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.

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.

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.

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.

In vitro analysis of green synthesized copper nanoparticles using Chloroxylon swietenia leaves for dye degradation and antimicrobial application.

Green fabrication of copper nanoparticles (CuNPs) is an environmentally friendly and cost-effective method of synthesis for biomedical and bioremediation applications. In recent times, bacterial pathogens contaminating or affecting food and food crops pose the greatest threat to the food industry. In addition to this issue, synthetic dyes released from the textile and dyeing industries are polluting aquatic ecosystems and agricultural lands. The combined impact of these two factors is considered a major threat to life. Therefore, the use of CuNPs will provide an effective and long-term solution as an antibacterial and dye removing agent. The current study focuses on the synthesis of CuNPs using the leaf extract of Chloroxylon swietenia (C-CuNPs). The formation of a peak at 390 nm and a change in color from yellow to dark brown confirmed the synthesis of C-CuNPs. Subsequent synthesis at pH 9 was suitable for preparing C-CuNPs. Structural and chemical characterization of C-CuNPs was performed using Fourier Transfer Infra-Red (FTIR), X-ray diffraction (XRD), Dynamic Light scattering (DLS), and Scanning Electron Microscopy (SEM) analysis. The synthesized C-CuNPs possess a crystalline nature, a functional group that resembles C. swietenia, and are negatively charged and spherical in shape. C-CuNPs were tested against Congo red, Coomassie blue, and crystal violet and they showed complete degradation within 24 h under optimum conditions. Disk diffusion and broth dilution assay were used to test the antibacterial activity of C-CuNPs against Staphylococcus nepalensis, Staphylococcus gallinarum, Pseudomonasstutzeri,Bacillus subtilis, and Enterococcus faecalis. Therefore, the present study represents the first report on C-CuNPs' ability to degrade synthetic dyes and kill foodborne bacterial pathogens. Thus, the study has shed light on the potential of green synthesized CuNPs as bioremediation and packaging material in the future.

Development of a Model System to Study Expression Profile of RAC2 Gene in Breast Cancer MDA-MB-231 Cell Line.

The RAC2 gene encoding GTPases involve cellular signaling of actin polymerization, cell migration, and formation of the phagocytic NADPH oxidase complex. Oncogenic mutations in the RAC2 gene have been identified in various cancers, and extensive research is in progress to delineate its signaling pathways and identify potential therapeutic targets in breast cancers. This paper explored developing a bioinformatics model system to understand the RAC2 gene expression pattern concerning estrogenic receptor status in breast cancers. We have used the MDA-MB-231 breast cancer cell line to identify RAC2 gene expression. To simplify the development of model system with one dataset, we retrieved the microarray dataset GSE27515 from the Gene Expression Omnibus (GEO) for the differential gene expression analysis. Then, network analysis, pathway enrichment analysis, volcano plot, ORA, and the up/downregulated genes were used to highlight genes involved in signaling network pathways. We observed that the RAC2 gene is upregulated in the GSM679722, GSM676923, and GSM679724 downregulated in the samples GSM676925, GSM676926, and GSM676927 from the GEO dataset. Our observation found that the RAC2 gene is upregulated in the estrogen receptor (ER) negative breast cancers and downregulated in ER-positive breast cancer, involving pathways such as focal adhesion, MAPK signaling, axon guidance, and VEGF signaling pathway.

Oxytetracycline Degrading Potential of Lysinibacillus sp. Strain 3+I Isolated from Poultry Manure.

