Biodiesel synthesis from chicken feather meal using S/AlMCM-41 catalyst and engine performance analysis.

In this study, Sulphated/AlMCM-41 (S/AlMCM-41) catalysts were synthesized and used to produce biodiesel from CFMO. Different percentages of S/AlMCM-41 catalysts were prepared and characterized by X-ray diffraction, BET studies, TPD, and SEM-EDS analysis. Sulphur incorporation to the MCM framework though reduced the surface area, and pore volume of the catalyst, sufficient acidity were produced in the catalyst surface. The existence of functional groups and the composition of the biodiesel obtained was analysed by FTIR and GC-MS. S/AlMCM-41 (80%) catalyst presented a high catalytic activity with maximum biodiesel conversion % when compared to other variants. The bio-ester produced from CFMO with S/AlMCM-41 (80%) catalyst possessed the higher calorific value of 50 MJ/kg and flashpoint of 153 °C and other properties analogous to the standard biodiesel. The engine performance was examined for biodiesel blends with neat diesel, where biodiesel blends performed better than neat diesel. The exhaust gas emission studies also highlighted that the obtained biodiesel showed emission characteristics similar to the standard biodiesel, whereas marginally higher emission for CO and CO2 of about 2.2 and 7.9% was reported.

Characterization of various acrylate based artificial teeth for denture fabrication.

Acrylic resins-based artificial teeth are frequently used for the fabrication of dentures has and contribute a very strong share in the global market. However, the scientific literature reporting the comparative analysis data of various artificial teeth is scarce. Focusing on that, the present study investigated various types of commercially available artificial teeth, composed of polymethyl methacrylate (PMMA). Artificial teeth are characterized for chemical analysis, morphological features, thermal analysis, and mechanical properties (surface hardness, compressive strength). Different types of artificial teeth showed distinct mechanical (compression strength, Vickers hardness) and thermal properties (thermal gravimetric analysis) which may be attributed to the difference in the content of PMMA and type and quantity of different fillers in their composition. Thermogravimetric analysis (TGA) results exhibited that vinyl end groups of PMMA degraded above 200 °C, whereas 340-400 °C maximum degradation temperature was measured by differential thermal analysis (DTA) for all samples. Crisma brand showed the highest compressive strength and young modulus (88.6 MPa and 1654 MPa) while the lowest value of Vickers hardness was demonstrated by Pigeon and Vital brands. Scanning electron microscope (SEM) photographs showed that Crisma, Pigeon, and Vital exhibited characteristics of a brittle fracture; however, Artis and Well bite brands contained elongated voids on their surfaces. According to the mechanical analysis and SEM data, Well bite teeth showed a significantly higher mechanical strength compared to other groups. However, no considerable difference was observed in Vickers hardness of all groups. Graphical abstract.

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation.

In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 µM, respectively, comparable to erlotinib (IC50 0.39 µM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.

Design, synthesis and molecular docking studies of thymol based 1,2,3-triazole hybrids as thymidylate synthase inhibitors and apoptosis inducers against breast cancer cells.

Natural product produced by plants has been the backbone for numerous anticancer agents. In the present work, natural bioactive thymol based 1,2,3-triazole hybrids have been synthesized and evaluated for anticancer activity in MCF-7 and MDA-MB-231 cancer cells. The synthesized molecules displayed desired pharmacokinetic predictions for an orally available drug. Among the synthesized hybrids, compound 4-((2-isopropyl-5-methylphenoxy)methyl)-1-o-tolyl-1H-1,2,3-triazole (10) was the most potent (IC50 6.17 µM) showing comparable cytotoxity to tamoxifen (IC50 5.62 µM) and 3.2 fold inhibition to 5-fluorouracil (IC50 20.09 µM) against MCF-7 cancer cells. Whereas against MDA-MB-231 cancer cells, compound 10 (IC50 10.52 µM) and 3-(4-((2-isopropyl-5-methylphenoxy)methyl)-1H-1,2,3-triazol-1-yl)benzoic acid (12) (IC50 11.41 µM) displayed 1.42 and 1.3 fold inhibition, respectively to tamoxifen (IC50 15.01 µM) whereas 2.4 fold and 2.2 activity to 5-Florouracil (IC50 25.31 µM). Furthermore, 10 and 12 significantly inhibited thymidylate synthase enzyme with 2.4 and 1.26 fold activity to standard drug, Pemetrexed (IC50 5.39 µM) suggesting their mode of action as thymidylate synthase inhibitors. Cell cycle arrest and annexin V induced apoptosis study of compound 10 showed cell cycle arrest at the G2/M phase and induction of apoptosis in MCF-7 cells. The molecular docking was accomplished onto thymidylate synthase (TS) protein. The active compounds exhibited promising binding interactions and binding affinities into active sites. Finally, density functional theory (DFT) calculations including chemical reactivity and molecular electrostatic potential (MEP) have been performed to confirm the data obtained from docking and biological experiments. The results from this study inferred that compound 10 could be served as a lead molecule for the treatment of breast cancer.

