BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic a...BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.展开更多
BACKGROUND:Heatstroke is the most hazardous heat-related illness and has a high fatality rate.We investigated whether glutamine supplementation could have a protective effect on heatstroke rats.METHODS:Twenty-five 12-...BACKGROUND:Heatstroke is the most hazardous heat-related illness and has a high fatality rate.We investigated whether glutamine supplementation could have a protective effect on heatstroke rats.METHODS:Twenty-five 12-week-old male Wistar rats(weight 305±16 g)were randomly divided into a control group(n=5),heatstroke(HS)group(n=10),and heatstroke+glutamine(HSG)group(n=10).Seven days before heat exposure,glutamine(0.4 g/[kg·d])was administered to the rats in the HSG group by gavage every day.Three hours after heat exposure,serum samples were collected to detect white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines in the rats.The small intestine tissue was stained to analyze pathological structural changes and apoptosis.Finally,immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70(HSP70).Multiple comparisons were analyzed by using one-way analysis of variance,and the Bonferroni test was conducted for the post hoc comparisons.RESULTS:After heat exposure,the core temperature of the HS group(40.65±0.31°C)was higher than the criterion of heatstroke,whereas the core temperature of the HSG group(39.45±0.14°C)was lower than the criterion.Glutamine supplementation restored the increased white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines that were induced by heatstroke to normal levels.The intestinal mucosa was injured,and the structure of tight junctions was damaged in the HS group;however,the structure of intestinal mucosal epithelial cells was stable in the HSG group.Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression.CONCLUSION:Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.展开更多
Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight g...Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight gain in growing pigs widespread.An accurate method for detecting L.intracellularis is particularly important for preventing and controlling PPE.Heat shock protein 60(Hsp60)is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms.Thus,the purpose of the current investigation was to produce a novel L.intracellularis Hsp60 monoclonal antibody(mAb)useful for immunodiagnostics.Three hybridomas secreted anti-Hsp60 termed 3E5,4E2,and 9G6 were generated,and the titers of ascitic fluids of 3E5,4E2,9G6 were 1:1024000,1:2048000 and 1:2048000,respectively.The Western blotting analysis demonstrated that recombinant Hsp60(rHsp60)was recognized by mAbs 3E5,4E2 and 9G6.Subsequently,analyses of specificity showed all the mAbs were highly specific to L.intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs,such as Escherichia coli,Salmonella Choleraesuis,Salmonella Typhimurium,and Brachyspira hyodysenteriae.Furthermore,the mAbs were useful for detecting L.intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs.Our research will provide a foundation for the development of immunological diagnostic tests.展开更多
The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributo rs to the failure of sensory and motor functional recovery following spinal cord injury.Heat shock transcriptio...The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributo rs to the failure of sensory and motor functional recovery following spinal cord injury.Heat shock transcription factor 1(HSF1),a master regulator of the heat shock response,plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system.However,the underlying mechanism has not been fully elucidated.In the present study,we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1(gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury.gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation.gHSF1 ove rexpression in gecko primary neuro ns significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3,and fa cilitated neuro nal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways.Furthermore,gHSF1 efficiently inhibited the macrophagemediated inflammatory response by inactivating 1kappa B-alpha/NF-kappaB signaling.Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation,and provide new avenues of investigation for promoting spinal co rd injury repair in mammals.展开更多
AIM:To evaluate the effectiveness of knock-down of heat shock protein 47(HSP47)on conjunctival bleb scarring in a rat model and its possible mechanism.METHODS:Male Sprague–Dawley rats were used for glaucoma filtratio...AIM:To evaluate the effectiveness of knock-down of heat shock protein 47(HSP47)on conjunctival bleb scarring in a rat model and its possible mechanism.METHODS:Male Sprague–Dawley rats were used for glaucoma filtration surgery(GFS)and were treated with either phosphate buffered solution,shControl,mitomycin C,or sh-HSP47 using a microsyringe immediately after GFS.The morphology of filtering blebs was observed postoperatively.The levels of HSP47 were analyzed at 2,5,8,and 11d after GFS via real‑time quantitative polymerase chain reaction(PCR)and Western blot.The silencing effect of HSP47,the expression of collagen I and III,and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS.The protein levels of transforming growth factor-β1(TGF-β1),phospho-Smad2(pSmad2),phospho-Smad3(p-Smad3),and phospho-p38(p-p38)were also analyzed using Western blot.RESULTS:Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention.The levels of HSP47 were increased significantly at 5,8,and 11d postoperatively compared to the control group(P<0.05,P<0.01,and P<0.001).The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection(P<0.01).Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47(P<0.01).Moreover,the protein levels of TGF-β1,p-Smad2/3,and p-p38 were dramatically inhibited after treatment with sh-HSP47(P<0.01).CONCLUSION:The inhibitory effects of HSP47 knockdown on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.展开更多
BACKGROUND We previously demonstrated that heat shock factor protein 4(HSF4)facilitates colorectal cancer(CRC)progression.DNA methylation,a major modifier of gene expression and stability,is involved in CRC developmen...BACKGROUND We previously demonstrated that heat shock factor protein 4(HSF4)facilitates colorectal cancer(CRC)progression.DNA methylation,a major modifier of gene expression and stability,is involved in CRC development and outcome.AIM To investigate the correlation between HSF4 methylation and CRC risk,and to uncover the underlying molecular mechanisms.METHODS Differences in β values of HSF4 methylation loci in multiple malignancies and their correlation with HSF4 mRNA expression were analyzed based on Shiny Methylation Analysis Resource Tool.HSF4 methylation-related genes were identified by LinkedOmics in CRC,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.Protein-protein interaction network of HSF4 methylation-related genes was constructed by String database and MCODE algorithm.RESULTS A total of 19 CpG methylation loci were identified in HSF4,and their β values were significantly increased in CRC tissues and exhibited a positive correlation with HSF4 mRNA expression.Unfortunately,the prognostic and diagnostic performance of these CpG loci in CRC patients was mediocre.In CRC,there were 1694 HSF4 methylation-related genes;1468 of which displayed positive and 226 negative associations,and they were involved in regulating phenotypes such as immune,inflammatory,and metabolic reprogramming.EGFR,RELA,STAT3,FCGR3A,POLR2K,and AXIN1 are hub genes among the HSF4 methylation-related genes.CONCLUSION HSF4 is highly methylated in CRC,but there is no significant correlation between it and the prognosis and diagnosis of CRC.HSF4 methylation may serve as one of the ways in which HSF4 mediates the CRC process.展开更多
BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that protect cells against cellular stresses or injury.However,it has been increasingly recognized that they also play crucial roles in regulating fundament...BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that protect cells against cellular stresses or injury.However,it has been increasingly recognized that they also play crucial roles in regulating fundamental cellular processes.HSP20 has been implicated in cell proliferation,but conflicting studies have shown that it can either promote or suppress proliferation.The underlying mechanisms by which HSP20 regulates cell proliferation and pluripotency remain unexplored.While the effect of HSP20 on cell proliferation has been recognized,its role in inducing pluripotency in human-induced pluripotent stem cells(iPSCs)has not been addressed.AIM To evaluate the efficacy of HSP20 overexpression in human iPSCs and evaluate the ability to promote cell proliferation.The purpose of this study was to investigate whether overexpression of HSP20 in iPSCs can increase pluripotency and regeneration.METHODS We used iPSCs,which retain their potential for cell proliferation.HSP20 overexpression effectively enhanced cell proliferation and pluripotency.Overexpression of HSP20 in iPSCs was characterized by immunocytochemistry staining and realtime polymerase chain reaction.We also used cell culture,cell counting,western blotting,and flow cytometry analyses to validate HSP20 overexpression and its mechanism.RESULTS This study demonstrated that overexpression of HSP20 can increase the pluripotency in iPSCs.Furthermore,by overexpressing HSP20 in iPSCs,we showed that HSP20 upregulated proliferation markers,induced pluripotent genes,and drove cell proliferation in a sirtuin 1(SIRT1)-dependent manner.These data have practical applications in the field of stem cell-based therapies where the mass expansion of cells is needed to generate large quantities of stem cell-derived cells for transplantation purposes.CONCLUSION We found that the overexpression of HSP20 enhanced the proliferation of iPSCs in a SIRT1-dependent manner.Herein,we established the distinct crosstalk between HSP20 and SIRT1 in regulating cell proliferation and pluripotency.Our study provides novel insights into the mechanisms controlling cell proliferation that can potentially be exploited to improve the expansion and pluripotency of human iPSCs for cell transplantation therapies.These results suggest that iPSCs overexpressing HSP20 exert regenerative and proliferative effects and may have the potential to improve clinical outcomes.展开更多
The objective of the paper was to detect HSP72 expression and HSP72 gene sequence in heat shocked mouse preimplantation embryos and the effects of different thermo conditions on hatching rates of embryos. The mouse bl...The objective of the paper was to detect HSP72 expression and HSP72 gene sequence in heat shocked mouse preimplantation embryos and the effects of different thermo conditions on hatching rates of embryos. The mouse blastocysts cultured in vitro were heat treated at 40℃ and 38℃ for 1 h, 2 h and 3 h and then recovered at 37℃ for 3 h, 2 h and 1 h, respectively, to detect their HSP72 gene expression by using RT-PCR after the total RNA extraction. The hatching rate of the blastocysts for different treated groups was recorded and the expression of HSP72 in the blastocysts was determined by Western blot. The results showed that all the groups of blastocysts, including the control, had the expression of HSP72 gene. The expression of HSP72 protein had the highest level in the embryos stressed at 38℃ for 2 h, and it was signifi cantly higher than that in the control group. The expression of HSP72 in the groups of blastocysts treated at 40℃ was not signifi cantly different from that in the control group. The embryos with induction of mild heat shock at 38℃ for 2 h, then subjected to heat shock at 40℃ for 2 h, had a signifi cant higher(P<0.05) hatching rate of 54.74% compared to 47.85% in the embryos treated directly at 40℃ for 2 h. The above results indicated that the mouse blastocysts were sensitive to heat shock and a mild heat shock induced HSP72 gene expression. Induction of HSP72 expression with mild heat shock helped embryos to tolerate more severe heat shocks.展开更多
Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) is the most destructive invasive pests in agricultural production and has a high tolerance to heat. Heat shock proteins play an essential role in life activities suc...Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) is the most destructive invasive pests in agricultural production and has a high tolerance to heat. Heat shock proteins play an essential role in life activities such as growth and development, reproduction and diapause of B. tabaci. At the same time, they are also crucial in resisting adverse environments and in adaptive evolution. The expression of heat shock protein in B. tabaci is not only related to temperature, but also to the tolerance of the environment. After receiving external stimuli, the expression level can be increased or decreased to maintain the stability of cells in vivo. This paper reviews the classification, biological characteristics, biological functions, and research status of HSPs in recent years. This mini-review will provide helpful information related to the use of heat shock proteins to study the occurrence and damage of B. tabaci. This has important theoretical and practical significance for revealing Hsps in explaining the population expansion mechanism of B. tabaci invasion and predicting population dynamics.展开更多
