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The unique use of selenium–troxerutin nanoconjugates as an effective management therapy for treating TNBC.

We report the synthesis of C-Fe3O4NPs@OVA as a nanocarrier for 5-CQA and found that the anticancer efficacy was significantly enhanced.

New series of 8-nitroquinolone based aromatic heterocyclic acyl hydrazones have been synthesized and characterized through various spectroscopic techniques. They were theoretically examined for molecular docking with various proteins related with...

Recent evidences have demonstrated that bio‐macromolecule assisted nanomaterials syntheses have been widely used for cancer treatment. The aim of this study was to investigate the effects and cellular mechanisms of silymarin‐routed synthesis of selenium nanowires (SeNWs) on cytotoxic and cell migration inhibitory potential against triple negative breast cancer (MDA‐MB‐231) cells. Characterizations of SeNWs were detected by XRD, scanning electron microscopy, and Raman spectrum. Cell proliferation and migration of MDA‐MB‐231 cells were evaluated by MTT and wound assays respectively. The study revealed that SeNWs significantly suppressed the cell viability and cell migration potential compared with the control group. Moreover, SeNWs significantly induce the apoptotic induction in triple negative breast cancer cells. Overall, the current findings highlight the potential cancer therapeutic applications of SeNWs in in vitro condition.

Lung carcinoma is an aggressive form of cancer, with an increasing rate of morbidity, dismal outlook, poor prognosis and limited therapeutic approaches. The present study is aimed to demonstrate the anticancer efficacy of a fabricated beta-sitosterol chitosan nanocomplex (BSC) in a human lung cancer cell line (A-549) and animal model. The nanocomplex was fabricated using beta-sitosterol and chitosan and its properties were investigated via FTIR, DLS, zeta potential, SEM, and TEM. In vitro and in vivo assessments were done employing various techniques to determine the viability and alterations in morphology of A-549 cells, and also the anti-tumor efficacy in a xenograft mice model. The outcomes revealed the apoptotic efficacy prompted by the BSC nanocomplex in both a time- and dose-dependent manner. Subsequently, AO/EB staining of the BSC nanocomplex at different concentrations led to the typical alteration in the morphology of the cells, comprising the shrinkage of cells and fragmented nucleus, resulting in apoptosis. The effect of the BSC nanocomplex on the cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry. There was a notable loss in the mitochondrial membrane potential, which ultimately caused an apoptotic effect in the treated cells. Also, the BSC nanocomplex reduced the migratory potential of the A-549 cells in vitro. Moreover, the in vivo studies corroborated our in vitro findings and emphasized the decrease in tumor volume of the established xenograft mice model. The histopathological study also confirmed the absence of any noteworthy effects caused by the BSC nanocomplex in the major organs of the treated mice. Thus, the present findings clearly demonstrate that the BSC nanocomplex paves a way as a new agent to be used for therapeutic targeting in cancer treatment.

Although chemotherapeutics plays a pivotal role in the therapy of many aggressive cancers, there are many pitfalls including multidrug resistance and lack of selectivity which result in progression of the cancer. Triple negative breast cancer (TNBC) is one such aggressive type of breast cancer with minimal therapeutic approaches. As TNBC is associated with high risk of metastasis and low survival percentage, an immense requisite to expand the therapeutic strategy is needed. In support of this quest, an attempt was made to exploit the anticancer efficacy of fabatin, a phytodefensin peptide obtained from the seeds of Vicia faba, along with the biocompatible nanocarrier silica as a therapeutic strategy against TNBC. The current work was intended to isolate the plant defensin cationic antimicrobial peptide fabatin from the seeds of Vicia faba and also to load it in mesoporous silica nanoparticles (F-SNP) to increase its efficiency in the TNBC system, both in vitro using MDA-MB-231 cells and in vivo in a xenograft mice model. In vitro studies demonstrated the efficient role of F-SNP against MDA-MB-231 cells with inhibitory concentration (IC50) of 7.8 ± 0.9 μg mL−1 while showing least significant effect on normal breast MCF-10A cells. The appearance of apoptotic bodies specifies the cell death promoted by isolated cationic defensin peptide fabatin. Moreover, expression studies evinced the downregulation of PI3K which further resulted in the upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins. Further in vivo studies supported our in vitro findings by confirming a significant reduction in tumor volume. Histopathological observations confirm the absence of noteworthy effect in F-SNP treated mice model. Our findings altogether indicated F-SNP to be a most promising drug with significant pharmaceutical potential in the treatment of TNBC cells.

Triple negative breast carcinoma (TNBC) is an aggressive form of cancer, with high rates of morbidity, mortality, poor prognosis and limited therapeutic options. The objective of the present study was to elaborate the anticancer activity of Troxerutin (TXN) in TNBC/MDA-MB-231 cells. Herein, we demonstrated the inhibitory effects of TXN on the breast cancer cell growth via induction of apoptosis. Mitochondrial membrane potential (∆Ψm), DNA damage and apoptotic nuclear changes were analyzed by flowcytometry, AO/EtBr and Hoechst staining, respectively. Furthermore, apoptotic protein and gene expressions were analyzed by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively. Our results indicated that TXN induces apoptosis as evidenced by inhibit the cell proliferation, enhanced apoptotic activation, altered mitochondrial membrane potential and elevated level of DNA damage in TNBC cells. Furthermore, the TXN inhibit anti-apoptotic protein expression with the subsequent upregulation of Cytochrome c, Caspase-9 and Caspase-3. Thus, TXN induces apoptosis in TNBC cells through inducing nuclear damage and altered apoptotic marker expressions. Therefore, TXN might be used as a potential therapeutic agent for the treatment of triple negative breast cancer.

