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Pollen had a wide range of effects on honey bee. Caged honey bee workers were used to determine the nutritional effects of four main types of pollen collected by honey bee colonies from the study area on the food consumption rates, bees age, the development of the hypopharyngeal (HPG) acini and acid gland (AG) sacs in honey bee workers. Additionally, chemical analysis of the selected pollen types was performed. Pollen diets were as follows: broad bean pollen, date palm pollen, clover pollen, maize pollen and mixture of the for mentioned typrs beside the control pollen diet. The highest mean consumption was observed between 4th and 6th of day aged bees in all diets (23.05 mg./bee/3days). The highest quantity of food consumption was recorded in the 18th day when the workers were fed on date palm pollen (75.42 mg), while the lowest recorded 59.17 mg from maize pollen treatment. The highest mean acinal surface area of HPG was 0.0451mm2, which measured at 9 days-old of bees in all diets. While the workers fed on mixture pollen diet had the highest significant mean recorded the acinal surface area of HPG 0.0450mm2 comparing of 0.0223mm2 in control. The considering increment in average volume of acid gland sac with had been obtained at 18 days-old (0.7276mm3) that resembles the highest significant degree, the greatest mean volume of AG sacs was observed when bees were fed on broad bean pollen (0.6419mm3), while the lowest mean was 0.3643mm3 in control.

Objective: To determine the prevalence of Charcot triad, Reynolds pentad, and Tokyo Guidelines criteria and clinical outcomes among patients with cholangitis across different age groups. Patients and Methods: We conducted a retrospective analysis of 257 consecutive hospitalized adult patients with acute cholangitis due to endoscopic retrograde cholangiopancreatography–confirmed choledocholithiasis between January 1, 2015, and December 31, 2019. Patients were divided into 3 age groups: less than 65 years, 65 to 79 years, and 80 years or older. Symptoms, vital signs, and laboratory data on admission were collected. Outcomes included length of hospitalization, intensive care unit stay, and 3-month mortality. Nominal variables were tested with the Pearson χ2 test, and continuous variables were tested with the Wilcoxon rank sum test. Results: Charcot triad decreased with older ages. In the group that was age 80 years or older, malaise was the most common symptom; 33.6% (37 of 110) presented with altered sensorium, 9.1% (10 of 110) had no pain, fever, or jaundice, and positive blood culture results were more frequent. Tokyo cholestasis criterion was present in 96.0% (247 of 257), while inflammation (considered essential for diagnosis) was present in 75.9% (195 of 257). Patients 80 years or older had significantly higher mean length of hospital stay (P

This study aimed at detecting the effects of COQ10 with and without vitamin E on some semen characteristics of the broiler breeder males. Twenty-five males at 43weeks of age divided into five categories of treatment with five replicates. The first treatment (control group) included drenching with corn oil capsules only. The second and fourth treatments were about drenching with capsules containing the COQ10 enzyme at a concentration of 5 mg / male / day with and without10 mg of vitamin E whereas the third and fifth treatments included drenching with capsules containing the Q10 enzyme at a concentration of 10 mg / male / day with and without 10 mg of vitamin E. This whole scheme of treatments was to study their effects on certain semen and seminal plasma properties. The results showed a significant increase (P

Graphical abstract, Modulation of the structure and function of biomaterials is essential for advancing bio-nanotechnology and biomedicine. Microtubules (MTs) are self-assembled protein polymers that are essential for fundamental cellular processes and key model compounds for the design of active bio-nanomaterials. In this in silico study, a 0.5 μs-long all-atom molecular dynamics simulation of a complete MT with approximately 1.2 million atoms in the system indicated that a nanosecond-scale intense electric field can induce the longitudinal opening of the cylindrical shell of the MT lattice, modifying the structure of the MT. This effect is field-strength- and temperature-dependent and occurs on the cathode side. A model was formulated to explain the opening on the cathode side, which resulted from an electric-field-induced imbalance between electric torque on tubulin dipoles and cohesive forces between tubulin heterodimers. Our results open new avenues for electromagnetic modulation of biological and artificial materials through action on noncovalent molecular interactions.

Ocimum forskolei (Habak), Lamiaceae, is an endemic species from Yemen and KSA; where our present study was aimed at investigating the Metabolic profiling coupled with LC HR-MS analysis of the dichloromethane fraction from the aerial parts of that plant with a special emphasis on ursolic acid as the major predominating compound from this fraction. Histopathological evaluation of ursolic acid in different doses against indomethacin-induced ulcers in rats revealed a highly significant and dose dependent protection. With the dose level of 50 mg/kg b.w., Ursolic acid gave an ulcer index of 1.33 ± 0.33 and 97.8% inhibition, compared to cimetidine as a standard with 3.0 ± 0.58 and 95.2%. To rationalize this activity, docking on various macromolecular targets was performed, followed by molecular dynamics on the most promising target; the M3 receptor. A high binding energy of -344 kJ/mol is predicted between Ursolic acid and the protein indicating the stability of the predicted pose.

A new series of N-acyl hydrazones (4a-g) derived from indole-3-propionic acid (IPA) were synthesized. These N-acyl hydrazones were prepared by the reaction of 3-(1H-indol-3-yl) propane hydrazide and aldehyde in the existence of glacial acetic acid as a catalyst. 1HNMR and FT-IR analyses were used to identify the synthesized compounds and they were in vitro evaluated as antibacterial agents against six different types of microorganisms by using well diffusion method. All the tested N-acyl hydrazones (4a-g) displayed moderate activity against the Gram-negative E.coli, comparable to that of Amoxicillin. Some of the tested N-acyl hydrazones also exhibited intermediate activity against some of the examined Gram-positive and Gram-negative bacteria. While no activity was exhibited by any of the examined compounds against the Gram-positive S. aureus.

Herein, the mono and dialkylation of pyridazino[4,5-b]indole were achieved with a set of alkylating agents, including amyl bromide, allyl bromide, benzyl bromide and ethyl chloroacetate in the presence of K2CO3/acetone or KOH/DMSO. The hydrazinolysis of mono and di-esters 10 and 11 gave the target hydrazides 12 and 13, which displayed promising, potent, and significant cytotoxic activity against the MCF-7 cell line with IC50 values of 4.25 and 5.35 μm compared to that of the standard drug 5-FU (IC50 6.98 μm), respectively. RT-PCR analysis of the most active compound 12 was performed to determine its mode of action through the up-regulation of pro-apoptotic genes and inhibition of anti-apoptotic and PI3K/AKT/mTOR genes. The findings were consistent with the proposed mechanism illustrated in the in silico study. Further, the in vivo analysis exhibited its potent anti-cancer activity through the prolongation of survival parameters, and inhibition of ascetic fluid parameters in EAC-bearing mice.