Oxytetracycline (OTC) which is a broad-spectrum veterinary tetracycline antibiotic is extensively used in poultry farms as a prophylactic, therapeutic, and growth stimulator. Upon administration, unmetabolized OTC is excreted from the animal body through droppings and accumulated in litter in the poultry industry. This study aimed at investigating the OTC degradation potential of an-OTC tolerant bacterial strain, isolated from poultry manure. The isolated strain's morphology, biochemical properties, and 16S ribosomal RNA (rRNA) gene sequence confirmed that it belonged to the Lysinibacillus genus. To measure the residual OTC concentration, a high-performance liquid chromatography method was used. OTC degradation rates were 2.579 mg L-1d-1 with Lysinibacillus strain 3+I and 1.149 mg L-1d-1 without Lysinibacillus strain 3+I. In the presence of strain 3+I, the half-life significantly reduced to 2.68 days, compared to 6.03 days without strain 3+I. The strain demonstrated 85% removal with the OTC concentration of 10 µg/ml. The influence of pH, temperature, carbon sources, and nitrogen source, which influence degradation, were also investigated. The optimum condition favouring degradation was pH 6 at a temperature of 30°C. In addition, Lysinibacillus sp. strain 3+I's ability to degrade OTC in poultry litter offers a promising approach to treat poultry manure and effluent containing OTC, preventing its contamination in the environment.

Isolation, Identification, Characterization, and Plasmid Profile of Urinary Tract Infectious Escherichia coli from Clinical Samples.

Objective: In recent times, urinary tract infection (UTI) is one of the most widely recognized bacterial diseases all over the planet. UTI influences individuals of any age and gender. The target of this study is to concentrate on the recurrence of uropathogens, the antimicrobial susceptibility pattern of the isolates, and the plasmid profile of people from the government clinics of Karaikudi. Methods: From July 2017 to December 2017, 100 urine tests were gathered and handled for the isolation of pathogenic microbes. In total, 89 isolates were found from the samples collected. Results: Escherichia coli was discovered as the most common bacterial isolate screened from the UTI-infected people, accounting for 28.09 percent of all isolates. E. coli was seen to be the highest prevalent bacterium for UTI in all age groups and demonstrated resistance to routinely used medications, especially cefpodoxime and novobiocin, which have been 100 percent resistant. The E. coli isolates screened were positive for beta-lactamase and film generation, and they have strong antimicrobial resistance. As a result, the E. coli strains with the highest prevalence of virulence determinants have become more resistant to many medications because they support the microorganism in overcoming the host's defense and colonizing or entering the urinary system. The amplified 16S rRNA product was analyzed, and phylogenetic relationships were determined. The presence of TEM (56 percent), CTX-M (64 percent), SHV (40 percent), and OXA (60 percent) was discovered. Among E. coli isolates, CTX-M was the most common extended spectrum-beta lactamase (ESBL). Multiplex PCR was also used to identify the existence of CTX-M subgroups in E. coli isolates. Conclusion: Finally, we urge that antibiotic selection should be predicated on the awareness of the specific prevalence and that novel antimicrobial medicines for urinary infections be developed to combat the overuse of antibiotics.

Fabrication, characterization, anti-inflammatory, and anti-diabetic activity of silver nanoparticles synthesized from Azadirachta indica kernel aqueous extract.

The Azadirachta indica is an excellent and pharmaceutically valuable phytochemicals enriched traditional medicinal plant. The purpose of the research was to assess the ability of A. indica aqueous kernel extract to synthesize silver nanoparticles as well as their anti-inflammatory and anti-diabetic activity in vitro. The obtained results state that the aqueous kernel extract of A. indica can fabricate the silver nanoparticles and be confirmed by standard analytical techniques. Under UV-visible spectrophotometer analysis, the absorbance peak was found at 430 nm was related to the surface plasmon resonance of silver nanoparticles. The FTIR (Fourier-transform infrared spectroscopy) analysis revealed that numbers of functional groups belong to the pharmaceutically valuable phytochemicals, which act as reducing, capping, and stabilizing agent on silver nanoparticles synthesis. The size and shape of the silver nanoparticles were examined as 19.27-22.15 nm and spherical in shape. Interestingly, this kernel fabricated silver nanoparticles possess a reasonable anti-inflammatory (69.77%) and anti-diabetic (73.5%) activity at 100 µg mL-1 and these were partially comparable with standards (anti-inflammatory: 81.15%; anti-diabetic: 87.9%). Thus, the aqueous kernel extract fabricated silver nanoparticles can be considered for further in-vivo study to assess the practical possibility to promote as a pharmaceutical agent.

