Prognostic significance of the skeletal muscle index and systemic inflammatory index in patients with lymph node-positive breast cancer after radical mastectomy.

BACKGROUND: The role of skeletal muscle index (SMI) and systemic inflammation index (SII) for patients with lymph node-positive breast cancer remain controversial. This retrospective study aims to evaluate the individual and synergistic value of SMI and SII in outcomes prediction in this population. METHODS: Lymph node-positive breast cancer patients who received mastectomy between January 2011 and February 2013 were included in this retrospective study. We used abdominal computed tomography (CT) to measure skeletal muscle mass at the third lumbar (L3) level. The optimal cut-off values of SMI and SII were determined through maximizing the Youden index on the receiver operating characteristic (ROC) curves. Kaplan-Meier method was used to assess the correlation between SMI, SII, and overall survival (OS). The prognostic value of SMI and SII were analyzed with the multivariable Cox proportional hazards model. RESULTS: Of 97 patients included in our study (mean age: 46 [range: 27-73] years; median follow-up: 62.5 months), 71 had low SMI (sarcopenia), 59 had low SII, and 56 had low SMI + SII. Kaplan-Meier survival curves showed that both high SMI (P = 0.021, 5-year OS: 84.0% vs. 94.1%) and high SII (P = 0.043, 5-year OS: 81.0% vs. 97.3%) were associated with worse OS. Additionally, patients with either low SMI or low SII had significantly better OS (P = 0.0059, 5-year OS: 100.0% vs. 84.6%) than those with high SMI + SII. Multivariable analysis confirmed the predictive values of high SMI (P = 0.024, hazard ratio [HR]: 9.87) and high SII (P = 0.048, HR: 6.87) for poor OS. Moreover, high SMI + SII was significantly associated with poor survival (P = 0.016, HR: 16.36). CONCLUSIONS: In this retrospective analysis, both SMI and SII independently predicted the prognosis of patients with lymph node-positive breast cancer. SMI + SII might be a stronger prognostic factor than either alone based on our findings, but should be further verified in a larger study.

Different inflammatory blood markers correlate with specific outcomes in incident HPV-negative head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58). CONCLUSION: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs.

The Assessment of Some Metabolic Markers by Combination of Ursolic Acid Supplementation and Resistance Training in Young Older Obese Women.

BACKGROUND: In this study, we explored the impacts of moderate-to-high intensity resistance circuit training (MHRCT) and Ursolic acid (UA) supplementation to improve these pathological changes in young older obese women (women between the ages of 50 and 70). METHODS: The study included twenty-five young older women (age > 50 years and ≤70 years) with stage I-II obesity (BMI ≥ 30 and <40 kg/m2), who received eight weeks placebo with MHRCT, and MHRCT with UA supplementation. UA or placebo orally was ingested as a capsule three times per day for eight weeks. The following parameters were evaluated post- and pre-intervention. Data were analyzed using ANOVA with repeated measures. RESULTS: Interleukin-15 (IL-15), Interleukin-6 (IL-6), Insulin, and HOMA-IR decreased significantly in the placebo and UA groups versus control, but the UA group significantly decreased compared with the placebo (p<0.05). In turn, the Brain-Derived Neurotrophic Factor (BDNF) and Irisin levels showed a significant increase in the placebo and UA groups versus control. However, the BDNF in the UA group significantly increased compared with the placebo (p < 0.05). CONCLUSION: We demonstrated that applying resistance training can reverse the pathological changes that may occur with aging and a sedentary lifestyle. Our results showed that UA could enhance the effects of this type of exercise. Therefore, a combination of the resistance training program and UA supplementation may be considered as a novel and influential intervention to metabolic derangements and may also decrease the burden associated with this condition.

