Crotamine derived from Crotalus durissus terrificus venom combined with drugs increases in vitro antibacterial and antifungal activities.

This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.

Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2.

Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine-tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele-specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA.

Evaluation of internal markers in digestibility estimation for sheep and goats.

The objective of this study was to compare the indirect methods of obtaining digestibility with the direct method of total fecal collection to estimate the apparent digestibility of nutrients in sheep and goats supplemented with non-protein nitrogen. Five goats and five sheep with no defined racial pattern were used, distributed in two 5 × 5 Latin squares, with split plots, considering the diets as plots and the apparent digestibility determination methodologies as subplots. The diets were composed of buffelgrass hay and the addition, via ruminal infusion, of increasing amounts of nitrogen supplementation in order to gradually raise the CP level of the basal diet in intervals of 2% points, that is, + 2, +4, + 6 and + 8%. Samples of the feeds offered, and the leftovers were collected daily during the five days of collection to determine the nutrient intake, as well as the total collection of feces to determine the apparent digestibility of the nutrients. The amount of fecal dry matter excreted was estimated by the concentration of Indigestible Acid Detergent Fiber (ADFi), Indigestible Neutral Detergent Fiber (NDFi), Indigestible Dry Matter at 244 h (DMi 244 h) and Indigestible Dry Matter at 264 h (DMi 264 h). Among the evaluated markers, DMi 264 h had the lowest accuracy in estimating fecal excretion and nutrient digestibility. For the goat species, the markers ADFi and DMi 244 h proved to be able to adequately predict fecal excretion and digestibility indices, while NDFi stood out for both species. Among the evaluated markers, NDFi is the one that most accurately estimates the nutrient digestibility of the diet for goats and sheep.

Forage cactus as an additive in corn without the cob silages of feedlot sheep diets.

This study aimed to assess the impact of adding forage cactus as an additive to the production of corn silage without the cob on the performance of feedlot sheep and subsequent silage losses. The experimental design was completely randomized, consisting of three treatments: corn silage without cob; 0% = 100% corn plant without the cob; 10% = 90% corn plant without cob + 10% forage cactus; 20% = 80% corn plant without cob + 20% forage cactus. Significant effects were observed for dry matter intake (P = 0.0201), organic matter (P = 0.0152), ether extract (P = 0.0001), non-fiber carbohydrates (P = 0.0007). Notably, nutrient digestibility showed significant differences in organic matter (P = 0.0187), ether extract (P = 0.0095), neutral detergent fiber (P = 0.0005), non-fiber carbohydrates (P = 0.0001), and metabolizable energy (P = 0.0001). Performance variables, including total weight gain (P = 0.0148), average daily weight gain (P = 0.0148), feeding efficiency, and rumination efficiency of dry matter (P = 0.0113), also exhibited significant effects. Consequently, it is recommended to include 20% forage cactus in corn silage, which, based on natural matter, helps meet animals' water needs through feed. This inclusion is especially vital in semi-arid regions and aids in reducing silage losses during post-opening silo disposal.

Impairment of SK-MEL-28 Development-A Human Melanoma Cell Line-By the Crataeva tapia Bark Lectin and Its Sequence-Derived Peptides.

Melanoma is difficult to treat with chemotherapy, prompting the need for new treatments. Protease inhibitors have emerged as promising candidates as tumor cell proteases promote metastasis. Researchers have developed a chimeric form of the Bauhinia bauhinioides kallikrein inhibitor, rBbKIm, which has shown negative effects on prostate tumor cell lines DU145 and PC3. Crataeva tapia bark lectin, CrataBL, targets sulfated oligosaccharides in glycosylated proteins and has also demonstrated deleterious effects on prostate and glioblastoma tumor cells. However, neither rBbKIm nor its derived peptides affected the viability of SK-MEL-28, a melanoma cell line, while CrataBL decreased viability by over 60%. Two peptides, Pep. 26 (Ac-Q-N-S-S-L-K-V-V-P-L-NH2) and Pep. 27 (Ac-L-P-V-V-K-L-S-S-N-Q-NH2), were also tested. Pep. 27 suppressed cell migration and induced apoptosis when combined with vemurafenib, while Pep. 26 inhibited cell migration and reduced nitric oxide and the number of viable cells. Vemurafenib, a chemotherapy drug used to treat melanoma, was found to decrease the release of interleukin 8 and PDGF-AB/BB cytokines and potentiated the effects of proteins and peptides in reducing these cytokines. These findings suggest that protease inhibitors may be effective in blocking melanoma cells and highlight the potential of CrataBL and its derived peptides.

