Objective The cellular apoptosis susceptibility(CAS) protein plays a regulatory role in the induction of cell death in tumor cells. The objective of this study was to investigate the association of the expression of C...Objective The cellular apoptosis susceptibility(CAS) protein plays a regulatory role in the induction of cell death in tumor cells. The objective of this study was to investigate the association of the expression of CAS protein with HBV infection in the development of HCC. Methods The expression level of CAS was measured with immunohistochemistry. The occurrence of HBs Ag, HBe Ag and HBV DNA in HCC were concurrently examined with immunohistochemistry and in situ hybridization, respectively. Results The results showed that the CAS protein was detected in 86%(43/50), 70%(7/10), 15%(3/20) and none(0/20) of livers from patients with HCC, cholangiocarcinoma, cirrhosis and hepatitis, respectively. Furthermore, the level of CAS protein was higher in poorly differentiated tumors than moderately or well differentiated HCC. Interestingly, the CAS was stained significantly stronger in HBV-infected HCC than in non-HBV infected tissues(P < 0.01). Conclusions The expression of CAS is facilitated by HBV infection in HCC, suggesting that CAS might be a prognostic marker and a putative therapeutic target for HCC.展开更多
AIM: To investigate the role of serum-and-glucocorticoid-inducible-kinase-1(SGK1) in colitis and its potential pathological mechanisms.METHODS: SGK1 expression in mucosal biopsies from patients with active Crohn's...AIM: To investigate the role of serum-and-glucocorticoid-inducible-kinase-1(SGK1) in colitis and its potential pathological mechanisms.METHODS: SGK1 expression in mucosal biopsies from patients with active Crohn's disease(CD) and normal controls was detected by immunohistochemistry. We established an acute colitis model in mice induced by 2,4,6-trinitrobenzene sulfonicacid, and demonstrated the presence of colitis using the disease activity index, the histologic activity index and hematoxylin and eosin staining. The cellular events and potential mechanisms were implemented with small interference RNA and an inhibitor of signaling molecule(i.e., U0126) in intestinal epithelial cells(IECs). The interaction between SGK1 and the signaling molecule was assessed by coimmunoprecipitation.RESULTS: SGK1 expression was significantly increased in the inflamed epithelia of patients with active CD and TNBS-induced colitis model(0.58 ± 0.055 vs 0.85 ± 0.06, P < 0.01). At the cellular level, silencing of SGK1 by small interference RNA(si SGK1) significantly inhibited the phosphorylation of mitogen-activated protein kinase kinase 1(MEK1) and the downstream molecule extracellular signal regulated protein kinase(ERK) 1/2, which induced the upregulation of p53 and Bcl-2-associated X protein, mediating the subsequent cellular apoptosis and proliferation in IECs. Cells treated with MEK1 inhibitor(i.e., U0126) before si SGK1 transfection showed a reversal of the si SGK1-induced cellular apoptosis. CONCLUSION: Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partly by triggering MEK/ERK activation.展开更多
A survivin small interfering RNA sequence specific for a human and mouse homogenous sequence was constructed.Survivin small interfering RNA could significantly inhibit glioma cell proliferation and induce apoptosis wh...A survivin small interfering RNA sequence specific for a human and mouse homogenous sequence was constructed.Survivin small interfering RNA could significantly inhibit glioma cell proliferation and induce apoptosis when it was transfected into either a human glioma cell line U251 or rat glioma C6 cells in vitro.In addition,treatment of rat orthotopic glioma models with survivin small interfering demonstrated the inhibition of glioma growth in vivo.Our experimental findings suggest that the use of RNA interference techniques to target the survivin sequence may be useful in the treatment of glioma.展开更多
OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiot...OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.展开更多
BACKGROUND:Studies have demonstrated that the mechanisms underlying cellular apoptosis signal transduction focus on two pathways:intracellular mitochondria and extracellular death receptor.The current evidence support...BACKGROUND:Studies have demonstrated that the mechanisms underlying cellular apoptosis signal transduction focus on two pathways:intracellular mitochondria and extracellular death receptor.The current evidence supports that signal transduction of cellular apoptosis also includes endoplasmic reticulum stress signal transduction. OBJECTIVE:To observe Caspase-12 expression and cellular apoptosis following ischemia in rats with progressive spinal cord compression,and to verify the influence of endoplasmic reticulum stress on the apoptosis induced by spinal cord injury. DESIGN,TIME AND SETTING:A randomized,controlled,animal trial was performed at the Institute of Neuroscience in Chongqing Medical University