PURPOSETo provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids (GA4K) program.METHODSExtensive analyses of 960 families with suspected genetic disorders including short-read exome (ES) and genome sequencing (srGS); PacBio HiFi long-read GS (HiFi-GS); variant calling for small-nucleotide (SNV), structural (SV) and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants and pedigrees are stored in PhenoTips database, with data sharing through controlled access (dbGAP).RESULTSDiagnostic rates ranged from 11% for cases with prior negative genetic tests to 34.5% in naïve patients. Incorporating SVs from GS added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs than srGS. Variants and genes of unknown significance (VUS/GUS) remain the most common finding (58% of non-diagnostic cases).CONCLUSIONComputational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated by HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation, and by providing HiFi variant (SNV/SV) resources from >1,000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses.

We present molecular dynamics (MD) trajectories of a single ring of B-lattice microtubule ring consisting of 13 tubulin heterodimers. The data contain trajectories of this molecular system ran under various conditions (two temperature values, three ionic strength values, three values of electric field (including no field), and four electric field orientations). Our data enable us to analyze the effects of the electric field on microtubule under a variety of conditions. This data set was a basis of our in silico discovery, which demonstrates that the electric field can open microtubule lattice [1] .

Plant microbiota have co-evolved with their associated plants in the entire holobiont, and their assemblages support diversity, health and productivity on our planet. Of importance is the in vitro cultivation and identification of their hub taxa for possible core microbiome modification. Therefore, we recently introduced the in situ-similis culturing strategy, based on the use of plant leaves as platform for in vitro growth of plant microbiota. Here, we augment the strategy by the incorporation of the Most Probable Number (MPN) method, based on the use of leaf strips and root segments immersed in plain semi-solid water agar, as growth milieu. Cultivability of bacterial endophytes of sunflower plants (Helianthus annuus L.) was monitored in terms of MPN population estimates, community composition through PCR-DGGE analysis and 16S rRNA gene sequencing of representative isolates. The method efficiently enriched the plant endophytes as MPN estimates exceeded log 7.0 g-1 leaf/root. Results of PCR-DGGE analyses indicated divergence in community composition of cultivable bacterial endophytes primarily attributed to the type of culture media, signaling a certain degree of plant-organ specificity and compatibility. Based on 16S rRNA gene sequencing of representative bacterial isolates, 20 genera comprising 32 species were enriched in leaf strips- and root segments-based media. They belonged to the three phyla Bacteroidetes, Firmicutes and Proteobacteria, especially Alpha- and Gammaproteobacteria. The MPN strategy furnished a diversified nutritive platform in terms of homologous/heterologous and ambient/limited oxygenic cultivation. As a result, cultivability was extended to more 8 genera - Bosea, Brevundimonas, Caulobacter, Chitinophaga, Pseudoxanthomonas, Scandinavium, Sphingobacterium, Starkeya - among them three genera, namely Caulobacter, Scandinavium and Starkeya, which were not yet reported for Sunflower, even with the use of metagenomics sequencing methods. Possible unknown species or even one new putative genus were enriched. Thus, not only potential members of the major microbiome but also the rare isolates of satellite microbiomes can be isolated using the presented in situ similis MPN-cultivation strategy. It is a feasible addition to traditional cultivation methods to probe deeper for both the major and rare taxa and fill the many cultivation gaps within plant microbiota.

Graphical abstract, Highlights • The plant microbiome culturomics is substantially lagging behind the human microbiome. • Conventional chemically-synthetic culture media recover, Improving cultivability of a wider range of bacterial and archaeal community members, living natively in natural environments and within plants, is a prerequisite to better understanding plant-microbiota interactions and their functions in such very complex systems. Sequencing, assembling, and annotation of pure microbial strain genomes provide higher quality data compared to environmental metagenome analyses, and can substantially improve gene and protein database information. Despite the comprehensive knowledge which already was gained using metagenomic and metatranscriptomic methods, there still exists a big gap in understanding in vivo microbial gene functioning in planta, since many differentially expressed genes or gene families are not yet annotated. Here, the progress in culturing procedures for plant microbiota depending on plant-based culture media, and their proficiency in obtaining single prokaryotic isolates of novel and rapidly increasing candidate phyla are reviewed. As well, the great success of culturomics of the human microbiota is considered with the main objective of encouraging microbiologists to continue minimizing the gap between the microbial richness in nature and the number of species in culture, for the benefit of both basic and applied microbiology. The clear message to fellow plant microbiologists is to apply plant-tailored culturomic techniques that might open up novel procedures to obtain not-yet-cultured organisms and extend the known plant microbiota repertoire to unprecedented levels.

Objective: To develop an optimal follow-up treatment for neonatal and nosocomial infections and to examine correlations between the C-reactive protein (C-RP) and platelets. Methods: A sample of 27 septic neonates and 14 non-septic neonates were selected for this study. The non-septic neonates served as a control group. Blood samples were collected from both groups and analyzed for bacterial contamination via blood culture, complete blood count (CBC), and C-RP, according to international laboratory standards. Blood collection and analysis were repeated every day during the follow-up treatments with antibiotics to evaluate the kinetics of C-RP. Results: Blood culture found E. coli and Staphylococcus aureus in the blood of the septic cases. Serum C-RP concentrations were at high levels (24 mg/dl) in the septic neonates and at normal levels (lower than 6 mg/dl) in the control group. Treatment with active antibiotics resulted in a drastic reduction of the C-RP values and helped to reach a normal level as in the control group. On the other hand, there were increases in the platelet levels as the C-RP levels decreased. This result indicates a strong negative association between C-RP and platelet levels in the septic group only. Statistical analysis shows significant differences between the mean C-RP serum concentrations of the sepsis and non-sepsis. Conclusion: blood culture, active antibiotics, and kinetic C-RP measurements during the medical follow-up treatment are strong driving parameters for the optimal and successful management of sepsis.

OBJECTIVE: The purpose of this study was to compare the efficacy of Leucocyte -platelet‑rich fibrin (L-PRF), and hydroxyapatite (HA) for reduction of pain and swelling, the incidence of dry socket, soft tissue healing, and bone regeneration after surgical removal of impacted mandibular third molar in human patients.Patients and Methods: Thirty-six patients (20 males and 16 females) requiring extraction of mandibular third molars were randomly grouped as L-PRF, HA, and Control‑treated. All the procedures were done on an outpatient basis without any complication such as lip numbness. The patients were assessed for postoperative pain, swelling and maximal inter-incisal distance on the 1st, 3rd and 7th postoperative days. Exposed bony socket wall (dry socket), as well as soft tissue healing (healthy granulation tissue Formation), were also assessed at 1st, 3rd, 7th and 14th day of postoperative periods depending on the standard methods. Assessment of daily and total analgesics consumption was done and Radiological assessment of the extraction site was done at 2 and 6 months interval. Results: Pain, swelling, interincisal distance, and soft tissue healing had statistically significant more improvement for L-PRF group compared to HA and control groups. Radiographic assessment showed comparatively lesser bone density values in PRF and control sites at 2 and 6 months than HA site. Conclusion: Our study showed that L-PRF is better graft materials than HA regarding pain, swelling, dry socket, and soft tissue healing post‑L-PRF placement in the extraction socket. Bone regeneration is induced quickly by HA as compared to PRF. However, study with a wide scale of clinical cases is very much essential to be more decisive regarding the efficacy of the graft materials.