Evaluation of the 3D error of 2 face-scanning systems: An in vitro analysis.

STATEMENT OF PROBLEM: Facial scanning systems have been developed as auxiliary tools for diagnosis and planning in dentistry. However, little is known about the trueness of these free software programs and apps for facial scanning. PURPOSE: The purpose of this in vitro study was to evaluate the trueness of 3D facial scanning by using Bellus3D and +ID ReCap Photo. MATERIAL AND METHODS: A mannequin head was used as the master model. The control group was created by scanning the mannequin head with a noncontact structured blue light 3D scanner (ATOS Core). Two facial scanning methods were used for the experimental groups: a facial scanning app (FaceApp) and the Plus identity photogrammetry methodology (ReCap Photo). In both methods, image capturing was performed under the same natural lighting conditions with a smartphone (iPhone X) calibrated with an app. Trueness was assessed from the 3D measurement error, which was calculated with a 3D mesh analysis software program (GOM Inspect). Two comparison groups were created: ATOS versus Bellus3D (B3D) and ATOS versus +ID with ReCap Photo (+IDRP). The results were statistically evaluated by using the Shapiro-Wilk and paired t tests (α=.05). RESULTS: B3D had a greater error than +IDRP in measuring the regions of the upper and lower lips, nose, and mentum (P<.01). This error was statistically higher for +IDRP (P<.01) in the right face area, but the left face area showed no statistically significant difference between the evaluated scanning methods (P=.93). The 3D global trueness of B3D was 0.34 ±0.14 mm, and that of +IDRP was 0.28 ±0.06 mm. CONCLUSIONS: Both methods evaluated in this study provided a 3D model of the face with clinically acceptable trueness and should be reliable tools for planning esthetic restorations.

Red propolis extract as a natural ionophore for confined sheep: performance and morphological and histopathological changes.

This study aimed to evaluate the effect of increasing levels of red propolis extract (RPE) in the diet of confined sheep on performance and histomorphometric parameters of rumen and intestine and histopathological parameters of liver and kidney. Thirty-five male sheep (17.08 ± 2.36 kg) were used, distributed in a completely randomized design, with five treatments (0, 7, 14, 21, and 28 mL day-1 RPE) and seven replications, submitted to 68 days of experiment. At the end of the experimental period, the animals were euthanized, and samples of rumen, intestine, liver, and kidney were collected to histomorphometry and histopathology analyzes. Higher RPE inclusions (21 and 28 mL day-1) maintained dry matter intake and increased total weight (5.78 x 6.14 and 6.95 kg, respectively) gain up to 20.24%. In the rumen, the inclusion of RPE led to an increase in the thickness of the epithelium and the highest level also increased the thickness of the keratinized portion of this epithelium (21.71 x 32.15 µm). The level of 21 mL day-1 provided larger ruminal papillae (1620.68 x 1641.70 µm) and greater ruminal absorption area (561791.43 x 698288.50 µm2). In intestine 21 and 28 mL-1 of RPE provided greater mucosal thickness (468.54 x 556.20 and 534.64 µm), higher goblet cell index (23.32 x 25.82 and 25.64) and higher hepatic glycogen index (1.47 x 1.64 and 1.62), supporting higher nutrients absortion and glicogenolise and intestinal health, corroborating the weight gain indices. The inclusion of RPE did not cause renal histopathological lesions. Therefore, levels of 21 and 28 mL day-1 of RPE can be used in sheep diets, promoting greater final weight gain, causing positive histomorphological changes in the rumen, intestine and liver, without causing kidney or liver damage.

Production, characterization, and dietary supplementation effect of rumen-protected fat on ruminal function and blood parameters of sheep.

