Upregulation of BRCA1 and 2 protein expression is associated with dysregulation in amino acids profiles in breast cancer.

BACKGROUND: The prevalence of breast cancer (BC) is high among cancers in Egypt, ranking it the most common cause of cancer mortality in women. BRCA1 and BRCA2 tumor suppressors proteins have a specific relationship with BC. Plasma free amino acids levels (PFAAs) have been reported to exhibit altered profiles among cancer patients. Thus, the present study aims to examine the alteration of the PFAAs profiles and investigate their association with BRCA1 and 2 circulating levels in Egyptian females diagnosed with BC and in females with family history of BC to establish potential early detection strategies for BC. METHODS AND RESULTS: This study included 26 BC patients, 22 females with family history of BC (relatives) in addition to 38 healthy females as control group. Quantitative measurement of PFAAs was determined by the ion exchange separation method through high performance liquid chromatography. BRCA1 and BRCA2 concentrations were determined using ELISA. Our results showed PFAAs profiles in BC patients and in females with BC family history with significant upregulation in mean plasma levels of Alanine, Phenylalanine, Glutamate and Cysteine and downregulation of Taurine, Threonine, Serine, Glycine, Valine, Methionine and Histidine levels compared to controls. Also, a significant positive correlation was observed between plasma BRCA1 and Valine levels while a significant negative correlation was observed between BRCA2 and Lysine plasma levels. CONCLUSION: PFAAs profile can potentially be used in early screening for BC patients and for susceptible females.

Cross-sectional community-based study to assess the awareness of toxoplasmosis in Saudi Arabia.

A few reports have been published and documented low level of awareness on toxoplasmosis among Saudi women. Herein, a cross sectional community based study was undertaken to evaluate basic knowledge on toxoplasmosis among residents in the Eastern province (Sharqiyah). Thisstudy was conducted between December 2022 and January 2023 on 334 females from different ages and educational backgrounds. Analysis of their responses revealed that only (24.9%) had heard about the disease. However, (69.8%) properly identified cats as the source of Toxoplasma gondii (T. gondii), but a smaller percentage (47.7%) knew that they might become infected through handling cat feces, and a few (26.3%) believed that bad hand hygiene can result in T. gondii infection. A few males (n = 26) have also participated, for the first time in Saudi Arabia, and displayed also low level of knowledge on toxoplasmosis. We do recommend establishing educational programs for females, in various Saudi provinces, to raise awareness on toxoplasmosis.

Efficacy of the Antimalarial MMV390048 against Babesia Infection Reveals Phosphatidylinositol 4-Kinase as a Druggable Target for Babesiosis.

The present study aimed to evaluate the anti-Babesia effect of MMV390048, a drug that inhibits Plasmodium by targeting the phosphatidylinositol 4-kinase (PI4K). The half inhibitory concentration (IC50) of MMV390048 against the in vitro growth of Babesia gibsoni was 6.9 ± 0.9 µM. In immunocompetent mice, oral treatment with MMV390048 at a concentration of 20 mg/kg effectively inhibited the growth of B. microti (Peabody mjr strain). The peak parasitemia in the control group was 30.5%, whereas the peak parasitemia in the MMV390048-treated group was 3.4%. Meanwhile, MMV390048 also showed inhibition on the growth of B. rodhaini (Australia strain), a highly pathogenic rodent Babesia species. All MMV390048-treated mice survived, whereas the mice in control group died within 10 days postinfection (DPI). The first 7-day administration of MMV390048 in B. microti-infected, severe combined immunodeficiency (SCID) mice delayed the rise of parasitemia by 26 days. Subsequently, a second 7-day administration was given upon recurrence. At 52 DPI, a parasite relapse (in 1 out of 5 mice) and a mutation in the B. microti PI4K L746S, a MMV390048 resistance-related gene, were detected. Although the radical cure of B. microti infection in immunocompromised host SCID mice was not achieved, results from this study showed that MMV390048 has excellent inhibitory effects on Babesia parasites, revealing a new treatment strategy for babesiosis: targeting the B. microti PI4K.

