International Journal Of Molecular Sciences[JOURNAL]
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200 papers
Depot-Specific White Adipose Tissue Remodeling Supports Non-Thermogenic Metabolic Homeostasis During Shallow Hibernation in Raccoon Dogs.
Zong R, Han Z, Liu R … +6 more , Yang M, Liu X, Zhang X, Hu J, Du R, Xu C
Int J Mol Sci · 2026 Jun · PMID 42353325 · Full text
White adipose tissue (WAT) is essential for maintaining energy homeostasis during hibernation by supplying lipolysis-derived fatty acids as a major fuel source. In raccoon dogs (), the activity of brown adipose tissue is...
White adipose tissue (WAT) is essential for maintaining energy homeostasis during hibernation by supplying lipolysis-derived fatty acids as a major fuel source. In raccoon dogs (), the activity of brown adipose tissue is diminished, providing a unique model to investigate how WAT supports metabolic homeostasis in a largely non-thermogenic state. Here, we integrated physiological, histological, transcriptomic, and molecular analyses of back-fat and tail-fat depots during autumn fattening and winter sleep. Despite reduced food intake, body weight loss, and mild hypothermia, raccoon dogs maintained systemic glucose and lipid homeostasis. Both WAT depots exhibited adipocyte atrophy and the coordinated suppression of core metabolic and biosynthetic pathways, indicating a shared program of metabolic depression. However, the two depots adopted distinct remodeling strategies. Back-fat showed collagen densification and vascular-associated remodeling, suggesting a structural adaptation that may preserve tissue integrity during winter sleep. In contrast, tail-fat displayed enhanced innate immune signaling and M2 macrophage enrichment, indicating immune niche remodeling that may support tissue protection during prolonged lipid mobilization. Together, these findings reveal that raccoon dogs maintain metabolic homeostasis during shallow hibernation through a non-thermogenic, WAT-centered strategy characterized by shared metabolic depression and depot-specific structural and immunometabolic remodeling.
Special Issue "Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024)".
Makarevich PI, Tkachuk VA
Int J Mol Sci · 2026 Jun · PMID 42353324 · Full text
The recent rapid advances in technological pipelines are urging faster and riskier translational moves from research to practice in regenerative medicine [...].
The recent rapid advances in technological pipelines are urging faster and riskier translational moves from research to practice in regenerative medicine [...].
as a Multi-Target Antidiabetic Agent: Mechanistic Insights and Metabolic Regulation.
Ziyanok-Demirtas S, Serin I
Int J Mol Sci · 2026 Jun · PMID 42353323 · Full text
Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological...
Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. (Retz.) R.Br. ex Sm (GS), traditionally known as "gurmar" ("sugar destroyer"), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of , focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure-molecular target-metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research.
Cadmium Is Accumulated as Electron-Dense Nanoparticles, Not Bound to Glutathione (GSH), Phytochelatins or Metallothioneins, and Extruded to the Culture Medium with GSH in the Marine Alga .
Cabezas P, Romero S, Méndez P … +5 more , Pichún B, Segura R, Osorio H, González A, Moenne A
Int J Mol Sci · 2026 Jun · PMID 42353322 · Full text
The mechanism of cadmium (Cd) accumulation was analyzed in the marine alga . The alga was cultivated with 10 µM Cd, with 10 µM of Cd and increasing concentrations of a sulfide donor (NaHS), or with a sulfide acceptor (hy...
The mechanism of cadmium (Cd) accumulation was analyzed in the marine alga . The alga was cultivated with 10 µM Cd, with 10 µM of Cd and increasing concentrations of a sulfide donor (NaHS), or with a sulfide acceptor (hypotaurine), and intracellular Cd levels were monitored for 7 d. Glutathione (GSH) and phytochelatins (PCs) levels, and metallothioneins (MTs) transcript levels were also quantified, along with the extrusion of Cd, GSH, and PCs to the culture medium. The results showed that the sulfide donor increased intracellular Cd levels, whereas the sulfide acceptor decreased them. GSH, PCs, and MTs levels did not correlate with intracellular Cd contents. Both Cd and GSH were extruded to the culture medium, along with lower amounts of PCs. TEM-EDXS analysis revealed electron-dense nanoparticles containing Cd and O, likely CdO or Cd bound to fatty acids; in the presence of NaHS, nanoparticles containing Cd and S (likely CdS) or Cd, S, and N (likely Cd bound to GSH) were also observed. In conclusion, Cd accumulates as insoluble nanoparticles-probably not bound to GSH, PCs, or MTs-and is extruded to the culture medium together with GSH in the marine alga .
