Physiological Mechanisms Of Action Research Articles

Physiological mechanism of action and partial separation of herbicide–active compounds from the Diaporthe sp. extract on Amaranthus tricolor L.

Thirteen fungi that produce compounds with herbicidal activities were isolated, identified, and extracted under the assumption that the mechanism of action occurs during seed exposure to the extract. The extracts from all the fungal strains considerably decreased the growth parameters of Amaranthus tricolor L. The EC010 strain extracts showed the greatest effect. Through ITS region gene sequencing methods, the isolated EC010 was identified as a genus of Diaporthe. The results showed a significant (p < 0.05) inhibitory effect of 91.25% on germination and a decrease in shoot and root length by 91.28% and 95.30%, respectively. The mycelium of Diaporthe sp. was extracted using sequential extraction techniques for the partial separation of the herbicidal fraction. According to the bioassay activities, the EtOAc fraction showed the highest inhibitory activity. The osmotic stress of the A. tricolor seeds was studied. Although the extract increased the accumulation of proline and soluble protein, the treated seeds showed lower imbibition. While the activity of α-amylase was dramatically decreased after treatment. A cytogenetic assay in the treated Allium cepa L. root revealed a decrease in the mitotic index, an altered mitotic phase index, and a promotion of mitotic abnormalities. Accordingly, the Diaporthe sp. may serve as a potential herbicidal compound resource.

Tangeretin-a special polymethoxyflavones: An insight into its pharmacological and therapeutic effects on diabetes

With global diabetes complication growing rapidly at an alarming rate each year, there is an increasing need to find suitable therapeutics for its management, regulation, and treatment which is cost-effective, safe, and naturally available. Continued dependence only on the available synthetic drug is not a solution. Therefore, there is a need to find suitable natural adjuncts to help manage diabetes. Flavonoids are a class of compounds that have been utilized for therapeutic purposes for generations due to their wide and varied pharmacological properties. One such important naturally available flavonoid is tangeretin belonging to a special class of methylated flavonoids found mostly only in citrus fruits. It is reported to possess a lot of pharmaceutic activities, and thus in this brief review, we elucidate its specific importance in the attenuation of diabetic and diabetes-related complications to get a better understanding of its physiological mechanism of action in the context relating to diabetes.

Recent advances in diverse nanosystems for nitric oxide delivery in cancer therapy.

Gas therapy has been proven to be a promising and advantageous treatment option for cancers. Studies have shown that nitric oxide (NO) is one of the smallest structurally significant gas molecules with great potential to suppress cancer. However, there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor. Therefore, the anti-cancer mechanism of NO is the key to cancer treatment, and rationally designed NO delivery systems are crucial to the success of NO biomedical applications. This review summarizes the endogenous production of NO, its physiological mechanisms of action, the application of NO in cancer treatment, and nano-delivery systems for delivering NO donors. Moreover, it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies. The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

Comparison of characteristics between peptides in fish meat and fermented products

In the pasca of the COVID-19 pandemic, many researchers have focused on finding drugs for the COVID-19. Peptide research is predicted to have a physiological mechanism of action and it does not cause side effects, therefore it is necessary to search for peptide sources. The aim of this study was to characterize peptides extracted from tamban fish (Sardinella fimbriata) and fermented products (Cincalok of Tanjungpinang). Peptide extract was obtained by maceration extraction using 95% PA (1:5) ethanol solvent, and then it filtered using MWCO 3 kDa and 10 kDa. The amino acid characteristics of the peptides was obtained using HPLC. Peptides of tamban fish had the pH of 7.6 and they are rich of amino acid histidine (890.18 mg/L), in addition to the amino acids glutamate, tyrosine, glycine, leucine, alanine, and aspartic acid. But the peptides of the fermented cincalok product had the pH of 6.4 and they are rich of amino acid leucine (1066.83 mg/L), in addition to the amino acids glutamate, valine, isoleucine, and alanine. Each of these peptides had the molecular weight of 10 kDa. The results of this study can be used as preliminary information to the pharmaceutical development of a new source of peptides.

