Synergistic Activity of Noble Trimetallic Nanofluids: Unveiling Unprecedented Antimicrobial Potential and Computational Insights.

Nanofluids hold significant promise in diverse applications, particularly in biomedicine, where noble trimetallic nanofluids outperformed their monometallic counterparts. The composition, morphology, and size of these nanofluids play pivotal roles in their functionality. Controlled synthesis methods have garnered attention, focusing on precise morphology, content, biocompatibility, and versatile chemistry. Understanding how reaction parameters such as time, reducing agents, stabilizers, precursor concentration, temperature, and pH affect size and shape during synthesis is crucial. Trimetallic nanofluids, with their ideal composition, size, surface structure, and synergistic properties, are gaining traction in antimicrobial applications. These nanofluids were tested against seven microorganisms, demonstrating a heightened antimicrobial efficacy. Computational analyses, including molecular docking, dynamics, density functional theory (DFT), molecular electrostatic potential (MESP) analysis, and absorption, distribution, metabolism, elimination, and toxicology studies (ADMET) provided insights into binding interactions, energy, reactivity, and safety profiles, affirming the antimicrobial potential of trimetallic nanofluids. These findings emphasize the importance of controlled synthesis and computational validation in harnessing the unique properties of trimetallic nanofluids for biomedical applications.

Two birds with one stone: oyster mushroom mediated bimetallic Au-Pt nanoparticles for agro-waste management and anticancer activity.

Agriculture has the most significant contribution in fulfilling the basic human need, sustaining life, and strengthening the economy of any country. To feed the exploding population of the world, there has been a quantum jump in the production of agricultural commodities, which has led to the production of a substantial considerable quantity of agricultural and agro-industrial wastes. The bulks of these wastes are lignocellulosic in nature and consist of three main polymeric constituents, i.e., cellulose, hemicellulose, and lignin, which are recalcitrant. The primary significant portions of these remain unutilized and are burnt in the field, leading to severe environmental aggression and wastage of resource. Farmers across the globe, including India, burn these agricultural wastes in their thousands of acre land, which contribute to spoiling the air quality index (AQI). This is very harmful, especially to children, pregnant women, old adults, and for patients suffering from respiratory diseases. The current manuscript sets up an agro-waste management platform by using paddy straw as a substrate for the production of nutritionally and medically rich oyster mushroom, Pleurotus florida (Pf) and which is further used in the green synthesis of bimetallic (gold-platinum) Au-Pt nanoparticle. Yield performance and biological efficiency of Pf were calculated from the degraded paddy straw. The green synthesized Au-Pt NPs were structurally characterized by ultraviolet-visible (UV-Vis), X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and zeta potential analysis. The prepared NPs showed a face-centered cubic crystal structure, icosahedral shape with a mean particle size of 16 nm. Furthermore, we examined the cytotoxic activity of Au-Pt NPs using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, intracellular reactive oxygen species (ROS) generation, and apoptosis by propidium iodide assay. We found that Au-Pt NPs exerted apoptotic activity on the human colon cancer cell line (HCT 116) in a dose-dependent manner from 12.5 to 200 µg/mL. Overall, our findings create a prototype and open a new door to synthesizing functional nanoparticle by using oyster mushroom as the substrate for paddy straw agro-waste management and the applicability of Pf in the synthesis of eco-friendly Au-Pt NPs. This is the first kind of approach that kills two birds with one stone.

Rapid eco-friendly synthesis, characterization, and cytotoxic study of trimetallic stable nanomedicine: A potential material for biomedical applications.

In the current scenario of the fight against cancer Integration of potential elements seems to be the best alternative since it overcomes the weaknesses of individuals and the combination of elements makes them formidable in the fight against the cancer war. Inspired by this objective and trusting our knowledge of paddy straw grown oyster mushroom, Pleurotus florida (Pf) mediated synthesis; a first-of-kind approach has been developed for the rapid synthesis of Au-Pt-Ag trimetallic nanoparticles (TMNPs). The developed method was successful, which was confirmed by Ultraviolet-Visible, X-ray diffraction, Transmission Electron Microscopy, Energy Dispersive Spectroscopy. Specifically, prepared TMNPs have been studied for their stability and size as a primary prerequisite for nanomedicine. Finally, the stable nanomedicine developed has been assessed for its performance against the highly metastatic breast cancer cell line (mda-mb-231). The performance was assessed using MTT assay and morphological readings, which were integrated with the cell viability data. We also determined the IC50 value, which was far superior to individual components and motivated us to postulate the possible breast cancer cell killing mechanism of TMNPs. The present study unlocks the new paths for the mushroom-mediated environmentally friendly, economic synthesis of trimetallic nanoparticles, which can be effectively used in cancer nanomedicine.

