ABSTRACT
Poly(ADP-ribose) polymerase-1 (PARP1) has been reported to play an important role in longevity. Here, we showed that the knockdown of the PARP1 extended the lifespan of Drosophila, with particular emphasis on the skeletal muscle. The muscle-specific mutant Drosophila exhibited resistance to starvation and oxidative stress, as well as an increased ability to climb, with enhanced mitochondrial biogenesis and activity at an older age. Mechanistically, the inhibition of PARP1 increases the activity of AMP-activated protein kinase alpha (AMPKα) and mitochondrial turnover. PARP1 could interact with AMPKα and then regulate it via poly(ADP ribosyl)ation (PARylation) at residues E155 and E195. Double knockdown of PARP1 and AMPKα, specifically in muscle, could counteract the effects of PARP1 inhibition in Drosophila. Finally, we showed that increasing lifespan via maintaining mitochondrial network homeostasis required intact PTEN induced kinase 1 (PINK1). Taken together, these data indicate that the interplay between PARP1 and AMPKα can manipulate mitochondrial turnover, and be targeted to promote longevity.
Subject(s)
Drosophila Proteins , Poly (ADP-Ribose) Polymerase-1 , Poly ADP Ribosylation , Animals , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Longevity/genetics , Muscles/metabolism , Poly (ADP-Ribose) Polymerase-1/metabolism , Protein Serine-Threonine Kinases/metabolismABSTRACT
Vascular calcification (VC) commonly accompanies the development of atherosclerosis, defined by the accumulation of calcium in the arterial wall, potentially leading to stroke and myocardial infarction. Severe and unevenly distributed calcification poses challenges for interventional procedures, elevating the risks of vascular dissection, acute vascular occlusion, restenosis, and other major adverse cardiovascular events. Platelets promote the development of atherosclerosis by secreting various inflammatory mediators, regulating cell migration, aggregation, adhesion, and initiating and expanding inflammatory responses. There is emerging evidence that platelets play a direct role in VC; however, this novel concept has not yet been critically assessed. This review describes the intricate mechanisms by which platelets promote VC, focusing on three key aspects and the potential opportunities for their therapeutic targeting: extracellular vesicles, platelet-regulatory proteins, and indices related to platelet function.
ABSTRACT
OBJECTIVE: Adipsic diabetes insipidus (ADI) is a life-threatening disease. It is characterized by arginine vasopressin deficiency and thirst absence. Data about clinical characteristics of ADI were scarce. This study investigated the clinical features of hospitalized ADI patients. METHODS: A retrospective study was conducted of hospitalized ADI patients admitted to the Endocrinology Department of Huashan Hospital between January 2014 and December 2021, and compared with central diabetes insipidus (CDI) patients with normal thirst. RESULTS: During the study period, there were a total of 507 hospitalized CDI patients, among which 50 cases were ADI, accounting for 9.9%. Forty percent of ADI patients were admitted due to hypernatremia, but there were no admissions due to hypernatremia in the control group. The lesions of ADI patients were more likely to be located in the suprasellar area (100% vs 66%, P < .05). Higher prevalence of hypothalamic dysfunction (76% vs 8%, P < .001), central hypothyroidism (100% vs 90%, P = .031), hyperglycemia (66% vs 32%, P < .001), dyslipidemia (92% vs 71%, P = .006), and hyperuricemia (64% vs 37%, P = .003) was found in the ADI group than in the control group. The proportions of hypernatremia were higher in the ADI group both at admission and at discharge (90% vs 8%, 68% vs 8%, respectively, both with P < .001), contributing to higher prevalence of complications, such as renal insufficiency, venous thrombosis, and infection. CONCLUSION: ADI patients were found with higher prevalence of hypernatremia, hypopituitarism, hypothalamic dysfunction, metabolic disorders, and complications, posing a great challenge for comprehensive management.
