Homoharringtonine: updated insights into its efficacy in hematological malignancies, diverse cancers and other biomedical applications.

HHT has emerged as a notable compound in the realm of cancer treatment, particularly for hematological malignancies. Its multifaceted pharmacological properties extend beyond traditional applications, warranting an extensive review of its mechanisms and efficacy. This review aims to synthesize comprehensive insights into the efficacy of HHT in treating hematological malignancies, diverse cancers, and other biomedical applications. It focuses on elucidating the molecular mechanisms, therapeutic potential, and broader applications of HHT. A comprehensive search for peer-reviewed papers was conducted across various academic databases, including ScienceDirect, Web of Science, Scopus, American Chemical Society, Google Scholar, PubMed/MedLine, and Wiley. The review highlights HHT's diverse mechanisms of action, ranging from its role in leukemia treatment to its emerging applications in managing other cancers and various biomedical conditions. It underscores HHT's influence on cellular processes, its efficacy in clinical settings, and its potential to alter pathological pathways. HHT demonstrates significant promise in treating various hematological malignancies and cancers, offering a multifaceted approach to disease management. Its ability to impact various physiological pathways opens new avenues for therapeutic applications. This review provides a consolidated foundation for future research and clinical applications of HHT in diverse medical fields.

Cold Alkali-Extractable Antioxidative Polysaccharide from Russula pseudocyanoxantha (Agaricomycetes), a Novel Mushroom, Stimulates Immune Responses in RAW264.7 Cells by Regulating the TLR/NF-κB Pathway.

In our previous study, we have established Russula pseudocyanoxantha as a unique species, playing a crucial role in indigenous diets through ages. The research also brought attention to bioactive potential of polysaccharide fraction extracted from the unexplored food using hot water. However, residue of the conventional process still contains therapeutic biopolymers that could further be utilized for pharmacological purposes instead of being discarded. Therefore, the current study aims to valorize the solid remnants, contributing to a deeper understanding of the novel taxon. Subsequently, the leftover was treated with cold alkali, leading to the preparation of a high-yield fraction (RP-CAP). Chemical characterization through FT-IR, GC-MS, HPTLC, and spectroscopy demonstrated presence of several monomers in the carbohydrate backbone, predominantly composed of ß-glucan. Furthermore, GPC chromatogram indicated presence of a homogeneous polymer with molecular weight of ~ 129.28 kDa. Subsequently, potent antioxidant activity was noted in terms of radical scavenging (O2·-, OH·, DPPH· and ABTS·+), chelating ability, reducing power and total antioxidant activity where EC50 values ranged from 472-3600 µg/mL. Strong immune-boosting effect was also evident, as the biopolymers stimulated murine macrophage cell proliferation, phagocytic activity, pseudopod formation, and NO as well as ROS synthesis particularly at the concentration of 100 µg/mL. In-depth analysis through RT-PCR revealed that the fraction stimulated synthesis of several inflammatory mediators, elucidating the mode of action through TLR/ NF-κB pathway. Therefore, the findings collectively suggest that RP-CAP possesses great potential to serve as a healthimproving component in functional food and pharmaceutical sectors.

Natural products of plant origin: an emerging therapeutic for dermatomycosis.

Dermatomycosis or superficial mycosis is considered one of the chronic fungal infections and a global challenge for the public health system. The severity of dermatomycosis is proportionately increasing with the emerging population of immunocompromised individuals, and it is becoming more prevalent, even life-threatening, in several tropical countries. In this context, improper long-term treatment with synthetic antifungal drugs and their related side effects imposes additional challenges in treating dermatomycosis. Thus, the present scenario highlights the need for a novel and accurate treatment with minimal or no side effects. The multifaceted therapeutic properties of various natural products have garnered the interest of scientific communities in recent years. Generally, plant-based products have low toxicity levels and offer diverse formulations and unique biomolecules for clinical applicability against dermatomycosis. Thus, this study presents an overview of the pathogenesis and different treatment strategies for dermatomycosis. In addition, we highlight the implementation of natural products of plant origin for treating dermatomycosis infections and reducing adverse events. Further, their mode of action and role in the development of pharmaceutical drugs are discussed.

Evaluation of iron-modified biochar on arsenic accumulation by rice: a pathway to assess human health risk from cooked rice.

