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ap junction proteins have a significant impact on the propagation of neuroinflammation after cerebral ischemia. Connexin 43 (Cx43 ), the principal connexin in the central nervous system, typically assembles hexameric hemichannels in an oligomeric state that dock with hemichannels on adjacent cells to form gap junction channels. Ordinarily, the likelihood of cell surface hemichannels opening is minimal. However, during cerebral ischemia, the excessive activation of Cx43 hemichannels leads to the liberation of a substantial quantity of ions (Na+, Cl-, Ca2+, and K+, glutamate, aspartate, and adenosine triphosphate (ATP), thereby resulting in impairment of adjacent cells and aggravation of neuronal injury. Furthermore, the activation of Cx43 hemichannels triggers the release of inflammatory factors, which exhibits a strong association with the activation of NLRP3 inflammasome after cerebral ischemia. Hence, the modulation of Cx43 hemichannels presents a potential avenue for mitigating neuroinflammation and subsequently diminishing cerebral ischemic injury. This article focuses on the relationship between Cx43 hemichannels and NLRP3 inflammasome activation, as well as its role in cerebral ischemia, all of which provide novel insights and therapeutic approaches for managing cerebral ischemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Connexin 43 (Cx43), which is thought to be engaged in the gap junction process and build the structural groundwork for the development of direct material signaling channels between cells, is crucial for maintaining the homeostatic balance of tissue metabolism. Recent research, however, has revealed fresh information about its distinct hemichannel function and highlighted the significance of its subcellular localization and self-fragmentation for cellular physiological activities and pathological processes. OBJECTIVE: To systematically summarize the molecular characteristics and expression of Cx43 in a variety of cells, concentrate on the pathological and physiological roles of channel-dependent Cx43 and channel-independent Cx43, and investigate the potential value in disease treatment by reviewing the pertinent literature in the database. METHODS: The Chinese and English keywords were “gap junction, connexin 43 (Cx43), hemichannel, channel-dependent Cx43, channel-independent Cx43, extracellular vesicles (EVs), mitochondria, GJA1-20k”, which were searched in PubMed and CNKI. Finally, 81 articles were selected for review. RESULTS AND CONCLUSION: (1) The canonical role of Cx43 is to form a gap junction channel. Channel-dependent Cx43 has primarily involved in disease physiopathological processes by directly constituting gap junction channels, but full attention should be paid to the issue of its structural and functional integrity. Adhesion is a crucial characteristic of gap junctions, which are strongly associated with barrier-like diseases. (2) The non-canonical role of Cx43 is nongap junction channel-dependent effect. In addition to being localized at the plasma membrane, inner mitochondrial membrane, extracellular vesicle surface, and other structures, Cx43 hexamer has also been found to play a role in positive pro-inflammatory mechanisms, mitochondrial functional metabolism, and targeted uptake of extracellular vesicles in inflammatory diseases. Selective shortened segments control mitochondrial homeostasis by encouraging the polymerization of peri-mitochondrial actin and are involved in the targeted translocation of full-length Cx43 to intracellular structural domains. (3) The development of targeted medicines and the solving of issues like the mechanism of seed cell transformation in tissue engineering-based therapies are both made possible by these two categories of impacts. The interactions of various types of Cx43, however, are frequently not fully taken into account in some of the existing original studies, which confuses the overall characteristics and skews the results. (4) It is necessary to systematically frame the physiological characteristics of Cx43 in different forms and its potential mechanisms in various diseases, so as to provide a reference for the exploration of the Cx43 integrity mechanism and the diagnosis and treatment of multiple diseases. [ABSTRACT FROM AUTHOR]

Stroke often leads to persistent post-stroke cognitive impairment (PSCI), which mainly manifests as impairment in learning and memory. The pathogenesis remains unclear as present, but it is closely related to mitochondrial dysfunction, and healthy mitochondria are essential for neuronal survival. Recent studies have shown that intercellular mitochondrial transfer can be linked to stroke through increasing neuronal viability, enhancing mitochondrial metabolism, and modulating neuroinflammation, thereby improving cognitive impairment. This review overviews the mechanisms of mitochondrial transfer and the key role of intercellular mitochondrial transfer in PSCI, and discusses that mitochondrial transplantation may serve as a novel therapeutic intervention for PSCI, providing references for its clinical management.

