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Current Molecular Medicine[JOURNAL]

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Recent Accomplishments in Exhaled Breath Condensate Analysis - Molecular Aspects.

Silkin SV, Pekov SI, Bocharov KV … +1 more , Popov IA

Curr Mol Med · 2025 Feb · PMID 39980287 · Publisher ↗

Nowadays, the research of exhaled breath condensate (EBC) analysis is widely discussed in the scientific community. The growing interest in EBC analysis results is related to the ample advantages of non-invasive techniqu... Nowadays, the research of exhaled breath condensate (EBC) analysis is widely discussed in the scientific community. The growing interest in EBC analysis results is related to the ample advantages of non-invasive techniques in healthcare and related fields. In particular, EBC analysis can be used to diagnose respiratory diseases, monitor the disease's course during therapy, and monitor drug intake and metabolism. This review aims to systematize the accumulated knowledge on EBC collection, concentration, storage, and analysis methods and compare them with similar procedures for exhaled breath (EB). We proposed a generalized chemical classification of EBC compounds that are biomarkers for various diseases. The potential transformation of substances during EB condensation was considered, and EBC analysis methods were systematically categorized based on this classification. Methods for EBC analysis using chromatographic separation with mass spectrometric detection (hyphenated methods) were separately discussed as the most promising methods for future research applications.

Aptamers for Brain Tumors: A Therapeutic Agent for Effectively Crossing the Blood-Brain Barrier.

Lakshmipriya T, Gopinath SCB

Curr Mol Med · 2025 · PMID 39976095 · Publisher ↗

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Exploring the Gut Microbiota as a Promising Target for Breast Cancer Treatment.

Gale Dari MA, Ghaedrahmati F, Moalemnia A … +7 more , Dezfouli MA, Savari F, Zamani AM, Ahmadi B, Nazarbeigi M, Farzaneh M, Zehtabi M

Curr Mol Med · 2026 · PMID 39957702 · Publisher ↗

Breast cancer is a heterogeneous disease and highly prevalent malignancy affecting women globally. Breast cancer treatments have been demonstrated to elicit significant and long-lasting effects on various aspects of a pa... Breast cancer is a heterogeneous disease and highly prevalent malignancy affecting women globally. Breast cancer treatments have been demonstrated to elicit significant and long-lasting effects on various aspects of a patient's life, including physical, emotional, social, and financial, highlighting the need for comprehensive cancer care. Recent research suggests that the composition and activity of the gut microbiota may play a crucial role in anticancer responses. Various compositional features of the gut microbial population have been found to influence both the clinical and biological aspects of breast cancer. Notably, the dominance of specific microbial populations in the human intestine may significantly impact the effectiveness of cancer treatment strategies. Therefore, the manipulation of the microbiota to improve the anticancer effects of conventional tumor treatments represents a promising strategy for enhancing the efficacy of cancer therapy. Emerging evidence indicates that alterations in the gut microbiota composition and activity have the potential to impact breast cancer risk and treatment outcomes. In this paper, we conduct a comprehensive investigation of various databases and published articles to explore the impact of gut microbial composition on both the molecular and clinical aspects of breast cancer. We also discuss the implications of our findings for future research directions and clinical strategies.

Epigenetic Mechanisms of Antibiotic Resistance.

Novozhilova PO, Bakina OV, Spirina LV … +1 more , Tarasenko NV

Curr Mol Med · 2026 · PMID 39950477 · Publisher ↗

Antibiotic resistance remains a major challenge in the use of antimicrobial agents and poses a threat to public health worldwide. This review discusses the epigenetic mechanisms underlying antibiotic resistance. Signific... Antibiotic resistance remains a major challenge in the use of antimicrobial agents and poses a threat to public health worldwide. This review discusses the epigenetic mechanisms underlying antibiotic resistance. Significant attention is also given to gene expression patterns that promote microbial adaptability and survival in the context of antibiotic therapy, as well as epigenetic mechanisms that contribute to modifying the activity of resistance genes. The authors argue that epigenetics plays a key role in the development and spread of antibiotic resistance. By offering new perspectives on the complex interaction between genetic and epigenetic regulations in microbial populations using metal nanoparticles, the authors shed light on potential therapeutic targets and strategies to combat antibiotic resistance. Exploring the disclosure of epigenetic mechanisms when interacting with metal nanoparticles on resistant cultures is insufficiently covered in the literature. This review not only presents the latest scientific findings in this field but also opens up avenues for further research that will help address the growing problem of antibiotic resistance.

