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Nanotechnology, an emerging field, holds significant promise with applications across diverse sectors, including medicine, agriculture, and the biological sciences. To address environmental concerns, the green biosynthesis of silver nanoparticles (AgNPs) using plant extracts is favoured. This study focuses on the formulation and characterisation of AgNPs using extracts from Withania coagulans (Stocks) Dunal, a medicinal plant that holds a unique phytochemical profile. The AgNPs derived from W. coagulans root (WcAgNPR) and fruit (WcAgNPF) extracts were characterised using ultraviolet and visible light (UV-Vis) spectral analysis, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR) spectroscopy. The findings reveal that both WcAgNPR and WcAgNPF exhibit substantial antioxidant potential, with robust iron reducing capabilities and potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity. Additionally, they demonstrate strong hydrogen peroxide scavenging abilities. Notably, WcAgNPR outperforms WcAgNPF in the phosphomolybdate assay for antioxidant potential. Both AgNPs display remarkable antimicrobial efficacy, with minimal inhibitory concentrations (MIC) below 10 µg.mL-1 against gram-positive bacteria (Staphylococcus aureus) and noteworthy activity against gram-negative Escherichia coli (WcAgNPF with a MIC of 30 µg.mL-1 and WcAgNPR with a MIC of 60 µg.mL-1). These findings highlight the silver nanoparticles' significant antioxidant and antimicrobial potential, suggesting their potential for in vivo use as antimicrobial agents with minimal oxidative damage.

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%–85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also known as miRNAs, have been identified in the last 20 years and significantly impact gene expression and protein translation. This atypical expression pattern is strongly associated with the onset and progression of various malignancies. Gene therapy, a novel form of biological therapy, is a prominent research area. Therefore, miRNAs have been used in the investigation of tumour gene therapy. This review examines the mechanisms of action of miRNAs, explores the correlation between miRNAs and HCC, and investigates the use of miRNAs in HCC gene therapy.

SARS-CoV-2, also referred to as severe acute respiratory syndrome coronavirus 2, is the virus responsible for causing COVID-19, an infectious disease that emerged in Wuhan, China, in December 2019. Among its crucial functions, NSP6 plays a vital role in evading the human immune system by directly interacting with a receptor called TANK-binding kinase (TBK1), leading to the suppression of IFNβ production. Consequently, in the present study we used the structural and biophysical approaches to analyze the effect of newly emerged mutations on the binding of NSP6 and TBK1. Among the identified mutations, four (F35G, L37F, L125F, and I162T) were found to significantly destabilize the structure of NSP6. Furthermore, the molecular docking analysis highlighted that the mutant NSP6 displayed its highest binding affinity with TBK1, exhibiting docking scores of −1436.2 for the wildtype and −1723.2, −1788.6, −1510.2, and −1551.7 for the F35G, L37F, L125F, and I162T mutants, respectively. This suggests the potential for an enhanced immune system evasion capability of NSP6. Particularly, the F35G mutation exhibited the strongest binding affinity, supported by a calculated binding free energy of −172.19 kcal/mol. To disrupt the binding between NSP6 and TBK1, we conducted virtual drug screening to develop a novel inhibitor derived from natural products. From this screening, we identified the top 5 hit compounds as the most promising candidates with a docking score of −6.59 kcal/mol, −6.52 kcal/mol, −6.32 kcal/mol, −6.22 kcal/mol, and −6.21 kcal/mol. The molecular dynamic simulation of top 3 hits further verified the dynamic stability of drugs-NSP6 complexes. In conclusion, this study provides valuable insight into the higher infectivity of the SARS-CoV-2 new variants and a strong rationale for the development of novel drugs against NSP6.