Arsenic (As) contamination of rice grain poses a serious threat to human health. Therefore, it is crucial to reduce the bioavailability of As in the soil and its accumulation in rice grains to ensure the safety of food and human health. In this study, mango (Mangifera indica) leaf-derived biochars (MBC) were synthesized and modified with iron (Fe) to produce FeMBC. In this study, 0.5 and 1% (w/w) doses of MBC and FeMBC were used. The results showed that 1% FeMBC enhanced the percentage of filled grains/panicle and biomass yield by 17 and 27%, respectively, compared to the control. The application of 0.5 and 1% FeMBC significantly (p < 0.05) reduced bioavailable soil As concentration by 33 and 48%, respectively, in comparison to the control. The even higher As flux in the control group as compared to the biochar-treated groups indicates the lower As availability to biochar-treated rice plant. The concentration of As in rice grains was reduced by 6 and 31% in 1% MBC and 1% FeMBC, respectively, compared to the control. The reduction in As concentration in rice grain under 1% FeMBC was more pronounced due to reduced bioavailability of As and enhanced formation of Fe-plaque. This may restrict the entry of As through the rice plant. The concentrations of micronutrients (such as Fe, Zn, Se, and Mn) in brown rice were also improved after the application of both MBC and FeMBC in comparison to the control. This study indicates that the consumption of parboiled rice reduces the health risk associated with As compared to cooked sunned rice. It emphasizes that 1% MBC and 1% FeMBC have great potential to decrease the uptake of As in rice grains.

Antioxidative and Antibacterial Hydro-Ethanolic Fraction from an Asian Edible Mushroom Lentinus sajor-caju (Agaricomycetes) Suppresses Inflammatory Responses by Downregulating COX-2 and iNOS Expression.

Mushrooms are prevalently important sources of pharmaceutically active metabolites. Various mushroom species belonging to the Lentinus genus are recognized for their nutritional and therapeutic properties. One such species is L. sajor-caju, which is renowned in Southeast Asian nations for its culinary value. The primary goal of this study is to investigate the potential medicinal properties of L. sajor-caju, specifically its antioxidant, antibacterial, and anti-inflammatory effects. A hydroethanolic extract was formulated using dried basidiocarps, which exhibited a high phenolic content of approximately 14% and a flavonoid content of approximately 2.7%. The extract demonstrated significant antioxidant potential in in vitro reactions. The extract is sufficiently capable of scavenging free radicals (DPPH and ABTS) and chelate Fe2+ with EC50 values spanning from 186 to 390 µg/mL. In addition, considerable antimicrobial activity against tested pathogenic microorganisms was observed, as indicated by low MIC50 values (256-358 µg/mL). Moreover, the fraction was found to prevent heat-induced protein denaturation which signifies its anti-inflammatory potential. When tested on the RAW 264.7 cell line, reduction in the nitrite production, and downregulation of COX-2 and iNOS mRNA expression was observed which are the key regulator of inflammatory signalling systems. The study, therefore, recommends the use of L. sajor-caju in the medical and pharmaceutical industries for the benefit of humanity.

Investigation of Antioxidant Activity, Myco-Chemical Content, and GC-MS Based Molecular Docking Analysis of Bioactive Chemicals from Amanita konajensis (Agaricomycetes), a Tribal Myco-Food from India.

In humans, a wide range of health disorders have been induced due to an imbalanced metabolism and an excess generation of reactive oxygen species (ROS). Different biological properties found in mushrooms seem to be the reason for their customary use as a favourite delicacy. Therefore, exploration of wild edible mushrooms as a source of various biological compounds is gaining much importance today. Amanita konajensis, one of the underutilized macrofungi popularly consumed in Eastern India, demands a systematic study of its medicinal values. The study aims to explore the myco-chemical contents of A. konajensis ethanolic extract (EtAK1) and screen their antioxidant potency through various in vitro assays. GC-MS analysis identified the chemical components of EtAK1. Further, structure-based virtual screening of the identified compounds was analysed for drug-like properties and molecular docking with the human p38 MAPK protein, a potent targeting pathway for human lung cancer. The morpho-molecular features proved the authenticity of the collected mushroom. The screening assays showed that EtAK1 was abundant in flavonoids, followed by phenolics, ß-carotene, and lycopene, and had strong antioxidant activity with EC50 values of 640-710 µg/mL. The GC-MS analyses of EtAK1 identified the occurrence of 19 bioactive compounds in the mushroom. In silico analysis revealed that anthraergostatetraenol p-chlorobenzoate, one of the compounds identified, displayed high binding affinity (ΔG = -10.6 kcal/mol) with human p38 MAPK. The outcome of this study will pave the way for the invention of myco-medicine using A. konajensis, which may lead to a novel drug for human lung cancer.

