Meta-analyses have shown that supervised isometric handgrip training reduces blood pressure in hypertensives. However, the mechanism(s) underlying these effects in medicated hypertensive patients, as well as the effects from home-based exercise training, is uncertain. The purpose of this study was to compare the effects of supervised and home-based isometric handgrip training on cardiovascular parameters in medicated hypertensives. In this randomized controlled trial, 72 hypertensive individuals (38–79 years old, 70% female) were randomly assigned to three groups: home-based, supervised isometric handgrip training or control groups. Home-based and supervised isometric handgrip training was completed thrice weekly (4 × 2 min at 30% of maximal voluntary contraction, with 1-min rest between bouts, alternating the hands). Before and after 12 weeks brachial, central and ambulatory blood pressures (BP), arterial stiffness, heart rate variability, vascular function, oxidative stress and inflammation markers were obtained. No significant (p > 0.05) effect was observed for ambulatory BP, arterial stiffness, heart rate variability, vascular function and oxidative stress and inflammatory markers in all three groups. Brachial BP decreased in the supervised group (Systolic: 132 ± 4 vs. 120 ± 3 mmHg; Diastolic: 71 ± 2 vs. 66 ± 2 mmHg, p < 0.05), whereas no significant differences were observed in the home-based (Systolic: 130 ± 4 vs. 126 ± 3 mmHg; diastolic: 73 ± 3 vs. 71 ± 3 mmHg) and control groups (p > 0.05). Supervised handgrip exercise also reduced central BP systolic (120 ± 5 vs. 109 ± 5 mmHg), diastolic (73 ± 2 vs. 67 ± 2 mmHg); and mean BP (93 ± 3 vs. 84 ± 3 mmHg), whereas no significant effects were found in the home-based (Systolic: 119 ± 4 vs. 115 ± 3 mmHg; Diastolic: 74 ± 3 vs. 71 ± 3 mmHg) and control groups (p > 0.05). In conclusion, supervised, but not home-based, isometric training lowered brachial and central BP in hypertensives.
RE increases muscle strength, maintains LBM, and reduces BF in cancer patients undergoing adjuvant and neoadjuvant therapies. Cancer patients and survivors should consider undertaking RE as an effective countermeasure for treatment-related adverse effects to the musculoskeletal system.
Metformin was shown to sensitize multidrug resistant breast cancer cells; however, the mechanisms involved in this capacity need to be clarified. We investigated oxidative stress and inflammatory-related pathways during the induction of doxorubicin resistance in MCF-7 and MDA-MB-231 human breast cancer cells (DOX-res group), and evaluated metformin-induced cellular responses that resulted in the prevention of doxorubicin resistance (Met-DOX group). Microarray analysis demonstrated that DOX-res changed the expression of genes involved in oxidative stress (OS) and the TGF- β1 pathway. The DOX-res group presented increased thiols and reduced lipoperoxidation, increased levels of nitric oxide, nuclear NF-kB and Nrf2, and reduced nuclear p53 labelling. Analysis of the TGF-β1 signaling pathway by RT-PCR array showed that DOX-res developed adaptive responses, such as resistance against apoptosis and OS. Metformin treatment modified gene expression related to OS and the IFN-α signaling pathway. The Met-DOX group was more sensitive to DOX-induced OS, presented lower levels of nitric oxide, nuclear NF-kB and Nrf2, and increased nuclear p53. Analysis of the IFN-α signaling pathway showed that Met-DOX presented more sensitivity to apoptosis and OS. Our findings indicate that metformin is a promising tool in the prevention of chemoresistance in patients with breast cancer submitted to doxorubicin-based treatments.
Viral infections cause high morbidity and mortality, threaten public health, and impose a socioeconomic burden. We have seen the recent emergence of SARS‐CoV‐2 (Severe Acute Respiratory Syndrome Coronavirus 2), the causative agent of COVID‐19 that has already infected more than 29 million people, with more than 900 000 deaths since its identification in December 2019. Considering the significant impact of viral infections, research and development of new antivirals and control strategies are essential. In this paper, we summarize 96 antivirals approved by the Food and Drug Administration between 1987 and 2019. Of these, 49 (51%) are used in treatments against human immunodeficiency virus (HIV), four against human papillomavirus, six against cytomegalovirus, eight against hepatitis B virus, five against influenza, six against herpes simplex virus, 17 against hepatitis C virus and one against respiratory syncytial virus. This review also describes future perspectives for new antiviral therapies such as nanotechnologies, monoclonal antibodies and the CRISPR‐Cas system. These strategies are suggested as inhibitors of viral replication by various means, such as direct binding to the viral particle, blocking the infection, changes in intracellular mechanisms or viral genes, preventing replication and virion formation. We also observed that a large number of viral agents have no therapy available and the majority of those approved in the last 32 years are restricted to some groups, especially anti‐HIV. Additionally, the emergence of new viruses and strains resistant to available antivirals has necessitated the formulation of new antivirals.
Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.
The epidemiological impact of viral diseases, combined with the emergence and reemergence
of some viruses, and the difficulties in identifying effective therapies, have encouraged
several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy
for the treatment of viral diseases is increasing. One of the strategies of immunotherapy
is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies,
which bind directly to the viral antigen and bring about activation of the immune system. With current
advancements in science and technology, several such antibodies are being tested, and some are already
approved and are undergoing clinical trials. The present work aims to review the status of mAb
development for the treatment of viral diseases.
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