Molecular Effects of Hassk. Empty Pod Extract in Colon Cancer: A Transcriptomic and Proteomic Perspective.
Chaiwichien A, Osotprasit S, Samrit T … +5 more , Smith SJ, Suwansa-Ard S, Cummins SF, Kueakhai P, Changklungmoa N
Int J Mol Sci · 2026 Jun · PMID 42353321 · Full text
This study elucidates the multi-targeted antineoplastic mechanisms of empty pod extract (PSET) against HCT-116 and HT-29 colorectal cancer (CRC) cells through integrated transcriptomic and proteomic analyses. Phytochemi...
This study elucidates the multi-targeted antineoplastic mechanisms of empty pod extract (PSET) against HCT-116 and HT-29 colorectal cancer (CRC) cells through integrated transcriptomic and proteomic analyses. Phytochemical profiling indicates that PSET is rich in bioactive metabolites, notably quercetin, rutin, and pyrogallol, which orchestrate its profound ability to inhibit tumor proliferation, migration, and invasion. Transcriptomic data revealed that PSET profoundly suppresses the oncogenic Wnt/β-catenin signaling axis while simultaneously activating p53-mediated cell cycle arrest. Complementary proteomic profiling uncovered critical metabolic vulnerabilities, demonstrating that PSET abrogates the Warburg effect by disrupting key glycolytic enzymes (e.g., ENO1, GAPDH, LDHA), thereby inducing metabolic starvation. Furthermore, the extract precipitated a catastrophic collapse of the cytoskeletal architecture and downregulated epithelial-mesenchymal transition (EMT) markers, effectively paralyzing the cells' metastatic machinery. The integrated transcriptomic and proteomic signatures also highlighted an irrecoverable state of cellular stress, characterized by an overwhelming unfolded protein response and dysregulated RNA splicing, ultimately driving the cells toward apoptosis. In conclusion, this integrated omics approach provides robust molecular validation that PSET systemically dismantles colorectal cancer survival networks, highlighting its strong potential as a natural, multi-targeted therapeutic agent.
Morphostructural Analysis of PAH-Rich Human Adipose Tissue: A Potential Silent Sequestration Site.
Stocco E, Barbon S, Contran M … +12 more , Manzo V, Brunelli D, Sorarù L, Franchin A, Gregoris E, Roman M, Gambaro A, Cairns WRL, De Caro R, Vindigni V, Macchi V, Porzionato A
Int J Mol Sci · 2026 Jun · PMID 42353320 · Full text
Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent pollutants that can be sequestered within human adipose tissue due to their lipophilic nature. While this accumulation poses toxicological risks dependin...
Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent pollutants that can be sequestered within human adipose tissue due to their lipophilic nature. While this accumulation poses toxicological risks depending on dose and individual susceptibility, the specific morphological impact of chronic PAH storage on tissue architecture remains poorly defined. Here, we performed a histopathological and morphometric analysis on human subcutaneous adipose tissue samples characterized by high pyrene levels. We evaluated tissue organization, collagen distribution, the presence of inflammatory, neural, and vascular alterations and adipocyte morphometry to assess the structural response to PAH sequestration. Despite high pyrene concentrations, PAH-positive tissues maintained preserved overall architecture with normal collagen distribution, absence of lymphocytic infiltration, low macrophages, unaltered nerve fiber patterns, without evidence of vascular remodeling. Morphometry revealed smaller adipocyte area in PAH-positive samples, although not statistically significant. Our experimental data indicate that high PAH accumulation does not necessarily induce subcutaneous adipose tissue remodeling, suggesting that biochemical or metabolic alterations might occur even in the absence of evident histological changes. Further studies, with a broadened cohort, are needed to define the threshold at which PAHs' presence translates into permanent tissue damage.
A Healthy Lifestyle Can Slow Immune System Aging and Reduce Age-Related Chronic Inflammation: A Narrative Review.