Innovative utilization of harvested mushroom substrate for green synthesis of silver nanoparticles: A multi-response optimization approach.

In this work, harvested mushroom substrate (HMS) has been explored for the first time through a comprehensive optimization study for the green synthesis of silver nanoparticles (AgNPs). A multiple response central composite design with three parameters: pH of the reaction mixture, temperature, and incubation period at three distinct levels was employed in the optimization study. The particle size of AgNPs, UV absorbance, and the percentage of Ag/Cl elemental ratio were considered as the response parameters. For each response variable examined the model used was found to be significant (P < 0.05). The ideal conditions were: pH 8.9, a temperature of 59.4 °C, and an incubation period of 48.5 h. The UV-visible spectra of AgNPs indicated that the absorption maxima for AgNP-3 were 414 nm, 420 for AgNPs-2, and 457 for AgNPs-1. The XRD analysis of AgNPs-3 and AgNPs-2 show a large diffraction peak at ∼38.2°, ∼44.2°, ∼64.4°, and ∼77.4°, respectively, which relate to the planes of polycrystalline face-centered cubic (fcc) silver. Additionally, the XRD result of AgNPs-1, reveals diffraction characteristics of AgCl planes (111, 200, 220, 311, 222, and 400). The TEM investigations indicated that the smallest particles were synthesized at pH 9 with average diameters of 35 ± 6 nm (AgNPs-3). The zeta potentials of the AgNPs are -36 (AgNPs-3), -28 (AgNPs-2), and -19 (AgNPs-1) mV, respectively. The distinct IR peak at 3400, 1634, and 1383 cm-1 indicated the typical vibration of phenols, proteins, and alkaloids, respectively. The AgNPs were further evaluated against gram (+) strain Bacillus subtilis (MTCC 736) and gram (-) strain Escherichia coli (MTCC 68). All of the NPs tested positive for antibacterial activity against both bacterial strains. The study makes a sustainable alternative to disposing of HMS to achieve the Sustainable Development Goals (SDGs).

Three New Species of Laccaria (Hydnangiaceae) from India (Darjeeling Hills) Based on Molecular and Morphological Evidence.

Three new species of Laccaria infundibuliformis, L. pallidus, and L. darjeelingensis, collected from Darjeeling, India, are described based on morphological and molecular evidence. Laccaria infundibuliformis is characterized by its small infundibuliform basidiocarps, and echinulate basidiospores with spines up to 1.36 µm long. Laccaria pallidus is characterized by medium-sized greyish-red basidiocarps, and echinulate basidiospores with spines up to 1.9 µm long. Laccaria darjeelingensis is characterized by dull red basidiocarps, and echinulate basidiospores with spines up to 1.27 µm long. Altogether, the study shows that these three Laccaria species are previously unknown to science.

A review for cancer treatment with mushroom metabolites through targeting mitochondrial signaling pathway: In vitro and in vivo evaluations, clinical studies and future prospects for mycomedicine.

