Obesity and Nutrigenetics Testing: New Insights.

BACKGROUND: Obesity results from interactions between environmental factors, lifestyle, and genetics. In this scenario, nutritional genomics and nutrigenetic tests stand out, with the promise of helping patients avoid or treat obesity. This narrative review investigates whether nutrigenetic tests may help to prevent or treat obesity. Scientific studies in PubMed Science Direct were reviewed, focusing on using nutrigenetic tests in obesity. The work showed that few studies address the use of tools in obesity. However, most of the studies listed reported their beneficial effects in weight loss. Ethical conflicts were also discussed, as in most countries, there are no regulations to standardize these tools, and there needs to be more scientific knowledge for health professionals who interpret them. International Societies, such as the Academy of Nutrition and Dietetics and the Brazilian Association for the Study of Obesity and Metabolic Syndrome, do not recommend nutrigenetic tests to prevent or treat obesity, especially in isolation. Advancing nutrigenetics depends on strengthening three pillars: regulation between countries, scientific evidence with clinical validity, and professional training.

Innovative Biomedical and Technological Strategies for the Control of Bacterial Growth and Infections.

Antibiotics comprise one of the most successful groups of pharmaceutical products. Still, they have been associated with developing bacterial resistance, which has become one of the most severe problems threatening human health today. This context has prompted the development of new antibiotics or co-treatments using innovative tools to reverse the resistance context, combat infections, and offer promising antibacterial therapy. For the development of new alternatives, strategies, and/or antibiotics for controlling bacterial growth, it is necessary to know the target bacteria, their classification, morphological characteristics, the antibiotics currently used for therapies, and their respective mechanisms of action. In this regard, genomics, through the sequencing of bacterial genomes, has generated information on diverse genetic resources, aiding in the discovery of new molecules or antibiotic compounds. Nanotechnology has been applied to propose new antimicrobials, revitalize existing drug options, and use strategic encapsulating agents with their biochemical characteristics, making them more effective against various bacteria. Advanced knowledge in bacterial sequencing contributes to the construction of databases, resulting in advances in bioinformatics and the development of new antimicrobials. Moreover, it enables in silico antimicrobial susceptibility testing without the need to cultivate the pathogen, reducing costs and time. This review presents new antibiotics and biomedical and technological innovations studied in recent years to develop or improve natural or synthetic antimicrobial agents to reduce bacterial growth, promote well-being, and benefit users.

Assessment of acute toxicity of crude extract rich in carotenoids from Cantaloupe melon (Cucumis melo L.) and the gelatin-based nanoparticles using the zebrafish (Danio rerio) model.

Cantaloupe melon is known for its carotenoid-rich orange pulp. However, carotenoids are sensitive to oxygen, light, and heat, potentially reducing their benefits. Nanoencapsulation can preserve these benefits but raises concerns about toxicity. We aimed to assess the safety and bioactive potential of crude extract-rich carotenoids (CE) and nanoparticles based on gelatin loaded with CE (EPG) by investigating parameters such as cardio or neurotoxicity, especially acute toxicity. EPG was obtained by O/W emulsification and characterized by different methods. Zebrafish embryos were exposed to CE and EPG at 12.5 mg/L and 50 mg/L for 96h and were investigated for survival, hatching, malformations, and seven days post fertilization (dpf) larvae's visual motor response. Adult fish underwent behavioral tests after acute exposure of 96h. CE and EPG showed no acute toxicity in zebrafish embryos, and both improved the visual motor response in 7dpf larvae (p = 0.01), suggesting the potential antioxidant and provitamin A effect of carotenoids in cognitive function and response in the evaluated model. Adult fish behavior remained with no signs of anxiety, stress, swimming pattern changes, or sociability that would indicate toxicity. This study highlights the safety and potential benefits of carotenoids in zebrafish. Further research is needed to explore underlying mechanisms and long-term effects.

Prospecting native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds.

