Search

Abstract This study explored the recovery of oil from lemon peel biomass and then tested it in a spark ignition as a substitute for gasoline. The study adopted the micro-arc oxidation coating technique, intending to improve the engine performance of the lemon peel oil-gasoline blends. The oil was recovered from discarded lemon peel biomass using steam distillation and then tested in the engine as a fuel by blending it with gasoline at volume ratios of 10, 20, and 30%. An endoscopic visualization approach was employed in this research work to assess the combustion initiation and flame characteristics of gasoline and lemon peel oil blends under different test conditions. Compared to gasoline and blends comprising 20 and 30% lemon peel oil, the 10% lemon peel oil mix produced higher thermal efficiency and lower emissions. The optical analysis demonstrated that premixed combustion with the 10% blend was found to be the highest, resulting in improved combustion and subsequently increased cylinder pressure. To improve the engine performance of the lemon peel oil blends with higher substitution (20 and 30%), the piston was coated with a ceramic coating. A novel technique, namely the micro-arc oxidation technique, was utilized for the coating. The coated piston engine fueled with a 20% lemon peel oil blend showed a 3% and 4.69% increase in thermal efficiency compared to the uncoated piston fueled with a 20% blend and sole gasoline, respectively. The hydrocarbon and carbon monoxide emissions of the engine with a coated piston fueled by the 20% lemon peel oil blend were reduced by 12.7% and 12%, respectively, as compared to gasoline operation in the engine with an uncoated piston.

The use and manufacture of nanomaterials are expanding, which is concerning for human health. Graphene oxide (GO), magnesium oxide (MgO), and quercetin (QU) have typically had significant growth because of their diverse range of applications in nanomedicine. They are utilised in the treatment of cancer, medication delivery, tissue engineering, healing of wounds, and biosensor. In this work, MgO-QU/GO nanocomposite was synthesized and its antioxidant was tested in a zebrafish model. Further obtained MgO-QU/GO nanocomposite was characterized through UV, XRD, FTIR, and SEM with EDAX analysis. Zebrafish adult seven test groups were used in the experiment with each group containing 10 fish follows fish fed the control, and exposed to MgO-QU/GO nanocomposite concentration 0+0.0+20.0+40.0+80.0+20+0.0+40+0.0+80+0 mg/L. The outcome shows that the toxicity of the utilised nanocomposite was comparatively low after zebrafish were exposed to MgO-QU/GO and recovered. Exploratory MgO-QU/GO treatment to zebra fish significant by decreased the Lipid Peroxidation (LPO) and elevated the antioxidant. These findings imply that nanocomposite at the concentration considered here might be a workable substitute for water recovery as they have no negative effects on the long-term life and welfare of humans and animals.

Current study establishes synthesis of AgNPs from Solanum trilobatum by a simple microwave protocol. Major phytoconstituents such as solasodine, solanine, solanidine were present in the leaves extract of Solanum trilobatum were examined and explored by GC-MS analysis. In vitro anti-oxidant analysis of green synthesized AgNPs from Solanum trilobatum leaf extract using DPPH and ABTS assays reveals that IC50 values (14.10 µg/ml and 12.90 µg/ml) equipotent anti-oxidant activity with reference standard trolox IC50 values (9.10 µg/ml and 9.80 µg/ml) respectively. UV–Visible spectroscopy analysis of green synthesized AgNPs shown its maximal absorbance of at 420 nm, which affirms that green mediated synthesis of silver nanoparticles from Solanum trilobatum. The results of FT-IR spectral analysis showed that flavonoids, sterols, saponin alkaloids, terpenoids, and polysaccharides were existed in Solanum trilobatum aqueous plant leaf extract, which were responsible for the reduction and subsequent capping of AgNPs. X-ray diffraction method confirmed that silver nanoparticles have spherical crystals with face-centered cubic structure. Zeta potential spectroscopy revealed the stability of green synthesized silver nanoparticles. The results of the particle size analyzer confirm that the average size of the green-synthesised AgNPs is 50 nm. Scanning electron microscope images of green synthesized silver nanoparticles show the formation of spheres and stones. HR-TEM results further affirm that sphere size of AgNPs. Further green synthesized AgNPs screened for its anti-microbial potential against bacterial cultures of E.coli (MTCC 452), P. aeruginosa (MTCC 1688), S. typhi (MTCC 733) and K. pneumonia (MTCC 39) and their result revealed that zone of inhibition 19 ± 0.11, 17 ± 0.08, 13 ± 0.07 and 16 ± 0.11 mm respectively. Finally, the explored phytocompounds from Solanum trilobatum and standard drugs tetracyclin was screened against four clinical pathogen membrane target proteins reveals that excellent binding affinity with maximal docking score -9.4 kcal/mol by solasodine against target protein Klebsiella pneumonia AcrB with the BDM91288 efflux pump (PDB ID 8P1I). Significance of silver nanoparticles (AgNPs) synthesis from Solanum trilobatum offers significant antimicrobial and antioxidant benefits. Silver nanoparticles from S. trilobatum act as promising candidates for therapeutic applications, particularly in combating infections and oxidative damage in biomedical applications.

In the pursuit of sustainable and environmentally friendly engineering materials, this study investigates the potential of Ipomoea carnea fibers (ICF) as a reinforcement agent in bran particulates epoxy matrix used to fabricate the composite laminates by a traditional process with varying filler weight fraction. The composite material’s characteristics were comprehensively analyzed using various techniques, including X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Mechanical Testing, Scanning Electron Microscopy (SEM), and Thermogravimetric Analysis (TGA). The results of this study reveal the promising potential of Ipomoea carnea fibers reinforced bran particulates epoxy composite as a novel engineering material. The analysis indicates improved mechanical properties such as tensile, flexural, and impact strength, enhanced thermal stability, and desirable morphological characteristics. Subsequently, the structural and chemical properties of the Ipomoea carnea fiber composite were explored using XRD and FTIR, shedding light on the crystalline nature (CI = 68.29%) and chemical bonding within the material. Bacterial inhibition was identified from the antibacterial activity; this viable material is for applications in various engineering sectors, including construction, automotive, and aerospace industries.

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-(4‑chloro-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.

