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.

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.

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.

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.

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.

Brucein D imparts a growth inhibitory effect in multiple myeloma cells by abrogating the Akt-driven signaling pathway.

The Akt signaling pathway is an oncogenic cascade activated in the bone marrow microenvironment of multiple myeloma (MM) cells and contributes to their uncontrolled proliferation. Abrogation of Akt signaling has been presented as one of the prime therapeutic targets in the treatment of MM. In the present report, we have investigated the effect of Brucein D (BD) on Akt-driven signaling events in MM cells. BD (300 nM) substantially inhibited cell viability and imparted growth-inhibitory effects in U266 cells as evidenced by cell viability assays and flow cytometric analysis. Effect of BD on cell viability was evaluated by MTT assay. Apoptotic cells and cell cycle arrest by BD were analyzed by flow cytometer. The results of the TUNEL assay and western blotting showed that BD induces apoptosis of MM cells by activating caspase-8 and 9 with subsequent reduction in the expression of antiapoptotic proteins (Bcl-2, Bcl-xl, survivin, cyclin D1, COX-2, VEGF, MMP-9). Analysis of activated kinases by Phospho-Kinase Array Kit revealed that Akt, p70S6K, HSP60, p53, and WNK1 were strongly expressed in untreated cells and BD treatment reversed this effect. Using transfection experiments, AKT depletion led to a decrease in phosphorylation of Akt, mTOR, p70S6K, and WNK. However, Akt overexpression led to increase in phosphorylation of these proteins. Depletion of Akt potentiated the apoptosis-inducing effect of BD whereas overexpression displayed resistance to BD-induced apoptosis suggesting the role of Akt in chemoresistance. Taken together, BD mitigates Akt-dependent signaling pathways in MM cells to impart its anticancer activity.

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.

Larvicidal and pupicidal activity of phyto-synthesized zinc oxide nanoparticles against dengue vector aedes aegypti.

This study aimed to assess the phyto-synthesizing potential of Tarenna asiatica methanol leaf extract as well as its larvicidal and pupicidal potential against Aedes aegypti larvae. According to the findings of this study, the methanol leaf extract of T. asiatica has the potential to synthesize zinc oxide nanoparticles from zinc acetate dehydrate. Standard analytical techniques such as UV-visible spectrophotometer, Fourier-transform infrared spectroscopy, X-ray Diffraction analysis, Scanning Electron Microscope, and Energy Dispersive X-Ray were used to characterize the phyto-synthesized nanoparticles. The zinc oxide nanoparticles synthesized ranged in size from 22.35 to 31.27 nm and was spherical in shape. These nanoparticles demonstrated excellent larvicidal activity against Aedes aegypti larvae in the second, third, and fourth in stars, as well as significant pupicidal activity. These findings suggest that the methanol leaf extract of T. asiatica synthesized zinc oxide nanoparticles, which could be used to develop mosquito repellents.

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.

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.

Optimized production of keratinolytic proteases from Bacillus tropicus LS27 and its application as a sustainable alternative for dehairing, destaining and metal recovery.

The present study describes the isolation and characterization of Bacillus tropicus LS27 capable of keratinolytic protease production from Russell Market, Shivajinagar, Bangalore, Karnataka, with its diverse application. The ability of this strain to hydrolyze chicken feathers and skim milk was used to assess its keratinolytic and proteolytic properties. The strain identification was done using biochemical and molecular characterization using the 16S rRNA sequencing method. Further a sequential and systematic optimization of the factors affecting the keratinase production was done by initially sorting out the most influential factors (NaCl concentration, pH, inoculum level and incubation period in this study) through one factor at a time approach followed by central composite design based response surface methodology to enhance the keratinase production. Under optimized levels of NaCl (0.55 g/L), pH (7.35), inoculum level (5%) and incubation period (84 h), the keratinase production was enhanced from 41.62 U/mL to 401.67 ± 9.23 U/mL (9.65 fold increase) that corresponds to a feather degradation of 32.67 ± 1.36% was achieved. With regard to the cost effectiveness of application studies, the crude enzyme extracted from the optimized medium was tested for its potential dehairing, destaining and metal recovery properties. Complete dehairing was achieved within 48 h of treatment with crude enzyme without any visible damage to the collagen layer of goat skin. In destaining studies, combination of crude enzyme and detergent solution [1 mL detergent solution (5 mg/mL) and 1 mL crude enzyme] was found to be most effective in removing blood stains from cotton cloth. Silver recovery from used X-ray films was achieved within 6 min of treatment with crude enzyme maintained at 40 °C.

