The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects.

PURPOSE: Fentanyl, a fully synthetic opioid, is widely used for severe pain management and has a huge abuse potential for its psychostimulant effects. Unlike other opioids, the neurotoxic effects of chronic fentanyl administration are still unclear. In particular, little is known about its effect on the cerebral cortex. The current study aims to test the chronic toxicity of fentanyl in the mice model. METHODS: Adult male Balb/c mice were chronically treated with low (0.05 mg/kg, i.p) and high (0.1 mg/kg, i.p) doses of fentanyl for 5 consecutive weeks, and various neurotoxic parameters, including apoptosis, oxidative stress, and neuroinflammatory response were assessed in the cortex. Potential histological as well as neurochemical changes were also evaluated. RESULTS: The results of this study show that chronic fentanyl administration induced intense levels of apoptosis, oxidative stress, and neuroinflammation in the cerebral cortex. These findings were found to be correlated with histopathological characteristics of neural degeneration and white matter injury. Moreover, fentanyl administration was found to reduce the expression of both NMDA receptor subunits and dopamine receptors and elevate the level of epidermal growth factor (EGF). CONCLUSION: Fentanyl administration induced neurotoxic effects in the mouse cerebral cortex that could be primarily mediated by the evoked oxidative-inflammatory response. The altered expression of NMDA receptors, dopamine receptors, and EGF suggests the pernicious effects of fentanyl addiction that may end in the development of toxic psychosis.

Acute Exercise Promptly Normalizes Myocardial Myosin Heavy-Chain Isoform mRNA Composition in Diabetic Rats: Implications for Diabetic Cardiomyopathy.

Background and Objectives: The acute effects of exercise on the myosin heavy-chain (MHC) isoform mRNA expression and the upstream transcription factors in diabetic and non-diabetic hearts remain unexplored. We aimed to determine the acute effect of a single exercise session on the expression of left ventricular MHC, MHC-α and MHC-ß, and thyroid receptor (TR), TR-α1 and TR-ß, isoform mRNA in diabetic and non-diabetic rats. Materials and Methods: Sprague-Dawley rats were assigned to four groups: non-diabetic control (CS), diabetic exercise (DIEX), sedentary diabetic (DIS), and non-diabetic exercise (CEX). Diabetes was induced via streptozotocin injection (55 mg/kg). DIEX and CEX rats performed an exercise session (60 min at 50 m/min and 0% grade) 6-7 weeks after diabetes induction. Results: MHC-α mRNA was lower in DIS (p = 0.03) and not different in DIEX (p = 0.1) relative to CS. DIS showed higher MHC-ß mRNA than the non-diabetic rats, CS and CEX (p = 0.02 and p = 0.009, respectively). MHC-ß mRNA in DIEX was normalized to non-diabetic levels in CS (p = 0.3). TR-α1 was higher in DIS and not different in DIEX relative to CS and CEX (p = 0.03 and p = 1.0, respectively). In CEX, exercise did not change MHC-α, MHC-ß, and TR-α1 relative to CS (p = 1.0). TR-ß was not different between groups. Conclusion: In conclusion, exercise appears to acutely normalize the myocardial MHC and TR isoform mRNA expression only in the diabetic heart. These responses may induce therapeutic mechanisms other than changing the MHC isoform composition.

Investigating the fate and toxicity of green synthesized gold nanoparticles in albino mice.

OBJECTIVE: This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice. SIGNIFICANCE: AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications. METHODS: The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed. RESULTS: Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury. CONCLUSIONS: The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure.

The Prevalence of CHEK1 and CHEK2 Mutations in Prostate Cancer: a Retrospective Cohort Study.

Background: Prostate cancer (PCa) is one of the most common types of cancer among men. Mutations and accumulation of chromosomal deviations are correlated with the development and aggressiveness of PCa. Cell cycle checkpoint pathways and DNA repair mechanisms are reported to deviate in cancers. Mammalian checkpoint kinase 1/2 (CHEK1/CHEK2) genes act as key signal transducers inside the genomic integrity checkpoints. CHEK1 and CHEK2 gene mutations were reported in a few different types of cancers. In PCa, CHEK2 mutations were studied, but CHEK1 gene variations were not well investigated. Objective: This study aimed to investigate the occurrence of variations in the CHEK1 and CHEK2 genes in PCa in the Jordanian population. Methods: Formalin-fixed paraffin-embedded PCa specimens of radical prostatectomy surgical procedures from 74 Jordanian patients were subjected to DNA extraction, polymerase chain reactions and Sanger sequencing to screen the mutations in selected exons of CHEK1 and CHEK2 tumor suppressor genes. Results: The presence of F281L (T/C) (1.4%) homologous missense point mutation in the kinase domain of the CHEK2 gene and P188P (1.4%) silent point mutation in the kinase domain of the CHEK1 gene. In addition, the 1100delC mutation was not detected in the studied PCa specimens. Conclusion: In line with previous reports, the presence of CHEK2 mutation with a frequency of 1.4% supported the possible role of genetic variants of this gene in the development of PCa. No 1100delC mutation was detected in this study. No association was found in this study between CHEK1 mutations and the development of PCa. Further studies are needed with larger cohorts along with a screening of more exons in order to shed more light on the frequency of CHEK2 gene mutations and their role in the development of PCa in Jordan.

