BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncologic...BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in HCC.METHODS Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in HCC.Using immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our results.The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint expression.Finally,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining assays.RESULTS Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor prognosis.Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor.In HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation levels.Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup.The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor prognosis.CONCLUSION As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.展开更多
BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased abil...BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.展开更多
BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.Howe...BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.However,its role in hepatic alveolar echinococcosis(HAE)remains unclear.AIM To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.METHODS We assessed the expression of NLRP3,caspase-1,interleukin(IL)-1β,and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE.A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE.Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis(E.multilocularis)in stimulating Kupffer cells and hepatocytes.Furthermore,immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assay were used to evaluate NLRP3,caspase-1,IL-1β,and IL-18 expression;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS).RESULTS NLRP3 inflammasome activation was significantly associated with ROS.Inhibition of ROS production decreased NLRP3-caspase-1-IL-1βpathway activation and mitigated hepatocyte damage and inflammation.CONCLUSION E.multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1βpathway in Kupffer cells,indicating that ROS may serve as a potential target for the treatment of HAE.展开更多
Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multipl...Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.展开更多
Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significa...Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.展开更多
Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an ...Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.展开更多
Plant growth and crop productivity are severely affected by abiotic stress on a global scale.WD40 repeat-containing proteins play a significant role in the development and environmental adaptation of eukaryotes.In thi...Plant growth and crop productivity are severely affected by abiotic stress on a global scale.WD40 repeat-containing proteins play a significant role in the development and environmental adaptation of eukaryotes.In this study,OsABT,a stress response gene,was cloned from rice(Oryza sativa L.cv.Nipponbare).OsABT encodes a protein containing seven WD40 domains.Expression analysis revealed that the OsABT gene was first up-regulated and then down-regulated following treatment with abscisic acid(ABA)and NaCl,but was down-regulated when treated with PEG8000.Subcellular localization results showed that OsABT was located in the cytoplasm and nucleus of Arabidopsis roots.OsABT transgenic Arabidopsis showed significantly increased tolerance to ABA and salt stress during plant seedling development.However,the transgenic lines were more sensitive to drought stress.Moreover,OsABT can interact with OsABI2,a component of ABA signaling pathway.These results showed that OsABT plays a positive regulatory role in response to salt stress and a negative role in response to drought stress in Arabidopsis.展开更多
BACKGROUND Spermatogonial stem cells(SSCs)are the origin of male spermatogenesis,which can reconstruct germ cell lineage in mice.However,the application of SSCs for male fertility restoration is hindered due to the un...BACKGROUND Spermatogonial stem cells(SSCs)are the origin of male spermatogenesis,which can reconstruct germ cell lineage in mice.However,the application of SSCs for male fertility restoration is hindered due to the unclear mechanisms of proliferation and self-renewal in humans.AIM To investigate the role and mechanism of SPOC domain-containing protein 1(SPOCD1)in human SSC proliferation.METHODS We analyzed publicly available human testis single-cell RNA sequencing(RNAseq)data and found that SPOCD1 is predominantly expressed in SSCs in the early developmental stages.Small interfering RNA was applied to suppress SPOCD1 expression to detect the impacts of SPOCD1 inhibition on SSC proliferation