Frontiers in Molecular Biosciences最新文献

Purpose: This study evaluated the effect of Tirzepatide on metabolic profiles, kidney function, and gut microbiota composition in mice with diabetic kidney disease (DKD) and clarify the relationship between gut microbiota alterations and the renoprotective effects.

Methods: Seven-week-old diabetic db/db mice and db/m controls were randomly assigned to three groups: db/db, db/db-T, and db/m. In the db/db-T group, mice received 10 nmol/kg Tirzepatide injections for a duration of 8 weeks. Biochemical and histopathological analyses were used to assess body weight, blood glucose, lipid profile, hepatic and renal function, and renal histopathological changes in mice. An antibiotic-pretreated group (ABX-db/db-T) was established to explore the impact of gut microbiome depletion on the therapeutic effects of Tirzepatide.The composition of gut microbiota was determined through 16S rRNA gene sequencing to assess microbial differences among groups.

Results: Tirzepatide notably decreased fasting blood glucose (FBG), food intake, body weight, glycated hemoglobin A1c (HbA1c), blood lipid levels, and liver function markers, while improving renal function in mice. The renoprotective effects of Tirzepatide were attenuated following gut microbiota depletion. Microbiota analysis revealed that Tirzepatide could reverse dysbiosis and reshape the gut microbial ecosystem. Tirzepatide treatment raised the proportion of beneficial genera, Clostridium_sensu_stricto_1 and Romboutsia, while reducing potentially pathogenic genera, Erysipelatoclostridium and Bacteroides. Moreover, these microbiota changes were significantly correlated with serum creatinine and urinary albumin/creatinine ratio.

Conclusion: Tirzepatide improves renal function and metabolic parameters in DKD mice through gut microbiome regulation. The underlying mechanism involves the modulation of gut-renal axis through the optimization of microbial composition, promoting the development of beneficial bacteria while inhibiting harmful microbes. These results establish a foundational understanding for the use of Tirzepatide in DKD and suggest that combined interventions targeting the gut microbiota may have potential clinical value.

The bHLH-PAS protein family consists of transcription factors that are involved in the regulation of key physiological processes such as the response to hypoxia, circadian rhythms, the detoxification of xenobiotics, and metabolic homeostasis. These proteins act as environmental sensors, integrating diverse signals into transcriptional responses. In recent years, increasing attention has been paid to their role in regulating endoplasmic reticulum stress (ER stress), which is an adaptive cellular response to disturbances in protein-folding. Prolonged or severe ER stress can activate the unfolded protein response (UPR) and apoptotic pathways, contributing to the development of numerous disorders, including neurodegenerative, cancerous, and inflammatory diseases. This review focuses on the functions of bHLH-PAS proteins, such as AHR, HIF, SIM, NPAS1-4, and CLOCK, with particular emphasis on their potential role in modulating ER stress. Molecular mechanisms through which these proteins regulate responses to hypoxia and other cellular stressors are also discussed, with a focus on their importance in maintaining homeostasis and their potential as therapeutic targets.

Cancer remains one of the leading causes of death worldwide. Among various diagnostic approaches, Raman spectroscopy (RS) has emerged as an advanced detection technology with the potential to distinguish cancerous tissues from normal ones. Notably, RS has been verified to show improved sensitivity, specificity, and accuracy for cancer diagnosis compared to conventional techniques. Recently, artificial intelligence (AI), developed to emulate human capabilities, has gained enough popularity and showcased its strength in learning high-level representations and recognizing complex patterns with remarkable efficiency. In this context, AI-assisted RS has been applied to the classification and prediction of cancer cells, achieving a higher accuracy of ∼90% in correct predictions from a single spectrum. However, there has been no comprehensive review about the use of AI-assisted RS in distinguishing different types of cancer cells. Although AI-assisted RS has been widely utilized by researchers and clinicians over the past a few years to diagnose various cancers, including gastrointestinal, head and neck, cervical, and endocrine-related cancers, an in-depth investigation has yet to be conducted. This review aims to provide a narrative overview of the latest applications of AI-assisted RS in cancer diagnosis, summarize the key findings and benefits, discuss the associated challenges in different types of cancers, and present additional studies on AI-assisted RS in non-cancer diseases, such as fungal infections. Through this review, we hope to enhance researchers' understanding of the potential value of AI-assisted RS in both cancer and non-cancer diseases, presenting a new diagnostic approach for clinical management, optimizing diagnostic efficacy, and ultimately improving patient survival outcomes.

