Application of green synthesized bimetallic nZVI-Cu nanoparticle as a sustainable alternative to chemical fertilizers to enhance growth and photosynthetic efficiency of rice seedlings.

Application of nanomaterials in agriculture has been extensively explored over the past decade leading to a wide ambit of nanoparticle-based agrochemicals. Metallic nanoparticles consisting of plant macro- and micro-nutrients have been used as nutritional supplements for plants through soil amendments, foliar sprays, or seed treatment. However, most of these studies emphasize monometallic nanoparticles which limit the range of usage and effectivity of such nanoparticles (NPs). Hence, we have employed a bimetallic nanoparticle (BNP) consisting of two different micro-nutrients (Cu & Fe) in rice plants to test its efficacy in terms of growth and photosynthesis. Several experiments were designed to assess growth (root-shoot length, relative water content) and photosynthetic parameters (pigment content, relative expression of rbcS, rbcL & ChlGetc.). To determine whether the treatment induced any oxidative stress or structural anomalies within the plant cells, histochemical staining, anti-oxidant enzyme activities, FTIR, and SEM micrographs were undertaken. Results indicated that foliar application of 5 mg L-1 BNP increased vigor and photosynthetic efficiency whereas 10 mg L-1 concentration induced oxidative stress to some extent. Furthermore, the BNP treatment did not perturb the structural integrity of the exposed plant parts and also did not induce any cytotoxicity. Application of BNPs in agriculture has not been explored extensively to date and this study is one of the first reports that not only documents the effectivity of Cu-Fe BNP but also critically explores the safety of its usage on rice plants making it a useful lead to design new BNPs and explore their efficacy.

Surface functionalization and size of polystyrene microplastics concomitantly regulate growth, photosynthesis and anti-oxidant status of Cicer arietinum L.

Microplastics are a recent entrant in the list of environmental pollutants, exhibiting great diversity owing to different sizes, surface charges, and morphologies. The present study explores the impact of varied size, surface functionalization, and concentration of polystyrene microplastics (PS MP) on plants. For this study, Cicer seedlings were exposed to two different sizes of PS (1 µm and 12 µm) with three different surface functionalization (plain, carboxylated, and aminated) and at three distinct concentrations (10, 50, and 100 mg/L). The growth and photosynthetic parameters (like pigment content, Hill activity, etc.) along with oxidative stress marker (ROS) and anti-oxidant enzyme activities (like Superoxide dismutase, Catalase, and Peroxidase) were assessed. The results incline towards the idea that with increasing concentration of PS, there was a decline in the growth of the seedlings. There was also a dose-dependent increase in oxidative stress due to the suppression of the action of antioxidant enzymes. The effect was more prominent for 12 µm PS, perhaps due to its larger size and adherence to roots resulting in mechanical damage as deduced from MDA levels in the seedlings. Besides, MP with negative surface charge was comparatively less toxic than uncharged or positively charged PS of 1 µm. Overall, it can be concluded that the impact of MP on plants does not rely on individual characteristics of the particles alone, rather it is a concerted result of various determinants like size, charge, and concentration.

Toxicity of polystyrene microplastics in freshwater algae Scenedesmus obliquus: Effects of particle size and surface charge.

Microplastics (MPs) are perpetual contaminants that are mostly generated by human activity and are deposited in aquatic ecosystem. MPs may react differently in aquatic organisms depending on their size, surface charge, and concentration. The current investigation examined the interactions of polystyrene (PS) microplastics (of varied charges and sizes) with Scenedesmus obliquus, a unicellular phytoplankton. It is observed that 1 µm PS-MPs produced increased oxidative stress than 12 µm PS-MPs as indicated by total reactive oxygen species (ROS), superoxide and hydroxyl radical generation, and lipid peroxidation results. Additionally, decreased photosynthetic effectiveness, membrane integrity and esterase activity were also observed for the lower sized MPs. Antioxidant enzyme activities like superoxide dismutase (SOD) activity and catalase (CAT) activity correlated well with the oxidative stress generation in the cells. The effects by both the sizes of MPs were dose dependent in nature. Given the importance of a rapidly developing scientific literature on the effects of MPs in freshwater organisms, understanding the dynamics of interactions with lower-level organisms becomes very relevant.

