BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transpl...BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.展开更多
BACKGROUND Background diabetic nephropathy(DN),a major complication of diabetes,is linked to gut microbiota dysbiosis.Elevated trimethylamine N-oxide(TMAO),a microbiota-derived metabolite,plays a central role in induc...BACKGROUND Background diabetic nephropathy(DN),a major complication of diabetes,is linked to gut microbiota dysbiosis.Elevated trimethylamine N-oxide(TMAO),a microbiota-derived metabolite,plays a central role in inducing renal injury during DN pathogenesis.AIM To investigate the role of TMAO in renal dysfunction and intestinal microbiota alterations associated with DN,hypothesizing that TMAO exacerbates renal injury and fibrosis through gut microbiota-dependent mechanisms.METHODS A DN model was successfully established using Zucker diabetic fatty(ZDF)rats.Blood samples were analyzed for renal function parameters,and serum TMAO levels were quantified via high-performance liquid chromatography-tandem mass spectrometry.Renal tissue morphology and fibrosis were assessed using hematoxylin and eosin and Masson staining,respectively.Additionally,16S rRNA sequencing was employed to profile fecal bacterial communities in rats with diabetes and DN.Fecal microbiota transplantation was conducted to verify alterations in TMAO production capacity in the gut microbiota of DN rats.RESULTS After 8 weeks of modeling,the ZDF rat model group exhibited blood glucose levels surpassing 16.7 mmol/L,and compared to the control group,renal function indicators,includingβ2-microglobulin,cystatin C,uric acid,and creatinine,were significantly elevated(P<0.05).Renal fibrosis was more pronounced in the ZDF model group,accompanied by heightened P-smad3 expression,in contrast to the TMAO inhibition group.Although Masson staining results did not reach statistical significance(P>0.05),notable alterations in intestinal flora structure were observed in DN rats,and fecal microbiota transplantation led to increased TMAO production within the intestinal flora of DN rats compared to controls(P>0.05).CONCLUSION DN is associated with gut microbiota alterations that potentiate TMAO generation,contributing to renal injury and fibrotic progression.While TMAO’s role in fibrosis warrants further validation,these findings implicate the gutkidney axis in DN pathogenesis.展开更多
Background： DNA hypomethylation of long interspersed nuclear elements- 1 （LINEs- 1 ） occurs during carcinogenesis, whereas intbmaation addressing LINE-1 methylation in Wilms tumor （WT） is limited. The main purpos...Background： DNA hypomethylation of long interspersed nuclear elements- 1 （LINEs- 1 ） occurs during carcinogenesis, whereas intbmaation addressing LINE-1 methylation in Wilms tumor （WT） is limited. The main purpose of our study was to quantity, LINE-1 methylation levels and evaluate their relationship with relative telomere length （TL） in WT. Methods： We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction （PCR） pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. Results： LINE-1 methylation levels were significantly lower （P 〈 0.05） and relative TLs were sigmificantly shorter （P 〈 0.05） in WT compared with normal kidney. There was a significant positive relationship between LINE- 1 methylation and relative TL in WT （r = 0.671, P = 0.001 ）. LINE- 1 Methylation levels were significantly associated with global DNA methylation （r = 0.332, P 〈 0.01 ）. In addition, relative TL was shortened and LINE- 1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2＇-deoxycytidine compared with untreated WT cell line. Conclusion： These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.展开更多
Quantified constraint satisfaction problems （QCSPs） are an extension to constraint satisfaction problems （CSPs） with both universal quantifiers and existential quantifiers. In this paper we apply variable ordering...Quantified constraint satisfaction problems （QCSPs） are an extension to constraint satisfaction problems （CSPs） with both universal quantifiers and existential quantifiers. In this paper we apply variable ordering heuristics and integrate standard dependency schemes in QCSP solvers. The technique can help to decide the next variable to be assigned in QCSP solving. We also introduce a new factor into the variable ordering heuristics： a variable＇s dep is the number of variables depending on it. This factor represents the probability of getting more candidates for the next variable to be assigned. Experimental results show that variable ordering heuristics with standard dependency schemes and the new factor dep can improve the performance of QCSP solvers.展开更多
This study emphasizes the significance of dual role of microRNAs(miRNAs)in the anti-cancer effects of neferine(Nef),a natural compound derived from lotus embryos,specifically in endometrial cancer(EC)Ishikawa cells.We...This study emphasizes the significance of dual role of microRNAs(miRNAs)in the anti-cancer effects of neferine(Nef),a natural compound derived from lotus embryos,specifically in endometrial cancer(EC)Ishikawa cells.We previously established that Nef induces apoptosis in EC cells,but did not delve into the specific miRNAs.Through a combination of mRNA and miRNA omics analyses,we identified miR-1266-5p as a key regulatory factor in this process.Subsequent phenotypic assays were performed to assess various cellular behaviors,including proliferation,apoptosis,calcium ion levels,mitochondrial membrane potential(MMP),and migration ability.Our findings demonstrate that down-regulation of miR-1266-5p could inhibit cell viability,induce cell apoptosis,increase intracellular Ca2+levels,decrease MMP,and suppress cell metastasis.Furthermore,the Ras/ERK and PI3K-AKT signaling pathways were identified as key mediators of miR-1266-5p on apoptosis and metastasis in Ishikawa cells.Overall,our study positions miR-1266-5p as a potential molecular marker for the diagnosis and prognosis of EC,as well as a promising candidate for therapeutic intervention.展开更多
基金Supported by the Major Science and Technology Project of Gansu Province-Social Development Field,No.25ZDFA007Health Industry Research Funding Project of Gansu Province,No.GSWSKY2024-54+3 种基金Youth Science and Technology Fund Program of Gansu Province,No.21JR11RA014National Natural Science Foundation of China,No.81273568Health Industry Research Funding Project of Gansu Province,No.GSWSKY2022-03Logistics Scientific Research Independent Project of the PLA.
