:By mainly using quantitative techniques,we found that Chinese rural LBC are more likely to have mental health issues than children who have no experience of being left behind,and they often suffer from depression,social anxiety,internet addiction,and suicidal ideation.These four mental health issues share influencing factors and positively correlate with each other.We also found that Chinese rural LBCs are somewhat resilient towards the risk factors of mental health issues,and national or social policies and interventions can really help them a lot.Conclusion:For Chinese rural LBC,there are important relationships among the common psychological disorders they often suffer,along with multiple factors that affect their mental health,which can help related scholars and practitioners pay attention to such mechanisms and think more comprehensively when they try to help the children who are left behind.
文摘Malignant melanoma(MM)is a highly aggressive skin cancer known for its rapid progression,potential for metastasis,and resistance to treatment.Despite advances in targeted therapies and immunotherapy,the prognosis for metastatic melanoma remains unfavorable.Recent research has shed light on the significance of epigenetic modifications in the pathogenesis of melanoma,revealing critical mechanisms of melanoma development and progression.Epigenetic modifications,including DNA and RNA modifications,histone modifications,chromatin remodeling,and non-coding RNA regulation,disrupt normal gene expression without modifying the DNA sequence,leading to cellular transformation,invasion,immune evasion,and therapeutic resistance.The reversible nature of epigenetic modifications opens up new opportunities for melanoma recognition and classification,as well as therapeutic applications,including the development of diagnostic and prognostic biomarkers and innovative targeted therapies aimed at restoring normal gene function and enhancing the efficacy of existing treatments.This review will focus on the multifaceted role of epigenetic dysregulation in melanoma.The future integration of epigenetic data and genomic profiling with clinical outcomes,likely facilitated by artificial intelligence(AI)algorithms,holds promise for personalized treatment strategies that are informed by precise and combinatorial diagnostic tools,ultimately improving melanoma care.The study aims to deliver a comprehensive overview of the current state of epigenetics in melanoma.
文摘The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities and obstacles.The huge and diversified nature of these datasets cannot always be managed using traditional data analysis methods.As a consequence,deep learning has emerged as a strong tool for analysing numerous omics data due to its ability to handle complex and non-linear relationships.This paper explores the fundamental concepts of deep learning and how they are used in multi-omics medical data mining.We demonstrate how autoencoders,variational autoencoders,multimodal models,attention mechanisms,transformers,and graph neural networks enable pattern analysis and recognition across all omics data.Deep learning has been found to be effective in illness classification,biomarker identification,gene network learning,and therapeutic efficacy prediction.We also consider critical problems like as data quality,model explainability,whether findings can be repeated,and computational power requirements.We now consider future elements of combining omics with clinical and imaging data,explainable AI,federated learning,and real-time diagnostics.Overall,this study emphasises the need of collaborating across disciplines to advance deep learning-based multi-omics research for precision medicine and comprehending complicated disorders.
基金funded by the Regional Ministry of Health of the Junta de Andalucıa(PI-0395-2016)the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement(No.101027215)+1 种基金supported by the PLACENTRAINING project,funded through the FEDER-UGR23 funding call(European Regional Development Fund University of Granada programGrant No.C-EXP-336UGR23)。
文摘Background:The mechanisms underlying the beneficial effects of exercise on the human placenta are poorly understood.The objective of the current study was to ascertain the influence of a supervised concurrent exercise intervention from gestational Week 17 until birth on key cytokines involved in placental development and function.Secondary aims were to explore:(a)the moderating effects of fetal sex and maternal weight status;and(b)whether gestational weight gain,lifestyle behaviors(diet,sleep patterns,and physical activity),and physical fitness(strength and cardiorespiratory fitness)mediated the effects of exercise on placental cytokines.Methods:Seventy-six pregnant women(33±4 years,mean±SD),divided into exercise(n=40)and control(n=36)groups,participated in this study.The exercise group followed a 60-min,3 days/week(aerobic+resistance)training program of moderate-to-vigorous intensity.Placental cytokines—including granulocyte-macrophage colony-stimulating factor(GM-CSF),granulocyte colony-stimulating factor(G-CSF),plateletderived growth factor AA(PDGF-AA),epidermal growth factor(EGF),monocyte chemoattractant protein-1(MCP-1),fractalkine,interleukin(IL)-8,IL-6,IL-1β,interleukin 1-receptor antagonist(IL-1ra),IL-10,tumor necrosis factor alpha(TNF-a),and interferon gamma(IFN-γ)were analyzed using Luminex multi-analyte profiling(x MAP)technology.Results:The exercise group presented higher placental levels of G-CSF and lower concentrations of EGF and IL-1ra than the control group(p<0.05).Significant effects of exercise on placental G-CSF and TNF-a(p<0.05)and a trend toward lower IL-6(p=0.08)were observed only in female placentas.Additionally,a reduction in weight gain partially mediated the effects of exercise on G-CSF(p<0.05).Conclusion:Maternal exercise during pregnancy is related to increased placental levels of G-CSF and lower EGF and IL-1ra levels.Some exercise-induced effects are observed exclusively in female placentas,including increased G-CSF and lower TNF-a and IL-6 concentrations.Notably,the increased levels of G-CSF observed with exercise might be due to a more adequate gestational weight gain.