Subject(s)
Diabetes Insipidus, Neurogenic , Diabetes Insipidus , Diabetes Mellitus , Hypernatremia , Humans , Hypernatremia/etiology , Hypernatremia/complications , Retrospective Studies , Diabetes Insipidus/etiology , Diabetes Insipidus/complications , Diabetes Insipidus, Neurogenic/epidemiology , Diabetes Insipidus, Neurogenic/etiology , ThirstABSTRACT
INTRODUCTION: The aim of the study was to investigate the association of parameters related to accommodation and convergence and axial elongation in basic intermittent exotropia (IXT) patients and the potential clinical predictors of axial length (AL) growth. METHODS: A total of 140 basic IXT patients were recruited in this study. The medians of AL growth in different age brackets were chosen to divide the subjects into group A (slower axial elongation group, n = 69) and group B (faster axial elongation group, n = 71). Parameters of dominant and nondominant eyes were compared and analyzed during the 12-month follow-up period. The parameters, including baseline refraction, angle of deviation, Newcastle control score (NCS), accommodative amplitude (AMP), accommodative facility (AMF), accommodative response, positive or negative relative accommodation (PRA/NRA), and near point of convergence (NPC), were analyzed via univariate and multivariate regression. RESULTS: Subjects in the faster axial elongation group tended to have more myopic spherical equivalents (t = 3.956, p < 0.001), greater AMPs of dominant eyes (t = -2.238, p = 0.027), and fewer near points of convergence (t = 2.347, p = 0.020) than in the slower axial elongation group. For dominant eyes, logistic and linear regression analysis revealed that more negative spherical equivalents (OR = 0.603, p < 0.001; ß = -0.045, p < 0.001), greater AMPs (OR = 1.201, p = 0.027; ß = 0.023, p = 0.010), and less near points of convergence (OR = 0.883, p = 0.021; ß = -0.012, p = 0.019) were correlated with the faster axial elongation. For nondominant eyes, a more myopic spherical equivalent (OR = 0.682; p = 0.001; ß = -0.029, p = 0.005) was the only parameter correlated with faster axial elongation through regression analysis. CONCLUSION: In children with basic IXT, faster axial elongation in the dominant eyes was associated with more myopic spherical equivalents, greater AMPs, and lower NPCs. These accommodative parameters can serve as potential clinical indicators for monitoring myopia progression in addition to AL.
Subject(s)
Accommodation, Ocular , Axial Length, Eye , Convergence, Ocular , Exotropia , Refraction, Ocular , Humans , Accommodation, Ocular/physiology , Exotropia/physiopathology , Male , Female , Axial Length, Eye/physiopathology , Child , Convergence, Ocular/physiology , Child, Preschool , Refraction, Ocular/physiology , Follow-Up Studies , Visual Acuity/physiology , Vision, Binocular/physiology , Retrospective StudiesABSTRACT
The maximum reflection at an open end of a standard rectangular waveguide is about -10 dB in its operating frequency range. It is often used without matching. For critical applications, it is desirable to further reduce the reflection coefficient. In this paper, a new technique is presented for the broadband impedance matching of an open-ended rectangular waveguide. The proposed technique employs three thin capacitive matching elements placed at proper intervals via a low-loss dielectric material. The capacitance of, and distance between, the matching elements are optimized for broadband impedance matching using a simulation tool. Based on the proposed technique, two design examples are presented for the matching of a WR75 waveguide radiator. A reflection coefficient of less than -16 dB and -20 dB has been achieved over a ratio bandwidth of 2.13:1 and 1.62:1, respectively.
ABSTRACT
A vegetated drainage ditch (VDD) system is an effective management practice for removing excess phosphorus (P) from agricultural runoff. However, the maximization of P removing efficiency by VDD remains a challenge. In this study, new VDDs with akadama clay barriers (particle size of clay: 1-6 mm; height of barrier: 5-15 cm and length of barrier: 10-90 cm) were designed in lab scale, and the mechanism of phosphate removal by akadama clay was investigated. It was found that a new VDD with akadama clay barriers (particle size:1 mm; height:10 cm and length: 90 cm) exhibited the highest removal efficiency of total P (TP) (97.1%), particulate P(PP) (96.9%), and dissolved P (DP) (97.4%), respectively. The retained P was mainly adsorbed in akadama clay barrier sections, and a low concentration of P was observed in soil sections in the new VDD. The maximum adsorption capacity of phosphate to akadama clay was 5.06 mg/g at 298 K, and XPS analysis indicated that phosphate was adsorbed by the inner-sphere complexation formation with the metal elements (Al, Fe). This study indicates that the new VDD with akadama clay barriers is a promising technique to efficiently remove P from agricultural runoff and significantly minimize the risk of P release into streams through runoff.
