Indirect Action Research Articles

Antioxidant Activity of Anthocyanins and Anthocyanidins: A Critical Review

Anthocyanins are the main plant pigments responsible for the color of flowers, fruits, and vegetative organs of many plants, and are applied also as safe food colorants. They are efficient antioxidants. In this review, the reactivity of anthocyanins and their aglycones, anthocyanidins, in the main antioxidant assays, and their reactions with reactive oxygen and nitrogen species, effects of interactions with other compounds and metal ions on the antioxidant activity of anthocyanins and the electrochemical properties of anthocyanins are presented. Numerous cases of attenuation of oxidative stress at the cellular and organismal levels by anthocyanins are cited. The direct and indirect antioxidant action of anthocyanins, the question of the specificity of anthocyanin action in complex extracts, as well as limitations of cellular in vitro assays and biomarkers used for the detection of antioxidant effects of anthocyanins, are critically discussed.

Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn's Disease.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by transmural inflammation and intestinal fibrosis involving mostly the small intestine and colon. The pathogenic mechanisms of CD remain incompletely understood and cures are unavailable. Current medical therapies are aimed at inducing prolonged remission. Most of the medical therapies such as corticosteroids have substantial adverse effects. Consequently, many dietary therapies have been explored for the management of CD. Up to now, exclusive enteral nutrition (EEN) has been considered the only established dietary treatment for IBD, especially CD. In this article, we aim to give a concise review about the current therapeutic options and challenges in the management of CD and aim to compare the efficacy of EEN with other dietary therapies and update on the possible mechanisms of the benefits of EEN and other nutritional therapies. We searched the literature up to August 2024 through PubMed, Web of Science, and other sources using search terms such as EEN, nutritional therapy, IBD, Crohn's disease, ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic benefits. EEN involves oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods for a defined period (usually 6 to 8 weeks). EEN treatment is demonstrated to have anti-inflammatory and healing effects in CD through various potential pathways, including altering gut bacteria and their metabolites, restoring the barrier function, direct anti-inflammatory action, and indirect anti-inflammatory action by eliminating mechanical stress in the bowel. However, efficacy of other nutritional therapies is not well established in CD, and mechanisms of action are largely unknown.

Photodegradation of ciprofloxacin and its interaction with Cu(II) in different water matrices: Insight into degradation pathways

Co-contamination of ciprofloxacin (CIP) and Cu(II) is common in marine aquaculture water. However, the transmission and transformation of these substances in natural water matrices are often overlooked. This study sought to assess the impact of Cu(II) on CIP degradation in distilled (DI) and simulated (SI) mariculture water, as well as to develop a relationship between Cu(II), CIP, and its degradation products. First, complexation assays and analog computations revealed that Cu (II) forms complexes by binding to the oxygen atoms of the carbonyl (C=O) and carboxyl (COOH) groups in the CIP molecule. Second, photodegradation experiments showed that Cu(II) significantly hindered the degradation effect of CIP in DI water, while Cu(II) did not significantly hinder the degradation of CIP in SI water. Furthermore, the effect of Cu(II) on the degradation mechanism of CIP was determined by combining quenching and EPR experiments, Materials Studio software calculations, and UPLC-MS results. It was demonstrated that Cu(II) enhanced the production of singlet oxygen (1O2), hydroxyl radicals (•OH), and superoxide radicals (•O2−) in DI water. In the presence of Cu(II), CIP undergoes hydroxylation and decarbonylation reactions, forming hydroxylated and nitroxylated products. Additionally, direct defluorination and cleavage of the piperazine ring occur, followed by complexation reactions with Cu(II). However, in SI water, the production of 1O2 depends on the indirect action of Cu(II) and the excited state transformation of organic matter. Experimental evidence has shown that CIP can create intermediate compounds that include O-O peroxide rings, with or without the presence of Cu(II). When Cu(II) is present, the cyclopropyl group of the CIP molecule is more prone to transformation and so degradation. Finally, the toxicity assessment results indicated that both Cu(II) and SI water increased the toxicity of the degradation products.

