2026-03-05
John Antonydas Gaspar, Krishnan M. Dhandapani, David C. Hess
MAGEB16 (Melanoma-associated antigen B16) is an X-linked cancer-testis antigen belonging to the MAGE-B family, whose expression is tightly regulated by a promoter DNA-methylation switch that restricts transcription primarily to the male germ line under normal physiological conditions. In addition to its established roles in spermatogenesis and oncogenesis, emerging functional, epigenomic, and genetic evidence points to MAGEB16 as an epigenetically sensitive modifier of early developmental programs implicated in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). In this study, we performed an integrative analysis combining MAGEB16’s chromosomal context, molecular interaction networks, and methylation-dependent regulatory features, alongside experimental depletion datasets from pluripotent stem cells, perinatal cord-blood methylome data from ASD cohorts, peripheral transcriptomics linked to neuropsychiatric risk and recently reported genetic variant associations. Our synthesis identifies underlying evidence indicating that MAGEB16 participates in epigenetically regulated lineage specification processes during early embryonic development. We propose a unified model in which MAGEB16 acts as a dosage- and timing-dependent regulator of early lineage commitment. Disruption of its epigenetic control, particularly during X-chromosome-enriched developmental periods, may influence neurodevelopmental pathways toward ASD-associated phenotypes. These findings position MAGEB16 as a candidate epigenetic-susceptibility factor linking germline-restricted regulatory changes, that could influence early brain development and increase the risk for neurodevelopmental conditions.
2026-02-09
Rizia Rocha-Silva, Geovana José, Marília Santos Andrade, Claudio Andre Barbosa de Lira
2026-01-22
Aniket Kakkar, Harpreet Singh, Yash Jasoria, Arvind Kumar, Shivani Chopra, Hitesh Chopra, Arun Kumar Mishra
Type 2 diabetes mellitus (T2DM) is increasingly recognized as a major risk factor for Alzheimer's disease (AD), with mounting evidence highlighting shared pathophysiological mechanisms. This review explores the intricate biological and molecular links between these two chronic disorders. Key overlapping pathways include impaired insulin signaling, chronic inflammation, oxidative stress, mitochondrial dysfunction, amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, and the formation of advanced glycation end-products (AGEs). Disruption of insulin signaling in the brain contributes to synaptic loss and neurodegeneration, while systemic metabolic disturbances aggravate blood-brain barrier dysfunction and neurovascular damage. Emerging studies also underscore the role of antidiabetic treatments, especially newer agents targeting the gut-brain axis, in modulating AD progression. The review further examines preclinical models, clinical observations, and the development of biomarkers to improve early detection and intervention. Despite growing insights, challenges remain in translating mechanistic knowledge into effective therapies. A multidisciplinary approach integrating metabolic control and neuroprotective strategies is essential for addressing the comorbid burden of T2DM and AD.
2026-01-22
Pengcheng Zhou, Mohammad Majd Hammour, Romina H. Aspera-Werz, Sabrina Ehnert, Maiju Myllys, Zaynab Hobloss, Reham Hassan, Daniela González, Rama Hendawi, Karolina Edlund, Sandra Hans, Matthias W. Laschke, Ahmed Ghallab, Jan G. Hengstler, Andreas Nüssler, Tanja C. Maisenbacher
Obesity and metabolic dysfunction-associated fatty liver disease (MAFLD) are increasingly recognized as risk factors for skeletal fragility, yet the mechanisms linking these conditions to impaired bone health remain poorly defined. The liver is central to vitamin D homeostasis through 25-hydroxylation, while skeletal responsiveness relies on vitamin D receptor (VDR) signaling. Disruption of either process may compromise bone remodeling. In this study, we investigated the long-term effects of Western diet (WD) feeding on hepatic vitamin D metabolism and bone integrity in a mouse model. Male C57BL/6N mice were fed a standard diet (SD) or WD for 48 weeks. WD-fed mice developed obesity, hepatic injury, and trabecular bone deterioration characterized by reduced bone mineral density and increased trabecular separation. Although trabecular architecture was compromised, three-point bending revealed no significant impairment in cortical bone mechanical properties. Histological analyses showed increased bone marrow adiposity and macrophage/monocyte lineage cells. Bone gene expression profiling indicated enhanced osteoclastogenic signaling. Hepatic transcriptomics demonstrated marked downregulation of key 25-hydroxylases ( Cyp2r1 , Cyp27a1 ) and vitamin D–binding protein, accompanied by reduced circulating 25‑hydroxyvitamin D. Bone tissue also exhibited decreased VDR protein abundance. Together, these findings suggest that long-term WD-induced obesity and hepatic dysfunction impair hepatic vitamin D metabolism and diminish skeletal vitamin D responsiveness, contributing to bone fragility. Targeting the liver–bone axis and restoring vitamin D homeostasis may provide therapeutic potential for obesity-related bone loss.
