Prevention of colon enlargement by TNF-α antagonist in a streptozotocin-induced diabetic rat model.

PURPOSE: We investigated the effect of tumor necrosis factor (TNF)-α antagonist on the structure and function of the streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat colon. METHODS: Thirty rats were divided into normal control (NC), diabetic control (DC), and diabetic etanercept (DE) groups. The DE group was injected with etanercept twice a week. Blood glucose, body weight, fecal pellet, colonic transit time, and plasma TNF-α were measured. The colon was dissected out, followed by weight and length measurements. Toluidine blue and Verhoeff's staining, immunohistochemistry for TNF-α, RAGE, iNOS, arginase, and western blot for RAGE were performed on the colonic tissue. RESULTS: Administration of TNF-α antagonist had no significant effect on the body weight and blood glucose level of the diabetic groups. However, the DE group had a shorter and lighter colon and less coarse and less dense collagen fibers in the submucosal layer than the DC group. Weaker immunoreactivity of TNF-α, RAGE, iNOS, and arginase I was observed in colon tissue sections of the DE groups compared with the DC group. Although the etanercept effect on colonic function was not significantly different, the preventive effect size of etanercept on colon remodeling was considerably large, as shown by calculated-Cohen's d >0.8. CONCLUSIONS: TNF-α signaling in the colonic tissue of diabetic rats has a strong effect on tissue remodeling, leading to colon enlargement. TNF-α antagonists may be beneficial in preventing diabetic-related pathology in the colon in combination with anti-diabetic drugs.

A paraventricular thalamus to insular cortex glutamatergic projection gates "emotional" stress-induced binge eating in females.

It is well-established that stress and negative affect trigger eating disorder symptoms and that the brains of men and women respond to stress in different ways. Indeed, women suffer disproportionately from emotional or stress-related eating, as well as associated eating disorders such as binge eating disorder. Nevertheless, our understanding of the precise neural circuits driving this maladaptive eating behavior, particularly in women, remains limited. We recently established a clinically relevant model of 'emotional' stress-induced binge eating whereby only female mice display binge eating in response to an acute "emotional" stressor. Here, we combined neuroanatomic, transgenic, immunohistochemical and pathway-specific chemogenetic approaches to investigate whole brain functional architecture associated with stress-induced binge eating in females, focusing on the role of Vglut2 projections from the paraventricular thalamus (PVTVglut2+) to the medial insular cortex in this behavior. Whole brain activation mapping and hierarchical clustering of Euclidean distances revealed distinct patterns of coactivation unique to stress-induced binge eating. At a pathway-specific level, PVTVglut2+ cells projecting to the medial insular cortex were specifically activated in response to stress-induced binge eating. Subsequent chemogenetic inhibition of this pathway suppressed stress-induced binge eating. We have identified a distinct PVTVglut2+ to insular cortex projection as a key driver of "emotional" stress-induced binge eating in female mice, highlighting a novel circuit underpinning this sex-specific behavior.

Orexins (hypocretins): The intersection between homeostatic and hedonic feeding.

Orexins are hypothalamic neuropeptides originally discovered to play a role in the regulation of feeding behaviour. The broad connections of orexin neurons to mesocorticolimbic circuitry suggest they may play a role in mediating reward-related behaviour beyond homeostatic feeding. Here, we review the role of orexin in a variety of eating-related behaviour, with a focus on reward and motivation, and the neural circuits driving these effects. One emerging finding is the involvement of orexins in hedonic and appetitive behaviour towards palatable food, in addition to their role in homeostatic feeding. This review discusses the brain circuitry and possible mechanisms underlying the role of orexins in these behaviours. Overall, there is a marked bias in the literature towards studies involving male subjects. As such, future work needs to be done to involve female subjects. In summary, orexins play an important role in driving motivation for high salient rewards such as highly palatable food and may serve as the intersection between homeostatic and hedonic feeding.

Acupuncture for Asthma: Its Potential Significance in Clinical Practice.

