Gene expression of multidrug-resistant ATP-binding cassette transporter (MDR1/ABCB1) in bovine mastitis

Purpose: To investigate the expression of multidrug-resistant ATP binding cassette transporter Pglycoprotein (MDR1/ABCB1/P-gp) in mastitis and its correlation with the expression of apoptosis regulation.Methods: Mastitic and normal mammary gland samples were collected after clinical examination and confirmed using field California mastitis test. Total RNA was extracted followed by cDNA synthesis and real-time PCR to detect the expression pattern of P-gp. Tissue sections were examined for pathological changes and immune reactivity to the apoptotic regulator, Bcl-2-associated X protein (BAX).Results: Stained sections from mastitic samples showed congestion, infiltration of inflammatory cells and hemorrhage. Using immunohistochemistry, it was shown that mastitis is associated with overexpression of the apoptosis regulator, Bcl-2-associated X protein (BAX). There was increased expression of the pro-apoptotic factor, Bax, in mastitic alveolar lining and lactic tubules compared with normal mammary gland tissues. Using real-time PCR, the expression level of MDR1/ABCB1 was determined to be 2.6-fold higher in mastitic tissues than in normal mammary tissues.Conclusion: Higher MDR1/P-gp level can modulate drug interventions by preventing intracellular accumulation of chemotherapeutics or anti-inflammatories via continuous efflux or export to extracellular fluids.Keywords: ABC transporter, P-glycoprotein, Drug exporters, Mastitis, Mammary glan

Substructural dynamics of the phase-I drug metabolizing enzyme, carbonyl reductase 1, in response to various substrate and inhibitor configurations

Purpose: To investigate the substructure and molecular dynamics change in the phase-I drug metabolizing enzyme, carbonyl reductase 1 (CBR1), in response to different substrate and inhibitor configurations, using a molecular dynamics approach. Methods: CBR1 structure and drug ligands, including 2,3-butanedione, prostaglandin E2 (PGE2), oracine, mitoxantrone, menadione, rutoside, barbital, and biochanin A, were retrieved and 3D optimized. Docking runs were performed using template docking into CBR1 active binding site with GSH. Molecular dynamic (MD) simulation was implemented for 100 ns. Results: The docking scores were positively correlated with the detected ligand’s affinities. Molecular dynamics simulation indicated that lower affinity ligands or weaker inhibitors produced less stable CBR1 with higher root mean square deviations (RMSD) of CBR1 backbone α-carbon atoms. Stronger inhibitors and substrates produced stable CBR1 structures with RMSD similar to or lower than CBR1- NADP complexes. Very low affinity ligands were unstable and were released from their sites within a few nanoseconds after commencing the simulation. Two flexible loops, LE92-PHE102 and VAL230- TYR251, were highly responsive to the nature of CBR1 ligands. Changes in the latter may be associated with lower CBR1 activity due to loss of stabilization of NADPH by the deviation of this loop’s residues. Conclusion: In this work, a model of CBR1 structural changes has been provided that can be used in the analysis of CBR1 future substrates and inhibitors. Docking followed by MD simulation and analysis of average backbone α-carbon RMSD and changes in ILE92-PHE102 and VAL230-TYR251 loops can be used in the model analysis of unknown or new drug candidates to predict their binding efficiencies

Anti-proliferative activity of leaves of Launaea capitata Asteraceae: Phytochemical, cytotoxicity and in silico studies

Purpose: To investigate the phytochemical contents of Launaea capitata (L. capitate) and its potential cytotoxic activity. Also, to examine its molecular modeling by docking of the isolated compounds.Methods: L. capitata was methanol-extracted and successively fractionated followed by determination of the total phenolic and flavonoid contents. Major constituents were isolated and purified. 3-(4, 5- Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity assays were conducted for all fractions. In silico studies were conducted using four anticancer target kinases, namely, protein kinase B (PKB/AKT), phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), and rapidly accelerated fibrosarcoma kinases (RAFK).Results: The results showed that total phenolic constituents ranged from 0.150 ± 0.004 to 60.229 ± 0.822 mg Gallic Acid Equivalent/g of dry extract, while the total flavonoid content varied from 0.004 ± 0.002 to 18.129 ± 1.599 mg quercetin equivalent/g of dry extract. Furthermore, the ethyl acetate fraction contained the highest amount of phenolic and flavonoid contents, which seemed to constitute the most effective anti-proliferative fraction. The plant’s major constituent was apigenin-7-O-glycoside and was isolated from the ethyl acetate fraction. The MTT cytotoxicity assay revealed the anti-proliferative activity of ethyl acetate and butanol fractions, and apigenin-7-O-glycoside with half-maximal concentration (IC50) comparable to that of doxorubicin. In silico studies revealed that apigenin-7-Oglycoside showed a better binding score and ligand efficiency when compared with standard ligands/inhibitors for AKT/PKB and PI3K, suggesting potential multiple targets for its anti-cancer activities.Conclusion: L. capitata contains considerable amounts of phenolic and flavonoid components. Its major constituent, apigenin-7-O-glycoside is a potential lead compound for developing new anticancer compounds. Keywords: Launaea capitata, Total phenolics, Total flavonoids, Docking, Cytotoxicit