between January and October in 2006. MATERIALS:Immunohistochemical kit,diaminobenzidine,and TUNEL kit were purchased from Beijing Zhongshan Biotechnology,China;rabbit anti-rat Caspase-12 monoclonal antibody was provided by Santa Cruz,USA. METHODS:Sixty Wistar rats,aged 3-4 months,were randomly assigned to a model group(n=50), which underwent spinal cord compression in the L_1 segment following L_1 laminectomy and articular process excision to establish a model of progressive spinal cord compression,and a sham-surgery group(n=10),which underwent only laminectomy.Starting with the first day after surgery,the rats were locally anesthetized,the skin was opened,and the screw was rotated by 1/4 of a cycle,twice weekly. MAIN OUTCOME MEASURES:At 3,7,14,21,and 28 days after surgery,rats from each group were anesthetized,and the spinal cords were resected.Pathological changes following spinal cord compression were determined using hematoxylin-eosin staining,Nissl dye,and transmission electron microscopy.The TUNEL method was used to observe neuronal apoptosis in the compressed spinal cord segments.Immunohistochemistry and Western blot were utilized to detect Caspase-12 expression in the compressed segments. RESULTS:Cellular swelling,neural degeneration,and altered endoplasmic reticulum structures were observed at 3 days following compression.Symptoms became gradually aggravated with increasing compression time.Compared with the sham-surgery group,the number of apoptotic neurons was remarkably increased in compressed segments of the model group(P<0.05),and Caspase-12 expression was also shown to increase(P<0.05). CONCLUSION:Neuronal apoptosis was a predominant pathological factor resulting in secondary spinal cord injury during progressive spinal cord compression,and Caspase-12 was shown to be possibly involved in neuronal apoptosis induced by progressive spinal cord compression.展开更多
Buyang Huanwu Decoction fraction extracted from Buyang Huanwu Decoction contains saponins of Astragalus, total paeony glycoside and safflower flavones. The aim of this study was to demonstrate the neuroprotective effe...Buyang Huanwu Decoction fraction extracted from Buyang Huanwu Decoction contains saponins of Astragalus, total paeony glycoside and safflower flavones. The aim of this study was to demonstrate the neuroprotective effect and mechanism of Buyang Huanwu Decoction fraction on ischemic injury both in vivo and in vitro. In vivo experiments showed that 50-200 mg/kg Buyang Huanwu Decoction fraction reduced infarct volume and pathological injury in ischemia/reperfusion rats, markedly inhibited expression of nuclear factor-κB and tumor necrosis factor-α and promoted nestin protein expression in brain tissue. Buyang Huanwu Decoction fraction (200 mg/kg) exhibited significant effects, which were similar to those of 100 mg/kg Ginkgo biloba extract. In vitro experimental results demonstrated that 10-100 mg/L Buyang Huanwu Decoction fraction significantly improved cell viability, decreased the release of lactate dehydrogenase and malondialdehyde levels, and inhibited the rate of apoptosis in HT22 cells following oxygen-glucose deprivation. Buyang Huanwu Decoction fraction (100 mg/L) exhibited significant effects, which were similar to those of 100 mg/L Ginkgo biloba extract. These findings suggest that Buyang Huanwu Decoction fraction may represent a novel, protective strategy against cerebral ischemia/reperfusion injury in rats and oxygen-glucose deprivation-induced damage in HT22 cells in vitro by attenuating the inflammatory response and cellular apoptosis.展开更多
Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition ...Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.展开更多
Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,...Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.展开更多
Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiven...Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.展开更多
Objective:To observe the effects of and explore the underlying mechanisms of Periplogenin(PPG)on the regulation of proliferation,apoptosis and migration of hepatocellular carcinoma Hep3B cell.Methods:Hep3B cells were ...Objective:To observe the effects of and explore the underlying mechanisms of Periplogenin(PPG)on the regulation of proliferation,apoptosis and migration of hepatocellular carcinoma Hep3B cell.Methods:Hep3B cells were divided into control group and PPG group.The Hep3B cells in the control group were not treated with PPG,and the other in the PPG group were intervened with 2.5,5 and 12.5µmol/mL PPG for 48 h.Cell viability was measured using the CCK-8 assay.Cell morphological changes was observed using by light microscope;the apoptotic state was observed by DAPI/PI staining.The colony-formation assay and scratch method was used for detecting the cell clone forming ability and cell migration ability,respectively.The cell apoptosis-related proteins Caspase-3,Cleaved Caspase-3,Bcl-2 and cell migration-related protein Matrix metalloproteinase-9(MMP-9)were detected