Biogenic synthesis of AgNPs via polyherbal formulation: Mechanistic neutralization and toxicological impact on acetylcholinesterase from Bungarus sindanus venom.

This study aims to examine the biogenic production, characterization, and anti-acetylcholinesterase (AAChE) properties of polyherbal formulation PHF-extract-synthesized silver nanoparticles (PHF-AgNPs). The Elapidae snake Bungarus sindanus has extremely dangerous venom for humans and contains a high amount of AChE (acetylcholinesterase). Inhibiting AChE leads to acetylcholine buildup, affecting neurotransmission. The study tested silver nanoparticles as AChE inhibitors using kinetics. Their production was confirmed through ultraviolet (UV) spectrometry at 425 nm (SPR peak of 1.94), and stabilizing functional groups were identified via Fourier transform infrared spectroscopy (FT-IR). The average length of 20 nm was confirmed by analyzing the scanning electron microscopy (SEM) data. Energy-dispersive X-ray spectroscopy (EDX) identified silver as the primary component of PHF-AgNPs (26%). Statistical analysis showed that the activity of AChE in krait venom decreased by up to 45% and 37% at a given dose of ACh (0.5 mM) by PHF and AgNPs, respectively. Utilizing the Lineweaver-Burk plot for kinetic analysis, a competitive type of inhibition is found. RESEARCH HIGHLIGHTS: Successfully synthesized PHF-extract-induced silver nanoparticles (PHF-AgNPs) demonstrated through UV spectrometry and characterized as crystalline with an average size of 45 nm by X-ray diffraction. PHF-AgNPs effectively inhibited acetylcholinesterase (AChE), an enzyme critical in neurotransmission, reducing its activity in krait venom by up to 45% at certain concentrations. Kinetic analysis revealed that the inhibition mechanism of AChE by PHF-AgNPs is competitive, offering potential for therapeutic applications in neurologically related conditions.

Role of bone marrow mesenchymal stem cell-derived exosomes in reducing neurotoxicity and depression-like behaviors induced by doxorubicin in rats.

Background: Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited nowadays due to its neurobiological side effects associated with depression. Bone marrow mesenchymal stem cells (BM-MSCs) derived exosomes are a promising regenerative therapy. In this study, we investigated the therapeutic potentiality of BM-MSCs derived exosomes against the neurotoxicity induced by DOX. Methods: Twenty-four male albino rats were divided equally in to three groups as follow: group 1 (control), group 2 (rats injected intraperitoneally (i.p|) with DOX at a dose 2.5mg/Kg), and group 3 (rats injected with DOX and BM-MSCs derived exosomes i.p at a dose 1.5ml/Kg). During the experiment the behavior tests were noted, after three weeks rats were sacrificed, serum and brain samples were collected for biochemical, molecular and histopathological examinations. Results: The results revealed that DOX causing impairment of the locomotor and increasing the anxiety like behavior of rats, marked neuropathological changes, significant elevation of MDA content and TNF-α concentration, reduction of phospholipase (PLD) and acetylcholinesterase (AChE) protein concentration in addition, there were up regulation of JNK, NF-κB and p38 genes and down regulation of Erk1. Conclusion: Exosomal therapy improved the substantial neurotoxicity of DOX through modulating the markers involved in the neurotoxic signalling pathway of DOX that resulting in improving the pathological lesions and the animal behaviours.

Effect of controlled release of HGF on extracellular vesicle secretion by urine-derived stem cells.

Introduction: The hepatic growth factor (HGF) stimulates DNA synthesis and cell proliferation and plays a role in tissue protection and regeneration. In this study, we have examined the effect of incubation of HGF with urine-derived stem cells (USCs) on the secretion of small extracellular vesicles (sEV) by the cells. Materials and Methods: HGF in the incubation medium was either a bolus administration or a controlled release of an equivalent amount from microbeads within the size range of 50-200 µm made with ultrapurified low-viscosity high-guluronic acid (UP-LVG) alginate. USCs were incubated with or without HGF for 3 days or 7 days before removal of the incubation media, followed by harvesting sEV by the precipitation method. The protein content of isolated sEV was measured by bicinchoninic acid assay (BCA) for these three groups: control (no HGF beads), bolus HGF, and HGF beads. We also performed nanoparticle tracking analysis (NTA), Western blot assay, and ELISA for the HGF content of samples. Results: We found a significantly higher concentration of proteins in the HGF microbead group (control release group) compared to the bolus group and the control group after 7 days (p < 0.0017). The NTA data aligned with the BCA; they showed a significantly higher concentration of particles within the size range of sEV (<200 nm) in the group treated with HGF beads compared to the two other groups on day 7 (p < 0.0001). Conclusion: We found that administration of HGF to USCs by controlled release of the growth factor significantly enhances the levels of sEV secretion during 7 days of incubation.