Combinations of direct-acting antivirals are needed to minimize drug-resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and testing of a number of drug regimens has led to conflicting results. Here we show that cobicistat, which is an-FDA approved drug-booster that blocks the activity of the drug metabolizing proteins Cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Cell-to-cell membrane fusion assays indicated that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with the putative CYP3A target and nucleoside analog remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. The cobicistat/remdesivir combination was able to potently abate viral replication to levels comparable to mock-infected cells leading to an almost complete rescue of infected cell viability. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19.

The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into eight experimental groups, fed on a normal diet or high-fat diet (HFD), then given mangosteen extract (400 mg /kg /day) and/or curcumin (80 mg/kg /day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Mangosteen pericarp extract (MPE) induced a remarkable decrease in BMI (from 0.86 to 0.81 gm/cm2), while curcuma either alone or in combination was more effective, as treated rats recorded BMIs of 0.78 and 0.79 gm/cm2, respectively. Regarding the antioxidant effects, MPE induced a significant increase of GSH in obese rats (123.86 ± 15.53 μg/ml vs 288.72 ± 121.37 μg/ml). As anti-atherogenic agents MPE demonstrate significant effect recorded higher level of HDL-C in treated animals, but ineefective as anti-dyslipidemic agent. Curcumin was more effective in reducing LDL-C levels in obese rats. Both extracts effectively reduced blood glucose. The present study demonstrated that MPE and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.

Micromeria fruticosa (L.) Druce subsp. Serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract of M. fruticose on two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosa on cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 &mu, g/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.

High-throughput cultivation methods have recently been developed to accelerate the recovery of microorganisms reluctant to cultivation. They simulate in situ environmental conditions for the isolation of environmental microbiota through the exchange of growth substrates during cultivation. Here, we introduce leaf-based culture media adopting the concept of the plant being the master architect of the composition of its microbial community. Pre-physical treatments of sunflower plant leaves, namely punching, freezing, and/or autoclavation, allowed the diffusion of electrolytes and other nutrients to configure the leaf surface as a natural pad, i.e., creating an “in situ similis” environment suitable for the growth of rarely isolated microbiota. We used surface inoculation and membrane-filtration methods to assess the culturability of endophytic bacteria from the sunflower phyllosphere and rhizosphere. Both methods supported excellent colony-forming unit (CFU) development when compared to standard R2A medium, with a special affinity to support better growth of epiphytic and endophytic populations of the phyllosphere compared with the rhizosphere. A 16S rRNA gene analysis of >122 representative isolates indicated the cultivation of a diverse set of microorganisms by application of the new methods. It indicated the predominance of 13 genera of >30 potential species, belonging to Firmicutes, Proteobacteria, and Actinobacteria, and especially genera not commonly reported for sunflower, e.g., Rhizobium, Aureimonas, Sphingomonas, Paracoccus, Stenotrophomonas, Pantoea, Kosakonia, and Erwinia. The strategy successfully extended diversity and richness in the endophyllosphere compared to the endorhizosphere, while CFUs grown on the standard R2A medium mainly pertain to Firmicutes, especially Bacillus spp. MALDI-TOF MS analysis clustered the isolates according to their niche and potential functions, where the majority of isolates of the endorhizosphere were clustered away from those of the endophyllosphere. Isolates identified as Gammaproteobacteria and Alphaproteobacteria were distinguishably sub-clustered, which was in contrast to the heterogeneous isolates of Firmicutes (Bacillus spp.). In conclusion, leaf in situ similis cultivation is an effective strategy to support the future application of culturomics of plant microbiota. This is an effort to access novel isolates that are more adapted and competitive in their natural environments, especially those subjected to abiotic stresses like those prevailing in arid/semi-arid zones, and, consequently, to support the application of agro-biotechnologies, among other technologies, to improving agriculture in such zones.

Diabetes, obesity, and metabolic syndrome represent the current global epidemic. In spite of the continuous development of related pharmaceuticals, complications of these conditions lower the patient's life quality and cause a burden on the health economy. Histone deacetylase inhibitors are slowly emerging as a line of management for several medical conditions. Many studies have described their potential role in diabetes, in terms of enhancing insulin secretion and decreasing insulin resistance. In obesity, these agents showed a very interesting role in converting white fat cells to their brown counterpart, as well as shifting the metabolic pathways toward less adiposity. Although these effects are characterized at the cellular and preclinical levels, few clinical studies have been reported. This chapter includes an overview of the relation between histone deacetylation and the development of diabetes and obesity, as well as the possible future role of histone deacetylase inhibitors in the management of these conditions.

Introduction Mesenchymal stem cells (MSCs) isolated from bone marrow have different developmental origins, including neural crest. MSCs can differentiate into neural progenitor-like cells (NPCs) under the influence of bFGF and EGF. NPCs can terminally differentiate into neurons that express beta-III-tubulin and elicit action potential. The main aim of the study was to identify key genetic markers involved in differentiation of MSCs into NPCs through transcriptomic analysis. Method Total RNA was isolated from MSCs and MSCs-derived NPCs followed by cDNA library construction for transcriptomic analysis. Sample libraries that passed the quality and quantity assessments were subjected to high throughput mRNA sequencing using NextSeq®500. Differential gene expression analysis was performed using the DESeq2 R package with MSC samples being a reference group. The expression of eight differentially regulated genes was counter validated using real-time PCR. Results In total, of the 3,252 differentially regulated genes between MSCs and NPCs with two or more folds, 1,771 were upregulated genes, whereas 1,481 were downregulated in NPCs. Amongst these differential genes, 104 transcription factors were upregulated, and 45 were downregulated in NPCs. Neurogenesis related genes were upregulated in NPCs and the main non-redundant gene ontology (GO) terms enriched in NPCs were the autonomic nervous system, cell surface receptor signalling pathways), extracellular structure organisation, and programmed cell death. The main non-redundant GO terms enriched in MSCs included cytoskeleton organisation cytoskeleton structural constituent, mitotic cell cycle), and the mitotic cell cycle process Gene set enrichment analysis also confirmed cell cycle regulated pathways as well as Biocarta integrin pathway were upregulated in MSCs. Transcription factors enrichment analysis by ChEA3 revealed Foxs1 and HEYL, amongst the top five transcription factors, inhibits and enhances, respectively, the NPCs differentiation of MSCs. Conclusions The vast differences in the transcriptomic profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma, has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity by natural killer (NK) cells toward myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody-dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to antitumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor-associated macrophages using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant antitumor efficacy of single-agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc–FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in vivo and mediates ADCP of myeloma cells though a FcγR-dependent manner in vitro. Together, these findings propose a novel immune-mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Mol Cancer Ther; 17(7); 1454–63. ©2018 AACR.