Subject(s)
Phosphorus , Water Pollutants, Chemical , Agriculture , Clay , Environment , Water Movements , Water Pollutants, Chemical/analysisABSTRACT
Previous studies have indicated that low-dose new generation of P2Y12 receptor antagonists may be more suitable compared with clopidogrel at a standard dose for the dual antiplatelet therapy (DAPT) for East Asian patients receiving percutaneous coronary intervention (PCI). However, there remains no consensus in clinical practice. Thus, in this study, we aimed to determine the efficacy and safety of low-dose P2Y12 receptor antagonists, compared to clopidogrel at a standard dose, in DAPT in East Asian patients after PCI. We systematically searched literatures for randomized controlled trials (RCT) comparing low-dose P2Y12 receptor antagonists with standard-dose clopidogrel for the treatment of East Asian patients undergoing PCI. The endpoints of efficacy include major adverse cardiac events (MACEs), all-cause mortality, and the number of target vessel revascularization. The indicators of safety include major and minor bleeding events. Heterogeneity was evaluated by I2 statistic test. Begg's and Egger's tests were used to evaluate publication bias. In total, 2,747 subjects from 8 RCT studies were included. Low-dose new P2Y12 receptor antagonists, that is, ticagrelor or prasugrel, showed significantly lower incidence of MACEs, as compared with standard-dose clopidogrel, in the East Asian patients who are in DAPT after undergoing PCI. Further, no difference was noted for the risk of major and minor bleeding events. In East Asian patients undergoing PCI and receiving DAPT, the use of low-dose P2Y12 receptor antagonists, ticagrelor or prasugrel, has been determined to be superior than clopidogrel at standard dose; this has been evidenced by a lower incidence of MACEs without increasing the risk of bleeding.
Subject(s)
Aspirin/administration & dosage , Fibrinolytic Agents/administration & dosage , Percutaneous Coronary Intervention/adverse effects , Purinergic P2Y Receptor Antagonists/administration & dosage , Thrombosis/prevention & control , Aspirin/adverse effects , Asia, Eastern , Fibrinolytic Agents/adverse effects , Humans , Purinergic P2Y Receptor Antagonists/adverse effects , Thrombosis/etiologyABSTRACT
BACKGROUND AND AIMS: Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive chronic hepatitis B (CHB) patients. To evaluate the effect of combination therapy [interferon (IFN) plus nucleos(t)ide analogues (NAs)] versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. METHODS: All available controlled clinical studies, published from Jan 2000 to Sep 2018, with CHB receiving IFN and NA combination therapy or IFN monotherapy were included. Risk ratio (RR) and their 95% confidence intervals (CIs) was estimated with a fixed-effects model when I2 <50% for the test for heterogeneity. Publication bias was measured using Egger's test. RESULTS: Twelve studies were included. Our meta-analysis demonstrated that IFN and NA combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment (EOT). Sub-analysis showed IFN plus adefovir dipivoxi (ADV) therapy had a better HBeAg seroconversion or seroclearance rate at EOT or at the end of follow-up (EOF). CONCLUSION: Compared with IFN monotherapy, the combined therapy had a higher e-antigen serological response at EOT, but failed to improve the sustained response at EOF. Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. The effect of other combination therapies is not superior to IFN monotherapy.