IntroductionNuclear 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.MethodsThis 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.ResultsFinally, 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.ConclusionOverall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

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.

Actinomycetes provide a potentially limitless source of novel bioactive compound, possessing a wide range of potential therapeutic uses. Around 25,000 microbial secondary metabolites have been recognized; actinomycetes produce some 75%, of them, with fungi yielding 15%, Bacillus spp. 6%, and other bacteria producing around 1–3%. Species of Streptomyces provide 50–60 percent of the known antibiotics. Over the last seventy or so years, a vast array of microorganisms has been isolated from soils and other readily accessible environments and the screened for antibiotics. Such screening programs have significantly reduced the likelihood that novel antimicrobial compounds, particularly active against drug resistant species, will now be found. Fortunately, unusual marine environments may act as a future source of actinomycetes and other microorganisms capable of producing new secondary metabolite possessing antifungal, antibacterial, anticancer, insecticidal, enzyme inhibitory and other therapeutic properties. The aim of this review is to highlight marine actinomycetes as a novel source of such potentially critical novel antibiotic and bioactive compounds.

ZnO and ZnO-Y2O3 nanocomposites (NCs) were investigated for their photocatalytic degradation of Methylene blue (MB) dye. X-ray diffraction study demonstrates that the hexagonal structure of ZnO has crystallite size compared to ZnO-Y2O3 NCs and confirms the cubic configuration of Y2O3. Scanning electron microscopy shows that the ZnO nanoparticles are spherical and ZnO-Y2O3 NCs have smaller particles with less agglomeration. The decreased recombining of excited e−/h+ of ZnO-Y2O3 NCs is confirmed over fluorescence study. ZnO-Y2O3 exhibits a more significant degradation efficiency (96%) than ZnO nanoparticles (86%) in 120 min. ZnO-Y2O3 NCs have antibacterial as well as antioxidant activity.

Nigericin is a potent antibiotic derived from Streptomyces hygroscopicus which acts as a polyether ionophore. The anticancer property of nigericin was extensively studied, and it has been proven to inhibit cancer cell proliferation, progression, and invasion in prostate, colorectal, nasopharyngeal, and lung cancer. It also stimulates bacterial clearance in macrophages. The protective role of nigericin in sepsis, which is the foremost risk factor for acute lung injury and acute respiratory distress syndrome. Since bacteremia is frequently associated with lung injury, in this study we evaluated the potency of nigericin against an lipopolysaccharide (LPS)-induced sepsis mice model. BALB/c mice were challenged with intratracheal administration of LPS and simultaneously treated with 10 mg/kg and 20 mg/kg nigericin for 3 consecutive days. The mice were euthanized, and the lung tissue was excised to determine the lung wet/dry ratio. Bronchoalveolar lavage fluid was collected and assessed for protein content, LDH, and immune cell count. The antioxidant activity of nigericin was evaluated by measuring the MPO, MDA, SOD, and GSH activities in the lung tissues. The proinflammatory cytokines TNF-α and IL-6 were quantified to assess the anti-inflammatory potency against LPS-induced inflammation. iNOS, COX-2 and PGE-2 levels in lung tissue of nigericin-treated LPS-challenged mice were estimated to assess the immunomodulatory activity of nigericin. Finally, the antiapoptotic potency and cytoprotective effect of nigericin were analyzed by estimating apoptotic protein levels in lung tissue and assessing lung tissue histopathology with hematoxylin & eosin staining. Nigericin treatment significantly reduced immune cell infiltration, synthesis of proinflammatory cytokines, immunomodulatory proteins, and proapoptotic proteins in LPS-challenged mice. It also increased antioxidants and antiapoptotic protein Bcl2, thereby ameliorating lung tissue from LPS-induced inflammation. Our results indicate nigericin suppressed the LPS induced sepsis in an in vivo model and has the therapeutic potency to cure sepsis induced acute lung injury.

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 IC 50 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.

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.

In this research, we formulated new chemotherapeutic copper nanoparticles (Cu NPs) containing Allium noeanum Reut. ex Regel leaf for treating human endometrial cancer. For investigating the antioxidant activitiy, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was used. MTT test was used on normal (Human umbilical vein endothelial cells (HUVECs)) and human endometrial cancer (Ishikawa, HEC-1-A, HEC-1-B, and KLE) cell lines for comparing the anti-human endometrial cancer properties of Cu(NO3)2, A. noeanum leaf aqueous extract, and copper nanoparticles. Copper nanoparticles had high cell death and anti-human endometrial cancer effects against Ishikawa, HEC-1-A, HEC-1-B, and KLE cell lines. The IC50 of A. noeanum leaf aqueous extract and copper nanoparticles against HEC-1-B cell line were 548 and 331 µg/mL, respectively; against HEC-1-A cell line were 583 and 356 µg/mL, respectively; against KLE cell line were 609 and 411 µg/mL, respectively; and against Ishikawa cell line were 560 and 357 µg/mL, respectively. Among the above cell lines, the best result of anti-human endometrial cancer properties of copper nanoparticles was gained in the cell line of HEC-1-B. This study indicated excellent anti-human endometrial cancer potentials of copper nanoparticles containing A. noeanum in the in vitro condition.

Introduction: Epithelial-mesenchymal transition (EMT) is a process of transdifferentiation where epithelial cells attain mesenchymal phenotype to gain invasive properties and thus, can contribute to metastasis of tumor cells. Objectives: The antimetastatic and antitumor efficacy of brusatol (BT) was investigated in a hepatocellular carcinoma (HCC) model. Methods: We evaluated the action of BT on EMT process using various biological assays in HCC cell lines and its effect on tumorigenesis in an orthotopic mouse model. Results: We found that BT treatment restored the expression of Occludin, E-cadherin (epithelial markers) while suppressing the levels of different mesenchymal markers in HCC cells and tumor tissues. Moreover, we observed a decline in the expression of transcription factors (Snail, Twist). Since the expression of these two factors can be regulated by STAT3 signaling, we deciphered the influence of BT on modulation of this pathway. BT suppressed the phosphorylation of STAT3Y705 and STAT3 depletion using siRNA resulted in the restoration of epithelial markers. Importantly, BT (1mg/kg) reduced the tumor burden in orthotopic mouse model with a concurrent decline in lung metastasis. Conclusions: Overall, our results demonstrate that BT interferes with STAT3 induced metastasis by altering the expression of EMT-related proteins in HCC model.

