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BACKGROUND AND AIMS: This study aims to identify the cause of disinfection failure of multiple flexible gastrointestinal endoscopes and to enhance the cleaning and disinfection procedures. METHODS: Samples from endoscopy devices, surrounding objects, cleaning water, automatic sterilizer, and integrated endoscopic washing workstation in a Digestive Endoscopy Center were collected and analyzed for microbial contamination and DNA/gene contents, between May and July 2021. RESULTS: The sample analysis revealed that the sink irrigation tubing of the washing workstation was contaminated with Burkholderia cepacia. After effective disinfection measures, the B. cepacia detection in the disinfected endoscope dropped from 13.23% to 0% (p=0.041). The presence of B. cepacia was confirmed through homology search and gene sequencing. CONCLUSIONS: The primary reason for endoscope disinfection failure is the contamination of the sink irrigation tubing by the B. cepacia bacteria. These findings emphasize the need for thorough cleaning of irrigation tubings in integrated endoscopic washing workstations, which is generally neglected in routine maintanance.
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BACKGROUND: The relationship between integrated lifestyles, mental status and their impact on overall well-being has attracted considerable attention. This study aimed to evaluate the association between lifestyle factors, depression and diabetic retinopathy (DR) in adults aged 18-64 years. METHODS: A cohort of 3482 participants diagnosed with diabetes was drawn from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999-2018. DR was defined based on self-reported diabetic retinopathy diagnoses by professional physicians, relying on Diabetes Interview Questionnaires. Subgroup analysis was employed to assess lifestyle and psychological factors between participants with DR and those without, both overall and stratified by diabetic duration. Continuous variables were analyzed using the student's t test, while weighted Rao-Scott χ2 test were employed for categorical variables to compare characteristics among the groups. RESULTS: Of the 3482 participants, 767 were diagnosed with diabetic retinopathy, yielding a weighted DR prevalence of 20.8%. Patients with DR exhibited a higher prevalence of heavy drinking, depression, sleep deprivation, and insufficient physical activity compared to those without DR. Furthermore, multivariable logistic regression analysis revealed that sleeping less than 5 h (OR = 3.18, 95%CI: 2.04-4.95, p < 0.001) and depression (OR = 1.35, 95%CI:1.06-1.64, p = 0.025) were associated with a higher risk of DR, while moderate drinking (OR = 0.49, 95%CI: 0.32-0.75, p = 0.001) and greater physical activity (OR = 0.64, 95%CI: 0.35-0.92, p = 0.044) were identified as protective factors. CONCLUSIONS: Adults aged 18-64 years with DR exhibited a higher prevalence of lifestyle-related risk factors and poorer mental health. These findings underscore the need for concerted efforts to promote healthy lifestyles and positive emotional well-being in this population.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Adulto , Humanos , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/diagnóstico , Inquéritos Nutricionais , Estudos Transversais , Fatores de Risco , Estilo de Vida , Prevalência , Nível de Saúde , Diabetes Mellitus Tipo 2/epidemiologiaRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. METHODS: A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. RESULTS: Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2-3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. CONCLUSIONS: In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.
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Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Prognóstico , Capacidade Vital , Biomarcadores , Fibrose , Estudos RetrospectivosRESUMO
Idiopathic pulmonary fibrosis (IPF) is considered an age-related disease. Age-related changes, along with other factors such as obesity, hormonal imbalances, and various metabolic disorders, lead to ectopic fat deposition (EFD). This accumulation of fat outside of its normal storage sites is associated with detrimental effects such as lipotoxicity, oxidative stress, inflammation, and insulin resistance. This narrative review provides an overview of the connection between ectopic and visceral fat deposition in aging, obesity, and IPF. It also elucidates the mechanism by which ectopic fat deposition in the airways and lungs, pericardium, skeletal muscles, and pancreas contributes to lung injury and fibrosis in patients with IPF, directly or indirectly. Moreover, the review discusses the impact of EFD on the severity of the disease, quality of life, presence of comorbidities, and overall prognosis in IPF patients. The review provides detailed information on recent research regarding representative lipid-lowering drugs, hypoglycemic drugs, and lipid-targeting drugs in animal experiments and clinical studies. This may offer new therapeutic directions for patients with IPF.
