Evaluation of the toxic metals, proximate composition and length-weight relationships of selected fish species from the Gadananathi River, Southern Tamil Nadu.

The present study reveals toxic metals, proximate composition, and growth conditions in seven fish species, aiding their nutritional importance and conditions. The samples of seven different small indigenous fish species, including Xenentodon cancila, Glossogobious giuris, Pseudambassis ranga, Puntius dorsolis, Mystus vittatus, Dawkinsia filamentosa, and Dawkinsia tambraparaniei, were collected in river Gadananathi, Tamilnadu, India. A total 14 fish samples were analyzed for lead, cadmium, and copper using atomic absorption spectrometry. The standard procedures were used to determine the length-weight and proximate composition of the seven fishes. The findings revealed that the seven fish species had variable amounts of metal buildup. Cu levels were highest in D. tambraparniei gills and lowest in M. vittatus gills and livers; nonetheless, substantial amounts of Cu were found in P. dorsalis livers. In the length-weight correlations of the regression parameters of coefficient value r2, the "a" and "b" values revealed a positive allometric growth rate in all fish species except G. giuris and M. vittatus. However, X. cancila had the highest composition in the proximate analysis, while D. tambraparniei and D. filamentosa had the highest protein content mean value at a significant level (P ≤ 0.05). Overall, discrepancies in nutritional content might be related to species, environmental circumstances, fish age and size, and food availability.

The effect of porcelain filler particulates madar fiber reinforced epoxy composite - A comprehensive study for biomedical applications.

Environmental consciousness motivates scientists to devise an alternative method for producing natural fiber composite materials in order to decrease the demand for synthetic fibers. This study explores the potential of a novel composite material derived from madar fiber-reinforced epoxy with porcelain filler particulates, designed specifically for biomedical instrumentation applications. The primary focus is to assess the material's structural, mechanical, and antibacterial properties. X-ray Diffraction analysis was employed to discern the crystalline nature of the composite, revealing enhanced crystallinity due to the inclusion of porcelain particulates. Fourier-Transform Infrared Spectroscopy confirmed the chemical interactions and bonding mechanisms between madar fiber, epoxy matrix, and porcelain filler. Mechanically, the composite exhibited superior properties when addition of porcelain fillers, maximum results obtain in tensile strength of 51.28 MPa, flexural strength of 54.21 MPa, and impact strength of 0.0155 kJ/m2, making it ideal for robust biomedical applications. Scanning Electron Microscopy provided detailed insights into the morphology and distribution of the reinforcing agents within the epoxy matrix, emphasizing the fibrillated structure of madar fiber and the uniform dispersion of porcelain particulates. Importantly, antibacterial assays demonstrated the composite's potential resistance against common pathogenic bacteria, which is crucial for biomedical instrumentation. Collectively, this research underscores the promising attributes of the madar fiber reinforced epoxy composite with porcelain particulates, suggesting its suitability for advanced biomedical applications.

c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy.