Pycnogenol a promising remedy for diabetic keratopathy in experimentally induced corneal alkali burns in diabetic rats.

AIM: This study aimed to investigate the efficiency of topically applied pycnogenol (PYC) in healing the standardized alkaline corneal ulcer in diabetic and normal rats. MATERIALS AND METHODS: The corneal alkali-burn injury (CA-I) model was unilaterally developed in Wistar rats by filter paper saturated with 0.01 M of NaOH and touching the eyes for 45 s. Rats were divided into four groups: Normal control (NC), normal PYC (NPYC), diabetic control (DC), and diabetic PYC (DPYC). Both NPYC and DPYC groups were daily treated with PY eye drops three times, whereas NC and DC ones were treated with ordinary saline for six successive days. RESULTS: The wound healing of corneal epithelial was improved in the NPYC group compared to the NC group. Meanwhile, it was significantly improved (P < 0.05) in the DPYC group than in the DC group. Histological examination revealed that corneal re-epithelialization was more accomplished in the DPYC group than in the DC group. In addition, the inflammatory cells were augmented in the DC group more than those in the DPYC one. CONCLUSION: The findings obtained revealed the efficiency of PYC for enhancing the corneal re-epithelialization and reducing the inflammatory reaction post alkali burn in rats, and thus it could be beneficially valuable as a treatment for the diabetic keratopathy.

Moving-Target Defense in Depth: Pervasive Self- and Situation-Aware VM Mobilization across Federated Clouds in Presence of Active Attacks.

Federated clouds are interconnected cooperative cloud infrastructures offering vast hosting capabilities, smooth workload migration and enhanced reliability. However, recent devastating attacks on such clouds have shown that such features come with serious security challenges. The oblivious heterogeneous construction, management, and policies employed in federated clouds open the door for attackers to induce conflicts to facilitate pervasive coordinated attacks. In this paper, we present a novel proactive defense that aims to increase attacker uncertainty and complicate target tracking, a critical step for successful coordinated attacks. The presented systemic approach acts as a VM management platform with an intrinsic multidimensional hierarchical attack representation model (HARM) guiding a dynamic, self and situation-aware VM live-migration for moving-target defense (MtD). The proposed system managed to achieve the proposed goals in a resource-, energy-, and cost-efficient manner.

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension.

BACKGROUND: The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. METHODS: Thirty male Wistar rats weighing 150-200 g were equally divided into: 1-Control group (fed normal laboratory diet for 24 weeks), 2-Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3-Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. RESULTS: High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. CONCLUSION: Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

Microanalysis of Two Members of Oxicam Drugs by Quenching the Fluorescence of Newly Isolated Carbonaceous Materials From Incense Ash.

For the first time ever, useful fluorescent (FL) carbonaceous materials (CMTS) were isolated from incense ash using facile procedure on two steps; dispersion of the CMTS in water followed by filtration. The CMTS were characterized using the following techniques; dynamic light scattering (DLS), transmission electron microscopy (TEM) and Fourier transform infrared (FT-IR) spectroscopy. The CMTS exhibit excitation wavelength dependent fluorescence emission, so it can be used as a FL probe. The FL probe was employed for sensing and quantitative determination of two members of oxicam family (tenoxicam (TEN) and meloxicam (MEL)) that belongs to non-steroidal anti-inflammatory drugs (NSAIDs). The method is based on the quenching of the FL intensity of the isolated CMTS by inner filter effect mechanism (IFE). The FL intensity decreases in linear relationship with increasing the concentrations of the two cited drugs within the range of 4.0 - 30.0 µg/mL with mean percentage recoveries of 100.04 ± 0.95 and 100.07 ± 1.06 with detection limits of 1.31 µg/mL and 1.06 µg/mL for TEN and MEL, respectively. Finally, the developed sensing system was validated as per ICH guidelines and it was proved to be accurate and precise and applied successfully for quantitative determination of the two cited drugs in their capsule dosage forms with excellent percentage recoveries reaching to 97.66 ± 0.39and 98.19 ± 1.12 for TEN and MEL, respectively.

Compounds from the Medicines for Malaria Venture Box Inhibit In Vitro Growth of Babesia divergens, a Blood-Borne Parasite of Veterinary and Zoonotic Importance.

