Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which ca...Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which cause gastrointestinal diseases. Connexins function in gap junctional homeostasis, and their downregulation is closely related to gastric carcinogenesis. Investigations into H. pylori infection and the fine-tuning of connexins in cells or tissues have been reported in previous studies. Therefore, in this review, the potential mechanisms of H. pylori-induced gastric cancer through connexins are summarized in detail.展开更多
Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Among neurons, gap ...Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Among neurons, gap junctions form electrical synapses that function primarily for communication. However, in neurodegenerative states due to disease or injury gap junctions may be detrimental to survival. Electrical synapses may facilitate hyperactivity and bystander killing among neurons, while gap junction hemichannels in glia may facilitate inflammatory signaling and scar formation. Advances in understanding mechanisms of plasticity of electrical synapses and development of molecular therapeutics to target glial gap junctions and hemichannels offer new hope to pharmacologically limit neuronal degeneration and enhance recovery.展开更多
Connexins family in humans consists of 21 highly conserved proteins that are responsible for contact formation between cells. On the cell surface, connexins form hemichannels, or connexons. Two hemichannels brought to...Connexins family in humans consists of 21 highly conserved proteins that are responsible for contact formation between cells. On the cell surface, connexins form hemichannels, or connexons. Two hemichannels brought together form a gap junction, a form of intercellular contact that allows for direct transfer of material and signals between the adjacent cells. Gap junctions serve for transporting ions and other soluble, low molecular weight molecules therefore synchronizing the microenvironment of the contacting cells and maintaining cell and tissue homeostasis. Impairment of gap junctions is associated with different pathological conditions. Importantly, it has been described in atherosclerosis, which causes local cellular dysfunction in the arterial wall tissues followed by the development of atherosclerotic plaque. There are 3 main connexins expressed in human cardiovascular system: Cx37, Cx40, and Cx43. Alterations in the arterial wall cells observed in atherosclerosis include changes in the expression pattern of the main connexins and impairment of intercellular contacts and communication. According to the currently available data, Cx37 and Cx40 have anti-atherogenic and vasculoprotective properties, while Cx43 appears to be more pro-atherogenic. However, the effects of connexins are cell type-dependent and in many cases, remain to be studied in detail. In this review, we summarize the available knowledge on connexins of the arterial wall cells involved in atherosclerosis development.展开更多
BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varyin...BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varying degrees.Although the same variation locus have been reported,the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder,palmoplantar keratosis,and congenital hypotrichosis.CASE SUMMARY This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED.The proband(IV4)was a male patient with normal sweat gland function and dental development,no skeletal dysplasia,no cognitive disability,and no hearing impairments.His parents were not consanguineously married.Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longit-udinal ridges,in addition to mild bilateral palmoplantar hyperkeratosis.GJB6,GJB2,and GJA1 have been reported to be the causative genes of HED;therefore,we subjected the patient’s samples to Sanger sequencing of these three genes.In this family,the variation locus was at GJB6(c.31G>A,p.Gly11Arg).Overex-pression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models,and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot,respectively.CONCLUSION We report another HED phenotype associated with GJB6 variations,which can help clinicians to diagnose HED despite its varying presentations.展开更多
Objective: To explore the effect of connexin 32 (Cx32) on the cell proliferation, migration, invasion of human hepatocellular carcinoma (HCC) cell line Huh7 and its mechanism. Methods: Firstly, bioinformatics techniqu...Objective: To explore the effect of connexin 32 (Cx32) on the cell proliferation, migration, invasion of human hepatocellular carcinoma (HCC) cell line Huh7 and its mechanism. Methods: Firstly, bioinformatics techniques were used to analyze the difference in expression of Cx32 between HCC tissues and normal liver tissues, and the relationship between Cx32 expression and important clinicopathological features of HCC was also explored. Subsequently, Cx32 expression in HCC cell lines and normal hepatic epithelial cell line was detected in vitro. Huh7 cell line with stable over⁃expression of Cx32 was further established, and the change in cell proliferation ability was measured by MTT assay, changes in migration and invasion capacities were detected by wound⁃healing assay and transwell assay, on this cell line. Finally, western blot and immunofluorescence (IF) were used to investigate the alterations of expression of epithelial⁃mesenchymal transition (EMT) markers. Results: Bioinformatics analyses showed that Cx32 mRNA and protein expression levels in HCC tissues were lower than those in normal liver tissues, and the mRNA expression level of Cx32 was negatively correlated with T stage, histological grade and clinical stage of HCC patients (all P<0.05). Results of in vitro experiments revealed Cx32 protein expression in different HCC cell lines was down⁃regulated compared to that in normal hepatic epithelial cell line LO2. Cx32 stably over⁃expressed (Cx32 OE) Huh7 cell line was successfully constructed by lentivirus infection and showed high expression of Cx32 protein in the cell line. Compared to the control group and (or) the negative control (NC) group, the Cx32 OE group exhibited decreased OD490 value, wound healing rate and invasive cell number (all P<0.05). Furthermore, an increase in the expression of epithelial marker E⁃cadherin, and a decrease in the expression of mesenchymal markers Snail and Vimentin, were observed in Cx32⁃OE Huh7 cell line. Conclusion: Cx32 is low expressed in HCC tissues and cells, while the proliferation, migration and invasion ability of Huh7 cells can be inhibited by over⁃expression of Cx32, of which the underlying mechanism may be related to the inhibition of EMT process.展开更多
基金supported by the “New Xiangya Talent Projects” of the Third Xiangya Hospital of Central South University (JY201710)
文摘Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which cause gastrointestinal diseases. Connexins function in gap junctional homeostasis, and their downregulation is closely related to gastric carcinogenesis. Investigations into H. pylori infection and the fine-tuning of connexins in cells or tissues have been reported in previous studies. Therefore, in this review, the potential mechanisms of H. pylori-induced gastric cancer through connexins are summarized in detail.
