Homeostasis Research Articles (Page 1)

Dietary intake plays a pivotal role in sustaining optimal melatonin levels, while the relationship between dietary patterns and circulating melatonin levels remains unclear. This study aims to investigate the associations between dietary patterns, nutrient intake, and serum melatonin levels in the Chinese population. This cross-sectional study included 6,521 Chinese adults. Three dietary patterns were identified through principal component analysis. Multivariable linear regression was used to assess the associations between dietary patterns and serum melatonin levels. The covariance analysis and partial least squares regression was used to evaluate the association between micronutrient intake and serum melatonin concentrations. The Dietary pattern 2 (DP2), characterized by high intake of fatty foods and red meat with the lowest Dietary Variety Score (DVS), and DP3 featuring high consumption of red meat, fruits, and vegetables but low intake of white meat and aquatic products with low DVS, were significantly associated with lower serum melatonin levels (DP2: β = - 0.12, P-trend < 0.001; DP3: β = - 0.13, P-trend < 0.001). Insufficient nutrient and quality intake of dietary fiber, potassium, vitamin B2, calcium, and magnesium was found in DP2, whereas DP3 showed inadequate intake of protein, cholesterol, vitamin B2, niacin, calcium, phosphorus, magnesium, selenium, and iron. Specific dietary patterns, low dietary diversity and nutrient deficiencies are associated to reduced melatonin levels. These findings reveal distinct mechanisms linking overall dietary patterns to serum melatonin concentrations, underscoring the importance of appropriate dietary patterns and nutrients intake in sustaining optimal circulating melatonin homeostasis in humans.

Abstract Acupuncture can restore normal physiological function by regulating the viscera, improving blood circulation, harmonizing the Yin and Yang, regulating the qi, benefiting the brain, and calming the mind to aid sleep. Acupuncture, as either an alternative or complementary treatment, can improve primary insomnia (PI) and significantly improve sleep quality. Various acupuncture methods have been used, including filiform needling, electroacupuncture, auricular acupuncture, scalp acupuncture, and acupoint embedding. Acupuncture treatment for PI regulates central neurotransmitters, hypothalamus secretion, melatonin-mediated biological clock regulation, and insomnia-related hormones to improve sleep quality. The design models, intervention characteristics, and clinical outcomes of various acupuncture procedures were analyzed. The main mechanisms of effect were summarized from a neuroimaging perspective by analyzing the results of different imaging methods. Functional magnetic resonance imaging indicators of multiple brain areas responsible for psychological, cognitive, and executive control were correlated with improvements in thinking and sleep symptoms after treatment. These were associated with an increase in the low-frequency oscillation amplitude in specific brain regions, such as the superior frontal gyrus, right middle frontal gyrus, and right dorsal anterior cingulate, as well as an increase in the ratio of low-frequency amplitude in the inferior gyrus and double-border superior gyrus. In addition, the therapy has been observed to improve regional homogeneity and reduce Epworth Sleepiness Scale scores in the superior frontal gyrus, right auxiliary motor area, right dorsal anterior, and middle cingulate gyrus. Moreover, acupuncture may immediately modulate the default mode network, which could be the central mechanism underlying PI treatment. A single imaging index is insufficient to define the pathophysiological processes linking insomnia with cognitive impairment. Acupuncture is indicated for the treatment of PI.

Toxoplasma gondii is a zoonotic apicomplexan parasite that relies on highly orchestrated gene expression programs to coordinate its cell cycle progression. Although epigenetic mechanisms are recognized as pivotal drivers of developmental gene regulation in parasitic life cycles, the contributions of chromatin remodeling complexes to these processes remain largely unexplored. In this study, we focus on two core ATPase subunits of the SWI/SNF chromatin remodeling complex and investigate their roles in parasite biology and gene regulation. Our findings reveal that these SWI/SNF ATPases work coordinately, occupying the promoters of many tachyzoite-specific genes. Their deletion causes diminished chromatin accessibility and transcriptional reprogramming, downregulating tachyzoite-specific genes and unlocking certain transcripts normally confined to merozoite stage. Loss of these genes severely impairs parasite fitness and causes division defects, with incomplete endopolygeny accompanied by starch accumulation. TgSNF2b also interacts with the MORC remodeler to modulate chromatin architecture and gene expression. These findings provide new insights into the epigenetic regulation of gene expression and cell division in T. gondii and open new avenues for innovative strategies in toxoplasmosis control.