Babesiosis is an infectious disease with an empty drug pipeline. A search inside chemical libraries for novel potent antibabesial candidates may help fill such an empty drug pipeline. A total of 400 compounds (200 drug-like and 200 probe-like) from the Malaria Box were evaluated in the current study against the in vitro growth of Babesia divergens (B. divergens), a parasite of veterinary and zoonotic importance. Novel and more effective anti-B. divergens drugs than the traditionally used ones were identified. Seven compounds (four drug-like and three probe-like) revealed a highly inhibitory effect against the in vitro growth of B. divergens, with IC50s ≤ 10 nanomolar. Among these hits, MMV006913 exhibited an IC50 value of 1 nM IC50 and the highest selectivity index of 32,000. The atom pair fingerprint (APfp) analysis revealed that MMV006913 and MMV019124 showed maximum structural similarity (MSS) with atovaquone and diminazene aceturate (DA), and with DA and imidocarb dipropionate (ID), respectively. MMV665807 and MMV665850 showed MMS with each other and with ID. Of note, a high concentration (0.75 IC50) of MMV006913 caused additive inhibition of B. divergens growth when combined with DA at 0.75 or 0.50 IC50. The Medicines for Malaria Venture box is a treasure trove of anti-B. divergens candidates according to the obtained results.

Phytochemical and antimicrobial investigation of the leaves of five Egyptian mango cultivars and evaluation of their essential oils as preservatives materials.

The sterols, hydrocarbons and fatty acids constituents of the leaves of five mango cultivars locally implanted in Egypt were identified. The effect of their essential oils (EOs) against food borne microorganisms was studied as preservative materials. The chemical constituents of the EOs isolated from mango leaves were identified by Gas Chromatography-Mass spectrometry (GC-MS) technique. Trans-caryophyllene, α-humulene and α-elemene were identified as terpene hydrocarbons, while 4-hydroxy-4-methyl-2-pentanone as oxygenated compounds were recorded in all tested cultivars with variable amounts. Results showed that Staphylococcus aureus and Escherichia coli were the most sensitive microorganisms tested for Alphonso EOs. On the other hand, Salmonella typhimrium was found to be less susceptible to the EOs of the studied cultivars. The EOs of different mango cultivars induced a steady decrease in the activity of amylase, protease and lipase at the minimum inhibitory concentration (MIC). The treatment of the tested bacteria with the EOs of mango cultivars caused a steady loss in enterotoxins even when applied at the sub-MIC. Bacteria-inoculated apple juice treated with minimum bactericidal concentration of Alphonso oil was free from the bacteria after 5 days of incubation at 25 °C. Eighteeen volatile compounds were found to reduce the activity of the amylase enzyme and the most active was cedrelanol (-7.6 kcal mol-1) followed by alpha-eudesmol (-7.3 kcal mol-1) and humulene oxide (-7 kcal mol-1). The binding mode of both of cedrelanol and alpha-eudesmol with amylase enzyme was illustrated.

Attenuation of sleep deprivation dependent deterioration in male fertility parameters by vitamin C.

PURPOSE: Male fertility is multifaceted and its integrity is as well multifactorial. Normal spermatogenesis is dependent on competent testicular function; namely normal anatomy, histology, physiology and hormonal regulation. Lifestyle stressors, including sleep interruption and even deprivation, have been shown to seriously impact male fertility. We studied here both the effects and the possible underlying mechanisms of vitamin C on male fertility in sleep deprived rats. METHODS: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (remained in their cages with free access to food and water), sleep deprivation (SD) group (subjected to paradoxical sleep deprivation for 5 consequent days, rats received intra-peritoneal injections of vehicle daily throughout the sleep deprivation), and sleep deprivation vitamin C-treated (SDC) group (subjected to sleep deprivation for 5 consequent days with concomitant intra-peritoneal injections of 100 mg/kg/day vitamin C). Sperm analysis, hormonal assay, and measurement of serum oxidative stress and inflammatory markers were performed. Testicular gene expression of Nrf2 and NF-κß was assessed. Structural changes were evaluated by testicular histopathology, while PCNA immunostaining was conducted to assess spermatogenesis. RESULTS: Sleep deprivation had significantly altered sperm motility, viability, morphology and count. Serum levels of cortisol, corticosterone, IL-6, IL-17, MDA were increased, while testosterone and TAC levels were decreased. Testicular gene expression of Nrf2 was decreased, while NF-κß was increased. Sleep deprivation caused structural changes in the testes, and PCNA immunostaining showed defective spermatogenesis. Administration of vitamin C significantly countered sleep deprivation induced deterioration in male fertility parameters. CONCLUSION: Treatment with vitamin C enhanced booth testicular structure and function in sleep deprived rats. Vitamin C could be a potential fertility enhancer against lifestyle stressors.

