Search Results (227)

Background: Long pulse width stimulation (LPWS; 120–150 ms) has the potential to stimulate denervated muscles in persons with spinal cord injury (SCI). We examined whether testosterone treatment (TT) + LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in SCI persons with denervation. We hypothesized that one year of combined TT + LPWS would downregulate gene expression of muscle atrophy and upregulate gene expression of muscle hypertrophy and increase mitochondrial health in SCI persons with lower motor neuron (LMN) injury. Methods: Ten SCI participants with chronic LMN injury were randomized into either 12 months, twice weekly, of TT + LPWS (n = 5) or a TT+ standard neuromuscular electrical stimulation (NMES; n = 5). Measurements were conducted at baseline (week 0), 6 months following training (post-intervention 1), and one week following 12 months of training (post-intervention 2). Measurements included body composition assessment using magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA). Metabolic profile assessment encompassed measurements of resting metabolic rate, carbohydrate and lipid profiles. Finally, muscle biopsy was captured to measure RNA signaling pathways and mitochondrial oxidative phosphorylation. Results: Compliance and adherence were greater in the TT + NMES compared to the TT + LPWS group. There was a 25% increase in the RF muscle CSA following P1 measurement in the TT + LPWS group. There was a recognizable non-significant decrease in intramuscular fat in both groups. There was a trend (p = 0.07) of decrease in trunk fat mass following TT + LPWS, with an interaction (p = 0.037) in android lean mass between groups. There was a trend (p = 0.08) in mean differences in DXA-visceral adipose tissue (VAT) between groups at P1 measurements. For genes targeting muscle atrophy, TT + LPWS showed a trending decline in MURF1 and FOXO3 genes returning to similar levels as TT + NMES before 12 months. Conclusions: These pilot data demonstrated the safety of applying LPWS in persons with SCI. Six months of TT + LPWS demonstrated increases in rectus femoris muscle CSA. The effects on muscle size were modest between groups. Signaling pathway analysis suggested downregulation of genes involved in muscle atrophy pathways. Future clinical trials may consider a home-based approach with more frequent applications of LPWS. Full article

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is exacerbated by glucocorticoid exposure. Although there is growing interest in natural therapies for muscle atrophy, the effects of Quercus acuta Thunb. fruit extract (QA) on sarcopenia or glucocorticoid-induced muscle loss had not been previously investigated. QA is an evergreen oak known for its antioxidant and anti-inflammatory properties, with polyphenolic components reported to enhance oxidative and metabolic homeostasis in various tissues. Based on these properties, we hypothesized that QA could counteract muscle atrophy by modulating anabolic and catabolic signaling pathways. The research utilized both in vitro (C2C12 myotubes) and in vivo (ICR mice) models to assess QA’s effects. Daily oral administration of QA (100–200 mg/kg) was given to mice with dexamethasone (Dex)-induced muscle atrophy. Techniques included H&E staining to assess muscle mass and fiber cross-sectional area (CSA), Western blot, and ELISA analyses to investigate signaling pathways. Confocal imaging was also used to confirm cellular changes. In vitro QA treatment improved myotube integrity by increasing myogenic differentiation markers (MyoD, MyoG) and suppressing atrophy-related E3 ligases, specifically MuRF-1 and FBX32/Atrogin-1. Confocal imaging showed that QA inhibited the nuclear localization of FOXO1 and reduced FBX32 expression. In vivo, daily oral administration of QA significantly preserved gastrocnemius muscle mass and fiber cross-sectional area in Dex-treated mice. QA restored the IGF-1/PI3K/Akt signaling pathway and attenuated FOXO1-dependent proteolytic activation. Collectively, these findings demonstrate that QA possesses potent anti-atrophic and myoprotective effects mediated through the modulation of the IGF-1/Akt-FOXO axis. QA has potential as a novel natural therapeutic for preventing glucocorticoid-induced sarcopenia. Full article

