Evaluation of oyster mushroom (Pleurotus ostreatus)-derived anthraquinone on the induction of apoptosis and suppression of MMP-2 and MMP-9 expression in breast cancer cells.

Introduction: Breast cancer results from tissue degradation caused by environmental and genetic factors that affect cells in the body. Matrix metalloproteinases, such as MMP-2 and MMP-9, are considered potential putative markers for tumor diagnosis in clinical validation due to their easy detection in body fluids. In addition, recent reports have suggested multiple roles for MMPs, rather than simply degeneration of the extracellular matrix, which comprises mobilizing growth factors and processing surface molecules. Methods: In this study, the chemotherapeutic effects of anthraquinone (AQ) extracted from edible mushrooms (Pleurotus ostreatus Jacq. ex Fr.) cells was examined in MCF-7 breast cancer cells. The cytotoxic potential and oxidative stress induced by purified anthraquinone were assessed in MCF-7 cells using MTT and ROS estimation assays. Gelatin Zymography, and DNA fragmentation assays were performed to examine MMP expression and apoptotic induction in the MCF-7 cells treated with AQ. The genes crucial for mutations were examined, and the mutated RNA knockout plausibility was analyzed using the CRISPR spcas9 genome editing software. Results: MCF-7 cells were attenuated in a concentration-dependent manner by the administration of AQ purified from P. ostreatus compared with the standard anticancer drug paclitaxel. AQ supplementation decreased oxidative stress and mitochondrial impairment in MCF-7 cells. Treatment with AQ and AQ with paclitaxel consistently decreased the expression of crucial marker genes such as MMP2 and MMP9. The mutated genes MMP2, MMP7, and MMP9 were assessed and observed to reveal four putative gene knockdown potentials for breast cancer treatment. Conclusions: The synergistic application of AQ and paclitaxel exerted a strong inhibitory effect on the MCF-7 breast cancer cells. Extensive studies are imperative to better understand the action of bioactive mixes on the edible oyster fungus P. ostreatus. The gene knockout potential detected by CRISPR SpCas9 will aid in elite research into anticancer treatments.

A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways.

Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.

Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy.

Drug repositioning or repurposing has gained worldwide attention as a plausible way to search for novel molecules for the treatment of particular diseases or disorders. Drug repurposing essentially refers to uncovering approved or failed compounds for use in various diseases. Cancer is a deadly disease and leading cause of mortality. The search for approved non-oncologic drugs for cancer treatment involved in silico modeling, databases, and literature searches. In this review, we provide a concise account of the existing non-oncologic drug molecules and their therapeutic potential in chemotherapy. The mechanisms and modes of action of the repurposed drugs using computational techniques are also highlighted. Furthermore, we discuss potential targets, critical pathways, and highlight in detail the different challenges pertaining to drug repositioning for cancer immunotherapy.

Chemical composition and mosquitocidal properties of essential oil from Indian indigenous plants Ocimum tenuiflorum L. and Ocimum americanum L. against three vector mosquitoes.

Mosquitoes stand out as the most perilous and impactful vectors on a global scale, transmitting a multitude of infectious diseases to both humans and other animals. The primary objective of the current research was to assess the effectiveness of EOs from Ocimum tenuiflorum L. and Ocimum americanum L. in controlling Anopheles stephensi Liston. Culex quinquefasciatus Say and Aedes aegypti L. mosquitoes. The larvae, pupae and eggs of the mosquitoes were exposed to four different concentrations (6.25-50 ppm). The tested EOs resulted in >99-100 % mortality at 120 h for the eggs of all examined mosquito species. It also showed robust larvicidal and pupicidal activity with LC50 and LC90 values of 17-39, 23-60 ppm and 46-220, and 73-412 ppm against Aedes, Culex and Anopheles mosquito species, respectively, at 24 h of treatment. The Suitability Index or Predator Safety Factor demonstrated that the EOs extracted from O. tenuiflorum L. and O. americanum L. did not cause harm to P. reticulata, D. indicus (water bug), G. affinis and nymph (dragonfly). GC-MS analysis identified the major probable constituents of the oil, including Phenol, 2-Methoxy-4-(1-Propenyl)- (28.29 %); 1-Methyl-3-(1'-Methylcyclopropyl) Cyclopentene (46.46 %); (E,E,E)-3,7,11,15-Tetramethylhexadeca-1,3,6,10,14-Pentaene (18.91 %) and 1,3-Isobenzofurandione, 3a,4,7,7a-Tetrahydro-4,7-Dimethyl (33.02 %). These constituents may play a significant role in the mosquitocidal activity of the oil. The same results were identified in the formulation prepared from the EOs. This marks the first report confirming the successful utilization of EOs derived from O. tenuiflorum L. and O. americanum L. in mosquito population control initiatives.

