Physiological and Pathogenesis Significance of Chorein in Health and Disease.

This comprehensive review explores the physiological and pathophysiological significance of VPS13A, a protein encoded by the VPS13A gene. The VPS13A gene is associated with Chorea-acanthocytosis (ChAc), a rare hereditary neurodegenerative disorder. The review covers essential aspects, beginning with the genetics of VPS13A, highlighting its role in the pathogenesis of ChAc, and addressing the spectrum of genetic variants involved. It delves into the structure and function of the VPS13A protein, emphasizing its presence in various tissues and its potential involvement in protein trafficking and lipid homeostasis. Molecular functions of VPS13A in the brain tissue and other cell types or tissues with respect to their role in cytoskeletal regulation and autophagy are explored. Finally, it explores the intriguing link between VPS13A mutations, lipid imbalances, and neurodegeneration, shedding light on future research directions. Overall, this review serves as a comprehensive resource for understanding the pivotal role of VPS13A in health and disease, particularly in the context of ChAc. Key words: Chorein , Tumor, Actin, Microfilament, Gene expression, Chorea-acanthocytosis.

Challenging behaviour and its correlates in preschool-aged children with an intellectual disability in Saudi Arabia.

BACKGROUND: Young children with an intellectual disability have a higher risk of developing challenging behaviour (CB). Early identification of risk factors for CB allows for earlier intervention. The aim of the current study was to assess the prevalence and correlates of CB in preschool-aged children with an intellectual disability in Riyadh (Saudi Arabia). METHODS: One hundred twenty parents of preschool-aged (3-6 years old) children who had been diagnosed (DSM-5 criteria) with an intellectual disability completed an online cross-sectional survey that included demographic, CB and child adaptive skills measures. The relationship between CB and 15 potential correlates (e.g. gender and degree of disability) was examined using independent samples t-tests and chi-squared tests. RESULTS: Most preschool-aged (3-6 years old) children with an intellectual disability exhibited CB (78.8%, 95% CI [70.3, 85.8]), with a 63.2% prevalence rate for self-injurious behaviours (95% C [53.8, 72.0]), a 57.6% rate for aggressive destructive behaviours (95% CI [48.2, 66.7]) and a 25% rate for stereotypy (95% CI [17.7, 34.0]). The likelihood of a child engaging in self-injurious and stereotyped behaviours was higher in those with autism and intellectual disability. Children with Down syndrome displayed fewer stereotyped behaviours. Low adaptive skill levels were associated with increased overall CB, self-injurious and stereotyped behaviours. CONCLUSIONS: The identified correlates of CB in this population and cultural context align with the international evidence base. Findings have implications for the importance of early systematic screening of CB in preschool-aged children in Saudi Arabia and other similar contexts. Preventative measures are suggested for preschool-aged children with an intellectual disability who are more likely to demonstrate CB, such as those with autism and poor adaptive behaviours.

The protective role of luteolin against the methotrexate-induced hepato-renal toxicity via its antioxidative, anti-inflammatory, and anti-apoptotic effects in rats.

Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1ß) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.

Long-term treatment with finasteride induces apoptosis and pathological changes in female mice.

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

Dose- and duration-dependent cytotoxicity and genotoxicity in human hepato carcinoma cells due to CdTe QDs exposure.

Nanotechnology has achieved more commercial attention over recent years, and its application has increased concerns about its discharge in the environment. In this study, we have chosen human hepatic carcinoma (HuH-7) cells because liver tissue has played an important role in human metabolism. Therefore, the objective of this study was to determine DNA damaging and apoptotic potential of cadmium telluride quantum dots (CdTe QDs; average particle size (APS) 10 nm, 1-25 µg/ml) on HuH-7 cells and the basic molecular mechanism of its cellular toxicity. Cytotoxicity of different concentrations of CdTe QDs on HuH-7 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) tests. Moreover, reactive oxygen species (ROS) generation, mitochondrial membrane potential, DNA damage, and Hoechst 33342 fluorescent staining morphological analysis of necrotic/apoptotic cells were detected; cellular impairment in mitochondria and DNA was confirmed by JC-1 and comet assay, respectively. A dose- and time-dependent cytotoxicity effect of CdTe QDs exposure was observed HuH-7 cells; the significant (p < 0.05) cytotoxicity was found at 25 µg/ml of CdTe QDs exposure. The percentage of cytotoxicity of CdTe QDs (25 µg/ml) in HuH-7 cells reached 62% in 48 h. CdTe QDs elicited intracellular ROS generation and mitochondrial depolarization, and DNA integrity cells collectively advocated the apoptotic cell death at higher concentration. DNA damage was observed in cells due to CdTe QDs exposure, which was mediated by oxidative stress. This study exploring the effects of CdTe QDs in HuH-7 cells has provided valuable insights into the mechanism of toxicity induced by CdTe QDs.

