Therapeutic properties, biological effects, antiliver cancer, and anticolon cancer effects of some natural compounds: A biochemical approach.

Natural compounds, such as carotenoids, flavonoids, anthocyanins, or terpenoids, are physiologically active components found in plants (pigments), often known as phytochemicals or phytonutrients. The in vitro cytotoxic and anticolon cancer effects of biologically bavachin, bavachinin, artepillin C, and aromadendrin compounds against SW48, SNU-C1, COLO 205, RKO, LS411N, and SW1417 cancer cell lines were assessed. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be antidiabetic, anticancer, and antibacterial candidates for drug design. IC50 results were obtained between 14-19 and 5-119 µM for α-amylase and α-glucosidase, respectively. Good inhibitor Bavachinin was detected for both enzymes (IC50 for α-amylase: 14.37 µM and IC50 for α-glucosidase: 5.27 µM). The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against pancreatic α-amylase and α-glucosidase were assessed by conducting the molecular docking study. The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against some of the expressed surface receptor proteins (CD44, CD47, CXCR4, EGFR, folate receptor, HER2, and endothelin receptor) in the mentioned cell lines were investigated using the molecular docking calculations. The results illustrated the atomic-level properties and potential interactions. These chemicals have high binding affinities to the enzymes and proteins, according to the docking scores. In addition, the compounds formed strong contacts with the enzymes and receptors. Thus, these compounds could be potential inhibitors for enzymes and cancer cells.

Unraveling Extremely Damaging IRAK4 Variants and Their Potential Implications for IRAK4 Inhibitor Efficacy.

Interleukin-1-receptor-associated kinase 4 (IRAK4) possesses a crucial function in the toll-like receptor (TLR) signaling pathway, and the dysfunction of this molecule could lead to various infectious and immune-related diseases in addition to cancers. IRAK4 genetic variants have been linked to various types of diseases. Therefore, we conducted a comprehensive analysis to recognize the missense variants with the most damaging impacts on IRAK4 with the employment of diverse bioinformatics tools to study single-nucleotide polymorphisms' effects on function, stability, secondary structures, and 3D structure. The residues' location on the protein domain and their conservation status were investigated as well. Moreover, docking tools along with structural biology were engaged in analyzing the SNPs' effects on one of the developed IRAK4 inhibitors. By analyzing IRAK4 gene SNPs, the analysis distinguished ten variants as the most detrimental missense variants. All variants were situated in highly conserved positions on an important protein domain. L318S and L318F mutations were linked to changes in IRAK4 secondary structures. Eight SNPs were revealed to have a decreasing effect on the stability of IRAK4 via both I-Mutant 2.0 and Mu-Pro tools, while Mu-Pro tool identified a decreasing effect for the G198E SNP. In addition, detrimental effects on the 3D structure of IRAK4 were also discovered for the selected variants. Molecular modeling studies highlighted the detrimental impact of these identified SNP mutant residues on the druggability of the IRAK4 ATP-binding site towards the known target inhibitor, HG-12-6, as compared to the native protein. The loss of important ligand residue-wise contacts, altered protein global flexibility, increased steric clashes, and even electronic penalties at the ligand-binding site interfaces were all suggested to be associated with SNP models for hampering the HG-12-6 affinity towards IRAK4 target protein. This given model lays the foundation for the better prediction of various disorders relevant to IRAK4 malfunction and sheds light on the impact of deleterious IRAK4 variants on IRAK4 inhibitor efficacy.

Low altitude return ameliorates semen parameters after high altitude exposure.