Magnetic nanocarriers has become popularised in the research field as well as in the biomedical application due to their unique exotic possession, and processability. The present study involves the synthesis of nanocarrier, Iron Oxide nanoparticle conjugated with silibinin (SLN-Fe2O3) using co-precipitation method and also to detect their efficacy against the colon cancer cell. The synthesized SLN-Fe2O3 were undertaken for several analysis including UV-visible spectroscopy, dynamic light scattering, scanning electron microscope, Fourier transform infra-red spectroscopy, zeta potential analysis, and X-ray diffraction analysis. The analysis had end up in confirming the polydispersity and crystalline nature of the synthesized SLN-Fe2O3 with an average size of 70 nm. Further the synthesized SLN-Fe2O3 was undertaken for in vitro (AO/EtBR and DAPI) studies to find their effectiveness against human colon cancer using HT-29 cell line. The fragmentation occurs in nuclear material of the SLN-Fe2O3 treated cells had revealed that the cell death was due to the induction of apoptotic signals in the treated cancer cells. Thus the current study had clearly validated the potency of synthesized Iron Oxide nanoparticles conjugated with silibinin (SLN-Fe2O3) against the colon cancer cell and holds a promising therapeutic potency in treating cancer cells.

We investigated the effect of encapsulated Chitosan-nanoparticles by using Salvia leucantha essential oil on the insecticidal activity against H. armigera, S. litura and P. xylostella. The encapsulated nanoparticles were characterized by UV–vis, SEM, EDX, FTIR and ZP. Phytochemical analysis of essential oil revealed that the presence of alkaloid, flavonoids, phenolics, and glycosides etc., and GC/MS analysis identified at least 12 compounds, the most abundant constituents were bornyl acetate, 1-Octadecanesulphonyl Chloride, spathulenol and caryophyllene oxide. Bioassays was conducted to find out the toxicity against H. armigera and LC50 values of essential oil was 175.39 ppm (larva I) 542.09 ppm (pupa), and encapsulations of essential oil was 14.56 ppm (I) 63.28 ppm (pupa), respectively. Life history parameters and food efficiency utilization measures were significantly affected with concomitant decline in the activities of digestive enzymes after treatment of encapsulated Chitosan-nanoparticles for H. armigera, S. litura and P. xylostella. From the results the nanomatierals are effective and eco-friendly bio-insecticides for not only control bollworm and also other lepidopteran insects such as Spodoptera litura and Plutella xylostella at different crop ecosystem.

Mosquito borne diseases are on the rise because of their fast spread worldwide and the lack of effective treatments. Here we are focusing on the development of a novel anti-malarial and virucidal agent with biocidal effects also on its vectors. We have synthesized a new quinoline (4,7-dichloroquinoline) derivative which showed significant larvicidal and pupicidal properties against a malarial and a dengue vector and a lethal toxicity ranging from 4.408 µM/mL (first instar larvae) to 7.958 µM/mL (pupal populations) for Anopheles stephensi and 5.016 µM/mL (larva 1) to 10.669 µM/mL (pupae) for Aedes aegypti. In-vitro antiplasmodial efficacy of 4,7-dichloroquinoline revealed a significant growth inhibition of both sensitive strains of Plasmodium falciparum with IC50 values of 6.7 nM (CQ-s) and 8.5 nM (CQ-r). Chloroquine IC50 values, as control, were 23 nM (CQ-s), and 27.5 nM (CQ-r). In vivo antiplasmodial studies with P. falciparum infected mice showed an effect of 4,7-dichloroquinoline compared to chloroquine. The quinoline compound showed significant activity against the viral pathogen serotype 2 (DENV-2). In vitro conditions and the purified quinoline exhibited insignificant toxicity on the host system up to 100 µM/mL. Overall, 4,7-dichloroquinoline could provide a good anti-vectorial and anti-malarial agent.

Microbes or parasites spread vector-borne diseases by mosquitoes without being affected themselves. Insecticides used in vector control produce a substantial problem for human health. This study synthesized zinc oxide nanoparticles (ZnO NPs) using Lawsonia inermis L. and were characterized by UV–vis, FT-IR, SEM with EDX, and XRD analysis. Green synthesized ZnO NPs were highly toxic against Anopheles stephensi, whose lethal concentrations values ranged from 5.494 ppm (I instar), 6.801 ppm (II instar), 9.336 ppm (III instar), 10.736 ppm (IV instar), and 12.710 ppm (pupae) in contrast to L. inermis treatment. The predation efficiency of the teleost fish Gambusia affinis and the copepod Mesocyclops aspericornis against A. stephensi was not affected by exposure at sublethal doses of ZnO NPs. The predatory potency for G. affinis was 45 (I) and 25.83% (IV), copepod M. aspericornis was 40.66 (I) and 10.8% (IV) while in an ZnO NPs contaminated environment, the predation by the fish G. affinis was boosted to 71.33 and 34.25%, and predation of the copepod M. aspericornis was 60.35 and 16.75%, respectively. ZnO NPs inhibited the growth of several microbial pathogens including the bacteria (Escherichia coli and Bacillus subtilis) and the fungi (Alternaria alternate and Aspergillus flavus), respectively. ZnO NPs decreased the cell viability of Hep-G2 with IC50 value of 21.63 µg/mL (R2 = 0.942; P 0.001) while the concentration increased from 1.88 to 30 µg/mL. These outcomes support the use of L. inermis mediated ZnO NPs for mosquito control and drug development.

