Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signali...Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.展开更多
In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment,which renders it a valuable tool for both ...In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment,which renders it a valuable tool for both scientific research and clinical applications.However,the conventional approach for improving classification accuracy often involves labeling cells with fluorescence,which can lead to potential phototoxicity.This study proposes a label-free in-vivo flow cytometry technique,called dynamic YOLOv4(D-YOLOv4),which improves classification accuracy by integrating absorption intensity fluctuation modulation(AIFM)into YOLOv4 to demodulate the temporal features of moving red blood cells(RBCs)and platelets.Using zebrafish as an experimental model,the D-YOLOv4 method achieved average precisions(APs)of 0.90 for RBCs and 0.64 for thrombocytes(similar to platelets in mammals),resulting in an overall AP of 0.77.These scores notably surpass those attained by alternative network models,thereby demonstrating that the combination of physical models with neural networks provides an innovative approach toward developing label-free in-vivoflow cytometry,which holds promise for diverse in-vivo cell classification applications.展开更多
Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnosti...Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.展开更多
In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, ...In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, no study has been done so far to study the influence of friction on the red blood cell indentation response using optical tweezers. In this study, we have developed a new approach to determine the coefficient of friction as well as the frictional forces of the red blood cell. This approach therefore allowed us to simultaneously carry out the indentation and traction test, which allowed us to extract the interfacial properties of the microbead red blood cell couple, among other things, the friction coefficient. This property would be extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. But taking into account the hypothesis of friction as defined by the isotropic Coulomb law. The experiment performed for this purpose is the Brinell Hardness Test (DB).展开更多
The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for sol...The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,and surgical resection is one of the main ways to treat gastric cancer.However,the immune status of postoperative patients is crucial for ...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,and surgical resection is one of the main ways to treat gastric cancer.However,the immune status of postoperative patients is crucial for prognosis and survival,and immune cells play an important role in this process.Therefore,it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells,especially total T cells(CD3+),helper T cells(CD3+CD4+),and suppressor T cells(CD3+CD8+),and its relationship to sur-vival.AIM To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery,detect the levels of total T cells,helper T cells and suppressor T cells.METHODS A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study.Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells,helper T cells and inhibitory T cells.To explore the relationship between these immune markers and patient survival.RESULTS The results showed that the levels of total T cells,helper T cells,and suppressor T cells changed in patients after gastric cancer surgery.There was a significant positive correlation between total T cells,helper T cells and suppressor T cells(r=0.35,P<0.01;r=0.56,P<0.01).However,there was a negative correlation between helper T cells and suppressor T cells(r=-0.63,P<0.01).Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group(28.87±24.98 months vs 18.42±16.21 months).The survival curve shows that the curve of patients in the high-level group is shifted to the upper right,and that of the low-level group is shifted downward.There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time.CONCLUSION By detecting peripheral blood immune cells with flow cytometry,we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.展开更多
BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is ...BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.展开更多
BACKGROUND Chronic eczema significantly impacts daily life,social interactions,and quality of life;however,no curative treatment has been identified.AIM To determine the clinical efficacy of acupoint injection for chr...BACKGROUND Chronic eczema significantly impacts daily life,social interactions,and quality of life;however,no curative treatment has been identified.AIM To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells.METHODS Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group(n=40),which received conventional Western medicine treatment,or an observation group(n=40),which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide.Response and adverse reaction rates,as well as differences in the levels of serum cytokines IFN-γ,IL-2,IL-4,and IL-10 before and after treatment were investigated.RESULTS No difference in overall response rates were found between the observation and control groups(100%vs 90%,respectively;P>0.05);however,the observation group had a higher marked response rate than the control group(87.5%vs 52.5%;P<0.05).Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment(P<0.05),particularly in the observation group(P<0.05).The observation group had an adverse reaction rate of 2.5%(1/40),which did not differ significantly from that of the control group(P>0.05).The observation group exhibited higher post-treatment INF-γand IL-2 but lower IL-4 levels than the control group(P<0.05);however,no significant inter-group difference was observed in post-treatment IL-10 levels(P>0.05).CONCLUSION Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema.Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels,inhibition of inflammatory reactions,and mitigation of immune imbalance.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury(IRI)and regulating immune rejection.However,some studies have in...BACKGROUND Mesenchymal stem cells(MSCs)have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury(IRI)and regulating immune rejection.However,some studies have indicated that the effects of MSCs are not very significant.Therefore,approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study.AIM To enhance the therapeutic potential of human menstrual blood-derived stromal cells(MenSCs)in the mouse liver ischemia-reperfusion(I/R)model via interferon-γ(IFN-γ)priming.METHODS Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γpriming,and indoleamine 2,3-dioxygenase(IDO)levels were measured by quantitative real-time reverse transcription polymerase chain reaction,western blotting,and ELISA to evaluate the efficacy of IFN-γpriming.In vivo,the liver I/R model was established in male C57/BL mice,hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury,and regulatory T cell(Treg)numbers in spleens were determined by flow cytometry to assess immune tolerance potential.Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs.In vitro,we established a hypoxia/reoxygenation(H/R)model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis.Transmission electron microscopy,western blotting,and immunofluorescence were used to analyze autophagy levels.RESULTS IFN-γ-primed MenSCs secreted higher levels of IDO,attenuated liver injury,and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs.Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers.In the H/R model,autophagy inhibitors increased the level of H/R-induced apoptosis,indicating that autophagy exerted protective effects.In addition,primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy.Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin(mTOR)pathway and activating the AMPK pathway.CONCLUSION IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels.MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI,and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance.Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.展开更多
The study of the morphology of White Blood Cells (WBCs) further contributes to the clinical diagnosis of blood diseases. In this research paper, we come up with an image segmentation enhancement by combining Fourier F...The study of the morphology of White Blood Cells (WBCs) further contributes to the clinical diagnosis of blood diseases. In this research paper, we come up with an image segmentation enhancement by combining Fourier Fast Transform on smear blood capture and classical thresholding. The Fast Fourier Transform (FFT) is a very powerful tool in image processing and it was used to segment and extract the WBCs. Our image processing method uses a Fast Fourier Transform combined with filtering and an Inverse Fast Fourier Transform for the extraction and visualization of the high frequency region of the image. In order to remove residual Red Blood Cells acting as noise in the expected result, a final thresholding step is added at the end of the processing. The results presented in this article report the tests performed using our mathematical implementation. Moreover, we were able to detect and differentiate the sub-families of WBCs.展开更多
Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is inv...Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.展开更多
Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and t...Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.展开更多
White blood cells (WBC) or leukocytes are a vital component ofthe blood which forms the immune system, which is accountable to fightforeign elements. The WBC images can be exposed to different data analysisapproaches ...White blood cells (WBC) or leukocytes are a vital component ofthe blood which forms the immune system, which is accountable to fightforeign elements. The WBC images can be exposed to different data analysisapproaches which categorize different kinds of WBC. Conventionally, laboratorytests are carried out to determine the kind of WBC which is erroneousand time consuming. Recently, deep learning (DL) models can be employedfor automated investigation of WBC images in short duration. Therefore,this paper introduces an Aquila Optimizer with Transfer Learning basedAutomated White Blood Cells Classification (AOTL-WBCC) technique. Thepresented AOTL-WBCC model executes data normalization and data augmentationprocess (rotation and zooming) at the initial stage. In addition,the residual network (ResNet) approach was used for feature extraction inwhich the initial hyperparameter values of the ResNet model are tuned by theuse of AO algorithm. Finally, Bayesian neural network (BNN) classificationtechnique has been implied for the identification of WBC images into distinctclasses. The experimental validation of the AOTL-WBCC methodology isperformed with the help of Kaggle dataset. The experimental results foundthat the AOTL-WBCC model has outperformed other techniques which arebased on image processing and manual feature engineering approaches underdifferent dimensions.展开更多
