Efficacy and safety of sitagliptin with basal-plus insulin regimen versus insulin alone in non-critically ill hospitalized patients with type 2 diabetes: SITA-PLUS hospital trial.

AIMS: To compare the efficacy and safety of basal-plus (BP) insulin regimen with or without sitagliptin in non-critically ill patients with type 2 diabetes (T2D). METHODS: This open-label, randomized clinical trial included inpatients with a previous diagnosis of T2D and blood glucose (BG) between 180 and 400 mg/dL. Participants received basal and correctional insulin doses (BP regimen) either with or without sitagliptin. The primary outcome was the difference in the mean daily BG among the groups. RESULTS: Seventy-six patients (mean age 60 years, 64 % men) were randomized. Compared with BP insulin therapy alone, the sitagliptin-BP combination led to a lower mean daily BG (158.8 vs 175.0 mg/dL, P = 0.014), a higher percentage of readings within a BG range of 70-180 mg/dL (75.9 % vs 64.7 %, P < 0.001), and a lower number of BG readings >180 mg/dL (P < 0.001). Sitagliptin-BP resulted in fewer basal and supplementary insulin doses (P = 0.024 and P = 0.017, respectively) and lower daily insulin injections (P = 0.023) than those with insulin alone. The proportion of patients with hypoglycemia was similar in the two groups. CONCLUSIONS: For inpatients with T2D and hyperglycemia, the sitagliptin and BP regimen combination is safe and more effective than insulin therapy alone. CLINICALTRIALS: gov identifier: NCT05579119.

Phytochemicals and Their Usefulness in the Maintenance of Health.

Inflammation is the immune system's first biological response to infection, injury, or irritation. Evidence suggests that the anti-inflammatory effect is mediated by the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ, as well as the non-cytokine mediator, prostaglandin E2. Currently, the mechanism of action and clinical usefulness of phytochemicals is known; their action on the activity of cytokines, free radicals, and oxidative stress. The latter are of great relevance in the development of diseases, such that the evidence collected demonstrates the beneficial effects of phytochemicals in maintaining health. Epidemiological evidence indicates that regular consumption of fruits and vegetables is related to a low risk of developing cancer and other chronic diseases.

Phytochemicals and modulation of exercise-induced oxidative stress: a novel overview of antioxidants.

The practice of physical exercise induces a series of physiological changes in the body at different levels, either acutely or chronically. During exercise, the increase in oxygen consumption promotes the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are necessary to maintain homeostasis. ROS/RNS activate cellular signaling pathways, such as the antioxidant cytoprotective systems, inflammation, and cell proliferation, which are crucial for cell survival. However, in exhaustive-extended physical exercise, workloads can exceed the endogenous antioxidant defenses, which may be related to impairment of muscle contraction, fatigue, and a decrease in athletic performance. This review addresses the role of some antioxidants from plant-derived extracts called phytochemicals that can mediate the response to oxidative stress induced by physical exercise by activating signaling pathways, such as Nrf2/Keap1/ARE, responsible for the endogenous antioxidant response and possibly having an impact on sports performance.

Bauhinia forficata Link, Antioxidant, Genoprotective, and Hypoglycemic Activity in a Murine Model.

Bauhinia forficata L. is a tree used in alternative medicine as an anti-diabetic agent, with little scientific information about its pharmacological properties. The hypoglycemic, antioxidant, and genoprotective activities of a methanolic extract of B. forficata leaves and stems combined were investigated in mice treated with streptozotocin (STZ). Secondary metabolites were determined by qualitative phytochemistry. In vitro antioxidant activity was determined by the DPPH method at four concentrations of the extract. The genoprotective activity was evaluated in 3 groups of mice: control, anthracene (10 mg/kg), and anthracene + B. forficata (500 mg/kg) and the presence of micronuclei in peripheral blood was measured for 2 weeks. To determine the hypoglycemic activity, the crude extract was prepared in a suspension and administered (500 mg/kg, i.g.) in previously diabetic mice with STZ (120 mg/kg, i.p.), measuring blood glucose levels every week as well as the animals' body weight for six weeks. The extract showed good antioxidant activity and caused a decrease in the number of micronuclei. The diabetic mice + B. forficata presented hypoglycemic effects in the third week of treatment, perhaps due to its secondary metabolites. Therefore, B. forficata is a candidate for continued use at the ethnomedical level as an adjuvant to allopathic therapy.

