Advancements in silk fibroin and silk sericin-based biomaterial applications for cancer therapy and wound dressing formulation: A comprehensive review.

Silks are a class of proteins generated naturally by different arthropods, including silkworms, spiders, scorpions, mites, wasps, and bees. This review discusses the silk fibroin and sericin fabricated by Bombyx mori silkworm as versatile fibers. It is predominantly composed of hydrophobic silk fibroin and hydrophilic silk sericin. Fibroin is defined as a structural protein that bestows silk with strength, while sericin is characterized as a gum-like protein, tying the two fibrous proteins together and endowing silk proteins with elasticity. Due to their versatile structures, biocompatibility, and biodegradability, they could be tailored into intricate structures to warrant particular demands. The intrinsic functional groups of both proteins enable their functionalization and cross-linking with various biomaterials to endow the matrix with favorable antioxidant and antibacterial properties. Depending on the target applications, they can be integrated with other materials to formulate nanofibrous, hydrogels, films, and micro-nanoparticles. Given the outstanding biological and controllable physicochemical features of fibroin and sericin, they could be exploited in pharmaceutical applications involving tissue engineering, wound repair, drug delivery, and cancer therapy. This review comprehensively discusses the advancements in the implementation of different formulations of silk fibroin and sericin in wound healing and drug delivery systems, particularly for cancer treatment.

Gender-specific responses in gene expression of Nile tilapia (Oreochromis niloticus) to heavy metal pollution in different aquatic habitats.

Monitoring heavy metal accumulation is essential for assessing the viability of aquatic ecosystems. Our methodology involved integrating analysis of immunological, stress, inflammatory, and growth-related gene expression in male and female Nile tilapia with on-site recordings of physicochemical parameters. Additionally, we assessed the effect of different physicochemical parameters on heavy metal bioavailability and residual concentration in fish and water. Samples of fish and water were gathered from three different localities: Lake Brullus, a brackish lake sited in northern Egypt; Lake Nasser, an artificial freshwater reservoir located in southern Egypt; and El-Qanater El-Khayria, a middle-freshwater location belonging to the Rashid branch of the river Nile. The assessment of heavy metal residues (Fe, Cu, Zn, Mn, and Ni) revealed that their concentrations were higher in fish specimens compared to their counterparts in water (except for Ni). In addition, Lake Brullus emerges as the most polluted area, exhibiting elevated levels of heavy metals concentrations in water and fish specimens. In contrast, Lake Nasser showed the least degree of heavy metals pollution. Gene expression analysis revealed gender-specific responses to heavy metal exposure at the three investigated water bodies. The expression of hepatic antioxidant genes (GST and MT) and inflammatory-related genes (CC-chemokine and TNFα) increased in males compared to females. In females, the immune and pro-inflammatory-related genes (IgM and CXC2-chemokine) transcripts were upregulated. Additionally, growth-related genes were downregulated in both Lake Brullus and El-Qanater; on the contrary, fish samples from Lake Nasser exhibited a normal expression pattern of growth-related genes. Stress-related genes (HSP70 and HSP27) showed significant downregulation in gills of both genders from Lake Brullus. The minimal presence of heavy metal contaminants in Lake Nasser seems to endorse the normal patterns of gene expression across all gene categories. A potential gender-specific gene expression response towards pollution was noticed in genes associated with inflammation and antioxidant activities. This highlights the importance of considering gender-related responses in future environmental assessments.

Novel tropane analogues as Hsp90 inhibitors targeting colon cancer: Synthesis, biological estimation, and molecular docking study.