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Fibrose Pulmonar Idiopática , Gordura Intra-Abdominal , Animais , Humanos , Gordura Intra-Abdominal/metabolismo , Qualidade de Vida , Obesidade/complicações , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/metabolismo , Envelhecimento , Lipídeos/uso terapêuticoRESUMO
As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet ß cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body's energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent "contributor" to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet ß cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet ß cell function, and the underlying mechanism remains to be further discussed.
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Apolipoproteína C-III , Glucose , Ilhotas Pancreáticas , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Apolipoproteína C-III/antagonistas & inibidores , Apolipoproteína C-III/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Glucose/metabolismo , Humanos , Animais , Hipertrigliceridemia/metabolismo , Ilhotas Pancreáticas/metabolismoRESUMO
Background: Cases of infective endocarditis (IE) with > 30 mm vegetations are rare and are associated with high mortality. Clinical experience, clear therapeutic standards, and outcome evidence about these cases are still lacking. Methods: Detailed clinical data from patients suffering from IE complicated with > 30 mm vegetations were collected from a hospital medical record system. Age- and sex-matched IE cases with 10-20 mm vegetations were used as a control group. Results: Twenty-two patients with > 30 mm IE vegetations confirmed by biopsy and transthoracic echocardiography (TTE) were included. Thirteen (59.0%) patients had basic cardiac diseases, mainly congenital heart disease (CHD), rheumatic heart disease, and device-related issues. Fever (81.8%), heart murmur (86.4%), heart failure (86.4%), and embolism (50.0%) were common clinical manifestations and complications. TTE showed the diameter of vegetations was 34.5 (30.0-39.8) mm. The vegetations were usually accompanied by severe valvular regurgitation and pulmonary hypertension, and were most often located in the mitral valve (38.4%). Laboratory examinations indicated anemia, hypoalbuminemia, heart failure and inflammation. The rate of positive blood culture was 68.2%. Streptococcus viridans was the most frequent pathogen (26.7%). All individuals underwent vegetectomy and valve replacement or repair surgery, within 2 days of diagnosis. Compared with 10-20 mm vegetations group, > 30 mm vegetations group had more complicated basic cardiac diseases, more special microbial infection, higher levels of procalcitonin (PCT) and D-dimer, more common heart failure and embolism. They received more biological valve replacements, and had longer intensive care unit length of stay (ICU-LOS). A few patients developed significant postoperative adverse events, including intracerebral hemorrhage (ICH), septic shock, and new symptomatic thrombosis. Re-exploratory thoracotomy was performed in two cases. All patients survived during 6-month follow-up without IE recurrence in > 30 mm vegetations group, while there was one death and one recurrence in the 10-20 mm vegetations group. Conclusions: For IE complicated with > 30 mm vegetations, clinical characteristics are diverse and vegetations on TTE are prone to misdiagnosis as thrombus or tumors. This article also emphasizes the use of > 30 mm IE vegetations as an independent indication for early surgery to improve prognosis.
