Galectin-1 (Gal-1) and Galectin-3 (Gal-3) levels in seminal plasma and serum in azoospermic patients versus fertile men: A cross-sectional study.

INTRODUCTION: Galectin-1 (Gal-1) and galectin-3 (Gal-3) are expressed by many immune cells and receive considerable attention in the context of immunity. We aimed to compare between seminal plasma and serum levels of Gal-1 and Gal-3 in azoospermic patients and fertile men. MATERIALS AND METHODS: This cross-sectional study was conducted at the andrology outpatient clinic from January (2022) to September (2022). A total of 90 participants were enrolled and divided into two equal groups: azoospermic and normal group. Semen analysis was done for all participants. Hormonal profile including FSH, LH, serum prolactin, total testosterone and estradiol was performed as well as assessment of serum and seminal levels of Gal-1 and Gal-3 by ELISA commercial kits. Finally, scrotal Duplex was done in standing and supine position. RESULTS: Serum and seminal levels of Gal-1 and Gal-3 were statistically significant higher in azoospermic patients compared with normal individuals (p < 0.001 for all). In addition, in healthy individuals there were statistically significant positive correlations between serum levels of Gal-1 and age, FSH, LH levels (r = 0.296, p = 0.005; r = 0.333, p = < 0.001; r = 0.312, p = 0.003, respectively) and serum levels of Gal-2 and FSH and LH (r = 0.436, p < 0.001; r = 0.350, p < 0.001, respectively), whereas serum Gal-3 showed a borderline positive correlation with age (r = 0.2, p = 0.059). Additionally, statistically significant positive correlations between seminal levels of Gal-1 and Gal-3 and free testosterone in healthy individuals were reported (r = 0.205, p = 0.053; r = 0.219, p = 0.038, respectively). On the other hand, there were negative correlations between serum and seminal levels of Gal-1 and Gal-3, total and progressive sperm motility, sperm count and abnormal sperm forms in healthy individuals (r = -0.382, p < 0.001; r = -0.405, p < 0.001; r = -0.376, p < 0.001; r = -0.364, p < 0.001) (r = -0.394, p < 0.001; r = -0.467, p < 0.001; r = -0.413, p < 0.001; r = -0.433, p < 0.001); (r = -0.372, p < 0.001; r = -0.377, p < 0.001; r = -0.317, p = 0.002; r = -0.311, p = 0.003)(r = -0.445, p < 0.001; r = -0.498, p < 0.001; r = -0.453, p < 0.001; r = -0.463, p < 0.001, respectively). Furthermore, statistically significant positive correlations between serum levels of Gal-1 and Gal-3 and age in azoospermic patients were reported (r = 0.511, p < 0.001; r = 0.390, p = 0.008, respectively). On the other hand, there were negative correlations between seminal Gal-1 and estradiol (E2) and seminal Gal-3 and FSH and LH in azoospermic patients (r= -0.318, p = 0.033; r = -0.322, p = 0.031; r = -0.477, p < 0.001, respectively). Also, negative correlations between serum Gal-3 and total and free testosterone in azoospermic patients were detected (r = -0.396, p = 0.007; r = -0.375, p = 0.011, respectively). CONCLUSIONS: Elevated serum and seminal levels of Gal-1 and Gal-3 have detrimental effects on spermatogenesis. Furthermore, the current study demonstrated potential regulatory effects of reproductive hormones on Gal-1 and Gal-3. Thus, future studies are needed to confirm such findings.

Novel cationic cryptides in Penaeus vannamei demonstrate antimicrobial and anti-cancer activities.

Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.

Discovery of novel brain permeable human ACSS2 inhibitors for blocking breast cancer brain metastatic growth.