byWestern Blot.Results:Compared with the control group,the cell proliferation level and the cell number in each PPG group were decreased,accompanying by cell volume reduction,chromatin pyknosis,and nuclear rupture in Hep3B cells.After PPG treatment,the clone formation level and cell mobility of Hep3B cells were decreased.Compared with the control group,the level of Bcl-2 protein was decreased,while the proportion of Cleaved Caspase-3/Caspase-3 protein was increased.The expression of MMP-9 proteins was decreased,with significantly statistically differences(P<0.05).Conclusion:Periplogenin could inhibit the proliferation,and migration of Hep3B cells and also promote the cell apoptosis in a dose-dependent manner,which might be related to the activation of Caspase signaling pathway and inhibition of MMP-9 activity.展开更多
In critical care medicine,sepsis is a dangerous systemic condition that is highly prevalent and is associated with high morbidity and mortality rates^([1]).The high mortality rate associated with sepsis is closely rel...In critical care medicine,sepsis is a dangerous systemic condition that is highly prevalent and is associated with high morbidity and mortality rates^([1]).The high mortality rate associated with sepsis is closely related to multi-organ dysfunction,with heart injury being particularly critical and considered the starting point of multi-organ injury^([2]).展开更多
The evolution of microstructure during hot deformation is key to achieving good mechanical properties in aluminum alloys.We have developed a cellular automaton(CA) based model to simulate the microstructural evolution...The evolution of microstructure during hot deformation is key to achieving good mechanical properties in aluminum alloys.We have developed a cellular automaton(CA) based model to simulate the microstructural evolution in 7075 aluminum alloy during hot deformation.Isothermal compression tests were conducted to obtain material parameters for 7075 aluminum alloy,leading to the establishment of models for dislocation density,nucleation of recrystallized grains,and grain growth.Integrating these aspects with grain topological deformation,our CA model effectively predicts flow stress,dynamic recrystallization(DRX) volume fraction,and average grain size under diverse deformation conditions.A systematic comparison was made between electron back scattered diffraction(EBSD) maps and CA model simulated under different deformation temperatures(573 to 723 K),strain rates(0.001 to 1 s^(-1)),and strain amounts(30% to 70%).These analyses indicate that large strain,high temperature,and low strain rate facilitate dynamic recrystallization and grain refinement.The results from the CA model show good accuracy and predictive capability,with experimental error within 10%.展开更多
Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. How...Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. However, this process is also associated with apoptosis, upregulated secretion of inflammatory cytokine, and promoted surrounding tissue damage. When cellular senescence accumulates to a certain extent, it triggers geriatric diseases, such as chronic inflammation, immune senescence-associated tumors and incontrollable infections. Cellular senescence gene SENEX, which was cloned in 2004, has been demonstrated to play a unique gatekeeper function in human endothelial cells when stress-induced pre-mature senescence and apoptosis occurr. The phenomenon that CD4+CD25+ Treg cells accumulated in the aged population has been well studied in recent years. Now Treg accumulation related to immune-pathology has attracted more interest. CD4+CD25+ Treg did not decline and age, but accumulated and suppressed immunoreaction. The enhanced Treg number and function may be associated with stress-induced premature senescence-mediated unique cellular senescence protection mechanisms, and SENEX may play a critical role in this process. In this article, we summarize the cellular senescence and SENEX gene in the accumulation and functional activity of CD4+CD25+ Treg in the elderly.展开更多
Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a...Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a new type of1,2,3,4-tetrahydro-β-carboline(THC)derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv.oryzae(Xoo),Xanthomonas axonopodis pv.citri(Xac),and Pseudomonas syringae pv.actinidiae(Psa).The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria,the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL^(-1)respectively,and compound A8 exhibited the best inhibitory activity against Psa with EC50value of 4.87 mg mL^(-1).Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker,with protective efficiencies of 52.67 and 79.79%at 200 mgmL^(-1),respectively.Meanwhile,compound A8 showed good control efficiency(84.31%)against kiwifruit bacterial canker at 200 mg mL^(-1).Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system,damage the cell membrane,and induce the apoptosis of Xoo cells.Taken together,our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broadspectrum bactericides.展开更多
Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landra...Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows.However,the functions of miR-24-3p on GCs are unclear.In this study,using flow cytometry,5-ethynyl-2′-de-oxyuridine(EdU)staining,and cell count,we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes,moreover,miR-24-3p inhibited GC apoptosis.Mechanistically,on-line prediction,bioinformatics analysis,a luciferase reporter assay,RT-qPCR,and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B(P27/CDKN1B).Furthermore,the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression.These findings suggest that miR-24-3p regulates the physiological functions of GCs.展开更多
Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techni...Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.展开更多
Background Atresia and degeneration,a follicular developmental fate that reduces female fertility and is triggered by granulosa cell(GC)apoptosis,have been induced by dozens of miRNAs.Here,we report a miRNA,miR-423,th...Background Atresia and degeneration,a follicular developmental fate that reduces female fertility and is triggered by granulosa cell(GC)apoptosis,have been induced by dozens of miRNAs.Here,we report a miRNA,miR-423,that inhibits the initiation of follicular atresia(FA),and early apoptosis of GCs.Results We showed that miR-423 was down-regulated during sow FA,and its levels in follicles were negatively correlated with the GC density and the P4/E2 ratio in the follicular fluid in vivo.The in vitro gain-of-function experiments revealed that miR-423 suppresses cell apoptosis,especially early apoptosis in GCs.Mechanically speaking,the miR-423 targets and interacts with the 3’-UTR of the porcine SMAD7 gene,which encodes an apoptosis-inducing factor in GCs,and represses its expression and pro-apoptotic function.Interestingly,FA and the GC apoptosis-related lncRNA NORHA was demonstrated as a ceRNA of miR-423.Additionally,we showed that a single base deletion/insertion in the miR-423 promoter is significantly associated with the number of stillbirths(NSB)trait of sows.Conclusion These results demonstrate that miR-423 is a small molecule for inhibiting FA initiation and GC early apoptosis,suggesting that treating with miR-423 may be a novel approach for inhibiting FA initiation and improving female fertility.展开更多
BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometr...BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.展开更多
Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(A.hygrometricus)on human acute lymphoblastic leukemia cells.Methods:Extensive screening of the antipro...Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(A.hygrometricus)on human acute lymphoblastic leukemia cells.Methods:Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms,A.hygrometricus,Phallus sp.,Lentinus sp.,Tricholoma sp.,and Serpula sp.was performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Apoptosis determination,cell cycle profiling,intracellular reactive oxygen species(ROS)and reactive nitrogen species(RNS),and mitochondrial membrane potential were analyzed by flow cytometry.The activity of caspases was measured colorimetrically,and the expression pattern of mitochondrial proteins was analyzed.Results:The methanol extract of A.hygrometricus and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line,respectively.The mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 stage.The extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 cells.The methanol extract induced apoptosis by downregulating the expression of Bcl-2,increasing the expression of Bax,and activating the caspase cascade.Conclusion:The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.展开更多
BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation...BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.展开更多
文摘Objective The cellular apoptosis susceptibility(CAS) protein plays a regulatory role in the induction of cell death in tumor cells. The objective of this study was to investigate the association of the expression of CAS protein with HBV infection in the development of HCC. Methods The expression level of CAS was measured with immunohistochemistry. The occurrence of HBs Ag, HBe Ag and HBV DNA in HCC were concurrently examined with immunohistochemistry and in situ hybridization, respectively. Results The results showed that the CAS protein was detected in 86%(43/50), 70%(7/10), 15%(3/20) and none(0/20) of livers from patients with HCC, cholangiocarcinoma, cirrhosis and hepatitis, respectively. Furthermore, the level of CAS protein was higher in poorly differentiated tumors than moderately or well differentiated HCC. Interestingly, the CAS was stained significantly stronger in HBV-infected HCC than in non-HBV infected tissues(P < 0.01). Conclusions The expression of CAS is facilitated by HBV infection in HCC, suggesting that CAS might be a prognostic marker and a putative therapeutic target for HCC.