The study aimed to prospect in silico native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds (TTIp). From the most stable theoretical model of TTIp (TTIp 56/287), in silico cleavage was performed for the theoretical identification of native peptides and generation of analogous peptides. The anti-SARS-CoV-2 potential was investigated through molecular dynamics (MD) simulation between the peptides and binding sites of transmembrane serine protease 2 (TMPRSS2), responsible for the entry of SARS-CoV-2 into the host cell. Five native and analogous peptides were obtained and validated through chemical and physical parameters. The best interaction potential energy (IPE) occurred between TMPRSS2 and one of the native peptides obtained by cleavage with trypsin and its analogous peptide. Thus, both peptides showed many hydrophobic residues, a common physical-chemical property among the peptides that inhibit the entry of enveloped viruses, such as SARS-CoV-2, present in specific drugs to treat COVID-19.

In silico structure-based design of peptides or proteins as therapeutic tools for obesity or diabetes mellitus: A protocol for systematic review and meta analysis.

BACKGROUND: In silico studies using dynamic simulation or molecular docking have boosted the screening and identification of molecules and/or targets in studies aimed at treating diseases such as obesity and diabetes mellitus, optimizing the development of new drugs. This study aims to describe a systematic review protocol on peptides and proteins evaluated in silico as potential therapeutic agents for obesity or diabetes mellitus. METHODS: This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols and was registered in the International Prospective Register of Systematic Reviews database (number: CRD42022355540). The databases to be searched will be PubMed, ScienceDirect, Scopus, Web of Science, virtual health library, and EMBASE. It will be included in silico studies that evaluate the simulation by dynamics or molecular docking of proteins or peptides involved in treating obesity or diabetes mellitus. Two independent reviewers will select studies, extract data, and assess methodological quality using the adapted Strengthening the reporting of empirical simulation studies. A narrative synthesis of the included studies will be performed for the systematic reviews. RESULTS: This protocol contemplates the production of 2 systematic reviews to be developed focusing on obesity or diabetes mellitus. CONCLUSION: The reviews will enable knowledge of peptides and proteins involved in research treating these diseases and will emphasize the importance of in silico studies in this context and for the development of future studies.

Prospecting in silico antibacterial activity of a peptide from trypsin inhibitor isolated from tamarind seed.

Bacterial infections have become a global concern, stimulating the growing demand for natural and biologically safe therapeutic agents with antibacterial action. This study was evaluated the genotoxicity of the trypsin inhibitor isolated from tamarind seeds (TTI) and the antibacterial effect of TTI theoric model, number 56, and conformation number 287 (TTIp 56/287) and derived peptides in silico. TTI (0.3 and 0.6 mg.mL-1) did not cause genotoxicity in cells (p > 0.05). In silico, a greater interaction of TTIp 56/287 with the Gram-positive membrane (GP) was observed, with an interaction potential energy (IPE) of -1094.97 kcal.mol-1. In the TTIp 56/287-GP interaction, the Arginine, Threonine (Thr), and Lysine residues presented lower IPE. In molecular dynamics (MD), Peptidotrychyme59 (TVSQTPIDIPIGLPVR) showed an IPE of -518.08 kcal.mol-1 with the membrane of GP bacteria, and the Thr and Arginine residues showed the greater IPE. The results highlight new perspectives on TTI and its derived peptides antibacterial activity.

In silico structure-based designers of therapeutic targets for diabetes mellitus or obesity: A protocol for systematic review.

Obesity is a significant risk factor for several chronic non-communicable diseases, being closely related to Diabetes Mellitus. Computer modeling techniques favor the understanding of interaction mechanisms between specific targets and substances of interest, optimizing drug development. In this article, the protocol of two protocols of systematic reviews are described for identifying therapeutic targets and models for treating obesity or diabetes mellitus investigated in silico. The protocol is by the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P) and was published in the International Prospective Register of Systematic Reviews database (PROSPERO: CRD42022353808). Search strategies will be developed based on the combination of descriptors and executed in the following databases: PubMed; ScienceDirect; Scopus; Web of Science; Virtual Health Library; EMBASE. Only original in silico studies with molecular dynamics, molecular docking, or both will be inserted. Two trained researchers will independently select the articles, extract the data, and assess the risk of bias. The quality will be assessed through an adapted version of the Strengthening the Reporting of Empirical Simulation Studies (STRESS) and the risk of bias using a checklist obtained from separate literature sources. The implementation of this protocol will result in the elaboration of two systematic reviews identifying the therapeutic targets for treating obesity (review 1) or diabetes mellitus (review 2) used in computer simulation studies and their models. The systematization of knowledge about these treatment targets and their in silico structures is fundamental, primarily because computer simulation contributes to more accurate planning of future either in vitro or in vivo studies. Therefore, the reviews developed from this protocol will guide decision-making regarding the choice of targets/models in future research focused on therapeutics of obesity or Diabetes Mellitus contributing to mitigate of factors such as costs, time, and necessity of in vitro and/or in vivo assays.