Microwave assisted one-pot synthesis, photophysical and physicochemical studies of novel biologically active heterocyclic Donor (D)-π-Acceptor (A) chromophore.

A donor-π-acceptor (D-π-A) chromophore, 2-amino-4-(9-ethyl-9H-carbazol-3-yl)-8-methoxy-5,6-dihydrobenzo[h]quinoline-3-carbonitrile (AEDQ) was synthesized from the condensation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one, 9-ethyl-9H-carbazole-3-carbaldehyde, malononitrile and NH4OAc in ethanol. Spectroscopic techniques and elemental analysis were employed to establish the structure of AEDQ. Photophysical parameters and fluorescence quantum yield were calculated in the different polarity solvents to evaluate the interactions of the solvent with AEDQ chromophore. Further, the interaction of the AEDQ with cationic and anionic surfactants (CTAB, SDS) were also evaluated by using fluorescence spectroscopy techniques. The intensity of the fluorescence spectrum increased as the concentration of surfactants increased, suggesting that strong interaction occurs between AEDQ with surfactants, and this interaction arises from electrostatic forces. As a result, the AEDQ chromophore could be used to determine the CMC of surfactants. The disc diffusion and minimal inhibitory concentration (MIC) technique were used to test in-vitro antibacterial activity against Gram +ve and Gram -ve bacteria, and the results are compared with the standard drug, tetracycline. AEDQ also showed good ADMET, pharmacokinetics and drug-likeness properties, which are desirable for a good drug candidate. The molecule also fits well in the DNA gyrase A active pocket site with the binding free energy of -17.92 kcal/mol, which testifies its good antibacterial activity.

Design, Molecular Modeling and Synthesis of Metal-Free Sensitizers of Thieno Pyridine Dyes as Light-Harvesting Materials with Efficiency Improvement Using Plasmonic Nanoparticles.

Considering the thiophene unit as an electron-rich heterocycle, it is investigated with the aim of elucidating its potential efficiency for solar cell application. With the introduction of active substituents such as COOEt, CONH2 and CN into the thiophene segment, three novel thieno pyridine sensitizers (6a-c), based on donor-acceptor D-π-A construction, are designed and synthesized. The effect of the anchoring groups is investigated based on their molecular orbital's (MO's) energy gap (Eg). The electrostatic interaction between the synthesized dyes and metal nanoparticles, namely gold, silver and ruthenium, is believed to improve their performance as organic sensitizers. The dye-sensitized solar cells (DSSCs) are manufactured using the novel diazenyl pyridothiophene dyes, along with their metal nanoparticles conjugates as sensitizers, and were examined for efficiency improvement. Accordingly, using this modification, the photovoltaic performance was significantly improved. The promising results of conjugate (6b/AgNPs), compared with reported organic and natural sensitizers (JSC (1.136 × 10-1 mA/cm2), VOC (0.436 V), FF (0.57) and η (2.82 × 10-2%)), are attributed to the good interaction between the amide, methyl, amino and cyano groups attached to the thiophene pyridyl scaffolds and the surface of TiO2 porous film. Implementation of a molecular modeling study is performed to predict the ability of the thiophene moiety to be used in solar cell applications.

Synthesis, Antibacterial, and Anti HepG2 Cell Line Human Hepatocyte Carcinoma Activity of Some New Potentially Benzimidazole-5-(Aryldiazenyl)Thiazole Derivatives.