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.

Silver nanoparticles (AgNPs) fabricating potential of aqueous shoot extract of Aristolochia bracteolata and assessed their antioxidant efficiency.

This research was performed to evaluate the silver nanoparticles (AgNPs) fabricating potential of aqueous shoot extract of Aristolochia bracteolata and also assess the free radicals scavenging potential of synthesized AgNPs. The results obtained from this study showed that the aqueous shoot extract of A. bracteolata has the potential to synthesize the AgNPs and it was initially confirmed by color change in the reaction blend as yellow to dark brownish. Subsequently, a clear absorbance peak was found at 425 nm in UV-visible spectrum analysis. The functional groups involved in the capping and stabilization of AgNPs were confirmed by Fourier Transform-Infrared spectroscopy (FTIR) analysis and recorded about 10 sharp peaks 3688, 3401, 2980, 2370, 1948, 1642, 1480, 1280, 782, and 628 cm-1. The Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) observations revealed that the predominant shape of the AgNPs was spherical and size ranged from 41.43 to 60.51 nm. Interestingly, the green fabricated AgNPs showed significant free radicals scavenging activity and were confirmed with ferric reducing assay, 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), H2O2 radicals, and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals scavenging activity. Thus, after a few in-vivo antioxidant studies, Aristolochia bracteolata-mediated AgNPs can be considered as an antioxidant agent.

Spectral and structure characterization of Ferula assafoetida fabricated silver nanoparticles and evaluation of its cytotoxic, and photocatalytic competence.

This study aims to develop an eco-friendly method for rapidly synthesizing silver nanoparticles (AgNPs) using Asafoetida ethanol extracts and to validate AgNPs synthesis using UV-vis spectroscopy (absorption spectrum), FTIR (functional groups), XRD (crystallinity), FE-SEM (size of the particles) and SEM-EDAX (Purity). Furthermore, to evaluate the anti-proliferative effect of Ag NPs against grown cultured L6 cell lines, studies have shown that AgNPs biosynthesis inhibits cancer cell growth compared to control cell lines. UV-vis absorption verified the existence of Ag NPs, and the spectrum was observed at 480 nm. Functional groups are present in the synthesized Ag NPs were shifted on 528.48 cm-1 confirmed using an FT-IR spectrum. Consequently, anti-cancer efficacy observed the IC50 value of As Ag NPs against L6 cells was 1.0 µg/mL for 48 h. Finally, using a halogen lamp, studies explored the photocatalytic degradation of AgNPs against the methylene blue radioactive dye and achieved a 96 percent degradation rate in 90 min. Asafoetida mediated silver nanoparticles show grater photodegradation for methylene blue dye, which is present in textile industries, when exposed to solar light, and it has a wide range of potential applications in wastewater treatment. As a whole, biosynthesized silver nanoparticles showed excellent cytotoxic, antioxidant, and photocatalytic dye degradation effects.

Novel green synthesis and characterization of a chemotherapeutic supplement by silver nanoparticles containing Berberis thunbergii leaf for the treatment of human pancreatic cancer.

In recent years, silver nanoparticles have been used as modern chemotherapeutic drugs to treat several cancers such as pancreatic, breast, prostate, and blood cancers. No previous reports demonstrated the in vitro anti-human pancreatic cancer effects of the novel chemotherapeutic drug formulated by silver nanoparticles containing Berberis thunbergii leaf (AgNPs). The synthesized AgNPs were characterized using different techniques including UV-vis. and FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), and TEM. All techniques approved the synthesized silver nanoparticles. The SEM and TEM exhibited a uniform spherical morphology and an average size of about 15 nm for the biosynthesized nanoparticles, respectively. The 4-(dimethylamino)benzaldehyde,2,2-diphenyl-1- pikrilhydrazil (DPPH) test revealed similar antioxidant potentials for B. thunbergii leaf aqueous extract, AgNPs, and butylated hydroxytoluene. AgNPs inhibited half of the DPPH molecules in the concentration of 108 µg/mL. To survey the anti-human pancreatic cancer activities of AgNO3 , B. thunbergii leaf aqueous extract, and AgNPs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. AgNPs had very low cell viability and anti-human pancreatic cancer effects dose-dependently against PANC-1, AsPC-1, and MIA PaCa-2. The IC50 values of the AgNPs were 259, 268, and 141 µg/mL against PANC-1, AsPC-1, and MIA PaCa-2 cell lines, respectively. It is thought that the AgNPs obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials.

Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.

Assessment of hexavalent chromium (VI) biosorption competence of indigenous Aspergillus tubingensis AF3 isolated from bauxite mine tailing.

The intention of this research was to find the most eminent metal tolerant and absorbing autochthonous fungal species from the waste dump of a bauxite mine. Out of the 4 (BI-1, BI-II, BI-III, and BI-IV) predominant isolates, BI-II had an excellent metal tolerance potential against most of the metals in the subsequent order: Cr(VI) (1500), Cu(II) (600), Pb(II) (500), and Zn(II) (500-1500 µg mL-1). BI-II had shown tolerance to Cr(VI) up to 1500 mg L-1. The excellent metal tolerant isolate was characterized and identified as Aspergillus tubingensis AF3 through 18S rRNA sequencing method and submitted to GenBank and received an accession number (MN901243). A. tubingensis AF3 had the efficiency to absorb Cr(VI) and Cu(II) at <70 & 46.3% respectively under the standard growth conditions. Under the optimized conditions (25 °C, pH 7.0, 0.5% of dextrose, and 12 days of incubation), A. tubingensis AF3 absorbed 74.48% of Cr(VI) in 12 days (reduction occurred as 822.3, 719.13, 296.66, and 255.2 mg L-1 of Cr(VI) on the 3rd, the 6th, the 9th and the 12th day, respectively). The adsorbed metal was sequestered in the mycelia of the fungus in a precipitated form; it was confirmed by Scanning Electron Microscope (SEM) and Energy Dispersive X-ray analysis (EDX) analyses. The possible biosorption mechanisms were analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) analysis, the results showed the presence of N-H primary amines (1649.98 cm-1) and Alkanes (914.30 cm-1) in the cell wall of the fungus, while being treated with Cr(VI) they supported and enhanced the Cr(VI) absorption. The entire results concluded that the biomass of A. tubingensis AF3 had the potential to absorb a high concentration of Cr(VI).

Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties.

BACKGROUND: The current health concern to the entire world is the chronic respiratory disease caused by coronavirus 2 (COVID-19). A specific treatment or proper therapy is still lacking, and the investigations from across the world for proper drug/vaccine development towards disease control are in progress. The Coronavirus replication takes place by the conversion of the polypeptide into functional protein and this occurs due to the key enzyme Main protease (Mpro). Therefore, identification of natural and effective Mpro inhibitors could be a safe and promising approach for COVID-19 control. METHODS: The present in silico study evaluates the effect of bioactive compounds found in Eucalyptus and Corymbia species essential oil on Mpro by docking. Molecular docking of the major seven compounds of essential oil (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) with Mpro was studied by AutoDock 4.2, and the properties were analysed by PreADMET and Biovia Discovery Studio visualizer. RESULTS: The calculated parameters such as binding energy, hydrophobic interactions, and hydrogen bond interactions of 6LU7 (Mpro) with Eucalyptus and Corymbia volatile secondary metabolites represented its scope as an effective therapy option against covid-19. Among the docked compounds, eucalyptol shows the least binding energy without toxicity. CONCLUSIONS: The outcome of this study reported that the essential oil of Eucalyptus and Corymbia species, mainly eucalyptol can be utilized as a potential inhibitor against COVID-19 and also it can be used in its treatment. Hence, further analysis was required to explore its potential application in medicine.

Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells.