Objective To evaluate the effects of three antidepressants with different mechanisms on connexin expression and channel function of hippocampal astrocytes. Methods The cytotoxicity of antidepressants with different mechanisms on hippocampal astrocytes was assessed by CCK-8 assay. The effects of three antidepressants with different mechanisms on gap junction function and the expression level of connexin 43 protein （Cx43） were determined by cell inoculation fluorescence tracing and western blot. Results CCK-8 assay showed that 25.00 µmol/L fluoxetine, 0.10 µmol/L amitriptyline and 0.20 nmol/L venlafaxine had no cytotoxicity on hippocampal astrocytes （all P > 0.05）. In addition, 25.00 µmol/L fluoxetine, 0.10 µmol/L amitriptyline and 0.20 nmol/L venlafaxine could significantly inhibit the fluorescence transfer function of gap junction in hippocampal astrocytes （all P < 0.05）, whereas three antidepressants exerted on effects upon the expression of Cx43 in hippocampal astrocytes （all P > 0.05）. Conclusion Antidepressants can significantly reduce the gap junction function composed of Cx43 in hippocampal astrocytes.

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the expression of connexin43 (Cx43) in diabetic cystopathy (DCP) and study its significance. Methods Fifty guinea pigs were randomly divided into DCP group (n=30), sodium citrate group (n=10) and blank control group (n=10). Diabetic model was established by intraperitoneal injection of streptozotocin in DCP group. Diabetic bladder guinea pigs were screened by urodynamics test. The sodium group was intraperitoneally injected with sodium citrate solution, and the blank control group was injected intraperitoneally with normal saline. The location and distribution of Cx43 in the three groups of bladder detrusor were observed by immunohistochemical staining, and expressions of Cx43 proteins were detected by Western blot assay. Results Immunohistochemical staining showed that the intensity of Cx43-specific staining was significantly lower in DCP group than that in the other two groups. There was no significant difference in the positive staining intensity between sodium citrate group and blank control group. Western blot analysis showed that the expression of Cx43 protein was significantly lower in bladder tissue of DCP group (0.52±0.02) than that of blank control group (0.68±0.02) and sodium citrate group (0.70±0.03,P ＜0.01). There was no significant difference in the expression of Cx43 protein in the bladder tissue between the sodium citrate group and blank control group (P ＞0.01). Conclusion The decreased expression of Cx43 in detrusor tissue plays an important role in the formation of diabetic bladder and may be a new starting point for studying the pathogenesis of diabetic bladder. [ABSTRACT FROM AUTHOR]

BACKGROUND: Satellite glial cells which are the main glial cell type in the dorsal root ganglia can interact and communicate with dorsal root neuron cell bodies through various approaches to be involved in the occurrence and regulation of chronic pain. Previous studies have focused on the sensitized neuronal cell bodies of satellite glial cells, and there is less concern about inhibitory regulation between them. So far there has been no research on their exchange as well as no discussion on their internal relationship. OBJECTIVE: To review the possible interaction and communication mechanisms between satellite glial cells and neurons in terms of structural morphology, ion channels, protein receptors and interactions between adjacent satellite glial cells. METHODS: PubMed, Web of Science, SinoMed, and CNKI were retrieved with the keywords of “pain, satellite glial cell, DRG, gap junction” for relevant articles published from January 2008 to February 2019. We also traced highly relevant references cited in the literature. Finally, 77 eligible studies were included. RESULTS AND CONCLUSION: In the dorsal root ganglia, satellite glial cells surround single neurons to form satellite glial sheathes. “Neuron-satellite glial cell” functional units are the base for mutual regulation between adjacent neurons. Majority of the studies have considered that satellite glial cells play an important role in the development and maintenance of chronic pain diseases; however, some studies have found the inhibitory regulation between satellite glial cells and neurons, which activates P2Y1 receptor and glutamate transporters to inhibit the occurrence of pain. Therefore, to regulate P2Y1 receptor and glutamate transporter activities in the dorsal root ganglia can be used as a new target for the treatment of pain. [ABSTRACT FROM AUTHOR]

