{"title":"The Role of miRNAs in Podocyte Injury in Diabetic Nephropathy: Mechanisms and Clinical Applications.","authors":"Shan Hu, Jiafu Yan, Qiong Yuan, Tianjiao Meng, Zhi Cai, Yuanshuai Huang, Yuhan Wang","doi":"10.2174/0118761429363169250313083148","DOIUrl":"10.2174/0118761429363169250313083148","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the most frequent complications of diabetes and, if left uncontrolled, can progress to renal failure. In the early stage of DKD, significant pathological changes occur in podocytes, leading to proteinuria. However, the mechanism of pathological changes in podocytes has not been clarified. Existing clinical diagnostic methods tend to overlook these subtle pathophysiological changes in the early stages, leading to missed optimal treatment time. Moreover, existing treatment methods are limited. Emerging evidence strongly suggests that podocyte injury is associated with distinct specific miRNA expression profiles that precede the onset of overt proteinuria and glomerular filtration rate decline. This review explores the role of microRNAs in podocyte damage-related pathways in DKD, such as reactive oxygen species (ROS) production and inflammatory responses. Furthermore, we discuss the potential clinical application of miRNAs as molecular markers and their feasibility as a molecular therapy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429363169"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current Strategies for the Management of Psoriasis with Potential Pharmacological Pathways using Herbals and Immuno-biologicals","authors":"Kiran Singh Sharma, Sumit Kumar","doi":"10.2174/1874467217666230915125613","DOIUrl":"10.2174/1874467217666230915125613","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is an acute to chronic multifunctional inflammatory skin disorder mediated through T-cell activation, dendritic cell intervention, local vascular variations, atypical keratinocyte proliferation, and neutrophil activation, leading to a skin disorder with no permanent cure.</p><p><strong>Objective: </strong>This review aims to find a potent, secure, and dependable medication, with a more scientific examination of herbal resources and recent targeted immunobiological therapies.</p><p><strong>Method: </strong>Reports evaluating the effectiveness of biologics & herbal remedies for the topical therapy of psoriasis against control therapies were taken into consideration (placebo or active therapy). The work examined cellular circuits involved in inflammation with its immunogenetic mechanism behind various options available for treating psoriasis in addition to the role of agents inducing psoriasis.</p><p><strong>Results: </strong>The extent of psoriasis can range from small, localized spots to total body coverage, and it can happen at any stage of life. Several theories exist for clarification however, the exact cause of psoriasis is not entirely understood. Researchers have discovered genetic loci linkages, environmental changes, drug induction, lifestyle conditions, some infections, etc. resulting in this disorder. There are numerous known conventional medical treatments for psoriasis, ranging from topical and systemic medicines to phototherapy or combinations of both with recent immunobiological treatment. However, the majority of these treatments are ineffective and have a variety of side effects that limit their long-term usage, such as cutaneous atrophy, tissue toxicity, mutagenicity, and immunosuppression.</p><p><strong>Conclusion: </strong>Herbal extracts or isolated compounds can be considered as a substitute for conventional psoriasis treatment. Unfortunately, many investigations often provide a small amount of facts about the safety and effectiveness of topically applied herbal remedies for the treatment of psoriasis. Thus, further factual evidences and validations are needed to promote herbal options, which must be supported by rigorous animal studies or clinical trials using standardised materials and compositions.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e150923221163"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravikant Sharma, M D Abubakar, Priya Bisht, Mahesh Rachamalla, Arun Kumar, Krishna Murti, Velayutham Ravichandiran, Nitesh Kumar