BACKGROUND: c-MET is a receptor tyrosine kinase which is classically activated by HGF to activate its downstream signaling cascades such as MAPK, PI3K/Akt/mTOR, and STAT3. The c-MET modulates cell proliferation, epithelial-mesenchymal transition (EMT), immune response, morphogenesis, apoptosis, and angiogenesis. The c-MET has been shown to serve a prominent role in embryogenesis and early development. The c-MET pathway is deregulated in a broad range of malignancies, due to overexpression of ligands or receptors, genomic amplification, and MET mutations. The link between the deregulation of c-MET signaling and tumor progression has been well-documented. Overexpression or overactivation of c-MET is associated with dismal clinical outcomes and acquired resistance to targeted therapies. Since c-MET activation results in the triggering of oncogenic pathways, abrogating the c-MET pathway is considered to be a pivotal strategy in cancer therapeutics. Herein, an analysis of role of the c-MET pathway in human cancers and its relevance in bone metastasis and therapeutic resistance has been undertaken. Also, an attempt has been made to summarize the inhibitory activity of selected natural compounds towards c-MET signaling in cancers. METHODS: The publications related to c-MET pathway in malignancies and its natural compound modulators were obtained from databases such as PubMed, Scopus, and Google Scholar and summarized based on PRISMA guidelines. Some of the keywords used for extracting relevant literature are c-MET, natural compound inhibitors of c-MET, c-MET in liver cancer, c-MET in breast cancer, c-MET in lung cancer, c-MET in pancreatic cancer, c-MET in head and neck cancer, c-MET in bone metastasis, c-MET in therapeutic resistance, and combination of c-MET inhibitors and chemotherapeutic agents. The chemical structure of natural compounds was verified in PubChem database. RESULTS: The search yielded 3935 publications, of which 195 reference publications were used for our analysis. Clinical trials were referenced using ClinicalTrials.gov identifier. The c-MET pathway has been recognized as a prominent target to combat the growth, metastasis, and chemotherapeutic resistance in cancers. The key role of the c-MET in bone metastasis as well as therapeutic resistance has been elaborated. Also, suppressive effect of selected natural compounds on the c-MET pathway in clinical/preclinical studies has been discussed.

Caralluma pauciflorabased Ag-NPs activate ROS - induced apoptosis through down-regulation of AKT, mTOR and pI3K signaling in human gastric cancer (AGS) cells.

The phytochemicals found inCaralluma pauciflorawere studied for their ability to reduce silver nitrate in order to synthesise silver nanoparticles (AgNPs) and characterise their size and crystal structure. Thunbergol, 1,1,6-trimethyl-3-methylene-2-(3,6,9,13-tetram, Methyl nonadecanoate, Methyl cis-13,16-Docosadienate, and (1R,4aR,5S)-5-[(E)-5-Hydroxy-3-methylpent were the major compounds identified in the methanol extract by gas chromatography-mass spectrum analysis. UV/Vis spectra, Fourier-transform infrared spectroscopy, x-ray diffraction, scanning electron microscope with Energy Dispersive Xâray Analysis (EDAX), Dynamic Light Scattering (DLS) particle size analyser and atomic force microscope (AfM) were used to characterise theCaralluma paucifloraplant extract-based AgNPs. The crystal structure and estimated size of the AgNPs ranged from 20.2 to 43 nm, according to the characterization data. The anti-cancer activity of silver nanoparticles (AgNPs) synthesised fromCaralluma paucifloraextract. The AgNPs inhibited more than 60% of the AGS cell lines and had an IC50 value of 10.9640.318 g, according to the findings. The cells were further examined using fluorescence microscopy, which revealed that the AgNPs triggered apoptosis in the cells. Furthermore, the researchers looked at the levels of reactive oxygen species (ROS) in cells treated with AgNPs and discovered that the existence of ROS was indicated by green fluorescence. Finally, apoptotic gene mRNA expression analysis revealed that three target proteins (AKT, mTOR, and pI3K) were downregulated following AgNP therapy. Overall, the findings imply that AgNPs synthesised from Caralluma pauciflora extract could be used to treat human gastric cancer.

Evaluation of Zn-Cd-Sn-S nanostructures for in vitro pyrene degradation and antimicrobial activity.