In the present study we tested the biological effect of crab shell-chitosan reduced silver nanoparticles (Cs-AgNPs) and characterized viz., UV–vis Spectroscopy, FTIR, SEM, EDAX and XRD. After the treatment of Cs-AgNPs at different larval stages (Larva I, II, III, IV & pupa) of C. quinquefasciatus and for Helicoverpa armigera (III, IV larval stages) found to be lethal at concentration (LC50) of chitosan fabricated nanoparticles for larval instars and pupa, when compare to individual chitosan treatment. Significant reduction of egg output, hatchability and fecundity were noticed after the treatment of Cs-AgNPs (25–50 ppm) and (150–300 ppm) of chitosan alone. Predatory efficiency of guppy fish against mosquito larvae was also not significantly affected by nanoparticles applications. Tested nanoparticle was also possessed anti-bacterial properties against Escherichia coli, Bacillus subtilis, Klebsiella pneumonia and Salmonella aureus.

Background and Objectives: Microbes or parasites spread vector-borne diseases by mosquitoes without being affected themselves. Insecticides used in vector control produce a substantial problem for human health. Materials and Methods: This study synthesized zinc oxide nanoparticles (ZnO NPs) using Lawsonia inermis L. and were characterized by UV–vis, FT-IR, SEM with EDX, and XRD analysis. Results: Green synthesized ZnO NPs were highly toxic against Anopheles stephensi, whose lethal concentrations values ranged from 5.494 ppm (I instar), 6.801 (II), 9.336 (III), 10.736 (IV), and 12.710 ppm (pupae) in contrast to L. inermis treatment. The predation efficiency of the teleost fish Gambusia affinis and the copepod Mesocyclops aspericornis against A. stephensi was not affected by exposure at sublethal doses of ZnO NPs. The predatory potency for G. affinis was 45 (I) and 25.83 % (IV), copepod M. aspericornis was 40.66 (I) and 10.8 % (IV) while in an ZnO NPs contaminated environment, the predation by the fish G. affinis was boosted to 71.33 and 34.25 %, and predation of the copepod M. aspericornis was 60.35 and 16.75 %, respectively. ZnO NPs inhibited the growth of several microbial pathogens including the bacteria (Escherichia coli and Bacillus subtilis) and the fungi (Alternaria alternate and Aspergillus flavus), respectively. ZnO NPs decreased the cell viability of Hep-G2 with IC50 value of 21.63 µg/mL (R2=0.942; P) while the concentration increased from 1.88 to 30 µg/mL. Conclusion: These outcomes support the use of L. inermis mediated ZnO NPs for mosquito control and drug development.

Correction for 'Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO

In this article, we report the validation of cancer nanotherapy for the treatment of cancers using quercetin (Qtn). Much attention has been paid to the use of nanoparticles (NPs) to deliver drugs of interest in vitro/in vivo. Highly developed NPs-based nano drug delivery systems (NDDS) are an attractive approach to target cancer cell apoptosis, which is related to the onset and progression of cancer. Conventional chemotherapy has some notable drawbacks, such as lack of specificity, requirement of high drug doses, adverse effects, and gradual development of multidrug resistance (MDR), that decrease the efficacy of cancer therapy. To overcome these challenges of chemotherapy, the achievement of high drug loading in combination with low leakage at physiological pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. To assist drug delivery, we have prepared PVPylated-TiO

Three new ruthenium(II) complexes [(η6-p-cymene)RuX(L)]PF6 (X = Cl (1), Br (2) and I (3)) with 9-ethyl-N-(pyridin-2-ylmethylene)9H-carbazole-3-amine (L) have been prepared and characterised by elemental analysis and different spectral techniques (NMR studies, IR and HR-Mass spectroscopy). The molecular structure of the [(η6-p-cymene)RuI(L)]PF6 (3) complex was determined by single crystal XRD. The geometry around the Ru(II) centre is that of a classical “piano stool” with the iodine, the N,N′ ligand bonding in a bidentate manner and the π-bonds of the p-cymene occupying the coordination sites. In vitro studies of the complexes 1–3 on HepG2 human liver cancer cells showed excellent inhibitory concentration (IC50) values between 22 and 30 μM. The halogen leaving groups Cl−, Br− and I− presented in the complexes 1–3 showed a significant effect. Interestingly complex 3 displayed a significant growth inhibitory IC50 value of 22 μM compared to the other two complexes. Furthermore, cell cycle, cytotoxic, nuclear studies and cellular accumulation have shown that the new Ru(II) half sandwich complexes 1–3 were effective against HepG2 cancer cell proliferation. Density functional theory (DFT) was used to calculate the relevant molecular orbital energy levels, binding energies, bond angles and bond lengths of the synthesised Ru(II) complexes. The DFT study of the complexes 1–3 further supported the biological activity of the complexes and showed good agreement with experimental results.

In this article, we report the validation of cancer nanotherapy for treatment of cancers using quercetin (Qtn).