PCYT2 is the key regulatory enzyme in the biosynthesis of phosphatidylethanolamine (PE) via the CDP-ethanolamine Kennedy pathway. Deficiencies in this gene have been linked to metabolic, neurological, and cardiac disorders; however, most studies report that PE levels remain unchanged. This study aimed to identify the metabolic mechanisms that preserve PE levels when its synthesis is impaired in PCYT2-knockdown human fibroblasts. We investigated alternative pathways that could compensate for reduced PE synthesis, including phosphatidylcholine (PC) and PE base-exchange to phosphatidylserine (PS), followed by PE resynthesis via PS decarboxylation. These pathways were individually assessed using [14C]-ethanolamine, [3H]-choline, and [3H]-serine, and correlated with the expression and activity of the base-exchange genes PTSS1, PTSS2, and the PS decarboxylase PISD. The base-exchange activity was not significantly altered and mitochondrial PS decarboxylation was inhibited, indicating that these routes do not compensate for reduced PE synthesis in PCYT2-deficient cells. Chronic choline treatment increased ethanolamine and choline transport and upregulated the choline/ethanolamine transporter CTL1, yet PC synthesis and base-exchange activity remained unchanged, demonstrating that choline supplementation does not affect PE sythesis. Instead, PE homeostasis was maintained through reduced degradation and extensive phospholipid remodeling via the Lands' cycle, as evidenced by broad changes in fatty acid composition and increased phospholipid unsaturation. Remodeling extended beyond PC, PE, and PS to include phosphatidylinositol and sphingomyelin. These metabolic adaptations led to elevated reactive oxygen species production and enhanced mitochondrial fusion without significantly affecting autophagy or cell viability. Our findings suggest that in the absence of PCYT2 activity, PE levels are preserved primarily through reduced degradation and remodeling, rather than through alternative biosynthetic pathways.

Stress granules (SGs) are membraneless cytoplasmic condensates formed through liquidliquid phase separation (LLPS) in response to diverse cellular stressors. These dynamic macromolecular complexes serve as critical signaling hubs that orchestrate adaptive responses by sequestering translationally stalled mRNAs, RNA-binding proteins, and key signaling molecules. Substantial evidence implicates SGs in the pathogenesis of numerous disorders, where they dysregulate essential cellular pathways, including stress-induced cell death cascades. While regulated cell death constitutes a physiological process vital for tissue homeostasis, aberrant or excessive cell death represents a pathogenic driver in neurodegeneration, ischemic injuries, autoimmune disorders, infectious diseases, and oncological pathologies. Consequently, deciphering the molecular governance of cell death holds great potential for developing novel therapeutics. Although proteomic analyses reveal that SGs sequester multiple cell death regulators, the precise mechanisms through which these components modulate death pathways remain incompletely resolved. This review systematically examines the causal relationships between SGs dynamics and major cell death modalities, including apoptosis, necroptosis, pyroptosis, and ferroptosis. By synthesizing recent advances in SG biology and cell death regulation, we elucidate how stress-adapted SG proteomes functionally contribute to death pathway activation or suppression. This mechanistic synthesis not only resolves current controversies regarding SGs' function in different cell death models but also identifies targetable vulnerabilities at the SGs-death pathway interface, offering innovative frameworks for treating SGsassociated pathologies.