Subject(s)
Antiviral Agents/administration & dosage , Hepatitis B e Antigens/metabolism , Hepatitis B, Chronic/drug therapy , Interferon-alpha/administration & dosage , Nucleosides/administration & dosage , Antibodies, Viral/blood , Drug Therapy, Combination , Hepatitis B virus/drug effects , Hepatitis B virus/metabolism , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/virology , Humans , Lamivudine/administration & dosage , Randomized Controlled Trials as Topic , Seroconversion/drug effects , Tenofovir/administration & dosage , Treatment OutcomeABSTRACT
Threatened and endangered species are more vulnerable to climate change due to small population and specific geographical distribution. Therefore, identifying and incorporating the biological processes underlying a species' adaptation to its environment are important for determining whether they can persist in situ. Correlative models are widely used to predict species' distribution changes, but generally fail to capture the buffering capacity of organisms. Giant pandas (Ailuropoda melanoleuca) live in topographically complex mountains and are known to avoid heat stress. Although many studies have found that climate change will lead to severe habitat loss and threaten previous conservation efforts, the mechanisms underlying panda's responses to climate change have not been explored. Here, we present a case study in Daxiangling Mountains, one of the six Mountain Systems that giant panda distributes. We used a mechanistic model, Niche Mapper, to explore what are likely panda habitat response to climate change taking physiological, behavioral and ecological responses into account, through which we map panda's climatic suitable activity area (SAA) for the first time. We combined SAA with bamboo forest distribution to yield highly suitable habitat (HSH) and seasonal suitable habitat (SSH), and their temporal dynamics under climate change were predicted. In general, SAA in the hottest month (July) would reduce 11.7%-52.2% by 2070, which is more moderate than predicted bamboo habitat loss (45.6%-86.9%). Limited by the availability of bamboo and forest, panda's suitable habitat loss increases, and only 15.5%-68.8% of current HSH would remain in 2070. Our method of mechanistic modeling can help to distinguish whether habitat loss is caused by thermal environmental deterioration or food loss under climate change. Furthermore, mechanistic models can produce robust predictions by incorporating ecophysiological feedbacks and minimizing extrapolation into novel environments. We suggest that a mechanistic approach should be incorporated into distribution predictions and conservation planning.
Subject(s)
Adaptation, Physiological , Climate Change , Forests , Ursidae/physiology , Animals , Endangered SpeciesABSTRACT
There are two different types of fat present in mammals: white adipose tissue, the primary site of energy storage, and brown adipose tissue, which is specializes in energy expenditure. Factors that specify the developmental fate and function of brown fat are poorly understood. Bone morphogenic proteins (BMPs) play an important role in adipogenesis. While BMP4 is capable of triggering commitment of stem cells to the white adipocyte lineage, BMP7 triggers commitment of progenitor cells to a brown adipocyte lineage and activates brown adipogenesis. To investigate the differential effects of BMPs on the development of adipocytes, C3H10T1/2 pluripotent cells were pretreated with BMP4 and BMP7, followed by different adipogenic induction cocktails. Both BMP4 and BMP7 unexpectedly activated a full program of brown adipogenesis, including induction of the brown fat-defining marker uncoupling protein-1 (UCP1), increasing the expression of early regulators of brown fat fate PRDM16 (PR domain-containing 16) and induction of mitochondrial biogenesis and function. Implantation of BMP4-pretreated C3H10T1/2 cells into nude mice resulted in the development of adipose tissue depots containing UCP1-positive brown adipocytes. Interestingly, BMP4 could also induce brown fat-like adipocytes in both white and brown preadipocytes, thereby decreasing the classical brown adipocyte marker Zic1 and increasing the recently identified beige adipocyte marker TMEM26. The data indicate an important role for BMP4 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro and offers a potentially new therapeutic approach for the treatment of obesity.
Subject(s)
Adipocytes, Brown/drug effects , Adipogenesis/drug effects , Bone Morphogenetic Protein 4/pharmacology , Adipocytes, Brown/cytology , Adipocytes, Brown/metabolism , Adipogenesis/physiology , Animals , Bone Morphogenetic Protein 7/pharmacology , Cell Line , DNA-Binding Proteins/metabolism , Ion Channels/metabolism , Male , Mice , Mice, Nude , Mitochondrial Proteins/metabolism , Transcription Factors/metabolism , Uncoupling Protein 1ABSTRACT
BACKGROUND: Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. METHODS: Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹8F-fluorodeoxyglucose (¹8F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. RESULTS: Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. CONCLUSIONS: Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans.