Rumen-protected fat (RPF) was produced in the 1st experimental stage through melt-emulsification technique using buriti oil (BO) as core, at concentrations of 10% (BO10), 20% (BO20), and 30% (BO30) (w/w), and carnauba wax (CW) as encapsulant material. After obtention and characterization, protected fat microspheres were tested in a 2nd experimental stage on the sheep' diet using six castrated 2-year-old male Santa Ines with initial weight 48.9 ± 5.23 kg, fistulated in rumen and distributed in a double Latin square design with 3 treatments × 3 periods, to evaluate rumen pH, temperature, protozoal count, and blood parameters. There was no difference (P > 0.05) among RPF microspheres for microencapsulation yield. However, microencapsulation efficiency increased (P < 0.05) with BO addition ranging from 36 to 61.3% for BO10 and BO30, respectively. The inclusion of BO10 in the sheep's diet did not affect the ruminal dry matter degradability (DMD) of BO over time (P > 0.05); however, BO20 and BO30 had higher (P < 0.05) DMD values than BO10. No significant differences were observed among RPF for rumen pH and temperature (P > 0.05). There was an increase (P < 0.05) in the protozoal population in the rumen environment due to the microencapsulated BO30 inclusion. There was also increase (P < 0.05) in serum albumin, cholesterol, aspartate aminotransferase (ALT), and gamma-glutamyltransferase (GGT), and a reduction (P < 0.05) in serum triglycerides of the sheep when RPF microspheres increased in the diet. Melt-emulsification proved to be a good technique for microencapsulation of buriti oil into the carnauba wax matrix. RPF from buriti oil protected into carnauba wax is recommended for sheep diet because it increases energy density, without adverse effects on the protozoal populations and blood serum metabolites from the bypass effect in the rumen.

6-Shogaol Exerts a Neuroprotective Factor in Offspring after Maternal Immune Activation in Rats.

6-Shogaol is one of the main active phenolic components of ginger and has neuroprotective effects by protecting brain against the oxidative stress and regulate the levels of neurotrophic factors. The objective of the present study was to verify the effect of 6-shogaol on neurochemical parameters in offspring after maternal immune activation by lipopolysaccharide (LPS) in rats. Twelve pregnant Wistar rats received 100 µg/kg of LPS or saline solution on the gestational day 9.5. Male offspring participated in the study and from the postnatal days (PND) 30 and 55, respectively, they were supplemented with 6-shogaol or saline solution, by gavage at a dose of 10 mg/kg/day, orally for 5 days. In PND 37 and 62, analysis of kinase signaling regulated by extracellular signal 1/2 (ERK 1/2), levels of neurotrophic factor derived from the brain (BDNF), and neuron-specific enolase (NSE), lipid and protein oxidative damage was evaluated by 4-hydroxy-2-nonenal (HNE) and 3-nitrotyrosine (3-NT), respectively, and myeloperoxidase (MPO) activity was performed in the hippocampus. Prenatal exposure to LPS significantly decreased ERK and BDNF levels in PND 37 and 62, increased NSE levels and lipid damage in rats in PND 37, and increased 3-NT level in rats in PND 62. With treatment using 6-shogaol, an increase in ERK and BDNF levels was identified in PND 37 and 62 and a reduction in HNE and MPO activity in rats in PND 37 and 62, respectively. 6-Shogaol positively increased markers of neuronal growth, plasticity and synaptic activity and reduced oxidative damage in the hippocampus in an animal model of autism by maternal immune activation.

Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells.

BACKGROUND: Melanoma is the most lethal form of skin cancer, and its incidence has increased considerably in the last decades. Melanoma presents difficult treatment with strong resistance of tumor cells, due to its extremely invasive nature with high capacity to metastases. Berberine (BBR), an isoquinoline alkaloid, is a molecule found in several medicinal plants, and has been studied in several diseases, demonstrating antimicrobial, antidiabetic and anti-inflammatory properties and anti-tumorigenic effects. METHODS AND RESULTS: In SK-MEL-28 cells, 50 µM BBR treatment for 24 h decreased cell viability by 50 percent. This concentration generated cell death both by early apoptosis and necrosis, with an increase in the DNA damage index. BBR increased (*p < 0.05) the proportion of cells in G1/G0 phase and decreased (###p < 0.005) the percentage of cells in S phase. The alcaloid increased (****p < 0.001) ROS production compared to untreated controls with an increase in activated caspase 3 and phosphorylated p53 protein levels. In addition, BBR significantly enhanced ERK as well as both pro- and anti-inflammatory cytokine expression compared to untreated controls. CONCLUSIONS: BBR has important antiproliferative effects and may be alone or in adjunct therapy a promising candidate for melanoma treatment, a cancer with great incidence and high lethality.