Background: A widely studied model of hypoxia is represented by high altitude (HA). Hence, HA hypoxia (HAH) is a challenge for people residing in or visiting high altitudes (Young and Reeves, 2002). Adaptation to HAH affects the homeostasis of several organs and the endocrine and metabolic functions. The aim of this study was to investigate the effect of HAH on the rat's semen and oxidative stress parameters. Methods: This experimental study was carried out at Abha city, Saudi Arabia, high altitude, 2,800 m above sea level; Jazan city, 43 m above sea level, low altitude. A total of 72 rats were used in this study-8 rats as control; groups 1, 2, and 3 each of 8 rats and group 4 of 40 rats were kept at high altitude for 8, 16, 24, and 32 days, respectively. From group 4, 32 rats were taken to low altitude to testify the reversibility of the semen parameters. Results: There were significant gradual decreases in the number and motility of the epididymal sperms in groups of rats exposed to HA during the first 3 weeks of HA exposure (HG1-HG3) with a maximum decreases to be seen in HG3 (- 57.3 and - 39.1%, respectively). However, the sperm count started to recover gradually on week 4 of HA exposure (HG4) and during all the periods of the reversal protocol achieved by returning the rats to the LA area (RG1-RG4). The maximum improvement in the sperm count and motility was seen in RG3 and RG4 which were not significantly different when compared with each other. The ANOVA test revealed that, in spite of the improvement in the sperm count which reach (109.3 ± 6.057 and 113.9 ± 8.967) in RG3 and RG4, their levels remained significantly low as those obtained in the control LA rats (129.2 ± 11.67). Conclusion: Exposure of rats to hypoxia resulted in a decrease in the sperm count and motility and an increase in the sperm morphological abnormalities. To conclude, the current study showed that the adverse effect of hypobaric hypoxia on semen parameters is transient and reversible.

Zingerone ameliorates non-alcoholic fatty liver disease in rats by activating AMPK.

This study was conducted to test the protective potential of Zingerone against a high-fat diet (HFD)-mediated non-alcoholic fatty liver disease (NAFLD) development in rats and examined in this protection is mediated modulating AMP-activated protein kinase (AMPK). Animals were segregated based on their diet and treatment into four groups (n = 6 each): (a) fed standard diet (STD), (b) treated with Zingerone (100 mg/kg), (c) fed HFD, (d) HFD + Zingerone (100 mg/kg), and (e) HFD + Zingerone (100 mg/kg) + compound c (CC) (an AMPK inhibitor) (0.2 mg/kg). The treatment with Zingerone attenuated the gain in final body weights, preserved liver structure, and downregulated the transcription of Bax and cleaved caspase-3. In the HFD and STD-fed rats, Zingerone reduced levels of fasting glucose and insulin and circulatory levels of cholesterol (CHOL) and triglycerides (TGs). Concomitantly, Zingerone enhanced glutathione (GSH) and superoxide dismutase (SOD) levels, depleted levels of malondialdehyde (MDA), and enhanced the nuclear levels of the nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, it lowered the levels of inflammatory cytokines and the nuclear levels of the nuclear factor kappa beta p65 (NF-κB p65). All these biochemical changes were associated with an increment in the phosphorylation of AMPK (p-AMPK) (activation) and reduced mRNA levels of SREBP1 and SREBP2. All observed effects afforded by Zingerone were abolished by CC. In conclusion, Zingerone prevents hepatic oxidative stress, inflammation, and apoptosis by activating AMPK. PRACTICAL APPLICATIONS: The findings of this study identified Zingerone, isolated from ginger, as a very effective drug that not only can attenuate fasting hyperglycemia and hyperlipidemia, but also prevent hepatic deposition, steatosis, and oxidative damage induced by high-fat-fed rats by activating the AMPK/Nrf2 antioxidant axis and concomitant suppression of SREBP1, SREBp2, and NF-κB p65. These data list Zingerone as a potent stimulator of AMPK which suggests an effective strategy to treat and alleviate NAFLD and encourages further translational and clinical trials.

Genetic Association between Interleukin Genes and Alopecia Areata in Jordanian Patients.