The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence underwent interesting functionalization reactions to afford several series of benzimidazole-5-(aryldiazenyl)thiazole derivatives: 3a⁻c, 7a⁻c, and 8a⁻c. The antibacterial activities of the synthesized compounds were evaluated by calculation of the inhibition zone diameter (mm) and the determination of minimum inhibitory concentration (µg/mL) against selected pathogenic bacteria Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).Noticeable efficiency was found based on in vitro screening for their antioxidant activity and cytotoxicity effect against the human liver cancer cell line (HepG2) and human hepatocyte carcinoma cells at relatively high concentrations.

A comparative study of novel ruthenium(III) and iron(III) complexes containing uracil; docking and biological studies.

Structural and biological studies were conducted on the novel complexes [Fe(U)2(H2O)2]Cl3 (FeU) and [Ru(U)2(H2O)2]Cl3 (RuU) (U = 5,6-Diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) to develop an anticancer drug candidate. The two complexes have been synthesized and characterized. Based on our findings, these complexes have octahedral geometry. The DNA-binding study proved that both complexes coordinated with CT-DNA. The docking study confirmed the potency of both complexes in downregulating the topoisomerase I protein through their high binding affinity. Biological studies have established that both complexes can act as potent anticancer agents against three cancer cell lines. RuU or FeU complexes induce apoptosis in breast cancer cells by increasing caspase9 protein and inhibiting proliferating cell nuclear antigen (PCNA) activity. In addition, both complexes down-regulate topoisomerase I expression in breast cancer cells. Therefore, the RuU and FeU complexes' anticancer activities were mediated via both apoptosis induction and topoisomerase I down-regulation. In conclusion, both complexes have dual anticancer activity pathways that may be responsible for the selective cytotoxicity of the complexes. This makes them more suitable for the development of novel cancer treatment strategies.

Metal Oxide Heterojunction for Photocatalytic Activities.

There is a significant global demand for improvements in synthesis techniques and their optimal characteristics, especially for industrial-scale applications. Sol-gel-based solution combustion synthesis (SG-SCS) is a simple method to produce ordered porous materials. In this regard, Pearson's hard and soft acids and bases theory assists in selecting host-dopant reactivity to form a proper heterojunction. The formation of a heterojunction also changes the essential properties of the materials, improving photocatalysis via charge transfer or synergistic activities. A calcination temperature of 500 °C is ideal for this process based on the results of the stability assessment via a differential thermogravimetry ratio analysis (DTG). The nanoscale dimensions of the nanoparticles (NPs) and nanocomposites (NCs) generated were validated using X-ray diffraction and high-resolution transmission electron microscopy (HRTEM). Furthermore, the scanning electron microscopy micrographs and BET analyses confirmed the porosity nature of the materials. HRTEM, X-ray photoelectron spectroscopy, and energy-dispersive X-ray investigations established the materials composition. The study found that NCs degraded the acid orange 8 (AO8) color more efficiently than bare ZnO.

Behavior of Silica Nanoparticles Synthesized from Rice Husk Ash by the Sol-Gel Method as a Photocatalytic and Antibacterial Agent.

Silica nanoparticles (SiO2 NPs) are one of the most well-studied inorganic nanoparticles for many applications. They offer the advantages of tunable size, biocompatibility, porous structure, and larger surface area. Thus, in this study, a high yield of SiO2 NPs was produced via the chemical treatment of rice husk ash by the sol-gel method. Characteristics of the prepared SiO2 NPs were validated using different characterization techniques. Accordingly, the phase, chemical composition, morphological, and spectroscopic properties of the prepared sample were studied. The average particle size of the SiO2 NPs was found to be approximately 60-80 nm and the surface area was 78.52 m²/g. The prepared SiO2 NPs were examined as photocatalysts for the degradation of methyl orange (MO) dye under UV irradiation. It was found that the intensity of the characteristic absorption band of MO decreased gradually with exposure time increasing, which means the successful photodegradation of MO by SiO2 NPs. Moreover, the antibacterial activity of obtained SiO2 NPs was investigated by counting the coliform bacteria in the surface water using the most probable number (MPN) index method. The results revealed that the MPN of coliform bacteria untreated and treated by SiO2 NPs was estimated to be 170 CFU/100 mL and 10 CFU/100 mL, respectively, resulting in bacterial growth inhibition of 94.12%.

Thiolated Chitosan Microneedle Patch of Levosulpiride from Fabrication, Characterization to Bioavailability Enhancement Approach.

