Deciphering the Immunomodulatory Role of Cyclin-Dependent Kinase 4/6 Inhibitors in the Tumor Microenvironment.

Cancer is characterized by persistent cell proliferation driven by aberrant cell cycle regulation and stimulation of cyclin-dependent kinases (CDKs). A very intriguing and potential approach for the development of antitumor medicines is the suppression of CDKs that lead to induction of apoptosis and cell cycle arrest. The shift of the cell cycle from the G0/G1 phase to the S phase, which is characterized by active transcription and synthesis, depends on the development of the cyclin D-CDK4/6 complex. A precise balance between anticancer activity and general toxicity is demonstrated by CDK inhibitors, which can specifically block CDK4/6 and control the cell cycle by reducing the G1 to S phase transition. CDK4/6 inhibitors have recently been reported to exhibit significant cell growth inhibition via modulating the tumour microenvironment in cancerous cells. One significant new understanding is that these inhibitors serve important functions in the interaction among tumour cells and the host immune system in addition to being cytostatic. Herein, we discuss the biological significance of CDK4/6 inhibitors in cancer therapeutics, as well as their biological impact on T cells and other important immune cells. Furthermore, we explore the integration of preclinical findings of these pharmaceuticals' ability to enhance antitumor immunity.

Agri-biotechnology of coriander (Coriandrum sativum L.): an inclusive appraisal.

Bountiful expression of bioactivity of phytochemicals obtained from spice crops like coriander gifts them the label of being natural antioxidants. It is well-accepted and time-tested towards contributing to human wellbeing. The accomplishment of coriander production is fundamentally influenced by genetic, agroclimatic, and agronomic factors. Despite the fact that there are very restricted options to manage the first two factors, the third one is apparently imperative to arbitrate as far as the elevated yield and enhanced quality are concerned. On the other hand, an indomitable, object-oriented, controlled agrotechnological and biotechnological intervention can also contribute towards better yield and quality of coriander. There are several accounts of the successful use of such technologies in order to genetically improve the qualitative and quantitative indicators of coriander. However, often these areas are not comprehensively explored and utilized. In that context, the present review highlights the botanical features, origin and distribution, multi-dimensional importance, pre- and post-harvest crop management, phytochemical production, and germplasm conservation, including the in vitro-based regeneration methods along with molecular marker-based biotechnological and omics approaches attempted in coriander until date. In addition, the possibility of the yet-to-be-explored agri-biotechnological methods and their potential for genetic improvement of this crop has also been reviewed in this appraisal. KEY POINTS: • Coriander, used both as an herb and spice, is popular in the pharmaceutical and culinary industries. • The current review provides insight into agrotechnological and biotechnological interventions for better yield and quality. • Provides novel ideas to harness the comprehensive qualitative and quantitative genetic improvement based on the potential use of promising biotechnological tools and techniques.

Biomedical and Antioxidant Potentialities in Chilli: Perspectives and Way Forward.

Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.

Enzymatic Activity and Horizontal Gene Transfer of Heavy Metals and Antibiotic Resistant Proteus vulgaris from Hospital Wastewater: An Insight.

