Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=...Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.展开更多
BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.展开更多
BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated a...BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.展开更多
BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported ...BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.展开更多
In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is...In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.展开更多
BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-rel...BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 inhibitors.Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are unclear.AIM To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.METHODS The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English.We scanned the references of the selected literature to identify any further relevant studies.Six cases previously studied by us,including three that have not yet been published,were included in this review.RESULTS Thirty-one PD-1 inhibitor-related SC cases were evaluated.Median age of patients was 67 years(range,43–89),with a male to female ratio of 21:10.The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer.Agents that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent symptom.Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin G4.Biliary dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were noted.In 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells in the bile duct or peribiliary tract.Although corticosteroids were mainly used for PD inhibitor-related SC treatment,the response rate was 11.5%(3/26).CONCLUSION Some clinical and pathological features of PD-1 inhibitor-related SC were revealed.To establish diagnostic criteria for PD-1 inhibitor-related SC,more cases need to be evaluated.展开更多
Male sterility induced by a chemical hybridization agent (CHA) is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male s...Male sterility induced by a chemical hybridization agent (CHA) is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death (PCD) as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species (O2- and H202) and down-regulation of the activities of superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (POD). Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.展开更多
Background: Programmed cell death protein 4(PDCD4) is a novel tumor suppressor protein involved in pro?grammed cell death. Its association with cancer progression has been observed in multiple tumor models, but eviden...Background: Programmed cell death protein 4(PDCD4) is a novel tumor suppressor protein involved in pro?grammed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical signiicance and prognostic value of PDCD4 in solid tumors.Methods: A systematic literature review was performed to retrieve publications with available clinical informa?tion and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta?analysis Of Observational Studies in Epidemiology group. Pooled odds ratios(ORs), hazard ratios(HRs), and 95% conidence intervals(CIs) for survival analysis were calculated. Publication bias was examined by Begg's and Egger's tests.Results: Clinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was signiicantly associated with the diferentiation status of head and neck cancer(OR 4.25, 95% CI 1.87–9.66) and digestive system cancer(OR 2.87, 95% CI 1.84–4.48). Down?regulation of PDCD4 was signiicantly associated with short overall survival of patients with head and neck(HR: 3.44, 95% CI 2.38–4.98), breast(HR: 1.86, 95% CI 1.36–2.54), digestive system(HR: 2.12, 95% CI 1.75–2.56), and urinary system cancers(HR: 3.16, 95% CI 1.06–9.41).Conclusions: The current evidence suggests that PDCD4 down?regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be conirmed by large?scale prospective studies.展开更多
Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body.Programmed cell death(PCD)is a crucial component of several development and defense mechanisms...Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body.Programmed cell death(PCD)is a crucial component of several development and defense mechanisms.PCD is also important in terms of aging which avoids the accumulation of cellular damage by maintaining cell division.Depending on the execution of cell death and its role in destruction,PCD is categorized into several subtypes.The major different forms of PCD in animals are apoptosis,autophagy and necrosis,which can be distinct in morphological terms.More intense investigations of cell death have given close insight showing other important types of cellular destruction and their pivotal roles in treating disease conditions like cancer.Flavonoids have been acquired a great interest for disease therapies and chemoprevention through activation