Objectives: Alopecia areata (AA) is a multifactorial autoimmune disease with a strong genetic predisposition. A variety of genes involved in immunity and inflammatory responses, such as cytokines, are suspected to increase the risk of developing AA. In which, different interleukin (IL) genes that associated with several autoimmune diseases and AA in varied populations. The objective of this study was to investigate the possible genetic association of AA with ten variants of single nucleotide polymorphism (SNP) in IL12B,IL13,IL16,IL17A, and IL18 genes among Jordanian patients. Methods: In this case-control study, peripheral blood samples of 152 Jordanian AA patients and 150 controls (total of 302 subjects) were collected, genomic DNA extracted and genotyped, based on which their allele and genotype frequencies were assessed. Results: In the rs11073001 SNP located in the exon region of the IL16 gene, the A allele was distributed more frequently in AA patients (p =0.01). A difference was found between the patients and the controls for the rs17875491 SNP in the promoter region of the IL16 gene (p =0.04). The mean age of onset was 27.3±12.6 with male predominance. Most patients (68.4%) were asymptomatic but some reported experiencing associated sensations before the hair loss episodes. The patchy patterns of alopecia were the most common (90.3%). Nail changes were found in 7.3% of the patients. Conclusions: The findings support the hypothesis of the involvement of IL16 gene in the etiology of AA. Moreover, it emphasizes the variations in the genetic component of AA, as well as the clinical phenotypes among different ethnic groups.

Genetic predisposition of alopecia areata in jordanians: A case-control study.

Alopecia areata (AA) is a common non-scarring hair loss disease of defined patterns with varied patches size and body sites. The etiology of AA has a complex basis of autoimmunity, environment, and genetic variations. The latter factor is found to play a crucial role in AA risk. Thus, this study aimed to investigate the potential impact of specific immune-related gene polymorphisms among a cohort of Jordanian patients, which was previously reported in other populations. Blood samples of AA patients and control subjects were collected for genomic DNA (gDNA) extraction. Targeted single nucleotide polymorphisms (SNPs) of MASP2, TLR1, CTLA4, and C11orf30 were genotyped in duplicate using the Sequenom MassARRAY® system (iPLEX GOLD). Genotype and allele analysis reveals statistical differences in TLR1 rs4833095 (allele C, P = 0.044), MASP2 rs2273346 (genotype AA, P = 0.0026), and C11orf30 rs2155219 (genotype GG, P = 0.0069) distribution. These findings present the significant contribution of genetic variations in AA susceptibility in the Jordanian population, which is infrequently studied.

Role of dietary selenium in alleviating bisphenol A toxicity of liver albino rats: Histological, ultrastructural, and biomarker assessments.

Bisphenol A (BPA) is used as a plasticizer in polycarbonate plastics. It has been used in consumer products and epoxy resins for decades as protective coatings and linings for food and beverage bottles. This can trigger human reactions to BPA which interferes with estrogen receptors. Our study explored the ameliorative effects of selenium (Se) in male rats on liver damage caused by BPA. Rats were divided into four groups at random: The first one obtained olive oil and acted as a control. Se (0.5 mg/kg diet) was given for the second group. The third one was treated with BPA (10 mg/kg body weight/day) orally. Concomitantly Se (0.5 mg/kg diet) and BPA (10 mg/kg body weight/day) were given orally in the fourth one. Liver specimens were prepared for light, electron microscopes and the serum samples were screened for biochemical markers. In the BPA received group, histological findings indicated apoptotic hepatic histological changes such as sinusoidal congestion, cytoplasmic vacuolation and leukocyte infiltration. Ultrastructurally, the same group had mitochondrial degeneration, rough endoplasmic reticulum swelling, and nuclear pyknosis, as well as fat droplet deposition and lysosome enhancement. Liver enzymes: In the BPA group, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been substantially increased. Moreover, histological and ultrastructural improvements were seen in the rat population treated with BPA and Se, whereas ALT and AST levels were lowered and malondialdehyde (MDA), glutathione peroxidase (GPx), human C reactive protein (hCRP), and the serum levels of interleukin-6 (IL-6) were significantly modulated. PRACTICAL APPLICATIONS: Bisphenol A (BPA) is used in the manufacturing of polycarbonate plastic (e.g., water bottles, baby bottles) and epoxy resins (e.g., inner coating in metallic food cans). It is a non-polymer preservative for other plastics, one of the contaminants of the atmosphere and a common endocrine estrogenic disruptor. Our study explored the ameliorative effects of selenium (Se) in male rats on liver damage caused by BPA. Rats were divided into four groups at random: The first one obtained olive oil and acted as a control. Se (0.5 mg/kg diet) was given for the second group. The third one was treated with BPA (10 mg/kg body weight/day) orally. Concomitant Se (0.5 mg/kg diet) and BPA (10 mg/kg body weight/day) were given in the fourth one. Liver specimens were prepared for light, electron microscopes and the serum samples were screened for biochemical markers.