Phytochemicals in Skeletal Muscle Health: Effects of Curcumin (from Curcuma longa Linn) and Sulforaphane (from Brassicaceae) on Muscle Function, Recovery and Therapy of Muscle Atrophy.

The mobility of the human body depends on, among other things, muscle health, which can be affected by several situations, such as aging, increased oxidative stress, malnutrition, cancer, and the lack or excess of physical exercise, among others. Genetic, metabolic, hormonal, and nutritional factors are intricately involved in maintaining the balance that allows proper muscle function and fiber recovery; therefore, the breakdown of the balance among these elements can trigger muscle atrophy. The study from the nutrigenomic perspective of nutritional factors has drawn wide attention recently; one of these is the use of certain compounds derived from foods and plants known as phytochemicals, to which various biological activities have been described and attributed in terms of benefiting health in many respects. This work addresses the effect that the phytochemicals curcumin from Curcuma longa Linn and sulforaphane from Brassicaceae species have shown to exert on muscle function, recovery, and the prevention of muscle atrophy, and describes the impact on muscle health in general. In the same manner, there are future perspectives in research on novel compounds as potential agents in the prevention or treatment of medical conditions that affect muscle health.

Opuntia spp. in Human Health: A Comprehensive Summary on Its Pharmacological, Therapeutic and Preventive Properties. Part 2.

Plants of the genus Opuntia spp are widely distributed in Africa, Asia, Australia and America. Specifically, Mexico has the largest number of wild species; mainly O. streptacantha, O. hyptiacantha, O. albicarpa, O. megacantha and O. ficus-indica. The latter being the most cultivated and domesticated species. Its main bioactive compounds include pigments (carotenoids, betalains and betacyanins), vitamins, flavonoids (isorhamnetin, kaempferol, quercetin) and phenolic compounds. Together, they favor the different plant parts and are considered phytochemically important and associated with control, progression and prevention of some chronic and infectious diseases. Part 1 collected information on its preventive actions against atherosclerotic cardiovascular diseases, diabetes and obesity, hepatoprotection, effects on human infertility and chemopreventive capacity. Now, this second review (Part 2), compiles the data from published research (in vitro, in vivo, and clinical studies) on its neuroprotective, anti-inflammatory, antiulcerative, antimicrobial, antiviral potential and in the treatment of skin wounds. The aim of both reviews is to provide scientific evidences of its beneficial properties and to encourage health professionals and researchers to expand studies on the pharmacological and therapeutic effects of Opuntia spp.

Prognostic impact of the preoperatory neutrophil/lymphocyte index on early surgical complications of patients with colorectal cancer.

Colorectal cancer (CRC) is found among those with greatest frequency and exponential increase worldwide, with high mortality rates, which are observed as increasing due to the postsurgical complications that come to present. Systemic inflammation participates in the development and progression of cancer; therefore, inflammatory and/or immunological response markers such as the neutrophil/lymphocyte index (NLI) can aid us in predicting the poor results of our interventions. The purpose of our study was to determine the impact of an NLI of ≥2.6 as a predictor of early postsurgical complications. By means of a prospective cohort, we analyzed 158 patients with CRC who were submitted to elective surgery with a later 30-day follow-up. We found that the preoperatory NLI of ≥2.6 obtained an odds ratio (OR) = 2.24 (95% confidence interval [CI], 1.15-4.36) as a prognostic factor of early postsurgical complications according to the Clavien-Dindo classification scale, which represents a low prognostic impact due to its predictive yield with low accuracy, which is the opposite of what other reports have previously published. The use of chemotherapy before the surgical procedure was also determined to be a risk factor for post-surgical complications.

Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition.

Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.

Liver disorders in COVID-19, nutritional approaches and the use of phytochemicals.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.

Effect of Silymarin Supplementation in Lung and Liver Histological Modifications during Exercise Training in a Rodent Model.