Thermal adaptation plays a fundamental role in shaping the distribution and abundance of insects,and heat shock proteins(Hsps)play important roles in the temperature adaptation of various organisms.To better understan...Thermal adaptation plays a fundamental role in shaping the distribution and abundance of insects,and heat shock proteins(Hsps)play important roles in the temperature adaptation of various organisms.To better understand the temperature tolerance of the indigenous ZHJ2-biotype of whitefly Bemisia tabaci species complex,we obtained complete cDNA sequences for hsp90,hsp70,and hsp20 and analyzed their expression profiles under different high temperature treatments by real-time quantitative polymerase chain reaction.The high temperature tolerance of B.tabaci ZHJ2-biotype was determined by survival rate after exposure to different high temperatures for 1 h.The results showed that after 41°C heat-shock treatment for 1 h,the survival rates of ZHJ2 adults declined significantly and the estimated temperature required to cause 50% mortality(LT50)is 42.85°C for 1 h.Temperatures for onset(Ton)or maximal(Tmax)induction of hsps expression in B.tabaci ZHJ2-biotype were 35 and 39°C(or 41°C).Compared with previous studies,indigenous ZHJ2-biotype exhibits lower heat temperature stress tolerance and Ton(or Tmax)than the invasive B-biotype.展开更多
AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal me...AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSION The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.展开更多
Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most mal...Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.展开更多
Currently, insecticides are considered as the primary approach for controlling western flower thrips, Frankliniella occidentalis(Pergande)(Thysanoptera: Thripidae). However, the heavy use of insecticides resulted in h...Currently, insecticides are considered as the primary approach for controlling western flower thrips, Frankliniella occidentalis(Pergande)(Thysanoptera: Thripidae). However, the heavy use of insecticides resulted in high insect resistance and serious environmental pollution. Given its characteristics of ease of operation and environmental friendliness, insect control using high temperature is receiving considerable renewed research interest. However, although the combination of insecticides and high temperature to control F. occidentalis has been studied before, few studies have focused on the short-term effect of such treatment. In a laboratory study, F. occidentalis adults and second-instar nymphs were exposed to 45°C for 2 h. Then, their susceptibility to acetamiprid, spinosad, methomyl, and beta-cypermethrin was tested after different periods of recovery time(2–36 h). Additionally, the specific activity of three detoxification enzymes(esterase, glutathione S-transferase, and cytochrome p450(CYP) monooxygenase) of the treated insects was determined. The results indicated that the fluctuation of susceptibility to insecticides and detoxification enzyme activity during F. occidentalis recovery from heat shock are related. Furthermore, several recovery time points(2, 30, and 36 h) of significant susceptibility to four tested insecticides compared with the control were found during the treatment of adults that were heat-shocked. Recovery time points of higher susceptibility compared with the control depended on different insecticides during the second-instar nymph recovery from heat shock. Interestingly, the fluctuation of CYP monooxygenase activity exhibited a trend that was similar to the fluctuation of susceptibility to insecticides(especially spinosad) during the recovery from heat shock of adults. In addition, the glutathione S-transferase and CYP monooxygenase activity trend was similar to the trend of susceptibility to spinosad during the recovery from heat shock of second-instar nymphs. Our results provide a new approach for controlling F. occidentalis using the combined heat shock and insecticide. This effectively enhances the control efficiency of heat shock and significantly reduces the application of insecticides.展开更多
In vitro gynogenesis is an important tool used in haploid or homozygous double-haploid plant breeding.However,because of low repeatability,embryoid induction rate and quality,the molecular mechanisms remain poorly und...In vitro gynogenesis is an important tool used in haploid or homozygous double-haploid plant breeding.However,because of low repeatability,embryoid induction rate and quality,the molecular mechanisms remain poorly understood.Heat shock treatment can promote the transformation of the gametophytic pathway into the sporophyte pathway,which induces the occurrence of haploid.In this study,unfertilized ovaries were heat shocked for 0 h(A0)before flowering and for 0 h(A1),4 h(A3),8 h(A5),12 h(A7),and 24 h(A8),respectively,at 37℃at the first day of the flowering stage.The ovule enlargement rate was increased from 0%at 25℃to 96.8%at 37℃(24 h treatment).Thus,we aimed to investigate the gene expression patterns in unfertilized ovules of watermelon after different periods of heat shock by using RNA-Seq technology.The results showed that compared with A3,A5,A7,and A8,the biosynthesis of amino acid,glycine,serine and threonine metabolic pathways in A1 has changed significantly.This indicated that heat shock treatment affected the synthesis and transformation of amino acids during ovule expansion.The transcriptome data suggested gene expressions of ovule growth were significantly changed by heat-specific influences.The results provide new information on the complex relationship between in vitro gynogenesis and temperature.This provides a basis for further study of the mechanism of heat shock affecting the expansion of watermelon ovule.展开更多
Objective The neuroprotective function of heat shock protein A5(HSPA5)in ischemic stroke has been confirmed.This study aimed to investigate the effects of early aerobic exercise on neurological function recovery from ...Objective The neuroprotective function of heat shock protein A5(HSPA5)in ischemic stroke has been confirmed.This study aimed to investigate the effects of early aerobic exercise on neurological function recovery from cerebral ischemia/reperfusion and to determine whether these effects are associated with the expression level of HSPA5 in the ischemic penumbra.Methods A total of 72 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group[middle cerebral artery occlusion(MCAO)-Ex,n=18],ischemia and sedentary group(MCAO-St,n=18),sham-surgery and exercise group(Sham-Ex,n=18),or sham-surgery and sedentary group(Sham-St,n=18).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 min,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 min once a day for 5 consecutive days.After reperfusion,the motor function of the rats was scored by the Bederson neurological function test,balance beam test,and screen test.Nissl staining was conducted to assess morphological and structural change of nerve cells in the ischemic penumbra.The reverse transcription-quantitative polymerase chain reaction was applied to detect the mRNA expression of HSPA5.Western blot analysis was conducted to determine the protein expression of HSPA5.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was carried out in the ischemic penumbra after MCAO.Results Rats receiving early treadmill exercise had lower Bederson neurological function,balance beam,and screen test scores on the 3rd,7th,and 14th days after MCAO;in addition,more neurons survived in the ischemic penumbra after MCAO,and higher mRNA and protein expression of HSPA5 and fewer TUNEL-positive stained cells were observed.Conclusion Our study demonstrated that early aerobic exercise can improve neurological function recovery after ischemia/reperfusion.Furthermore,the increased level of HSPA5 in the ischemic penumbra might be one of the mechanisms of enhanced neurological function recovery.展开更多
