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
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
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
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
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
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
Objective Metabotropic glutamate receptor 5 （mGluR5） is concentrated in zones of active neurogenesis in the prenatal and postnatal rodent brain and plays an important role in the regulation of neurogenesis. However,...Objective Metabotropic glutamate receptor 5 （mGluR5） is concentrated in zones of active neurogenesis in the prenatal and postnatal rodent brain and plays an important role in the regulation of neurogenesis. However, little is known about mGluR5 in the prenatal human brain. Here, we aimed to explore the expression pattern and cellular distribution of mGluR5 in human fetal hippocampus. Methods Thirty-four human fetuses were divided into four groups according to gestational age： 9-11, 14-16, 22-24 and 32-36 weeks. The hippocampus was dissected out and prepared. The protein and mRNA expression of mGluR5 were evaluated by Western blot and immunohistochemistry or real-time PCR. The cellular distribution of mGluR5 was observed with double-labeling immunofluorescence. Results Both mGluR5 mRNA and protein were detected in the prenatal human hippocampus by real-time PCR and immunoblotting, and the expression levels increased gradually over time. The immunohistochemistry results were consistent with immunoblotting and showed that mGluR5 immunoreactivity was mainly present in the inner marginal zone （IMZ）, hippocampal plate （HP） and ventricular zone （VZ）. The double-labeling immunoftuorescence showed that mGluR5 was present in neural stem cells （nestin-positive）, neuroblasts （DCX-positive） and mature neurons （NeuN-positive）, but not in typical astrocytes （GFAP- positive）. The cells co-expressing mGluR5 and nestin were mainly located in the IMZ, HP and subplate at 11 weeks, all layers at 16 weeks, and CA 1 at 24 weeks. As development proceeded, the number of mGluR5/nestin double-positive cells decreased gradually so that there were only a handful of double-labeled cells at 32 weeks. However, mGluR5/DCX double-positive cells were only found in the HP, IZ and IMZ at 11 weeks. Conclusion The pattern ofmGluR5 expression by neural stern/progenitor cells, neuroblasts and neurons provides important anatomical evidence for the role of mGluR5 in the regulation of human hippocampal development.展开更多
Neurofibromatosis type 2 is a well known disease of the human skin. Its microscopic and ultramicroscopic features are also well defined. Aim： The aim of this work was to study the involvement of catecholaminergic ner...Neurofibromatosis type 2 is a well known disease of the human skin. Its microscopic and ultramicroscopic features are also well defined. Aim： The aim of this work was to study the involvement of catecholaminergic nerve fibers in the human skin neurofibromatosis. Bioptic fragments of the human skin have been harvested from healthy and diseased subjects. On these specimens the following analysis were performed： 1） light microscopic observation after colouring with hematoxyline-Eosine. 2） lmmunochemical staining for Protein Gene Product 9.5.3） Fluorescent staining for catecholaminergic nerve fibers. 4） Quantitative analysis of images by means of the Quantimet analyzer Leica. 5） Statistical analysis of the quantitative morphological data comparing the healthy with diseased subjects. Comparing the light microscopy images in normal and pathological subjects the authors can affirm that the skin neurofibromatosis induces a strong decrease of the nerve fibers cutted in small pieces and destroyed. Also the catecholaminergic nerve fibers are strongly reduced and destroyed. Quantitative analysis of images and statistical analysis of the morphological data confirm that neurofibromatosis induces strong changes of the skin nerve fibers. The authors＇ results confirm that the neurofibromatosis type 2 induces an almost total destruction of the skin nerve fibers.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
Henry Vandyke Carter(1831–1897),physician and illustrator from Saint George’s Hospital in London,England.He worked with Henry Williamson Gray(1827–1861)on anatomical dissections and Carter’s illustrations contribu...Henry Vandyke Carter(1831–1897),physician and illustrator from Saint George’s Hospital in London,England.He worked with Henry Williamson Gray(1827–1861)on anatomical dissections and Carter’s illustrations contributed significantly to the success of the Treaty of Anatomy,Descriptive and Surgical.Henry Carter never achieved any credit or royalty for his work.This book is currently regarded as one of the most influential human anatomy textbooks.The paper aims to present a brief review of Henry Carter’s contributions to the medical field.展开更多
