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
Epilepsy,a chronic neurological disorder,is characterized by dysfunction in neural networks.Gap junctions and hemichannels,which are integral to the astrocyte connection network,play a critical role in epilepsy.Connex...Epilepsy,a chronic neurological disorder,is characterized by dysfunction in neural networks.Gap junctions and hemichannels,which are integral to the astrocyte connection network,play a critical role in epilepsy.Connexins,the components of astrocyte gap junctions and hemichannels,can be activated to transfer glutamate,adenosine triphosphate,and other chemicals,potentially leading to seizures.Connexins therefore hold signifcant potential for epilepsy treatment.This review focuses on connexin 43 and provides a brief overview of other connexins and pannexin 1.Understanding the relationship between connexins and epilepsy ofers theoretical support for developing new antiseizure medications.展开更多
Alzheimer's disease(AD),the leading cause of dementia,remains a formidable challenge to neurology.Despite decades of research focused on amyloid-β(Aβ)and tau pathologies,most clinical trials targeting these mole...Alzheimer's disease(AD),the leading cause of dementia,remains a formidable challenge to neurology.Despite decades of research focused on amyloid-β(Aβ)and tau pathologies,most clinical trials targeting these molecules failed,highlighting the need for alternative strategies[1].Recent attention has turned to neuroinflammation,particularly the role of microglia,the brain's resident immune cells[1].Microglia are central to AD progression.They can degrade Aβplaques and protect neurons,but may also exacerbate neurotoxicity through chronic inflammation[1].展开更多
Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of lo...Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.展开更多
BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a r...BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic function.AIM To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining.The mice were treated with exogenous GDNF and Gap 19,a selective Cx43 inhibitor.The Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain reaction.The levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent assay.RESULTS Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.CONCLUSION GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism.GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.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.
基金supported by Natural Science Foundation of Beijing Municipality(grant number L222078)National Science Foundation of China(grant number 82071448)。
文摘Epilepsy,a chronic neurological disorder,is characterized by dysfunction in neural networks.Gap junctions and hemichannels,which are integral to the astrocyte connection network,play a critical role in epilepsy.Connexins,the components of astrocyte gap junctions and hemichannels,can be activated to transfer glutamate,adenosine triphosphate,and other chemicals,potentially leading to seizures.Connexins therefore hold signifcant potential for epilepsy treatment.This review focuses on connexin 43 and provides a brief overview of other connexins and pannexin 1.Understanding the relationship between connexins and epilepsy ofers theoretical support for developing new antiseizure medications.
基金supported by the National Natural Science Foundation of China(32170980)Guangdong Basic and Applied Basic Research Foundation(2022B1515020012)+7 种基金Shenzhen Fundamental Research Program(RCJC20231211090018040,ZDSYS20220606100801003)the 2023 Key Support Project of the Liaoning Provincial Department of Science and Technology([2023]61-7)the Ciberned(CB06/05/0076)the Spanish MICINN grant(PID2022-143020OB-I00)the Basque Government grant(IT1551-22)the Slovenian Research Agency grant J4-60077the Science and Technology Planning Project of Guangdong Province(2021B1212040006)the Sanming Project of Medicine in Shenzhen(SZSM202411023,SZSM202411013).
文摘Alzheimer's disease(AD),the leading cause of dementia,remains a formidable challenge to neurology.Despite decades of research focused on amyloid-β(Aβ)and tau pathologies,most clinical trials targeting these molecules failed,highlighting the need for alternative strategies[1].Recent attention has turned to neuroinflammation,particularly the role of microglia,the brain's resident immune cells[1].Microglia are central to AD progression.They can degrade Aβplaques and protect neurons,but may also exacerbate neurotoxicity through chronic inflammation[1].
基金supported by NIH/NIDCR grant R01DE025664 to IPC.
文摘Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.
文摘BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic function.AIM To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining.The mice were treated with exogenous GDNF and Gap 19,a selective Cx43 inhibitor.The Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain reaction.The levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent assay.RESULTS Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.CONCLUSION GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism.GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.