A systematic review and meta-analysis of the effect of thymol as an anti-inflammatory and wound healing agent: A review of thymol effect on inflammation and wound healing: A review of thymol effect on inflammation and wound healing.

Thymol (THY) exhibits antibacterial and antioxidant properties. Recent studies have also shown that THY presents anti-inflammatory and healing properties. This review focused on in vitro and in vivo investigations related to THY utilization, as an anti-inflammatory and/or wound healing agent. PubMed, WebOfScience, and Scopus were examined. Independent reviewers conducted all diagram steps. PRISMA was followed for data extraction. RoB 2 and SYRCLE were utilized to assess the risk of bias for in vitro and animal studies. Meta-analysis was performed for in vitro and in vivo articles that investigated THY as an anti-inflammatory agent. Thirty-six and 15 articles were included in the qualitative analysis and meta-analysis, respectively. Studies showed high risk of bias related to sampling, allocation procedures, randomization, and blinding. Even so, for in vitro studies, significant result was observed for IL-2. For in vivo studies, significant results were found for IL-1, IL-17, TNF-α, AST, MPO, and CRP, with higher levels noticed in control groups. THY presents significant properties as anti-inflammatory, ameliorating affections of the digestive system, cardiovascular problems, respiratory system and dermal damages, and burns. Researches are needed to clarify THY dose-response relationship and its mechanism of action, especially in the application of THY as a healing agent.

The Aging Process: A Metabolomics Perspective.

Aging process is characterized by a progressive decline of several organic, physiological, and metabolic functions whose precise mechanism remains unclear. Metabolomics allows the identification of several metabolites and may contribute to clarifying the aging-regulated metabolic pathways. We aimed to investigate aging-related serum metabolic changes using a metabolomics approach. Fasting blood serum samples from 138 apparently healthy individuals (20−70 years old, 56% men) were analyzed by Proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS), and for clinical markers. Associations of the metabolic profile with age were explored via Correlations (r); Metabolite Set Enrichment Analysis; Multiple Linear Regression; and Aging Metabolism Breakpoint. The age increase was positively correlated (0.212 ≤ r ≤ 0.370, p < 0.05) with the clinical markers (total cholesterol, HDL, LDL, VLDL, triacylglyceride, and glucose levels); negatively correlated (−0.285 ≤ r ≤ −0.214, p < 0.05) with tryptophan, 3-hydroxyisobutyrate, asparagine, isoleucine, leucine, and valine levels, but positively (0.237 ≤ r ≤ 0.269, p < 0.05) with aspartate and ornithine levels. These metabolites resulted in three enriched pathways: valine, leucine, and isoleucine degradation, urea cycle, and ammonia recycling. Additionally, serum metabolic levels of 3-hydroxyisobutyrate, isoleucine, aspartate, and ornithine explained 27.3% of the age variation, with the aging metabolism breakpoint occurring after the third decade of life. These results indicate that the aging process is potentially associated with reduced serum branched-chain amino acid levels (especially after the third decade of life) and progressively increased levels of serum metabolites indicative of the urea cycle.

Nitrogen balance and microbial protein synthesis in dairy cows fed with peanut meal to replace soybean meal.

This research was carried out to evaluate the effect of replacing dietary soybean meal with peanut meal, on intake and digestibility, microbial protein synthesis, and nitrogen balance in lactating cows. Twelve crossbred Holstein × Gyr cows at 84 days in milk (DIM) were distributed in a triple 4 × 4 Latin square. The treatments consisted of increasing peanut meal levels (0, 330, 670, and 1000 g/kg dry matter basis) in replacement of soybean meal in the diet. Replacing soybean meal with peanut meal had no effect on the intake and digestibility of dry matter and nutrients. Nitrogen balance and percentage of retained were similar among treatments. Microbial nitrogen synthesis and microbial protein synthesis efficiency were similar among treatments. Thus, in regions where its cost is lower, peanut meal can totally replace soybean meal in dairy cow diets without affecting nitrogen balance and microbial protein synthesis.

