International Journal Of Molecular Sciences[JOURNAL]
Sun
200 papers
Effect of Biodegradable PLA-Based and Conventional LDPE Mulch Films on Pathogenic and Functional Soil Microbial Communities.
Zaborowska M, Wyszkowska J, Borowik A … +1 more , Kucharski J
Int J Mol Sci · 2026 Jun · PMID 42353245 · Full text
Plastics and microplastics are widespread in the environment, yet knowledge about their impact on agricultural soils, including their microbiological properties, remains limited. Therefore, this study addressed the resea...
Plastics and microplastics are widespread in the environment, yet knowledge about their impact on agricultural soils, including their microbiological properties, remains limited. Therefore, this study addressed the research question regarding the impact of secondary microplastics, biodegradable poly(lactic acid) (PLA) mulch film, and low-density polyethylene (LDPE) film on the abundance, structure, and functions of soil bacteria, with particular emphasis on the presence of bacterial pathogens. PLA and LDPE were applied to the soil at a dose of 4 g kg d.m. of soil. The aim of the experiment was to evaluate and compare the effectiveness of soil bioaugmentation with the strain and its biostimulation with humic acids in mitigating the negative effects of microplastics. The response of culturable bacteria revealed high sensitivity of organotrophic bacteria to both microplastics, with a stronger inhibitory effect from PLA, as well as stimulation of actinomycetes. 16S rRNA gene amplicon sequencing indicated that the materials differentially influenced the bacterial response. PLA most strongly stimulated and favored the dominance of and , whereas LDPE promoted the growth of and as well as genera and . Both microplastics were colonized by potential pathogens, including , , , and . PLA additionally stimulated the proliferation of sp. and sp., while both PLA and LDPE reduced the abundance of sp. and sp. Bioaugmentation using the strain was more effective in restoring the balance of the soil microbiome than biostimulation with humic acids. The results indicate that microbial preparations based on may serve as an important tool in restoring the balance of soil exposed to microplastics.
Natural Compounds for the Treatment of Cutaneous Squamous Cell Carcinoma: A Systematic Review.
Forno-Bell N, Arciniegas Ruiz S, Walker H … +1 more , Aghili SP
Int J Mol Sci · 2026 Jun · PMID 42353244 · Full text
Cutaneous squamous cell carcinoma (cSCC) is one of the most common non-melanoma skin cancers worldwide. Although surgery and adjuvant therapies are often effective, the treatment of high-risk or advanced lesions remains...
Cutaneous squamous cell carcinoma (cSCC) is one of the most common non-melanoma skin cancers worldwide. Although surgery and adjuvant therapies are often effective, the treatment of high-risk or advanced lesions remains challenging due to recurrence, resistance, toxicity, and limited long-term control. Natural compounds have, therefore, gained interest as multi-target agents for cancer prevention and treatment. This systematic review aimed to evaluate the antitumoral activity of natural compounds against cSCC. A systematic literature search was conducted following PRISMA 2020 guidelines. Sixty studies met the inclusion criteria and were analyzed using a conservative, mechanism-based classification framework. The included studies evaluated purified compounds, crude extracts, essential oils, formulations, and combination treatments. Despite chemical diversity, antitumoral activity converged on defined biological processes, including apoptosis, non-apoptotic regulated cell death, redox modulation, oncogenic signaling inhibition, cell-cycle arrest, epigenetic regulation, photodynamic ROS generation, and chemopreventive or immune-mediated mechanisms. Mechanistic specificity was higher among purified compounds, while complex extracts showed broader, context-dependent effects. Several agents demonstrated consistent in vitro and in vivo activity, which supports their translational relevance. Natural compounds target shared biological vulnerabilities in cSCC through mechanistically convergent pathways. The framework presented here supports mechanism-guided prioritization and may facilitate the translation of promising compounds into clinically relevant strategies.
Prognostic Significance of Inflammatory Markers in Patients with Immune Thrombocytopenia.
Oğuz Davutoğlu N, Gemici Aİ, Kocaköse M … +4 more , Uylaş S, Tanır Ş, Pektaş G, Pektaş MB
Int J Mol Sci · 2026 Jun · PMID 42353243 · Full text
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a...
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP.
Insights into Reproductive Immunology and Placental Pathology, 2nd Edition.
