{"title":"2-DG Promotes the Proliferation, Differentiation, Migration, and Resistance to Oxidative Stress of Mesenchymal Stem Cells through Hippo Signaling.","authors":"Liang Dong, Lang Li","doi":"10.2174/0115665240327407250206112910","DOIUrl":"https://doi.org/10.2174/0115665240327407250206112910","url":null,"abstract":"<p><strong>Background: </strong>Hippo signaling regulates the behavior and fate of mesenchymal stem cells (MSCs), which are crucial for the repair and cure of acute respiratory distress syndrome (ARDS). However, whether 2-deoxy-D-glucose (2-DG), a specific activator of Hippo signaling, would further enhance the reparative effect of MSCs in ARDS remains unclarified.</p><p><strong>Objective: </strong>This study aimed to determine whether 2-DG could promote the proliferation, differentiation, migration, and resistance to oxidative stress of mouse bone marrow-derived MSCs (mBMSCs).</p><p><strong>Methods: </strong>mBMSCs were isolated from C57BL/6 mice and differentiated into alveolar type II epithelial (ATII) cells by noncontact coculture. The specific activator and inhibitor 2-DG and 4-[(5,10-dimethyl-6-Oxo-6,10-dihydro-5h-pyrimido[5,4-B]thieno[3,2- E][1,4]diazepin-2-Yl)amino]benzenesulfonamide (XMU-MP-1) were used to activate and inhibit Hippo signaling, respectively. Oxidative stress-induced injuries were induced by H2O2 treatment.</p><p><strong>Results: </strong>We observed that 2-DG activated Hippo signaling and promoted mBMSC proliferation in a dose-dependent manner. 2-DG also promoted the differentiation of mBMSCs into ATII cells and enhanced not only the horizontal and vertical migration of mBMSCs but also mBMSC homing to injured lung tissue. H2O2 treatment inhibited Hippo signaling and reduced the viability of mBMSCs by decreasing the Bcl-2/Bax ratio, but 2-DG activated Hippo signaling and conferred mBMSCs with resistance to oxidative stress by increasing the Bcl-2/Bax ratio. However, XMU-MP-1 suppressed these effects to some extent.</p><p><strong>Conclusion: </strong>Through Hippo signaling, 2-DG promoted the proliferation, migration, differentiation, and resistance to oxidative stress of mBMSCs, suggesting a novel strategy for enhancing the reparative effects of MSCs in ARDS.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tooba Dedmari, Sameena Ramzan, Mubashir Hussain Masoodi, Reyaz Hassan Mir
{"title":"Detailed Review of Melatonin and its Role in Managing the Symptoms of Depression.","authors":"Tooba Dedmari, Sameena Ramzan, Mubashir Hussain Masoodi, Reyaz Hassan Mir","doi":"10.2174/0115665240315801250127113448","DOIUrl":"https://doi.org/10.2174/0115665240315801250127113448","url":null,"abstract":"<p><p>Depression, which is emerging as one of the most widely prevalent neuropsychiatric disorders worldwide, has affected people across all age groups. However, it is currently primarily affecting adults aged 18 to 25. The condition is characterized by disrupted sleep cycles, diurnal variation, and disturbed core body temperature rhythms. Currently, the anti-depressant medications that are prescribed and authorized, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), benzodiazepines, anxiolytics, and antihistamines have demonstrated effective outcomes. However, the findings from the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study are disappointing. The results show that currently available antidepressants yield only minimal improvements in effectiveness for patients who did not respond to their initial medication. Melatonin has emerged as a promising option for tackling these issues. Moreover, due to its diverse abilities to regulate circadian rhythms and promote synchronization, melatonin offers an alternative therapeutic approach to alleviate the side effects and target the underlying causes of depression linked to an impaired circadian system. This review intends to provide a comprehensive overview of melatonin, including aspects such as its structural analysis, biosynthesis, regulation, catabolism, and involvement in various physiological processes, particularly highlighting its antidepressant activity.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Luo, Fan Yang, Xiaoping Fu, Tingting Yu, Wenqian Tang, Juan Xue