The present work describes the fabrication of the quaternary Zn-Cd-Sn-S nanostructure and its use in photocatalytic remediation of the biological contaminant pyrene from water resources. Nanostructures fabricated were characterized by XRD, UV-DRS, FTIR, DLS, EDX, and SEM. In addition, an agar well diffusion test was conducted to determine the antimicrobial activity. Zn-Cd-Sn-S (ZCSS) nanostructures were evaluated for their photocatalytic degrading potential by using pyrene as a model pollutant and evaluating the effects of parameters like initial pyrene concentration, nanocatalyst dosage, solution pH, and light sources during batch adsorption. Nanostructures had a size of 16.74 nm according to the XRD analysis. With a 300 min time interval, ZCSS nanostructures achieved the highest removal rate of 86.3%. Pyrene degradation metabolites were identified using GC-MS analysis of the degraded samples. A Freundlich isothermal (R2 0.9) and pseudo-first-order (R2 0.952) reaction kinetic path best fit the adsorption results for pyrene by the fabricated ZCSS nanostructure, based on the adsorption and kinetic studies. Zn-Cd-Sn-S exhibited the highest antibacterial activity against Staphylococcusaureus (22.4 mM). Due to the combined synergistic actions of the constituent metals, this quaternary nanostructure exhibited exceptional photocatalytic activity. To our est knowledge, the ZCSS nanostructure was made and used to remove pyrene by photocatalysis and fight microbes. Ultimately, the ZCSS nanostructure was found to be an effective photocatalyst for eradicating pathogenic microbes from water.

Nerolidol, Bioactive Compound Suppress Growth of HCT-116 Colorectal Cancer Cells Through Cell Cycle Arrest and Induction of Apoptosis.

Colon cancer is the most prevalent cancer and causes the highest cancer-associated mortality in both men and women globally. It has a high incidence and fatality rate, which places a significant burden on the healthcare system. The current work was performed to understand the beneficial roles of nerolidol on the viability and cytotoxic mechanisms in the colon cancer HCT-116 cells. The MTT cytotoxicity assay was done to investigate the effect of nerolidol at different doses (5-100 µM) on the HCT-116 cell viability. The impacts of nerolidol on ROS accumulation and apoptosis were investigated using DCFH-DA, DAPI, and dual staining assays, respectively. The flow cytometry analysis was performed to study the influence of nerolidol on the cell cycle arrest in the HCT-116 cells. The outcomes of the MTT assay demonstrated that nerolidol at different doses (5-100 µM) substantially inhibited the HCT-116 cell viability with an IC50 level of 25 µM. The treatment with nerolidol appreciably boosted the ROS level in the HCT-116 cells. The findings of DAPI and dual staining revealed higher apoptotic incidences in the nerolidol-exposed HCT-116 cells, which supports its ability to stimulate apoptosis. The flow cytometry analysis demonstrated the considerable inhibition in cell cycle at the G0/G1 phase in the nerolidol-exposed HCT-116 cells. Our research showed that nerolidol can inhibit the cell cycle, increase ROS accumulation, and activate apoptosis in HCT-116 cells. In light of this, it may prove to be a potent and salutary candidate to treat colon cancer.

Leonurine ameliorates the STAT3 pathway through the upregulation of SHP-1 to retard the growth of hepatocellular carcinoma cells.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that directs the transcription of genes involved in the promotion of cell survival and proliferation, inflammation, angiogenesis, invasion, and migration. Overactivation of STAT3 is often witnessed in human cancers, thereby making it a good target in oncology. Herein the efficacy of Leonurine (Leo), a bioactive alkaloid present in Herba leonuri, was investigated for its STAT3-inhibitory potential in hepatocellular carcinoma (HCC) cells. Leo downregulated the persistent as well as IL-6-driven activation of STAT3. Leo abrogated the nuclear localization and DNA interacting ability of STAT3. Leo was also found to impart STAT3 inhibition by mitigating the activation of upstream kinases such as JAK1, JAK2, and Src both in constitutive and IL-6 inducible systems. Leo curbed the STAT3-driven luciferase gene expression and the depletion of STAT3 resulted in the reduced responsiveness of HCC cells to Leo. Pervanadate exposure counteracted Leo-induced STAT3 inhibition suggesting the involvement of a protein tyrosine phosphatase. SHP-1 was significantly elevated upon Leo exposure whereas the depletion of SHP-1 was found to revert the effect of Leo on STAT3. Leo induced apoptosis and also significantly potentiated the cytotoxic effect of paclitaxel, doxorubicin, and sorafenib. Leo was found to be non-toxic up to the dose of 10 mg/kg in NCr nude mice. In conclusion, Leo was demonstrated to induce cytotoxicity in HCC cells by mitigating the persistent of activation of STAT3 pathway.