基金supported by NIH grant R01EY012857(JO)the Frederic B.Asche endowment and Research to Prevent Blindness.KBM is supported by T32EY007024
文摘Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Among neurons, gap junctions form electrical synapses that function primarily for communication. However, in neurodegenerative states due to disease or injury gap junctions may be detrimental to survival. Electrical synapses may facilitate hyperactivity and bystander killing among neurons, while gap junction hemichannels in glia may facilitate inflammatory signaling and scar formation. Advances in understanding mechanisms of plasticity of electrical synapses and development of molecular therapeutics to target glial gap junctions and hemichannels offer new hope to pharmacologically limit neuronal degeneration and enhance recovery.
基金the Russian Science Foundation (Grant # 18-15-00254).
文摘Connexins family in humans consists of 21 highly conserved proteins that are responsible for contact formation between cells. On the cell surface, connexins form hemichannels, or connexons. Two hemichannels brought together form a gap junction, a form of intercellular contact that allows for direct transfer of material and signals between the adjacent cells. Gap junctions serve for transporting ions and other soluble, low molecular weight molecules therefore synchronizing the microenvironment of the contacting cells and maintaining cell and tissue homeostasis. Impairment of gap junctions is associated with different pathological conditions. Importantly, it has been described in atherosclerosis, which causes local cellular dysfunction in the arterial wall tissues followed by the development of atherosclerotic plaque. There are 3 main connexins expressed in human cardiovascular system: Cx37, Cx40, and Cx43. Alterations in the arterial wall cells observed in atherosclerosis include changes in the expression pattern of the main connexins and impairment of intercellular contacts and communication. According to the currently available data, Cx37 and Cx40 have anti-atherogenic and vasculoprotective properties, while Cx43 appears to be more pro-atherogenic. However, the effects of connexins are cell type-dependent and in many cases, remain to be studied in detail. In this review, we summarize the available knowledge on connexins of the arterial wall cells involved in atherosclerosis development.
文摘BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varying degrees.Although the same variation locus have been reported,the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder,palmoplantar keratosis,and congenital hypotrichosis.CASE SUMMARY This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED.The proband(IV4)was a male patient with normal sweat gland function and dental development,no skeletal dysplasia,no cognitive disability,and no hearing impairments.His parents were not consanguineously married.Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longit-udinal ridges,in addition to mild bilateral palmoplantar hyperkeratosis.GJB6,GJB2,and GJA1 have been reported to be the causative genes of HED;therefore,we subjected the patient’s samples to Sanger sequencing of these three genes.In this family,the variation locus was at GJB6(c.31G>A,p.Gly11Arg).Overex-pression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models,and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot,respectively.CONCLUSION We report another HED phenotype associated with GJB6 variations,which can help clinicians to diagnose HED despite its varying presentations.
基金National Natural Science Foundation of China(No.81402514)Support Program for Excellent Young Talents in Universities of Anhui Province(No.gxyq2022042)"512 Talent Cultivation Plan" of Bengbu Medical College(No.by51202208)。
文摘Objective: To explore the effect of connexin 32 (Cx32) on the cell proliferation, migration, invasion of human hepatocellular carcinoma (HCC) cell line Huh7 and its mechanism. Methods: Firstly, bioinformatics techniques were used to analyze the difference in expression of Cx32 between HCC tissues and normal liver tissues, and the relationship between Cx32 expression and important clinicopathological features of HCC was also explored. Subsequently, Cx32 expression in HCC cell lines and normal hepatic epithelial cell line was detected in vitro. Huh7 cell line with stable over⁃expression of Cx32 was further established, and the change in cell proliferation ability was measured by MTT assay, changes in migration and invasion capacities were detected by wound⁃healing assay and transwell assay, on this cell line. Finally, western blot and immunofluorescence (IF) were used to investigate the alterations of expression of epithelial⁃mesenchymal transition (EMT) markers. Results: Bioinformatics analyses showed that Cx32 mRNA and protein expression levels in HCC tissues were lower than those in normal liver tissues, and the mRNA expression level of Cx32 was negatively correlated with T stage, histological grade and clinical stage of HCC patients (all P<0.05). Results of in vitro experiments revealed Cx32 protein expression in different HCC cell lines was down⁃regulated compared to that in normal hepatic epithelial cell line LO2. Cx32 stably over⁃expressed (Cx32 OE) Huh7 cell line was successfully constructed by lentivirus infection and showed high expression of Cx32 protein in the cell line. Compared to the control group and (or) the negative control (NC) group, the Cx32 OE group exhibited decreased OD490 value, wound healing rate and invasive cell number (all P<0.05). Furthermore, an increase in the expression of epithelial marker E⁃cadherin, and a decrease in the expression of mesenchymal markers Snail and Vimentin, were observed in Cx32⁃OE Huh7 cell line. Conclusion: Cx32 is low expressed in HCC tissues and cells, while the proliferation, migration and invasion ability of Huh7 cells can be inhibited by over⁃expression of Cx32, of which the underlying mechanism may be related to the inhibition of EMT process.