The small heat shock protein(sHSP) chaperones are required for protecting cellular proteins from damage,as well as refolding denatured proteins.This study was carried out to investigate the temporal-spatial expression...The small heat shock protein(sHSP) chaperones are required for protecting cellular proteins from damage,as well as refolding denatured proteins.This study was carried out to investigate the temporal-spatial expression patterns of two sHSP genes in rice.These two genes,named as Os16.9A and Os16.9B,are reverse duplicated genes that adjacently located on chromosome 1 and probably share the same or overlapping DNA region as a promoter.The interval sequence between the start codons of the two genes which are transcribed in opposite directions is only about 2.6 kb.Semi-quantitative RT-PCR was carried out to detect the expression of the two genes under normal growth conditions and different stress conditions.The expression patterns of the two genes were in detail investigated by using β-glucuronidase(GUS) reporter gene fusion system.Results showed that heat shock stress can induce high level expression of the two genes.Under normal growth conditions,Os16.9A and Os16.9B expressed in vegetative organs and young panicles.GUS staining combined with cytological observations showed that the two genes expressed mainly in the vascular tissues of roots,stems and young panicles,implicating that Os16.9A and Os16.9B play important roles not only for heat shock response,but also for normal development in rice.展开更多
Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cel...Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.展开更多
Heat shock proteins 10/60(hsp10/60)are a family of conserved ubiquitously expressed heat shock proteins which are produced by cells in response to exposure to stressful conditions.Besides the chaperone and housekeepin...Heat shock proteins 10/60(hsp10/60)are a family of conserved ubiquitously expressed heat shock proteins which are produced by cells in response to exposure to stressful conditions.Besides the chaperone and housekeeping functions,they are also known to be involved in immune response during bacterial infection.In this study,we identified and annotated 10 hsp10/60 genes through bioinformatic analysis in Japanese flounder(Paralichthys olivaceus).Among them one member of hsp10(hspe)family and nine members of hsp60(hspd)family were identified.Phylogenetic and selection pressure analysis showed that the hsp10/60 genes were evolutionarily constrained and their function was conserved.Besides,hsp10/60 genes were involved in different embryonic and larval stages and acted as the sentinel role in an unchallenged organism.In addition,we also observed the expression patterns of hsp10/60 genes after Edwardsiella tarda infection,for the first time in Japanese flounder.Eight out of 10 genes were differentially expressed after bacterial challenges,the significantly regulated expressions of flounder hsp10/60 genes after bacterial infections suggested their involvement in immune response in flounder.Our results provide valuable information for clarifying the evolutionary relationship,and early insights of the immune functions of hsp10/60 genes in Japanese flounder.展开更多
Anadara broughtonii is one of the main commercially important species of shellfish in northern China.A.broughtonii lives in relatively stable subtidal zone where the clam could respond to environmental changes with mi...Anadara broughtonii is one of the main commercially important species of shellfish in northern China.A.broughtonii lives in relatively stable subtidal zone where the clam could respond to environmental changes with minimum energy.Therefore,slight fluctuations in water environment may have a great impact on physiological processes such as feeding and metabolism.Large-scale mortality often occurs during the intermediate rearing processes,and high temperatures in summer are considered the leading cause of mortality.To understand the physiological and molecular response patterns of A.broughtonii at high temperatures and to estimate the appropriate metabolism temperature for A.broughtonii,the effects of temperature on the respiratory metabolism and food intake at different growth stages were studied.The response patterns of heat shock protein genes to heat stress and post-stress recovery were also explored.Results show that the temperature and growth stage of A.broughtonii were two important factors affecting metabolism and feeding.The optimum temperature for feeding and physiological activities in each shell-length group was 24℃.The temperature at which the peak metabolic rate occurred in each shell-length group increased with the increase in shell length.With the increase in heat stress,the expression of three heat shock protein genes(Abhsp60,Abhsp70,and Abhsp90)in the tissues of two size groups of A.broughtonii increased significantly when temperature was above 24℃and reached a peak at 30℃.After heat shock at 30℃for 2 h,the expression of the three heat shock protein genes rapidly increased,peaked at 2 h after the heat shock,and then gradually decreased to the level of the control group at 48 h after the heat shock.The three heat shock protein genes respond rapidly to heat stress and can be used as indicators to the cellular stress response in A.broughtonii under an environmental stress.展开更多
Near-infrared(NIR)-light-triggered photothermal therapy(PTT)is a promising treatment for breast cancer.However,its therapeutic efficiency is often compromised due to the heatinduced up-regulation of heat shock protein...Near-infrared(NIR)-light-triggered photothermal therapy(PTT)is a promising treatment for breast cancer.However,its therapeutic efficiency is often compromised due to the heatinduced up-regulation of heat shock proteins,which confer photothermal resistance.To solve this urgent problem,PEGylated two-dimensional boron nanosheets(B-PEG)-which allow both multimodal imaging and photothermal conversion-were loaded with gambogic acid(GA),which can inhibit heat shock protein 90(Hsp90).Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment.It could be used to administer mild PTT as well as chemotherapy for breast cancer,provide improved anti-tumor effects,and reduce the toxicity of PTT,all while inhibiting breast cancer growth.This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.展开更多
文摘BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.