Synthesis and utilization of biomass-derived sulfonated heterogeneous catalyst-BT-SO3H for microalgal biodiesel production.

The study investigates the potential of utilizing banana trunk-derived porous activated biochar enriched with SO3H- as a catalyst for eco-friendly biodiesel production from the microalga Chlorella vulgaris. An extensive analysis, employing advanced techniques such as XRD, FTIR, TGA, XPS, NH3-TPD, BET, SEM-EDX, and TEM, was conducted to elucidate the physicochemical properties of BT-SO3H catalysts. The synthesized catalyst demonstrated its efficiency in converting the total lipids of Chlorella vulgaris into biodiesel, with varying concentrations of 3%, 5%, and 7%. Notably, using a 5% BT-SO3H concentration resulted in remarkably higher biodiesel production about 58.29%. Additionally, the fatty acid profile of C. vulgaris biodiesel indicated that C16:0 was the predominant fatty acid at 24.31%, followed by C18:1 (19.68%), C18:3 (11.45%), and C16:1 (7.56%). Furthermore, the biodiesel produced via 5% BT-SO3H was estimated to have higher levels of saturated fatty acids (SFAs) at 34.28%, monounsaturated fatty acids (MUFAs) at 30.70%, and polyunsaturated fatty acids (PUFAs) at 24.24%. These findings highlight the promising potential of BT-SO3H catalysts for efficient and environmentally friendly biodiesel production from microalgal species.

Introducing a novel chemotherapeutic drug formulated with anthraflavic acid for treating human breast carcinoma and type 2 diabetes mellitus.

Introduction: Molecular docking as a versatile theoretical method was used to investigate the biological activities of anthraflavic acid in the presence of α-amylase. The outcomes revealed that anthraflavic acid has a considerable binding affinity to the enzyme with a docking score of -7.913 kcal/mol. These outcomes were further evaluated with free binding energy calculations, and it was concluded that anthraflavic acid could be a potential inhibitor for α-amylase. Material and methods: Anthraflavic acid was explored in anti-human breast carcinoma tests. The in vitro cytotoxic and anti-breast carcinoma effects of biologically synthesized anthraflavic acid against MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines were assessed. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the anti-breast carcinoma properties of anthraflavic acid could significantly kill the MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines in a time- and concentration-dependent manner. Also, we used human umbilical vein endothelial cells (HUVECs) to determine the cytotoxicity potentials of anthraflavic acid using MTT assay. Results: The IC50 values of anthraflavic acid were 159, 193, 253, 156, 241, and 218 µg/ml against MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines. Conclusions: It seems the anti-human breast carcinoma effect of recent nanoparticles is due to their antioxidant effects.

Hibiscus rosa-sinensis as a potential hyperaccumulator in metal contaminated magnesite mine tailings.

Mining is one of the major contributors for land degradation and severe heavy metals based soil pollution. In this study, the physicochemical properties of magnesite mine soil was investigated and assess the optimistic and eco-friendly remediation approach with Hibiscus rosa-sinensis with the effect of pre-isolated Acidithiobacillus thiooxidans. The physicochemical properties analysis results revealed that most the parameter were either too less or beyond the permissible limits. The pre-isolated A. thiooxidans showed remarkable multi-metal tolerance up to 800 µg mL-1 concentration of Cr, Cd, Pb, and Mn. Heavy metal content in polluted soil was reduced to avoid more metal toxicity by diluting with fertile control soil as 80:20 and 60:40. The standard greenhouse experiment was performed to evaluate the phytoextraction potential of H. rosa-sinensis under the influence of A. thiooxidans in various treatment groups (G-I to G-V). The outcome of this investigation was declared that the multi-metal tolerant A. thiooxidans from G-III and G-II showed remarkable effect on growth and phytoextraction ability of H. rosa-sinensis on metal polluted magnesite mine soil in 180 d greenhouse study. These results suggested that the combination of H. rosa-sinensis and A. thiooxidans could be used as an excellent hyper-accumulator to extract metal pollution from polluted soil.