Drug screening of food and drug administration-approved compounds against Babesia bovis in vitro.

Babesia (B.) bovis is one of the main etiological agents of bovine babesiosis, causes serious economic losses to the cattle industry. Control of bovine babesiosis has been hindered by the limited treatment selection for B. bovis, thus, new options are urgently needed. We explored the drug library and unbiasedly screened 640 food and drug administration (FDA) approved drug compounds for their inhibitory activities against B. bovis in vitro. The initial screening identified 13 potentially effective compounds. Four potent compounds, namely mycophenolic acid (MPA), pentamidine (PTD), doxorubicin hydrochloride (DBH) and vorinostat (SAHA) exhibited the lowest IC50 and then selected for further evaluation of their in vitro efficacies using viability, combination inhibitory and cytotoxicity assays. The half-maximal inhibitory concentration (IC50) values of MPA, PTD, DBH, SAHA were 11.38 ± 1.66, 13.12 ± 4.29, 1.79 ± 0.15 and 45.18 ± 7.37 µM, respectively. Of note, DBH exhibited IC50 lower than that calculated for the commonly used antibabesial drug, diminazene aceturate (DA). The viability result revealed the ability of MPA, PTD, DBH, SAHA to prevent the regrowth of treated parasite at 4 × and 2 × of IC50. Antagonistic interactions against B. bovis were observed after treatment with either MPA, PTD, DBH or SAHA in combination with DA. Our findings indicate the richness of FDA approved compounds by novel potent antibabesial candidates and the identified potent compounds especially DBH might be used for the treatment of animal babesiosis caused by B. bovis.

Value of Galectin-3 assay in children with heart failure secondary to congenital heart diseases: a prospective study.

BACKGROUND: Galectin-3 is a new biomarker, which plays an important role in tissue inflammation, cardiac remodeling, and fibrosis. It can be readily measured in the circulation to detect early heart failure (HF). This study aimed to assess the value of galectin-3 assay in early diagnosis of children with heart failure secondary to congenital heart disease (CHD) and correlate it with the patients' outcome. METHODS: This prospective cohort study included 75 children diagnosed to have CHD; {Group A: 45 CHD children with HF symptoms and reduced ejection fraction (REF) and Group B: 30 CHD children with no HF symptoms and normal ejection fraction (NEF)}. They were compared to 40 age- and sex-matched controls (Group C). Children with CHD undergone history taking, Ross HF classification, Echocardiographic assessment and laboratory investigations including serum galactin-3 level. RESULTS: Galectin-3 serum level increased in CHD children, and it showed significant increase in (Gp A) compared to Gp B or Gp C (p = ≤ 0.001). In addition, serum level of Galactin-3 was correlated positively with Ross classification (r = 0.68, p = 0.018) and negatively correlated to EF% (r= -0.61, p ≤ 0.001). Galactin-3 showed better diagnostic value than Ross HF classification in early diagnosis of HF in CHD children with a cut point (≥ 10.4), significantly had 96.7% sensitivity, 90% specificity, 91% positive predictive value, 93.2% negative predictive value, with area under the curve (AUC = 0.96) and 93% accuracy. While there was a significant correlation between Ross HF classification and HF outcome in (Gp A) children (p = 0.05), we did not find any significant correlation between serum galectin-3 level and HF mortality in same group (p = 0.08). CONCLUSIONS: Galectin-3 assay is a promising marker for early diagnosis of HF in children with CHD; but it has no role in detecting HF mortality.