基金supported by the Research Foundation of Hwa Mei Hospital,University of Chinese Academy of Sciences,China(2020HMKY22)Zhejiang Medicine and Health Science and Technology Project(2021KY1015)Ningbo Key Support Medical Discipline(2022-F16)。
文摘BACKGROUND:Heatstroke is the most hazardous heat-related illness and has a high fatality rate.We investigated whether glutamine supplementation could have a protective effect on heatstroke rats.METHODS:Twenty-five 12-week-old male Wistar rats(weight 305±16 g)were randomly divided into a control group(n=5),heatstroke(HS)group(n=10),and heatstroke+glutamine(HSG)group(n=10).Seven days before heat exposure,glutamine(0.4 g/[kg·d])was administered to the rats in the HSG group by gavage every day.Three hours after heat exposure,serum samples were collected to detect white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines in the rats.The small intestine tissue was stained to analyze pathological structural changes and apoptosis.Finally,immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70(HSP70).Multiple comparisons were analyzed by using one-way analysis of variance,and the Bonferroni test was conducted for the post hoc comparisons.RESULTS:After heat exposure,the core temperature of the HS group(40.65±0.31°C)was higher than the criterion of heatstroke,whereas the core temperature of the HSG group(39.45±0.14°C)was lower than the criterion.Glutamine supplementation restored the increased white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines that were induced by heatstroke to normal levels.The intestinal mucosa was injured,and the structure of tight junctions was damaged in the HS group;however,the structure of intestinal mucosal epithelial cells was stable in the HSG group.Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression.CONCLUSION:Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.
基金supported by the National Key Research and Development Program of China(2021YFD1800400)the National Natural Science Foundation of China(31872480)+1 种基金the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(19)2020)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(PAPD).
文摘Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight gain in growing pigs widespread.An accurate method for detecting L.intracellularis is particularly important for preventing and controlling PPE.Heat shock protein 60(Hsp60)is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms.Thus,the purpose of the current investigation was to produce a novel L.intracellularis Hsp60 monoclonal antibody(mAb)useful for immunodiagnostics.Three hybridomas secreted anti-Hsp60 termed 3E5,4E2,and 9G6 were generated,and the titers of ascitic fluids of 3E5,4E2,9G6 were 1:1024000,1:2048000 and 1:2048000,respectively.The Western blotting analysis demonstrated that recombinant Hsp60(rHsp60)was recognized by mAbs 3E5,4E2 and 9G6.Subsequently,analyses of specificity showed all the mAbs were highly specific to L.intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs,such as Escherichia coli,Salmonella Choleraesuis,Salmonella Typhimurium,and Brachyspira hyodysenteriae.Furthermore,the mAbs were useful for detecting L.intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs.Our research will provide a foundation for the development of immunological diagnostic tests.
基金supported by the National Natural Science Foundation of China,No.31871211 (to YJunW)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributo rs to the failure of sensory and motor functional recovery following spinal cord injury.Heat shock transcription factor 1(HSF1),a master regulator of the heat shock response,plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system.However,the underlying mechanism has not been fully elucidated.In the present study,we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1(gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury.gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation.gHSF1 ove rexpression in gecko primary neuro ns significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3,and fa cilitated neuro nal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways.Furthermore,gHSF1 efficiently inhibited the macrophagemediated inflammatory response by inactivating 1kappa B-alpha/NF-kappaB signaling.Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation,and provide new avenues of investigation for promoting spinal co rd injury repair in mammals.
基金Supported by the National Natural Science Foundation of China(No.81500719)Shaanxi Science and Technology Project(No.2022SF-434)Xi’an Science and Technology Project(No.21YXYJ0044).
文摘AIM:To evaluate the effectiveness of knock-down of heat shock protein 47(HSP47)on conjunctival bleb scarring in a rat model and its possible mechanism.METHODS:Male Sprague–Dawley rats were used for glaucoma filtration surgery(GFS)and were treated with either phosphate buffered solution,shControl,mitomycin C,or sh-HSP47 using a microsyringe immediately after GFS.The morphology of filtering blebs was observed postoperatively.The levels of HSP47 were analyzed at 2,5,8,and 11d after GFS via real‑time quantitative polymerase chain reaction(PCR)and Western blot.The silencing effect of HSP47,the expression of collagen I and III,and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS.The protein levels of transforming growth factor-β1(TGF-β1),phospho-Smad2(pSmad2),phospho-Smad3(p-Smad3),and phospho-p38(p-p38)were also analyzed using Western blot.RESULTS:Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention.The levels of HSP47 were increased significantly at 5,8,and 11d postoperatively compared to the control group(P<0.05,P<0.01,and P<0.001).The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection(P<0.01).Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47(P<0.01).Moreover,the protein levels of TGF-β1,p-Smad2/3,and p-p38 were dramatically inhibited after treatment with sh-HSP47(P<0.01).CONCLUSION:The inhibitory effects of HSP47 knockdown on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.
基金Supported by National Natural Science Foundation of China,No.82260601Joint Foundation of Kunming Medical University and Yunnan Provincial Science and Technology Department,No.202201AY070001-256+1 种基金Grant for Clinical Medical Center of Yunnan Provincial Health Commission,No.2021LCZXXF-XH03Young Academic Talents Cultivation Foundation of Yunnan Province,No.202205AC160070.
文摘BACKGROUND We previously demonstrated that heat shock factor protein 4(HSF4)facilitates colorectal cancer(CRC)progression.DNA methylation,a major modifier of gene expression and stability,is involved in CRC development and outcome.AIM To investigate the correlation between HSF4 methylation and CRC risk,and to uncover the underlying molecular mechanisms.METHODS Differences in β values of HSF4 methylation loci in multiple malignancies and their correlation with HSF4 mRNA expression were analyzed based on Shiny Methylation Analysis Resource Tool.HSF4 methylation-related genes were identified by LinkedOmics in CRC,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.Protein-protein interaction network of HSF4 methylation-related genes was constructed by String database and MCODE algorithm.RESULTS A total of 19 CpG methylation loci were identified in HSF4,and their β values were significantly increased in CRC tissues and exhibited a positive correlation with HSF4 mRNA expression.Unfortunately,the prognostic and diagnostic performance of these CpG loci in CRC patients was mediocre.In CRC,there were 1694 HSF4 methylation-related genes;1468 of which displayed positive and 226 negative associations,and they were involved in regulating phenotypes such as immune,inflammatory,and metabolic reprogramming.EGFR,RELA,STAT3,FCGR3A,POLR2K,and AXIN1 are hub genes among the HSF4 methylation-related genes.CONCLUSION HSF4 is highly methylated in CRC,but there is no significant correlation between it and the prognosis and diagnosis of CRC.HSF4 methylation may serve as one of the ways in which HSF4 mediates the CRC process.