Intestinal Barrier Permeability in Obese Individuals with or without Metabolic Syndrome: A Systematic Review.

Altered intestinal barrier permeability has been associated with obesity and its metabolic and inflammatory complications in animal models. The purpose of this systematic review is to assess the evidence regarding the association between obesity with or without Metabolic Syndrome (MetS) and alteration of the intestinal barrier permeability in humans. A systematic search of the studies published up until April 2022 in Latin America & Caribbean Health Sciences Literature (LILACS), PubMed, Scopus, Embase, and ScienceDirect databases was conducted. The methodological quality of the studies was assessed using the Newcastle-Ottawa scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of the evidence. Eight studies were included and classified as moderate to high quality. Alteration of intestinal barrier permeability was evaluated by zonulin, lactulose/mannitol, sucralose, sucrose, lactulose/L-rhamnose, and sucralose/erythritol. Impaired intestinal barrier permeability measured by serum and plasma zonulin concentration was positively associated with obesity with MetS. Nonetheless, the GRADE assessment indicated a very low to low level of evidence for the outcomes. Thus, clear evidence about the relationship between alteration of human intestinal barrier permeability, obesity, and MetS was not found.

Anti-inflammatory agents as modulators of the inflammation in adipose tissue: A systematic review.

Obesity is characterized by an adipose tissue mass expansion that presents a risk to health, associated with a chronic increase in circulating inflammatory mediators. Anti-inflammatory agents are an obesity alternative treatment. However, the lack of effective agents indicates the need to assess the mechanisms and identify effective therapeutic targets. The present work identified and described the mechanisms of action of anti-inflammatory agents in adipose tissue in experimental studies. The review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO-CRD42020182897). The articles' selection was according to eligibility criteria (PICOS). The research was performed in PubMed, ScienceDirect, Scopus, Web of Science, VHL, and EMBASE. The methodological quality evaluation was assessed using SYRCLE. Initially, 1511 articles were selected, and at the end of the assessment, 41 were eligible. Among the anti-inflammatory agent classes, eight drugs, 28 natural, and five synthetic compounds were identified. Many of these anti-inflammatory agents act in metabolic pathways that culminate in the inflammatory cytokines expression reduction, decreasing the macrophages infiltration in white and adipose tissue and promoting the polarization process of type M1 to M2 macrophages. Thus, the article clarifies and systematizes these anti-inflammatory agents' mechanisms in adipose tissue, presenting targets relevant to future research on these pathways.

Mechanisms of action of anti-inflammatory proteins and peptides with anti-TNF-alpha activity and their effects on the intestinal barrier: A systematic review.

Several studies in animal models of intestinal inflammation have been performed with the aim of understanding the mechanisms of action of anti-inflammatory proteins and peptides that reduce TNF-α. In order to present the best targets, effects and strategies for the treatment of intestinal inflammation in experimental models, this systematic review (SR) aimed to answer the following question: what are the mechanisms of action of molecules with anti-TNF-α activity on the intestinal barrier? The SR protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, number CRD42019131862) and guided by the methodological procedures used for the elaboration of the SR. Articles that were part of the SR were selected considering the eligibility criteria according to the PICO (Population, Intervention, Comparison/Control and Outcomes) and were searched in the PubMed, Scopus, Web of Science, Excerpta Medica Database (EMBASE) and ScienceDirect databases. Twenty-five articles reporting studies in rats and mice were selected and the risk of bias was assessed using the tool from the SYstematic Review Center for Laboratory Animal Experimentation (SYRCLE). A descriptive synthesis of the results obtained was carried out. Based on the results, the anti-inflammatory molecules that reduced TNF-α acted mainly on the TNF-TNFR1/TNFR2 and TLR4/MD2 complex signaling pathways, and consequently on the NF-κB pathway. This improved the aspects of the inflammatory diseases studied. In addition, these mechanisms also improved the macroscopic, histological and permeability aspects in the intestine of the animals. These findings point to the potential of protein and peptide molecules that act on inflammatory pathways for medical applications with specific and promising strategic targets, aiming to improve inflammatory diseases that affect the intestine. This systematic review also highlights the need for more details during the methodological description of preclinical studies, since this was a limitation found.

