https://doi.org/10.1016/j.btre.2022.e00714

Antineoplastic activity of biogenic silver and gold nanoparticles to combat leukemia: Beginning a new era in cancer theragnostic

Polyphenols, although not classified as nutrients, provide health benefits beyond the mere maintenance of normal health in humans and animals alike. Traditionally, much of the focus in polyphenol research has been their antioxidant property. Of late, polyphenols are receiving greater interest for their potential gut-health promoting effects. The gut microbiota modifies the ingested polyphenols to produce ‘microbial derivatives’ that are postulated to mediate beneficial effects in the host. Microbial modifications convert the large variety of polyphenols from the diet to fewer end-products. Polyphenol-derived intermediate- and end-products can affect the intestinal ecology as significant constituents are not fully absorbed and are metabolized in the liver and excreted back into the gut through the biliary secretions. Some of these accumulated metabolites may exert prebiotic-like effects on the gut microflora, leading to stimulation of bacterial growth, and in the process, promoting certain probiotic bacteria. The unabsorbed dietary phenolics and their metabolites exert antimicrobial or bacteriostatic activities by selectively inhibiting the growth of pathogenic bacteria, while at the same time stimulating the growth of commensal bacteria. This, in turn, leads to an altered microbiota composition in the gut lumen. Eventually, health benefits to the host come directly from the action of the polyphenolic compounds and metabolites on the tissue and organ systems, and indirectly through the positive impact of microbial fermentation. This review thus aims to discuss the benefits of polyphenols from varied sources with a focus on their gut metabolism and the ensuing health promoting effects.

Polyphenolic bioactives as an emerging group of nutraceuticals for promotion of gut health: A review

Today, neurodegenerative diseases have become a remarkable public health challenge due to their direct relation with aging. Accordingly, understanding the molecular and cellular mechanisms occurring in the pathogenesis of them is essential. Both protein aggregations as a result of the ubiquitin-proteasome system (UPS) inefficiency and gut microbiota alternation are the main pathogenic hallmarks. Polyphenols upregulating this system may decrease the developing rate of neurodegenerative diseases. Most of the dietary intake of polyphenols is converted into other microbial metabolites, which have completely different biological properties from the original polyphenols and should be thoroughly investigated. Herein, several prevalent neurodegenerative diseases are pinpointed to explain the role of gut microbiota alternations and the role of molecular changes, especially UPS down-regulation in their pathogenesis. Some of the most important polyphenols found in our diet are explained along with their microbial metabolites in the body.

Role of Polyphenols on Gut Microbiota and the Ubiquitin-Proteasome System in Neurodegenerative Diseases.

Coronavirus disease 2019 (COVID-19) has gained prominence as a global pandemic. Studies have suggested that systemic alterations persist in a considerable proportion of COVID-19 patients after hospital discharge. We used proteomic and metabolomic approaches to analyze plasma samples obtained from 30 healthy subjects and 54 COVID-19 survivors 6 months after discharge from the hospital, including 30 non-severe and 24 severe patients. Through this analysis, we identified 1019 proteins and 1091 metabolites. The differentially expressed proteins and metabolites were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Among the patients evaluated, 41% of COVID-19 survivors reported at least one clinical symptom and 26.5% showed lung imaging abnormalities at 6 months after discharge. Plasma proteomics and metabolomics analysis showed that COVID-19 survivors differed from healthy control subjects in terms of the extracellular matrix, immune response, and hemostasis pathways. COVID-19 survivors also exhibited abnormal lipid metabolism, disordered immune response, and changes in pulmonary fibrosis-related proteins. COVID-19 survivors show persistent proteomic and metabolomic abnormalities 6 months after discharge from the hospital. Hence, the recovery period for COVID-19 survivors may be longer. 

/pdf/plasma-proteomic-and-metabolomic-characterization-of-covid-1vt247kk.pdf

Plasma proteomic and metabolomic characterization of COVID-19 survivors 6 months after discharge

Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome. 

/pdf/benefits-and-implications-of-resveratrol-supplementation-on-2b5jow35.pdf

Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature

Despite all the other cells that have the potential to prevent cancer development and metastasis through tumour suppressor proteins, cancer cells can upregulate the ubiquitin-proteasome system (UPS) by which they can degrade tumour suppressor proteins and avoid apoptosis. This system plays an extensive role in cell regulation organized in two steps. Each step has an important role in controlling cancer. This demonstrates the importance of understanding UPS inhibitors and improving these inhibitors to foster a new hope in cancer therapy. UPS inhibitors, as less invasive chemotherapy drugs, are increasingly used to alleviate symptoms of various cancers in malignant states. Despite their success in reducing the development of cancer with the lowest side effects, thus far, an appropriate inhibitor that can effectively inactivate this system with the least drug resistance has not yet been fully investigated. A fundamental understanding of the system is necessary to fully elucidate its role in causing/controlling cancer. In this review, we first comprehensively investigate this system, and then each step containing ubiquitination and protein degradation as well as their inhibitors are discussed. Ultimately, its advantages and disadvantages and some perspectives for improving the efficiency of these inhibitors are discussed.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200390

Ubiquitin-proteasome system and the role of its inhibitors in cancer therapy.