of several PCD mechanisms.The significant potential of natural flavonoids in the induction of distinct signaling cascades is being a massive approach for targeting uncontrolled cell growth.For these reasons,understanding PCD mechanisms is a promising approach for the interventions in treating cancer.Thus,it is intriguing that understanding the different forms of PCD mechanism induced by flavonoids with more accurate descriptions on the biochemical and cellular processes are gaining more significance in cancer research.Here,we provide a brief overview on the different types of PCD and aim to discuss the functional role of flavonoids in promoting different types of cell death as well as an extensive brief review on their mechanism of action has been highlighted.展开更多
The maize (Zea mays) spikelet consists of two florets, each of which contains three developmentally synchronized anthers. Morphologically, the anthers in the upper and lower florets proceed through apparently simila...The maize (Zea mays) spikelet consists of two florets, each of which contains three developmentally synchronized anthers. Morphologically, the anthers in the upper and lower florets proceed through apparently similar developmental programs. To test for global differences in gene expression and to identify genes that are coordinately regulated during maize anther development, RNA samples isolated from upper and lower floret anthers at six developmental stages were hybridized to cDNA microarrays. Approximately 9% of the tested genes exhibited statistically significant differences in expression between anthers in the upper and lower florets. This finding indicates that several basic biological processes are differentially regulated between upper and lower floret anthers, including metabolism, protein synthesis and signal transduction. Genes that are coordinately regulated across anther development were identified via cluster analysis. Analysis of these results identified stage-specific, early in development, late in development and bi-phasic expression profiles. Quantitative RT-PCR analysis revealed that four genes whose homologs in other plant species are involved in programmed cell death are up-regulated just prior to the time the tapetum begins to visibly degenerate (i.e., the mid-microspore stage). This finding supports the hypothesis that developmentally normal tapetal degeneration occurs via programmed cell death.展开更多
Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery.However,transplanted stem cells show a high death percentage,creating challenges to successful transplantat...Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery.However,transplanted stem cells show a high death percentage,creating challenges to successful transplantation and prognosis.Thus,it is necessary to investigate the mechanisms underlying stem cell death,such as apoptotic cascade activation,excessive autophagy,inflammatory response,reactive oxygen species,excitotoxicity,and ischemia/hypoxia.Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success.Notably,a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate,highlighting the challenges in exploring mechanisms and therapeutic targets.In this review,we focus on programmed cell death in transplanted stem cells.We also discuss some promising strategies and challenges in promoting survival for further study.展开更多
Nitric oxide (NO) is a key signaling molecule in different physiological processes of plants, including programmed cell death (PCD). PCD of tillers plays an important role in surviving which are major components o...Nitric oxide (NO) is a key signaling molecule in different physiological processes of plants, including programmed cell death (PCD). PCD of tillers plays an important role in surviving which are major components of grain yield. PCD was triggered in wheat leaves of main stem and tillers by NO content under different nitrogen treatments. In wheat, NO could be synthesized endogenously by nitrate reductase (NR). As an inducible enzyme, NR activity was closely related to substrate concentration. Therefore, different nitrogen levels would change NR activity and NO production. The objective of this study was to determine the effects of NR activity, NO production, and the correlation between them on different tillers growth, development, senescence, and kernel protein content under different nitrogen levels. Field-experiments were conducted in 2009-2011 growing seasons, using two wheat cultivars with different spike-types. Results showed that for main stem and primary tillers, NR activity and NO content reached high level at heading stage, while for secondary tiller, the level of NR activity was low, but NO content was high in the present research. The NO synthesis depending on NR activity in wheat leaves was significant in the early growing stage, but the NO synthesis weakened with the progress of growing period. NO was related to the senescence of wheat leaves, but PCD was more sensitive to marked changes of NO content than NO content itself. N application had marked influence on the aging process of primary tiller, while had little influence on that of main stem and secondary tiller. Moreover, N fertilizer application could increase spike rate and protein content of primary tiller by N fertilizer application.展开更多