{"title":"Arsenic Exposure and Amyloid Precursor Protein Processing: A Focus on Alzheimer's Disease.","authors":"Ravikant Sharma, M D Abubakar, Priya Bisht, Mahesh Rachamalla, Arun Kumar, Krishna Murti, Velayutham Ravichandiran, Nitesh Kumar","doi":"10.2174/0118761429272806231020045840","DOIUrl":"10.2174/0118761429272806231020045840","url":null,"abstract":"<p><strong>Background: </strong>Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition.</p><p><strong>Aims: </strong>Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer's disease.</p><p><strong>Methods: </strong>The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer's disease through the published article from Pubmed and Scopus.</p><p><strong>Description: </strong>According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by β-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article.</p><p><strong>Conclusion: </strong>A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer's disease.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429272806"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"All-trans Retinoic Acid Increased Transglutaminase 2 Expressions in BV-2 Cells and Cultured Astrocytes.","authors":"Katsura Takano-Kawabe, Tatsuhiko Izumo, Tomoki Minamihata Minamihata, Mitsuaki Moriyama","doi":"10.2174/0118761429254388230922112915","DOIUrl":"10.2174/0118761429254388230922112915","url":null,"abstract":"<p><strong>Background: </strong>Activation of microglia and astrocytes has been observed in Alzheimer's disease (AD). Transglutaminase 2 (TG2) is reported to be activated in AD and involved in cell proliferation, differentiation, and inflammation. Moreover, amyloid β (Aβ) aggregation is detected as a characteristic pathology in the AD brain, and is known to be a substrate of TG2. All-trans retinoic acid (ATRA) can modify cell proliferation and differentiation, and is reported to have therapeutic effects on AD pathology.</p><p><strong>Objective: </strong>We aimed to assess the effects of ATRA in microglia and astrocytes on TG2 expression and glial functions.</p><p><strong>Methods: </strong>After treatment with ATRA, TG2 expression and TG activity were assayed in both murine microglia BV-2 cells and cultured rat brain astrocytes. Endocytosis activity in BV-2 cells and Aβ aggregation by astrocytes conditioned medium were also assessed.</p><p><strong>Results: </strong>In both BV-2 cells and cultured astrocytes, ATRA increased TG2 expression and TG activity. The increase was blocked by AGN194310, an RA receptor antagonist. ATRA enhanced the endocytosis activity in BV-2 cells, and the addition of AGN194310 reversed it. The addition of cystamine, a competitive TG inhibitor, also reduced ATRA-enhanced endocytosis activity. On the other hand, Aβ aggregation was potentiated by ATRA-treated astrocytes conditioned medium compared to control astrocytes conditioned medium.</p><p><strong>Conclusion: </strong>These results suggest that ATRA increased TG2 expression and TG activity via RA receptor in microglia and astrocytes. ATRA-enhanced TGs might be involved in phagocytosis and Aβ aggregation. Adequate control of TGs expression and function in microglia and astrocytes can be an important factor in AD pathology.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429254388"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yejiao Ruan, Guangrong Lu, Yaojun Yu, Yue Luo, Hao Wu, Yating Shen, Zejun Gao, Yao Shen, Zhenzhai Cai, Liyi Li
{"title":"PF-04449913 Inhibits Proliferation and Metastasis of Colorectal Cancer Cells by Down-regulating MMP9 Expression through the ERK/p65 Pathway.","authors":"Yejiao Ruan, Guangrong Lu, Yaojun Yu, Yue Luo, Hao Wu, Yating Shen, Zejun Gao, Yao Shen, Zhenzhai Cai, Liyi Li","doi":"10.2174/1874467217666230915125622","DOIUrl":"10.2174/1874467217666230915125622","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer remains a life-threatening malignancy with increasing morbidity and mortality worldwide. Therefore, new and effective anti-colorectal cancer therapeutics are urgently needed.