{"title":"The Emerging Role of Long Non-Coding RNA 01296 in Human Malignancies.","authors":"Lei Luo, Fan Yang, Xiaoping Fu, Tingting Yu, Wenqian Tang, Juan Xue","doi":"10.2174/0115665240352933250116050706","DOIUrl":"https://doi.org/10.2174/0115665240352933250116050706","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) refer to a group of RNA molecules that exceed a length of 200 nucleotides and lack the ability to code proteins. Numerous studies suggest that lncRNAs significantly contribute to the onset and progression of various forms of cancers. A specific lncRNA, known as long non-coding RNA 01296 (LINC01296), is extensively expressed in human malignancies. The level of LINC01296 has been shown to correlate with the progression and prognosis of cancers. Moreover, numerous scientific investigations have provided evidence that the dysregulation of LINC01296 functioning as a competitive endogenous RNA (ceRNA) exerts a profound influence on various aspects of cancer cell behavior, including proliferation, apoptosis, invasion, metastasis, and cell cycle progression, by means of regulating target genes and signaling pathways. An increasing body of data strongly suggests that LINC01296 may serve as a valuable biomarker for predicting cancer prognosis and could represent a promising therapeutic target for cancer intervention. In this comprehensive review, we summarize the recent advancements in our understanding of the role, underlying mechanisms, and clinical significance of LINC01296 in malignant tumors. The findings suggest that LINC01296 may be both a reliable biomarker and a potential therapeutic target for cancers.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liu Ruifang, Chai Ruiting, Yang Zhaoyang, Li Candong
{"title":"Role of Immune Cells in Mediating the Causal Effect of Gut Microbiota on Type 2 Diabetes.","authors":"Liu Ruifang, Chai Ruiting, Yang Zhaoyang, Li Candong","doi":"10.2174/0115665240322713241114051433","DOIUrl":"https://doi.org/10.2174/0115665240322713241114051433","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have suggested that gut microbiota and immune system regulation have potential links with type 2 diabetes (T2D). However, the causal association between gut microbiota and T2D and whether immune cells mediate this interaction is unclear.</p><p><strong>Methods: </strong>A two-sample, two-step Mendelian randomization (MR) study utilizing an initial inverse-variance weighted (IVW) method was performed to explore the causal impact of gut microbiota on T2D and the intermediary role of immune cells.</p><p><strong>Results: </strong>The MR analysis assigned 4 gut microbiota and metabolic pathways that increase the risk of T2D (G_Prevotella, g_Anaerotruncus, g_Streptococcus.s_ Streptococcus_parasanguinis, and the pathway of PANTO-PWY) and 4 other gut microbiota and metabolic pathways that have a protective effect against T2D (PWY5667, PWY-6892, PWY-7221, and the bacterial g_Paraprevotella.s_Paraprevotella_ clara). Furthermore, 17 immune cell traits have been identified as associated with T2D. The finding from mediation MR analysis revealed that PANTO-PWY increases T2D risk via CD3 on HLA DR+ CD4+, whereas PWY-7221 reduces T2D risk through CD4 on CD4 Treg.</p><p><strong>Conclusion: </strong>The research reveals a mediated causal link between the gut microbiota and T2D via immune cells.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methyl-CpG-Binding Domain Protein 2 is Involved in Th17 Cell Differentiation by Negatively Regulating Leptin Expression.","authors":"Yang Xia, Xiufeng Zhang, Dingjiang Wu","doi":"10.2174/0115665240341834250121080510","DOIUrl":"https://doi.org/10.2174/0115665240341834250121080510","url":null,"abstract":"<p><strong>Background: </strong>Among Th lineages from naïve CD4+T cells, Th17 cells producing IL-17 are strongly related to the pathogenesis of neutrophilic asthma. Leptin is involved in inflammation and immunity. Little is known about MBD2's epigenetic regulation in CD4+T cell differentiation.</p><p><strong>Objective: </strong>Our study is intended to delve into the mode by which MBD2 interacts with Leptin to govern Th17 cell differentiation.