Objective To evaluate the changes in postoperative plasmaβ-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the imp...Objective To evaluate the changes in postoperative plasmaβ-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasmaβ-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA andβ-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasmaβ-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P<0.00001],24 hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P<0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasmaβ-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.展开更多
In 2015,the discovery of mammalian fossils,paleolithic artifacts,and burned bones in the Maoershan Cave of the Guilin Basin,northeastern Guangxi,indicated that it is a late Middle Pleistocene Paleolithic site.In 2021,...In 2015,the discovery of mammalian fossils,paleolithic artifacts,and burned bones in the Maoershan Cave of the Guilin Basin,northeastern Guangxi,indicated that it is a late Middle Pleistocene Paleolithic site.In 2021,stratigraphic sectioning and the systematic screening of small mammal sand samples were conducted.This paper presents a comprehensive account of the new material of the fruit bat Rousettus leschenaultii,accompanied by a concise overview of the non-volant micromammals that coexisted with it in the Quaternary sediments of the Maoershan Cave.This finding marks the second occurrence of fruit bat fossils in China,contributing to our understanding of the dental morphology and past geographical distribution of Rousettus.The micromammalian assemblage of the Maoershan Cave is composed of 3 orders,9 families,26 genera,and 30 species,and exhibits notable similarities with those of the late Middle Pleistocene Yumi Cave,Xinglong Cave,Yanhui Cave,Mawokou Cave,Zhongliangshan,and Chuan Cave faunas.The biochronology of the micromammalian assemblage from the Maoershan Cave has been determined to be consistent with the late Middle Pleistocene,providing a new assemblage in the Pleistocene mammalian faunal sequence in southern China.The presence of abundant oriental forested elements indicates that the Guilin Basin used to be a humid and warm subtropical forest paleoenvironment similar to the contemporary environment during the late Middle Pleistocene.展开更多
BACKGROUND It is well known that in case of high initial strictures of bile ducts surgical treatment is associated with a high risk of damage to the hepatoduodenal ligament elements,often involved in rough scarring,an...BACKGROUND It is well known that in case of high initial strictures of bile ducts surgical treatment is associated with a high risk of damage to the hepatoduodenal ligament elements,often involved in rough scarring,and with a significant risk of stricture recurrence.AIM To compare the long-term outcomes of different surgical treatment options for patients with high-grade benign biliary strictures.METHODS From 2012 to 2022,193 patients were treated at the A.V.Vishnevsky Surgical Center.All of them had different levels of strictures according to Bismuth-Strasberg classification:Type E1-2 in 32 patients,type E3-99,type E4-62.123 patients underwent open reconstructive interventions,70 percutaneous endobiliary interventions.RESULTS Long-term results were available for 192(99%)patients with a follow-up of 4.7±1.6 years after reconstructive surgery;3.0±1.4 years after percutaneous interventions.Excellent and good results(according to Terblanche classification)were achieved in 35%(42/122)of patients after open reconstructive surgery and in 13%(9/70)of patients after percutaneous transhepatic interventions(P-value<0.05).CONCLUSION Technically,the most difficult bile duct strictures for reconstructive and percutaneous transhepatic interventions with a high recurrence rate are Bismuth-Strasberg type E4 and E5.The comparative analysis of long-term results of percutaneous and open procedures showed a statistically significant advantage of percutaneous procedures compared to open reconstructive procedures.展开更多
Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cel...Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.展开更多
Oxidative stress is characterized by elevated intracellular reactive oxygen species(ROS)levels.At physiological levels,ROS work as signaling molecules,helping cells go through the cell cycle normally and keeping their...Oxidative stress is characterized by elevated intracellular reactive oxygen species(ROS)levels.At physiological levels,ROS work as signaling molecules,helping cells go through the cell cycle normally and keeping their balance.They also balance several physiological processes.However,a shift in the delicate balance between antioxidants and ROS results in aberrant cell death and deleterious effects.Elevated ROS is implicated in many diseases and disorders like diabetes,autoimmune diseases,infertility,and cardiovascular disorders.The imbalance disrupts normal cellular functions,including cell division.ROS are important regulators of the cell cycle,exerting both favorable and harmful effects depending on their levels in the system,time of action,and cellular context.The present review article highlights the role of ROS as a predisposing factor of cell cycle arrest and its effect on various stages of the cell cycle.It also considers the role ROS plays in disorders that are caused by oxidative stress,presents the interplay between ROS and cell division and explores the therapeutic intervention beneficial in managing these disorders.展开更多
