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Previous research has shown that elevated temperature and environmental hypoxia are associated with a reduced representation of larger‐bodied species in communities of ectotherms, suggesting their competitive disadvantage resulting from increased oxygen demands and limited oxygen availability. To investigate this, we conducted a comparative analysis of two pairs of competing zooplankton species: Daphnia galeata (smaller‐bodied) and Daphnia pulex (larger‐bodied), as well as D. pulex (smaller‐bodied) and Daphnia magna (larger‐bodied). We monitored their population dynamics under different oxygen concentrations and temperatures, and additionally measured hemoglobin concentration in the latter pair. Contrary to expectations, the results demonstrated that the larger‐bodied species outcompeted the smaller‐bodied ones in all experimental treatments involving the first pair of species. In the second pair, elevated temperature favored the smaller‐bodied species, while environmental hypoxia had the opposite effect. The competitive advantage of D. pulex under elevated temperature likely stemmed from their ability to allocate energy from somatic growth to reproduction, as indicated by the increased number of reproducing females. Conversely, the competitive advantage of D. magna under environmental hypoxia may be attributed to their ability to reallocate energy from reproduction to somatic growth, as indicated by lower reproductive effort and greater plasticity in hemoglobin production. These findings indicate that elevated temperature and hypoxia can independently and jointly influence interspecific competitive abilities by impacting the pace of life. However, the numerical dominance of smaller‐sized species in warm and hypoxic zooplankton communities cannot be explained by their enhanced competitive abilities resulting from a more favorable oxygen supply demand balance. [ABSTRACT FROM AUTHOR]

Streptococcus mutans, a gram-positive oral pathogen, is the primary causative agent of dental caries. Biofilm formation, a critical characteristic of S. mutans, is regulated by quorum sensing (QS). This study aimed to utilize pharmacoinformatics techniques to screen and identify effective phytochemicals that can target specific proteins involved in the quorum sensing pathway of S. mutans. A computational approach involving homology modeling, model validation, molecular docking, and molecular dynamics (MD) simulation was employed. The 3D structures of the quorum sensing target proteins, namely SecA, SMU1784c, OppC, YidC2, CiaR, SpaR, and LepC, were modeled using SWISS-MODEL and validated using a Ramachandran plot. Metabolites from Azadirachta indica (Neem), Morinda citrifolia (Noni), and Salvadora persica (Miswak) were docked against these proteins using AutoDockTools. MD simulations were conducted to assess stable interactions between the highest-scoring ligands and the target proteins. Additionally, the ADMET properties of the ligands were evaluated using SwissADME and pkCSM tools. The results demonstrated that campesterol, meliantrol, stigmasterol, isofucosterol, and ursolic acid exhibited the strongest binding affinity for CiaR, LepC, OppC, SpaR, and Yidc2, respectively. Furthermore, citrostadienol showed the highest binding affinity for both SMU1784c and SecA. Notably, specific amino acid residues, including ASP86, ARG182, ILE179, GLU143, ASP237, PRO101, and VAL84 from CiaR, LepC, OppC, SecA, SMU1784c, SpaR, and YidC2, respectively, exhibited significant interactions with their respective ligands. While the docking study indicated favorable binding energies, the MD simulations and ADMET studies underscored the substantial binding affinity and stability of the ligands with the target proteins. However, further in vitro studies are necessary to validate the efficacy of these top hits against S. mutans. [ABSTRACT FROM AUTHOR]

The present study investigated the antioxidant potential of aqueous methanolic extracts of Hemidesmus indicus (L.) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this plant extract was assessed via antioxidant assays (DPPH, ABTS radical scavenging, and FRAP). Furthermore, 69 phytocompounds in total were derived from this plant using the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen 69 phytocompounds were docked against the Kelch–Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 Å) along with the standard drug (CPUY192018). H. indicus (L.) R.Br. extract (100 µg × mL−1) showed 85 ± 2.917%, 78.783 ± 0.24% of DPPH, ABTS radicals scavenging activity, and 161 ± 4 μg × mol (Fe (II)) g−1 ferric ion reducing power. The three top-scored hits, namely Hemidescine (−11.30 Kcal × mol−1), Beta-Amyrin (−10.00 Kcal × mol−1), and Quercetin (−9.80 Kcal × mol−1), were selected based on their binding affinities. MD simulation studies showed that all the protein–ligand complexes (Keap1–HEM, Keap1–BET, and Keap1–QUE) were highly stable during the entire simulation period, compared with the standard CPUY192018–Keap1 complex. Based on these findings, the three top-scored phytocompounds may be used as significant and safe Keap1 inhibitors, and could potentially be used for the treatment of oxidative-stress-induced health complications. [ABSTRACT FROM AUTHOR]