Bio/phyremediation potential of Leptospirillum ferrooxidans and Ricinus communis on metal contaminated mine sludge.

The heavy metal pollution is a serious environmental pollution around the globe and threatens the ecosystem. The physicochemical traits (pH, Electrical conductivity, hardness, NPK, Al, Fe, Cd, Cr, Pb, Mg, and Mn) of soil sample collected from the polluted site were analyzed and found that the most of the metal contents were beyond the acceptable limits of national standards. The metals such as Mn (1859.37 ± 11.25 mg kg-1), Cd (24.86 ± 1.85 mg kg-1), Zn (795.64 ± 9.24 mg kg-1), Pb (318.62 ± 5.85 mg kg-1), Cr (186.84 ± 6.84 mg kg-1), and Al (105.84 ± 5.42 mg kg-1) were crossing the permissible limits. The pre-isolated L. ferrooxidans showed considerable metal tolerance to metals such as Al, Cd, Cr, Pb, Mg, and Mn at up to the concentration of 750 µg mL-1 and also have remediation potential on polluted soil in a short duration of treatment. The greenhouse study demonstrated that the bio/phytoremediation potential of metal tolerant L. ferrooxidans and R. communis under various remediation (A, B, and C) groups. Surprisingly, remediation group C demonstrated greater phytoextraction potential than the other remediation groups (A and B). These results strongly suggest that coexistence of L. ferrooxidans and R. communis had a significant positive effect on phytoextraction on metal-contaminated soil.

Anti-cancer potential of selenium-chitosan-polyethylene glycol-carvacrol nanocomposites in multiple myeloma U266 cells.

Multiple myeloma (MM) is an incurable cancer that is characterized by malignant plasma cell proliferation. Approximately 10% of all blood cancers are MM, and there is no standard curative therapy. In this work, we intended to synthesize, characterize, and assess the anticancer effects of selenium/chitosan/polyethylene glycol-carvacrol nanocomposites (SCP-Car-NCs) on MM U266 cells in vitro. Various characterization techniques were used to characterize the synthesized SCP-Car-NCs. Several in vitro free radical scavenging experiments were conducted to test the ability of synthesized SCP-Car-NCs to scavenge the different free radicals. The cytotoxicity of SCP-Car-NCs was assessed on Vero and U266 cells using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. By using various fluorescence staining techniques, the amount of reactive oxygen species (ROS) generation, MMP, and apoptosis were measured. Using commercial test kits, the levels of oxidative stress and apoptotic biomarkers in control and treated U266 cells were assessed. The highest peak in the UV spectral analysis was found to be at 271 nm, demonstrating the development of SCP-Car-NCs. Fourier transform infrared analysis showed that the synthesized SCP-Car-NCs contained a variety of stretching and bonding. The X-ray diffraction study confirmed the crystallinity of SCP-Car-NCs. The dynamic light scattering analysis showed that the SCP-Car-NCs had an average size of 171 nm. The different free radicals, such as the 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, and peroxyl radicals, were significantly scavenged by the SCP-Car-NCs. According to the MTT assay results, the SCP-Car-NCs decreased the viability of U266 cells while having no impact on the proliferation of Vero cells. The SCP-Car-NCs significantly boosted ROS production, decreased the MMP level, and promoted apoptosis, as evidenced by the fluorescence staining experiments. In U266 cells treated with SCP-Car-NCs, the level of thiobarbituric acid reactive substances increased while superoxide dismutases and glutathione levels were reduced. In the SCP-Car-NCs treated U266 cells, it was found that the Bax, caspase-3, and -9 activities had increased while the Bcl-2 level had decreased. In conclusion, our findings show that SCP-Car-NCs treatment reduced the viability and increased apoptosis in the U266 cells, providing a new insight on SCP-Car-NCs' potential for usage in the future to treat MM.