Almond seedlings which were grown at fruit field / Horticulture and Land Scape Design / College of Agriculture and Forestry during 2012 growing season were fertilized with three levels of nitrogen (0, 50 and 100 gm N/seedling ) by using urea fertilizer (46 % N) as a sourse of nitrogen, three levels of humus liquid fertilizer (18% humic acid) (0, 5 and 10 ml humus/L/seedling) and foliar spray with two concentrations of gibberellic acid (0 and 75 mg GA3 / L), to improve seedlings vegetative growth and budding success percentage. Results indicated that the treatments of 100g N/seedling +5 ml humus / L / seedling + 0 mg GA3 / L. gave the highest means leaves N concentrations (1.14 %) and seedling leaves area (2119.40 cm2/seedling), Meanwhil the treatment of 100g N/seedling +10 ml humus / L / seedling + 0 mg GA3 / L. gave the highest means of leaves chlorophyll (60.20 SPAD unit) and budding successes (100 %). The highest means of seedling height increament was obtaind at the treatment of 100g N/seedling +0 ml humus / L / seedling + 0 mg GA3 / L. (100.49 cm).

Background Statin-induced myopathy has been linked to the C allele of a single nucleotide polymorphism (SNP) (rs4149056) of SLCO1B1 gene. This effect is more significant, but not restricted to simvastatin. Many studies have included European, American, African and Southeast Asian ancestries, but few were carried out on Middle Eastern population. Aim To detect the prevalence of SLCO1B1 rs4149056 (521T > C) in Emirati population. Method We recruited 282 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical approval was obtained before the study starts. Besides basic data collection, venous blood samples were collected. Fasting blood glucose, Lipid profile, and insulin levels were measured. Genotyping for rs4149056 (521T > C) was tested in triplicates through Real Time-PCR using TaqMan® Drug Metabolism Genotyping Assay. rs2306283 (388A > G) was analyzed for comparison. In addition, presence of minor alleles of both SNPs define stronger association with statin-induced myopathy. Results The study included 282 individuals, 52.8% were males with median age of 39.5 years. 10% had Diabetes Mellitus and 23% were hypertensive. Median of body mass index (BMI) was 27.68 kg/m2 in males and 28.38 kg/m2 in females. One-hundred ninety-seven (69.9%) showed abnormal lipid profile (either increased LDL-cholesterol or triglycerides or both). For rs4149056, C allele was present in 21.3% (2.8% homozygous C and 18.4% heterozygous CT). Although homozygous C genotype prevalence was low, compared with Caucasians (4%) and Africans (0%), C allele was associated with a trend of having higher BMI and abnormal lipid profile. C allele subjects were all pre-diabetics with mean glycated hemoglobin above 6%. Mean BMI in CC, CT, and TT genotypes was 30.91 ± 4.4, 29.48 ± 4.2, 27.96 ± 5.5 kg/m2 respectively, with lack of such a trend observed with the different genotypes of the rs2306283 (used for comparison). Abnormal lipid profile was observed in 7/8(87.5%), 38/52(73.1%) and 152/222(70%) of the CC, CT, and TT genotypes respectively. Conclusion There is lower prevalence of statin-induced myopathy-linked C allele of rs4149056 in SLCO1B1 gene in Emirati population, compared to Caucasians and Africans. However, there is a trend of higher glycosylated hemoglobin and BMI associated with normal lipid profile in patients having this allele.

This study was investigated the protective role of (CoQ10) on reproductive dysfunction of males quail induced by hydrogen peroxide (H2O2). Forty Japanese quail male 45 days old were randomly allotted into four groups with ten replicate one per each , and treated for 28 days as follows : (G1): the first control group (G2): reserved standard ratio and (1%) H2O2 in drinking water. (G3): reserved production ratio + (100 mg Co Q10/kg diet) and (1%) H2O2 in drinking water. (G4): reserved production ratio + (100 mg Co Q10/kg diet) and normal water. The results showed that exposure of birds to H2O2 caused decrease in serum glutathione level (GSH), testosterone, luteinizing hormones (LH) and follicle stimulating hormone (FSH) hormones and this reflects on histology of testis by reducing seminiferous tubules diameter , area of germinal layer and germinal layer thickness. Whereas supplement of CoQ10 caused an increase the concentrations of theses, hormones in-group G4 as compared with group G2. It can noted that an addition was able to restore the oxidative stress birds (G3) to a state close to the natural state (G1). Though testicular histological modifications were made strides in grown-up Japanese quail male treated with CoQ10. In conclusion, the comes about of the display think about appeared that utilize of Co Q10 can easing the pernicious impacts on male regenerative work takingafter introduction toH2O, maybe through enhancement the antioxidant parameters or testicular capacities or other related endocrine organs.

Graphical abstract, The plant-based-sea water culture medium is introduced to in vitro cultivation and in situ recovery of the microbiome of halophytes. The ice plant (Mesembryanthemum crystallinum) was used, in the form of juice and/or dehydrated plant powder packed in teabags, to supplement the natural sea water. The resulting culture medium enjoys the combinations of plant materials as rich source of nutrients and sea water exercising the required salt stress. As such without any supplements, the culture medium was sufficient and efficient to support very good in vitro growth of halotolerant bacteria. It was also capable to recover their in situ culturable populations in the phyllosphere, ecto-rhizosphere and endo-rhizosphere of halophytes prevailing in Lake Mariout, Egypt. When related to the total bacterial numbers measured for Suaeda pruinosa roots by quantitative-PCR, the proposed culture medium increased culturability (15.3–19.5%) compared to the conventional chemically-synthetic culture medium supplemented with (11.2%) or without (3.8%) NaCl. Based on 16S rRNA gene sequencing, representative isolates of halotolerant bacteria prevailed on such culture medium were closely related to Bacillus spp., Halomonas spp., and Kocuria spp. Seed germination tests on 25–50% sea water agar indicated positive interaction of such bacterial isolates with the germination and seedlings’ growth of barley seeds.

This study conducted in the Physiological Laboratory of the Department of Animal Production/College of Agriculture/Tikrit University, with the aim of finding out the effect of the genotype and sex of local chickens and Brahma chickens on some hematological traits. Used 24 blood samples, twelve samples from local chickens and Brahma chicken, with six samples for both sexes. After performing the hematological analyzes, the following results showed A significant effect of the genotype was observed in the TCH, HB, MCV and MCH. Moreover, it showed a significant increasing for domestic chickens compared to Brahma chickens. The total number of red and white blood cells did not significantly affect the genotype. Sex had a significant effect on most of the studied traits (HCT, HB, RBC, MCV, and, MCHC), where males significantly outperformed females. The interaction between genotype and sex had a noteworthy impact (p≤ 0.05) on most ofthe considered characteristics, and it by and large demonstrated a noteworthy diminish within the examined characteristics in female Brahma chickens compared to male and female residential chickens and indeed male Brahma. However, not effect in WBC count. From the results local chickens recorded to exceed expectations in most of the physiological characteristics and for both genders, the immune status of both genetic structure was rise to, and this may show the versatility of the Brahma chickens to the Iraqi airspace.

Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.

Cassytha filiformis, a leafless and perennial vine with small scales as a replacement of the leaves is currently being used in the treatment of various disease conditions such as jaundice. Macroscopic/ organoleptic characters, microscopic, chemo-microscopic characters, numerical standards, and elemental analysis were determined from the whole plant of C. filiformis. Findings from this study revealed the presence of some diagnostic microscopical features such as paracytic stomata, unicellular covering trichomes with cystoliths, prismatic calcium oxalate crystals and annular xylem vessels. Quantitative physical constants include moisture contents (5.5 %), ash value (17 %), acid insoluble ash value (1 %), total tannins (27.3 %), swelling index (165 %), water, ethanol and oil extractive indices (20.6, 13.6 and 1.6%, respectively). Trace metals such as Fe (165.4279 ppm), Mn (14.4093 ppm) and Ni (2.7933 ppm) detected in C. filiformis were higher than FAO/WHO (1984) permissible limit for edible plants, While others: Pb (0.0568 ppm), Zn (0.1094 ppm), Cd (0.0103 ppm) and Cu (0.0535 ppm) were found to be within the safety limit. The aim of this work was to study the pharmacognostic, characters, elemental analysis and numerical standard of C. filiformis. Key words: Atomic absorption spectrophotometer (AAS), Rumfar gada, Lauraceae, pharmacognosy.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common causes of secondary osteoporosis. Given that glucocorticoids are considered as a main component of the treatment protocols for a variety of inflammation and immune-mediated diseases besides its use as adjuvant to several chemotherapeutic agents, it is crucial to find ways to overcome this critical adverse effect. Caffeic acid phenethyl ester (CAPE), which is a natural compound derived from honeybee propolis displayed promising antiosteoporotic effects against mechanical bone injury in various studies. The current work aimed at investigating the potential protective effect of CAPE against GIO in vivo with emphasis on the modulation of oxidative status and receptor activator of NF-kB ligand (RANKL)/osteoprotegrin (OPG) signaling. The results showed that CAPE opposed dexamethasone (DEX)-mediated alterations in bone histology and tartarate-resistant acid phosphatase (TRAP) activity. In addition, CAPE restored oxidative balance, Runt-related transcription factor 2 (RunX2) expression and reduced caspase-3 activity in femur tissues. Co-administration of CAPE with DEX normalized RANKL/OPG ratio and Akt activation indicating a reduction in DEX-osteoclastogenesis. In conclusion, concurrent treatment of CAPE with DEX exhibited promising effects in the protection against DEX-induced osteoporosis through opposing osteoclastogenesis and protecting osteoblasts. The potent antioxidant activity of CAPE is, at least in part, involved in its anti-apoptotic effects and modulation of RunX2 and RANKL/OPG signals. The use of CAPE-enriched propolis formulas is strongly recommended for patients on chronic glucocorticoid therapy to help in the attenuation of GIO.

Purpose Serum troponin (cTnT) levels, a commonly measured biomarker of myocardial injury, has rarely been considered in risk models after cardiac surgery. Materials and methods Retrospective study of patients undergoing any cardiac surgery between 2004 and 2012. Patients with a history of recent myocardial injury ( P value approach was used to determine categories of peak cTnT associated with in-hospital death. A multivariable analysis was performed to identify independent predictors of mortality. Results A total of 5318 patients without evidence of preoperative ischemia underwent a number of cardiac surgical interventions ranging from isolated coronary revascularization to combined valve coronary artery bypass grafting. The unadjusted in-hospital mortality rate was 3.3% (n = 175 patients). Four categories of peak cTnT were identified using the minimum P value approach: less than or equal to 0.6 ng/mL, 0.7 to 1.9 ng/mL, 2.0 to 3.1 ng/mL, and greater than 3.1 ng/mL with unadjusted mortality rates of 1.0%, 3.6%, 10.1%, and 33.1%, respectively. Multivariate logistic regression demonstrated that all peak cTnT levels greater than 0.6 ng/mL were independent predictors of in-hospital mortality in a dose-dependent manner. Conclusions We demonstrate that in patients without preoperative myocardial ischemia, the demonstration of myocardial injury (>0.6 ng/mL) in the postoperative period is highly predictive of in-hospital death.

Epigenetic regulation of gene expression without changing DNA sequences is a promising strategy in developing therapeutic agents for human diseases, especially cancer. Histone deacetylases (HDACs) are a family of enzymes involved in epigenetic modulation of gene expression by chromatin remodeling. Deacetylation of the lysine side chains of histones by HDAC proteins renders DNA transcriptionally inactive, resulting in the inhibition of expression of tumor suppressor genes, leading to tumorigenesis and tumor progression. Therefore, inhibiting HDAC enzymes has become an attractive strategy to modulate gene expression as a strategy for developing anticancer drugs. There are currently four FDA-approved cancer drugs in clinical use, and many more are in different stages of clinical trials. However, their clinical utility is limited due to undesirable side effects, mainly attributed to their lack of selectivity and the presence of a hydroxamic acid moiety as the metal-binding group. There are eighteen different isoforms of HDACs belonging to four classes that have been identified in humans. A major challenge in HDAC inhibitor development is how to make them selective for these HDAC isoforms and classes. We report the design and synthesis of new classes of HDAC inhibitors and the evaluation of their anticancer activity and selectivity.

Diabetes is a worldwide health problem with increasing incidence. The current management modalities did not succeed to decrease comorbidities. This study aimed at enhancing the regenerative solution for diabetes by improving the differentiation of mesenchymal stromal cells (MSC) into glucose-sensitive, insulin-secreting cells through an epigenetic modification approach. A 3-day treatment protocol with the epigenetic modifiers, either decitabine (5-aza-2'-deoxycytidine; Aza); a DNA methylation inhibitor or Vorinostat (suberoylanilide hydroxamic acid; SAHA); a histone deacetylase inhibitor was added to two different human stem cell lines. The cells followed a multi-step differentiation protocol that provided the critical triggers in a temporal approach. Aza-pretreated group showed higher intracellular expression of insulin and the transcription factor 'PDX-1'. The cells responded to the high glucose challenge by secreting insulin in the media, as shown by ELISA. Gene expression showed induction of the genes for insulin, the glucose transporter 2, glucokinase, as well as the transcription factors MafA and NKX6.1. Although SAHA showed upregulation of insulin secretion, in comparison to control, the cells could not respond to the high glucose challenge. Interestingly, Aza-treated cells showed a significant decrease in the global DNA methylation level at the end of the culture. In conclusion, this additional step with Aza could enhance the response of MSC to the classical differentiation protocol for insulin-secreting cells and may help in establishing a regenerative solution for patients with diabetes.