Colorectal cancer (CRC) persists as a significant global health challenge, distinguished by intricate molecular modifications and a notable propensity for resistance to standard therapeutic interventions. Among the regulatory factors contributing to CRC pathogenesis, microRNAs (miRNAs) have emerged as pivotal regulators of gene expression, presenting innovative prospects for diagnostic and therapeutic advancements. Notably, microRNA-143 (miR-143) has attracted considerable attention as a tumor-suppressive miRNA, exhibiting diverse functions in the development, progression, and therapeutic response of CRC. This review delineates an exhaustive examination of the molecular mechanisms by which miR-143 modulates critical oncogenic pathways, encompassing KRAS signaling, epithelial-mesenchymal transition, and metabolic reprogramming. We underscore recent progress in the molecular biosciences that position miR-143 as a promising biomarker for the early detection and prognosis of CRC. Furthermore, we investigate its emergent function in the modulation of sensitivity to chemotherapeutic and targeted therapeutic agents, emphasizing its potential utility in predicting and mitigating drug resistance in CRC cells. By synthesizing contemporary findings within the domains of molecular diagnostics and therapeutic interventions, this review accentuates the clinical potential of targeting miR-143 in the personalized management of CRC and the prediction of drug resistance.

The structure of a protein is closely linked to its function. Many proteins undergo conformational changes while working in living cells. Consequently, proteins in various structural states coexist in the native cellular environment. Understanding the structural heterogeneity of proteins in living cells is essential for understanding the kinetics of protein reactions. Single-molecule Förster resonance energy transfer (smFRET) is a powerful tool for probing the structure of biomolecules at the single-molecule level. Confocal smFRET measurements, which obtain the smFRET distribution of freely diffusing single molecules, have been successfully applied to cytosolic proteins in living cells. Previous studies on CRAF, a member of the RAF kinase family, revealed the coexistence of at least three conformational states and critical interactions with 14-3-3 proteins. In this study, we applied the method to, in addition to wild-type (WT) CRAF, to mutants at important sites, and to co-expression with other proteins related to RAF activation. The detailed analyses comparing those results suggest the presence of a fourth minor conformational state of CRAF in addition to the previously identified three major states. This fourth state may be related to RAF dimers. Supported by a newly introduced burst intensity analysis, we also found that the three major components can be classified into two groups: two interconvertible components and one independent component. Furthermore, in-cell smFRET measurement of wild-type BRAF, another RAF family member, revealed that its structural distribution consists primarily of a single species, which seemingly corresponds to the lowest FRET component among the three structural states of WT-CRAF. This finding suggests that BRAF has a fundamentally different structural and regulatory mechanism than CRAF.

Background: Gliomas are highly aggressive intracranial tumors associated with poor prognosis. Glioma stem cells (GSCs) have been shown to play a pivotal role in tumor progression. Previous studies indicate that GPM6B expression correlates with glioma grade and neuronal differentiation. However, the precise mechanisms of GPM6B in glioma remain unknown. In this study, we aim to elucidate the regulatory role of GPM6B in glioma.

Methods: The relationship between the expression of GPM6B and glioma was analyzed using the CGGA and TCGA databases. Western blot analysis was performed to further validate GPM6B expression in clinical samples. The interaction between GPM6B and the Wnt signaling pathway was explored using co-immunoprecipitation, mass spectrometry, quantitative real-time PCR, and Western blot. These findings were further confirmed in cells transduced with different lentiviral constructs. Tumor sphere formation and extreme limiting dilution assays were conducted to assess the stemness of glioma stem cells. Finally, the role of GPM6B in glioma progression was validated in nude mouse models.