CXCR4 expression is elevated in TNBC patient derived samples and Z-guggulsterone abrogates tumor progression by targeting CXCL12/CXCR4 signaling axis in preclinical breast cancer model.

Environmental factors such as exposure to ionizing radiations, certain environmental pollutants, and toxic chemicals are considered as risk factors in the development of breast cancer. Triple-negative breast cancer (TNBC) is a molecular variant of breast cancer that lacks therapeutic targets such as progesterone receptor, estrogen receptor, and human epidermal growth factor receptor-2 which makes the targeted therapy ineffective in TNBC patients. Therefore, identification of new therapeutic targets for the treatment of TNBC and the discovery of new therapeutic agents is the need of the hour. In this study, CXCR4 was found to be highly expressed in majority of breast cancer tissues and metastatic lymph nodes derived from TNBC patients. CXCR4 expression is positively correlated with breast cancer metastasis and poor prognosis of TNBC patients suggesting that suppression of CXCR4 expression could be a good strategy in the treatment of TNBC patients. Therefore, the effect of Z-guggulsterone (ZGA) on the expression of CXCR4 in TNBC cells was examined. ZGA downregulated protein and mRNA expression of CXCR4 in TNBC cells and proteasome inhibition or lysosomal stabilization had no effect on the ZGA-induced CXCR4 reduction. CXCR4 is under the transcriptional control of NF-κB, whereas ZGA was found to downregulate transcriptional activity of NF-κB. Functionally, ZGA downmodulated the CXCL12-driven migration/invasion in TNBC cells. Additionally, the effect of ZGA on growth of tumor was investigated in the orthotopic TNBC mice model. ZGA presented good inhibition of tumor growth and liver/lung metastasis in this model. Western blotting and immunohistochemical analysis indicated a reduction of CXCR4, NF-κB, and Ki67 in tumor tissues. Computational analysis suggested PXR agonism and FXR antagonism as targets of ZGA. In conclusion, CXCR4 was found to be overexpressed in majority of patient-derived TNBC tissues and ZGA abrogated the growth of TNBC tumors by partly targeting the CXCL12/CXCR4 signaling axis.

Bioremediation efficiency of free and immobilized form of Aspergillus niger and Aspergillus tubigenesis biomass on tannery effluent.

Untreated tannery effluent discharge, which causes severe environmental pollution. This research was performed to assess the bioremediation (multi-pollutant adsorption) potential of pre-identified and multi metal tolerant Aspergillus niger and Aspergillus tubigenesis through a stirred tank bioreactor in free and immobilized form. Physicochemical property analysis results showed that most of the tannery effluent properties were beyond the permissible limits. These A. niger and A. tubigenesis effectively immobilized on corncob and coir solid support material. The stirred tank bioreactor based bioremediation study revealed that the fungal biomass (Aspergillus niger and Aspergillus tubigenesis) immobilized coir and corncob material demonstrated remarkable multi-pollutant (TSS: 22.5% & 13.5%, TS: 29% & 22%, BOD: 21% & 10%, TDS: 28% & 19%, COD: 30% & 22%, Cr: 27% & 19%, Cu: 28% & 12%, and Pb: 48% & 29% respectively) adsorption potential in a week of treatment. Moreover, it reduced the toxicity of tannery effluent and promotes the sprouting of Oriza sativa seeds, as demonstrated by petri plate bioassay. These finding suggest that the metal-tolerant fungal isolates A. niger and A. tubigenesis demonstrated impressive bioremediation proficiencies in an immobilized state. A field investigation is required to assess the feasibility of this strategy on tannery effluent.

T-2 toxin induces dermal inflammation and toxicity in mice: The healing potential of menthol.