Rheumatoid arthritis is a common auto-immune disease that affects nearly 1% of the total population worldwide and primarily occurs in the age group of 30–50. The copper oxide nanoparticles (CuONPs) were gained extensive research interests due to their immense biological benefits. This investigation was aimed to synthesize the CuONPs from R. rubescens leaves and examining its anti-arthritic potential against CFA-stimulated arthritis in rats. The formulated CuONPs from R. rubescens was characterized by UV–vis spectroscopy, TEM, XRD, and FT-IR. Arthritis was induced to animals by injecting 0.1 ml of CFA via an intra-planter route. Bodyweight and arthritis score was measured and tabulated and inflammatory markers i.e. IL-10, IL-6, TNF-α, IL-1β, Cox-2 and PGE2 in the serum was examined via ELISA kits. The status of TBARS, antioxidant enzymes, and liver marker enzymes were examined via standard procedures. The hind limb histology was examined microscopically by H&E staining. The UV–vis, XRD, and TEM studies were proved the existence of metallic RR-CuONPs. The RR-CuONPs treated arthritic animals displayed the enhanced bodyweight, reduced paw volume, and arthritic score. RR-CuONPs treatment also improved the antioxidant enzymes and diminished the pro-inflammatory markers. Histopathological investigation proved that the RR-CuONPs were suppressed the bone joints by preventing the inflammatory cell penetration and bone damage. The findings of this investigation were evidenced by the anti-inflammatory and anti-arthritic potentials of fabricated RR-CuONPs against CFA-stimulated arthritis in rats.

Leukemia is considered as a multistep progression by progressively genetic modifications that make the conversion of normal human hematopoietic progenitor/stem cells into leukemic cells. In this current investigation, we optimized the reaction of parameters to control the nanoparticle size that was examined via SEM. A various characterization techniques, for example UV–visible spectroscopy, FTIR and EDX were carried out for the synthesized ZnONPs from Rhizoma paridis saponins plant extract. The RPS-ZnONPs were evaluated to inspect their cytotoxic activity against Molt-4 cells via MTT test. Apoptosis was determined through the ROS, MMP and AO/EtBr fluorescent staining techniques. Moreover, pro and anti-apoptotic signaling protein expression was inspected through RT-PCR method. We observed the fabricated RPS-ZnONPs have a crystalline nature, spherical formand various biomolecules were exist. As well, we detected the cytotoxicity effect of synthesized RPS-ZnONPs at a range of 23.5 μg followed to 24hrs treatment. Apoptosis was triggered via the RPS-ZnONPs along with augmented ROS, decreased MMP and altered dual staining. Moreover, the apoptosis were identified through significant up-regulation of Bax, caspase-9 and caspase-3, but the anti-apoptotic protein expression i.e., Bcl-2 was down regulated. Though, this study, we investigated the synthesis, characterization and anticancer activity of ZnONPs of Rhizoma paridis saponins plant extract (RPS-ZnONPs) were useful for treatments of leukemia. Keywords: Zinc oxide nanoparticle, Rhizoma paridis saponins, Apoptosis, Leukemia, Molt-4 cell lines

The present research exploration is intended to inspect the chemotherapeutic potency of fisetin in 1,2‑dimethylhydrazine (DMH)-stimulated colon carcinoma in Wistar rats. The 20 mg/kgb·wt of DMH was injected to the investigational rats via subcutaneous route once in a week for 15 weeks to induce colon cancer in a rat model. Fisetin at 50 mg/kgb·wt dose were administered throughout the experimental period. Biochemical methods were employed to study the antioxidant, lipid peroxidation, Phase-I & II enzymes. Pro-inflammatory cytokines and apoptotic proteins were measured using Elisa methods. Colon tissue damages were examined using hematoxylin and eosin staining. Our result suggested that fisetin treatment efficiently decreased the tumor incidence andnumber by restoring the antioxidant status, phase-II enzymes and inhibiting the actions of phase-I enzymes and lipid peroxidative events in DMH-induced colon tumorigenesis model. Further, we noticed that fisetin treatment significantly inhibited the pro-inflammatory cytokine production. Moreover, we observed that fisetin treatment remarkably inhibited the anti-apoptotic Bcl-2 and induced pro-apoptotic Caspase-9 and Caspase-3 expression, thereby induces apoptosis in DMH-induced colon tumorigenesis model. From this observation, we conclude that fisetin (50 mg/kgb·wt) can efficiently prevent chemically induced colon cancer by enhancing antioxidant status and modulating inflammatory and apoptotic signalling events. Keywords: Fisetin, DMH, Colon cancer, Antioxidant, Caspase-9, Apoptosis

Regulation of intracellular concentration of calcium levels is crucial for cell signaling, homeostasis, and in the pathology of diseases including cancer. Agonist-induced entry of calcium ions into the non-excitable cells is mediated by store-operated calcium channels (SOCs). This pathway is activated by the release of calcium ions from the endoplasmic reticulum and further regulated by the calcium uptake through mitochondria leading to calcium-dependent inactivation of calcium-release activated calcium channels (CARC). SOCs including stromal interaction molecules (STIM) and ORAI proteins have been implicated in tumor growth, progression, and metastasis. In the present study, we analyzed the mRNA and protein expression of genes mediating SOCs—STIM1, STIM2, ORAI1, ORAI2, ORAI3, TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPM1, and TRPM7 in head and neck squamous cell cancer (HNSC) patients using TCGA and CPTAC analysis. Further, our in silico analysis showed a significant correlation between the expression of SOCs and genes involved in the mitochondrial dynamics (MDGs) both at mRNA and protein levels. Protein-protein docking results showed lower binding energy for SOCs with MDGs. Subsequently, we validated these results using gene expression and single-cell RNA sequencing datasets retrieved from Gene Expression Omnibus (GEO). Single-cell gene expression analysis of HNSC tumor tissues revealed that SOCs expression is remarkably associated with the MDGs expression in both cancer and fibroblast cells.