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BACKGROUND AND AIM: The influence of gastric acid inhibitors (GAIs) on nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is controversial. Herein, the influences of different GAIs on NSAID-induced intestinal injury and the underlying mechanisms are clarified. METHODS: Indomethacin (IND; 10 mg/kg/day) was administered to mice to induce small intestinal injury. Disease activity was examined macroscopically and histologically. The permeability of small intestine was evaluated by measuring plasma lipopolysaccharide levels. 16S rDNA sequencing was performed to determine the composition of intestinal flora. RESULTS: Among the four GAIs, ilaprazole (IPZ) significantly attenuated IND-induced small intestinal injury and maintained the integrity of the mucosal barrier. Omeprazole (OPZ) and vonoprazan (VPZ) ameliorated ulceration without significant differences, while rabeprazole (RPZ) failed to protect against the injury. To explore the potential mechanism, we investigated changes in the gut microbiota mediated by GAIs. After 5-day administration, GAIs significantly altered the composition of the gut microbiota. The IND group had a significant decrease in alpha diversity compared with the control group, and this decrease was reversed by OPZ and IPZ treatment, respectively. After IPZ treatment, the community membership was more assembled in the control group than the IND group. Further, we found that Lactobacillus was significantly increased in the groups of OPZ, IPZ, and VPZ, while Bacteroides was significantly increased in the RPZ group. CONCLUSION: Our results indicated that GAIs have different influences on the mucosal barrier, possibly by altering the composition of intestinal microbiota, and the impacts mediated by various GAIs in the IND-induced intestinal damage model seem different.
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Indometacina , Enteropatias , 2-Piridinilmetilsulfinilbenzimidazóis , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , DNA Ribossômico , Indometacina/efeitos adversos , Enteropatias/patologia , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Lipopolissacarídeos , Camundongos , Omeprazol/efeitos adversos , Potássio , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis , Rabeprazol/efeitos adversos , SulfonamidasRESUMO
BACKGROUND: Laparoscopic cholecystectomy is a common surgical option for gallstone disease with minimal trauma and rapid recovery. Ascites is a relatively uncommon complication after laparoscopic cholecystectomy and is more frequently observed in patients with preoperative abnormal liver function. However, patients without underlying liver disease develop refractory ascites after laparoscopic cholecystectomy are rare. We report a case of massive ascites caused by lymphatic injury after laparoscopic cholecystectomy. CASE PRESENTATION: A 63-year-old woman complained of abdominal discomfort and distension at the twelfth day after a laparoscopic cholecystectomy for gallbladder stones. Subsequently, the patient developed spontaneous bacterial peritonitis and a decreased output of urine. Abdominal computed tomography (CT) identified abdominal effusion. The patient received abdominocentesis and the volume of slightly turbid yellow ascites averaged 1500-2000 ml per day. The results of laboratory analysis of ascitic fluid showed the following: serum-ascites albumin-gradient (SAAG), 11-12 g/L; albumin, 11-14 g/L; triglycerides, 0.91 mmol/L. After the diuretic therapy, repeated large-volume paracentesis with albumin supplementation, administration of antibiotics and renal vasodilating medications, the patient's symptoms did not relieve. Lymphoscintigraphy found a small amount of radioactive filling in the abdominal cavity. The patient finally received surgery with detection and ligation of the lymphatic leak. The ascites disappeared and the patient recovered well. CONCLUSIONS: For patients with atypical characteristics of chylous ascites, lymphoscintigraphy could help to localize and qualify the diagnosis. Surgical treatment could be considered when conservative treatment fails.
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Colecistectomia Laparoscópica , Ascite Quilosa , Cálculos Biliares , Albuminas , Ascite/etiologia , Ascite/cirurgia , Colecistectomia Laparoscópica/efeitos adversos , Ascite Quilosa/diagnóstico , Ascite Quilosa/etiologia , Ascite Quilosa/terapia , Feminino , Cálculos Biliares/complicações , Cálculos Biliares/cirurgia , Humanos , Pessoa de Meia-IdadeRESUMO
It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or cooperatively once a day for 2 weeks. Then, several indexes of insulin resistance were examined. The results showed that glucose infusion rates in the hyperinsulinaemic-euglycaemic clamp test, plasma adiponectin content and GLUT4 translocation, as well as Akt phosphorylation in fat cells, were higher, not GLUT4 protein and GLUT4 mRNA expression, but HOMA index was lower in the galanin + leptin group than either one of them. Furthermore, treatment with MK-2206, an Akt inhibitor, blocked the combined effects of galanin + leptin on alleviation of insulin resistance. These results suggest that galanin can improve the leptin-induced mitigative effects on insulin resistance in the fat cells, and those provided new insights into the potential tactics for prevention and remedy of insulin resistance.
