Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cell...In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.展开更多
BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the exist...BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
This review outlines the effects of different types of cells with immune function on acute lung injury(ALI)inflammation and the regulation of inflammatory responses between these cells via cell-cell interactions.It is...This review outlines the effects of different types of cells with immune function on acute lung injury(ALI)inflammation and the regulation of inflammatory responses between these cells via cell-cell interactions.It is expected to provide some possible strategies for the research and treatment of ALI and acute respiratory distress syndrome(ARDS).展开更多
Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regu...Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.展开更多
Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, a...Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, along with endothelial dysfunction of the corpora cavernosa and impaired blood flow to the penis considered underlying factors. However, the current treatments are limited to Phosphodiesterase-5 (PDE5) inhibitors. ED is the primary symptom of andropathy. This study reports the clinical efficacy of human stem cell-conditioned medium cream for ED treatment. Ten men without underlying diseases suspected of andropause with ED (mean age 43.2 ± 4.4 y, Hb 15.2 ± 0.6 gm/dL, AST/ALT 30.2/37.9 ± 12.4/14.0, eGFR 82.7 ± 12.4 mL/min/1.73 m2) were targeted. The cream was applied twice daily to the genital and scrotal areas. The erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Male Symptoms (AMS) scale were used to evaluate the participants before and 30 days after use, and the results were compared using paired t-tests. The post-use qualitative opinions were collected through interviews. Significant improvements were observed compared to baseline in the IIEF-5 (11.8 ± 4.6→17.2 ± 5.1, P < 0.001), and AMS (46.3 ± 6.7→37.6 ± 5.3, P < 0.001) scores post cream use. EHS did not show a statistically significant difference, but a trend towards improvement was observed. Qualitative feedback included increased morning erection, improved maintenance of erection during intercourse, and reduced post work fatigue. Human stem cell-conditioned medium contains endothelial growth factors that potentially contribute to the improvement of ED and andropause by enhancing corporal endothelial function. Future studies should include control groups to further investigate the efficacy of these treatments.展开更多
Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Me...Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.展开更多
The main objective of this study was to evaluate the pharmacological potential of the hydroethanol extract of Strychnos camptoneura trunk bark on reproductive functions in male guinea pigs exposed to cypermethrin. The...The main objective of this study was to evaluate the pharmacological potential of the hydroethanol extract of Strychnos camptoneura trunk bark on reproductive functions in male guinea pigs exposed to cypermethrin. The results showed that administration of the hydroethanolic extract (100 and 250 mg/kg) of Strychnos camptoneura trunk bark after exposure of the animals to cypermethrin induced a highly significant (p Strychnos camptoneura trunk bark produced a highly significant (p Strychnos camptoneura trunk bark may have protective effects against cypermethrin-induced male infertility due to its androgenic, spermatogenic and antiradical properties.展开更多
Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The st...Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.展开更多
Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.Thi...Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.This resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance imaging.This technique measures subtle changes in blood flow,volume,and oxygenation that occur over time.Although vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.展开更多
Carbazole moiety-based 2PACz([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)self-assembled monolayers(SAMs)are excellent hole-selective contact(HSC)materials with abilities to excel the charge-transferdynamics of perovski...Carbazole moiety-based 2PACz([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)self-assembled monolayers(SAMs)are excellent hole-selective contact(HSC)materials with abilities to excel the charge-transferdynamics of perovskite solar cells(PSCs).Herein,we report a facile but powerful method to functionalize the surface of 2PACz-SAM,by which reproducible,highly stable,high-efficiency wide-bandgap PSCs can be obtained.The 2PACz surface treatment with various donor number solvents improves assembly of 2PACz-SAM and leave residual surface-bound solvent molecules on 2PACz-SAM,which increases perovskite grain size,retards halide segregation,and accelerates hole extraction.The surface functionalization achieves a high power conversion efficiency(PCE)of 17.62%for a single-junction wide-bandgap(~1.77 e V)PSC.We also demonstrate a monolithic all-perovskite tandem solar cell using surfaceengineered HSC,showing high PCE of 24.66%with large open-circuit voltage of 2.008 V and high fillfactor of 81.45%.Our results suggest this simple approach can further improve the tandem device,when coupled with a high-performance narrow-bandgap sub-cell.展开更多
Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is a bacterial pathogen of tomato and of the model plants Arabidopsis and Nicotiana benthamiana (N. benthamiana). Like numerous Gram-negative bacterial pathogens of ...Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is a bacterial pathogen of tomato and of the model plants Arabidopsis and Nicotiana benthamiana (N. benthamiana). Like numerous Gram-negative bacterial pathogens of animals and plants, Pst DC3000 exploits the conserved type III secretion system (TTSS) to deliver multiple virulence effectors directly into the host cells. Type III effectors (T3Es) collectively participate in causing disease, by mechanisms that are not well clarity. Elucidating the virulence function of individual effector is fundamental for understanding bacterial infection of plants. Here, we focused on studying one of these effectors, HopAA1-1, and analyzed its potential function and subcellular localization in N. benthamiana. Using an Agrobacterium-mediated transient expression system, we found that HopAA1-1 can trigger domain-dependent cell death in N. benthamiana. The observation using confocal microscopy showed that the YFP-tagged HopAA1-1 localizes to diverse cellular components containing nucleus, cytoplasm and cell membrane, which was demonstrated through immunoblot analysis of membrane fractionation and nuclear separation. Enforced HopAA1-1 subcellular localization, by tagging with a nuclear localization sequence (NLS) or a nuclear export sequence (NES), shows that HopAA1-1-induced cell death in N. benthamiana is suppressed in the nucleus but enhanced in the cytoplasm. Our research is lay a foundation for revealed the molecular pathogenesis of Pseudomonas syringae pv. tomato.展开更多
Objective:The secretome,comprising bioactive chemicals released by mesenchymal stem cells(MSCs),holds therapeutic promise in regenerative medicine.This review aimed to explore the therapeutic potential of the MSC secr...Objective:The secretome,comprising bioactive chemicals released by mesenchymal stem cells(MSCs),holds therapeutic promise in regenerative medicine.This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology,particularly for treating erectile dysfunction(ED),and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales,mechanisms,preclinical investigations,and therapeutic potential of the MSC secretome in this context.Methods:The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED.Subsequently,it delved into the existing knowledge regarding the MSC secretome,exploring its therapeutic potential.The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome.展开更多
The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease(MASLD)and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions,underscori...The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease(MASLD)and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions,underscoring the critical demand for novel treatments.A recent publication by Li et al proposes mesenchymal stem cells as promising effectors for the treatment of MASLD.This editorial is a continuum of the article published by Jiang et al which focuses on the significance of strategies to enhance the functionality of mesenchymal stem cells to improve efficacy in curing MASLD,including physical pretreatment,drug or chemical pretreatment,pretreatment with bioactive substances,and genetic engineering.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphoc...In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.展开更多
BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to deco...BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.展开更多
The cuticular wax,acting as the ultimate defense barrier,is essential for the normal morphogenesis of plant organs.Despite this importance,the connection between wax composition and leaf development has not been thoro...The cuticular wax,acting as the ultimate defense barrier,is essential for the normal morphogenesis of plant organs.Despite this importance,the connection between wax composition and leaf development has not been thoroughly explored.In this study,we characterized a new maize mutant,ragged leaf4(rgd4),which exhibits crinkled and ragged leaves starting from the sixth leaf stage.The phenotype of rgd4 is conferred by ZmCER1,which encoding an aldehyde decarbonylase involved in wax biosynthesis.ZmCER1 function deficient mutant displayed reduced cuticular wax density and disordered bulliform cells(BCs),while ZmCER1 overexpressing plants exhibited the opposite effects,indicating that ZmCER1 regulates cuticular wax biosynthesis and BCs development.Additionally,as the density of cuticular wax increased,the water loss rate of detached leaf decreases,suggesting that ZmCER1 is positively correlated with plant drought tolerance.展开更多
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金National Natural Science Foundation of China,No.82172196,No.82372507,and No.81971891.
