Shigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization ...advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.
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Many food-derived phytochemicals and their derivatives represent a cornucopia of new anti-cancer compounds. Luteolin (3,4,5,7-tetrahydroxy flavone) is a flavonoid found in different ...plants such as vegetables, medicinal herbs, and fruits. It acts as an anticancer agent against various types of human malignancies such as lung, breast, glioblastoma, prostate, colon, and pancreatic cancers. It also blocks cancer development in vitro and in vivo by inhibition of proliferation of tumor cells, protection from carcinogenic stimuli, and activation of cell cycle arrest, and by inducing apoptosis through different signaling pathways. Luteolin can additionally reverse epithelial-mesenchymal transition (EMT) through a mechanism that involves cytoskeleton shrinkage, induction of the epithelial biomarker E-cadherin expression, and by down-regulation of the mesenchymal biomarkers N-cadherin, snail, and vimentin. Furthermore, luteolin increases levels of intracellular reactive oxygen species (ROS) by activation of lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells, and by activation of ER stress-associated proteins expressions, including phosphorylation of eIF2α, PERK, CHOP, ATF4, and cleaved-caspase 12. Accordingly, the present review article summarizes the progress of recent research on luteolin against several human cancers.
Proanthocyanidins are condensed tannins with various pharmacological properties. These phytochemicals are considered as ‘offense and defense molecules because of their human health benefits. The ...validation of their diverse health aspects, namely, antioxidant, anticancer, antidiabetic, neuroprotective, and antimicrobial has earned them repute in thermochemistry. Proanthocyanidins are oligo- or polymers of monomeric flavan-3-ols produced as an end product of flavonoid biosynthetic pathway. Agricultural wastes and food processing wastes contain immense amount of proanthocyanidins, exploitation of which can be a sustainable source of dietary supplements and functional ingredients. The current review article discusses recent developments in the health promoting properties of proanthocyanidins and the associated hurdles.
Neuroinflammation, a protective response of the central nervous system (CNS), is associated with the pathogenesis of neurodegenerative diseases. The CNS is composed of neurons and glial cells ...consisting of microglia, oligodendrocytes, and astrocytes. Entry of any foreign pathogen activates the glial cells (astrocytes and microglia) and overactivation of these cells triggers the release of various neuroinflammatory markers (NMs), such as the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-1β (IL-10), nitric oxide (NO), and cyclooxygenase-2 (COX-2), among others. Various studies have shown the role of neuroinflammatory markers in the occurrence, diagnosis, and treatment of neurodegenerative diseases. These markers also trigger the formation of various other factors responsible for causing several neuronal diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), ischemia, and several others. This comprehensive review aims to reveal the mechanism of neuroinflammatory markers (NMs), which could cause different neurodegenerative disorders. Important NMs may represent pathophysiologic processes leading to the generation of neurodegenerative diseases. In addition, various molecular alterations related to neurodegenerative diseases are discussed. Identifying these NMs may assist in the early diagnosis and detection of therapeutic targets for treating various neurodegenerative diseases.
Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present ...review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial-mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.
It has become evident over the past several years that the intestinal microbial ecosystem plays a critical role in the development and prevention of cardiovascular diseases (CVDs) and other metabolic ...disorders, such as hypertension, obesity, diabetes mellitus, and metabolic syndrome. The intestinal microbiota ecosystem functions as a major virtual endocrine organ that interacts and responds to molecules' signals within the host. Several meta-organismal pathways are involved in the gut-host interaction, including trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFA). Host phenotype and cardiovascular diseases (CVDs) varying from hypertension, insulin resistance, and obesity to more specific inflammatory processes, such as atherosclerosis and hypercoagulability, have shown to be affected by the gut-host interaction. Additionally, several studies that involved animals and humans demonstrated a striking connection between the development of new CVDs and an imbalance in the gut microbiota composition along with the presence of their derived metabolites. Through this review article, we aim to evaluate the role of the normal gut microbiota ecosystem, its association with CVDs, effects of the therapies used to control and manage CVDs in the gut microbiota environment and explore potential therapeutic interventions to amplify disease outcomes in patients with CVDs.