Neurodegeneration is a progressive loss of neuronal function in certain parts of brain and spinal cord which lead to many neurodegenerative disorders. Phytocompounds has become a reliable treatment for numerous diseases as they uphold various biological properties within them. The present study had explored the neuroprotective efficacy of spathulenol (component of essential oil) in vitro in SH-SY5Y neuroblastoma cells by inducing neuronal damage through treatment with 6-hydroxydopamine (6-OHDA). To demonstrate the efficacy of spathulenol various assays involving testing its potency on reducing the ROS production, maintaining the mitochondrial integrity, and also its role in neuroprotection was validated through SH-SY5Y cells. The cells were treated with 6-OHDA (100 μM) and spathulenol (1 to 20 μM). Our results depicted that the cells treated with 6-OHDA alone causes membrane blebbing and cell shrinkage while the treatment with both 6-OHDA and spathulenol had ensued recovery of damaged cells in dose dependent way. The study had also highlighted the neuroprotective property of spathulenol amidst 6-OHDA treatment through relieving the cells from oxidative stress and also by maintaining the mitochondrial membrane integrity. These results had evinced the use of spathulenol in restoring the abnormal cellular conditions induced by 6-OHDA in neuronal cells highlighting it as a potential promising therapy for treating neurodegenerative diseases.

Lectins are proteins that show a variety of biological activities. Nevertheless, information on lectin from Gluttonous beauts and their anticancer activities are very limited. In this study, we purified a lectin from hemolymph of G. beauts and identified its molecular weight to be 66 kDa. The effect of lectin at different concentrations (μg/mL) on the cell growth and apoptosis were evaluated against MCF-7 and MCF-10A cells, whereas cytotoxicity to the MCF-7 cells mediated by lectin was observed and the mechanism of action of the lectin in including apoptosis in cancer cells via the intrinsic pathway was also proposed. The MCF-7 cells were employed for in vitro studies on cytotoxicity, induction of apoptosis and apoptotic DNA fragmentation. In MCF-10A cells lectin did not show any adverse effect even at higher concentration. Cell cycle analysis also showed a significant cell cycle arrest on selected cells after lectin treatment. Western blotting suggested that lectin up regulates the apoptotic protein expression in MCF-7 cells while it down regulates the level of Bcl-2 expression.

A main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. We investigated the toxicity of magnetic nanoparticles (MNP) produced by Magnetospirillum gryphiswaldense (strain MSR-1) on chloroquine-resistant (CQ-r) and sensitive (CQ-s) Plasmodium falciparum, dengue virus (DEN-2), and two of their main vectors, Anopheles stephensi and Aedes aegypti, respectively. MNP were studied by Fourier-transform infrared spectroscopy and transmission electron microscopy. They were toxic to larvae and pupae of An. stephensi, LC50 ranged from 2.563 ppm (1st instar larva) to 6.430 ppm (pupa), and Ae. aegypti, LC50 ranged from 3.231 ppm (1st instar larva) to 7.545 ppm (pupa). MNP IC50 on P. falciparum were 83.32 μg ml−1 (CQ-s) and 87.47 μg ml−1 (CQ-r). However, the in vivo efficacy of MNP on Plasmodium berghei was low if compared to CQ-based treatments. Moderate cytotoxicity was detected on Vero cells post-treatment with MNP doses lower than 4 μg ml−1. MNP evaluated at 2–8 μg ml−1 inhibited DEN-2 replication inhibiting the expression of the envelope (E) protein. In conclusion, our findings represent the first report about the use of MNP in medical and veterinary entomology, proposing them as suitable materials to develop reliable tools to combat mosquito-borne diseases.

Mosquitoes are arthropods of huge medical and veterinary relevance, since they vector pathogens and parasites of public health importance, including malaria, dengue and Zika virus. Currently, nanotechnology is considered a potential eco-friendly approach in mosquito control research. We proposed a novel method of biofabrication of silver nanoparticles (AgNP) using chitosan (Ch) from crab shells. Ch-AgNP nanocomposite was characterized by UV-vis spectroscopy, FTIR, SEM, EDX and XRD. Ch-AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi obtaining LC50 ranging from 3.18 ppm (I) to 6.54 ppm (pupae). The antibacterial properties of Ch-AgNP were proved against Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi, while no growth inhibition was reported in assays conducted on Proteus vulgaris. Concerning non-target effects, in standard laboratory considtions the predation efficiency of Danio rerio zebrafishes was 68.8% and 61.6% against I and II instar larvae of A. stephensi, respectively. In a Ch-AgNP-contaminated environment, fish predation was boosted to 89.5% and 77.3%, respectively. Quantitative analysis of antioxidant enzymes SOD, CAT and LPO from hepatopancreas of fresh water crabs Paratelphusa hydrodromous exposed for 16 days to a Ch-AgNP-contaminated aquatic environment were conducted. Notably, deleterious effects of Ch-AgNP contaminating aquatic enviroment on the non-target crab P. hydrodromous were observed, particularly when doses higher than 8-10ppm are tested. Overall, this research highlights the potential of Ch-AGNP for the development of newer control tools against young instar populations of malaria mosquitoes, also highlighting some risks concerned the employ of nanoparticles in aquatic environments.

