Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet

Background: Physical activity(PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat highcarbohydrate(HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training(LIT), and high-intensity interval training(HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult rats.Methods: Twelve-week-old Wistar rats were randomly allocated to 4 groups(12 rats/group): control(CTL), sedentary(SED), LIT, and HIIT.Biometric indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA interventions.Results: The SED group had slower cardiac conduction(p = 0.0426) and greater thoracic aortic contractile responses(p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group(p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group(both p < 0.05). The LIT and HIIT groups had lower visceral(p = 0.0057 for LIT, p = 0.0120 for HIIT)and epididymal fat(p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL group.Conclusion: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation,mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome,metabolome and associated immune parameters

Tuberculosis(TB)is one of the deadliest infectious diseases in the world.The meta-bolic disease type 2 diabetes(T2D)significantly increases the risk of developing ac-tive TB.Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication.Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection,in-jury and neoplastic changes.Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients.In this study,using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility,we investigated how the intestinal microbiota may impact the development of T2D,and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis(Mtb).Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic animals.The observed differences were comparable to previous clini-cal reports in TB patients,in which it was shown that Mtb infection causes rapid loss of microbial diversity.Furthermore,diversity index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice vs.Mtb-infected T2D mice.Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters,microbiota and the immune-metabolome of TB/T2D comorbidity.This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut mi-crobiota and the gut-lung axis.

Mathematical analysis of a Wolbachia invasive model with imperfect maternal transmission and loss of Wolbachia infection

Arboviral infections,especially dengue,continue to cause significant health burden in their endemic regions.One of the strategies to tackle these infections is to replace the main vector agent,Ae.aegypti,with the ones incapable of transmitting the virus.Wolbachia,an intracellular bacterium,has shown promise in achieving this goal.However,key factors such as imperfect maternal transmission,loss of Wolbachia infection,reduced reproductive capacity and shortened life-span affect the dynamics of Wolbachia in different forms in the Ae.aegypti population.In this study,we developed a Wolbachia transmission dynamic model adjusting for imperfect maternal transmission and loss ofWolbachia infection.The invasive reproductive number that determines the likelihood of replacement of the Wolbachia-uninfected(WU)population is derived and with it,we established the local and global stability of the equilibrium points.This analysis clearly shows that cytoplasmic incompatibility(CI)does not guarantee establishment of the Wolbachia-infected(WI)mosquitoes as imperfect maternal transmission and loss of Wolbachia infection could outweigh the gains from CI.Optimal release programs depending on the level of imperfect maternal transmission and loss of Wolbachia infection are shown.Hence,it is left to decision makers to either aim for replacement or co-existence of both populations.

A novel role for polymeric immunoglobulin receptor in tumour development: beyond mucosal immunity and into hepatic cancer cell transformation

Chronic inflammation is well known as a significant driver of carcinogenesis in settings of human disease,including liver disease and hepatocellular carcinoma(HCC).