Breast-cancer brain metastasis (BCBM) poses a significant clinical challenge, resulting in an end-stage diagnosis and hindered by limited therapeutic options. The blood-brain barrier (BBB) acts as an anatomical and physiological hurdle for therapeutic compounds, restricting the effective delivery of therapies to the brain. In order to grow and survive in a nutrient-poor environment, tumors in the brain must adapt to their metabolic needs, becoming highly dependent on acetate. These tumors rely on the conversion of acetate to acetyl-CoA by the enzyme Acetyl-CoA synthetase 2 (ACSS2), a key metabolic enzyme involved in regulating fatty acid synthesis and protein acetylation in tumor cells. ACSS2 has emerged as a crucial enzyme required for the growth of tumors in the brain. Here, we utilized a computational pipeline, combining pharmacophore-based shape screen methodology with ADME property predictions to identify novel brain-permeable ACSS2 inhibitors. From a small molecule library, this approach identified 30 potential ACSS2 binders, from which two candidates, AD-5584 and AD-8007, were validated for their binding affinity, predicted metabolic stability, and, notably, their ability to traverse the BBB. We show that treatment of BCBM cells, MDA-MB-231BR, with AD-5584 and AD-8007 leads to a significant reduction in lipid storage, reduction in colony formation, and increase in cell death in vitro . Utilizing an ex vivo orthotopic brain-slice tumor model, we show that treatment with AD-8007 and AD-5584 significantly reduces tumor size and synergizes with radiation in blocking BCBM tumor growth ex vivo. Importantly, we show that following intraperitoneal injections with AD-5584 and AD-8007, we can detect these compounds in the brain, confirming their BBB permeability. Thus, we have identified and validated novel ACSS2 inhibitor candidates for further drug development and optimization as agents for treating patients with breast cancer brain metastasis.

Predictive factors of erectile dysfunction in Egyptian individuals after contracting COVID-19: A prospective case-control study.

This study aimed to screen healthy individuals who contracted COVID-19 for erectile dysfunction (ED) and to determine the potential risk factors that can predict ED in these individuals. One hundred and seven cases versus 90 controls agreed to participate in the study. Two structured interviews with 1 month interval were conducted. All participants were evaluated by the validated Arabic version of the international index of erectile function (IIEF-5) and assessment of the psychological state by Hamilton depression rating scale (HDRS). Interestingly, the study had demonstrated a significant difference in mean testosterone level between cases and controls (3.91 ± 2.31, 5.04 ± 2.22, p < 0.001 respectively). Additionally, the study had demonstrated a significant difference in mean IIEF-5 score between cases and controls (22.63 ± 2.79, 23.54 ± 1.26, p < 0.041 respectively). Moreover, there were significant differences in mean anxiety and stress scores of the cases before and after COVID-19 (4.95 ± 4.03, 6.19 ± 3.55, p = 0.022, 12.75 ± 9.98, 15.30 ± 7.42, p = 0.024 respectively). A multiple logistic regression model for predicting ED occurrence post-COVID-19 had revealed that smoking, baseline IIEF-5 score and COVID-19 severity (p = 0.022, p = 0.017, p = 0.021, p = 0.009, p = 0.008 respectively) were the only significant independent variables.

HIV-1 Env-Dependent Cell Killing by Bifunctional Small-Molecule/Peptide Conjugates.

A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small-molecule CD4 mimic that binds to gp120. The second component, comprised of the peptide DKWASLWNW ("Trp3"), was derived from the N-terminus of the HIV-1 gp41 Membrane Proximal External Region (MPER) and found previously to bind to the gp41 subunit of Env. The resulting bifunctional conjugates were shown to inhibit virus cell infection with low micromolar potency and to induce lysis of the HIV-1 virion. Crucially, virolysis was found to be dependent on the covalent linkage of the BNM-III-170 and Trp3 domains, as coadministration of a mixture of the un-cross-linked components proved to be nonlytic. However, a significant magnitude of lytic activity was observed in Env-negative and other control pseudoviruses, suggesting parallel mechanisms of action of the conjugates involving Env interaction and direct membrane disruption. Computational modeling suggested strong membrane-binding activity of BNM-III-170, which may underly the nonspecific virolytic effects of the conjugates. To investigate the scope of the membrane effect, cell-based cytotoxicity and membrane permeability assays were performed employing flow cytometry. Here, we observed a dose-dependent and specific cytotoxic effect on HIV-1 Env-expressing cells by the small-molecule bifunctional inhibitor. Most importantly, Env-negative cells were not susceptible to the cytotoxic effect upon exposure to this construct at concentrations where cell-killing effects were observed for Env-positive cells. Computational structural modeling supports a mechanism in which the bifunctional inhibitors bind to the gp120 and gp41 subunits in tandem in open-state Env trimers and induce relative motion of the gp120 subunits consistent with models of Env inactivation. This observation supports the idea that the cell-killing effect of the small-molecule bifunctional inhibitor is due to specific Env conformational triggering. This work lays important groundwork to advance a small-molecule bifunctional inhibitor approach for eliminating Env-expressing infected cells and the eradication of HIV-1.