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Tecido Adiposo/patologia , Diabetes Mellitus Experimental/patologia , Galanina/farmacologia , Resistência à Insulina , Leptina/farmacologia , Adipócitos/metabolismo , Adiponectina/sangue , Tecido Adiposo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Desoxiglucose/metabolismo , Diabetes Mellitus Experimental/sangue , Comportamento Alimentar/efeitos dos fármacos , Técnica Clamp de Glucose , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperinsulinismo/sangue , Hiperinsulinismo/complicações , Masculino , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos WistarRESUMO
BACKGROUND AND OBJECTIVE: The stomach plays an important role in obesity and obesity-related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes. METHODS: We performed gene microarray and real time-polymerase chain reaction (RT-PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes. RESULTS: In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co-regulated in both comparisons. Seven differentially expressed genes were validated by RT-PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G-protein coupled receptor biological processes, and primarily participated in the PI3K-Akt and AGE-RAGE signaling pathways. CONCLUSIONS: Obesity and obesity-related diabetes are associated with important gene expression and pathway alterations in the stomach.
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Biomarcadores/análise , Diabetes Mellitus/metabolismo , Mucosa Gástrica/metabolismo , Regulação da Expressão Gênica , Obesidade/complicações , Transcriptoma , Adulto , Estudos de Casos e Controles , Biologia Computacional , Diabetes Mellitus/etiologia , Diabetes Mellitus/patologia , Feminino , Mucosa Gástrica/patologia , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Transdução de SinaisRESUMO
Astrocytes, one of the most abundant and heterogeneous types of glial cell in the brain and spinal cord, are responsible for various essential functions in the healthy central nervous system, including maintaining the blood brain barrier integrity, regulating neuron differentiation and supporting, nourishing, protecting, insulating and repairing neurons. They also fulfill a range of other homeostatic maintenance functions. Astrocytes are activated after traumatic brain injury. They then exhibit heterogeneous gene expression and changes in morphology, proliferative capacity and various functions in response either acute or chronic brain injury and associated secondary brain injury. Some biomarkers and imaging tools have been used to monitor astrogliosis after traumatic brain injury. Initially, morphological characteristics and the physiology of astrocytes are reviewed. Subsequently, alterations of astrocytes are described, which includes both the complex mechanisms and roles of reactive astrocytes. The roles of biomarkers and signaling pathways following traumatic brain injury have been summarized as well as the morphological and functional changes in astrocytes. In the latter case, by considering astrocytes as therapeutic targets of traumatic brain injury, the mechanisms of the latest drug treatments are explained. This review highlights the beneficial effects of astrogliosis according to some recent findings, which provides new insights for the treatment of traumatic brain injury.
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Astrócitos/patologia , Astrócitos/fisiologia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Animais , Lesões Encefálicas Traumáticas/complicações , Movimento Celular , Proliferação de Células , Encefalite/etiologia , Encefalite/patologia , Encefalite/fisiopatologia , HumanosRESUMO
Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in liver, is prevalent in obesity. Genetic factors that link obesity to NAFLD remain obscure. Apolipoprotein C3 (APOC3) is a lipid-binding protein with a pivotal role in triglyceride metabolism. Humans with APOC3 gain-of-function mutations and mice with APOC3 overproduction are associated with hypertriglyceridemia. Nonetheless, it remains controversial whether APOC3 is culpable for diet-induced NAFLD. To address this fundamental issue, we fed APOC3-transgenic and wild-type littermates a high fructose diet or high fat diet, followed by determination of the effect of APOC3 on hepatic lipid metabolism and inflammation and the progression of NAFLD. To gain mechanistic insight into NAFLD, we determined the impact of APOC3 on hepatic triglyceride synthesis and secretion versus fatty acid oxidation. APOC3-transgenic mice were hypertriglyceridemic, culminating in marked elevation of triglycerides, cholesterols, and non-esterified fatty acids in plasma. Despite the prevailing hypertriglyceridemia, APOC3-transgenic mice, relative to wild-type littermates, had similar weight gain and hepatic lipid content without alterations in hepatic expression of key genes involved in triglyceride synthesis and secretion and fatty acid oxidation. APOC3-transgenic and wild-type mice had similar Kupffer cell content without alterations in hepatic expression of pro- and anti-inflammatory cytokines. APOC3 neither exacerbated diet-induced adiposity nor aggravated the degree of steatosis in high fructose or high fat-fed APOC3-transgenic mice. These effects ensued independently of weight gain even after 10-month high fat feeding. We concluded that APOC3, whose dysregulation is liable for hypertriglyceridemia, is not a predisposing factor for linking overnutrition to NAFLD in obesity.