</p><p><strong>Method: </strong>In this study, we have studied the anti-tumor properties and potential mechanisms of PF-04449913. Colorectal cancer cell viability was reduced by PF-04449913 in a dose-dependent manner. The migration and invasion ability of malignant colon cells were attenuated by the drug, as demonstrated by the Transwell test. Moreover, PF-04449913 repressed the phosphorylation levels of ERK and other proteins, and the expression levels of MMP9. The anti-tumor effects of the drug in vivo were demonstrated in BALB/c-nude mice models, and PF-04449913 inhibited the malignant phenotype of colorectal cancer cells, including reduction of tumor size and promotion of apoptosis. At the molecular level, PF-04449913 induced a significant decrease in ERK and p65 protein phosphorylation levels and inhibited MMP9 protein expression.</p><p><strong>Results: </strong>Both in vivo and in vitro results showed PF-04449913 to demonstrate antitumor effects, which have been proposed to be mediated through blockade of the ERK/p65 signaling pathway, and subsequent repression of MMP9 expression.</p><p><strong>Conclusion: </strong>Our study provides a new perspective on the potential clinical application of PF-04449913 in the treatment of colorectal cancer.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e150923221164"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Review of the Role of Metabolic Factors in Determining the Post-surgical Adhesion and its Therapeutic Implications, with a Focus on Extracellular Matrix and Oxidative Stress.","authors":"Mahmoud Tavakkoli, Rozita Khodashahi, Mohsen Aliakbarian, Hoda Rahimi, Kiarash Ashrafzadeh, Gordon Ferns, Ebrahim Khaleghi, Mohammad-Hassan Arjmand","doi":"10.2174/0118761429246636230919122745","DOIUrl":"10.2174/0118761429246636230919122745","url":null,"abstract":"<p><p>The potential role of metabolic reprogramming in fibrogenesis has recently attracted interest. Extracellular matrix stiffness, inflammation, and subsequent oxidative stress are essential mediators in the causation of fibrosis. The prevention of post-surgical adhesion is a challenge in medicine. It is defined as a fibrotic disorder in which adhesive bands develop after abdominal or pelvic surgery. Despite many studies related to the pathogenesis of post-surgical adhesion (PSA), many unknowns exist. Therefore, evaluating different pathways may help characterize and identify the cause of fibrotic scar formation post-operation. Glucose and lipid metabolism are crucial metabolic pathways in the cell's energy production that may be targeted by hypoxia-induced factor alpha and profibrotic cytokines such as TGF-β to mediate fibrogenesis. Inhibition of upregulated metabolic pathways may be a viable strategy for ameliorating post-surgical adhesion. In this review, we have discussed the potential role of altered glucose and lipid metabolism in extracellular matrix (ECM) stiffness and oxidative stress as crucial mediators in fibrosis.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429246636"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of Chrysin and Chrysin Nanocrystals on Chlorpyrifos-Induced Dysfunction of the Hypothalamic-Pituitary-Testicular Axis in Rats","authors":"Tahereh Farkhondeh, Babak Roshanravan, Fariborz Samini, Saeed Samarghandian","doi":"10.2174/0118761429305457240826093330","DOIUrl":"10.2174/0118761429305457240826093330","url":null,"abstract":"<p><strong>Aims and background: </strong>The escalating global concerns regarding reproductive health underscore the urgency of investigating the impact of environmental pollutants on fertility. This study aims to focus on Chlorpyrifos (CPF), a widely-used organophosphate insecticide, and explores its adverse influence on the hypothalamic-pituitary-testicular axis in Wistar male rats. This study explores the potential protective effects of chrysin nanocrystal (CHN), a flavonoid with known antioxidant and anti-inflammatory properties, against CPF-induced impairments in male Wistar rats.</p><p><strong>Methods: </strong>Chrysin nanocrystals were prepared using a solvent precipitation method. Six sets of male Wistar rats were subjected to 30 days of treatment, comprising a control group, a group treated solely with CPF, groups treated with CHN at doses of 5 mg/kg and 10 mg/kg, and groups co-treated with CPF and CHN. Serum levels of reproductive hormones, enzyme biomarkers of testicular function, oxidative stress, and inflammatory biomarkers were assessed. Additionally, histological examinations were conducted on the hypothalamus, testes, and epididymis.