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on the brain structure and function, through potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicentre observational cohort study, entirely based on a healthcare worker sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of severe acute respiratory syndrome coronavirus 2 variants Alpha to Delta, compared with healthy controls tested before the pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities on axial fluid-attenuated inversion recovery images. Global and regional grey matter integrity assessment, analysing changes in grey matter volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical white matter hyperintensities, thalamic and occipital volume loss and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting the right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.

Morning Engagement of Hepatic Insulin Receptors Improves Afternoon Hepatic Glucose Disposal and Storage.

Morning insulin delivery primes the liver for increased hepatic glucose uptake (HGU) later in the day, but the mechanism (direct hepatic and/or indirect insulin action) remains unclear.This study compared insulin infusion via physiologic (hepatic portal vein) and clinical (peripheral) routes to assess their impact on afternoon hepatic glucose disposal.Morning peripheral insulin delivery failed to induce a significant enhancing effect on afternoon HGU and glycogen storage, unlike morning hepatic portal vein insulin delivery, which did.These findings highlight the importance of achieving appropriate hepatic insulin exposure in the morning to effectively prime the liver for efficient glucose disposal.

Characteristics of soil pore structure response to electric field strength and their effects on Cr(VI) removal from a historically chromium-contaminated soil

The characteristics of soil pore structure response to electric field strength and their effects on the migration of hexavalent chromium during electrokinetic remediation remain unclear. This paper investigates the effects of soil actual voltage and pore redistribution on hexavalent chromium removal under various voltage gradients during electrokinetic remediation. The electric field across the soil was the dominant factor that affected the soil properties, pore structure, and transportation of hexavalent chromium. The removal efficiency of dissolved hexavalent chromium was significantly enhanced from 36.1 % to 80.5 % as the theoretical voltage gradients increased from 0.5 V·cm−1 to 3 V·cm−1 due to the highest voltage proportion (52.7 %) of the soil chamber at 3 V·cm−1, while it only increased to 82.0 % at 4 V·cm−1. The optimal actual electric field strength of 1.00–1.50 V·cm−1 across the soil matrix facilitated the efficient electromigration of hexavalent chromium. The electric field force exerted a direct (0.70) or indirect action intensity (1.55) on soil pore structure by altering soil chemical properties. Soil mesopores and ultra-micropores transformed into micropores through collapsing, shrinking, ion migration, weakening electrostatic repulsion, and enhancing adhesive bonding among particles with increasing electric field. The distribution and structure of soil pores were more homogenous under optimal electric field conditions, thereby improving the migration path of hexavalent chromium. Soil mesopores facilitated hexavalent chromium removal and the formed micropores were opposite. These findings have significant scientific and practical implications for applying the in-situ electrokinetic techniques in the remediation of metal-contaminated soils.

Antioxidant and Cytoprotective Effects of Different Compounds on Cyclophosphamide-induced Nephrotoxicity

Abstract: Cyclophosphamide is a drug derived from nitrogenous mustards and is mainly indicated for the anti-neoplastic clinic. When it is metabolized in the liver, it produces acrolein, a cytotoxic metabolite capable of generating damage to the body. The oxidative, nitrative and nitrosative stress are responsible for mediating this side effect since the toxicity of the drug induces the production of reactive species of oxygen (ROS) and nitrogen (RNS). These radicals are unstable and react with other molecules that can result in cellular lesions such as lipid peroxidation, enzymatic inactivation, and excessive activation of pro-inflammatory genes, producing molecules such as malonaldehyde (MDA) and nitric oxide (NO), representing oxidative stress markers. One of the consequences of these mechanisms is nephrotoxicity. In contrast, some compounds have direct or indirect antioxidante action, which are the objects of this study: gallic acid, aminoguanidine, chrysin, hesperidine, naringin, morin-5'-sulfonic acid sodium salt and spirulina. All of them are responsible for the nephroprotective activity when administered during experiments in vitro or in vivo. Thus, this observational bibliographic research is characterized as qualitative descriptive and explanatory, since it focuses on analyzing the antioxidant properties of compounds with possible potentials to inhibit the nephrotoxicity induced by cyclophosphamide and describe the results, in addition to clarifying the biochemical activities involved in the process.

