Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.

Objective To investigate the role and molecular mechanisms of bladder cancer-derived exosomal long non-coding RNA(lncRNA)CIAT1 in mediating collective invasion and to evaluate its clinical significance and potential therapeutic value.Methods High-throughput sequencing was used to identify lncRNAs that are highly expressed in exosomes from bladder cancer and lymph node metastatic tissues.CIAT1 was selected for further validation in clinical bladder cancer samples.By constructing CIAT1-overexpressing and knockdown bladder cancer cells,we demonstrated in vitro that CIAT1-contained exosomes target cancer-associated fibroblasts(CAFs)to induce collective invasion.The underlying mechanism of CIAT1 in bladder cancer collective invasion was explored through RNA pull-down,RNA immunoprecipitation(RIP),dual-luciferase reporter assays,chromatin isolation by RNA purification(ChIRP)and chromatin immunoprecipitation(ChIP).Results CIAT1 was significantly upregulated in exosomes derived from bladder cancer tissues compared to adjacent normal tissues by High-throughput sequencing(fold change>1.5,P<0.05)and clinical sample validation(P<0.01).In vitro experiments,exosomal CIAT1 was selectively internalized by cancer-associated fibroblasts(CAFs),significantly enhancing collective invasion of bladder cancer via regulating CAFs.In co-culture models,CIAT1 overexpression group showed increased total number and total length of collective invasion chains compared to the control group(P<0.01 for both).Mechanistically,CIAT1 was packaged into exosomes via binding to hnRNPA2B1,and internalized by CAFs,where it activated N-cadherin transcription by modulating H3K4me3 histone modification at the N-cadherin promoter.Consistently,the CIAT1 overexpression group exhibited elevated collective invasion chain numbers and lengths compared to the control group(P<0.01 for both).However,blocking N-cadherin reversed the pro-invasive effects of CIAT1,with no significant differences in chain numbers or lengths between the CIAT1 overexpression+N-cadherin blockade group and controls(P>0.05 for both).Further clinical correlation analysis confirmed that CIAT1-regulated N-cadherin is closely associated with collective invasion in bladder cancer patients(P<0.01).Conclusions Exosomal CIAT1 derived from bladder cancer cells targets CAFs to activate N-cadherin transcription,thereby promoting bladder cancer collective invasion.

Objective To investigate the role and molecular mechanisms of bladder cancer-derived exosomal long non-coding RNA(lncRNA)CIAT1 in mediating collective invasion and to evaluate its clinical significance and potential therapeutic value.Methods High-throughput sequencing was used to identify lncRNAs that are highly expressed in exosomes from bladder cancer and lymph node metastatic tissues.CIAT1 was selected for further validation in clinical bladder cancer samples.By constructing CIAT1-overexpressing and knockdown bladder cancer cells,we demonstrated in vitro that CIAT1-contained exosomes target cancer-associated fibroblasts(CAFs)to induce collective invasion.The underlying mechanism of CIAT1 in bladder cancer collective invasion was explored through RNA pull-down,RNA immunoprecipitation(RIP),dual-luciferase reporter assays,chromatin isolation by RNA purification(ChIRP)and chromatin immunoprecipitation(ChIP).Results CIAT1 was significantly upregulated in exosomes derived from bladder cancer tissues compared to adjacent normal tissues by High-throughput sequencing(fold change>1.5,P<0.05)and clinical sample validation(P<0.01).In vitro experiments,exosomal CIAT1 was selectively internalized by cancer-associated fibroblasts(CAFs),significantly enhancing collective invasion of bladder cancer via regulating CAFs.In co-culture models,CIAT1 overexpression group showed increased total number and total length of collective invasion chains compared to the control group(P<0.01 for both).Mechanistically,CIAT1 was packaged into exosomes via binding to hnRNPA2B1,and internalized by CAFs,where it activated N-cadherin transcription by modulating H3K4me3 histone modification at the N-cadherin promoter.Consistently,the CIAT1 overexpression group exhibited elevated collective invasion chain numbers and lengths compared to the control group(P<0.01 for both).However,blocking N-cadherin reversed the pro-invasive effects of CIAT1,with no significant differences in chain numbers or lengths between the CIAT1 overexpression+N-cadherin blockade group and controls(P>0.05 for both).Further clinical correlation analysis confirmed that CIAT1-regulated N-cadherin is closely associated with collective invasion in bladder cancer patients(P<0.01).Conclusions Exosomal CIAT1 derived from bladder cancer cells targets CAFs to activate N-cadherin transcription,thereby promoting bladder cancer collective invasion.

AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*

Objective To observe the clinical manifestations of 3 cases with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis antibody overlapping syndrome (MNOS), aiming to expand the understanding of the clinical spectrum of such syndromes. Methods Retrospective analysis was performed on the data of 3 patients with MNOS who were positive for both MOG antibodies and NMDAR antibodies. Clinical features, neuroimaging characteristics, and outcomes were collected, and cell-based assay (CBA) technique was used for diagnosis. Results One case presented both positive MOG antibodies and NMDAR antibodies, but the clinical manifestations were typical symptoms of anti-NMDAR encephalitis. In one case, the clinical and cranial magnetic resonance imaging (MRI) features of demyelinating disease recurred after anti-NMDAR encephalitis, with atypical symptoms of MNOS such as numbness and weakness in limbs, blurred vision, and diplopia. The last case presented both positive MOG antibodies and NMDAR antibodies, but the clinical manifestations were typical symptoms of anti-NMDAR encephalitis. In MNOS, MOG antibody-associated disease and anti-NMDAR encephalitis may appear simultaneously or sequentially, with epilepsy being the most common symptom. Cranial MRI findings showed that the patients presented and mainly involved supratentorial lesions, which may also involve the brainstem, but no spinal cord lesions were found. All patients showed slightly abnormal cerebrospinal fluid. Patients showed a good response to first-line immunotherapy during the acute phase of the disease, with a favorable prognosis. But most patients were prone to relapse. Conclusion In MNOS patients, anti-NMDAR encephalitis may present with clinical and(or)MRI features of demyelinating disease simultaneously or sequentially. The clinical manifestations of patients are complex and diverse. Patients with atypical symptoms require to improving the understanding of MNOS and timely treatment.