Objectives:Ovarian cancer,a leading cause of gynecological malignancy-related mortality,is charac-terized by limited therapeutic options and a poor prognosis.Although pyrimethamine has emerged as a promising candidate...Objectives:Ovarian cancer,a leading cause of gynecological malignancy-related mortality,is charac-terized by limited therapeutic options and a poor prognosis.Although pyrimethamine has emerged as a promising candidate demonstrating efficacy in treating various tumors,the precise mechanisms of its antitumor effects remain obscure.This study was specifically designed to investigate the mode of action underlying the antitumor effects of pyrimethamine in preclinical settings.Methods:The effects of pyrimethamine on cellular proliferation were meticulously assessed using both the cell counting kit 8(CCK-8)assay and the colony formation assay,with the effects further confirmed in a murine model.A confocal microscope was utilized to monitor the dynamic alterations in mitochondria within ovarian cancer cells.Additionally,adenosine triphosphate(ATP)and reactive oxygen species(ROS)assays were conducted to measure mitochondrial damage induced by pyrimethamine in ovarian cancer cell lines.The mitochondrial membrane potential was assessed using fluorescent dyes as an indicator of mitochondrial functional status.Furthermore,transcriptome analysis and immunohistochemical techniques were employed to detect the impact of pyrimethamine on ovarian cancer cells.Results:Our results demonstrated that pyrimethamine induced ovarian cancer cell death through mitochondrial dysfunction and lethal mitophagy.Transcriptome profiling analysis and Western blot demonstrated that activation of the p38/JNK/ERK signaling pathway was implicated in the process of pyrimethamine-induced mitophagy in ovarian cancer cells.Importantly,combination treatment with pyrimethamine and paclitaxel in vitro and in vivo showed a synergistic antitumor effect.Conclusions:Altogether,these findings indicate that the antitumor effects of pyrimethamine result from the induction of lethal mitophagy via regulation of the p38/JNK/ERK pathway in ovarian cancer.Considering the low toxicity and high tolerance associated with pyrimethamine,it is suggested that pyrimethamine be evaluated in the treatment of ovarian cancer,either as a monotherapy or in combination with paclitaxel.展开更多
Correction to:Journal of Biomedical Research https://doi.org/10.7555/JBR.26.20120003,published on June 8,2012.We sincerely apologize for the misuse of images in Fig.4 of our article.Specifically,the image in Fig.4D,de...Correction to:Journal of Biomedical Research https://doi.org/10.7555/JBR.26.20120003,published on June 8,2012.We sincerely apologize for the misuse of images in Fig.4 of our article.Specifically,the image in Fig.4D,depicting immunohistochemistry staining for Jagged1 expression,was partially incorrect because of our oversight.Upon reviewing the laboratory records,we have successfully located the original images from 12 years ago.We are now providing the corrected version of Fig.4D below.This correction does not alter the conclusions as originally reported.展开更多
BACKGROUND Alzheimer’s disease(AD)is a progressive neurodegenerative disorder currently lacking effective therapeutic interventions.Pathological hallmarks of AD include intracellular neurofibrillary tangles(NFTs)and ...BACKGROUND Alzheimer’s disease(AD)is a progressive neurodegenerative disorder currently lacking effective therapeutic interventions.Pathological hallmarks of AD include intracellular neurofibrillary tangles(NFTs)and extracellular amyloid beta(Aβ)plaques.Neuroplastin 65(NP65),highly expressed in the brain,has been previously shown to mitigate cognitive impairments and decrease Aβplaques in the AD mouse model,suggesting that NP65 is involved in AD neuropathology.However,direct evidence linking NP65 expression to AD pathogenesis in human brain remains absent.AIM To quantify NP65 isoform expression gradients across distinct neuroanatomical regions in the healthy brain and investigate the alterations of NP65 expression in the AD brain.METHODS Immunohistochemical,immunofluorescent and western blot analyses were used to investigate NP65 expression in 19 postmortem brains(AD=10,controls=9).Double immunostaining with 6E10 and or phosphorylated-microtubule-associated protein tau(AT-8,a marker for NFT)markers was performed to assess NP65 colocalization with Aβplaques and NFTs.RESULTS In controls,NP65 was highly expressed in a wide-range of brain areas.AD cases showed significantly increased NP65 immunoreactivity across multiple brain regions,including the frontal and temporal cortex,hippocampus,and cerebellum,compared to controls.Western blot analysis consistently confirmed significantly elevated NP65 expression in the hippocampus of AD patients relative to controls.Double immunostaining demonstrated partial colocalization of NP65 with NFTs and Aβplaques in AD brain tissue.CONCLUSION Our findings demonstrate a significant increase of NP65 protein,which colocalizes with NFTs and Aβplaques in AD brains,providing direct evidence supporting a critical role of NP65 expression in the neuropathological mechanisms of this disease.展开更多
