ABSTRACT
BACKGROUND: Depression tends to develop in correlation with hypothyroidism, however it's unclear how testosterone traits contribute to this association. We examined the causal association between depression, testosterone traits, and hypothyroidism using Mendelian randomization (MR). METHOD: We conducted univariable and multivariable MR studies using summary-level statistics from genome-wide association studies (GWAS) of Hypothyroidism (n = 213,990), broad depression (n = 322,580), probable major depressive disorder (probable MDD) (n = 174,519), and International Classification of Diseases (ICD)-9 or ICD-10-coded MDD (n = 217,584) from European ancestry. The inverse variance weighted (IVW) method was used as the main MR analysis. RESULTS: In univariate MR analysis, there is a positive causal relationship between hypothyroidism and broad depression (P = 0.0074; OR = 1.0066; 95%CI: 1.0018-1.0114) and probable MDD (P = 0.0242; OR = 1.0056; 95%CI: 1.0007-1.0105). In females, there is a causal relationship between hypothyroidism and decreased total testosterone (P < 0.001; OR = 0.9747; 95%CI: 0.9612-0.9885) and sex hormone binding globulin (SHBG) levels (P = 0.0418; OR = 0.9858; 95%CI: 0.9723-0.9995). In females, there is an inverse causal relationship between total testosterone and broad depression (P = 0.0349; OR = 0.9898; 95%CI: 0.9804-0.9993). Furthermore, in multivariate MR analysis, after adjusting for total testosterone in females, hypothyroidism only has a positive causal relationship with probable MDD, and the relationship with broad depression is no longer significant. Most notably, after adjusting for hypothyroidism, the inverse causal effect of female total testosterone levels on broad depression becomes more significant (P = 0.0154; OR = 0.9878; 95%CI: 0.9780-0.9977). CONCLUSION: Hypothyroidism increases the risk of broad depression and probable MDD development. Total Testosterone appears to play an important role in the relationship between hypothyroidism and broad depression in female.
Subject(s)
Depressive Disorder, Major , Genome-Wide Association Study , Hypothyroidism , Mendelian Randomization Analysis , Testosterone , Humans , Testosterone/blood , Female , Male , Depression , Sex Hormone-Binding Globulin/analysis , AdultABSTRACT
Objective: To examine the risk factors linked with occupational blood exposure (OBE) among nursing staff (NS), we pinpoint deficiencies in the compliance with policies of infection prevention and control, and assess the expenditures associated with infection prevention and control. Methods: Healthcare workers that completed an "Occupational Blood Exposure Report Form" were divided into NS (observation) group and non-NS (control) group. Univariate and multivariable analyses were conducted to compare both groups in various aspects. We also explored design patents intended to minimize occupational exposure. Results: The highest incidence of OBE was observed in the department of neurosurgery. Among NS, OBE incidence was found to be influenced by independent risk factors, such as gender, age, occupational title, work location, and incidence of sharps injuries. Protective factors against OBEs included the use of arterial blood gas needles and suture needles. Personal protective equipment (PPE) usage rates were low in both groups prior to OBEs (0.74% vs 0.00%, P > 0.05). Correct emergency management could be improved promptly by both groups following an OBE (P > 0.05). However, the observation group exhibited a higher proportion of blood expression after a sharps injury and a higher re-evaluation rate at 6 months post-exposure compared to the control group (P < 0.05). In 2018, the per capita costs of infection prevention and control for NS were the Chinese Yuan (RMB) 339.43 per individual. In response to these findings, two utility model patents have been authorized. Conclusion: The risk and protective factors related to the occurrence of OBEs were investigated in this study, suggesting that there is a need for improvement in the rate of PPE usage and the re-evaluation rate of OBEs among NS. Additionally, focused training on emergency blood expression and compliance with policies among non-NS personnel is deemed necessary.
ABSTRACT
Fat infiltration in skeletal muscle (also known as myosteatosis) is now recognized as a distinct disease from sarcopenia and is directly related to declining muscle capacity. Hence, understanding the origins and regulatory mechanisms of fat infiltration is vital for maintaining skeletal muscle development and improving human health. In this article, we summarized the triggering factors such as aging, metabolic diseases and metabolic syndromes, nonmetabolic diseases, and muscle injury that all induce fat infiltration in skeletal muscle. We discussed recent advances on the cellular origins of fat infiltration and found several cell types including myogenic cells and non-myogenic cells that contribute to myosteatosis. Furthermore, we reviewed the molecular regulatory mechanism, detection methods, and intervention strategies of fat infiltration in skeletal muscle. Based on the current findings, our review will provide new insight into regulating function and lipid metabolism of skeletal muscle and treating muscle-related diseases.