Resin Nano-Ceramic Material Surface Roughness, Color Stability, and Bacterial Adhesion Evaluation After Different Scaling Methods / Rugosidade superficial, estabilidade de cor e adesão bacteriana de resina nano-cerâmica após diferentes métodos de raspagem

Objective: TThe study evaluated in vitro the changes in roughness, color stability, and bacterial count of a CAD/CAM Resin Nano-Ceramic material surface treated by various scaling procedures. Material and Methods: 70 disks (5mm diameter, 0.5 mm thickness) of Resin Nano-Ceramic (Lava ™Ultimate, 3M, ESPE) material were cemented in standardized cavities prepared in bovine teeth. A custom-made scaling apparatus of a double pan balance was used for different scaling methods, simulating standard clinical conditions. The specimens were assigned to three main groups: no scaling(C), ultrasonic scaling (U), and manual scaling (M). Each group was then divided into three subgroups according to scaling tip material; stainless steel tip (St), plastic tip (P), and titanium tip (Ti). The surface texture was analyzed quantitatively and qualitatively with a tactile profilometer and atomic force microscopy. A spectrophotometer was used for color measurement. Streptococcus mutans were counted in a colony counter. All the data were tabulated and statistically analyzed. Results: Two-way ANOVA was used to study the effect while One-way ANOVA was performed to compare between study groups. The significance level was set at p ≤ 0.05. The ultrasonic titanium tip(UTi) revealed the significant highest mean value of alterations (p < 0.001). The integrity of the material surface was altered in the form of deep scratches on the ultrasonically scaled surfaces and numerous smaller scratches on the hand-scaled surfaces. Conclusion: The plastic instrument would appear to be the instrument of choice during a routine maintenance procedure for Resin Nano-Ceramic materials (AU).

Objetivo: Este estudo avaliou in vitro as alterações na rugosidade, estabilidade de cor e quantidade de bactérias da superfície de uma resina nano-cerâmica produzida em CAD/CAM tratada por diferentes procedimentos de raspagem. Material e Métodos: 70 discos (5 mm diâmetro, 0,5 espessura) de resina nano-cerâmica (Lava ™Ultimate, 3M, ESPE) foram cimentadas em cavidades padronizadas preparadas em dentes bovinos. Um aparato customizado de raspagem com pratos duplos de balança foram usados para os diferentes métodos de raspagem, simulando uma condição clínica padronizada. Os espécimes foram distribuídos em três principais grupos: Sem raspagem (C), raspagem ultrassônica (U) e raspagem manual (M). Cada grupo foi dividido em três subgrupos de acordo com a ponta do material de raspagem; ponta de aço inoxidável (St), ponta plástica (P), ponta de titânio (Ti). A textura da superfície foi analisada qualitativamente e quantitativamente por um perfilômetro tátil e microscopia de força atômica. Um espectrofotometro foi usado para a mensuração da cor. Estreptococos mutans foram contados em um contador de colônias. Todos os dados foram tabulados e analisados estatisticamente. Resultados: Anova dois fatores foi utilizado para estudar os efeitos, enquanto ANOVA um fator foi utilizado para comparar os grupos experimentais. O nível de significância foi estabelecido em p≤ 0,05. A ponta de ultrassom de titânio (UTi) revelou o valor significante mais alto de alterações (p < 0,001). A integridade da superfície d matérias foi alterada na forma ranhuras profundas, nas superfícies raspada por ultrassom e numerosas ranhuras menores nas superfícies raspadas à mão. Conclusão: O instrumento plástico poderia apresentar-se como um instrumento de escolha durante o pocedimento de manutenção routineira para materiais de resina nano-ceramica. (AU)

Effect of oregano essential oil supplementation on performance, biochemical, hematological parameters and intestinal histomorphometry of Japanese quail (Coturnix coturnix Japonica).