Effect of amoxicillin/clavulanic acid in attenuating pregabalin-induced condition place preference.

Substance abuse is a worldwide problem with serious repercussions for patients and the communities where they live. Pregabalin (Lyrica), is a medication commonly used to treat neuropathic pain. Like other analgesic medications there has been concern about pregabalin abuse and misuse. Although it was initially suggested that pregabalin, like other gabapentinoids, has limited abuse liability, questions still remain concerning this inquiry. Changes in glutamate system homeostasis are a hallmark of adaptations underlying drug dependence, including down-regulation of the glutamate transporter 1 (GLT-1; SLC1A2) and the cystine/glutamate antiporter (xCT; SLC7A11). In this study, it was found that pregabalin (90 mg/kg) produces a conditioned place preference (CPP), indicative of reinforcing effects that suggest a potential for abuse liability. Moreover, like other drugs of abuse, pregabalin also produced alterations in glutamate homeostasis, reducing the mRNA expression of Slc1a2 and Slc7a11 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Amoxicillin clavulanic acid, a ß-lactam antibiotic, blocked the reinforcing effects of pregabalin and normalized glutamate homeostasis. These results suggest that pregabalin has abuse potential that should be examined more critically, and that, moreover, the mechanisms underlying these effects are similar to those of other drugs of abuse, such as heroin and cocaine. Additionally, these results support previous findings showing normalization of glutamate homeostasis by ß-lactam drugs that provides a novel potential therapeutic approach for the treatment of drug abuse and dependence.

Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.

The widespread recreational use of synthetic cannabinoids (SCs) has become a serious health issue. Reports of life-threatening intoxications related to SC consumption have markedly increased in recent years, including neurotoxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity. We investigated the impact of acute administration of the synthetic cannabinoid XLR-11 (3 mg/kg, i.p. for 5 consecutive days) on the liver in BALB/c mouse animal model. Using real-time quantitative RT-PCR, MDA assay, and TUNEL assay, we found consistent up-regulation of a variety of genes involved in oxidative stress (NOX2, NOX4, and iNOS), inflammation (TNF-α, IL-1ß, IL-6), and apoptosis (Bax) in the liver of XLR-11 treated mice compared to control mice. These finding were supported with an elevation of MDA levels and TUNEL positive cells in the liver of XLR-11 treated mice which further confirm increased oxidative stress and apoptosis, respectively. Histopathological analysis of the liver of XLR-11 treated mice confirmed pronounced hepatic necrosis associated with inflammatory cell infiltration. Furthermore, elevated ALT and AST serum levels were also identified in XLR-11 treated mice indicating possible liver damage. Overall, SC-induced hepatotoxicity seems to be mainly mediated by activated oxidative stress and inflammatory processes in the liver, but the specific mechanisms involved require further investigations. However, the present study shed light on the potential deleterious role of acute administration of SCs in the progression to acute hepatic injury which enhances our understanding of the adverse effect of SC consumption.

Molecular and cellular effects of gold nanoparticles treatment in experimental diabetic myopathy.

Background: This study aims to address the effects of gold nanoparticles (AuNPs) on diabetic myopathy in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Adult male rats were separated into three groups (n = 15): non-diabetic control (ND), diabetic (D), and diabetic treated with AuNPs (2.5 mg/kg, D + AuNPs) intraperitoneally for 4 weeks. A single injection of 50 mg/kg STZ was used to induce diabetes. Results: Treatment with AuNPs lowered blood glucose levels. Skeletal muscle mRNA expression of two muscle-specific E3 ubiquitin-ligases enzymes, F-box-only protein 32 (FBXO32) and muscle RING-finger protein-1 (MuRF1) were upregulated in the D group. Diabetic rats showed significant increases in the skeletal muscle expression levels of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), and a decrease in glucose transporter 4 (GLUT4) expression. Superoxide dismutase (SOD) activity decreased and malondialdehyde (MDA) level increased in skeletal muscles of D group. Compared to the D group, expression levels of FBXO32, MuRF1, PAI-1 TNF-α, and TGF-ß1 were decreased in the D + AuNPs group, and mRNA of GLUT4 increased. Furthermore, in D + AuNPs group, skeletal muscle MDA levels decreased while SOD activity increased. Conclusion: In experimental models, AuNPs can ameliorate muscle atrophy by reducing hyperglycemia, inflammation, and oxidative stress, and by suppressing the ubiquitin-proteasome proteolytic process.