Antimicrobial activity of probiotic bacteria-mediated cadmium oxide nanoparticles against fish pathogens.

The current research was designed to investigate the antibacterial activity of probiotic bacteria mediated cadmium oxide nanoparticles (CdO NPs) on common fish pathogenic bacteria like Serratia marcescens, Aeromonas hydrophila, Vibrio harveyi, and V. parahaemolyticus. CdO NPs were synthesized using probiotic bacteria as follows: Lactobacillus species with different precursor of cadmium sulfate concentrations (5, 10, and 20 mM). The average crystalline sizes of the CdO NPs were determined based on the XRD patterns using the Debye-Scherrer equation for different precursor concentrations. Specifically, sizes of 40, 48, and 67 nm were found at concentrations of 5, 10, and 20 mM, respectively. The antibacterial efficacy of CdO NPs was estimated using a well diffusion assay, which demonstrated the best efficacy of 20 mM CdO NPs against all pathogens. AFM analysis of nanoparticle-treated and untreated biofilms was performed to further validate the antibacterial effect. Antibacterial activity of CdO nanoparticles synthesized at varying concentrations (5, 10, and 20 mM) against fish pathogens (S. marcescens, A. hydrophila, V. harveyi, and V. parahaemolyticus). The results indicated the highest inhibitory effect of 20 mM CdO NPs across all concentrations (30, 60, and 90 µg/mL), demonstrating significant inhibition against S. marcescens. These findings will contribute to the development of novel strategies for combating aquatic diseases and advancing aquaculture health management practices.

Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives.

The curry powder spices turmeric (Curcuma longa L.), which contains curcumin (diferuloylmethane), an orange-yellow chemical. Polyphenols are the most commonly used sources of curcumin. It combats oxidative stress and inflammation in diseases, such as hyperlipidemia, metabolic syndrome, arthritis, and depression. Most of these benefits are due to their anti-inflammatory and antioxidant properties. Curcumin consumption leads to decreased bioavailability, resulting in limited absorption, quick metabolism, and quick excretion, which hinders health improvement. Numerous factors can increase its bioavailability. Piperine enhances bioavailability when combined with curcumin in a complex. When combined with other enhancing agents, curcumin has a wide spectrum of health benefits. This review evaluates the therapeutic potential of curcumin with a specific emphasis on its approach based on molecular signaling pathways. This study investigated its influence on the progression of cancer, inflammation, and many health-related mechanisms, such as cell proliferation, apoptosis, and metastasis. Curcumin has a significant potential for the prevention and treatment of various diseases. Curcumin modulates several biochemical pathways and targets involved in cancer growth. Despite its limited tissue accumulation and bioavailability when administered orally, curcumin has proven useful. This review provides an in-depth analysis of curcumin's therapeutic applications, its molecular signaling pathway-based approach, and its potential for precision medicine in cancer and human health.

Unravelling the Untapped Pharmacological Potential of Plant Molecules as Inhibitors of BACE1: In Silico Explorations for Alzheimer's Disease.

Alzheimer's disease (AD) is an extremely complex, heterogeneous, and multifactorial neurodegenerative disease clinically characterized by progressive memory loss and progressive decline in cognitive function. There is currently no effective treatment for the onset and/or progression of the pathophysiological diseases of AD. The global prevalence of this disease has increased in recent years due to modern lifestyle. Therefore, there is an urgent need to develop a drug with significant neuroprotective potential. Since plant metabolites, especially polyphenols, have important pharmacological properties acting against ß-amyloid (Aß), Tau, neuroinflammation, and oxidative stress, such phytochemicals were selected in the present research. Using the Schrödinger tool (Maestro V.13.6), the drug potency of these metabolites was studied after installation in the highly configured workstation. Among the 120 polyphenols docked, amygdalin showed notable docking values of - 11.2638, followed by eriocitrin (- 10.9569), keracyanin (- 10.7086), and amaroswerin (- 9.48126). The prominent MM-GBSA values of these molecules were - 62.8829, - 52.1914, - 68.6307, and - 63.1074, respectively. The MM-GBSA energy values demonstrated the drug stability of these molecules for ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1)-causing AD. In the absorption and distribution assessment, these phytochemicals showed significantly better values than the inhibitors CNP520. The chosen phytochemicals have been demonstrated as non-hepatotoxic; however, the BACE1 inhibitor CNP520 is hepatotoxic. In both the molecular docking and ADMET assessments, these natural chemicals have shown optimism as potential drug candidates for Alzheimer's disease. However, in order to understand the detailed biological metabolism of these compounds in AD, they need to be evaluated in in vivo studies to validate its efficacy.