The effects of high-sensitivity C-reactive protein on the clinical outcomes in obstructive sleep apnea patients undergoing off-pump coronary artery bypass grafting.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity and high-sensitivity C-reactive protein (Hs-CRP), and their respective impact on the clinical outcomes in patients undergoing off-pump cardiac artery bypass grafting (OPCABG). METHODS: We enrolled consecutive eligible patients listed for elective OPCABG who underwent cardiorespiratory polygraphy before surgery between January 2019 and December 2019 in this prospective observational single-center study. Baseline, intraoperative, and postoperative clinical data were compared between absent-mild and moderate-severe OSA groups. Regression analysis investigated the relationship between Hs-CRP level and severity of OSA, and further assessed the factors influencing postoperative atrial fibrillation, duration of hospitalization, and hospital cost. RESULTS: Patients with moderate-severe OSA accounted for 42.3% (52/123) of the cohort. Partial pressure of carbon dioxide (PCO2), Hs-CRP, apnea hypopnea index (AHI), mean apnea time, maximum apnea time, and oxygen desaturation index ODI ≥ 3% were significantly higher in the moderate-severe OSA group than in the absent-mild OSA group. Left ventricle ejection fraction (LVEF), lowest arterial oxygen saturation (SaO2), and mean SaO2 were significantly lower in the moderate-severe OSA group. Moderate-severe OSA was associated with elevated Hs-CRP level (OR = 2.356, 95% CI 1.101-5.041, P = 0.027). Hs-CRP was an independent risk factor for post-CABG atrial fibrillation (POAF) (OR = 1.212, P = 0.01). Hs-CRP level independently correlated with duration of hospitalization (B = 0.456, P = 0.001) and hospital cost (B = 1.111, P = 0.044). CONCLUSION: Hs-CRP level was closely related to OSA severity and have potential utility in predicting POAF, duration of hospitalization, and hospital costs in patients undergoing OPCABG.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

BACKGROUND: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. AIMS: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. METHODS: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. RESULTS: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. DISCUSSION: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

Clinical disease activity and flare in SLE: Current concepts and novel biomarkers.

Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs primarily in females of childbearing age, with increased prevalence and severity in minority populations. Despite improvements in treatment modalities, SLE patients frequently experience periods of heightened disease activity and flare that can lead to permanent organ damage, increased morbidity, and early mortality. Such outcomes impair quality of life and inflict a significant socioeconomic burden. Predicting changes in SLE disease activity could allow for closer monitoring and preemptive treatment, but existing clinical, demographic and serologic markers have been only modestly predictive. Novel, proactive approaches to clinical disease management are thus critically needed. Panels of blood biomarkers can detect a breadth of immune pathway dysregulation that captures SLE heterogeneity and disease activity. Alterations in the balance of pro-inflammatory and regulatory soluble mediators have been associated with changes in clinical disease activity and are detectable several weeks prior to clinical flare occurrence. A soluble mediator score has been highly predictive of impending flare in both European American and African American SLE patients, and this score does not require a priori knowledge of specific pathway activation in the patient. We review current concepts of disease activity and flare in SLE, focusing on the potential of novel blood biomarkers to characterize and predict changes in disease activity. Measuring the disordered immune response in SLE in this way promises to improve disease management and prevent organ damage in SLE.

Similarities and differences between HIV and SARS-CoV-2.

In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.

Patient Global Assessment of Disease Activity and Radiographic Progression in Early Arthritis: Three-Year Results From the ESPOIR Cohort.

OBJECTIVE: To determine whether patient global assessment of disease activity (PtGA) over the first year of disease course, as part of a Boolean-based definition of remission and considered individually, had a significant relationship with structural progression over 3 years in patients with early arthritis. METHODS: We conducted a prospective, observational study using ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) cohort data. Remission states were defined as 1) 4-variable remission, which included a tender joint count in 28 joints, a swollen joint count in 28 joints (SJC28), a C-reactive protein (CRP; mg/dl) level, and PtGA (scored 0-10, all scores of ≤1); 2) PtGA near remission, which included the same parameters as 4-variable remission with only PtGA >1 (of a maximum possible score of 10); 3) 3-variable remission (sum of the proportion of patients in 4-variable remission and the proportion of patients in PtGA near remission); or 4) nonremission. The strictest status satisfied both at 6 and 12 months was considered. Radiographic progression was determined as a change of ≥5 points in the total Sharp/van der Heijde score (ΔSHS) from baseline to 3 years. The predictive capacities for radiographic damage of different remission definitions were assessed by odds ratio (OR). The association between each individual component of remission with ΔSHS was tested through multivariate linear regression analyses. RESULTS: Among 520 patients, 7% achieved 4-variable remission and 12% achieved PtGA near remission. Radiographic progression was observed in 29% of patients who achieved 4-variable remission (OR versus nonremission; OR 0.32 [95% confidence interval (95% CI) 0.15, 0.68]) and in 45% of patients with PtGA near remission (OR 0.65 [95% CI 0.38, 1.11]); the comparison was not statistically different (OR 0.49 [95% CI 0.20, 1.18]). In 3-variable remission, radiographic progression was observed in 39%. Of the individual components, only the SJC28 and CRP level were associated with radiographic progression. CONCLUSION: All definitions of remission led to low structural degradation in early arthritis, and 4-variable remission led to less radiographic progression than PtGA near remission, but without a statistically significant difference. Both 4-variable remission and 3-variable remission appear to be useful targets when aiming for structural nonprogression.

Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.

Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.

OBJECTIVE: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS: We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.

Cardiovascular Risk Assessment and Therapeutic Implications in Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) suffer from a magnitude of excess cardiovascular risk. A paradoxical lipid pattern has been observed in rheumatoid arthritis patients where low levels of total cholesterol and low-density lipoprotein are associated with a higher risk of cardiovascular disease. This paper aims to break down the evidence explaining why patients with low to normal LDL, and total cholesterol have such excess cardiovascular risk. A component of the enhanced cardiovascular risk is systemic inflammation and the subsequent pro-atherogenic dyslipidemia patterns. Due to this "lipid paradox," current risk algorithms and guidelines designed for the general population may underestimate cardiovascular risk in patients with rheumatoid arthritis. The purpose of this paper is to critically evaluate some of the discrepancies and layers of cardiovascular risk in RA patients, the role RA medication may have in mitigating or increasing cardiovascular risk, and the possible role of statin therapy.

Clinical Utility of the Inflammatory Factors Combined With Lipid Markers in the Diagnostic and Prognostic Assessment of Ischemic Stroke: Based on Logistic Regression Models.

BACKGROUND: In this study, we developed novel logistic regression models for the diagnostic and prognostic assessment of ischemic stroke. METHODS: A total of 288 ischemic stroke patients and 300 controls admitted to The First Affiliated Hospital of Soochow University were included in the testing group. Two validation groups from The Affiliated Kunshan Hospital of Jiangsu University and The Second Affiliated Hospital of Soochow University were included to assess our novel assessment models. RESULTS: Results from the testing group indicated that the diagnostic assessment model for ischemic stroke prediction was: Logit(P) = 437.116 - 87.329 (Hypertension) - 89.700 (Smoking history) - 87.427 (Family history of ischemic stroke) - .090 (high-density lipoprotein cholesterol [HDL-C]) - 1.984 (low-density lipoprotein cholesterol [LDL-C]) - 17.005 (Lp(a)) - 15.486 (Apo A/Apo B), and the final prognostic assessment model of ischemic stroke was: Logit(P) = 458.437-92.343 (Hypertension) - 89.763 (Smoking history) + .251 (NLR) - .088 (HDL-C) - 1.994 (LDL-C) - 2.883 (hs-CRP) - .058 (IL-6) - 6.356 (TNF-α) - 16.485 (Lp(a)) - 17.658 (Apo A/Apo B). In the validation groups, our novel diagnostic assessment model showed good identification (with 87.5% sensitivity and 84.2% specificity in The Affiliated Kunshan Hospital of Jiangsu University, with 85.5% sensitivity and 89.0% specificity in The Second Affiliated Hospital of Soochow University). Moreover, our novel prognostic assessment model has a high value in identifying poor prognosis patients in the validation groups from The Affiliated Kunshan Hospital of Jiangsu University (χ2 = 8.461, P = .004), and The Second Affiliated Hospital of Soochow University (χ2 = 7.844, P = .005). CONCLUSIONS: The diagnostic and prognostic assessment models we have established are of great value in the diagnosis and prognostic evaluation of ischemic stroke.

Validity and reliability of the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with axial spondyloarthritis (axSpA) in Singapore.

INTRODUCTION: The Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) are commonly used instruments for measuring disease activity. However, few studies have assessed their psychometric properties in patients with axial spondyloarthritis (axSpA). We aimed to assess the validity and reliability of ASDAS-CRP and BASDAI in patients with axSpA in Singapore. METHODS: Cross-sectional data from 280 patients with axSpA from a dedicated axSpA clinic in a Singapore tertiary referral hospital from 2011 to 2019 were used. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through 12 a priori hypotheses by correlation of overall ASDAS-CRP and BASDAI score with other patient-reported outcomes measures (PROMs). Structural validity was evaluated via confirmatory factor analysis using maximum-likelihood method, where Comparative Fit Index (CFI) >0.95, Tucker-Lewis Index (TLI) >0.95, Root Mean Square Error of Approximation (RMSEA) <0.06 and Standardized Root Mean Residuals (SRMR) <0.08 were indicative of good fit. RESULTS: Among 280 patients (78.2% Male; 92.5% Chinese), ASDAS-CRP showed poor internal consistency of 0.33, while BASDAI showed high internal consistency of 0.87. Convergent and divergent construct validity were demonstrated by fulfillment of 11 out of 12 a priori hypotheses when ASDAS-CRP and BASDAI were compared with other PROMs. Our proposed ASDAS-CRP and BASDAI model showed good fit for a 1-factor structure respectively (CFI = 0.993, TLI = 0.984, RMSEA = 0.036, SRMR = 0.026 for ASDAS-CRP; CFI = 0.993, TLI = 0.985, RMSEA = 0.057, SRMR = 0.022 for BASDAI), demonstrating structural validity. CONCLUSION: This study supports the use of both ASDAS-CRP and BASDAI in measuring disease activity in patients with axSpA in Singapore.