Objective:To explore the effect of Hupo powder(HP)on autophagy in menstrual blood-derived stem cells(MenSCs)with endometriosis(EMT).Methods:EMT MenSCs(E-MenSCs)and healthy MenSCs(H-MenSCs)were isolated from the menstr...Objective:To explore the effect of Hupo powder(HP)on autophagy in menstrual blood-derived stem cells(MenSCs)with endometriosis(EMT).Methods:EMT MenSCs(E-MenSCs)and healthy MenSCs(H-MenSCs)were isolated from the menstrual blood of patients with EMT and healthy female participants,respectively.We identified their stem cells’characteristics via adipogenic and osteogenic differentiation.Twelve male SpragueeDawley rats received 0.9% NaCl and HP-dispensing granules by gastric irrigation to prepare blank serum and medicated serum,respectively.We used serum concentrations of 5%,10%,and 20%,each at administered times of 12,24,and 48 h to select the best condition.These cells were divided into three groups:blank serum of the control group,blank serum of the model group,and medicated serum of the HP group.H-MenSCs were used in the control group,while E-MenSCs were used in the model and HP groups.We analyzed cell viability using a cell counting kit-8 assay,observed cell morphology,evaluated the amounts of auto-phagosomes and autolysosomes by transmission electron microscopy,and detected the protein expression of autophagy markers(LC3-II and Beclin1)by Western blot.Results:E-MenSCs and H-MenSCs became long fusiform with a diffuse radial pattern,forming lipid droplets and calcium nodules after adipogenic and osteogenic differentiation.We then used the best conditiond 20% serum and 48 hdfor the subsequent experiments.In contrast to the model group,the HP group exhibited lower cell viability(=0.007),larger amounts of autophagosomes and autolysosomes(P<0.001 and P=0.001,respectively),and higher expression of LC3-II and Beclin1(P=0.021 and P=0.019,respectively).Conclusion:Hupo powder can promote autophagy in E-MenSCs,which might be one of the mechanisms underlying its therapeutic effects.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
Objective:To compare the effect of human chorionic gonadotropin(hCG)-producing peripheral blood mononuclear cells(PBMCs)and PBMCs activated by hCG in vitro and expressions of related immune genes in mouse implantation...Objective:To compare the effect of human chorionic gonadotropin(hCG)-producing peripheral blood mononuclear cells(PBMCs)and PBMCs activated by hCG in vitro and expressions of related immune genes in mouse implantation.Methods:hCG-producing PBMCs(transfected PBMC)and PBMCs activated by hCG in vitro were introduced into isolated mouse endometrial cells,while cell cultures were divided into four groups:the control,PBMC,transfected,and activated PBMC groups.The expression of studied genes(IL-1β,IL-6,Lif,and Vegf)was evaluated and blastocyst attachment on the cocultured cells(isolated endometrial cells and PBMC cells)was monitored in all four groups.Results:Data showed that expression decreased in the PBMC group compared to the treated PBMC(transfected and activated PBMCs)and increased in transfected PBMC compared to the activated PBMC.Attachment and migration of blastocysts were dramatically enhanced in the transfected PBMC group compared to the activated PBMC group(P<0.05).Conclusions:Use of hCG-producing PBMCs(transfected PBMC)has more influence on endometrial receptivity.展开更多
Some human diseases are recognized through of each type of White Blood Cell(WBC)count,so detecting and classifying each type is important for human healthcare.The main aim of this paper is to propose a computer-aided ...Some human diseases are recognized through of each type of White Blood Cell(WBC)count,so detecting and classifying each type is important for human healthcare.The main aim of this paper is to propose a computer-aided WBCs utility analysis tool designed,developed,and evaluated to classify WBCs into five types namely neutrophils,eosinophils,lymphocytes,monocytes,and basophils.Using a computer-artificial model reduces resource and time consumption.Various pre-trained deep learning models have been used to extract features,including AlexNet,Visual Geometry Group(VGG),Residual Network(ResNet),which belong to different taxonomy types of deep learning architectures.Also,Binary Border Collie Optimization(BBCO)is introduced as an updated version of Border Collie Optimization(BCO)for feature reduction based on maximizing classification accuracy.The proposed computer aid diagnosis tool merges transfer deep learning ResNet101,BBCO feature reduction,and Support Vector Machine(SVM)classifier to forma hybridmodelResNet101-BBCO-SVM an accurate and fast model for classifying WBCs.As a result,the ResNet101-BBCO-SVM scores the best accuracy at 99.21%,compared to recent studies in the benchmark.The model showed that the addition of the BBCO algorithm increased the detection accuracy,and at the same time,decreased the classification time consumption.The effectiveness of the ResNet101-BBCO-SVM model has been demonstrated and beaten in reasonable ratios in recent literary studies and end-to-end transfer learning of pre-trained models.展开更多
Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheime...Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.展开更多
Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not r...Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.展开更多
The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervo...The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.展开更多
基金supported by the Russian Science Foundation grant(No.22-15-00120)supported by the grant(No.21-2-10-59-1)from the Foundation for the Development of Theoretical Physics and Mathematics BASIS.
文摘Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.
基金supported by the National Natural Science Foundation of China(62075042 and 62205060)the Research Fund of Guangdong-Hong Kong-Macao Joint Laboratory for Intelligent Micro-Nano Optoelectronic Technology(2020B1212030010)+1 种基金Fund for Research on National Major Research Instruments of China(Grant No.62027824)Fund for Science and Technology Innovation Cultivation of Guangdong University Students(No.pdjh2022b0543).