Globally, the issue of microbial resistance to medicines and heavy metals is getting worse. There are few reports or data available for Proteus vulgaris (P. vulgaris), particularly in India. This investigation intends to reveal the bacteria's ability to transmit genes and their level of resistance as well. The wastewater samples were taken from several hospitals in Lucknow City, India, and examined for the presence of Gram-negative bacteria that were resistant to antibiotics and heavy metals. The microbial population count in different hospital wastewaters decreases with increasing concentrations of metal and antibiotics. Among all the examined metals, Ni and Zn had the highest viable counts, whereas Hg, Cd, and Co had the lowest viable counts. Penicillin, ampicillin, and amoxicillin, among the antibiotics, demonstrated higher viable counts, whereas tetracycline and erythromycin exhibited lower viable counts. The MIC values for the P. vulgaris isolates tested ranged from 50 to 16,00 µg/ml for each metal tested. The multiple metal resistance (MMR) index, which ranged from 0.04 to 0.50, showed diverse heavy metal resistance patterns in all P. vulgaris isolates (in the case of 2-7 metals in various combinations). All of the tested isolates had methicillin resistance, whereas the least number of isolates had ofloxacin, gentamycin, or neomycin resistance. The P. vulgaris isolates displayed multidrug resistance patterns (2-12 drugs) in various antibiotic combinations. The MAR indexes were shown to be between (0.02-0.7). From the total isolates, 98%, 84%, and 80% had urease, gelatinase, and amylase activity, whereas 68% and 56% displayed protease and beta-lactamase activity. Plasmids were present in all the selected resistant isolates and varied in size from 42.5 to 57.0 kb and molecular weight from 27.2 to 37.0 MD. The transmission of the antibiotic/metal resistance genes was evaluated between a total of 7 pairs of isolates. A higher transfer frequency (4.4 × 10-1) was observed among antibiotics, although a lower transfer frequency (1.0 × 10-2) was observed against metals in both the media from the entire site tested. According to exponential decay, the population of hospital wastewater declined in the following order across all sites: Site II > Site IV > Site III > Site I for antibiotics and site IV > site II > site I >site III for metal. Different metal and antibiotic concentrations have varying effects on the population. The metal-tolerant P. vulgaris from hospital wastewater was studied in the current study had multiple distinct patterns of antibiotic resistance. It could provide cutting-edge methods for treating infectious diseases, which are essential for managing and assessing the risks associated with hospital wastewater, especially in the case of P. vulgaris.

Phytocompound identification of aqueous Zingiber officinale rhizome (ZOME) extract reveals antiproliferative and reactive oxygen species mediated apoptotic induction within cervical cancer cells: an in vitro and in silico approach.

The prevalence of cervical cancer in women is in the fourth position among various other types of cancer globally. Many established therapies, including surgery, chemotherapy, and immunomodulation, are present, but high levels of side effects cause mortality and morbidity among the patients. Zingiber officinale rhizome (ZOME) has been potentially used to cure a variety of ailments and diseases. The aqueous ZOME extract also contains ample phytochemical constituents having anticancer effects on different cancers. The cell viability of HeLa cells was evaluated using MTT assay with IC50 at 97 µg/mL. Furthermore, a significant level of ROS generation causes the apoptosis of the cells. Nuclear staining dye DAPI and Hoechst 33342 showed DNA's fragmented and condensed form. Propidium Iodide staining showed necrotic or late-apoptotic cells. While acidic organelle dye LysoTracker and MitoTracker dye along with dual staining showed significant results. In silico studies were carried out using identified phytochemicals from GC-MS analysis with pharmacokinetics properties (ADMET), and targeted toward receptor proteins for molecular docking. Ligands with high docked scores were subjected to molecular dynamics simulations at 310 K for 100 ns. In vitro and in silico investigations in our studies showed that aqueous ZOME extract can be used as an efficient therapy against cervical cancer treatment as it showed significant cytotoxic and antiproliferative effects toward the HeLa cell line.Communicated by Ramaswamy H. Sarma.

Nanotechnological interventions of the microbiome as a next-generation antimicrobial therapy.

The rise of antimicrobial resistance (AMR) impacts public health due to the diminished potency of existing antibiotics. The microbiome plays an important role in the host's immune system activity and shows the history of exposure to antimicrobials and its manipulation in combating antimicrobial resistance. Advancements in gene technologies, DNA sequencing, and computational biology have emerged as powerful platforms to better understand the relationship between animals and microorganisms (MOs). The past few years have witnessed an increase in the use of nanotechnology, both in industry and in academia, as tools to tackle antimicrobial resistance. New strategies of microbiome manipulation have been developed, such as the use of prebiotics, probiotics, peptides, antibodies, an appropriate diet, phage therapy, and the use of various nanotechnological techniques. Owing to the research outcomes, targeted delivery of antimicrobials with some modifications with nanoparticles can lead to the destruction of resistant microbial cells. In addition, nanoparticles have been studied for their potential antimicrobial effects both in vitro and in vivo. In this review, we highlight key opportunistic areas for applying nanotechnologies with the aim of manipulating the microbiome for the treatment of antimicrobial resistance. Besides providing a detailed review on various nanomaterials, technologies, opportunities, technical needs, and potential approaches for the manipulation of the microbiome to address these challenges, we discuss future challenges and our perspective.