Selenium improved arsenic toxicity tolerance in two bell pepper (Capsicum annuum L.) varieties by modulating growth, ion uptake, photosynthesis, and antioxidant profile.

Bell pepper (Capsicum annuum L.); an important spice crop of the region is a rich source of vitamins and antioxidants having many health benefits. Many biotic and abiotic factors contribute towards growth and yield losses of this crop. Arsenic (As) toxicity is a global issue, but it is particularly critical in developing countries. The current study was designed to evaluate the efficacy of selenium (Se) in mitigating the toxic effects of As in two varieties (HSP-181 A and PS09979325) of Capsicum annuum L. Different concentrations of As (0, 50, and 100 µM) and Se (0, 5, and 10 µM) were tested using 14 days old seedlings of C. annuum L. The As stress caused a significant (P ≤ 0.001) reduction in growth, uptake of nutrients, and eco-physiological attributes in both varieties however, the response was specific. While the overproduction of osmo-protectants and antioxidants intensified the symptoms of oxidative stress. The maximum reduction in shoot length (45%), fresh weight (29%), and dry weight (36%) was observed in under 100 µM As stress. The organic acids exudation from the roots of both cultivars were significantly increased with the increase in As toxicity. The Se treatment significantly (p ≤ 0.001) improved growth, nutrient uptake, gas exchange attributes, antioxidant production, while decreased oxidative stress indicators, and As uptake in the roots and shoots of all the subjects under investigation. It is concluded from the results of this study that Se application increased photosynthetic efficiency and antioxidant activity while decreasing As levels, organic acid exudation, and oxidative stress indicators in plants. Overall, the var. PS09979325 performed better and may be a good candidate for future pepper breeding program.

Journey into tomorrow: cardiovascular wellbeing transformed by nano-scale innovations.

Worldwide, cardiovascular diseases (CVDs) account for the vast majority of deaths and place enormous financial strains on healthcare systems. Gold nanoparticles, quantum dots, polymeric nanoparticles, carbon nanotubes, and lipids are innovative nanomaterials promising in tackling CVDs. In the setting of CVDs, these nanomaterials actively impact cellular responses due to their distinctive properties, including surface energy and topographies. Opportunities to more precisely target CVDs have arisen due to recent developments in nanomaterial science, which have introduced fresh approaches. An in-depth familiarity with the illness and its targeted mechanisms is necessary to use nanomaterials in CVDs effectively. We support the academic community's efforts to prioritize Nano-technological techniques in addressing risk factors linked with cardiovascular diseases, acknowledging the far-reaching effects of these conditions. The significant impact of nanotechnology on the early detection and treatment of cardiovascular diseases highlights the critical need for novel approaches to this pressing health problem, which is affecting people worldwide.

Nano revolution in cardiovascular health: Nanoparticles (NPs) as tiny titans for diagnosis and therapeutics.

Cardiovascular diseases (CVDs) are known as life-threatening illnessescaused by severe abnormalities in the cardiovascular system. They are a leading cause of mortality and morbidity worldwide.Nanotechnology integrated substantialinnovations in cardiovascular diagnostic and therapeutic at the nanoscale. This in-depth analysis explores cutting-edge methods for diagnosing CVDs, including nanotechnological interventions and crucial components for identifying risk factors, developing treatment plans, and monitoring patients' progress with chronic CVDs.Intensive research has gone into making nano-carriers that can image and treat patients. To improve the efficiency of treating CVDs, the presentreview sheds light on a decision-tree-based solution by investigating recent and innovative approaches in CVD diagnosis by utilizing nanoparticles (NPs). Treatment choices for chronic diseases like CVD, whose etiology might take decades to manifest, are very condition-specific and disease-stage-based. Moreover, thisreview alsobenchmarks the changing landscape of employing NPs for targeted and better drug administration while examining the limitations of various NPs in CVD diagnosis, including cost, space, time, and complexity. To better understand and treatment of cardiovascular diseases, the conversation moves on to the nano-cardiovascular possibilities for medical research.We also focus on recent developments in nanoparticle applications, the ways they might be helpful, and the medical fields where they may find future use. Finally, this reviewadds to the continuing conversation on improved diagnosis and treatment approaches for cardiovascular disorders by discussing the obstacles and highlighting the revolutionary effects of nanotechnology.

