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.

Antioxidant Activity and Anticarcinogenic Effect of Extracts from Bouvardia ternifolia (Cav.) Schltdl.

According to the available ethnobotanical data, the Bouvardia ternifolia plant has long been used in Mexican traditional medicine to relieve the symptoms of inflammation. In the present study, the cytotoxic effect of extracts obtained from the flowers, leaves and stems of B. ternifolia using hexane, ethyl acetate (AcOEt) and methanol (MeOH) was evaluated by applying them to the SiHa and MDA-MB-231 cancer cell lines. An MTT reduction assay was carried out along with = biological activity assessments, and the content of total phenols, tannins, anthocyanins, betalains and saponins was quantified. According to the obtained results, nine extracts exhibited a cytotoxic effect against both the SiHa and MDA lines. The highest cytotoxicity was measured for leaves treated with the AcOEt (ID50 of 75 µg/mL was obtained for MDA and 58.75 µg/mL for SiHa) as well as inhibition on ABTS•+ against DPPH• radical, while MeOH treatment of stems and AcOEt of flowers yielded the most significant antioxidant capacity (90.29% and 90.11% ABTS•+ radical trapping). Moreover, the highest phenolic compound content was measured in the stems (134.971 ± 0.294 mg EAG/g), while tannins were more abundant in the leaves (257.646 mg eq cat/g) and saponins were most prevalent in the flowers (20 ± 0 HU/mg). Screening tests indicated the presence of flavonoids, steroids, terpenes and coumarins, as well as ursolic acid, in all the studied extracts. These results demonstrate the biological potential of B. ternifolia.

Antitumor Effect of Epigallocatechin Gallate and Vincristine in Mice with L5178Y Lymphoma.

The main objective of research into new therapies is the search for more efficacy and fewer toxic effects in cancer treatments. On one hand, vincristine (VCR) is a chemotherapeutic used in different kinds of tumors. On the other hand, epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in diverse investigations, so the objective of this work is to evaluate the antitumor effects of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG, and their combination allowed tumor growth and survival time recording. After tumor collection, measurements, and immunohistochemistry for p53, Bcl2, and Cyclin D1 were performed. The results showed that the EGCG/vincristine combination had a greater antitumor effect than those effects of vincristine and EGCG. It can be attributed to the fact that the greatest inhibition of Bcl2 was present in gathering of EGCG harvest with vincristine. Therefore, the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival on both substances independently.

Chiranthodendron pentadactylon Larreat (Sterculiaceae), a Potential Nephroprotector against Oxidative Damage Provoked by STZ-Induced Hyperglycemia in Rats.

BACKGROUND: Chiranthodendron pentadactylon, known in Mexico as the "tree of the little hands", flower's infusion is used to treat kidney failure associated with diseases such as diabetes. The aim of this work is to evaluate the antioxidant effect of the methanolic extract of its flowers on oxidative damage in kidneys caused by streptozotocin in rats. METHODS: The extract phytochemical profile was performed with HPLC. Antioxidant potential in vitro was determined with DPPH and total phenolic tests; antioxidant evaluation in vivo was performed in diabetic rats administered daily via the intragastric route (100 and 200 mg/kg) for 6 weeks; serum glucose/creatinine, food/water consumption, and urinary volume were measured. Relative weight, protein/DNA ratios and oxidative stress were measured in renal tissue. RESULTS: The extract showed 20.53% of total phenolic content and IC50 of 18.05 µg/mL in DPPH, and this was associated with ferulic acid, phloretin and α-amyrin. Both doses showed a moderate decrease in the protein/DNA ratio in renal tissue, and the same behavior was observed for total urinary protein loss and serum creatinine, while the best antioxidant effect was exerted by a lower dose, which increased catalase activity and decreased lipid peroxidation in the kidneys. CONCLUSIONS: Results demonstrated that C. pentadactylon methanolic flower's extract improves renal function through antioxidant mechanisms during experimental diabetes.

Anti-Inflammatory Potential of Pteropodine in Rodents.