BACKGROUND: Exercise training induces adaptive physiological and morphological modifications in the entire organism; however, excessive loads of training may increase damage in tissues. The purpose of this study was to evaluate the effect of silymarin in lung and liver histological changes in rats subjected to exercise training (ET). METHODS: Male Wistar rats were subjected to an 8-week ET treadmill program 5 days per week, 60 min/session, and were previously administered 100 mg ascorbic acid or 100 mg of silymarin. RESULTS: Silymarin increased alveolar and bronchial muscle size, improve vascularization, and reduced tissue inflammation. In liver, silymarin promoted the reduction of lipid content. CONCLUSION: Silymarin supplementation may improve inflammation in pulmonary tissue after 8 weeks of the ET treadmill program, improve cell recovery, and reduce intrahepatic lipid content.

Effect of Silymarin Supplementation on Physical Performance, Muscle and Myocardium Histological Changes, Bodyweight, and Food Consumption in Rats Subjected to Regular Exercise Training.

(1) Background: Regular exercise induces physiological and morphological changes in the organisms, but excessive training loads may induce damage and impair recovery or muscle growth. The purpose of the study was to evaluate the impact of Silymarin (SM) consumption on endurance capacity, muscle/cardiac histological changes, bodyweight, and food intake in rats subjected to 60 min of regular exercise training (RET) five days per week. (2) Methods: Male Wistar rats were subjected to an eight-week RET treadmill program and were previously administered SM and vitamin C. Bodyweight and food consumption were measured and registered. The maximal endurance capacity (MEC) test was performed at weeks one and eight. After the last training session, the animals were sacrificed, and samples of quadriceps/gastrocnemius and cardiac tissue were obtained and process for histological analyzes. (3) Results: SM consumption improved muscle recovery, inflammation, and damaged tissue, and promoted hypertrophy, vascularization, and muscle fiber shape/appearance. MEC increased after eight weeks of RET in all trained groups; moreover, the SM-treated group was enhanced more than the group with vitamin C. There were no significant changes in bodyweight and in food and nutrient consumption along the study. (5) Conclusion: SM supplementation may enhance physical performance, recovery, and muscle hypertrophy during the eight-week RET program.

Asthma: New Integrative Treatment Strategies for the Next Decades.

Asthma is a chronic disease whose main anatomical-functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.

Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications.

Silymarin (SM) is a mixture of flavolignans extracted from the seeds of species derived from Silybum marianum, commonly known as milk thistle or St. Mary'sthistle. These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times. Several properties had been attributed to the major SM flavolignans components, identified as silybin, isosilybin, silychristin, isosilychristin, and silydianin. Previous research reported antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response. Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes. The disruption of Nrf2 signaling has been associated with different pathological conditions. Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway; in particular, they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system, but also as antioxidants or with additional actions regarding Nrf2 regulation. Thus, the study of these molecules makes them appear attractive as novel targets for the treatment or prevention of several diseases.

Garlic (Allium sativum L.): A Brief Review of Its Antigenotoxic Effects.

Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.

Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful nuclear transcription factor that coordinates an antioxidant cytoprotector system complex stimulated by the increase in inoxidative stress (OS). In the present manuscript, we conduct a review on the evidence that shows the effect different modalities of physical exercise exert on the antioxidant metabolic response directed by Nrf2. During physical exercise, the reactive oxygen species (ROS) are increased; therefore, if the endogenous and exogenous antioxidant defenses are unable to control the elevation of ROS, the resulting OS triggers the activation of the transcriptional factor Nrf2 to induce the antioxidant response. On a molecular basis related to physical exercise, hormesis maintenance (exercise preconditioning) and adaptative changes in training are supported by a growing body of evidence, which is important for detailing the health benefits that involve greater resistance to environmental aggressions, better tolerance to constant changes, and increasing the regenerative capacity of the cells in such a way that it may be used as a tool to support the prevention or treatment of diseases. This may have clinical implications for future investigations regarding physical exercise in terms of understanding adaptations in high-performance athletes but also as a therapeutic model in several diseases.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 2: Plants, Vegetables, and Natural Resin.