文摘In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment,which renders it a valuable tool for both scientific research and clinical applications.However,the conventional approach for improving classification accuracy often involves labeling cells with fluorescence,which can lead to potential phototoxicity.This study proposes a label-free in-vivo flow cytometry technique,called dynamic YOLOv4(D-YOLOv4),which improves classification accuracy by integrating absorption intensity fluctuation modulation(AIFM)into YOLOv4 to demodulate the temporal features of moving red blood cells(RBCs)and platelets.Using zebrafish as an experimental model,the D-YOLOv4 method achieved average precisions(APs)of 0.90 for RBCs and 0.64 for thrombocytes(similar to platelets in mammals),resulting in an overall AP of 0.77.These scores notably surpass those attained by alternative network models,thereby demonstrating that the combination of physical models with neural networks provides an innovative approach toward developing label-free in-vivoflow cytometry,which holds promise for diverse in-vivo cell classification applications.
基金This study was supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022)National Key Research and Development Program of China(2021YFC2301801).
文摘Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.
文摘In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, no study has been done so far to study the influence of friction on the red blood cell indentation response using optical tweezers. In this study, we have developed a new approach to determine the coefficient of friction as well as the frictional forces of the red blood cell. This approach therefore allowed us to simultaneously carry out the indentation and traction test, which allowed us to extract the interfacial properties of the microbead red blood cell couple, among other things, the friction coefficient. This property would be extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. But taking into account the hypothesis of friction as defined by the isotropic Coulomb law. The experiment performed for this purpose is the Brinell Hardness Test (DB).
基金Supported by National Natural Science Foundation of China,No.81702923,and No.81971503Open Project of State Key Laboratory of Medical Immunology,No.NKLMI2023K03+1 种基金Shanghai Shen Kang Hospital Development Center Clinical Science and Technology Innovation Project,No.SHDC12020104Basic Medical Research Project of Naval Medical University,No.2022QN072.
文摘The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,and surgical resection is one of the main ways to treat gastric cancer.However,the immune status of postoperative patients is crucial for prognosis and survival,and immune cells play an important role in this process.Therefore,it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells,especially total T cells(CD3+),helper T cells(CD3+CD4+),and suppressor T cells(CD3+CD8+),and its relationship to sur-vival.AIM To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery,detect the levels of total T cells,helper T cells and suppressor T cells.METHODS A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study.Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells,helper T cells and inhibitory T cells.To explore the relationship between these immune markers and patient survival.RESULTS The results showed that the levels of total T cells,helper T cells,and suppressor T cells changed in patients after gastric cancer surgery.There was a significant positive correlation between total T cells,helper T cells and suppressor T cells(r=0.35,P<0.01;r=0.56,P<0.01).However,there was a negative correlation between helper T cells and suppressor T cells(r=-0.63,P<0.01).Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group(28.87±24.98 months vs 18.42±16.21 months).The survival curve shows that the curve of patients in the high-level group is shifted to the upper right,and that of the low-level group is shifted downward.There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time.CONCLUSION By detecting peripheral blood immune cells with flow cytometry,we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.
基金Supported by National Natural Science Foundation of China,No.81470982.
文摘BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.
基金Supported by Jinshan District Medical and Health Science and Technology Innovation Funding Project,No.2021-3-07.
文摘BACKGROUND Chronic eczema significantly impacts daily life,social interactions,and quality of life;however,no curative treatment has been identified.AIM To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells.METHODS Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group(n=40),which received conventional Western medicine treatment,or an observation group(n=40),which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide.Response and adverse reaction rates,as well as differences in the levels of serum cytokines IFN-γ,IL-2,IL-4,and IL-10 before and after treatment were investigated.RESULTS No difference in overall response rates were found between the observation and control groups(100%vs 90%,respectively;P>0.05);however,the observation group had a higher marked response rate than the control group(87.5%vs 52.5%;P<0.05).Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment(P<0.05),particularly in the observation group(P<0.05).The observation group had an adverse reaction rate of 2.5%(1/40),which did not differ significantly from that of the control group(P>0.05).The observation group exhibited higher post-treatment INF-γand IL-2 but lower IL-4 levels than the control group(P<0.05);however,no significant inter-group difference was observed in post-treatment IL-10 levels(P>0.05).CONCLUSION Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema.Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels,inhibition of inflammatory reactions,and mitigation of immune imbalance.
