Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study.

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.

Melanogenesis Inhibitors from the Endophytic Fungus Aspergillus amstelodami.

Two new compounds, named 3,4-dimethoxyphenyl α-d-ribofuranoside (1) and 3ß-(ß-d-glucopyranosyloxy)olean-12-ene-23,28,30-trioic acid (2), together with thirteen known compounds, were isolated from the white beans culture of the marine derived endophytic fungus Aspergillus amstelodami. Structure elucidation of the new compounds was carried out by one-, two-dimensional spectroscopy, and high resolution electrospray ionization mass. The antimelanogenic and anti-allergic activity of the isolated compounds were investigated. Compounds 4, 7, 1, 3, 11, 6 and 9 selectively suppressed melanin production in B16 melanoma cells, using arbutin as a positive control. Their IC50 values were 30.8±5.57, 38.5±6.08, 52.6±6.64, 98.0±1.16, 100.4±3.05, 112.0±0.22 and 144.7±2.35 µm, respectively, while that of arbutin was 151.7±1.27 µm. The tested compounds did not show any significant anti-allergic activity in RBL-2H3 cells, as compared to quercetin.

Urinary biomarkers for early detection of platinum based drugs induced nephrotoxicity.

BACKGROUND: Nephrotoxicity is a major hazard complicating the use of platinum based drugs (PBD), which can hinder using higher doses protocols to maximize the therapeutic gain. Shortage of serum creatinine level as an accurate biomarker for acute kidney injuries (AKI) necessitates searching for novel biomarkers with better sensitivity and specificity in patients on PBD. METHODS: In a prospective cohort design, 132 patients receiving PBD were selected for the study. AKI was diagnosed by continuous follow up of serum creatinine level according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 2012. Serum creatinine and urinary biomarkers (KIM-1, NGAL and cystatin C) was measured in the day of treatment and for 3 days after PBD cycle. RESULTS: AKI occurred in 35 patients (26.52% of patients). KIM-1, Cystatin C, and NGAL showed significant increase in samples collected in the day of AKI in comparison to their corresponding basal levels (P <  0.0001). In addition, significant increase in urinary levels of the biomarkers in samples collected 1 day before AKI in comparison to their basal levels (P <  0.0001, P <  0.0001, and P = 0.013 for KIM-1, NGAL and Cystatin C respectively). Furthermore KIM-1 data showed a significant increase 2 days before serum creatinine rise in comparison to the corresponding KIM-1 levels in patients who developed AKI (P = 0.001). CONCLUSIONS: Urinary KIM-1, Cystatin C and NGAL can predict PBD induced AKI in earlier stages than serum createnine. KIM-1 is the most sensitive biomarker for early detection of AKI in patients receiving PBD.

Cladamide: a new ceramide from the endophytic fungus Cladosporium cladosporioides.

A new ceramide, named cladamide (1), in addition to cinnamic acid (2), para-coumaric acid (3), stigmasterol-3-O-ß-D-glucoside (4), and uracil (5), was isolated from the white beans culture of Cladosporium cladosporioides, a marine-derived endohpytic fungus isolated from the leaves of the mangrove, Avicennia marina (Forssk.) Vierh. Structure elucidation of compound 1 was established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC50 = 0.057 ± 0.003 µM), followed by compound 4 (IC50 = 0.068 ± 0.003 µM) and compound 1 (IC50 = 0.099 ± 0.005 µM) compared to donepezil, the positive control, (IC50 = 0.044 ± 0.002 µM). Compounds 2 and 5 showed lower activity (IC50 = 0.182 ± 0.009 and 0.236 ± 0.012 µM, respectively). The results were further validated by molecular docking study.

Impact of green antioxidants on decreasing the aflatoxins percentage in peanut oil seed (Arachis hypogaea L.) during storage.

The present study conducted an experimental investigation to impede the degradation of peanut (Arachis hypogaea L.) seeds and enhance their quality while being stored. The efficacy of eco-friendly chemicals such as ascorbic acid, salicylic acid, acetic acid, and propionic acid in seed preservation was evaluated over a period of six months. After a period of six months of storage in a greenhouse, an examination was conducted on peanut seeds that had undergone treatment. Rhizoctonia was observed after Cephalothorax, whereas Aspergillus, Fusarium, and Penicillium were the prevailing fungi throughout the storage period. The optimal outcomes were obtained from the conversion of acetic acid to propionic acid. The study observed a decline in seed oil, protein, carbohydrates, germination percentage, energy, index, length, vigour index, dead and rotten seeds, rotted seedlings, and surviving healthy seedlings, with an increase in storage duration ranging from zero to six months. The application of 100% propionic acid to peanut seeds throughout the storage duration resulted in decreased occurrences of deceased seeds, decaying seeds, and deteriorated seedlings. Peanut seeds that underwent treatment with green chemical agents of moderate and high intensity were found to be free of aflatoxin B1. The highest levels of chlorophylls a and b, carotenoids, and total phenols were observed in seeds stored in greenhouses and treated with 100% propionic acid and acetic acid extract. The application of propionic acid 100%, acetic acid 100%, salicylic acid 4 g/l and ascorbic acid 4 g/l proved to be the most effective treatments for peanut seeds, exhibiting the lowest total aflatoxin level of 0.40. The correlation coefficient between shoot fresh weight and shoot dry weight was found to be 0.99, whereas the correlation coefficient between root dry weight and shoot length was 0.67. The seed chemical analysis, seedling characteristics, and germination characteristics were subjected to clustering analysis, resulting in the formation of two distinct groups. The first group consisted of germination percentage and energy levels across all time points (0-6 months), while the second group consisted of the remaining characteristics. The findings of this research propose the utilisation of 100% propionic acid as a viable method for preserving peanut seeds and preventing their deterioration during storage. The application of 100% acetic acid has been found to be effective in enhancing the quality of seeds and minimising losses.