Cancer is one of the leading causes of death worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens, or teratogens. Genotoxins are also involved in the pathogenesis of several chronic degenerative diseases, including hepatic, neurodegenerative, and cardiovascular disorders; diabetes; arthritis; cancer; chronic inflammation; and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown the antigenotoxic potential of different fruits and plants (Part 1). In this review (Part 2), we present a research overview conducted on some plants and vegetables (spirulina, broccoli, chamomile, cocoa, ginger, laurel, marigold, roselle, and rosemary), which are frequently consumed by humans. In addition, an analysis of some phytochemicals extracted from those vegetables and the analysis of a resin (propolis),whose antigenotoxic power has been demonstrated in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay, was also performed.

Ethical Concerns in Sport: When the Will to Win Exceed the Spirit of Sport.

Background: The need to advance and achieve success is deeply ingrained in human evolution. As a species, humans developed instincts that allowed them to survive and transmit their genes along generations. The will to win is an instinct that has been maintained in the species for millions of years. Sport is an activity as old as humans themselves and is subject to rules; Objective: The proposal of this work is to explore some of the most recurrent practices to achieve the athletes' goals, and the origins and historical use of methods or substances to improve performance and its regulation, as well as to review the impact of new technologies on achieving better results and to make a proposal of what actions should be takenin order to prevent bad practices; Methods: A narrative literature review of ethical sports issues and decision-making was performed in the English language; Results: Practically all behavior with regards to the theme of sports is regulated by ethical codes that must be followed by sportspersons, as well as by everyone involved in the athlete's healthcare and in the athlete's administrative, marketing, and business aspects. Notwithstanding this, winning and reaping glory implies a reward far greater than fame and fortune, which can lead to poor ethical practices in athletes, as well as in interested parties who detract from the intrinsic value of the spirit of sports. The will to win could exceed the limits of what is permitted in fair-play, like the use of prohibited methods or substances; Conclusions: In this work, we review some of the bioethical aspects ofsports. Additionally, recommendations are offered for good practices and to prevent falling into poor ethical behavior.

Morphological and biochemical effects of weekend alcohol consumption in rats: Role of concentration and gender.

AIM: To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats. METHODS: Wistar rats weighing 170-200 g were divided into groups as follows: (1) Control groups; and (2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations: (1) Group of males or females with a consumption of a solution of alcohol at 40%; and (2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy. RESULTS: In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocellular disorganization. CONCLUSION: The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides.

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known  as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are  involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular  disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive  phytocompounds able to counteract the effects of physical and chemical mutagens. Several  studies  have  shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as  the  analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various  tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Nrf2 modulates cell proliferation and antioxidants defenses during liver regeneration induced by partial hepatectomy.

The objective was to determine the regulatory dynamic of Nrf2 during liver regeneration and the administration of EtOH and/or the G. schiedeanum extract. Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy; they were then divided into three groups (groups 1-3). During the experiment, animals in Group 1 drank only water. The other two groups (2-3) received an intragastric dose of ethanol (1.5 g/kg BW, solution at 40% in isotonic saline solution). Additionally, rats in group 3 received a geranium extract daily at a dose of 300 mg/kg BW i.g. EtOh and/or Geranium schiedeanum was administered to rats with regenerating livers for 7 days. At the end of treatment, the activity was determined of the antioxidant enzymes, DNA concentration, TBARS, and TAC, in addition to the expression of Nrf-2, Cyclin D1, and Nqo1. EtOH increased ROS and Nrf-2, which activated the antioxidant defenses and delayed liver proliferation. On the other hand, Geranium schiedeanum exerted an antioxidant effect, diminishing ROS, but Nrf-2 expression increased, favoring liver proliferation through the increase of DNA concentration and the overexpression of Cyclin D1, however it did not activate the antioxidant defenses. In sum, it can be concluded that Nrf-2 possesses a regulatory dynamic that is evident in the presence of a toxic agent (EtOH) and/or a phytochemical agent with antioxidant capacity (Geranium schiedeanum) during liver regeneration.