Morphological variations of the nucleus in starchy endosperm cell were observed by theelectron-transmisson microscope during endosperm development in rice. Along with thedevelopment of the starchy endosperm, the nucle...Morphological variations of the nucleus in starchy endosperm cell were observed by theelectron-transmisson microscope during endosperm development in rice. Along with thedevelopment of the starchy endosperm, the nuclei of the cells showed chromatin condensation,the typical feature of programmed cell death (PCD). The nuclei also showed nucleusdeformation, disruption of nuclear envelope, nucleoplasm leaking into the cytoplasm andnucleus disintegration resulting in nuclear residue formation. From the nucleus deformationto the nucleus disintegration, the morphological changes of the nucleus were orderlyprogressive. This indicated that the cell death of starchy endosperm in rice wasprogrammed cell death. Evans Blue staining observation showed that the cell death wasinitially detected in the central part of starchy endosperm in rice, then expandedoutward. The activities of superoxide dismutase (SOD) and catalase (CAT) in rice starchyendosperm both descended continuously as development progressed. The analysis of DNA ofrice starchy endosperm did not show the presence of DNA laddering. The above resultsshowed that the cell death of starchy endosperm in rice was a special form of PCD.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is caused by an abnormal immune response.Programmed cell death 1(PD-1)is an immunostimulatory molecule,which interacts with PD ligand(PD-L1)playing a prime important role amon...BACKGROUND Inflammatory bowel disease(IBD)is caused by an abnormal immune response.Programmed cell death 1(PD-1)is an immunostimulatory molecule,which interacts with PD ligand(PD-L1)playing a prime important role among autoimmune diseases.Bifidobacterium infantis(B.infantis)can promote the differentiation of CD(cluster of differentiation)4^(+)T cells into regulatory T cells(Tregs).Tregs participate in the development of IBD and may be related to disease activity.B.infantis amplify the expression level of PD-1,PD-L1 and Tregs’nuclear transcription factor forkhead box protein 3(Foxp3).But the mechanism of B.infantis on PD-1/PD-L1 signaling remains unclear.AIM To explore the mechanism of B.infantis regulating the immune response in IBD.METHODS Forty-eight-week-old BALB/c mice were randomly divided into five groups:The control group,dextran sulphate sodium(DSS)model group,DSS+B.infantis group,DSS+B.infantis+anti-PD-L1 group,and DSS+anti-PD-L1 group.The control group mice were given drinking water freely,the other four groups were given drinking water containing 5%DSS freely.The control group,DSS model group,and DSS+anti-PD-L1 group were given normal saline(NS)400μL daily by gastric lavage,and the DSS+B.infantis group and DSS+B.infantis+anti-PDL1 group were given NS and 1×109 colony-forming unit of B.infantis daily by gastric lavage.The DSS+B.infantis+anti-PD-L1 group and DSS+anti-PD-L1 group were given 200μg of PD-L1 blocker intraperitoneally at days 0,3,5,and 7;the control group,DSS+anti-PD-L1 group,and DSS+B.infantis group were given an intraperitoneal injection of an equal volume of phosphate buffered saline(PBS).Changes in PD-L1,PD-1,Foxp3,interleukin(IL)-10,and transforming growth factorβ(TGF-β)1 protein and gene expression were observed.Flow cytometry was used to observe changes in CD4^(+),CD25^(+),Foxp3^(+)cell numbers in the blood and spleen.RESULTS Compared to the control group,the expression of PD-1,Foxp3,IL-10,and TGF-β1 was significantly decreased in the intestinal tract of the DSS mice(P<0.05).Compared to the control group,the proportion of CD4^(+),CD25^(+),Foxp3^(+)cells in spleen and blood of DSS group was visibly katabatic(P<0.05).B.infantis upgraded the express of PD-L1,PD-1,Foxp3,IL-10,and TGF-β1(P<0.05)and increased the proportion of CD4^(+),CD25^(+),Foxp3^(+)cells both in spleen and blood(P<0.05).After blocking PD-L1,the increase in Foxp3,IL-10,and TGF-β1 protein and gene by B.infantis was inhibited(P<0.05),and the proliferation of CD4^(+),CD25^(+),Foxp3^(+)cells in the spleen and blood was also inhibited(P<0.05).After blocking PD-L1,the messenger ribonucleic acid and protein expression of PD-1 were invariant.CONCLUSION It is potential that B.infantis boost the proliferation of CD4^(+),CD25^(+),Foxp3^(+)T cells in both spleen and blood,as well as the expression of Foxp3 in the intestinal tract by activating the PD-1/PD-L1 pathway.展开更多
BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis aft...BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy.CASE SUMMARY Both case 1 and case 2 presented with common symptoms of fatigue,nausea,and vomiting.However,case 3 showed rare acute severe symptoms such as hoarse voice,bucking,and difficulty in breathing even when sitting.Following two cycles of immunotherapy in case 3,the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis.These symptoms were relieved after 10 d of steroid treatment.Case 3 was the first patient with these specific symptoms,which provided a new insight into the diagnosis of hypophysitis.In addition,we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy.Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment.Cases 1 and 2 were treated with the low-dose hormone,and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment.CONCLUSION The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.展开更多
This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart...This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.展开更多
[Objective] This study aimed to investigate the effects of heat shock factor AtHsfAla on programmed cell death in Arabidopsis thaliana under cold stress. [ Method] AtHsfAla-silenced transgenic (NT) and wild-type (W...[Objective] This study aimed to investigate the effects of heat shock factor AtHsfAla on programmed cell death in Arabidopsis thaliana under cold stress. [ Method] AtHsfAla-silenced transgenic (NT) and wild-type (WT) A. thaliana seedlings were used as experimental materials to induce the formation of callus; the callus were cultured to single cells by suspension culture, subjected to cold stress, stained with DAPI, prepared into cell smears and observed under a fluorescence microscope. [ Result] Under cold stress, cell nucleus of wild-type A. thaliana displayed morphological changes, but no apoptotic bodies were found; apoptotic bodies were observed in AtHsfAla-silenced transgenic A. thaliana cells, and the cytoplasm was remarkably concentrated. [ Conclusion] Under cold stress, heat shock factor AtHsfAla exerted inhibitory effects on programmed cell death in A. thaliana, which was of great significance for clarifying the mechanism of stress responses in plants.展开更多
BACKGROUND Recurrent hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis.To date,the safety and efficacy of programmed cell death ligand 1(...BACKGROUND Recurrent hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis.To date,the safety and efficacy of programmed cell death ligand 1(PD-L1)inhibitors are still unknown.CASE SUMMARY A 59-year-old male was identified as having a tumor thrombus in the inferior vena cava 3 years after surgery.The patient underwent a second surgery and adjuvant chemotherapy.However,the level of alpha-fetoprotein was elevated after 2 mo,and lung metastases and mediastinal lymph node metastases were identified.The expression of PD-L1 in HCC and inferior vena cava tumor thrombus tissues was analyzed by immunohistochemistry.Then,the patient received atezolizumab immunotherapy.The level of alpha-fetoprotein dropped to normal,the mediastinal lymph node metastases decreased in size and the lung metastases disappeared after 3 mo of immunotherapy.The patient had no signs of recurrence at 21 mo of follow-up.A 60-year-old male underwent left hepatic tumor resection,inferior vena cava incision and thrombus removal,followed by regular chemotherapy.The patient developed lung and splenic metastases after surgery.Pembrolizumab was used for six courses,and the splenic metastasis shrank,after which splenectomy was performed.The patient continued to receive pembrolizumab for thirteen courses,and the lung metastases showed no progression.A 34-year-old male was diagnosed with liver cancer with inferior vena cava tumor thrombus.The patient underwent right hepatectomy and received tislelizumab for three courses.He is still receiving immunotherapy and in good condition.CONCLUSION Anti-PD-L1 therapy in HCC patients with inferior vena cava tumor thrombus and metastasis is associated with relatively good patient outcomes.展开更多
BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing ap...BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.展开更多
BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)...BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.展开更多
基金supported by grants from the National Natural Science Foundation of China[No.32060819]。
文摘Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.
文摘BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.
文摘BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.
基金Supported by CAMS Innovation Fund for Medical Science(CIFMS),No.CAMS-2016-I2M-3-025Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.