L-Proline: A Promising Tool for Boosting Cryotolerance and Fertilizing Ability of Cryopreserved Sperm in Animals.

Sperm cryopreservation technology significantly contributes to the safeguarding of genetic resources, particularly for endangered species, and supports the use of artificial insemination in domestic animals. Therefore, cryopreservation can negatively affect sperm health and function leading to reduce the freezing ability and fertility potential. Therefore, it is essential to prioritize the improvement of cryotolerance in cryopreserved sperm to enhance reproductive efficiency and ensure sustainability in livestock herds. The main reason for sperm dysfunction after thawing may be related to the excessive amount of oxidative stress (OS) produced during cryopreservation. Scientists have different ways for counteracting this OS including the use of plant extracts, enzymes, minerals, anti-freezing proteins, and amino acids. Recently, one such amino acid is L-proline (LP), which has multiple roles such as osmotic and OS defense, nitrogen, and carbon metabolism, as well as cell survival and signaling. LP has been found in seminal plasma and has recently been added to the freezing extender to improve the various post-thaw parameters of sperm. This improvement is related to the ability of LP to reduce the OS, sustain the plasma membrane and to act as an osmoregulatory agent. Moreover, LP can suppress cell apoptosis by modulating intracellular redox in sperm. This review addresses the ongoing research on the addition of L-proline as an osmoregulatory agent in freezing extenders to increase the cryotolerance of animal spermatozoa to freeze-thaw.

Prenatal developmental sequences of the esophageal epithelium in the New Zealand white rabbits: Light and electron microscopic analysis.

Several morphogenetic sequences occur during esophageal development and birth defects occur due to defects in foregut morphogenesis. This work aimed to record the cellular events in the morphogenesis of rabbits' esophageal epithelium. On the 16th day of gestation, the esophageal epithelium varied from stratified ciliated columnar to stratified squamous type. The surface epithelium presented mucous cells with mucigen granules of various sizes occupying their supranuclear cytoplasm. Cytoplasmic vacuolation was evident in all layers of the esophageal epithelium at this age. On the 18th gestational day, some light cells could be detected in the middle portion of the epithelium, while others occupied the whole epithelial length. On the 21st day, mucous cells are more frequently observed at the apical esophageal part as well as at the surface epithelium. Numerous elongated dark cells could be distinguished embedded between the basal cells. On the 24th gestational day the number of the mucous cells reached its peak. Reaching the 30th gestational day, several lamellar bodies, a keratinized layer and mitotic divisions could be demonstrated, and the number of both mucous and dark cells was greatly decreased. Collectively, detection of surface mucous and dark cells together with the non-cornified surface in some regions of the rabbit esophageal epithelium at the end of gestation ensure a postnatal development to reach the adult epithelium essential to sustain the passage of the harsh raw food. Future immunohistochemical studies are recommended to investigate the components of secretions in mucous cells and functional studies to highlight the dark cells significance. RESEARCH HIGHLIGHTS: Esophageal epithelium of fetal rabbit was analyzed by light and transmission microscopy. Surface epithelium presented mucous cells with mucigen granules of various sizes. They reached their maximum number on 24th day then decreased. On the 16th day, cytoplasmic vacuolation was evident in all epithelial layers. On the 21st day, numerous elongated dark cells could be distinguished embedded between the basal cells. Before birth, several lamellar bodies, a keratinized layer and mitotic divisions could be demonstrated, and the number of both mucous and dark cells was greatly decreased.

The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma.

Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.

Hydrothermal assisted biogenic synthesis of silver nanoparticles: A potential study on virulent candida isolates from COVID-19 patients.