Ajuga bracteosa (family: Lamiaceae), commonly known as kauri booti, is an important ethnomedicinal plant. The current research was conducted to appraise and compare the in vitro antioxidant and antibacterial profiles as well as in vivo wound healing potentials of Ajugarin I and A. bracteosa extract. Ajugarin I and polyphenols in A. bracteosa were enumerated by reversed-phase high-performance liquid chromatography analysis that confirmed significant amounts of Ajugarin I (2.2 ± 0.02 μg/mg DW) and other phenolic compounds (14 out of 17 standards). A. bracteosa (374.4 ± 0.20 µg AAE/mg of DW, 201.9 ± 0.20 µg AAE/mg of DW, 87 ± 0.30%) showed a higher antioxidant profile compared to Ajugarin I (221.8 ± 0.50 µg AAE/mg of DW, 51.8 ± 0.40 µg AAE/mg of DW, 27.65 ± 0.80%) with 1.86-, 3.89-, and 3.15-fold greater activity in ferric reducing antioxidant power, total antioxidant capacity, and free radical scavenging assays, respectively. Likewise, A. bracteosa showed antibacterial activity against 3/5 strains (MIC 25–200 μg/ml) than Ajugarin I (2/5 strains; MIC 50–200 μg/ml). Hemolytic (

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds are under clinical investigation for various diseases. In particular, marine natural compounds are gaining more attention in the new drug development process. The present study aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the 4 SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds, namely, chrysophaentin A (−6.6 kcal/mol), geodisterol sulfates (−6.6 kcal/mol), hymenidin (−6.4 kcal/mol), plinabulin (−6.4 kcal/mol), and tetrodotoxin (−6.3 kcal/mol) expressed minimized binding energy and molecular interactions, such as covalent and hydrophobic interactions, with the SARS CoV-2 main protease. Using molecular dynamic studies, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (ROG), and hydrogen bond (H-Bond) values were calculated for the SARS-CoV-2 main protease with a hymenidin docked complex. Additionally, in silico drug-likeness and pharmacokinetic property assessments of the compounds demonstrated favorable druggability. These results suggest that marine natural compounds are capable of fighting SARS-CoV-2. Further in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.

The present study was the first comprehensive investigation of genetic mutation and expression levels of the p53 signaling genes in cutaneous melanoma through various genetic databases providing large datasets. The mutational landscape of p53 and its signaling genes was higher than expected, with TP53 followed by CDKN2A being the most mutated gene in cutaneous melanoma. Furthermore, the expression analysis showed that TP53 , MDM2 , CDKN2A , and TP53BP1 were overexpressed, while MDM4 and CDKN2B were under-expressed in cutaneous melanoma. Overall, TCGA data revealed that among all the other p53 signaling proteins, CDKN2A was significantly higher in both sun and non-sun-exposed healthy tissues than in melanoma. Likewise, MDM4 and TP53BP1 expressions were markedly greater in non-sun-exposed healthy tissues compared to other groups. However, CDKN2B expression was higher in the sun-exposed healthy tissues than in other tissues. In addition, various genes were expressed significantly differently among males and females. In addition, CDKN2A was highly expressed in the SK-MEL-30 skin cancer cell line, whereas, Immune cell type expression analysis revealed that the MDM4 was highly expressed in naïve B-cells. Furthermore, all six genes were significantly overexpressed in extraordinarily overweight or obese tumor tissues compared to healthy tissues. MDM2 expression and tumor stage were closely related. There were differences in gene expression across patient age groups and positive nodal status. TP53 showed a positive correlation with B cells, MDM2 with CD8+ T cells, macrophages and neutrophils, and MDM4 with neutrophils. CDKN2A/B had a non-significant correlation with all six types of immune cells. However, TP53BP1 was positively correlated with all five types of immune cells except B cells. Only TP53, MDM2 , and CDKN2A had a role in cutaneous melanoma-specific tumor immunity. All TP53 and its regulating genes may be predictive for prognosis. The results of the present study need to be validated through future screening, in vivo, and in vitro studies.

