Galangin attenuates cadmium-evoked nephrotoxicity: Targeting nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B signaling.

The kidney is highly vulnerable to cadmium-evoked oxidative injury. Galangin is a natural flavone with reported antioxidant properties. This study investigated the potential modulating activity of galangin against cadmium-induced nephrotoxicity and explored the underlining mechanisms. Western blot analysis, spectrophotometric, ELISA, and histopathological techniques were employed. The results revealed that galangin suppressed tubular injury and improved glomerular function in the cadmium-intoxicated rats as evidenced by downregulation of kidney injury molecule-1, serum creatinine, and blood urea nitrogen. Galangin reduced cadmium-evoked inflammatory response and oxidative stress as indicated by reduced levels of interleukin-1 beta and TNF-α, decreased DNA damage, and improved antioxidant potential of the renal tissues. Mechanistically, galangin suppressed the nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome and efficiently decreased caspase-1 activity in the cadmium-intoxicated rats. Equally important, it inhibited the cadmium-induced nuclear translocation of nuclear factor kappa B and upregulated nuclear factor erythroid 2-related factor 2 signaling. The results highlight the ability of galangin to attenuate cadmium-evoked nephrotoxicity and support its therapeutic implementation although clinical investigations are warranted.

Advances on concrete strength properties after adding polypropylene fibers from health personal protective equipment (PPE) of COVID-19: Implication on waste management and sustainable environment.

Using Health personal protective equipment (PPE) such as face masks, safety foot shoes and protective suits has expanded dramatically due to COVID-19 pandemic leading to a widespread distribution of the PPE, particularly the face masks, in the environments including streets, dump sites, seashores and other risky locations. The environmental degradation of polypropylene, the essential plastic component in single-use face masks (SUM), takes between 20 and 30 years and thus it is essential to develop experimental approaches to recycle the polypropylene or to reuse it in different ways. This paper explores the integration of SUM into concrete structures to improve its mechanical properties. We first to cut the inner nose wire and ear loops, then distribute the PPE material among five different mixed styles. The PPE were applied by volume at 0%, 1%, 1.5%, 2.0%, and 2.5%, with tests focusing on UCS, STS, FS, and PV to determine the concrete's overall consistency and assess the improvement in its mechanical properties. The results showed that adding PPE improves the strength properties and general performance of the concrete specimens. The pattern of rising intensity started to fade after 2%. The findings demonstrated that adding PPE fibers enhanced the UCS by 9.4% at the optimum 2% PPE. The PPE fibers, on the other side, are crucial in calculating the STS and FS of the reinforcement concrete.

Assessment of the reuse of Covid-19 healthy personal protective materials in enhancing geotechnical properties of Najran's soil for road construction: Numerical and experimental study.

The COVID-19 pandemic has not only caused a global health crisis, but it has also had significant environmental and human consequences. During the COVID-19 pandemic, this study focused on emerging challenges in managing healthy personal protective materials (HPPM) in Kingdom of Saudi Arabia, using silty sand (SM) soil as an example since it covers large areas in KSA and in the whole world. The main objective of this paper is to find a novel way to minimize pandemic-related waste by using HPPM as waste materials in road construction. For the first time, a series of experiments was conducted on a mixture of different percentages of shredded HPPM (0, 0.5, 1 and 2%) added to the silty sand (SM) soil for road applications, including soil classification according to the USCS, modified compaction, UCS, UPV, and CBR. In addition, a numerical simulation was performed using geotechnical-based software Plaxis 3D to study the performance of the soil-HPPM mix as a subbase layer in the paving structure under heavy traffic loading. The modified compaction test results show that there is an increase in the optimum moisture content with increasing the HPPM contents from 0.5% to 1% and 2%. However, a reduction in the maximum dry density is observed. The values of dry density and water content at 0%, 0.5%, 1% and 2% pf HPPM are 2.045, 1.98, 1.86 and 1.8 g/cm3 and 7.65% 8%, 8.5% and 9.5%, respectively. The soaked CBR values at 0, 0.5, 1 and 2% HPPM are 23, 30, 8, 2% with the maximum value attained with the addition of 0.5% HPPM. The results of UCS were with the same percentages of HPPM 430, 450, 430 and 415 kPa, respectively, with the maximum value attained with 0.5% HPPM addition as well. In contrast, the values of UVP at 0%, 0.5%, 1% and 2% are 978.5, 680.3, 489.4 and 323.6 m/s, respectively, confirming the trends obtained by modified compaction test results. The simulation results confirm this conclusion that the soil-HPPM mix show a superior performance when used as a subbase layer and reduced vertical displacement by a percentage of 11% compared to the normal subbase material. By eliminating HPPM especially facemasks from the landfill lifecycle, incorporating them into high quality construction material production has the potential to deliver significant environmental benefits.