Palatability and nycterohemeral patterns of ingestive behavior of sheep fed different roughage sources.

The aim of this study was to evaluate the nycterohemeral patterns of ingestive behavior at 24, 48, and 72 h (Trial I) of sheep fed different roughages and the palatability index (Trial II) for sheep and goats fed different roughages used in a semiarid region. In the study, five sources of roughage were evaluated, namely: (1) Nopalea cochenillifera (L.) Salm-Dyck cladodes + urea + sugarcane bagasse (NUB); (2) Opuntia stricta (Haw.) Haw cladodes + urea + sugarcane bagasse (OUB); (3) Tifton hay; (4) corn silage; and (5) sorghum silage. Five Soinga sheep were used and arranged in a 5 × 5 Latin square design in Trial I. Six female Santa Ines sheep and six female Saanen goats were used to study the preferences for different roughages in Trial II, and three tests were carried out to determine the palatability index, comparing two roughage types at a time: test 1 - corn silage versus Nopalea cladodes + urea + sugarcane bagasse (NUB); test 2 - corn silage versus Opuntia cladodes + urea + sugarcane bagasse (OUB); and test 3 - NUB versus OUB. The highest dry matter (DM) intake was for diets composed by NUB. Feeding time (min/d) was higher for sorghum silage (291 min d-1), while rumination time was higher (P < 0.05) for corn silage (604.0 min d-1), sorghum silage (561.7 min d-1), and Tifton hay (529.7 min d-1). No difference (P > 0.05) was observed for feeding, rumination, and idleness time between species (sheep and goats), and there was no roughage × species interaction (P > 0.05). The palatability indexes were 76 and 77% (tests 1 and 2) for NUB and OUB, respectively. Sheep fed with roughage containing cactus cladodes associated with urea and sugarcane bagasse spent less time on ingestion and rumination activities. The ingestive behavior can be evaluated in a period of 48 h, using instantaneous scanning.

Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability.

Ubiquitin-conjugating enzymes (E2) enable protein ubiquitination by conjugating ubiquitin to their catalytic cysteine for subsequent transfer to a target lysine side chain. Deprotonation of the incoming lysine enables its nucleophilicity, but determinants of lysine activation remain poorly understood. We report a novel pathogenic mutation in the E2 UBE2A, identified in two brothers with mild intellectual disability. The pathogenic Q93E mutation yields UBE2A with impaired aminolysis activity but no loss of the ability to be conjugated with ubiquitin. Importantly, the low intrinsic reactivity of UBE2A Q93E was not overcome by a cognate ubiquitin E3 ligase, RAD18, with the UBE2A target PCNA. However, UBE2A Q93E was reactive at high pH or with a low-pKa amine as the nucleophile, thus providing the first evidence of reversion of a defective UBE2A mutation. We propose that Q93E substitution perturbs the UBE2A catalytic microenvironment essential for lysine deprotonation during ubiquitin transfer, thus generating an enzyme that is disabled but not dead.

A scoping review of physical activity interventions for older adults.