New derivatives of tropane scaffold were prepared from the reaction of their thione or thioamide derivatives with α-halocarbonyl compounds. The structures of all new derivatives were assured and proved with their spectral data. The novel tropane derivatives were examined for their cytotoxicity on two colon tumor cell lines; Caco2 and HCT116 cells. The most active compounds 3, 4, 5, 9d and 14a displayed significant antitumor activities with IC50 range of 9.50 - 30.15 µM compared to doxorubicin. Moreover, they revealed reduced cytotoxic effect on WI-38 normal ones, signifying their great safety. With the aim of better understanding the inhibitory potential of such compounds on heat-shock protein 90 (Hsp90), there activities were assessed against such enzyme demonstrating high inhibitory activities with IC50 range of 56.58-78.85 nM. Western blotting was carried out to ensure the inhibitory activity on Hsp90, results showed that 3 markedly suppressed Hsp90 expression on Caco2 cell line. Additionally, a molecular docking analysis of the most potent derivatives at the Hsp90 binding site was carried out in order to approve the performed in vitro assays.

Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019.

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.

Health-related factors of the Iraqi adult population during the 2020 COVID-19 pandemic: physical activity, eating behavior, quality of life, general health, and mood states cross-talk.

BACKGROUND: The lockdown and social distancing caused by Coronavirus disease 2019 (COVID-19) may have changed Physical Activity Level (PAL), eating behavior, and health habits due to long-term confinement worldwide. OBJECTIVE: This study aimed to evaluate the PAL, eating behavior, Quality of Life (QoL), General Health (GH), and mood states during COVID-19 confinement in a large sample of Iraqi adults. METHODS: 3738 healthy adults (age 18-70 years) residing in Halabjeh, Iraq answered the online questionnaires including the short form of international physical activity, GH, three-factor eating (TFEQ-R18), and a short form of the profile of mood states (POMS-SF) questionnaires. Data analysis was done by Chi-square, and Spearman's correlation using SPSS statistical software at a significant level of (P < 0.05). RESULTS: The results showed unfavorable PAL, eating behavior, QoL, GH, and mood states in the total population. Low PAL was observed in 69.96% of the men and 75.99% of the women; only 3.60% of the men and 0.77% of the women had a high PAL. There was a significantly positive relationship between low PAL and the incidence of COVID-19 both in men and women (P = 0.801; r = 0.001; and P = 0.682; r = 0.011), respectively; While a significant negative relationship was observed between the moderate and high PAL and the incidence of COVID-19 in men (P = 0.011; r=-0.682 and P = 0.027, r=-0.589), and women (P = 0.001; r=-0.796 and P = 0.018, r=-0.623). No significant relationships were observed between PAL and eating behavior (men: P = 0.086; r = 0.256 and women: P = 0.365, r=-0.121); While, the results show significant positive relationships between PAL with QoL in men (P = 0.012; r = 0.623) and women (P = = 0.001; r = 0.837). based on the results, significant negative relationships between PAL with GH and mood state scores were observed in both men (P = 0.001; r=-0.837 and P = 0.001, r=-0.786) and women (P = 0.010; r=-0.652 and P = 0.001, r=-0.745), respectively. CONCLUSIONS: The Iraqi adult population showed low PAL, GH, QoL, and mood state during COVID-19 which might be due to the confinement. Also, the significant relationships between low PAL with GH, and mood state recommends physical activity as a valuable health optimizing factor during the COVID-19 pandemic.

Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors.

With the aim of developing cyclin-dependent kinase 2 (CDK2) inhibitors with strong antibreast cancer efficacy, new tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives were synthesized. The newly synthesized tri- and tetracyclic derivatives were achieved from the reaction of 4-(4-morpholin-4-yl-phenyl)-1,3,4,5,6,7-hexahydro-benzo[6,7]cyclohepta[1,2-d]pyrimidine-2-thione (5) with α-haloketone derivatives as hydrazonyl chlorides, phenacyl bromide derivatives, chloroacetone, and ethyl substituted acetate derivatives. The MCF-7 and MDA-MB-231 breast cancer cell lines were utilized to examine the anticancer properties. Compounds 5 and 8 were shown to be the most effective, with half-maximal inhibitory concentration (IC50 ) values between 5.73 and 9.11 µM, which are on the level with doxorubicin. Mechanistic studies showed that 5 and 8 caused tumor cell death by inducing apoptosis and they also produced cancer arrest in the S phase of the cell cycle. In addition, compounds 5 and 8 showed strong anti-CDK2 action (IC50 = 0.112 and 0.18 µM, respectively) comparable to roscovitine (IC50 = 0.127 µM). Moreover, the docking result demonstrated that derivatives 5 and 8 fit into the CDK2 active site in the proper orientation.