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. An in vitro analysis of the Ethyl acetate extract from A. flavus showed significant cytostatic effects (IC50: 16.25 μg/mL) against breast cancer cells (MCF-7). A morphological analysis of the cells and a flow cytometry of the cells with annexin V/Propidium Iodide suggested that the extract induced apoptosis in the MCF-7 cells. The extract of A. flavus increased reactive oxygen species (ROS) generation and caused a loss of mitochondrial membrane potential in MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was subjected to a gas chromatography-mass spectrometry (GC-MS) analysis. Interestingly, nine phytochemicals that induced cytotoxicity in the breast cancer cell line were found in the extract. The in silico molecular docking and molecular dynamics simulation studies revealed that two compounds, 2,4,7-trinitrofluorenone and 3α, 5 α-cyclo-ergosta-7,9(11), 22t-triene-6beta-ol exhibited significant binding affinities (−9.20, and −9.50 Kcal/mol, respectively) against Bcl-2, along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer. [ABSTRACT FROM AUTHOR]

The effect of nanoplastics (NPs) has been shown to interact with the effect of pollutants, including antibiotics. However, little is known about studies performed on freshwater organisms. In this study, we aimed to test the hypothesis that both NPs and antibiotics affect the life history traits of freshwater planktonic Daphnia magna, a model organism in ecotoxicological research, as well as the metabolic and taxonomic fingerprint of their gut microbiota, and whether there is an interaction in the effect of both stressors. To assess this, we experimented with the effect of different spherical polystyrene nanoplastic concentrations and antibiotic enrofloxacin measured through (i) the Daphnia body size and their selected reproductive parameters (the clutch size, egg volume, and total reproductive investment), (ii) the metabolomic diversity of gut microbiota (the respiration rate and the relative use of different carbon sources), and (iii) the microbial taxonomic diversity in the Daphnia intestine. Our results supported the hypothesis as each of the stressors on its own significantly influenced most of the measured parameters, and because there was a significant interaction in the effect of both stressors on all of the measured parameters. Therefore, the results suggest an interactive negative effect of the stressors and a possible link between the observed effects at the different levels of a biological organisation. [ABSTRACT FROM AUTHOR]

Numerous studies have revealed that artificial light at night alters the natural patterns of light in space and time and may have various ecological impacts at different ecological levels. However, only a few studies have assessed its effect on interactions between organisms in aquatic environments, including predator–prey interactions in lakes. To fill this gap, we performed a preliminary enclosure experiment in which we compared the foraging effect of juvenile perch (Perca fluviatilis) on a natural lake zooplankton community in the absence and presence of light of high-pressure sodium (HPS) lamps mimicking artificial light emitted by a boat. The results revealed that even short-lasting exposure to HPS lamps may result in increasing fish predation, which in turn decreased the mean body size in zooplankton populations (e.g. Bosmina thersites) and affected the relative proportion between different taxa in zooplankton communities. [ABSTRACT FROM AUTHOR]