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

Background: Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients. Methods: Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients. Results: Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 . Conclusions: Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.

Biosynthesis of gold nanoparticles using leaf extract of Dittrichia viscosa and in vivo assessment of its anti-diabetic efficacy.

Several studies have reported the anti-diabetic effect of biologically synthesized gold nanoparticles (AuNPs). This study was designed to investigate the in vivo anti-diabetic activity of AuNPs synthesized using the leaf extract of Dittrichia viscosa in a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes in rats. AuNPs were synthesized using the leaf extract of D. viscosa, and the synthesized AuNPs were characterized by UV-visible spectrophotometer, dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM). To study the anti-hyperglycemic effect of the AuNPs formed using D. viscosa extract, adult male Sprague-Dawley rats were divided into three groups (6-8 rats/group) as follows: control group, a diabetic group without treatment, and a diabetic group treated intraperitoneally with a daily injection of AuNPs at a dose of 2.5 mg/kg for 21 days. Diabetes was induced by maintaining the rats on HFD for 2 weeks, followed by a single intraperitoneal injection of 45 mg/kg of STZ. Serum and liver samples were collected at the end of the treatment period and used to measure glucose levels and hepatic gene expression and activity of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in the liver gluconeogenic pathway. The AuNPs formed using D. viscosa extract were mainly spherical with a size range between 20 and 50 nm with good stability and dispersity, as indicated by the zeta potential and DLS measurements. Treatment with AuNP significantly lowered the blood glucose level, the gene expression, and the activity of hepatic PEPCK in comparison to the diabetic untreated group (P < 0.05). This study suggests that AuNPs synthesized using D. viscosa leaf extract can alleviate hyperglycemia in HFD/STZ-induced diabetes in rats, which could be through the reduction of hepatic gluconeogenesis by inhibiting the expression and activity of the hepatic PEPCK gene. Schematic illustration of the biosynthesis of AuNPs showing their distinctive morphology under the EM. The generated particles were injected into animals and serum glucose levels were reported in addition to the PEPCK expression and activity.

Synthesis, Characterization, and Assessment of Anti-Cancer Potential of ZnO Nanoparticles in an In Vitro Model of Breast Cancer.

Advanced innovations for combating variants of aggressive breast cancer and overcoming drug resistance are desired. In cancer treatment, ZnO nanoparticles (NPs) have the capacity to specifically and compellingly activate apoptosis of cancer cells. There is also a pressing need to develop innovative anti-cancer therapeutics, and recent research suggests that ZnO nanoparticles hold great potential. Here, the in vitro chemical effectiveness of ZnO NPs has been tested. Zinc oxide (ZnO) nanoparticles were synthesized using Citrullus colocynthis (L.) Schrad by green methods approach. The generated ZnO was observed to have a hexagonal wurtzite crystal arrangement. The generated nanomaterials were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-visible spectroscopy. The crystallinity of ZnO was reported to be in the range 50-60 nm. The NPs morphology showed a strong absorbance at 374 nm with an estimated gap band of 3.20 eV to 3.32 eV. Microscopy analysis proved the morphology and distribution of the generated nanoparticles to be around 50 nm, with the elemental studies showing the elemental composition of ZnO and further confirming the purity of ZnO NPs. The cytotoxic effect of ZnO NPs was evaluated against wild-type and doxorubicin-resistant MCF-7 and MDA-MB-231 breast cancer cell lines. The results showed the ability of ZnO NPs to inhibit the prefoliation of MCF-7 and MDA-MB-231 prefoliation through the induction of apoptosis without significant differences in both wild-type and resistance to doxorubicin.

Correlation of Sperm Mitochondrial DNA 7345 bp and 7599 bp Deletions with Asthenozoospermia in Jordanian Population.