Immunity is usually classified into two categories: innate immunity and adaptive immunity, distinguished by the process and characteristics of the immunological impact. It was widely assumed that only adaptive immunity possessed memory features; however, current research has revealed that innate immunity, like adaptive immunity, possesses memory properties as well. “Trained immunity”, also known as “innate immune memory”, is a phenomenon that occurs when the immune system’s innate cells are stimulated and then undergo epigenetic reprogramming and metabolic alterations. When it comes to innate immunity, macrophages are essential since they have immunological memory capabilities and play a significant role in the body’s immunity. The concept of innate immune memory expands the definition of immunological memory and offers a broader view of immune response research. This article reviews the properties, mechanism, and significance of macrophage innate immune memory in disease.

The tumor microenvironment (TME), which includes both cellular and non-cellular elements, is now recognized as one of the major regulators of the development of primary tumors, the metastasis of which occurs to specific organs, and the response to therapy. Development of immunotherapy and targeted therapies have increased knowledge of cancer-related inflammation Since the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) limit immune cells from entering from the periphery, it has long been considered an immunological refuge. Thus, tumor cells that make their way “to the brain were believed to be protected from the body’s normal mechanisms of monitoring and eliminating them. In this process, the microenvironment and tumor cells at different stages interact and depend on each other to form the basis of the evolution of tumor brain metastases. This paper focuses on the pathogenesis, microenvironmental changes, and new treatment methods of different types of brain metastases. Through the systematic review and summary from macro to micro, the occurrence and development rules and key driving factors of the disease are revealed, and the clinical precision medicine of brain metastases is comprehensively promoted. Recent research has shed light on the potential of TME-targeted and potential treatments for treating Brain metastases, and we’ll use that knowledge to discuss the advantages and disadvantages of these approaches.

In the last ten years, it has become increasingly clear that tumor-infiltrating myeloid cells drive not just carcinogenesis via cancer-related inflammatory processes, but also tumor development, invasion, and metastasis. Tumor-associated macrophages (TAMs) in particular are the most common kind of leucocyte in many malignancies and play a crucial role in establishing a favorable microenvironment for tumor cells. Tumor-associated macrophage (TAM) is vital as the primary immune cell subset in the tumor microenvironment (TME).In order to proliferate and spread to new locations, tumors need to be able to hide from the immune system by creating an immune-suppressive environment. Because of the existence of pro-tumoral TAMs, conventional therapies like chemotherapy and radiotherapy often fail to restrain cancer growth. These cells are also to blame for the failure of innovative immunotherapies premised on immune-checkpoint suppression. Understanding the series of metabolic changes and functional plasticity experienced by TAMs in the complex TME will help to use TAMs as a target for tumor immunotherapy and develop more effective tumor treatment strategies. This review summarizes the latest research on the TAMs functional status, metabolic changes and focuses on the targeted therapy in solid tumors.

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also in the macrophages that compose the tumor microenvironment. This supports the idea that LGMN is a pivotal protein in regulating tumor development, invasion, and dissemination. Targeting LGMN with siRNA or chemotherapeutic medicines and peptides can suppress cancer cell proliferation in culture and reduce tumor growth in vivo. Furthermore, legumain can be used as a marker for cancer detection and targeting due to its expression being significantly lower in normal cells compared to tumors or tumor-associated macrophages (TAMs). Tumor formation is influenced by aberrant expression of proteins and alterations in cellular architecture, but the tumor microenvironment is a crucial deciding factor. Legumain (LGMN) is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. Its precise biological mechanism encompasses a number of routes, including effects on tumor-associated macrophage and neovascular endothelium in the tumor microenvironment. The purpose of this work is to establish a rationale for thoroughly investigating the function of LGMN in the tumor microenvironment and discovering novel tumor early diagnosis markers and therapeutic targets by reviewing the function of LGMN in tumor genesis and progression and its relationship with tumor milieu.