Antioxidant stability enhancement of carotenoid rich-extract from Cantaloupe melon (Cucumis melo L.) nanoencapsulated in gelatin under different storage conditions.

The study evaluated the potential and antioxidant stability of nanoencapsulated carotenoid-rich extract (CE) from Cantaloupe melon (EPG). DPPH and ABTS radical scavenging assays were used to investigate the nanoencapsulation effect on antioxidant potential. CE and EPG stability were evaluated at 25 °C and 5 °C, with and without light (1600 lx) for 60 days, determining the ß-carotene concentration by UHPLC and antioxidant potential by ABTS. The antioxidant potential of carotenoids increased after nanoencapsulation (57-59%). After 60 days, there was low retention of ß-carotene (0-43.6%) in the CE, mainly at 25 °C light (0.00%) and dark (10.0%), and total loss of activity in the four conditions. EPG preserved the ß-carotene concentration in the dark at 25 °C (99.0%) and in the light (83.1%) and dark (99.0%) at 5 °C, maintaining the antioxidant potential (68.7-48.3%). Therefore, EPG enhanced and stabilized the antioxidant potential of carotenoids, beneficial to human health.

Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognised by the WHO as a pandemic in 2020. Host preparation to combat the virus is an important strategy to avoid COVID-19 severity. Thus, the relationship between eating habits, nutritional status and their effects on the immune response and further implications in viral respiratory infections is an important topic discussed in this review. Malnutrition causes the most diverse alterations in the immune system, suppressing of the immune response and increasing the susceptibility to infections such as SARS-CoV-2. On the other hand, obesity induces low-grade chronic inflammation caused by excess adiposity, which increases angiotensin-converting enzyme 2. It decreases the immune response favouring SARS-CoV-2 virulence and promoting respiratory distress syndrome. The present review highlights the importance of food choices considering their inflammatory effects, consequently increasing the viral susceptibility observed in malnutrition and obesity. Healthy eating habits, micronutrients, bioactive compounds and probiotics are strategies for COVID-19 prevention. Therefore, a diversified and balanced diet can contribute to the improvement of the immune response to viral infections such as COVID-19.

Obesity and the increased risk for COVID-19: mechanisms and nutritional management.

The global COVID-19 (coronavirus disease 2019) pandemic has become a complex problem that overlaps with a growing public health problem, obesity. Obesity alters different components of the innate and adaptive immune responses, creating a chronic and low-grade state of inflammation. Nutritional status is closely related to a better or worse prognosis of viral infections. Excess weight has been recognised as a risk factor for COVID-19 complications. In addition to the direct risk, obesity triggers other diseases such as diabetes and hypertension, increasing the risk of severe COVID-19. The present review explains the diets that induce obesity and the importance of different foods in this process. We also review tissue disruption in obesity, leading to impaired immune responses and the possible mechanisms by which obesity and its co-morbidities increase COVID-19 morbidity and mortality. Nutritional strategies that support the immune system in patients with obesity and with COVID-19 are also discussed in light of the available data, considering the severity of the infection. The discussions held may contribute to combating this global emergency and planning specific public health policy.

Mechanisms of action of molecules with anti-TNF-alpha activity on intestinal barrier inflammation: A systematic review protocol.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), among cytokines that mediate the inflammatory process, plays an important role in diseases involving the loss of intestinal barrier integrity. Several molecules with anti-TNF-alpha activity have been studied aiming to develop new therapies. The purpose of this paper is to describe the systematic review protocol of experimental studies that determine mechanisms of action of molecules with anti-TNF-alpha activity on intestinal barrier inflammation. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P). The databases to be searched are PubMed, EMBASE, Scopus, ScienceDirect, and Web of Science. Experimental studies in rats or mice that assessed the activity of anti-TNF-alpha molecules in models of intestinal barrier inflammation will be included in the systematic review. Studies characteristics, experimental model, and main results will be described and the bias risk assessment will be performed. Two independent reviewers will perform study selection, data extraction, and methodological quality assessment. A narrative synthesis will be made for the included studies. Also, if sufficient data is available, a meta-analysis will be conducted. I statistics will be used to assess heterogeneity. RESULTS: The present protocol will assist in producing a systematic review that identifies the mechanisms underlying the reduction of TNF-alpha in intestinal barrier inflammation models. CONCLUSION: The systematic review may contribute to the theoretical basis of research on new molecules with anti-TNF-alpha potential and, consequently, in the development of new therapies employed in humans. PROSPERO REGISTRATION NUMBER: CRD42019131862.

