New insights into how adenovirus might lead to obesity: An oxidative stress theory

Obesity has become a worldwide epidemic that leads to many serious weight-related disorders. Recently, infection by viruses has been proposed as a possible cause of the obesity epidemic. Of the many viruses screened, adenovirus 36 has been found to be a strong candidate virus that is associated with obesity, based on evidence in various model systems as well as clinical data. The mechanism of how the adenovirus could lead to obesity is not known and this paper proposes some new insights into how oxidative stress could be a possible mechanism of how adenovirus might lead to obesity. This paper reviews the relevant literature of both the effect of adenovirus on cells' anti-oxidant response and the link between obesity and oxidative stress.     

氧化损伤和微重力致骨质疏松症的研究进展

伴随着人口老龄化日益严重,骨质疏松症作为"悄无声息的流行病"逐渐引起人们的注意。氧化损伤和力学刺激是造成骨质疏松的两个主要原因。一方面氧化损伤可通过刺激FoxOs信号通路抑制成骨细胞分化,造成骨质疏松,另一方面机体在长期缺乏负荷力刺激时也会发生废用性骨丢失,二者之间存在着紧密的联系。Nrf2作为细胞应对氧化损伤的主要防御机制,可调控多种抗氧化蛋白酶转录,在氧化损伤所造成的骨质疏松中扮演着重要角色。本文综述了氧化损伤和微重力造成骨质疏松的机制以及Nrf2对抗氧化损伤的调节和对修复骨质发育的影响。     

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress

Background: Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR.

Objective: This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes.

Conclusion: The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.     

Oxidative stress in patients with cardiovascular disease and chronic renal failure

Abstract

Oxidative response regulates many physiological response in human health, but if not properly regulated it could also lead to a number of deleterious effects. The importance of oxidative stress injury depends on the molecular target, the severity of the stress, and the mechanism by which the oxidative stress is imposed: it has been implicated in several diseases including cancer, neurodegenerative diseases, malaria, rheumatoid arthritis and cardiovascular and kidney disease. Most of the common diseases, such as hypertension, atherosclerosis, heart failure, and renal dysfunction, are associated with vascular functional and structural alterations including endothelial dysfunction, altered contractility, and vascular remodeling. Common to these processes is increased bioavailability of reactive oxygen species (ROS), decreased nitric oxide (NO) levels, and reduced antioxidant capacity. Oxidative processes are up-regulated also in patients with chronic renal failure (CRF) and seem to be a cause of elevated risk of morbidity and mortality in these patients.

In this review, we highlight the role of oxidative stress in cardiovascular and renal disease.     

Bariatric Surgery and the Role of the Clinical Endocrinologist: 2011 Update

ObjectiveTo discuss the emerging roles of bariatric surgery and clinical endocrinology within the context of obesity and diabetes mellitus comprehensive care plans and cost-effective strategies.MethodsRelevant literature is reviewed and clinical cases are presented.ResultsThe global obesity epidemic poses many challenges to clinical endocrinologists and has fomented a coordinated effort among specialists to revolutionize management paradigms. Technologic innovation drives the need for accelerated learning and research efforts in bariatric surgery. The national shortage of physicians with expertise in nutritional medicine compounds the management problems for this expanding patient population. Certain issues merit continued attention and research, such as gastric banding for mild obesity, surgery for treatment of diabetes, sleeve gastrectomy, and nutritional and metabolic consequences.ConclusionClinical endocrinologists should have a central role in the perioperative decision-making for patients undergoing bariatric surgery. (Endocr Pract. 2011;17:788-797)     

Fundamental research is the basis for understanding and treatment of many human diseases

There are numerous examples of how fundamental research has been required to understand and treat human disease. This article focuses on three human diseases of lipid metabolism in which advancements in understanding and treatment would not have been possible without basic research. Fabry disease is an inherited metabolic disorder caused by the lack of a specific enzyme in glycosphingolipid catabolism. Cardiovascular disease is a complex and multifactorial disease but as many as half of the cases can be attributed to abnormal levels of plasma cholesterol. The incidence of liver disease is increasing due to the current epidemic of obesity. It is only recently that curiosity-driven research has yielded valuable insight into the mechanism by which liver disease evolves.     