Till now the exact mechanism and effect of biogenic silver nanoparticles on fungus is an indefinable question. To focus on this issue, the first time we prepared hydrothermal assisted thyme coated silver nanoparticles (T/AgNPs) and their toxic effect on Candida isolates were determined. The role of thyme (Thymus Vulgaris) in the reduction of silver ions and stabilization of T/AgNPs was estimated by Fourier transforms infrared spectroscopy, structure and size of present silver nanoparticles were detected via atomic force microscopy as well as high-resolution transmission electron microscopy. The biological activity of T/AgNPs was observed against Candida isolates from COVID-19 Patients. Testing of virulence of Candida species using Multiplex PCR. T/AgNPs proved highly effective against Candida albicans, Candida kruzei, Candida glabrata and MIC values ranging from 156.25 to 1,250 µg/mL and MFC values ranging from 312.5 to 5,000 µg/mL. The structural and morphological modifications due to T/AgNPs on Candida albicans were detected by TEM. It was highly observed that when Candida albicans cells were subjected to 50 and 100 µg/mL T/AgNPs, a remarkable change in the cell wall and cell membrane was observed.

Neuroprotective role of medicinal plant extracts evaluated in a scopolamine-induced rat model of Alzheimer's disease.

Background:Alzheimer's disease is a debilitating neurological brain disease with memory impairment among the first signs. Scopolamine (SCO), a muscarinic receptor antagonist that disrupts cognition and memory acquisition, is considered a psychopharmacological AD model. We investigate the effectiveness of medicinal plants in mitigating the SCO-induced neurobehavioural damage in rats. Materials and Methods: Animals were injected with Scopolamine hydrobromide trihydrate (2.2 mg/kg IP.) daily for 2 months. Each treatment group was administered one of four medicinal spice extracts (Nigella sativa, 400 mg/kg; rosemary, 200 mg/kg; sage, 600 mg/kg and ginseng; 200 mg/kg 90 minutes after SCO injection. Animals were subjected to cognitive-behavioural tests (NOR, Y-maze and MWM). After the experiment, we extracted the brains for histopathological examination and biochemical assessment for oxidative stress (levels of TT, CAT and TBARS) and gene expression of acetylcholinesterase and brain monoamines. Results: As expected, SCO treatment impaired memory and cognition, increased oxidative stress, decreased neurotransmitters and caused severe neurodegenerative changes in the brain. Conclusion: Surprisingly, these effects were measurably moderated by the administration of all four plant extracts, indicating a neuroprotective action that we suggest could alleviate AD disease manifestations.

Perspectives and Challenges on the Potential Use of Exosomes in Bioartificial Pancreas Engineering.

Exosomes are enclosed within a single outer membrane and exemplify a specific subtype of secreted vesicles. Exosomes transfer signalling molecules, including microRNAs (miRNAs), messenger RNA (mRNA), fatty acids, proteins, and growth factors, making them a promising therapeutic tool. In routine bioartificial pancreas fabrication, cells are immobilized in polymeric hydrogels lacking attachment capability for cells and other biological cues. In this opinion article, we will discuss the potential role that exosomes and their specific biofactors may play to improve and sustain the function of this bioartificial construct. We will particularly discuss the challenges associated with their isolation and characterization. Since stem cells are an attractive source of exosomes, we will present the advantages of using exosomes in place of stem cells in medical devices including the bioartificial pancreas. We will provide literature evidence of active biofactors in exosomes to support their incorporation in the matrix of encapsulated islets. This will include their potential beneficial effect on hypoxic injury to encapsulated islets. In summary, we propose that the biofactors contained in secreted exosomes have significant potential to enhance the performance of islets encapsulated in polymeric material hydrogels with perm-selective properties to provide immunoisolation for islet transplants as an insulin delivery platform in diabetes.

Deltamethrin and Its Nanoformulations Induce Behavioral Alteration and Toxicity in Rat Brain through Oxidative Stress and JAK2/STAT3 Signaling Pathway.