ABSTRACT
Fat infiltration in skeletal muscle is now recognized as a standard feature of aging and is directly related to the decline in muscle function. However, there is still a limited systematic integration and exploration of the mechanisms underlying the occurrence of myosteatosis in aging across species. Here, we re-analyzed bulk RNA-seq datasets to investigate the association between fat infiltration in skeletal muscle and aging. Our integrated analysis of single-nucleus transcriptomics in aged humans and Laiwu pigs with high intramuscular fat content, identified species-preference subclusters and revealed core gene programs associated with myosteatosis. Furthermore, we found that fibro/adipogenic progenitors (FAPs) had potential capacity of differentiating into PDE4D+/PDE7B+ preadipocytes across species. Additionally, cell-cell communication analysis revealed that FAPs may be associated with other adipogenic potential clusters via the COL4A2 and COL6A3 pathways. Our study elucidates the correlation mechanism between aging and fat infiltration in skeletal muscle, and these consensus signatures in both humans and pigs may contribute to increasing reproducibility and reliability in future studies involving in the field of muscle research.
Subject(s)
Adipogenesis , Aging , Muscle, Skeletal , Aged , Animals , Humans , Adipogenesis/physiology , Cell Differentiation , Muscle, Skeletal/physiology , Swine , Datasets as Topic , RNA-Seq , Transcriptome , Adipocytes , Stem CellsABSTRACT
Leucine is involved in promoting fatty acid oxidation and lipolysis, mediating lipid metabolism and energy homeostasis, thus it has been widely used in livestock production. However, the effects of leucine on fat deposition and nutrition in Shaziling pigs remain unclear. A total of 72 Shaziling pigs (150 days old, weight 35.00 ± 1.00 kg) were randomly divided into 2 groups and fed with basal diet (control group) or basal diet containing 1% leucine (leucine group) for 60 days. The results showed that leucine significantly increased the average daily feed intake but decreased the ratio of feed to gain (P < 0.05), increased the loin muscle area and serum glucose content (P < 0.05) of Shaziling pigs. Besides, leucine regulated the re-distribution of fatty acids from adipose tissue to muscle as it significantly increased the contents of C18:1n-9 and C22:6n-3 (DHA) in the longissimus thoracis while decreased the contents of C22:5n-3 (DPA), C20:5n-3 (EPA), and DHA in the adipose tissue of Shaziling pigs (P < 0.05). Lipidomic analysis showed that the contents of phosphatidylethanolamines (PEs), cardiolipins (CLs), and phosphatidylglycerols (PGs) in the longissimus thoracis and the contents of lysophosphatidylethanolamines (LPEs), ceramides (Cers), phosphatidylinositols (PIs) in adipose tissue of Shaziling pigs were decreased in leucine group (P < 0.05). Collectively, this study clarified that dietary addition of 1% leucine have a better effect on growth performance and the deposition of beneficial fatty acids in the muscle of Shaziling pigs, which is conductive to the production of high quality and healthy pork. In addition, leucine altered the lipid composition of muscle and fat in Shaziling pigs. The related results provide a theoretical basis and application guidance for regulating fat deposition in Shaziling pigs, which is important for the healthy breeding of Shaziling pigs.
Subject(s)
Pork Meat , Red Meat , Swine , Animals , Leucine/metabolism , Leucine/pharmacology , Body Composition , Red Meat/analysis , Pork Meat/analysis , Diet/veterinary , Adipose Tissue/chemistry , Fatty Acids/analysis , Nutritive Value , Animal Feed/analysis , Meat/analysisABSTRACT
Objective: The objective of this study is to examine the qualification rate of hand disinfection in the surgical department wards and analyze the influencing factors. Methods: A surprise assessment was carried out to evaluate the daily adherence to hand hygiene protocols in the surgical department wards. We aimed to investigate the factors that impact the qualification rate of hand disinfection. Results: In this study, the qualification rate of hand disinfection was determined to be 64.38%. Notably, this rate exhibited significant variations based on gender, age, surgical site, and department category. Specifically, the qualification rate of hand disinfection among female participants stood at 82.35%, surpassing the qualification rate observed among male counterparts of 52.83%. Furthermore, doctors in the age group of 41-50 years demonstrated the highest qualification rate, and the abdominal surgical site exhibited the most noteworthy qualification rate, reaching 79.49%. The outcomes of the multiple logistic regression analysis highlighted the significance of age and gender as influential factors impacting the qualification rate. Specifically, doctors aged 51 years or older exhibited the lowest hand hygiene compliance, whereas female doctors demonstrated a notably higher qualification rate compared to their male counterparts. Conclusion: The disheartening qualification rate of hand disinfection highlights a concerning lack of awareness regarding hand hygiene among surgeons in their professional duties. Consequently, targeted interventions are imperative, focusing on intensified training, educational initiatives, enhanced supervision, and internal performance evaluations for key groups. The findings not only serve as a valuable database but also offer a viable roadmap for similar hospitals to reinforce the management of nosocomial infections.