MEDICINAL PLANTS OF THE AQUATIC FLORA OF THE POLTAVA CITY AND SURROUNDING AREA

The article is devoted to the generalization of literary data on the medicinal properties of plants of aquatic flora of the territory of the Poltava city and its surroundings, studied in the course of original research. From the compiled floristic list, a spectrum of medicinal plants was selected, their degree of introduction into medical practice, belonging to protected lists, frequency of occurrence in the study area was analyzed. It was established that 45 (78%) of the 58 species of vascular plants have medicinal properties, including 4 species are officinal, 18 species are folk medicine plants, 23 species are promising for use in pharmacy. For each species, an annotation of its medicinal properties is compiled, which indicates the type of medicinal raw materials and medicinal forms, chemical composition, directions and mechanisms of physiological action on the human body, indications for the use of medicinal preparations.&#x0D; It was found that, despite the high participation of medicinal plants in the aquatic flora of the Poltava city and its surroundings, their harvesting in the research area is not appropriate for various reasons: official species (Acorus calamus, Iris pseudacorus, Nuphar lutea, Nymphaea alba) – because of their limited distribution, belonging to various protection lists, and as for mass anthropotolerant species, promising for use in pharmacy (in particular, Ceratophyllum demersum, Lemna minor, Phragmites australis, Typha angustifolia, T. latifolia), their use is limited due to the ability to accumulate harmful substances from polluted ecotopes in urban territory.&#x0D; The compromise solutions for harvesting valuable species of medicinal plants that have a limited distribution in nature or grow in polluted ecotopes can be introduction (artificial cultivation of plants ex situ) and biotechnology (cultivation of cells, tissues and organs isolated from the plant on artificial nutrient media in vitro, which allow obtaining a specific target product).

IBCOx-12 The Endoscopic Sleeve Gastroplasty Produces Durable Physiologic Changes: Results from a Randomized US Clinical Trial

Abstract Background Obesity is associated with faster gastric emptying and altered appetite. Endoscopic sleeve gastroplasty (ESG) has gained global adaptation, but our understanding of its physiologic mechanism of action and durability is limited. We sought to determine changes in gastric emptying, weight loss, and eating behaviors after ESG when compared to moderate-intensity lifestyle interventions (LS) in the short and long-term. Methods This is an a priori designed sub-study of a large ongoing multicenter US RCT (MERIT trial), where adults with BMI 30-40 kg/m2 were randomized to ESG versus moderate-intensity LS alone. We measured gastric emptying (T1/2) using a 4- hour gastric emptying breath test at baseline, 3 and 12 months into the study. We reported weight loss outcomes as percent total body weight lost (%TBWL). Changes in three eating behaviour domains (Cognitive Restraint [CR], Emotional Eating [EE], Uncontrolled Eating [UE]) were assessed using the Three-Factor Eating Questionnaire (TFEQ) at 6 months. The primary outcome was the change in T1/2 (minutes) at 3 months, and secondary outcomes were changes in T1/2 at 12 months, %TBWL, and eating behaviours. We used the t-test for the analyses. Linear regression was performed to determine the association between gastric emptying and weight loss. Results 46 patients were randomized in the study (ESG n=26; LS n=20). Baseline characteristics were similar between the two groups. Out of n=46, n=43, and n=31 subjects have reached 3 and 12 months, respectively. Three patients dropped out of the study. At 3 months, T1/2 (minutes) was delayed in the ESG group (n=24) compared to the LS group (n=19) (170.8 vs. 87.5; p&amp;lt;0.0001). At 12 months, T1/2 was still delayed in the ESG group (n=17) vs. control group (n=14) (133.4 vs. 87.6; p=0.0005), and delayed compared to baseline. %TBWL in the ESG group was 12.3%, 15.1% and 15.7% at 3, 6 and 12 months (p &amp;lt;0.01 compared to baseline), while it was 2.3%, 2.2% and 0.3% (p&amp;gt;0.05 compared to baseline) in the LS group. Greater delays in gastric emptying at 3 months correlated with weight loss at all time points. (Figure 1) At 6 months, significant improvements in the EE and UE domains were seen in both groups, but for CR, only significant improvements were seen in the ESG group. Percent total fasting ghrelin, GLP-1, and PYY increased at 12 months in the ESG group compared to LS control (51%, 51%, 6.3% vs. -9%, 4%, -10.5%). Only 1 SAE managed endoscopically with full recovery was reported in the ESG group. Conclusions ESG produces sustained physiologic alterations in appetite regulatory pathways and durable weight-loss. This provides further evidence supporting the clinical adoption of the technique as a durable and effective obesity therapy.