Background: Osteoarthritis is a severe degenerative joint disease characterized by swelling, joint pain, degradation of cartilage extracellular matrix, synovitis, callus formation, and loss of normal joint movements, which leads to functional limitations and seriously affect the patient’s life quality. Objective: The current research work was focussed to synthesize and characterize the chitosan-sodium alginate-polyethylene glycol-d-pinitol nanocomposites (CSP-dP-NCs) and evaluate its antiarthritic activity against the freund’s complete adjuvant (FCA)-triggered arthritis in animals. Methodology: The CSP-dP-NCs were synthesized by standard method. The development and properties of formulated CSP-dP-NCs were confirmed by several characterization techniques like UV–visible, photoluminescence, X-ray diffractometer (XRD), Fourier Transform-Infrared (FT-IR), scanning electron microscopic (SEM), energy dispersive X-ray (EDX), and dynamic light scattering (DLS) analyses. The arthritis was induced in experimental rats via administering 0.1 ml of FCA subcutaneously and then treated with 10 and 25 mg/kg of synthesized CSP-dP-NCs for 25 days. The bodyweight of animals were tabulated and then haematological parameters, organ index, and paw volume was examined. The levels of liver marker enzymes were assessed by standard techniques. The contents and pro-inflammatory cytokines and antioxidant parameters were quantified using assay kits. Results: The findings of characterization studies confirmed the development of CSP-dP-NCs with size ranging from 180 nm, tetragonal appearance, and narrowed distribution. The CSP-dP-NCs treated arthritic animals demonstrated the improved bodyweight and haematological parameters. The levels of thymus and spleen index and hind paw volume was decreased by the CSP-dP-NCs. The administration of CSP-dP-NCs to the arthritic rats also exhibited the decreased contents of IL-6, IL-10, IL-1β, TNF-α, MDA levels and increased the GSH level, CAT and SOD activities. The activities of ALP, ALT, and ASP also decreased in arthritic rats by the CSP-dP-NCs treatment. Conclusion: Altogether, the findings of this study demonstrated the antiarthritic activity of formulated CSP-dP-NCs against FCA-induced arthritic rats via modulating oxidative stress and inflammatory parameters. Hence, it could be the effective drug for the arthritis treatment in the future.

This experiment evaluated antioxidant, anti-human breast cancer activities, and cytotoxicity effects of green synthesis of Au nanoparticles (AuNPs) containing Foeniculum Vulgare aqueous extract. Mixing Foeniculum Vulgare aqueous with Au chloride solution produced Au nanoparticles. The characteristics of Au nanoparticles determined using Fourier Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), UV–Visible Spectroscopy (UV–Vis), and Field Emission Scanning Electron Microscopy (FE‐SEM). To check the cytotoxicity and anti-breast cancer effects of Au chloride, Foeniculum Vulgare aqueous extract, and AuNPs on common breast cancer cell lines i.e., ZR-75-30, T47D, and HCC1187 was used MTT assay. AuNPs showed no cytotoxicity and the most effective anti-breast cancer features compared to other items that were tested. They had no cytotoxic effects on normal cell line (HUVEC) and had very low cell viability, high anti-breast cancer activities dose-dependently against ZR-75-30, T47D, and HCC1187 cell lines. In the presence of butylated hydroxytoluene as the positive control, the DPPH test was used to evaluate the antioxidant features of Au chloride, Foeniculum Vulgare aqueous extract, and Au nanoparticles. AuNPs showed the best antioxidant properties compared to other items that were tested. Perhaps remarkable anti-human breast cancer activities of Au nanoparticles synthesized by Foeniculum Vulgare aqueous extract due to its antioxidant properties. After clinical trial and confirmation of results, this formulation can be used as an effective drug to treat breast cancer.

The purpose of this study was aimed to investigate the zinc oxide nanoparticles (ZnONPs) synthesizing efficiency of aqueous leaf extract of Phyllanthus acidus. Furthermore, the antioxidant and anticancer activities of synthesized ZnONPs were also investigated through the in-vitro approach. The obtained results show that the aqueous extract of P. acidus can synthesize ZnONPs, as evidenced by a sharp absorbance peak at 375 nm. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed that the aqueous extract contained significant numbers of functional groups, which were involved in reducing zinc nitrate into ZnONPs. Also, they participate in the capping and stabilization of synthesized ZnONPs and their size ranged from 27.14–35.74 nm with a spherical shape . The results obtained in ABTS radical scavenging activity 1, 1-diphenyl-2-picryl-hydroxyl (DPPH), hydrogen peroxide (H2O2), and 2,2′-Azino-Bis(3-ethylbenzene thiazoline-6-sulfonic acid) (ABTS) assays declared has excellent in-vitro radicals scavenging activity with reasonable IC50 values. Interestingly, these green synthesized ZnONPs have an excellent anticancer activity against human epidermoid carcinoma (Hep3) cell line in an in-vitro approach. These findings imply that an aqueous leaf extract of P. acidus can be used to synthesize pharmaceutically valuable ZnONPs. To consider such nanomaterials as potential therapeutic agents, optimization and in-vivo biomedical studies are required.

Background: Gastric cancer (GC) is one of the common cancers that have a direct impact on the numerous facets of life. GC still remains a life threatening with one million mortalities per year worldwide. Objective: In this work, we planned to formulate the Neodymium/Zinc oxide nanocomposites by using the Avaram Senna flower extract (AS-Nd/ZnONCs) and examine its anticancer potential against the GC AGS cells via inhibition of PI3K/AKT/mTOR signaling pathway. Methodology: The developed AS-Nd/ZnONCs were characterized by various techniques like UV–vis spectroscopy, XRD, FE-SEM, EDAX, FT-IR, and photoluminescence studies. Antibacterial assay was performed by well diffusion method. The anticancer potential of AS-Nd/ZnONCs were investigated against AGS cells by MTT, ROS and MMP measurement, and apoptotic cell death using respective fluorescence staining techniques. The cell adhesion and antioxidants status were detected by standard method. The mRNA expression of PI3K/AKT/mTOR signaling molecules was studied via RT-PCR technique. Results: The formulated AS-Nd/ZnONCs exhibited the hexagonal wurtzite structure with 33.56 nm size. The outcomes of antibacterial assay proved that the AS-Nd/ZnONCs has remarkable antibacterial activity. The MTT assay evidenced that the AS-Nd/ZnONCs dose-dependently suppressed the AGS cell viability. Fluorescence staining results demonstrated that the AS-Nd/ZnONCs provoked the apoptotic cell death in AGS cells. AS-Nd/ZnONCs treatment effectively inhibited the PI3K/AKT/mTOR signaling cascade and triggered the apoptotic pathway in the AGS cells. Conclusion: In conclusion, our findings confirmed that the formulated AS-Nd/ZnONCs could be a hopeful chemopreventive agent in the future to treat the GC.

