Pyrimidine-triazole-tethered tert-butyl-piperazine-carboxylate suppresses breast cancer by targeting estrogen receptor signaling and ß-catenin activation.

Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and tert-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial-mesenchymal transition (EMT), possibly via the Wnt/ß-catenin pathway.

Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells.

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4­chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

Discovery of oxazine-linked pyrimidine as an inhibitor of breast cancer growth and metastasis by abrogating NF-κB activation.

Introduction: Nuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay. Methods: This work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells. Results: Finally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells. Conclusion: Overall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

Biofabrication of bimetallic selenium@zinc nanoparticles using Champia parvula aqueous extract: Investigation of anticancer activity and its apoptosis induction.

Selenium@zinc nanoparticles, or Se@Zn NPs, are extensively employed in various environmental, industrial and biological domains. However, the biological potential of Se@Zn NPs has not been thoroughly investigated. This study focused on fabricating Se@Zn NPs from algae using an aqueous extract of Champia parvula seaweed. Analytical techniques were used to describe the successfully synthesized Se@Zn NPs. In addition, a biological function analysis of the Se@Zn NPs was conducted. The Ultraviolet-visible spectroscopy (UV-vis) spectrum showed a specific absorbance peak for the Se@Zn NPs at 350-400 nm. The biomolecules involved in forming Se@Zn NPs were identified by their potential functional groups, as revealed by Fourier transform infrared spectroscopy (FTIR). By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Se@Zn NPs were shown to be spherical and to have a diameter range of 100-200 nm. NPs with a crystallite diameter of 54.8 nm and chemical compositions of zinc and selenium (1:1.5 ratio) were revealed by X-ray diffraction analysis (XRD) and energy dispersive x-ray spectroscopy (EDS). IC50 values were determined for the anticancer activity against A549, MCF-7 and HeLa cells. Cell morphological changes in fluorescence microscopy and apoptosis mechanisms by flow cytometry analysis were investigated, which show that Se@Zn NPs induced apoptosis in various cancer cells. DNA fragmentation and ROS levels were studied by fluorescence microscopy. In conclusion, conditions required for therapeutic and preventative applications may be met by the green synthesis of Se@Zn NPs.

An investigation on the conversion of infertile soil into fertile soil using crop waste as a remedial (compost) approach and its influence on Vigna mungo biometric and biomolecule profile.

The sustainable management of huge volume of agricultural waste in India can be resolved through composting and used as soil amendment. Agriculture waste compost amendments can optimistically alter the physicochemical (pH, C, N, & P) as well as biological nature (microbial activity/biomass and enzymatic activity) of infertile soil. Hence this study, the agriculture wastes such as sugarcane trash, corn stover, and pearl millet stalks were converted to composite through decomposition pit. Interestingly, test crops residues individual composites and their mixed form contained considerable quantity of vital elements like TC, TN, TP, TK, and C:N ratio and can effectively convert infertile soil to fertile soil. These test crop composites also had a significant impact on MBN (42.3 µg g-1), MBC (198.4 µg g-1), and MBP (196.4 µg g-1) in test soil, as well as dehydrogenase and alkaline phosphatase enzyme activity. However, the mixed composite effects are significantly greater than the individual test crop composite effects. Furthermore, it effectively remediates/converts infertile soil to fertile soil, and it ultimately demonstrated positive effects on Vigna mungo biometric (SH, RH, WB, and DB) and biomolecule (total chlorophyll, total carbohydrate, and total proteins) profiles, followed by individual test crop composites. According to the findings of this study, the incorporation of crop residue-based mixed composite significantly transforms infertile soil into fertile soil and promotes the growth of V. mungo.

Investigation of bionano additives in red algae Cyanidioschyzon merolae ultrasonified MgO/MWCNT catalyzed biodiesel in optimized engine performance.

Renewable energy research is burgeoning with the anticipation of finding neat liquid fuel. Ultra sonification assisted biodiesel was derived from red algae Cyanidioschyzon merolae, with biodiesel yield of 98.9%. The results of GC MS of the prepared biodiesel showed higher concentration of methyl palmitate, methyl oleate, and stearate. This composition is appreciable, as this plays significance in desirable pour & cloud point properties. NMR spectrum revealed the ester linkages, presence of olefins, and α methyl position in olefins. Mixture of 30 wt% of biodiesel in diesel exhibited work efficiency, and also exhibited low pour point and, lower viscosity values. CeO2 and Fe2O3 nano particles were bio reduced, and were added as nano additive in biodiesel. 1:1 ratio of CeO2 and Fe2O3 added to biodiesel maximised the combustion ability of fuel owing to the oxygen storage capacity of CeO2. Further, this combination produced a satisfactory calorific value. Imbalanced ratios disrupted the catalytic and oxygen storage effects, reduced the overall energy release and calorific value of the biodiesel blend. Pour point and cetane number value of biodiesel blend ultrasonifacted with 1:1 mass ratio of Fe2O3 and CeO2 was observed to be around -7 °C and 53 °C respectively, and was better than other compositions. 1:1 mass ratio of NPS blended with 30 wt% BD in diesel showed tremendous increase in brake thermal efficiency, torque, and power. HC, NOX, and SOX emissions were reduced by 42.8%, 19.3%, and 57% respectively with 1:1 Fe2O3 and CeO2 mixed biodiesel blend. CeO2 favourably improved the oxygen storage capacity of the fuel, whereas Fe2O3 showed decrease in formation of gums and sediments in biodiesel.

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.

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.

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.

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.

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.

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.