EGCG Mitigates Apoptosis of Lens Epithelial Cells in Age-Related Cataract via the PAK1/Cleaved Caspase-3 Pathway.

Zhang Y, Su D, Sun Z … +7 more , Fu Y, Chen X, Hu Y, Zhang X, Zheng S, Ma X, Hu S

Curr Mol Med · 2025 · PMID 39949100 · Publisher ↗

BACKGROUND: Oxidative damage and apoptosis of lens epithelial cells (LECs) are the primary factors contributing to the development of age-related cataracts (ARC). The potential protective effects of epigallocatechin gall... BACKGROUND: Oxidative damage and apoptosis of lens epithelial cells (LECs) are the primary factors contributing to the development of age-related cataracts (ARC). The potential protective effects of epigallocatechin gallate (EGCG) on LECs remain unclear despite its remarkable antioxidant and anti-apoptotic properties. The aim of this study was to explore the role of serine/threonine-protein kinase (PAK1) in EGCG-mediated attenuation of HO-induced apoptosis of LECs and . METHODS: PAK1 expression was assessed in the anterior capsule of the lens from mice and patients with and without ARC using western blotting and immunohistochemistry. Human lens epithelial B3 (HLE-B3) cells were pre-treated with EGCG+HO or HO only, and PAK1 expression was determined using qRT-PCR and western blotting. Apoptosis (following PAK1 overexpression or silencing) and cell survival were assessed using Hoechst 33342 staining and a cell counting Kit-8 assay, respectively. Cleaved caspase-3 was measured in transected cells, aged/young mice, and mice treated with EGCG via western blotting. RESULTS: PAK1 expression was significantly lower in ARC LECs than in control LECs. In HLE-B3 cells, EGCG+HO treatment upregulated PAK1 mRNA and protein expression when compared with HO alone. PAK1 overexpression alleviated HO- induced apoptosis in LECs, while low expression weakened EGCG's protective effects. PAK1 overexpression reduced cleaved caspase-3 expression in HO-treated cells, whereas PAK1 silencing increased its expression in EGCG+HO-treated cells. EGCG decreased cleaved caspase-3 expression in HO-treated cells. These results suggest that PAK1 inhibits cleaved caspase-3 expression, thereby enhancing EGCG's attenuation of HO-induced LEC apoptosis. CONCLUSION: The PAK1/cleaved caspase-3 pathway plays a key role in EGCG's protective effects on the development of ARC. This provides a new therapeutic target for the use of EGCG in preventing and treating ARC.

Mechanism of Astragaloside IV in Promoting Osteogenic Differentiation.

Zhu Y, Lin C, Zhang X … +3 more , Qiu Z, Shi L, Li J

Curr Mol Med · 2025 · PMID 39945270 · Publisher ↗

BACKGROUND: This study focuses on exploring the impact of Astragaloside IV [AS-IV] on osteogenic differentiation. METHODS: Osteogenic differentiation was induced in rat osteoblasts, following which treatment with AS-IV a... BACKGROUND: This study focuses on exploring the impact of Astragaloside IV [AS-IV] on osteogenic differentiation. METHODS: Osteogenic differentiation was induced in rat osteoblasts, following which treatment with AS-IV at varied doses was performed. Using Alizarin red staining and alkaline phosphatase (ALP) detection assay, the osteogenic differentiation of the cells was investigated. The expressions of osteogenic differentiation-related genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathwayassociated protein expressions were examined using Western blot. After osteoblasts were transfected with protein tyrosine phosphatase non-receptor type 2 (PTPN2) overexpression plasmid, the impact of PTPN2 on osteoblasts treated with AS-IV was examined. RESULTS: AS-IV treatment enhanced osteogenic differentiation and up-regulated the expression of osteogenic differentiation-related genes, as well as the levels of p- PI3K/PI3K and p-AKT/AKT, while reducing phosphatase and tensin homolog (PTEN) protein production in osteoblasts. Overexpression of PTEN inhibited osteogenic differentiation, and PTPN2 overexpression counteracted the effects of AS-IV on osteogenic differentiation. CONCLUSION: AS-IV contributing to osteogenic differentiation may be related to the PTPN2-mediated PTEN/PI3K/Akt pathway.

Single Cell RNA Sequencing in Colorectal Cancer Immunology: Recent Updates, Application, and Emerging Challenges.