In this study, a first attempt has been made to deliver levosulpiride transdermally through a thiolated chitosan microneedle patch (TC-MNP). Levosulpiride is slowly and weakly absorbed from the gastrointestinal tract with an oral bioavailability of less than 25% and short half-life of about 6 h. In order to enhance its bioavailability, levosulpiride-loaded thiolated chitosan microneedle patches (LS-TC-MNPs) were fabricated. Firstly, thiolated chitosan was synthesized and characterized by nuclear magnetic resonance (1HNMR) spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Thiolated chitosan has been used in different drug delivery systems; herein, thiolated chitosan has been used for the transdermal delivery of LS. LS-TC-MNPs were fabricated from different concentrations of thiolated chitosan solution. Furthermore, the levosulpiride-loaded thiolated chitosan microneedle patch (LS-TC-MNP) was characterized by FTIR spectroscopic analysis, scanning electron microscopy (SEM) study, penetration ability, tensile strength, moisture content, patch thickness, and elongation test. LS-TC-MNP fabricated with 3% thiolated chitosan solution was found to have the best tensile strength, moisture content, patch thickness, elongation, drug-loading efficiency, and drug content. Thiolated chitosan is biodegradable, nontoxic and has good absorption and swelling in the skin. LS-TC-MNP-3 consists of 100 needles in 10 rows each with 10 needles. The length of each microneedle was 575 µm; they were pyramidal in shape, with sharp pointed ends and a base diameter of 200 µm. The microneedle patch (LS-TC-MNP-3) resulted in-vitro drug release of 65% up to 48 h, ex vivo permeation of 63.6%, with good skin biocompatibility and enhanced in-vivo pharmacokinetics (AUC = 986 µg/mL·h, Cmax = 24.5 µg/mL) as compared to oral LS dispersion (AUC = 3.2 µg/mL·h, Cmax = 0.5 µg/mL). Based on the above results, LS-TC-MNP-3 seems to be a promising strategy for enhancing the bioavailability of levosulpiride.

Economic and fast electro-flotation extraction of heavy metals from wastewater.

Fast electroflotation extraction of heavy metals from wastewater is described. The results of experimental investigations of the extraction of iron, aluminium and chromium hydroxides from aqueous solutions in the presence of surfactants of various natures and ions of calcium by electroflotation are presented. It was found that the presence of Ca2+ in the solution at a concentration of 0.5 g/L reduced the degree of electroflotation extraction of Al(OH)3, Fe(OH)3, Cr(OH)3 regardless of the nature of the electrolyte. The addition of surfactants in the system in the presence of Ca2+ increased the amount of extraction of the dispersed phase. The greatest effect is achieved with the help of anionic surfactant sodium dodecyl sulphate, while the degree of extraction reached 98%. The high efficiency of the process of electroflotation extraction of the dispersed phase was due to the hydrophobization of the particle surface owing to the adsorption of surfactants on the surface of hydroxides. The recent method is useful to treat wastewater contaminated with aluminium, iron and chromium metal ions. The reason is that this method is very fast working within 20 min; Moreover, pH 7.0 working made this method ideal for utilisation in natural water treatment economically.

Macroalgae in biomonitoring of metal pollution in the Bay of Bengal coastal waters of Cox's Bazar and surrounding areas.

Although coastal water marine algae have been popularly used by others as indicators of heavy metal pollution, data within the Bay of Bengal for the estuarine Cox's Bazar region and Saint Martin's Island has remained scarce. Using marine algae, the study herein forms an effort in biomonitoring of metal contamination in the aforementioned Bangladesh areas. A total of 10 seaweed species were collected, including edible varieties, analyzed for metal levels through the use of the technique of EDXRF. From greatest to least, measured mean metal concentrations in descending order have been found to be K > Fe > Zr > Br > Sr > Zn > Mn > Rb > Cu > As > Pb > Cr > Co. Potential toxic heavy metals such as Pb, As, and Cr appear at lower concentration values compared to that found for essential mineral elements. However, the presence of Pb in Sargassum oligocystum species has been observed to exceed the maximum international guidance level. Given that some of the algae species are cultivated for human consumption, the non-carcinogenic and carcinogenic indices were calculated, shown to be slightly lower than the maxima recommended by the international organizations. Overall, the present results are consistent with literature data suggesting that heavy metal macroalgae biomonitoring may be species-specific. To the best of our knowledge, this study represents the first comprehensive macroalgae biomonitoring study of metal contamination from the coastal waters of Cox's Bazar and beyond.

