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Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.

Triazole-based thiosemicarbazone derivatives (6a–u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

Fabrication of electrospun nanofibers based on the blending of modified natural polymer, hydroxyl propyl starch (HPS) as one of the most renewable resources, with synthetic polymers, such as polyurethane (PU) is of great potential for biomedical applications. The as-prepared nanofibers were used as antimicrobial sheets via blending with biosynthesized silver nanoparticles (AgNPs), which were prepared in a safe way with low cost using the extract of Nerium oleander leaves, which acted as a reducing and stabilizing agent as well. The biosynthesized AgNPs were fully characterized by various techniques (UV-vis, TEM, DLS, zeta potential and XRD). The obtained results from UV-vis depicted that the AgNPs appeared at a wavelength equal to 404 nm affirming the preparation of AgNPs when compared with the wavelength of extract (there are no observable peaks). The average particle size of the fabricated AgNPs that mediated with HPS exhibited a very small size (less than 5 nm) with excellent stability (more than −30 mv). In addition, the fabricated nanofibers were also fully characterized and the obtained data proved that the diameter of nanofibers was enlarged with increasing the concentration of AgNPs. Additionally, the findings illustrated that the pore sizes of electrospun sheets were in the range of 75 to 350 nm. The obtained results proved that the presence of HPS displayed a vital role in decreasing the contact angle of PU nanofibers and thus, increased the hydrophilicity of the net nanofibers. It is worthy to mention that the prepared nanofibers incorporated with AgNPs exhibited incredible antimicrobial activity against pathogenic microbes that actually presented in human wounds. Moreover, P. aeruginosa was the most sensitive species to the fabricated nanofibers compared to other tested ones. The minimal inhibitory concentrations (MICs) values of AgNPs-3@NFs against P. aeruginosa, and E. faecalis, were 250 and 500 mg/L within 15 min, respectively.

The formation of new scaffolds to enhance healing magnitude is necessarily required in biomedical applications. Granulation tissue formation is a crucial stage of wound healing in which granulation tissue grows on the surface of a wound by the formation of connective tissue and blood vessels. In the present study, porous hydrogels were synthesized using chitosan incorporating latex of the Calotropis procera plant by using a freeze–thaw cycle to stimulate the formation of granulation tissue and angiogenesis in wound healing applications. Structural analysis through Fourier transform infrared (FTIR) spectroscopy confirmed the interaction between chitosan and Calotropis procera. Latex extract containing hydrogel showed slightly higher absorption than the control during water absorption analysis. Thermogravimetric analysis showed high thermal stability of the 60:40 combination of chitosan (CS) and Calotropis procera as compared to all other treatments and controls. A fabricated scaffold application on a chick chorioallantoic membrane (CAM) showed that all hydrogels containing latex extract resulted in a significant formation of blood vessels and regeneration of cells. Overall, the formation of connective tissues and blood capillaries and healing magnitude decreased in ascending order of concentration of extract.

Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein–protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis. Graphical Abstract

Chitosan and its nanoparticles (NPs) could be extracted from numerous fungal species and used as effectual carriers for bioactive compounds. The fungal chitosan (FC) was innovatively acquired from Fusarium oxysporum grown mycelia, characterized and used for NP synthesis and loading with bee venom (BV). The nano-FC (NFC) had 192.4 nm mean NP diameter, 38.22% loading capacity, and 92.42% entrapment efficiency. BV release from NFC was pH and time dependent; burst BV release was detected at the first 6 h, followed by gradual releases up to 30 h. The in vitro anticancer potentiality valuation, of NFC, BV, and NFC/BV nanoconjugates against HeLa cervix carcinoma, revealed that they all had potent dose-dependent anticancer activity; BV/NFC nanoconjugates were the most effective with IC50=200 μg/mL. The fluorescent staining of treated HeLa cells with BV/NFC nanoconjugates, with DAPI and acridine orange/propidium iodide combination, indicated the appearance of early apoptosis, secondary apoptosis, and secondary necrosis markers and their increment with exposure prolongation. The production of NFC from F. oxysporum and their loading with BV are strongly counseled for production of potent natural antitumor agent with augmented activity against cervix carcinoma.