Deltamethrin (DM) is the most powerful synthetic pyrethroid that has toxicity to the central nervous system and results in behavioral changes in both animals and humans. This effect is mediated by inducing alterations in the action of neurotransmitters and brain pathological changes. Nanocarrier encapsulated pesticides may decrease the toxicity of pesticides. Thus, this study aimed to determine the effect of an inorganic metal carrier (silica Nps) and polymeric capsule (chitosan Nps) of deltamethrin nano-formulations on antioxidant levels and oxidative stress in the brain and on behavior of the male albino rat. Sixty male albino rats were equally divided into four groups. Group I: control group; group II given DM liquefied in corn oil at 3.855 mg/kg BW; group III receiving silica-loaded deltamethrin (S/DM Nps) at 8.795 mg/kg BW; and group IV: given chitosan encapsulated deltamethrin (CS/DM Nps) at 30.44 mg/kg BW. All treatments were given orally for four weeks. Following this, behavioral tests were conducted to record locomotor activity, anxiety like behaviors, exploration, and the short memory of rats. In addition, brain antioxidant/oxidant, serum neurotransmitters such as acetylcholine esterase (AchE) and monoamine oxidase (MAO), JAK2 and STAT3 gene and proteins expression were measured. The DM group showed a highly significant elevation in malondialdehyde content, MAO, AchE, vascular endothelial growth factor (VEGF) levels, and the expression level of neurogenic genes, JAK2 and STAT3, in comparison with the control group. Both S/DM Nps and CS/DM Nps significantly decreased MAO, AchE, and VEGF compared with the DM group. Moreover, both S/DM Nps and CS/DM Nps significantly decreased the gene and proteins expression of JAK2 and STAT3 compared with the DM group. These alterations were evidenced by the deficiency in memory and learning behaviors that were accompanied by histopathological findings of the hippocampus and the cortex. It was concluded that the nano formulations containing DM induced less neurobehavioral toxicity than free DM. Additionally, the use of nanocarriers reduced the damage to health and the environment.

The association between micro-RNA gene polymorphisms and the development of hepatocellular carcinoma in Egyptian patients.

INTRODUCTION: The development and progression of hepatocellular carcinoma (HCC) is a multistage process involving the deregulation of genes that are crucial to cellular processes. Multiple risk factors are correlated with HCC. MicroRNA is differentially expressed in the development of different types of malignancies, including hepatic malignancy. Single nucleotide polymorphisms (SNPs) are the most common sequence variation in the human genome. SNPs in miRNAs may affect transcription, processing, or target recognition and result in malignant disease. The aim of the study was to determine the association between microRNA gene polymorphisms and the development of HCC in Egyptian patients. MATERIAL AND METHODS: This study included 200 individuals who were matched in age and sex. Tumour staging was done using the BCLC staging system. Quantification and genotyping of microRNA were performed. RESULTS: Among the 200 patients, 2 groups were described: group I included 90 HCC patients with a male majority (72.2%), and group II comprised 110 controls. Three microRNA SNPs were assayed in both patients and controls. There was a significant association between rs10061133 miR-499b and the risk of HCC. The genotypes GG or G allele were significantly associated with an increased risk of HCC (GG: OR = 2.91, 95% CI: 1.23-4.22, p = 0.013; G allele: OR = 1.79, 95% CI: 1.12-2.15, p = 0.026) compared with the genotype of AA or AG or A allele. CONCLUSIONS: There is an association between the miRNA SNPs and the susceptibility to HCC, to explore some roles and mechanisms of SNPs within miRNAs in the occurrence and development of HCC.

Effect of Alginate Microbead Encapsulation of Placental Mesenchymal Stem Cells on Their Immunomodulatory Function.

In this research we have used different cytokines and progesterone to enhance the immunomodulatory capacity of placental-derived stem cells (PLSCs) prior to their encapsulation. We assessed the effect of microencapsulation of the cells without (control) or after 3-day treatment with interferon gamma (INFγ), interleukin10 (IL-10), or progesterone (P4). Treated PLSCs demonstrated strong immunosuppressive effects on phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMNCs). INFγ treatment resulted in the strongest immune inhibition among the treated groups. The treatments enhanced soluble human leukocyte antigen (sHLAG) secretion compared to control. The IL-10-treated group showed the highest effect on HLAG secretion compared to other groups. Alginate encapsulation of PLSCs did not affect cell viability, or sHLAG secretion. Also, after treatment the encapsulated PLSCs inhibited PHA-activated PBMNCs in the same manner as unencapsulated cells. We studied two groups of encapsulated PLSCs, one without perm-selective poly-L-ornithine (PLO)-coating and the other with PLO-coating, and measured levels of sHLAG secreted. We found no difference in sHLAG secretion between both groups. In summary, our data show that immunomodulatory function of the PLSC is not affected by encapsulation. These findings provide good promise for potential use of encapsulated PLSCs for immunomodulation treatment of disease by stem cell therapy.