This study was performed to evaluate the efficacy of two levels of dietary oregano essential oil (OEO) on growth performances, biochemical, hematological parameters, and intestinal histomorphology in Japanese quail. A total number of 99 quail chicks were divided into three groups (33 quails per group): Control, OEO 150 mg kg-1, and OEO 300 mg kg-1 treated groups for 42 days. Feed conversion ratio (FCR), feed intake, weight gain, and edible organ weight were recorded. Biochemical and hematological parameters were determined. Histomorphological examination of hepatic and intestinal tissues was performed. FCR was significantly improved and feed intake was significantly decreased in OEO 150 mg kg-1 group compared to control. No detectable changes were observed in the lipid profile. Meanwhile, total protein, albumin, globulin, and H/L ratio were significantly increased in OEO 300 mg kg-1 at day 21. Uric acid and creatinine were significantly increased in the OEO 300 mg kg-1 group at day 42. A significant increase was observed in the whole thickness of the small intestine in the OEO 150 mg kg-1 group besides a significant increase in villi length, width, and crypt depth. Vacuolar and fatty degeneration of the hepatocytes along with Kupffer cell hypertrophy was observed in OEO 300 mg kg-1 group. It was concluded that OEO 150 mg kg-1 improved the quail's performance, intestinal histomorphometry as well as hematological parameters with no negative impacts on biochemical parameters.

Prevalence of Cigarette Smoking Usage among Adolescent Students in Northern Saudi Arabia.

BACKGROUND: Cigarette smoking is a major public health issue in the Kingdom of Saudi Arabia (KSA) in recent years, particularly among adolescents. Therefore, the aim of this study was to determine the prevalence of cigarette smoking usage among adolescent students in the north of the country. MATERIALS AND METHODS: This cross-sectional study investigated 305 adolescent students from the Northern KSA population, their ages ranging from 11 to 19 years old. RESULTS: Of the 287 respondents, 56/287(19.5%) were found to be current smokers. Of the 56 current smokers, 14/52 (27%), 29/52 (55.8%), and 9/52 (17.2%) smoked 1-3, 4-10 and 11+ cigarettes/day, respectively. For duration most had smoked for 26-36 months. CONCLUSIONS: The findings of the present study indicate that cigarette smoking use is still an important risk behavior among adolescent students. The findings of this study found a significant association of cigarette smoking usage and adolescents various believes and attitude for initiation of smoking and perception toward knowledge of other factors that contribute to the burden of tobacco use.

Adult congenital heart disease registry at Cairo University: a report of the first 100 patients.

AIMS: To establish a clinical registry for adult patients with congenital heart disease (CHD) managed in Cairo University Hospitals, aiming at description of the pattern and clinical profile of such patients. METHODS: Patients were recruited from both Cardiovascular Medicine Department Outpatient Clinic and inpatient wards of Cairo University Hospitals. Clinical data were collected from hospital records and directly from patients by treating cardiologists. Collected data were then registered in a dedicated database system and subsequently analyzed. RESULTS: Patients (49% males) ranged in age from 16 to 63 years, with a median of 25 years. Fifty-one patients were in the age-group from 20 to 30 years, with only 9% aged 50 years or older. Seventy-eight patients had acyanotic lesions, with atrial septal defect being the most common primary diagnosis (20% of total lesions). The remaining 22 patients had cyanotic heart disease, with tetralogy of Fallot being the predominant diagnosis (45% of cyanotic lesions). Six patients presented with infective endocarditis in the setting of CHD. Four women (8% of females) presented during pregnancy. Forty-six patients were sent for surgical correction/repair, while percutaneous intervention was planned in 20 patients. CONCLUSIONS: A new registry of adult patients with CHD managed in Cairo University Hospitals provides useful information, including the extent to which congenital heart defects are underdiagnosed and undertreated during infancy and childhood. In addition, those who were previously treated early in life require long-term follow-up in specialized centers. Establishment of a multidisciplinary team with expert physicians (cardiologists, dentists, obstetricians, and psychiatrists), cardiac surgeons, and nurses may be facilitated by development of a dedicated database system. Continuous financial support is a major challenge.