BACKGROUND: Alterations in sperm mitochondrial DNA (mtDNA) affect the functions of some OXPHOS proteins which will affect sperm motility and may be associated with asthenozoospermia. The purpose of this study was to investigate the correlation between 7599-bp and 7345-bp sperm mtDNA deletions and asthenozoospermia in Jordan. METHODS: Semen specimens from 200 men including 121 infertile and 79 healthy individuals were collected at the Royal Jordanian Medical Services In-vitro fertilization (IVF) units. The mtDNA was extracted followed by mtDNA amplification. Polymerase chain reaction (PCR) was conducted for the target sequences, then DNA sequencing was performed for the PCR products. Chi-square, Fisher's and Spearman's tests were used to calculate the correlation. RESULTS: The results showed a significant correlation between the presence of 7599-bp mtDNA deletion and infertility where the frequency of the 7599-bp deletion was 63.6% in the infertile group compared to the fertile 34.2% (p<0.001, (OR=3.37, 95% CI=1.860 to 6.108)). Additionally, the sperm motility showed a significant association with the frequency of the 7599-bp deletion (p=0.001, r=-0.887). The 7345-bp mtDNA deletion showed no assoctiation with the infertility (p=0.65, (OR=0.837, 95% CI= 0.464-1.51)) or asthenozoospermia (p=0.98, r=0.008). CONCLUSION: We demonstrated a significant correlation between asthenozoospermia and the 7599-bp mtDNA deletion but not the 7345-bp mtDNA deletion in the infertile men in Jordan. Screening for deletions in sperm mtDNA can be used as a pre-diagnostic molecular marker for male infertility.

Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin-induced type 1 diabetes in rats.

This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-ß1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.

Pretreatment with Salvadora persica L. (Miswak) aqueous extract alleviates paracetamol-induced hepatotoxicity, nephrotoxicity, and hematological toxicity in male mice.

BACKGROUND AND AIM: Paracetamol (PCM) ingestion is one of the most frequent global causes of toxicity. Salvadora persica L. is a plant that among many other effects exhibits potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. In this study, we investigated the possible protective effect of S. persica aqueous extract in the PCM overdose-induced liver and kidney injury and hematological changes in a mice model. MATERIALS AND METHODS: Mice were given PCM with and without S. persica pretreatment. Blood cell counts and liver and kidney function biomarkers were measured. Liver and kidney samples were histologically examined. RESULTS: A single overdose of PCM caused significant elevations of alanine and aspartate transaminases, alkaline phosphate, bilirubin, urea, uric acid, and creatinine compared with the control group. In addition, PCM toxicity significantly lowered red blood cell count but insignificantly increased both white blood cell and platelet counts in comparison to the control mice. Pretreatment with S. persica significantly prevented PCM-induced changes in hepatic and renal biomarkers. S. persica also caused marked reversal of hematological changes. Histologically, the liver and kidney showed inflammation and necrosis after PCM treatment, which were significantly reduced in mice pretreated with S. persica. CONCLUSION: Taken together, S. persica significantly inhibited PCM-induced renal, hepatic, and hematological toxicity, pointing to its possible use in the treatment of liver and renal disorders.

Effect of Estrogen and Progesterone Hormones on the Expression of Angiotensin II Receptors in the Heart and Aorta of Male Rats.

BACKGROUND: Activation of the Angiotensin II type 1 receptor (AT1R) has been implicated in the pathogenesis of the cardiovascular disease, while activation of Angiotensin II type 2 receptor (AT2R) leads to effects that are opposite to those mediated by AT1R. The interaction between female sex hormones and the renin-angiotensin system was proven to play an essential role in the pathological changes in the cardiovascular system. OBJECTIVES: To investigate the direct effect of estrogen and progesterone on arterial and cardiac AT1R and AT2R expression in vivo in male. METHOD: Male adult rats were assigned into four groups: Group 1 (control), group 2 (progesterone treated group; 10mg/kg), group 3 (estrogen treated group; 20µg/kg) and group 4 (progesterone; 10mg/kg + estrogen; 20µg/kg treated group). All treatments were administrated subcutaneously every second day for 21days. RESULTS: Estrogen treatments increase the left ventricle (LV) protein expression of AT1R, and progesterone treatment decreased the LV protein expression of AT2R. In the aorta, estrogen treatment increased the mRNA expression levels of AT1R, while progesterone treatment increased the AT2R mRNA expression levels. Estrogen treatment decreases the LV and aortic endothelial nitric-oxide synthase (eNOS) mRNA levels while progesterone treatments decrease the LV eNOS mRNA levels but increase the aortic eNOS mRNA levels. The serum angiotensin II levels were increased by estrogen treatment only. CONCLUSION: Both estrogen and progesterone treatments appear to have a harmful effect on the male rat hearts, possibly by increasing the protein expression of AT1R (for estrogen), decrease the protein and mRNA expression of AT2R (for progesterone), and decrease the eNOS mRNA levels (for both). However, it seems that progesterone but not estrogen exerts a vascular protective effect in males.