Potential role of aryl hydrocarbon receptor signaling in childhood obesity

BackgroundThere is a growing concern that junk food has contributed to the childhood obesity epidemic. Recently, experimental studies suggested that the aryl hydrocarbon receptor (AHR) gene is strongly linked to western diet-induced obesity.AimThis study investigated the potential role of AHR signaling in childhood obesity and the possible associations of the AHR-aryl hydrocarbon receptor repressor (AHRR)-cytochrome P450 1B1 (CYP1B1) axis with fatty acid homeostasis and the appetite-related hormones, leptin and ghrelin.Subjects and methodsThe study included 80 children; 54 obese and 26 non-obese of matched age and sex. Demographic data, anthropometric measurements, and lipid profile were assessed. Expression of AHR signaling genes was analyzed in blood cells by qRT-PCR. Serum insulin, leptin and ghrelin levels were measured using ELISA.ResultsThe statistical power of this study, calculated using G*Power version 3.1.9.2, was 90% (α = 0.05). AHR and CYP1B1 gene expression levels were upregulated in the obese group compared to controls, whereas AHRR, stearoyl-CoA desaturase 1 (SCD1), and peroxisome proliferator–activated receptor-γ₂ (PPARγ₂) were downregulated. Serum leptin correlated positively, while serum ghrelin correlated negatively with both AHR and CYP1B1. Stratification of obese children by age revealed more activated AHR signaling in younger than in older children. Receiver-operating-characteristic (ROC) analysis revealed that AHR, AHRR and CYP1B1 could discriminate between obese and normal weight children. Multivariate analysis showed that AHRR, CYP1B1 and ghrelin could be significant independent predictors of obesity.ConclusionThis study provides new insights into the molecular mechanisms contributing to childhood obesity by revealing alterations in the AHR-AHRR-CYP1B1 axis, which could serve as a promising therapeutic target for childhood obesity.     

Therapeutic options of TCM for organ injuries associated with COVID-19 and the underlying mechanism

BackgroundCoronavirus disease-2019 (COVID-19) caused by infection with severe acute respiratory coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout China and in other countries since the end of 2019. The World Health Organization (WHO) has declared that the epidemic is a public health emergency of international concerns. The timely and appropriate measures for treating COVID-19 in China, which are inseparable from the contribution of traditional Chinese medicine (TCM), have won much praise of the world.PurposeThis review aimed to summarize and discuss the essential role of TCM in protecting tissues from injuries associated with COVID-19, and accordingly to clarify the possible action mechanisms of TCM from the perspectives of anti-inflammatory, antioxidant and anti-apoptotic effects.MethodsElectronic databases such as Pubmed, ResearchGate, Science Direct, Web of Science, medRixv and Wiley were used to search scientific literatures.ResultsThe present review found that traditional Chinese herbs commonly used for the clinical treatment of organ damages caused by COVID-19, such as Scutellaria baicalensis, Salvia miltiorrhizaSalvia miltiorrhiza, and ginseng, could act on multiple signaling pathways involved in inflammation, oxidative stress and apoptosis.ConclusionTCM could protect COVID-19 patients from tissue injuries, a protection that might be, at least partially, attributed to the anti-inflammatory, antioxidant and anti-apoptotic effects of the TCM under investigation. This review provides evidence and support for clinical treatment and novel drug research using TCM.     

Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract

BackgroundA number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin.HypothesisSince an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C^® could have an antiviral activity too.Study designAntiviral activity of Bioaron C^®, an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections.MethodsThese studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect.ResultsOur studies demonstrated an impressive activity of Bioaron C^® against members of the orthomyxoviridae – influenza A and influenza B viruses. Replication of both analysed influenza A virus strains – H1N1 and H3N2 – as well as replication of two analysed influenza B viruses – strains Yamagatal and Beiying – was significantly reduced after addition of Bioaron C^® to the infected cell cultures. In contrast antiviral activity of Bioaron C^® against other RNA viruses showed a heterogeneous pattern. Bioaron C^® inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C^® was detected against adenovirus – a non-enveloped DNA virus.ConclusionsThese results represent the first proof of a selective antiviral activity of Bioaron C^® against influenza viruses and create basis for further analyses of type and molecular mechanisms of the antiviral activity of this herbal medicine.     

Re-assess Vector Indices Threshold as an Early Warning Tool for Predicting Dengue Epidemic in a Dengue Non-endemic Country

BackgroundDespite dengue dynamics being driven by complex interactions between human hosts, mosquito vectors and viruses that are influenced by climate factors, an operational model that will enable health authorities to anticipate the outbreak risk in a dengue non-endemic area has not been developed. The objectives of this study were to evaluate the temporal relationship between meteorological variables, entomological surveillance indices and confirmed dengue cases; and to establish the threshold for entomological surveillance indices including three mosquito larval indices [Breteau (BI), Container (CI) and House indices (HI)] and one adult index (AI) as an early warning tool for dengue epidemic.Conclusion/SignificanceThere was little evidence of quantifiable association among vector indices, meteorological factors and dengue transmission that could reliably be used for outbreak prediction. Our study here provided the proof-of-concept of how to search for the optimal model and determine the threshold for dengue epidemics. Since those factors used for prediction varied, depending on the ecology and herd immunity level under different geological areas, different thresholds may be developed for different countries using a similar structure of the two-stage model.     