Synergistic Role of Plant Extracts and Essential Oils against Multidrug Resistance and Gram-Negative Bacterial Strains Producing Extended-Spectrum ß-Lactamases.

Plants, being the significant and natural source of medication for humankind against several ailments with characteristic substances hidden on them, have been recognized for many centuries. Accessibility of various methodologies for the revelation of therapeutically characteristic items has opened new avenues to redefine plants as the best reservoirs of new structural types. The role of plant metabolites to hinder the development and movement of pathogenic microbes is cherished. Production of extended-spectrum ß-lactamases is an amazing tolerance mechanism that hinders the antibacterial treatment of infections caused by Gram-negative bacteria and is a serious problem for the current antimicrobial compounds. The exploration of the invention from sources of plant metabolites gives sustenance against the concern of the development of resistant pathogens. Essential oils are volatile, natural, complex compounds described by a solid odor and are framed by aromatic plants as secondary metabolites. The bioactive properties of essential oils are commonly controlled by the characteristic compounds present in them. They have been commonly utilized for bactericidal, virucidal, fungicidal, antiparasitic, insecticidal, medicinal, and antioxidant applications. Alkaloids are plant secondary metabolites that have appeared to have strong pharmacological properties. The impact of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial development and efflux pump activity was assessed on Pseudomonas aeruginosa. Plant-derived chemicals may have direct antibacterial activity and/or indirect antibacterial activity as antibiotic resistance modifying agents, increasing the efficiency of antibiotics when used in combination. The thorough screening of plant-derived bioactive chemicals as resistance-modifying agents, including those that can act synergistically with antibiotics, is a viable method to overcome bacterial resistance. The synergistic assessment studies with the plant extract/essential oil and the antibiotic compounds is essential with a target for achieving a redesigned model with sustainable effects which are appreciably noticeable in specific sites of the plants compared to the entirety of their individual parts.

Metallic and metal oxide-derived nanohybrid as a tool for biomedical applications.

Nanotechnology covers a variety of scientific areas including chemistry, material science, physics, biomedicine, biology, and engineering. Metal nanohybrid with extraordinary properties is highly researched in comparison to bulky individual nanoparticles. Especially, metal and metal oxide nanoparticles are a new class of functional nanohybrids having broad, intriguing physio-chemical properties showing applications in nanoscience and biomedical research. Engineered inorganic nanoparticles have paved an essential component in the advancement of nanotechnologies. Synthesis is done through various physical, chemical, and biological methods with their special features and manipulation at the nano level in their physiochemical properties, controlling their shape, size, and surface functionality. Application of metal and metal oxide nanohybrid are discussed, including, gene delivery, theranostics, and catalysis. Due to the versatile application of nanohybrids, it can be used in the detection of tumors, cell tracking, and visualizing the specific region of disease. Development of accurate, multifunctional imaging and ambient data are indispensable for futuristic applications. Nanohybrids (NHs) can load therapeutic drugs in their sector of core and shell and have the ability to release them in a controlled and sequential manner of a delivery system. Novel nanohybrid with their multidimensional, integrated mechanistic property has also shown a great effect on environmental pollution control also. A proteomics and transcriptomics approach for the nanohybrid action of mechanism has been discussed and also includes limitations of MNHs and MONHs. The current manuscript critically reviewed several available recent kinds of literature and has the potential to offer a better understanding of metallic and metallic oxide nanohybrids having a multifunctional role in various biomedical applications.

Potential Therapeutic Role of Mesenchymal-Derived Stem Cells as an Alternative Therapy to Combat COVID-19 through Cytokines Storm.