Background: Both hormonal and genetic data reveal that the stress hormone cortisol and its regulating genes may affect the level of testosterone in humans. It is uncertain whether type 2 diabetes mellitus would manifest similarly. Furthermore, a genetic strategy to screen out the stress system genes that may contribute to testosterone decline in humans is less understood. Objectives: In this study, we aimed to elucidate the link between stress and testosterone levels, both hormonally and genetically. Method: This study comprised 37 individuals with type 2 diabetes mellitus and 50 healthy individuals. For the analysis of hormones and the targeted genes, we used the RIA system and bioinformatics expertise. Results: The patients had significantly elevated cortisol and lower testosterone readings, according to data from hormonal analyses. The bioinformatics approach reveals that SHBG was intracellularly suppressed by 2 defined stress system genes: FKB5 and CYP17. TCF4/TCF8, ATRX, and AR in skeletal muscle were inversely related to stress system genes. Furthermore, all testosterone regulated genes were positively linked with SHBG in the current study. A strong relationship between GNAS and PKA with CYP17 and FKBP5 reveals that the Gαs-cAMP/PKA signaling pathway may be one of the regulatory pathways through which the suppression of testosterone system genes happens. In conclusion, this study demonstrated that beyond stress, the key stress system genes might affect cortisol levels, which in turn affect testosterone figures via the Gαs-cAMP/PKA signaling pathway.

Malaria, a highly perilous infectious disease, impacted approximately 230 million individuals globally in 2019. Mosquitoes, vectors of over 10% of worldwide diseases, pose a significant public health menace. The pressing need for novel antimalarial drugs arises due to the imminent threat faced by nearly 40% of the global population and the escalating resistance of parasites to current treatments. This study comprehensively addresses prevalent parasitic and viral illnesses transmitted by mosquitoes, leading to the annual symptomatic infections of 400 million individuals, placing 100 million at constant risk of contracting these diseases. Extensive investigations underscore the pivotal role of traditional plants as rich sources for pioneering pharmaceuticals. The latter half of this century witnessed the ascent of bioactive compounds within traditional medicine, laying the foundation for modern therapeutic breakthroughs. Herbal medicine, notably influential in underdeveloped or developing nations, remains an essential healthcare resource. Traditional Indian medical systems such as Ayurveda, Siddha, and Unani, with a history of successful outcomes, highlight the potential of these methodologies. Current scrutiny of Indian medicinal herbs reveals their promise as cutting-edge drug reservoirs. The propensity of plant-derived compounds to interact with biological receptors positions them as prime candidates for drug development. Yet, a comprehensive perspective is crucial. While this study underscores the promise of plant-based compounds as therapeutic agents against malaria and dengue fever, acknowledging the intricate complexities of drug development and the challenges therein are imperative. The journey from traditional remedies to contemporary medical applications is multifaceted and warrants prudent consideration. This research aspires to offer invaluable insights into the management of malaria and dengue fever. By unveiling plant-based compounds with potential antimalarial and antiviral properties, this study aims to contribute to disease control. In pursuit of this goal, a thorough understanding of the mechanistic foundations of traditional antimalarial and antidengue plants opens doors to novel therapeutic avenues.

Caralluma tuberculata, a medicinal and edible plant of the genus Caralluma, belongs to the family Asclepiadaceae. Traditionally, its succulent stems are used as folk medicine for life-threatening diabetes mellitus (DM) disease. Its antidiabetic potential is ascribed to the presence of various secondary metabolites (e.g., pregnane glycosides, flavone glycosides, megastigmane glycosides, polyphenols, ferulic acid, quercetin, and bitter principles, among others) that act as effective and safe antidiabetic agents. The mechanisms of these bioactive secondary metabolites in C. tuberculata herbal medicine include lowering the blood glucose level, stimulating B cells of the pancreas to release more insulin, enhancing the sensitivity of the insulin receptor, inhibiting the action of glucagon and the hydrolysis of glycogen, and increasing the use of glucose in tissues and organ. However, overexploitation, alterations in natural environmental conditions, lower seed viability, and slow growth rate are responsible for the extinction of species from natural habitats, then becoming critically endangered species according to the International Union for Conservation of Nature Red List categories. Therefore, its limited availability does not meet the higher worldwide market demand of C. tuberculata as an antidiabetic drug. Thus, for its conservation and sustainable utilization, researchers across the globe are working on devising strategies to conserve and improve biomass along with the secondary metabolite profiles of C. tuberculata using in vitro approaches. The current review describes the recent progress on antidiabetic phytoconstituents, their cellular mechanisms, and their subsequent clinical outcomes in the drug discovery management of DM. Moreover, in vitro methods such as callus culture, micropropagation, and nano-elicitation strategies for conserving and producing bioactive secondary metabolites have been concisely reviewed and discussed.