Appreciation of Genetic Parameters and Molecular Characterization in Some Promising Accessions of Soybean (Glycine max L.).

BACKGROUND AND OBJECTIVE: Soybean crop occupies a high position among cereal crops because it is a highly nutritious plant. This investigation aimed to take advantage of the imported soybean lines in improving the local varieties. MATERIALS AND METHODS: Three local varieties and 4 imported lines of soybean plant were planted during two seasons for estimating some genetic parameters including (Heritability in broad sense, PCV (%), GCV (%), DZ, expected genetic advance and genetic advance as percentage of mean) in some agro-morphological traits besides molecular characterization for the seven soybean materials using 6 SCoT primers. RESULTS: The four imported soybean genotypes besides the local cultivar Giza 111 exhibited highly trend for all studied traits in both seasons. Heritability and genetic advance were exhibited significance and high values in most studied traits under both seasons. CONCLUSION: The imported soybean genotypes confirmed significant excellence in all studied traits and recorded highly genetic stability for both seasons depending on results obtained of all genetic parameters. Therefore, the decision to use it as a new and good genetic source to improve, develop and raise the productivity of Egyptian soybean varieties as well as its resistance to biotic and abiotic stresses will be right and fruitful.

Assessment of Water Stress Tolerance in Wheat Genotypes Based on Half Diallel Analysis and DNA Fingerprinting.

BACKGROUND AND OBJECTIVE: Deficit or scarcity of water resources are considering as one of the most serious environmental phenomenon that hinder agricultural production in many countries and the present study evaluated some wheat accessions for water stress tolerance under Egyptian conditions. MATERIAL AND METHODS: Five wheat genotypes and their ten F1 crosses from half diallel analysis were tested under both levels of irrigation (normal and drought stress conditions) through estimating some agro-morphological traits in addition, determining DNA fingerprinting meanwhile using five RAPD-PCR primers. RESULTS: Final results detected that 4 parents and the best 5 F1 crosses were the most desirable genotypes for water stress tolerance depending on all results obtained for all calculated parameters under normal and water deficit treatments. CONCLUSION: Traditional breeding and DNA fingerprinting could be used to clarify and sort all genotypes to generate the best of them for water stress resistance which will be in the future as a nucleus for producing resistance wheat varieties for drought stress under Egyptian conditions.

The role and limitations of mammary ductoscope in management of pathologic nipple discharge.

Mammary ductoscope allows visualization of the breast ductal wall and sampling of the abnormal area for diagnostic purposes. We are reporting our center experience in application of mammary ductoscope in detecting the underlying etiology of pathologic nipple discharge. Between November 2005 and December 2006 a total of 54 women, with spontaneous persistent nonlactational unilateral uniductal nipple discharge of no palpable lesions and negative breast sono-mammography, were included in the study for morphologic assessment of ductal epithelium, ductal lavage and ductoscopically guided procedures as punch biopsy and ductoscopically guided microdochectomy. Forty-one patients (76%) with nipple discharge were positive ductoscopically. Thirteen patients (24%) appeared normal. Ductoscopic lavage has a much more cellular yield than ordinary squeezing cytology. Ductal thickening by the ductoscope (11 cases) revealed to be hyperplasia on pathology (five cases), papilloma (two cases), atypical ductal hyperplasia (two cases), ductal carcinoma in situ (one case), and invasive breast carcinoma (one case). There was a significant association between intraductal visual observations and histopathologic diagnosis. Mammary Ductoscope is a promising tool in management of pathologic nipple discharge. Biopsy and ablation techniques can be performed during ductoscopy with correlation between visual findings and histopathology, but there are still some limitations of in clinical practice.

Hepatitis C and B virus in schistosomiasis patients on oral or parenteral treatment.