Gestational Exposure to Synthetic Steroid Hormones Impaired Sperm Quantity and Quality in Wistar Rats.

This study was designed to investigate the effect of prenatal exposure to synthetic sex steroid on sperm quantity and quality, relative testicular and epididymal weights, and reproductive hormones level in adult Wistar rats. Forty male Wistar rats were divided into two groups: a test group (n = 20) that included mature rats that were born to dams exposed to gestational treatment with hydroxyprogesterone and a control group (n = 20) that included mature rats born to untreated dams. Compared to the control group, the test group showed a significant reduction in the sperm count, viability and motility, relative testicular and epididymal weights together with increased abnormal spermatozoa (p < 0.001). The reproductive hormonal assay revealed significantly lower serum testosterone and higher levels of FSH and LH among the test groups compared to the control (p < 0.05 for all). Prenatal exposure to synthetic progesterone negatively affected sperm production and function, relative testicular and epididymal weights, and reproductive hormone levels.

Why human prepuce is a valuable resource in science? Histological, ultrastructural, immunohistochemical and statistical analysis / ¿Por qué el prepucio humano es un recurso valioso en la ciencia? Análisis histológicos, ultraestructurales, inmunohistoquímicos y estadísticos

SUMMARY: This research was to examine the histological and ultrastructural characteristics of prepuce samples, as well as vimentin and S100 protein localization and statistical analysis. Urologists have long struggled with the prepuce, which is used to treat a variety of urethral problems. Skin biopsies were collected from the prepuce at the moment of circumcision and processed for light microscopy, electron microscope examination, immunohistochemical techniques, and statistical analysis in a total of six boys. Histologically, the prepuce epidermis displayed focal spiky ridges, which are saw-toothed interspersed with sulci, slight hyperpigmentation, looser connective tissue and plentiful vascular components. Immunohistochemically, the existence of melanocytes and Langerhans cells in the epidermis, as well as smooth muscles in the dermis, was stained positively for vimentin. Also, there was a positive reactivity of the Langerhans cells in the epidermis and around Meissner's corpuscles in the dermis for S100 protein staining. Ultrastructurally, the prepuce's intercellular gaps were widened, melanocytes rested on a folded basement membrane, and desmosomal content was reduced, with a prominent active euchromatic nucleus. Cytoplasmic projections were distended and elongated, and the interstitial blood vessels were surrounded by endothelial cells and rested on a basement membrane. There were also minimal collagen fibers in the interstitium. The prepuce's histological and ultrastructural features, as well as immunohistological studies using vimentin and S100 protein as intermediate filaments and statistical analysis, all demonstrated that it is a useful scientific resource.