Genetic diversity assessment and biotechnological aspects in Aristolochia spp.

Aristolochia, belonging to the family Aristolochiaceae, has immense ecological significance due to its large size and huge geographic distribution. In the context of dealing with a genus with a huge number of species like Aristolochia, these markers come in handy to precisely identify a particular species and enumerate the genetic diversity. Also, certain species of Aristolochia are economically important due to the presence of secondary metabolites and vast use in traditional and modern medicine. But, the presence of profitable biochemical constituents in Aristolochia is very low and the breeding process of the plant is highly dependable on pollinators. Hence, identifying different biotechnological approaches to fasten the reproductive cycle of Aristolochia and increase the secondary metabolites is of great interest to the researchers. In this study, a comprehensive review has been established on different types of morphological/anatomical markers (starch grains with "Maltese cross"), phytochemical markers (aristolochic acid, triterpenoid, aristolactam etc.) and genetic markers (ISSR, SSR, DNA bar-coding) for various Aristolochia spp. We have also discussed the applications of different biotechnological tools in Aristolochia spp. which include discrete approaches to promote in vitro germination, in vitro shooting, root induction, somatic embryogenesis, synthetic seed production, acclimatization and hardening and sustainable production of secondary metabolites. In a nutshell, the present review is a first of kind approach to comprehensively demonstrate the genetic diversity studies and biotechnological aspects in Aristolochia spp. KEY POINTS: • Insights into the in vitro propagation of Aristolochia spp. • In vitro production and optimization of secondary metabolites. • Assessment of genetic diversity by molecular markers.

In Silico Analysis of the Apoptotic and HPV Inhibitory Roles of Some Selected Phytochemicals Detected from the Rhizomes of Greater Cardamom.

Occurrence of cervical cancer, caused due to persistent human papilloma virus (HPV) infection, is common in women of developing countries. As the conventional treatments are expensive and associated with severe side effects, there is a need to find safer alternatives, which is affordable and less toxic to the healthy human cells. Present study aimed to evaluate the anti-HPV and apoptotic potential of four compounds from the greater cardamom (Amomum subulatum Roxb. var. Golsey), namely rhein, phytosphingosine, n-hexadecenoic acid and coronarin E. Their anti-HPV and apoptotic potential were studied against viral E6, E7 and few anti-apoptotic proteins of host cell (BCL2, XIAP, LIVIN) by in silico docking technique. Phytochemicals from the plant extract were analysed and identified by LC/MS and GC/MS. Involvement of the target proteins in various biological pathways was determined through KEGG. Structural optimization of the three-dimensional structures of the ligands (four phytochemicals and control drug) was done by Avogadro1.1. Receptor protein models were built using ProMod3 and other advanced tools. Pharmacophore modelling of the selected phytochemicals was performed in ZINCPharmer. Swiss ADME studies were undertaken to determine drug likeness. The ligands and proteins were digitally docked in DockThor docking program. Protein flexibility-molecular dynamic simulation helped to study protein-ligand stability in real time. Finally, the correlation of evaluated molecules was studied by the use of principal component analysis (PCA) based on the docking scores. All the ligands were found to possess apoptotic and anti-cancer activities and did not violate Lipinsky criteria. n-Hexadecanoic acid and its analogues showed maximum efficacy against the target proteins. All the protein-ligand interactions were found to be stable. The uncommon phytochemicals identified from rhizomes of greater cardamom have anti-cancer, apoptotic and HPV inhibitory potentials as analysed by docking and other in silico studies, which can be utilized in drug development after proper experimental validation.

Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study.