The insertion/deletion in the DNA-binding region allows the discrimination and subsequent identification of the glucocorticoid receptor 1 (gr1) and gr2 nucleotide sequences in gilthead sea bream (Sparus aurata): Standardizing the gr nomenclature for a better understanding of the stress response in teleost fish species

Cortisol carries out its physiological mechanism of action through the recognition by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) 1 (GR1) and GR2. Previous studies reported that the main difference between gr1 and gr2 nucleotide sequences resides in a 27-nucleotide insertion/deletion in the DNA-binding region, respectively. However, in gilthead sea bream (Sparus aurata) the annotation for gr1 and gr2 seems contradictory. The gr2 sequence possesses the characteristic 27-nucleotide insertion that, in fact, is associated with the gr1 nucleotide sequence. Thus, this study aimed to elucidate the nucleotide sequences for the gr1 and gr2 in gilthead sea bream. The Clustal Omega alignment for different fish species corroborated the presence of such 27-nucleotide insertion/deletion in the DNA-binding region for gr1 and gr2, respectively. Then, we design specific primers set for the amplification of the gilthead sea bream gr1 by polymerase chain reaction (PCR). Importantly, the gr1 nucleotide partial sequence has a high similarity with other gr1 sequences already published for other fish species, being present in all of them the 27-nucleotide insertion in the DNA-binding region. We also detected that in European sea bass the gr1 and gr2 sequences had not been named according to the 27-nucleotide insertion/deletion criteria in the DNA-binding region. Thus, our study makes an urgent call to the scientific community to discuss the establishment of an updated agreement that allows homogenizing the criteria for the nomenclature defining the gr1 and gr2 nucleotide sequences for a better understanding of the stress response in teleost fish species.

Evidence-Based Clinical Guidelines from the American Society of Pain and Neuroscience for the Use of Implantable Peripheral Nerve Stimulation in the Treatment of Chronic Pain.

The objective of this peripheral nerve stimulation consensus guideline is to add to the current family of consensus practice guidelines and incorporate a systematic review process. The published literature was searched from relevant electronic databases, including PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from database inception to March 29, 2021. Inclusion criteria encompassed studies that described peripheral nerve stimulation in patients in terms of clinical outcomes for various pain conditions, physiological mechanism of action, surgical technique, technique of placement, and adverse events. Twenty randomized controlled trials and 33 prospective observational studies were included in the systematic review process. There is Level I evidence supporting the efficacy of PNS for treatment of chronic migraine headaches via occipital nerve stimulation; chronic hemiplegic shoulder pain via stimulation of nerves innervating the trapezius, supraspinatus, and deltoid muscles; failed back surgery syndrome via subcutaneous peripheral field stimulation; and lower extremity neuropathic and lower extremity post-amputation pain. Evidence from current Level I studies combined with newer technologies facilitating less invasive and easier electrode placement make peripheral nerve stimulation an attractive alternative for managing patients with complex pain disorders. Peripheral nerve stimulation should be used judiciously as an adjunct for chronic and acute postoperative pain following adequate patient screening and positive diagnostic nerve block or stimulation trial.

Comparing systemic inflammation in pregnancy for patients participating in group versus individual prenatal care

Group Prenatal Care (GPNC) has been associated with improved birth outcomes when compared to Individual Prenatal Care (IPNC) particularly for Black patients, though the physiologic mechanisms of action are unclear. Inflammation may contribute to earlier delivery and fetal growth restriction. Our objective was to examine whether GPNC was associated with reduced maternal inflammation during gestation.

Postoperative Use of Blood Flow Restriction in Orthopedics.

Blood flow restriction (BFR) therapy is being used more frequently for rehabilitation from orthopedic injuries. Several physiologic mechanisms of action, at local and systemic levels, have been proposed. Numerous studies have investigated the effects of BFR training in healthy athletes; however, limited clinical data exist supporting the use of BFR after surgery. Given that BFR training may facilitate muscle development using low-load resistance exercises, it offers a unique advantage for the post-surgical patient who cannot tolerate traditional high resistance training. [Orthopedics. 2021;44(6):e694-e698.].

Мультипотентный гепатопротектор Ларнамин в клинической практике

В статье проанализирована литература о физиологических механизмах действия и доказательной базе L-орнитин-L-аспартата — действующего вещества препарата Ларнамин. Продемонстрированы многогранные свойства препарата: дезинтоксикационное, анаболическое, гепатопротекторное, вазодилатирующее, способность стимулировать продукцию соматотропного гормона и инсулина. Описаны результаты клинических исследований, подтверждающие эффективность L-орнитин-L-аспартата при печеночной энцефалопатии, хронических диффузных заболеваниях печени, в т.ч. при алкогольной и неалкогольной жировой болезни печени. Препарат эффективен также при остром панкреатите, алкогольной интоксикации. Переносимость препарата удовлетворительная, вероятность и выраженность побочных эффектов минимальны.