Dengue is an arbovirus mainly vectored by Aedes mosquitoes. Its prevention and control depends to effective vector control measures. Cancer causes millions of death every year. Most of the anticancer drugs have high toxicity and low specificity of action, leading to systemic toxicity and severe side effects. Thus, the development of effective tools is a priority. We fabricated zinc oxide nanoparticles using the Myristica fragrans extract as a reducing and stabilizing agent. Nanoparticles were studied using UV–vis spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, dynamic light scattering, energy dispersive X-ray analysis, field emission scanning electron microscopy and transmission electron microscopy. ZnO nanorods were highly effective against A. aegypti young instars, with LC50 ranging from 3.44 (larva I) to 14.63 ppm (pupa). Nanorods showed adult LC50 of 15.004 ppm. ZnO nanorods exhibited dose-dependent cytotoxicity against human hepato-cancer cells (HepG2). After 48 and 24 h of incubation, the IC50 were 20 and 22 μg/ml, respectively. Nanorods triggered the induction of apoptosis. Overall, this study highlights that the possibility to employ M. fragrans-synthesized ZnO nanorods in mosquito control, as well as in the development of novel chemotherapeutic agents with reduced systemic toxicity.

Magnetic nanoparticles have shown an increasing number of applications in the field of molecular medicine. In the present study we investigated the controlled synthesis of biocompatible polymer coated iron oxide nanoparticles (Fe2O3) loaded with baicalein and evaluated these for their drug loading and release behaviour. Moreover, the loaded particles were evaluated for their anti-proliferation, cell cycle arrest and apoptosis activation properties in triple negative breast cancer cells. The structure, morphology and magnetic properties of the prepared materials were studied by using scanning electronic microscopy, transmission electronic microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis, thermogravimetric analysis, dynamic light scattering analysis and zeta potential analysis. DLS and TEM analysis confirms that the size of the synthesized iron oxide nanoparticles are about 90–100 nm and that they are extremely crystalline and spherical in nature. FTIR analysis confirms that the baicalein molecules were conjugated with PEG-coated iron oxide nanoparticles. X-ray diffraction patterns indicate that the magnetic nanoparticles were highly pure with a spinel structure. Baicalein loaded nanoparticles show a controlled release profile in response to various pH levels. We found significant cell cycle arrest at various phases in the treated group and subsequent apoptotic cell death to be evidenced by AO/EtBr, DAPI and PI of fluorescence microscopy analysis. The TUNEL assay evidences that DNA damage occurs in the treated cells. Further baicalein loaded iron oxide nanoparticles exhibit significant down-regulation of the anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic proteins evidenced by Western blotting. Our findings clearly demonstrate that baicalein loaded iron oxide nanoparticles could efficiently deliver the drug of interest, and initiate and execute the apoptotic process in triple negative breast cancer cells. This could open a new window in polymer surface chemistry to develop metal oxide based drug delivery systems for all kinds of cancer therapeutics.

Mosquitoes are vectors of devastating pathogens and parasites, causing millions of deaths every year. Dengue is a mosquito-borne viral infection found in tropical and subtropical regions around the world. Recently, dengue transmission has strongly increased in urban and semiurban areas, becoming a major international public health concern. Aedes aegypti (Diptera: Culicidae) is a primary vector of dengue. Shedding light on genetic deviation in A. aegypti populations is of crucial importance to fully understand their molecular ecology and evolution. In this research, haplotype and genetic analyses were conducted using individuals of A. aegypti from 31 localities in the north, southeast, northeast and central regions of Tamil Nadu (South India). The mitochondrial DNA region of cytochrome c oxidase 1 (CO1) gene was used as marker for the analyses. Thirty-one haplotypes sequences were submitted to GenBank and authenticated. The complete haplotype set included 64 haplotypes from various geographical regions clustered into three groups (lineages) separated by three fixed mutational steps, suggesting that the South Indian Ae. aegypti populations were pooled and are linked with West Africa, Columbian and Southeast Asian lineages. The genetic and haplotype diversity was low, indicating reduced gene flow among close populations of the vector, due to geographical barriers such as water bodies. Lastly, the negative values for neutrality tests indicated a bottle-neck effect and supported for low frequency of polymorphism among the haplotypes. Overall, our results add basic knowledge to molecular ecology of the dengue vector A. aegypti, providing the first evidence for multiple introductions of Ae. aegypti populations from Columbia and West Africa in South India.

Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating pathogens and parasites. The standard method of utilisation of morphological characters becomes challenging due to various factors such as phenotypical variations. We explored the complementary approach of CO1 gene-based identification, analysing ten species of mosquito vectors belonging to three genera, Aedes, Culex and Anopheles from India. Analysed nucleotide sequences were found without pseudo genes and indels; they match with high similarity in nucleotide Basic Local Alignment Search Tool (BLASTn) search. The partial CO1 sequence of Anopheles niligricus was the first time record submitted to National Center for Biotechnology Information (NCBI). Mean intra- and interspecies divergence was found to be 1.30 and 3.83 %, respectively. The congeneric divergence was three times higher than the conspecifics. Deep intraspecific divergence was noted in three of the species, and the reason could be explained more accurately in the future by improving the sample size across different locations. The transitional and transversional substitutions were tested individually. Ts and Tv substitutions in all the 1st, 2nd and 3rd codons were estimated to be (0.44, 99.51), (40.35, 59.66) and (59.16, 40.84), respectively. Saturation of the sequences was resolved, since both the Ts and Tv exhibited a linear relationship suggesting that the sequences were not saturated. NJ and ML tree analysis showed that the individuals of the same species clustered together based on the CO1 sequence similarity, regardless of their collection site and geographic location. Overall, this study adds basic knowledge to molecular evolution of mosquito vectors of medical and veterinary importance and may be useful to improve biotechnological tools employed in Culicidae control programmes.