BACKGROUND: To inform implementation and future research, this scoping review investigates the volume of evidence for physical activity interventions among adults aged 60+. Our research questions are: (1) what is the evidence regarding interventions designed to increase total physical activity in adults aged 60+ years, in accordance with three of the four strategic objectives of GAPPA (active societies, active environments, active people); (2) what is the current evidence regarding the effectiveness of physical activity programmes and services designed for older adults?; and (3) What are the evidence gaps requiring further research? METHODS: We searched PEDro, MEDLINE, CINAHL and Cochrane from 1 January 2010 to 1 November 2020 for systematic reviews and meta-analyses of physical activity interventions in adults aged 60+. We identified interventions designed to: (1) increase physical activity; and (2) deliver physical activity programmes and services in home, community or outpatient settings. We extracted and coded data from eligible reviews according to our proposed framework informed by TIDieR, Prevention of Falls Network Europe (PROFANE), and WHO's International Classification of Functioning, Disability and Health (ICF). We classified the overall findings as positive, negative or inconclusive. RESULTS: We identified 39 reviews of interventions to increase physical activity and 342 reviews of programmes/services for older adults. Interventions were predominantly structured exercise programmes, including balance strength/resistance training, and physical recreation, such as yoga and tai chi. There were few reviews of health promotion/coaching and health professional education/referral, and none of sport, workplace, sociocultural or environmental interventions. Fewer reported outcomes of total physical activity, social participation and quality of life/well-being. We noted insufficient coverage in diverse and disadvantaged samples and low-middle income countries. CONCLUSIONS: There is a modest but growing volume of evidence regarding interventions designed to increase total physical activity in older adults, although more interventional studies with long term follow-up are needed, particularly for GAPPA 1. Active Societies and GAPPA 2. Active Environments. By comparison, there is abundant evidence for GAPPA 3. specific programmes and services, but coverage of sport and workplace interventions, and diverse samples and settings is lacking. Comprehensive reviews of individual studies are now needed as well as research targeting neglected outcomes, populations and settings.

Production, characterization, and immobilization of protease from the yeast Rhodotorula oryzicola.

The protease was produced extracellularly in submerged fermentation by the yeast Rhodotorula oryzicola using different sources of nitrogen and maximum activity (6.54 × 10-3 U/mg) was obtained in medium containing 2% casein (w/v). Purification of the protease by gel filtration chromatography resulted in a 3.07-fold increase of specific protease activity. The optimal pH and temperature for enzyme activity were 6.51 and 63.04 °C, respectively. Incubation in the presence of some salts enhanced enzyme activity, which peaked under 0.01 M BaCl2 . The enzyme retained about 90% of enzymatic activity at temperatures 50-60 °C. The commercially available enzyme carriers evaluated, silica gel, Celite 545, and chitosan effectively immobilized the protease. The enzyme immobilized in Celite 545 retained 73.53% of the initial activity after 15 reuse cycles. These results are quite promising for large-scale production and immobilization of protease from R. oryzicola, as the high operational stability of the immobilized enzyme lowers production costs in biotechnological applications that require high enzymatic activity and stability under high temperatures.

Dietary patterns and chronic kidney disease outcomes: A systematic review.

Chronic kidney disease (CKD) is a serious public health problem and its prevalence is growing in many countries, often related to issues resulting from the lifestyle in growing economies and the population's life expectancy. Nutritional therapy is a beneficial but still neglected strategy for preventing CKD and delaying disease progression. The aim of this study was to assess the association of dietary patterns with CKD development and progression. Observational studies conducted in adult humans and the correlation between the adopted dietary pattern and prevalent and incident cases of CKD were assessed. A significant association was observed between unhealthy dietary patterns and an increased risk of developing or worsening CKD, as well as an adverse effect. Whereas healthy eating patterns characterized by the consumption of fruit, vegetables and dietary fibre showed nephroprotective outcomes.

Preclinical safety assessment of the crude extract from Sida rhombifolia L. aerial parts in experimental models of acute and repeated-dose 28 days toxicity in rats.

Sida rhombifolia (Malvaceae) is popularly used as a treatment for several pathological conditions; however, there is a lack of studies that identify its compounds and that evaluate comprehensively the safety of its consumption. Therefore, the aim of this study was to determinate the phytochemical constitution of the crude extract of Sida rhombifolia (CESR), and its safety in models of acute and repeated doses (28 days) toxicity. The tested dose for the model of acute toxicity was 2000 mg/kg doses for the repeated dose model were 150, 300 e 600 mg/kg. Hematological, biochemical, histopathological and oxidative markers were investigated. HPLC-DAD-MS analysis evidenced the presence of caffeic acid, coumarin, and rutin. In the acute toxicity model the only altered parameters were tissue ROS, and AST and BUN in serum. As for the repeated dose experiment both hematological and biochemical markers remained within the values of reference for the species. Obtained results demonstrate that the CESR did not present significant toxic effects when administrated orally to male and female rats in acute and repeated doses.

Lipotoxicity-associated inflammation is prevented by guarana (Paullinia cupana) in a model of hyperlipidemia.

Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.