The impact of elevated temperature at the reproductive stage of a crop is one of the critical limitations that influence crop growth and productivity globally. This study was aimed to reveal how sowing time and changing field temperature influence on the regulation of oxidative stress indicators, antioxidant enzymes activity, soluble sugars (SS), and amino acids (AA) in Indian Mustard. The current study was carried out during the rabi 2017–2018 and 2018–2019 where, five varieties of mustard viz . Pusa Mustard 25 (PM-25) (V1), PM-26 (V2), BPR-541-4 (V3), RH-406 (V4), and Urvashi (V5) were grown under the field conditions on October 30 (normal sowing; S1), November 18 (late sowing; S2) and November 30 (very late sowing; S3) situations. The S1 and S3 plants, at mid-flowering stage, showed a significant variation in accumulation of SS (8.5 and 17.3%), free AA (235.4 and 224.6%), and proline content (118.1 and 133%), respectively, and played a crucial role in the osmotic adjustment under stress. The results showed that S3 sowing, exhibited a significant induction of the hydrogen peroxide (H 2 O 2 ) (110.2 and 86.6%) and malondialdehyde (23.5 and 47.5%) concentrations, respectively, which indicated the sign of oxidative stress in plants. Interestingly, the polyphenol oxidase, peroxidase, superoxide dismutase, and catalase enzyme activities were also significantly increased in S3 plants compared to S1 plants, indicating their significant roles in ameliorating the oxidative stress. Furthermore, the concentration of fatty acid levels such as palmitic, stearic, oleic, and linoleic acids level also significantly increased in S3 plants, which influenced the seed and oil quality. The study suggests that the late sowing significantly impaired the biochemical mechanisms in Indian mustard. Further, the mustard variety V4 (RH-406) was found to be effective for cultivation as well as environmental stress adoption in Indian soils, and it could be highly useful in breeding for developing heat-tolerant genotypes for ensuring the food security.

Advances in proteome research have opened the gateway to understanding numerous metabolic pathways and fundamental mechanisms involved in abiotic stress tolerance. In the present study, the antioxidant capacity of four tomato genotypes i.e., Kashi Amrit, Kashi Anupam, EC-317-6-1, and WIR-4360 was determined under drought stress to ascertain the scavenging potential for reactive oxygen species (ROS). A significant increase in the superoxide dismutase (SOD), Ascorbate peroxidase (APX), and catalase (CAT) activities in all the four genotypes under drought stress was observed, which seemed to be associated with a protective role against ROS (p < 0.001). Based on the antioxidant enzyme activities, a proteomic approach was applied to study differential protein expression in two selected genotypes from different species i.e., EC-317-6-1 (Solanum pimpinellifolium) and Kashi Amrit (Solanum lycopersicum) grown under irrigated, drought, and re-watering conditions. To reveal the protein network regulated under these conditions, two-dimensional gel electrophoresis was employed to identify and quantify the number of proteins in drought-sensitive (Kashi Amrit) and tolerant (EC-317-6-1) genotypes. Matrix-assisted laser desorption/ionization-time of flight analysis (MALDI-TOF) revealed a total of 453 spots after fine-tuning factors i.e., smoothness, saliency, and minimum area that responded to drought. Out of 453 total spots, 93 spots were identified in Kashi Amrit and 154 in EC-317-6-1 under irrigated conditions, whereas 4 spots were identified in Kashi Amrit and 77 spots in EC-317-6-1 under drought conditions. Furthermore, differentially expressed proteins were distinguished according to the fold change of their expression. Information provided in this report will be useful for the selection of proteins or genes in analyzing or improving drought tolerance in tomato cultivars. These findings may assist in the construction of a complete proteome database encompassing various divergent species which could be a valuable source for the improvement of crops under drought-stress conditions in the future.

Traditional mulch material (farmyard manure) has long been used in agriculture. However, recent developments have also introduced the scientific community and farmers to advanced chemicals such as potassium polyacrylamide (KPAM), which has revolutionised the concept of the soil water-holding capacity to many compared with other materials being used. To compare the effect of different organic and inorganic soil amendment materials under water stress conditions, a two-year (2018 and 2019) field study was conducted. The main plots consisted of irrigation treatments, i.e., I0 (control irrigation), I1 (drought-induced by skipping irrigation at the 4th leaf stage), and I2 (drought-induced by skipping irrigation at the anthesis stage). The subplots included a control treatment and soil amended with different conditioners such as potassium polyacrylamide (KPAM, 30 kg/ha), farmyard manure (FYM, 4 tons/ha), and biochar (10 tons/ha); these were mixed thoroughly with the soil before sowing. The results showed a significant reduction in the water relation parameters (water potential up to 35.77% and relative water content up to 21%), gas exchange parameters (net CO2 assimilation rate up to 28.85%, stomatal conductance up to 43.18%, and transpiration rate up to 49.07%), and yield attributes (biological yield up to 8.45% and grain yield up to 32.22%) under drought stress conditions. In addition, water stress also induced an increase in the synthesis of osmoprotectants (proline up to 77.74%, total soluble sugars up to 27.43%, and total free amino acids up to 11.73%). Among all the soil conditioners used, KPAM significantly reduced the negative effects of drought stress on the wheat plants. Thus, it could be concluded that the use of soil conditioners is a promising method for dealing with the negative consequences of drought stress for achieving sustainable crop yields.