Potential Application of Diffusion-Weighted Whole-Body Imaging with Background Body Signal Suppression for Disease Activity Assessment in Takayasu Arteritis-In Search of the "Golden Mean": Case Report.

The case report describes our first experience of "diffusion-weighted whole-body imaging with background body signal suppression" (DWIBS) application for disease activity assessment in a young female patient with Takayasu arteritis (TA). Despite the normal level of inflammatory markers, clinical signs of disease recurrence were present. In our case, DWIBS did not only help to identify the disease recurrence in the patient with false-negative inflammatory markers but also revealed new foci involved in the TA process. DWIBS can be a potentially new imaging method, useful during the follow-up in patients with TA.

Assessment of the relationship between C-reactive protein-to-albumin ratio and slow coronary flow in patients with stable angina pectoris.

BACKGROUND: The relationship between severity of coronary artery disease and inflammatory parameters has been previously demonstrated. However, there is a lack of data regarding the role of C-reactive protein-to-albumin ratio (CAR) in slow coronary flow (SCF) in patients with stable angina pectoris (SAP). In this study, we aimed to investigate the relationship between CAR and presence of SCF in patients with SAP. PATIENTS AND METHODS: This study enrolled 217 patients undergoing coronary angiography for SAP. SCF was detected in 81 (37.3%) patients, and the control group included 136 patients. All clinical, demographical, and laboratory parameters were entered into a dataset and compared between SCF group and the controls. RESULTS: The mean age of the patients was 66.1 ± 12.1 years (male: 57.1%). C-reactive protein and CAR were significantly higher in patients with SCF compared with controls (P = 0.004 and < 0.001, respectively). Logistic regression analysis demonstrated that high CAR level was an independent determinant of SCF (odds ratio: 1.023; 95% confidence interval: 1.013-1.034; P < 0.001). CONCLUSION: Higher CAR level may be a valuable predictor of SCF in patients with SAP who undergo coronary angiography. Inflammation may play an important role in the pathogenesis of SCF.

Assessment of Pharmacology, Safety, and Metabolic activity of Capsaicin Feeding in Mice.

Capsaicin (CAP) activates transient receptor potential vanilloid subfamily 1 (TRPV1) to counter high-fat diet (HFD)-induced obesity. Several studies suggest that CAP induces the browning of white adipocytes in vitro or inguinal white adipose tissue (iWAT) in vivo. However, there is a lack of data on the dose-response for CAP to inhibit HFD-induced obesity. Therefore, we first performed experiments to correlate the effect of various doses of CAP to prevent HFD-induced weight gain in wild-type (WT) mice. Next, we performed a subchronic safety study in WT mice fed a normal chow diet (NCD ± CAP, 0.01% in NCD) or HFD ± CAP (0.01% in HFD) for eight months. We analyzed the expression of adipogenic and thermogenic genes and proteins in the iWAT from these mice, conducted histological studies of vital organs, measured the inflammatory cytokines in plasma and iWAT, and evaluated liver and kidney functions. The dose-response study showed that CAP, at doses above 0.001% in HFD, countered HFD-induced obesity in mice. However, no difference in the anti-obesity effect of CAP was observed at doses above 0.003% in HFD. Also, CAP, above 0.001%, enhanced the expression of sirtuin-1 and thermogenic uncoupling protein 1 (UCP-1) in the iWAT. Safety analyses suggest that CAP did not cause inflammation. However, HFD elevated plasma alanine aminotransferase and creatinine, caused iWAT hypertrophy and hepatic steatosis, and CAP reversed these. Our data suggest that CAP antagonizes HFD-induced metabolic stress and inflammation, while it does not cause any systemic toxicities and is well tolerated by mice.

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway.

Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, ß-catenin, and GSK-3ß. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.

Assessment of alcohol consumption in depression follow-up using self-reports and blood measures including inflammatory biomarkers.