基金Supported by National Natural Science Foundation of China,No.81470806the National Natural Science Foundation of Jiangsu Province,No.BK20141496the Public Health Ministry of Jiangsu Province in the Talents in Medical Science Program,No.RC201179
文摘AIM: To investigate the role of serum-and-glucocorticoid-inducible-kinase-1(SGK1) in colitis and its potential pathological mechanisms.METHODS: SGK1 expression in mucosal biopsies from patients with active Crohn's disease(CD) and normal controls was detected by immunohistochemistry. We established an acute colitis model in mice induced by 2,4,6-trinitrobenzene sulfonicacid, and demonstrated the presence of colitis using the disease activity index, the histologic activity index and hematoxylin and eosin staining. The cellular events and potential mechanisms were implemented with small interference RNA and an inhibitor of signaling molecule(i.e., U0126) in intestinal epithelial cells(IECs). The interaction between SGK1 and the signaling molecule was assessed by coimmunoprecipitation.RESULTS: SGK1 expression was significantly increased in the inflamed epithelia of patients with active CD and TNBS-induced colitis model(0.58 ± 0.055 vs 0.85 ± 0.06, P < 0.01). At the cellular level, silencing of SGK1 by small interference RNA(si SGK1) significantly inhibited the phosphorylation of mitogen-activated protein kinase kinase 1(MEK1) and the downstream molecule extracellular signal regulated protein kinase(ERK) 1/2, which induced the upregulation of p53 and Bcl-2-associated X protein, mediating the subsequent cellular apoptosis and proliferation in IECs. Cells treated with MEK1 inhibitor(i.e., U0126) before si SGK1 transfection showed a reversal of the si SGK1-induced cellular apoptosis. CONCLUSION: Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partly by triggering MEK/ERK activation.
基金supported by the Natural Science Foundation of Jilin Province,No.2011146,2012150the Natural Science Foundation of Jilin Technology Division,No.201133139 and 201032235
文摘A survivin small interfering RNA sequence specific for a human and mouse homogenous sequence was constructed.Survivin small interfering RNA could significantly inhibit glioma cell proliferation and induce apoptosis when it was transfected into either a human glioma cell line U251 or rat glioma C6 cells in vitro.In addition,treatment of rat orthotopic glioma models with survivin small interfering demonstrated the inhibition of glioma growth in vivo.Our experimental findings suggest that the use of RNA interference techniques to target the survivin sequence may be useful in the treatment of glioma.
基金supported by Jiangsu Provincial Special Programme of Medical Science(BL2014035) Changzhou Science and Technology Support Program(CE20155060+2 种基金CE20165048) Changzhou High-Level Medical Talents Training Project(2016CZBJ006) Changzhou Municipal Commissions o
文摘OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.
基金the National Natural Science Foundation of China,No.30270437Chunhui Program of the Ministry of Education in 2003, No.200407
文摘BACKGROUND:Studies have demonstrated that the mechanisms underlying cellular apoptosis signal transduction focus on two pathways:intracellular mitochondria and extracellular death receptor.The current evidence supports that signal transduction of cellular apoptosis also includes endoplasmic reticulum stress signal transduction. OBJECTIVE:To observe Caspase-12 expression and cellular apoptosis following ischemia in rats with progressive spinal cord compression,and to verify the influence of endoplasmic reticulum stress on the apoptosis induced by spinal cord injury. DESIGN,TIME AND SETTING:A randomized,controlled,animal trial was performed at the Institute of Neuroscience in Chongqing Medical University between January and October in 2006. MATERIALS:Immunohistochemical kit,diaminobenzidine,and TUNEL kit were purchased from Beijing Zhongshan Biotechnology,China;rabbit anti-rat Caspase-12 monoclonal antibody was provided by Santa Cruz,USA. METHODS:Sixty Wistar rats,aged 3-4 months,were randomly assigned to a model group(n=50), which underwent spinal cord compression in the L_1 segment following L_1 laminectomy and articular process excision to establish a model of progressive spinal cord compression,and a sham-surgery group(n=10),which underwent only laminectomy.Starting with the first day after surgery,the rats were locally anesthetized,the skin was opened,and the screw was rotated by 1/4 of a cycle,twice weekly. MAIN OUTCOME MEASURES:At 3,7,14,21,and 28 days after surgery,rats from each group were anesthetized,and the spinal cords were resected.Pathological changes following spinal cord compression were determined using hematoxylin-eosin staining,Nissl dye,and transmission electron microscopy.The TUNEL method was used to observe neuronal apoptosis in the compressed spinal cord segments.Immunohistochemistry and Western blot were utilized to detect Caspase-12 expression in the compressed segments. RESULTS:Cellular swelling,neural degeneration,and altered endoplasmic reticulum structures were observed at 3 days following compression.Symptoms became gradually aggravated with increasing compression time.Compared with the sham-surgery group,the number of apoptotic neurons was remarkably increased in compressed segments of the model group(P<0.05),and Caspase-12 expression was also shown to increase(P<0.05). CONCLUSION:Neuronal apoptosis was a predominant pathological factor resulting in secondary spinal cord injury during progressive spinal cord compression,and Caspase-12 was shown to be possibly involved in neuronal apoptosis induced by progressive spinal cord compression.