A technical–scientific content management system on water reuse as an environmental education tool: the experience of a Portugal/Brazil partnership

ABSTRACT This study presents the Instituto Reúso de Água (IRdA) as a high-quality environmental education tool. The results measured the reach of IRdA's direct (webinars, learning series, and mentoring) and indirect (technical–scientific repository and the production of more easily assimilated data) educational actions since its conception (Period 01), operation of the platform (Period 02), and operation of IRdA (Period 03), through its digital platform and social media. The direct actions proved to be effective in disseminating knowledge, highlighting a preference for the topic ‘regulation’ and adherence to content produced in different video formats. On the other hand, the indirect actions showed that the scientific approach is less accessed due to its complex language. However, when presented into more accessible data, scientific content gains confidence and can be of great relevance for the transformation of society. The results corroborate the current trend of greater educational reach in a free and digital format to build a society truly committed to water reuse and its more efficient management.

Overexpression of NUDT16L1 sustains proper function of mitochondria and leads to ferroptosis insensitivity in colorectal cancer

Cancer research is continuously exploring new avenues to improve treatments, and ferroptosis induction has emerged as a promising approach. However, the lack of comprehensive analysis of the ferroptosis sensitivity in different cancer types has limited its clinical application. Moreover, identifying the key regulator that influences the ferroptosis sensitivity during cancer progression remains a major challenge. In this study, we shed light on the role of ferroptosis in colorectal cancer and identified a novel ferroptosis repressor, NUDT16L1, that contributes to the ferroptosis insensitivity in this cancer type. Mechanistically, NUDT16L1 promotes ferroptosis insensitivity in colon cancer by enhancing the expression of key ferroptosis repressor and mitochondrial genes through direct binding to NAD-capped RNAs and the indirect action of MALAT1. Our findings also reveal that NUDT16L1 localizes to the mitochondria to maintain its proper function by preventing mitochondrial DNA leakage after treatment of ferroptosis inducer in colon cancer cells. Importantly, our orthotopic injection and Nudt16l1 transgenic mouse models of colon cancer demonstrated the critical role of NUDT16L1 in promoting tumor growth. Moreover, clinical specimens revealed that NUDT16L1 was overexpressed in colorectal cancer, indicating its potential as a therapeutic target. Finally, our study shows the therapeutic potential of a NUDT16L1 inhibitor in vitro, in vivo and ex vivo. Taken together, these findings provide new insights into the crucial role of NUDT16L1 in colorectal cancer and highlight its potential as a promising therapeutic target.

Thyroid Hormone Regulates Postnatal Development of the Rete Testis in Mice.

Thyroid hormone regulates the rate of testis maturation in mammals. Manipulations of thyroid hormone levels in neonatal animals affect various aspects of testis biology. However, there were no studies examining the effects of thyroid hormone on the rete testis (RT). Here, we used animal models of neonatal hyperthyroidism (injections of triiodothyronine, or T3) and hypothyroidism (goitrogen PTU treatment) and found that higher levels of thyroid hormone accelerate RT development, while lower levels of thyroid hormone delay it. T3 and PTU treatments influence RT size, proliferation of RT cells, and expression of DMRT1 and androgen receptor in the RT. T3 supplementation accelerates RT development in an organ testicular culture, which indicates the local action of thyroid hormone. Additionally, it was found that follicle stimulated hormone could be involved in the regulation of both RT proliferation and RT size. The fact that RT cells in a cell culture do not respond to T3 suggests indirect action of thyroid hormone on the RT in vivo or the loss of the responsiveness to the hormone in vitro.