BACKGROUND: Omicron (B.1.1.529), a variant of SARS-CoV-2 is currently spreading globally as a dominant strain. Due to multiple mutations at its Spike protein, including 15 amino acid substitutions at the receptor binding domain (RBD), Omicron is a variant of concern (VOC) and capable of escaping vaccine generated immunity. So far, no specific treatment regime is suggested for this VOC. METHODS: The three-dimensional structure of the Spike RBD domain of Omicron variant was constructed by incorporating 15 amino acid substitutions to the Native Spike (S) structure and structural changes were compared that of the Native S. Seven phytochemicals namely Allicin, Capsaicin, Cinnamaldehyde, Curcumin, Gingerol, Piperine, and Zingeberene were docked with Omicron S protein and Omicron S-hACE2 complex. Further, molecular dynamic simulation was performed between Crcumin and Omicron S protein to evaluate the structural stability of the complex in the physiological environment and compared with that of the control drug Chloroquine. RESULTS: Curcumin, among seven phytochemicals, was found to have the most substantial inhibitory potential with Omicron S protein. Further, it was found that curcumin could disrupt the Omicron S-hACE2 complex. The molecular dynamic simulation demonstrated that Curcumin could form a stable structure with Omicron S in the physiological environment. CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.

Biotechnology of camptothecin production in Nothapodytes nimmoniana, Ophiorrhiza sp. and Camptotheca acuminata.

Cancer is probably the deadliest human disease in recent years. In the past few years, rapid clinical progress has been made in the field of anticancer drug development. Plant secondary metabolites have been noted as extremely efficacious as promising natural source for anticancer therapy for many years. Camptothecin (CPT) is one of the popularly used anti-tumor drugs possessing clinically proven properties against a plethora of human malignancies that include ovarian and colorectal cancers. For the first time, CPT was obtained from the extracts of a Chinese medicinal tree, Camptotheca acuminata Decne. from the family Cornaceae. Subsequently, CPT was also isolated from the bark of Nothapodytes foetida (Wight) Sleumer (Icacinaceae). However, the availability of enough natural sources for obtaining CPT is a major constraint. Due to overexploitation and harvesting, loss of habitat, excessive trading, and unfavorable environmental factors, the natural source of CPT has become extinct or extremely limited and hence they are red listed under endangered species. Conventional propagation has also failed to meet the ever-expanding demand for CPT production. With this, biotechnological toolkits have constantly been used as a boon to produce sustainable source, utilization, and ex situ conservation of medicinal plants. The approaches serve as a supplement to traditional agriculture in the mass production of plant metabolites with potent bioactivities. Non-availability of enough anticancer medicine and the requirement to satisfy current demands need a sustainable source of CPT. With this background, we present a comprehensive review on CPT discovery, its occurrence in the plant kingdom, biosynthesis, phytochemistry, pharmacological properties, clinical studies, patterns of CPT accumulation, and biotechnological aspects of CPT production in three plants, viz., N. nimmoniana, Ophiorrhiza species, and C. acuminata.Key points• Biotechnological approaches on production of camptothecin from Nothapodytes nimmoniana, Ophiorrhiza species, and Camptotheca acuminata• In vitro propagation of camptothecin-producing plants• Genetic diversity and transgenic research on camptothecin-producing plants.

Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects.

Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.

In silico study of some selective phytochemicals against a hypothetical SARS-CoV-2 spike RBD using molecular docking tools.