RESUMEN: El presente trabajo de investigación se realizó para examinar las características histológicas y ultraestructurales de las muestras de prepucio, así como la localización y el análisis estadístico de la vimentina y la proteína S100. Los urólogos han intentado trabajar durante mucho tiempo con el prepucio, que se usa para tratar una variedad de problemas uretrales. Se recolectaron biopsias de piel del prepucio de seis niños en el momento de la circuncisión y se procesaron para microscopía óptica, examen con microscopio electrónico, técnicas inmunohistoquímicas y análisis estadístico. Histológicamente, la epidermis del prepucio mostraba crestas puntiagudas focales, intercaladas con surcos, hiperpigmentación leve, tejido conectivo más laxo y abundantes componentes vasculares. Inmunohistoquímicamente, la existencia de melanocitos y células dendríticas epidérmicas (células de Langerhans), así como músculo liso en la dermis, se tiñeron positivamente para vimentina. Además, hubo una reactividad positiva de las células dendríticas epidérmicas en la epidermis y alrededor de los corpúsculos del tacto (de Meissner) en la dermis para la tinción de la proteína S100. Ultraestructuralmente, los espacios intercelulares del prepucio se ensancharon, los melanocitos descansaban sobre una membrana basal plegada y el contenido desmosómico se redujo, con un núcleo eucromático activo prominente. Las proyecciones citoplasmáticas estaban distendidas y alargadas, y los vasos sanguíneos intersticiales estaban rodeados por células endoteliales y descansaban sobre una membrana basal. También había fibras de colágeno mínimas en el intersticio. Las características histológicas y ultraestructurales del prepucio, así como los estudios inmunohistológicos utilizando vimentina y proteína S100 como filamentos intermedios y el análisis estadístico, demostraron que es un recurso científico útil.

Reference values (RV), MNS and MTS for morphological characteristics of normal and abnormal human spermatozoon describing Teratozoospermic Index (TZI) & Sperm Deformity Index (SDI) in Sudanese infertile couples using CASA System / Valores de referencia (RV), MNS y MTS para las características morfológicas de espermatozoides humanos normales y anormales que describen el Índice Teratozoospérmico (TZI) y el Índice de Deformidad del Esperma (SDI) en parejas infértiles de Sudán que utilizan el sistema CASA

A scientific determination of fertilization ability of the sperm can be made by motility, viability and morphological examinations that are called as potential fertility criteria. Some previous studies documented only the total morphological defect rates without including the morphologic subjects. As it is recorded in many studies, the success of IUI, ICSI and IVF depends mainly on the quality of the collected semen. 1) Determine and classify the common morphological defects and rates of sperms. 2) Analyze the effect of age on the sperm abnormalities and to assess the impact of environment on changing normal sperm characteristics. 3) Determine the common types of semen abnormalities (Asthenoterato-zoospermia, Asthenozoospermia, Azoopyospermia, Azoospermia, Hypospermia, Oligoasthenoteratozoospermia, Oligoasthenozoopyospermia, Oligoasthenozoospermia and Teratozoospermia). 4) Determine the range of teratozoospermic index (TZI) and sperm deformity index (SDI). A prospective case series study for 566 men of infertile couples who were requesting semen analysis was applied to those came to the ULTRALAB laboratory center main campus and ULTRALAB branch of the Sudan Assisted Reproduction Center (SARC), Khartoum, Sudan. Data collection was done for 20 months from April 1st, 2010 to December 31st, 2011. analysis of semen samples was done using Computer Assisted Semen Analysis (CASA). 1) The study demonstrates that there are differences in normality and abnormality of sperm morphology parameters of sperm between Sudanese population and other studies including WHO standards. 2) SDI and TZI were higher in overall semen as well as in abnormal semen samples. 3) Common semen abnormalities were oligoasthenoteratozoospermia, asthenoteratozoospermia and asthenozoospermia. There are differences in sperm morphology of both normal and abnormal parameters between Sudanese population and other studies including WHO standards.