Characterization and anti-aging effects of Opuntia ficus-indica (L.) Miller extracts in a D-galactose-induced skin aging model.

Opuntia ficus-indica (L.) Miller (OFI), belonging to the family Cactaceae, is widely cultivated not only for its delicious fruits but also for its health-promoting effects, which enhance the role of OFI as a potential functional food. In this study, the in vitro collagenase and elastase enzyme inhibitory effects of extracts from different parts of OFI were evaluated. The most promising extracts were formulated as creams at two concentrations (3 and 5%) to investigate their effects on a D-galactose (D-gal)-induced skin-aging mouse model. The ethanolic extracts of the peel and cladodes exhibited the highest enzyme inhibitory effects. Cream made from the extract of OFI peel (OP) (5%) and cream from OFI cladodes extract (OC) (5%) significantly decreased the macroscopic aging of skin scores. Only a higher concentration (5%) of OC showed the normalization of superoxide dismutase (SOD) and malondialdehyde (MDA) skin levels and achieved significant improvements as compared to the vitamin E group. Both OC and OP (5%) showed complete restoration of the normal skin structure and nearly normal collagen fibres upon histopathological examination. The Ultra-Performance Liquid Chromatography High Resolution Mass Spectrometry (UHPLC-ESI-TOF-MS) metabolite profiles revealed the presence of organic acids, phenolic acids, flavonoids, betalains, and fatty acids. Flavonoids were the predominant phytochemical class (23 and 22 compounds), followed by phenolic acids (14 and 17 compounds) in the ethanolic extracts from the peel and cladodes, respectively. The anti-skin-aging effects could be attributed to the synergism of different phytochemicals in both extracts. From these findings, the OFI peel and cladodes as agro-waste products are good candidates for anti-skin-aging phytocosmetics.

Impact of Dietary Administration of Seaweed Polysaccharide on Growth, Microbial Abundance, and Growth and Immune-Related Genes Expression of The Pacific Whiteleg Shrimp (Litopenaeus vannamei).

This work aims to determine the impact of dietary supplementation of polysaccharide, extracted from brown seaweeds Sargassum dentifolium on growth indices, feed utilization, biochemical compositions, microbial abundance, expressions of growth and immunity-related genes, and stress genes of the Pacific Whiteleg shrimp Litopenaeus vannamei. A total of 360 post-larvae of L. vannamei were randomly distributed into a 12-glass aquarium (40 L of each) at a stocking density of 30 shrimp with an initial weight of (0.0017 ± 0.001 g). During the 90-day experiment trial, all shrimp larvae were fed their respective diets at 10% of total body weight, three times a day. Three experimental diets were prepared with different seaweed polysaccharide (SWP) levels. The basal control diet had no polysaccharide level (SWP0), while SWP1, SWP2, and SWP3 contained polysaccharides at concentrations of 1, 2, and 3 g kg-1 diet, respectively. Diets supplemented with polysaccharide levels showed significant improvements in weight gain and survival rate, compared to the control diet. Whole-body biochemical composition and the microbial abundance (the total count of heterotrophic bacteria and Vibrio spp.) of L. vannamei showed significant differences among polysaccharide-treated diets compared to the control. At the end of the feeding experiment, the dietary supplementation of polysaccharide levels enhanced the expression of growth-related genes (Insulin-like growth factors (IGF-I, IGF-II), immune-related genes (ß -Glucan-binding protein (ß-Bgp), Prophenoloxidase (ProPO), Lysozyme (Lys), and Crustin), and stress genes (Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) in the muscle tissue of L. vannamei. However, the current study concluded that the inclusion rate of 2 g kg-1 of polysaccharide as a dietary additive administration enhanced both weight gain and survival rate of L. vannamei, while the incorporation level of 3 g kg-1 reduces the abundance of pathogenic microbes and enhances the growth-, immunity- and stress-related gene expressions of L. vannamei.

Prognostic and survival impact of BCL9 and RPS6KB1 copy number variation detected from circulating free DNA in hepatocellular carcinoma.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a noninvasive substitute to liver biopsy for hepatocellular carcinoma (HCC) molecular profiling. This study aimed to use cfDNA to investigate copy number variation (CNV) in the BCL9 and RPS6KB1 genes and its impact on prognosis in HCC. METHODS: Real-Time Polymerase Chain Reaction was used to determine the CNV and cfDNA integrity index in 100 HCC patients. RESULTS: CNV gain in BCL9 and RPS6KB1 genes was detected in 14% and 24% of patients, respectively. Gain in CNV of BCL9 associated with risk of HCC in alcohol drinkers and hepatitis C seropositivity. In patients with RPS6KB1 gain, HCC risk increased with a high body mass index, smoking, schistosomiasis, and Barcelona clinical liver cancer stage (BCLC) A. Gain in both genes showed a high risk of HCC with elevated liver enzymes, Schistosomiasis, BCLC C, and PS > 1. The integrity of cfDNA was higher in patients with CNV gain in RPS6KB1 than those harboring CNV gain in BCL9. Lastly, BCL9 gain and BCL9 + RPS6KB1 gain led to higher mortality rates and reduced survival times. CONCLUSION: cfDNA was used to detect BCL9 and RPS6KB1 CNVs, which influence prognosis and can be used as independent predictors of HCC patient survival.

Therapeutic potential of two formulated novel chitosan derivatives with prominent antimicrobial activities against virulent microorganisms and safe profiles toward fibroblast cells.

The development of new antimicrobial agents has been drawing considerable attention due to the extreme escalation of multi-drug resistant microorganisms. We thus sought to ameliorate the antimicrobial activities of the chitosan (Cs) biopolymer by coupling chitosan with cyclohexanone and 2-N-methyl pyrrolidone, synthesizing two novel Schiff bases (CsSB1 and CsSB2), respectively. FT-IR, TGA, DSC, SEM, and potentiometric titration were employed to characterize the formulated chitosan derivatives. The findings exposed that the degrees of deacetylation were 88.12% and 89.98% for CsSB1 and CsSB2, respectively. The antimicrobial capacities of CsSB1 and CsSB2 were substantially enhanced compared with prime chitosan. Furthermore, the CsSB1 and CsSB2 demonstrated minimum inhibitory concentrations (MIC) of 50 µg/ml in relation to all studied microorganisms, whereas chitosan revealed MIC value of 50 µg/ml only for E. coli. Furthermore, CsSB1 with a concentration of 250 µg/ml manifested the highest antibacterial activity against Gram-positive bacteria. Correspondingly, CsSB2 revealed a comparable trend of microbial hindrance with lower activities. Besides, the two derivatives could thwart the growth of Candida albicans (C. albicans). The cytotoxicity assay of the biomaterials accentuated their biocompatibility with fibroblasts. Collectively, the two formulated chitosan derivatives could competently rival the native chitosan, particularly for future applications in wound healing.

Probiotic Potential of the Marine Isolate Enterococcus faecium EA9 and In Vivo Evaluation of Its Antisepsis Action in Rats.

This study aims to obtain a novel probiotic strain adapted to marine habitats and to assess its antisepsis properties using a cecal ligation and puncture (CLP) model in rodents. The marine Enterococcus faecium EA9 was isolated from marine shrimp samples and evaluated for probiotic potential after phenotypical and molecular identification. In septic animals, hepatic and renal tissues were histologically and biochemically evaluated for inflammation and oxidative stress following the probiotic treatment. Moreover, gene expressions of multiple signaling cascades were determined using RT-PCR. EA9 was identified and genotyped as Enterococcus faecium with a 99.88% identity. EA9 did not exhibit any signs of hemolysis and survived at low pH and elevated concentrations of bile salts. Moreover, EA9 isolate had antibacterial activity against different pathogenic bacteria and could thrive in 6.5% NaCl. Septic animals treated with EA9 had improved liver and kidney functions, lower inflammatory and lipid peroxidation biomarkers, and enhanced antioxidant enzymes. The CLP-induced necrotic histological changes and altered gene expressions of IL-10, IL-1ß, INF-γ, COX-2, SOD-1, SOD-2, HO-1, AKT, mTOR, iNOS, and STAT-3 were abolished by the EA9 probiotic in septic animals. The isolate Enterococcus faecium EA9 represents a promising marine probiotic. The in vivo antisepsis testing of EA9 highlighted its potential and effective therapeutic approach.

miR-516a-3P, a potential circulating biomarker in hepatocellular carcinoma, correlated with rs738409 polymorphism in PNPLA3.

Aim: The aim was to investigate the expression profile of miR-516a-3P and its correlation with the PNPLA3 rs738409 polymorphism in Egyptian hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) patients. Materials & methods: miR-516a-3P was quantified and rs738409 was genotyped by quantitative reverse transcription PCR. Results: miR-516a-3P was significantly upregulated in HCC patients compared with HCV patients (p = 0.001). Receiver operating characteristic curve analysis confirmed that miR-516a-3P discriminates HCC from HCV (p = 0.001). A significant (p = 0.015) correlation between miR-516a-3p level and PNPLA3 rs738409 genotypes was recorded in HCV patients, yet it was not recorded in either healthy individuals or HCC patients. miR-516a-3p level was significantly (p = 0.001) higher in HCV patients carrying the rs738409 GG genotype than in those carrying the CC genotype. Conclusion: miR-516a-3P is a potential biomarker in HCC. PNPLA3 rs738409 GG carriers affect miR-516a-3P expression in HCV, and this may highlight a new mechanism in liver disease.

In the past decade, miRNAs were established as biomarkers in various cancers, including liver cancer. Information about the deregulation of miR-516a-3p and its efficiency as a biomarker in hepatitis C virus (HCV) and liver cancer patients is lacking globally and in Egypt. This study proved for the first time that miR-516a-3p is differentially expressed in HCV and liver cancer patients and is statistically efficient in discriminating between them, so it might be used for early detection of HCC. Genetic variants that affect expression levels of genes are called expression quantitative trait loci (eQTL), and those acting on genes on other chromosomes are called trans-eQTL. The authors speculate that rs738409 is a genetic variant that might have a trans-eQTL effect on the miR-516a-3p gene in HCV patients.

IGF-1 receptor regulates upward firing rate homeostasis via the mitochondrial calcium uniporter.

Regulation of firing rate homeostasis constitutes a fundamental property of central neural circuits. While intracellular Ca2+ has long been hypothesized to be a feedback control signal, the molecular machinery enabling a network-wide homeostatic response remains largely unknown. We show that deletion of insulin-like growth factor-1 receptor (IGF-1R) limits firing rate homeostasis in response to inactivity, without altering the distribution of baseline firing rates. The deficient firing rate homeostatic response was due to disruption of both postsynaptic and intrinsic plasticity. At the cellular level, we detected a fraction of IGF-1Rs in mitochondria, colocalized with the mitochondrial calcium uniporter complex (MCUc). IGF-1R deletion suppressed transcription of the MCUc members and burst-evoked mitochondrial Ca2+ (mitoCa2+) by weakening mitochondria-to-cytosol Ca2+ coupling. Overexpression of either mitochondria-targeted IGF-1R or MCUc in IGF-1R-deficient neurons was sufficient to rescue the deficits in burst-to-mitoCa2+ coupling and firing rate homeostasis. Our findings indicate that mitochondrial IGF-1R is a key regulator of the integrated homeostatic response by tuning the reliability of burst transfer by MCUc. Based on these results, we propose that MCUc acts as a homeostatic Ca2+ sensor. Faulty activation of MCUc may drive dysregulation of firing rate homeostasis in aging and in brain disorders associated with aberrant IGF-1R/MCUc signaling.

Growth Performance, Immune-Related and Antioxidant Genes Expression, and Gut Bacterial Abundance of Pacific White Leg Shrimp, Litopenaeus vannamei, Dietary Supplemented With Natural Astaxanthin.

The current study examines the effect of dietary supplementation of ethanolic extract of Arthrospira platensis NIOF17/003, which is mainly natural astaxanthins (97.50%), on the growth performance, feed utilization, bacterial abundance, and immune-related and antioxidant gene expressions of the Pacific white leg shrimp, Litopenaeus vannamei. A total of 360 healthy L. vannamei postlarvae (0.19 ± 0.003 g) were divided into four groups (0, 2, 4, and 6 g natural astaxanthins/kg diet) each in three replicates, at an initial density of 30 PLs per tank (40 L capacity). The shrimp were fed the tested diets three times a day at a rate of 10% of their total body weight for 90 days. Diets supplemented with different astaxanthin levels significantly improved shrimp growth performance and feed conversion ratio compared to the control diet. No significant differences were observed in survival rates among all experimental groups. The immune-related genes (prophenoloxidase, lysozyme, beta-glucan binding protein, transglutaminase, and crustin) mRNA levels were significantly upregulated in groups fed with different concentrations of the natural astaxanthins in a dose-dependent manner. The prophenoloxidase gene is the highest immune-upregulated gene (14.71-fold change) in response to astaxanthin supplementation. The superoxide dismutase mRNA level was significantly increased with increasing dietary astaxanthin supplementation. In addition, increasing astaxanthin supplementation levels significantly reduced the count of heterotrophic bacteria and Vibrio spp. in the culture water and shrimp intestine. Overall, the current results concluded that diet supplementation with natural astaxanthin, extracted from Arthrospira platensis, enhanced the growth performance, immune response, and antioxidant status of L. vannamei.

An overview and update on the chemical composition and potential health benefits of Opuntia ficus-indica (L.) Miller.

Opuntia ficus-indica (OFI), widely recognized as prickly pear, is native to Mexico and it is distributed in many areas of the world because of its socioeconomic, agronomic, and ecological benefits, besides its large amounts of functional, nutraceutical, and biological activities. Various parts of this plant including the fruit pulp and peel, cladode, and seeds are scientifically proven to have therapeutic potentials and are safe for human use. The contents of phytochemical compounds in each part of the OFI are different. Each pharmacological activity depends on the phytochemical compounds, the components used, and the extraction type. In this review, we summarize the active constituents from different parts of OFI and their pharmacological effects including the antioxidant, wound healing, skin protective, hepatoprotective, anticancer, antidiabetic, antihypercholesterolemic, and anti-obesity activities. Besides its effects on the bone health, cardiovascular system, kidneys, and gastrointestinal tract, its gastroprotective, anti-ulcer, anti-inflammatory, antiviral, neuroprotective, sedative, analgesic, anxiolytic and antimicrobial effects and effects on cognitive and memory function are also mentioned. PRACTICAL APPLICATIONS: Over the past few decades, the health benefits of Opuntia ficus-indica (OFI) have received much attention. All parts of the plant, including the fruit pulp and peel, cladode, and seeds have found use in the treatment of many diseases. The chemical composition of OFI provides both a high nutritional value and various health benefits. Therefore, the aim of this review is to present the up-to-date research carried out on OFI phytochemicals, showing the most important biological activities reported.

