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•Present research is focused on creating more individualized and accurate therapy solutions to address the issues that occur in conventional treatment approaches for breast ...cancer.•One of the important category of compounds that are best for breast cancer treatment include phytotherapeutic compounds.•Several molecular targets and signalling pathways connected to the instigation and succession of cancer can be targeted by natural substances.•This review focuses on the description of the molecular function played by a number of significant natural chemicals in breast cancer.
Cancer of the breast is the mainly prevalent class of cancer in females diagnosed over the globe. It also happens to be the 2nd most prevalent reason of cancer-related deaths among females worldwide. Some of the most common type’s therapies for carcinoma of the breast involve radiation therapy, chemotherapy, and resection. Many studies are being conducted to develop new therapeutic strategies for better diagnosis of breast cancer. An enormous number of anticancer medications have been developed as a result of growing understanding of the molecular pathways behind the advancement of cancer. Over the past few decades, the general survival rate has not greatly increased due to the usage of chemically manufactured medications. Therefore, in order to increase the effectiveness of current cancer treatments, new tactics and cutting-edge chemoprevention drugs are required. Phytochemicals, which are naturally occurring molecules derived from plants, are important sources for both cancer therapy and innovative medication development. These phytochemicals frequently work by controlling molecular pathways linked to the development and spread of cancer. Increasing antioxidant status, inactivating carcinogens, preventing proliferation, causing cell cycle arrest and apoptosis, and immune system control are some of the specific ways. This primary objective of this review is to provide an overview of the active ingredients found in natural goods, including information on their pharmacologic action, molecular targets, and current state of knowledge. We have given a thorough description of a number of natural substances that specifically target the pathways linked to breast carcinoma in this study. We've conducted a great deal of study on a few natural compounds that may help us identify novel targets for the detection of breast carcinoma.
Abstract
Geranium wallichianum
D. Don ex Sweet is a well-known medicinal plant in Kashmir Himalya. The evidence for its modern medicinal applications remains majorly unexplored. The present study was ...undertaken to elucidate the detailed antimicrobial promises of different crude extracts (methanolic, ethanolic, petroleum ether, and ethyl acetate) of
G. wallichainum
against common human bacterial and fungal pathogens in order to scientifically validate its traditional use. The LC–MS analysis of
G. wallichainum
yielded 141 bioactive compounds with the vast majority of them having therapeutic applications. Determination of minimum inhibitory concentrations (MICs) by broth microdilution method of
G. wallichainum
was tested against bacterial and fungal pathogens with MICs ranging from 0.39 to 400 µg/mL. Furthermore, virtual ligands screening yielded elatine, kaempferol, and germacrene-A as medicinally most active constituents and the potential inhibitors of penicillin-binding protein (PBP), dihydropteroate synthase (DHPS), elongation factor-Tu (Eu-Tu), ABC transporter, 1,3 beta glycan, and beta-tubulin. The root mean square deviation (RMSD) graphs obtained through the molecular dynamic simulations (MDS) indicated the true bonding interactions which were further validated using root mean square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. The effective binding of elatine, kaempferol, and germacrene-A with these proteins provides ground for further research to understand the underlying mechanism that ceases the growth of these microbes.
Gum Arabic (GA) has a protective role against experimental nephrotoxicity and hepatotoxicity. This study explores the possible ameliorating effect of Gum Arabic on the liver tissues of the uremic ...rats.
50 adult male albino rats were divided into 5 groups; Group I, (negative control). Group II: two flank incisions were made and the kidneys were kindly manipulated. Group III: the rats have received a daily oral dose of GA. Group IV: subtotal nephrectomy in the left kidney was done followed by total nephrectomy on the right kidney 1 week later to induce uremia. Group V: the rats received GA one day after the second operation and daily for 5 weeks. At the end of the work, the rats were sacrificed, blood samples were collected for biochemical analysis. The abdomen was opened and the liver was dissected for light, electron microscopic and immunohistochemical studies.
The biochemical results were increased in the uremic group, but greatly improved after GA administration. Light and electron studies showed histopathological changes of the liver tissues in the uremic group, which was improved after GA administration and confirmed by the morphometric measures.
GA ameliorates the histopathological changes of the liver tissues caused by uremic toxins and has a protective effect against the development of hepatocellular carcinoma.
•Uremic toxins cause pathological changes in the liver tissues.•Gum Arabic; as an antioxidant, contains antioxidant minerals and enzymes.•Gum Arabic is a physiological modulator for a variety of body functions as cell proliferation, apoptosis, angiogenesis regulation, and inflammation.•GA ameliorates the histopathological changes in the liver tissues.
Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance genes (AMRs) are acquired, ...expressed, disseminated, and traded mainly through integrons, the key players capable of transferring genes from bacterial chromosomes to plasmids and their integration by integrase to the target pathogenic host. Moreover, integrons play a central role in disseminating and assembling genes connected with antibiotic resistance in pathogenic and commensal bacterial species. They exhibit a large and concealed diversity in the natural environment, raising concerns about their potential for comprehensive application in bacterial adaptation. They should be viewed as a dangerous pool of resistance determinants from the “One Health approach.” Among the three documented classes of integrons reported viz., class-1, 2, and 3, class 1 has been found frequently associated with AMRs in humans and is a critical genetic element to serve as a target for therapeutics to AMRs through gene silencing or combinatorial therapies. The direct method of screening gene cassettes linked to pathogenesis and resistance harbored by integrons is a novel way to assess human health. In the last decade, they have witnessed surveying the integron-associated gene cassettes associated with increased drug tolerance and rising pathogenicity of human pathogenic microbes. Consequently, we aimed to unravel the structure and functions of integrons and their integration mechanism by understanding horizontal gene transfer from one trophic group to another. Many updates for the gene cassettes harbored by integrons related to resistance and pathogenicity are extensively explored. Additionally, an updated account of the assessment of AMRs and prevailing antibiotic resistance by integrons in humans is grossly detailed—lastly, the estimation of AMR dissemination by employing integrons as potential biomarkers are also highlighted. The current review on integrons will pave the way to clinical understanding for devising a roadmap solution to AMR and pathogenicity.
Graphical Abstract
The graphical abstract displays how integron-aided AMRs to humans: Transposons capture integron gene cassettes to yield high mobility integrons that target res sites of plasmids. These plasmids, in turn, promote the mobility of acquired integrons into diverse bacterial species. The acquisitions of resistant genes are transferred to humans through horizontal gene transfer.
Although advances in diagnostics and therapeutics have prolonged the survival of triple-negative breast cancer (TNBC) patients, metastasis, therapeutic resistance, and lack of targeted therapies ...remain the foremost hurdle in the effective management of TNBC. Thus, evaluation of new therapeutic agents and their efficacy in combination therapy is urgently needed. The third-generation retinoid adapalene (ADA) has potent antitumor activity, and using ADA in combination with existing therapeutic regimens may improve the effectiveness and minimize the toxicities and drug resistance. The current study aimed to assess the anticancer efficacy of adapalene as a combination regimen with the PI3K inhibitor (GDC-0941) in TNBC
in vitro
models. The Chou–Talalay’s method evaluated the pharmacodynamic interactions (synergism, antagonism, or additivity) of binary drug combinations. Flow cytometry, Western blotting, and
in silico
studies were used to analyze the mechanism of GDC–ADA synergistic interactions in TNBC cells. The combination of GDC and ADA demonstrated a synergistic effect in inhibiting proliferation, migration, and colony formation of tumor cells. Accumulation of reactive oxygen species upon co-treatment with GDC and ADA promoted apoptosis and enhanced sensitivity to GDC in TNBC cells. The findings indicate that ADA is a promising therapeutic agent in treating advanced BC tumors and enhance sensitivity to GDC in inhibiting tumor growth in TNBC models while reducing therapeutic resistance.
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•COVID-19 pandemic has traumatized the entire world. During this outbreak, an upsurge in MDR-associated pathogenic microbial organisms has been recorded.•The increasing human ...microbial diseases pose a severe danger to global human safety.•The infectious microbes have developed multiple tolerance strategies to overcome the negative drug impacts.•Several naturally occurring chemicals produced from bacteria, plants, animals, marine species, and other sources with antimicrobial characteristics have been reviewed.•These compounds show promise in minimizing the globally increasing microbial diseases.
Human infectious diseases caused by various microbial pathogens, in general, impact a large population of individuals every year. These microbial diseases that spread quickly remain to be a big issue in various health-related domains and to withstand the negative drug impacts, the antimicrobial-resistant pathogenic microbial organisms (pathogenic bacteria and pathogenic fungi) have developed a variety of resistance processes against many antimicrobial drug classes. During the COVID-19 outbreak, there seems to be an upsurge in drug and multidrug resistant-associated pathogenic microbial species. The preponderance of existing antimicrobials isn’t completely effective, which limits their application in clinical settings. Several naturally occurring chemicals produced from bacteria, plants, animals, marine species, and other sources are now being studied for antimicrobial characteristics. These natural antimicrobial compounds extracted from different sources have been demonstrated to be effective against a variety of diseases, although plants remain the most abundant source. These compounds have shown promise in reducing the microbial diseases linked to the development of drug tolerance and resistance. This paper offers a detailed review of some of the most vital and promising natural compounds and their derivatives against various human infectious microbial organisms. The inhibitory action of different natural antimicrobial compounds, and their possible mechanism of antimicrobial action against a range of pathogenic fungal and bacterial organisms, is provided. The review will be useful in refining current antimicrobial (antifungal and antibacterial) medicines as well as establishing new treatment strategies to tackle the rising number of human bacterial and fungal-associated infections.