BACKGROUND The clinical application of doxorubicin(DOX)is limited by its potential to cause cardiac cardiotoxicity.AIM To investigate the correlation between calumenin(CALU)and mitochondrial kinetic-related proteins i...BACKGROUND The clinical application of doxorubicin(DOX)is limited by its potential to cause cardiac cardiotoxicity.AIM To investigate the correlation between calumenin(CALU)and mitochondrial kinetic-related proteins in rats with DOX cardiomyopathy.METHODS A rat model of DOX-induced cardiomyopathy was used to evaluate the effects of DOX.We observed the effect of DOX on electrical conduction in cardiomyocytes using the electromapping technique.Masson staining was performed to evaluate myocardium fibrosis.Electron microscopy was used to observe the changes in pathological ultrastructure of the myocardium.Western blotting and ELISAs were performed to detect protein levels and intracellular free Ca^(2+)concentration.RESULTS DOX slowed conduction and increased conduction dispersion in cardiomyocytes.The myocardial pathology in rats treated with DOX exhibited a significant deterioration,as demonstrated by an increase in mitochondrial Ca^(2+)concentration and a decrease in the expression of CALU,optic atrophy-1,and Bcl-2.Additionally,there was an increase in the expression of connexin 43(Cx43)and the mitochondrial mitotic proteins dynamin-related protein 1,CHOP,Cytochrome C,and Bax in DOX rats.Decreased expression of CALU in cardiomyocytes triggered an increase in cytoplasmic free calcium concentration,which would normally be taken up by mitochondria,but decreased expression of mitochondrial outer membrane fusion proteins triggered a decrease in mitochondrial Ca^(2+)uptake,and the increase in cytoplasmic free calcium concentration triggered cell apoptosis.CONCLUSION Increased cytoplasmic free calcium ion concentration induces calcium overload in ventricular myocytes,leading to decreased Cx43 protein,slowed conduction in myocytes,and increased conduction dispersion,resulting in arrhythmias.展开更多
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.
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.
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(81070998)the Youth Fund of the College of Medicine,Xi'an Jiaotong University(YQN0802)the Fundamental Research Funds for the Central Universities (xjj2011022)
文摘Objective Metabotropic glutamate receptor 5 （mGluR5） is concentrated in zones of active neurogenesis in the prenatal and postnatal rodent brain and plays an important role in the regulation of neurogenesis. However, little is known about mGluR5 in the prenatal human brain. Here, we aimed to explore the expression pattern and cellular distribution of mGluR5 in human fetal hippocampus. Methods Thirty-four human fetuses were divided into four groups according to gestational age： 9-11, 14-16, 22-24 and 32-36 weeks. The hippocampus was dissected out and prepared. The protein and mRNA expression of mGluR5 were evaluated by Western blot and immunohistochemistry or real-time PCR. The cellular distribution of mGluR5 was observed with double-labeling immunofluorescence. Results Both mGluR5 mRNA and protein were detected in the prenatal human hippocampus by real-time PCR and immunoblotting, and the expression levels increased gradually over time. The immunohistochemistry results were consistent with immunoblotting and showed that mGluR5 immunoreactivity was mainly present in the inner marginal zone （IMZ）, hippocampal plate （HP） and ventricular zone （VZ）. The double-labeling immunoftuorescence showed that mGluR5 was present in neural stem cells （nestin-positive）, neuroblasts （DCX-positive） and mature neurons （NeuN-positive）, but not in typical astrocytes （GFAP- positive）. The cells co-expressing mGluR5 and nestin were mainly located in the IMZ, HP and subplate at 11 weeks, all layers at 16 weeks, and CA 1 at 24 weeks. As development proceeded, the number of mGluR5/nestin double-positive cells decreased gradually so that there were only a handful of double-labeled cells at 32 weeks. However, mGluR5/DCX double-positive cells were only found in the HP, IZ and IMZ at 11 weeks. Conclusion The pattern ofmGluR5 expression by neural stern/progenitor cells, neuroblasts and neurons provides important anatomical evidence for the role of mGluR5 in the regulation of human hippocampal development.