A Potential MRI Agent and an Anticancer Drug Encapsulated within CPMV Virus-Like Particles.

BACKGROUND: Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition. OBJECTIVES: The plant virus Cowpea Mosaic Virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the internal cavity of empty Virus-Like Particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications. METHODS: The encapsidation of magnetic materials and anticancer drugs was achieved. SuperscriptCPMV denotes molecules attached to the external surface of CPMV and CPMVSubscript denotes molecules within the interior of the capsid. RESULTS: Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis) (TCPMVCis) is reported. TCPMVCis exhibited a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 µM and 3.9 µM, respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents. CONCLUSION: Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines with its potency increased by 2.3-folds.

Gold nanoparticles as a promising treatment for diabetes and its complications: Current and future potentials

Diabetes and its complications represent a major cause of morbidity and mortality in diabetes patients. This review is aimed to find the potential of gold nanoparticles (AuNPs) to act as therapeutic agents for diabetes and its complications. Here, we outline the literature related to the self-therapeutic effects of AuNPs. The first goal of this review is to highlight and summarize some of the existing studies (10 years ago) in terms of several parameters such as the size of AuNPs, dose, administration route, experimental model, experimental analysis, and findings. The second goal is to describe the self-therapeutic effects of AuNPs against the pathogenesis determinants of diabetic complications. AuNPs have been found to have inhibitory effects on transforming growth factor-ß, antiglycation, antiangiogenic, anti-hyperglycemic, anti-inflammatory, and antioxidant effects. AuNPs treatment effectively disrupts multiple pathogenesis determinants in an animal model of diabetes and diabetic complications. The present review provides insight into the potential applications of AuNPs, which may help reduce the incidence of diabetes and its complications

Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113.

The authors wish to make the following corrections to this paper [...].

TP53, SPOP and PIK3CA Genes Status in Prostate Cancer.

Recent advances in molecular biology make the identification of prostate cancer (PC) subsets a priority for more understanding of the molecular pathogenesis and treatment options. Genetic alterations in many genes such as TP53, SPOP and PIK3CA genes have been reported in PC with variable frequencies worldwide. We aimed to investigate genetic alterations in the hotspot lesions of TP53, SPOP and PIK3CA genes by direct sequencing and the expression of TP53 and PIK3CA by RT-PCR in prostate cancer, and to explore the correlation between TP53, SPOP and PIK3CA alterations and tumorigenesis of prostate cancer. Seventy-nine FFPE prostate samples from patients who underwent radical prostatectomy were obtained, subjected to genomic DNA extraction and sequenced for mutations in exons 5, 6, 7 and 8 of TP53 gene, exons 4 and 5 of SPOP gene and exons 9 and 20 of PIK3CA gene. RT-PCR was performed for the expression evaluation of the PIK3CA gene. Our results showed a high frequency of TP53 mutations (11/79, 13.9 %) in the selected population. On the other hand, SPOP and PIK3CA genes did not show any genetic alteration in the sequenced exons. PIK3CA gene overexpression was detected in 6% of the cohort by RT-PCR. TP53 mutation is the most frequent genetic alteration and likely has a major role in the pathogenesis of PC in the Jordanian population.
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Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage.

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.

CAG Repeats in the androgen receptor gene is associated with oligozoospermia and teratozoospermia in infertile men in Jordan.

CAG trinucleotide repeats are coded for the polyglutamine tract in the N-terminal of the androgen receptor (AR) gene which varies in normal individuals from 6 to 36 residues. In this study, we inspected the impact of the CAG repeats on the spermatogenic defects by measuring the size of AR-CAG repeats length in a cohort of 260infertile and 169 fertile Jordanian men. The infertile group included three subgroups of a zoospermic, oligozoospermic and teratozoospermia men. The CAG allele size was determined by direct sequencing. The results showed a significant association between the length of the AR-CAG repeats and men's infertility (p = .001). In particular, the current cohort demonstrated a significant association between the AR-CAG length polymorphism and oligozoospermia (p < .001) and teratozoospermia (p < .001) but not azoospermia. According to distributions of allele frequency, the risk of oligozoospermia was 5.5-fold greater than normal when alleles frequency > 20 repeats, while the risk of teratozoospermia was > 10.6 folds greater than normal when allele frequency > 22 repeats. In conclusion, our results underscored that the long repeats of the AR-CAG polymorphism within the normal range might be associated with abnormal spermatogenesis such as teratozoospermia and oligozoospermia and contributing to infertility in Jordanian men.