Levels and health risk assessment of heavy metals in dried fish consumed in Bangladesh.

As a cheap source of high-quality protein, healthy fats and essential nutrients, dried fish is a common item in the daily diet of the Bangladesh populace. In this study, ten types of widely consumed dried fish (H. neherius, T. lepturu, P.chinensis, P. affinis, A. mola, P. microdon, I. megaloptera, C. dussumieri, L. calcarifer, and G. chapra) were analyzed for Cr, Mn, Fe, Co, Cu, Zn, Se, Rb, Hg, Pb, Ni and As by using an Energy Dispersive X-ray Fluorescence (EDXRF) technique. The concentration of the studied metals was found in the order Fe > Zn > Hg > Cu > Se > Cr > Mn > Co > Rb > Pb, while As and Ni were below the limit of detection. All fish species showed moderate to high pollution, where the species H. Neherius and P. Chinensis are the most and least polluted ones, respectively. The probable source of contamination is the leaching from the drying pans into the fish samples, atmospheric deposition, anthropogenic contamination, etc. of the water body where these fish were harvested. The calculated hazard index for the general population was below the maximum limiting value (i.e., < 1) except for Hg to children. The carcinogenic risk showed values lower than the acceptable limit for cancer risks (10-6 to 10-4). Periodic monitoring of trace metals in the aquatic organisms along with fish is recommended to avoid any unexpected health hazards caused by the toxic heavy metals via fish consumption.

Microplastics pollution in salt pans from the Maheshkhali Channel, Bangladesh.

Microplastics (MP) were recognized as an emergent pollution problem due to their ubiquitous nature and bioaccumulative potential. Those present in salt for consumption could represent a human exposure route through dietary uptake. The current study, conducted in Bangladesh, reports microplastics contamination in coarse salt prepared for human consumption. Sea salt samples were collected from eight representative salt pans located in the country's largest salt farming area, in the Maheshkhali Channel, along the Bay of Bengal. Microplastics were detected in all samples, with mean concentrations ranging from 78 ± 9.33 to 137 ± 21.70 particles kg-1, mostly white and ranging in size from 500-1000 µm. The prevalent types were: fragments (48%) > films (22%) > fibers (15%) > granules and lines (both 9%). Fourier transform mid-IR and near-IR spectra (FT-MIR-NIR) analysis registered terephthalate (48%), polypropylene (20%), polyethylene (17%), and polystyrene (15%) in all samples. These results contribute to the MP's pollution knowledge in sea salts to understand and reduce this significant human exposure route and environmental pollution source in the future.

Enhancement of Ceramics Based Red-Clay by Bulk and Nano Metal Oxides for Photon Shielding Features.

We prepared red clays by introducing different percentages of PbO, Bi2O3, and CdO. In order to understand how the introduction of these oxides into red clay influences its attenuation ability, the mass attenuation coefficient of the clays was experimentally measured in a lab using an HPGe detector. The theoretical shielding capability of the material present was obtained using XCOM to verify the accuracy of the experimental results. We found that the experimental and theoretical values agree to a very high degree of precision. The effective atomic number (Zeff) of pure red clay, and red clay with the three metal oxides was determined. The pure red clay had the lowest Zeff of the tested samples, which means that introducing any of these three oxides into the clay will greatly enhance its Zeff, and consequently its attenuation capability. Additionally, the Zeff for red clay with 10 wt% CdO is lower than the Zeff of red clay with 10 wt% Bi2O3 and PbO. We also prepared red clay using 10 wt% CdO nanoparticles and compared its attenuation ability with the red clay prepared with 10 wt% PbO, Bi2O3, and CdO microparticles. We found that the MAC of the red clay with 10 wt% nano-CdO was higher than the MAC of the clay with microparticle samples. Accordingly, nanoparticles could be a useful way to enhance the shielding ability of current radiation shielding materials.

Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents.

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6-18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC50 1.1 µM), HCT-116 (IC50 2.6 µM), and HepG2 (IC50 1.4 µM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC50 in the range 1.95-4.24 µM, whereas the standard drug, Pemetrexed, showed IC50 7.26 µM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential.