</p><p><strong>Methods: </strong>CD4+T cells were harvested from the spleen tissue of C57BL/6 mice. Th17 cell differentiation was determined by flow cytometry, and ELISA measured IL-17. Western blot and RT-qPCR were employed to detect the expression of MBD2, Leptin and RORγt. CO-IP was utilized to assess the relationship between MBD2 and Leptin.</p><p><strong>Results: </strong>Under the overexpression or silencing of the MBD2 and Leptin genes, the differentiation of Th17 cells, IL-17 secretion, and RORγt expression all manifested positive changes. Leptin expression showed a positive variance upon overexpression or silencing of the MBD2 gene; however, there was no significant disparity in the expression of MBD2 under the overexpression or silencing of the Leptin gene. MBD2 can interact directly with Leptin.</p><p><strong>Conclusion: </strong>MBD2 is capable of inducing the differentiation of naïve CD4+T cells into Th17 cells by augmenting the expression of Leptin.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guangyu Cheng, Jie Liu, HongLi Zhang, YouXiang Cui, ShuJie Xu, Lichun Wang
{"title":"Sortilin as a Culprit in the Atherosclerosis Plaque Progression: Evidence from Clinical and Experimental Studies.","authors":"Guangyu Cheng, Jie Liu, HongLi Zhang, YouXiang Cui, ShuJie Xu, Lichun Wang","doi":"10.2174/0115665240342078250114165535","DOIUrl":"https://doi.org/10.2174/0115665240342078250114165535","url":null,"abstract":"<p><p>Sortilin acts as a key receptor for lipids, growth factors, cytokines, and enzymes and participates in pathological cargo loading and transferring of extracellular vesicles. Emerging evidence suggests a significant role of sortilin in hyperlipidemia and the risk of atherosclerosis. Recent epidemiological evidence demonstrated that sortilin has been implicated in atherosclerosis plaque progression in patients with coronary or peripheral artery disease. The present study presents a comprehensive review of the contribution of sortilin to atherosclerosis progression. Here, recent experimental and clinical findings are summarized to determine the effects of sortilin on atherosclerosis progression and the related underlying mechanisms.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Livio Tarchi, Gaia Maiolini, Gianluca Villa, Paolo Rovero, Francesco De Logu, Romina Nassini, Rachele Garella, Chiara Sassoli, Valdo Ricca, Giovanni Castellini, Roberta Squecco
{"title":"The Hormetic Potential of GDF15 in Skeletal Muscle Health and Regeneration: A Comprehensive Systematic Review.","authors":"Livio Tarchi, Gaia Maiolini, Gianluca Villa, Paolo Rovero, Francesco De Logu, Romina Nassini, Rachele Garella, Chiara Sassoli, Valdo Ricca, Giovanni Castellini, Roberta Squecco","doi":"10.2174/0115665240327723241018073535","DOIUrl":"https://doi.org/10.2174/0115665240327723241018073535","url":null,"abstract":"<p><strong>Background: </strong>Growth Differentiation Factor 15 (GDF15) has been described as influencing skeletal physiology. Nevertheless, no systematic appraisal of the effect of GDF15 on skeletal muscle tissues has been developed to the present day.</p><p><strong>Objective: </strong>The aim of the present work was to review the evidence on the topic.</p><p><strong>Methods: </strong>In this preregistered systematic review (https://osf.io/wa8xr), articles were retrieved from MEDLINE/PubMed, EMBASE, and WebOfScience. Inclusion criteria comprised studies on humans or animal models, assessment of peripheral or local tissue GDF15 concentrations, as well as the direct expression of GDF15 in skeletal muscle, and direct or indirect correlates of GDF15 with physical activity/ sarcopenia/trophism/ function.</p><p><strong>Results: </strong>A total of 646 studies were retrieved, and 144 finally included. Molecular inducers or inhibitors of GDF15 in skeletal muscle tissues were described. GDF15 was reported to promote skeletal muscle health, metabolic homeostasis, and overall physical conditioning. In pathology, GDF15 seems to be correlated to the degree of muscle impairment and mitochondrial stress. GDF15 has also been described as having the potential to stratify patients based on clinical prognosis and functional outcome.