Nanozymes for medical biotechnology and its potential applications in biosensing and nanotherapeutics.

Recent past years have witnessed the development of several artificial enzymes, using different materials to mimic natural enzymes with respect to their structure and functions. The nanozymes are nanomaterials possessing similar characteristics to the natural enzymes and have emerged recently as an innovative class of artificial enzymes. The nanozymes have got remarkable attention from the researchers and notable developments have been achieved owing to their unique properties compared with natural enzymes and classic artificial enzymes. In this regard, several nanomaterials have been scrutinized so far to mimic different natural enzymes for wider applications ranging from imaging, sensing, water treatment, pollutant removal, and therapeutics. The applications of nanozymes in biomedicine research are fast-growing and various nanozymes have been implicated in diagnostic medicine, targeted cancer therapy. Such abilities make them an appropriate alternative for the development of affordable, sustainable and safe diagnostic as well as therapeutic agents.

Potential Target Metabolites From Gut Microbiota Against Hepatocellular Carcinoma: A Network Pharmacology and Molecular Docking Study.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, posing significant challenges and economic burdens on healthcare systems. Gut microbiota metabolites have shown promise in cancer treatment, but the specific active metabolites and their key targets remain unclear. This study employed a network pharmacology-based approach to identify potent metabolites of gut microbiota and their key targets. Active metabolites produced by gut microbiota were retrieved using the database gutMGene, and targets associated with these metabolites were identified using the Swiss Target Prediction tool. HCC-related targets were obtained from the GeneCards database, and overlapping targets were selected through a Venn diagram tool. An integrated metabolites-target-pathway network was analyzed to identify active inhibitors against HCC, including p-cresol glucuronide, secoisolariciresinol, glycocholic acid, enterodiol, and citric acid. Molecular docking tests were performed to validate the findings and assess the binding affinity of the metabolites with their target proteins. The study identified AKT1, EGFR, ALB, and TNF genes as potential therapeutic targets against hepatic cancer. The metabolites, p-cresol glucuronide, secoisolariciresinol, glycocholic acid, enterodiol, and citric acid, exhibited significant binding affinity with their respective target proteins. The study also revealed multiple signaling pathways and biological processes associated with the metabolites, demonstrating their preventive effect against HCC. This research utilizes a network pharmacology-based approach to identify potent metabolites of gut microbiota and their key targets for the treatment of HCC. The findings were validated through molecular docking tests, providing a foundation for future studies on anti-HCC metabolites and their mechanisms of action. Furthermore, this study offers insights into the development of novel anti-HCC drugs utilizing gut microbiota metabolites.

Exploring the Antimicrobial and Pharmacological Potential of NF22 as a Potent Inhibitor of E. coli DNA Gyrase: An In Vitro and In Silico Study.

Toward the search for novel antimicrobial agents to control pathogenic E. coli-associated infections, a series of novel norfloxacin derivatives were screened for antimicrobial activities. The norfloxacin derivative, 1-ethyl-6-fluoro-7-(4-(2-(2-(3-hydroxybenzylidene)hydrazinyl)-2-oxoethyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (NF22) demonstrated excellent antibacterial activities against E. coli ATCC 25922 (MIC = 0.0625 µg/mL) and MDR E. coli 1-3 (MIC = 1, 2 and 1 µg/mL). The time-kill kinetic studies have demonstrated that the NF22 was advantageous over norfloxacin and ciprofloxacin in killing the control and MDR E. coli strains. The checkerboard assay showed that NF22 in combination with tetracycline had a synergistic effect against the E. coli strains. The experimental findings are supported by molecular modeling studies on DNA gyrase, explaining the interactions involved for compound NF22, compared to norfloxacin and ciprofloxacin. Further, the compound was also evaluated for various pharmacokinetics (absorption, metabolism, distribution, toxicity and excretion) as well as drug-likeness properties. Our data have highlighted the potential of norfloxacin by restoring its efficacy against E. coli which could lead to the development of new antimicrobial agents.

Subtractive proteomics to identify targets for vaccine development against vancomycin-resistant Enterococcus faecalis.

Aim: Due to the increased level of vancomycin resistance in Enterococci species, an aggressive treatment involving targeted antibiotics is required to manage this frequently occurring infection. Materials & methods: Here, subtractive proteomics and reverse vaccinology approaches were employed to identify potential target and for the prediction of B cell and T cell epitopes against vancomycin-resistant Enterococcus faecalis (VRE V583). Results: The results exhibited the presence of 73 out of 805 non-homologous protein sequences in the proteome which can be employed as unique targets to develop the novel drugs and vaccine to counter the deadly infections caused by this microbe. Conclusion: The identified novel target in VRE V583 will equip our knowledge to design effective vaccine against probable protease EEP proteins.

Proteome-Wide Mapping and Reverse Vaccinology Approaches to Design a Multi-Epitope Vaccine against Clostridium perfringens.