Subject(s)
Adipose Tissue, Brown/metabolism , Adiposity , Energy Metabolism , Glucose/metabolism , Thyroid Hormones/metabolism , Adipose Tissue, Brown/diagnostic imaging , Adipose Tissue, Brown/drug effects , Adiposity/drug effects , Adult , Antithyroid Agents/therapeutic use , Energy Metabolism/drug effects , Female , Fluorodeoxyglucose F18 , Follow-Up Studies , Graves Disease/blood , Graves Disease/diagnostic imaging , Graves Disease/drug therapy , Graves Disease/metabolism , Humans , Male , Methimazole/therapeutic use , Middle Aged , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Positron-Emission Tomography , Thyroid Hormones/blood , Tomography, X-Ray Computed , Whole Body Imaging , Young AdultABSTRACT
Neutrophil-to-lymphocyte ratio (NLR) is an emerging systemic inflammation marker associated with disease progression and mortality in patients. However, there is limited research on the predictive value of NLR in the general population. This study aimed to investigate the relationship between NLR and all-cause mortality in an elderly Chinese population. A retrospective cohort study was conducted based on health examination in a community in Shanghai, China, between 2015 and 2020. Among 6364 participants (aged ≥ 55 years), a total of 169 (2.66%) participants died during a median follow-up period of 5.37 years. The median NLR was 1.63. Multivariate analysis revealed that the upper 2 quartiles of NLR were positively associated with all-cause mortality (Q3 vs Q1: hazard ratio [HR] = 1.82; Q4 vs Q1: HR = 2.22). The stratified and interaction analyses showed that age, sex, body mass index (BMI), history of diabetes, or history of hypertension did not significantly modify the association between NLR and all-cause mortality. Elevated NLR was independently associated with an increased risk of all-cause mortality in the elderly Chinese population.
Subject(s)
Lymphocytes , Neutrophils , Humans , Retrospective Studies , Male , China/epidemiology , Female , Aged , Middle Aged , Mortality/trends , Aged, 80 and over , Cause of Death , Lymphocyte Count , Leukocyte CountABSTRACT
AIM: To investigate the difference of medial rectus (MR) and lateral rectus (LR) between acute acquired concomitant esotropia (AACE) and the healthy controls (HCs) detected by magnetic resonance imaging (MRI). METHODS: A case-control study. Eighteen subjects with AACE and eighteen HCs were enrolled. MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner. Extraocular muscles (EOMs) were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator. To form posterior partial volumes (PPVs), the LR and MR cross-sections in the image planes 8, 10, 12, and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness. The data were classified according to the right eye, left eye, dominant eye, and non-dominant eye, and the differences in mean cross-sectional area, maximum cross-sectional area, and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively. RESULTS: There were no significant differences between the two groups of demographic characteristics. The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes (P=0.028). The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was signiï¬cantly greater than the HCs group (P=0.009, P=0.016). For the dominant eye, the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group (P=0.013), but not in the MR muscle (P=0.698). CONCLUSION: The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia. The LR muscle become larger to compensate for the enhanced convergence in the AACE.
ABSTRACT
Craniopharyngioma patients often suffer from a diminished quality of life after surgery, which is usually associated with metabolic disorders and hypothalamic obesity. However, the precise etiology of these conditions remains elusive. To identify the metabolic changes after surgery, we conducted a cross-sectional study using metabolomic and lipidomic analysis to profile metabolic alterations in adult-onset craniopharyngioma patients with postoperative obesity. A cohort of 120 craniopharyngioma patients who had undergone surgery were examined. Differential analyses, including clinical characteristics, serum metabolome, and lipidome, were conducted across distinct body mass index (BMI) groups. Our findings indicated no statistically significant differences in age, sex, and fasting blood glucose among postoperative craniopharyngioma patients when stratified by BMI. However, a noteworthy difference was observed in uric acid and blood lipid levels. Further investigation revealed that alterations in metabolites and lipids were evidently correlated with increased BMI, indicating that postoperative obesity of craniopharyngioma patients affected their whole-body metabolism. Additionally, the multi-omics analysis identified specific metabolites and lipids, including uric acid and DG(18:2/20:4), as contributors to the metabolic disorders associated with postoperative obesity of craniopharyngioma patients. This work provides valuable insight into the involvement of metabolites and lipids in metabolic disorders subsequent to craniopharyngioma surgery.