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects.

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83. Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection.

The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. METHODS: This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial number: UMIN000020281. RESULTS: Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. CONCLUSIONS: This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.

Antibodies to extractable nuclear antigens (ENAS) in systemic lupus erythematosus patients: correlations with clinical manifestations and disease activity.

The aim was to explore possible correlations of antibodies to extractable nuclear antigens (ENA) with clinical manifestations and disease activity indices in systemic lupus erythematosus (SLE) patients. A total of 70 consecutive SLE patients (64 females) were included. Disease activity was assessed by SLE activity index (SLEDAI), and British Isles Lupus Assessment Group (BILAG). Anti-Ro/SSA correlated positively with, headache (r=0.24, p=0.04), blurring of vision (r=0.25, p=0.03) and SLEDAI (r=0.25, p=0.04) and negatively with C3 (r=-0.35, p=0.003). Anti-Ro/SSA correlated with anti La/SSB antibodies (r=0.69, p<0.001), but not with anti-DNA, anti-RNP and anti-Sm antibodies. Anti-La/SSB antibodies correlated with headache (r=0.26, p=0.03), SLEDAI (r=0.25, p=0.03) and negatively with C3 (r=-0.34, p=0.004). Anti-La/SSB did not correlate with anti-RNP or anti-Sm antibodies. Anti-Sm antibodies correlated with disease duration (r=0.34, p=0.003), 24 hours urinary proteins (r=0.31, p=0.008), SLEDAI (r=0.31, p=0.009), BILAG renal score (r=0.29, p=0.02) and negatively with age at onset (r=-0.27, p=0.02), WBCs (r=-0.29, p=0.014) and C4 (r=-0.25, p=0.049). In multivariate analyses, anti-Ro/SSA antibodies remained associated with headache, blurring of vision and C3 and anti-La/SSB antibodies remained associated with C3 and with headache. Anti-Sm antibodies were independently associated with disease duration and total SLEDAI scores, while anti-RNP antibodies remained significantly associated with BILAG mucocutaneous scores only. Antibodies to ENAs are associated with clinical aspects of SLE and may play a role in the assessment of disease activity. Insight into these ENAs may lead to new approaches to diagnostic testing, accurate evaluation of disease activity and lead to target approach for SLE.

Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naïve and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis.

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.

Crocin Abrogates Carbon Tetrachloride-Induced Renal Toxicity in Rats via Modulation of Metabolizing Enzymes and Diminution of Oxidative Stress, Apoptosis, and Inflammatory Cytokines.

This work aimed at investigating the potential modulatory effects and mechanisms of crocin against CCl4 -induced nephrotoxicity. Forty male rats were allocated for three weeks treatment with corn oil, CCl4 , crocin, or crocin plus CCl4 . Crocin effectively mitigated CCl4 -induced kidney injury as evidenced by amelioration of alterations in kidney histopathology, renal weight/100 g body weight ratio and kidney functions. Crocin modulated CCl4 -induced disturbance of kidney cytochrom-P450 subfamily 2E1 and glutathione-S-transferase. The attenuation of crocin to kidney injury was also associated with suppression of oxidative stress via reduction of lipid peroxides along with induction of renal glutathione content and enhancement of superoxide dismutase, glutathione peroxidase, and catalase activities. Crocin mitigated CCl4 -induced elevation of the renal levels of tumor necrosis factor-alpha, interleukin-6, prostaglandin E2, and active caspases-3. Collectively, crocin alleviated CCl4 -induced renal damage via modulation of kidney metabolizing enzymes, suppression of oxidative stress, inhibition of inflammatory cytokines, PGE2, and active caspase3 in kidney.

Quercetin protects against acetaminophen-induced hepatorenal toxicity by reducing reactive oxygen and nitrogen species.

