ABSTRACT The human skin microbiome is a complex network of microorganisms, including bacteria, fungi, viruses, and archaea, that exist in a mutualistic relationship with the host. These microorganisms play important roles in maintaining skin homeostasis, defense against pathogens, regulation of immune response, and antimicrobial peptide synthesis. Dysbiosis, defined as an imbalance of microbial communities, has been linked to dermatological conditions including atopic dermatitis (AD), acne, psoriasis, and chronic wounds. Despite compelling mechanistic insights, the translation of microbiome science into clinically effective therapies remains inconsistent and prematurely optimistic. Emerging therapeutic strategies aim to restore and modulate the skin microbiome with precision, thereby moving beyond conventional broad‐spectrum antimicrobial approaches. These encompass probiotics, prebiotics, synbiotics, live biotherapeutic products (LBPs), bacteriophage therapy, microbiome engineering, postbiotics, microbial consortia treatment, and antimicrobial peptides that selectively target microbial communities instead of eliminating them. While these strategies are biologically plausible and have initial‐phase evidence, their clinical stability, reproducibility, and scalability are uncertain. Major limitations include inter‐individual variability of microbiomes, transient colonization, methodological limitations in functional profiling, and regulatory uncertainties surrounding them. This review article critically evaluates microbiome‐directed dermatologic therapies at the crossroads of real therapeutic potential and translational overextension. The field is not just hype; its clinical application has advanced more rapidly than the supporting evidence base justifies. Progress in this domain requires a shift from descriptive and associative research toward mechanism‐driven, precision‐based interventions. Such interventions must be validated against robust clinical endpoints. By critically assessing biological plausibility, clinical evidence, and translational barriers, this review provides a balanced perspective on the field and outlines realistic pathways for its evolution into a viable therapeutic paradigm.
ABSTRACT Peripheral tumors and chemotherapy reshape host physiology, yet model selection for cancer‐related neurobehavioral deterioration often remains empirical. In lung cancer, this deterioration often presents clinically as a somatic‐psychological symptom cluster that includes fatigue, pain‐related symptoms, sleep disturbance, and distress. We asked whether chemotherapy‐treated subcutaneous and orthotopic Lewis lung carcinoma models reproduce a comparable symptom‐related state or instead reflect distinct systemic and neurobehavioral contexts. Male C57BL/6J mice bearing subcutaneous tumors (STCG) or orthotopic tumors (OTCG), together with normal controls, were followed through chemotherapy using behavioral measures of fatigue‐related performance, pain/discomfort responses, sleep‐related responses, center‐zone exploration and passive coping. These trajectories were interpreted alongside plasma metabolic profiles and targeted peripheral and brain pathological readouts. The two models diverged. STCG preserved survival and showed an active sickness‐like pattern, including impaired rotarod performance, delayed sleep onset and a trend toward shortened thermal response latency. OTCG showed survival attrition, late‐stage systemic deterioration, reduced thermal nociceptive responsiveness, prolonged pentobarbital‐induced sleep duration and stronger behavioral suppression. Plasma metabolomics revealed broader remodeling in OTCG, involving ketone body, glutathione, one‐carbon and redox‐related pathways. Both tumor‐bearing models showed peripheral oxidative stress and brain alterations involving Claudin‐5, glial activation and synaptic markers. Exploratory within‐model networks identified fatigue‐related performance as a highly connected node, with differing behavioral and biological associations. These findings suggest that the two models capture complementary but non‐interchangeable metabolic and neurobehavioral states under the tested chemotherapy conditions.
ABSTRACT Sexual reproduction is one of the crucial driving forces of evolution. Ciliates, single‐celled eukaryotes with nuclear dimorphism, undergo a unique sexual process, conjugation, during which the macronucleus (MAC) and micronucleus (MIC) are extensively reorganized. Previous studies have shown that macronuclear development in Blepharisma can involve functionally differentiated micronuclei. Here, we investigated the conjugation process in two multi‐micronucleate species, Blepharisma sinuosum and B. stoltei . In B. sinuosum , approximately two‐thirds of MICs enter meiosis, but only one meiotic MIC completes the divisions that generate pronuclei; the remaining MICs persist as somatomicronuclei and develop into secondary MAC anlagen. The new MICs undergo variable additional mitoses, producing different MIC numbers among exconjugants. In both B. sinuosum and B. stoltei , primary MAC anlagen derived from the synkaryon and secondary MAC anlagen derived from somatomicronuclei show coordinated late development, supporting a model in which both nuclear sources contribute to the developing MAC. Compared with B. sinuosum , B. stoltei exhibits greater individual variation in the number of meiotic MICs, new MICs, and primary and secondary MAC anlagen. These results expand the species‐level cytological basis for understanding the diversity of macronuclear development during ciliate conjugation.
ABSTRACT Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, highlights the need for advanced immunomodulatory therapies. We isolated three novel polysaccharides (SVP1–SVP3) from Sanghuangporus vaninii , characterized their physicochemical properties, and formulated them into hydrogels. These were applied to 2,4‐dinitrofluorobenzene (DNFB)‐induced AD mouse models to investigate their therapeutic effects and underlying mechanisms. SVP hydrogels, notably SVP3, significantly attenuated AD pathology including scratching frequency, dermatitis severity, epidermal hyperplasia, and mast cell infiltration compared to the blank hydrogel control. Crucially, SVP3 alleviated immune dysregulation by lowering CD4 + T cells and increasing CD8 + T cells, suppressing the secretion of both Th1 and Th2 signature cytokines, and remodeling the disordered inflammatory cytokine network. Mechanistic analysis indicated suppressed activation of the TLR4/MyD88/NF‐κB pathway accompanied by decreased protein expression, alongside inhibited nuclear translocation of p‐NF‐κB p65 and p‐STAT3. Our findings suggest that SVP3 alleviates AD symptoms partly through modulation of TLR4/MyD88/NF‐κB signaling, supporting its value as a promising therapeutic strategy for immunomodulation in inflammatory skin disorders.
ABSTRACT Unacylated ghrelin (unAG) is a metabolically active hormone, acutely stimulating fatty acid oxidation in skeletal muscle while promoting lipogenesis and inhibiting lipolysis in adipose tissue. Given these acute effects, we hypothesized that repeated unAG administration would improve skeletal muscle insulin response and that this would be associated with reduced muscle lipid storage. We treated healthy male Sprague–Dawley rats with twice‐daily subcutaneous unAG (200 μg; 400 μg total daily) for 5 days. UnAG treatment did not alter glucose uptake or AKT activation basally, or in response to low or high insulin concentrations when assessed ex vivo in oxidative or glycolytic skeletal muscle, or when muscle was pre‐exposed to a high‐palmitate stress. Protein content of mitochondrial markers (CPT1B, citrate synthase, COXIV) also remained unchanged with treatment in both muscle types. Interestingly, UnAG‐treated animals had a reduced glycemic response to pyruvate administration; however, content of hepatic glucose production‐associated proteins and liver AKT response to insulin remained unchanged. UnAG treatment tended to increase LPL protein content in visceral adipose tissue ( p = 0.07), but did not alter AKT or HSL phosphorylation in response to an insulin bolus in either subcutaneous or visceral adipose tissue. Finally, triacylglycerol content in the red and white gastrocnemius muscle, as well as in the liver, was unchanged by unAG administration. Overall, these findings indicate that short‐term unAG treatment improves pyruvate tolerance, but that it does not exert persistent metabolic changes to skeletal muscle, liver, or adipose tissue substrate metabolism in healthy rats.