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study / Estado oxidante-antioxidante em crianças egípcias com anemia falciforme: estudo baseado em um único centro

OBJECTIVE: the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. METHODS: the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. RESULTS: mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r = -0.3, p = 0.04). PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. CONCLUSION: children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. .

OBJETIVO: o presente estudo foi realizado com o objetivo de investigar o estado oxidante-antioxidante em crianc¸as egípcias com anemia falciforme. MÉTODOS: dosamos os níveis séricos da capacidade antioxidante total (CAT), paraoxonase (PON), vitamina E, nitrito e malondialdeído (MDA) em 40 crianças estáveis com anemia falciforme homozigótica (24 meninos e 16 meninas), e 20 controles pareados por idade/sexo aparente-mente saudáveis. RESULTADOS: os níveis séricos médios da CAT, PON, vitamina E e nitrito foram significativamente menores, ao passo que o nível sérico médio de MDA foi significativamente maior em crianças com anemia falciforme (AF), em comparação aos controles. Não foram encontradasdiferenças significativas nos níveis médios de CAT, PON, nitrito, vitamina E e MDA em pacientescom AF em tratamento com hidroxiureia, em comparação aos que receberam hidroxiureia. Encontramos uma correlação negativa significativa entre o nitrito sérico e a ocorrência decrises vaso-oclusivas agudas (CVO) (r = -0,3, p = 0,04). Descobrimos que o nível de PON está correlacionado positivamente com o peso e o IMC dos pacientes (r = -0,4; p = 0,01; r = -0,7; p < 0,001, respectivamente), porém não com a frequência de CVO. A área sob a curva (ASC) donitrito sérico na previsão da ocorrência de CVO foi 0,782, em comparação a 0,701 para PON e 0,650 para CAT (p = 0,006). O MDA não está correlacionado a nitrito, PON, CAT ou vitamina E. Não foram detectadas correlações significativas entre nitrito sérico e hemoglobina ou enzimas antioxidantes. CONCLUSÃO: crianças com AF apresentam estresse oxidativo crônico que pode resultar emaumento das CVO. Em crianças com AF, a redução nos níveis de ...

Power-free chip enzyme immunoassay for detection of prostate specific antigen (PSA) in serum.

A power-free, portable "Chip EIA" was designed to render the popular Enzyme Linked Immunosorbent Assay (ELISA) more suitable for point-of-care testing. A number of microfluidic platforms have enabled miniaturization of the conventional microtitre plate ELISA, however, they require external pumping systems, valves, and electric power supply. The Chip EIA platform has eliminated the need for pumps and valves through utilizing a simple permanent magnet and magnetic nanoparticles. The magnetic nanoparticles act as solid support to capture the target and are then moved through chambers harboring different reagents necessary to perform a sandwich ELISA. The use of magnetic nanoparticles increases the volume-to-surface ratio reducing the assay time to 30 min. Changing the color of horseradish peroxidase (HRP) substrate to green indicates a positive result. In addition, a quantitative read-out was obtained through the use of cellphone camera imaging and analyzing the images using Matlab®. Cell phones, including smart ones, are readily available almost everywhere. The Chip EIA device was used to assay total prostate specific antigen (tPSA) in 19 serum samples. The PSA Chip EIA was tested for accuracy, precision, repeatability, and the results were correlated to the commercial Beckman Colter, Hybritech immunoassay® for determination of tPSA in serum samples with a Pearson correlation coefficient (R(2)=0.96). The lower detection limit of the PSA Chip EIA was 3.2 ng/mL. The assay has 88.9% recovery and good reproducibility (% CV of 6.5). We conclude that the developed Chip EIA can be used for detection of protein biomarkers in biological specimens.