Search Results (28)

Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. Methods: We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Results: Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, and Enterocloster bolteae characterised Asian Chinese participants, while Oscillibacter sp. and Clostridium innocuum characterised European Caucasians. Cross-omic correlations highlighted negative correlations of Phocaeicola vulgatus with amino acids (r = −0.84 to −0.76), while E. ramosum and C. innocuum positively correlated with long-chain triglycerides (r = 0.55–0.62). Conclusions: Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians. Full article

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood–brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus–immune–brain axis in long COVID and inform effective clinical management. Full article

Per- and polyfluoroalkyl substances (PFAS) are used in consumer products and manufacturing. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) are long-chain PFAS composed of 9, 10, and 11 carbons, respectively, which exert sublethal toxicity to aquatic species. Here, we review the data regarding the environmental fate and ecotoxicology of these understudied long-chain PFAS in fish. The objectives of this study were to (1) compile the literature to compare physiological or molecular signaling pathways disrupted by PFNA, PFDA, or PFUnDA; and (2) uncover potential biomarkers and pathways of toxicity of longer-chain PFAS using gene ontology computational approaches to shed light on their mechanism of action. Studies show that PFAS have a range of effects on fish, including developmental issues, changes in gene expression, and behavioral modifications. Based on our review, PFNA has been studied more frequently in fish compared to PFDA and PFUnDA; however, longer-chained PFAS are proposed to pose greater toxicity. Based on the computational approach, prominent pathways affected by PFNA include insulin signaling [“Insulin -> CEBPA/CTNNB/FOXA/FOXO”, “Insulin -> STAT Expression Targets”], immune system signaling [“TNF -> STAT Expression Targets”, “IL6 Expression Targets”, and “IL2 Expression Targets”], and growth hormone/prolactin signaling [“GH1/PRLR Expression Targets”, “PRL/GHR -> STAT Expression Targets”, “PRL/PRLR Expression Targets”]. Several transcripts related to cholesterol metabolism were also affected by PFNA. This review summarizes the current knowledge on the distribution, fate, and ecotoxicology of PFNA, PFDA, and PFUnDA in teleost fish, highlighting potential physiological and molecular responses that could aid in assessing long-chain PFAS toxicity in future studies. Full article

(1) Background: This study evaluated the effects of BiotiQuest^® Sugar Shift^®, a novel probiotic formulation, for its impact on gut microbiome composition and metabolic health in type 2 diabetes mellitus (T2D). T2D is characterized by chronic inflammation and gut microbiome imbalances, yet the therapeutic potential of targeted probiotics remains underexplored. (2) Methods: In a 12-week randomized, double-blind, placebo-controlled trial, 64 adults with T2D received either Sugar Shift or placebo capsules twice daily. Each dose provided 18 billion CFU of eight GRAS-certified bacterial strains and prebiotics. Clinical samples were analyzed for metabolic markers, and microbiome changes were assessed using 16S rRNA sequencing and metagenomics. (3) Results: Sugar Shift significantly reduced serum lipopolysaccharide (LPS) levels, improved insulin sensitivity (lower HOMA-IR scores), and increased short-chain fatty acid (SCFA)-producing genera, including Bifidobacterium, Faecalibacterium, Fusicatenibacter, and Roseburia. Pro-inflammatory taxa like Enterobacteriaceae decreased, with reduced LPS biosynthesis genes and increased SCFA production genes. The Lachnospiraceae:Enterobactericeae ratio emerged as a biomarker of reduced inflammation. (4) Conclusions: These findings demonstrate the potential of Sugar Shift to restore gut homeostasis, reduce inflammation, and improve metabolic health in T2D. Further studies are warranted to explore its long-term efficacy and broader application in metabolic disease management. Full article

