The threat of arsenic contamination in water is a challenging issue worldwide. Millions of people utilize untreated groundwater having high levels of arsenic in developing countries. Design Expert ...6.0.8 has been used to design experiments and carried out statistical analysis for optimization of different parameters. It is of prime importance to develop cheap environment friendly bio-sorbent for protecting health of the poor from ill effects of arsenic. In the present investigation, we prepared bio-sorbent from the solid waste seed biomass of
Mangifera indica
(M),
Artocarpus heterophyllus
(JF), and
Schizizium commune
(JP). The characterization of bio-sorbents has been done by using different techniques namely FTIR and XRD. Arsenic concentration was estimated using ICP and adsorption parameters optimized for pH, adsorbent dose, and initial arsenic concentration. At pH 8.4, kinetics study of arsenic removal was M (94%), JF (93%), and JP (92%) for initial concentration of 2.5 ppm. The adsorption kinetics was well explained by Freundlich model and pseudo-second reaction order.
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.
Tuberculosis (TB) is the leading cause of death from a single infectious agent. The estimated total global TB deaths in 2019 were 1.4 million. The decline in TB incidence rate is very slow, while the ...burden of noncommunicable diseases (NCDs) is exponentially increasing in low- and middle-income countries, where the prevention and treatment of TB disease remains a great burden, and there is enough empirical evidence (scientific evidence) to justify a greater research emphasis on the syndemic interaction between TB and NCDs. The current study was proposed to build a disease-gene network based on overlapping TB with NCDs (overlapping means genes involved in TB and other/s NCDs),
Parkinson's disease, cardiovascular disease, diabetes mellitus, rheumatoid arthritis, and lung cancer. We compared the TB-associated genes with genes of its overlapping NCDs to determine the gene-disease relationship. Next, we constructed the gene interaction network of disease-genes by integrating curated and experimentally validated interactions in humans and find the 13 highly clustered modules in the network, which contains a total of 86 hub genes that are commonly associated with TB and its overlapping NCDs, which are largely involved in the Inflammatory response, cellular response to cytokine stimulus, response to cytokine, cytokine-mediated signaling pathway, defense response, response to stress and immune system process. Moreover, the identified hub genes and their respective drugs were exploited to build a bipartite network that assists in deciphering the drug-target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drugs combination or drug repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs, and give a synergistic effect with better outcomes. Thus, understanding the
(Mtb) infection and associated NCDs is a high priority to contain its short and long-term effects on human health. Our network-based analysis opens a new horizon for more personalized treatment, drug-repurposing opportunities, investigates new targets, multidrug treatment, and can uncover several side effects of unrelated drugs for TB and its overlapping NCDs.
Prostate cancer (PCa) is the most prevalent cancer (20%) in males and is accountable for a fifth (6.8%) cancer-related deaths in males globally. Smoking, obesity, race/ethnicity, diet, age, chemicals ...and radiation exposure, sexually transmitted diseases, etc. are among the most common risk factors for PCa. However, the basic change at the molecular level is the manifested confirmation of PCa. Thus, this study aims to evaluate the molecular signature for PCa in comparison to benign prostatic hyperplasia (BPH). Additionally, representation of differentially expressed genes (DEGs) are conducted with the help of some bioinformatics tools like DAVID, STRING, GEPIA, Cytoscape. The gene expression profile for the four data sets GSE55945, GSE104749, GSE46602, and GSE32571 was downloaded from NCBI, Gene Expression Omnibus (GEO). For the extracted DEGs, different types of analysis including functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction, survival analysis and transcription factor (TF) prediction were conducted. We obtained 633 most significant upregulated genes and 1219 downregulated genes, and a sum total of 1852 DEGs were found from all four datasets after assessment. The key genes, including
,
,
, and
, are targeted by TF such as AR, Sp1, TP53, NF-KB1, STAT3, RELA. Moreover, miR-21-5p also found significantly associated with all the four key genes. Further, The Cancer Genome Atlas data (TCGA) independent database was used for validation of key genes
,
,
, PTEN expression in prostate adenocarcinoma. All four key genes were found to be significantly correlated with overall survival in PCa. Therefore, the therapeutic target may be determined by the information of these key gene's findings for the diagnosis, prognosis and treatment of PCa.