Disuse-induced muscle atrophy (DMA), commonly resulting from immobilization, is driven by chronic inflammation and oxidative stress, which disrupts the balance between protein synthesis and degradation. Quinic acid (QA), a natural compound with known antioxidant and anti-inflammatory properties, was investigated for its potential to counteract muscle atrophy. Using a DMA-induced immobilization model in male C57BL/6N (8 weeks) mice, we found that oral QA administration significantly restored the weight and cross-sectional area of atrophic muscles and improved muscle function, as measured by grip strength and treadmill performance. QA also reduced the expression of pro-inflammatory cytokines (Tnf, Il6, and Myostatin) and E3 ubiquitin ligases (Trim63 and Fbxo32), while increasing antioxidant enzyme levels and serum IL-15 in DMA. In tumor necrosis factor-α-stimulated L6 myotubes, QA reversed inflammation- and oxidative stress-induced gene changes, suppressed NF-ĸB activation, and downregulated protein degradation pathways mediated by FoxO3α. Furthermore, QA restored the expression of myogenesis-related genes and reactivated PI3K/Akt and mTOR/p70S6K/4EBP1 signaling pathways, enhancing protein synthesis. Collectively, our findings demonstrate that QA mitigates immobilization-induced muscle atrophy by modulating inflammation, oxidative stress, and key anabolic and catabolic signaling pathways. These results suggest that QA is a promising functional compound for preserving skeletal muscle health under conditions of disuse. Full article

To explore the induction of low temperature the Tiger Puffer (Takifugu rubripes) In this study, the influence of temperature on the pituitary gland during masculinization was investigated through chronic hypothermia stress experiments. Metabolomics was used to analyze the metabolic regulatory network of the pituitary gland under hypothermia stress. ELISA technology was employed to determine the activity content of oxidative stress-related enzymes in the pituitary gland. Further, TUNEL fluorescence labeling and qPCR were used to detect the apoptosis level of pituitary cells. Finally, to assess the impact of low-temperature stress on muscle tissue, HE staining and qPCR techniques were employed. The results showed that after 45 days of low-temperature stress, the differential metabolites of the pituitary gland were mainly enriched in the amino acid metabolic signaling pathway, and the contents of amino acids such as GSH and its synthetic precursors in the pituitary tissue changed significantly. The contents of oxidative stress indicators such as ROS and MDA all showed a trend of first increasing and then decreasing. The qPCR results of TUNEL fluorescence labeling and apoptosis-related genes were consistent, indicating that the apoptotic level of pituitary cells first increased and then decreased with the stress process. Histological analysis revealed that low temperature led to muscle cell atrophy and increased interstitial space in muscle tissue. The expression changes in genes related to muscle development further confirmed that low temperature significantly inhibited muscle growth and development. Therefore, this study speculates that after being subjected to chronic low-temperature stress, the pituitary gland of the red-finned Oriental pufferfish can alleviate the oxidative stress response of the body by strengthening the amino acid metabolic pathway, and the fish body has shown a physiological trend of gradually adapting to low-temperature stress, but the growth and development of muscles are still significantly inhibited. The results of this study can provide theoretical support for understanding the physiological adaptation mechanism of the red-finned Oriental pufferfish to low-temperature stress and lay a foundation for subsequent in-depth exploration of the pituitary response mechanism to low temperatures. Full article

Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility. Full article

Glucocorticoid therapy, using agents like dexamethasone (Dexa), often leads to muscle atrophy by increasing protein degradation via the ubiquitin–proteasome system while suppressing protein synthesis. Stigmasterol, a phytosterol with known bioactivities, has an unexplored role in muscle atrophy. This study investigated stigmasterol’s protective effects against Dexa-induced muscle atrophy and its impact on the FoxO3 and mTORC1 signaling pathways. Differentiated C2C12 myotubes were treated with Dexa (50 µM) ± stigmasterol (10 µM), and the morphology, viability, and protein levels in the FoxO3/MuRF1/MAFbx catabolic and mTOR/p70S6K/4E-BP1 anabolic signaling pathways were assessed. C57BL/6 mice received Dexa (20 mg/kg/day i.p.) ± stigmasterol (3 mg/kg/day oral) for 21 days, and the body/muscle mass, bone mineral density (BMD), fiber cross-sectional area (CSA), and muscle protein expression were measured. Stigmasterol (10 µM) was non-toxic and attenuated Dexa-induced reductions in myotube diameter and fusion in vitro, concurrent with suppressing Dexa-induced upregulation of FoxO3/MuRF1/MAFbx proteins and preventing the Dexa-induced dephosphorylation of mTOR/p70S6K/4E-BP1 proteins. In vivo, stigmasterol mitigated Dexa-induced losses in body weight, muscle mass, BMD, and fiber CSA. This protection was associated with attenuated upregulation of FoxO3 and MAFbx proteins in muscle tissue. Stigmasterol protected against Dexa-induced muscle atrophy in vitro and in vivo via modulation of the FoxO3–MAFbx catabolic pathway. These findings suggest stigmasterol inhibits excessive glucocorticoid-induced muscle protein breakdown. It therefore warrants further investigation as a potential therapeutic agent for glucocorticoid myopathy. Full article

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, and depression, are marked by progressive neuronal dysfunction and loss, yet current treatments remain largely symptomatic with limited disease-modifying efficacy. Glucagon-like peptide-1 (GLP-1), an incretin hormone traditionally associated with metabolic regulation, has emerged as a promising neuroprotective agent. Its receptor, GLP-1R, is expressed in key brain regions implicated in cognition, emotion, and motor control, including the hippocampus, frontal cortex, and substantia nigra. GLP-1R agonists (GLP-1RAs) activate multiple intracellular signaling cascades—cAMP/PKA, PI3K/Akt, and MAPK pathways—that collectively promote neuronal survival, enhance synaptic plasticity, reduce oxidative stress, inhibit apoptosis, and modulate neuroinflammation. These agents also regulate autophagy, promote remyelination, and reprogram microglial phenotypes toward anti-inflammatory states. Preclinical models have shown that GLP-1RAs reduce amyloid-β and tau pathology in AD, preserve dopaminergic neurons in PD, protect astrocytes and neural progenitors after ischemic stroke, and alleviate depressive behaviors. Notably, GLP-1RAs such as liraglutide, exenatide, and dulaglutide can cross the blood–brain barrier and have demonstrated safety and potential efficacy in early-phase clinical trials. These studies report attenuation of cortical atrophy, preservation of cerebral glucose metabolism, and improvements in quality of life, though changes in core AD biomarkers remain inconclusive. Ongoing large-scale trials (e.g., EVOKE, ELAD) are further exploring their therapeutic impact. This review consolidates the mechanistic basis and translational potential of GLP-1RAs in age-related neurodegenerative diseases, highlighting both their promise and the challenges that must be addressed in future clinical applications. Full article

Background: Skeletal muscle is essential not only for structural integrity but also metabolic homeostasis. Muscle atrophy, the loss of muscle mass and function, is closely linked to chronic and metabolic disorders and is driven by chronic inflammation, oxidative stress, impaired myogenesis, and disrupted protein homeostasis. The present study aimed to evaluate the protective effects and underlying mechanisms of Rosa canina extract (RCE), a polyphenol-rich plant known for its antioxidant and anti-inflammatory properties, in vitro and in vivo models of muscle atrophy. Methods: We investigated the effects of RCE in TNF-α-treated L6 myotubes and a mouse model (eight-week-old male C57BL/6N) of immobilization-induced muscle atrophy. Markers of inflammation, oxidative stress, myogenesis, protein turnover, and anabolic signaling were analyzed via RT-PCR, Western blotting and ELISA. Muscle mass, performance, micro-CT imaging, and histological cross-sectional area were assessed in vivo. Results: RCE suppressed pro-inflammatory cytokines, restored antioxidant enzyme expression, and preserved myogenic markers. It inhibited muscle proteolysis by downregulating the genes involved in protein degradation and promoted protein synthesis by via activation of the PI3K/Akt/mTOR pathway. In mice, RCE mitigated muscle mass loss, preserved fiber cross-sectional area, improved strength and endurance, and restored muscle volume. Conclusions: RCE attenuated muscle atrophy by targeting inflammation, oxidative stress, proteolysis, and impaired anabolism. These findings highlight RCE as a promising natural therapeutic for preserving muscle health and metabolic homeostasis. Full article