ABSTRACT
Purpose: Based on the two mediating variables of self-efficacy and coping style, a multiple mediating model was constructed to explore the mechanism by which psychological resilience affects depression in patients with recurrent schizophrenia. Methods: A total of 210 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, were enrolled. The Connor Davidson Resilience Scale (CD-RISC), Self-rating Depression Scale (SDS), General Self-Efficacy Energy Scale (GSES) and Simplified Coping Style Questionnaire (SCSQ) were used to evaluate resilience, self-efficacy, coping style and depression. Path analysis was performed by constructing a structural equation model, and the mediating effect between variables was verified by the bias-corrected nonparametric percentile bootstrap method. Results: Resilience, self-efficacy and positive coping together explained 53.2% of the variance in depression. (1) The total scores of self-efficacy, coping style, resilience and depression in patients with recurrent schizophrenia were 2.54±0.61, 31.73±9.62, 58.06±17.26 and 50.48±12.55, respectively. (2) Pearson analysis showed that the scores of self-efficacy, positive coping, resilience and depression were significantly correlated with depression (r=-0.24-0.51, P<0.01). (3) The path analysis showed that resilience directly affects depression (ß=-0.401); additionally, resilience indirectly affects depression through self-efficacy (ß=-0.179) and through the chain mediating effect of self-efficacy and positive coping style (ß=-0.024). Conclusion: There is a high incidence of depression in patients with recurrent schizophrenia in China, and intervention is needed. This research revealed that resilience directly affects depression in patients with recurrent schizophrenia and that self-efficacy and positive coping play a part in mediating resilience and depression in patients with recurrent schizophrenia in China. Implementing targeted interventions based on action paths to improve the level of resilience and reduce the incidence of depression has guiding significance in the field of occupational rehabilitation of patients with recurrent schizophrenia.
ABSTRACT
Melatonin has been reported to play crucial roles in regulating meat quality, improving reproductive properties, and maintaining intestinal health in animal production, but whether it regulates skeletal muscle development in weaned piglet is rarely studied. This study was conducted to investigate the effects of melatonin on growth performance, skeletal muscle development, and lipid metabolism in animals by intragastric administration of melatonin solution. Twelve 28-d-old DLY (Durocâ ×â Landraceâ ×â Yorkshire) weaned piglets with similar body weight were randomly divided into two groups: control group and melatonin group. The results showed that melatonin supplementation for 23 d had no effect on growth performance, but significantly reduced serum glucose content (Pâ <â 0.05). Remarkably, melatonin increased longissimus dorsi muscle (LDM) weight, eye muscle area and decreased the liver weight in weaned piglets (Pâ <â 0.05). In addition, the cross-sectional area of muscle fibers was increased (Pâ <â 0.05), while triglyceride levels were decreased in LDM and psoas major muscle by melatonin treatment (Pâ <â 0.05). Transcriptome sequencing showed melatonin induced the expression of genes related to skeletal muscle hypertrophy and fatty acid oxidation. Enrichment analysis indicated that melatonin regulated cholesterol metabolism, protein digestion and absorption, and mitophagy signaling pathways in muscle. Gene set enrichment analysis also confirmed the effects of melatonin on skeletal muscle development and mitochondrial structure and function. Moreover, quantitative real-time polymerase chain reaction analysis revealed that melatonin supplementation elevated the gene expression of cell differentiation and muscle fiber development, including paired box 7 (PAX7), myogenin (MYOG), myosin heavy chain (MYHC) IIA and MYHC IIB (Pâ <â 0.05), which was accompanied by increased insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 5 (IGFBP5) expression in LDM (Pâ <â 0.05). Additionally, melatonin regulated lipid metabolism and activated mitochondrial function in muscle by increasing the mRNA abundance of cytochrome c oxidase subunit 6A (COX6A), COX5B, and carnitine palmitoyltransferase 2 (CPT2) and decreasing the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), acetyl-CoA carboxylase (ACC) and fatty acid-binding protein 4 (FABP4) (Pâ <â 0.05). Together, our results suggest that melatonin could promote skeletal muscle growth and muscle fiber hypertrophy, improve mitochondrial function and decrease fat deposition in muscle.