The Aurora family of serine/threonine kinases in mammals are key regulators of mitotic progression and are commonly upregulated in human tumors. Since AURKA’s increased expression has been linked to ...cancer, AURKA inhibitors could reduce AURKA expression and function as potent therapeutic drugs. The study’s objective was to find and categorize inhibitors with a stronger affinity for AURKA. This study also aimed to identify AURKA’s expression profile and prognostic significance across pan-cancers. We looked into therapeutic compounds that were structurally comparable to MK8745 for their potential to selectively inhibit AURKA. We used drug likeliness analysis, MD simulation studies to evaluate the therapeutic possibility of screened MK8745 analogues. AURKA was found to be strongly upregulated in several cancers and is linked to worse overall and relapse-free survival. The Molecular docking and dynamic analysis revealed two new MK8745 analogues to be potent AURKA inhibitors with higher binding affinities and stabilities than MK8745. Furthermore, MK8745 analogues are potential replacements for MK8745 because they have strong binding affinity, which is consistent with MDS results, and have appropriate ADMET properties. Through basic, clinical, and preclinical research, the identification of novel compounds may open the door for their prospective use in the prevention of cancer.
Graphical abstract
The current scientific community is facing a daunting challenge to unravel reliable natural compounds with realistic potential to treat neurological disorders such as Alzheimer's disease (AD). The ...reported compounds/drugs mostly synthetic deemed the reliability and therapeutic potential largely due to their complexity and off-target issues. The natural products from nutraceutical compounds emerge as viable preventive therapeutics to fill the huge gap in treating neurological disorders. Considering that Alzheimer's disease is a multifactorial disease, natural compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs so far used to treat Alzheimer's disease. A wide range of plant extracts and phytochemicals reported to possess the therapeutic potential to Alzheimer's disease includes curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and other phytochemicals such as huperzine A, limonoids, and azaphilones. Reported targets of these natural compounds include inhibition of acetylcholinesterase, amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc. We tenaciously aimed to review the in-depth potential of natural products and their therapeutic applications against Alzheimer's disease, with a special focus on a diversity of medicinal plants and phytocompounds and their mechanism of action against Alzheimer's disease pathologies. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against Alzheimer's disease with lesser side effects as compared to currently available treatments.
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Interleukin 19 (IL-19) is a cytokine produced by monocytes and belongs to the family of IL-10. The IL-19 protein stimulates fibronectin (FN) expression and assembly, metastasis, and ...cell division in breast cancer (BC) cells. IL-19, which is connected to breast pathogenesis and has an autocrine action in BC cells, is a key predictor of prognosis for many tumour forms, including breast cancer. Augmented IL-19 expression has been related to poorer clinical outcomes for patients with BC and directly enhances proliferation and migration while also serving as a microenvironment for tumour formation. The main aim of our study was to examine the expression profile, functional role, and prognostic significance of interleukin-19 in BC pathogenesis and also to find out the molecular mechanism of IL-19 in BC. In this work, we used the various computational approach and tools, to evaluate the expression profile and prognostic implication of IL-19 in BC and discover the role of IL-19 in BC pathogenesis. IL-19 was shown to be highly upregulated in BC as compared to other interleukins. Also, its levels were highly overexpressed in liminal BC patients, mostly in 3rd stage groups under the age group of 21–40 years. IL-19 levels were increased in BC and elevated expression of IL-19 was examined to have worse overall survival (OS). The KEGG analysis andgene ontology of IL-19 depict that IL-19 is significantly augmented in cytokine activity and receptor-ligand activity and also in the JAK-STAT signaling pathway. Moreover, IL-19 showed a high correlation with IL20RA, as later is involved with the JAK-STAT signaling pathway. The in-vivo and in-vitro studies have also reflected that upregulation of IL-19 enhances tumor development and affects clinical outcomes in BC patients through several pathways including the JAK TAT signalling pathway. Overall, our study indicates that IL-19 increases tumour growth and that inhibiting it in addition to standard treatments will greatly improve BC patient’s therapeutic responses.
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