文摘In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.
基金approved by the medical ethics committee of the authors’institution(protocol number:56733164-203-E.5863).
文摘BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金Yunnan Fundamental Research Projects(202201AU070167&202301AT070258),and the Yunnan Key Laboratory of Formulated Granules(202105AG070014).
文摘This review outlines the effects of different types of cells with immune function on acute lung injury(ALI)inflammation and the regulation of inflammatory responses between these cells via cell-cell interactions.It is expected to provide some possible strategies for the research and treatment of ALI and acute respiratory distress syndrome(ARDS).
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)the National Natural Science Foundation of China No.81930070(to SF)+1 种基金Multi-fund Investment Key Projects,No.21JCZDJC01100(to ZW)the Tianjin Science and Technology Planning Project,No.22JRRCRC00010(to SF)。
文摘Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.
文摘Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, along with endothelial dysfunction of the corpora cavernosa and impaired blood flow to the penis considered underlying factors. However, the current treatments are limited to Phosphodiesterase-5 (PDE5) inhibitors. ED is the primary symptom of andropathy. This study reports the clinical efficacy of human stem cell-conditioned medium cream for ED treatment. Ten men without underlying diseases suspected of andropause with ED (mean age 43.2 ± 4.4 y, Hb 15.2 ± 0.6 gm/dL, AST/ALT 30.2/37.9 ± 12.4/14.0, eGFR 82.7 ± 12.4 mL/min/1.73 m2) were targeted. The cream was applied twice daily to the genital and scrotal areas. The erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Male Symptoms (AMS) scale were used to evaluate the participants before and 30 days after use, and the results were compared using paired t-tests. The post-use qualitative opinions were collected through interviews. Significant improvements were observed compared to baseline in the IIEF-5 (11.8 ± 4.6→17.2 ± 5.1, P < 0.001), and AMS (46.3 ± 6.7→37.6 ± 5.3, P < 0.001) scores post cream use. EHS did not show a statistically significant difference, but a trend towards improvement was observed. Qualitative feedback included increased morning erection, improved maintenance of erection during intercourse, and reduced post work fatigue. Human stem cell-conditioned medium contains endothelial growth factors that potentially contribute to the improvement of ED and andropause by enhancing corporal endothelial function. Future studies should include control groups to further investigate the efficacy of these treatments.
基金supported by the National Natural Science Foundation of China(No.81972681,82103677)Tianjin Education Commission Research Plan Project(No.2021KJ201)+1 种基金Shenzhen High-level Hospital Construction Fund(No.G2022139)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-009A).
文摘Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.
文摘The main objective of this study was to evaluate the pharmacological potential of the hydroethanol extract of Strychnos camptoneura trunk bark on reproductive functions in male guinea pigs exposed to cypermethrin. The results showed that administration of the hydroethanolic extract (100 and 250 mg/kg) of Strychnos camptoneura trunk bark after exposure of the animals to cypermethrin induced a highly significant (p Strychnos camptoneura trunk bark produced a highly significant (p Strychnos camptoneura trunk bark may have protective effects against cypermethrin-induced male infertility due to its androgenic, spermatogenic and antiradical properties.
文摘Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.
文摘Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.This resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance imaging.This technique measures subtle changes in blood flow,volume,and oxygenation that occur over time.Although vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.
基金supported by the National Research Foundation of Korea (NRF)the Ministry of Science,ICT (2022M3J1A1085285,2019R1A2C1084010,and 2022R1A2C2006532)the Korea Electric Power Corporation (R20XO02-1)。
文摘Carbazole moiety-based 2PACz([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)self-assembled monolayers(SAMs)are excellent hole-selective contact(HSC)materials with abilities to excel the charge-transferdynamics of perovskite solar cells(PSCs).Herein,we report a facile but powerful method to functionalize the surface of 2PACz-SAM,by which reproducible,highly stable,high-efficiency wide-bandgap PSCs can be obtained.The 2PACz surface treatment with various donor number solvents improves assembly of 2PACz-SAM and leave residual surface-bound solvent molecules on 2PACz-SAM,which increases perovskite grain size,retards halide segregation,and accelerates hole extraction.The surface functionalization achieves a high power conversion efficiency(PCE)of 17.62%for a single-junction wide-bandgap(~1.77 e V)PSC.We also demonstrate a monolithic all-perovskite tandem solar cell using surfaceengineered HSC,showing high PCE of 24.66%with large open-circuit voltage of 2.008 V and high fillfactor of 81.45%.Our results suggest this simple approach can further improve the tandem device,when coupled with a high-performance narrow-bandgap sub-cell.