Numerous studies have revealed a negative correlation between the body size and temperature among a variety of aquatic ectotherms. Many studies at individual and population levels indicated that this mechanism may be explained by the decrease of competitive abilities of larger- over smaller-bodied individuals, as the production of larger-bodied individuals is more limited due to greater susceptibility to decreased oxygen concentrations (i.e., environmental hypoxia) at elevated temperatures. However, this hypothesis is still not tested at the community level. To test this, we performed several experiments on the food thresholds (which is a proxy for competitive ability) of 6 zooplankton (Daphnia) species varying in body size, at high or low oxygen concentrations. Contrary to the hypothesis tested, hypoxia increased threshold food concentrations to a relatively greater extent in smaller species than in larger ones. This may be attributed to the better evolutionary adaptations of larger-bodied daphnids to oxygen-poor environments manifested in higher production of haemoglobin. The results obtained in this study cannot exclude the possibility that environmental hypoxia is responsible for the temperature-size pattern in aquatic ectotherms, as our experiments did not take into account the long-term energetic costs of expedited haemoglobin synthesis, which could shift size-dependent competitive power. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of guanidine carbonate and curcumin-loaded hollow mesoporous silica nanoparticles (GuC-HMSNAP) can be used as a therapeutic and to induce MCF-7 cell death. Due to its biological safety and high drug loading capacity, HMSNAP is becoming an increasingly important nanocarrier for cancer research. The features of drug-loaded nanocarriers are significantly altered particle size, pore size, surface area, and pore volume, confirming that a significant amount of drugs can be loaded in the nanocarriers while simultaneously allowing the maximum amount of drugs to be released from the nanocarriers. Here, guanidine-mediated apoptosis is analysed through western blotting; the results suggest that drug complexes result in downregulation of phosphorylation in Ser471 of Akt, Ser259 of c-Raf, and Ser241 of PDK1, upregulation of phosphorylation in GSK-3β Ser9, cleaved caspases, and cleaved PARP, which then partially induces intrinsic cell death in MCF-7. As a whole, our results demonstrate that GuC-HMNSAP is an efficient nanocarrier for effectively inducing cancer cell death. The current study focuses on developing a tumour-targeted functionalised nanocarrier that wraps hollow mesoporous silica nanoparticles. The guanidine carbonate and curcumin are immobilised on the surface of 3-aminopropyl-triethoxy silane (APTES)-decorated hollow mesoporous silica nanoparticles (HMSNP), as confirmed through XPS and NMR analysis. XPS analysis demonstrates that the shape of the hysteresis loops is modified and that pore volume and pore diameter are consequently decreased compared to control. Guanidine (85%) and guanidine–curcumin complex (90%) were successfully encapsulated in HMSNAP and showed a 90% effective and sustained release at pH 7.4 for up to 72 h. Acridine orange/ethidium bromide dual staining determined that GuC-HMNSAP induced more late apoptosis and necrosis at 48 and 72 h compared with Gu-HMNSAP-treated cells. Molecular investigation of guanidine-mediated apoptosis was analysed using western blotting. It was found that cleaved caspases, c-PARP, and GSK-3β (Ser9) had increased activity in MCF-7 cells. GuC-HMSNAP increased the activity of phosphorylation of oncogenic proteins such as Akt (Ser473), c-Raf (Ser249), PDK1 (Ser241), PTEN (Ser380), and GSK-3β (Ser9), thus inducing cell death in MCF-7 cells. Altogether, our findings confirm that GuC-HMNSAP induces cell death by precisely associating with tumour-suppressing proteins, which may lead to new therapeutic approaches for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute and severe infections. Increasing resistance to antibiotics has given rise to the urgent need for an alternative antimicrobial agent. A promising strategy is the inhibition of iron sequestration in the bacteria. The current work aimed to screen for inhibitors of pyoverdine-mediated iron sequestration in P. aeruginosa. As a drug target, we choose l-ornithine-N5-monooxygenase (PvdA), an enzyme involved in the biosynthesis of pyoverdine that catalyzes the FAD-dependent hydroxylation of the side chain amine of ornithine. As drug repurposing is a fast and cost-efficient way of discovering new applications for known drugs, the approach may help to solve emerging clinical problems. In this study, we use data about molecules from drug banks for screening. A total of 15 drugs that are similar in structure to l-ornithine, the substrate of PvdA, and 30 drugs that are sub-structures of l-ornithine were virtually docked against PvdA. N-2-succinyl ornithine and cilazapril were found to be the top binders with a binding energy of −12.8 and −9.1 kcal mol−1, respectively. As the drug-likeness and ADME properties of the drugs were also found to be promising, molecular dynamics studies were performed to further confirm the stability of the complexes. The results of this in silico study indicate that N-2-succinyl ornithine could potentially be explored as a drug for the treatment of P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5–ligand complexes. Four bioactive molecules (Bufadienolide (−12.30 kcal mol−1), Stigmasterol (−11.40 kcal mol−1), Isovitexin (−11.20 kcal mol−1), and Apigetrin (−11.20 kcal mol−1)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (−9.80 kcal mol−1). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED. [ABSTRACT FROM AUTHOR]