Capsaicinoid and Capsinoids as an Ergogenic Aid: A Systematic Review and the Potential Mechanisms Involved.

Capsaicinoids and capsinoids (CAP) are natural substances found primarily in chili peppers and other spicy foods that agonize the transient receptor potential vanilloid-1 in the mouth, stomach, and small intestine. Several studies have shown CAP to be a potential antiobesity agent and to exhibit an analgesic effect in both rodents and humans. However, there is no scientific consensus about the effects of CAP on physical exercise performance and its physiological mechanisms of action. This systematic review aimed to better elucidate the effects of CAP compounds as ergogenic aids and to discuss underlying mechanisms of action by which this supplement may potentially enhance endurance performance and muscular strength. Among 22 studies included in the review, 14 examined the effects of capsaicinoid or capsinoid compounds on endurance and resistance exercise performance in animals, with 9 studies showing benefits on performance. In humans, 8 studies were included: 3 demonstrated significant acute endurance benefits and 2 showed acute resistance exercise performance benefits compared with a placebo condition. Therefore, while more mechanistic studies are necessary to confirm these outcomes in humans, the available scientific literature appears to suggest that these compounds could be considered an effective nutritional strategy to improve exercise performance.

Study Protocol: The Coaching Alternative Parenting Strategies (CAPS) Study of Parent-Child Interaction Therapy in Child Welfare Families.

BackgroundChild maltreatment (CM) constitutes a serious public health problem in the United States with parents implicated in a majority of physical abuse and neglect cases. Parent-Child Interaction Therapy (PCIT) is an intensive intervention for CM families that uses innovative “bug-in-ear” coaching to improve parenting and child outcomes, and reduce CM recidivism; however, the mechanisms underlying its effects are little understood. The Coaching Alternative Parenting Strategies (CAPS) study aims to clarify the behavioral, neural, and physiological mechanisms of action in PCIT that support positive changes in parenting, improve parent and child self-regulation and social perceptions, and reduce CM in child welfare-involved families.MethodsThe CAPS study includes 204 child welfare-involved parent-child dyads recruited from Oregon Department of Human Services to participate in a randomized controlled trial of PCIT versus a services-as-usual control condition (clinicaltrials.gov, NCT02684903). Children ages 3–8 years at study entry and their parents complete a pre-treatment assessment prior to randomization and a post-treatment assessment 9–12 months post study entry. Dyads randomized to PCIT complete an additional, abbreviated assessment at mid-treatment. Each assessment includes individual and joint measures of parents’ and children’s cardiac physiology at rest, during experimental tasks, and in recovery; observational coding of parent-child interactions; and individual electroencephalogram (EEG) sessions including attentional and cognitive control tasks. In addition, parents and children complete an emotion regulation task and parents report on their own and their child’s adverse childhood experiences and socio-cognitive processes, while children complete a cognitive screen and a behavioral measure of inhibitory control. Parents and children also provide anthropometric measures of allostatic load and 4–5 whole blood spots to assess inflammation and immune markers. CM recidivism is assessed for all study families at 6-month follow-up. Post-treatment and follow-up assessments are currently underway.DiscussionKnowledge gained from this study will clarify PCIT effects on neurobehavioral target mechanisms of change in predicting CM risk reduction, positive, responsive parenting, and children’s outcomes. This knowledge can help to guide efforts to tailor and adapt PCIT to vary in dosage and cost on the basis of individual differences in CM-risk factors.

Caffeine Ingestion Enhances Repetition Velocity in Resistance Exercise: A Randomized, Crossover, Double-Blind Study Involving Control and Placebo Conditions.

We aimed to examine the effects of placebo and caffeine compared to a control condition on mean velocity in the bench press exercise. Twenty-five resistance-trained men participated in this randomized, crossover, double-blind study. The participants performed the bench press with loads of 50%, 75%, and 90% of one-repetition maximum (1RM), after no supplementation (i.e., control), and after ingesting caffeine (6 mg/kg), and placebo (6 mg/kg of dextrose). At 50% 1RM, there was a significant effect of caffeine on mean velocity compared to control (effect size [ES] = 0.29; p = 0.003), but not when compared to placebo (ES = 0.09; p = 0.478). At 75% 1RM, there was a significant effect of caffeine on mean velocity compared to placebo (ES = 0.34; p = 0.001), and compared to control (ES = 0.32; p < 0.001). At 90% 1RM, there was a significant effect of caffeine on mean velocity compared to placebo (ES = 0.36; p < 0.001), and compared to control (ES = 0.46; p < 0.001). There was no significant difference between placebo and control in any of the analyzed outcomes. When evaluated pre-exercise and post-exercise, 20% to 44% and 28% to 52% of all participants identified caffeine and placebo trials beyond random chance, respectively. Given that the blinding of the participants was generally effective, and that there were no significant ergogenic effects of placebo ingestion, the improvements in performance following caffeine ingestion can be mainly attributed to caffeine’s physiological mechanisms of action.

