Current Issues in Molecular Biology最新文献

Renal fibrosis (RF) represents a major pathological outcome of chronic kidney disease, currently accompanied by extremely limited therapeutic strategies. To decipher key cellular and molecular drivers, we integrated single-cell and bulk transcriptomic profiles for comprehensive analysis. Based on the RF-related single-cell and bulk transcriptomic data, key cell subtypes were identified through Scissor analysis, custom signature matrix construction via CIBERSORTx, and Weighted Gene Co-Expression Network Analysis (WGCNA). Subsequently, key subtype-related biomarkers were identified through the expression analysis, and functional enrichment analysis for biomarkers was conducted to elucidate the potential mechanisms by which biomarkers regulate RF. Through comprehensive profiling, thick ascending limb (TAL) cells were predominant and displayed marked heterogeneity in renal fibrosis (RF), with cortical TAL (CTAL) and adaptive TAL (aTAL) identified as principal subtypes. A set of candidate biomarkers was identified. Quantitative polymerase chain reaction (qPCR) validation in mouse models confirmed aberrant expression of these biomarkers, with STAT1 and PARP8 upregulated and HS6ST2, PTGER3, and TMEM207 downregulated in RF. Furthermore, functional enrichment analyses indicated that these biomarkers were associated with pathways underlying metabolic reprogramming and immune perturbation. Our study implicates CTAL and aTAL as central cellular players in RF and identifies their associated biomarkers. These experimentally validated biomarkers provide novel targets and repurposing opportunities for RF therapeutic intervention.

Multiple Myeloma is a malignancy of the plasma cells of the bone marrow. This cancer rapidly becomes refractory to many of the currently available chemotherapeutic regimens used against it, requiring an alternative option or supplementary therapy. Pterostilbene is a naturally occurring compound in a variety of commonly consumed plants that exhibits strong antioxidant properties and, lately, has shown increasing activity as an anti-neoplastic compound. A review of the literature published since 2015 on Google Scholar and PubMed was conducted, with a focus on randomized controlled trials and an exclusion of review articles, unless pertinent to pathophysiology of Multiple Myeloma or background on Pterostilbene as a compound. Though data is limited in the use of Pterostilbene as an agent to combat Multiple Myeloma, studies have shown that it, along with synthetic derivatives, can induce apoptosis and limit proliferation of Multiple Myeloma cell lines. While safety has been evaluated in several settings with promising results, for Pterostilbene to be considered as a supplementary treatment in Multiple Myeloma, safe and effective doses of the compound in this patient population must be investigated and established via pre-clinical and clinical trials in the future.

Mitochondrial transfer in mammals has been proven to occur both under physiological conditions and during pathological conditions. It has been shown that neighboring cells can exchange mitochondria via nanotunnel tubes. However, there is evidence that free mitochondria, as well as whole mitochondria and individual mitochondrial fragments, can be transported between cells within extracellular vesicles (EVs). This review discusses the methodological aspects of isolation and a minimal set of methods for characterizing mitochondria-rich EVs (mitoEVs), as well as methodological approaches for studying the nucleic acid, protein, and lipid composition. It has been shown that mitoEVs, as well as extracellular mitochondria, contain a characteristic set of nucleic acids of mitochondrial origin. First and foremost, the dominant fraction of mitochondrial nucleic acids is mitochondrial DNA (mtDNA), a circular double-stranded molecule approximately 16.6 thousand base pairs in length. The mechanisms involved in EV internalization include clathrin-dependent endocytosis, caveolin-dependent endocytosis, raft-mediated endocytosis, and macropinocytosis. Mitochondrial-enriched autologous and xenogeneic EVs are thought to be internalized by similar mechanisms. The review also presents the main sources (stem cells, platelet concentrate, peripheral blood mononuclear cells) for obtaining mitochondria-rich EVs for therapeutic purposes.