The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body's circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3β(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy. [ABSTRACT FROM AUTHOR]

Temperature has a wide range of effects on the biology and ecology of ectotherms, including fish. However, the literature provides only a few studies assessing its effect on their cognitive abilities. We tested the effect of temperature on the spatial learning rate of zebrafish by comparing the daily rate of change in the number of fish choosing the correct arm first and behavioural performance (i.e., distance travelled, time needed to locate the daily food reward and swimming speed) in two temperatures (21 and 31°C) in 7 successive sessions. The daily rate of change in behavioural performance was expressed as the percentage difference between the value in a given session and the value in the previous session. Two experiments were performed in a T‐maze with single feeders in the arms, one empty and the other with a food reward. In each of the experiments, we used 10 naive fish, which were placed in the T‐maze individually once a day. The fish were fed between sessions to avoid increasing differences in hunger levels and, in turn, increasing the differences in motivation to find the food between the temperature treatments. The results revealed that the learning rate was greater at the higher temperature, which was apparent in a greater percentage reduction in the time and distance travelled needed to locate the daily food reward between successive sessions at the higher temperature than at the lower temperature. The results show there was a significant effect of temperature on the daily rate of change in the number of fish choosing the correct arm, distance travelled and time needed to locate the daily food reward, which may be attributed to the positive effect of temperature on learning rate, and may indicate the importance of temperature for the cognitive testing of zebrafish. [ABSTRACT FROM AUTHOR]

Lower doses of capsaicin (8-methyl-N-vanillyl-6-nonenamide) have the potential to serve as an anticancer drug, however, due to its pungency, irritant effect, poor water solubility and high distribution volume often linked to various off-target effects, its therapeutic use is limited. This study aimed to determine the biodistribution and anticancer efficacy of capsaicin loaded solid lipid nanoparticles (SLNs) in human hepatocellular carcinoma in vitro. In this study, SLNs of stearic acid loaded with capsaicin was formulated by the solvent evaporation-emulsification technique and were instantly characterized for their encapsulation efficiency, morphology, loading capacity, stability, particle size, charge and in vitro drug release profile. Synthesized SLNs were predominantly spherical, 80 nm diameter particles that proved to be biocompatible with good stability in aqueous conditions. In vivo biodistribution studies of the formulated SLNs showed that 48 h after injection in the lateral tail vein, up to 15% of the cells in the liver, 1.04% of the cells in the spleen, 3.05% of the cells in the kidneys, 3.76% of the cells in the heart, 1.31% of the cells in the lungs and 0% of the cells in the brain of rats were determined. Molecular docking studies against the identified targets in HepG2 cells showed that the capsaicin is able to bind Abelson tyrosine-protein kinase, c-Src kinase, p38 MAP kinase and VEGF-receptor. Molecular dynamic simulation showed that capsaicin-VEGF receptor complex is highly stable at 50 nano seconds. The IC50 of capsaicin loaded SLNs in HepG2 cells in vitro was 21.36 μg × ml−1. These findings suggest that capsaicin loaded SLNs are stable in circulation for a period up to 3 d, providing a controlled release of loaded capsaicin and enhanced anticancer activity. [ABSTRACT FROM AUTHOR]