文摘BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.
基金Supported by the Chinese People’s Liberation Army,No.2021yxky056.
文摘BACKGROUND Background diabetic nephropathy(DN),a major complication of diabetes,is linked to gut microbiota dysbiosis.Elevated trimethylamine N-oxide(TMAO),a microbiota-derived metabolite,plays a central role in inducing renal injury during DN pathogenesis.AIM To investigate the role of TMAO in renal dysfunction and intestinal microbiota alterations associated with DN,hypothesizing that TMAO exacerbates renal injury and fibrosis through gut microbiota-dependent mechanisms.METHODS A DN model was successfully established using Zucker diabetic fatty(ZDF)rats.Blood samples were analyzed for renal function parameters,and serum TMAO levels were quantified via high-performance liquid chromatography-tandem mass spectrometry.Renal tissue morphology and fibrosis were assessed using hematoxylin and eosin and Masson staining,respectively.Additionally,16S rRNA sequencing was employed to profile fecal bacterial communities in rats with diabetes and DN.Fecal microbiota transplantation was conducted to verify alterations in TMAO production capacity in the gut microbiota of DN rats.RESULTS After 8 weeks of modeling,the ZDF rat model group exhibited blood glucose levels surpassing 16.7 mmol/L,and compared to the control group,renal function indicators,includingβ2-microglobulin,cystatin C,uric acid,and creatinine,were significantly elevated(P<0.05).Renal fibrosis was more pronounced in the ZDF model group,accompanied by heightened P-smad3 expression,in contrast to the TMAO inhibition group.Although Masson staining results did not reach statistical significance(P>0.05),notable alterations in intestinal flora structure were observed in DN rats,and fecal microbiota transplantation led to increased TMAO production within the intestinal flora of DN rats compared to controls(P>0.05).CONCLUSION DN is associated with gut microbiota alterations that potentiate TMAO generation,contributing to renal injury and fibrotic progression.While TMAO’s role in fibrosis warrants further validation,these findings implicate the gutkidney axis in DN pathogenesis.
基金National Natural Science Foundation of China （No. 81301773）.
文摘Background： DNA hypomethylation of long interspersed nuclear elements- 1 （LINEs- 1 ） occurs during carcinogenesis, whereas intbmaation addressing LINE-1 methylation in Wilms tumor （WT） is limited. The main purpose of our study was to quantity, LINE-1 methylation levels and evaluate their relationship with relative telomere length （TL） in WT. Methods： We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction （PCR） pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. Results： LINE-1 methylation levels were significantly lower （P 〈 0.05） and relative TLs were sigmificantly shorter （P 〈 0.05） in WT compared with normal kidney. There was a significant positive relationship between LINE- 1 methylation and relative TL in WT （r = 0.671, P = 0.001 ）. LINE- 1 Methylation levels were significantly associated with global DNA methylation （r = 0.332, P 〈 0.01 ）. In addition, relative TL was shortened and LINE- 1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2＇-deoxycytidine compared with untreated WT cell line. Conclusion： These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.
基金supported in part by the National Natural Science Foundation of China under Grant No. 61070039
文摘Quantified constraint satisfaction problems （QCSPs） are an extension to constraint satisfaction problems （CSPs） with both universal quantifiers and existential quantifiers. In this paper we apply variable ordering heuristics and integrate standard dependency schemes in QCSP solvers. The technique can help to decide the next variable to be assigned in QCSP solving. We also introduce a new factor into the variable ordering heuristics： a variable＇s dep is the number of variables depending on it. This factor represents the probability of getting more candidates for the next variable to be assigned. Experimental results show that variable ordering heuristics with standard dependency schemes and the new factor dep can improve the performance of QCSP solvers.
基金supported by the National Key Research&Develop-ment Program of China(2022YFF1100305)the Xunta de Galicia(Excelencia-ED431F2022/01)+1 种基金the Juan de la Cierva Incorporación(IJC 2020-046055-I)the Ramón y Cajal grant(RYC 2020-030365-I).
文摘This study emphasizes the significance of dual role of microRNAs(miRNAs)in the anti-cancer effects of neferine(Nef),a natural compound derived from lotus embryos,specifically in endometrial cancer(EC)Ishikawa cells.We previously established that Nef induces apoptosis in EC cells,but did not delve into the specific miRNAs.Through a combination of mRNA and miRNA omics analyses,we identified miR-1266-5p as a key regulatory factor in this process.Subsequent phenotypic assays were performed to assess various cellular behaviors,including proliferation,apoptosis,calcium ion levels,mitochondrial membrane potential(MMP),and migration ability.Our findings demonstrate that down-regulation of miR-1266-5p could inhibit cell viability,induce cell apoptosis,increase intracellular Ca2+levels,decrease MMP,and suppress cell metastasis.Furthermore,the Ras/ERK and PI3K-AKT signaling pathways were identified as key mediators of miR-1266-5p on apoptosis and metastasis in Ishikawa cells.Overall,our study positions miR-1266-5p as a potential molecular marker for the diagnosis and prognosis of EC,as well as a promising candidate for therapeutic intervention.