Cąkała-Jakimowicz M, Domaszewska-Szostek A, Puzianowska-Kuźnicka M
Int J Mol Sci · 2026 Jun · PMID 42353319 · Full text
Age-related decline in immune system function is characterized by reduced numbers of naïve lymphocytes, the accumulation of senescent cells, impaired function of all immune cell types, and chronic low-grade inflammation...
Age-related decline in immune system function is characterized by reduced numbers of naïve lymphocytes, the accumulation of senescent cells, impaired function of all immune cell types, and chronic low-grade inflammation (inflammaging). These alterations contribute to increased susceptibility to infections and malignancies, as well as to autoimmunity and other age-associated diseases. This article reviews current evidence on lifestyle interventions that may mitigate immune aging. Lifestyle-related strategies, including regular physical activity, nutritional interventions (e.g., different diets, caloric restriction, and other fasting-related approaches), stress reduction, and vaccination, are discussed as key modulators of immune function and systemic inflammation. Notably, vitamin D supplementation has been shown to reduce the incidence of autoimmune diseases by 22%. In comparison, caloric restriction has led to a decrease in CRP and TNF-α by 40% and 50%, respectively. Emerging complementary approaches, such as mind-body practices and controlled cold exposure, show promise, though current evidence remains limited and inconsistent. Therefore, integrated lifestyle strategies may slow aging-related immune decline and support healthy aging. However, longitudinal trials are required to define the optimal intervention parameters, population-specific thresholds, and the long-term durability of immune rejuvenation.
Assessment of Addictive Behavior in Rats with Partial Knockout of the Dopamine Transporter Gene.
Lebedev AA, Shabanov PD, Lyakso EE … +7 more , Frolova OV, Kleshnev EA, Nikolaev AS, Sizov VV, Netesa MA, Balaganskii IA, Pyurveev SS
Int J Mol Sci · 2026 Jun · PMID 42353318 · Full text
Animals with knockout of the dopamine transporter gene (DAT-KO) display hyperdopaminergic phenotypes, including attention-deficit/hyperactivity-like behaviors. A previous behavioral analysis of heterozygous rats with par...
Animals with knockout of the dopamine transporter gene (DAT-KO) display hyperdopaminergic phenotypes, including attention-deficit/hyperactivity-like behaviors. A previous behavioral analysis of heterozygous rats with partial knockout (DAT-HET) suggested increased susceptibility to addictive behaviors. The aim of this study was to investigate elements of addictive behaviors and the mechanisms underlying dopamine release in DAT-HET rats. Offspring derived from DAT-knockout breeding underwent genotyping and behavioral assessment using the marble burying test, a manipulative behavior test using nesting material, and a modified version of the Iowa Gambling Task. Feeding behavior was studied using a binge-eating model. Reinforcing properties were investigated using intracranial self-stimulation under fixed-ratio (FR) and variable-ratio (VR) schedules. Dopamine (DA) release and clearance dynamics were assessed using fast-scan cyclic voltammetry (FSCV). DAT-HET rats exhibited moderate hyperactivity, increased impulsive choice, and compulsive responses. Male DAT-HET rats also showed increased compulsive overeating compared with wild-type (WT) rats of both sexes and female DAT-HET rats. In addition, DAT-HET rats demonstrated a preference for VR self-stimulation, which resembles risk- and thrill-seeking behavior in humans. In DAT-KO rats, impaired DA clearance resulted from complete loss of dopamine transporter function. In DAT-HET rats, increased DA release amplitude was observed, and dopamine persisted longer in the extracellular space than in WT rats. These findings underscore the importance of the DAT-HET model for studying impulsivity, compulsivity, and factors underlying the predisposition to addictive behavior.
Special Issue "Role of Immune Cells in Non-Infectious Inflammatory Diseases and Cancers".
Bezsonov EE
Int J Mol Sci · 2026 Jun · PMID 42353317 · Full text
Inflammation is at the heart of many different non-infectious diseases, including cancer [...].
Inflammation is at the heart of many different non-infectious diseases, including cancer [...].
Exercise Training Regulates Cortical GPCR-Mediated Signaling Networks Through cAMP, Calcium, and Neuroactive Ligand-Receptor Interaction Pathways in Diabetic-Obese Rats: An In Silico Study.