文摘BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 inhibitors.Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are unclear.AIM To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.METHODS The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English.We scanned the references of the selected literature to identify any further relevant studies.Six cases previously studied by us,including three that have not yet been published,were included in this review.RESULTS Thirty-one PD-1 inhibitor-related SC cases were evaluated.Median age of patients was 67 years(range,43–89),with a male to female ratio of 21:10.The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer.Agents that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent symptom.Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin G4.Biliary dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were noted.In 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells in the bile duct or peribiliary tract.Although corticosteroids were mainly used for PD inhibitor-related SC treatment,the response rate was 11.5%(3/26).CONCLUSION Some clinical and pathological features of PD-1 inhibitor-related SC were revealed.To establish diagnostic criteria for PD-1 inhibitor-related SC,more cases need to be evaluated.
基金supported by the National High Technology Research and Development Program of China (2011AA10A106)the National Natural Science Foundation of China (31171611, 31371697)+1 种基金the Technological Innovation and Over Planning Projects of Shaanxi Province, China (2014KTZB02-01-02, 2011KTZB02-01-01)the Projects Opening Up New Function of Precision Instrument of Northwest A&F University, China (dysb130210)
文摘Male sterility induced by a chemical hybridization agent (CHA) is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death (PCD) as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species (O2- and H202) and down-regulation of the activities of superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (POD). Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.
文摘Background: Programmed cell death protein 4(PDCD4) is a novel tumor suppressor protein involved in pro?grammed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical signiicance and prognostic value of PDCD4 in solid tumors.Methods: A systematic literature review was performed to retrieve publications with available clinical informa?tion and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta?analysis Of Observational Studies in Epidemiology group. Pooled odds ratios(ORs), hazard ratios(HRs), and 95% conidence intervals(CIs) for survival analysis were calculated. Publication bias was examined by Begg's and Egger's tests.Results: Clinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was signiicantly associated with the diferentiation status of head and neck cancer(OR 4.25, 95% CI 1.87–9.66) and digestive system cancer(OR 2.87, 95% CI 1.84–4.48). Down?regulation of PDCD4 was signiicantly associated with short overall survival of patients with head and neck(HR: 3.44, 95% CI 2.38–4.98), breast(HR: 1.86, 95% CI 1.36–2.54), digestive system(HR: 2.12, 95% CI 1.75–2.56), and urinary system cancers(HR: 3.16, 95% CI 1.06–9.41).Conclusions: The current evidence suggests that PDCD4 down?regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be conirmed by large?scale prospective studies.
基金supported by the Program of National Research Foundation of Korea through the Ministry of Education
文摘Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body.Programmed cell death(PCD)is a crucial component of several development and defense mechanisms.PCD is also important in terms of aging which avoids the accumulation of cellular damage by maintaining cell division.Depending on the execution of cell death and its role in destruction,PCD is categorized into several subtypes.The major different forms of PCD in animals are apoptosis,autophagy and necrosis,which can be distinct in morphological terms.More intense investigations of cell death have given close insight showing other important types of cellular destruction and their pivotal roles in treating disease conditions like cancer.Flavonoids have been acquired a great interest for disease therapies and chemoprevention through activation of several PCD mechanisms.The significant potential of natural flavonoids in the induction of distinct signaling cascades is being a massive approach for targeting uncontrolled cell growth.For these reasons,understanding PCD mechanisms is a promising approach for the interventions in treating cancer.Thus,it is intriguing that understanding the different forms of PCD mechanism induced by flavonoids with more accurate descriptions on the biochemical and cellular processes are gaining more significance in cancer research.Here,we provide a brief overview on the different types of PCD and aim to discuss the functional role of flavonoids in promoting different types of cell death as well as an extensive brief review on their mechanism of action has been highlighted.