基金the Science and Technology Foundation of Shenyang in China,No.F10-217-1-00
文摘In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cell on the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cell suspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 x 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after cell transplantation, more than 80% of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improvements were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electrophysiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After cell transplantation, no immunological rejections were observed. These findings suggest that human umbilical cord mesenchymal stem cell-loaded amniotic membrane can be used for the repair of radial nerve injury.
文摘MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.
基金supported by NIH/NCCAM center grant # 1P01 AT002644725-01"Center for Chinese Herbal Therapy(CHT) for Asthma"to Dr.Xiu-Min Li
文摘OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS： Effects of ASHMI and its components aqueous extracts of Lingzhi （Ganoderma lucidum）, Kushen （Sophora flavescens） and Gancao （Glycyrrhiza uralensis）, on Th2 cytokine secretion by murine memory Th2 cells （D10.G4.1） and eotaxin-1 secretion by human lung fibroblast （HLF-1） cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS： Individual Lingzhi, Kushen and Gancao extracts and ASHMI （the combination of individual extracts） inhibited production of interleukin （IL）-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration （IC2s） values （mg/mL） forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values （mg/mL） for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION： By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.
文摘The arrangement of various biological structures should generally ensure the safety of crucial structures and increase their working efficiency; however, other principles governing the relative positions of structures in humans have not been reported. The present study therefore investigated other principles using nerves and their companion vessels in the human body as an example. Nerves and blood vessels usually travel together and in the most direct way towards their targets. Human embryology, histology, and gross anatomy suggest that there are many possible positions for these structures during development. However, for mechanical reasons, tougher or stronger structures should take priority. Nerves are tougher than most other structures, followed by arteries, veins, and lymphatic vessels. Nerves should therefore follow the most direct route, and be followed by the arteries, veins, and lymphatic vessels. This general principle should be applicable to all living things.
基金Binational Science Foundation(BSF)grant number 2015077German Israeli Science Foundation(GIF)grant I-63-410.20-2017,Israeli Science Foundation(ISF)grant 1085/18,and Core Fund Form Tel-Aviv University.
文摘The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.
文摘An overview of a long-gap peripheral nerve therapy： A long- gap peripheral nerve transection injury is an irreparable injury to the living body, and mostly leads to permanent loss of re- lated motor and sensory functions. In such long gap injuries, nerve end-to-end suture is physically impossible. Therefore, bridging a long nerve-gap is critical to re-establish adequate mechanical support for separated nerve ends, and prevent the diffusion of neurotrophic and neurotropic factors secreted by transected stumps （Deumens et al., 2010）.
基金Supported by the College of Medicine and Health Science,Sultan Qaboos University with the fund[Micro/Immu-Immu2013/Int/07]
文摘Objective:The antimicrobial activity of the ethanol extract of the Auklandia(Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.Methods:The antimicrobial activity of the ethanol extract was tested against clinical isolates ofsome multidrug-resistant bacteria using the agar well diffusion method.Commercial antibioticswere used as positive reference standards to determine the sensitivity of the clinical isolates.Results:The extracts showed significant inhibitory activity against clinical isolates of methicillinresistantStaphylococcus aureus,Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumonia,Extended Spectrum Beta-Lactemase,Acinetobacter baumannii.The minimum inhibitory concentration values obtained using the agar dilution test ranged from 2.0μg/μL-12.0μg/μL.In the contrary the water extract showed no activity at all against the tested isolates.Furthermore,theresults obtained by examining anti-resistant activity of the plant ethanolic extract showed thatat higher concentration of the plant extract(12μg)all tested bacteria isolates were inhibited with variable inhibition zones similar to those obtained when we applied lower extract concentrationusing the well diffusion assay.Conclusion:The results demonstrated that the crude ethanolicextract of the Auklandia(Saussurea lappa)root plant has a wide spectrum of activity suggestingthat it may be useful in the treatment of infections caused by the above clinical isolates(humanpathogens).
文摘A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NMR and GC-MS after a semi-preparative HPLC separation. Under optimized conditions, donepezil was derivatized by 9-fluorenylmethyl chloroformate in chloroform and carbonate buffer at pH 9.5 in the presence of NaI after solid-phase extraction from a plasma sample. The reaction product was quantified on a reversed-phase TRACER EXCEL ODS-A, 5 μm column using a mixture of acetonitrile–10 mM acetate buffer(pH 6.0)–THF(60:35:5, v/v/v) as the mobile phase with fluorescence detection at 264 nm(ex) and 313 nm(em). Fluoxetine was used as the internal standard. The total run-time of the analysis was about 10 min, and a clean chromatogram was obtained. The developed method was linear over the range of 1–100 ng/mL in 500 μL of plasma samples(r2>0.998). The intra-day and inter-day precision values were in the range of 2.6%–11.6%. The limit of quantification was 1 ng/mL.