Cancer nanotheranostic materials are useful in real-time monitoring of drug delivery and therapeutic action against tumor cells as they co-deliver therapeutic and imaging functions. In this study, we report the use of natural fluorescent protein (R-phycoerythrin (PE)) in the preparation of novel multifunctional chitosan–silver–phycoerythrin nanocomposites (CS–Ag–PE NCs) and the theranostic potentials of the synthesized nanocomposites (NCs) were evaluated against triple negative breast cancer (MDA-MB-231) cells. Absorption behavior of the synthesized CS–Ag NCs and CS–Ag–PE NCs at different pH was studied by UV-Vis and FT-IR spectroscopy for determining the interaction of silver with chitosan and CS–Ag NCs with PE. Morphological features of CS–Ag NCs and CS–Ag–PE NCs and cellular uptake of CS–Ag–PE NCs were evaluated by TEM. Flow cytometry analyses were performed to determine the conjugation efficiency of CS–Ag-NCs to PE, stability of the CS–Ag–PE NCs and cellular localization of NCs at dose-dependent concentrations. Further, we substantiated the effect of CS–Ag–PE NCs in the activation of ROS mediated caspase-dependent intrinsic apoptosis by analyzing the expression of apoptotic proteins and bcl-2 family genes, respectively. The ionic interaction between PE and CS–Ag NCs resulted in a stable theranostic fluorescent NC complex that enabled the real time probing of delivery, distribution and therapeutic functions of NCs in cancer cells. The theranostic NCs of this study exhibited apoptotic induction potential in cancer cells but low toxicity in normal breast cells.

Recently, it has been highlighted an overlooked connection between the biting activity of Anopheles mosquitoes and the spread of cancer. The excellent physico-chemical properties of graphene quantum dots (GQDs) make them a suitable candidate for biomedical applications. We focused on the toxicity of GQDs against Plasmodium falciparum and its vector Anopheles stephensi, and their impact on predation of non-target mosquito predators. Biophysical methods, including UV–vis, photoluminescence, FTIR and Raman spectroscopy, XRD analysis and TEM, confirmed the effective GQD nanosynthesis. LC50 against A. stephensi ranged from 0.157 (larva I) to 6.323 ppm (pupa). The antiplasmodial activity of GQDs was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. IC50 were 82.43 (CQ-s) and 85.17 μg/ml (CQ-r). In vivo experiments conducted on Plasmodium berghei infecting albino mice showed moderate activity of GQDs if compared to chloroquine. Concerning non-target effects, the predation efficiency of Gambusia affinis, Anax immaculifrons and Hoplobatrachus tigerinus post-treatment with GQDs was enhanced. Lastly, GQDs were toxic against MCF-7 breast cancer cell lines with an IC50 = 24.81 μg/ml, triggering apoptosis in treated cells. Overall, we highlighted the multipurpose potential of GQDs for the development of newer drugs in the fight against Anopheles vectors, Plasmodium parasites and breast cancer cells.

The control of dengue vectors with effective tools is crucial. Here, we fabricated silver nanoparticles (AgNP) using a cheap method relying to a mangrove extract (Sonneratia alba) as a reducing and stabilizing agent. AgNP were characterized by UV–vis spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray diffraction. LC50 of S. alba extract against Aedes aegypti ranged from 192.03 ppm (larva I) to 353.36 ppm (pupa). LC50 of AgNP ranged from 3.15 (I) to 13.61 ppm (pupa). Sub-lethal doses of AgNP magnified predation rates of guppy fishes, Poecilia reticulata, against Ae. aegypti and Chironomus kiiensis larvae. Mangrove-fabricated AgNP were evaluated for their antimicrobial potential against Bacillus subtilis, Klebsiella pneumoniae, and Salmonella typhi, using the agar disc diffusion and minimum inhibitory concentration protocol. Notably, S. alba-synthesized AgNP tested at doses ranging from 5 to 15 µg/mL down-regulated the expression of the envelope (E) gene and protein in dengue virus (serotype DEN-2), while only little cytotoxicity rates (i.e.

The green synthesis of zinc oxide nanoparticles (ZnONPs) using Borassus flabellifer fruit extract was characterized by UV–visible spectroscopy, FT-IR, XRD, TEM, Zeta potential and EDS analysis. The UV–visible spectrum showed an absorption peak at 368 nm that reflects surface Plasmon resonance (SPR) ZnONPs. TEM photograph showed that the green synthesized ZnONPs were porous in nature and rod like structure with an average size of 55 nm. The Zeta potential value of −21.5 mV revealed the surface charge of green synthesized ZnONPs. In this study, we examined the synthesized DOX-ZnONPs exhibited a dose-dependent cytotoxicity against MCF-7 and HT-29. The inhibitory concentration (IC50) was found to be 0.125 μg mL−1 for MCF-7 and HT-29 cells. An induction of apoptosis was evidenced by nuclear stain Hoechst 33258. In vivo toxicity assessment showed that DOX-ZnONPs have low systemic toxicity in murine model system. The results prove that the DOX-ZnONPs has low toxicity and high therapy efficacy, which provides convincing evidence for the green biosynthesized ZnO as a promising candidate for a drug delivery system.