Liver cancer is a critical clinical condition with augmented malignancy, rapid progression, and poor prognosis. Liver cancer often initiates as fibrosis, develops as cirrhosis, and results in cancer. For centuries, medicinal plants have been incorporated in various liver-associated complications, and recently, research has recognized that many bioactive compounds from medicinal plants may interact with targets related to liver disorders. Phyllanthin from the Phyllanthus species is one such compound extensively used by folklore practitioners for various health benefits. However, most practices continue to be unrecognized scientifically. Hence, in this work, we investigated the protective role of phyllanthin on diethylnitrosamine (DEN) induced liver carcinoma in Wistar Albino rats and the anti-tumor potential on human hepatocellular carcinoma (HCC) HepG2 cells. The DEN-challenged liver cancer in experimental rats caused increased liver weight, 8-OHD, hepatic tissue injury marker, lipid peroxidation, and tumor markers levels. Remarkably, phyllanthin counteracted the DEN effect by ameliorating all the liver function enzymes, oxidative DNA damage, and tumor-specific markers by enhanced anti-oxidant capacity and induced caspase-dependent apoptosis through the mTOR/ PI3K signaling pathway. MTT assay demonstrated that phyllanthin inhibited the HepG2 cell growth in a dose-dependent manner. Fascinatingly, phyllanthin did not demonstrate any substantial effect on the normal cell line, HL7702. In addition, HepG2 cells were found in the late apoptotic stage upon treatment with phyllanthin as depicted by acridine orange/ethidium bromide staining. Overall, this work offers scientific justification that phyllanthin can be claimed to be a safe candidate with potential chemotherapeutic activity against HCC.

Osteogenic differentiation and mineralization potential of zinc oxide nanoparticles from Scutellaria baicalensis on human osteoblast-like MG-63 cells.

Development of biologically inspired green synthesis of silver nanoparticles has been extensively scrutinized owing to its uses in biomedical industry. In the last two decades, the demands of nanomaterial in bone remodelling have increased. Scutellaria baicalensis is a flowering plant usually used for many ailments. This work explores the zinc oxide nanoparticles (ZnO NPs) by green route method from S. baicalensis and the therapeutic potentials of Sb-ZnONPs on differentiation of osteoblast and osteoclast formation inhibition. The characterization of the fabricated ZnO-NPs from S. baicalensis was done via different spectroscopic and microscopic techniques; ultraviolet-visible spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The Osteogenic-related tests (MTT, Mineralization assay and Real-time PCR) were used to evaluate the properties of SB-ZnONPs on the growth and proliferation of human osteoblast-like MG-63 cells. The characterization of SB-ZnONPs discovered the crystalline properties with high zinc content and the existence of bioactive mixtures from S. baicalensis extract. In addition, SB-ZnONPs showed insignificant cytotoxicity with enhanced differentiation, proliferation, and mineralization on MG-63 cells. Overall, these results denote that SB-ZnONPs is expected to be a natural source for the development of medical agents to in bone healing and remodelling.

Identification of protocatechuic acid as a novel blocker of epithelial-to-mesenchymal transition in lung tumor cells.

Protocatechuic acid (PA) is widely distributed and commonly occurring natural compound that can exert antioxidant, anti-inflammatory, as well as anti-cancer effects. Epithelial-to-mesenchymal transition (EMT) is important cellular process that can control tumor invasion and metastasis. Here, we investigated whether PA can modulate the EMT process in basal and transforming growth factorß-induced A549 and H1299 cells. We found that PA suppressed expression of mesenchymal markers (Fibronectin, Vimentin, and N-cadherin), MMP-9, MMP-2, twist, and snail but stimulated the levels of epithelial markers (E-cadherin and Occludin). In addition, PA can affect TGFß-induced expression of both mesenchymal and epithelial markers. Moreover, PA abrogated migratory and invasive potential of tumor cells by reversing the EMT process. Furthermore, we found that PA suppressed EMT process by abrogating the activation of PI3K/Akt/mTOR signaling cascade in lung cancer cells.