文摘Neurofibromatosis type 2 is a well known disease of the human skin. Its microscopic and ultramicroscopic features are also well defined. Aim： The aim of this work was to study the involvement of catecholaminergic nerve fibers in the human skin neurofibromatosis. Bioptic fragments of the human skin have been harvested from healthy and diseased subjects. On these specimens the following analysis were performed： 1） light microscopic observation after colouring with hematoxyline-Eosine. 2） lmmunochemical staining for Protein Gene Product 9.5.3） Fluorescent staining for catecholaminergic nerve fibers. 4） Quantitative analysis of images by means of the Quantimet analyzer Leica. 5） Statistical analysis of the quantitative morphological data comparing the healthy with diseased subjects. Comparing the light microscopy images in normal and pathological subjects the authors can affirm that the skin neurofibromatosis induces a strong decrease of the nerve fibers cutted in small pieces and destroyed. Also the catecholaminergic nerve fibers are strongly reduced and destroyed. Quantitative analysis of images and statistical analysis of the morphological data confirm that neurofibromatosis induces strong changes of the skin nerve fibers. The authors＇ results confirm that the neurofibromatosis type 2 induces an almost total destruction of the skin nerve fibers.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘Henry Vandyke Carter(1831–1897),physician and illustrator from Saint George’s Hospital in London,England.He worked with Henry Williamson Gray(1827–1861)on anatomical dissections and Carter’s illustrations contributed significantly to the success of the Treaty of Anatomy,Descriptive and Surgical.Henry Carter never achieved any credit or royalty for his work.This book is currently regarded as one of the most influential human anatomy textbooks.The paper aims to present a brief review of Henry Carter’s contributions to the medical field.
基金Supported by Beijing Natural Science Foundation(7232130)Fundamental Research Funds for the Central Universities(2024-JYB-JBZD-024)CZ015-High Level Traditional Chinese Medicine Hospital SM Project(DZMG-LJRC0006)。
文摘Objective To evaluate the changes in postoperative plasmaβ-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasmaβ-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA andβ-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasmaβ-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P<0.00001],24 hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P<0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasmaβ-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.
文摘In 2015,the discovery of mammalian fossils,paleolithic artifacts,and burned bones in the Maoershan Cave of the Guilin Basin,northeastern Guangxi,indicated that it is a late Middle Pleistocene Paleolithic site.In 2021,stratigraphic sectioning and the systematic screening of small mammal sand samples were conducted.This paper presents a comprehensive account of the new material of the fruit bat Rousettus leschenaultii,accompanied by a concise overview of the non-volant micromammals that coexisted with it in the Quaternary sediments of the Maoershan Cave.This finding marks the second occurrence of fruit bat fossils in China,contributing to our understanding of the dental morphology and past geographical distribution of Rousettus.The micromammalian assemblage of the Maoershan Cave is composed of 3 orders,9 families,26 genera,and 30 species,and exhibits notable similarities with those of the late Middle Pleistocene Yumi Cave,Xinglong Cave,Yanhui Cave,Mawokou Cave,Zhongliangshan,and Chuan Cave faunas.The biochronology of the micromammalian assemblage from the Maoershan Cave has been determined to be consistent with the late Middle Pleistocene,providing a new assemblage in the Pleistocene mammalian faunal sequence in southern China.The presence of abundant oriental forested elements indicates that the Guilin Basin used to be a humid and warm subtropical forest paleoenvironment similar to the contemporary environment during the late Middle Pleistocene.