C. perfringens is a highly versatile bacteria of livestock and humans, causing enteritis (a common food-borne illness in humans), enterotoxaemia (in which toxins are formed in the intestine which damage and destroy organs, i.e., the brain), and gangrene (wound infection). There is no particular cure for the toxins of C. perfringens. Supportive care (medical control of pain, intravenous fluids) is the standard treatment. Therefore, a multiple-epitope vaccine (MEV) should be designed to battle against C. perfringens infection. Furthermore, the main objective of this in silico investigation is to design an MEV that targets C. perfringens. For this purpose, we selected the top three proteins that were highly antigenic using immuno-informatics approaches, including molecular docking. B-cells, IFN-gamma, and T cells for target proteins were predicted and the most conserved epitopes were selected for further investigation. For the development of the final MEV, epitopes of LBL5, CTL17, and HTL13 were linked to GPGPG, AAY, and KK linkers. The vaccine N-end was joined to an adjuvant through an EAAK linker to improve immunogenicity. After the attachment of linkers and adjuvants, the final construct was 415 amino acids. B-cell and IFN-gamma epitopes demonstrate that the model structure is enhanced for humoral and cellular immune responses. To validate the immunogenicity and safety of the final construct, various physicochemical properties, and other properties such as antigenicity and non-allergens, were evaluated. Furthermore, molecular docking was carried out for verification of vaccine compatibility with the receptor, evaluated in silico. Also, in silico cloning was employed for the verification of the proper expression and credibility of the construct.

In Silico Subtractive Proteomics Approach for Identification of Potential Drug Targets in Staphylococcus saprophyticus.

Staphylococcus saprophyticus is a uropathogenic bacteria responsible for acute urinary tract infections (UTIs) mainly in young female patients. Patients suffering from urinary catheterization, pregnant patients, the elderly as well as those with nosocomial UTIs are at greater risk of the colonizing S. saprophyticus infection. The causative factors include benign prostatic hyperplasia, indwelling catheter, neurogenic bladder, pregnancy, and history of frequent UTIs. Recent findings have exhibited that S. saprophyticus is resistant to several antimicrobial agents. Moreover, there is a global concern regarding the increasing level of antimicrobial resistance, which leads to treatment failure and reduced effectiveness of broad-spectrum antimicrobials. Therefore, a novel approach is being utilized to combat resistant microbes since the past few years. Subtractive proteome analysis has been performed with the entire proteome of S. saprophyticus strain American Type Culture Collection (ATCC) 15305 using several bioinformatics servers and software. The proteins that were non-homologous to humans and bacteria were identified for metabolic pathway analysis. Only four cytoplasmic proteins were found possessing the potential of novel drug target candidates. The development of innovative therapeutic agents by targeting the inhibition of any essential proteins may disrupt the metabolic pathways specific to the pathogen, thus causing destruction as well as eradication of the pathogen from a particular host. The identified targets can facilitate in designing novel and potent drugs against S. saprophyticus strain ATCC 15305.

The Therapeutic Prospects of Naturally Occurring and Synthetic Indole Alkaloids for Depression and Anxiety Disorders.

Depression and anxiety are the most common disorders among all age groups. Several antidepressant drugs including benzodiazepine, antidepressant tricyclics, azapirone, noradrenaline reuptake inhibitors, serotonin selective reuptake inhibitors, serotonin, noradrenaline reuptake inhibitors, and monoamine oxidase inhibitors have been used to treat these psychiatric disorders. However, these antidepressants are generally synthetic agents and can cause a wide range of side effects. The potential efficacy of plant-derived alkaloids has been reviewed against various neurodegenerative diseases including Alzheimer's disease, Huntington disease, Parkinson's disease, schizophrenia, and epilepsy. However, data correlating the indole alkaloids and antidepressant activity are limited. Natural products, especially plants and the marine environment, are rich sources of potential new drugs. Plants possess a variety of indole alkaloids, and compounds that have an indole moiety are related to serotonin, which is a neurotransmitter that regulates brain function and cognition, which in turn alleviates anxiety, and ensures a good mood and happiness. The present review is a summary of the bioactive compounds from plants and marine sources that contain the indole moiety, which can serve as potent antidepressants. The prospects of naturally occurring as well as synthetic indole alkaloids for the amelioration of anxiety and depression-related disorders, structure-activity relationship, and their therapeutic prospects have been discussed.

Anti-angiogenesis Potential of Phytochemicals for the Therapeutic Management of Tumors.

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models. The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.

Quorum Sensing Interfering Strategies and Their Implications in the Management of Biofilm-Associated Bacterial Infections

Abstract The bacterial species employ various types of molecular communication systems recognized as quorum sensing for the synchronization of differential gene expression to regulate virulence traits and biofilm formation. A variety of quorum sensing inhibitors; molecules that interfere with quorum sensing among bacteria have been examined which can block the action of autoinducers. Moreover, the studies have scrutinized various enzymes for their quorum quenching activity resulting in the degradation of signaling molecules or blocking of gene expression. So far, the studies have found that these approaches are not only capable to reduce the pathogenicity and biofilm formation but also resulted in increased bacterial susceptibility to antibiotics and bacteriophages. The effectiveness of these strategies has been validated in different animal models and it seems that these practices will be transformed in near future to develop the medical devices including catheters, implants, and dressings for the prevention of bacterial infections. Although many of these approaches are still in the research stage, the increasing library of quorum quenching molecules and enzymes will open innovative perspectives for the development of antibacterial approaches which will extend the therapeutic arsenal against the pathogenic bacterial species.