Due to its extensive biological functions, melatonin has been widely used in animal production in recent years. The purpose of this study was to investigate the effects of melatonin on growth performance, muscle development, and lipid metabolism of weaned piglets. Twelve 28-d-old DLY (Durocâ ×â Landraceâ ×â Yorkshire) weaned piglets were randomly divided into two groups: control group and melatonin group. The results showed that melatonin supplementation daily had no effect on growth performance, but increased muscle weight, eye muscle area, and decreased the liver weight in weaned piglets. Consistently, the cross-sectional area of myofiber increased, while triglyceride levels decreased in muscle. Melatonin induced the expression of genes related to skeletal muscle hypertrophy and fatty acid oxidation in muscle through transcriptome sequencing. Additionally, melatonin regulated cholesterol metabolism, protein digestion and absorption, and mitophagy signaling pathways in muscle. Gene set enrichment analysis also confirmed the effects of melatonin on skeletal muscle development and mitochondrial function. Moreover, melatonin supplementation elevated the gene expression of cell differentiation and muscle fiber development. Additionally, melatonin inhibited the mRNA expression related to fat synthesis while improved mitochondrial function in muscle. Together, our results suggest melatonin could promote skeletal muscle growth and muscle fiber hypertrophy, enhance mitochondrial function and decrease fat deposition in muscle.
Subject(s)
Melatonin , Swine Diseases , Animals , Swine , Lipid Metabolism , Melatonin/pharmacology , Melatonin/metabolism , Muscle, Skeletal/metabolism , Muscle Fibers, Skeletal/physiology , RNA, Messenger/genetics , Dietary Supplements , Hypertrophy/veterinary , Swine Diseases/metabolismABSTRACT
Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58â ±â 10.39 kg) were randomly divided into two treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 d. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of the lipolytic gene (hormone-sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially ceramides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorγ (PPARγ) expression and further inhibit adipogenic differentiation in adipose tissues of pigs by suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short-chain fatty acids (SCFAs) in the gut (P ≤ 0.05) but the abundance of Cers was negatively related to the production and functions of SCFAs (P ≤ 0.05). CLAs altered the distribution of the lipid in serum and inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing PPARγ expression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.
Meat quality is affected by fat deposition and conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. We explored the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition based on a Heigai pig model. We found CLAs reduced fat deposition in vivo and in vitro and changed lipids profiles in serum including decreased sphingolipids especially cermides (Cers) and sphingomyelins in the serum of Heigai pigs. We also demonstrated CLAs inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing peroxisome proliferator-activated receptorγ expression in adipose tissues. Furthermore, Pearson's correlation analysis showed hormone-sensitive lipase expression and the abundance of Cers are related to the production and functions of short-chain fatty acids in the gut. Our findings provide useful insights into the role of CLAs in regulating lipid composition in serum and lipid metabolism in adipose tissue and provide a new insight into producing high-quality pork in the pig industry by using nutritional strategies.