Background and objective Cisplatin is a standard first-line chemotherapeutic agents for treating advanced non-small cell lung cancer. Unfortunately, the clinical application cisplatin is restricted because it induces serious adverse reaction. The aim of this study is to investigate the influence and probable mechanism of berberine on cisplatin antineoplastic effect on lung cancer A549 cells. Methods The total Cx43 protein amount, localization of Cx43 on cell membrane, and gap junction function were observed after the A549 cells were treated with berberine. The influence of berberine on the antitumor action of cisplatin was detected by standard colony-forming assay. Protein kinase C (PKC) protein, which regulates the gap junction, was subsequently determined. Results Berberine did not affect cell survival at concentrations of 0 μM to 10 μM in the A549 cells. The gap junction function between the cells was enhanced through increased Cx43 protein expression and localization of Cx43 on the membrane after berberine treatment. The intercellular dye coupling through gap junction increased when the cells exposed to 0.1 μM, 1 μM, 10 μM berberine [33.3% (P=0.002,3), 67.0% (P

Connexin43 (Cx43) is the most abundant connexin and mainly distributes in astrocytes in the central nervous system (CNS). Cx43 comes form gap junctions (GJs) allowing direct cell-to-cell exchange, it can also come form hemichannels (HCs) to provide a direct link between the intracellular components and the extracellular environment. With aging of the population in worldwide, the prevalence of Alzheimer's disease, stroke and postoperative cognitive dysfunction increases rapidly. Neuroinflammation, a common process associated with those CNS diseases, is characterized by leukocyte recruitment, reactive gliosis, release of inflammatory factors and needs efficient communication. Recent studies reveal that Cx43 plays a key role in neuroinflammation, and its process characterized by the inhibition of Cx43GJs and the activation of HCs, which affects neurologic functions. The purpose of this review is to discuss the relations between Cx43 and neuroinflammation, and provide a novel target for the treatment of CNS diseases. [ABSTRACT FROM AUTHOR]