George S, Johdi NA

Curr Mol Med · 2026 · PMID 39945269 · Publisher ↗

Colorectal cancer poses a major global health issue, profoundly affecting both mortality and morbidity rates across the world. A key obstacle in understanding the pathogenesis of colorectal cancer lies in its high inter-... Colorectal cancer poses a major global health issue, profoundly affecting both mortality and morbidity rates across the world. A key obstacle in understanding the pathogenesis of colorectal cancer lies in its high inter-patient and spatial heterogeneity, making standard treatments ineffective. Commonly, the study on colorectal cancer relies on bulk RNA sequencing, offering an average gene expression profile for a heterogenous cell population. However, this approach obscures the heterogeneous characteristics of the cancer cells and hinders a comprehensive understanding of the complex interplay among different cell populations. Recently, the advent of single-cell RNA sequencing has been revolutionary, enabling researchers to analyze individual immune cells and overcome the limitations of bulk RNA sequencing. Through single-cell RNA sequencing, researchers have gained insights into the dynamic nature of the immune response to cancer and potential targets for immunotherapy. In this review, we discuss the technical aspects of single-cell RNA sequencing, the application of single-cell RNA sequencing in cancer immunology, and the potential of single-cell RNA in clinical settings. We believe that harnessing singlecell RNA sequencing in cancer research holds immense potential to drive the development of personalized immunotherapies, aiming to improve patient outcomes in colorectal cancer.

Detailed Review of Melatonin and its Role in Managing the Symptoms of Depression.

Dedmari T, Ramzan S, Masoodi MH … +1 more , Hassan Mir R

Curr Mol Med · 2026 · PMID 39917910 · Publisher ↗

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 co... 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.

The Emerging Role of Long Non-coding RNA 01296 in Human Malignancies.

Luo L, Yang F, Fu X … +3 more , Yu T, Tang W, Xue J

Curr Mol Med · 2025 · PMID 39901673 · Full text

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... 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.

Role of Immune Cells in Mediating the Causal Effect of Gut Microbiota on Type 2 Diabetes.

Ruifang L, Ruiting C, Zhaoyang Y … +1 more , Candong L

Curr Mol Med · 2025 · PMID 39901539 · Publisher ↗

BACKGROUND: 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 imm... BACKGROUND: 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. METHODS: 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. RESULTS: 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 (PWY- 5667, 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. CONCLUSION: The research reveals a mediated causal link between the gut microbiota and T2D via immune cells.

Methyl-CpG-Binding Domain Protein 2 is Involved in Th17 Cell Differentiation by Positively Regulating Leptin Expression.

Xia Y, Zhang X, Wu D

Curr Mol Med · 2025 · PMID 39865808 · Publisher ↗

BACKGROUND: 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 MBD... BACKGROUND: 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. OBJECTIVE: Our study is intended to delve into the mode by which MBD2 interacts with Leptin to govern Th17 cell differentiation. METHODS: 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. RESULTS: 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. CONCLUSION: MBD2 is capable of inducing the differentiation of naïve CD4+T cells into Th17 cells by augmenting the expression of Leptin.

Sortilin as a Culprit in the Atherosclerosis Plaque Progression: Evidence from Clinical and Experimental Studies.

Cheng G, Liu J, Zhang H … +3 more , Cui Y, Xu S, Wang L

Curr Mol Med · 2025 · PMID 39844542 · Publisher ↗

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... 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.

Elucidating the Causal Dynamics between Inflammatory Proteins and Atrial Fibrillation Risk Through Bidirectional Mendelian Randomization.

Lv Y, Huang B, Xu L … +1 more , Wu X

Curr Mol Med · 2025 · PMID 39838668 · Publisher ↗

BACKGROUND: 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 be... BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Hormetic Potential of GDF15 in Skeletal Muscle Health and Regeneration: A Comprehensive Systematic Review.

Tarchi L, Maiolini G, Villa G … +8 more , Rovero P, Logu F, Nassini R, Garella R, Sassoli C, Ricca V, Castellini G, Squecco R

Curr Mol Med · 2025 · PMID 39838667 · Publisher ↗

BACKGROUND: 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 th... BACKGROUND: 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. OBJECTIVE: The aim of the present work was to review the evidence on the topic. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association between Sputum Culture Conversion and Body Mass Index among Multidrug-Resistant Tuberculosis Patients in Punjab, Pakistan: A Multicenter Retrospective Study.

Akhtar AM, Khan IH, Shah FI … +5 more , Kanwal S, Majeed S, Ullah N, Shehzadi S, Ullah A

Curr Mol Med · 2025 · PMID 39835555 · Publisher ↗

BACKGROUND: 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... BACKGROUND: 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. MATERIAL AND METHODOLOGY: 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. RESULTS: 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. CONCLUSION: 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.