Iron homeostasis and iron-regulated ROS in cell death,senescence and human diseases

BackgroundIron is essential for many types of biological processes. However, excessive iron can be cytotoxic and can lead to many diseases. Since ferroptosis, which is an iron-dependent regulated form of necrosis, was recently discovered, iron and iron-catalysed oxidative stress have attracted much interest because of their sophisticated mechanism of cellular signalling leading to cell death and associated with various diseases.Scope of reviewIn this review, we first focus on how iron catalyses reactive oxygen species (ROS). Next, we discuss the roles of iron in cell death and senescence and, in particular, the downstream signalling pathways of ROS. Finally, we discuss the potential regulation mechanism of iron as a therapeutic target for various iron-related diseases.Major conclusionsBoth labile iron released from organelles upon various stresses and iron incorporated in enzymes produce ROS, including lipid ROS. ROS produced by iron activates various signalling pathways, including mitogen-activated protein kinase (MAPK) signalling pathways such as the apoptosis signal-regulating kinase 1 (ASK1)-p38/JNK pathway. These ROS-activated signalling pathways regulate senescence or cell death and are linked to cancer, ischaemia-reperfusion injury during transplantation and ageing-related neurodegenerative diseases.General significanceIron overload damages cells and causes harmful effects on the body through oxidative stress. Thus, understanding the spatiotemporal availability of iron and the role of iron in generating ROS will provide clues for the suppression of ROS and cytotoxic redox-active iron. Moreover, elucidating the molecular mechanisms and signalling pathways of iron-dependent cytotoxicity will enable us to find novel therapeutic targets for various diseases.     

Inhibition of HAdV-14 induced apoptosis by selenocystine through ROS-mediated PARP and p53 signaling pathways

BackgroundHuman Adenovirus (HAdV) can cause severe respiratory symptoms in people with low immunity and there is no targeted treatment for adenovirus infection. Anti-adenoviral drugs have high clinical significance for inhibiting adenovirus infection. Selenium (Se) plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of Se is mainly achieved by being converted into selenocystine (SeC). Se participates in the active sites of various selenoproteins in the form of SeC. The ability of SeC to resist the virus has raised high awareness due to its unique antioxidative activity in recent years. The antiviral ability of the SeC was determined by detecting the infection rate of the virus in the cells.MethodsThe experiment mainly investigated the antiviral mechanism of SeC by locating the virus in the cell, detecting the generation of ROS, observing the DNA status of the cell, and monitoring the mitochondrial membrane potential.ResultsIn the present study, SeC was designed to resist A549 cells infections caused by HAdV-14. SeC could prevent HAdV-14 from causing cell apoptosis-related to DNA damage. SeC significantly inhibited ROS generation and protect the cells from oxidative damage induced by ROS against HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway, and repaired DNA lesions by suppressing ATR, p53, and PARP signaling pathways.ConclusionSeC might provide an effective selenium species with antiviral properties for the therapies against HAdV-14.     

Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase

Abstract

The hypothesis that sulfocoumarin acting as inhibitors of human carbonic anhydrase (CA, EC 4.2.1.1) cancer-associated isoforms hCA IX and – hCA XII is being able to also inhibit thioredoxin reductase was verified and confirmed. The dual targeting of two cancer cell defence mechanisms, i.e. hypoxia and oxidative stress, may both contribute to the observed antiproliferative profile of these compounds against many cancer cell lines. This unprecedented dual anticancer mechanism may lead to a new approach for designing innovative therapeutic agents.     

Pomegranate extract and exercise provide additive benefits on improvement of immune function by inhibiting inflammation and oxidative stress in high-fat-diet-induced obesity in rats

BackgroundObesity is reported to be associated with immune dysfunction and a state of low-grade, chronic inflammation. Either pomegranate extract (PomE) or exercise (Ex) has been shown to have antiobesity, anti-inflammatory and antioxidant effects. Nevertheless, no study has addressed the additive benefits of PomE and Ex on the restoration of obesity-induced immune defects.ObjectiveThe present work aims to study the effect of PomE and Ex as a combined intervention on immune function and the underlying mechanism involved in inflammation and oxidative stress in rats with high-fat-diet (HFD)-induced obesity.ResultsOur results demonstrate that the combination of PomE and Ex showed additive benefits on inhibition of HFD-induced body weight increase and improvement of HFD-induced immune dysfunction, including (a) attenuating the abnormality of histomorphology of the spleen, (b) increasing the ratio of the CD4 +:CD8 + T cell subpopulations in splenocytes and peripheral blood mononuclear cells (PBMC), (c) inhibition of apoptosis in splenocytes and PBMC, (d) normalizing peritoneal macrophage phenotypes and (e) restoring immunomodulating factors in serum. We also find that immune dysfunction in HFD-fed rats was associated with increased inflammatory cytokine secretion and oxidative stress biomarkers, and that the combination of PomE and Ex effectively inhibited the inflammatory response and decreased oxidative damage.ConclusionsThe effect of PomE and Ex as a combined intervention is greater than the effect of either PomE or Ex alone, showing that PomE and Ex may be additively effective in improving immune function in HFD-fed rats by inhibiting inflammation and decreasing oxidative stress.     