Pteropodine (PT) is a component of some plants with potentially useful pharmacological activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the anti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect of PT was evaluated by determining the myeloperoxidase enzyme activity. PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 51, 66 and 70% inhibitory effect of 10, 20 and 40 mg/kg of PT, respectively, in the rat paw edema test. In the pleurisy assay, 40 mg/kg of PT induced a low neutrophil count (up to 36%) when compared to the negative control group, and 20 mg/kg of PT increased the content of lymphocytes by up to 28% and the pleural exudate volume decreased by 52% when compared to the negative control group, respectively. We also found an 81.4% inflammatory inhibition of the edema ear with 0.04 mg/ear of PT, and a significant myeloperoxidase enzyme inhibition by the three doses of PT tested. We conclude that PT exerted a potent anti-inflammatory effect in the acute inflammation model in rodents.

Effects of Spirulina maxima on a Model of Sexual Dysfunction in Streptozotocin-Induced Diabetic Male Rats.

Arthrospira (Spirulina) maxima (SM) is a cyanobacterium that has a long history of being used as human food. In recent years, several investigations have shown its beneficial biological effects, among which its antioxidant capacity has been highlighted. The purpose of this study was to evaluate the effects of SM on body weight, glycemia, sexual behavior, sperm quality, testosterone levels, sex organ weights, and the activity of antioxidant enzymes in diabetic male rats (a disease characterized by an increase in reactive oxygen species). The experiment consisted of six groups of sexually expert adult males (n = 6): (1) control (vehicle); (2) streptozotocin (STZ)-65 mg/kg; (3) SM-400 mg/kg; (4) STZ + SM-100 mg/kg; (5) STZ + SM-200 mg/kg; and (6) STZ + SM-400 mg/kg. Sexual behavior tests were performed during the first 3 h of the dark period under dim red illumination. Our results showed that SM significantly improved sexual behavior and sperm quality vs. diabetic animals. Likewise, while the enzymatic activities of SOD and GPx increased, TBARS lipoperoxidation decreased and testosterone levels increased. In view of the findings, it is suggested that SM may potentially be used as a nutraceutical for the treatment of diabetic male sexual dysfunction due to its antioxidant property.

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.

Investigation of the DNA Damage and Oxidative Effect Induced by Venlafaxine in Mouse Brain and Liver Cells.

Venlafaxine is an antidepressant used worldwide. Therefore, studies to confirm its safe use are mandatory. This report evaluated the drug DNA damage capacity in the brain and liver of ICR mice, and its oxidative effect on DNA, lipids, and proteins, as well as the amount of nitrites, also in the brain and liver. Determinations were made at 2, 6, 12, and 24 h post-treatment, excluding DNA oxidation that was observed at 2 h. The tested doses of venlafaxine were 5, 50, and 250 mg/kg. The results showed DNA damage in the brain with the two more elevated doses of venlafaxine at 2 and 6 h post-treatment and also at 12 h in the liver. The comet assay plus the FPG enzyme showed DNA damage in both organs with all doses. The two high doses increased lipoperoxidation in the two tissues from 6 to 12 h post-administration. Protein oxidation increased with the three doses, mainly from 2 to 12 h, and nitrite content was elevated only with the high dose in the liver. The drug was found to affect both tissues, although it was more pronounced in the liver. Interestingly, DNA oxidative damage was observed even with a dose that corresponds to the therapeutic range. The clinical relevance of these findings awaits further investigations.

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.

Development of a Nanostructured Electrochemical Genosensor for the Detection of the K-ras Gene.

In the scientific literature, it has been documented that electrochemical genosensors are novel analytical tools with proven clinical diagnostic potential for the identification of carcinogenic processes due to genetic and epigenetic alterations, as well as infectious diseases due to viruses or bacteria. In the present work, we describe the construction of an electrochemical genosensor for the identification of the k12p.1 mutation; it was based on use of Screen-Printed Gold Electrode (SPGE), Cyclic Voltammetry (CV), and Atomic Force Microscopy (AFM), for the monitoring the electron transfer trough the functionalized nanostructured surface and corresponding morphological changes. The sensitivity of the genosensor showed a linear response for the identification of the k12p.1 mutation of the K-ras gene in the concentration range of 10 fM to 1 µM with a detection limit of 7.96 fM in the presence of doxorubicin (Dox) as DNA intercalating agent and indicator of the hybridization reaction. Thus, the electrochemical genosensor developed could be useful for the identification of diseases related with the K-ras oncogene.

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.