Numerous studies have tested the combined effect of the threat of predation by fish and low oxygen concentrations on the phenotypic plasticity of Daphnia. These studies assessed the trade‐off between minimising predation risk and the negative effects of oxygen deficiencies in the context of depth selection behaviour. We tested whether this trade‐off also affects physiological and life history traits. We expected an interactive effect between the threat of fish predation and low oxygen concentrations, such, that the net effect of both stressors would be antagonistic (lower than the sum of each of the stressors acting separately), rather than additive (or synergistic) on the majority of traits investigated, but we predicted synergistic effects on heat shock proteins (HSPs).To test this, we performed life table experiments in different oxygen concentrations (normoxia and hypoxia) and levels of predation threat (the presence and absence of fish kairomones) on HSP70 and putative HSP110, haemoglobin concentration and life history traits with small‐bodied Daphnia galeata and large‐bodied Daphnia pulex originating from waterbodies where there were different risks of fish predation.As predicted, the net effect of both stressors was antagonistic for most of the physiological and ecological variables studied. The presence of kairomones resulted in decreased body size of adults, egg size, egg size in relation to brood chamber volume, and in increased clutch size in relation to body size. These effects were weaker in hypoxia than in normoxia, which may suggest an existence of adaptive responses caused by a lower perceived risk in hypoxia than in normoxia, as the foraging abilities of fish are limited by oxygen deficiencies.The presence of kairomones hampered the production of haemoglobin in hypoxia for the clones of larger‐bodied species, which suggests the existence of a trade‐off between reduced visibility under positive‐size selective predation risk and increased efficiency of oxygen transport to body tissues. The presence of kairomones and hypoxia resulted in an increased level of putative HSP110, and the effect of kairomones was stronger in hypoxia than in normoxia. More complex results were obtained for the effect of both stressors on the level of HSP70.The findings of our study provide a new insight on the interactions between planktivorous fish and zooplankton in aquatic food webs. More specifically, these findings suggest the existence of unexplored size‐dependent eco‐physiological trade‐offs between minimising predation risk and mitigating the negative effects of oxygen deficiencies. [ABSTRACT FROM AUTHOR]

Increased temperature in the epilimnion and hypoxia in the metalimnion of a lake would result in an increase of positive-size-selective fish predation on zooplankton and in turn in a decrease of mean body size in zooplankton populations and communities. We tested this hypothesis in four types of experiments with juvenile rudd (Scardinius erythrophthalmus) foraging on Daphnia longispina in an indoor twin column tank system. In each experiment of the first three types, one column contained one of three types of experimental treatments differing from the control treatment (in the other column) by the following: (i) elevated temperature in the epilimnion, (ii) hypoxia in the metalimnion and (iii) simultaneous elevated temperature in the epilimnion and hypoxia in the metalimnion. In the fourth type of experiment, the gradients of temperature and oxygen concentration in both columns were the same, but prior to the experiments, Daphnia and fish in the control treatment were acclimated to normoxia and, in the experimental treatment, to hypoxia. The results confirmed our hypothesis, since the predation rate of fish was greater in each of the first three experimental treatments than in the control. We did not detect an effect of the acclimation to hypoxia on the predation rate of the fish. [ABSTRACT FROM AUTHOR]

The vertical distribution of planktonic animals, such as Daphnia , in overlapping gradients of food concentration and risk of visual predation should depend on Daphnia population density and should be the result of the group effect of optimizing decisions taken by each individual (juvenile or adult), trading-off a high growth rate to low mortality risk. We tested this hypothesis by comparing the theoretical distributions from simulations based on an experimentally parameterized, optimizing individual-based model (consistent with the assumptions of the concept of the interference ideal free distribution with costs) with distributions observed in laboratory experiments. The simulations were generated for two scenarios, where the shape of the functional response of fish is consistent with either type II or III. The results confirmed the hypothesis. The greatest similarity of the distributions obtained in the experiments and simulations was found for the simulations based on the scenario assuming the type III rather than type II for both age classes of Daphnia. This was consistent with the results of the experiments for the model parameterization, which revealed the type III functional response of fish. Therefore, the results suggest that aggregating may be maladaptive as an anti-vertebrate-predation defense in the case of zooplankton. [ABSTRACT FROM AUTHOR]