Aims The Acute Cardiac Care Association (ACCA)–European Association of Percutaneous Coronary Intervention (EAPCI) Registry on ST-elevation myocardial infarction (STEMI) of the EurObservational programme (EORP) of the European Society of Cardiology (ESC) registry aimed to determine the current state of the use of reperfusion therapy in ESC member and ESC affiliated countries and the adherence to ESC STEMI guidelines in patients with STEMI. Methods and results Between 1 January 2015 and 31 March 2018, a total of 11 462 patients admitted with an initial diagnosis of STEMI according to the 2012 ESC STEMI guidelines were enrolled. Individual patient data were collected across 196 centres and 29 countries. Among the centres, there were 136 percutaneous coronary intervention centres and 91 with cardiac surgery on-site. The majority of centres (129/196) were part of a STEMI network. The main objective of this study was to describe the demographic, clinical, and angiographic characteristics of patients with STEMI. Other objectives include to assess management patterns and in particular the current use of reperfusion therapies and to evaluate how recommendations of most recent STEMI European guidelines regarding reperfusion therapies and adjunctive pharmacological and non-pharmacological treatments are adopted in clinical practice and how their application can impact on patients’ outcomes. Patients will be followed for 1 year after admission. Conclusion The ESC ACCA-EAPCI EORP ACS STEMI registry is an international registry of care and outcomes of patients hospitalized with STEMI. It will provide insights into the contemporary patient profile, management patterns, and 1-year outcome of patients with STEMI.

Objective Oxidative stress contributes to male infertility, and antioxidants have been recommended for treating idiopathic oligoasthenoteratozoospermia (OAT). There is, however, a lack of agreement on the type, dosing, and use of individual antioxidants or combinations thereof. The purpose of this study was to compare the effects of two doses of coenzyme Q10 (CoQ10) on semen parameters and antioxidant status in men with idiopathic OAT. Methods In this prospective study, patients with idiopathic OAT received 200 mg/day (n = 35) or 400 mg/day (n = 30) of CoQ10 orally for 3 months. All patients underwent semen analysis according to the fifth editions of the World Health Organization criteria. Total antioxidant capacity (TAC), catalase (CAT) activity, and superoxide dismutase (SOD) activity were measured both before and after treatment. Results Treatment with CoQ10 (200 mg/day or 400 mg/day) resulted in a significant increase in sperm concentration from baseline (8.22 ± 6.88 to 12.53 ± 8.11 million/mL, p= 0.019; 7.58 ± 5.41 to 12.33 ± 6.1 million/mL, p= 0.002, respectively), progressive motility (16.54% ±9.26% to 22.58% ±10.15%, p=0.011; 14.22% ±12.85% to 26.1% ±14.52%, p= 0.001, respectively), and total motility (25.68% ± 6.41% to 29.96% ± 8.09%, p= 0.016; 23.46% ± 12.59% to 34.82% ± 14.17%, p= 0.001, respectively). CoQ10 therapy also increased TAC (p= 0.009, p= 0.001, respectively), SOD activity (p= 0.004, p= 0.001, respectively), and CAT activity (p= 0.039, p= 0.024, respectively). Furthermore, antioxidant measures correlated significantly with seminal fluid parameters (r = 0.36-0.76). Conclusion CoQ10 supplementation improved semen parameters and antioxidant status in men with idiopathic OAT, with a greater improvement shown in men who took 400 mg/day than in those who took 200 mg/day.

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if intra-cellular components such as cytoskeletal proteins could be directly influenced by electric pulses within biomedically-attainable parameters. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the β-tubulin’s C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of novel therapeutic protocols.Author summaryα/β-tubulin heterodimers are the basic building blocks of microtubules, that form diverse cellular structures responsible for essential cell functions such as cell division and intracellular transport. The ability of tubulin protein to adopt distinct conformations contributes to control the architecture of microtubule networks, microtubule-associated proteins, and motor proteins; moreover, it regulates microtubule growth, shrinkage, and the transitions between these states. Previous recent molecular dynamics simulations demonstrated that the interaction of the tubulin protein macrodipole with external electric field modifies orientation and conformations of key loops involved in lateral contacts: as a result, the stability of microtubules can be modulated by such fields. In this study, we seek to exploit these findings by investigating the possibility of fine-tuning the dipolar properties of binding sites of major drugs, by means of the action of electric fields. This may open the way to control tubulin-drug interactions using electric fields, thus modulating and altering the biological functions relative to the molecular vectors of microtubule assembly or disassembly. The major finding of our study reveals that intense (> 20 MV/m) ultra-short (30 ns) electric fields induce changes in the major residues of selected binding sites in a field strength-dependent manner.

The embryology of the penis and urogenital region has been controversial and confusing. This is related to the fact that in literature, observations have been extrapolated to the human from many different species including mice, rats, red squirrels, pigs and dogs. Classic theories suggest that the penile urethra (columnar epithelium) forms as a result of fusion of the medial edges of the endodermal urethral folds like closing a zip in the midline. The ectodermal edges of the urethral groove fuse to form the median raphe. The glanular urethra (stratified squamous epithelium) is supposed to develop due to an ingrowth of ectoderm from the tip of the glans or due to endodermal cellular differentiation. Recent publications suggest that the human penile urethra develops due to distal migration of the ventral mesenchyme, including the urethral orifice (The Migration Hyposthesis). Hypospadias is probably due to imperfect deficient distal migration (The Disorganisation Hyposthesis).

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if electric pulses within biomedically-attainable parameters could directly influence intra-cellular components such as cytoskeletal proteins. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the bβ-tubulin’s C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of new therapeutic protocols.

Lankacidin C, which is an antibiotic produced by the organism Streptomyces rochei, shows considerable antitumor activity. The mechanism of its antitumor activity remained elusive for decades until it was recently shown to overstabilize microtubules by binding at the taxol binding site of tubulin, causing mitotic arrest followed by apoptosis. However, the exact binding mode of lankacidin C inside the tubulin binding pocket remains unknown, an issue that impedes proper structure-based design, modification, and optimization of the drug. Here, we have used computational methods to predict the most likely binding mode of lankacidin C to tubulin. We employed ensemble-based docking in different software packages, supplemented with molecular dynamics simulation and subsequent binding-energy prediction. The molecular dynamics simulations performed on lankacidin C were collectively 1.1 μs long. Also, a multiple-trajectory approach was performed to assess the stability of different potential binding modes. The identified binding mode could serve as an ideal starting point for structural modification and optimization of lankacidin C to enhance its affinity to the tubulin binding site and therefore improve its antitumor activity., The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b03470.