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Apolipoproteína C-III/genética , Apolipoproteína C-III/metabolismo , Regulação da Expressão Gênica , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Peso Corporal , Colesterol/metabolismo , Citocinas/metabolismo , Dieta Hiperlipídica , Feminino , Frutose/química , Predisposição Genética para Doença , Teste de Tolerância a Glucose , Hipertrigliceridemia/metabolismo , Inflamação , Resistência à Insulina/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/química , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Obesidade/metabolismo , Regiões Promotoras Genéticas , Transgenes , Triglicerídeos/metabolismo , Aumento de PesoRESUMO
BACKGROUND: Hyperuricemia is related to obesity and fat accumulation. This study aimed to observe the effects of laparoscopic sleeve gastrectomy (LSG) on serum uric acid (sUA) level and body fat distribution in obese patients. The relationships between post-LSG improvement in sUA levels and body fat distribution changes, as well as their sex-related differences, were also explored. METHODS: In total, 128 obese patients (48 men; 80 women) who underwent LSG were enrolled. Anthropometric indicators, glucose and lipid metabolic indicators, and sUA levels were measured pre-LSG and 6 months post-LSG. The body compositions were measured via dual-energy X-ray absorptiometry. The patients were divided into normal-sUA (NUA) and high-sUA (HUA) groups based on preoperative sUA levels. RESULTS: Compared with the NUA group, the reduction of sUA levels 6 months post-LSG was more significant in the HUA group. In addition, sUA reduction in the female HUA group was more significant than that of the male HUA group (P < 0.01). Changes in serum uric acid levels (ΔsUA) in the male HUA group was positively correlated with changes in body weight, body mass index, neck circumference, and hip circumference (r = 0.618, 0.653, 0.716, and 0.501, respectively; P < 0.05 in all cases). It was also positively correlated with changes in fat mass in the gynoid region, android region, and legs, (r = 0.675, 0.551, and 0.712, respectively; P < 0.05 in all cases), and negatively correlated with changes in total testosterone (ΔTT) (r = - 0.517; P = 0.040). Furthermore, ΔTT in this group was closely associated with the improved sex-related fat distribution. The ΔsUA in the female HUA group was positively correlated with changes in fasting serum C peptide and ΔLNIR (r = 0.449 and 0.449, respectively; P < 0.05 in both cases). In addition, it was also positively correlated with changes in visceral adipose tissue (VAT) fat mass, VAT fat volume, and VAT fat area (r = 0.749, 0.749, and 0.747, respectively; P < 0.01 in all cases). CONCLUSIONS: sUA levels of obese patients with hyperuricemia improved 6 months after LSG. Reduction of sUA after LSG was correlated with improved body fat distribution, and the relationships also displayed sex-based differences. Uric acid might be an important metabolic regulator associated with fat distribution and sex hormones.
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Distribuição da Gordura Corporal , Gastrectomia , Obesidade/sangue , Obesidade/cirurgia , Ácido Úrico/sangue , Adulto , Povo Asiático , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice.