基金National Key R&D Program of China,No.2022YFA1105603 and 2022YFC2304405Hangzhou Science and Technology Project,China,No.20200224+1 种基金National Natural Science Foundation of China,No.81900563Key Research&Development Plan of Zhejiang Province,China,No.2019C03015 and 2020C04016。
文摘BACKGROUND Mesenchymal stem cells(MSCs)have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury(IRI)and regulating immune rejection.However,some studies have indicated that the effects of MSCs are not very significant.Therefore,approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study.AIM To enhance the therapeutic potential of human menstrual blood-derived stromal cells(MenSCs)in the mouse liver ischemia-reperfusion(I/R)model via interferon-γ(IFN-γ)priming.METHODS Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γpriming,and indoleamine 2,3-dioxygenase(IDO)levels were measured by quantitative real-time reverse transcription polymerase chain reaction,western blotting,and ELISA to evaluate the efficacy of IFN-γpriming.In vivo,the liver I/R model was established in male C57/BL mice,hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury,and regulatory T cell(Treg)numbers in spleens were determined by flow cytometry to assess immune tolerance potential.Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs.In vitro,we established a hypoxia/reoxygenation(H/R)model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis.Transmission electron microscopy,western blotting,and immunofluorescence were used to analyze autophagy levels.RESULTS IFN-γ-primed MenSCs secreted higher levels of IDO,attenuated liver injury,and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs.Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers.In the H/R model,autophagy inhibitors increased the level of H/R-induced apoptosis,indicating that autophagy exerted protective effects.In addition,primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy.Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin(mTOR)pathway and activating the AMPK pathway.CONCLUSION IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels.MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI,and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance.Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.
文摘The study of the morphology of White Blood Cells (WBCs) further contributes to the clinical diagnosis of blood diseases. In this research paper, we come up with an image segmentation enhancement by combining Fourier Fast Transform on smear blood capture and classical thresholding. The Fast Fourier Transform (FFT) is a very powerful tool in image processing and it was used to segment and extract the WBCs. Our image processing method uses a Fast Fourier Transform combined with filtering and an Inverse Fast Fourier Transform for the extraction and visualization of the high frequency region of the image. In order to remove residual Red Blood Cells acting as noise in the expected result, a final thresholding step is added at the end of the processing. The results presented in this article report the tests performed using our mathematical implementation. Moreover, we were able to detect and differentiate the sub-families of WBCs.
基金National Natural Science Foundation of China,No.81972074 (to XY)Natural Science Foundation of Tianjin,No.19JCZDJC34900 (to XY)National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100 (to SF)。
文摘Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.
基金supported by the National Natural Science Foundation of China,No.82171380(to CD)Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program,No.202110304098Y(to DJ)。
文摘Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.
基金The Deanship of Scientific Research (DSR)at King Abdulaziz University (KAU),Jeddah,Saudi Arabia has funded this project,under Grant No.KEP-1–120–42.
文摘White blood cells (WBC) or leukocytes are a vital component ofthe blood which forms the immune system, which is accountable to fightforeign elements. The WBC images can be exposed to different data analysisapproaches which categorize different kinds of WBC. Conventionally, laboratorytests are carried out to determine the kind of WBC which is erroneousand time consuming. Recently, deep learning (DL) models can be employedfor automated investigation of WBC images in short duration. Therefore,this paper introduces an Aquila Optimizer with Transfer Learning basedAutomated White Blood Cells Classification (AOTL-WBCC) technique. Thepresented AOTL-WBCC model executes data normalization and data augmentationprocess (rotation and zooming) at the initial stage. In addition,the residual network (ResNet) approach was used for feature extraction inwhich the initial hyperparameter values of the ResNet model are tuned by theuse of AO algorithm. Finally, Bayesian neural network (BNN) classificationtechnique has been implied for the identification of WBC images into distinctclasses. The experimental validation of the AOTL-WBCC methodology isperformed with the help of Kaggle dataset. The experimental results foundthat the AOTL-WBCC model has outperformed other techniques which arebased on image processing and manual feature engineering approaches underdifferent dimensions.
基金This study was supported by the National Natural Science Foundation of China(81973895)the Key Research Projects of Beijing University of Chinese Medicine(2020-JYB-ZDGG-143-3).