Akt inhibition synergizes with polycomb repressive complex 2 inhibition in the treatment of multiple myeloma.

Polycomb repressive complex 2 (PRC2) components, EZH2 and its homolog EZH1, and PI3K/Akt signaling pathway are focal points as therapeutic targets for multiple myeloma. However, the exact crosstalk between their downstream targets remains unclear. We herein elucidated some epigenetic interactions following Akt inhibition and demonstrated the efficacy of the combined inhibition of Akt and PRC2. We found that TAS-117, a potent and selective Akt inhibitor, downregulated EZH2 expression at the mRNA and protein levels via interference with the Rb-E2F pathway, while EZH1 was compensatively upregulated to maintain H3K27me3 modifications. Consistent with these results, the dual EZH2/EZH1 inhibitor, UNC1999, but not the selective EZH2 inhibitor, GSK126, synergistically enhanced TAS-117-induced cytotoxicity and provoked myeloma cell apoptosis. RNA-seq analysis revealed the activation of the FOXO signaling pathway after TAS-117 treatment. FOXO3/4 mRNA and their downstream targets were upregulated with the enhanced nuclear localization of FOXO3 protein after TAS-117 treatment. ChIP assays confirmed the direct binding of FOXO3 to EZH1 promoter, which was enhanced by TAS-117 treatment. Moreover, FOXO3 knockdown repressed EZH1 expression. Collectively, the present results reveal some molecular interactions between Akt signaling and epigenetic modulators, which emphasize the benefits of targeting PRC2 full activity and the Akt pathway as a therapeutic option for multiple myeloma.

Antimicrobial resistance profiles and virulence genotyping of Salmonella enterica serovars recovered from broiler chickens and chicken carcasses in Egypt.

BACKGROUND: This study aimed to survey the prevalence, antimicrobial resistance, and virulence-associated genes of Salmonella enterica recovered from broiler chickens and retail shops at El-Sharkia Province in Egypt. Salmonella virulence factors were determined using the polymerase chain reaction assays targeting the invA, csgD, hilC, bcfC, stn, avrA, mgtC, ompF, sopE1 and pefA genes. RESULTS: One hundred tweenty out of 420- samples from broiler chickens' cloacal swabs, farm environmental samples, and freshly dressed whole chicken carcasses were positive Salmonella species. The isolates were serotyped as S. Enteritidis as the most dominant serotypes. Interestingly, none of the isolates were resistant to imipenem. The multidrug resistance was determined in 76.7% of the isolates with multidrug antibiotic resistance index of 0.2-0.6. Eight virulence genes (invA, csgD, hilC, stn, bcfC, mgtC, avrA, and ompf) were characterized among 120 S. enterica isolates with variable frequencies, while sopE1and pefA genes that were completely absent in all isolates. Based on the combination of presence and absence of virulence genes, the most common genetic profile (P7, 30%) was invA and csgD genes. CONCLUSION: S. Enteritidis and S. Typhimurium were the most common identified serotypes in the examined sources. Circulation of such strains in broiler farms required introducing special biosecurity and biocontrol measures for control of Salmonella. Such measures might limit the adverse effects of antibiotics and ensure the safety of the environment and animal-derived food.

Accurate non-bonded potentials based on periodic quantum mechanics calculations for use in molecular simulations of materials and systems.

Molecular dynamics simulations require accurate force fields (FFs) to describe the physical and chemical properties of complex materials and systems. FF parameters for valence interactions can be determined from high-quality Quantum Mechanical (QM) calculations. However, it has been challenging to extract long-range nonbonded interaction potentials from QM calculations since there is no unambiguous method to separate the total QM energy into electrostatics (polarization), van der Waals (vdW), and other components. Here, we propose to use density functional theory with dispersion corrections to obtain the equation of state for single element solid systems (of H, C, N, O, F, Cl, Br, I, P, He, Ne, Ar, Kr, Xe, and Rn) from which we obtain the pure 2-body vdW nonbonded potentials. Recently, we developed the polarizable charge equilibration (PQEq) model based on QM polarization energy of electric probe dipoles with no contributions from vdW. Together, the vdW and PQEq interactions form the nonbonded potential of our new transferrable reactive FF (RexPoN). They may also be useful to replace the nonbonded parts of standard FFs, such as OPLS, Amber, UFF, and CHARMM. We find that the individual 2-body vdW potential curves can be scaled to a universal vdW potential using just three specific atomic parameters. This simplifies extension to the rest of the periodic table for atoms that do not exhibit molecular packing. We validate the accuracy of these nonbonded interactions for liquid water, energetic, and biological systems. In all cases, we find that our new nonbonded potentials provide good agreement with QM and experimental data.