and apoptosis.Subsequently,we explored the target genes of SPOCD1 using RNA-seq and confirmed their role by restoring the expression of the target genes.In addition,we examined SPOCD1 expression in some non-obstructive azoospermia(NOA)patients to explore the correlation between SPOCD1 and NOA.RESULTS The uniform manifold approximation and projection clustering and pseudotime analysis showed that SPOCD1 was highly expressed in the early stages of SSC,and immunohistological results showed that SPOCD1 was mainly localized in glial cell line-derived neurotrophic factor family receptor alpha-1 positive SSCs.SPOCD1 knockdown significantly inhibited cell proliferation and promoted apoptosis.RNA-seq results showed that SPOCD1 knockdown significantly downregulated genes such as adenylate kinase 4(AK4).Overexpression of AK4 in SPOCD1 knockdown cells partially reversed the phenotypic changes,indicating that AK4 is a functional target gene of SPOCD1.In addition,we found a significant downregulation of SPOCD1 expression in some NOA patients,suggesting that the downregulation of SPOCD1 may be relevant for NOA.CONCLUSION Our study broadens the understanding of human SSC fate determination and may offer new theories on the etiology of male infertility.展开更多
BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unkno...BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.展开更多
The WW domain-containing oxidoreductase(WWOX) is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-f...The WW domain-containing oxidoreductase(WWOX) is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-free survival rate among breast cancer patients. Though several WWOX partners have been identified, the functional mechanisms of WWOX's role in cancers have not been fully addressed to date. In the current study, we found WWOX suppresses expression of KLF5—an oncogenic transcription factor—at protein level, and suppresses cancer cell proliferation in both bladder and breast cancer cell lines. Furthermore, we demonstrated that WWOX physically interacts with KLF5 via the former's WW domains and the latter's PY motifs. Interestingly, we found the expression of WWOX negatively correlates with KLF5 expression in a panel of breast cancer cell lines. Taken together, we conjecture that WWOX may suppress cancer cell proliferation partially by reducing the expression of KLF5.展开更多
为了研究植物乳杆菌WW(Lactobacillus plantarum WW)对高脂血症大鼠体脂的影响,将32只5周龄雄性SD大鼠随机分为4组:正常对照组(A)喂食基础饲料+无菌水、高脂模型组(B)饲喂高脂饲料+无菌水、脱脂乳对照组(C)饲喂高脂饲料+无菌脱脂乳、菌...为了研究植物乳杆菌WW(Lactobacillus plantarum WW)对高脂血症大鼠体脂的影响,将32只5周龄雄性SD大鼠随机分为4组:正常对照组(A)喂食基础饲料+无菌水、高脂模型组(B)饲喂高脂饲料+无菌水、脱脂乳对照组(C)饲喂高脂饲料+无菌脱脂乳、菌液干预组(D)饲喂高脂饲料+菌悬液(1×10^(10) CFU/mL),灌胃量为10 mL/kg m_b,12周后测定相关指标。结果显示:4组大鼠肾脏、脾脏和心脏指数差异不显著(P>0.05),而B组和C组肝脏指数显著高于A组和D组(P<0.05),说明L. plantarum WW无毒副作用,并且能够减少脂肪在肝脏的堆积;B组血清和肝脏血脂水平显著高于A组(P<0.05),说明造模成功;与B组相比,D组血清和肝脏各指标水平显著降低(P<0.05),粪便中总胆固醇、甘油三酯和总胆汁酸含量显著升高(P<0.05),说明L. plantarum WW能够促进胆固醇的排泄,进而降低大鼠体内胆固醇。这些结果表明植物乳杆菌WW可能是缓解高脂血症并用于功能性食品的潜在益生菌。展开更多
The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase(WWOX) gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from nor...The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase(WWOX) gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from normal human ovary tissues.The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV.After introduction of WWOX gene into cancer cells with liposome,the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reaction(RT-PCR) and immunoblotting.The growth activities of cancer cells were detected by Trypan blue staining.The clone formation assay in soft agar was employed to observe the proliferation of the cancer cells.Apoptosis was examined by DNA ladder and acridine orange-ethidium bromide fluorescent staining.The results showed that 72 h after WWOX gene transfection,the WWOX expression was increased significantly(P<0.01).The growth of ovarian cancer cells was decreased by 16.41% to 38.49%(P<0.01).The clone formation abilities were reduced(P<0.01).Some cancer cells presented the characteristic morphological changes of apoptosis with obvious ladder bands on electrophoresis.The apoptosis rate was(20.7±6.0)%(P<0.01).It was concluded that over-expression of WWOX gene could induce apoptosis and inhibit the growth of ovarian cancer cells,which might be potentially useful in the gene therapy of ovarian cancers.展开更多
基金Supported by the Anhui Provincial Health Scientific Research Project Provincial Financial Support Key Project,No.AHWJ2023A10110College Teaching Quality Engineering Project of Anhui Educational Committee,No.2021jyxm0954College Student Innovation Training Program of Bengbu Medical College,No.Byycxz22110.