ABSTRACT
Cuproptosis has been recently used to indicate unique biological processes triggered by Cu action as a new term. This study aimed to explore the relationship between cuproptosis-related lncRNA and hepatocellular carcinoma (HCC) with regard to immunity and prognosis. RNA sequencing and the clinical data were downloaded from the TCGA database. The cuproptosis-related genes were sorted out through literature study. The cuproptosis-related IncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The K-M survival analysis, receiver operating characteristic analysis, and C-index analysis were adopted to evaluate the prognostic prediction performance of the signature. The functional enrichment, immune infiltration and tumor mutation analysis were further analyzed. Subsequently, we predicted the differences in chemosensitivity from tumor gene expression levels for some chemotherapy drugs. The prognostic signature consisting of 5 overall survival-related CUPlncRNAs. It showed an extraordinary ability to predict the prognoses of patients with HCC. The signature can predict the abundance of immune cell infiltration, immune functions, expression of immune checkpoint inhibitors, m6A genes, which was supported by the GO biological process and KEGG analysis. And it may also have a guiding effect in the sensitivity of different chemotherapeutic drugs and tumor mutation burden. We constructed a new cuproptosis-related lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/genetics , RNA, Long Noncoding/genetics , Liver Neoplasms/genetics , Prognosis , Immunity , ApoptosisABSTRACT
Inter-organ crosstalk has gained increasing attention in recent times; however, the underlying mechanisms remain unclear. In this study, we elucidate an endocrine pathway that is regulated by skeletal muscle interferon regulatory factor (IRF) 4, which manipulates liver pathology. Skeletal muscle specific IRF4 knockout (F4MKO) mice exhibited ameliorated hepatic steatosis, inflammation, and fibrosis, without changes in body weight, when put on a nonalcoholic steatohepatitis (NASH) diet. Proteomics analysis results suggested that follistatin-like protein 1 (FSTL1) may constitute a link between muscles and the liver. Dual luciferase assays showed that IRF4 can transcriptionally regulate FSTL1. Further, inducing FSTL1 expression in the muscles of F4MKO mice is sufficient to restore liver pathology. In addition, co-culture experiments confirmed that FSTL1 plays a distinct role in various liver cell types via different receptors. Finally, we observed that the serum FSTL1 level is positively correlated with NASH progression in humans. These data indicate a signaling pathway involving IRF4-FSTL1-DIP2A/CD14, that links skeletal muscle cells to the liver in the pathogenesis of NASH.
Subject(s)
Follistatin-Related Proteins , Non-alcoholic Fatty Liver Disease , Mice , Humans , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Follistatin-Related Proteins/genetics , Follistatin-Related Proteins/metabolism , Liver/metabolism , Signal Transduction/physiology , Muscle, Skeletal/metabolism , Liver Cirrhosis/pathology , Mice, Inbred C57BLABSTRACT
Calorie restriction (CR) and exercise training (EX) are two critical lifestyle interventions for the prevention and treatment of metabolic diseases, such as obesity and diabetes. Brown adipose tissue (BAT) and skeletal muscle are two important organs for the generation of heat. Here, we undertook detailed transcriptional profiling of these two thermogenic tissues from mice treated subjected to CR and/or EX. We found transcriptional reprogramming of BAT and skeletal muscle as a result of CR but little from EX. Consistent with this, CR induced alterations in the expression of genes encoding adipokines and myokines in BAT and skeletal muscle, respectively. Deconvolution analysis showed differences in the subpopulations of myogenic cells, mesothelial cells and endogenic cells in BAT and in the subpopulations of satellite cells, immune cells and endothelial cells in skeletal muscle as a result of CR or EX. NicheNet analysis, exploring potential inter-organ communication, indicated that BAT and skeletal muscle could mutually regulate their fatty acid metabolism and thermogenesis through ligands and receptors. These data comprise an extensive resource for the study of thermogenic tissue molecular responses to CR and/or EX in a healthy state.