Black soldier fly (Hermetia illucens) larvae are a promising source of insect lipids, characterized by rapid fatty acid accumulation and a high lauric acid content. This study investigated the effects of dietary black soldier fly oil (BSFO) on muscle quality in largemouth bass (Micropterus salmoides). Experimental diets were formulated to be isonitrogenous, isolipidic, and isophosphoric, with 1.0% and 2.0% BSFO partially replacing soybean oil. A control group received 2.3% soybean oil without BSFO or glycerol monolaurate (GML), while positive controls were supplemented with 0.35% and 0.7% GML. Fish (initial weight: 25.08 ± 0.12 g) were cultured in pond cages for 56 days, and three replicates were established for each treatment group. Muscle quality and nutritional traits were evaluated, including proximate composition, fatty acid profiles, texture properties, fiber diameter, hydroxyproline content, antioxidant capacity, and expression of genes related to myogenesis, atrophy, apoptosis, and mTOR signaling. Compared with the control, the 2.0% BSFO group showed a significant increase in muscle hydroxyproline content (p < 0.05), while GML supplementation led to a significant decrease (p < 0.05). In the 1.0% BSFO group, muscle saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) contents were unchanged (p > 0.05), but n-3/n-6 polyunsaturated fatty acid (PUFA) ratios and highly unsaturated fatty acid (HUFA) levels were significantly elevated (p < 0.05). The dietary supplementation of BSFO enhanced the levels of high-quality fatty acids in the muscle tissue. Antioxidant capacity was also significantly enhanced in the 1.0% BSFO group (p < 0.05) but reduced in the GML groups (p < 0.05). Texture analysis showed that BSFO significantly improved muscle hardness, elasticity, chewiness, and gumminess (p < 0.05). Gene expression analysis revealed no significant effects of BSFO on genes related to myogenesis (myod and myog) and muscle atrophy (mstn and murf1), or apoptosis-related genes (caspase8, caspase9, and caspase3) (p > 0.05); mTOR signaling pathway-related genes (s6k1 and akt1) were significantly upregulated in the 2.0% BSFO group (p < 0.05). In contrast, 0.7% GML significantly upregulated genes related to myogenesis (myod, myf5, and myog), muscle atrophy (mstn, fbxo32, and murf1), and apoptosis (caspase8, caspase9, and caspase3) (p < 0.05). In summary, dietary supplementation with 2.0% BSFO effectively enhances muscle quality in largemouth bass without negatively impacting muscle development. Full article