Evaluación sérica y salival del factor de crecimiento transformante beta, factor de crecimiento endotelial vascular y factor de necrosis tumoral alfa en liquen plano oral.

Introduction: Lichen planus is one of the most common oral mucosal lesions. Transforming growth factor-? (TGF- ?) has a marked effect on epithelial–mesenchymal transition and immune cells function. Vascular Endothelial Growth Factor (VEGF) is a key regulator of vasculogenesis and angiogenesis. Tumor necrosis factor-? (TNF-?) mediates T-lymphocyte homing and apoptosis of epithelial cells. Objetive: The present study was conducted in order to compare the expression of serum and salivary TGF- ?, VEGF, TNF-? between OLP patients and control individuals to investigate if saliva can be used as an alternative to serum for diagnostic purposes and for monitoring disease. Materials and Methods: 23 OLP patients and 23 control individuals were included to evaluate serum and salivary TGF-?, VEGF, TNF-? using ELISA kits. Five milliliters of venous blood was collected and unstimulated saliva was collected by the spitting method. Results: Serum and salivary levels of TGF- ?, VEGF, TNF-? are higher in OLP patients compared to normal controls. Mean difference is higher in saliva than serum. Moreover, there was a significant difference in serum and salivary VEGF and TNF-? between symptomatic and asymptomatic groups. Conclusions: Saliva can be a used as a substitute for serum to evaluate levels of the assessed biomarkers.Introducción: El liquen plano oral es una de las lesiones de la mucosa oral más comunes. El factor de crecimiento transformante ? (TGF-?) tiene un efecto marcado sobre la transición epitelial-mesenquimal y la función de las células inmunes. El factor de crecimiento endotelial vascular (VEGF) es un regulador clave de la vasculogénesis y la angiogénesis. El factor de necrosis tumoral ? (TNF-?) media la localización de los linfocitos T y la apoptosis de las células epiteliales. Objetivo: El presente estudio se realizó con el fin de comparar la expresión en suero y saliva de TGF-?, VEGF, TNF-? entre pacientes con OLP y personas de control para investigar si la saliva se puede utilizar como alternativa al suero para fines de diagnóstico y monitoreo de la enfermedad. Material y Métodos: Se incluyeron 23 pacientes con OLP y 23 individuos control para evaluar los niéveles en suero y en saliva de TGF-?, VEGF, TNF-? utilizando kits ELISA. Se recogieron cinco mililitros de sangre venosa y se recogió saliva no estimulada por el método de escupir. Resultado: Los niveles séricos y salivales de TGF-?, VEGF, TNF-? son más altos en pacientes con OLP en comparación con los controles normales. La diferencia media es mayor en saliva que en suero. Además, hubo una diferencia significativa de VEGF y TNF-? en suero y saliva entre los grupos sintomáticos y asintomáticos. Conclusion: La saliva puede usarse como un sustituto del suero para evaluar los niveles de los biomarcadores estudiados

Flash Fiction from North Africa

Književno prevođenj

A longitudinal study of bovine viral diarrhea virus in a semi-closed management dairy cattle herd, 2020–2022

IntroductionBovine viral diarrhea virus (BVDV) brings great economic loss to the cattle industry worldwide. Developing a control/prevention strategy requires the prior assessment of certain epidemiological parameters. To determine the BVD incidence rate and associated risk factors, a dairy cattle herd in the eastern region of Saudi Arabia was monitored between 2020 and 2022.MethodsNasal swabs (n = 190), rectal swabs (n = 190), and sera (n = 190) were collected from 79 cows in this herd. Collected sera and swabs were tested using the commercially available ELISAs for the BVDV antibodies and antigens, respectively. Collected sera were also tested for the presence of BVDV nucleic acids using commercial real-time RT-PCR kits.Results and discussionOur data show BVDV seroprevalence (18.8%, 15%, and 8.2%) in the tested animals in 2020–2022, respectively. None of the collected nasal swabs, rectal swabs, or sera tested positive for the BVDV antigen, whereas 10.1%, 10%, and 18.1% of the tested sera were positive for BVDV nucleic acid in 2020–2022, respectively. The incidence rate was estimated at 0.02446 new cases/year despite the detection of BVDV in seronegative animals on single or two occasions at ≥6-month intervals. Young calves and bulls remained apparently unexposed to BVDV despite their presence with BVDV-infected females, with no significant physical separation. Both seropositivity and nucleic acid detectability showed significant positive and negative correlations, respectively, with reproductive performance. Collectively, the present study provides useful clues about the transmissibility of BVDV in the presence of possibly persistently infected animals. To the best of our knowledge, this is the first longitudinal study of BVDV in the Eastern Region of Saudi Arabia. Further detailed characterization of the circulating BVDVs is encouraged