Pleurotus sajor-caju-Mediated Synthesis of Silver and Gold Nanoparticles Active against Colon Cancer Cell Lines: A New Era of Herbonanoceutics.

Herbal medicines are widely used worldwide and much appreciated because of their fewer side effects and the ability to fight diseases at the root cause. Active 'phyto' ingredients require a scientific approach and a mechanism to distribute components at the target site for better therapeutic results. Nanotechnology, on the other hand, has created new hope for cancer treatment but is still far from being proven in clinical settings. This article combines a unique approach to synthesis with the use of Pleurotus sajor-caju, followed by microwave irritation of silver and gold nanoparticles that ensures the capping of the active phyto ingredient and further enhances the effects of nanomedicine to fight colon cancer, thus opening a new era of what we call herbonanoceutics. The article also compares the characteristics and properties of silver (Au) and gold (Ag) nanoparticles synthesized by an in house developed novel microwave-assisted rapid green synthesis method. The as-prepared Ag NPs and Au NPs were compared using ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and energy dispersive spectroscopy (EDS). Our comparative study revealed that both assemblies display face-centred cubic structures (FCCs) and are nanocrystalline in nature. The advantage of the approach was that the sizes of gold and silver were identical in range with a similar distribution pattern. This has helped us to study the activity against colon cancer cell line (HCT-116) without incoherence since size plays a key role in the application. More specifically, morphological changes, cell viability, the production of reactive oxygen species (ROS) and the fragmentation of DNA have been further reported to assess better the results obtained with the two metals. Our results suggest that the newly adopted synthesis method may ensure the dual benefits from phyto ingredients which further enhances the effectiveness of advanced nanomedicine.

LC-MS/MS method for the simultaneous quantification of luteolin, wedelolactone and apigenin in mice plasma using hansen solubility parameters for liquid-liquid extraction: Application to pharmacokinetics of Eclipta alba chloroform fraction.

Eclipta alba (Bhringraj) in ayurveda has been widely used as a traditional medicine for its multi-therapeutic properties for ages. Luteolin (LTL), wedelolactone (WDL) and apigenin (APG) are the three main bioactive phytochemicals present in Eclipta alba extract. However there was a lack of sensitive bioanalytical method for the pharmacokinetics of these free compounds in plasma which majorly contributes for their activities after oral administration of Eclipta alba. The present study aims to develop a sensitive, rapid and reliable liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous estimation of mice plasma concentrations of LTL, WDL and APG using quercetin as an internal standard for the pharmacokinetic analysis. Analytes were separated on Phenomenex Luna C18 (150 × 4.6 mm, 3.0 µm) column with mobile phase containing methanol: acetonitrile (90: 10, v/v) and 0.1% formic acid in 10 mM ammonium formate buffer in the ratio of 70: 30 (v/v) in isocratic mode. Liquid-liquid extraction was optimized using Hansen solubility parameters and diethyl ether finalized as an extraction solvent for the recovery ranging from 61 to 76% for all analytes in mice plasma. The validated method has an accuracy and precision over the linearity range of 0.1-200 ng/mL with a correlation coefficient (r2) of ≥0.997. The intra and inter-day assay accuracy was between 98.17 and 107% and 95.83-107.89% respectively and the intra and inter day assay precision ranged from 0.37-6.05% and 1.85-10.76%, respectively for all the analytes. This validated method can be used for future clinical investigation studies of Eclipta alba extracts.

Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects.

As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer.

Alternative methods in toxicology: CFU assays application, limitation and future prospective.