Using the AP1 Transcription Factor FOSL1 to Assess the Exacerbation of Psoriasis.

Sobolev V, Soboleva A, Katkova K … +6 more , Denisova E, Zhukova O, Potekaev N, Sakanyia L, Korsunskaya I, Mezentsev A

Curr Mol Med · 2025 · PMID 39835554 · Publisher ↗

BACKGROUND: The transcription factor AP1 plays a crucial role in the proliferation, apoptosis, and terminal differentiation of epidermal keratinocytes. OBJECTIVE: This study aimed to clarify whether the subunit of AP1, F... BACKGROUND: The transcription factor AP1 plays a crucial role in the proliferation, apoptosis, and terminal differentiation of epidermal keratinocytes. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 , and .

LncRNA-DANCR: A Key Player in Colorectal Cancer Development and Progression.

Anbiyaee O, Ghaedrahmati F, Azizidoost S … +3 more , Radmehr S, Farzaneh M, Salehi AM

Curr Mol Med · 2025 · PMID 39819535 · Publisher ↗

Colorectal Cancer (CRC) is a significant global health issue, being the third most common cancer worldwide and the second most frequent cause of cancerrelated deaths. It occurs when cells in the colon or rectum grow unco... Colorectal Cancer (CRC) is a significant global health issue, being the third most common cancer worldwide and the second most frequent cause of cancerrelated deaths. It occurs when cells in the colon or rectum grow uncontrollably, often developing from precancerous polyps. Genetic predisposition and environmental factors, such as diet and lifestyle, contribute to the disease. Recent research has focused on molecular targeted therapies and non-coding RNAs, particularly long noncoding RNAs (lncRNAs), which play a critical role in regulating CRC development and progression. DANCR interacts with microRNAs, proteins, and mRNAs, influencing gene expression and stability. DANCR functions as a promoter of tumor growth, invasion, metastasis, proliferation, migration, apoptosis, disease progression, and prognosis in various cancers. In CRC, DANCR influences both progression and clinical outcomes. This review aims to comprehensively explore the current knowledge regarding DANCR in CRC, including its molecular characteristics, expression patterns, and involvement in regulatory mechanisms, as well as its potential use as a diagnostic, prognostic, and therapeutic tool.

MicroRNA-130b is a Unique Autophagy-Related Epigenetic Predictor of FLOT-Chemotherapy in Gastric Cancers.

Spirina LV, Zinnurova AB, Bakina OV … +7 more , Avgustinovich AV, Afanas'ev SG, Volkov MY, Klyushina TS, Volkov AM, Tarasenko NV, Masunova NV

Curr Mol Med · 2025 · PMID 39819534 · Publisher ↗

INTRODUCTION: Liquid biopsies have great potential for precision medicine as they provide information about primary and metastatic tumors using minimally invasive techniques. MicroRNAs (miRNAs) are promising biomarkers f... INTRODUCTION: Liquid biopsies have great potential for precision medicine as they provide information about primary and metastatic tumors using minimally invasive techniques. MicroRNAs (miRNAs) are promising biomarkers for detecting gastric cancer (GC). The aim of the study was to identify miR molecules associated with autophagy in gastric cancer (GC) cells, determine their expression levels in GC and FLOT-treated patients, and assess the efficacy of FLOT therapy in GC patients. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways were used to analyze cellular pathways. MicroRNAs were isolated from the tissues. RESULTS: The study found a connection between the expression of the let-7a-5p gene and the size of primary tumors. Bioinformatics analysis identified multiple targets and signaling pathways associated with this phenomenon. We observed an increase in the levels of miR-21-3p and hsa-miR-130b-3p with lymph node involvement. miR-21-3p is associated with the activation of molecular pathways induced by H. pylori in cases of coinfection. Patients with complete regression had higher levels of expression of hsamir- 130b-3p. CONCLUSION: The bioinformatics analysis allowed us to identify the most significant targets among microRNAs. Based on the presented data, it becomes clear that GC is heterogeneous and that the process of autophagy is complex. The association between hsa-miR-130b-3p and tumor response to therapy is particularly interesting.

A Comprehensive Analysis of the Role of PAX9 in Head and Neck Squamous Cell Carcinoma.