</p><p><strong>Results: </strong>CHN exhibited antioxidant and anti-inflammatory properties, effectively counteracting CPF-induced reductions in Luteinizing Hormone (LH), serum testosterone, Follicle-Stimulating Hormone (FSH), and testicular enzyme biomarkers. Moreover, CHN enhanced antioxidant defenses, as evidenced by decreased malondialdehyde (MDA) and increased glutathione (GSH) levels in the hypothalamus, and testes, epididymis. Inflammatory markers, including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were significantly reduced in CHN co-treated groups compared to the CPF-only group. Histopathological analyses confirmed the protective effects of CHN on tissue integrity.</p><p><strong>Conclusion: </strong>Chrysin nanocrystal demonstrated promising potential in mitigating CPF-induced reproductive deficits in male rats through its anti-inflammatory and antioxidant properties. This study provides valuable insights into therapeutic interventions against environmental toxin-induced reproductive toxicity, emphasizing the potential of chrysin nanocrystals as a protective agent in the context of CPF exposure.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429305457"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amin Reza Nikpoor, Mahmoud Mahmoudi, Abbas Shapouri-Moghaddam, Zahra Rezaieyazdi, Samaneh Mollazadeh, Nafiseh Tabasi, Atena Mansouri, Reyhane Modarres Moghadam, Amir Abbas Momtazi, Soran K Najmaldin, Ramiar Kamal Kheder, Seyed-Alireza Esmaeili
{"title":"Curcumin and Berberine Arrest Maturation and Activation of Dendritic Cells Derived from Lupus Erythematosus Patients.","authors":"Amin Reza Nikpoor, Mahmoud Mahmoudi, Abbas Shapouri-Moghaddam, Zahra Rezaieyazdi, Samaneh Mollazadeh, Nafiseh Tabasi, Atena Mansouri, Reyhane Modarres Moghadam, Amir Abbas Momtazi, Soran K Najmaldin, Ramiar Kamal Kheder, Seyed-Alireza Esmaeili","doi":"10.2174/0118761429249908231221080806","DOIUrl":"10.2174/0118761429249908231221080806","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a complex autoimmune disease recognized by elevated activity of autoimmune cells, loss of tolerance, and decreased regulatory T cells producing inhibitory cytokines. Despite many efforts, the definitive treatment for lupus has not been fully understood. Curcumin (CUR) and berberine (BBR) have significant immunomodulatory roles and anti-inflammatory properties that have been demonstrated in various studies. This study aimed to investigate the anti-inflammatory properties of CUR and BBR on human monocyte-derived dendritic cells (DCs) with an special focus on the maturation and activation of DCs.</p><p><strong>Methods: </strong>Human monocytes were isolated from the heparinized blood of SLE patients and healthy individuals, which were then exposed to cytokines (IL-4 and GM-CSF) for five days to produce immature DCs. Then, the obtained DCs were characterized by FITC-uptake assay and then cultured in the presence of CUR, BBR, or lipopolysaccharide (LPS) for 48 h. Finally, the maturation of DCs was analyzed by the level of maturation using flow cytometry or real-time PCR methods.</p><p><strong>Results: </strong>The results showed promising anti-inflammatory effects of CUR and BBR in comparison with LPS, supported by a significant reduction of not only co-stimulatory and antigen-presenting factors such as CD80, CD86, CD83, CD1a, CD14, and HLA-DR but also inflammatory cytokines such as IL-12.</p><p><strong>Conclusion: </strong>CUR and BBR could arrest DC maturation and develop a tolerogenic DC phenotype that subsequently promoted the expression of inhibitory cytokines and reduced the secretion of proinflammatory markers.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429249908"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khaoula Balgouthi, Manaf AlMatar, Hamza Saghrouchni, Osman Albarri, Işıl Var