文摘BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that protect cells against cellular stresses or injury.However,it has been increasingly recognized that they also play crucial roles in regulating fundamental cellular processes.HSP20 has been implicated in cell proliferation,but conflicting studies have shown that it can either promote or suppress proliferation.The underlying mechanisms by which HSP20 regulates cell proliferation and pluripotency remain unexplored.While the effect of HSP20 on cell proliferation has been recognized,its role in inducing pluripotency in human-induced pluripotent stem cells(iPSCs)has not been addressed.AIM To evaluate the efficacy of HSP20 overexpression in human iPSCs and evaluate the ability to promote cell proliferation.The purpose of this study was to investigate whether overexpression of HSP20 in iPSCs can increase pluripotency and regeneration.METHODS We used iPSCs,which retain their potential for cell proliferation.HSP20 overexpression effectively enhanced cell proliferation and pluripotency.Overexpression of HSP20 in iPSCs was characterized by immunocytochemistry staining and realtime polymerase chain reaction.We also used cell culture,cell counting,western blotting,and flow cytometry analyses to validate HSP20 overexpression and its mechanism.RESULTS This study demonstrated that overexpression of HSP20 can increase the pluripotency in iPSCs.Furthermore,by overexpressing HSP20 in iPSCs,we showed that HSP20 upregulated proliferation markers,induced pluripotent genes,and drove cell proliferation in a sirtuin 1(SIRT1)-dependent manner.These data have practical applications in the field of stem cell-based therapies where the mass expansion of cells is needed to generate large quantities of stem cell-derived cells for transplantation purposes.CONCLUSION We found that the overexpression of HSP20 enhanced the proliferation of iPSCs in a SIRT1-dependent manner.Herein,we established the distinct crosstalk between HSP20 and SIRT1 in regulating cell proliferation and pluripotency.Our study provides novel insights into the mechanisms controlling cell proliferation that can potentially be exploited to improve the expansion and pluripotency of human iPSCs for cell transplantation therapies.These results suggest that iPSCs overexpressing HSP20 exert regenerative and proliferative effects and may have the potential to improve clinical outcomes.
基金Supported by the National Natural Science Foundation of China(3107218631172378+2 种基金31372313)the Natural Science Foundation of Shandong(ZR2010CM028)SDAIT-12-011-03
文摘The objective of the paper was to detect HSP72 expression and HSP72 gene sequence in heat shocked mouse preimplantation embryos and the effects of different thermo conditions on hatching rates of embryos. The mouse blastocysts cultured in vitro were heat treated at 40℃ and 38℃ for 1 h, 2 h and 3 h and then recovered at 37℃ for 3 h, 2 h and 1 h, respectively, to detect their HSP72 gene expression by using RT-PCR after the total RNA extraction. The hatching rate of the blastocysts for different treated groups was recorded and the expression of HSP72 in the blastocysts was determined by Western blot. The results showed that all the groups of blastocysts, including the control, had the expression of HSP72 gene. The expression of HSP72 protein had the highest level in the embryos stressed at 38℃ for 2 h, and it was signifi cantly higher than that in the control group. The expression of HSP72 in the groups of blastocysts treated at 40℃ was not signifi cantly different from that in the control group. The embryos with induction of mild heat shock at 38℃ for 2 h, then subjected to heat shock at 40℃ for 2 h, had a signifi cant higher(P<0.05) hatching rate of 54.74% compared to 47.85% in the embryos treated directly at 40℃ for 2 h. The above results indicated that the mouse blastocysts were sensitive to heat shock and a mild heat shock induced HSP72 gene expression. Induction of HSP72 expression with mild heat shock helped embryos to tolerate more severe heat shocks.
文摘Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) is the most destructive invasive pests in agricultural production and has a high tolerance to heat. Heat shock proteins play an essential role in life activities such as growth and development, reproduction and diapause of B. tabaci. At the same time, they are also crucial in resisting adverse environments and in adaptive evolution. The expression of heat shock protein in B. tabaci is not only related to temperature, but also to the tolerance of the environment. After receiving external stimuli, the expression level can be increased or decreased to maintain the stability of cells in vivo. This paper reviews the classification, biological characteristics, biological functions, and research status of HSPs in recent years. This mini-review will provide helpful information related to the use of heat shock proteins to study the occurrence and damage of B. tabaci. This has important theoretical and practical significance for revealing Hsps in explaining the population expansion mechanism of B. tabaci invasion and predicting population dynamics.
基金supported by the National Basic R&D Program of China(2009CB119200)the National Natural Science Foundation of China(30800722)
文摘Thermal adaptation plays a fundamental role in shaping the distribution and abundance of insects,and heat shock proteins(Hsps)play important roles in the temperature adaptation of various organisms.To better understand the temperature tolerance of the indigenous ZHJ2-biotype of whitefly Bemisia tabaci species complex,we obtained complete cDNA sequences for hsp90,hsp70,and hsp20 and analyzed their expression profiles under different high temperature treatments by real-time quantitative polymerase chain reaction.The high temperature tolerance of B.tabaci ZHJ2-biotype was determined by survival rate after exposure to different high temperatures for 1 h.The results showed that after 41°C heat-shock treatment for 1 h,the survival rates of ZHJ2 adults declined significantly and the estimated temperature required to cause 50% mortality(LT50)is 42.85°C for 1 h.Temperatures for onset(Ton)or maximal(Tmax)induction of hsps expression in B.tabaci ZHJ2-biotype were 35 and 39°C(or 41°C).Compared with previous studies,indigenous ZHJ2-biotype exhibits lower heat temperature stress tolerance and Ton(or Tmax)than the invasive B-biotype.