BACKGROUND: This world is currently witnessing a pandemic outbreak of 'COVID-19' caused by a positive-strand RNA virus 'SARS-CoV-2'. Millions have succumbed globally to the disease, and the numbers are increasing day by day. The viral genome enters into the human host through interaction between the spike protein (S) and host angiotensin-converting enzyme-2 (ACE2) proteins. S is the common target for most recently rolled-out vaccines across regions. A recent surge in single/multiple mutations in S region is of great concern as it may escape vaccine induced immunity. So far, the treatment regime with repurposed drugs has not been too successful. HYPOTHESIS: Natural compounds are capable of targeting mutated spike protein by binding to its active site and destabilizing the spike-host ACE2 interaction. MATERIALS AND METHODS: A hypothetical mutated spike protein was constructed by incorporating twelve different mutations from twelve geographical locations simultaneously into the receptor-binding domain (RBD) and docked with ACE2 and seven phytochemicals namely allicin, capsaicin, cinnamaldehyde, curcumin, gingerol, piperine and zingeberene. Molecular Dynamic (MD) simulation and Principal Component Analysis (PCA) were finally used for validation of the docking results. RESULT: The docking results showed that curcumin and piperine were most potent to bind ACE2, mutated spike, and mutated spike-ACE2 complex, thereby restricting viral entry. ADME analysis also proved their drug candidature. The docking complexes were found to be stable by MD simulation. CONCLUSION: This result provides a significant insight about the phytochemicals' role, namely curcumin and piperine, as the potential therapeutic entities against mutated spike protein of SARS-CoV-2.

Iron-pulsing, a novel seed invigoration technique to enhance crop yield in rice: A journey from lab to field aiming towards sustainable agriculture.

Bulk fertilizer application is one of the easiest means of improving yield of crops however it comes with several environmental impediments and consumer health menace. In the wake of this situation, sustainable agricultural practices stand as pertinent agronomic tool to increase yield and ensure sufficient food supply from farm to fork. In the present study, efficacy of iron-pulsing in improving the rice yield has been elucidated. This technique involves seed treatment with different concentrations (2.5, 5 and 10 mM) of iron salts (FeCl3 and FeSO4) during germination. FeCl3 or FeSO4 was used to treat the sets and depending on the concentration of the salts, the sets were named as C2.5, C5, C10 and S2.5, S5, S10 (where C and S stands for FeCl3 and FeSO4 respectively and the numbers succeeding them denotes the concentration of salt in mM). Our investigation identified 72 h of treatment as ideal duration for iron-pulsing. At this time point, the seedling emergence attributes and activities of α-amylase and protease increased. The relative water uptake of the seeds also increased through upregulation of aquaporin expression. The treatment efficiently maintained the ROS balance with the aid of antioxidant enzymes and increased the iron content within the treated seeds. After transplantation in field, photosynthetic rate and chlorophyll content enhanced in the treated plants. Finally, the post-harvest agro-morphological traits (represented through panicle morphology, 1000 seed weight, harvest index) and yield showed significant improvement with treatment. Sets C5 and S5 showed optimum efficiency in terms of yield improvement. To our best knowledge, this study is the first report deciphering the efficacy of iron-pulsing as a safe, cost effective and promising technique to escalate the yield of rice crops without incurring an environmental cost. Thus, iron-pulsing is expected to serve as a potential tool to address global food security in years to come.

Two species of Ulva inhibits the progression of cervical cancer cells SiHa by means of autophagic cell death induction.

Edible green algal seaweeds, namely Ulva intestinalis and Ulva lactuca constitute a significant repository of popular herbal medicines in the Traditional Chinese Medicinal system. The present study aimed to assess the anticancer potential of these algal members and its mode of action in cervical cancer cells SiHa. The algal samples primarily extracted in methanol was fractionated into hexane, chloroform, and aqueous algal fractions, which inhibited the proliferation of SiHa cells in a dose-dependent manner, with the algal chloroform fractions harbouring the lowest IC50 dose of 141.38 µg/ml in U. intestinalis and 445.278 µg/ml in U. lactuca. These algal chloroform fractions when studied for their in-depth mode of action, were found to damage and pulverise the nuclei, resulting in a concomitant increase in subG0-phase of SiHa cells, studied by flow cytometry. The algal treatment also caused an increase in the number of acidic vesicles and enhanced the expression of LC3BII, p62 and atg12 proteins, which together pointed out autophagy as the induced mode of cell death. Upregulated Bax and p53 expression along with decreased Bcl2 expression also correlated to autophagic cell death. Decreased expression of E6 viral oncogene was noted as a significant response to algal fractions. Lastly, these potent algal fractions when characterised pharmacologically through GC-MS analysis were found to be rich in unsaturated fatty acids, majorly palmitic acid. Hence, this study concludes that the two species of Ulva successfully decreased the proliferation of SiHa cervical cancer cells through autophagy, hinting at palmitic acid being the major responsible bioactive compound in both.