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

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

Rheumatoid arthritis (RA) results in increased rate of mortality in millions of people worldwide. Research utilizing Tin oxide – Chitosan- Polyethylene glycol Carvacrol (SCP-CAR) nanocomposites has gained increased attention because of its multipotent properties and application in diverse fields including medicinal preparations. The aim of the investigation was to synthesize and to examine the anti-arthritic ability of SCP-CAR nanocomposites against CFA -induced RA in rats. Arthritis induction was done by injecting 0.1 ml of Complete Freund’s adjuvant (CFA) intradermally. Body weight, weight of organs, hind paw volumes and arthritis score was assessed and the levels of inflammatory modulators such as IL-6, IL-1β, IL-10, TNF-α, PGE2 and COX-2 was examined using assay kits. Lipid peroxidation status, antioxidant enzyme activities and levels of liver function enzymes were evaluated using standard procedures. Histopathological changes observed in hind limb of experimental animals were viewed under microscope using H& E staining. The SCP-CAR nanocomposites treated arthritic animals showed increased bodyweight and reduced hind paw volume, organ weight and arthritis score together with elevated antioxidants status and depleted proinflammatory cytokines. Histopathological observation also showed reduction in bone destruction and penetration of inflammatory cells following treatment with SCP-CAR nanocomposites. Thus, together the findings depict the anti-arthritic and anti-inflammatory potential of SCP-CAR nanocomposites suggesting that it could be used as potent therapeutic agent to treat animals against arthritis induced by CFA.

In this article, we have shown an easy, one-step, protein-directed approach for the synthesis of water-soluble and functional graphene using ovalbumin. The obtained ovalbumin functionalized graphene was characterized by UV–visible spectroscopy, X-ray diffraction, Raman spectroscopy, and Fourier transform infrared spectroscopy. Atomic force microscopy was used to check the attachment/functionalization of ovalbumin on grapheme sheets. It was shown that the functionalization of ovalbumin on grapheme sheets makes the protein more thermally stable compare to free ovalbumin, which has been shown by using sodium dodecyl sulfate polyacrylamide gel electrophoresis.

In recent years, silver nanoparticles (AgNPs) have been used as key chemotherapeutic drugs to treat various cancers like prostate, breast, ovarian, and blood cancers. No previous reports demonstrated the in vitro anti-human pancreatic cancer properties of the novel chemotherapeutic drug formulated by silver nanoparticle compounds including Zingiber officinale leaf. To survey the anti-human pancreatic cancer activities of AgNO3, Zingiber officinale leaf aqueous extract, and silver nanoparticles, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. According to the Field Emission Scanning Electron Microscopes (FE-SEM) and Transmission electron microscopy (TEM) images, the silver nanoparticles were in an average size of 18.93 nm with a spherical shape. 2,2-diphenyl-1-picrylhydrazyl (DPPH) test revealed similar antioxidant potentials for Zingiber officinale leaf aqueous extract, silver nanoparticles, and butylated hydroxytoluene. Silver nanoparticles inhibited half of the DPPH molecules in the concentration of 172 µg/mL. Silver nanoparticles had very low cell viability and anti-human pancreatic cancer properties dose-dependently against AsPC-1, PANC-1, and MIA PaCa-2. The IC50 values of the silver nanoparticles were 295, 312, and 220 µg/mL against AsPC-1, PANC-1, and MIA PaCa-2 cell lines, respectively. It is thought that the silver nanoparticles 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.

Metallic nanoparticles, especially gold nanoparticles, are used in the therapy of various diseases. Recently, many chemotherapeutic supplements or drugs have been formulated with gold nanoparticles. One option for synthesizing gold nanoparticles is to use herbs. Many previous studies have shown that medicinal herbs increase the antioxidant and cytotoxicity properties of gold nanoparticles against tumor cell lines. In this study, gold nanoparticles were prepared and synthesized in an aqueous medium using Cannabis sativa L leaf extract as stabilizing and reducing agents. In addition, we evaluated the anti-leukemia effects of gold nanoparticles against acute T-cell leukemia and lymphoblastic leukemia cell lines. Characterization of gold nanoparticles was done with FE - SEM, FT - IR, UV–Vis and TEM. The MTT test is used for anti-HAuCl4, C. sativa and C. Acute leukemia effects of AuNPs. To investigate the antioxidant potentials of HAuCl4, C. sativa aqueous extract and gold nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as control. In UV–Vis, the clear peak at 538 nm wavelength showed the formation of gold nanoparticles. In the FT-IR, many antioxidant molecules with relevant bonds led to the perfect condition for gold reduction in gold nanoparticles. In addition, in TEM and FE-SEM images, gold nanoparticles were spherical, with an average size of 18.6 nm. The IC50 of gold nanoparticles were 329, 381, 275 and 218 µg / mL against MOLT-3, TALL-104, J.RT3-T3.5 and Clone E6-1 cell lines, and Jurkat, respectively. The best results of the anti-acute leukemia properties of gold nanoparticles were obtained in the Clone E6-1 cell line. Gold nanoparticles inhibited half of the DPPH at a concentration of 196 µg/mL. The above results confirm the excellent roles of the gold nanoparticles as new chemotherapeutic drugs in treating various types of acute leukemia.