Egypt leads the world in hepatitis C infection cases. Schistosomiasis and hepatitis C virus (HCV) co-infection is common in Egypt. Hepatitis B (HBsAg) is also encountered. Potassium antimony tartarate was used for schistosomiasis in endemic areas all over the world for more than 50 years, intravenously and was prohibited since late of the last century when the oral drugs were developed. Some authors postulated that schistosomiasis might contribute to persistence of HCV via biological factors. This study compared the prevalence of HCV and HBV among schistosomiasis patients in endemic areas given parenteral or oral route antischistosomiasis. A total of 102 manual workers patients were selected from different areas in Cairo and Gharbia Governorates. They were 82 males and 20 females; their age was ranged between 16-60 years (40 +/- 12). Sheets were filled out on each patient including name, age, sex, history of haematurea or bloody diarrhea, parasitic infection, intravenous injections, blood transfusion, dental care, shaving, previous treatment, and anti-schistosomiasis. They were divided into GI: 50 patients treated IV since 20-30 years ago with ages (49.4 +/- 7.4) and GII: 52 patients treated orally up to 8 years ago with ages (2.2 +/- 7.7). They were subjected to IHAT antischistosomal antibodies, circulating schistosome antigens in urine, HBsAg and HCVAb, the latter was confirmed by PCR for positivity, and Alanin transeferese (ALT). In GI, 42/50 (84%) had HCV compared to 4/52(7.7%) in GII, with statistical significant. HBsAg was detected in a patient. HCV patients showed abnormal liver function. 3/52 received oral treatment showed elevation of liver function (5.8%). 10% (10/50) of GI and 34.6% (18/52) of GII were schistosomal antigen in urine positive.

Trypanosoma evansi in dromedary camel: with a case report of zoonosis in greater Cairo, Egypt.

Trypanosoma evansi (Steel, 1885) Balbiani, is the cause of trypanosomiasis (Surra) which multiples in the blood and body fluids. The incubation period varies from 7-15 days. The mortality rate was up to 20% and fatality rate may reach up to 100% in untreated camels. Three hundred randomly selected camels were 200 males 4-6 years old and 100 females 10-15 years. They were examined clinically and diagnosed by Giemsa stained blood smear, anti- trypanosomiasis-antibodies by ELISA and urine Thymol turbidity test for natural infection with T. evani (Surra). The results showed that camels were naturally infected with T. evansi as indicated by stained blood film examination and/or ELISA. Infection in males was 6.0% (stained blood smears), 8.0% (ELISA) and 5.0% (urine thymol turbidity test). In females the infection rate was 9.0%, 24.0% and 12% respectively. By correlation with suggestive clinical manifestations, ELISA proved to be more sensitive and specific (13.3%) than stained blood films (10.0%) and urine Thymol turbidity test (7.3%). Regarding humans, one out of 30 was positive as indicated by ELISA and stained blood smear but was negative by urine thymol turbidity test. The human case was successfully treated as indicated clinically, parasitologically and serologically. This is the first reported Egyptian human case of trypanosomiasis evansi, a neglected zoonosis.

Zoonotic brucellosis: an underestimated or misdiagnosed disease in Egypt.

Over six months, 329 suggestive consecutive brucellosis human cases were diagnosed in attending the out-patients clinics of Al-Azhar and Ain Shams Universities Hospitals and Giza Governorate Farmers. They were 100 females and 229 males with ages ranged between 15-65 years old. A total of 213 (64.75%) were working in dairy farm and/or consumed raw milk, 16 (14.85%) used home slaughtering of sheep, and 100 (30.4%) were working in Giza Government slaughter-house. Clinically and by ELISA-IgM 259 out of 329 the subjects were proven brucellosis patients (77.8%). Besides, other patients had toxoplasmosis, or schistosomiasis mansoni or fascioliasis. Double infection was encountered with toxoplasmosis and either schistosomiasis or fascioliasis. The causes of endemic liver parasitosis that may give false-clinical diagnosis were excluded. Signs and symptoms of brucellosis patients were fever (91.5%), chills (84.1%), Myalgia (69.5%), headache (58.2%), fatigue (77.2%), anorexia (54.1%), tachycardia (38.6%), hepato-and/or splenomegaly (46.2%), lymphadenopaqthy (19.6%) lower back abdominal pain (8.8%) and/or constitutive symptoms (13.1%).

Interleukin (Il)-12, Il-5 and total IgE in hepatosplenic schistosomiasis with or without asthma.

There are a number of similarities between protective immune responses against schistosomiasis and asthma. Both are associated with elevated concentrations of IgE and eosinophilia. Chronic schistosomiasis is liked to Th1 like response with involvement of pro-inflammatory cytokines in schistosomal hepatosplenic disease process resulting in low level of IL-5. Meanwhile, association with asthma could modulate the immune response with shift to Th2 side resulting in marked elevation of IL-5 and eosinophilia. This work evaluated the levels of serum IgE, IL-5 and IL-12 in Schistosoma mansoni-infected asthmatic patients. A total of 100 subjects selected from Al-Azhar University's Hospitals were divided into three groups GI: 50 patients with hepatosplenic schistosomiasis associated with asthma. GII: 25 patients with hepatosplenic schistosomiasis without apparent asthma. GIII: 25 patients with neither bilharzial liver cirrhosis nor asthma as control group. All patients were subjected to full history taking and clinical examination, pulmonary function tests, total serum IgE, bilharzial antibody titre, stool and urine examination for parasites, liver function tests and serum IL-5 and IL-12. The results showed very high level of the total serum IgE in GI and GII compared to GIII. There was high significant difference in peripheral blood eosinophil%. GI & GII gave highest levels, IL-5 was elevated in GI, but low GII, I-12 was high in GII than GI.