High or toxic doses of acetaminophen (APAP), a mild analgesic and antipyretic drug, can cause life-threatening hepatic and renal dysfunction. This study is designed to investigate the potential protective role of quercetin to attenuate the hepatorenal toxicity induced by a high single oral dose (3g/kg) of APAP in rats. Three main groups of Sprague-Dawley rats were used: quercetin, APAP and quercetin plus APAP-receiving animals. Corresponding control animals were also used. Interestingly, oral supplementation of quercetin (15mg/kg/day) prior to APAP intoxication dramatically reduced APAP-induced hepatorenal toxicity as evidenced by measuring serum lipid profile, total protein, urea, creatinine, ALT, AST, ALP, G-GT and liver tissue content of TC and TG. Quercetin treatment markedly prevented the generation of TBARS and PCC with substantial improvement in terms of GSH and activities of antioxidant enzymes in both liver and kidney homogenates. The relationship between quercetin and NO levels which is still a matter of debate, was also investigated. NO levels in serum, liver and kidney tissues were significantly inhibited in quercetin pre-treated animals. Furthermore, quercetin administration significantly inhibited the reduction of liver and kidney contents of ATP parcels associated with this hepatorenal toxicity. These results suggest that the protective role of quercetin in the prevention of APAP-induced hepatorenal toxicity in rats was associated with the decrease of oxidative and nitrosative stress in hepatic and renal tissues as well as its capacity to improve the mitochondrial energy production. However, clinical studies are warranted to investigate such an effect in human subjects.

Modulator effects of meloxicam against doxorubicin-induced nephrotoxicity in mice.

Doxorubicin-induced renal toxicity overshadows its anticancer effectiveness. This study is aimed at assessing the possible modulator effects of meloxicam, a cyclooxigenase-2 inhibitor, on doxorubicin-induced nephrotoxicity in mice and exploring some of the modulator mechanisms. Forty male mice were divided for treatment, for 2 weeks, with saline, meloxicam (daily), doxorubicin (twice/week), or both meloxicam and doxorubicin. Doxorubicin induced a significant increase in relative kidney weight to body weight, kidney lipid perooxidation, plasma levels of interleukin-6 and tumor necrosis factor-α, kidney caspase-3 activity, and kidney prostaglandin E2 (PGE2) content. Doxorubicin disturbed kidney histology, abrogated renal function tests (serum creatinine, uric acid, and blood urea nitrogen), induced a significant decrease in antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and catalase) and reduced glutathione (GSH) content. The administration of meloxicam with doxorubicin mitigated all doxorubicin-disturbed parameters. Meloxicam ameliorated doxorubicin-induced renal injury via inhibition of inflammatory PGE2, inflammatory cytokines, caspase-3 activity, antioxidant effect, and free radical scavenging activity.

Boosting-based ensemble machine learning models for predicting unconfined compressive strength of geopolymer stabilized clayey soil.

The present research employs new boosting-based ensemble machine learning models i.e., gradient boosting (GB) and adaptive boosting (AdaBoost) to predict the unconfined compressive strength (UCS) of geopolymer stabilized clayey soil. The GB and AdaBoost models were developed and validated using 270 clayey soil samples stabilized with geopolymer, with ground-granulated blast-furnace slag and fly ash as source materials and sodium hydroxide solution as alkali activator. The database was randomly divided into training (80%) and testing (20%) sets for model development and validation. Several performance metrics, including coefficient of determination (R2), mean absolute error (MAE), root mean square error (RMSE), and mean squared error (MSE), were utilized to assess the accuracy and reliability of the developed models. The statistical results of this research showed that the GB and AdaBoost are reliable models based on the obtained values of R2 (= 0.980, 0.975), MAE (= 0.585, 0.655), RMSE (= 0.969, 1.088), and MSE (= 0.940, 1.185) for the testing dataset, respectively compared to the widely used artificial neural network, random forest, extreme gradient boosting, multivariable regression, and multi-gen genetic programming based models. Furthermore, the sensitivity analysis result shows that ground-granulated blast-furnace slag content was the key parameter affecting the UCS.

Impact of combined component separation technique and shoelace repair on big medline abdominal wall defect.