基金the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service (No 2002-35301-12234 and 2004-35301-14620)Hatch Act and State of Iowa funds
文摘The maize (Zea mays) spikelet consists of two florets, each of which contains three developmentally synchronized anthers. Morphologically, the anthers in the upper and lower florets proceed through apparently similar developmental programs. To test for global differences in gene expression and to identify genes that are coordinately regulated during maize anther development, RNA samples isolated from upper and lower floret anthers at six developmental stages were hybridized to cDNA microarrays. Approximately 9% of the tested genes exhibited statistically significant differences in expression between anthers in the upper and lower florets. This finding indicates that several basic biological processes are differentially regulated between upper and lower floret anthers, including metabolism, protein synthesis and signal transduction. Genes that are coordinately regulated across anther development were identified via cluster analysis. Analysis of these results identified stage-specific, early in development, late in development and bi-phasic expression profiles. Quantitative RT-PCR analysis revealed that four genes whose homologs in other plant species are involved in programmed cell death are up-regulated just prior to the time the tapetum begins to visibly degenerate (i.e., the mid-microspore stage). This finding supports the hypothesis that developmentally normal tapetal degeneration occurs via programmed cell death.
基金Supported by the National Natural Science Foundation of China,No.81772134,No.81971891,and No.81571939.
文摘Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery.However,transplanted stem cells show a high death percentage,creating challenges to successful transplantation and prognosis.Thus,it is necessary to investigate the mechanisms underlying stem cell death,such as apoptotic cascade activation,excessive autophagy,inflammatory response,reactive oxygen species,excitotoxicity,and ischemia/hypoxia.Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success.Notably,a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate,highlighting the challenges in exploring mechanisms and therapeutic targets.In this review,we focus on programmed cell death in transplanted stem cells.We also discuss some promising strategies and challenges in promoting survival for further study.
基金supported by the National Natural Science Foundation of China(31271661, 30871477)the National Basic Research Program of China(2009CB118602)+1 种基金the Special Fund for Agro-Scientific Research in the Public Interest of China(201203100)the National Science and Technology Support Program of China(2012BAD04B05)
文摘Nitric oxide (NO) is a key signaling molecule in different physiological processes of plants, including programmed cell death (PCD). PCD of tillers plays an important role in surviving which are major components of grain yield. PCD was triggered in wheat leaves of main stem and tillers by NO content under different nitrogen treatments. In wheat, NO could be synthesized endogenously by nitrate reductase (NR). As an inducible enzyme, NR activity was closely related to substrate concentration. Therefore, different nitrogen levels would change NR activity and NO production. The objective of this study was to determine the effects of NR activity, NO production, and the correlation between them on different tillers growth, development, senescence, and kernel protein content under different nitrogen levels. Field-experiments were conducted in 2009-2011 growing seasons, using two wheat cultivars with different spike-types. Results showed that for main stem and primary tillers, NR activity and NO content reached high level at heading stage, while for secondary tiller, the level of NR activity was low, but NO content was high in the present research. The NO synthesis depending on NR activity in wheat leaves was significant in the early growing stage, but the NO synthesis weakened with the progress of growing period. NO was related to the senescence of wheat leaves, but PCD was more sensitive to marked changes of NO content than NO content itself. N application had marked influence on the aging process of primary tiller, while had little influence on that of main stem and secondary tiller. Moreover, N fertilizer application could increase spike rate and protein content of primary tiller by N fertilizer application.
基金supported by the National Natural Science Foundation of China(30070363)the Foundation for Doctorate Research of Ministry of Education,China(200005041).