The outbreak of a new, potentially fatal virus, SARS-COV-2, which started in December 2019 in Wuhan, China, and since developed into a pandemic has stimulated research for an effective treatment and vaccine. For this research to be successful, it is necessary to understand the pathology of the virus. So far, we know that this virus can harm different organs of the body. Although the exact mechanisms are still unknown, this phenomenon may result from the body's secretion of prostaglandin E2 (PGE2), which is involved in several inflammation and immunity pathways. Noticeably, the expression of this molecule can lead to a cytokine storm causing a variety of side effects. In this paper, we discuss those side effects in SARS-COV-2 infection separately to determine whether PGE2 is, indeed, an important causative factor. Lastly, we propose a mechanism by which PGE2 production increases in response to COVID-19 disease and suggest the possible direct relation between PGE2 levels and the severity of this disease. Also see the video abstract here: https://youtu.be/SnPFAcjxxKw.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/bies.202000198

Why does COVID-19 pathology have several clinical forms?

COVID-19, a pandemic affecting virus, which is caused by the current SARS-CoV2 coronavirus.
The present research is performed on anti virus and immune-modulating therapies. Cytokine
storms are the toxic drivers and mortality caused by various human viral infections. In addition,
the intensity was linked to an elevated risk of acute respiratory failure, myocardial injury, and
mortality in SARS-CoV-2-infected patients. The Janus kinase (JAK) therapeutic inhibitor class
showed significant clinical benefits in anti-inflammatory and anti-viral effects. Among them,
filgotinib has been approved as an active JAK inhibitor by decreasing biomarkers with main
immune reaction functions and markers supporting matrix-degradation, angiogenesis, leukocyte
adhesion, and recruitment in both research trials. In this study, we tried to get an insight into the
choice of this drug in controlling the jack, to treat Covid 19 using drug design methods will be
discussed.

/pdf/the-potential-of-jak-stat-pathway-inhibition-as-a-new-3x2ku6fx8x.pdf

The Potential of JAK/STAT Pathway Inhibition as a New Treatment Strategy to Control Cytokine Release Syndrome in COVID-19

Abstract The genus Astragalus L. with about 3000 species is the largest genus of flowering plants. It is also the largest genus in the flora of Iran with more than 850 taxa. Astragalus cyclophyllon Beck is an endemic taxon belonging to Astragalus sect. Incani DC. It occurs scattered in the steppe and semi-steppe areas of the western and central parts of Iran. This species is one of the most important forage taxa of Astragalus . According to IUCN criteria it has been classified as a vulnerable taxon in Iran, as it occurs in habitats intensely used by herders for their livestock. Here we evaluate the genetic diversity of the populations of this species in Iran to see whether genetic diversity is high or if reductions have already happened. For this purpose, sampling was done in all geographical areas with A. cyclophyllon populations in Iran. In total, 80 individuals representing 29 populations were studied using 33 quantitative and qualitative morphological characters and 10 inter-simple sequence repeat (ISSR) primers. ISSR revealed 240 bands which all were polymorphic. Neighbor-joining cluster analysis divided the individuals in four groups, Principal Coordinate Analysis and Bayesian population assignment analysis in Structure resulted in three genetic units. Morphological variation showed no correlation with the molecular data. The mean of Gst and Nm indices are 0.516 and 0.468, respectively, which indicate a very high genetic differentiation and low gene flow between the studied populations. According to these results, we conclude that genetic diversity is high in this species and that, therefore, the major threat for A. cyclophyllon is currently not related to inbreeding depression in populations, but might be due to livestock grazing that could change the population demographic structure by reducing regular establishment of new offspring. 

/pdf/high-genetic-diversity-in-an-endemic-and-vulnerable-species-2g8xq8d9.pdf

Fatemeh Aliabadi

Papers

Ubiquitin-proteasome system and the role of its inhibitors in cancer therapy.

Role of Polyphenols on Gut Microbiota and the Ubiquitin-Proteasome System in Neurodegenerative Diseases.

Why does COVID-19 pathology have several clinical forms?

The Potential of JAK/STAT Pathway Inhibition as a New Treatment Strategy to Control Cytokine Release Syndrome in COVID-19

High genetic diversity in an endemic and vulnerable species: evidence from Astragalus cyclophyllon (Fabaceae) in Iran