Botany, traditional usages, phytochemistry, pharmacology, and toxicology of Guilandina bonduc L.: a systematic review.

Guilandina bonduc L. is popularly known as a fever nut that grows widely in evergreen forests and moist deciduous forests with a pantropical distribution. The plant is highly therapeutic in various systems of medicine, including Ayurveda, Siddha, and homeopathy. The purpose of this review is to analyze the published data on G. bonduc, including traditional uses, taxonomic position, botanical description, phytochemistry, pharmacological properties, and toxicological assessment of its various parts. Phytochemical and pharmacological studies were the main focus of this review. The previously published research on G. bonduc was tracked from scientific databases such as Online Library, Google, Taylor and Francis, PubMed, Research Gate, Scopus, Springer, Wiley, Web of Sciences. Numerous phytochemical, pharmaceutical, and pharmacological studies have been carried out on the various parts of G. bonduc. To date, more than 97 phytochemicals have been isolated from the leaves, roots, stems, stem bark, flowers, twigs, and seeds of this plant. The phytochemicals isolated from the plants are flavonoids, homoisoflavonoids, terpenoids, diterpenoids, steroids, fatty acids, alkanes, acids, phenols, ketones, esters, amides, azides, silanes, and ether groups. This plant has been extensively studied in in vitro and in vivo pharmacological experiments, where it showed analgesic, anti-inflammatory, antioxidant, antiviral, antidiabetic, abortive, anticataleptic, immunomodulatory, and antiestrogenic effects. This comprehensive review revealed that phytochemicals isolated from various parts of G. bonduc have significant therapeutic efficacy, with promising anticancer, antidiabetic, hepatoprotective, antioxidant, and antimicrobial activities. This review provides a good source of information for the development of a drug using modern scientific tools, in view of its underexplored traditional uses. Further studies on preclinical and clinical trials and toxicological studies on the bioactive molecules of G. bonduc to validate its traditional uses are warranted.

Computational approaches for modeling and structural design of biological systems: A comprehensive review.

The convergence of biology and computational science has ushered in a revolutionary era, revolutionizing our understanding of biological systems and providing novel solutions to global problems. The field of genetic engineering has facilitated the manipulation of genetic codes, thus providing opportunities for the advancement of innovative disease therapies and environmental enhancements. The emergence of bio-molecular simulation represents a significant advancement in this particular field, as it offers the ability to gain microscopic insights into molecular-level biological processes over extended periods. Biomolecular simulation plays a crucial role in advancing our comprehension of organismal mechanisms by establishing connections between molecular structures, interactions, and biological functions. The field of computational biology has demonstrated its significance in deciphering intricate biological enigmas through the utilization of mathematical models and algorithms. The process of decoding the human genome has resulted in the advancement of therapies for a wide range of genetic disorders, while the simulation of biological systems contributes to the identification of novel pharmaceutical compounds. The potential of biomolecular simulation and computational biology is vast and limitless. As the exploration of the underlying principles that govern living organisms progresses, the potential impact of this understanding on cancer treatment, environmental restoration, and other domains is anticipated to be transformative. This review examines the notable advancements achieved in the field of computational biology, emphasizing its potential to revolutionize the comprehension and enhancement of biological systems.

Multitargeted pharmacokinetics, molecular docking and network pharmacology-based identification of effective phytocompounds from Sauropus androgynus (L.) Merr for inflammation and cancer treatment.

According to worldwide health data, cancer, and inflammatory illnesses are on the rise and are among the most common causes of death. Across the world, these types of health problems are now considered top priorities for government health organizations. Hence, this study aimed to investigate medicinal plants' potential for treating cancer and inflammatory disorders. This network pharmacology analysis aims to learn more about the potential targets and mechanisms of action for the bioactive ingredients in Sauropus androgynus (L.) Merr L. The compound-target network and protein-protein interaction analysis were built using the STRING database. Using Network Analyst, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes, pathway enrichment was performed on the hub genes. 1-hexadecanol was shown to inhibit drug-metabolizing enzymes in a pharmacokinetic investigation. Those samples of 1-hexadecanol were found to be 1-hexadecanol (BBB 0.783), GI High, Pgp Substrate Yes, CYP2C19 Inhibitor Yes, CYP2D6 Yes, and HI -89.803. The intermolecular binding energies for 1-hexadecanol (4-DRI, -8.2 kcal/mol) are evaluated. These results from a study on S. androgynus used molecular docking and network pharmacology to gain insight into the prime target genes and potential mechanisms identified for AKT1, mTOR, AR, PPID, FKBP5, and NR3C1. The PI3K-Akt signalling pathway has become an important regulatory node in various pathological processes requiring coordinated actions. Stability and favourable conformations have been resolved by considering nonbonding interactions such as electrostatic and hydrogen bonds in MD simulations of the perfect molecules using the Desmond package. Thus, using an appropriate platform of network pharmacology, molecular docking, and in vitro experiments, this study provides for the first time a clearer knowledge of the anti-cancer and anti-inflammatory molecular bioactivities of S. androgynus. Further in vitro and in vivo confirmations are strongly needed to determine the efficacy and therapeutic effects of 1-hexadecanol in the biological process.Communicated by Ramaswamy H. Sarma.