Chloroform fraction of Chaetomorpha brachygona, a marine green alga from Indian Sundarbans inducing autophagy in cervical cancer cells in vitro.

Sundarbans Mangrove Ecosystem (SME) is a rich repository of bioactive natural compounds, with immense nutraceutical and therapeutic potential. Till date, the algal population of SME was not explored fully for their anticancer activities. Our aim is to explore the potential of these algal phytochemicals against the proliferation of cervical cancer cells (in vitro) and identify the mode of cell death induced in them. In the present work, the chloroform fraction of marine green alga, Chaetomorpha brachygona was used on SiHa cell line. The algal phytochemicals were identified by GCMS, LCMS and column chromatography and some of the identified compounds, known for significant anticancer activities, have shown strong Bcl-2 binding capacity, as analyzed through molecular docking study. The extract showed cytostatic and cytotoxic activity on SiHa cells. Absence of fragmented DNA, and presence of increased number of acidic vacuoles in the treated cells indicate nonapoptotic cell death. The mode of cell death was likely to be autophagic, as indicated by the enhanced expression of Beclin 1 and LC3BII (considered as autophagic markers) observed by Western blotting. The study indicates that, C. brachygona can successfully inhibit the proliferation of cervical cancer cells in vitro.

Lignan enriched fraction (LRF) of Phyllanthus amarus promotes apoptotic cell death in human cervical cancer cells in vitro.

Phyllanthus amarus is widely grown in this sub-continent and used traditionally to treat many common ailments. In the present study, lignan rich fraction of P. amarus extract was used on cervical cancer cell lines (HeLa, SiHa and C33A) to study it's mechanism of cell death induction. As the cells were treated with IC50 doses of LRF, characteristic apoptotic features were observed. Increased sub G0 population were observed both in Hela and C33 cells, while G1/S arrest was observed in SiHa cells than their untreated counterparts. Increased production of ROS and change in MMP were also detected in the treated cells. Presence of γH2AX, was observed by immunofluorescence. Reduced expression of HPV (16/18) as well as ET-1, an autocrine growth substance, were observed in the treated cells. Immunoblotting as well as ICFC studies showed enhanced expressions of BAX, Caspase 3 and PARP (cleaved) in the treated cells. A major lignan, phyllanthin was isolated from the chloroform fraction and showed strong irreversible affinities for viral E6 and MDM2 in in silico analysis. The study conclusively indicates that LRF has the potential to induce apoptotic cell death in cervical cancer cells by activation of p53 and p21 against DNA damage.

Enhancement of nitrogen assimilation and photosynthetic efficiency by novel iron pulsing technique in Oryza sativa L. var Pankaj.

Rice is a major food crop. Due to urbanization and climate change, rice production is declining, posing a threat to the increasing food demand. For this, a modified technique of priming is used to enhance plant vigor. In the present study an endogenous rice cultivar was treated with two different iron salts for 72 h and grown for 14 days in nutrient solution. This increased the iron content of the samples which further escalated the photosynthetic efficiency and carbon assimilation in the treated plants. Photosynthesis being correlated to nitrogen assimilation, nitrogen assimilation intermediates and protein content were also elevated in treated plants. Plants showed no symptoms of stress as evident from low malondialdehyde content and increased antioxidant enzymes' activity. From this study it can be inferred that, treatment with iron during germination, helps to trigger growth by facilitating photosynthesis and nitrogen assimilation.

Betulinic acid induces DNA damage and apoptosis in SiHa cells.