Sarcopenia, characterized by progressive skeletal muscle mass, strength, and functional loss, imposes a substantial global health burden. Irisin, a myokine derived from fibronectin type III domain-containing protein 5 (FNDC5), is critical for muscle health. Here, we investigate its role in mitigating glucocorticoid-induced sarcopenia using a mouse and C2C12 myotubes model. We quantified FNDC5/irisin levels in skeletal muscle and plasma and assessed muscle function (body weight, grip strength, wire-hanging, and locomotor activity), histology, and mitochondrial features following irisin administration to dexamethasone-treated mice. Western blot analyzed synthesis/hydrolysis regulators, apoptosis markers, and mitochondrial regulators in mouse muscle tissues and C2C12 myotubes. The results show that FNDC5/irisin was significantly downregulated in sarcopenic mice and atrophic C2C12 myotubes; exogenous irisin rescued muscle mass loss and functional impairment, improving body weight, muscle mass, grip strength, and mobility. Mechanistically, irisin bound SIRT1 with −12.7 kcal/mol affinity, activating a deacetylation cascade that suppressed FoxO3a transcriptional activity (attenuating proteasomal degradation) and enhanced mTORC1-mediated protein synthesis in C2C12 myotubes. Additionally, irisin potentiated PGC-1α signaling in mouse myocytes, promoting mitochondrial biogenesis and restoring contractile function in dystrophic fibers. Collectively, these findings demonstrate irisin alleviates glucocorticoid-induced muscle atrophy via SIRT1-dependent pathways, rebalancing muscle physiology and systemic energy homeostasis. This highlights irisin-based therapeutics as a promising exercise surrogate for sarcopenia management, offering novel clinical avenues. Full article

Chronic infection with Helicobacter pylori is the leading environmental cause of gastric carcinogenesis, yet the molecular pathways remain incompletely defined. This review links H. pylori-derived outer membrane vesicles (OMVs) and host epithelial exosomes through their shared cargo of heat shock protein 60 (GroEL/Hsp60). We proposed the concept of the “muco-microbiotic layer” as a fifth, functionally distinct layer of the gastric wall, where bacterial and host extracellular vesicles (EVs) interact within the mucus–microbiota interface. In this compartment, OMVs carrying bacterial GroEL and exosomes containing human Hsp60 engage in bidirectional communication that may promote chronic inflammation and epithelial transformation, with putative participation of molecular mimicry. The high structural homology between microbial and human Hsp60 enables repeated immune exposure to trigger cross-reactive responses—potentially leading to autoimmune-driven tissue damage, immune tolerance, and immune evasion in pre-neoplastic lesions. This vesicular crosstalk aligns with the evolution from non-atrophic gastritis to atrophy, from intestinal metaplasia to dysplasia, and lastly adenocarcinoma. Therapeutically, targeting EV-mediated Hsp60/GroEL signaling might offer promising strategies: EV-based biomarkers for early detection, monoclonal antibodies against extracellular Hsp60/GroEL, modulation of vesicle release, and probiotic-derived nanovesicles to restore mucosal balance. Hence, recognizing the muco-microbiotic layer and its vesicle-mediated signaling provides a new framework for understanding the infection–inflammation–cancer axis and for developing diagnostic and therapeutic approaches in H. pylori-associated gastric cancer. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder that significantly impacts the lives of patients and their families. The pathological features of AD include the accumulation of amyloid-β (Aβ) and Tau, which disrupt neuronal function and communication, ultimately leading to neuronal loss and brain atrophy. Efforts to understand the molecular mechanisms underlying these pathological changes have led to advancements in diagnostic techniques and potential therapeutic interventions. However, the complexity of AD necessitates further research to develop more effective treatments and, ideally, preventive measures. Extensive research suggests that diminishing mTOR signaling increases lifespan and health span across various species. Increased PI3K/mTOR signaling has been linked to the progression of AD pathology, leading to neuronal degeneration and impairments in cognitive function. In this study, we explored the therapeutic potential of PF-04691502, a dual PI3K/mTOR inhibitor, in Alzheimer’s disease (AD)-like pathology using male and female B6.Cg-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax mice (APP/PS1), a well-established transgenic model of AD. Eighteen-month-old APP/PS1 and wild-type mice received oral administration of PF-04691502 at a dose of 1 mg/kg for 12 weeks. Following the treatment period, spatial learning and memory were evaluated using the Morris water maze. Subsequently, the mice brains were collected for neuropathological and biochemical assessments. Our findings showed that PF-04691502 enhanced cognitive performance in APP/PS1 mice and significantly reduced insoluble Aβ accumulation in the brain. Mechanistically, these effects were associated with enhanced autophagy induction. Treatment with PF-04691502 increased the LC3-II/LC3-I ratio, upregulated Beclin-1, and elevated LAMP-2 levels, indicative of stimulated autophagosome formation and lysosomal activity. Overall, these preclinical results suggest that PF-04691502 holds promise as a potential therapeutic agent for AD and other aging-related neurodegenerative diseases involving mTOR pathway dysregulation. Full article

