Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens

Bacteriophages represent an effective, natural, and safe strategy against bacterial infections. Multiple studies have assessed phage therapy’s efficacy and safety as an alternative approach to combat the emergence of multi drug-resistant pathogens. This systematic review critically evaluates and summarizes published articles on phages as a treatment option for Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis infection models. It also illustrates appropriate phage selection criteria, as well as recommendations for successful therapy. Published studies included in this review were identified through EMBASE, PubMed, and Web of Science databases and were published in the years between 2010 to 2020. Among 1082 identified articles, 29 studies were selected using specific inclusion and exclusion criteria and evaluated. Most studies (93.1%) showed high efficacy and safety for the tested phages, and a few studies also examined the effect of phage therapy combined with antibiotics (17.2%) and resistance development (27.6%). Further clinical studies, phage host identification, and regulatory processes are required to evaluate phage therapy’s safety and efficacy and advance their clinical use

Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression

Gastrointestinal (GI) cancer is a prevailing global health disease with a high incidence rate which varies by region. It is a huge economic burden on health care providers. GI cancer affects different organs in the body such as the gastric organs, colon, esophagus, intestine, and pancreas. Internal and external factors like smoking, obesity, urbanization, genetic mutations, and prevalence of Helicobacter pylori and Hepatitis B and Hepatitis C viral infections could increase the risk of GI cancer. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in fruits, grains, and vegetables. Consumption of phytochemicals may protect against chronic diseases like cardiovascular disease, neurodegenerative disease, and cancer. Multiple studies have assessed the chemoprotective effect of selected phytochemicals in GI cancer, offering support to their potential towards reducing the pathogenesis of the disease. The aim of this review was to summarize the current knowledge addressing the anti-cancerous effects of selected dietary phytochemicals on GI cancer and their molecular activities on selected mechanisms, i.e., nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), detoxification enzymes, adenosine monophosphate activated protein kinase (AMPK), wingless-related integration site/β-catenin (wingless-related integration site (Wnt) β-catenin, cell apoptosis, phosphoinositide 3-kinases (PI3K)/ protein kinase B AKT/ mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK). In this review phytochemicals were classified into four main categories: (i) carotenoids, including lutein, lycopene, and β-carotene; (ii) proanthocyanidins, including quercetin and ellagic acid; (iii) organosulfur compounds, including allicin, allyl propyl disulphide, asparagusic acid, and sulforaphane; and (iv) other phytochemicals including pectin, curcumins, p-coumaric acid and ferulic acid. Overall, phytochemicals improve cancer prognosis through the downregulation of β-catenin phosphorylation, therefore enhancing apoptosis, and upregulation of the AMPK pathway, which supports cellular homeostasis. Nevertheless, more studies are needed to provide a better understanding of the mechanism of cancer treatment using phytochemicals and possible side effects associated with this approach

The Influence of Gut Microbial Species on Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic disorder with an alarming incidence rate and a considerable burden on the patient’s life and health care providers. An increase in blood glucose level and insulin resistance characterizes it. Internal and external factors such as urbanization, obesity, and genetic mutations could increase the risk of DM. Microbes in the gut influence overall health through immunity and nutrition. Recently, more studies have been conducted to evaluate and estimate the role of the gut microbiome in diabetes development, progression, and management. This review summarizes the current knowledge addressing three main bacterial species: Bifidobacterium adolescentis, Bifidobacterium bifidum, and Lactobacillus rhamnosus and their influence on diabetes and its underlying molecular mechanisms. Most studies illustrate that using those bacterial species positively reduces blood glucose levels and activates inflammatory markers. Additionally, we reported the relationship between those bacterial species and metformin, one of the commonly used antidiabetic drugs. Overall, more research is needed to understand the influence of the gut microbiome on the development of diabetes. Furthermore, more efforts are required to standardize the model used, concentration ranges, and interpretation tools to advance the field further

Flavonoids’ Dual Benefits in Gastrointestinal Cancer and Diabetes: A Potential Treatment on the Horizon?

Diabetes and gastrointestinal cancers (GI) are global health conditions with a massive burden on patients’ lives worldwide. The development of both conditions is influenced by several factors, such as diet, genetics, environment, and infection, which shows a potential link between them. Flavonoids are naturally occurring phenolic compounds present in fruits and vegetables. Once ingested, unabsorbed flavonoids reaching the colon undergo enzymatic modification by the gut microbiome to facilitate absorption and produce ring fission products. The metabolized flavonoids exert antidiabetic and anti-GI cancer properties, targeting major impaired pathways such as apoptosis and cellular proliferation in both conditions, suggesting the potentially dual effects of flavonoids on diabetes and GI cancers. This review summarizes the current knowledge on the impact of flavonoids on diabetes and GI cancers in four significant pathways. It also addresses the synergistic effects of selected flavonoids on both conditions. While this is an intriguing approach, more studies are required to better understand the mechanism of how flavonoids can influence the same impaired pathways with different outcomes depending on the disease

Immunomodulation by Gut Microbiome on Gastrointestinal Cancers: Focusing on Colorectal Cancer

Gastrointestinal cancer (GI) is a global health disease with a huge burden on a patient’s physical and psychological aspects of life and on health care providers. It is associated with multiple disease related challenges which can alter the patient’s quality of life and well-being. GI cancer development is influenced by multiple factors such as diet, infection, environment, and genetics. Although activating immune pathways and components during cancer is critical for the host’s survival, cancerous cells can target those pathways to escape and survive. As the gut microbiome influences the development and function of the immune system, research is conducted to investigate the gut microbiome–immune interactions, the underlying mechanisms, and how they reduce the risk of GI cancer. This review addresses and summarizes the current knowledge on the major immune cells and gut microbiome interactions. Additionally, it highlights the underlying mechanisms of immune dysregulation caused by gut microbiota on four major cancerous pathways, inflammation, cellular proliferation, apoptosis, and metastasis. Overall, gut-immune interactions might be a key to understanding GI cancer development, but further research is needed for more detailed clarification

Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

Diabetes mellitus (DM) is a prevailing global health metabolic disorder, with an alarming incidence rate and a huge burden on health care providers. DM is characterized by the elevation of blood glucose due either to a defect in insulin synthesis, secretion, binding to receptor, or an increase of insulin resistance. The internal and external factors such as obesity, urbanizations, and genetic mutations could increase the risk of developing DM. Flavonoids are phenolic compounds existing as secondary metabolites in fruits and vegetables as well as fungi. Their structure consists of 15 carbon skeletons and two aromatic rings (A and B) connected by three carbon chains. Flavonoids are furtherly classified into 6 subclasses: flavonols, flavones, flavanones, isoflavones, flavanols, and anthocyanidins. Naturally occurring flavonoids possess anti-diabetic effects. As in vitro and animal model’s studies demonstrate, they have the ability to prevent diabetes and its complications. The aim of this review is to summarize the current knowledge addressing the antidiabetic effects of dietary flavonoids and their underlying molecular mechanisms on selected pathways: Glucose transporter, hepatic enzymes, tyrosine kinase inhibitor, AMPK, PPAR, and NF-κB. Flavonoids improve the pathogenesis of diabetes and its complications through the regulation of glucose metabolism, hepatic enzymes activities, and a lipid profile. Most studies illustrate a positive role of specific dietary flavonoids on diabetes, but the mechanisms of action and the side effects need more clarification. Overall, more research is needed to provide a better understanding of the mechanisms of diabetes treatment using flavonoids

Flavonoids against the SARS-CoV-2 induced inflammatory storm

The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities