Genome-wide association studies of salinity tolerance in local aman rice.

The present study aimed to identify and characterize new sources of salt tolerance among 94 rice varieties from varied geographic origins. The genotypes were divided into five groups based on their morphological characteristics at both vegetative and reproductive stages using salinity scores from the Standard Evaluation System (SES). The experiment was designed as per CRD (Completely Randomized Design) with 2 sets of salinity treatments for 8 dS/meter and 12 dS/meter, respectively compared with one non-salinized control set. Using a Soil Plant Analysis Development (SPAD) meter, assessments of the apparent chlorophyll content (greenness) of the genotypes were done to comprehend the mechanism underlying their salt tolerance.  To evaluate molecular genetic diversity, a panel of 1 K RiCA SNP markers was employed. Utilizing TASSEL 5.0 software, 598 filtered SNPs were used for molecular analysis. Whole-genome association studies (GWAS) were also used to investigate panicle number per plant (pn, tiller number per plant (till), SPAD value (spad), sterility (percent) (str), plant height (ph) and panicle length (pl. It is noteworthy that these characteristics oversee conveying the visible signs of salt damage in rice. Based on genotype data, diversity analysis divided the germplasm groups into four distinct clusters (I, II, III and IV). For the traits studied, thirteen significant marker-trait associations were discovered. According to the phenotypic screening, seven germplasm genotypes namely Koijuri, Asha, Kajal, Kaliboro, Hanumanjata, Akundi and Dular, are highly tolerant to salinity stress. The greenness of these genotypes was found to be more stable over time, indicating that these genotypes are more resistant to stress. Regarding their tolerance levels, the GWAS analysis produced comparable results, supporting that salinity-tolerant genotypes having minor alleles in significant SNP positions showed more greenness during the stress period. The Manhattan plot demonstrated that at the designated significant SNP position, the highly tolerant genotypes shared common alleles. These genotypes could therefore be seen as important genomic resources for accelerating the development and release of rice varieties that are tolerant to salinity.

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.

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.

Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice.

Chemoresistance and chemotherapy-related ovarian damage are well-reported in breast cancer (BC) young patients. Herein, the inhibition of the mitochondrial fission was invested to explore its chemosensitizing role in Paclitaxel (PTX)-resistant cells, and its ability to restore the ovarian integrity in mice receiving PTX or cisplatin chemotherapy. To establish these aims, PTX-resistance was generated in BC cells, which were treated with PTX in combination with Drp1 deficiency, via mdivi-1, or Drp1-specific siRNA transfection. Furthermore, the alterations in the ovarian structure and the endocrine-related hormones were explored in mice receiving repetitive doses of PTX or cisplatin. We found that combining PTX with mdivi-1 improved cell responsiveness to PTX, induced apoptosis- and autophagy-mediated cell death, and relieved cellular oxidative stress. Additionally, the expression of PCNA1 and cyclin B1 genes were downregulated, meanwhile, p53, p21, and mitochondrial fusion proteins (Mfu1&Mfu2) were increased. The in vivo investigations in mice demonstrated that PTX induced gonadotoxic damage similar to cisplatin, whereas dual treatment of mice with PTX+ mdivi-1 failed to restore their normal follicular count and the circulating levels of E2 and AMH hormones. These results suggested that combining Drp1 inhibition with PTX resensitized breast cancer cells to PTX but failed to offer enough protection against chemotherapy-related gonadotoxicity.

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility.

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.

Drought-Induced miRNA Expression Correlated with Heavy Metal, Phenolic Acid, and Protein and Nitrogen Levels in Five Chickpea Genotypes.

Drought is a prime stress, drastically affecting plant growth, development, and yield. Plants have evolved various physiological, molecular, and biochemical mechanisms to cope with drought. Investigating specific biochemical pathways related to drought tolerance mechanisms of plants through biotechnology approaches is one of the quickest and most effective strategies for enhancing crop production. Among them, microRNAs (miRNAs) are the principal post-transcriptional regulators of gene expression in plants during plant growth under biotic and abiotic stresses. In this study, five different chickpea genotypes (Inci, Hasan bey, Arda, Seçkin, and Diyar 95) were grown under normal and drought stress. We recorded the expression levels of microRNAs in these genotypes and found differential expression (miRNA396, miR408, miRNA414, miRNA528, and miRNA1533) under contrasting conditions. Results revealed that miRNA414 and miRNA528 considerably increased in all genotypes under drought stress, and expression levels of miRNA418, miRNA1533, and miRNA396 (except for the Seçkin genotype) were found to be higher under the watered conditions. These genotypes were also investigated for heavy metal, phenolic acid, protein, and nitrogen concentrations under normal and drought stress conditions. The Arda genotype showed a significant increase in nitrogen (5.46%) and protein contents (28.3%), while protein contents were decreased in the Hasan bey and Seçkin genotypes subjected to drought stress. In the case of metals, iron was the most abundant element in all genotypes (Inci = 15.4 ppm, Hasan bey = 29.6 ppm, Seçkin = 37.8 ppm, Arda = 26.3 ppm, and Diyar 95 = 40.8 ppm) under normal conditions. Interestingly, these results were related to miRNA expression in the chickpea genotypes and hint at the regulation of multiple pathways under drought conditions. Overall, the present study will help us to understand the miRNA-mediated regulation of various pathways in chickpea genotypes.

Morphological, Mineralogical, and Biochemical Characteristics of Particulate Matter in Three Size Fractions (PM10, PM2.5, and PM1) in the Urban Environment.

Air pollution in megacities is increasing due to the dense population index, increasing vehicles, industries, and burning activities that negatively impact human health and climate. There is limited study of air pollution in many megacities of the world including Pakistan. Lahore is a megacity in Pakistan in which the continuous investigation of particulate matter is very important. Therefore, this study investigates particulate matter in three size fractions (PM1, PM2.5, and PM10) in Lahore, a polluted city in south Asia. The particulate matter was collected daily during the winter season of 2019. The average values of PM1, PM2.5, and PM10 were found to be 102.00 ± 64.03, 188.31 ± 49.21, and 279.73 ± 75.04 µg m-3, respectively. Various characterization techniques including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX) were used. FT-IR and XRD techniques identified the minerals and compounds like quartz, peroxides, calcites and vaterite, feldspar group, kaolinite clay minerals, chrysotile, vaterite, illite, hematite, dolomite, calcite, magnesium phosphate, ammonium sulfate, calcium iron oxide, gypsum, vermiculite, CuSO4, and FeSO4. Morphology and elemental composition indicated quartz, iron, biological particles, carbonate, and carbonaceous particles. In addition, various elements like C, O, B, Mg, Si, Ca, Cl, Al, Na, K, Zn, and S were identified. Based on the elemental composition and morphology, different particles along with their percentage were found like carbonaceous- (38%), biogenic- (14%), boron-rich particle- (14%), feldspar- (10%), quartz- (9%), calcium-rich particle- (5%), chlorine-rich particle- (5%), and iron-rich particle (5%)-based. The main sources of the particulate matter included vehicular exertion, biomass consumption, resuspended dust, biological emissions, activities from construction sites, and industrial emissions near the sampling area.

Physicochemical Attributes and Antioxidant Potential of Kernel Oils from Selected Mango Varieties.

The current study appraises the variations in the yield and physicochemical and antioxidant attributes among kernel oils from the seven most widely consumed varieties of Pakistani mangoes, namely, Anwar Ratul, Dasehri, Fajri, Laal Badshah, Langra, Safed Chaunsa, and Sindhri. The yield of mango kernel oil (MKO) among the tested varieties of mangoes varied significantly (p < 0.05), ranging from 6.33% (Sindhri) to 9.88% (Dasehri). Physicochemical properties, including the saponification value, refractive index, iodine no., P.V, % acid value, free fatty acids, and unsaponifiable matter, for MKOs were noted to be 143.00-207.10 mg KOH/g, 1.443-1.457, 28.00-36.00 g/100 g, 5.5-2.0 meq/kg, 1.00-7.7%, 0.5-3.9 mg/g, and 1.2-3.3%, respectively. The fatty acid composition determined by GC-TIC-MS revealed the presence of 15 different fatty acids with variable contributions of saturated (41.92-52.86%) and unsaturated (47.140-58.08%) fatty acids. Among unsaturated fatty acids, values of monounsaturated and polyunsaturated fatty acids ranged from 41.92 to 52.85 and 7.72 to 16.47%, respectively. Oleic acid (25.69-48.57%), stearic acid (24.71-38.53%), linoleic acid (7.72-16.47%), and palmitic acid (10.00-13.26%) were the prominent fatty acids. The total phenolic content (TPC) and DPPH radical scavenging (IC50) capacity of MKOs varied from 7.03 to 11.00 mg GAE/g and 4.33 to 8.32 mg/mL, respectively. The results of most of the tested attributes varied significantly (p < 0.05) among the varieties selected. It can be concluded from the findings of this research work that MKOs from the tested varieties are potential sources of valuable ingredients for the development of nutrapharmaceuticals due to their potent antioxidant properties and high oleic fatty acid profile.

Avocado Seeds-Mediated Alleviation of Cyclosporine A-Induced Hepatotoxicity Involves the Inhibition of Oxidative Stress and Proapoptotic Endoplasmic Reticulum Stress.

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.

SNP Based Trait Characterization Detects Genetically Important and Stable Multiple Stress Tolerance Rice Genotypes in Salt-Stress Environments.

Soil salinity is a major constraint to rice production in coastal areas around the globe, and modern high-yielding rice cultivars are more sensitive to high salt stress, which limits rice productivity. Traditional breeding programs find it challenging to develop stable salt-tolerant rice cultivars with other stress-tolerant for the saline environment in Bangladesh due to large yield variations caused by excessive salinity fluctuations during the dry (boro) season. We examined trait characterization of 18 advanced breeding lines using SNP genotyping and among them, we found line G6 (BR9621-B-1-2-11) (single breeding line with multiple-stress-tolerant QTL/genes) possessed 9 useful QTLs/genes, and two lines (G4:BR9620-2-7-1-1 and G14: IR 103854-8-3-AJY1) carried 7 QTLs/genes that control the desirable traits. To evaluate yield efficiency and stability of 18 rice breeding lines, two years of field experiment data were analyzed using AMMI (additive main effect and multiplicative interaction) and GGE (Genotype, Genotype Environment) biplot analysis. The AMMI analysis of variance demonstrated significant genotype, environment, and their interaction, accounting for 14.48%, 62.38%, and 19.70% of the total variation, respectively, and revealed that among the genotypes G1, G13, G14, G17, and G18 were shown to some extent promising. Genotype G13 (IR 104002-CMU 28-CMU 1-CMU 3) was the most stable yield based on the AMMI stability value. The GGE biplot analysis indicates 76% of the total variation (PC1 48.5% and PC2 27.5%) which is performed for revealing genotype × environment interactions. In the GGE biplot analysis, genotypes were checked thoroughly in two mega-environments (ME). Genotype G14 (IR103854-8-3-AJY1) was the winning genotype in ME I, whereas G1 (BR9627-1-3-1-10) in ME II. Because of the salinity and stability factors, as well as the highest averages of grain yield, the GGE and AMMI biplot model can explain that G1 and G13 are the best genotypes. These (G1, G6, G13, G14, G17, and G18) improved multiple-stress-tolerant breeding lines with stable grain yield could be included in the variety release system in Bangladesh and be used as elite donor parents for the future breeding program as well as for commercial purposes with sustainable production.

Arthrospira platensis nanoparticles defeat against diabetes-induced testicular injury in rat targeting, oxidative, apoptotic, and steroidogenesis pathways.

Varieties of studies have been used to investigate the health benefits of Spirulina (Arthrospira platensis); however, more research is needed to examine if its nano form may be utilized to treat or prevent several chronic diseases. So, we designed this study to explore the effect and the cellular intracellular mechanisms by which Arthrospira platensis Nanoparticles (NSP) alleviates the testicular injury induced by diabetes in male Wistar rats. Eighty Wistar male rats (n = 80) were randomly allocated into eight groups. Group 1 is untreated rats (control), Group 2 including STZ-induced diabetic rats with 65 mg/kg body weight STZ (STZ-diabetic), Group 3-5: including diabetic rats treated with NSP1, NSP2, and NSP3 at 0.25, 0.5, and 1 mg/kg body weight, respectively, once daily orally by the aid of gastric gavage for 12 consecutive weeks and groups 6-8 include normal rats received NSP (0.25, 0.5, and 1 mg/kg body weight once daily orally. The identical volume of normal saline was injected into both control and diabetic rats. After 12 weeks of diabetes induction, the rats were killed. According to our findings, NSP administration to diabetic rats enhances the total body weight and the weight of testes and accessory glands; in addition, NSP significantly reduced nitric oxide and malondialdehyde in testicular tissue improved sperm parameters. Intriguingly, it raises testicular GSH and SOD activity by a significant amount (p < 0.05). As well, Oral administration of NSP to diabetic rats resulted in a decrease in the blood glucose levels, HA1C, induced in the diabetic group, which overcame the diabetic complications NSP caused down-regulation of apoptotic genes with upregulation of BCL-2 mRNA expression (p < 0.05) and prominent up-regulation of steroidogenesis genes expression level in testes in comparison to the diabetic rats which resulted in improving the decreased levels of testosterone hormone, FSH, and LH induced by diabetes. In the same way, our histopathological findings support our biochemical and molecular findings; in conclusion, NSP exerted a protective effect against reproductive dysfunction induced by diabetes not only through its high antioxidant and hypoglycemic action but also through its down-regulation of Apoptotic genes and up-regulation of steroidogenesis regulatory genes expression level in diabetic testes.

Alterations of Oxidative Stress Indicators, Antioxidant Enzymes, Soluble Sugars, and Amino Acids in Mustard [Brassica juncea (L.) Czern and Coss.] in Response to Varying Sowing Time, and Field Temperature.

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 (H2O2) (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.

Fabrication of Nanofibers Based on Hydroxypropyl Starch/Polyurethane Loaded with the Biosynthesized Silver Nanoparticles for the Treatment of Pathogenic Microbes in Wounds.

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.

Anti-Alzheimer's disease potential of Arabian coffee versus Date palm seed extract in male rats.

Coffee is among the most commonly consumed beverage all over the world. Studies have increasingly suggested caffeine and coffee as effective therapeutic interventions against Alzheimer's disease (AD). We have therefore utilized the aluminum chloride rat model for AD to compare the influence of moderately caffeinated (Arabian) and decaffeinated (Date palm seed) coffee on cognitive impairment and pathological events in AD. AD rats given Arabian or Date palm seed coffee were protected against memory impairment and had lower serum levels of the abnormal protein (amyloid-beta; Aß1-42), the central pathogenic contributor to AD, and transforming growth factor-beta (TGF-ß). Interestingly, Date palm seed (decaffeinated) coffee seems to provide more pronounced protection against AD than Arabian (moderately caffeinated) coffee as evidenced by the greater decrease in serum Aß levels. These results suggest a surprising therapeutic potential of moderate caffeine intake in Arabian coffee to ameliorate AD through decreasing serum Aß levels. However, Date palm seed (decaffeinated) coffee, rich in flavonoids, appears to provide a better AD-modifying ability through a direct reduction of Aß production. PRACTICAL APPLICATIONS: Consumption of moderately caffeinated Arabian coffee attenuated AD-induced cognitive impairment via its anti-amyloidogenic potential, decreasing Aß levels. Moreover, intake of decaffeinated Date seed extract, rich in flavonoids, exerted a superior anti-AD potential through a direct reduction of Aß production. Both of them were also safe and maintained hepatic and renal functions in a rat model of AlCl3 -induced AD. Further clinical studies are warranted to confirm current results and to recommend the regular drinking of Arabian coffee or Date seed extract as a protective approach to delay AD progression in vulnerable individuals or in early disease stages.

Synthesis of New Triazole-Based Thiosemicarbazone Derivatives as Anti-Alzheimer's Disease Candidates: Evidence-Based In Vitro Study.

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.

Sustainable Development of Chitosan/Calotropis procera-Based Hydrogels to Stimulate Formation of Granulation Tissue and Angiogenesis in Wound Healing Applications.

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.

Oriental Hornet (Vespa orientalis) Larval Extracts Induce Antiproliferative, Antioxidant, Anti-Inflammatory, and Anti-Migratory Effects on MCF7 Cells.

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.

Green coffee methanolic extract and silymarin protect against CCl4-induced hepatotoxicity in albino male rats.