2026-01-12
Stephen E. Langabeer
2026-01-11
Pallav Sengupta, Sulagna Dutta
2026-01-08
Nalae Kang, Eun-A. Kim, Yeon-Ji Lee, Seong-Yeong Heo, Jun-Ho Heo, Won-Kyu Lee, Yong-Kyun Ryu, Taeho Kim, Soo-Jin Heo
Tetraselmis sp., a marine microalga amenable to mass cultivation, possesses antiviral properties, partly attributed to chlorophyll a. However, the underlying antiviral mechanisms remain poorly characterized. In this study, we investigated the antiviral activity and mode of action of chlorophyll a derived from Tetraselmis sp. by performing transcriptomic analyses on three experimental groups: untreated, uninfected cells; Zika virus (ZIKV)-infected cells; and chlorophyll a-treated, ZIKV-infected cells. Treatment with 5 µM chlorophyll a induced differential expression of genes associated with interferon-inducible antiviral responses. Gene ontology analysis revealed significant enrichment of biological processes such as “response to external stimulus” and “response to biotic stimulus.” Notably, Venn diagram analysis of 130 differentially expressed genes (DEGs) demonstrated restoration of key interferon-stimulated genes, including interferon-induced protein with tetratricopeptide repeats (IFIT)1, IFIT2, IFIT3, and IFIT5, which was further validated by quantitative PCR and immunocytochemistry. These findings suggest that chlorophyll a from Tetraselmis sp. exerts antiviral effects primarily through modulation of interferon-mediated pathways.
2026-01-07
Evelin G. Cuadros-Buenaventura, Lenin Javier Ramírez-Cando, Ronny Alexander Ordoñez Sánchez, Johnny Chimborazo, Santiago Ballaz
Mancozeb, a polymeric dithiocarbamate complex fungicide with zinc and manganese salts, has the potential to be neurotoxic to humans. Unfortunately, the parent molecule maneb has attracted far too much attention, limiting the available evidence on mancozeb neurotoxicity to preclinical research and non-human cells. We sought to evaluate mancozeb cytotoxicity in neuroblastoma SH-SY5Y cells at lower concentrations than those used for maneb in in vitro investigations in order to quantify its risk for humans. Commercial mancozeb showed concentration- and time-dependent neurotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction test (EC 50 = 5.9 µM and 1.7 µM at 24 h and 72 h respectively). Using the trypan blue exclusion dye, cell death toll reached around 100% after 24- and 72-hour exposure to mancozeb 1 µM and 0.5 µM respectively. Reactive oxygen species generated by mancozeb, which peaked at 4 µM, could be the cause of cell death. The number and length of neurites were concentration-dependently reduced by mancozeb at sub-µM concentrations, and this was accompanied by changes in cell biomechanical characteristics (stiffness) as determined by atomic force microscopy. The uncertainty factor obtained from our cytotoxic studies, when performing risk assessment of mancozeb, varied from 200 to 2000, which may result in detectable neurotoxicity in humans in accordance with international regulatory agencies recommendations.
2026-01-06
Amisha S. Raikar, Ananya Verma, Mayuri B. Naik, Sweta M. Prabhu, Keshav Raj Paudel, Kamal Dua
Respiratory diseases are global health challenges demanding innovative immunotherapy solutions. Toll-like receptors (TLRs) play a crucial role in immune responses, making them attractive therapeutic targets. This review examines nanoparticle-based Toll-like receptor agonists as a promising approach for respiratory immunotherapy. Nanoparticles offer targeted drug delivery and sustained release, ideal for enhancing TLR agonist efficacy. This article explores TLRs' role in immunomodulation, nanoparticle applications, design considerations, preclinical efficacy, safety assessments, challenges, and future prospects. Promising results from animal studies suggest enhanced immunological responses and reduced inflammation compared to conventional treatments. Safety concerns are addressed with insights from toxicity studies. Challenges include regulatory hurdles and biocompatibility, with strategies proposed for optimization. Nanoparticle-based TLR agonists hold great potential to transform respiratory disease treatment, warranting further research and collaboration for successful clinical translation.
2026-01-04
Nitika Yadav, Abhishek Yadav, Neharica Joshi, Shubhangi Gupta, Yashendra Sethi
Extrapulmonary tuberculosis continues to challenge clinicians with its protean manifestations, particularly when involving the gastrointestinal tract. While ileocecal TB is well-characterized, isolated involvement of the liver, stomach, and esophagus, Duodenum remains exceptionally rare and diagnostically elusive. We describe four rare presentations of gastrointestinal tuberculosis from a tertiary care center in India. Case 1 involves hepatic tuberculosis mimicking intrahepatic cholestasis, diagnosed via liver biopsy and special staining. Case 2A details isolated gastric TB presenting with nonspecific dyspepsia, ultimately diagnosed through endoscopic ultrasound-guided FNAC. Case 2B describes esophageal tuberculosis with bronchoesophageal fistula—an exceedingly rare entity—confirmed radiologically and histologically. Case 2C describes a case of duodenal tuberculosis presenting as partial gastric outlet obstruction (GOO). All cases demonstrated clinical and radiological resolution following standard anti-tubercular therapy. These cases posit the diagnostic complexity of gastrointestinal TB when it involves uncommon sites. Heightened clinical suspicion and timely histopathological confirmation remain key to averting morbidity. Early recognition facilitates successful medical management and obviates unnecessary surgical interventions.