文摘AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSION The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.
基金funding support from the National Natural Science Foundation of China(Grant Nos.81672467,81702773,81702389,and 81672368)the Major National R&D Project(Grant Nos.2018ZX10723204,2018ZX10302205,and 2018ZX09J18107)the Natural Science Foundation of Beijing(Grant No.7172207)。
文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.
基金funded by the National Natural Science Foundation of China (31372003)the Shandong Modern Agricultural Technology and Industry System, China (SDAIT-02-021-11)+2 种基金the Taishan Scholarship Construction Engineering Special Fund, Chinathe Startup Fund for Distinguished Scholars (631316)supported by the Qingdao Agricultural University,China
文摘Currently, insecticides are considered as the primary approach for controlling western flower thrips, Frankliniella occidentalis(Pergande)(Thysanoptera: Thripidae). However, the heavy use of insecticides resulted in high insect resistance and serious environmental pollution. Given its characteristics of ease of operation and environmental friendliness, insect control using high temperature is receiving considerable renewed research interest. However, although the combination of insecticides and high temperature to control F. occidentalis has been studied before, few studies have focused on the short-term effect of such treatment. In a laboratory study, F. occidentalis adults and second-instar nymphs were exposed to 45°C for 2 h. Then, their susceptibility to acetamiprid, spinosad, methomyl, and beta-cypermethrin was tested after different periods of recovery time(2–36 h). Additionally, the specific activity of three detoxification enzymes(esterase, glutathione S-transferase, and cytochrome p450(CYP) monooxygenase) of the treated insects was determined. The results indicated that the fluctuation of susceptibility to insecticides and detoxification enzyme activity during F. occidentalis recovery from heat shock are related. Furthermore, several recovery time points(2, 30, and 36 h) of significant susceptibility to four tested insecticides compared with the control were found during the treatment of adults that were heat-shocked. Recovery time points of higher susceptibility compared with the control depended on different insecticides during the second-instar nymph recovery from heat shock. Interestingly, the fluctuation of CYP monooxygenase activity exhibited a trend that was similar to the fluctuation of susceptibility to insecticides(especially spinosad) during the recovery from heat shock of adults. In addition, the glutathione S-transferase and CYP monooxygenase activity trend was similar to the trend of susceptibility to spinosad during the recovery from heat shock of second-instar nymphs. Our results provide a new approach for controlling F. occidentalis using the combined heat shock and insecticide. This effectively enhances the control efficiency of heat shock and significantly reduces the application of insecticides.
基金supported by the earmarked fund for China Agriculture Research System (CARS-25)the Fundamental Research Funds of the Chinese Academy of Agricultural Sciences (Y2018YJ15 and Y2019XK16-03)+1 种基金the Agricultural Science and Technology Innovation Program, Chinese Academy of Agricultural Sciences (CAAS-ASTIP2018-ZFRI)the National Key R&D Program of China (2018YFD0201310)
文摘In vitro gynogenesis is an important tool used in haploid or homozygous double-haploid plant breeding.However,because of low repeatability,embryoid induction rate and quality,the molecular mechanisms remain poorly understood.Heat shock treatment can promote the transformation of the gametophytic pathway into the sporophyte pathway,which induces the occurrence of haploid.In this study,unfertilized ovaries were heat shocked for 0 h(A0)before flowering and for 0 h(A1),4 h(A3),8 h(A5),12 h(A7),and 24 h(A8),respectively,at 37℃at the first day of the flowering stage.The ovule enlargement rate was increased from 0%at 25℃to 96.8%at 37℃(24 h treatment).Thus,we aimed to investigate the gene expression patterns in unfertilized ovules of watermelon after different periods of heat shock by using RNA-Seq technology.The results showed that compared with A3,A5,A7,and A8,the biosynthesis of amino acid,glycine,serine and threonine metabolic pathways in A1 has changed significantly.This indicated that heat shock treatment affected the synthesis and transformation of amino acids during ovule expansion.The transcriptome data suggested gene expressions of ovule growth were significantly changed by heat-specific influences.The results provide new information on the complex relationship between in vitro gynogenesis and temperature.This provides a basis for further study of the mechanism of heat shock affecting the expansion of watermelon ovule.
基金This study was funded by Basic Research Projects in Shanxi Province(No.2015021178)Start-up Funds for Doctoral Research at Shanxi Datong University(No.2014-B-01).
文摘Objective The neuroprotective function of heat shock protein A5(HSPA5)in ischemic stroke has been confirmed.This study aimed to investigate the effects of early aerobic exercise on neurological function recovery from cerebral ischemia/reperfusion and to determine whether these effects are associated with the expression level of HSPA5 in the ischemic penumbra.Methods A total of 72 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group[middle cerebral artery occlusion(MCAO)-Ex,n=18],ischemia and sedentary group(MCAO-St,n=18),sham-surgery and exercise group(Sham-Ex,n=18),or sham-surgery and sedentary group(Sham-St,n=18).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 min,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 min once a day for 5 consecutive days.After reperfusion,the motor function of the rats was scored by the Bederson neurological function test,balance beam test,and screen test.Nissl staining was conducted to assess morphological and structural change of nerve cells in the ischemic penumbra.The reverse transcription-quantitative polymerase chain reaction was applied to detect the mRNA expression of HSPA5.Western blot analysis was conducted to determine the protein expression of HSPA5.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was carried out in the ischemic penumbra after MCAO.Results Rats receiving early treadmill exercise had lower Bederson neurological function,balance beam,and screen test scores on the 3rd,7th,and 14th days after MCAO;in addition,more neurons survived in the ischemic penumbra after MCAO,and higher mRNA and protein expression of HSPA5 and fewer TUNEL-positive stained cells were observed.Conclusion Our study demonstrated that early aerobic exercise can improve neurological function recovery after ischemia/reperfusion.Furthermore,the increased level of HSPA5 in the ischemic penumbra might be one of the mechanisms of enhanced neurological function recovery.