Biogenic “phosphorus” effect of terrestrial lakes and its significance to oil shale during the Carnian period in the late Triassic

The Triassic lacustrine organic-rich shale (LORS) in Member 7 of the Yanchang Formation (Carnian stage) in the southern Ordos Basin is relatively well developed. Additionally, its organic matter abundance, lake biomass and biodiversity, exceed the maximum values of the other strata deposited during the same period. Apatite is one of the most important minerals and is closely related to biological activities. However, the types and genesis of the continental sedimentary apatite and its significance to shale oil are not clear. Here, the stratigraphy, petrology, and sedimentology of the phosphorus-bearing rock series in the Ma Quan section are studied and its sedimentary environment and phosphorus formation are discussed. The current research shows that apatite in the study area can be divided into three categories: collophanite, bone fossils, and spherical microfossils. These three types of biogenic “phosphorus” products provide effective records of the transformation of the biological substances into sedimentary organic matter. There are two main formation mechanisms: the direct action of organisms and the interaction between the organisms. Bone fossils and spherical microfossils are formed by the direct action of organisms, while collophanite is formed by the indirect action of organisms. The phosphatization methods of the organisms mainly include “coating”, “replacement”, and “filling”, and the presence of a ubiquitous phosphate filler potentially reflects a sufficient phosphate supply. Apatite also is highly important for the development of organic matter in oil shale. First, it changes the productivity conditions. Second, the apatite in the shell of spherical microfossils has a certain protective effect on the organic matter in the inner cavity. In the current study, the geological processes of collophanite deposition and mineralization are explained, an important basis for prospecting phosphate resources is provided, and a new field for the study of the organic matter enrichment mechanism of source rocks is established. At the same time, the process of lake biogenic phosphorus formation provides evidence from the continental deposits in the eastern margin of the Tethys region for exploring deep global changes.

The development of regulation of pharmaceuticals turn-over in EU and the USA in 1992-2020. Report 3. The making of the EU legislation of pharmaceuticals turn-over in 2001-2020

This article proceeds the topic of the article "The development of regulation of the circulation of medicines in the EU and the USA in 1992-2020." The history of development of European pharmaceutical legislation in 2001-2020 is considered. The acts of indirect action adopted by EU Parliament at first stage of development of legislation concerning medications failed to fully harmonize normative base of the EU Member States in pharmaceutical market. Since 2000, the EU Parliament and the EU Council adopt laws of direct action - the Regulations. Alongside with the pharmaceutical Code, the Regulations for single segments of pharmaceutical market constituted set of laws related to turn-over of medications. The legislators, at developing EU laws, took into account the US regulatory standards. Despite differences in history, legislative traditions and structure, regulatory systems of the USA and the EU concerning medications turn-over were basically harmonized.

The future is (ever) promising: Elected representatives’ promises in routine parliamentary discourse

This study investigates how elected representatives make promises to the electorate as part of their routine, everyday parliamentary discourse. Departing from the dominant focus on pre-election pledges in existing scholarship, we examine how representatives’ practices of making promises vary systematically over time (before/after elections/mid-term), by government role (government/opposition), party membership (catch-all/identity-based parties), and addressed electorate (inclusive/exclusive). Drawing upon research in speech acts, political discourse, and corpus pragmatics, we employ manual and computational text analysis on session transcripts from the Israeli parliament to identify variations in representatives’ use of direct or indirect action promises ( N = 709), expressing different orientations of commitment. Documenting that promises continue to be prevalent after elections (especially among coalition members), we argue that the practices of making promises fulfill a critical role in representation that extends far beyond the election campaign, maintaining continuous accountability throughout the electoral cycle.

Xenogenous implanted dental follicle stem cells promote periodontal regeneration through inducing the N2 phenotype of neutrophils

BackgroundPeriodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period.MethodsTo trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation.ResultsIn vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation.ConclusionThe xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration.