Therapeutic Potential and Molecular Mechanisms of the Multitargeted Flavonoid Fisetin.

Flavonoids effectively treat cancer, inflammatory disorders (cardiovascular and nervous systems), and oxidative stress. Fisetin, derived from fruits and vegetables, suppresses cancer growth by altering cell cycle parameters that lead to cell death and angiogenesis without affecting healthy cells. Clinical trials are needed in humans to prove the effectiveness of this treatment for a wide range of cancers. According to the results of this study, fisetin can be used to prevent and treat a variety of cancers. Despite early detection and treatment advances, cancer is the leading cause of death worldwide. We must take proactive steps to reduce the risk of cancer. The natural flavonoid fisetin has pharmacological properties that suppress cancer growth. This review focuses on the potential drug use of fisetin, which has been extensively explored for its cancer-fighting ability and other pharmacological activities such as diabetes, COVID-19, obesity, allergy, neurological, and bone disorders. Researchers have focused on the molecular function of fisetin. In this review, we have highlighted the biological activities against chronic disorders, including cancer, metabolic illnesses, and degenerative illnesses, of the dietary components of fisetin.

Association of nanoparticles and Nrf2 with various oxidative stress-mediated diseases.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the cellular antioxidant defense system at the posttranscriptional level. During oxidative stress, Nrf2 is released from its negative regulator Kelch-like ECH-associated protein 1 (Keap1) and binds to antioxidant response element (ARE) to transcribe antioxidative metabolizing/detoxifying genes. Various transcription factors like aryl hydrocarbon receptor (AhR) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) and epigenetic modification including DNA methylation and histone methylation might also regulate the expression of Nrf2. Despite its protective role, Keap1/Nrf2/ARE signaling is considered as a pharmacological target due to its involvement in various pathophysiological conditions such as diabetes, cardiovascular diseases, cancers, neurodegenerative diseases, hepatotoxicity and kidney disorders. Recently, nanomaterials have received a lot of attention due to their unique physiochemical properties and are also used in various biological applications, for example, biosensors, drug delivery systems, cancer therapy, etc. In this review, we will be discussing the functions of nanoparticles and Nrf2 as a combined therapy or sensitizing agent and their significance in various diseases such as diabetes, cancers and oxidative stress-mediated diseases.

Green Synthesis of Magnesium Oxide Nanoparticles by Using Abrus precatorius Bark Extract and Their Photocatalytic, Antioxidant, Antibacterial, and Cytotoxicity Activities.

The current research is concerned with the synthesis of magnesium oxide (MgO) nanoparticles (NPs) from Abrus precatorius L. bark extract via the green chemistry method. The synthesized MgO NPs was confirmed by using several characterization methods like XRD, FTIR, SEM, TEM, and UV-visible analysis. The synthesized MgO NPs displayed a small particle size along with a specific surface area. Abrus precatorius bark synthesized MgO NPs with a higher ratio of dye degradation, and antioxidant activity showed a higher percentage of free radical scavenging in synthesized MgO NPs. Zebrafish embryos were used as a model organism to assess the toxicity of the obtained MgO nanoparticles, and the results concluded that the MgO NPs were nontoxic. In addition, the anticancer properties of MgO nanoparticles were analyzed by using a human melanoma cancer cell line (A375) via MTT, XTT, NRU, and LDH assessment. MgO NPs treated a human melanoma cancer cell line and resulted in apoptosis and necrosis based on the concentration, which was confirmed through a genotoxicity assay. Moreover, the molecular mechanisms in necrosis and apoptosis were conferred to depict the association of magnesium oxide nanoparticles with the human melanoma cancer cell line. The current study on MgO NPs showed a broad-scope understanding of the use of these nanoparticles as a medicinal drug for melanoma cancer via its physiological mechanism and also a novel route to obtain MgO NPs by using the green chemistry method.