RANTES gene polymorphisms (-403G>A and -28C>G) associated with hepatitis B virus infection in a Saudi population.

Besides the host immune response, genetic and environmental factors play crucial roles in the manifestation of hepatitis B virus (HBV) infection. "Regulated on activation normal T-cell expressed and secreted" factor (RANTES) plays a vital role in CD4(+), CD8(+) T-lymphocyte and dendritic cell activation and proliferation in inflammation. Single nucleotide polymorphisms (SNPs) in the RANTES gene are associated with several viral and non-viral diseases. Association studies have invariably indicated a lack of association between RANTES gene SNPs and HBV infection in ethnic populations, even though RANTES gene SNPs exhibit distinct ethnic distributions. Despite the high prevalence of HBV infections in Saudi Arabia, no studies have been made concerning a possible relationship between RANTES gene polymorphisms and susceptibility to and progression of HBV infection. We examined -403G>A and -28C>G RANTES gene variants in 473 healthy controls and 484 HBV patients in ethnic Saudi populations. Significant differences were found in the genotype and allele distributions of the SNPs between the controls and the HBV patients. Both SNPs were significantly linked to viral clearance in these subjects. Our data demonstrate for the first time in a Saudi population, a relationship between the RANTES gene polymorphisms and the clinical course of HBV infection and underscore the importance of evaluating the genetic background of the affected individual to determine how it may affect disease progression.

Isolation and characterization of butachlor-catabolizing bacterial strain Stenotrophomonas acidaminiphila JS-1 from soil and assessment of its biodegradation potential.

AIMS: Isolation, characterization and assessment of butachlor-degrading potential of bacterial strain JS-1 in soil. METHODS AND RESULTS: Butachlor-degrading bacteria were isolated using enrichment culture technique. The morphological, biochemical and genetic characteristics based on 16S rDNA sequence homology and phylogenetic analysis confirmed the isolate as Stenotrophomonas acidaminiphila strain JS-1. The strain JS-1 exhibited substantial growth in M9 mineral salt medium supplemented with 3.2 mmol l(-1) butachlor, as a sole source of carbon and energy. The HPLC analysis revealed almost complete disappearance of butachlor within 20 days in soil at a rate constant of 0.17 day(-1) and half-life (t((1/2))) of 4.0 days, following the first-order rate kinetics. The strain JS-1 in stationary phase of culture also produced 21.0 microg ml(-1) of growth hormone indole acetic acid (IAA) in the presence of 500 microg ml(-1) of tryptophan. The IAA production was stimulated at lower concentrations of butachlor, whereas higher concentrations above 0.8 mmol l(-1) were found inhibitory. CONCLUSIONS: The isolate JS-1 characterized as Stenotrophomonas acidaminiphila was capable of utilizing butachlor as sole source of carbon and energy. Besides being an efficient butachlor degrader, it substantially produces IAA. SIGNIFICANCE AND IMPACT OF THE STUDY: The bacterial strain JS-1 has a potential for butachlor remediation with a distinctive auxiliary attribute of plant growth stimulation.

Complexed and total PSA in patients with benign prostatic hyperplasia and prostate cancer.

This study compares the diagnostic utility of complexed prostate-specific antigen (cPSA), total PSA (tPSA) and their ratios with free PSA (fPSA) for benign prostatic hyperplasia (BPH) and prostate cancer. This is though to be the first study to evaluate cPSA in the ethnic population of Saudi Arabia. Serum samples were collected from 54 patients (aged over 50) and assayed for tPSA, cPSA and fPSA. Thirty-five patients were histologically and clinically proven to have BPH and 19 patients were proven to have cancer. Sensitivity, specificity and ROC curves were calculated. With a cPSA cut-off of 4 ng/mL the sensitivity was 79%, the specificity was 34%, and the positive and negative predictive values (PPV and NPV) were 39% and 75%, respectively. At the same cut-off for tPSA, the sensitivity was 84%, the specificity was 29%, and the PPV and NPV were 39 and 77%, respectively. The sensitivity for both tests was lower at a cut-off of 20 ng/mL but the specificity increased to 77% for cPSA and 69% for tPSA. The areas under the receiver operating characteristic (ROC) curves were found to be 0.608 for tPSA and 0.559 for cPSA (P = 0.69). The incidence of prostate cancer in the Saudi population may be lower than that in Western populations. The data presented show little advantage in using cPSA over tPSA for discriminating BPH and prostate cancer in the population studied.