Acupuncture has been used for the prevention and treatment of asthma. However, the mechanisms underlying the effects of acupuncture in asthma are not fully understood. This article discusses the possible mechanisms underlying the effects of acupuncture in the prevention and treatment of asthma. Existing evidence has shown that acupuncture might facilitate the prevention and treatment of asthma via its anti-inflammatory effects. Acupuncture has been shown to modulate Th1/Th2 balance, block inflammatory cells and mediators, improve airway remodeling, and regulate hypothalamic-pituitary-adrenal axis function. Acupuncture appears to exert its antiasthmatic properties through multiple pathways.

Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines.

Background: Cervical cancer is one of the most prevalent gynecological cancers worldwide and contributes in high mortality of Indonesian women. The efficacy of chemotherapy as a standart therapy for cervical cancer decreases because it frequenly rises adverse effects. Recent studies have found that metformin has a potential anticancer effect mostly through reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK). This study aimed to investigate the effect of metfomin on expression of cyclin D1 and p53 and apoptosis in HeLa cancer cell line. Methods: HeLa cells were treated with various doses of metformin and doxorubicin as a positive control. Cytotoxic effect of metformin was determined using the MTT assay. Immunocytochemistry was used to assess cyclin D1 and p53 expression and apoptosis levels of treated HeLa cells were analyzed using flowcytometry. Data of cyclin D1 expression was statistically analyzed using the Kruskal-Wallis test followed by the Tamhane test, whilst ANOVA and Tukey post Hoc tests were used to analyze data of p53 and apoptosis level. The significant value was p< 0.05. Results: Metformin was able to inhibit proliferation of HeLa cells with IC50 60 mM. HeLa cells treated with 60 and 120 mM metformin had lower cyclin D1 expression than HeLa cells treated without metformin and reached a significant difference (p= 0.001). Moreover, 30 mM or higher doses of metformin increase significantly p53 expression (p< 0.001). Induction of apoptosis was observed in HeLa cells treated with all doses of metformin and reached statistically difference (p= 0.04 and p < 0.001). Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leading to inhibition of cell proliferation and induction of apoptosis. Other cyclin family members, CDK inhibitors and AMPK signaling should be further investigated in order to know mechanism of metformin action.

Improvement in inflammation and airway remodelling after acupuncture at BL13 and ST36 in a mouse model of chronic asthma.

BACKGROUND: Asthma is a chronic inflammatory disease that affects millions of people worldwide. Chronic asthma is commonly resistant to steroid therapy. Acupuncture has an anti-inflammatory effect and has been widely used as an add-on therapy for asthma. OBJECTIVE: To evaluate the effects of acupuncture on the inflammatory response and airway remodelling in the bronchioles of an asthma mouse model. METHODS: A chronic asthma model was produced in female BALB/c mice by ovalbumin (OVA) sensitisation. 32 mice were randomised into four groups: control; asthma (OVA); OVA+BL13; and OVA+BL13+ST36. OVA was administered by intraperitoneal injection on days 0 and 14 followed by aerosol exposure of 1% OVA three times a week for 6 weeks. Manual acupuncture (MA) was performed three times a week for 6 weeks at BL13 alone, or BL13 in combination with ST36, in the two MA-treated groups. At the end of the experiment, blood samples were collected to determine eosinophil and neutrophil counts and lung tissue was prepared for histological examination. RESULTS: A pronounced reduction in the neutrophil count was achieved after MA at BL13+ST36 (P=0.005) while the eosinophil count was lowered after MA both at BL13 (P=0.007) and BL13+ST36 (P=0.006). Reduction in the bronchiolar epithelial and smooth muscle thickness and the number of goblet cells was observed after MA at BL13 (P=0.001, P=0.001 and P=0.002, respectively) and BL13+ST36 (P=0.001, P=0.002 and P=0.001, respectively). CONCLUSION: Acupuncture can reduce the inflammatory response and prevent airway remodelling in a chronic asthma mouse model.