Blood is a fluid connective tissue which plays a vital role for normal body function. It consist different type of blood cells which is continuously reproduce inside the bone marrow from hematopoietic system. Xenobiotics could be specifically toxic to the hematopoietic system and they can cause hematological disorders by disturbing the normal functions. In vitro hematopoietic colony-forming cell assays play a crucial role to evaluate potential toxic effects of new xenobiotics and also helpful in bridging the gap between preclinical toxicology studies in animal models and clinical investigations. Use of these assays in conjunction with, high-throughput screening reduces the cost and time associated with these assays. This article provides a critical view over in vitro hematopoietic colony-forming cell assays in assessment of hematotoxicity.

Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis.

Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation of Eclipta alba extract and discovered that particularly the chloroform fraction of Eclipta alba (CFEA) is selectively inducing cytotoxicity to breast cancer cells over non-tumorigenic breast epithelial cells. Our unbiased mechanistic hunt revealed that CFEA specifically activates the intrinsic apoptotic pathway by disrupting the mitochondrial membrane potential, upregulating Hsp60 and downregulating the expression of anti-apoptotic protein XIAP. By utilizing Hsp60 specific siRNA, we identified a novel pro-apoptotic role of Hsp60 and uncovered that following CFEA treatment, upregulated Hsp60 is localized in the endoplasmic reticulum (ER). To our knowledge, this is the first evidence of ER specific localization of Hsp60 during cancer cell apoptosis. Further, our LC-MS approach identified that luteolin is mainly attributed for its anti-cancer activities. Moreover, oral administration of CFEA not only offers potential anti-breast cancer effects in-vivo but also mitigates tumor induced hepato-renal toxicity. Together, our studies offer novel mechanistic insight into the CFEA mediated inhibition of breast cancer and may potentially open up new avenues for further translational research.

Saraca indica bark extract shows in vitro antioxidant, antibreast cancer activity and does not exhibit toxicological effects.

Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy.

microRNAs: role in leukemia and their computational perspective.

MicroRNAs (miRNAs) belong to the family of noncoding RNAs (ncRNAs) and had gained importance due to its role in complex biochemical pathways. Changes in the expression of protein coding genes are the major cause of leukemia. Role of miRNAs as tumor suppressors has provided a new insight in the field of leukemia research. Particularly, the miRNAs mediated gene regulation involves the modulation of multiple mRNAs and cooperative action of different miRNAs to regulate a particular gene expression. This highly complex array of regulatory pathway network indicates the great possibility in analyzing and identifying novel findings. Owing to the conventional, slow experimental identification process of miRNAs and their targets, the last decade has witnessed the development of a large amount of computational approaches to deal with the complex interrelations present within biological systems. This article describes the various roles played by miRNAs in regulating leukemia and the role of computational approaches in exploring new possibilities.

Next generation sequencing: potential and application in drug discovery.

The world has now entered into a new era of genomics because of the continued advancements in the next generation high throughput sequencing technologies, which includes sequencing by synthesis-fluorescent in situ sequencing (FISSEQ), pyrosequencing, sequencing by ligation using polony amplification, supported oligonucleotide detection (SOLiD), sequencing by hybridization along with sequencing by ligation, and nanopore technology. Great impacts of these methods can be seen for solving the genome related problems of plant and animal kingdom that will open the door of a new era of genomics. This may ultimately overcome the Sanger sequencing that ruled for 30 years. NGS is expected to advance and make the drug discovery process more rapid.

Hematological malignancies: role of miRNAs and their in silico aspects.

Hematological malignancies is a broad term that includes blood cell cancers including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), Myelodysplastic syndrome, acute lymphocytic leukemia (ALL), multiple myelomas (MM) and lymphomas. miRNAs are ~22-nt long non-coding RNAs that play a very important role in gene regulation by binding to mRNA at their complementary sequence. These miRNAs are conceptually connected with various signal and pathway networks that make them capable of regulating various diseases including hematological malignancies. These miRNAs are not only playing regulatory roles in hematological malignancies, but are also providing new potent markers for efficient diagnosis and prognosis for hematological malignancies patients. Since the discovery of very first miRNA, the importance and role of miRNAs have been established in various fields, and there is a need to search for new potent miRNAs and their targets. A large amount of sequence data have been generated in last few years, which has further generated the need to develop efficient and reliable computational tools to analyze and extract out relevant information promptly from raw data. Here, we review various possible roles played by miRNA in hematological malignancies, principles involved in miRNA gene identification, target prediction and their preceding role in hematological malignancies research.