Background To explore the pyrimido quinolin derivative, 4-methyl pyrimido (5, 4-c) quinoline-2,5(1H, 6H)-dione and its potential antiviral activity against influenza virus. Methods Pyrimido quinolin derivative was synthesized and characterized. Madin–Darby Canine Kidney (MDCK) cells were cultured and antiviral assays were performed to evaluate its antiviral activity against pandemic influenza A/H1N1 (2009) virus. Results and discussion The effective inhibitory concentration (EC50) of synthesized compound against influenza virus was determined as 21 μM. RT-PCR analysis revealed that, at the 21 μM concentration of test compound found to inhibit the influenza viral RNA synthesis. The western blot study revealed that 21 μM of test compound was significantly inhibited the viral neuraminidase (NA) expression. Conclusion The present study well documented that the test compound was found to be a potent inhibitor of pandemic influenza A/H1N1 (2009) virus replication in MDCK cells. Further viral inhibitory studies were evident that the 4-methyl pyrimido (5, 4-c) quinoline-2,5(1H, 6H)-dione could be effective against influenza viral replication.

The studies on protein-dye interactions are important in biological process and it is regarded as vital step in rational drug design. The interaction of thionine (TH) with human serum albumin (HSA) was analyzed using isothermal titration calorimetry (ITC), spectroscopic, and molecular docking technique. The emission spectral titration of HSA with TH revealed the formation of HSA-TH complex via static quenching process. The results obtained from absorption, synchronous emission, circular dichroism, and three-dimensional (3D) emission spectral studies demonstrated that TH induces changes in the microenvironment and secondary structure of HSA. Results from ITC experiments suggested that the binding of TH dye was favored by negative enthalpy and a favorable entropy contribution. Site marker competitive binding experiments revealed that the binding site of TH was located in subdomain IIA (Sudlow site I) of HSA. Molecular docking study further substantiates that TH binds to the hydrophobic cavity of subdomain IIA (Sudlow site I) of HSA. Further, we have studied the cytotoxic activity of TH and TH-HSA complex on breast cancer cell lines (MCF-7) by MTT assay and LDH assay. These studies revealed that TH-HSA complex showed the higher level of cytotoxicity in cancer cells than TH dye-treated MCF-7 cells and the significant adverse effect did not found in the normal HBL-100 cells. Fluorescence microscopy analyses of nuclear fragmentation studies validate the significant reduction of viability of TH-HSA-treated human MCF-7 breast cancer cells through activation of apoptotic-mediated pathways.

Mosquito vectors (Diptera: Culicidae) are responsible for transmission of serious diseases worldwide. Mosquito control is being enhanced in many areas, but there are significant challenges, including increasing resistance to insecticides and lack of alternative, cost-effective, and eco-friendly products. To deal with these crucial issues, recent emphasis has been placed on plant materials with mosquitocidal properties. Furthermore, cancers figure among the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Nanotechnology is a promising field of research and is expected to give major innovation impulses in a variety of industrial sectors. In this study, we synthesized titanium dioxide (TiO2) nanoparticles using the hydrothermal method. Nanoparticles were subjected to different analysis including UV–Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), zeta potential, and energy-dispersive spectrometric (EDX). The synthesized TiO2 nanoparticles exhibited dose-dependent cytotoxicity against human breast cancer cells (MCF-7) and normal breast epithelial cells (HBL-100). After 24-h incubation, the inhibitory concentrations (IC50) were found to be 60 and 80 μg/mL on MCF-7 and normal HBL-100 cells, respectively. Induction of apoptosis was evidenced by Acridine Orange (AO)/ethidium bromide (EtBr) and 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. In larvicidal and pupicidal experiments conducted against the primary dengue mosquito Aedes aegypti, LC50 values of nanoparticles were 4.02 ppm (larva I), 4.962 ppm (larva II), 5.671 ppm (larva III), 6.485 ppm (larva IV), and 7.527 ppm (pupa). Overall, our results suggested that TiO2 nanoparticles may be considered as a safe tool to build newer and safer mosquitocides and chemotherapeutic agents with little systemic toxicity.

Dengue is a mosquito-borne viral disease that has rapidly spread in all regions of the world in recent years. Female mosquitoes, mainly Aedes aegypti, transmit dengue. Approximately 3,900 million people, in 128 countries, are at risk of dengue infection. Recently, a focus has been provided on the potential of green-synthesized nanoparticles as inhibitors of the production of dengue viral envelope (E) protein in Vero cells and downregulators of the expression of dengue viral E gene. Algae are an outstanding reservoir of novel compounds, which may help in the fight against mosquito-borne diseases. In this research, silver nanoparticles (AgNP) were rapidly synthesized using a cheap extract of the alga Centroceras clavulatum. AgNP were characterized by UV–vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). In mosquitocidal assays, LC50 values of C. clavulatum extract against A. aegypti larvae and pupae were 269.361 ppm (larva I), 309.698 ppm (larva II), 348.325 ppm (larva III), 387.637 ppm (larva IV), and 446.262 ppm (pupa). C. clavulatum extract also exhibited moderate antioxidant activity, both in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays. LC50 values of C. clavulatum-synthesized AgNP were 21.460 ppm (larva I), 23.579 ppm (larva II), 25.912 ppm (larva III), 29.155 ppm (larva IV), and 33.877 ppm (pupa). Furthermore, C. clavulatum-synthesized AgNP inhibited dengue (serotype dengue virus type-2 (DEN-2)) viral replication in Vero cells. Notably, 50 μg/ml of green-synthesized AgNP showed no cytotoxicity on Vero cells while reduced DEN-2 viral growth of more than 80%; 12.5 μg/ml inhibited viral growth of more than 50%. Cellular internalization assays highlighted that untreated infected cells showed high intensity of fluorescence emission, which denotes high level of viral internalization. Conversely, AgNP-treated infected cells showed reduced levels of fluorescence, failing to show significant viral load. Overall, our study showed that alga-mediated synthesis of metal nanoparticles may be considered to develop newer, safer, and cheap tools in the fight against the dengue virus, serotype DEN-2, and its vector A. aegypti, with little cytotoxicity on mammalian cells.