基金supported by a grant from the Major Programs of Anhui Science and Technology Special Funds,No.08010302099the Doctor Funds of Anhui Medical University,No.XJ200813
文摘Buyang Huanwu Decoction fraction extracted from Buyang Huanwu Decoction contains saponins of Astragalus, total paeony glycoside and safflower flavones. The aim of this study was to demonstrate the neuroprotective effect and mechanism of Buyang Huanwu Decoction fraction on ischemic injury both in vivo and in vitro. In vivo experiments showed that 50-200 mg/kg Buyang Huanwu Decoction fraction reduced infarct volume and pathological injury in ischemia/reperfusion rats, markedly inhibited expression of nuclear factor-κB and tumor necrosis factor-α and promoted nestin protein expression in brain tissue. Buyang Huanwu Decoction fraction (200 mg/kg) exhibited significant effects, which were similar to those of 100 mg/kg Ginkgo biloba extract. In vitro experimental results demonstrated that 10-100 mg/L Buyang Huanwu Decoction fraction significantly improved cell viability, decreased the release of lactate dehydrogenase and malondialdehyde levels, and inhibited the rate of apoptosis in HT22 cells following oxygen-glucose deprivation. Buyang Huanwu Decoction fraction (100 mg/L) exhibited significant effects, which were similar to those of 100 mg/L Ginkgo biloba extract. These findings suggest that Buyang Huanwu Decoction fraction may represent a novel, protective strategy against cerebral ischemia/reperfusion injury in rats and oxygen-glucose deprivation-induced damage in HT22 cells in vitro by attenuating the inflammatory response and cellular apoptosis.
基金funded by the GRRC Program of Gyeonggi province[GRRC-KyungHee2023(B01)],Republic of Korea.
文摘Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.
基金supported by the National Key R&D Program of China(Grant No.:2021YFC2101500)the National Natural Science Foundation of China(Grant Nos.:22078264,21978235,22108224,and 21978236)+2 种基金the Natural Science Basic Research Program of Shaanxi,China(Grant Nos.:2023-JC-JQ-17 and 2023-JCQN-0109)the Xi'an Science and Technology Project,China(Project No.:20191422315KYPT014JC016)Key Research and Development Program of Shaanxi,China(Grant No.:2022ZDLSF05-12).
文摘Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.
基金support from the National Natural Science Foundation of China(Grants No.82304827,82074098,81841001)the Fundamental Research Funds for the Central public welfare research institutes(ZZ13-ZD-07),the National Key Research and Development Programof China(2020YFA0908000,2022YFC2303600)+7 种基金the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No:ZYYCXTD-C-202002)The Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation(B2302051)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grants No.ZZ13-YQ-108)the Shenzhen Science and Technology Innovation Commission(Grants No.JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002)Supported by Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034)Supported by Shenzhen key Laboratory of Kidney Diseases(ZDSYS201504301616234)Supported by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(NO.SZGSP001).
文摘Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.