Introduction Resting-state plasma proteins are predictive of exercise performance, but limited data exist regarding acute changes in the plasma proteome with exercise. Hypothesis: Prominent changes in the plasma proteome occur with acute exercise, a subset of which also relate to peak VO 2 as an objective measure of cardiorespiratory fitness. Methods: Among community-based participants in the multi-ethnic Dallas Heart Study who participated in the third study phase (2020-2024) and underwent protocol cardiopulmonary exercise testing, we measured aptamer-based plasma proteomics (SomaLogic; 7172 aptamers corresponding to 6490 unique proteins) at rest and immediately post-exercise in 73 participants (146 paired samples). We tested for associations between log2 protein levels and rest/exercise status using linear mixed effects models adjusted for age, sex, BMI, rest and exercise heart rate and systolic blood pressure. For proteins that changed with exercise, we assessed associations of rest protein values with percent peak VO2 using linear regression models adjusted for age, sex, and BMI. Finally, associations with HF were assessed in a case-control study of 58 prevalent cases and matched controls using logistic regression. The Bonferroni method was used for multiple testing correction. Results: Mean age was 54±11 years, 64% were male, BMI was 28.3±8.7 kg/m 2 , and percent peak VO2 was 85±33%. After multiple testing correction, 415 protein aptamers changed from rest to exercise: 242 increased and enriched for pathways related to RNA processing and translation; 173 decreased and enriched for pathways related to extracellular matrix organization, and immune response. Of these, 4 proteins were also associated with peak VO2 after multiple test correction: higher peak VO 2 associated with decrease in LEP consistent with prior reports, and with increases in CIB1, ITGB1|ITGA11, and CYB5R3. In addition to proteins involved in metabolism (LEP, CYB5R3), these proteins reflect processes related to signal transduction (ITGB1, LEP), extracellular matrix organization (ITGB1|ITGA11) and biological pathway regulation (CIB1). Higher resting ITGB1|ITGA11 value was also associated with decreased odds of HF (OR per 1-sd 0.20 [95% CI 0.067-0.55], p= 0.003). Conclusions: Acute exercise impacts the plasma proteome, with exercise-induced changes in LEP, CIB1, ITGB1|ITGA11, and CYB5R3 associated with cardiorespiratory fitness. Higher resting values of ITGB1|ITGA11 associate with lower HF risk.

The kidney’s intricate physiology relies on finely tuned gene regulatory networks that coordinate cellular responses to metabolic, inflammatory, and fibrotic stress. Beyond protein-coding transcripts, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators of renal biology. By modulating transcriptional, post-transcriptional, and epigenetic pathways, ncRNAs govern podocyte integrity, tubular adaptation, intercellular signaling, and immune activation. Dysregulation of these networks is now recognized as a hallmark of major kidney diseases, ranging from diabetic nephropathy and acute kidney injury to chronic kidney disease, glomerulopathies, and polycystic kidney disease. Mechanistic studies have revealed how pathogenic ncRNAs drive apoptosis, inflammation, fibrosis, and cystic remodeling, while protective ncRNAs mitigate these processes, highlighting their dual roles as both disease mediators and therapeutic targets. The exceptional stability of ncRNAs in urine, plasma, and exosomes further positions them as minimally invasive biomarkers with diagnostic and prognostic value. Translational advances include anti-miR and mimic-based therapies (e.g., lademirsen targeting miR-21, miR-29 mimics, anti-miR-17 oligonucleotides), alongside lncRNA silencing strategies, although challenges in delivery, safety, and redundancy remain significant. This review integrates molecular mechanisms with translational perspectives, providing a comprehensive synthesis of how ncRNAs shape renal pathophysiology. By bridging mechanistic insights with emerging diagnostic and therapeutic applications, we highlight the potential of ncRNAs to transform nephrology, paving the way for biomarker-driven precision medicine and novel interventions aimed at intercepting kidney injury at its regulatory roots. In clinical terms, ncRNA-based biomarkers and therapeutics promise earlier detection, more precise risk stratification, and individualized treatment selection within precision nephrology.