BACKGROUND: During the last few decades, patients worldwide have been interested in using alternative medicine in treating diseases to avoid the increased side effects of chemical medications. Green coffee is unroasted coffee seeds that have higher amounts of chlorogenic acid compared to roasted coffee. Green coffee was successfully used to protect against obesity, Alzheimer disease, high blood pressure and bacterial infection. METHODS: This study aimed to investigate the probable protective activity of the green coffee methanolic extract, silymarin and their combination on CCl4-induced liver toxicity in male rats. Thirty Sprague - Dawley male albino rats were divided into 5 groups; control negative (G1) just got the vehicle (olive oil) and the other four groups received CCl4 dissolved in olive oil through an intraperitoneal injection and were divided into untreated control positive group (G2), the third group (G3) was treated with green coffee methanolic extract, the fourth group (G4) was treated with silymarin, and the fifth group (G5) was treated with a combination of green coffee methanolic extract and silymarin. RESULTS: In the positive control group treated with CCl4 (G2), the CCl4-induced toxicity increased lipid peroxidation, IL-6, kidney function parameters, liver function enzymes, total cholesterol, triglycerides and low-density lipoproteins, and decreased irisin, antioxidants, CYP450 and high-density lipoprotein levels. Hepatic tissues were also injured. However, treating the injured rats in G3, G4 and G5 significantly improved the altered parameters and hepatic tissues. CONCLUSIONS: Green coffee methanolic extract, silymarin, and their combination succeeded in protecting the male rats against CCl4 hepatotoxicity due to their antioxidant activity. Effect of green coffee methanolic extract mixed with silymarin in G5 was more efficient than that of green coffee methanolic extract in G3 or silymarin in G4.

Augmented anticancer activity of curcumin loaded fungal chitosan nanoparticles.

Fungal chitosan (FCt) from Amylomyces rouxii, with 88.7% deacetylation degree and 112.4 kDa molecular weight, was utilized for nanoparticles (NPs) formation via ionic gelation. FCt-NPs were employed as carriers for curcumin (CUR) to augment its availability and anticancer bioactivity. The synthesis of CUR/FCt-NPs composite was succeeded as evidenced from their FTIR spectra. The scanning micrographs of synthesized CUR/FCt-NPs indicated their spherical shapes and well-distribution; they had average diameters of 115 ± 21 nm and positive zeta potentials of +33.8 mV. The NPs loading capacity for CUR was 21.6% and the encapsulation efficiency reached 83.8%. The CUR was vastly released in the beginning 5 h then gradually released up to 90 h, with higher release in pH 5.2 than in pH 7.0. The treatment of cancer cells, HCT-116 and A-549, with CUR/FCt NPs lead to time-dependent decrement of cells' viability; the dead cells were 67.6% from HCT-116 and 73.8% from A-546 after 96 h of exposure. Fluorescent imaging indicated that most cancer cells entered the apoptosis phase after treatment with 150 µM of CUR/FCt-NPs for 72 h. The efficiency of FCt-NPs was proved as carriers for loading CUR and augmenting its anticancer activity toward human cancer cells, using these natural and biosafe agents.

Augmented control of drug-resistant Candida spp. via fluconazole loading into fungal chitosan nanoparticles.

Fungal chitosan (ACT) extraction from Amylomyces rouxii, its transforming into nano-form, loading with fluconazole (Flu) and evaluation of synthesized nanoconjugates against drug-resistant (DR) Candida spp., were investigated. The produced ACT was characterized with 112.4 kDa molecular weight and 88.7% deacetylation degree. Synthesis of chitosan nanoparticles (NACT), and loading them with Flu were succeeded, using ionic gelation protocol, to generate stable Flu/NACT nanoconjugate' particles with mean size of 82 nm and zeta potential of +3.36 mV. The NACT entrapment efficiency was 78.7% and the drug loading capacity was 60.2%. Flu slowly released from NACT during the first 5 h, then release dramatically increased to the maximum (94.8%) after 12 h. The infra-red spectrum of Flu/NACT nanoconjugates confirmed the strong cross-linkage between their molecules. The antimycotic activity of NACT and Flu/NACT was proved against DR strains of C. albicans (2 strains), C. parapsilosis and C. glabrata, using qualitative and quantitative assays; Flu/NACT exhibited significant powerful activity, which was confirmed via observations with scanning microscopy. Finished cotton textiles with Flu/NACT had augmented potentiality for inhibiting challenged DR Candida spp., using in vitro assay. Accordingly, the synthesis and application of Flu/NACT nanoconjugates was astoundingly recommended for controlling DR Candida spp.