基金National Natural Science Foundation of China(82205209)Shenzhen Science and Technology Program(JCYJ20210324120405015)。
文摘Objective:To observe the effects of and explore the underlying mechanisms of Periplogenin(PPG)on the regulation of proliferation,apoptosis and migration of hepatocellular carcinoma Hep3B cell.Methods:Hep3B cells were divided into control group and PPG group.The Hep3B cells in the control group were not treated with PPG,and the other in the PPG group were intervened with 2.5,5 and 12.5µmol/mL PPG for 48 h.Cell viability was measured using the CCK-8 assay.Cell morphological changes was observed using by light microscope;the apoptotic state was observed by DAPI/PI staining.The colony-formation assay and scratch method was used for detecting the cell clone forming ability and cell migration ability,respectively.The cell apoptosis-related proteins Caspase-3,Cleaved Caspase-3,Bcl-2 and cell migration-related protein Matrix metalloproteinase-9(MMP-9)were detected byWestern Blot.Results:Compared with the control group,the cell proliferation level and the cell number in each PPG group were decreased,accompanying by cell volume reduction,chromatin pyknosis,and nuclear rupture in Hep3B cells.After PPG treatment,the clone formation level and cell mobility of Hep3B cells were decreased.Compared with the control group,the level of Bcl-2 protein was decreased,while the proportion of Cleaved Caspase-3/Caspase-3 protein was increased.The expression of MMP-9 proteins was decreased,with significantly statistically differences(P<0.05).Conclusion:Periplogenin could inhibit the proliferation,and migration of Hep3B cells and also promote the cell apoptosis in a dose-dependent manner,which might be related to the activation of Caspase signaling pathway and inhibition of MMP-9 activity.
基金supported by Jiangsu Traditional Chinese Medicine Science and Technology Development Program(MS2022099)The Postgraduate Research&Practice Innovation Program of Jiangsu Ocean University(No.KYCX2022-34)。
文摘In critical care medicine,sepsis is a dangerous systemic condition that is highly prevalent and is associated with high morbidity and mortality rates^([1]).The high mortality rate associated with sepsis is closely related to multi-organ dysfunction,with heart injury being particularly critical and considered the starting point of multi-organ injury^([2]).
基金Funded by the Central Government Guides Local Funds for Science and Technology Development(No.YDZJSX20231A045)the Fundamental Research Program of Shanxi Province(Nos.202103021223288 and 202103021224282)。
文摘The evolution of microstructure during hot deformation is key to achieving good mechanical properties in aluminum alloys.We have developed a cellular automaton(CA) based model to simulate the microstructural evolution in 7075 aluminum alloy during hot deformation.Isothermal compression tests were conducted to obtain material parameters for 7075 aluminum alloy,leading to the establishment of models for dislocation density,nucleation of recrystallized grains,and grain growth.Integrating these aspects with grain topological deformation,our CA model effectively predicts flow stress,dynamic recrystallization(DRX) volume fraction,and average grain size under diverse deformation conditions.A systematic comparison was made between electron back scattered diffraction(EBSD) maps and CA model simulated under different deformation temperatures(573 to 723 K),strain rates(0.001 to 1 s^(-1)),and strain amounts(30% to 70%).These analyses indicate that large strain,high temperature,and low strain rate facilitate dynamic recrystallization and grain refinement.The results from the CA model show good accuracy and predictive capability,with experimental error within 10%.
文摘Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. However, this process is also associated with apoptosis, upregulated secretion of inflammatory cytokine, and promoted surrounding tissue damage. When cellular senescence accumulates to a certain extent, it triggers geriatric diseases, such as chronic inflammation, immune senescence-associated tumors and incontrollable infections. Cellular senescence gene SENEX, which was cloned in 2004, has been demonstrated to play a unique gatekeeper function in human endothelial cells when stress-induced pre-mature senescence and apoptosis occurr. The phenomenon that CD4+CD25+ Treg cells accumulated in the aged population has been well studied in recent years. Now Treg accumulation related to immune-pathology has attracted more interest. CD4+CD25+ Treg did not decline and age, but accumulated and suppressed immunoreaction. The enhanced Treg number and function may be associated with stress-induced premature senescence-mediated unique cellular senescence protection mechanisms, and SENEX may play a critical role in this process. In this article, we summarize the cellular senescence and SENEX gene in the accumulation and functional activity of CD4+CD25+ Treg in the elderly.
基金the supports from National Natural Science Foundation of China(21877021,32160661,and 32202359)the Guizhou Provincial S&T Project China(2018[4007])+2 种基金the the Guizhou Province China[Qianjiaohe KY number(2020)004]the Program of Introducing Talents of Discipline to Universities of China(D20023,111 Program)the Guizhou University(GZU)Found for Newly Enrolled Talent China(202229)。
文摘Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a new type of1,2,3,4-tetrahydro-β-carboline(THC)derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv.oryzae(Xoo),Xanthomonas axonopodis pv.citri(Xac),and Pseudomonas syringae pv.actinidiae(Psa).The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria,the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL^(-1)respectively,and compound A8 exhibited the best inhibitory activity against Psa with EC50value of 4.87 mg mL^(-1).Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker,with protective efficiencies of 52.67 and 79.79%at 200 mgmL^(-1),respectively.Meanwhile,compound A8 showed good control efficiency(84.31%)against kiwifruit bacterial canker at 200 mg mL^(-1).Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system,damage the cell membrane,and induce the apoptosis of Xoo cells.Taken together,our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broadspectrum bactericides.