The Potential Utility of Circulating Oncofetal H19 Derived miR-675 Expression versus Tissue lncRNA-H19 Expression in Diagnosis and Prognosis of HCC in Egyptian Patients.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Interestingly, lncRNA-H19 acts independently in HCC and influences miR-675 expressions. We aimed to assess the potential utility of tissue lncRNA-H19 versus miR-675 expressions as a non-invasive biomarker for HCC diagnosis and prognosis in Egyptian patients. Ninety-one HCC patients and 91 controls included in this study were investigated for expression of lncRNA-H19 and miR675 using RT-qPCR. Our results showed that the expression of lncRNA-H19 and microRNA-675 were higher in patients than in controls (p < 0.001 for both). Additionally, lncRNA-H19 expression was higher in tumorous than in non-tumorous tissue (p < 0.001). Linear regression revealed that miR-675 expression was a significantly higher positive predictor than lncRNA-H19 for tumor size, pathologic grade, and AFP level; similarly, for cyclin D1 and VEGF protein expression. By using the ROC curve, the sensitivity of miR-675 was higher than lncRNA-H19 for discriminating HCC from controls (95-89%, respectively) and the sensitivity of lncRNA-H19 was higher in tumorous than in non-tumorous tissues (76%). The high expressions of both were associated with low OS (p < 0.001, 0.001, respectively). Oncofetal H19-derived miR-675 expression could be considered a potential noninvasive diagnostic and prognostic biomarker, outstanding the performance of the expression of tissue lncRNA-H19 for HCC.

IL28B, TLR7 SNPs, and cytomegalovirus infection are risk factors for advanced liver disease in chronic hepatitis C patients.

BACKGROUND: Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). This study aimed to study the association of IL28B, toll-like receptor (TLR) 7, cytomegalovirus and advanced liver disease. METHODS: Four groups were included; control (n = 125, 25.9%), CHC (n = 114, 23.6%), liver cirrhosis (n = 120, 24.8%), and HCC (n = 124, 25.7%). RESULTS: In CHC group, patients were mainly F1 (60%) followed by F2. IL28B genotype CC percentage was higher in control group than the CHC and cirrhosis groups. CT and TT genotypes were higher in the CHC and cirrhosis groups than control group. The C allele was higher in the control group than the CHC, cirrhosis and HCC groups and the opposite with the T allele. Control and CHC had same TLR7 alleles. Cirrhosis patients and HCC had lower TLR 7 A allele and higher G allele than the control group. Both cirrhosis and HCC groups had statistically significant higher percentage of the AG and GG genotypes than the control group. Patients with HCC had higher cytomegalovirus infection percentage than cirrhosis and CHC group (38.7% vs 20% vs 16.7%), respectively. CONCLUSION: IL28B, TLR7 SNPs and cytomegalovirus infection are risk factors for advanced liver disease in hepatitis C patients.

Role of Resveratrol as Radiosensitizer by Targeting Cancer Stem Cells in Radioresistant Prostate Cancer Cells (PC-3).