Objective The aim was to assess the potential role of serum thrombomodulin level as a biochemical diagnostic marker in neonates with septic shock. Background Neonatal septic shock is a significant cause of morbidity and mortality. Thrombomodulin is expressed on vascular endothelial cells and is found in the body in a bound form and a soluble form. Patients and methods This prospective cohort study was done on 120 neonates who were divided into two groups: patients' group included 80 neonates with septic shock, and control group included 40 healthy neonates. Detailed history, thorough clinical examination, and laboratory investigations including level of serum soluble thrombomodulin were done. Results Neonates with septic shock had statistically significant higher level of serum soluble thrombomodulin than controls. Serum soluble thrombomodulin levels were significantly higher in patients with gram-positive bacteria in comparison with gram-negative ones. Nonsurviving septic neonates had statistically significant increase in serum soluble thrombomodulin levels than survived septic neonates. There was a statistically significant positive correlation between serum soluble thrombomodulin levels and quantitative C-reactive protein (CRP) values. The cutoff value of 20 of serum soluble thrombomodulin levels had a sensitivity of 91.5%, a specificity of 84.7%, positive predicted value of 91.9%, negative predicted value of 88.3% with accuracy 92.94% in the diagnosis of septic shock. Serum soluble thrombomodulin showed a higher accuracy in the diagnosis of septic shock than quantitative CRP values. Conclusion Serum soluble thrombomodulin level has a more sensitivity diagnostic role in septic shock than quantitative CRP value. Higher serum soluble thrombomodulin levels predict the prognosis of septic shock.

Heavy metals are common environmental pollutants to the aquatic ecosystems. Several aquatic species have been used as bioindicators and biomonitoring subjects for heavy metals pollution. In the present study, the effects of cadmium (Cd) and manganese (Mn) on the survival, attachment, locomotion, and feeding behaviours of the gastropod snail Biomphalaria alexandrina were determined. The short-term (96 h) LC50 for Cd and Mn were found to be 0.219 and 154.2 mg/l, respectively. Long-term exposures (16-20 days) to ascending concentrations of Cd (0.01-1 mg/l) and Mn (50-500 mg/l) also caused gradual decreases in the survival rate of B. alexandrina in a dose-dependent manner. Attachment, locomotion and feeding behaviours of snails exposed to lethal and sublethal concentrations of Cd and Mn at acute (96 h) and chronic exposure (24 days) intervals, respectively, were also recorded. Compared to controls, a significant decrease (p ≤ 0.05) was recorded in the different behaviours of exposed snails. These changes in behaviour would potentially impact the snail's ability to survive in the wild. Although Cd caused a more severe decline in snail survivorship than Mn, the behavioural effects of Mn were much more severe than Cd when the metals were roughly matched for lethality. In sum, the present study demonstrates B. alexandrina to be a sensitive bioindicator and model organism to assess heavy metals risk factors for severe toxicity in freshwater ecosystems.

Driver mutations propel oncogenesis and occur much less frequently than passenger mutations. The need for automatic and accurate identification of driver mutations has increased dramatically with the exponential growth of mutation data. Current computational solutions to identify driver mutations rely on sequence homology. Here we construct a machine learning-based framework that does not rely on sequence homology or domain knowledge to predict driver missense mutations. A windowing approach to represent the local environment of the sequence around the mutation point as a mutation sample is applied, followed by extraction of three sequence-level features from each sample. After selecting the most significant features, the support vector machine and multimodal fusion strategies are employed to give final predictions. The proposed framework achieves relatively high performance and outperforms current state-of-the-art algorithms. The ease of deploying the proposed framework and the relatively accurate performance make this solution applicable to large-scale mutation data analyses.

Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase with a crucial role in several key cellular functions including tumor cell proliferation and survival. Yet, GSK-3β has emerged as an attractive target for the development of anti-cancer agents. Several small-molecule have been developed as GSK-3β inhibitors. Amongst, several pyrazolopyrimidines based ATP-competitive inhibitors were identified as promising GSK-3β inhibitors. In this work, several pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and assessed for their potential anticancer activity. The new compounds are categorized under two templates, Template A and Template B. In these templates two different linkers with varying lengths and electronic properties were used to link additional aromatic ring systems to the core pyrazolopyrimidine scaffold. The aromatic ring systems were designed with different electronic and bonding properties to test their GSK-3β inhibitory activity and consequently their anticancer properties. All compounds under investigation showed GSK-3β inhibitory properties with IC50's ranging from 0.17- 1.01 µM compared to Tideglusib (standard GSK-3β inhibitor) which showed IC50 of 0.22 µM. Furthermore, the compounds were tested for their potential cytotoxicity against two breast cancer cells (MCF-7 and MDA-MB-231) and lung cancer cells (A549). Only one compound from Template B which possesses the longer hydrazide linker and 2,3-dihydroxy phenyl aromatic ring (compound 27), showed considerable cytotoxic effects against MCF-7, MDA-MB-231 and A549 cells (IC50's of 2.4, 2.4 and 2.3 µM, respectively). Compounds 21, 24, 25 and 26 showed weaker cytotoxic effects against cell lines under investigation (IC50's ranged from 29 to 93 µM). DNA content flow-cytometry analysis was undertaken to evaluate the potential effects of compound 27 on the cell cycle distribution of cell lines under investigation. Compound 27 induced significant antiproliferative effect and accumulation of cells in G0/G1-phase after 24 h of exposure. Longer exposure (48 h) to compound 27 resulted in cell cycle arrest in G2/M-phase. Additional assessment for programmed/non-programed cell death using annexin-V/FITC and acridine orange staining coupled with flow-cytometric analysis showed the ability of compound 27 to induce apoptosis as well as autophagy in all cells under investigation. In conclusion, compound 27 represents a promising GSK-3β inhibitor with potential anticancer properties via the induction of cell cycle arrest with subsequent cellular stress and induction of apoptosis and autophagy. Citation Format: Ahmed T. Negmeldin, Mohammed K. AbdElhameid, Dalia Y. Alsaeedy, Fatiha Hammed, Rasha M. Allam, Walid El-Sayed, Ahmed M. Al-Abd. Design, synthesis, and assessment of anticancer properties of pyrazolopyrimidine derivatives as Glycogen Synthase Kinase-3β inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-236.