According to the World Health Organization and the Food and Agricultural Organization of the United Nations, T-2 is one of the most harmful food-toxic chemicals, penetrates intact skin. The current study examined the protective benefits of menthol topical treatment on T-2 toxin-induced cutaneous toxicity in mice. Lesions were observed on the skin of the T-2 toxin-treated groups at 72 and 120 h. The T-2 toxin (2.97 mg/kg/bw)-treated group developed skin lesions, skin inflammation, erythema, and necrosis of skin tissue in contrast to the control group. Our findings reveal that topical application of 0.25% and 0.5% MN treated groups resulted in no erythema or inflammation, and normal skin was observed with growing hairs. The 0.5% MN administered group demonstrated an 80% blister and erythema healing effect in in vitro tests. In addition, MN dose-dependently suppressed ROS and lipid peroxidation mediated by the T-2 toxin up to 120%. Histology discoveries and the immunoblotting investigations with the downregulation of i-NOS gene expression confirmed the validity of menthol activity. Further molecular docking experiments of menthol against the i-NOS protein demonstrated stable binding efficacy with conventional hydrogen bond interactions, indicating compelling evidence of menthol's anti-inflammatory effects on the T-2 toxin-induced skin inflammation.

Valorization of pineapple peel waste for fungal pigment production using Talaromyces albobiverticillius: Insights into antibacterial, antioxidant and textile dyeing properties.

The present study explores natural pigments as sustainable alternatives to synthetic textile dyes. Due to their therapeutic applications and easy production, fungal pigments have gained attention. However, data on pigment production using solid-state fermentation and optimization is limited. Milk whey was used to grow Talaromyces sp., followed by an evaluation of pigment production in solid and liquid media. Pineapple peels were used as a cost-effective substrate for pigment production, and a one-factor-at-a-time approach was used to enhance pigment production. Pineapple peel-based media produced 0.523 ± 0.231 mg/g of pigment after eight days of incubation. The crude pigment had promising antibacterial and significant antioxidant properties. The extraction fungal pigment's possible use as an eco-friendly textile dye was assessed through fabric dyeing experiments with different mordants. This work contributes to the valorization of agricultural waste and provides insight into using fungal pigments as sustainable alternatives to synthetic textile dyes.

Convalescent action of menthol against T-2 mycotoxin-induced toxicity: An in vitro study with HaCaT cells.

Only T-2 mycotoxin is emitted as an aerosol and is the most toxic fungal secondary metabolite among mycotoxins. In its clinical condition, the skin is severely irritated and painful due to lesions and alimentary toxic aleukia. Herein, we have assessed various bioactive molecules, viz. kaempferol, menthol, curcumin, and quercetin, against T-2-induced toxicity in HaCaT cells. Menthol offered exceptional protection, protecting 92% of HaCaT cells after exposure to 300 nM T-2 and reducing LDH leakage by up to 42%. Its pre-treatment provided considerable protection against T-2 toxicity, as evidenced by the assessment of mitochondrial membrane potential. Propidium iodide staining revealed a cell cycle halt at the G1, S, and M phases and a significant increase in the sub-G1 percentage in T-2-challenged cells, indicating cell death. However, pre-treatment with menthol promoted cell cycle progression in cells exposed to T-2. Immunoblotting results demonstrated that menthol resulted in a discernible down-regulation of i-NOS expression in T-2-challenged HaCaT cells.

Silk sericin conjugated magnesium oxide nanoparticles for its antioxidant, anti-aging, and anti-biofilm activities.