Type 2 diabetes (T2D) is a global public health issue characterized by excess weight, abdominal obesity, dyslipidemia, hyperglycemia, and a progressive increase in insulin resistance. Human population studies of T2D development and its effects on systemic metabolism are confounded by many factors that cannot be controlled, complicating the interpretation of results and the identification of early biomarkers. Aged, sedentary, and overweight/obese non-human primates (NHPs) are one of the best animal models to mimic spontaneous T2D development in humans. We sought to identify and distinguish a set of plasma and/or fecal metabolite biomarkers, that have earlier disease onset predictability, and that could be evaluated for their predictability in subsequent T2D studies in human cohorts. In this study, a single plasma and fecal sample was collected from each animal in a colony of 57 healthy and dysmetabolic NHPs and analyzed for metabolomics and lipidomics. The samples were comprehensively analyzed using untargeted and targeted LC/MS/MS. The changes in each animal’s disease phenotype were monitored using IVGTT, HbA1c, and other clinical metrics, and correlated with their metabolic profile. The plasma and fecal lipids, as well as bile acid profiles, from Healthy, Dysmetabolic (Dys), and Diabetic (Dia) animals were compared. Following univariate and multivariate analyses, including adjustments for weight, age, and sex, several plasma lipid species were identified to be significantly different between these animal groups. Medium and long-chain plasma phosphatidylcholines (PCs) ranked highest at distinguishing Healthy from Dys animals, whereas plasma triglycerides (TG) primarily distinguished Dia from Dys animals. Random Forest (RF) analysis of fecal bile acids showed a reduction in the secondary bile acid glycoconjugate, GCDCA, in diseased animals (AUC 0.76[0.64, 0.89]). Moreover, metagenomics results revealed several bacterial species, belonging to the genera Roseburia, Ruminococcus, Clostridium, and Streptococcus, to be both significantly enriched in non-healthy animals and associated with secondary bile acid levels. In summary, our results highlight the detection of several elevated circulating plasma PCs and microbial species associated with fecal secondary bile acids in NHP dysmetabolic states. The lipids and metabolites we have identified may help researchers to differentiate individual NHPs more precisely between dysmetabolic and overtly diabetic states. This could help assign animals to study groups that are more likely to respond to potential therapies where a difference in efficacy might be anticipated between early vs. advanced disease. Full article

Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change. Full article

The human CERS2 gene encodes a ceramide synthase enzyme, known as CERS2 (ceramide synthase 2). This protein is also known as LASS2 (LAG1 longevity assurance homolog 2) and TMSG1 (tumor metastasis-suppressor gene 1). Although previously described as a tumor suppressor for different types of cancer, such as prostate or liver cancer, it has also been observed to promote tumor growth in adenocarcinoma. In this review, we focus on the influence of CERS2 in bladder cancer (BC), approaching the existing literature about its structure and activity, as well as the miRNAs regulating its expression. From a mechanistic point of view, different explanations for the role of CERS2 as an antitumor protein have been proposed, including the production of long-chain ceramides, interaction with vacuolar ATPase, and its function as inhibitor of mitochondrial fission. In addition, we reviewed the literature specifically studying the expression of this gene in both BC and biopsy-derived tumor cell lines, complementing this with an analysis of public gene expression data and its association with disease progression. We also discuss the importance of CERS2 as a biomarker and the presence of CERS2 mRNA in extracellular vesicles isolated from urine. Full article

Background: There is increasing evidence of the benefits of adjuvant and neoadjuvant immunotherapy in the treatment of solid malignancies like oral squamous cell carcinoma (OSCC). To optimize (neo-)adjuvant treatment, the systemic immunomodulatory effects of tumor surgery itself need to be considered. Currently, there is little evidence on the immunological effects of major surgery, such as free microvascular flap reconstruction. The current study aims to analyze how and to what extent maxillofacial surgery affects systemic parameters of immune tolerance. Methods: A total of 50 peripheral whole blood samples from patients (Group 1 (G1) = extensive OSCC surgery; Group 2 (G2) = free flap reconstruction without persistent malignant disease; Group 3 (G3) = minor maxillofacial surgery) undergoing surgery were included for real-time quantitative polymerase chain reaction (RT-qPCR) to examine changes in mRNA expression of the biomarkers IL-6, IL-10, FOXP3, and PD-L1. Blood samples were taken immediately before and after surgery as well as on the second, fourth, and tenth postoperative days. Differences in mRNA expression between groups and time points were calculated using statistical tests, including Mann–Whitney U-test and Pearson correlation analysis. Results: Comparing postoperative expression of G1 and G3, there was a significantly higher PD-L1 expression (p = 0.015) in G1 compared to G3 and a significantly lower IL-6 (p = 0.001) and FOXP3 (p = 0.016) expression. Interestingly, IL-10 expression was higher pre- (0.05) and postoperative (p < 0.001) in G1 compared to G3. Additionally, in G1, there was a significant overexpression of IL-10 post-surgery compared to the preoperative value (p = 0.03) and a downregulated expression of FOXP3 between pre- and 2 d post-surgery (p = 0.04). Furthermore, there was a significant correlation between the duration of surgery and the perioperative expression changes of the analyzed biomarkers. As the duration of surgery increased, the expression of IL-10 and PD-L1 increased, and the expression of IL-6 and FOXP3 decreased. Conclusion: Extensive surgery in OSCC patients is associated with a transient shift toward postoperative systemic immune tolerance compared with patients undergoing minor surgery. However, even extensive surgery causes no signs of long-lasting systemic immunosuppression. The degree of immune tolerance that occurred was associated with the duration of surgery. This supports efforts to minimize the duration of surgery. Full article

Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. Method: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. Results: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = −0.423, p = 0.018) and ANRIL levels (r = −0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = −0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = −0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). Conclusions: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis. Full article

Recent findings qualified aldehydes as potential biomarkers for disease diagnosis. One of the possibilities is to use electrochemical biosensors in point-of-care (PoC), but these need further development to overcome some limitations. Currently, the primary goal is to enhance their metrological parameters in terms of sensitivity and selectivity. Previous findings indicate that peptide OBPP4 (KLLFDSLTDLKKKMSEC-NH₂) is a promising candidate for further development of aldehyde-sensitive biosensors. To increase the affinity of a receptor layer to long-chain aldehydes, a structure stabilization of the peptide active site via the incorporation of different linkers was studied. Indeed, the incorporation of linkers improved sensitivity to and binding of aldehydes in comparison to that of the original peptide-based biosensor. The tendency to adopt disordered structures was diminished owing to the implementation of suitable linkers. Therefore, to improve the metrological characteristics of peptide-based piezoelectric biosensors, linkers were added at the C-terminus of OBPP4 peptide (KLLFDSLTDLKKKMSE-linker-C-NH₂). Those linkers consist of proteinogenic amino acids from group one: glycine, L-proline, L-serine, and non proteinogenic amino acids from group two: β-alanine, 4-aminobutyric acid, and 6-aminohexanoic acid. Linkers were evaluated with in silico studies, followed by experimental verification. All studied linkers enhanced the detection of aldehydes in the gas phase. The highest difference in frequency (60 Hz, nonanal) was observed between original peptide-based biosensors and ones based on peptides modified with the GSGSGS linker. It allowed evaluation of the limit of detection for nonanal at the level of 2 ppm, which is nine times lower than that of the original peptide. The highest sensitivity values were also obtained for the GSGSGS linker: 0.3312, 0.4281, and 0.4676 Hz/ppm for pentanal, octanal, and nonanal, respectively. An order of magnitude increase in sensitivity was observed for the six linkers used. Generally, the linker’s rigidity and the number of amino acid residues are much more essential for biosensors’ metrological characteristics than the amino acid sequence itself. It was found that the longer the linkers, the better the effect on docking efficiency. Full article

The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling/COL6) in SDM and four key pathways (Fatty acid β-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1/2, CASQ1/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration. Full article

Psoriasis is immune-mediated skin disorder affecting thousands of people. Sphingolipids (SLs) are bioactive molecules present in the epidermis, involved in the following cellular processes: proliferation, differentiation, and apoptosis of keratinocytes. Alterations in SLs synthesis have been observed in psoriatic skin. To investigate if the imbalance in lipid skin metabolism could be related to psoriasis, we analyzed the gene expression in non-lesioned and lesioned skin of patients with psoriasis available in two datasets (GSE161683 and GSE136757) obtained from National Center for Biotechnology Information (NCBI). The differentially expressed genes (DEGs) were searched for using NCBI analysis, and Gene Ontology (GO) biological process analyses were performed using the Database of Annotation, Visualization, and Integrated Discovery (DAVID) platform. Venn diagrams were done with InteractiVenn tool and heatmaps were constructed using Morpheus software. We observed that the gene expression of cytoplasmic phospholipase A₂ (PLA2G4D), glycerophosphodiester phosphodiesterase domain containing 3 (GDP3), arachidonate 12-lipoxygenase R type (ALOX12B), phospholipase B-like 1 (PLBD1), sphingomyelin phosphodiesterase 3 (SMPD3), ganglioside GM2 activator (GM2A), and serine palmitoyltransferase long chain subunit 2 (SPTLC2) was up-regulated in lesioned skin psoriasis when compared with the non-lesioned skin. These genes are related to lipid metabolism and more specifically to sphingolipids. So, in the present study, the role of sphingolipids in psoriasis pathogenesis is summarized. These genes could be used as prognostic biomarkers of psoriasis and could be targets for the treatment of patients who suffer from the disease. Full article