Chiang YY, Widjaya MA, Lee SD
Int J Mol Sci · 2026 Jun · PMID 42353316 · Full text
Exercise-induced regulation of cortical GPCR pathways in diabetic obesity remains unclear. This study aimed to investigate exercise-associated GPCR-related transcriptomic pathway changes in the cerebral cortex of diabeti...
Exercise-induced regulation of cortical GPCR pathways in diabetic obesity remains unclear. This study aimed to investigate exercise-associated GPCR-related transcriptomic pathway changes in the cerebral cortex of diabetic-obese rats. Cerebral cortical samples from male Zucker Fatty Diabetes Mellitus (ZFDM) rats subjected to a 12-week swimming program were examined using RNA sequencing, functional enrichment, GSOAP clustering, and STRING-based protein-protein interaction (PPI) analysis. Exercise training reduced fasting glucose and body weight. RNA sequencing identified 817 exercise-responsive transcripts (403 upregulated and 414 downregulated; < 0.05), including 48 associated with GPCR signaling. Results showed that these 48 genes mapped to three major GPCR-related networks: cAMP signaling, with increased Adcyap1r1, Gipr, Tshr, and Vipr2 and decreased Vip, Chrm1, Gabbr2, and Sst; calcium signaling, with increased Ntsr1 and Trhr and decreased Chrm1; and neuroactive ligand-receptor interaction, with increased Trh, Trhr, and Crh and decreased Opr-related transcripts. These findings provide hypothesis-generating evidence for interpreting cortical GPCR-related transcriptomic pathway associations in diabetic-obese conditions.
Super-Resolution 3D Imaging Reveals Disarray of Dyadic Calcium Ion Channels in Failing Hearts Expressing Low Thyroid Hormone Function.
Ashkezari A, Schmalzle M, Charest A … +10 more , Kumar S, Modi R, Nasta N, Bertolini A, Saba A, Cifani P, Zhang Y, Gerdes AM, Stout RF, Ojamaa K
Int J Mol Sci · 2026 Jun · PMID 42353315 · Full text
Ventricular remodeling occurring in heart failure (HF) involves structural disarray of the sarcolemma T-tubule (TT)-sarcoplasmic reticulum (SR) dyad junctions, thereby disrupting the close apposition of L-type Ca channel...
Ventricular remodeling occurring in heart failure (HF) involves structural disarray of the sarcolemma T-tubule (TT)-sarcoplasmic reticulum (SR) dyad junctions, thereby disrupting the close apposition of L-type Ca channels (Ca1.2) with ryanodine receptors (RyR2) that trigger SR Ca release and myofilament contraction. In a rat ischemic heart failure model expressing low thyroid hormone (TH) function, we used 3D stochastic optical reconstruction microscopy (STORM) to image RyR2 clusters with Ca1.2 channels, and the associated protein junctophilin-2 (Jph2). We tested whether treatment with T3, the biologically active form of TH, throughout progression of the disease would preserve T-tubule structure and dyadic ion channel organization. Confocal microscopy of isolated cardiomyocytes (CMs) stained with ANEPPS membrane dye showed significantly decreased TT density in diseased CMs while T3 treatment attenuated TT disorganization. 3D STORM images of dyadic ion channels labeled with fluorescent-tagged antibodies to RyR-Dylight550, Jph-CF647 and Ca1.2/IgG-Dylight488 were captured. A density-based algorithm defined RyR2 clusters, and a 400 nm spherical 3D volume of interest around each RyR2 cluster's centroid determined the number of Ca1.2 and Jph2 localizations associated with each RyR2 cluster. Analysis revealed significant reduction in RyR2 cluster size and number with reduced co-localized Jph2 in failing CMs. T3 treatment increased RyR2 cluster numbers and cluster volumes albeit non-significantly, with increased co-clustering of Jph2. The number of Ca1.2 co-localized with RyR2 clusters trended lower in the failing CMs. These results support maintaining TH homeostasis in optimizing the nanoscale organization of Ca ion channels in triggering Ca release and myofibrillar contraction in patients with heart disease.
IL-13Rα2 Regulates C2C12 Myoblast Proliferation via the Akt-Cyclin D1-CDK4 Pathway.