Prevention of radial artery occlusion by simultaneous ulnar and radial compression (PRO-SURC). A randomized duplex ultrasound follow-up study.

BACKGROUND: There might be a beneficial effect of transient ulnar artery compression in prevention of radial artery occlusion (RAO) after trans-radial catheterization. OBJECTIVE: The objective of this study was to assess, by Duplex ultrasound, the efficacy of simultaneous ulnar and radial artery compression (SURC), in prevention of RAO, compared to conventional and patent hemostasis techniques. PATIENTS AND METHODS: Four hundred and fifty consecutive patients undergoing elective trans-radial catheterization were enrolled. Patients were randomized in 1:1:1 fashion into 3 groups; conventional hemostasis (Group A, n = 150 patients), patent hemostasis (Group B, n = 150 patients), and SURC technique (Group C, n = 150 patients). RAO was assessed by duplex ultrasound at 1-h post TR band removal (primary endpoint), and at 1-month. RESULTS: The primary endpoint, RAO 1-h post TR-band removal, was significantly lower among patients of group C as compared to those of group A and B (1.3%, 6.7%, and 7.3%, respectively -p = 0.03). This was still consistent at 1-month (0.7%, 8%, and 6%, respectively -p = 0.03). Multiple regression analyses revealed that lower radial artery diameter (RAD) after flow-mediated dilatation (FMD) independently predicted RAO at 1-h, while RAD at 1-h post-TR band removal was the only independent predictor of RAO at 1-month. Receiver operator characteristic (ROC) analysis showed that RAD at 1-h post-TR band removal at cut-off ≤1.75 mm could predict RAO at 1-month with high accuracy (AUC = 0.9, CI = 0.8-1.0, p < 0.001-86% sensitivity, and 95% specificity). CONCLUSION: A technique of SURC is associated with less incidence of early and late RAO compared to conventional hemostasis techniques.

Design, synthesis, cytotoxicity, and molecular docking studies of novel thiazolyl-hydrazone derivatives as histone lysine acetyl-transferase inhibitors and apoptosis inducers.

Compounds containing both thiazole and arylsulfone moieties are recognized for their high biological activity and ability to fight a variety of ailments. Thus, in this context, new derivatives of (thiazol-2-yl)hydrazone with an arylsulfone moiety were synthesized as CPTH2 analogs with potent anti-histone lysine acetyl-transferase activity. Compounds 3, 4, 10b, and 11b showed an excellent inhibitory effect on P300 (E1A-associated protein p300), compared to CPTH2. Among all the tested derivatives, compound 10b revealed the highest activity against both P300 and pCAF. In addition, the new hits were tested for anticancer efficacy against two leukemia cell lines. Most of them showed a moderate to potent antitumor effect on the k562 and CCRF-CEM cell lines. Interestingly, the activity of compound 10b against the k562 cell line was found to be higher than that of CPTH2. Furthermore, it showed a good safety profile, better than CPTH2 on normal cells. Molecular docking analysis was carried out to reveal the crucial binding contacts in the inhibition of the P300 and pCAF enzymes.

Comparing genetic markers efficiencies for discrimination between two commercially important holothuroids in the Mediterranean Sea, Holothuria polii and Holothuria sanctori.