Szukiewicz D
Int J Mol Sci · 2026 Jun · PMID 42353242 · Full text
This Special Issue, the second one dedicated to reproductive immunology and placental pathology, is a response to the need to summarize the latest trends in research topics in this field [...].
This Special Issue, the second one dedicated to reproductive immunology and placental pathology, is a response to the need to summarize the latest trends in research topics in this field [...].
Two Species of Wild Long-Fruited Jute () Characterization and Phylogenetic Analysis of the Complete Chloroplast Genomes.
An X, Du G, Dong J … +1 more , An X
Int J Mol Sci · 2026 Jun · PMID 42353241 · Full text
Jute ( spp.) is the most important bast fiber crop, providing raw materials for textiles, bio-composites, and papermaking. This study analyzed the chloroplast genomes of two wild long-fruited jute species: Qiaojianyehuan...
Jute ( spp.) is the most important bast fiber crop, providing raw materials for textiles, bio-composites, and papermaking. This study analyzed the chloroplast genomes of two wild long-fruited jute species: Qiaojianyehuangma (QJYHM) and Maliyehuangma (MLYHM). The chloroplast genomes exhibited typical circular quadripartite structures (LSC, SSC, IRa/IRb), containing 129 genes (37 tRNA, 8 rRNA, 84 mRNA). Overall GC content was 36.76%, indicating high genetic conservation. Compared with cultivated varieties, wild varieties exhibit differences in LSC region length, IR boundary positions, and repetitive sequences, reflecting minor sequence variations in the chloroplast genome that occurred during domestication. Codon preference analysis showed both wild species favor A/U-ending synonymous codons, with a strong preference for methionine's AUG codon. Repetitive sequence analysis revealed 280 and 252 dispersed repeats in Qiaojianyehuangma and Maliyehuangma, respectively, primarily mononucleotide SSRs. Based on Ka/Ks analysis, it was discovered that most chloroplast genes were under purifying selection. In contrast, positive selection signals were detected in , , and , implying their involvement in adaptive evolution. We identified 161 polymorphic sites (97 SNPs, 64 InDels), with as a mutation hotspot. Phylogenetic analysis clustered both wild species with with a 100% bootstrap value, forming a well-supported sister group. This study provides basic chloroplast genome data for two wild accessions, revealing their conserved genomic features and minor sequence variations.
Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.
Sun Z, Liu Y, Wang K … +3 more , Zhang H, Zhou R, Shao W
Int J Mol Sci · 2026 Jun · PMID 42353240 · Full text
Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, and residual inflammatory risk persists despite optimal lipid and glucose control. Emerging evidence indicates that metabolic reprogramming w...
Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, and residual inflammatory risk persists despite optimal lipid and glucose control. Emerging evidence indicates that metabolic reprogramming within immune cells constitutes a central driver of cardiovascular immune injury. In this review, we propose a unifying framework in which glyco-lipotoxicity acts as a primary metabolic trigger, inducing mitochondrial dysfunction, oxidative stress, and activation of the NLRP3 inflammasome and cGAS-STING pathways. Hyperglycaemia and dyslipidaemia reshape intracellular metabolic circuits, enhancing glycolysis and disrupting oxidative phosphorylation, thereby promoting sustained pro-inflammatory phenotypes. Crucially, metabolic intermediates function as cofactors for epigenetic remodelling. This establishes trained immunity in both circulating innate immune cells and haematopoietic stem/progenitor cells, which serves as the cellular basis for persistent metabolic memory. This persistent immunometabolic imprint amplifies sterile inflammation and accelerates vascular and myocardial remodelling. Furthermore, these processes are systemically propagated through cross-organ communication networks, including the heart-adipose, gut-heart, and cardio-hematopoietic axes, forming a multidimensional inflammatory amplification loop. We also summarise emerging therapeutic strategies targeting the metabolic-epigenetic axis, aiming to reverse maladaptive trained immunity and mitigate residual CVD risk. By integrating immunometabolism, epigenetic regulation, and organ crosstalk, this review highlights metabolic reprogramming as a pivotal mechanistic nexus and potential precision target for cardiovascular protection.
In Vivo Efficacy of an Inhibitor of Complement and FcRn in Models of Glomerulonephritis and Collagen-Induced Arthritis Using Human C2 Knock-In Mice.