文摘Morphological variations of the nucleus in starchy endosperm cell were observed by theelectron-transmisson microscope during endosperm development in rice. Along with thedevelopment of the starchy endosperm, the nuclei of the cells showed chromatin condensation,the typical feature of programmed cell death (PCD). The nuclei also showed nucleusdeformation, disruption of nuclear envelope, nucleoplasm leaking into the cytoplasm andnucleus disintegration resulting in nuclear residue formation. From the nucleus deformationto the nucleus disintegration, the morphological changes of the nucleus were orderlyprogressive. This indicated that the cell death of starchy endosperm in rice wasprogrammed cell death. Evans Blue staining observation showed that the cell death wasinitially detected in the central part of starchy endosperm in rice, then expandedoutward. The activities of superoxide dismutase (SOD) and catalase (CAT) in rice starchyendosperm both descended continuously as development progressed. The analysis of DNA ofrice starchy endosperm did not show the presence of DNA laddering. The above resultsshowed that the cell death of starchy endosperm in rice was a special form of PCD.
基金Supported by the Doctoral Start-up Foundation of Liaoning Province,No.2021-BS-114.
文摘BACKGROUND Inflammatory bowel disease(IBD)is caused by an abnormal immune response.Programmed cell death 1(PD-1)is an immunostimulatory molecule,which interacts with PD ligand(PD-L1)playing a prime important role among autoimmune diseases.Bifidobacterium infantis(B.infantis)can promote the differentiation of CD(cluster of differentiation)4^(+)T cells into regulatory T cells(Tregs).Tregs participate in the development of IBD and may be related to disease activity.B.infantis amplify the expression level of PD-1,PD-L1 and Tregs’nuclear transcription factor forkhead box protein 3(Foxp3).But the mechanism of B.infantis on PD-1/PD-L1 signaling remains unclear.AIM To explore the mechanism of B.infantis regulating the immune response in IBD.METHODS Forty-eight-week-old BALB/c mice were randomly divided into five groups:The control group,dextran sulphate sodium(DSS)model group,DSS+B.infantis group,DSS+B.infantis+anti-PD-L1 group,and DSS+anti-PD-L1 group.The control group mice were given drinking water freely,the other four groups were given drinking water containing 5%DSS freely.The control group,DSS model group,and DSS+anti-PD-L1 group were given normal saline(NS)400μL daily by gastric lavage,and the DSS+B.infantis group and DSS+B.infantis+anti-PDL1 group were given NS and 1×109 colony-forming unit of B.infantis daily by gastric lavage.The DSS+B.infantis+anti-PD-L1 group and DSS+anti-PD-L1 group were given 200μg of PD-L1 blocker intraperitoneally at days 0,3,5,and 7;the control group,DSS+anti-PD-L1 group,and DSS+B.infantis group were given an intraperitoneal injection of an equal volume of phosphate buffered saline(PBS).Changes in PD-L1,PD-1,Foxp3,interleukin(IL)-10,and transforming growth factorβ(TGF-β)1 protein and gene expression were observed.Flow cytometry was used to observe changes in CD4^(+),CD25^(+),Foxp3^(+)cell numbers in the blood and spleen.RESULTS Compared to the control group,the expression of PD-1,Foxp3,IL-10,and TGF-β1 was significantly decreased in the intestinal tract of the DSS mice(P<0.05).Compared to the control group,the proportion of CD4^(+),CD25^(+),Foxp3^(+)cells in spleen and blood of DSS group was visibly katabatic(P<0.05).B.infantis upgraded the express of PD-L1,PD-1,Foxp3,IL-10,and TGF-β1(P<0.05)and increased the proportion of CD4^(+),CD25^(+),Foxp3^(+)cells both in spleen and blood(P<0.05).After blocking PD-L1,the increase in Foxp3,IL-10,and TGF-β1 protein and gene by B.infantis was inhibited(P<0.05),and the proliferation of CD4^(+),CD25^(+),Foxp3^(+)cells in the spleen and blood was also inhibited(P<0.05).After blocking PD-L1,the messenger ribonucleic acid and protein expression of PD-1 were invariant.CONCLUSION It is potential that B.infantis boost the proliferation of CD4^(+),CD25^(+),Foxp3^(+)T cells in both spleen and blood,as well as the expression of Foxp3 in the intestinal tract by activating the PD-1/PD-L1 pathway.