Kurosaka M, Kohda K
Int J Mol Sci · 2026 Jun · PMID 42353314 · Full text
Interleukin-13 receptor α2 (IL-13Rα2) has traditionally been considered a decoy receptor; however, its cellular functions beyond the immune system remain unclear. We aimed to investigate the role of IL-13Rα2 in C2C12 myo...
Interleukin-13 receptor α2 (IL-13Rα2) has traditionally been considered a decoy receptor; however, its cellular functions beyond the immune system remain unclear. We aimed to investigate the role of IL-13Rα2 in C2C12 myoblast proliferation and differentiation. IL-13Rα2 expression was knocked down in C2C12 cells using siRNA. Myogenic differentiation was evaluated by myosin heavy chain (MyHC) immunostaining and by quantifying the expression of myogenic regulatory and fusion-related genes. Myoblast proliferation was assessed using BrdU incorporation and cell number analyses, and signaling events induced by IL-13Rα2 knockdown were analyzed via immunoblotting and immunocytochemical analysis. IL-13Rα2 knockdown did not alter myogenic differentiation or the expression of fusion-associated genes. In contrast, IL-13Rα2 knockdown significantly increased BrdU incorporation and cell number, accompanied by increased Akt phosphorylation and decreased ERK phosphorylation. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) levels were also increased. Akt inhibition abolished the enhanced proliferation and normalized Cyclin D1/CDK4 levels, whereas ERK activation did not further modify the knockdown-associated phenotype. These findings demonstrate that IL-13Rα2 negatively regulates myoblast proliferation by modulating the Akt-Cyclin D1-CDK4 signaling pathway, while being dispensable for myogenic differentiation.
Molecular Genetic and Biochemical Characterization of Hyperphenylalaninemia Based on Expanded Neonatal Screening Data from 2023 to 2024 in the Russian Federation.
Lotnik EE, Chukhrova AL, Ryadninskaya NV … +19 more , Kadnikova VA, Zakharova EY, Baydakova GV, Osadchii AR, Anisimova IV, Voronin SV, Kutsev SI, Savostyanov KV, Bilalov FS, Koroteev AL, Trofimov DY, Bairova TA, Seitova GN, Mordanov SV, Matulevich SA, Golikhina TA, Nikolaeva EB, Polyakov AV, Shchagina OA
Int J Mol Sci · 2026 Jun · PMID 42353313 · Full text
Since January 2023, the Russian Federation has implemented expanded neonatal screening for 36 hereditary disorders, which has changed the diagnostic algorithm for hyperphenylalaninemia/phenylketonuria (HPA/PKU) by introd...
Since January 2023, the Russian Federation has implemented expanded neonatal screening for 36 hereditary disorders, which has changed the diagnostic algorithm for hyperphenylalaninemia/phenylketonuria (HPA/PKU) by introducing tandem mass spectrometry (MS/MS) on the second day of life, followed by confirmatory biochemical and molecular testing in newborns at risk. We analyzed 1247 newborns aged 5-15 days with elevated phenylalanine levels (≥120 µmol/L) and a phenylalanine to tyrosine ratio of at least 1 detected during the first stage of screening using MS/MS. At the reference center, newborns underwent repeat biochemical testing and stepwise molecular analysis of HPA-associated genes. Two pathogenic variants in HPA-associated genes were identified in 538 newborns, including 534 newborns with biallelic pathogenic variants in and 4 with BH4-deficient forms (, ). The incidence of molecularly confirmed HPA was 1:4518 newborns (95% CI: 1:4152-1:4925). The variant spectrum was dominated by p.Arg408Trp (c.1222C>T) (33.4%). Genotype-based analysis indicated that 73 newborns (13.7%) were likely responsive to cofactor therapy, whereas 222 (41.6%) were potentially responsive. These findings define the molecular epidemiology of HPA in Russia and support early genetic stratification for diagnosis and treatment.
Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression.
McGraw MK, Parajuli N
Int J Mol Sci · 2026 Jun · PMID 42353312 · Full text
Acute kidney injury, a broad term associated with diverse etiologies, is a common pathological condition that develops into chronic disease via mechanisms that have yet to be fully understood. Key processes that promote...