文摘BACKGROUND It is well known that in case of high initial strictures of bile ducts surgical treatment is associated with a high risk of damage to the hepatoduodenal ligament elements,often involved in rough scarring,and with a significant risk of stricture recurrence.AIM To compare the long-term outcomes of different surgical treatment options for patients with high-grade benign biliary strictures.METHODS From 2012 to 2022,193 patients were treated at the A.V.Vishnevsky Surgical Center.All of them had different levels of strictures according to Bismuth-Strasberg classification:Type E1-2 in 32 patients,type E3-99,type E4-62.123 patients underwent open reconstructive interventions,70 percutaneous endobiliary interventions.RESULTS Long-term results were available for 192(99%)patients with a follow-up of 4.7±1.6 years after reconstructive surgery;3.0±1.4 years after percutaneous interventions.Excellent and good results(according to Terblanche classification)were achieved in 35%(42/122)of patients after open reconstructive surgery and in 13%(9/70)of patients after percutaneous transhepatic interventions(P-value<0.05).CONCLUSION Technically,the most difficult bile duct strictures for reconstructive and percutaneous transhepatic interventions with a high recurrence rate are Bismuth-Strasberg type E4 and E5.The comparative analysis of long-term results of percutaneous and open procedures showed a statistically significant advantage of percutaneous procedures compared to open reconstructive procedures.
基金supported by grants from the National Natural Science Foundation of China(No.81770483)Shanghai Tenth Hospital’s improvement plan for NSFC(No.04.03.17.070).
文摘Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.
文摘Oxidative stress is characterized by elevated intracellular reactive oxygen species(ROS)levels.At physiological levels,ROS work as signaling molecules,helping cells go through the cell cycle normally and keeping their balance.They also balance several physiological processes.However,a shift in the delicate balance between antioxidants and ROS results in aberrant cell death and deleterious effects.Elevated ROS is implicated in many diseases and disorders like diabetes,autoimmune diseases,infertility,and cardiovascular disorders.The imbalance disrupts normal cellular functions,including cell division.ROS are important regulators of the cell cycle,exerting both favorable and harmful effects depending on their levels in the system,time of action,and cellular context.The present review article highlights the role of ROS as a predisposing factor of cell cycle arrest and its effect on various stages of the cell cycle.It also considers the role ROS plays in disorders that are caused by oxidative stress,presents the interplay between ROS and cell division and explores the therapeutic intervention beneficial in managing these disorders.
基金supported by the Natural Science Foundation of Sichuan Province,China,grant number:2021YJ0011.
文摘Objectives:Ovarian cancer,a leading cause of gynecological malignancy-related mortality,is charac-terized by limited therapeutic options and a poor prognosis.Although pyrimethamine has emerged as a promising candidate demonstrating efficacy in treating various tumors,the precise mechanisms of its antitumor effects remain obscure.This study was specifically designed to investigate the mode of action underlying the antitumor effects of pyrimethamine in preclinical settings.Methods:The effects of pyrimethamine on cellular proliferation were meticulously assessed using both the cell counting kit 8(CCK-8)assay and the colony formation assay,with the effects further confirmed in a murine model.A confocal microscope was utilized to monitor the dynamic alterations in mitochondria within ovarian cancer cells.Additionally,adenosine triphosphate(ATP)and reactive oxygen species(ROS)assays were conducted to measure mitochondrial damage induced by pyrimethamine in ovarian cancer cell lines.The mitochondrial membrane potential was assessed using fluorescent dyes as an indicator of mitochondrial functional status.Furthermore,transcriptome analysis and immunohistochemical techniques were employed to detect the impact of pyrimethamine on ovarian cancer cells.Results:Our results demonstrated that pyrimethamine induced ovarian cancer cell death through mitochondrial dysfunction and lethal mitophagy.Transcriptome profiling analysis and Western blot demonstrated that activation of the p38/JNK/ERK signaling pathway was implicated in the process of pyrimethamine-induced mitophagy in ovarian cancer cells.Importantly,combination treatment with pyrimethamine and paclitaxel in vitro and in vivo showed a synergistic antitumor effect.Conclusions:Altogether,these findings indicate that the antitumor effects of pyrimethamine result from the induction of lethal mitophagy via regulation of the p38/JNK/ERK pathway in ovarian cancer.Considering the low toxicity and high tolerance associated with pyrimethamine,it is suggested that pyrimethamine be evaluated in the treatment of ovarian cancer,either as a monotherapy or in combination with paclitaxel.