Cancer is responsible for lifelong disability and decreased quality of life. Cancer-associated changes in metabolism, in particular carbohydrate, lipid, and protein, offer a new paradigm of metabolic hits. Hence, targeting the latter, as well as related cross-linked signalling pathways, can reverse the malignant phenotype of transformed cells. The systemic toxicity and pharmacokinetic limitations of existing drugs prompt the discovery of multi-targeted and safe compounds from natural products. Mushrooms possess biological activities relevant to disease-fighting and to the prevention of cancer. They have a long-standing tradition of use in ethnomedicine and have been included as an adjunct therapy during and after oncological care. Mushroom-derived compounds have also been reported to target the key signature of cancer cells in in vitro and in vivo studies. The identification of metabolic pathways whose inhibition selectively affects cancer cells appears as an interesting approach to halting cell proliferation. For instance, panepoxydone exerted protective mechanisms against breast cancer initiation and progression by suppressing lactate dehydrogenase A expression levels and reinducing lactate dehydrogenase B expression levels. This further led to the accumulation of pyruvate, the activation of the electron transport chain, and increased levels of reactive oxygen species, which eventually triggered mitochondrial apoptosis in the breast cancer cells. Furthermore, the inhibition of hexokinase 2 by neoalbaconol induced selective cytotoxicity against nasopharyngeal carcinoma cell lines, and these effects were also observed in mouse models. Finally, GL22 inhibited hepatic tumour growth by downregulating the mRNA levels of fatty acid-binding proteins and blocking fatty acid transport and impairing cardiolipin biosynthesis. The present review, therefore, will highlight how the metabolites isolated from mushrooms can target potential biomarkers in metabolic reprogramming. Full article

The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or “long COVID”), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms. Full article

In response to muscle injury, muscle stem cells are stimulated by environmental signals to integrate into damaged tissue to mediate regeneration. L-leucine (L-leu), a branched-chain amino acid (BCAA) that belongs to the essential amino acids (AAs) of the animal, has gained global interest on account of its muscle-building and regenerating effects. The present study was designed to investigate the impact of L-leu exposure to promote the proliferation of equine skeletal muscle satellite cells (SCs) on the regulation of RNA networks, including mRNA, long non-coding RNA (lncRNA), covalently closed circular RNA (circRNA), and microRNA (miRNA) in skeletal muscles. Equine SCs were used as a cell model and cultured in different concentrations of L-leu medium. The cell proliferation assay found that the optimal concentration of L-leu was 2 mM, so we selected cells cultured with L-leu concentrations of 0 mM and 2 mM for whole-transcriptiome sequencing, respectively. By high-throughput sequencing analysis, 2470 differentially expressed mRNAs (dif-mRNAs), 363 differentially expressed lncRNAs (dif-lncRNAs), 634 differentially expressed circRNAs (dif-circRNAs), and 49 differentially expressed miRNAs (dif-miRNAs) were significantly altered in equine SCs treated with L-leu. To identify the function of autoimmunity and anti-inflammatory responses after L-leu exposure, enrichment analysis was conducted on those differentially expressed genes (DEGs) related to lncRNA, circRNA, and miRNA. The hub genes were selected from PPI Network, including ACACB, HMGCR, IDI1, HAO1, SHMT2, PSPH, PSAT1, ASS1, PHGDH, MTHFD2, and DPYD, and were further identified as candidate biomarkers to regulate the L-leu-induced proliferation of equine SCs. The up-regulated novel 699_star, down-regulated novel 170_star, and novel 360_mature were significantly involved in the competing endogenous RNA (ceRNA) complex network. The hub genes involved in cell metabolism and dif-miRNAs may play fundamental roles in the L-leu-induced proliferation of equine SCs. Our findings suggested that the potential network regulation of miRNAs, circ-RNAs, lncRNAs, and mRNAs plays an important role in the proliferation of equine SCs, so as to build up new perspectives on improving equine performance and treatment strategies for the muscle injuries of horses. Full article