Objective To make a systematic analysis of the interaction between osteoporosis and smoking to elucidate the molecular mechanisms underlying osteoporosis susceptibility affected by smoking. Methods First, a two-way ANOVA analysis was conducted using microarray data to search all potential genes associated with both smoking and osteoporosis. We further explored the potential biologically related metabolic pathways through gene pathway enrichment analysis. Then the interaction genes within enriched pathways were verified by genome-wide gene-environment interaction analysis. Finally, protein-protein interaction analysis was applied to identify the core regulatory network in which those verified genes involved. Results We identified 441 risk genes closely associated with both smoking and osteoporosis by microarray analysis. Through gene pathway analysis, we identified a vital metabolism pathway, gap junction, which is a potential mediator between smoking and osteoporosis process. Finally, we verified some critical genes by genome-wide gene-environment interaction analysis, and revealed a potential smoking-osteoporosis interaction core regulatory network that included 13 proteins by protein network analysis. Conclusion We have discovered a new regulatory framework connecting smoking and osteoporosis, which provides new clues about disease etiologies and novel promising drug targets. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on the myocardial remodeling and connexin 43 (Cx43) expression of rats with cardiac failure caused by pressure overload. Methods Forty-five male SD rats were randomly divided into the heart failure group ( group F), heart failure + rhBNP group (group B), and sham operation group (group SO) with 15 rats in each group. In the group F and group B, we established the rat models of pressure overload-induced heart failure by abdominal aortic constriction, while in the SO group, rats did not receive coarctation of the abdominal aorta. Rats in the group B were subcutaneously injected with rhBNP (25 μg/kg/d), while rats in the group SO and group F wrere injected intraperitoneally with normal saline for 8 weeks. The left ventricular function, hemodynamics, QT dispersion, left ventricular myocardial pathology, myocardial fibrosis and collagen deposition, and myocardial Cx43 protein expression were detected in each group. Results Compared with the SO group, the left ventricular function, hemodynamics, QT dispersion, left ventricular myocardial histopathology, myocardial fibrosis deposition, myocardial Cx43 protein expression were statistically significant in the group F ( all P < 0.05 ), which showed that heart failure model was established successfully. Compared with group F, the heart function of rats increased, the mean arterial pressure and QT dispersion decreased, the disordered arrangement of myocardial cells reduced, collagen deposition decreased between cardiac myocytes, and the expression of Cx43 increased in the group B (all P < 0.05 ). Conclusion rhBNP can improve the cardiac function and hemodynamic indexes in rats with heart failure under pressure overload, up-regulate the myocardial expression of Cx43 protein, and inhibit myocardial remodeling. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of estrogen (E2) on the connexin43 (Cx43) expression of renal interlobar arteries after renal ischemia-reperfusion injury (I/R). Methods The experiment was carried out in vivo using an SD rat I/R model. SD rats were randomly divided into normal group, sham-operation group, I/R group, and estrogen-intervention group. The functional changes of the kidney were analyzed after 24 hours of I/R; nephridial tissue section was stained by hematoxylin-eosin (HE), and Paller scores were used to evaluate the degree of kidney damage. Pressure myography was utilized to detect the vasomotor function of renal interlobar arteries. Immunofluorescence technique, qRT-PCR and Western blot were applied to determine the expression of Cx43 in renal interlobar arteries in different groups. Results Estrogen markedly decreased the levels of Cr and BUN in the serum of I/R rats (P<0.05), and the damage of the kidney tissue could be improved noticeably. The vasomotor rate of renal interlobar arteries was (24.80±3.70)% after I/R and (41.60±3.50)% after treatment with estrogen, which was higher than that of I/R group (P<0.05). The expression of Cx43 was lower in renal interlobar arteries of estrogen-intervention group than that in I/R group (P<0.01). Conclusion Estrogen may reduce vascular tension and boost dilation of the artery by inhibiting Cx43 expression and GJ function. Therefore, estrogen may attenuate the damage of I/R and improve renal function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of methylselenocysteine (MSC) on the function of homotypic gap junction (GJ) composed of connexin (Cx) 26 and its regulation of chemotherapeutic drug cytotoxicity., Methods: The Tet-on HeLa cells transfected with and stably expressing Cx26 were used as the tool cells. Effects of MSC on cell growth, GJ function, and Cx26 protein expression were examined by MTT method, parachute assay, and Western blot analysis, respectively. The cytotoxicity of chemotherapeutic drugs was determined by standard colony-forming assay, and the relationship between MSC's effect on cytotoxicity of these chemotherapeutic drugs and its regulation of GJ was further analyzed., Results: In Tet-on HeLa cells, doxycycline (Dox) can induce the expression of Cx26, which could then form functional GJs. Within a concentration range of 50 μmol/L, MSC had no significant effect on HeLa cell growth. Non-toxic concentrations of MSC can enhance GJs in a concentration-dependent manner and exert its effect at the nanomolar level. This effect was associated with an induction of Cx26 protein expression by MSC. Among the three common chemotherapeutic agents with different mechanisms of action, etoposide (Eto) presented cytotoxicity differences between HeLa cells cultured at low density (nonconfluent, no GJ formed) and high density (confluent, GJ formed). What's more, the inhibitory effect of Eto combined with MSC on HeLa cell colony formation was stronger than that of Eto alone, and this effect occurred only in HeLa cells with GJ formation., Conclusion: MSC can potentiate the cytotoxicity of Eto by enhancing the GJs composed of Cx26, indicating that combined strategy of selenide and chemotherapy shows potential value in the treatment of malignant tumors., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Gastrointestinal motility dysfunction was an important clinical manifestation of many gastrointestinal diseases and other diseases, and the incidence rate of gastrointestinal dysfunction in gastrointestinal diseases was above 70 %. Gap junction protein 43 (connexin 43, Cx43) was the most important gap junction protein in cell gap junction communication, which played a key role in the formation and regulation of gastrointestinal motility. The treatment effect of Traditional Chinese and Western medicine on gastrointestinal diseases was significant, but the molecular mechanismwas not yet clear. The progress of Cx43 in the regulation of gastrointestinal motility disorders from the gap junction communication in Cx43 is reviewed in this article, which lays foundation for further research on the mechanismof the regulation of gastrointestinal motility disorders in Traditional and Modern medicine. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Lung Cancer is the property of Chinese Journal of Lung Cancer and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate the effect of connexin43 (Cx43) protein on autophagy in cisplatin (DDP)-resistant testicular cancer I-10 cells., Methods: The expression of Cx43 proteins in testicular cancer I-10 cells and I-10/DDP cells were detected with Western blotting. I-10/DDP cells were transfected with a full- length mouse Cx43 vector (mCx43) via Lipofectamine 2000 , the empty vector or Lipofectamine 2000 (blank control group), and the changes in the expressions of LC3 and p62 proteins were determined with Western blotting. mCherry-GFP-LC3B transfection and transmission electron microscopy were used to analyze the changes in autophagy of the cells with Cx43 overexpression., Results: Cx43 was significantly decreased in I-10/DDP cells compared with I-10 cells ( P &lt; 0.01). Transfection of the I-10/DDP cells with mCx43 vector resulted in significantly increased Cx43 expression in the cells ( P &lt; 0.01) and caused significantly decreased expression of LC3-Ⅱ ( P &lt; 0.01) and increased expression of p62 ( P &lt; 0.05) as compared with the negative control cells. Both transmission electron microscopy and mCherry-GFP-LC3B transfection showed that the number of autophagosomes was obviously reduced in mCx43-transfected cells as compared with the negative control cells., Conclusions: Cx43 inhibits autophagy in cisplatin-resistant testicular cancer I-10 /DDP cells.