Maxillary neoplasms in four dromedary camels

Four camels (Camelus dromedarius) presented to the Veterinary Teaching Hospital at King Faisal University with maxillary masses. On radiographs, the masses were multicystic and expanded the maxillary bone. The tumors were diagnosed by histopathologic examination as conventional ameloblastoma, two cases as intraosseous squamous cell carcinoma, and central odontogenic fibroma with ossification. To the authors’ knowledge, this is the first report of ameloblastoma in a camel, the first detailed description of maxillary squamous cell carcinoma in camels, and the first report of central odontogenic fibroma in any animal species

1,2,3-Triazolyl-tetrahydropyrimidine conjugates as potential Sterol Carrier Protein-2 Inhibitors: Larvicidal activity against the Malaria Vector Anopheles arabiensis and In Silico Molecular Docking Study

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure–activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules’ potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.Fil: Venugopala, Katharigatta N.. Durban University Of Technology; Sudáfrica. King Faisal University; Arabia SauditaFil: Shinu, Pottathil. King Faisal University; Arabia SauditaFil: Tratrat, Christophe. King Faisal University; Arabia SauditaFil: Deb, Pran Kishore. Philadelphia University Jordan; JordaniaFil: Gleiser, Raquel M.. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (P). Grupo Vinculado Centro de Relevamiento y Evaluación de Recursos Agrícolas y Naturales; ArgentinaFil: Chandrashekharappa, Sandeep. National Institute Of Pharmaceutical Education And Research, Raebareli; IndiaFil: Chopra, Deepak. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Attimarad, Mahesh. King Faisal University; Arabia SauditaFil: Nair, Anroop B.. King Faisal University; Arabia SauditaFil: Sreeharsha, Nagaraja. Vidya Siri College Of Pharmacy; India. King Faisal University; Arabia SauditaFil: Mahomoodally, Fawzi M.. University Of Mauritius; MauricioFil: Haroun, Michelyne. King Faisal University; Arabia SauditaFil: Kandeel, Mahmoud. Faculty Of Veteinary Medicine; Egipto. King Faisal University; Arabia SauditaFil: Asdaq, Syed Mohammed Basheeruddin. Almaarefa University; Arabia SauditaFil: Mohanlall, Viresh. Durban University Of Technology; SudáfricaFil: Al-Shari, Nizar A.. Jordan University Of Science And Technology; JordaniaFil: Morsy, Mohamed A.. King Faisal University; Arabia Saudita. Faculty Of Medicine; Egipt

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Genome-Wide Identification of B3 DNA-Binding Superfamily Members (ABI, HIS, ARF, RVL, REM) and Their Involvement in Stress Responses and Development in Camelina sativa

The B3 DNA-binding superfamily is a group of gene families that contain a B3 domain in their proteins. Members of this superfamily are involved in responses to stresses including salt, drought, and cold stress. The B3 DNA-binding superfamily has not been fully studied in Camelina sativa. A total of eighty-seven members of this superfamily were identified in C. sativa. The identified genes were placed into five groups based on a phylogenetic analysis. All the proteins were predicted to be nuclear. The RAV and ARF gene family had the most conserved motifs, with nine out of ten motifs being preserved, while the REM gene family was discovered to have the fewest, with just one conserved motif being present. The RAV and REM gene families showed the least protein&ndash;protein interactions. The CsARF5 and CsARF7 genes showed the highest potent interaction score with multiple auxin-responsive proteins. A qPCR analysis was carried out on six genes that showed stress-induced expression changes. CsREM17, CsREM5, and CsRAVL5 were discovered to be considerably increased in response to drought stress, while CsARF10, CsARF4, and CsREM34 were found to be downregulated to a large extent. The B3 DNA-binding superfamily regulates abscisic acid signaling, which in turn influences plant growth and stress resistance