Mechanism of the action of bioactive proteins of vegetables in diabetes mellitus type 2: Systematic review protocol.

BACKGROUND: Diabetes mellitus type 2 (DM2) is a chronic disease of significant prevalence causing hyperglycemia and several comorbidities. Evidences highlight the performance of non - protein bioactive compounds found in vegetables in the control of hyperglycemia. This study describes a protocol of a systematic review, which analyzes the action of proteins and bioactive peptides of plants in DM2. METHODS: The Preferred Reporting Items guide this protocol for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P) was used. The databases that will be used for searching will be PubMed, ScienceDirect, Scopus, Web of Science, EMBASE, and Virtual Health Library, Brazil (VHL). Studies that use bioactive proteins and peptides of vegetal origin in DM2 will be included in the systematic review. The studies will be identified using clinical parameters and the effect on insulin resistance. The characteristics of the studies as control groups, test substance, dosage, intervention time, and the main results will be described. Selection of studies, data extraction, and methodological quality assessment will be performed independently by two experienced reviewers. RESULTS: This protocol will be the basis for a systematic review identifying the mechanism of action of plant proteins and peptides in type 2 diabetes mellitus. CONCLUSION: Systematic reviews from this protocol will provide support for the construction of researches that analyze the effect of plant bioactive proteins and peptides on the control of hyperglycemia and how these molecules act in the control of DM2. PROSPERO REGISTRATION NUMBER: CRD42019110956.

Nanoencapsulation improved water solubility and color stability of carotenoids extracted from Cantaloupe melon (Cucumis melo L.).

Cantaloupe melon carotenoids were encapsulated in porcine gelatin, whey protein isolate and concentrate by emulsification O/W to evaluate which agent could promote an increase in water solubility, and color stability in yogurt. The average particle size obtained was 59.3 (2.60) nm-161.0 (27.30) nm. Encapsulated crude extract in porcine gelatin presented the smallest size and polydispersity index [0.4 (0.04)], and showed sphericity, smooth surface and low agglomeration in SEM. These results associated to the good chemical interaction between the raw materials shown by FTIR, justify the increase in water solubility [0.072 (0.007) mg.mL-1] compared to the crude extract [0.026 (0.003) mg.mL-1]. The yogurt added with this nanoencapsulate remained stable for 60 days, unlike the crude extract. The results show that the nanoencapsulation using gelatin increased water solubility and the potential of application of melon carotenoids in food as natural dyes.

Biochemical characterisation of a Kunitz-type inhibitor from Tamarindus indica L. seeds and its efficacy in reducing plasma leptin in an experimental model of obesity.

A trypsin inhibitor isolated from tamarind seed (TTI) has satietogenic effects in animals, increasing the cholecystokinin (CCK) in eutrophy and reducing leptin in obesity. We purified TTI (pTTI), characterised, and observed its effect upon CCK and leptin in obese Wistar rats. By HPLC, and after amplification of resolution, two protein fractions were observed: Fr1 and Fr2, with average mass of [M + 14H]+ = 19,594,690 Da and [M + 13H]+ = 19,578,266 Da, respectively. The protein fractions showed 54 and 53 amino acid residues with the same sequence. pTTI presented resistance to temperature and pH variations; IC50 was 2.7 × 10-10 mol.L-1 and Ki was 2.9 × 10-11 mol.L-1. The 2-DE revealed spots with isoelectric points between pH 5 and 6, and one near pH 8. pTTI action on leptin decrease was confirmed. We conclude that pTTI is a Kunitz trypsin inhibitor with possible biotechnological health-related application.

Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels.

OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30-60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated.

Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels

OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30-60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated. .