Objective: To observe the effect of electroacupuncture (EA) on expression of cerebral Cx43 protein in acute cerebral infarction (ACI) rats so as to explore its mechanisms underlying improvement of ACI., Methods: Sixty male SD rats were randomly divided into sham operation, model and EA preconditioning groups ( n ＝20 in each group). Fourteen days before modeling, the rats in the EA preconditioning group accepted EA stimulation (3 Hz/15 Hz, 1 mA) at Dingzhongxian (MS5) and Dingpangxian (MS8) for 30 min, once daily, 6 times a week for 2 weeks. The ACI model was established by occlusion of the middle cerebral artery for 120 min, followed by reperfusion. Twenty-four hours after modeling, the neurological function was evaluated according to the Zea-Longa's score criteria. The triphenyltetrazolium chloride (TTC) staining method was used to detect the cerebral infarct volume. The expression levels of Cx43, phosphorylated (p)-Cx43 and PKC proteins in the right cerebral cortical infarction region were detected by Western blot., Results: The neurological function scores and the infarct volume were significantly higher in the model group than those in the sham operation group ( P <0.05), and obviously lower in the EA preconditioning group than in the model group ( P <0.05). The expression level of cerebral Cx43 protein was significantly increased ( P <0.05), and those of p-Cx43 and PKC proteins were notably decreased in the model group relevant to the sham operation group ( P <0.05). In the EA preconditioning group, the expression level of Cx43 was significantly decreased and those of p-Cx43 and PKC proteins were significantly increased than those in the model group ( P <0.05)., Conclusion: EA pretreatment can relieve neurological damage and reduce cerebral infarction volume in ACI rats, which may be related to its function in promoting Cx43 protein phosphorylation via up-regulating PKC expression in the ischemic cerebral region.

Objective: To investigate the mutation characteristics of GJB6 (gap juction bata 6) gene in 318 Han Chinese pedigrees with non-syndromic hearing loss. Method: Polymerase chain reaction was used to detect the coding region of GJB6 gene in 318 Han Chinese pedigrees with non-syndromic hearing loss.Gene arrays and second generation sequencing were used to detect 118 genes which had reported to be accosiated with deafness in members of pedigree which possibly carried pathogenic GJB6 gene mutation. Result: Here,we have screened the mutations of GJB6 gene in 318 Han Chinese pedigrees with non-syndromic hearing loss and found one pedigree carrying both GJB6 and GJB2 gene deletion.Clinical and molecular genetic evaluation revealed the variable phenotype of hearing impairments including age-at-onset,audiometric configuration and severity in these subjects.Mutational analysis of the GJB2 and GJB6 gene coding region showed a heterozygous 235 del C of GJB2 gene and a novel 228 del G of GJB6 gene. Conclusion: GJB6 gene 228 del G absent varies among 94 unrelated Chinese controls.Our finding suggest that GJB6 gene 228 del G absent varies among 94 unrelated Chinese controls.Our finding suggest that GJB6 gene 228 del G maybe a novel pathogenic mutation associated with non-syndromic hearing loss., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)