Betulinic acid (BA) is a naturally occurring terpenoid found principally in the bark of birch trees as well as in numerous other plants. BA is reported to inhibit cancer progression and induce apoptosis in multiple tumor types. In the present study we have investigated the cytotoxicity and potential genotoxicity of BA in SiHa cells. The cell viability was measured by using MTT assay and the morphological changes, DNA damage, changes in cell cycle and mitochondrial membrane potential (MMP) were used for the assessment of apoptosis. BA was shown to destroy SiHa cells preferentially in a concentration dependent manner with a 50% inhibition of the cells at 39.83 µg/ml. The growth inhibition of the cells by BA was coupled with DNA strand breaks, morphological changes, disruption of MMP, reactive oxygen species (ROS) generation and the cell arrest at G0/G1 stage of cell cycle. BA induced apoptosis in SiHa cells was confirmed by positive Annexin V FITC-PI staining. Our results indicate that BA effectively induced DNA damage and apoptosis in SiHa cells. The mechanism of apoptosis was caspase independent and through mitochondrial pathways.

Structure-activity relationship on DNA binding and anticancer activities of a family of mixed-ligand oxidovanadium(V) hydrazone complexes.

The title family of mixed-ligand oxidovanadium(V) hydrazone complexes are [VVO(HL1)(hq)] (1) and [VVO(HL2)(hq)] (2), where (HL1)2- and (HL2)2- are the dinegative form of 2-hydroxybenzoylhydrazone of acetylacetone (H3L1) and benzoylacetone (H3L2), respectively, and hq- is the mononegative form of 8-hydroxyquinoline (Hhq). Complexes were used to determine their binding constant with CT DNA using various spectroscopic techniques namely, electronic absorption, fluorescence and circular dichroism spectroscopy. The binding constant values suggest the intercalative mode of binding with the CT DNA and follow the order: 2 > 1. The bulky size as well as electron withdrawing property of the phenyl group (which is present in the ß-diketone part of the hydrazone moiety in complex 2 in place of a CH3 group in complex 1) is responsible for the higher activity of 2 than 1. Complexes were screened for cytotoxic activity on cervical cancer cells and were found to be potentially active (IC50 value for 1 and 2 is 33 and 29 µM, respectively), even better than the widely used cis-platin (IC50 = 63.5 µM) and carboplatin (IC50 =  > 200 µM) which is evident from the respective IC50 value. Nuclear staining experiment suggests that these complexes kill the SiHa cancer cells through apoptotic mode. The molecular docking study also suggested the intercalative mode of binding of these complexes with CT DNA and HPV 18 DNA.

Exploring the effect of substituent in the hydrazone ligand of a family of µ-oxidodivanadium(v) hydrazone complexes on structure, DNA binding and anticancer activity.

The reaction of 2-hydroxybenzoylhydrazine (H2bh) separately with equimolar amounts of [VIVO(aa)2] and [VIVO(ba)2] in CHCl3 afforded the complexes [VO3(HL1)2] (1) and [VO3(HL2)2] (2) respectively in good to excellent yield ((HL1)2- and (HL2)2- represent respectively the dianionic form of 2-hydroxybenzoylhydrazones of acetylacetone (H3L1) and benzoylacetone (H3L2) (general abbreviation H3L)). From X-ray structure analysis, the VV-O-VV angle was found to be ∼115° and 180° in 1 and 2 respectively. Upon one-electron reduction selectively at one V centre at an appropriate potential, each of 1 and 2 generated mixed-valence [(HL)VVO-(µ-O)-OVIV(HL)]- species 1A and 2A respectively, which showed valence delocalization at room temperature and localization at 77 K, and the VIV-O-VV bond angles were calculated to be 177.5° and 180° respectively. The intercalative mode of binding of the two complexes 1 and 2 with CT DNA has been suggested by UV-visible spectroscopy (Kb = 7.31 × 105 M-1 and 8.71 × 105 M-1 respectively for 1 and 2), fluorescence spectroscopy (Ksv = 6.85 × 105 M-1 and 8.53 × 105 M-1 respectively for 1 and 2) and circular dichroism spectroscopy. Such intercalative mode of binding of these two complexes with CT DNA and HPV DNA has also been confirmed by molecular docking study. Both complexes 1 and 2 exhibited promising anti-cancer activity against SiHa cervical cancer cells with IC50 values of 28 ± 0.5 µM and 25 ± 0.5 µM respectively for 24 h which is significantly better than that of widely used cisplatin (with IC50 value of 63.5 µM). Nuclear staining experiments reveal that these complexes kill the SiHa cells through apoptotic mode. It is interesting to note that these two complexes are non-toxic to normal T293 cell line. Complex 2 showed higher DNA binding ability with CT DNA and HPV DNA as well as better anti-cancer properties towards SiHa cervical cancer cells in comparison to complex 1, a fact which can be explained by considering the lower energy of LUMO (which favours electron transition from DNA to the metal complex) and also the higher surface area of complex 2 in comparison to complex 1 due to the presence of one extra electron-withdrawing phenyl group in the former.