Reactive oxygen species (ROS) are produced under normal physiological conditions and may have beneficial and harmful effects on biological systems. ROS are involved in many physiological processes ...such as differentiation, proliferation, necrosis, autophagy, and apoptosis by acting as signaling molecules or regulators of transcription factors. In this case, maintaining proper cellular ROS levels is known as redox homeostasis. Oxidative stress occurs because of the imbalance between the production of ROS and antioxidant defenses. Sources of ROS include the mitochondria, auto‐oxidation of glucose, and enzymatic pathways such as nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. The possible ROS pathways are NF‐κB, MAPKs, PI3K‐Akt, and the Keap1‐Nrf2‐ARE signaling pathway. This review covers the literature pertaining to the possible ROS pathways and strategies to inhibit them. Additionally, this review summarizes the literature related to finding ROS inhibitors.
Oxidative stress occurs because of the imbalance between the production of ROS and antioxidant defenses. Sources of ROS include the mitochondria, auto‐oxidation of glucose, and enzymatic pathways such as nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. The possible ROS pathways are NF‐κB, MAPKs, PI3K‐Akt, and the Keap1‐Nrf2‐ARE signaling pathway. Various diseases associated with ROS imbalance and types of ROS inhibitors are also discussed in this manuscript.
Neurodegeneration is a debilitating condition that causes nerve cell degeneration or death. Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), ...frontotemporal dementia (FTD), and Lewy body dementia (LBD) are posing a larger population burden of dementia worldwide. Neurodegenerative dementia is one of the main challenges in public health with its main characteristics being permanent loss of memory, impairment in cognition, and impaired daily functions. The published literature about genetic studies of these disorders suggests genetic underpinning in the pathogenesis of neurodegenerative dementia. In the process of underlining the pathogenesis of NDD, growing evidence has related genetic variations in the triggering receptor expressed on myeloid cells 2 (TREM2). This review paper aims to provide a detailed information regarding the association of TREM2 and NDDs leading to dementia. A central consideration is AD that accounts for almost 50%–70% of all late‐life dementias alone or in combination with other neurological disorders. Other prevalent neurodegenerative conditions that lead to dementia are also discussed. Such studies are important as they can give a comprehensive knowledge of TREM2's role in various NDDs, in order to maximize the potential for developing new therapeutic approaches.
Role of TREM2 in neurodegenerative dementias.
Plants including Rhizoma polgonati, Smilax china, and Trigonella foenum-graecum contain a lot of diosgenin, a steroidal sapogenin. This bioactive phytochemical has shown high potential and interest ...in the treatment of various disorders such as cancer, diabetes, arthritis, asthma, and cardiovascular disease, in addition to being an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry. This review aims to provide an overview of the in vitro, in vivo, and clinical studies reporting the diosgenin’s pharmacological effects and to discuss the safety issues. Preclinical studies have shown promising effects on cancer, neuroprotection, atherosclerosis, asthma, bone health, and other pathologies. Clinical investigations have demonstrated diosgenin’s nontoxic nature and promising benefits on cognitive function and menopause. However, further well-designed clinical trials are needed to address the other effects seen in preclinical studies, as well as a better knowledge of the diosgenin’s safety profile.
Desert ecosystems harbor a unique microbial diversity that is crucial for ecological stability and biogeochemical cycles. An in-depth understanding of the biodiversity, compositions, and functions of ...these microbial communities is imperative to navigate global changes and confront potential threats and opportunities applicable to agricultural ecosystems amid climate change.
This study explores microbial communities in the rhizosphere and endosphere of desert plants native to the Arabian Peninsula using next-generation sequencing of the 16S rRNA gene (V3-V4 hypervariable region).
Our results reveal that each microbial community has a diverse and unique microbial composition. Based on alpha and beta diversity indices, the rhizosphere microbiome is significantly diverse and richer in microbial taxa compared to the endosphere. The data reveals a shift towards fast-growing microbes with active metabolism, involvement in nutrient cycling, nitrogen fixation, and defense pathways. Our data reveals the presence of habitat-specific microbial communities in the desert, highlighting their remarkable resilience and adaptability to extreme environmental conditions. Notably, we observed the existence of radiation-resistant microbes such as Deinococcus radiotolerans, Kocuria sp., and Rubrobacter radiotolerans which can tolerate high levels of ionizing radiation. Additionally, examples of microbes exhibiting tolerance to challenging conditions include Nocardioides halotolerans, thriving in high-salinity environments, and hyperthermophilic microbes such as Quasibacillus thermotolerans. Moreover, functional analysis reveals enrichment in chaperon biosynthesis pathways associated with correct protein folding under heat stress conditions.
Our research sheds light on the unique diversity of desert microbes and underscores their potential applications to increase the resilience of agriculture ecosystems, offering a promising strategy to fortify crops against the challenges posed by climate change, ultimately supporting sustainable food production for our ever-expanding global population.
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