What are individual‐level nature amends? Rescaling biodiversity offsetting from the community members' perspective

AbstractEffective solutions to biodiversity loss are multidimensional, requiring engagement from diverse stakeholders across various sectors and commitment levels. In this context, voluntary actions from community members emerge as a valuable addition to the large‐scale nature conservation activities conducted by states and municipalities. Such actions complement biodiversity protection measures and legal requirements aimed at companies. This article delves into the rescaling of biodiversity offsetting to the community members level and explores it from the perspective of community members. Through workshops organized in four Finnish municipalities, participants were prompted to reflect on biodiversity offsetting in their daily lives. The results show community members' limited resources to conduct pro‐biodiversity actions and highlight their diverse interpretations of the topic. Beyond direct biodiversity‐enhancing action, like maintaining rural biotopes, eradicating alien species, or protecting forests, workshop participants called for indirect actions. These included education, eco‐taxes, and the development of sharing economies. Thus, rather than solely focusing on biodiversity offsetting or the mitigation hierarchy, these suggestions underscore the need for diverse pro‐biodiversity actions at the community member's level. Furthermore, the results highlight the need for support that enables community members and communities' work for biodiversity. Introducing the concept of nature amends addresses this need, enhancing the mitigation hierarchy's capacity to incorporate community members in nature conservation endeavors.

Multiple Mechanisms of Haematococcus pluvialis-Derived Carotenoids to Inhibit Glycidyl Ester Formation in Rice Oil and a Chemical Model at High Temperatures.

The common presence of glycidyl esters (GEs) in refined vegetable oils has been a concern for food safety. The present study aimed to investigate the inhibitory effects of three carotenoids derived from Haematococcus pluvialis microalga on GE formation in both rice oil and a chemical model during heating. The addition of astaxanthin (AS), lutein (LU), and β-carotene (CA) at 0.6 mg/g in rice oil can reduce GE formation by 65.0%, 57.1%, and 57.5%, respectively, which are significantly higher than those achieved by common antioxidants such as l-ascorbyl palmitate (39.0%), α-tocopherol (18.5%), tert-butyl hydroquinone (42.7%), and quercetin (26.2%). UPLC-Q-TOF-MS/MS analysis showed that two new compounds, that is, propylene glycol monoester and diester of palmitic acid, were formed in the CA-added chemical model, which provided direct experimental evidence for the inhibition of antioxidants including AS, LU, and CA against GE formation not only by indirect antioxidative action but also by direct radical reactions to competitively prevent the formation of cyclic acyloxonium intermediates. Furthermore, it was interestingly found that only AS could react with the GEs. The adduct of AS with GEs, astaxanthin-3-O-propanetriol esters, was preliminarily identified using Q-TOF-MS/MS in the heated AS-GE model, suggesting that reacting with GEs might represent another distinct mechanism of AS to eliminate GEs.

AN OVERVIEW ON SHEET METAL HYDROFORMING TECHNOLOGIES

The hydroforming process is a nonconventional method for producing sheet metal deep drawing pieces, under the direct or indirect action of a high pressure fluid on the inner or outer side of work piece wall. This process it`s known since the 1900s and it has continuously developed, being today a field of research in the universities from country and abroad. The design of the hydroforming process can be done according to empirical, analytical and numerical methods to obtain high precision of the hydroforming piece and to ensure a large deformation of the material. The hydroforming parts can be used in various fields such as the automotive, aircraft and aerospace industries, having relatively low costs compared to parts obtained by other types of processing such as rolling, forging or stamping. The paper gives an overview regarding the sheet metal hydroforming processes, methods and the equipment used, as well as the process limits and defects that can occur during hydroforming.

The stimulant cathine from Khat causes tachycardia indirectly in the rat.