Se realizó una determinación científica de la capacidad de fertilización de los espermatozoides mediante motilidad, viabilidad y exámenes morfológicos denominados criterios de fertilidad potencial. Algunos estudios previos documentan solamente el total de las tasas de defectos morfológicos sin incluir a los sujetos morfológicos. Como se registra en muchos estudios, el éxito de IUI, ICSI y FIV depende principalmente de la calidad del semen recolectado. Los objetivos de este trabajo fueron: 1) Determinar y clasificar los defectos morfológicos comunes y las tasas de espermatozoides; 2) Analizar el efecto de la edad en las anomalías de los espermatozoides y evaluar el impacto del medio ambiente en el cambio de las características normales de los espermatozoides; 3) Determinar los tipos comunes de anomalías en el semen (astenoterato-zoospermia, astenozoospermia, azoopiepermia, azoospermia, hipospermia, oligoastenoteratozoospermia, oligoastenozoopermia, oligoastenozoospermia y teratozoospermia); 4) Determinar el rango del índice teratozoospérmico (TZI) y el índice de deformidad del esperma (IDE). Se realizó un estudio prospectivo de series de casos en 566 hombres, de parejas infértiles, que solicitaban análisis de semen en laboratorios ULTRALAB y la sucursal de ULTRALAB del Centro de Reproducción Asistida de Sudán (SARC), Jartum, Sudán. La recolección de datos se realizó durante 20 meses, desde el 1 de abril de 2010 hasta el 31 de diciembre de 2011. El análisis de las muestras de semen se realizó mediante el análisis de semen asistido por computadora (CASA). Existen diferencias en la normalidad y anormalidad de los parámetros de la morfología de los espermatozoides entre la población sudanesa y otros estudios, incluidas las normas de la Organización Mundial de la Salud. Los parámetros SDI y TZI fueron más altos en el semen general, así como en muestras de semen anormales. Las anomalías comunes del semen fueron oligoastenatoatoospermia, astenoteratozoospermia y astenozoospermia. Existen diferencias en la morfología de los espermatozoides de los parámetros normales y anormales entre la población sudanesa y otros estudios que incluyen las normas de la Organización Mundial de la Salud.

Effect of high altitude hypoxia on the postnatal development of rat testis: histological and histometric study / Efecto de la hipoxia a gran altitud en el desarrollo postnatal en testículos de rata: estudio histológico e histométrico

The study was carried out at two different altitudes in the southern region of Saudi Arabia: Abha, 2,800 meters above sea level, the high altitude (HA) area and Jazan, 40 meters above sea level the low altitude (LA) area. Following exposure to high altitude, and up to the third week of postnatal development, some of the seminiferous tubules showed detachment from the basal lamina, spaces of different sizes within the epithelial layer with vacuoles in the center and Pyknotic nuclei were noted in the spermatogonia and primordial germ cells. Rounded spermatids were seen in the lumen only on day 35 of hypoxic group, no spermatozoa were recognized until day 45 of postnatal development. On day 45 hypoxic rat testes revealed various types of atrophy and degeneration in the seminiferous tubules and in the interstitial tissue, there was detachment of the basal laminae of the tubules and a profound decrease in cellularity. Significant decrease in epithelial height was noticed in these animals (P <0.05). Also, the diameter of the tubules showed slight decrease with concomitant increase in interstitial spaces in all hypoxic rats.

El estudio se llevó a cabo en dos sitios de altitud diferentes en la región sur de Arabia Saudita: en Abha, a 2.800 metros sobre el nivel del mar, la zona de gran altitud (GA) y en Jazan, a 40 metros sobre el nivel del mar, la zona de baja altitud. Después de la exposición a GA, y hasta la tercera semana del desarrollo postnatal, se observaron espermatogonias y células germinales primordiales en algunos túbulos seminíferos, un desprendimiento de la lámina basal, espacios de diferentes tamaños dentro de la capa epitelial, con vacuolas en el centro y núcleos picnóticos. Se encontraron espermátidas redondeadas a nivel del lumen en el día 35 de la hipoxia, y no se observaron espermatozoides hasta el día 45 del desarrollo postnatal. En el día 45, los testículos de las ratas hipóxicas revelaron varios tipos de atrofia y degeneración en los túbulos seminíferos y el tejido intersticial; no hubo separación de las láminas basales de los túbulos y se registró una profunda disminución de la celularidad. Además, se observó una disminución significativa en la altura del epitelio de estos animales (P <0,05). El diámetro de los túbulos mostró una ligera disminución con el aumento concomitante en los espacios intersticiales en todas las ratas hipóxicas.