Acute kidney injury, a broad term associated with diverse etiologies, is a common pathological condition that develops into chronic disease via mechanisms that have yet to be fully understood. Key processes that promote chronic disease transition include mitochondrial dysfunction and aberrant complement system activation, specifically inducing inflammation and accumulation of pro-fibrotic changes. Although emerging evidence strongly indicates that these two processes are closely intertwined, identification of appropriate therapeutic targets remains limited. Among complement proteins, terminal portions of the cascade, including complement 5 (C5), exert particularly robust effects on mitochondrial function across tissues, including the kidney. Moreover, C5 is the most terminal portion of the cascade to produce a highly pro-inflammatory anaphylatoxin, positioning C5 as an ideal clinical target during kidney injury/disease. In this review, we will hence summarize current knowledge regarding mitochondrial contributions to kidney pathophysiology through the lens of the close relationship between mitochondria and the complement system, particularly C5.
Regular Aerobic Exercise Can Effectively Ameliorate the Skeletal Muscle and Mitochondrial Function Impairments Caused by Deficiency in Zebrafish.
Cai W, Zhou W, Wu X … +14 more , Lei J, Wang H, Wu Q, Zhou S, Sun K, Li X, Zhang Z, Zhang J, Ouyang J, Li Y, Jiang Z, Liu X, Yuan W, Zheng L
Int J Mol Sci · 2026 Jun · PMID 42353311 · Full text
The Popeye domain-containing protein 1 (Popdc1), also known as Bves, plays a crucial role in maintaining skeletal muscle homeostasis, with its variants leading to limb-girdle muscular dystrophy type R25. Skeletal muscles...
The Popeye domain-containing protein 1 (Popdc1), also known as Bves, plays a crucial role in maintaining skeletal muscle homeostasis, with its variants leading to limb-girdle muscular dystrophy type R25. Skeletal muscles of patients with the homozygous missense variant of Bves exhibit impaired membrane trafficking, while skeletal muscle fibers in homozygous mutant zebrafish are significantly reduced and disorganized. However, the mechanism by which the absence of induces skeletal muscle atrophy remains unclear. In this study, we discovered a novel mechanism whereby deficiency drives skeletal muscle atrophy by disrupting mitochondrial structure and function. Our findings indicate that knockout leads to a significant decrease in zebrafish's ability to swim, atrophy of skeletal muscle tissue, loss of cell membrane localization signals, and abnormalities in mitochondrial structure and function. After an 8-week intervention of regular aerobic exercise, the symptoms of skeletal muscle atrophy in knockout zebrafish were significantly alleviated, and the expression levels of genes and proteins related to mitochondrial were effectively rescued. These findings establish a connection between deficiency-induced disruption of mitochondrial structure and function and the onset and progression of skeletal muscle tissue atrophy symptoms, thereby laying a molecular foundation for exercise rehabilitation strategies in atrophic myopathy.
Decoding the Gut-Fat-Heart Axis: From Molecular Communication Networks to Clinical Translation Strategies.
Sun Z, Shao W, Zhang H … +3 more , Wang K, Liu Y, Zhou R
Int J Mol Sci · 2026 Jun · PMID 42353310 · Full text
The prevention and treatment of cardiovascular disease (CVD) are undergoing a paradigm shift from a lipid-centric approach to a holistic metabolic perspective. Central to this evolution is the gut-fat-heart axis, a sophi...
The prevention and treatment of cardiovascular disease (CVD) are undergoing a paradigm shift from a lipid-centric approach to a holistic metabolic perspective. Central to this evolution is the gut-fat-heart axis, a sophisticated three-dimensional communication network that integrates neural, endocrine, and immunometabolic signaling to regulate systemic lipid homeostasis. This manuscript systematically explores how the gut microbiota acts as a "metabolic organ" to remotely control host health through the production of bioactive metabolites and the modulation of molecular communication networks. At the physiological level, microbial products such as short-chain fatty acids (SCFAs) and modified bile acids regulate energy balance and lipid synthesis via the FXR-FGF15/19 axis and G protein-coupled receptors. Furthermore, gut hormones like GLP-1 and neuro-reflex pathways involving the vagus nerve provide rapid control over postprandial lipid clearance and feeding behavior. Conversely, pathological dysbiosis triggers the accumulation of harmful metabolites, such as trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS), which drive lipotoxicity, vascular inflammation, and "dysfunctional HDL" formation. These processes accelerate the progression of atherosclerosis, heart failure, and metabolic syndrome. Finally, the article outlines promising clinical translation strategies, including the development of TMA lyase inhibitors, next-generation probiotics, and the use of phytochemicals to reshape the microbial landscape. By decoding the molecular dialogues within the gut-fat-heart axis, this research provides a novel strategic vantage point for the integrated management of cardiovascular-kidney-metabolic (CKM) syndrome.