文摘Objective:To explore the effect of Hupo powder(HP)on autophagy in menstrual blood-derived stem cells(MenSCs)with endometriosis(EMT).Methods:EMT MenSCs(E-MenSCs)and healthy MenSCs(H-MenSCs)were isolated from the menstrual blood of patients with EMT and healthy female participants,respectively.We identified their stem cells’characteristics via adipogenic and osteogenic differentiation.Twelve male SpragueeDawley rats received 0.9% NaCl and HP-dispensing granules by gastric irrigation to prepare blank serum and medicated serum,respectively.We used serum concentrations of 5%,10%,and 20%,each at administered times of 12,24,and 48 h to select the best condition.These cells were divided into three groups:blank serum of the control group,blank serum of the model group,and medicated serum of the HP group.H-MenSCs were used in the control group,while E-MenSCs were used in the model and HP groups.We analyzed cell viability using a cell counting kit-8 assay,observed cell morphology,evaluated the amounts of auto-phagosomes and autolysosomes by transmission electron microscopy,and detected the protein expression of autophagy markers(LC3-II and Beclin1)by Western blot.Results:E-MenSCs and H-MenSCs became long fusiform with a diffuse radial pattern,forming lipid droplets and calcium nodules after adipogenic and osteogenic differentiation.We then used the best conditiond 20% serum and 48 hdfor the subsequent experiments.In contrast to the model group,the HP group exhibited lower cell viability(=0.007),larger amounts of autophagosomes and autolysosomes(P<0.001 and P=0.001,respectively),and higher expression of LC3-II and Beclin1(P=0.021 and P=0.019,respectively).Conclusion:Hupo powder can promote autophagy in E-MenSCs,which might be one of the mechanisms underlying its therapeutic effects.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
文摘Objective:To compare the effect of human chorionic gonadotropin(hCG)-producing peripheral blood mononuclear cells(PBMCs)and PBMCs activated by hCG in vitro and expressions of related immune genes in mouse implantation.Methods:hCG-producing PBMCs(transfected PBMC)and PBMCs activated by hCG in vitro were introduced into isolated mouse endometrial cells,while cell cultures were divided into four groups:the control,PBMC,transfected,and activated PBMC groups.The expression of studied genes(IL-1β,IL-6,Lif,and Vegf)was evaluated and blastocyst attachment on the cocultured cells(isolated endometrial cells and PBMC cells)was monitored in all four groups.Results:Data showed that expression decreased in the PBMC group compared to the treated PBMC(transfected and activated PBMCs)and increased in transfected PBMC compared to the activated PBMC.Attachment and migration of blastocysts were dramatically enhanced in the transfected PBMC group compared to the activated PBMC group(P<0.05).Conclusions:Use of hCG-producing PBMCs(transfected PBMC)has more influence on endometrial receptivity.
文摘Some human diseases are recognized through of each type of White Blood Cell(WBC)count,so detecting and classifying each type is important for human healthcare.The main aim of this paper is to propose a computer-aided WBCs utility analysis tool designed,developed,and evaluated to classify WBCs into five types namely neutrophils,eosinophils,lymphocytes,monocytes,and basophils.Using a computer-artificial model reduces resource and time consumption.Various pre-trained deep learning models have been used to extract features,including AlexNet,Visual Geometry Group(VGG),Residual Network(ResNet),which belong to different taxonomy types of deep learning architectures.Also,Binary Border Collie Optimization(BBCO)is introduced as an updated version of Border Collie Optimization(BCO)for feature reduction based on maximizing classification accuracy.The proposed computer aid diagnosis tool merges transfer deep learning ResNet101,BBCO feature reduction,and Support Vector Machine(SVM)classifier to forma hybridmodelResNet101-BBCO-SVM an accurate and fast model for classifying WBCs.As a result,the ResNet101-BBCO-SVM scores the best accuracy at 99.21%,compared to recent studies in the benchmark.The model showed that the addition of the BBCO algorithm increased the detection accuracy,and at the same time,decreased the classification time consumption.The effectiveness of the ResNet101-BBCO-SVM model has been demonstrated and beaten in reasonable ratios in recent literary studies and end-to-end transfer learning of pre-trained models.
基金supported by the National Natural Science Foundation of China,No.82074533(to LZ).
文摘Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.
基金supported by NIH Core Grants P30-EY008098the Eye and Ear Foundation of Pittsburghunrestricted grants from Research to Prevent Blindness,New York,NY,USA(to KCC)。
文摘Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.
基金funding from European Regional Development Fund(project No 13.1.1-LMT-K-718-05-0005)under grant agreement with the Research Council of Lithuania(LMTLT)。
文摘The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.