Role of chicken fat waste and hydrogen energy ratio as the potential alternate fuel with nano-additives: Insights into resources and atmospheric remediation process.

The main focus of the study was to witness the effects of chicken waste-based biodiesel blends along with constant hydrogen injection in a modified diesel engine. Furthermore, the nanoparticle multiwall carbon nanotubes (MWCNT) effects on the engine efficiency were also examined. A series of tests was conducted in the single cylinder, water cooled engine fuelled with diesel, CB100N, CB10N, CB30N, and CB50N. Throughout the entire run, constant hydrogen injection of 5 LPM has been maintained. The parameters such as brake thermal efficiency, brake specific fuel consumption, heat release rate and the emissions of different pollutants were determined for a variety of engine speeds. ASTM standards were applied to measure the viscosity, density and calorific value. From the reported findings, it was clear that the addition of the chicken waste biodiesel could be a sustainable substitute for the existing fossil fuels. Although the emission of the pollutants was dropped significantly, there was a massive drop in the BTE values. To compensate such shortage of power, the biodiesel was dispersed with MWCNT at the concentration of 80 ppm. Compared to the regular biodiesel, MWCNT inclusion increased the BTE by 14%. Further, the consumption of the fuel was also reduced marginally. Considering the pollutants, the catalytic activity of the MWCNT reduced the emissions of CO, NOx, and HC at various engine speeds. Besides, 10% reduction in NOx had been reported at lower engine speeds and was reduced to 8% at higher speed regimes. Compiling all together, increasing the concentration of the biodiesel blends obviously reduced the performance values and however, there was a great advantage in terms of the emission magnitudes irrespective of the engine operating conditions.

Synthesis of AgNPs from leaf extract of Naringi crenulata and evaluation of its antibacterial activity against multidrug resistant bacteria.

The biosynthesis of AgNPs using a methanolic extract of Naringi crenulata is described in this study. UV-visible spectroscopy, X-ray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), particle size analyzer (PSA), scanning electron microscope (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) were used to characterize the synthesized AgNPs. The UV-visible spectrum revealed a sharp peak at 420 nm, which represents silver's strong Plasmon resonance. FTIR and XRD confirmed the functional groups (N-H stretch, alkanes, O-H stretch, carboxylic acid, N-H bend, C-X fluoride, and C-N stretch) and face-centered cubic crystalline structure of synthesized AgNPs. SEM and TEM analyses revealed that the synthesized nanoparticles had a spherical morphology with an average diameter of 32.75 nm. The synthesized AgNPs have antibacterial activity against multidrug-resistant bacteria pathogens such as Vibrio cholerae, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Klebsiella pneumoniae. AgNPs can be synthesized using a methanolic extract of Naringi crenulate, and the resulting particle may have wide range of biological applications.

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.

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.

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.

Fangchinoline targets epithelial-mesenchymal transition process by modulating activation of multiple cell-signaling pathways.