A Restricted Two-Stage Multi-Locus Multi-Allele Genome-Wide Association Study Reveals Genomic Loci and Candidate Genes Controlling Plant-Height-Related Traits in Soybean Under Normal and Shade Conditions.
Wu X, Chen Z, Peng R … +12 more , Liu X, Yang J, Ma J, Zhou C, Cai D, Liao Y, Chang X, Liu J, Liu W, Yong T, Yang F, Yang W
Int J Mol Sci · 2026 Jun · PMID 42353309 · Full text
Soybean is an important global crop used for oil, food, and feed production. To increase yield and land-use efficiency, growers often plant soybean at a high density or use intercropping systems. Under these systems, soy...
Soybean is an important global crop used for oil, food, and feed production. To increase yield and land-use efficiency, growers often plant soybean at a high density or use intercropping systems. Under these systems, soybeans frequently experience shade stress, which directly affects agronomic traits such as plant height. Although researchers have well documented the genetic basis of plant height under normal conditions, the loci responsible for height variation under shade stress remain largely unexplored. Therefore, we performed a restricted two-stage multi-locus multi-allele genome-wide association study (RTM-GWAS) using SNP linkage disequilibrium block (SNPLDB) markers to identify QTLs associated with soybean plant height under shade stress. We evaluated a natural population of 181 soybean accessions for plant height traits under both normal and shaded conditions across four environments for three years. Using the Soybean40K chip, we derived 11,463 SNPLDB markers and identified 42, 33, and 28 significant SNPLDBs associated with plant height, average internode length, and number of main-stem nodes, respectively. For each SNPLDB, we estimated haplotype (allele) effects and assembled QTL-allele matrices to summarize the population's genetic composition. Four SNPLDB loci proved stable across multiple environments, exhibiting high -lg() values and explaining substantial phenotypic variation. Finally, we projected that 80 candidate genes resided within 180 kb of these stable loci, and we identified four strong candidate genes linked to plant height traits based on combined positional and functional evidence. These results clarify genetic factors that influence soybean height under shading and could aid development of high-yielding soybean varieties.
The Vicious Cycle of Inflammation: How Obesity, Dialysis Catheters, and NETosis Determine Albumin Levels and Prognosis in Hemodialysis Patients.
Lecyk J, Lica-Miler M, Kwiatkowska A … +6 more , Szubert I, Dziedziejko V, Marcinowska Z, Kapczuk P, Safranow K, Kwiatkowska E
Int J Mol Sci · 2026 Jun · PMID 42353308 · Full text
In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the 'obesity paradox' and the association between body composition and inflammation. This study assessed the relation...
In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the 'obesity paradox' and the association between body composition and inflammation. This study assessed the relationship between body composition, traditional inflammatory markers, the new NETosis indicators (neutrophil extracellular traps), and their association with 12-month mortality. The study included 99 maintenance hemodialysis (HD) patients. Their body composition was assessed using bioelectrical impedance analysis. Blood serum was tested for inflammatory markers (hs-CRP-high sensitive c-reactive protein, IL-6 interleukin-6, TNF-α tumor necrosis factor alfa, IL-1β interleukin-1 beta), NETosis markers (citrullinated histone CH3, myeloperoxidase -MPO, elastase), and nutritional status parameters (albumin, transferrin). No correlation between BMI -body mas index and inflammation was demonstrated. Higher adipose tissue, particularly visceral, was significantly positively correlated with IL-6 and hs-CRP levels, while muscle mass was negatively correlated with inflammation. Dialysis catheter use was associated with higher CH3 levels (NETosis indicator) and lower albumin concentrations. Low albumin levels and high TNF-α levels were independent predictors of death. Body composition, rather than BMI, is associated with the severity of inflammation. Visceral obesity is positively correlated with increased inflammation, while muscle mass shows an inverse association. Dialysis catheters are linked to higher NETosis markers and lower albumin levels, which are associated with a poorer prognosis.