Surface capping and size-dependent toxicity of gold nanoparticles on different trophic levels.

In the present study, the toxicity of gold nanoparticles (Au NPs) was evaluated on various trophic organisms. Bacteria, algae, cell line, and mice were used as models representing different trophic levels. Two different sizes (CIT30 and CIT40) and surface-capped (CIT30-polyvinyl pyrrolidone (PVP)-capped) Au NPs were selected. CIT30 Au NP aggregated more rapidly than CIT40 Au NP, while an additional capping of PVP (CIT30-PVP capped Au NP) was found to enhance its stability in sterile lake water medium. Interestingly, all the forms of NPs evaluated were stable in the cell culture medium during the exposure period. Size- and dose-dependent cytotoxicities were observed in both bacteria and algae, with a strong dependence on reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release. CIT30-PVP capped Au NP showed a significant decrease in toxicity compared to CIT30 Au NP in bacteria and algae. In the SiHa cell line, dose- and exposure-dependent decline in cell viability were noted for all three types of Au NPs. In mice, the induction of DNA damage was size and dose dependent, and surface functionalization with PVP reduced the toxic effects of CIT30 Au NP. The exposure to CIT30, CIT40, and CIT30-PVP capped Au NPs caused an alteration of the oxidative stress-related endpoints in mice hepatocytes. The toxic effects of the gold nanoparticles were found to vary in diverse test systems, accentuating the importance of size and surface functionalization at different trophic levels.

Antiproliferative activity of methanolic extracts from two green algae, Enteromorpha intestinalis and Rizoclonium riparium on HeLa cells.

BACKGROUND: Natural compounds can be alternative sources for finding new lead anti-cancer molecules. Marine algae have been a traditional source for bioactive compounds. Enteromorpha intestinalis and Rhizoclonium riparium are two well distributed saline/brackish water algae from Sundarbans. There's no previous report of these two for their anti-proliferative activities. METHODS: Cytotoxicity of the algal methanolic extracts (AMEs) on HeLa cells were assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) reduction assay. Morphological examinations were done by Haematoxylin, Hoechst 33258 and Acridine orange staining. DNA fragmentation was checked. Gene expressions of Cysteine aspartate protease (Caspase) 3, Tumor protein (TP) 53, Bcl-2 associated protein X (Bax) were studied by Reverse transcription- polymerase chain reaction (RT-PCR) keeping Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as internal control. Protein expressions were studied for Caspase 3, phospho-p53, Bax, Microtubule associated proteins-1/ light chain B (MAP1/LC3B) by western blot. RESULTS: The AMEs were found to be cytotoxic with Inhibitory concentration 50 (IC50) values 309.048 ± 3.083 µg/ml and 506.081 ± 3.714 µg/ml for E. intestinalis and R. riparium extracts respectively. Treated cells became round with blebbings with condensed nuclei. Acidic lysosomal vacuoles formation occurred in treated cells. Expression of apoptotic genes in both mRNA and protein level was lowered. Expression of LC3B-II suggested occurrence of autophagy in treated cells. CONCLUSIONS: These two algae can be potent candidates for isolating new lead anticancer molecules. So they need further characterization at both molecular and structural levels.