文摘BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy.CASE SUMMARY Both case 1 and case 2 presented with common symptoms of fatigue,nausea,and vomiting.However,case 3 showed rare acute severe symptoms such as hoarse voice,bucking,and difficulty in breathing even when sitting.Following two cycles of immunotherapy in case 3,the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis.These symptoms were relieved after 10 d of steroid treatment.Case 3 was the first patient with these specific symptoms,which provided a new insight into the diagnosis of hypophysitis.In addition,we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy.Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment.Cases 1 and 2 were treated with the low-dose hormone,and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment.CONCLUSION The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.
文摘This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.
基金Supported by National Natural Science Foundation of China(31260061,31060039)Key Laboratory of Special Biological Resource Development and Utilization of Universities in Yunnan Province(GXZD201601)+1 种基金Key Discipline Construction Project of Kunming UniversityNational College Students Innovation Project of China
文摘[Objective] This study aimed to investigate the effects of heat shock factor AtHsfAla on programmed cell death in Arabidopsis thaliana under cold stress. [ Method] AtHsfAla-silenced transgenic (NT) and wild-type (WT) A. thaliana seedlings were used as experimental materials to induce the formation of callus; the callus were cultured to single cells by suspension culture, subjected to cold stress, stained with DAPI, prepared into cell smears and observed under a fluorescence microscope. [ Result] Under cold stress, cell nucleus of wild-type A. thaliana displayed morphological changes, but no apoptotic bodies were found; apoptotic bodies were observed in AtHsfAla-silenced transgenic A. thaliana cells, and the cytoplasm was remarkably concentrated. [ Conclusion] Under cold stress, heat shock factor AtHsfAla exerted inhibitory effects on programmed cell death in A. thaliana, which was of great significance for clarifying the mechanism of stress responses in plants.
基金Supported by The Special Research Foundation of the National Nature Science Foundation of China,No.81972262 and No.81972255The Guangdong Basic and Applied Basic Research Foundation,No.2018A030313645,No.2020A1515010117 and No.2016A030313840+4 种基金Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology,No.[2013]163the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes,No.KLB09001Guangdong Science and Technology Department,No.2015B050501004Guangdong Science and Technology Department,No.2017B030314026Sun Yat-sen University Clinical Research 5010 Program,No.2018008.
文摘BACKGROUND Recurrent hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis.To date,the safety and efficacy of programmed cell death ligand 1(PD-L1)inhibitors are still unknown.CASE SUMMARY A 59-year-old male was identified as having a tumor thrombus in the inferior vena cava 3 years after surgery.The patient underwent a second surgery and adjuvant chemotherapy.However,the level of alpha-fetoprotein was elevated after 2 mo,and lung metastases and mediastinal lymph node metastases were identified.The expression of PD-L1 in HCC and inferior vena cava tumor thrombus tissues was analyzed by immunohistochemistry.Then,the patient received atezolizumab immunotherapy.The level of alpha-fetoprotein dropped to normal,the mediastinal lymph node metastases decreased in size and the lung metastases disappeared after 3 mo of immunotherapy.The patient had no signs of recurrence at 21 mo of follow-up.A 60-year-old male underwent left hepatic tumor resection,inferior vena cava incision and thrombus removal,followed by regular chemotherapy.The patient developed lung and splenic metastases after surgery.Pembrolizumab was used for six courses,and the splenic metastasis shrank,after which splenectomy was performed.The patient continued to receive pembrolizumab for thirteen courses,and the lung metastases showed no progression.A 34-year-old male was diagnosed with liver cancer with inferior vena cava tumor thrombus.The patient underwent right hepatectomy and received tislelizumab for three courses.He is still receiving immunotherapy and in good condition.CONCLUSION Anti-PD-L1 therapy in HCC patients with inferior vena cava tumor thrombus and metastasis is associated with relatively good patient outcomes.
文摘BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.
文摘BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.