Cao H, Nash A, Dai Y … +7 more , Hsu A, Turner AL, Jayawardana K, Vyas S, Barr A, Wymann S, Hardy MP
Int J Mol Sci · 2026 Jun · PMID 42353239 · Full text
A therapeutic antibody, CSL305, has been developed, which combines inhibition of the complement classical and lectin pathways via complement C2 binding with an ability to act as an antagonist of the neonatal Fc receptor...
A therapeutic antibody, CSL305, has been developed, which combines inhibition of the complement classical and lectin pathways via complement C2 binding with an ability to act as an antagonist of the neonatal Fc receptor (FcRn). CSL305 binds to human C2 (huC2) but shows no binding or activity against mouse C2 precluding its use in mouse models of disease to fully assess in vivo efficacy. To circumvent this, a mouse strain was developed that replaced the expression of mouse C2 with huC2 by homologous recombination. These mice (huC2 "knock-in"; KI) were shown to express huC2 protein and to have complement activity. Interestingly, male huC2-KI mice showed much stronger complement activity compared to female mice and were also sensitive to inhibition by CSL305. Two models of disease using male huC2-KI mice were then used to assess the in vivo efficacy of CSL305. The first was an attenuated passive anti-glomerular basement membrane (GBM) glomerulonephritis model involving complement activation as its primary mechanism of action. CSL305 showed dose-dependent inhibition of disease as measured by urine albumin, with reductions in kidney cellular infiltration and plasma C3 cleaved fragments C3b/C3c/iC3b also observed. The second model was a collagen autoantibody-induced arthritis (CAIA) mouse model. Here, CSL305 showed a significant and dose-dependent inhibition of clinical score in both prophylactic and therapeutic settings, mediated exclusively via its FcRn mechanism of action. Although the animal models used in this study were found to preclude the demonstration of a synergistic effect on both mechanisms, CSL305 does act in vivo as both a complement inhibitor and as a FcRn antagonist to ameliorate disease.
Polar Overdominance Inheritance of Variants Is Associated with Birth Weight in a Sex-Specific Manner.
Pomares O, Pérez-Nadador I, Mejorado-Molano FJ … +4 more , Parra-Rodríguez A, Soriano-Guillén L, Laborda J, Garcés C
Int J Mol Sci · 2026 Jun · PMID 42353238 · Full text
is a paternally expressed gene encoding a transmembrane protein belonging to the Delta-Notch signaling family, increasingly recognized for its role in fetal growth regulation. This study explores the relationship between...
is a paternally expressed gene encoding a transmembrane protein belonging to the Delta-Notch signaling family, increasingly recognized for its role in fetal growth regulation. This study explores the relationship between genetic variants (SNV) and birth weight and the potential sex-specific differences in this association. This cross-sectional study consists of a sample of 949 participants (499 males and 450 females) with available birth weight information obtained from official birth certificates. Five SNVs located within or near the gene (rs1802710, rs876374, rs7155375, rs57098752, and rs7149242) were genotyped using Real-Time PCR with predesigned TaqMan™ Assays. Three SNVs (rs1802710, rs876374 and rs7149242) were significantly associated with birth weight in males, but not in females. Interestingly, heterozygous males had a higher mean birth weight than homozygous males. Further confirming this association, heterozygotes for these SNVs were more frequent among males with birth weight above the population mean (3.4 kg) compared to those below it. variants are associated with birth weight in a sex-dependent manner and with an inheritance pattern compatible with polar overdominance. This places as a genetic factor to be considered when evaluating health conditions related to higher or lower than normal birth weight.
Hafnium-Substituted Wells-Dawson Polyoxometalate as a High-Performance Contrast Agent for Transmission Electron Microscopy of Biological Ultrastructure.
Milosavljević A, Ćetković M, Kravić-Stevović T … +5 more , Stojanović M, Čolović MB, Savić ND, Parac-Vogt TN, Krstić D
Int J Mol Sci · 2026 Jun · PMID 42353237 · Full text
Transmission electron microscopy (TEM) is a key tool for ultrastructural analysis, yet its performance critically depends on contrast agents, many of which are constrained by toxicity and regulatory concerns. In this stu...