Subject(s)
Linoleic Acids, Conjugated , Swine , Animals , Linoleic Acids, Conjugated/pharmacology , Linoleic Acids, Conjugated/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Adipose Tissue/metabolism , Subcutaneous Fat/metabolism , Fatty Acids/metabolism , Lipid MetabolismABSTRACT
Pork is the most consumed meat in the world, and its quality is associated with human health. Intramuscular fat (IMF) deposition (also called marbling) is a key factor positively correlated with various quality traits and lipo-nutritional values of meat. However, the cell dynamics and transcriptional programs underlying lipid deposition in highly marbled meat are still unclear. Here, we used Laiwu pigs with high (HLW) or low (LLW) IMF contents to explore the cellular and transcriptional mechanisms underlying lipid deposition in highly-marbled pork by single-nucleus RNA sequencing (snRNA-seq) and bulk RNA sequencing. The HLW group had higher IMF contents but less drip loss than the LLW group. Lipidomics results revelled the changes of overall lipid classes composition (e.g., glycerolipids including triglycerides, diglycerides, and monoglycerides; sphingolipids including ceramides and monohexose ceramide significantly increased) between HLW and LLW groups. SnRNA-seq revealed nine distinct cell clusters, and the HLW group had a higher percentage of adipocytes (1.40% vs. 0.17%) than the LLW group. We identified 3 subpopulations of adipocytes, including PDE4D+/PDE7B+ (in HLW and LLW), DGAT2+/SCD+ (mostly in HLW) and FABP5+/SIAH1+ cells (mostly in HLW). Moreover, we showed that fibro/adipogenic progenitors could differentiate into IMF cells and contribute to 43.35% of adipocytes in mice. In addition, RNA-seq revealed different genes involved in lipid metabolism and fatty acid elongation. Our study provides new insights into the cellular and molecular signatures of marbling formation; such knowledge may facilitate the development of new strategies to increase IMF deposition and the lipo-nutritional quality of high marbled pork.
ABSTRACT
This study aimed to determine the effects of fermented mixed feed (FMF) supplementation (0%, 5% and 10%) on the intestinal microbial community and metabolism, and the compositions of volatile flavor compounds and inosine monophosphate (IMP) contents in the longissimus thoracis. In this study, 144 finishing pigs (Duroc × Berkshire × Jiaxing Black) were randomly allocated to 3 groups with 4 replicate pens per group and 12 pigs per pen. The experiment lasted 38 days after 4 days of acclimation. The 16S rRNA gene sequences and an untargeted metabolomics analysis showed FMF altered the profiles of microbes and metabolites in the colon. Heracles flash GC e-nose analysis showed that 10% FMF (treatment 3) had a greater influence on the compositions of volatile flavor compounds than 5% FMF (treatment 2). Compared to 0% FMF (treatment 1), the contents of total aldehydes, (E,E)-2,4-nonadienal, dodecanal, nonanal and 2-decenal were significantly increased by treatment 3, and treatment 3 increased IMP concentrations and gene expressions related to its synthesis. Correlations analysis showed significantly different microbes and metabolites had strong correlations with the contents of IMP and volatile flavor compounds. In conclusion, treatment 3 regulated intestinal microbial community and metabolism, that in turn altered the compositions of volatile compounds, which contributed to improving pork flavor and umami.
Subject(s)
Pork Meat , Red Meat , Animals , Metabolomics , RNA, Ribosomal, 16S/genetics , SwineABSTRACT
Hypoxia-inducible factor (HIF) has received much attention as a potential pulmonary hypertension (PH) treatment target because inhibition of HIF reduces the severity of established PH in rodent models. However, the limitations of small-animal models of PH in predicting the therapeutic effects of pharmacologic interventions in humans PH are well known. Therefore, we sought to interrogate the role of HIFs in driving the activated phenotype of PH cells from human and bovine vessels. We first established that pulmonary arteries (PAs) from human and bovine PH lungs exhibit markedly increased expression of direct HIF target genes (CA9, GLUT1, and NDRG1), as well as cytokines/chemokines (CCL2, CSF2, CXCL12, and IL6), growth factors (FGF1, FGF2, PDGFb, and TGFA), and apoptosis-resistance genes (BCL2, BCL2L1, and BIRC5). The expression of the genes found in the intact PAs was determined in endothelial cells, smooth muscle cells, and fibroblasts cultured from the PAs. The data showed that human and bovine pulmonary vascular fibroblasts from patients or animals with PH (termed PH-Fibs) were the cell type that exhibited the highest level and the most significant increases in the expression of cytokines/chemokines and growth factors. In addition, we found that human, but not bovine, PH-Fibs exhibit consistent misregulation of HIFα protein stability, reduced HIF1α protein hydroxylation, and increased expression of HIF target genes even in cells grown under normoxic conditions. However, whereas HIF inhibition reduced the expression of direct HIF target genes, it had no impact on other "persistently activated" genes. Thus, our study indicated that HIF inhibition alone is not sufficient to reverse the persistently activated phenotype of human and bovine PH-Fibs.