Resistance to apoptosis stands as a roadblock to the successful pharmacological execution of anticancer drug effect. A comprehensive insight into apoptotic signaling pathways and an understanding of the mechanisms of apoptosis resistance are crucial to unveil new drug targets. At this juncture, researchers are heading towards natural sources in particular, mushroom as their potential drugs leads to being the reliable source of potent bioactive compounds. Given the continuous increase in cancer cases, the potent anticancer efficacy of mushrooms has inevitably become a fascinating object to researchers due to their higher safety margin and multitarget. This review aimed to collect and summarize all the available scientific data on mushrooms from their extracts to bioactive molecules in order to suggest their anticancer attributes via a mitochondrion -mediated intrinsic signaling mechanism. Compiled data revealed that bioactive components of mushrooms including polysaccharides, sterols and terpenoids as well as extracts prepared using 15 different solvents from 53 species could be effective in the supportive treatment of 20 various cancers. The underlying therapeutic mechanisms of the studied mushrooms are explored in this review through diverse and complementary investigations: in vitro assays, pre-clinical studies and clinical randomized controlled trials. The processes mainly involved were ROS production, mitochondrial membrane dysfunction, and action of caspase 3, caspase 9, XIAP, cIAP, p53, Bax, and Bcl-2. In summary, the study provides facts pertaining to the potential beneficial effect of mushroom extracts and their active compounds against various types of cancer and is shedding light on the underlying targeted signaling pathways.

Myco-remediation of plastic pollution: current knowledge and future prospects.

To date, enumerable fungi have been reported to participate in the biodegradation of several notorious plastic materials following their isolation from soil of plastic-dumping sites, marine water, waste of mulch films, landfills, plant parts and gut of wax moth. The general mechanism begins with formation of hydrophobin and biofilm proceding to secretion of specific plastic degarding enzymes (peroxidase, hydrolase, protease and urease), penetration of three dimensional substrates and mineralization of plastic polymers into harmless products. As a result, several synthetic polymers including polyethylene, polystyrene, polypropylene, polyvinyl chloride, polyurethane and/or bio-degradable plastics have been validated to deteriorate within months through the action of a wide variety of fungal strains predominantly Ascomycota (Alternaria, Aspergillus, Cladosporium, Fusarium, Penicillium spp.). Understanding the potential and mode of operation of these organisms is thus of prime importance inspiring us to furnish an up to date view on all the presently known fungal strains claimed to mitigate the plastic waste problem. Future research henceforth needs to be directed towards metagenomic approach to distinguish polymer degrading microbial diversity followed by bio-augmentation to build fascinating future of waste disposal.

Anticancer activity and other biomedical properties of ß-sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches.

Sterols, including ß-sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of ß-sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. ß-sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of ß-sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of ß-sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of ß-sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of ß-sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of ß-sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. ß-sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of ß-sitosterol have also shown anti-cancer effects. However, research in the field of drug delivery and the detailed mode of action of ß-sitosterol-mediated anticancer activities remains limited. ß-sitosterol, as a non-toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, ß-sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of ß-sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on ß-sitosterol as a potent superfood in combating cancer.

Unraveling lipid peroxidation-mediated regulation of redox homeostasis for sustaining plant health.

Lipid peroxidation (LPO) is a complex process that, depending on the context, can either result in oxidative injury or promote redox homeostasis. LPO is a series of reactions in which polyunsaturated fatty acids are attacked by free radicals that result in the synthesis of lipid peroxides. LPO can alter membrane fluidity and operation and produce secondary products that amplify oxidative stress. LPO can activate cellular signaling pathways that promote antioxidant defense mechanisms that provide oxidative stress protection by elevating antioxidant enzyme action potentials. Enzymatic and nonenzymatic mechanisms tightly regulate LPO to prevent excessive LPO and its adverse consequences. This article emphasizes the dual nature of LPO as a mechanism that can both damage cells and regulate redox homeostasis. In addition, it also highlights the major enzymatic and nonenzymatic mechanisms that tightly regulate LPO to prevent excessive oxidative damage. More importantly, it emphasizes the importance of understanding the cellular and biochemical complexity of LPO for developing strategies targeting this process for efficient management of plant stress.

Spermine induced endogenous signal ameliorates osmotic stress in Lens culinaris.