Transmission electron microscopy (TEM) is a key tool for ultrastructural analysis, yet its performance critically depends on contrast agents, many of which are constrained by toxicity and regulatory concerns. In this study, Wells-Dawson (WD)-type polyoxometalates (POMs), including Parent WD-POM, Lacunary WD-POM, Zr-WD 1:2 POM, and Hf-WD 1:2 POM, were investigated as alternative contrast agents for TEM imaging of rat kidney tissue. Among the tested compounds, Hf-WD 1:2 POM provided the most consistent contrast enhancement, enabling clear visualization of subcellular structures with minimal background interference and no detectable aggregation. Its contrast performance depended on both concentration and incubation time, with higher concentration (0.01 mol/L) and prolonged incubation (24 h) yielding increased signal-to-noise ratio (SNR), although SNR alone did not fully reflect image quality. In comparison with conventional staining agents (uranyl acetate and Uranyless), Hf-WD 1:2 POM achieved significantly improved contrast effectiveness without inducing detectable tissue damage. These findings identify Hf-WD 1:2 POM as a promising non-radioactive alternative for TEM imaging and support the potential of POMs as versatile platforms for the development of advanced contrast agents.
Systemic Effects of Repeated Intraperitoneal Application of Graphene Oxide and Polyethylene Glycol-Functionalized Graphene Oxide Nanoparticles in Long Evans Male Rats.
Keremidarska-Markova M, Ilieva B, Doncheva-Stoimenova D … +8 more , Shkodrova M, Atanasova D, Andreeva M, Badi DA, Hristova-Panusheva K, Kamenska T, Krasteva N, Chichova M
Int J Mol Sci · 2026 Jun · PMID 42353236 · Full text
Recently, nanosized graphene oxide (nGO) has gained significant scientific interest in biomedical strategies. However, before clinical translation, GO-based nanomaterials must be thoroughly evaluated for safety and bioco...
Recently, nanosized graphene oxide (nGO) has gained significant scientific interest in biomedical strategies. However, before clinical translation, GO-based nanomaterials must be thoroughly evaluated for safety and biocompatibility. Therefore, this study investigated the in vivo effects of pristine GO and polyethylene glycol-functionalized GO (nGO-PEG) nanoparticles in male Long Evans rats, following repeated intraperitoneal administration (4 mg/kg body weight). The effects of the nanoparticles were assessed using a range of physiological and pathological markers including body weight (BW) gain, organ coefficients, diuresis, histological, hematological and biochemical parameters. Both nGO and nGO-PEG significantly suppressed BW gain and reduced diuresis in treated rats. Nanoparticle exposure resulted in significant kidney enlargement and reduced testes weight. Mild histological alterations were observed in all examined organs, with nGO showing a tendency toward slightly more pronounced changes than nGO-PEG. Serum levels of aspartate aminotransferase, alanine aminotransferase, and creatinine were significantly elevated in nGO-treated rats, whereas nGO-PEG significantly increased the urinary levels of creatinine and urea. Both nGO- and nGO-PEG-treated rats exhibited elevated serum glucose concentrations. Significant hematological changes were detected in rats treated with both nanoparticles with pronounced effects observed following nGO-PEG administration. Our results suggest possible hematological and metabolic disturbances, as well as hepatic injury and renal toxicity in rats at repeated exposure to nGO and nGO-PEG.
UV-DDB as a Dynamic Regulator Linking Base Excision and Nucleotide Excision Repair via AAG Interaction.
Eom J, Ko Y, Choi J … +7 more , Yang S, Kang SJ, Kim S, Song YB, An S, Lee JY, Jang S
Int J Mol Sci · 2026 Jun · PMID 42353235 · Full text
Base excision repair (BER) and nucleotide excision repair (NER) are traditionally regarded as independent pathways; however, accumulating evidence indicates that ultraviolet (UV)-damaged DNA-binding protein (UV-DDB), a c...