Subject(s)
Hypertension, Pulmonary , Animals , Humans , Hypertension, Pulmonary/metabolism , Endothelial Cells/metabolism , Phenotype , Cytokines/metabolism , Pulmonary Artery/metabolism , Intercellular Signaling Peptides and Proteins , Hypoxia/complications , Fibroblasts/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Cells, CulturedABSTRACT
BACKGROUND: The etiology and mechanism of persistent geotropic horizontal direction-changing positional nystagmus (DCPN) are still unclear. Whether this pattern of nystagmus is a subtype of benign paroxysmal positional vertigo (BPPV) remains controversial. OBJECTIVE: The goal of this study was to observe the clinical characteristics of persistent geotropic horizontal DCPN involving the lateral semicircular canal. METHODS: The analysis was performed to participants with episodic positional vertigo in our clinic from 2014 to 2021. Participants were included via positional test. We observed and summarized the distribution data, vertigo history, follow-up tests, and recurrence situations of 189 persistent geotropic horizontal DCPN participants. RESULTS: The mean age at the first time showing of persistent geotropic horizontal DCPN was 56±14.7 and more women than men were affected by persistent geotropic horizontal DCPN (female-to-male ratio 2.4â:â1). Overall, 58.7% (57/94) of participants who came for the first-week follow-up test were asymptomatic. Thirty-three participants experienced recurrence (female-to-male ratio: 4.5â:â1). Fifty-three (28.0%) participants experienced the conversion of the patterns of DCPN in the history, the follow-up tests and the recurrence compared to the first showing of persistent geotropic horizontal DCPN. 24(12.1%) participants still experienced persistent geotropic horizontal DCPN attack in the follow-up tests and the recurrences without benign paroxysmal positional vertigo history. CONCLUSION: Persistent geotropic horizontal DCPN affected more women than men. The persistent geotropic horizontal DCPN that with conversion to transient geotropic horizontal DCPN or to persistent apogeotropic horizontal DCPN might be a subtype of BPPV or in a stage of BPPV process. However, the persistent geotropic horizontal DCPN without conversion might be an independent disease that is not related to BPPV.
Subject(s)
Benign Paroxysmal Positional Vertigo , Nystagmus, Pathologic , Humans , Male , Female , Benign Paroxysmal Positional Vertigo/diagnosis , Nystagmus, Pathologic/diagnosis , Nystagmus, Physiologic , Vestibular Function Tests , Semicircular CanalsABSTRACT
BACKGROUND: In addition to its contractile properties and role in movement, skeletal muscle plays an important function in regulating whole-body glucose and lipid metabolism. A central component of such regulation is mitochondria, whose quality and function are essential in maintaining proper metabolic homeostasis, with defects in processes such as autophagy and mitophagy involved in mitochondria quality control impairing skeletal muscle mass and function, and potentially leading to a number of associated diseases. Cold exposure has been reported to markedly induce metabolic remodeling and enhance insulin sensitivity in the whole body by regulating mitochondrial biogenesis. However, changes in lipid metabolism and lipidomic profiles in skeletal muscle in response to cold exposure are unclear. Here, we generated lipidomic or transcriptome profiles of mouse skeletal muscle following cold induction, to dissect the molecular mechanisms regulating lipid metabolism upon acute cold treatment. RESULTS: Our results indicated that short-term cold exposure (3 days) can lead to a significant increase in intramuscular fat deposition. Lipidomic analyses revealed that a cold challenge altered the overall lipid composition by increasing the content of triglyceride (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), while decreasing sphingomyelin (SM), validating lipid remodeling during the cold environment. In addition, RNA-seq and qPCR analysis showed that cold exposure promoted the expression of genes related to lipolysis and fatty acid biosynthesis. These marked changes in metabolic effects were associated with mitophagy and muscle signaling pathways, which were accompanied by increased TG deposition and impaired fatty acid oxidation. Mechanistically, HIF-1α signaling was highly activated in response to the cold challenge, which may contribute to intramuscular fat deposition and enhanced mitophagy in a cold environment. CONCLUSIONS: Overall, our data revealed the adaptive changes of skeletal muscle associated with lipidomic and transcriptomic profiles upon cold exposure. We described the significant alterations in the composition of specific lipid species and expression of genes involved in glucose and fatty acid metabolism. Cold-mediated mitophagy may play a critical role in modulating lipid metabolism in skeletal muscle, which is precisely regulated by HIF-1α signaling.