Subject(s)
Adipose Tissue, Brown , Caloric Restriction , Mice , Animals , Adipose Tissue, Brown/metabolism , Endothelial Cells , Transcriptome , Thermogenesis/physiology , Muscle, Skeletal/metabolism , Energy Metabolism/physiologyABSTRACT
Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.
Subject(s)
Lipidomics , Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Weight Loss , Triglycerides , Phosphatidylcholines , BiomarkersABSTRACT
BACKGROUND: This population-based cross-sectional study aimed to evaluate the prevalence of oral mucosal lesions (OMLs) in children in a rural area in China as epidemiological data on these conditions from such areas are insufficient. METHODS: A total of 3145 children in Xiangyun of Yunnan were enrolled. A socio-economic questionnaire and a field survey of OMLs were administered. We gathered information on factors (sex, age, caregiver, parental education, and last-month household income) that might be associated with OMLs in these children. RESULTS: OMLs in children in Xiangyun of Yunnan had a prevalence of 1.8% (95% CI; 1.3-2.3%). The most prevalent OML was oral ulcer (n = 11; 18.3%), followed by linea alba (n = 10; 16.7%), whereas the least prevalent OMLs were frenal tag (n = 1; 1.7%) and herpes labialis (n = 1; 1.7%). On unadjusted or adjusted regression, school-aged children had about 50% lower risk of OMLs than preschoolers. CONCLUSIONS: These findings indicate that the prevalence of OMLs in Xiangyun of Yunnan is lower than previously reported. Additionally, the age might be associated with the occurrence of OMLs in children in Xiangyun of Yunnan, China.
Subject(s)
Mouth Diseases , Child , China/epidemiology , Cross-Sectional Studies , Humans , Mouth Mucosa , PrevalenceABSTRACT
Objectives: Epidemiological data of oral mucosal lesions (OMLs) are required to develop practical oral care policies. However, limited data are available for rural areas in China. We aimed to estimate the spectrum and frequency of OMLs and to identify their associated socioeconomic status (SES) and systemic health in a remote rural area in Yunnan, China. Methods: We screened patients for OMLs in an oral medicine clinic in rural Yunnan, China, from August 2020 to February 2021. OMLs were documented. SES, including the highest education level achieved and the previous month's household income, as well as the patient's systemic health, including a history of smoking, alcohol use, and chronic disease, were obtained from the Medical History/Health Questionnaire Form and patient medical records. Results: A total of 146 patients were found to have OMLs. The most frequent OML was aphthous ulcer (n = 41, 28.1%), followed by burning mouth syndrome (BMS) (n = 16, 11.0%), viral ulcer (n = 14, 9.6%), and oral lichen planus (OLP) (n = 9, 6.2%). In these patients, the most common chronic diseases were sleep apnea (n = 35, 24.0%), hypertension (n = 23, 15.8%), bronchitis (n = 16, 11.0%), reflux (including gastroesophageal reflux disease) (n = 12, 8.2%), and arthritis (n = 11, 7.5%). On adjusted regression, the patients without chronic diseases had a lower risk of BMS than those with chronic diseases [odds ratio (OR), 0.2; 95% confidence interval (CI), 0.03-0.9]. Age was an independent protective factor for viral ulcers (OR, 1.0; 95% CI, 0.9-1.0). Patients with low-income levels had a lower risk of OLP than those with high-income levels (OR, 0.2; 95% CI, 0.05-0.9). Conclusions: Our oral medicine clinic data in remote Yunnan, China, showed the most frequent OML was aphthous ulcer, which was followed by BMS, viral ulcer, and OLP. Oral care policies should be prioritized among patients with aphthous ulcer. Preventive strategy of BMS should be targeted to people with chronic disease for health equalities. Therefore, an individualized strategy for interventions of OMLs might be optimal, based on the specific epidemiologic characteristics in rural settings.