Doxorubicin is a commonly used chemotherapeutic agent to treat several malignancies, including aggressive tumors like triple-negative breast cancer. It has a limited therapeutic index owing to its ...extreme toxicity and the emergence of drug resistance. As a result, there is a pressing need to find innovative drugs that enhance the effectiveness of doxorubicin while minimizing its toxicity. The rationale of the present study is that combining emerging treatment agents or repurposed pharmaceuticals with doxorubicin might increase susceptibility to therapeutics and the subsequent establishment of improved pharmacological combinations for treating triple-negative breast cancer. Additionally, combined treatment will facilitate dosage reduction, reducing the toxicity associated with doxorubicin. Recently, the third-generation retinoid adapalene was reported as an effective anticancer agent in several malignancies. This study aimed to determine the anticancer activity of adapalene in TNBC cells and its effectiveness in combination with doxorubicin, and the mechanistic pathways in inhibiting tumorigenicity. Adapalene inhibits tumor cell growth and proliferation and acts synergistically with doxorubicin in inhibiting growth, colony formation, and migration of TNBC cells. Also, the combination of adapalene and doxorubicin enhanced the accumulation of reactive oxygen species triggering hyperphosphorylation of Erk1/2 and caspase-dependent apoptosis. Our results demonstrate that adapalene is a promising antitumor agent that may be used as a single agent or combined with present therapeutic regimens for TNBC treatment.
Surfactin lipopeptide is an eco-friendly microbially synthesized bioproduct that holds considerable potential in therapeutics (antibiofilm) as well as in agriculture (antifungal). In the present ...study, production of surfactin by a marine strain
MS20 was carried out, followed by physico-chemical characterization, anti-biofilm activity, plant growth promotion, and quantitative Reverse Transcriptase-Polymerase Chain Reaction (q RT-PCR) studies. From the results, it was inferred that MS20 was found to produce biosurfactant (3,300 mg L
) under optimized conditions. From the physicochemical characterization Thin layer chromatography (TLC), Fourier Transform Infrared (FTIR) Spectroscopy, Liquid Chromatography/Mass Spectroscopy (LC/MS), and Polymerase Chain Reaction (PCR) amplification it was revealed to be surfactin. From bio-assay and scanning electron microscope (SEM) images, it was observed that surfactin (MIC 50 μg Ml
) has appreciable bacterial aggregation against clinical pathogens
MTCC424,
MTCC43,
MTCC9751, and Methicillin resistant
(MRSA) and mycelial condensation property against a fungal phytopathogen
. In addition, the q-RTPCR studies revealed 8-fold upregulation (9.34 ± 0.11-fold) of
A-A gene compared to controls. Further, treatment of maize crop (infected with
) with surfactin and MS20 led to the production of defense enzymes. In conclusion, concentration and synergy of a carbon source with inorganic/mineral salts can ameliorate surfactin yield and, application wise, it has antibiofilm and antifungal activities. In addition, it induced systemic resistance in maize crop, which makes it a good candidate to be employed in sustainable agricultural practices.
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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.
•Breast cancer is the primary reason for female fatalities globally. Since its incidence has overtaken lung cancer.•Because it is the most complicated and heterogeneous illness, patients' clinical ...care and prognoses vary greatly.•Additionally, available therapies including surgery, radiation, and chemotherapy continue to be unsuccessful due to several factors such as severe side effects, intra-tumoral heterogeneity, drug resistance and lack of targeted therapy. Therefore, there is a need to search for better treatment options.•Due to the fact that anti-cancer drugs are abundant in marine life and have been demonstrated to be essential in the treatment of tumors throughout time. It has the potential to harbor novel anti-cancer medications.•Therefore, we examined Stypoldione, a marine natural substance which is discovered in brown algae (Stypopodium zonale)for its anti-cancer potential against breast cancer for which it has not been studied yet.•Using a network pharmacology method, we looked into the anti-cancer potential of stypoldione against breast cancer. We verified our research using a number of computer-aided techniques, including UALCAN, cBioportal, TIMER, docking, and MD modeling.