文摘C-type natriuretic peptide （CNP） is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B （NPR-B）. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods （such as immunolocalization, real time polymerase chain reaction and Western Blot）, and then to evaluate the influence of CNP on sperm function in vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.
基金The part of a Pham D thesis supported by Tehran University of Medical Sciences(Grant No.23049-92-02-92)
文摘In this study, we developed a simple and sensitive HPLC method for the determination of lisinopril in human plasma. The sample clean-up was carried out by solid-phase extraction(SPE) using a cation-exchange(Strata-SCX~?) extraction cartridge. After a pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, the reaction mixture was analyzed on an Agilent Zorbax SB~?-C_(18)(150 mm×4.6 mm, 5 μm). The flow rate was set at 1.0 mL/min. Fluorescence detection was performed at an excitation wavelength of 470 nm and an emission wavelength of 530 nm. The mobile phase consisted of a mixture of methanol and 0.02 M sodium dihydrogen phosphate(pH = 3.0, 60:40, v/v). The average extraction recovery of lisinopril and fluvoxamine(internal standard) was >85%. The method exhibited a linear calibration curve over the concentration range of 1–1000 ng/mL with a correlation coefficient(r^2) of ≥0.98 and a limit of quantification(LOQ) equal to 2 ng/mL. The within-run and between-run precisions were satisfactory with an RSD of 3.8%–13.7%(accuracy: from 95.0% to 96.4%) and 4.273%–14.3%(accuracy: from 94.4% to 98.5%), respectively.
文摘BACKGROUND： Cell culture in vitro trials have demonstrated that neurotrophin-3 （NT-3） can enhance the survival of sensory neurons and sympathetic neurons, and can also support embryo-derived motor neurons. This effect is dependent on nerve growth factor on the surface of cells. Understanding the role of NT-3 and its receptor in the early development of human embryonic brains will help to investigate the correlation between early survival of nerve cells and the microenvironment of neural regeneration. OBJECTIVE： To observe the proliferation of cerebral neurons in the development of human embryonic brain, and to investigate the location, expression and distribution of NT-3 and its receptor TrkC during human brain development. DESIGN, TIME AND SETTING： An observation study on cells was performed in the Department of ttuman Anatomy, Histology and Embryology, Chengdu Medical College in September 2007. MATERIALS： Fifteen specimens of flesh human embryo, aged 6 weeks, were used in this study. METHODS： The proliferation of cerebral neurons was detected using proliferating cell nuclear antigen, and the immunocytochemistry ABC technique was applied to observe the location, expression and distribution of NT-3 and its receptor TrkC in the brain of the human embryo. MAIN OUTCOME MEASURES： Location, expression and distribution of NT-3 and its receptor in the brain of the human embryo. RESULTS： In the early period （aged 6 weeks） of human embryonic development, proliferating cell nuclear antigen-positive reactive substances were mainly observed in the nucleus of the forebrain ventricular zone and subventricular zone, and the intensity was stronger in the subventricular zone than the forebrain ventricle. NT-3 positive reactive substance was mainly distributed in the cytoblastema of the forebrain neuroepithelial layer and nerve cell process, while TrkC was mainly distributed in the cell membrane of the forebrain ventricular zone and subventricular zone. During embryonic development, NT-3 and TrkC showed a positive immune reaction to a greater or lesser extent in ependymal epithelium. CONCLUSION： During early human embryonic development, cerebral nerve cells proliferate in the ventricular zone and subventricular zone, and NT-3 is expressed in the neural axon. The results show that the highly expressed NT-3 could promote the proliferation of neural axons and maintain the neuron body＇s survival.
基金supported by grants from the National Natural Science Foundation of China (81271239, 81771205, and 91632113)the Natural Science Foundation and Major Basic Research Program of Shanghai Municipality, China (16JC1420500 and 16JC1420502)+1 种基金the CAMS Innovation Fund for Medical Sciences (2017-I2M-3-008)sponsored by the China Human Brain Bank Consortium
文摘Dear Editor Research on neurodegenerative diseases is a hot topic worldwide[1],and MRI,genetics and epigenetics,and animal models have been commonly used.Considering species differences,research on human brain samples is irreplaceable(2)Many countries and regions have built brain banks to collect and store brain tissue from donors.Samples provided by a brain bank can be used to study synaptic structure,protein,DNA,RNA[3,4],and lipids to illuminate the pathological mechanisms underlying neurodegenerative diseases.When brain tissue is used for gene expression research,the quantitative real-time polymerase chain reaction(RT-qPCR)is an accurate method,which simultaneously amplifies and quantifies the expression of target genes by measuring the intensity of fluorescence in each PCR cycle.
文摘Agrizim and bayleton,two commonly usedagricultural fungicides in India,wereinvestigated for their genotoxicpotentialities on cultured humanlymphocytes by studying chromosomalaberrations and sister chromatid exchangesin the presence and absence of