Hepatic Levels of DHA-Containing Phospholipids Instruct SREBP1-Mediated Synthesis and Systemic Delivery of Polyunsaturated Fatty Acids.

SummaryPolyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and arachidonic acid (ARA), play fundamental roles in mammalian physiology. Although PUFA imbalance causes various disorders, mechanisms of the regulation of their systemic levels are poorly understood. Here, we report that hepatic DHA-containing phospholipids (DHA-PLs) determine the systemic levels of PUFAs through the SREBP1-mediated transcriptional program. We demonstrated that liver-specific deletion of Agpat3 leads to a decrease of DHA-PLs and a compensatory increase of ARA-PLs not only in the liver but also in other tissues including the brain. Together with recent findings that plasma lysophosphatidylcholine (lysoPC) is the major source of brain DHA, our results indicate that hepatic AGPAT3 contributes to brain DHA accumulation by supplying DHA-PLs as precursors of DHA-lysoPC. Furthermore, dietary fish oil-mediated suppression of hepatic PUFA biosynthetic program was blunted in liver-specific Agpat3 deletion. Our findings highlight the central role of hepatic DHA-PLs as the molecular rheostat for systemic homeostasis of PUFAs.

Biochemical features of blood vessel extracellular calcium-sensing receptor and their physiological mechanism of action in the regulation of vascular tone and blood pressure

The extracellular calcium-sensing receptor (CaR) is a G protein coupled receptor superfamily that has ability to sense very small changes in extracellular Ca2+ with primary physiological function of maintenance of constant blood Ca2+ levels. In addition to being expressed in tissues involved in [Ca2+]o homeostasis, it is also expressed in tissues not involved in mineral homeostasis, suggestive of additional physiological functions such as control vasomotor tone and blood pressure. However, the exact cellular mechanisms involved in these responses remain unclear. Stimulation of CaRs on perivascular nerves is proposed to evoke synthesis and release of nitric oxide (NO) from pre-synaptic terminals, which activate large conductance Ca2+-activated K+ channels in adjacent VSMCs that induce membrane hyperpolarisation and subsequent vasorelaxation. Plus, activation of CaRs on endothelial cells is reported to generate NO or vasoactive lipids or induce activation of intermediate conductance Ca2+-activated K+ channels to induce vasorelaxations. In contrast, CaR-induced activation of Gq and MAPK kinase-mediated pathways in VSMCs are linked to vasoconstriction and cell proliferation respectively. Taken together, these findings indicate that stimulation of vascular CaRs is reported to induce both constrictions and relaxations. In the endothelium intact artery, CaR mediated vasorelaxations are the dominant physiological phenomenon.

Dynamic Physiological Phenotyping of Drought-Stressed Pepper Plants Treated With "Productivity-Enhancing" and "Survivability-Enhancing" Biostimulants.

The improvement of crop productivity under abiotic stress is one of the biggest challenges faced by the agricultural scientific community. Despite extensive research, the research-to-commercial transfer rate of abiotic stress-resistant crops remains very low. This is mainly due to the complexity of genotype × environment interactions and in particular, the ability to quantify the dynamic plant physiological response profile to a dynamic environment. Most existing phenotyping facilities collect information using robotics and automated image acquisition and analysis. However, their ability to directly measure the physiological properties of the whole plant is limited. We demonstrate a high-throughput functional phenotyping system (HFPS) that enables comparing plants’ dynamic responses to different ambient conditions in dynamic environments due to its direct and simultaneous measurement of yield-related physiological traits of plants under several treatments. The system is designed as one-to-one (1:1) plant–[sensors+controller] units, i.e., each individual plant has its own personalized sensor, controller and irrigation valves that enable (i) monitoring water-relation kinetics of each plant–environment response throughout the plant’s life cycle with high spatiotemporal resolution, (ii) a truly randomized experimental design due to multiple independent treatment scenarios for every plant, and (iii) reduction of artificial ambient perturbations due to the immobility of the plants or other objects. In addition, we propose two new resilience-quantifying-related traits that can also be phenotyped using the HFPS: transpiration recovery rate and night water reabsorption. We use the HFPS to screen the effects of two commercial biostimulants (a seaweed extract –ICL-SW, and a metabolite formula – ICL-NewFo1) on Capsicum annuum under different irrigation regimes. Biostimulants are considered an alternative approach to improving crop productivity. However, their complex mode of action necessitates cost-effective pre-field phenotyping. The combination of two types of treatment (biostimulants and drought) enabled us to evaluate the precision and resolution of the system in investigating the effect of biostimulants on drought tolerance. We analyze and discuss plant behavior at different stages, and assess the penalty and trade-off between productivity and resilience. In this test case, we suggest a protocol for the screening of biostimulants’ physiological mechanisms of action.