Leaves of the Khat plant are widely consumed in the Horn of Africa, Yemen and the Jazan region of Saudi Arabia. I have investigated the mode of cardiovascular and autonomic actions of the stimulant cathine from Khat in terms of direct or indirect adrenergic actions in anaesthetised male and female rats, and in isolated tissues. Male and female rats were anaesthetised with pentobarbitone and changes in diastolic blood pressure and cardioaccelerator responses were examined in vehicle-treated or chemically sympathectomised rats. Cathine produced marked tachycardia and smaller blood pressure responses in vehicle-treated animals, with significant rises in heart rate occurring at cathine (0.1mg/kg). In sympathectomised rats, cardiac actions were greatly attenuated in both male and female animals, with no differences between male and female rats. Although pressor responses to cathine were relatively small, sympathectomy significantly reduced these responses in female, but not male, rats. In rat aorta and spleen, cathine produced almost no direct contractions. It is concluded that cathine acts predominantly indirectly, presumably by the release of noradrenaline, in both male and female rats to produce cardiovascular actions. This may have implications for adverse cardiovascular actions of consumption of the plant Khat, particularly with dried Khat, in which actions of cathine may predominate over those of cathinone.

Incretin-mediated control of cardiac energy metabolism.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) are incretin hormones that stimulate insulin secretion and improve glycemic control in individuals with type 2 diabetes (T2D). Data from several cardiovascular outcome trials for GLP-1 receptor (GLP-1R) agonists have demonstrated significant reductions in the occurrence of major adverse cardiovascular events in individuals with T2D. Although the cardiovascular actions attributed to GLP-1R agonism have been extensively studied, little is known regarding the cardiovascular consequences attributed to GIP receptor (GIPR) agonism. As there is now an increasing focus on the development of incretin-based co-agonist therapies that activate both the GLP-1R and GIPR, it is imperative that we understand the mechanism(s) through which these incretins impact cardiovascular function. This is especially important considering that cardiovascular disease represents the leading cause of death in individuals with T2D. With increasing evidence that perturbations in cardiac energy metabolism are a major contributor to the pathology of diabetes-related cardiovascular disease, this may represent a key component through which GLP-1R and GIPR agonism influence cardiovascular outcomes. Not only do GIP and GLP-1 increase the secretion of insulin, they may also modify glucagon secretion, both of which have potent actions on cardiac substrate utilization. Herein we will discuss the potential direct and indirect actions through which GLP-1R and GIPR agonism impact cardiac energy metabolism while interrogating the evidence to support whether such actions may account for incretin-mediated cardioprotection in T2D.

Barley polysaccharides inhibit colorectal cancer by two relatively independent pathways

Colorectal cancer is one of the most common types of cancer worldwide that can lead to serious injury and death. Although polysaccharides are widely recognized as having antitumor activity, there has been little research on the role of barley polysaccharides (BP)11BP: barley polysaccharides. in colorectal cancer. The results of our research suggest that BP (300 mg/kg) had a significant inhibitory effect on colorectal cancer, and this effect was achieved through two pathways. First, BP can directly promote the secretion of protective metabolites like 5-(4-Hydroxyphenyl)-5-phenylimidazolidine-2,4-dione and 2,3-Bis(4-hydroxyphenyl)propionitrile thereby inhibiting the cancer pathways such as ERK, PI3K, WNT, JAK-STAT, Calcium, and Cell cycle cancer pathways to alleviate inflammation. Second, BP also can enrich beneficial intestinal bacteria such as Colidextribacter, Bilophila, and UCG-003 improve the intestinal barrier, promote the production of beneficial metabolites such as 5,8-Epoxy-5,8-dihydro-3-hydroxy-8′-apo-b,y-carotenal and L-Glutamic acid, and thus inhibit cancer pathways such as ERK, PI3K, Nuclear receptor, Cell cycle, Apoptosis and TGF-β. In conclusion, our findings suggest for the first time that BP can alleviate colorectal cancer by two relatively independent pathways: direct action and indirect action via the gut microbiota on both colon tumor cells and microbiota.