基金supported by the National Natural Science Foundation of China(32272849)the National Key R&D Program of China(2021YFF1000602)the earmarked fund for CARS-35-PIG。
文摘Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows.However,the functions of miR-24-3p on GCs are unclear.In this study,using flow cytometry,5-ethynyl-2′-de-oxyuridine(EdU)staining,and cell count,we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes,moreover,miR-24-3p inhibited GC apoptosis.Mechanistically,on-line prediction,bioinformatics analysis,a luciferase reporter assay,RT-qPCR,and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B(P27/CDKN1B).Furthermore,the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression.These findings suggest that miR-24-3p regulates the physiological functions of GCs.
基金Supported by the National Natural Science Foundation of China,No.82000586 and No.82241221and Shanghai Immune Therapy Institute.
文摘Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.
基金supported by the National Key R&D Program of China(2022YFD1600903)the National Natural Science Foundation of China(32072693)the College Students’Innovative Entrepreneurial Training Plan Program(202110307028).
文摘Background Atresia and degeneration,a follicular developmental fate that reduces female fertility and is triggered by granulosa cell(GC)apoptosis,have been induced by dozens of miRNAs.Here,we report a miRNA,miR-423,that inhibits the initiation of follicular atresia(FA),and early apoptosis of GCs.Results We showed that miR-423 was down-regulated during sow FA,and its levels in follicles were negatively correlated with the GC density and the P4/E2 ratio in the follicular fluid in vivo.The in vitro gain-of-function experiments revealed that miR-423 suppresses cell apoptosis,especially early apoptosis in GCs.Mechanically speaking,the miR-423 targets and interacts with the 3’-UTR of the porcine SMAD7 gene,which encodes an apoptosis-inducing factor in GCs,and represses its expression and pro-apoptotic function.Interestingly,FA and the GC apoptosis-related lncRNA NORHA was demonstrated as a ceRNA of miR-423.Additionally,we showed that a single base deletion/insertion in the miR-423 promoter is significantly associated with the number of stillbirths(NSB)trait of sows.Conclusion These results demonstrate that miR-423 is a small molecule for inhibiting FA initiation and GC early apoptosis,suggesting that treating with miR-423 may be a novel approach for inhibiting FA initiation and improving female fertility.
基金National Natural Science Foundation of China,No.82173063 and No.81972220Wuxi Taihu Lake Talent Plan Supporting for Leading Talents in Medical and Health Profession+2 种基金Wuxi Medical Key Discipline,No.ZDXK2021002China Postdoctoral Science Foundation,No.2022M711370Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX23_2573.
文摘BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.
基金indebted toWest Bengal-Department of Science and Technology(1158[Sanc]/ST BT-13015/15/2021-ST SEC)for project funding,University Grants Commission for providing fellowship and contingency to Ribhu Ray,Indian Council of Medical Research for providing fellowship and contingency to Anirban Chouni and UGC-UPE and UGC-CAS program at the Department of Botany,University of Calcutta for financial support.
文摘Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(A.hygrometricus)on human acute lymphoblastic leukemia cells.Methods:Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms,A.hygrometricus,Phallus sp.,Lentinus sp.,Tricholoma sp.,and Serpula sp.was performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Apoptosis determination,cell cycle profiling,intracellular reactive oxygen species(ROS)and reactive nitrogen species(RNS),and mitochondrial membrane potential were analyzed by flow cytometry.The activity of caspases was measured colorimetrically,and the expression pattern of mitochondrial proteins was analyzed.Results:The methanol extract of A.hygrometricus and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line,respectively.The mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 stage.The extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 cells.The methanol extract induced apoptosis by downregulating the expression of Bcl-2,increasing the expression of Bax,and activating the caspase cascade.Conclusion:The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.
基金Supported by the National Natural Science Foundation of China,No.3206080019 and No.32060182Science and Technology Support Plan of Guizhou Province in China,No.[2020]4Y129Qiannan Prefecture Science and Technology Plan Project,No.[2022]01.
文摘BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.