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Apolipoproteína C-III/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hipertrigliceridemia/complicações , Células Secretoras de Insulina/patologia , Animais , Apolipoproteína C-III/genética , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Glucose/metabolismo , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/patologia , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , ObesidadeRESUMO
Evidence indicates that central galanin is involved in regulation of insulin resistance in animals. This study investigates whether type 1 galanin receptor (GAL1) in the brain mediates the ameliorative effect of galanin on insulin resistance in skeletal muscles of type 2 diabetic rats. Rats were intracerebroventricularly (i.c.v.) injected with galanin(1-13)-bradykinin(2-9) amide (M617), a GAL1 agonist, and/or Akti-1/2, an Akt inhibitor, via caudal veins once per day for 10 days. Insulin resistance in muscle tissues was evaluated by glucose tolerance and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) tests, peroxisome proliferator-activated receptor-γ (PPARγ), glucose transporter 4 (GLUT4) mRNA expression levels, Akt phosphorylation, and GLUT4 and vesicle-associated membrane protein 2 (VAMP2) concentration at plasma membranes in muscle cells. The results show that i.c.v. treatment with M617 increased glucose tolerance, 2-NBDG uptake, PPARγ levels, Akt phosphorylation, GLUT4 protein, and GLUT4 mRNA expression levels as well as GLUT4 and VAMP2 concentration at plasma membranes. All increases may be blocked by pretreatment with Akti-1/2. These results suggest that activated central GAL1 may trigger the Akt signaling pathway to alleviate insulin resistance in muscle cells. Therefore, the impact of galanin on insulin resistance is mediated mainly by GAL1 in the brain, and the GAL1 agonist may be taken as a potential antidiabetic agent for treatment of type 2 diabetes mellitus. © 2016 Wiley Periodicals, Inc.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Resistência à Insulina/fisiologia , Receptor Tipo 1 de Galanina/metabolismo , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Bradicinina/administração & dosagem , Bradicinina/análogos & derivados , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Galanina/administração & dosagem , Galanina/análogos & derivados , Galanina/uso terapêutico , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , PPAR gama/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Wistar , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Proteína 2 Associada à Membrana da Vesícula/metabolismoRESUMO
BACKGROUND: Currently, the only FDA-approved systemic therapy for hepatocellular carcinoma (HCC) is the multi-receptor tyrosine kinase inhibitor, sorafenib, which provides only modest clinical benefit. We recently showed that treatment with a phosphatidylserine (PS) targeting agent suppresses tumor growth by targeting tumor vasculature and reactivating antitumor immunity. METHODS: We tested the hypothesis that sorafenib increases PS exposure on tumor vasculature, thereby enhancing the antitumor efficacy of PS targeting. We evaluated the efficacy of combining a PS targeting agent (2aG4) with sorafenib in murine xenograft models of human HCC. RESULTS: Our results demonstrate that combination of 2aG4 and sorafenib had a superior therapeutic effect over single agent therapy. Mechanistic studies showed that sorafenib significantly increased PS exposure on tumor vasculature; the percentage of PS-positive vessels increased from 19 to 52, 23 to 68, and 30 to 55 % in PLC/PRF/5, C3A, and Huh7 tumors, respectively. Combination therapy significantly decreased tumor microvessel density and the level of M2 macrophages, while increasing the apoptotic index of tumor endothelial cells and the frequency of M1 macrophages. Furthermore, we report the findings of a Phase I clinical study of bavituximab, a chimeric version of 2aG4, combined with sorafenib in HCC patients. The Phase I results demonstrate the appropriate dose of bavituximab to be given with sorafenib in future clinical trials. CONCLUSIONS: Overall, these results strongly support the combination of bavituximab with sorafenib as a promising systemic therapeutic strategy for the treatment for advanced HCC patients.