Cancer is a complex syndrome with a high mortality rate worldwide due to the lack of effective treatments. The lack of effective coordination between tumor cells and immune system components may be an important reason for the failure of tumor cells to be successfully eliminated after treatment. Tumor microenvironment (TME) barriers hinder the entry and dispersion of nanotherapeutic medicines in tumors. Extracellular vesicles (EVs) are membrane-bound structures responsible for cell-to-cell coordination and carry different biomolecules responsible for physiological and pathological communication between cells. Their role has been a mystery for decades, and over the past two decades, their structure and content have revealed some amazing facts.Recent studies have shown that exosomes play a key role in intercellular communication during the pathogenesis of diseases such as cancer and are responsible for cancer proliferation and metastasis. Inspired by the structure of their endogenous lipid membranes, researchers have tried to mimic their fine structure in the laboratory and tried to load certain biological and chemical drugs. Therefore, exosomes have received particular attention in nanotechnology, and these lipid polymeric micelles have emerged as potential candidates for nanocarriers in nanotechnology to overcome various obstacles in targeted drug delivery. In view of the importance of exosomes, this review highlights the potential of exosomes for use in nanodrug-based medication delivery. The majority of the investigation in these fields has not yet moved out of the laboratory. It will take a lot of time and work to implement these experimental findings in clinical settings.

Background: Medicinal herbs are used to cure parasitic protozoan diseases. Protozoan parasites continue difficult to treat, but diverse extracts from both terrestrial and aquatic plants have been shown to provide a variety of medical benefits for people's personal health. One of the main issues in the management of health and disease is the absence of treatment resistance in parasites. It affects millions of people's health globally, poses a threat to get worse, and threatens to cause financial losses. Drug resistance in parasites is progressively complex and challenging the treatment of parasitic disorders, which is disappointing because it does not receive serious consideration from every part of society. Methods: In this regard, our focus has been on examining the antiparasitic plants of the Asteraceae family and their potential use in the management of protozoan parasites. Results: This review is divided into a i) analysis of traditional parasite treatments using Asteraceae plants (ii) an overview of the major chemical classes found in Asteraceae and their effects on parasites; (iii) with special focus on flavonoids, terpenoids, and alkaloids, antiparasitic properties. In-depth information on isolated bioactive compounds that can inhibit protozoan parasites such Plasmodium, Leishmania, Trypanosoma, Entamoeba, and Toxoplasma is provided in this study. It also includes information on Asteraceae plant extracts that have been reported around the globe. Conclusion: These medicinal plants can be further studied to determine whether they have the potential to be turned into novel pharmaceuticals or utilised as a medicinal plant to treat a variety of protozoan diseases.

Diseases affecting the brain and spinal cord fall under the umbrella term “central nervous system disease”. Most medications used to treat or prevent chronic diseases of the central nervous system cannot cross the blood–brain barrier (BBB) and hence cannot reach their intended target. Exosomes facilitate cellular material movement and signal transmission. Exosomes can pass the blood–brain barrier because of their tiny size, high delivery efficiency, minimal immunogenicity, and good biocompatibility. They enter brain endothelial cells via normal endocytosis and reverse endocytosis. Exosome bioengineering may be a method to produce consistent and repeatable isolation for clinical usage. Because of their tiny size, stable composition, non-immunogenicity, non-toxicity, and capacity to carry a wide range of substances, exosomes are indispensable transporters for targeted drug administration. Bioengineering has the potential to improve these aspects of exosomes significantly. Future research into exosome vectors must focus on redesigning the membrane to produce vesicles with targeting abilities to increase exosome targeting. To better understand exosomes and their potential as therapeutic vectors for central nervous system diseases, this article explores their basic biological properties, engineering modifications, and promising applications.