Subject(s)
Lipid Metabolism , Mitophagy , Animals , Mice , Fatty Acids/metabolism , Glucose/metabolism , Lipids , Muscle, Skeletal/metabolism , Cold TemperatureABSTRACT
Skeletal muscle plays important roles in normal biological activities and whole-body energy homeostasis in humans. The growth and development of skeletal muscle also directly influence meat production and meat quality in animal production. Therefore, regulating the development and homeostasis of skeletal muscle is crucial for human health and animal production. Adipose tissue, which includes white adipose tissue (WAT) and brown adipose tissue (BAT), not only functions as an energy reserve but also has attracted substantial attention because of its role as an endocrine organ. The novel signalling molecules known as "adipokines" and "lipokines" that are secreted by adipose tissue were identified through the secretomic technique, which broadened our understanding of the previously unknown crosstalk between adipose tissue and skeletal muscle. In this review, we summarize and discuss the secretory role of adipose tissues, both WAT and BAT, as well as the regulatory roles of various adipokines and lipokines in skeletal muscle development and homeostasis. We suggest that adipokines and lipokines have potential as drug candidates for the treatment of skeletal muscle dysfunction and related metabolic diseases and as promising nutrients for improving animal production.
Subject(s)
Adipokines , Adipose Tissue , Animals , Humans , Adipokines/metabolism , Adipose Tissue/metabolism , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Homeostasis , Muscle Development , Muscle, Skeletal/metabolism , Energy Metabolism/physiologyABSTRACT
Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis and crucial for systemic metabolism. Under chronic cold exposures and high-fat diet challenges, BAT undergoes robust remodeling to adapt to physiological demands. However, whether and how BAT regenerates after acute injuries are poorly understood. Here, we established a novel BAT injury and regeneration model (BAT-IR) in mice and performed single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to determine cellular and transcriptomic dynamics during BAT-IR. We further defined distinct fibro-adipogenic and myeloid progenitor populations contributing to BAT regeneration. Cell trajectory and gene expression analyses uncovered the involvement of MAPK, Wnt, and Hedgehog (Hh) signaling pathways in BAT regeneration. We confirmed the role of Hh signaling in BAT development through Myf5Cre-mediated conditional knockout (cKO) of the Sufu gene to activate Hh signaling in BAT and muscle progenitors. Our BAT-IR model therefore provides a paradigm to identify conserved cellular and molecular mechanisms underlying BAT development and remodeling.
ABSTRACT
Conjugated linoleic acid (CLA) is a potential nutritional strategy to regulate meat quality in pigs and produce high-quality pork. However, the effects of CLA on nutritional quality, lipid dynamics, microbiota, and their metabolites in the gut of pigs remain unclear. Our study explored the effects of CLA on lipo-nutritional quality based on a Heigai pig model and investigated the regulatory mechanism using an integrated analysis of multiple omics. A total of 58 Heigai finishing pigs (body weight: 85.58 ± 10.39 kg) were randomly divided into 2 treatments and fed diets containing 1% soyabean oil and 1% CLA for 40 days. 1% CLA significantly decreased the backfat thickness (P < 0.05) and increased the intramuscular fat (IMF) content (P < 0.05). The expression of lipid metabolism-related genes was significantly changed (P < 0.05) and lipidome analysis showed the alternations of lipid dynamics in the longissimus dorsi muscle (LDM). In addition, based on the microbiome and metabolomic analyses, the relative abundances of Parabacteroides, Bacteroides, and Lachnospiraceae_UCG-010 increased and CLA changed the metabolome profiles and the short-chain fatty acid (SCFA) composition in the gut, which were significantly increased (P < 0.05). Additionally, Pearson's correlation analysis indicated that differential microbial genera and SCFAs induced by CLA had tight correlations with the backfat thickness, IMF content and lipids in the LDM. CLA enhances the lipid accumulation and metabolism in muscle and these changes are associated with the production and functions of the differential bacteria and SCFAs in the gut of pigs.