The Silk sericin protein was conjugated with magnesium oxide (MgO) nanoparticles to form SS-MgO-NPs . UV, XRD, FTIR, SEM, DLS, and EDX were used to confirm the formation of SS-MgO-NPs. The absorption band of SS-MgO-NPs using UV-visible spectra was observed at 310 nm, with an average size of the nanoparticles was 65-88 nm analyzed from DLS. The presence of alcohol, CN, and CC, alkanes, alkenes, and cis alkenes, in silk sericin, is confirmed by FT-IR and may act as a stabilizing agent. Later SS-MgO-NPs were evaluated for antioxidant, antibacterial, anti-biofilm, ,anti-aging, and anticancer properties. The SS-MgO-NPs inhibited the formation of biofilm of Pseudomonas aeruginosa and Bacillus cereus. The blood compatibility of SS-MgO-NPs, delaying coagulation was observed using human, blood, and goat blood samples. The SS-MgO-NPs exhibited significant anticancer activity on MCF-7 (IC50 207.6 µg/mL) cancer cell lines. Correspondingly, SS-MgO-NPs demonstrated dose-dependent inhibition of the enzymes in the following order collagenase > elastase > tyrosinase > hyaluronidase, with IC50 values of 75.3, 85.3, 133.6, and 156.3 µgmL-1, respectively. This exhibits the compoundposses anti-aging properties. So, in in vitro settings, SS-MgO-NPs can be used as an antibacterial, anti-aging, and anticancer agent. Additionally, in vivo research is necessary to validate its therapeutic applications.

De Novo Design of Imidazopyridine-Tethered Pyrazolines That Target Phosphorylation of STAT3 in Human Breast Cancer Cells.

In breast cancer (BC), STAT3 is hyperactivated. This study explored the design of imidazopyridine-tethered pyrazolines as a de novo drug strategy for inhibiting STAT3 phosphorylation in human BC cells. This involved the synthesis and characterization of two series of compounds namely, 1-(3-(2,6-dimethylimidazo [1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-(substituted)piperazin-1-yl)ethanone and N-substituted-3-(2,6-dimethylimidazo[1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazoline-1-carbothioamides. Compound 3f with 2,3-dichlorophenyl substitution was recognized among the tested series as a lead structure that inhibited the viability of MCF-7 cells with an IC50 value of 9.2 µM. A dose- and time-dependent inhibition of STAT3 phosphorylation at Tyr705 and Ser727 was observed in MCF-7 and T47D cells when compound 3f was added in vitro. Calculations using density functional theory showed that the title compounds HOMOs and LUMOs are situated on imidazopyridine-pyrazoline and nitrophenyl rings, respectively. Hence, compound 3f effectively inhibited STAT3 phosphorylation in MCF-7 and T47D cells, indicating that these structures may be an alternative synthon to target STAT3 signaling in BC.

Nano-Zirconium Dioxide Catalyzed Multicomponent Synthesis of Bioactive Pyranopyrazoles That Target Cyclin Dependent Kinase 1 in Human Breast Cancer Cells.

Small molecules are being used to inhibit cyclin dependent kinase (CDK) enzymes in cancer treatment. There is evidence that CDK is a drug-target for cancer therapy across many tumor types because it catalyzes the transfer of the terminal phosphate of ATP to a protein that acts as a substrate. Herein, the identification of pyranopyrazoles that were CDK inhibitors was attempted, whose synthesis was catalyzed by nano-zirconium dioxide via multicomponent reaction. Additionally, we performed an in-situ analysis of the intermediates of multicomponent reactions, for the first-time, which revealed that nano-zirconium dioxide stimulated the reaction, as estimated by Gibbs free energy calculations of spontaneity. Functionally, the novel pyranopyrazoles were tested for a loss of cell viability using human breast cancer cells (MCF-7). It was observed that compounds 5b and 5f effectively produced loss of viability of MCF-7 cells with IC50 values of 17.83 and 23.79 µM, respectively. In vitro and in silico mode-of-action studies showed that pyranopyrazoles target CDK1 in human breast cancer cells, with lead compounds 5b and 5f having potent IC50 values of 960 nM and 7.16 µM, respectively. Hence, the newly synthesized bioactive pyranopyrazoles could serve as better structures to develop CDK1 inhibitors against human breast cancer cells.