A Complete Review of Mexican Plants with Teratogenic Effects.

In Mexico, the use of medicinal plants is the first alternative to treat the diseases of the most economically vulnerable population. Therefore, this review offers a list of Mexican plants (native and introduced) with teratogenic effects and describes their main alterations, teratogenic compounds, and the models and doses used. Our results identified 63 species with teratogenic effects (19 native) and the main alterations that were found in the nervous system and axial skeleton, induced by compounds such as alkaloids, terpenes, and flavonoids. Additionally, a group of hallucinogenic plants rich in alkaloids employed by indigenous groups without teratogenic studies were identified. Our conclusion shows that several of the identified species are employed in Mexican traditional medicine and that the teratogenic species most distributed in Mexico are Astragalus mollissimus, Astragalus lentiginosus, and Lupinus formosus. Considering the total number of plants in Mexico (≈29,000 total vascular plants), to date, existing research in the area shows that Mexican plants with teratogenic effects represent ≈0.22% of the total species of these in the country. This indicates a clear need to intensify the evaluation of the teratogenic effect of Mexican plants.

Potential protective effect of beta-caryophyllene against cadmium chloride-induced damage to the male reproductive system in mouse.

Cadmium is a metal that can affect the male reproductive process, possibly leading to infertility. In contrast, beta-caryophyllene (BC) is a sesquiterpene that has shown antigenotoxic, anticancer, and antioxidant properties. Therefore, the aim of the present study was to determine the protective effect of BC against the deleterious effects of cadmium chloride (CC) on various mouse testicular and sperm parameters. We tested three doses of BC (20, 200, and 400 mg/kg) given before and during exposure to 3 mg/kg CC (six days after a single administration). Our results show significant alleviation of the damage induced by CC after the three doses of BC. Regarding the sperm concentration and morphology, the protection with the high dose was complete, and regarding sperm mobility and viability, the protection was more than 74%. In the comet assay, the highest dose showed a reduction of 92.5% in the damage induced by CC, and regarding the number of micronuclei in the spermatids, the reduction was 83.3%. In the oxidative evaluation, regarding sperm lipoperoxidation, the improvement was complete with the high dose, and in the ABTS.+ test, the improvement in the response to the BC high dose was 26.3%. Regarding testicular lipoperoxidation and protein oxidation, the protective effects of the high BC dose were 87.6% and 89.9%, respectively. We also found that BC protected against the histological and morphometric alterations induced by CC. Therefore, our study clearly demonstrates the beneficial, chemopreventive effect of BC against the mouse sperm and testicular alterations induced by CC.

A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer.

Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1ß, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.

Comparison of the Antibacterial Activity and Effect on Membrane Permeability of Hibiscus Acid and a Commercial Chlorhexidine Mouthrinse Against Pathogenic Oral Bacteria and Determination of Hibiscus Acid Toxicity.

The main aim of this study was to determine and compare the antimicrobial effect of hibiscus acid and a commercial 0.12% (w/v) chlorhexidine mouthrinse against Streptococcus mutans, Streptococcus sanguinis, Capnocytophaga gingivalis, and Staphylococcus aureus, and to determine the effect on bacterial cell membrane permeability and the toxicity of hibiscus acid in a mouse model. Hibiscus acid was obtained from acetone extract of Hibiscus sabdariffa calyces. Chlorhexidine (0.12% w/v) mouthrinse was purchased from a local pharmacy. The antimicrobial activity of hibiscus acid and mouthrinse were determined using the gel diffusion technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the solutions were determined using the broth dilution method. The effect on bacterial cell membrane permeability of hibiscus acid and mouthrinse was determined by crystal violet assay. The toxicity of hibiscus acid was investigated in a mouse model (registration number: UAEH2019-A1-S-8288). Hibiscus acid and mouthrinse showed antibacterial activity against all oral pathogenic bacteria. However, hibiscus acid showed a lower antibacterial effect compared with chlorhexidine mouthrinse. The MIC and MBC for hibiscus acid were 3 and 5 mg/mL, respectively, and was between 30 and 50 µg/mL for mouthrinse. The crystal violet test results indicate that hibiscus acid and mouthrinse alter the permeability of the bacterial membrane. Finally, hibiscus acid did not show toxicity in mouse studies.

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.