Subject(s)
Gastrointestinal Microbiome , Linoleic Acids, Conjugated , Pork Meat , Red Meat , Animals , Adipose Tissue/metabolism , Animal Feed , Body Composition , Fatty Acids/metabolism , Linoleic Acids, Conjugated/pharmacology , Linoleic Acids, Conjugated/metabolism , Meat/analysis , Nutritive Value , SwineABSTRACT
BACKGROUND: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. METHODS: Immunofluorescence was used to detect the location and expression of trypsinogen in chronic pancreatitis and normal tissues. Microarray and single-cell RNA-seq (scRNA-seq) were used to screen core genes and pathways in pancreatic stellate cells (PSCs). Western blotting and immunofluorescence were used to verify trypsinogen expression in PSCs after silencing Rabep1. Immunofluorescence and flow cytometry were used to validate trypsinogen activation and PSC activation after intervening in the endocytosis pathway. RESULTS: Endocytosed trypsinogen was found in PSCs in CP clinical samples. Bioinformatic analysis showed that Rabep1 is a core gene that regulates trypsinogen endocytosis through the endocytosis pathway, verified by Western blot and immunofluorescence. Immunofluorescence and flow cytometry analyses confirmed the activation of trypsinogen and PSCs through the endocytosis pathway in PSCs. CONCLUSION: This study discovered a new mechanism by which trypsinogen affects the activation of PSCs and the occurrence and development of CP. Through communication between pancreatic acinar cells and PSCs, trypsinogen can be endocytosed by PSCs and activated by the Rabep1 gene.
Subject(s)
Pancreatic Stellate Cells , Pancreatitis, Chronic , Acute Disease , Cells, Cultured , Endocytosis , Humans , Pancreatic Stellate Cells/pathology , Pancreatitis, Chronic/genetics , Pancreatitis, Chronic/metabolism , Pancreatitis, Chronic/pathology , Trypsinogen/genetics , Trypsinogen/metabolismABSTRACT
Purpose: To explore the mediating effect of self-efficacy on the relationship between perceived social support and resilience in patients with recurrent schizophrenia in China. Patients and Methods: In this cross-sectional study, a total of 176 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, completed a general data questionnaire, the Connor Davidson Resilience Scale (CD-RISC), the Perceived Social Support Scale (PSSS) and the General Self-Efficacy Energy Scale (GSES). Results: Among the 176 patients, the mean GSES score was 2.02±0.61, the mean PSSS score was 56.77±14.61, and the mean CD-RISC score was 58.06±17.26. Self-efficacy played a partial mediating role between social support and resilience, and the mediating effect accounted for 42.56% of the total effect. Conclusion: The resilience level of patients with recurrent schizophrenia in China is moderate and needs to be improved. This research revealed that self-efficacy played a part in mediating perceived social support and resilience in patients with recurrent schizophrenia in China. Perceived social support can indirectly affect resilience in patients with recurrent schizophrenia through self-efficacy. Comprehensive interventions in perceived social support and self-efficacy would help to improve the resilience of patients with recurrent schizophrenia.
ABSTRACT
Changing fatty acid composition is a potential nutritional strategy to shape microbial communities in pigs. However, the effect of different n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on serum fatty acid composition, microbiota, and their metabolites in the intestine of pigs remains unclear. Our study investigated the changes in serum fatty acid composition and metabolome-microbiome responses induced by dietary n-6/n-3 PUFA ratio based on a Heigai-pig model. A total of 54 Heigai finishing pigs (body weight: 71.59 ± 2.16 kg) fed with 3 types of diets (n-6/n-3 PUFA ratios are 8:1, 5:1, and 3:1) were randomly divided into 3 treatments with 6 replications (3 pigs per replication) for 75 days. Results showed that dietary n-6/n-3 PUFA ratio significantly affected biochemical immune indexes including glucose (Glu), triglycerides (TG), total cholesterol (TChol), non-esterified fatty acid (NEFA), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total thyroxine (TT4), and medium- and long-chain fatty acid composition, especially n-3 PUFA and n-6/n-3 PUFA ratio in the serum. However, no significant effects were found in the SCFAs composition and overall composition of the gut microbiota community. In the low dietary n-6/n-3 PUFA ratio group, the relative abundance of Cellulosilyticum, Bacteroides, and Alloprevotella decreased, Slackia and Sporobacter increased. Based on the metabolomic analysis, dietary n-6/n-3 PUFA ratio altered the metabolome profiles in the colon. Moreover, Pearson's correlation analysis indicated that differential microbial genera and metabolites induced by different n-6/n-3 PUFA ratio had tight correlations and were correlated with the n-6 PUFA and n-3 PUFA content in longissimus dorsi muscle (LDM) and subcutaneous adipose tissue (SAT). Taken together, these results showed that lower dietary n-6/n-3 PUFA ratio improved serum fatty acid composition and metabolome-microbiome responses of Heigai pigs and may provide a new insight into regulating the metabolism of pigs and further better understanding the crosstalk with host and microbes in pigs.