文摘Correction to:Journal of Biomedical Research https://doi.org/10.7555/JBR.26.20120003,published on June 8,2012.We sincerely apologize for the misuse of images in Fig.4 of our article.Specifically,the image in Fig.4D,depicting immunohistochemistry staining for Jagged1 expression,was partially incorrect because of our oversight.Upon reviewing the laboratory records,we have successfully located the original images from 12 years ago.We are now providing the corrected version of Fig.4D below.This correction does not alter the conclusions as originally reported.
基金the National Natural Science Foundation of China,No.81771441 and No.81371213the Natural Science Foundation of Shanghai,No.21ZR1468400.
文摘BACKGROUND Alzheimer’s disease(AD)is a progressive neurodegenerative disorder currently lacking effective therapeutic interventions.Pathological hallmarks of AD include intracellular neurofibrillary tangles(NFTs)and extracellular amyloid beta(Aβ)plaques.Neuroplastin 65(NP65),highly expressed in the brain,has been previously shown to mitigate cognitive impairments and decrease Aβplaques in the AD mouse model,suggesting that NP65 is involved in AD neuropathology.However,direct evidence linking NP65 expression to AD pathogenesis in human brain remains absent.AIM To quantify NP65 isoform expression gradients across distinct neuroanatomical regions in the healthy brain and investigate the alterations of NP65 expression in the AD brain.METHODS Immunohistochemical,immunofluorescent and western blot analyses were used to investigate NP65 expression in 19 postmortem brains(AD=10,controls=9).Double immunostaining with 6E10 and or phosphorylated-microtubule-associated protein tau(AT-8,a marker for NFT)markers was performed to assess NP65 colocalization with Aβplaques and NFTs.RESULTS In controls,NP65 was highly expressed in a wide-range of brain areas.AD cases showed significantly increased NP65 immunoreactivity across multiple brain regions,including the frontal and temporal cortex,hippocampus,and cerebellum,compared to controls.Western blot analysis consistently confirmed significantly elevated NP65 expression in the hippocampus of AD patients relative to controls.Double immunostaining demonstrated partial colocalization of NP65 with NFTs and Aβplaques in AD brain tissue.CONCLUSION Our findings demonstrate a significant increase of NP65 protein,which colocalizes with NFTs and Aβplaques in AD brains,providing direct evidence supporting a critical role of NP65 expression in the neuropathological mechanisms of this disease.
基金Supported by Technology Development of Jilin Province,No:20190701069GHNatural Science Foundation of Inner Mongolia Autonomous Region,No:2018MS08036,No:2017MS(LH)0824.
文摘BACKGROUND The clinical application of doxorubicin(DOX)is limited by its potential to cause cardiac cardiotoxicity.AIM To investigate the correlation between calumenin(CALU)and mitochondrial kinetic-related proteins in rats with DOX cardiomyopathy.METHODS A rat model of DOX-induced cardiomyopathy was used to evaluate the effects of DOX.We observed the effect of DOX on electrical conduction in cardiomyocytes using the electromapping technique.Masson staining was performed to evaluate myocardium fibrosis.Electron microscopy was used to observe the changes in pathological ultrastructure of the myocardium.Western blotting and ELISAs were performed to detect protein levels and intracellular free Ca^(2+)concentration.RESULTS DOX slowed conduction and increased conduction dispersion in cardiomyocytes.The myocardial pathology in rats treated with DOX exhibited a significant deterioration,as demonstrated by an increase in mitochondrial Ca^(2+)concentration and a decrease in the expression of CALU,optic atrophy-1,and Bcl-2.Additionally,there was an increase in the expression of connexin 43(Cx43)and the mitochondrial mitotic proteins dynamin-related protein 1,CHOP,Cytochrome C,and Bax in DOX rats.Decreased expression of CALU in cardiomyocytes triggered an increase in cytoplasmic free calcium concentration,which would normally be taken up by mitochondria,but decreased expression of mitochondrial outer membrane fusion proteins triggered a decrease in mitochondrial Ca^(2+)uptake,and the increase in cytoplasmic free calcium concentration triggered cell apoptosis.CONCLUSION Increased cytoplasmic free calcium ion concentration induces calcium overload in ventricular myocytes,leading to decreased Cx43 protein,slowed conduction in myocytes,and increased conduction dispersion,resulting in arrhythmias.