Diabetic foot ulcers (DFUs) and diabetic peripheral neuropathy (DPN) are severe complications in type 2 diabetes mellitus (T2DM). Selenium (Se) is an important element with antioxidant properties, which is crucial for human homeostasis. In this narrative mini review, we summarise the evidence on the potential association of Se with DPN and DFUs. Generally, in most of the limited number of studies, serum Se levels were significantly lower in subjects with DPN or DFUs. In addition, one study demonstrated that urinary Se levels were lower in the DPN group. Nevertheless, further investigations are needed to confirm these preliminary findings.

Selenocysteine (Sec)-containing peptides possess distinctive chemical properties, offering broad potential in biological regulation and therapeutic development. Herein, we report the design of highly electrophilic Ts-protected Sec precursors and the development of a nickel/phenanthroline-catalyzed reductive coupling strategy that enables the efficient arylation of Sec residues using aryl halides under mild conditions. This method exhibits a broad substrate scope and excellent functional group tolerance, accommodating thiol, guanidino, carboxylic acid, and amino groups. Moreover, it can be applied to the synthesis of cyclic peptides and late-stage functionalization of a bioactive peptide.

Spotlight on membrane fluidity of normal and cancer cells: Implications for cancer diagnosis and treatment.

Comparing two anti-inflammatory reflexes: Splanchnic and hypothalamic-pituitary-adrenal.

Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.

Polysaccharides from edible fungi spent mushroom substrates: A review of their extraction, purification, structural characteristics, and biological activities.

Policy, management, and the 'Level of Fouling' scale to transform marine invasion risk reduction from recreational boats.

Mitochondria-targeted NIR fluorescent probe for detection of hydrogen sulfide and its application in monitoring food freshness and bioimaging.

A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis.

Knockout of collagen V in development, but not in skeletal maturity, leads to long-term deficits in supraspinatus tendon mechanics in mice.

Cannabidiol attenuates diet-induced metabolic endotoxemia, neuroinflammation, and anxiety-like behaviors in male aged rats.

Mitophagy attenuates pyroptosis in human gingival fibroblasts through inhibition of NLRP3 inflammasome activation.

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative CNS disorder characterized by a state of "virtual hypoxia." Angiogenesis, one of the main homeostatic responses to hypoxia, has been implicated in the pathophysiology of MS. The study objective was to determine whether angiogenic and hypoxia-related molecules are dysregulated in the serum and CNS of patients with progressive multiple sclerosis (PMS). Baseline serum samples were obtained from a phase II trial of Ibudilast in PMS (n = 203 analyzed) and matched to healthy controls (n = 53). Participants on previous therapeutics (interferons or glatiramer acetate) were excluded from analysis (n = 131). Angiogenic factors were measured using a commercially available bead-based multiplex assay, and hypoxia biomarkers were measured using a custom bead-based multiplex assay. To interrogate the expression of selected hypoxia and angiogenic markers in the CNS, we analyzed publicly available transcriptomic databases and in-house generated data from normal appearing white matter of 2 SPMS donors and 2 nonneurologic disease controls. Circulating markers of hypoxia (such as hypoxia inducible factor-1-a, heme oxygenase-1, and heat shock protein-90) were increased in serum. Conversely, markers of angiogenesis (such as vascular endothelial growth factor-A [VEGF-A], heparin-binding epidermal growth factor, and hepatocyte growth factor) were reduced suggesting a blunting of the angiogenic response. Several of these changes were confirmed in the PMS CNS transcriptome. Lower levels of VEGF-A were associated with disability worsening on the timed-25 foot-walk test at 24 (p = 0.02) and 48 (p = 0.02) weeks and predicted disability worsening (hazard ratio 0.31, 95% CI 0.14-0.69, p = 0.034). Conversely, higher leptin levels trended to predict cognitive worsening on the symbol digit modalities test. Hypoxia-angiogenesis signals are dysregulated in PMS. Increased hypoxia and an insufficient angiogenic adaptive response may play a role in PMS pathophysiology and be a relevant pathway, both in understanding disease mechanisms and as a possible therapeutic target.