基金supported by grants from the National Natural Science Foundation of China (30671178)the Shanxi Province Science Foundation for Youths, China (2014021029-2)
文摘The small heat shock protein(sHSP) chaperones are required for protecting cellular proteins from damage,as well as refolding denatured proteins.This study was carried out to investigate the temporal-spatial expression patterns of two sHSP genes in rice.These two genes,named as Os16.9A and Os16.9B,are reverse duplicated genes that adjacently located on chromosome 1 and probably share the same or overlapping DNA region as a promoter.The interval sequence between the start codons of the two genes which are transcribed in opposite directions is only about 2.6 kb.Semi-quantitative RT-PCR was carried out to detect the expression of the two genes under normal growth conditions and different stress conditions.The expression patterns of the two genes were in detail investigated by using β-glucuronidase(GUS) reporter gene fusion system.Results showed that heat shock stress can induce high level expression of the two genes.Under normal growth conditions,Os16.9A and Os16.9B expressed in vegetative organs and young panicles.GUS staining combined with cytological observations showed that the two genes expressed mainly in the vascular tissues of roots,stems and young panicles,implicating that Os16.9A and Os16.9B play important roles not only for heat shock response,but also for normal development in rice.
文摘Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.
基金This work was supported by the National Key Research and Development Program of China(No.2018YFD0900601)the Natural Science Foundation of Shandong Province(No.ZR2017MC072).
文摘Heat shock proteins 10/60(hsp10/60)are a family of conserved ubiquitously expressed heat shock proteins which are produced by cells in response to exposure to stressful conditions.Besides the chaperone and housekeeping functions,they are also known to be involved in immune response during bacterial infection.In this study,we identified and annotated 10 hsp10/60 genes through bioinformatic analysis in Japanese flounder(Paralichthys olivaceus).Among them one member of hsp10(hspe)family and nine members of hsp60(hspd)family were identified.Phylogenetic and selection pressure analysis showed that the hsp10/60 genes were evolutionarily constrained and their function was conserved.Besides,hsp10/60 genes were involved in different embryonic and larval stages and acted as the sentinel role in an unchallenged organism.In addition,we also observed the expression patterns of hsp10/60 genes after Edwardsiella tarda infection,for the first time in Japanese flounder.Eight out of 10 genes were differentially expressed after bacterial challenges,the significantly regulated expressions of flounder hsp10/60 genes after bacterial infections suggested their involvement in immune response in flounder.Our results provide valuable information for clarifying the evolutionary relationship,and early insights of the immune functions of hsp10/60 genes in Japanese flounder.
基金Supported by the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.2018SDKJ0501-4)the National Key Research and Development Program(No.2019YFD0901303)。
文摘Anadara broughtonii is one of the main commercially important species of shellfish in northern China.A.broughtonii lives in relatively stable subtidal zone where the clam could respond to environmental changes with minimum energy.Therefore,slight fluctuations in water environment may have a great impact on physiological processes such as feeding and metabolism.Large-scale mortality often occurs during the intermediate rearing processes,and high temperatures in summer are considered the leading cause of mortality.To understand the physiological and molecular response patterns of A.broughtonii at high temperatures and to estimate the appropriate metabolism temperature for A.broughtonii,the effects of temperature on the respiratory metabolism and food intake at different growth stages were studied.The response patterns of heat shock protein genes to heat stress and post-stress recovery were also explored.Results show that the temperature and growth stage of A.broughtonii were two important factors affecting metabolism and feeding.The optimum temperature for feeding and physiological activities in each shell-length group was 24℃.The temperature at which the peak metabolic rate occurred in each shell-length group increased with the increase in shell length.With the increase in heat stress,the expression of three heat shock protein genes(Abhsp60,Abhsp70,and Abhsp90)in the tissues of two size groups of A.broughtonii increased significantly when temperature was above 24℃and reached a peak at 30℃.After heat shock at 30℃for 2 h,the expression of the three heat shock protein genes rapidly increased,peaked at 2 h after the heat shock,and then gradually decreased to the level of the control group at 48 h after the heat shock.The three heat shock protein genes respond rapidly to heat stress and can be used as indicators to the cellular stress response in A.broughtonii under an environmental stress.
基金the support from the Guangdong Basic and Applied Basic Research Foundation(2019B1515120043 and File no.2022A1515012154)the National Natural Science Foundation of China(File no.82104354 and File no.81960334)+1 种基金the Shenzhen Fundamental Research Program(File no.JCYJ20180507181817604)the Science and Technology Development Fund,Macao SAR(File no.0016/2021/A)
文摘Near-infrared(NIR)-light-triggered photothermal therapy(PTT)is a promising treatment for breast cancer.However,its therapeutic efficiency is often compromised due to the heatinduced up-regulation of heat shock proteins,which confer photothermal resistance.To solve this urgent problem,PEGylated two-dimensional boron nanosheets(B-PEG)-which allow both multimodal imaging and photothermal conversion-were loaded with gambogic acid(GA),which can inhibit heat shock protein 90(Hsp90).Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment.It could be used to administer mild PTT as well as chemotherapy for breast cancer,provide improved anti-tumor effects,and reduce the toxicity of PTT,all while inhibiting breast cancer growth.This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.