Results: The expression of GPM6B was negatively correlated with glioma grade and prognosis. GPM6B was co-localized with Integrin β1 on the cell membrane. The interaction between GPM6B and Integrin β1 inhibited the expression of β-catenin and its downstream proteins, including p-STAT3, c-Myc, and SOCS3. Moreover, SOCS3 promoted the degradation of GPM6B. Overexpression of GPM6B suppressed tumor sphere formation and reduced the sphere formation efficiency of glioma stem cells. In addition, GPM6B overexpression markedly inhibited the tumorigenic effects of β-catenin and SOCS3. These findings were confirmed in vivo experiments.

Conclusion: The expression of GPM6B was negatively correlated with the grade and prognosis of glioma. GPM6B promoted the transformation of glioma stem cells and inhibited growth of glioma by suppressing Integrin β1-mediated regulation of β-catenin, while reducing its own degradation through inhibition of the ubiquitinase SOCS3, thereby stabilizing its function in glioma. Collectively, these results identify GPM6B as a critical regulator of glioma stemness and a potential therapeutic target for glioma, providing new insights into glioma biology and offering a foundation for future translational research.

Salvia is a genus of Lamiaceae family with more than 1,000 species having diverse utility. The wide range of uses encompasses food, flavor, cosmetics, aromatherapy, horticulture, and medicine. It has been attributed to the presence of bioactive compounds belonging to essential oils, phenolic compounds, and flavonoids that are extensively studied using spectroscopic and chromatographic techniques. This review aims to investigate in-depth previously published literature from 2020 to 2025 on 59 Salvia species. It was performed with several key search words focused on the chemical compounds in Salvia spp. and their pharmacological efficacy. Salvia species were enriched with essential oils comprising important components: α-pinene, β-pinene, limonene, linalool, caryophyllene, germacrene, myrcene, α-thujone, and humulene. Potential health benefits owing to anticancer, antioxidant, antidiabetic, anti-inflammatory, antithrombotic, antirheumatic, and antiviral properties were reported from Salvia species. Salvia phytochemicals have been studied as regulating anticancer mechanisms at the cellular level by effectively modulating host cell responses in multiple ways. This review summarizes and discusses recent studies on the metabolite profiling of Salvia plants and bioactivities of the extracts and compounds. It may provide future perspectives on the in silico and pharmacognostic studies on potent Salvia compounds. Isolation and evaluation of bioactive compounds from the least studied species is recommended.

Introduction: Osgood-Schlatter disease (OSD) is characterized by its relatively frequent occurrence and unknown pathomechanism. It mainly affects young athletes. Matrix metalloproteinases (MMPs) may be involved in the pathogenesis, while Thrombospondin 2 is involved in healing process. Purpose of this study was to determine changes in MMP-8, MMP-13 and Thrombospondin 2 levels in patients with OSD compared to control group (CG).

Methods: The study was conducted on 140 patients with OSD (age range: 11-15), CG consisted of 100 individuals with minor hand injuries (age range: 12-15). Levels of MMPs and Thrombospondin 2 were determined in plasma using an immunoenzymatic method (ELISA).

Results: Concentrations of MMP-13 (median: 496.5 ng/mL; p < 0.0001) and Thrombospondin 2 (median: 21.05 pg/mL; p < 0.0001) were higher in patients with OSD, while MMP-8 values (median: 26.60 ng/mL; p < 0.001) were lower in patients with OSD compared to CG (58.08 ng/mL; 14.43 pg/mL; 95.91 ng/mL; respectively). Significant correlations were found between the parameters studied, and the highest AUC (area under curve) was obtained for MMP-13 in the OSD group.

Discussion: The studied compounds have potential as additional tests to distinguish OSD from other diseases, and MMP-13 may be involved in the pathogenesis of OSD.