Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies.

BACKGROUND: Vitamin D exerts multiple beneficial effects in humans, including neuronal, immune, and bone homeostasis and the regulation of cardiovascular functions. Recent studies correlate vitamin D with cancer cell growth and survival, but meta-analyses on this topic are often not consistent. METHODS: A systematic search of the PubMed database and the Clinical Trial Register was performed to identify all potentially relevant English-language scientific papers containing original research articles on the effects of vitamin D on human health. RESULTS: In this review, we analyzed the antioxidant and anti-inflammatory effects of vitamin D against acute and chronic diseases, focusing particularly on cancer, immune-related diseases, cardiomyophaties (including heart failure, cardiac arrhythmias, and atherosclerosis) and infectious diseases. CONCLUSIONS: Vitamin D significantly reduces the pro-oxidant systemic and tissue biomarkers involved in the development, progression, and recurrence of chronic cardiometabolic disease and cancer. The overall picture of this review provides the basis for new randomized controlled trials of oral vitamin D supplementation in patients with cancer and infectious, neurodegenerative, and cardiovascular diseases aimed at reducing risk factors for disease recurrence and improving quality of life.

Disseminated Coccidioidomycosis: Cutaneous, Soft Tissue, Osseous, and "Shotgun Intraparenchymal" Brain Disease.

Coccidioidomycosis is a disease found in the southwestern United States and caused by inhalation of arthroconidia of Coccidioides immitis and posadasii. Although the disease is most commonly asymptomatic or respiratory, it has a propensity to disseminate to any tissue in the body with the most common being skin, bone, joints, and central nervous system. This case demonstrates the dissemination of coccidioidomycosis to several foci along with a rare form of parenchymal dissemination with an unusual neuroradiological finding.

Chemotherapy-Induced Hepatotoxicity in HIV Patients.

Human immunodeficiency virus (HIV) affects more than 37 million people globally, and in 2020, more than 680,000 people died from HIV-related causes. Recently, these numbers have decrease substantially and continue to reduce thanks to the use of antiretroviral therapy (ART), thus making HIV a chronic disease state for those dependent on lifelong use of ART. However, patients with HIV have an increased risk of developing some type of cancer compared to patients without HIV. Therefore, treatment of patients who are diagnosed with both HIV and cancer represents a complicated scenario because of the risk associated with drug-drug interaction (DDIs) and related toxicity. Selection of an alternative chemotherapy or ART or temporarily discontinuation of ART constitute a strategy to manage the risk of DDIs. Temporarily withholding ART is the less desirable clinical plan but risks and benefits must be considered in each scenario. In this review we focus on the hepatotoxicity associated with a simultaneous treatment with ART and chemotherapeutic drugs and mechanisms behind. Moreover, we also discuss the effect on the liver caused by the association of immunotherapeutic drugs, which have recently been used in clinical trials and also in HIV patients.

Multiple Effects of Ascorbic Acid against Chronic Diseases: Updated Evidence from Preclinical and Clinical Studies.

Severe disease commonly manifests as a systemic inflammatory process. Inflammation is associated withthe enhanced production of reactive oxygen and nitrogen species and with a marked reduction in the plasma concentrations of protective antioxidant molecules. This imbalance gives rise to oxidative stress, which is greater in patients with more severe conditions such as sepsis, cancer, cardiovascular disease, acute respiratory distress syndrome, and burns. In these patients, oxidative stress can trigger cell, tissue, and organ damage, thus increasing morbidity and mortality. Ascorbic acid (ASC) is a key nutrient thatserves as an antioxidant and a cofactor for numerous enzymatic reactions. However, humans, unlike most mammals, are unable to synthesize it. Consequently, ASC must be obtained through dietary sources, especially fresh fruit and vegetables. The value of administering exogenous micronutrients, to reestablish antioxidant concentrations in patients with severe disease, has been recognized for decades. Despite the suggestion that ASC supplementation may reduce oxidative stress and prevent several chronic conditions, few large, randomized clinical trials have tested it in patients with severe illness. This article reviews the recent literature on the pharmacological profile of ASC and the role of its supplementation in critically ill patients.

The acute and chronic effects of resistance training with blood flow restriction on hormonal responses in untrained young men: A comparison of frequency.

The present study aimed to determine the effect of low-intensity training with blood flow restriction (BFR) on the response rate of anabolic hormones. Forty healthy and untrained young men, aged 18 to 25 years old, were randomly divided into five groups: one session of BFR training (BFR1), two sessions of BFR training (BFR2), one session of resistance training without BFR (WBFR1), two sessions of resistance training without BFR (WBFR2), and the control group (without training). BFR groups had three sets of 20 repetitions with 20-30% 1RM, and none-BFR groups had three sets of 10 repetitions with 70-80% 1RM for six weeks. Both BFR1 and WBFR1 groups trained 3day a week (1 session in a day and three sessions a week), BFR2 and WBFR2 groups trained three days a week (but two sessions a day and six sessions in a week) and Control group did not perform any training. The mean changes in growth hormone(GH), testosterone(TS), and vascular endothelial growth factor (VEGF) hormones were determined by ELISA technique before, after a first training session and after six weeks of the training program. To the analysis of data, two way repeated measures ANOVA at a significant level of P<0.05  also were used. The results showed a significant increase in GH levels in each of the four training groups as compared with the pre-test and the control group after a first training session and after six weeks of the training program (P<0.05). There was no significant increase in TS levels in each of the four training groups, as compared with the pre-test and the control group in both acute and chronic TS response (P>0.05). Only the WBFR1 group did not significantly increase in VEGF levels after the first training session (P>0.05). In chronic VEGF response, there were no significant changes observed in all training groups as compared with the control group(P>0.05). Despite the effectiveness of low-intensity BFR training, such as high-intensity resistance training on hormonal responses, two sessions per day training with the same volume does not necessarily result in larger responses in all hormones than one session per day training.