Medical health systems continue to be challenged due to newly emerging COVID-19, and there is an urgent need for alternative approaches for treatment. An increasing number of clinical observations indicate cytokine storms to be associated with COVID-19 severity and also to be a significant cause of death among COVID-19 patients. Cytokine storm involves the extensive proliferative and hyperactive activity of T and macrophage cells and the overproduction of pro-inflammatory cytokines. Stem cells are the type of cell having self-renewal properties and giving rise to differentiated cells. Currently, stem cell therapy is an exciting and promising therapeutic approach that can treat several diseases that were considered incurable in the past. It may be possible to develop novel methods to treat various diseases by identifying stem cells' growth and differentiation factors. Treatment with mesenchymal stem cells (MSCs) in medicine is anticipated to be highly effective. The present review article is organized to put forward the positive arguments and implications in support of mesenchymal stem cell therapy as an alternative therapy to cytokine storms, to combat COVID-19. Using the immunomodulatory potential of the MSCs, it is possible to fight against COVID-19 and counterbalance the cytokine storm.

In vitro elucidation of antioxidant, antiproliferative, and apoptotic potential of yeast-derived ß-1,3-glucan particles against cervical cancer cells.

Cancer is the leading cause of mortality worldwide and in particular is the fourth most common cause of mortality in women every year. Conventional treatments for cancer are chemotherapy and radiation therapy, which have various kinds of side effects. Hence, there is a high need to develop alternative, efficient, and safer therapies for cancer treatment. ß-Glucan, a novel polysaccharide isolated from baker's yeast Saccharomyces cerevisiae, shows noteworthy cytotoxicity toward a variety of cancer cell lines in vitro. In this research, we characterized the ß-glucan with high-performance thin-layer chromatography (HPTLC) analysis and found that d-glucose units with ß-1,3 links are the major component of the extracted ß-glucan particles. Fourier transform IR (FTIR) analysis confirmed a ß-(1→3)-linked glucan structure. In vitro cell cytotoxicity was evaluated by MTT with IC50 136 µg/ml, and therapeutic potential was assessed by various assays using values below and above the IC50. A significant reactive oxygen species (ROS) generation at 50-150 µg/ml of concentrations indicated the apoptosis of cervical cancer cells. Along with ROS generation, these concentrations were also found to induce morphological changes such as fragmentation in DNA upon staining HeLa cells with DAPI. Mitochondrial membrane potential was significantly reduced after increasing the dose of treatment, assessed with the help of MitoTracker dye. Hence, by all these experimental supports, we observed that ß-glucan has the potential to slow down the growth of cervical cancer cells, and it can be further investigated for unfolding its complete anticancer potential.

Nanoparticles Mediated Target-specific Drug Delivery in Prostate Cancer: An In-depth Review.

Nanotechnology has been extensively exploited for its enormous therapeutic and diagnostic potential in the management of multiple disorders. It employs nanomaterials as drug carriers with enhanced efficacy and limited side effects on normal tissues. A lot of nanomaterials have been studied and produced, imminently reforming the treatment and diagnostics of numerous malignancies, including cancer. The purpose of the present study is to explore the role of nanotechnology-based devices/therapies that have a vital function in the therapeutics and diagnostics of cancer with potential impact at three levels: early detection, tumor imaging, and drug delivery methods. Concentrating on cancer, promising nanotechnology-based approaches have been planned to satisfy the need for targeted specificity of traditional agents of chemotherapeutics, in addition to early recognition of malignant and precancerous lesions. Prostate cancer is the fifth most wellknown cancer worldwide and the second most usually detected cancer in men. Therefore, there is a crucial need to improve therapeutic prospects for the diagnosis and treatment of prostate cancer via the exploitation of the potential of nanomaterials for cell-targeted specificity and improved primary diagnosis of precancerous tumors. The present review, therefore, focuses on summarizing all prospective applications of nanotechnology in the prognosis and diagnosis of prostate cancer, which would further help researchers to elucidate a more potent therapeutic approach for the better management of prostate cancer in the days ahead.