Jones, Jessicados Santos, Julia MatzenbacherReneau, Paul
5页
查看更多>>摘要：Obesity has become a worldwide pandemic as well as a major contributing factor to the increasing rate of type 2 diabetes (T2D). However, there is an intriguing variance demonstrated by a subset of obesity defined as metabolically healthy obesity (MHO). MHO individuals are less prone to develop obesity-related metabolic complications, such as metabolic syndrome (MetS) and further T2D. The exact reason why an MHO person does not present the cluster of risk factors associated with insulin resistance is unknown due to the challenge to mimic MHO in experimental settings. However, MHO individuals present lower sedentary behaviors in comparison to individuals with MetS, which might indicate that an adaptation to skeletal muscle, such as increased insulin sensitivity and glucose transporter (GLUT4), could play a major role in their healthy characteristics. The hypothesis invoked in this paper is that lower exposure to bisphenol together with increased levels of physical exercise underlie the physiological aspects behind MHO characteristics. Evidence suggests that exposure to ?obseogens,? such as bisphenol A (BPA), appears to impair insulin secretion and insulin response in cells containing GLUT4. Epidemiological studies have associated higher levels of BPA, as well as bisphenol S and F, in children with a risk for MetS development. Therefore, the combination between low bisphenol exposure and increased physical exercise may not necessarily affect body weight, but it could modify several metabolic pathways inhibiting insulin resistance, which characterize the heathy status of the MHO. If confirmed, this hypothesis could lead to therapeutic approaches to reverse MetS and inhibit T2D onset.
McCarty, Mark F.Assanga, Simon IlokiLujan, Lidianys Lewis
6页
查看更多>>摘要：During the last half of the twentieth century, age-adjusted mortality from pancreatic cancer in Japan rose about nine-fold in both sexes. Well-characterized risk factors such as smoking, obesity/metabolic syndrome, and heavy alcohol use appear to explain only a modest part of this rise. It is proposed that a diet relatively low in protein, and particularly low in animal protein, was a key determinant of the low risk for pancreatic cancer in midcentury Japan. It is further proposed that pancreatic acinar cells, owing to their extraordinarily high rate of protein synthesis, are at high risk for ER stress; that such stress plays a fundamental role in the induction of most pancreatic cancers; and that low-protein diets help to offset such stress by modulating activities of the kinases GCN2 and mTORC1 while increasing autocrine and systemic production of fibroblast growth factor 21. This model appears to clarify the role of various risk factors and protective factors in pancreatic cancer induction. A vegan or quasi-vegan low-protein diet may have broader potential for decreasing risk for a range of common ?Western? cancers.
查看更多>>摘要：As the COVID-19 pandemic continues, researchers seek to identify efficacious treatments. Current approaches to COVID-19 therapeutics focus on antiviral agents, convalescent plasma, monoclonal antibodies, immunomodulators and more traditional therapies such as steroids [1-6]. Reversing disturbances in coagulation has also been identified as a priority area for candidate therapies, such as through the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 adaptive clinical trial (ACTIV-4) which is currently evaluating aspirin, heparins and apixaban [7]. Since there is a clear relationship between mechanisms of coagulation and the immune response, it is possible that reversing disturbances in coagulation may diminish the dysregulated immune response observed in COVID-19. The basis for this hypothesis is described below and is followed by discussion of a proposed candidate therapy - activated protein C. By treating COVID-19 patients using a novel approach, which does not focus on immune-based or antiviral treatments, but instead which addresses both the anti-thrombotic and inflammatory consequences of infection, the hope is that new therapeutic targets can be considered and new candidate therapies, such as activated protein C, may be evaluated.
查看更多>>摘要：Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 asso-ciated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.
Khurana, IshaAllawadhi, PrinceKhurana, AmitSrivastava, Amit Kumar...