Recent insights on tea metabolites, their biosynthesis and chemo-preventing effects: A review.

Tea manufactured from the cultivated shoots of Camellia sinensis (L.) O. Kuntze is the most commonly consumed nonalcoholic drink around the world. Tea is an agro-based, environmentally sustainable, labor-intensive, job-generating, and export-oriented industry in many countries. Tea includes phenolic compounds, flavonoids, alkaloids, vitamins, enzymes, crude fibers, protein, lipids, and carbohydrates, among other biochemical constituents. This review described the nature of tea metabolites, their biosynthesis and accumulation with response to various factors. The therapeutic application of various metabolites of tea against microbial diseases, cancer, neurological, and other metabolic disorders was also discussed in detail. The seasonal variation, cultivation practices and genetic variability influence tea metabolite synthesis. Tea biochemical constituents, especially polyphenols and its integral part catechin metabolites, are broadly focused on potential applicability for their action against various diseases. In addition to this, tea also contains bioactive flavonoids that possess health-beneficial effects. The catechin fractions, epigallocatechin 3-gallate and epicatechin 3-gallate, are the main components of tea that has strong antioxidant and medicinal properties. The synergistic function of natural tea metabolites with synthetic drugs provides effective protection against various diseases. Furthermore, the application of nanotechnologies enhanced bioavailability, enhancing the therapeutic potential of natural metabolites against numerous diseases and pathogens.

Emerging role of nutritional short-chain fatty acids (SCFAs) against cancer via modulation of hematopoiesis.

The understanding of gut microbiota has emerged as a significant frontier in development of strategies to maintain normal human body's homeostasis and preventing the disease development over the last decade. The composition of the gut microbiota influences the clinical benefit of immune checkpoints in patients with advanced cancer, but the mechanisms underlying this relationship are unclear. Cancer is among the leading causes of mortality worldwide. So far, there is no universal treatment for cancer and despite significant advances, a lot of improvement on cancer therapy is required. Owing to its role in preserving the host's health and maintaining cellular integrity, the human gut microbiome has recently drawn a lot of interest as a target for cancer treatment. Dietary fiber is fermented by the gut microbiota to generate short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, which are physiologically active metabolites. SCFAs can modulate the pathophysiology of the tumor environment through various critical signaling pathways. In addition, SCFAs can bind to carcinogens and other toxic chemicals, thus facilitating their biotransformation and elimination through different excretory mechanisms. This review discusses the mechanisms of action of short-chain fatty acids in modulating hematopoiesis of various immune system cells and the resultant beneficial anti-cancer effects. It also provides future perspectives on cancer therapy.

Minor tropical fruits as a potential source of bioactive and functional foods.

Tropical fruits are defined as fruits that are grown in hot and humid regions within the Tropic of Cancer and Tropic of Capricorn, covering most of the tropical and subtropical areas of Asia, Africa, Central America, South America, the Caribbean and Oceania. Depending on the cultivation area covered, economic value and popularity these tropical fruits are divided into major and minor tropical fruits. There is an annual increment of 3.8% in terms of commercialization of the tropical fruits. In total 26 minor tropical fruits (Kiwifruit, Lutqua, Carambola, Tree Tomato, Elephant apple, Rambutan, Bay berry, Mangosteen, Bhawa, Loquat, Silver berry, Durian, Persimon, Longan, Passion fruit, Water apple, Pulasan, Indian gooseberry, Guava, Lychee, Annona, Pitaya, Sapodilla, Pepino, Jaboticaba, Jackfruit) have been covered in this work. The nutritional composition, phytochemical composition, health benefits, traditional use of these minor tropical fruits and their role in food fortification have been portrayed.

Recent Developments and Anticancer Therapeutics of Paclitaxel: An Update.

Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species and is used as a chemotherapeutic agent against various cancers. The biosynthesis of paclitaxel is a complex pathway, making its total chemical synthesis commercially non-viable; hence, alternative novel sources - like plant cell culture and heterologous expression systems, are being investigated to overcome this issue. Advancements in the field of genetic engineering, microbial fermentation engineering, and recombinant techniques have significantly increased the achievable yields of paclitaxel. Indeed, paclitaxel selectively targets microtubules and causes cell cycle arrest in the G2/M phase, inducing a cytotoxic effect in a concentration and time-dependent manner. Innovative drug delivery formulations, like the development of albumin-bound nanoparticles, nano-emulsions, nano-suspensions, liposomes, and polymeric micelles, have been applied to enhance the delivery of paclitaxel to tumor cells. This review focuses on the production, biosynthesis, mechanism of action, and anticancer effects of paclitaxel.