Sea cucumber (bche-de-mer, Echinodermata: Holothuroidea) is one of the top internationally traded seafood varieties. Besides its direct nutritional benefits, it is continuously used in the traditional medicine in different areas and cultures in the world. This world-wide interest triggered various issues related to stocks declining and risks of species extinction. For these reasons, the current study was designed to provide molecular tools for accurate discrimination between two sea cucumber species that prevail the Mediterranean of these echinoderms in Egypt, that are Holothuria polii and H. sanctori. The power of three gene markers, i.e., 16S rDNA, 28S rDNA, and Histone H3 in achieving accurate DNA-based identification, as well as elucidating clear phylogenetic and genetic diversity differences between those two species was assessed. Among the three genes, 16S rDNA showed the highest potentials as genetic and phylogenetic species discrimination marker. Both 28S rDNA and H3 exhibited the least number of holothuroid reference sequences in the GenBank database. For genetic diversity within each species population, 16S rDNA exhibited the best potentials, followed by H3. 28S rDNA showed no genetic polymorphism at all. Moreover, the collective data of both H3 and 16S rDNA suggested a possible role of asexual reproduction behavior in H. sanctori in the reduction of genetic diversity, as a possible response to overfishing. Hence, the current research can recommend the simultaneous application of both 16S rDNA and H3 as accurate markers for genetic discrimination among H. polii, H. sanctori and other different holothuroid species.

Novel sulfonyl thiazolyl-hydrazone derivatives as EGFR inhibitors: Design, synthesis, biological evaluation and molecular docking studies.

New hydrazonoyl-sulfonylthiazoles were designed and synthesized as EGFR inhibitors. The new sulfonylthiazole derivatives were assessed in vitro to measure their effect on EGFR. They revealed marked inhibitory activity against EGFR kinase having IC50 range from 0.037 to 0.317 µM compared to reference drug dasatinib (IC50 = 0.077 µM). Six derivatives of the newly synthesized compounds showed potent inhibitory activity relative to dasatinib. Furthermore, the new hits were examined concerning their cytotoxic effect on human breast cancer cell line (MCF7), hepatic cancer cell line (HepG2) using MTT assay. N-(2-Benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-thiazol-2-yl)-hydrazine (IC50 = 1.24 µM) revealed higher potency than dasatinib (IC50 = 11.6 µM) against MCF7cell line. Besides, N-(2-benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-5-p-tolylazo-thiazol-2-yl)-hydrazine exhibited excellent cytotoxicity against HepG2cell line (IC50 = 3.61 µM), exceeding that of dasatinib (IC50 = 14.10 µM). In addition to low cytotoxic effect on normal (WI-38) cells, describing the high safety profiles of these compounds. Moreover, molecular docking was done in order to determine the possible binding modes of such compounds inside the binding site of EGFR.

The role of BCL9 genetic variation as a biomarker for hepatitis C-related hepatocellular carcinoma in Egyptian patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered one of the most common cancers related to mortality around the world, and susceptibility is related with genetic, lifestyle, and environmental factors. Copy number variation of the Bcell CLL/lymphoma 9 (BCL9) gene is a type of structural variation which can influence gene expression and can be related with specific phenotypes and diseases and has a role in hepatocarcinogenesis. Our aims were to assess the copy number variation (CNV) in the BCL9 gene and explore its role in HCV-related HCC Egyptian patients. A total of 50 HCV-related HCC patients were enrolled in the study (including 25 early HCC and 25 late HCC cases); the copy number of the BCL9 gene was detected using quantitative polymerase reaction. RESULTS: There was a highly statistically significant difference between the two groups (early and late HCC patients) in gender, bilharziasis, performance status, child score class, child grade, focal lesion size, portal vein, and ascites. CNV was detected and represented by the gain in the BCL9 gene in 14% of patients, and all of them were males. Also, it was noticed that the ratio of gain in BCL9 copy number in late individuals was about 1.5 times than that in early HCC individuals. Moreover, our results showed that the distribution of performance status > 1, average and enlarged liver, focal lesion size, thrombosed portal vein, and AFP was higher in patients with BCL9 copy number gain. CONCLUSION: We detected about 14% gain in BCL9 copy number in Egyptian HCC patients. But the variation in copy number of the BCL9 gene did not affect HCC development in our patients' cohort.