8页
查看更多>>摘要：Bilirubin has been proven to possess significant anti-inflammatory, antioxidant and antiviral activities. Recently, it has been postulated as a metabolic hormone. Further, moderately higher levels of bilirubin are positively associated with reduced risk of cardiovascular diseases, diabetes, metabolic syndrome and obesity. However, due to poor solubility the therapeutic delivery of bilirubin remains a challenge. Nanotechnology offers unique advantages which may be exploited for improved delivery of bilirubin to the target organ with reduced risk of systemic toxicity. Herein, we postulate the use of intravenous administration or inhalational delivery of bilirubin nanomedicine (BNM) to combat systemic dysfunctions associated with COVID-19, owing to the remarkable preclinical efficacy and optimistic results of various clinical studies of bilirubin in non-communicable disorders. BNM may be used to harness the proven preclinical pharmacological efficacy of bilirubin against COVID-19 related systemic complications.
查看更多>>摘要：Lichen planus is a chronic mucocutanous disorder histopathologically characterized with a keratinocytes apoptosis, subsequent basal cell layer liquefaction and accumulation of the inflammatory infiltrate in papillary dermis. A formation of apoptotic bodies in basal cell layer is due to a cytotoxic lymphocyte attack to the basal keratinocytes. It has been demonstrated that the cytotoxic molecules included in this attack are perforin and granzyme B. Both molecules are found upregulated in CD8+ lymphocytes that are in close contact to keratinocytes. However, their amount is lower in lichen planus than in other skin disease characterized by liquefaction and vacuolar degeneration of the basal epidermal layer. This could speculate about other cytotoxic molecule such as granulysin that could mediate keratinocyte apoptosis. Therefore, in this article we hypothesize about the crucial role of granulysin molecule in keratinocytes killing that could contribute to a lichen planus pathogenesis.
查看更多>>摘要：COVID-19 is a serious disease that has infected more than 40 million people. Beside significant mortality, the SARS-CoV-2 infection causes considerable and sustained morbidity, dubbed long COVID. This paper argues that some of this morbidity may be due to a persistent systemic infection. Persistent infection is indicated by continued virus RNA shedding. The virus' superantigen could overstimulate anti-virus immune responses, and thereby induce negative feedback loops, that para-doxically allow the virus to persist. The superantigen would induce strong immune response to any residual infection. This hypothesis suggests that clearing the virus infection completely would be an appropriate intervention against long COVID.
Melendez-Flores, Jesus D.Cavazos-Benitez, Alexandra CarolinaEstrada-Bellmann, Ingrid
4页
查看更多>>摘要：Parkinson?s disease (PD) is the second most common neurodegenerative condition characterized by motor and non-motor symptoms causing a great burden in patients? quality of life. PD has been associated with various metabolic factors such as diabetes, hypertension, and more recently chronic kidney disease where proteinuria has been associated with an increased risk. The presence of small amounts of albumin in urine, microalbuminuria, is a common biomarker for endothelial damage and a predictive factor for not only cardiovascular but also neurological dysfunction. Multiple studies have assessed potential biomarkers for PD progression with great heterogeneity, we hypothesize the use of microalbuminuria as a potential marker that correlates with PD severity and might represent a feasible and simple method of evaluating PD patients in clinical practice. Evidence supporting the present hypothesis comes from oxidative stress, insulin resistance, and endothelial dysfunction. Oxidative stress is a key element in PD pathogenesis; studies have shown lower antioxidant capacity as PD progresses. On the other side, insulin signaling plays an important role in neuronal growth and survival, with its resistance being associated with PD. Microalbuminuria has been associated with both processes; increased levels of oxidative stress markers and decreased insulin sensitivity, hence its screening in PD might reflect these common pathological mechanisms. Moreover, the low vitamin D levels observed in PD patients, which are correlated with endothelial dysfunction and disease severity, might contribute to microalbuminuria induction. More evidence on this vascular approach comes from white matter lesions (WML), observed in brain imaging, which have been significantly associated with motor and non-motor function in PD patients and are independently associated with microalbuminuria. In this manner, an oxidant and insulin resistant environment, along with low vitamin D levels in PD patients, which are associated with microalbuminuria, might contribute altogether to WML. As the latter are correlated with motor and non-motor function, microalbuminuria might thus give insight on PD status. Prospective cohort studies with an adequate sample size, follow-up, and a thorough battery of clinical tests for PD are needed to confirm this hypothesis.
NSTL
Elsevier