Agonists for PPARα are used clinically to reduce triglycerides and improve high-density lipoprotein (HDL) cholesterol levels in patients with hyperlipidemia. Whether the mechanism of PPARα activation to lower serum lipids occurs in the liver or other tissues is unknown. To determine the function of hepatic PPARα on lipid profiles in diet-induced obese mice, we placed hepatocyte-specific peroxisome proliferator-activated receptor-α (PPARα) knockout ( PparaHepKO) and wild-type ( Pparafl/fl) mice on high-fat diet (HFD) or normal fat diet (NFD) for 12 wk. There was no significant difference in weight gain, percent body fat mass, or percent body lean mass between the groups of mice in response to HFD or NFD. Interestingly, the PparaHepKO mice on HFD had worsened hepatic inflammation and a significant shift in the proinflammatory M1 macrophage population. These changes were associated with higher hepatic fat mass and decreased hepatic lean mass in the PparαHepKO on HFD but not in NFD as measured by Oil Red O and noninvasive EchoMRI analysis (31.1 ± 2.8 vs. 20.2 ± 1.5, 66.6 ± 2.5 vs. 76.4 ± 1.5%, P < 0.05). We did find that this was related to significantly reduced peroxisomal gene function and lower plasma β-hydroxybutyrate in the PparaHepKO on HFD, indicative of reduced metabolism of fats in the liver. Together, these provoked higher plasma triglyceride and apolipoprotein B100 levels in the PparaHepKO mice compared with Pparafl/fl on HFD. These data indicate that hepatic PPARα functions to control inflammation and liver triglyceride accumulation that prevent hyperlipidemia.

SARS-CoV-2, which initially emerged in November of 2019, wreaked havoc across the globe by leading to clinical acute respiratory distress syndrome and continues to evade current therapies today due to mutating strains. Diabetes mellitus is considered an important risk factor for progression to severe COVID disease and death, therefore additional research is warranted in this group. Individuals with diabetes at baseline have an underlying inflammatory state with elevated levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, both of which cause these individuals to have higher susceptibility to SARS- CoV2 infection. The detrimental effects of SARS-CoV-2 has been attributed to its ability to induce a vast cell mediated immune response leading to a surge in the levels of pro-inflammatory cytokines. This paper will be exploring the underlying mechanisms and pathophysiology in individuals with diabetes and insulin resistance making them more prone to have worse outcomes after SARS- CoV2 infection, and to propose an adjunctive therapy to help combat the cytokine surge seen in COVID-19. It will also look at the immunomodulatory effects of glutathione, an antioxidant shown to reduce immune dysregulation in other diseases; Vitamin D, which has been shown to prevent COVID-19 patients from requiring more intensive care time possibly due to its ability to decrease the expression of certain pro-inflammatory cytokines; and steroids, which have been used as immune modulators despite their ability to exacerbate hyperglycemia.

Immunothrombosis has emerged as a dominant pathological process exacerbating morbidity and mortality in acute-and long-COVID-19 infections. The hypercoagulable state is due in part to immune system dysregulation, inflammation and endothelial cell damage, as well as a reduction in defense systems. One defense mechanism in particular is glutathione (GSH), a ubiquitously found antioxidant. Evidence suggests that reduction in GSH increases viral replication, pro-inflammatory cytokine release, and thrombosis, as well as decreases macrophage-mediated fibrin removal. The collection of adverse effects as a result of GSH depletion in states like COVID-19 suggest that GSH depletion is a dominant mechanism of immunothrombosis cascade. We aim to review the current literature on the influence of GSH on COVID-19 immunothrombosis pathogenesis, as well as the beneficial effects of GSH as a novel therapeutic for acute-and long-COVID-19.

Obesity and hyperlipidemia are known to be risk factors for various pathological disorders, including various forms of infectious respiratory disease, including the current Coronavirus outbreak termed Coronavirus Disease 19 (COVID-19). This review studies the effects of hyperlipidemia and obesity on enhancing the inflammatory response seen in COVID-19 and potential therapeutic pathways related to these processes. In order to better understand the underlying processes of cytokine and chemokine-induced inflammation, we must further investigate the immunomodulatory effects of agents such as Vitamin D and the reduced form of glutathione as adjunctive therapies for COVID-19 disease.

Objective To investigate the effects of personalized, adaptive, current-steering functional electrical stimulation (FES) of the lower leg to improve gait in people with foot drop. Design A one-group, pre-test post-test study. Setting Two gait analysis centers. Participants Thirty-two participants exhibiting symptoms of foot drop. Interventions Adaptive, current-steering FES enables precise control over dorsiflexor and evertor muscles, allowing for personalized treatment to correct key foot drop characteristics including dorsiflexion at heel strike and ankle inversion during swing phase. All participants received adaptive FES of the dorsiflexors and evertors during back-to-back walking sets. Participants completed up to three walking sets of unstimulated walking (pre-test) followed by lower-leg stimulated walking (post-test). Main Outcomes Measures The primary outcome measures include ankle dorsiflexion at heel strike and mean ankle inversion during swing phase. Secondary outcome measures include foot angle at heel strike and single-side heel strike to toe strike time (heel-toe time). Results The differences in pre-test versus post-test primary and secondary outcome measures were statistically significant (p<0.0125) within our cohort. With adaptive, current-steering FES, ankle dorsiflexion at heel strike increased an average 5.2 degrees, and ankle inversion during swing phase was reduced by an average -3.6 degrees, bringing the ankle to a more neutral position for stabilization. Conclusion Gait augmentation using adaptive, current-steering FES improved gait in a population exhibiting symptoms of foot drop. By significantly increasing ankle dorsiflexion at heel strike and decreasing ankle inversion during swing phase, adaptive FES enabled a more neutral ankle at heel strike, which is associated with greater ankle stability and decreased fall risk.