文摘Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is a bacterial pathogen of tomato and of the model plants Arabidopsis and Nicotiana benthamiana (N. benthamiana). Like numerous Gram-negative bacterial pathogens of animals and plants, Pst DC3000 exploits the conserved type III secretion system (TTSS) to deliver multiple virulence effectors directly into the host cells. Type III effectors (T3Es) collectively participate in causing disease, by mechanisms that are not well clarity. Elucidating the virulence function of individual effector is fundamental for understanding bacterial infection of plants. Here, we focused on studying one of these effectors, HopAA1-1, and analyzed its potential function and subcellular localization in N. benthamiana. Using an Agrobacterium-mediated transient expression system, we found that HopAA1-1 can trigger domain-dependent cell death in N. benthamiana. The observation using confocal microscopy showed that the YFP-tagged HopAA1-1 localizes to diverse cellular components containing nucleus, cytoplasm and cell membrane, which was demonstrated through immunoblot analysis of membrane fractionation and nuclear separation. Enforced HopAA1-1 subcellular localization, by tagging with a nuclear localization sequence (NLS) or a nuclear export sequence (NES), shows that HopAA1-1-induced cell death in N. benthamiana is suppressed in the nucleus but enhanced in the cytoplasm. Our research is lay a foundation for revealed the molecular pathogenesis of Pseudomonas syringae pv. tomato.
文摘Objective:The secretome,comprising bioactive chemicals released by mesenchymal stem cells(MSCs),holds therapeutic promise in regenerative medicine.This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology,particularly for treating erectile dysfunction(ED),and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales,mechanisms,preclinical investigations,and therapeutic potential of the MSC secretome in this context.Methods:The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED.Subsequently,it delved into the existing knowledge regarding the MSC secretome,exploring its therapeutic potential.The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome.
文摘The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease(MASLD)and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions,underscoring the critical demand for novel treatments.A recent publication by Li et al proposes mesenchymal stem cells as promising effectors for the treatment of MASLD.This editorial is a continuum of the article published by Jiang et al which focuses on the significance of strategies to enhance the functionality of mesenchymal stem cells to improve efficacy in curing MASLD,including physical pretreatment,drug or chemical pretreatment,pretreatment with bioactive substances,and genetic engineering.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
文摘In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.
文摘BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.
基金supported by Professor Zhukuan Cheng from Institute of Genetics and Developmental Biology,Chinese Academy of Sciencessupported by the Funds of Key R&D Program of Shandong Province(2022LZGC006)Key R&D Program of Shandong Province(2023LZGC006)。
文摘The cuticular wax,acting as the ultimate defense barrier,is essential for the normal morphogenesis of plant organs.Despite this importance,the connection between wax composition and leaf development has not been thoroughly explored.In this study,we characterized a new maize mutant,ragged leaf4(rgd4),which exhibits crinkled and ragged leaves starting from the sixth leaf stage.The phenotype of rgd4 is conferred by ZmCER1,which encoding an aldehyde decarbonylase involved in wax biosynthesis.ZmCER1 function deficient mutant displayed reduced cuticular wax density and disordered bulliform cells(BCs),while ZmCER1 overexpressing plants exhibited the opposite effects,indicating that ZmCER1 regulates cuticular wax biosynthesis and BCs development.Additionally,as the density of cuticular wax increased,the water loss rate of detached leaf decreases,suggesting that ZmCER1 is positively correlated with plant drought tolerance.