文摘BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in HCC.METHODS Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in HCC.Using immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our results.The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint expression.Finally,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining assays.RESULTS Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor prognosis.Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor.In HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation levels.Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup.The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor prognosis.CONCLUSION As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.
基金2018 Henan Medical Science and Technology Research Plan Project,China,No.SBGJ2018019.
文摘BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.
基金Supported by the National Major Research and Development Project of“Precision Medicine Research”,No.2017YFC0909900Qinghai Province Science and Technology Department Programme,No.2019-SF-131the Qinghai Province Health and Family Planning Commission Programme,No.2016-wjzd-04.
文摘BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.However,its role in hepatic alveolar echinococcosis(HAE)remains unclear.AIM To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.METHODS We assessed the expression of NLRP3,caspase-1,interleukin(IL)-1β,and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE.A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE.Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis(E.multilocularis)in stimulating Kupffer cells and hepatocytes.Furthermore,immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assay were used to evaluate NLRP3,caspase-1,IL-1β,and IL-18 expression;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS).RESULTS NLRP3 inflammasome activation was significantly associated with ROS.Inhibition of ROS production decreased NLRP3-caspase-1-IL-1βpathway activation and mitigated hepatocyte damage and inflammation.CONCLUSION E.multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1βpathway in Kupffer cells,indicating that ROS may serve as a potential target for the treatment of HAE.
基金This study was financially supported by the Young Teachers Support Program of Hubei University of Chinese Medicine(2021ZZX025)Hubei Province College Students’innovation and entrepreneurship training program(S202210507018).
文摘Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.
文摘Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.
基金supported by the National Natural Science Foundation of China,Nos.81601961(to KWY),81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.
基金supported by the Major Program of the Zhejiang Province for Food Crop Breeding(Grant No.2016C02050-6)the Key Program of Hangzhou Agricultural Scientific Research(Grant No.20191203B08)。
文摘Plant growth and crop productivity are severely affected by abiotic stress on a global scale.WD40 repeat-containing proteins play a significant role in the development and environmental adaptation of eukaryotes.In this study,OsABT,a stress response gene,was cloned from rice(Oryza sativa L.cv.Nipponbare).OsABT encodes a protein containing seven WD40 domains.Expression analysis revealed that the OsABT gene was first up-regulated and then down-regulated following treatment with abscisic acid(ABA)and NaCl,but was down-regulated when treated with PEG8000.Subcellular localization results showed that OsABT was located in the cytoplasm and nucleus of Arabidopsis roots.OsABT transgenic Arabidopsis showed significantly increased tolerance to ABA and salt stress during plant seedling development.However,the transgenic lines were more sensitive to drought stress.Moreover,OsABT can interact with OsABI2,a component of ABA signaling pathway.These results showed that OsABT plays a positive regulatory role in response to salt stress and a negative role in response to drought stress in Arabidopsis.
基金the National Natural Science Foundation for Young Scholars of China,No.82201771National Natural Science Foundation of China,No.32270912+2 种基金Natural Science Foundation of Changsha,No.kq2202491Research Grant of CITIC-Xiangya,No.YNXM202109 and No.YNXM202115Hunan Provincial Grant for Innovative Province Construction,No.2019SK4012。
文摘BACKGROUND Spermatogonial stem cells(SSCs)are the origin of male spermatogenesis,which can reconstruct germ cell lineage in mice.However,the application of SSCs for male fertility restoration is hindered due to the unclear mechanisms of proliferation and self-renewal in humans.AIM To investigate the role and mechanism of SPOC domain-containing protein 1(SPOCD1)in human SSC proliferation.METHODS We analyzed publicly available human testis single-cell RNA sequencing(RNAseq)data and found that SPOCD1 is predominantly expressed in SSCs in the early developmental stages.Small interfering RNA was applied to suppress SPOCD1 expression to detect the impacts of SPOCD1 inhibition on SSC proliferation and apoptosis.Subsequently,we explored the target genes of SPOCD1 using RNA-seq and confirmed their role by restoring the expression of the target genes.In addition,we examined SPOCD1 expression in some non-obstructive azoospermia(NOA)patients to explore the correlation between SPOCD1 and NOA.RESULTS The uniform manifold approximation and projection clustering and pseudotime analysis showed that SPOCD1 was highly expressed in the early stages of SSC,and immunohistological results showed that SPOCD1 was mainly localized in glial cell line-derived neurotrophic factor family receptor alpha-1 positive SSCs.SPOCD1 knockdown significantly inhibited cell proliferation and promoted apoptosis.RNA-seq results showed that SPOCD1 knockdown significantly downregulated genes such as adenylate kinase 4(AK4).Overexpression of AK4 in SPOCD1 knockdown cells partially reversed the phenotypic changes,indicating that AK4 is a functional target gene of SPOCD1.In addition,we found a significant downregulation of SPOCD1 expression in some NOA patients,suggesting that the downregulation of SPOCD1 may be relevant for NOA.CONCLUSION Our study broadens the understanding of human SSC fate determination and may offer new theories on the etiology of male infertility.
