Adiponectin but not leptin is involved in early hepatic disease in morbidly obese patients

Background  

Pathologic changes in the liver are common in morbidly obese patients, and insulin resistance may potentiate the progression of nonalcoholic steatohepatitis to fibrosis and cirrhosis. This study investigates the impact of leptin and adiponectin in morbidly obese diabetic and nondiabetic patients with regard to histopathologic changes in the liver.     

Substance use behaviors, mental health problems, and use of mental health services in a probability sample of college students

This research examined 1) the prevalence of substance use behaviors in college students, 2) gender and academic level as moderators of the associations between mental health problems and substance use, and 3) mental health service use among those with co-occurring frequent binge drinking and mental health problems. As part of the Healthy Minds Study, a probability sample of 2843 college students completed an Internet survey on mental health problems, substance use behaviors, and utilization of mental health care. Response propensity weights were used to adjust for differences between respondents and non-respondents. Major depression, panic disorder, and generalized anxiety disorder were positively associated with cigarette smoking. Frequent binge drinking was negatively associated with major depression and positively associated with generalized anxiety disorder, and these associations were significantly stronger for males than females. Among students with co-occurring frequent binge drinking and mental health problems, 67% perceived a need for mental health services but only 38% received services in the previous year. There may be substantial unmet needs for treatment of mental health problems and substance use among college students.     

IRAK-4 kinase activity is required for IRAK-4-dependent innate and adaptive immune responses

Interleukin-1 receptor-associated kinase (IRAK)-4 is a serine-threonine kinase that plays an important role in innate and adaptive immune responses. While the requirement of IRAK-4 kinase activity has been studied in the context of IL-1R signaling, it is not clear whether IRAK-4 requires its kinase function for all of its roles in the immune system. IRAK-4 kinase-dead knock-in (IRAK-4KD/KD) mice were generated to further elucidate whether IRAK-4 kinase activity is required for IRAK-4 to induce cytokine production. IRAK-4KD/KD mice were impaired in their ability to produce cytokines in response to in vivo challenge with lipopolysaccharide (LPS), a potent TLR4 ligand. Cytokine production was also reduced in macrophages and dendritic cells from IRAK-4KD/KD mice in response to LPS and other TLR ligands. In addition, adaptive immune responses were impaired in IRAK-4KD/KD mice. Although in vitro T cell proliferation in response to TCR activation was unaffected in IRAK-4-deficient mice, in vivo T cell responses to lymphocytic choriomeningitits virus infection were significantly impaired in IRAK-4-knockout mice or mice expressing the kinase-dead mutant of IRAK-4. Collectively, these results indicate that IRAK-4 kinase activity is required for IRAK-4-dependent signaling in innate and adaptive immunity.     

Leptin regulates OPG and RANKL expression in Gingival Fibroblasts and Tissues of Chronic Periodontitis Patients

Objective: Chronic periodontitis is a bone-destructive disease affecting periodontal support structures. Although leptin has a protective effect against periodontitis, the underlying mechanism remains unclear. Therefore, this study aimed to investigate the possible role of leptin by examining its relationship with OPG and RANKL in human gingival tissues obtained from patients with chronic periodontitis.Method: Twenty-two patients with chronic periodontitis were enrolled (10 with moderate periodontitis and 12 with severe periodontitis) in the experimental group, and 12 healthy individuals were enrolled in the control group. Gingival tissue samples were collected, and the protein levels and localization of leptin, OPG, and RANKL were studied using immunohistochemistry (IHC). The staining intensities of leptin, OPG, and RANKL were correlated with the periodontal clinical index. Moreover, real-time quantitative PCR (RT-qPCR) was used to determine OPG and RANKL mRNA levels in gingival fibroblasts stimulated with gradient concentrations of leptin protein in vitro.Result: Leptin, OPG, and RANKL were located in the cytoplasm of gingival epithelial cells and the connective tissue. Leptin was widely and significantly expressed in the control group, whereas it was lightly stained in the severe group. RANKL was lightly stained in the control group, whereas it was widely and significantly expressed in the severe group. The control and the moderate groups had similar OPG levels, which were significantly higher than that in the severe group. Leptin was positively correlated with OPG(r = 0.905, p < 0.01) and negatively correlated with RANKL (r = -0.635, p < 0.01). In vitro low concentrations of leptin led to an increased OPG/RANKL mRNA ratio, whereas the opposite effect was observed at high concentrations.Conclusion: Leptin can regulate OPG and RANKL expression in gingival fibroblasts and may thus play a role in the development of chronic periodontitis by modulating the OPG/RANKL ratio.     