</p><p><strong>Conclusion: </strong>A hormetic hypothesis for GDF15 on skeletal muscle was proposed. In fact, GDF15 exhibited beneficial effects when expressed at high levels facing acute stressors (i.e., \"myoprotection\"). Conversely, GDF15 exhibited maladaptive effects, such as chronic low-grade inflammation, when chronically expressed in pathological processes (e.g., obesity, aging). GDF15 may be a potential molecular target for disease-modifying interventions. The current review underscores the need for further research on GDF15 to elucidate its therapeutic potential across different pathological states. The study protocol, registered before data collection and analysis, can be retrieved at https://osf.io/wa8xr. It should be noted that the study deviated from the protocol after peer review, including other electronic databases beyond MEDLINE/PubMed alone.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elucidating the Causal Dynamics between Inflammatory Proteins and Atrial Fibrillation Risk Through Bidirectional Mendelian Randomization.","authors":"Yuan Lv, Bin Huang, Liyin Xu, Xianjun Wu","doi":"10.2174/0115665240347233250119190837","DOIUrl":"https://doi.org/10.2174/0115665240347233250119190837","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with significant morbidity and mortality. Inflammation has been implicated in the pathogenesis of AF, but the causal relationship between specific inflammatory proteins and AF risk is not well established. This study aims to clarify this relationship using a bidirectional two-sample Mendelian Randomization (TSMR) approach.</p><p><strong>Methods: </strong>Employing a bidirectional Mendelian Randomization (MR) method, we analyzed genetic variants as instrumental variables (IVs) to investigate the influence of 91 circulating inflammatory proteins on AF risk. This approach allowed us to assess the potential causal effects of inflammatory proteins on AF and vice versa, thus providing a comprehensive understanding of the bidirectional nature of their relationship.</p><p><strong>Results: </strong>Seven inflammatory proteins were significantly associated with AF risk. Three proteins increased the risk: Fibroblast Growth Factor 5 (FGF-5) with an odds ratio (OR) of 1.0743 (95% CI: 1.0466-1.1027, p=7.41E-08), Tumor Necrosis Factor (TNF) with an OR of 1.0832 (95% CI: 1.0261-1.1434, p=0.0038), and Interleukin-2 Receptor Subunit Beta (IL-2RB) with an OR of 1.0814 (95% CI: 1.0151-1.1519, p=0.0153). Four proteins showed a protective effect: CD40 Ligand Receptor (CD40) with an OR of 0.9671 (95% CI: 0.9392-0.9959, p=0.0254), Fms-related Tyrosine Kinase 3 Ligand (FIt3L) with an OR of 0.9553 (95% CI: 0.9173-0.9949, p=0.0274), Leukemia Inhibitory Factor Receptor (LIF-R) with an OR of 0.9254 (95% CI: 0.8678- 0.9868, p=0.0181), and Sulfotransferase 1A1 (ST1A1) with an OR of 0.9461 (95% CI: 0.9097-0.9839, p=0.0056). The reverse MR analysis revealed no significant effects of AF on the levels of these inflammatory proteins, suggesting a unidirectional causality from proteins to AF.</p><p><strong>Conclusion: </strong>This bidirectional MR study provides robust evidence for a causal relationship between specific inflammatory proteins and AF risk. The identified proteins could serve as potential biomarkers for AF risk stratification and targets for therapeutic intervention, offering new insights into the pathophysiology of AF and avenues for future research.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vladimir Sobolev, Anna Soboleva, Ksenia Katkova, Elena Denisova, Olga Zhukova, Nikolay Potekaev, Luiza Sakanyia, Irina Korsunskaya, Alexandre Mezentsev
{"title":"Using the AP1 Transcription Factor FOSL1 to Assess the Exacerbation of Psoriasis.","authors":"Vladimir Sobolev, Anna Soboleva, Ksenia Katkova, Elena Denisova, Olga Zhukova, Nikolay Potekaev, Luiza Sakanyia, Irina Korsunskaya, Alexandre Mezentsev","doi":"10.2174/0115665240343441241231102305","DOIUrl":"https://doi.org/10.2174/0115665240343441241231102305","url":null,"abstract":"<p><strong>Background: </strong>The transcription factor AP1 plays a crucial role in the proliferation, apoptosis, and terminal differentiation of epidermal keratinocytes.