Zeng L, Yun W, Luo WL

Curr Mol Med · 2025 · PMID 39819533 · Full text

BACKGROUND: Paired box 9 (PAX9) has been linked to several human disorders; however, its relevance in Head And Neck Squamous Cell Carcinoma (HNSCC) remains unknown. METHODS: The difference in PAX9 mRNA expression in pan-... BACKGROUND: Paired box 9 (PAX9) has been linked to several human disorders; however, its relevance in Head And Neck Squamous Cell Carcinoma (HNSCC) remains unknown. METHODS: The difference in PAX9 mRNA expression in pan-cancer was analyzed utilizing The Cancer Genome Atlas (TCGA), and the level of PAX9 protein expression across various types of cancer was assessed utilizing the Human Protein Atlas (HPA) and UALCAN databases, as well as the cellular localization of PAX9. UALCAN studied the methylation levels of PAX9 in pan-cancer. The predictive significance of PAX9 in pan-cancer was assessed utilizing the Kaplan-Meier Plotter website. Functional enrichment analysis was carried out with the "cluster Profiler" program. By employing CCK8 and colony formation methods, the influence of PAX9 on the growth of HNSCC cells was evaluated. By conducting a transwell experiment, we assessed the influence of PAX9 on the migration of HNSCC cells. Western blotting was used to determine the levels of Bax and Bcl-2, two proteins involved in the regulation of apoptosis. A nude mouse model was established to study the impact of PAX9 overexpression on the growth of subcutaneous HNSCC tumors. RESULTS: In HNSCC, the expression of PAX9 was found to be low, while levels of promoter methylation rose considerably. Low PAX9 expression has been linked to a decrease in overall survival (OS) rates among individuals with HNSCC. Furthermore, overexpressing the PAX9 gene decreased HNSCC cell proliferation, migration, and invasion while boosting apoptosis rates. CONCLUSION: The abnormal expression of PAX9 is linked to various cancers. In HNSCC, PAX9 is a potential tumor suppressor, inhibiting tumor invasion and migration. The results reveal a potentially significant new therapeutic target for HNSCC.

Ag85B-induced M1 Macrophage Polarization via the TLR4/TRAF6/NF-κB Axis Leading to Bronchial Epithelial Cell Damage and TH17/Treg Imbalance.

Zhou L, Luo L, Luo L … +4 more , Luo H, Ding Y, Lu Z, Xiao Y

Curr Mol Med · 2025 · PMID 39819414 · Publisher ↗

BACKGROUND: Antigen 85B (Ag85B) is a signature antigen of Mycobacterium tuberculosis (MTB). In this study, we aimed to investigate the impact of macrophages stimulated with Ag85B on bronchial epithelial cells and T cells... BACKGROUND: Antigen 85B (Ag85B) is a signature antigen of Mycobacterium tuberculosis (MTB). In this study, we aimed to investigate the impact of macrophages stimulated with Ag85B on bronchial epithelial cells and T cells, as well as the underlying mechanisms involved. METHODS: We used Ag85B to stimulate macrophage and investigated the impact of Ag85B on macrophage polarization. We assessed the impact of TLR4 on Ag85Bmediated macrophage polarization by silencing TLR4. Additionally, the regulatory role of TLR4 on the TRAF6/NF-κB pathway was evaluated through immunoblotting. Activated macrophages with Ag85B were co-cultured with mouse bronchial epithelial cells (MBECs) and T cells, respectively. Through immunoblotting quantification, biochemical methods, and flow cytometry, we explored the effects and molecular mechanisms of Ag85B-induced macrophage activation on bronchial epithelial cell damage and T-cell transformation. RESULTS: In macrophages stimulated with Ag85B, levels of M1 polarization-related genes (CXCL9, CXCL10, and iNOS) and cytokines (IL-6, TNF-α, IL-1β, and IL-12) were increased, and the M1/M2 ratio was elevated. TLR4 silence inhibited the effects of Ag85B on macrophages and decreased TRAF6 and p-NF-κB/NF-κB levels. TRAF6 overexpression reversed the inhibitory effect of TLR4 on macrophage stimulation with Ag85B. After co-culturing with macrophages induced by Ag85B, MBEC cell proliferation was inhibited, apoptosis was promoted, and the TH17/Treg ratio of T cells was increased. Silencing TLR4 reversed the impact of Ag85B-induced macrophage polarization on bronchial epithelial cells and T cells, which was further reversed by TRAF6 overexpression. CONCLUSION: Ag85B promoted M1 polarization in macrophages through the TLR4/TRAF6/NF-κB axis, resulting in bronchial epithelial cell damage and an imbalance in TH17/Treg cells.
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