Immunological perspective of self versus tumor antigens: insights from the RIP-gp model

Self-reactive T cells in the body are controlled by mechanisms of peripheral tolerance that limit their activation and induction of immune pathology. Our understanding of these mechanisms has been advanced by the use of tissue-specific promoters to express neo-self-antigens. Here, we present findings using the RIP-gp (rat insulin promoter-glycoprotein) transgenic mouse, which expresses the lymphocytic choriomeningitis virus glycoprotein (LCMV-gp) specifically in the pancreatic β islet cells. T cells responsive to this antigen remain ignorant of the LCMV-gp expressed by the islets, and breaking tolerance is dependent upon the maturation status of antigen-presenting cells, the avidity of the T-cell receptor ligation, and the level of major histocompatibility complex expression in the pancreas. Furthermore, decreased activity of Casitas B-lineage lymphoma b, a negative regulator of T-cell receptor signaling, can allow recognition and destruction of the pancreatic islets. This review discusses the roles of these factors in the context of anti-tissue responses, both in the setting of autoimmunity and in anti-tumor immunity.     

Task-based functional magnetic resonance imaging prediction of postsurgical cognitive outcomes in temporal lobe epilepsy: A systematic review,meta-analysis,and new data

Task-based functional magnetic resonance imaging (tfMRI) has developed as a common alternative in epilepsy surgery to the intracarotid amobarbital procedure, also known as the Wada procedure. Prior studies have implicated tfMRI as a comparable predictor of postsurgical cognitive outcomes. However, the predictive validity of tfMRI has not been established. This preregistered systematic review and meta-analysis (CRD42020183563) synthesizes the literature predicting postsurgical cognitive outcomes in temporal lobe epilepsy (TLE) using tfMRI. The PubMed and PsycINFO literature databases were queried for English-language articles published between January 1, 2009 and December 31, 2020 associating tfMRI laterality indices or symmetry of task activation with outcomes in TLE. Their references were reviewed for additional relevant literature, and unpublished data from our center were incorporated. Nineteen studies were included in the meta-analysis. tfMRI studies predicted postsurgical cognitive outcomes in left TLE ($\widehat{\rho }$ = −.27, 95% confidence interval [CI] = −.32 to −.23) but not right TLE ($\widehat{\rho }$ = −.02, 95% CI = −.08 to .03). Among studies of left TLE, language tfMRI studies were more robustly predictive of postsurgical cognitive outcomes ($\widehat{\rho }$ = −.27, 95% CI = −.33 to −.20) than memory tfMRI studies ($\widehat{\rho }$ = −.27, 95% CI = −.43 to −.11). Further moderation by cognitive outcome domain indicated language tfMRI predicted confrontation naming ($\widehat{\rho }$ = −.32, 95% CI = −.41 to −.22) and verbal memory ($\widehat{\rho }$ = −.26, 95% CI = −.35 to −.17) outcomes, whereas memory tfMRI forecasted only verbal memory outcomes ($\widehat{\rho }$ = −.37, 95% CI = −.57 to −.18). Surgery type, birth sex, level of education, age at onset, disease duration, and hemispheric language dominance moderated study outcomes. Sensitivity analyses suggested the interval of postsurgical follow-up, and reporting and methodological practices influenced study outcomes as well. These findings intimate tfMRI is a modest predictor of outcomes in left TLE that should be considered in the context of a larger surgical workup.