Aminoglycoside Resistance Genes in Acinetobacter baumannii Clinical Isolates.

BACKGROUND: Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen associated with serious hospital acquired infections. It is resistant to multiple antibiotics. The therapy for infections due to this bacterium is a combination of aminoglycosides with carbapenem antibiotics. There are recent reports of the prevalence of ami-noglycoside resistance among A. baumannii. The aim of the present study was to determine the prevalence of phosphotransferases APH (3')-Via (aphA6), acetyltransferases AAC (3)-Ia (aacC1), nucleotidyl transferases ANT (2'')-Ia (aadB), and ANT (3") -Ia (aadA1) genes among clinical isolates of A. baumannii and its relation to resis-tance to amikacin and gentamicin. METHODS: The study included all clinical samples from intensive care units (ICUs) patients with suspected hospital acquired infections. Positive cultures were identified by Gram stain and complete biochemical identifications. An-tibiotic susceptibility was carried out by disc diffusion method. Minimum inhibitory concentration determination (MIC) to amikacin and gentamicin was performed by microdilution method. Polymerase chain reaction (PCR) was performed for detection of aadB, aadA1, aphA6, aadC1 genes. RESULTS: The study included 1,200 bacterial isolates from patients admitted to ICUs during the period of the study. A. baumannii represented 100 isolates from Gram negative bacilli. The study of MIC of A. baumannii to amikacin and gentamicin revealed that 50 (50%) of the isolates had resistance by MIC study with 36 (72%) of those having high level aminoglycoside resistance (HLAR) and 14 (28%) had non-high-level aminoglycoside resistance. The most common prevalent resistant genes among A. baumannii resistance to aminoglycosides was aadB (42%), fol-lowed by aphA6 (26%). Less prevalent genes were aadA1 (18%) and aacC1 (12%). There were 24 isolates with negative PCR for the studied genes. In a comparison between the prevalence of resistant genes among A. baumannii with HLAR and non HLAR, there was a non-significant increase of aphA6 (30.6%) and aadB (44.4%) in HLAR isolates compared to non HLAR (14.3%, 35.7%, respectively; p = 0.2), with a significant increase in aacC1 28.6% in HLAR compared to 5.6% in non HLAR (p = 0.02). CONCLUSIONS: Half of the clinical isolates of A. baumannii have resistance to the aminoglycosides amikacin and gen-tamicin. Most isolates have a high resistance level to aminoglycosides. The isolates have different types of amino-glycoside modifying genes. Further studies are required to detect other genes associated with resistance to amino-glycosides.

Cocktail Babesia bovis antigens for global detection of Babesia bovis infection in cattle.

The diagnostic performance of a cocktail formula consisting of two Babesia (B.) bovis recombinant proteins, including spherical body protein 1 (BbSBP-1) and spherical body protein 4 (BbSBP-4), was evaluated in the present study for the global detection of B. bovis infection in cattle and for the differentiation between B. bovis and B. bigemina infections. The efficacy and the practicality of the rBbSBP-1 and rBbSBP-4 cocktail formula for differentiation between the infection caused by both parasites were assessed using indirect enzyme-linked immunosorbent assay (iELISA) with serum samples collected from cattle experimentally infected by B. bovis (n = 33) or B. bigemina (n = 30). Cocktail antigen exhibited the highest optical density (OD) values with B. bovis-infected sera and the lowest OD values with normal bovine sera or B. bigemina-infected sera in comparison with the single antigen. A total of 581 field serum samples collected from four countries with known B. bovis endemicity: Ghana (n = 154), Egypt (n = 162), Thailand (n = 96), and South Africa (n = 169) were screened also in the current study using iELISA and the results were compared to those of indirect fluorescent antibody test (IFAT) as a reference. A cocktail formula (rBbSBP-1 and rBbSBP-4) exhibited the highest concordance rate (89.90%) and kappa value (0.73). The obtained results revealed the reliability of the rBbSBP-1 and rBbSBP-4 cocktail antigen for the detection of specific antibodies to B. bovis in cattle and demonstrated the usefulness of cocktail antigen for differentiation between B. bovis and B. bigemina infections compared with the single antigen in cattle, which will be useful for epidemiological surveys and control of bovine babesiosis.

The first molecular detection of Clostridium perfringens from pneumonic cases associated with foot and mouth disease in cattle and buffalo in Egypt.

Panting syndrome and respiratory infection have been recorded in complicated cases of foot and mouth disease (FMD) in cattle. However, investigations on the causative agents of respiratory disease in such cases are scarce. In this study, 30 animals (13 buffalo and 17 cattle) suffering from respiratory distress associated with signs of FMD were examined. Serum samples were collected and FMD infection was confirmed. Bacteriological examination of lungs from eight necropitized cases revealed the presence of C. perfringens. Multiplex polymerase chain reaction (mPCR) was performed on the positive samples followed by sequencing analysis. The alpha toxin gene (plc) of C. perfringens was identified in six cases. The present investigation highlights the role of clostridial infection as a complication of FMD in cattle and buffalo. This is the first report identifying the C. perfringens toxins from lung of animals with respiratory distress associated with FMD infection.

Association of Tumor Necrosis Factor Alpha-Induced Protein 3 Interacting Protein 1 (TNIP1) Gene Polymorphism (rs7708392) with Lupus Nephritis in Egyptian Patients.

Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Previous studies suggest that mutant A20 binding inhibitor of NF-κB 1 (ABIN1) protein encoded by tumor necrosis factor alpha-induced protein 3 interacting protein 1 (TNIP1) gene is associated with LN via NF-κB dysregulation. The aim of the current study was to evaluate the association of TNIP1 gene SNP rs7708392 with SLE and LN in Egyptian patients. 5' nuclease Allelic discrimination was used to evaluate the frequency of TNIP1 SNP rs7708392 in 53 patients with LN, 57 SLE patients without nephritis and 85 healthy controls. The genotyping analysis revealed that the CC genotype was more frequent in controls than SLE patients, while GC and GG genotypes were more common in SLE patients. Moreover, the GG genotype and the G allele were significantly more prevalent among LN patient than non-LN patients (P < 0.001). In LN patients, the most common genotype was GG (56.6%), while among the non-LN patients; the CG genotype was the most common (59.6%). Regression analysis demonstrated that SLE patients carrying only one G allele had a 3.4 folds increased risk for LN. Our results suggested that TNIP1 SNP (rs7708392) might be associated with the LN in Egyptian SLE patients. TNIP1 SNP (rs7708392) might be used to identify patients at risk of developing LN, which could help in early detection and treatment before progression to end-stage renal disease, improving patients' outcome and quality of life.

Evaluation of the inhibitory effect of N-acetyl-L-cysteine on Babesia and Theileria parasites.

N-acetyl-L-cysteine is known to have antibacterial, antiviral, antimalarial, and antioxidant activities. Therefore, the in vitro inhibitory effect of this hit was evaluated in the present study on the growth of Babesia and Theileria parasites. The in vitro growth of Babesia bovis, Babesia bigemina, Babesia divergens, Theileria equi, and Babesia caballi that were tested was significantly inhibited (P < 0.05) by micromolar concentrations of N-acetyl-L-cysteine. The inhibitory effect of N-acetyl-L-cysteine was synergistically potentiated when used in combination with diminazene aceturate on B. bovis and B. caballi cultures. These results indicate that N-acetyl-L-cysteine might be used as a drug for the treatment of babesiosis, especially when used in combination with diminazene aceturate.