Physiology of Transcranial Direct Current Stimulation.

Direct current stimulation is a neuromodulatory noninvasive brain stimulation tool, which was first introduced in animal and human experiments in the 1950s, and added to the standard arsenal of methods to alter brain physiology as well as psychological, motor, and behavioral processes and clinical symptoms in neurological and psychiatric diseases about 20 years ago. In contrast to other noninvasive brain stimulation tools, such as transcranial magnetic stimulation, it does not directly induce cerebral activity, but rather alters spontaneous brain activity and excitability by subthreshold modulation of neuronal membranes. Beyond acute effects on brain functions, specific protocols are suited to induce long-lasting alterations of cortical excitability and activity, which share features with long-term potentiation and depression. These neuroplastic processes are important foundations for various cognitive functions such as learning and memory formation and are pathologically altered in numerous neurological and psychiatric diseases. This explains the increasing interest to investigate transcranial direct current stimulation (tDCS) as a therapeutic tool. However, for tDCS to be used effectively, it is crucial to be informed about physiological mechanisms of action. These have been increasingly elucidated during the last years. This review gives an overview of the current knowledge available regarding physiological mechanisms of tDCS, spanning from acute regional effects, over neuroplastic effects to its impact on cerebral networks. Although knowledge about the physiological effects of tDCS is still not complete, this might help to guide applications on a scientifically sound foundation.

Anti-Hypertensive Peptides Derived from Caseins: Mechanism of Physiological Action, Production Bioprocesses, and Challenges for Food Applications.

This review is focused on the state-of-art of peptides with inhibitory activity towards angiotensin I-converting enzyme (ACE)-thus, with anti-hypertensive potential-derived from enzymatic hydrolysis of caseins. Firstly, molecular characteristics of caseins relevant to a better understanding of this subject were concisely commented. Next, a brief description of the pathophysiology of hypertension was explained, focusing on the ACE role in regulation ofblood pressure in human body. Then, casein-derived peptides with ACE inhibitory capacity were specifically addressed. The main in vitro and in vivo bioassays often reported in literature to assess the anti-hypertensive potential of peptides were presented, illustrated with recently published studies, and discussed in terms of advantages and limitations of both approaches. Characteristics related to amino acid composition and sequenceof peptides with high ACE-inhibitory potential were also commented. Process parameters of enzymatic hydrolysis (types and origins of casein substrates, types of enzymes, pH, temperature, and times of reactions) were discussed.Patents dealing with casein-derived anti-hypertensive peptides were examined not only in terms of amino acid sequences, but also regarding their novelty claims in hydrolysis process parameters. Finally, some trends, challenges, and opportunities inferred from this literature analysis were commented, emphasizing the importance of this research topic in food products development.

Impact of SGLT2i on cardiovascular outcomes and heart failure in patients with type 2 diabetes

The concurrent management of type 2 diabetes mellitus and heart failure presents several challenges and unmet clinical needs. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new generation of oral hypoglycemic agents, they inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels and contributing to a modest reduction in HbA1C. In two pivotal randomized clinical trial, SGLT2i have showed a clinically important reduction in cardiovascular mortality and hospitalization due to heart failure. However, also important adverse effects such as increased risk of bone fractures and lower limb amputations were found. Currently, physiological mechanisms leading to cardiovascular benefits with SGLT2i are not completely understood, but it seems accepted that some of these benefits are related to non-glycemic effects. In this review, we analyze the available clinical evidence focusing in cardiovascular outcomes and heart failure, physiological mechanism of action, and comment on future directions of research.