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fosfatidilserinas/antagonistas & inibidores , Adulto , Idoso , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/irrigação sanguínea , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Dose Máxima Tolerável , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Fenótipo , Compostos de Fenilureia/administração & dosagem , Fosfatidilserinas/metabolismo , Rituximab/farmacologia , Sorafenibe , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the prevalence and clinical characteristics of ketosis-prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes. METHODS: A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients. RESULTS: Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. ß-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone. CONCLUSION: KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of ≤35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible ß-cell dysfunction.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/metabolismo , Adolescente , Adulto , Idade de Início , Peptídeo C/sangue , China/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) often coexist and have adverse outcomes. The aim of our study was to elucidate metabolic abnormalities in patients with DM-NAFLD versus those with T2DM alone. METHODS: Patients were divided into two groups: 26 T2DM patients with NAFLD and 26 gender-, age-, and body mass index-matched patients with T2DM alone. Patients took a 75-g oral glucose tolerance test (OGTT), which measured serum insulin and C-peptide (C-p) levels at baseline (0 min), 30 min, 60 min, and 120 min after glucose challenge. RESULTS: Patients with DM-NAFLD or T2DM alone had similar blood glucose levels. ß-cell hypersecretion was more obvious in patients with DM-NAFLD. In addition, fasting, early-phase, and late-phase C-peptide levels were significantly increased in patients with DM-NAFLD (ΔC-p 0-30 min, P < 0.05; Area Under the Curve (AUC) C-p/PG 30-120 min ratio, P < 0.01; and AUC C-p 30-120 min, P < 0.01). Hepatic and extrahepatic insulin resistance during the OGTT did not differ significantly between groups. Hepatic insulin sensitivity independently contributed to the early phase (0-30 min) of the OGTT in patients with T2DM and NAFLD, whereas a significant deficit in late insulin secretion independently contributed to the 30-120 min glucose status in patients with T2DM only. CONCLUSIONS: In patients with similar levels of insulin resistance and hyperglycemia, DM-NAFLD was associated with higher serum insulin levels than T2DM alone. Hyperinsulinemia is caused mainly by ß-cell hypersecretion. The present study demonstrates pathophysiological differences in mechanisms of insulin resistance in patients with DM-NAFLD versus T2DM alone.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Fígado Gorduroso/sangue , Resistência à Insulina , Insulina/metabolismo , Glicemia , Peptídeo C/sangue , Feminino , Humanos , Secreção de Insulina , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não AlcoólicaRESUMO
Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.
Assuntos
Anuros , Catelicidinas , Animais , Camundongos , Sequência de Aminoácidos , Fatores Imunológicos/farmacologia , Aeromonas hydrophila , Proteínas de Anfíbios/farmacologia , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/isolamento & purificação , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Células RAW 264.7 , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/isolamento & purificação , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/imunologia , População do Leste AsiáticoRESUMO
BACKGROUND: LRRC59 is a leucine-rich repeats-containing protein located in the endoplasmic reticulum (ER), it serves as a prognostic marker in several cancers. However, there has been no systematic analysis of its role in the tumor immune microenvironment, nor its predictive value of prognosis and immunotherapy response in different cancers. METHODS: A comprehensive pan-cancer analysis of LRRC59 was conducted from various databases to elucidate the associations between its expression and the prognosis of cancer, genetic alterations, tumor metabolism, and tumor immunity. Additionally, further functional assays were performed in hepatocellular carcinoma (HCC) to study its biological role in regulating cell proliferation, migration, apoptosis, cell cycle arrest, and sensitivity to immunotherapy. RESULTS: The pan-cancer analysis reveals a significant upregulation of LRRC59 in pan-cancer, and its overexpression is correlated with unfavorable prognosis in cancer patients. LRRC59 is negatively correlated with immune cell infiltration, tumor purity estimation, and immune checkpoint genes. Finally, the validation in HCC demonstrates LRRC59 is significantly overexpressed in cancer tissue and cell lines, and its knockdown inhibits cell proliferation and migration, promotes cell apoptosis, induces cell cycle arrest, and enhances the sensitivity to immunotherapy in HCC cells. CONCLUSIONS: LRRC59 emerges as a novel potential prognostic biomarker across malignancies, offering promise for anti-cancer drugs and immunotherapy.