In the dark, the pineal gland secreted melatonin hormone after produced from tryptophan that is Responsible for organizing many vital functions such as Wake up and sleep, circadian rhythm, Immune response and reproduction. As well as that Melatonin act as antioxidant and inflammatory. Thirty-six of 45 days-old Japanese quail male randomly divided to four treatments nine replicates per each. The control treatment consisted of the basal diet and normal water, 2nd treatment of (1%) hydrogen peroxide in drinking water.3rd and 4th treatment the ratio supplemented with (20 mg melatonin / kg diet) with or without(1%) hydrogen peroxide in drinking water. At 28 days, hematological parameters, antioxidant measurement determined and testes histological assessment. From the results noted a significant reduction in the total counting of red blood cells (RBC) and the relative weight of the testicles with a deterioration in antioxidants status, represented by a significant increase in MDA level and a significant decrease in GSH level of with H2O2 treatment . The supplemented of melatonin led to a decrease in the total number of WBC, PCV, and the concentration of Hb. Moreover, the treatment with the use of melatonin led to an improvement in antioxidants indicators represented by an increase in the level of GSH and a decrease MDA level. As the fourth treatment did not record significant differences compared to the first treatment. Adding melatonin at 20 mg melatonin / kg diet lead to significant improvement in area of germinal layer and its thickness.

Triple negative breast cancer (TNBC) cells are resistant to hormonal/targeted therapies. This study aims to investigate epigenetic differences between TNBC and other types of breast cancer and the effect of epigenetic modulation on the response of TNBC cells to hormonal therapy. Thus, we investigated (i) the expression of different epigenetic markers, (ii) the effect of epigenetic modifying agents on the expression of ERα and HER2/ERBB2 and (iii) the effect on the response to tamoxifen in four breast cancer cell lines with different hormonal receptor status. Our results revealed a differential expression patterns of epigenetic markers in the four breast cancer cells. In TNBC cells, histone deacetylases (HDAC) 1 and 2 were less expressed, whereas HDACs 4 and 6 were overexpressed. Interestingly, treatment with epigenetic modifiers resulted in (i) a pronounced increase in the expression of ERα and HER2/ERBB2 along with (ii) an increase in the sensitivity of TNBC cells to tamoxifen. Collectively, this study indicates a different epigenetic background for TNBC cells, which represses the expression of ERα and HER2/ERBB2. Furthermore, we provide here the rationale for the use of epigenetic modifiers to enhance the response of TNBC to hormonal therapy through upregulation of ERα.

Adipogenesis is an important biological process that is linked to obesity and metabolic disorders. On the other hand, fat regeneration is crucial as a restorative approach following mastectomy or severe burn injury. Furthermore, optimizing an in-vitro model of adipogenesis, which would help in understanding the possible effects and/or side effects of fat-soluble drugs and anti-obesity remedies, in addition to the developmental studies. Epigenetic is an important factor that is involved in cellular differentiation and commitment. This study aimed at investigating the effect of DNA methylation and histone deactylases inhibitors, 5-Aza-deoxycytidine (5-Aza-dC) and Suberoylanilide hydroxamic acid (SAHA), on the adipogenic differentiation process. The two modifiers were applied according to our previously published protocol, followed by three cycles of a classical, two-step adipogenesis protocol. The cells pretreated with SAHA showed enhanced expression of the many adipogenic genes, including peroxisome proliferator-activated receptor-γ as well as the accumulation of intracytoplasmic fat as shown by oil red and Nile red staining and the secretion of adipokines, such as MCP-1 and IP-10. On contrary, 5-Aza-dC inhibited all these markers. In conclusion, adding the reported step with SAHA to the differentiation protocols could have an impact on the progress of the in-vitro fat regenerative approach. The possible role of 5-Aza-dC in the inhibition of adipogenesis can be of clinical interest and will need further characterization in the future.

Sharp‐wave ripples (SWRs) are spontaneous, synchronized neural population events in the hippocampus widely thought to play a role in memory consolidation and retrieval. They occur predominantly in sleep and quiet immobility, and in primates, they also appear during active visual exploration. Typical measures of SWRs in behaving rats include changes in the rate of occurrence, or in the incidence of specific neural ensemble activity contained within the categorical SWR event. Much less is known about the relevance of spatiotemporal SWR features, though they may index underlying activity of specific cell types including ensemble‐specific internally generated sequences. Furthermore, changes in SWR features during active exploratory states are unknown. In this study, we recorded hippocampal local‐field potentials and single‐units during periods of quiescence and as macaques performed a memory‐guided visual search task. We observed that (a) ripples during quiescence have greater amplitudes and larger postripple waves (PRW) compared to those in task epochs, and (b) during “remembered” trials, ripples have larger amplitudes than during “forgotten” trials, with no change in duration or PRWs. We further found that spiking activity influences SWR features as a function of cell type and ripple timing. As expected, larger ripple amplitudes were associated with putative pyramidal or putative basket interneuron (IN) activity, even when the spikes in question exceed the duration of the ripple. In contrast, the PRW was attenuated with activity from low firing rate cells and enhanced with activity from high firing rate cells, with putative IN spikes during ripples leading to the most prominent PRW peaks. The selective changes in SWR features as a function of time window, cell type, and cognitive/vigilance states suggest that this mesoscopic field event can offer additional information about the local network and animal's state than would be appreciated from SWR event rates alone.

Functions of proteins and interactions between them are primarily based on electric and electrodynamic forces. Charge distribution and fluctuations of the individual atomic groups on proteins generates local electric field that ultimately determines how proteins bind and interact. Possibility of modifying and possibly controlling protein function by external electric field lends itself as a tool for both understanding and controlling biological processes. Here we demonstrate, using molecular dynamics, that intense, yet experimentally attainable, electric field affects tubulin dimer conformation within several nanoseconds. We focused on the effects of electric field on the structure and dynamics of C-terminus of beta tubulin. The tail of C-terminus (i) is important for interactions with other proteins such as motor proteins and microtubule severing proteins, (ii) is a major site for mutations and post-translational modifications, (iii) possesses a significant fraction of tubulin electric charge hence it is a natural target of electric field effects.

In order to improve the culturability and biomass production of rhizobacteria, we previously introduced plant-only-based culture media. We herein attempted to widen the scope of plant materials suitable for the preparation of plant-only-based culture media. We chemically analyzed the refuse of turfgrass, cactus, and clover. They were sufficiently rich to support good in vitro growth by rhizobacteria isolates representing Proteobacteria and Firmicutes. They were also adequate and efficient to produce a cell biomass in liquid batch cultures. These culture media were as sufficient as artificial culture media for the cultivation and recovery of the in situ rhizobacteria of barley (Hordeum murinum L.). Based on culture-dependent (CFU plate counting) and culture-independent analyses (qPCR), mowed turfgrass, in particular, supported the highest culturable population of barley endophytes, representing >16% of the total bacterial number quantified with qPCR. This accurately reflected the endophytic community composition, in terms of diversity indices (S', H', and D') based on PCR-DGGE, and clustered the plant culture media together with the qPCR root populations away from the artificial culture media. Despite the promiscuous nature of the plant materials tested to culture the plant microbiome, our results indicated that plant materials of a homologous nature to the tested host plant, at least at the family level, and/or of the same environment were more likely to be selected. Plant-only-based culture media require further refinements in order to provide selectivity for the in vitro growth of members of the plant microbiome, particularly difficult-to-culture bacteria. This will provide insights into their hidden roles in the environment and support future culturomic studies.