AIMS: Alcohol consumption has been suggested a major role in the pathogenesis and prognosis of depression. However, reliable identification of hazardous drinking continues to be problematic. We compared the accuracy of different biomarkers and self-reports of alcohol consumption in the follow-up study of depression. METHODS: Data from 202 patients with major depressive disorder were obtained through self-reports, AUDIT and AUDIT-C questionnaires and biomarker analyses. The clinical assessments and measurements of biomarkers (GT, CDT, GT-CDT-combination, MCV, ALT, AST, hs-CRP, IL-6) were performed at baseline and after six months of treatment. Based on self-reported alcohol intake at baseline the patients were classified to three subgroups. RESULTS: About 27.2% of patients were categorized to high-risk drinkers, 26.3% low-risk drinkers and 46.5% abstainers. High-risk drinkers showed significantly higher mean values of GT, CDT, GT-CDT-combination and IL-6 than abstainers, diagnostic accuracy being highest with the combined marker of GT-CDT. The accuracy of AUDIT and AUDIT-C to detect high-risk drinking was also significant. During follow-up, the differences observed in the biomarkers at baseline disappeared together with recovery from depression. CONCLUSIONS: Our data suggest the combined use of GT-CDT and AUDIT questionnaires to improve the identification of drinking of patients with depression. This approach could be useful for improving treatment adherence and outcome in depressed patients.

Effects of Mild Hypothermia on Cardiac and Neurological Function in Piglets Under Pathological and Physiological Stress Conditions.

To investigate the different effects of mild hypothermia on pathological and physiological stress conditions in piglets, 30 pigs were randomized into four groups: cardiac arrest and mild hypothermia (CA-MH group), cardiac arrest and normothermia (CA-NH group), non-CA-MH (NCA-MH group), and a sham operation. The same hypothermia intervention was implemented in both CA-MH and NCA-MH groups. The CA-NH group did not undergo therapeutic hypothermia after resuscitation. The hemodynamic parameters were recorded. Cerebral metabolism variables and neurotransmitters in the extracellular fluid were collected through microdialysis tubes. The serum of venous blood was used to detect levels of inflammatory factors. The cerebral function was evaluated. At 24 and 72 hours after resuscitation, the cerebral performance category and neurological deficit score in the CA-NH group had higher values. Heart rate and cardiac output (CO) in the CA-MH group during cooling were lower than that of the CA-NH group, but CO was higher after rewarming. Glucose was higher during cooling, and extracellular lactate and lactate/pyruvate ratio in the CA-MH group were lower than that of the CA-NH group. Noradrenaline and 5-hydroxytryptamine in the CA-MH and NCA-MH groups were lower than that of the CA-NH group and sham group during cooling, respectively. Inflammatory factor levels, including interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, and tumor necrosis factor-α, in the CA-MH group were lower than that of the CA-NH group at cooling for 12 hours. These values in the NCA-MH group were higher than that of the sham group. Under a light and an electron microscope, the worse pathological results of heart and brain were observed in the two cardiac arrest groups. Mild hypothermia can provide limited organ protection in the specific pathological condition caused by ischemia-reperfusion, but it may produce a negative effect in a normal physiological state.

Performance of routine assessment of patient index data 3 (RAPID3) in monitoring disease activity of Chinese rheumatoid arthritis patients.

AIM: To explore the performance of routine assessment of patient index data 3 (RAPID3) in reflecting disease activity in Chinese rheumatoid arthritis (RA) patients. METHOD: The clinical data of 189 consecutive RA patients, including RAPID3 questionnaire, Disease Activity Score based on 28-joint count (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI), and ultrasonography of hand and wrist joints were collected. The consistency between RAPID3 and DAS28, CDAI, SDAI in RA patients with different disease activities was performed by Spearman's correlations, kappa and/or weighted kappa coefficients. RESULT: RAPID3 score was significantly associated with DAS28 and erythrocyte sedimentation rate (ESR), DAS28 with C-reactive protein (CRP), CDAI, SDAI (r = 0.797, 0.786, 0.784, and 0.760 respectively, P < 0.001 for all). RAPID3 was also significantly correlated with tender joint count, swollen joint count, ESR and CRP. The agreement of RAPID3 with DAS28 scoring systems was better in patients with moderate/high disease activity than those in remission/low disease activity. Ultrasonographic subclinical synovitis was presented in 42.3%-48.6% of patients in remission/low disease activity defined by various scoring criteria including RAPID3 with no significant difference observed (P = 0.22, >0.05). CONCLUSION: RAPID3 showed good correlation with DAS28 scoring systems, especially in patients with moderate/high disease activity. RAPID3 is a reliable and convenient tool to monitor disease activity.