Epithelial-mesenchymal transition (EMT) is a key process, which can promote the transition of tumor cells into other organs by weakening the cell-cell junctions. Tumor cell invasion and metastasis arising because of EMT can determine the prognosis of cancer. EMT can be induced by several growth factors including transforming growth factor-ß (TGF-ß), which can exert their effects by affecting several cell-signaling pathways. Fangchinoline (FCN), a kind of bisbenzylisoquinoline, belongs to the family Menispermaceae. FCN can display substantial antitumor effects against various malignant cell lines but its possible impact on EMT has not been explored. We examined the potential impact of FCN in affecting the activation of EMT in human colon cancer cells. We evaluated the influence of FCN on EMT in colon cancer cells by using Western blot analysis and reverse transcription-polymerase chain reaction assays. The cellular invasion and migration were observed by Boyden chamber and wound healing assays. Thereafter, the effect of the drug on proliferation and invasion was also evaluated by real-time cell analysis. FCN suppressed the levels of TGF-ß-induced mesenchymal markers, such as fibronectin, vimentin, MMP-9, MMP-2, N-cadherin, Twist, and Snail. However, FCN markedly enhanced the expression of epithelial markers such as occludin and E-cadherin. These results imply that FCN can potentially inhibit tumor metastasis through abrogating EMT. In addition, FCN downregulated c-Met/PI3K/Akt/mTOR and Wnt/ß-catenin cell signaling pathways and mitigated tumor migration as well as invasion. Overall, our study suggests a potential novel role of FCN as an antimetastatic agent against human colon cancer cells.

Leelamine Exerts Antineoplastic Effects in Association with Modulating Mitogen­Activated Protein Kinase Signaling Cascade.

Mitogen­activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptosis in cancer cells. Herein, the effect of leelamine (LEE, a triterpene derived from bark of pine trees) on the activation of MAPK in hepatocellular carcinoma (HCC) and breast cancer (BC) cells was investigated. LEE induced potent cytotoxicity of HCC (HepG2 and HCCLM3) and BC (MDA-MB-231 and MCF7) cells over normal counterparts (MCF10A). LEE significantly enhanced the phosphorylation of p38 and JNK MAPKs in a dose-dependent fashion and it did not affect the phosphorylation of ERK in HCC and BC cells. The apoptosis-driving effect of LEE was further demonstrated by cleavage of procaspase-3/Bid and suppression of prosurvival proteins (Bcl-xL and XIAP). Furthermore, LEE also reduced the SDF1-induced-migration and -invasion of HCC and BC cells. Taken together, the data demonstrated that LEE promotes apoptosis and induces an anti-motility effect by activating p38 and JNK MAPKs in HCC and BC cells.

Green synthesis of Zirconium nanoparticles using Punica granatum (pomegranate) peel extract and their antimicrobial and antioxidant potency.

The biosynthesis of metal oxide nanoparticles provides an excellent alternative to the chemical synthesis approach. The aim of the current study was a green and eco-friendly synthesis of zirconium nanoparticles (ZrNPs) from fruit peels of Punica granatum (Pomegranate). The synthesis of ZrNPs was confirmed using a UV-visible spectrophotometer. The functional groups present on surface of ZrNPs were analyzed using FTIR. The average size of obtained ZrNPs was analyzed using SEM and DLS and it was around 20-60 nm. The antimicrobial activity of obtained ZrNPs was tested against Gram-positive strains (Bacillus subtilis and Staphylococcus aureus), Gram-negative strains (Escherichia coli and Klebsiella pneumoniae) and Fungi (Aspergillus niger) by agar well diffusion method. ZrNPs showed maximum zone of inhibition against S. aureus (19 mm) and A. niger (18 mm) at the maximum concentration of 200 µg/mL. The antioxidant scavenging activity of obtained ZrNPs was analyzed using the following methods: DPPH radical scavenging activity, Hydroxyl radical scavenging activity, Ferric reducing antioxidant power and hydrogen peroxide radical scavenging activity. This the first and foremost study on ZrNPs synthesized using P. granatum fruit peel extract reporting their efficacy as antimicrobial agents against Bacteria and Fungi. Considering the tolerance of zirconium towards human body, it can also be used as antimicrobial coating material on human implants.