Myokines are secreted by muscle and play crucial roles in muscle repair and regeneration and also impact diverse physiological effects through crosstalk with other metabolic organs. However, aging is associated with a progressive decline in muscle mass, which in turn leads to reduced myokine secretion. This decline may contribute to the development of sarcopenia, leading to an increased risk of metabolic disorders such as type 2 diabetes. Accordingly, interest in identifying novel myokines and elucidating their biological functions is increasing. In this study, we explored the function of biglycan (BGN), a novel myokine, in aging-related metabolic tissues. BGN levels decreased in the muscle tissue and plasma of older adults and aged mice, whereas exercise intervention restored BGN expression in aged mice. BGN counteracted the expression of atrophy-related genes involved in muscle degradation and mitigated muscle mass loss by regulating AKT/mTOR signaling pathway. Notably, BGN decreased the expression of the senescence marker p21 and senescence-associated secretory phenotype (SASP)-related genes in hepatocytes. Additionally, BGN attenuated senescence-induced lipid accumulation and ROS generation. Our results suggest that BGN has beneficial effects against muscle atrophy and hepatocellular senescence, indicating its potential as a protective factor for age-related diseases. Full article

Background: COVID-19 has been associated with multisystemic sequelae, including persistent neurocognitive impairment and emerging metabolic alterations. Growing evidence suggests that glial dysfunction and inflammation may play a pivotal role in both cognitive decline and new-onset diabetes following SARS-CoV-2 infection. Objectives: This study aimed to assess the prevalence and characteristics of cognitive impairments in post-COVID-19 patients and to explore their correlation with new-onset diabetes, neuroanatomical changes, and psychological symptoms, with a specific focus on gender differences. Methods: A total of 245 patients (mean age 56.8 ± 12 years), previously diagnosed with COVID-19, were enrolled between April 2021 and August 2023. Participants underwent a comprehensive neuropsychological assessment (MMSE, Rey-Osterrieth Figure, FAB, Hamilton, STAI, IES-R), structured interviews, and, in a subset, brain MRI. Individuals with pre-existing neurological disorders were excluded. Data were analyzed for cognitive performance, neuroimaging abnormalities, and metabolic outcomes, including new-onset diabetes. Results: Cognitive dysfunction was identified in 87% of participants: mild in 47%, moderate in 21.6%, and severe in 10.8%. Glial alterations on MRI were observed in 51%, hippocampal atrophy in 9%, and temporal lobe reduction in 4%. Notably, 12% of patients developed new-onset diabetes post-COVID, of whom 80% exhibited mild to moderate cognitive deficits. Depressive symptoms were present in 80.9%, and anxiety in 93.5%, with significantly higher incidence in female patients. PTSD symptoms correlated with greater cognitive impairment. Ongoing research into the mechanisms underlying these persistent cognitive impairments in subjects with and without types 1 and 2 diabetes. This paper presents the final data of the research published in the previous article referenced in the bibliography. Conclusions: This study highlights a significant association between cognitive decline and new-onset diabetes in post-COVID patients, likely mediated by systemic inflammation and glial dysfunction. Particularly noteworthy are the findings of neuroanatomical alterations, including nonspecific glial signal changes, hippocampal atrophy, and temporal lobe volume reductions, suggesting post-infectious cerebral vulnerability with potential long-term consequences. These results support the need for integrating cognitive screening, brain neuroimaging, and metabolic monitoring into post-COVID care pathways—especially for women and individuals presenting with anxiety or depressive symptoms. An early and interdisciplinary approach is essential to address the neuro-metabolic and cerebral sequelae of long COVID. Full article

The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article