Animal venoms and toxins are potential bioresources that have been known to mankind as a therapeutic tool for more than a century through folk and traditional medicine. The purified “disintegrin protein” (64 kDa) from the venom of the Indian cobra snake (Naja naja) exhibited cytotoxic effects of various types of human cancer cell lines such as breast cancer (MCF-7), lung cancer (A549) and liver cancer (HepG2). In vitro cytotoxicity, DNA fragmentation, an apoptotic assay and a cell cycle analysis were performed to evaluate the anticancer activity of disintegrin against the above cell lines. The IC50 value of disintegrin was determined to be 2.5 ± 0.5 μg/mL, 3.5 ± 0.5 μg/mL, and 3 ± 0.5 μg/mL for the MCF-7, A549 and HepG2 cell lines respectively. Moreover, the increased distribution of G0/G1 and S phase led to decreased populations of cells in the G2/M phase of MCF-7, HepG2 and A549 cells.

The anti-influenza A/HK (H3N2) virus activity of β-santalol was evaluated in MDCK cells and investigated the effect of β-santalol on synthesis of viral mRNAs. β-Santalol was investigated for its antiviral activity against influenza A/HK (H3N2) virus using a cytopathic effect (CPE) reduction method. β-Santalol exhibited anti-influenza A/HK (H3N2) virus activity of 86% with no cytotoxicity at the concentration of 100 μg/ml reducing the formation of a visible CPE. Oseltamivir also showed moderate antiviral activity of about 83% against influenza A/HK (H3N2) virus at the concentration of 100 μg/ml. Furthermore, the mechanism of anti-influenza virus action in the inhibition of viral mRNA synthesis was analyzed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), and the data indicated an inhibitory effect in late viral RNA synthesis compared with oseltamivir in the presence of 100 μg/ml of β-santalol. β-Santalol should be further studied for therapeutic and prophylactic potential especially for influenza epidemics and pandemics.

In this article, we report the validation of cancer nanotherapy for the treatment of cancers using quercetin (Qtn). Much attention has been paid to the use of nanoparticles (NPs) to deliver drugs of interest in vitro/in vivo. Highly developed NPs-based nano drug delivery systems (NDDS) are an attractive approach to target cancer cell apoptosis, which is related to the onset and progression of cancer. Conventional chemotherapy has some notable drawbacks, such as lack of specificity, requirement of high drug doses, adverse effects, and gradual development of multidrug resistance (MDR), that decrease the efficacy of cancer therapy. To overcome these challenges of chemotherapy, the achievement of high drug loading in combination with low leakage at physiological pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. To assist drug delivery, we have prepared PVPylated-TiO2NPs containing Qtn with high loading efficiency (26.6% w/w) as a NDDS. The Qtn-PVPylated-TiO2NPs are uptaken via endocytosis by cancer cells and can generate intracellular reactive oxygen species (ROS) in order to increase mitochondrial membrane potential loss (Δψm) and enable release of cytochrome-c, followed by dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. These novel nanocombinations can be utilized to improve cancer nanotherapy by induction of apoptosis in vitro. Analysis at the molecular level revealed that the Qtn-PVPylated-TiO2NPs nanocombinations induced Δψm-mediated apoptotic signaling pathways. Overall, this study demonstrated that careful design of non-toxic nanocarriers for cancer nanotherapy can yield affordable NDDS.

Mosquito-borne diseases represent a deadly threat for millions of people worldwide. The Culex genus, with special reference to Culex quinquefasciatus, comprises the most common vectors of filariasis across urban and semi-urban areas of Asia. In recent years, important efforts have been conducted to propose green-synthesized nanoparticles as a valuable alternative to synthetic insecticides. However, the mosquitocidal potential of carbon nanoparticles has been scarcely investigated. In this study, the larvicidal and pupicidal activity of carbon nanoparticle (CNP) and silver nanoparticle (AgNP) was tested against Cx. quinquefasciatus. UV-Vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, and Raman analysis confirmed the rapid and cheap synthesis of carbon and silver nanoparticles. In laboratory assays, LC50 (lethal concentration that kills 50 % of the exposed organisms) values ranged from 8.752 ppm (first-instar larvae) to 18.676 ppm (pupae) for silver nanoparticles and from 6.373 ppm (first-instar larvae) to 14.849 ppm (pupae) for carbon nanoparticles. The predation efficiency of the water bug Lethocerus indicus after a single treatment with low doses of silver and carbon nanoparticles was not reduced. Moderate evidence of genotoxic effects induced by exposure to carbon nanoparticles was found on non-target goldfish, Carassius auratus. Lastly, the plant extract used for silver nanosynthesis was tested for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Overall, our results pointed out that AgNP and CNP can be a candidate for effective tools to reduce larval and pupal populations of filariasis vectors, with reduced genotoxicity and impact on behavioral traits of other aquatic organisms sharing the same ecological niche of Cx. quinquefasciatus.