Base excision repair (BER) and nucleotide excision repair (NER) are traditionally regarded as independent pathways; however, accumulating evidence indicates that ultraviolet (UV)-damaged DNA-binding protein (UV-DDB), a core NER factor, stimulates BER DNA glycosylases, including alkyladenine DNA glycosylase (AAG). Despite this functional link, the molecular basis of the UV-DDB/AAG interaction and its regulation by DNA remain unclear. This study investigated the direct interaction between AAG and UV-DDB using electrophoretic mobility shift assays (EMSA), surface plasmon resonance (SPR), biolayer interferometry (BLI) and AlphaFold3-based structural modeling under DNA-free and DNA-bound conditions. SPR analysis revealed that AAG and UV-DDB form a high-affinity complex in the absence of DNA (KD ≈ 17.5 nM), which is maintained but reduced approximately 2.6-fold upon binding to apurinic/apyrimidinic site (AP site)-containing dsDNA (KD ≈ 46.2 nM). BLI analysis independently confirmed this interaction under both DNA-free and DNA-bound conditions, with inter-platform differences consistent with previously reported BLI/SPR variability. EMSA showed UV-DDB-mediated ternary complex formation accompanied by redistribution of binary AAG/DNA species. AlphaFold3 modeling predicted that AAG associates with DDB1 in the DNA-free state, whereas under DNA-bound conditions, DDB2 recognizes the AP site while AAG repositions toward the lesion with multiple active site residues placed in close proximity. These findings support a model in which DNA binding acts as a molecular switch that reconfigures the UV-DDB/AAG interaction, potentially enabling UV-DDB to function as a recruitment platform that facilitates directional progression of AAG through the BER cycle, and providing a structural basis for coordinated integration of BER and NER.
Siebold ex Van Houtte Fruit Extract Mitigates Fructose/Streptozotocin Induced Type 2 Diabetes in Rats.
Yayla M, Binnetoglu D, Toktay E … +6 more , Gul HF, Akgun S, Gozcu S, Ermis U, Ozdemir Sarikaya B, Uyanik MD
Int J Mol Sci · 2026 Jun · PMID 42353234 · Full text
We aimed to investigate the potential antidiabetic effects of an ethanol extract derived from the fruit of (MF) on insulin resistance, oxidative stress, inflammation, and apoptosis associated with diabetes. In our study...
We aimed to investigate the potential antidiabetic effects of an ethanol extract derived from the fruit of (MF) on insulin resistance, oxidative stress, inflammation, and apoptosis associated with diabetes. In our study, diabetes was induced through the administration of a 10% fructose solution and 40 mg/kg Streptozotocin (STZ). Once diabetes had been induced, metformin (Met) 300 mg/kg and the MF extract (250 mg/kg and 500 mg/kg) were administered orally once daily for 30 days. At the end of the experiment, markers of insulin resistance, oxidative stress, inflammation and apoptosis were evaluated in the serum, muscle and liver tissues of the different groups. The MF extract significantly improved the levels of HOMA-IR, insulin receptor (InR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT4)-key components of peripheral insulin resistance associated with type 2 diabetes. Fructose/streptozotocin induced oxidative stress, inflammation, and apoptosis were mitigated by increasing Nuclear factor erythroid 2-related factor 2 (NRF2) expression, which restored antioxidant levels (Superoxide dismutase (SOD) and Glutathione (GSH)), significantly improved cytokine levels (Tumor necrosis factor alpha (TNF-α) and Interleukin-1 beta (IL-1β)), and downregulated apoptotic proteins (caspase-3 and caspase-9). We demonstrated the antidiabetic effect of MF extract using a fructose/streptozotocin-induced type 2 diabetes model. MF extract shows promise for future use in herbal medicine.
Tenascin-C Drives Inflammatory VSMC Phenotypic Switching Through NF-κB Signaling in Saphenous Vein Graft Restenosis.
Jiang L, Gao H, Gu T … +1 more , Shi E
Int J Mol Sci · 2026 Jun · PMID 42353233 · Full text
Vein graft restenosis is a leading cause of long-term failure after coronary artery bypass grafting (CABG), driven by maladaptive vascular smooth muscle cell (VSMC) responses to arterialization-induced inflammation. The...
Vein graft restenosis is a leading cause of long-term failure after coronary artery bypass grafting (CABG), driven by maladaptive vascular smooth muscle cell (VSMC) responses to arterialization-induced inflammation. The key molecular mediators of this pathological remodeling, however, remain incompletely defined. Here, we integrated multi-omics analyses of human and canine vein graft specimens with in vitro functional assays to identify tenascin-C (TNC)-a matricellular extracellular matrix protein-as a critical regulator of VSMC dysfunction. TNC was specifically enriched in a synthetic, pro-inflammatory VSMC subpopulation. Pro-inflammatory stimuli potently induced TNC expression, which was functionally linked to VSMC phenotypic modulation, hyperproliferation, and enhanced migration. Mechanistically, TNC acts upstream of NF-κB signaling; siRNA-mediated TNC knockdown significantly reduced nuclear p65 protein levels and attenuated inflammatory responses. Our integrated computational and experimental data suggest that TNC, NF-κB, and TNF-α function within a sequential pro-inflammatory signaling cascade that sustains vascular inflammation and promotes neointimal hyperplasia. These findings reposition TNC from a passive structural component to an active driver of vascular pathology and highlight the TNC-NF-κB axis as a candidate target for therapeutic intervention to improve vein graft patency.