</p><p><strong>Objective: </strong>This study aimed to clarify whether the subunit of AP1, FOSL1 protein, can be used to assess the exacerbation of psoriasis by evaluating its changes in protein and mRNA levels in cultured epidermal keratinocytes and skin specimens of the patients prescribed with bathwater PUVA (Psoralen and UVA) therapy. This study aimed to investigate FOSL1, a subunit of the transcription factor AP-1, as a potential biomarker for psoriasis by examining its protein and mRNA expression in skin specimens from patients undergoing bathwater PUVA (Psoralen and UVA) therapy and cultured epidermal keratinocytes.</p><p><strong>Methods: </strong>The distribution of FOSL1 in patients' skin was explored by immunohistochemistry. Changes in gene and protein expression were quantitatively assessed by qPCR and ELISA, respectively.</p><p><strong>Results: </strong>Immunohistochemistry analysis revealed that FOSL1 accumulated in lesional skin. The expression of FOSL1 significantly increased during disease flare-ups but decreased following the treatment with bathwater PUVA therapy. Furthermore, silencing FOSL1 led to a marked reduction in the expression of ten FOSL1 target genes associated with the disease.</p><p><strong>Conclusion: </strong>Our study suggests that FOSL1 shows potential as a biomarker for psoriasis. This is supported by two key findings: first, the expression of FOSL1 correlates with disease activity, and second, its expression is linked to changes in the expression of genes previously implicated in the pathogenesis of psoriasis, namely MMP1, MMP9, IVL, CCNA2, CCL2, HMOX1, PLAU, PLAUR, and THBD.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Majeed Akhtar, Iqra Hamid Khan, Fatima Iftikhar Shah, Shamsa Kanwal, Sufia Majeed, Najeeb Ullah, Somia Shehzadi, Asmat Ullah
{"title":"Association between Sputum Culture Conversion and Body Mass Index among Multidrug-Resistant Tuberculosis Patients in Punjab, Pakistan: A Multicenter Retrospective Study.","authors":"Abdul Majeed Akhtar, Iqra Hamid Khan, Fatima Iftikhar Shah, Shamsa Kanwal, Sufia Majeed, Najeeb Ullah, Somia Shehzadi, Asmat Ullah","doi":"10.2174/0115665240342370241230194338","DOIUrl":"https://doi.org/10.2174/0115665240342370241230194338","url":null,"abstract":"<p><strong>Background: </strong>The global challenge of Multidrug-resistant Tuberculosis (MDR-TB) presents a substantial public health concern, requiring extended and complex treatment regimens. Understanding the factors impacting treatment results, particularly sputum culture conversion and Body Mass Index (BMI), is crucial. This retrospective cohort investigation conducted in Punjab, Pakistan, sought to explore the correlation between BMI and sputum culture conversion in individuals diagnosed with MDR-TB.</p><p><strong>Material and methodology: </strong>Data from 2663 confirmed MDR-TB patients across multiple Programmatic Management of Drug-Resistant Tuberculosis PMDT sites in Punjab, Pakistan, were retrospectively analyzed. Demographic and clinical characteristics, BMI, comorbidities, previous TB treatments, and drug resistance were evaluated. Cox proportional hazards regression models were employed to assess the association between time to sputum culture conversion and patient characteristics.</p><p><strong>Results: </strong>The study compared MDR-TB treatment outcomes based on BMI categories (≥18.5 vs. <18.5 Kg/m^2). It involved 1626 employed patients, with a mean age of 33 ± 15 years, displaying baseline body weights averaging 48±7 kg (normal weight) and 37±6 kg (underweight). On average, sputum culture conversion occurred at four months, with approximately 37% achieving conversion within this period. Among several factors studied, the univariate analysis identified BMI <18.5 Kg/m^2, prior firstline drug treatment, and comorbidities as significantly associated with failure to achieve sputum culture conversion within 6 months. In multivariate analysis, the inability to achieve conversion was notably linked to BMI <18.5 Kg/m^2, previous first-line drug treatment, and resistance to fluoroquinolone drugs.</p><p><strong>Conclusion: </strong>This study provided valuable insights into sputum culture conversion, BMI, and drug resistance among MDR-TB patients. While around half of the patients achieved sputum culture conversion within six months, factors, such as comorbidities, previous TB treatment, and drug resistance, significantly influenced treatment outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}