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies.

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8-16 and 19-26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 µM compared to standard drug Erlotinib (IC50 0.30 µM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.

Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities.

PURPOSE: Depression is a mood disorder accompanied by intensive molecular and neurochemical alterations. Currently, available antidepressant therapies are not fully effective and are often accompanied by several adverse impacts. Accordingly, the ultimate goal of this investigation was to clarify the possible antidepressant effects of prodigiosins (PDGs) loaded with selenium nanoparticles (PDGs-SeNPs) in chronic unpredictable mild stress (CUMS)-induced depression-like behavior in rats. METHODS: Sixty Sprague Dawley rats were randomly allocated into six groups: control, CUMS group (depression model), fluoxetine (Flu, 10 mg/kg)+CUMS, PDGs+CUMS (300 mg/kg), sodium selenite (Na2SeO3, 400 mg/kg)+CUMS, and PDGs-SeNPs+CUMS (200 mg/kg). All treatments were applied orally for 28 consecutive days. RESULTS: PDGs-SeNPs administration prevented oxidative insults in hippocampal tissue, as demonstrated by decreased oxidant levels (nitric oxide and malondialdehyde) and elevated innate antioxidants (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase), in addition to the upregulated expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in rats exposed to CUMS. Additionally, PDGs-SeNPs administration suppressed neuroinflammation in hippocampal tissue, as determined by the decreased production of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6), increased anti-inflammatory cytokine interleukin-10, and decreased inflammatory mediators (prostaglandin E2, cyclooxygenase-2, and nuclear factor kappa B). Moreover, PDGs-SeNPs administration in stressed rats inhibited neuronal loss and the development of hippocampal apoptosis through enhanced levels of B cell lymphoma 2 and decreased levels of caspase 3 and Bcl-2-associated X protein. Interestingly, PDGs-SeNPs administration improved hormonal levels typically disrupted by CUMS exposure and significantly modulated hippocampal levels of monoamines, brain-derived neurotrophic factor, monoamine oxidase, and acetylcholinesterase activities, in addition to upregulating the immunoreactivity of glial fibrillary acidic protein in CUMS model rats. CONCLUSION: PDGs-SeNPs may serve as a prospective antidepressant candidate due to their potent antioxidant, anti-inflammatory, and neuroprotective potential.

Phytochemicals from Leucas zeylanica Targeting Main Protease of SARS-CoV-2: Chemical Profiles, Molecular Docking, and Molecular Dynamics Simulations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a contemporary coronavirus, has impacted global economic activity and has a high transmission rate. As a result of the virus's severe medical effects, developing effective vaccinations is vital. Plant-derived metabolites have been discovered as potential SARS-CoV-2 inhibitors. The SARS-CoV-2 main protease (Mpro) is a target for therapeutic research because of its highly conserved protein sequence. Gas chromatography-mass spectrometry (GC-MS) and molecular docking were used to screen 34 compounds identified from Leucas zeylanica for potential inhibitory activity against the SARS-CoV-2 Mpro. In addition, prime molecular mechanics-generalized Born surface area (MM-GBSA) was used to screen the compound dataset using a molecular dynamics simulation. From molecular docking analysis, 26 compounds were capable of interaction with the SARS-CoV-2 Mpro, while three compounds, namely 11-oxa-dispiro[4.0.4.1]undecan-1-ol (-5.755 kcal/mol), azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl) (-5.39 kcal/mol), and lorazepam, 2TMS derivative (-5.246 kcal/mol), exhibited the highest docking scores. These three ligands were assessed by MM-GBSA, which revealed that they bind with the necessary Mpro amino acids in the catalytic groove to cause protein inhibition, including Ser144, Cys145, and His41. The molecular dynamics simulation confirmed the complex rigidity and stability of the docked ligand-Mpro complexes based on the analysis of mean radical variations, root-mean-square fluctuations, solvent-accessible surface area, radius of gyration, and hydrogen bond formation. The study of the postmolecular dynamics confirmation also confirmed that lorazepam, 11-oxa-dispiro[4.0.4.1]undecan-1-ol, and azetidin-2-one-3, 3-dimethyl-4-(1-aminoethyl) interact with similar Mpro binding pockets. The results of our computerized drug design approach may assist in the fight against SARS-CoV-2.