Laser-Based Photobiomodulation for Orthodontic Pain: Mechanistic Evidence from Experimental Tooth-Movement Models.
Kunimatsu R, Okazaki K, Nakatani A … +1 more , Tanimoto K
Int J Mol Sci · 2026 Jun · PMID 42353232 · Full text
Orthodontic pain, a fundamental biological response to mechanically induced tooth movement, is primarily associated with sterile inflammation and neurogenic processes within the periodontal ligament (PDL). Although photo...
Orthodontic pain, a fundamental biological response to mechanically induced tooth movement, is primarily associated with sterile inflammation and neurogenic processes within the periodontal ligament (PDL). Although photobiomodulation therapy (PBMT) has been widely investigated as a nonpharmacological approach for pain attenuation, its mechanisms of action remain incompletely understood, and current interpretations are often limited to peripheral anti-inflammatory effects. This review re-examines the biological basis of orthodontic pain by integrating evidence derived predominantly from in vitro and in vivo experimental studies. Particular emphasis is placed on neurogenic inflammation, neuropeptide regulation, and neuron-glia interactions along the trigeminal nociceptive pathway. PBMT can reduce periodontal inflammatory/neuropeptide-related markers and pain-related behaviors in selected models; however, evidence for direct central neuron-glia modulation remains largely marker-based and parameter-dependent. Direct functional validation of trigeminal circuit modulation (e.g., electrophysiological recordings or calcium imaging) remains limited in orthodontic pain models; thus, the proposed neuroimmune mechanisms should be interpreted as testable hypotheses for future work. By synthesizing mechanistic insights across multiple biological levels, this review proposes a broader framework for understanding PBMT-mediated pain modulation extending beyond conventional peripheral models. These perspectives may help clarify inconsistencies in the reported outcomes and provide a rationale for future hypothesis-driven experimental and translational research.
Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.
Simonov V, Rastorguev S
Int J Mol Sci · 2026 Jun · PMID 42353231 · Full text
Mitochondrial DNA (mtDNA) mutations are associated with a diverse spectrum of diseases and pose a significant threat to human health. Despite their importance as therapeutic targets, the unique structural and electrochem...
Mitochondrial DNA (mtDNA) mutations are associated with a diverse spectrum of diseases and pose a significant threat to human health. Despite their importance as therapeutic targets, the unique structural and electrochemical properties of mitochondria-most notably the impermeable inner mitochondrial membrane and the high membrane potential-present formidable challenges for the targeted delivery of therapeutic agents. Currently, there are no approved curative treatments for patients harboring pathogenic mtDNA mutations. In this review, we discuss recent advancements in gene therapy for mitochondrial genome-related disorders, with a particular focus on allotopic expression of mtDNA-encoded genes and mitochondrial genome editing technologies. We conclude that allotopic expression currently stands as the most promising approach for near-term clinical implementation. But we also pay great attention to programmable nucleases and base editors utilizing RNA-independent DNA recognition which are evolving with remarkable speed.
The Predictive Role of ctDNA and CTCs in Patients with Advanced Non-Small Cell Lung Cancer Receiving Immunotherapy: A Systematic Review and Meta-Analysis.
Kakouri AC, Spiliotaki M, Deltas C … +2 more , Papagregoriou G, Charalambous H
Int J Mol Sci · 2026 Jun · PMID 42353230 · Full text
Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) have emerged as promising non-invasive biomarkers for the immunotherapy response in advanced non-small cell lung cancer (NSCLC). However, their clinical...
Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) have emerged as promising non-invasive biomarkers for the immunotherapy response in advanced non-small cell lung cancer (NSCLC). However, their clinical utility remains uncertain due to variability in findings across studies. We conducted a systematic review and meta-analysis of studies from 2014 to 2024, assessing the predictive value of ctDNA and CTCs in advanced NSCLC patients receiving immunotherapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Forty-four studies were included (28 ctDNA, 16 CTC cohorts). High baseline ctDNA was associated with worse OS (pooled HR = 1.38, 95% CIs: 1.17-1.63), while baseline CTC detection predicted worse PFS (pooled HR of 3.65 (95% CIs: 1.58-8.41) and OS (pooled HR = 2.30, 95% CIs: 1.54-3.44). An on-treatment ctDNA decrease or clearance was associated with improved PFS (pooled HR = 0.34, 95% CIs: 0.25-0.47) and OS (pooled HR = 0.33, 95% CIs: 0.24-0.44). Evidence for other ctDNA- and CTC-derived biomarkers (blood tumour mutational burden, genomic alterations, dynamic CTC changes, and CTC PD-L1 expression) was limited or inconsistent. The interpretation of these findings is limited by heterogeneity in assay platforms, biomarker definitions, the analytical threshold, and sampling timepoints across studies. While ctDNA and CTCs show significant potential as predictive biomarkers in advanced NSCLC, further validation is needed in larger prospective studies using standardized assays. At present, ctDNA and CTC monitoring can complement but cannot replace radiological assessments in guiding immunotherapy decisions for NSCLC patients.
Genome-Wide Characterization of TCP Transcription Factors in Common Glasswort () and Their Expression Analysis Under Salt Stress.
Wu L, Yang S, Wang F … +11 more , Yang W, Yin C, Hao Z, Wang Z, Jia R, Fu M, Wu S, Tang B, Qin Y, Cheng Y, Wang G
Int J Mol Sci · 2026 Jun · PMID 42353229 · Full text
TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) are plant-specific regulators involved in growth, development, and responses to abiotic stresses, yet their roles in halophytes remain largely unexplored. In t...
TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) are plant-specific regulators involved in growth, development, and responses to abiotic stresses, yet their roles in halophytes remain largely unexplored. In this study, we performed a genome-wide identification of TCP family members in the extreme halophyte , uncovering 15 non-redundant genes () classified into PCF, CIN, and CYC/TB1 subfamilies. Gene structure and conserved motif analyses revealed that are largely intronless and maintain the canonical TCP domain, while showing subfamily-specific variations in motif composition and secondary/tertiary structures. Promoter analysis identified abundant stress and hormone-responsive -elements, particularly ABRE and STRE, suggesting potential involvement in salt stress signaling. Protein-protein interaction network prediction highlighted CIN and PCF members as hub nodes, indicating central roles in growth and stress response regulation. Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis showed that most SeurTCP genes were responsive to salinity treatment, although the extent of transcriptional variation differed among subfamilies. Collectively, our results indicate that SeurTCPs balance conserved structural functions with subfamily-specific regulatory roles, contributing to adaptation to extreme saline environments. This study provides valuable candidate genes for elucidating plant salt tolerance mechanisms and for potential crop improvement.
A Novel Lytic Podovirus AP-20-A Infecting : Mosaic Genome with Cross-Phylum Homology and Implications for Inoculant Establishment.
Kozlova AP, Roumiantseva ML, Saksaganskaia AS … +4 more , Vladimirova ME, Muntyan VS, Gorbunova MK, Gorshkov AN
Int J Mol Sci · 2026 Jun · PMID 42353228 · Full text
This study characterizes AP-20-A, a lytic podovirus infecting , isolated from agricultural chernozem. Its 49.4 kbp genome shows negligible intergenomic similarity with known rhizobiophages (<2%). Core structural proteins...
This study characterizes AP-20-A, a lytic podovirus infecting , isolated from agricultural chernozem. Its 49.4 kbp genome shows negligible intergenomic similarity with known rhizobiophages (<2%). Core structural proteins-the major capsid protein (MCP) and terminase large subunit (TerL)-show closest homology to podoviruses infecting , rather than to alphaproteobacterial viruses, suggesting cross-phylum horizontal gene transfer. This exchange is ecologically plausible, as and co-exist in the rhizosphere. Over 63% of predicted proteins are functionally uncharacterized, with structural homologs detected in bacteria, archaea, and eukaryotes. We report the first identification in a rhizobiophage of a Tad2-like domain, predicted to block the bacterial Thoeris type II anti-phage defense. AP-20-A infected 56% of native strains; agrocenose isolates showed higher resistance than phytocenose isolates, evidence of local co-evolution. Among susceptible strains, 60% entered putative pseudolysogeny (with one strain exhibiting growth stimulation), whereas a symbiotically elite inoculant strain was completely lysed within hours. Some host strains carry additional AbiE systems; whether these independent defense-counterdefense layers interact during infection remains unknown. We conclude that resident phages represent a selective force that can disrupt inoculant establishment, underscoring the need to integrate soil virome assessment into agricultural microbiome management.