Domestic cats are among the most popular companion animals worldwide, with steadily increasing ownership and life expectancy. Paradoxically, despite their high prevalence and shared environmental exposures with humans, cats remain markedly underrepresented in molecular oncology research. Cancer is a leading cause of feline mortality, and alimentary lymphoma (AL) has emerged as one of the most common feline malignancies, yet its molecular landscape remains poorly characterized. This review summarizes current knowledge on feline AL, including epidemiology, risk factors, classification schemes, diagnostic challenges, treatment outcomes, and survival, with particular emphasis on low-grade alimentary lymphoma (LGAL), the most prevalent subtype. We discuss the complex relationship between chronic inflammatory enteropathies and lymphoma, highlighting diagnostic ambiguities and the inflammatory-neoplastic continuum. Importantly, we provide a critical overview of existing genomic, transcriptomic, epigenomic, proteomic, and metabolomic studies in feline AL, revealing a striking paucity of high-throughput, multi-omics analyses based on clinical material. Recent advances in feline genome assembly and annotation offer new opportunities to address these gaps. Furthermore, we compare feline AL with its human gastrointestinal T-cell lymphoma counterparts, demonstrating substantial molecular homology across key oncogenic pathways, including JAK/STAT signaling. This comparative perspective underscores the potential of feline AL as a naturally occurring model for the human disease. We conclude that comprehensive molecular characterization of feline AL is urgently needed to improve diagnostics, prognostication, and targeted therapies, with likely translational benefits for both veterinary and human oncology. Aim: The goal of this review is to summarize the current knowledge on feline alimentary lymphoma, including its origin, risk, classification, treatment approaches, and especially molecular landscape, which still remains poorly investigated with modern high-throughput techniques.

With the intensification of global climate change, the increasing frequency and severity of extreme weather events seriously affected agroecosystems and human health. Zoysia japonica Steud. (Z. japonica) is a warm season turfgrass with outstanding drought tolerance; therefore, gaining insight into the breeding and ecological restoration of drought-tolerant lawn grass species is of great significance. This study aimed to investigate the adaptive strategies of drought-resistant z047 and z388 by integrating transcriptome analysis and experimental physiological measurements in a drought field. Physiological experiments have demonstrated that z047 plants exhibited a stronger water retention capacity, lower cell membrane damage, and higher above-ground biomass. In addition, the relative water content and permanent wilting coefficient of z047 plants were superior to wild type plants. Our results verified that there were 108 and 208 significantly differentially expressed genes (DEGs) (fold change (FC) ≥ 4, p < 0.01) screened from z047 plants under drought stress for 7 and 14 days, respectively. Moreover, remarkable upregulation of MAPKKK17 and MAPKKK16 genes involved in the MAPK signalling pathway may be closely related to their drought tolerance. Collectively, this study reveals the molecular and physiological synergistic mechanism of drought tolerance in Z. japonica, thus providing a theoretical basis for molecular breeding of drought-tolerant plant cultivars and ecological restoration in arid areas.

Corticotropin-releasing hormone (CRH) and its receptors CRHR1 and CRHR2 are major actors in the stress response and are well established as components of the hypothalamic-pituitary-adrenal (HPA) axis. Evidence also suggests they are expressed in peripheral tissues and, more interestingly, in the skin. While CRHR1 expression in keratinocytes is documented in terms of presence or absence, data on CRHR2 remain sparse. Moreover, there is no detailed description of the exact localization of CRHR1/2 receptors within the different layers of the epidermis, leaving this question fully unexplored. To better understand the link between stress and skin disorders, we aimed to investigate the differential expression of CRHR1 and CRHR2 in keratinocytes, depending on their level of differentiation. In vitro results demonstrated that CRHR1 appears to be more abundant at early stages of differentiation and CRHR2 at more advanced stages.

Cisplatin-induced ovarian damage is a significant concern for young women receiving chemotherapy. Although propolis, a polyphenol- and flavonoid-rich natural product, has been proposed as a protective agent, its effects on cisplatin-related ovarian injury remain insufficiently defined. This study aimed to investigate whether propolis mitigates cisplatin-induced ovarian toxicity. In this study, 36 adult female Wistar rats were randomly allocated into six groups: Control, Propolis (50 mg/kg), Propolis (100 mg/kg), Cisplatin (7 mg/kg), Cisplatin + Propolis (50 mg/kg), and Cisplatin + Propolis (100 mg/kg). Cisplatin was administered as a single intraperitoneal dose on day 1, while propolis was given orally by gavage once daily for 14 days. Biochemical, histopathological, and endoplasmic reticulum (ER)-stress-related parameters were evaluated. Histopathologically, cisplatin caused significant vascular congestion, hemorrhage, edema, and follicular degeneration (p < 0.01), accompanied by marked reductions in primordial, primary, secondary, and tertiary follicle counts and a significant increase in atretic follicles. Propolis co-administration significantly ameliorated these lesions and partially preserved follicular counts, particularly at the 100 mg/kg dose (p < 0.01). Cisplatin markedly increased malondialdehyde (MDA) levels and ER stress markers (GRP78, ATF6, and CHOP), while reducing glutathione (GSH). Propolis treatment ameliorated these changes, decreased TNF-α and caspase-3 levels, and attenuated oxidative, inflammatory, and apoptotic responses. Propolis exerts strong antioxidant, anti-inflammatory, anti-apoptotic, and ER-stress-modulating effects that collectively counteract cisplatin-induced ovarian injury.