DNA-Mimic Antirestriction Proteins ArdA Could Regulate Gene Expression in .
Utkina AA, Kudryavtseva AA, Berezov RV … +6 more , Mekhantseva KV, Melkina OE, Rastorguev SM, Skutel MA, Isaev AB, Manukhov IV
Int J Mol Sci · 2026 Jun · PMID 42353307 · Full text
Antirestriction proteins protect mobile genetic elements from the host's restriction-modification systems. Here, we investigated the ability of ArdA and ArdB antirestriction proteins to regulate gene expression in an eng...
Antirestriction proteins protect mobile genetic elements from the host's restriction-modification systems. Here, we investigated the ability of ArdA and ArdB antirestriction proteins to regulate gene expression in an engineered K-12 MG1655-based biosensor strain. This biosensor strain harbors a -based reporter system controlled by the AllR-repressed promoter. Although structurally similar, DNA-mimic ArdA proteins interact with AllR differently. Recently described small sArdC and well-known ArdA from the conjugative plasmid R64 appear to bind AllR and open the promoter, while the other tested antirestriction proteins (small sArdN protein and various full-sized ArdA proteins from different sources) have no effect on gene expression under AllR-controlled promoter. Direct binding between ArdA and AllR was experimentally confirmed using pull-down assays with His-tagged ArdA. Our study opens up prospects for the specific use of antirestriction proteins for the regulation of gene expression. Surprisingly, ArdB, a non-DNA-mimic antirestriction protein used initially as a control, was also able to open the promoter, apparently through nonspecific interaction with DNA. We verified this effect with a distant ArdB homolog from a rhizobacterium, which was also able to open the promoter.
RNA-Binding Protein Occupancy Composition Predicts Long Noncoding RNA Subcellular Localization.
Tani H
Int J Mol Sci · 2026 Jun · PMID 42353306 · Full text
The subcellular localization of long noncoding RNAs (lncRNAs) is a central determinant of their function, yet its molecular determinants remain incompletely defined, and most existing predictors rely on the primary seque...
The subcellular localization of long noncoding RNAs (lncRNAs) is a central determinant of their function, yet its molecular determinants remain incompletely defined, and most existing predictors rely on the primary sequence. Because RNA-binding proteins (RBPs) are the proximal effectors of RNA compartmentalization, this study tested whether the composition of RBPs bound to a lncRNA is predictive of its nuclear or cytoplasmic localization. Enhanced crosslinking and immunoprecipitation (eCLIP) occupancy for 139 RBPs in K562 cells was integrated with the cytoplasmic-nuclear relative concentration indices (CN-RCIs) derived from matched subcellular fractionation, and localization was modeled under chromosome-grouped cross-validation with nested regularization. RBP-occupancy composition predicted localization beyond the transcript size and total binding amount (incremental cross-validated coefficient of determination, delta-R-squared = 0.17; receiver-operating-characteristic area under the curve, AUC = 0.73, a moderate-strength association; Freedman-Lane permutation, = 0.005). This increment persisted (delta-R-squared = 0.12; = 0.005) against an expanded baseline that additionally absorbed the transcript abundance, intron content and exon number, indicating predictive information that is not reducible to these transcript features, and the classifier was well calibrated (Brier score = 0.10; expected calibration error = 0.02). The signed coefficient profile separated RBP function systematically: factors acting in nuclear processes (splicing, 3'-end processing, and nuclear-matrix association) carried negative, nuclear-direction weights, whereas factors acting in cytoplasmic processes (translation and messenger RNA stability) carried positive, cytoplasmic-direction weights (Mann-Whitney = 0.013). The profile generalized across cell lines: a K562-trained model predicted HepG2 localization (transfer AUC = 0.71 using 76 shared RBPs), and HepG2 reproduced the association independently (AUC = 0.77). The association is correlational and of moderate strength; it is presented as an interpretable, RBP-occupancy-based complement to sequence-based predictors of lncRNA localization.
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