AIM OF WORK: Here, we examined the role of resveratrol as a radiosensitizer by targeting cancer stem cells in radioresistant prostate cancer cells (PC-3) using stem cell markers CD44, CD49b and CD29, SOX2, OCT4, CXCR4, DCLK1 and EMT markers such as VIM and E-cadherin. MATERIAL AND METHODS: This study was an in vitro study involving PC-3 cell line which was dividing into four groups. Group I (CO): Control group composed of cells grown in the same medium without treatment with ionizing radiation or resveratrol. Group II (IR): Cells were treated with ionizing radiation alone. Group III (RV): Cells were treated with resveratrol alone. Group VI (IR&RV): The cells were treated with ionizing radiation and resveratrol in combination. The viability of cells was assessed by MTT assay. Genes of interest were measured by RT-PCR and the radiosensitizing efficacy of RV on proliferating cancer cells was determined by clonogenic assay. RESULTS: Ionizing radiation significantly reduced PC-3 viability, lowered stem cell markers and affected epithelial to mesenchymal transition (EMT) genes expression at all doses (2, 4, 6 and 8 Gray). Resveratrol significantly decreased PC-3 viability and lowered stem cell markers and EMT genes expression at concentrations 35, 70 and 140 µM. Combining resveratrol treatment with ionizing radiation leads to significant reduction in cell viability and stem cell markers genes which was noticed with increasing the radiation dose when compared to ionizing radiation alone treated group. CONCLUSION: Resveratrol has a radiosensitizing effect, that ability is triggered by reducing the expression of cancer stem cell markers and affecting EMT markers. Resveratrol showed to be a good candidate for further studies as anticancer drug in the treatment of human prostate cancer.

Nanonaringenin and Vitamin E Ameliorate Some Behavioral, Biochemical, and Brain Tissue Alterations Induced by Nicotine in Rats.

Nicotine is the major alkaloid present in cigarettes that induces various biochemical and behavioral changes. Nanonaringenin (NNG) and vitamin E are antioxidants that are reported to mitigate serious impairments caused by some toxins and oxidants. Thus, we aimed to investigate the efficacy of NNG, vitamin E, and their combinations to ameliorate behavioral, biochemical, and histological alterations induced by nicotine in rats. Adult male albino rats were randomly grouped into six equal groups (10 rats/group): control, N (nicotine 1 mg/kg b.w./day S/C from 15th to 45th day, 5 days a week), NNG (25 mg/kg b.w./day orally for 45 days), N + NNG, N + E (nicotine + vitamin E 200 mg/kg b.w./day orally), and N + NNG + E (nicotine + NNG + vitamin E at the aforementioned doses). Behavioral tests were conducted on day 15 and 30 postnicotine injection, while memory tests, brain neurotransmitters, antioxidants, and histopathological examination were examined at day 30 only. As a result, nicotine impaired rats' activity (hypoactivity and hyperactivity) and memory, induced anxiolytic and anxiogenic effects on rats, and altered neurotransmitters (acetylcholinesterase, serotonin, and dopamine), and redox markers (MDA, H2O2, GSH, and catalase) levels in brain homogenates. Thickening and congestion of the meninges and degeneration of the cerebral neurons and glia cells were observed. Cosupplementation with NNG, vitamin E, and their combination with nicotine was beneficial in the alleviation of activity impairments and improved short memory and cognition defects and exploratory behaviors. Our results indicate the antioxidant potential of NNG and vitamin E by modulating redox markers and neurotransmitters in the brain. Thus, data suggest that the prophylactic use of NNG, vitamin E, and/or their combination for (45 days) may have a successful amelioration of the disrupted behavior and cognition and biochemical and histopathological alterations induced by nicotine.

Clinical and Laboratory Characteristics of Elderly Patients with Pruritus.

INTRODUCTION: For elderly, pruritus is considered the most common complaint in outpatient clinic. Pruritus occurs in association with primary skin disorders and can also be caused by many diseases and drugs. The aim of the work was to study clinical and laboratory characteristics of elderly patients with pruritus in Sohag, Egypt. PATIENTS AND METHODS: A cross-sectional study was conducted on 225 patients aged ≥60 years of both sexes complaining of pruritus and 160 age- and sex-matched patient group complaining of non-pruritic dermatological diseases. CBC, ESR, renal function tests, serology for HBV and HCV and blood glucose levels were done routinely in all patients (both groups). Skin biopsy was done in some selected cases. RESULTS: The mean duration of pruritus was 4.23 ± 4.9 months and was generalized in 73.8% of cases with moderate severity in 35.1% with winter exacerbation in 20%. Dermatological causes of pruritus were detected in 54.2%, followed by systemic causes in 29.8%. Eczema was the most common skin cause of senile itching in 33.7%, while renal diseases were the most common systemic cause in 46.2%. CONCLUSION: Senile pruritus is a common problem in elderly. Early and proper management is mandatory to improve their quality of life.