基金Supported by The Key Projects of Natural Science Research of Anhui Province in China,No.201904a07020043.
文摘BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.
基金supported by National Natural Science Foundation of China (81272930, 81322038, 31260208, and U1132605)the Science and Technological Key Project of Yunnan Province (2012FB185)West Light Foundation of the Chinese Academy of Sciences (to R.L.)
文摘The WW domain-containing oxidoreductase(WWOX) is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-free survival rate among breast cancer patients. Though several WWOX partners have been identified, the functional mechanisms of WWOX's role in cancers have not been fully addressed to date. In the current study, we found WWOX suppresses expression of KLF5—an oncogenic transcription factor—at protein level, and suppresses cancer cell proliferation in both bladder and breast cancer cell lines. Furthermore, we demonstrated that WWOX physically interacts with KLF5 via the former's WW domains and the latter's PY motifs. Interestingly, we found the expression of WWOX negatively correlates with KLF5 expression in a panel of breast cancer cell lines. Taken together, we conjecture that WWOX may suppress cancer cell proliferation partially by reducing the expression of KLF5.
文摘为了研究植物乳杆菌WW(Lactobacillus plantarum WW)对高脂血症大鼠体脂的影响,将32只5周龄雄性SD大鼠随机分为4组:正常对照组(A)喂食基础饲料+无菌水、高脂模型组(B)饲喂高脂饲料+无菌水、脱脂乳对照组(C)饲喂高脂饲料+无菌脱脂乳、菌液干预组(D)饲喂高脂饲料+菌悬液(1×10^(10) CFU/mL),灌胃量为10 mL/kg m_b,12周后测定相关指标。结果显示:4组大鼠肾脏、脾脏和心脏指数差异不显著(P>0.05),而B组和C组肝脏指数显著高于A组和D组(P<0.05),说明L. plantarum WW无毒副作用,并且能够减少脂肪在肝脏的堆积;B组血清和肝脏血脂水平显著高于A组(P<0.05),说明造模成功;与B组相比,D组血清和肝脏各指标水平显著降低(P<0.05),粪便中总胆固醇、甘油三酯和总胆汁酸含量显著升高(P<0.05),说明L. plantarum WW能够促进胆固醇的排泄,进而降低大鼠体内胆固醇。这些结果表明植物乳杆菌WW可能是缓解高脂血症并用于功能性食品的潜在益生菌。
文摘The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase(WWOX) gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from normal human ovary tissues.The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV.After introduction of WWOX gene into cancer cells with liposome,the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reaction(RT-PCR) and immunoblotting.The growth activities of cancer cells were detected by Trypan blue staining.The clone formation assay in soft agar was employed to observe the proliferation of the cancer cells.Apoptosis was examined by DNA ladder and acridine orange-ethidium bromide fluorescent staining.The results showed that 72 h after WWOX gene transfection,the WWOX expression was increased significantly(P<0.01).The growth of ovarian cancer cells was decreased by 16.41% to 38.49%(P<0.01).The clone formation abilities were reduced(P<0.01).Some cancer cells presented the characteristic morphological changes of apoptosis with obvious ladder bands on electrophoresis.The apoptosis rate was(20.7±6.0)%(P<0.01).It was concluded that over-expression of WWOX gene could induce apoptosis and inhibit the growth of ovarian cancer cells,which might be potentially useful in the gene therapy of ovarian cancers.