Breast cancer is the primary factor contributing to female mortality worldwide. The incidence has overtaken lung cancer. It is the most difficult illness due to its heterogeneity and is made up of several subtypes, including Luminal A and B, basal-like, Her-2 overexpressed and TNBC. Amongst different breast carcinoma subtypes, TNBC is the most deadly breast cancer subtype. The hostile nature of TNBC is mainly attributed to its lack of three hormonal receptors and hence lack of targeted therapy. Furthermore, the current diagnostic options like radiotherapy, surgery and chemotherapy render unsuccessful due to recurrence, treatment side effects and drug resistance. The majority of anticancer drugs come from natural sources or is developed from them, making nature a significant source of many medicines. Marine-based constituents such as nucleotides, proteins, peptides, and amides are receiving a lot of interest in the field of cancer treatment due to their bioactive properties. The role of stypoldione in this study as a prospective treatment for breast carcinoma was examined, and we sought to comprehend the molecular means/pathways this chemical employs in breast carcinoma. The most promising possibility for an anti-cancer treatment is stypoldione, a marine chemical produced from the brown alga Stypopodium zonale. We investigated stypoldione's mode of action in breast cancer using the network pharmacology method, and we confirmed our research by using a number of computational tools, including UALCAN, cBioportal, TIMER, docking, and simulation. The findings revealed 92 common targets between the chemical and breast cancer target network. Additionally, we found that stypoldione targets a number of unregulated genes in breast cancer, including: ESR1, HSP90AA1, CXCL8, PTGS2, APP, MDM2, JAK2, KDR, LCK, GRM5, MAPK14, KIT, and several signaling pathways such as FOXO signaling pathway, VEGF pathway, calcium signaling pathway, MAPK/ERK pathway and Neuroactive ligand-receptor interaction. The examined medication demonstrated a strong affinity for the major targets, according to a docking analysis. The best hit compound produced a stable protein-ligand pair, as predicted by molecular dynamics simulations. Our results are supported by the fact that when in-vitro assays were done on melanoma usingstypoldionecompound it was found that its mechanisms of action involved the PI3K/mTOR/Akt and NF-kB pathways. This study wasset out to inspect the possible value of stypoldione as a breast cancer cure and to get a deeper understanding of the molecular mechanisms by which this drug acts on breast cancer.
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•Due to limited efficacy, side effects and development of resistance against current chemotherapy there is a need for developing targeted therapy and one such promising approach is ...the exploration of natural compounds through cost-effective and less time-consuming computational tools such as network pharmacology and molecular docking and simulation studies.•On screening we found one such natural compound Juglanthraquinone C which has revealed promising prospective as an anti-cancer agent in breast carcinoma due to its ability to reduce inflammation, inhibit tumor growth, and suppress metastasis, as well as its synergistic effects with chemotherapy, which makes it a promising candidate for breast cancer treatment.•By using the network pharmacology and other in silico approaches we for the first time revealed the potential therapeutic targets of this compound in breast carcinoma and found that the compound and breast carcinoma target network shared 31 common targets.
Breast cancer is the leading cause of death among women worldwide. Despite the recent treatment options like surgery, chemotherapy etc. the lethality of breast cancer is alarming. Natural compounds are considered a better treatment option against breast carcinoma because of their lower side effects and specificity in targeting important proteins involved in the aberrant activation of pathways in breast cancer. A recently discovered compound called Juglanthraquinone C, which is found in the bark of the Juglans mandshurica Maxim (Juglandaceae) tree has shown promising cytotoxicity in hepatocellular carcinoma. However, not much data is available on the molecular mechanisms followed by this compound. Therefore, we aimed to investigate the molecular mechanism followed by Juglanthraquinone C against breast cancer. We used the network pharmacology technique to analyse the mechanism of action ofJuglanthraquinone Cin breast cancer and validated our study by applying various computational tools such as UALCAN, cBioportal, TIMER, docking and simulation. The results showed the compound and breast cancer target network shared 31 common targets. Moreover, we observed thatJuglanthraquinone C targets multiple deregulated genes in breast cancer such as TP53, TGIF1, IGF1R, SMAD3, JUN, CDC42, HBEGF, FOS and signaling pathways such as PI3K-Akt pathway, TGF-β signaling pathway, MAPK pathway and HIPPO signaling pathway. A docking examination revealed that the investigated drug had a high affinity for the primary target TGIF1 protein. A stable protein–ligand combination was generated by the best hit molecule, according to molecular dynamics modeling. The main aim of this study was to examine Juglanthraquinone C's significance as a prospective breast cancer treatment and to better understand the molecular mechanism this substance uses in breast cancer since there is a need to discover new therapeutics to decrease the load on current therapeutics which also are currently ineffective due to several side effects and development of drug resistance.
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