In this study, zinc oxide nanoparticles (ZnONPs) were synthesized in an aqueous medium using the plant extract as stabilizing and reducing agents. The synthesized ZnONPs were characterized using different techniques including Ultraviolet–visible (UV–Vis) and Fourier-transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-ray Spectrometry (EDS). According to the XRD analysis, 21.46 was measured for ZnONPs crystal size. SEM images exhibited a uniform spherical morphology in size of 27.92 nm for the biosynthesized nanoparticles respectively. For evaluating anti-osteosarcoma and cytotoxicity effects of ZnONPs, Zn(NO3)2·6H2O, and Alhagi maurorum aqueous extract, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The result of this test showed that ZnONPs have no cytotoxicity on normal cell line (Human umbilical vein endothelial cells (HUVECs)) and have potent anti-osteosarcoma features dose-dependently against G-292, clone A141B1, MG-63, HOS, Hs 707(A).T, and Saos-2 cell lines. For evaluating the antioxidant features of ZnONPs, Zn(NO3)2·6H2O, and Alhagi maurorum aqueous extract, we used the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, in this test butylated hydroxytoluene was a positive control, the results of this test showed that the ZnONPs have an effective antioxidant feature. Probably, potent anti-human osteosarcoma activities of ZnONPs formulated with Alhagi maurorum aqueous seed extract because of antioxidant properties.

Coronavirus disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Up to date, there has been no specific cure to treat the disease. Indonesia is one of the countries that is still fighting to control virus transmission. Yet, at the same time, Indonesia has a rich biodiversity of natural medicinal products that potentially become an alternative cure. Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4′-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of −10.8, −9.9, −9.5, −9.3 and −9.2 kcal/mol respectively. The docking scores are considered to be more favorable compared to MLN-4760 as a potent inhibitor.

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3βS9 with a parallel increase in β-TrCP and phosphorylation of GSK-3βY216. Lithium chloride treatment increased the phosphorylation of GSK-3βS9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells.

The present work describes purification and characterization of an extracellular cellulase from a newly isolated cellulolytic bacterial strain Bacillus pumilus EWBCM1. The candidate strain was tested for its abilities to hydrolyze the structural polysaccharides through the depolymerising activities of carboxymethylcellulase. The purification of cellulase was carried out by ammonium sulphate precipitation, DEAE cellulose and sephadex G-100. Purified cellulase was found to be 47.56 fold along with 1.46 U/mg of protein and the molecular weight of cellulase was 47 kDa through SDS-PAGE electrophoresis. The optimum activity of cellulase was registered at pH 10 at 50 °C. In the present study, metal ions inferred the addition of 5 mM CaCl2 (128%) was recorded good activity than the other tested metal ions. Maximum activity of purified cellulase was recorded in 3% of NaCl and 5% of surfactants medium. The bioactive of purified cellulase was carried out with various commercial detergent and antimicrobial activity.

ABSTRACT Introduction: The adhesion of bacteria to implanted devices in the human body is a major risk factor that can affect the long-term success of these devices. Staphylococcus epidermidis (S. epidermidis) have few virulence factors which have been identified and reported including autolysin (AtlE), Polysaccharide Intercellular Adhesin (PIA), Fibrinogen Binding Protein (SdrG) and Lipase enzymes (GehC and GehD). These virulence factors play an important role in the pathogenesis of S. epidermidis. Aim: To investigate the role of some of the virulence factors of S. epidermidis in the adhesion to three different types of intravascular cannulae used in hospitals. Materials and Methods: Three different types of most commonly used intravascular cannulae in hospitals were tested in this study. Polytetrafluoroethylene (PTFE), Siliconized Polytetrafluoroethylene (SPTFE) and Vialon cannulae were incubated with different S. epidermidis strains, including the mutant strains that were deficient in a specific virulence factor, each separately. The virulence factors tested with each strain were AltE, PIA, SdrG and Lipase enzymes (GehC and GehD). The number of detached bacteria were determined by plating serial dilutions on agar plates. Experiments were repeated and expressed as means and standard deviations with at least three experiments. Results were computed and analysed using Statistical Package for Social Sciences (SPSS) version-20 program. Tabulated values were compared with a student’s t-test. Statistical significance was defined as p

Constitutive activation of NF-κB is associated with proinflammatory diseases and suppression of the NF-κB signaling pathway has been considered as an effective therapeutic strategy in the treatment of various cancers including hepatocellular carcinoma (HCC). Herein, we report the synthesis of 1,2 oxazines and their anticancer potential. The antiproliferative studies presented 3-((4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)methyl)-4-phenyl-4,4a,5,6,7,7a-hexahydrocyclopenta [e][1,2]oxazine(3i) as a lead cytotoxic agent against HCC cells. Flow cytometric analysis showed that 3i caused a substantial increase in the subG1 cell population. Annexin-V-FITC-PI staining showed a significant increase in the percentage of apoptotic cells on treatment with 3i. Transfection with p65 siRNA significantly reduced the 3i induced DNA fragmentation indicating that 3i may primarily mediate its proapoptotic effects by abrogating the NF-κB signaling. In addition, treatment of HCC cells with 3i decreased the DNA binding ability of NF-κB and NF-κB-dependent luciferase expression. Taken together, this report introduces 1,2-oxazine that potently targets the NF-κB signaling pathway in HCC cells. Keywords: Oxazine, NF-κB, Anticancer, DNA fragmentation

A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound 5e IC50 value was found to be 18 μM. Thouracil amide compounds 5a and 5e inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound 5e interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.

Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.

Lung cancer is the leading type of malignancy in terms of occurrence and mortality in the global context. STAT3 is an oncogenic transcription factor that is persistently activated in many types of human malignancies, including lung cancer. In the present report, new oxadiazole conjugated indazoles were synthesized and examined for their anticancer potential in a panel of cancer cell lines. Among the new compounds, 2-(3-(6-chloro-5-methylpyridin-3-yl)phenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole (CHK9) showed consistently good cytotoxicity towards lung cancer cells with IC50 values ranging between 4.8–5.1 µM. The proapoptotic effect of CHK9 was further demonstrated by Annexin-FITC staining and TUNEL assay. In addition, the effect of CHK9 on the activation of STAT3 in lung cancer cells was examined. CHK9 reduced the phosphorylation of STAT3Y705 in a dose-dependent manner. CHK9 had no effect on the activation and expression of JAK2 and STAT5. It also reduced the STAT3-dependent luciferase reporter gene expression. CHK9 increased the expression of proapoptotic (p53 and Bax) proteins and decreased the expression of the antiapoptotic (Bcl-2, Bcl-xL, BID, and ICAM-1) proteins. CHK9 displayed a significant reduction in the number of tumor nodules in the in vivo lung cancer model with suppression of STAT3 activation in tumor tissues. CHK9 did not show substantial toxicity in the normal murine model. Overall, CHK9 inhibits the growth of lung cancer cells and tumors by interfering with the STAT3 signaling pathway.

Evodiamine (EVO) is an indoloquinazoline alkaloid that exerts its various anti-oncogenic actions by blocking phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), c-Met, and nuclear factor kappa B (NF-κB) signaling pathways, thus leading to apoptosis of tumor cells. We investigated the ability of EVO to affect hepatocyte growth factor (HGF)-induced c-Met/Src/STAT3 activation cascades in castration-resistant prostate cancer (CRPC). First, we noted that EVO showed cytotoxicity and anti-proliferation activities in PC-3 and DU145 cells. Next, we found that EVO markedly inhibited HGF-induced c-Met/Src/STAT3 phosphorylation and impaired the nuclear translocation of STAT3 protein. Then, we noted that EVO arrested the cell cycle, caused apoptosis, and downregulated the expression of various carcinogenic markers such as B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), cyclin D1, cyclooxygenase 2 (COX-2), survivin, vascular endothelial growth factor (VEGF), and matrix metallopeptidases 9 (MMP-9). Moreover, it was observed that in cPC-3 and DU145 cells transfected with c-Met small interfering RNA (siRNA), Src/STAT3 activation was also mitigated and led to a decrease in EVO-induced apoptotic cell death. According to our results, EVO can abrogate the activation of the c-Met/Src/STAT3 signaling axis and thus plays a role as a robust suppressor of tumor cell survival, proliferation, and angiogenesis.

Overexpression of chemokine receptor type 4 (CXCR4) has been found to be associated with increased cell proliferation, metastasis and also act as an indicator of poor prognosis in patients with breast cancer. Therefore, new agents that can abrogate CXCR4 expression have potential against breast cancer metastasis. In this study, we examined the potential effect of thymoquinone (TQ), derived from the seeds of Nigella sativa, on the expression and regulation of CXCR4 in breast cancer cells. TQ was found to inhibit the expression of CXCR4 in MDA-MB-231 triple negative breast cancer (TNBC) cells in a dose- and time-dependent manner. It was noted that suppression of CXCR4 by TQ was possibly transcriptionally regulated, as treatment with this drug caused down-regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and suppression of NF-κB binding to the CXCR4 promoter. Pretreatment with a proteasome inhibitor and/or lysosomal stabilization did not affect TQ induced suppression of CXCR4. Down-regulation of CXCR4 was further correlated with the inhibition of CXCL12-mediated migration and invasion of MDA-MB-231 cells. Interestingly, it was observed that the deletion of p65 could reverse the observed anti-invasive/anti-migratory effects of TQ in breast cancer cells. TQ also dose-dependently inhibited MDA-MB-231 tumor growth and tumor vascularity in a chick chorioallantoic membrane assay model. We also observed TQ (2 and 4 mg/kg) treatment significantly suppressed multiple lung, brain, and bone metastases in a dose-dependent manner in a metastasis breast cancer mouse model. Interestingly, H&E and immunohistochemical analysis of bone isolated from TQ treated mice indicated a reduction in number of osteolytic lesions and the expression of metastatic biomarkers. In conclusion, the results indicate that TQ primarily exerts its anti-metastatic effects by down-regulation of NF-κB regulated CXCR4 expression and thus has potential for the treatment of breast cancer.

Hepatocellular carcinoma (HCC) is a fatal disease and ranked fifth in cancer related mortality. Persistent activation of NF-κB is responsible for the oncogenesis, metastasis, tumor evasion, anti-apoptosis, angiogenesis and proliferation in HCC. Therefore, designing of chemically novel, biologically potent small molecules that target NF-κB signaling cascade have gained prominent clinical interest. Herein we synthesized a novel class of 4-(substituted)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one by reacting 2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one with various alkyl halides by using combustion derived bismuth oxide. We evaluated the antiproliferative efficacy of newly synthesized compounds against HCC cells and identified 4-(4-nitrobenzyl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (NPO) as lead anticancer agent. In addition, we investigated the effect of NPO on the DNA binding ability of NF-κB and NF-κB regulated luciferase expression in HCC cells. The results demonstrated that NPO can induce significant growth inhibitory effects in HepG2, HCCLM3 and Huh-7 cells in dose and time-dependent manner. Interestingly, NPO induced significant downregulation in p65 DNA binding ability, p65 phosphorylation and subsequent expression of NF-κB dependent luciferase gene expression in diverse HCC cell lines. Further, in silico docking analysis suggested that NPO can show direct physical interaction with NF-κB. Finally, NPO was found to significantly abrogate tumor growth at a dose of 50 mg/kg in an orthotopic mouse model. Thus, we report the potential anticancer effects of NPO as a novel inhibitor of NF-κB signaling pathway in HCC.

Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC), and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole (CMO) as the lead compound. Further, we examined the effect of CMO on cell cycle distribution (flow cytometry), apoptosis (annexin V-propidium iodide-FITC staining), and phosphorylation of NF-κB signaling pathway proteins (IκB and p65) in HCC cells. We found that CMO induced antiproliferative effect in dose- and time-dependent manner. Also, CMO significantly increased the percentage of sub-G1 cell population and induced apoptosis. Furthermore, CMO found to decrease the phosphorylation of IκB (Ser 32) in the cytoplasmic extract and p65 (Ser 536) in the nuclear extract of HCC cells. It also abrogated the DNA binding ability and transcriptional activity of NF-κB. CMO induced the cleavage of PARP and caspase-3 in a time-dependent manner. In addition, transfection with p65 small interfering RNA blocks CMO-induced caspase-3/7 activation. Molecular docking analysis revealed that CMO interacts with the hydrophobic region of p65 protein. Thus, we are reporting CMO as an inhibitor of NF-κB signaling pathway.

Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also expensive. Thus identification of pharmacological agents that do not have these disadvantages is required. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa), is one such agent that has been extensively studied over the last three to four decades for its potential anti-inflammatory and/or anti-cancer effects. Curcumin has been found to suppress initiation, progression, and metastasis of a variety of tumors. These anti-cancer effects are predominantly mediated through its negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. It also abrogates proliferation of cancer cells by arresting them at different phases of the cell cycle and/or by inducing their apoptosis. The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers.

Infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) have become a rising threat to public health. There is an urgent need for development of promising new therapeutic agents against drug resistant bacteria like S. aureus. This report discusses purification and characterization of proteins from Indian Russell's viper snake venom. Novel 15‐kDa proteins called “Viperatoxin” (VipTx‐I and VipTx‐II) were extracted from the whole venom and evaluated using in vitro antimicrobial experiments. The N‐terminal amino acid sequence of “Viperatoxin” showed high sequence homology to daboiatoxin isolated from the same venom and also matched phospholipase A2 (PLA2) enzymes isolated from other snake venoms. In an in vitro plate assay, VipTx‐II but not VipTx‐I showed strong antimicrobial effects against S. aureus and Burkholderia pseudomallei (KHW & TES), Proteus vulgaris and P. mirabilis. The VipTx‐II was further tested by a broth‐dilution assay at 100–3.125 μg/ml concentrations. The most potent bactericidal effect was found at the lowest dilutions (MICs of 6.25 μg/ml) against B. pseudomallei, S. aureus and P. vulgaris (MICs of 12.25 μg/ml). Electron microscopic investigation revealed that the protein‐induced bactericidal potency was closely associated with pore formation and membrane damage, even at the lowest concentrations (

This study was aimed to evaluate the possible protective effects of ursolic acid (UA) against gamma radiation induced damage both in vitro as well as in vivo. It was observed that the exposure to gamma radiation dose- and time-dependently caused a significant decrease in the cell viability, while the treatment of UA attenuated this cytotoxicity. The production of free radicals including reactive oxygen species (ROS) and NO increased significantly post-irradiation and further induced lipid peroxidation and oxidative DNA damage in cells. These deleterious effects could also be effectively blocked by UA treatment. In addition, UA also reversed gamma irradiation induced inflammatory responses, as indicated by the decreased production of TNF-α, IL-6, and IL-1β. NF-κB signaling pathway has been reported to be a key mediator involved in gamma radiation-induced cellular damage. Our results further demonstrated that gamma radiation dose- and time-dependently enhanced NF-κB DNA binding activity, which was significantly attenuated upon UA treatment. The post-irradiation increase in the expression of both phospho-p65, and phospho-IκBα was also blocked by UA. Moreover, the treatment of UA was found to significantly prolong overall survival in mice exposed to whole body gamma irradiation, and reduce the excessive inflammatory responses. Given its radioprotective efficacy as described here, UA as an antioxidant and NF-κB pathway blocker, may function as an important pharmacological agent in protecting against gamma irradiation-induced injury.

Daidzin (DDZ) extracted from Pueraria lobate (Fabaceae) is a widely known phytoestrogen. DDZ can display anti-cancer activities against breast and prostate cancers, but its anti-oncogenic actions in multiple myeloma (MM) cells have not been studied. The signal transducer and activator of transcription 3 (STAT3) can control key processes including proliferation, differentiation, and survival in MM cells. Here, we noted that DDZ abrogated STAT3 activation (both constitutive as well as inducible) at Tyr705 and Ser727 in MM cells. Additionally, DDZ mitigated the phosphorylation of STAT3 upstream Janus-activated kinases (JAK1/2) and c-Src kinases. Pervanadate (tyrosine phosphatase blocker) exposure altered the DDZ-induced inhibition of STAT3 activation, thus affecting the action of this phytoestrogen on apoptosis. Moreover, DDZ impeded proliferation and augmented the apoptotic effects of bortezomib (Bor) in MM cells. Overall, the data indicate that DDZ may act as a potent suppressor of STAT3 signaling cascade, and the co-treatment of DDZ and Bor could be a promising therapeutic strategy, specifically in MM.

Fangchinoline (FCN) derived from Stephaniae tetrandrine S. Moore can be employed to treat fever, inflammation, rheumatism arthralgia, edema, dysuria, athlete’s foot, and swollen wet sores. FCN can exhibit a plethora of anti-neoplastic effects although its precise mode of action still remains to be deciphered. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) can closely regulate carcinogenesis and thus we analyzed the possible action of FCN may have on these two signaling cascades in tumor cells. The effect of FCN on NF-κB and AP-1 signaling cascades and its downstream functions was deciphered using diverse assays in both human chronic myeloid leukemia (KBM5) and multiple myeloma (U266). FCN attenuated growth of both leukemic and multiple myeloma cells and repressed NF-κB, and AP-1 activation through diverse mechanisms, including attenuation of phosphorylation of IκB kinase (IKK) and p65. Furthermore, FCN could also cause significant enhancement in TNFα-driven apoptosis as studied by various molecular techniques. Thus, FCN may exhibit potent anti-neoplastic effects by affecting diverse oncogenic pathways and may be employed as pro-apoptotic agent against various malignancies.

Here, we determined the anti-neoplastic actions of formononetin (FT) against multiple myeloma (MM) and elucidated its possible mode of action. It was observed that FT enhanced the apoptosis caused by bortezomib (Bor) and mitigated proliferation in MM cells, and these events are regulated by nuclear factor-κB (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, and activator protein-1 (AP-1) activation. We further noted that FT treatment reduced the levels of diverse tumorigenic proteins involved in myeloma progression and survival. Interestingly, we observed that FT also blocked persistent NF-κB, PI3K/AKT, and AP-1 activation in myeloma cells. FT suppressed the activation of these oncogenic cascades by affecting a number of signaling molecules involved in their cellular regulation. In addition, FT augmented tumor growth-inhibitory potential of Bor in MM preclinical mouse model. Thus, FT can be employed with proteasomal inhibitors for myeloma therapy by regulating the activation of diverse oncogenic transcription factors involved in myeloma growth.

[This corrects the article DOI: 10.1371/journal.pone.0163209.].