{"title":"Mutations in Rv0678, Rv2535c, and Rv1979c Confer Resistance to Bedaquiline in Clinical Isolates of Mycobacterium Tuberculosis.","authors":"Khaoula Balgouthi, Manaf AlMatar, Hamza Saghrouchni, Osman Albarri, Işıl Var","doi":"10.2174/0118761429314641240815080447","DOIUrl":"10.2174/0118761429314641240815080447","url":null,"abstract":"<p><strong>Introduction: </strong>Reduced bedaquiline (BDQ) sensitivity to antimycobacterial drugs has been linked to mutations in the Rv0678, pepQ, and Rv1979c genes of Mycobacterium tuberculosis (MTB). Resistance-causing mutations in MTB strains under treatment may have an impact on novel BDQ-based medication regimens intended to reduce treatment time. Due to this, we investigated the genetic basis of BDQ resistance in Turkish TB patients with MTB clinical isolates. Furthermore, mutations in the genes linked to efflux pumps were examined as a backup resistance mechanism.</p><p><strong>Methods: </strong>We scrutinized 100 MTB clinical isolates from TB patients using convenience sampling. Eighty MDR and twenty pan-drug susceptible MTB strains were among these isolates. Sequencing was performed on all strains, and genomic analyses were performed to find mutations in BDQ resistance-associated genes, including Rv0678 and pepQ(Rv2535c), which correspond to a putative Xaa-Pro aminopeptidase, and Rv1979c. Of the 74 isolates with PepQ (Rv2535c) mutations, four isolates (2.96%) exhibited MGIT-BDQ susceptibility.</p><p><strong>Results: </strong>Twenty-one (19.11%) of the ninety-one isolates carrying mutations, including Rv1979c, were MGIT-BDQ-sensitive. Nonetheless, out of the 39 isolates with Rv0678 mutations, four (2.96%) were sensitive to MGIT-BDQ. It was found that resistance-associated variants (RAVs) in Rv0678, pepQ, and Rv1979c are often linked to BDQ resistance.</p><p><strong>Conclusion: </strong>In order to include variations in efflux pump genes in genome-based diagnostics for drug-resistant MTB, further evidence about their involvement in resistance is needed.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429314641"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lu Zou, Xiao Yu, Ling Tang, Chunrong Guo, Zhumei Sun, Shaobin Li, Yanqi Cheng, Fufeng Li, Hong Fang
{"title":"Targeting Airway Remodeling in Asthma: Anti-EMT Effects of Xuanfei Pingchuan Prescription <i>via</i> TGFβ1/Smad Pathway Modulation.","authors":"Lu Zou, Xiao Yu, Ling Tang, Chunrong Guo, Zhumei Sun, Shaobin Li, Yanqi Cheng, Fufeng Li, Hong Fang","doi":"10.2174/0118761429360075250320062131","DOIUrl":"10.2174/0118761429360075250320062131","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic airway disease characterized by Airway Remodeling (AR) and persistent inflammation, with Epithelial-Mesenchymal Transition (EMT) playing a crucial role in fibrosis and smooth muscle proliferation. The Transforming Growth Factor-Beta1 (TGFβ1)/Smad pathway is a key driver of EMT in asthma. Current treatments do not effectively prevent AR progression. Traditional Chinese Medicine, particularly the Xuanfei Pingchuan (XFPC) prescription, has shown potential in managing asthma, but its role in EMT regulation remains unclear.</p><p><strong>Methods: </strong>This study explored the role of \"phlegm and stasis\" in airway remodeling (AR) in asthma from the perspective of EMT and investigated the effects and underlying mechanisms of XFPC prescription on EMT in AR. <i>In vitro</i>, human bronchial epithelial (16HBE) cells were induced into EMT with TGFβ1 and treated with XFPC drug-containing serum, with EMT marker expression analyzed <i>via</i> RT-qPCR and Western blot. <i>In vivo</i>, an ovalbumin (OVA)-induced asthma model in Sprague Dawley rats was used to evaluate the effects of different XFPC doses through histopathology, immunofluorescence, and molecular analyses. Additionally, Smurf2 cDNA transfection was conducted to assess the role of Smurf2 in EMT regulation.</p><p><strong>Results: </strong>The results confirmed that XFPC prescription suppressed the pathway of transforming-growth factor-beta1 (TGFβ1)-Smad by reducing Smad ubiquitination regulator 2 (Smurf2), Smad2, Smad3, TGFβ1 receptor (TβRI), N-cadherin, α-SMA, and Vimentin in terms of expressions at messenger ribonucleic acid (mRNA) and protein levels. However, XFPC prescription up-regulated expressions of SnoN and E-cadherin at protein and mRNA levels to inhibit EMT. The result also confirmed that XFPC prescription decreased the ubiquitination of Smad7.</p><p><strong>Conclusion: </strong>XFPC prescription could suppress AR in TGFβ1 induced 16HBE cells and OVA-sensitized animal models through TGFβ1/Smad pathway.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e18761429360075"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}