Human umbilical artery endothelial cells from Large-for-Gestational-Age newborn have increased antioxidant efficiency and gene expression

Obesity is a public health problem worldwide, and especially in women in reproductive age where more than one in three have obesity. Maternal obesity is associated with an increased maternal, placental, and newborn oxidative stress, which has been proposed as a central factor in vascular dysfunction in large-for-gestational-age (LGA) newborn. However, cellular and molecular mechanisms behind this effect have not been elucidated. Untreated human umbilical artery endothelial cells (HUAEC) from LGA (LGA-HUAEC) presented higher O₂⁻ levels, superoxide dismutase activity and heme oxygenase 1 messenger RNA (mRNA) levels, paralleled by reduced GSH:GSSG ratio and NRF2 mRNA levels. In response to an oxidative challenge (hydrogen peroxide), only HUAEC from LGA exhibited an enhanced Glutathione Peroxidase 1 (GPX1) expression, as well as a more efficient antioxidant machinery measured by the biosensor probe, HyPer. An open state of chromatin in the TSS region of GPX1 in LGA-HUAEC was evidenced by the DNase-HS assay. Altogether, our data indicate that LGA-HUAEC have an altered cellular and molecular antioxidant system. We propose that a chronic pro-oxidant intrauterine milieu, as evidenced in pregestational obesity, could induce a more efficient antioxidant system in fetal vascular cells, which could be maintained by epigenetic mechanism during postnatal life.     

Neutralizing the free radicals could alleviate the disease severity following an infection by positive strand RNA viruses

Free radical release due to oxidative stress is gaining importance in the field of viral pathogenesis. Recent studies suggest the involvement of oxidative stress and ROS levels in regulating disease virulence during RNA virus infection. Most of the RNA virus infections lead to vascular dysfunction and disease severity. However, the biology of free radicals in maintaining vascular endothelium integrity is not completely understood. In the present review, we discuss some of the common features in positive-strand RNA virus infections such as dengue and SARS-CoV-2 and suggest that anti-oxidant therapy could pave the way to develop therapeutic strategies in combating emerging and re-emerging RNA viruses.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12192-022-01269-x.     

肥胖/糖尿病与肿瘤的相关性及其分子机制的研究进展

全球范围内,肥胖、糖尿病和肿瘤的发病率持续上升,已成为严重危害人类生命健康、降低人类生活质量的全球性重大公共卫生问题。近来研究发现,肥胖/糖尿病与肿瘤的关系密切,然而其分子机制尚不十分明确。目前已发现的可能的分子机制有胰岛素抵抗作用、糖代谢异常、慢性炎症反应、免疫系统失调、肥胖相关基因过度表达、癌基因与抑癌基因的异常表达、白色脂肪组织的功能紊乱等。阐明肥胖/糖尿病与肿瘤的关系及相关的分子机制,对个人和全社会都具有非常重要的意义,因此本文围绕肥胖/糖尿病与肿瘤的关系及其分子机制进行全面系统的综述。     

Prenatal exposure to the contaminant perfluorooctane sulfonate elevates lipid peroxidation during mouse fetal development but not in the pregnant dam

Abstract

Perfluorooctane sulfonate (PFOS), a member of the perfluorinated chemical family, has been convincingly demonstrated to affect lipid metabolism in animals and humans and readily crosses the placenta to exert its effects on the developing fetuses. While its exact mechanism is still not clear, PFOS exposure has long been suggested to exert its toxicity via oxidative stress and/or altered gene expression. Levels of PFOS and malondialdehyde in various organs and cell cultures have been widely determined as general indicators of non-specific lipid peroxidation after PFOS exposure. In this study, the oxidation of precise polyunsaturated fatty acids and their metabolites, derived from enzymatic and non-enzymatic pathways was determined following PFOS exposure in both adult and maternal/fetal mice. CD-1 mice were exposed to 3 mg/kg body weight/day of PFOS in corn oil by oral gavage until late gestation (GD17). We demonstrated that lipid peroxidation was particularly and exclusively affected in fetuses exposed to PFOS, but this was not the case in the maternal mice, where limited effects were observed in the enzymatic oxidation pathway. In this study, we demonstrated that PFOS-induced lipid peroxidation might have a greater impact in free radical generation in fetuses than in dams and could be responsible for affecting fetal development. In addition, antioxidant enzymes, such as superoxide dismutase and catalase, appeared to maintain oxidative stress homeostasis partially in adult mice exposed to PFOS. Taken together, our results might elucidate the mechanism of how PFOS induces oxidative stress in vivo.