Osteoarthritis (OA) is a prevalent degenerative disease of the musculoskeletal system worldwide. Self-assembled hydrogels, as a novel drug delivery system, have demonstrated significant advantages in the treatment of OA. Through non-covalent interactions such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and π-π stacking, these hydrogels spontaneously form a three-dimensional network structure under physiological conditions without the need for chemical crosslinking agents, offering excellent biocompatibility, injectability, and controllable degradation properties. This system enables in -situ gelation within the joint, minimally invasive injection, sustained and controlled drug release, and intelligent responsive release. It is suitable for various delivery forms, including single-drug targeted delivery, exosome-based composite synergistic delivery, and microenvironment-responsive precise delivery, effectively inhibiting inflammation and promoting cartilage repair. Despite facing challenges in clinical translation, such as consistency in large-scale production, long-term safety evaluation, and regulatory standards, continued optimization in material design and preparation processes holds promise for self-assembled hydrogels to become a key platform for precise and minimally invasive OA treatment, offering new solutions for joint disease therapy.

Cancer continues to be a significant cause of death worldwide, particularly cancers with high incidence and mortality such as colorectal, breast, and lung, motivating the continued search for novel anticancer agents. Among potential new molecules with anticancer effects, members of the benzazolo[3,2-a]quinolinium salts (BQs) family, including ABQ-48, have shown promising cytotoxic activity in various cancer models. This study aimed to evaluate the cytotoxic potential and mechanism of action of ABQ-48 (3-amino-7-benzylbenzimidazo[3,2-a]quinolinium chloride) across non-small cell lung carcinoma (NCI-H460), colorectal adenocarcinoma (COLO-205), and breast ductal carcinoma (T-47D) cell lines. Cancer cells were treated for 48 h with ABQ-48, cisplatin, or vehicle, and cytotoxicity was assessed by determining IC₅₀ by fluorescence analysis. Mechanistic evaluation included Annexin V apoptosis detection, caspase-3/7/8 activation assays, mitochondrial membrane permeability analysis, and DNA fragmentation assessment. ABQ-48 exhibited dose-dependent cytotoxicity in all three cancer cell lines, with IC₅₀ values of 6.02 µM (NCI-H460), 14.33 µM (COLO-205), and 33.59 µM (T-47D), surpassing cisplatin's overall efficacy. Annexin V assays confirmed apoptotic induction, while caspase activation demonstrated engagement of both intrinsic and extrinsic pathways. ABQ-48 demonstrates potent anticancer activity through activation of multiple programmed cell death mechanisms, supporting further investigation as promising therapeutic candidate.

Euphorbia helioscopia L. (Zeqi, ZQ) is a traditional Chinese herb used to treat various tumors, but its molecular mechanisms against hepatocellular carcinoma (HCC) remain unclear. This study aims to elucidate the anti-HCC mechanisms of ZQ using chemical profiling, bioinformatics, Mendelian randomization (MR), and experimental validation. A total of 104 compounds were identified from ZQ, with 18 targeting HCC-related proteins. Bioinformatics and MR analyses revealed PTK2 as a core target associated with HCC risk. ZQ significantly suppressed H22 tumor growth in male ICR mice and inhibited PTK2/PI3K/AKT phosphorylation. Molecular docking and dynamics simulations confirmed stable binding between key ZQ compounds and PTK2. These results suggest that ZQ exerts anti-HCC effects through PTK2 inhibition and modulation of the PI3K/AKT pathway, supporting its potential as a multi-targeted therapeutic for HCC.