The present study evaluates the alleviation of polyethylene glycol (PEG) mediated osmotic stress by exogenous spermine (SP) application on seeds of Lens culinaris. Seeds were soaked overnight with SP (0.05 M) and PEG (10%) separately. Third set was prepared by combined treatment with SP (0.05 M) and PEG (10%). Further, various physiological parameters, defense enzymes, phenol, flavonoid, nitric oxide (NO), proline content, chromosomal abnormality studies etc. was conducted after 5 days of incubation. PEG application significantly hampered the seed germination, root length, shoot length, relative water content and vigour index. Application of PEG induced electrolytic leakage in root cells. PEG application also significantly reduced the activities of different defense parameters viz. peroxidase, polyphenol oxidase, phenylalanine ammonia lyase and ß-1,3 glucanase, total phenol and flavonoid accumulation over control. Reactive oxygen species, lipid peroxidation, cell death was found significantly high in PEG treated sets. However, NO level has been significantly decreased by PEG treatment. Cytological studies showed reduced mitotic index and highest abnormalities under osmotic stress. Contrary to that, application of SP either alone or in combination with PEG showed improved responses of aforesaid defense parameters compared to control and solely PEG treated sets. Interestingly, cytological abnormalities were also reduced in SP treated roots. Overall, these results suggests that SP application on seeds reduced the PEG induced damage and intricately improved the defense mechanisms which might help to fight against oxidative stress.

Studies of Antioxidant and Cytotoxic Activity in Ready-to-Drink Wild Ganoderma Teas: An In Vitro Approach.

Ganoderma is a medicinally important mushroom and has been used since ancient times. However, mostly G. lucidum has been used for therapeutic purposes, in form of tea, dietary and drug supplements but other species of Ganoderma are still remaining underexploited. This study is the first approach to valorize Ganoderma teas prepared from different wild species of Ganoderma other than G. lucidum with respect to both phytochemically and therapeutically through investigation of their phytochemical, carbohydrate contents and exploring their antioxidant activity. Phytochemical contents such as phenol and flavonoids were quantified using spectrophotometry methods. The carbohydrate content of the teas was estimated by phenol sulphuric acid method. The biochemical analysis revealed the teas contained a notable amount of phenolic compounds ranging from 19.15 to 40.2 µg GAE/mg of extract and also showed significant content of flavonoids. Further, antioxidant potential in terms of DPPH and ABTS radical scavenging ability and total antioxidant capacity was also evaluated. According to the results, G. resinaceum tea showed better potential in scavenging DPPH (EC50 36 ug/mL) and ABTS radicals (EC50 3 9 ug/mL) whereas the least effect was shown for the tea of G. ahmedi. Therefore, tea showing the best results, i.e. G. resinaceum tea, was also analyzed for cytotoxicity on breast cancer cells. It was found that the tea made from G. resinaceum inhibited cellular growth and proliferation in a dose-dependent manner with maximum growth inhibition (61%) observed at the highest concentration of 2.3 mg/mL. The presence of a greater quantity of carbohydrates in G. resinaceum tea also justified the remarkable anticancer potential of the tea. Overall, our findings indicated that a few wild species of Ganoderma other than G. lucidum have great potential to be valued as a healthy beverage with immense therapeutic benefits.

Chemical Characterization and Biological Functions of Hot Alkali-Soluble Crude Polysaccharide from the Water-Insoluble Residue of Macrocybe lobayensis (Agaricomycetes) Fruit Bodies.

Macrocybe lobayensis owe popularity in several traditional cultures not only for delectable taste but also for its nutraceutical profile conveying great health benefits. Previous investigations have enumerated several bioactivities of the valuable mushroom such as antioxidant, anti-ageing, immune-modulation, and anti-tumor properties where polysaccharides played the key role. Macrofungi polymers are generally isolated by the conventional hot water process discarding the residue which still contains plenty of therapeutic components. The present study thus aimed to re-use such leftover of the edible macrofungus by immersing it in NaOH solution at high temperature supporting circular economy. Consequently a polysaccharide fraction, namely ML-HAP, was isolated that was found to be consisted of a homogenous heteropolysaccharide with molecular weight of ~ 128 kDa and ß-glucan as the chief ingredient as evident by spectroscopy, gel-permeation chromatography, high performance thin-layer chromatography, and Fourier transform infrared. Antioxidant activity assays revealed that the macromolecules possess good radical scavenging, metal ion binding and reducing power. Nevertheless, strong immune-potentiation was also recorded as the extract triggered murine macrophage cell viability, pinocytosis, nitric oxide production and morpho-dynamics within 24 h where the best effect was executed at the level of 100 µg/mL. Altogether, the polysaccharides extracted from M. lobayensis exhibited a potent application prospect in functional food, pharmaceutical, nutraceutical and health care industries that could raise economic value of the underexplored mushroom.

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications.

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.