Myocardial Injury in Rheumatic Diseases: Immune and Microcirculatory and Molecular Mechanisms of Cardiomyopathies.
Lucki M, Lucka E, Grygiel-Górniak B … +3 more , Iwańczyk S, Mitkowski P, Lesiak M
Int J Mol Sci · 2026 Jun · PMID 42353227 · Full text
Immune-mediated myocardial injury is an important yet underrecognized manifestation of systemic rheumatic diseases and represents a biologically heterogeneous process extending beyond traditional cardiovascular complicat...
Immune-mediated myocardial injury is an important yet underrecognized manifestation of systemic rheumatic diseases and represents a biologically heterogeneous process extending beyond traditional cardiovascular complications such as pericardial disease or accelerated atherosclerosis. This review aimed to summarize current evidence regarding the molecular mechanisms underlying autoimmune myocardial injury and propose an integrated pathogenic framework. A structured narrative review of the literature was performed, focusing on molecular and cellular mechanisms, disease-specific pathogenic pathways, advances in cardio-immunology, and contemporary diagnostic approaches in autoimmune myocardial disease. Current evidence indicates that myocardial injury in rheumatic diseases results from complex interactions involving autoantibody-mediated injury, immune complex deposition, endothelial dysfunction, coronary microvascular dysfunction, dysregulated innate and adaptive immunity, oxidative stress, mitochondrial dysfunction, immunometabolic reprogramming, and regulated cardiomyocyte death. These mechanisms contribute to heterogeneous clinical manifestations, including myocarditis, arrhythmias, inflammatory cardiomyopathy, and heart failure. An integrated immune-microvascular-immunometabolic framework may represent a central mechanism driving myocardial injury and progression to inflammatory cardiomyopathy, supporting earlier diagnosis, improved risk stratification, and the development of precision therapeutic strategies.
Alternative Splicing in Plant Development and Abiotic Stress Responses: A Multifunctional Regulatory Mechanism.
Seok HY, Lee SY, Kim D … +1 more , Moon YH
Int J Mol Sci · 2026 Jun · PMID 42353226 · Full text
Alternative splicing (AS) is a major post-transcriptional regulatory mechanism that greatly expands transcriptomic and proteomic diversity in plants. Recent studies have demonstrated that AS dynamically regulates gene ex...
Alternative splicing (AS) is a major post-transcriptional regulatory mechanism that greatly expands transcriptomic and proteomic diversity in plants. Recent studies have demonstrated that AS dynamically regulates gene expression during plant development and under diverse environmental conditions through isoform-specific modulation of transcript stability, translation efficiency, protein localization, and signaling pathways. In this review, we summarize recent advances in understanding the roles of AS in plant development and abiotic stress responses. Mechanistically, splice site selection is regulated through coordinated interactions among -regulatory elements, RNA-binding proteins, RNA secondary structures, transcriptional kinetics, chromatin organization, and spliceosomal dynamics. AS plays critical roles in various developmental processes, including seed germination, vegetative growth, flowering transition, and senescence, while also contributing to plant adaptation to abiotic stresses such as osmotic, temperature, and oxidative stresses. Particular emphasis is placed on the diverse regulatory outcomes of AS, including isoform-specific protein functions, AS-coupled nonsense-mediated decay, transcript stability control, and context-dependent isoform switching. We further discuss the varying levels of experimental evidence supporting reported AS events, ranging from transcriptome-wide observations to genetically and biochemically validated isoform functions. Moreover, recent advances in long-read sequencing, single-cell transcriptomics, proteogenomics, and genome-engineering technologies are accelerating the functional characterization of splice isoforms and uncovering the complexity of AS-mediated regulatory networks. Collectively, these advances highlight AS as a central mechanism coordinating plant developmental plasticity and environmental adaptation.
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