Male sexual dysfunction is considered one of the major consequences of diabetes mellitus. The medicinal plant, Mimosa pudica Linn. is believed to have numerous therapeutic effects, including anti-diabetic, anti-obesity, aphrodisiac, and a sexual behaviour-enhancing properties. In the present study, the significant effect of ethanolic extract of M. pudica L. to scavenge excessive free radicals and alleviate the deleterious effects of alloxan-induced diabetes on the male sexual system of rats was demonstrated. The rats treated with the M. pudica L. extract recovered their body weight, the weight of their reproductive organs, the characteristics of the sperm and the histocellular arrangement of the testes. In addition, significant levels of hormones (testosterone, follicle-stimulating hormone and luteinising hormone) increased in both serum and testicular homogenates of male diabetic rats treated with M. pudica L. extract. Further, antioxidant enzymes, SOD, CAT, GSH, and GPx levels are increased, and oxidative stress markers MDA and ROS are reduced in both serum and testicular homogenates of M. pudica L. extract treated male rats. Furthermore, an in silico molecular docking study was performed to predict high potential compounds of M. pudica L. extract against the PDE5 receptor. Two bioactive compounds, namely 3-Dibenzofuranamine (-11.1 kcal × mol -1 ), Stigmasta-7,16-dien-3-ol (-10.4 kcal × mol -1 ) showed the highest binding affinities with PDE5 enzyme, much higher than the reference drug sildenafil (-9.9 kcal × mol -1 ). According to these findings, bioactive compounds rich in ethanolic extract of M. pudica L. have significant aphrodisiac performance in diabetic rats.Communicated by Ramaswamy H. Sarma.

Numerous studies have indicated that temperature improves the visual capabilities of different ectotherms, including a variety of fish species. However, none of these studies has directly tested whether elevated temperature extends the visual detection distance - the distance from which a visual stimulus is detected. To test this hypothesis, we investigated the effect of temperature on the visual detection distance of zebrafish ( Danio rerio ) larvae by measuring the largest distance from a moving target that induced a neural response in the optic tectum. We applied advanced methods of functional calcium imaging such as selective plane illumination microscopy in combination with a miniature OLED screen. The screen displayed an artificial, mobile prey, appearing in the visual field of the larvae. We performed experiments in three temperature treatments (18, 23 and 28°C) on transgenic fish expressing a fluorescent probe (GCaMP5G) that changes intensity in response to altered Ca 2+ concentrations in the nerves in the optic tectum. Based on the obtained data, we also measured three additional parameters of the neural response in the optic tectum, each being a proxy of sensitivity to changes in the stimulus movement. We did not confirm our hypothesis, since the visual detection distance shortened as the temperature increased. Moreover, all of the three additional parameters indicated a negative effect of the temperature on the speed of the neural response to the stimuli. However, the obtained results could be explained not only by worse visual capabilities at the elevated temperature, but also by the differences in the visual field and in turn, the retinotopic location of the visual stimulus between the temperature treatments, since the stimulus in the experiments moved horizontally rather than forward and backward from the fish's eye., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 μg ml -1 IC 50 value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.

Objective: Site-specific and toxic-free drug delivery, is an interesting area of research. Nanoengineered drug delivery systems possess a remarkable potential for effective treatment of various types of cancers., Methods: In this study, novel Folic Acid (FA) conjugated keratin nanoparticles (NPs) were assembled with encapsulation and delivery of Rutin (Rt) into breast cancer cells through the overexpressed folate receptor. The biocompatible, Rt encapsulated FA conjugated keratin NPs (FA@Ker NPs) were successfully formulated by a modified precipitation technique. Their morphological shape and size, size distribution, stability, and physical nature were characterized and confirmed. The drug (Rt) encapsulation efficiency, loading capacity and release kinetics were also studied., Results: The observed results of molecular docking and density functionality theory of active drug (Rt) showed a strong interaction and non-covalent binding of the folate receptor and facilitation of endocytosis in breast cancer cells. Further, in vitro cytotoxic effect of FA@Ker NPs was screened against MCF-7 cancer cells, at 55.2 µg/mL of NPs and found to display 50% of cell death at 24h. Moreover, the NPs enhanced the uptake of Rt in MCF-7 cells, and the apoptotic effect of condensed nuclei and distorted membrane bodies was observed. Also, NPs entered into the mitochondria of MCF-7 cells and significantly increased the level of ROS which led to cell death., Conclusion: The developed FA@Ker NPs might be a promising way to enhance anti-cancer activity without disturbing normal healthy cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)