BACKGROUND: Closure of large anterior abdominal wall defects, regardless of their etiology, is challenging. There is no standardized information describing definitive management. Therefore, we conducted this study to illustrate our experience on large midline abdominal wall defect repair using an effective modified reconstructive technique. METHODS: This retrospective study was conducted at Al Naqib Hospital in Aden/Yemen between 2012 and 2019. Twenty-six patients with large midline abdominal wall defects of various etiologies underwent surgical repair using a combination of shoelace repair and the component separation technique. The procedure involved bilateral longitudinal division of the anterior rectus sheet and creation of a posterior layer by approximation of the medial edges of the divided rectus sheet (shoelace abdominoplasty) and anterior external oblique muscle aponeurosis separation (component separation technique) to approximate the lateral edges of the divided rectus sheet and move the rectus muscles toward the midline for constructing the anterior abdominal wall layer. The posterior and anterior layers and bilateral separated sheets were covered with a polypropylene mesh in all patients, except in those who underwent emergency damage control surgery. RESULTS: Four, one, and two patients developed seroma, skin necrosis and chronic pain, and post-surgical wound infection, respectively. No recurrent herniation was recorded during the median follow-up of 5 years. CONCLUSION: This technique is effective in restoring the integrity of the abdominal wall in large midline abdominal wall defects and has an acceptable aesthetic appearance. In our study, minimal complications were reported, and no cases of recurrent hernias were diagnosed during follow-up.

Numerical simulation and diagnosis geotechnical parameters of historical buildings in Najran City, Kingdom of Saudi Arabia.

This research aims to assess geoenvironmental risks and identify the primary deterioration drivers in ancient buildings in Najran City, utilizing various analytical tools to help make informed judgments. The samples extruded from historical buildings were examined using field inspection, experimental data, SEM, EDX, and XRD analyses, in addition to lab and field observations and meteorological data. The dissolution of clay minerals and salt crystallization are the key contributors to the degradation and cracking of historical buildings in Najran City, according to lab and field observations. When the daytime high temperature surpasses 44 °C, wind erosion and humidity might cause continuous wetting-drying cycles on the investigated building surfaces. Test results indicated that the average unconfined compressive strength of the extruded earthen wall samples was 2 MPa and the water absorption was within the upper allowed limit (i.e., 15%). A finite element model of a typical earthen historical building was developed using PLAXIS 3D software to assess the behavior and nonlinear response of the silty sand soil layer underlying the building and the earthen historical buildings themselves using a plastic material model. The field observations confirm the results of the simulation, which clearly explained the failure mechanism. The integrated geotechnical and numerical simulations could provide insights for assessing geoenvironmental risks, identify the primary deterioration drivers in ancient buildings, and provide an understanding of material qualities and failure causes not only in the studied area but in other similar regions elsewhere.

miRNAs as potential game-changers in melanoma: A comprehensive review.

Melanoma is the sixth most frequent malignancy. It represents 1.7% of all cancer cases worldwide. Many risk factors are associated with melanoma including ultraviolet radiation skin phenotype, Pigmented Nevi, Pesticides, and genetic and epigenetic factors. Of the main epigenetic factors affecting melanoma are microribonucleic acids (miRNAs). They are short nucleic acid chains that have the potential to prevent the expression of a number of target genes. They could target a number of genes related to melanoma initiation, stemness, angiogenesis, apoptosis, proliferation, and potential resistance to treatment. Additionally, they can control several melanoma signaling pathways, including P53, WNT/-catenin, JAK/STAT, PI3K/AKT/mTOR axis, TGF- ß, and EGFR. MiRNAs also play a role in the resistance of melanoma to essential treatment regimens. The stability and abundance of miRNAs might be important factors enhancing the use of miRNAs as markers of prognosis, diagnosis, stemness, survival, and metastasis in melanoma patients.

The future for the treatment of genotype 4 chronic hepatitis C.

Hepatitis C virus genotype 4 (HCV-4) is the most common type of hepatitis C virus (HCV) in the Middle East and Africa, in particular Egypt. Since the development of new protease inhibitors, the response of HCV-4 to the standard regimen of treatment (pegylated interferon/ribavirin) lags behind other genotypes and has become the most resistant type to treat. The development of therapeutic strategies for all patients with HCV-4 whether they are naïve, have experienced a virological breakthrough, are relapsers or non-responders is still a considerable challenge. New types of interferon (Consensus Interferon, Y-shaped, Albinterferon...) and new direct action antiviral drugs (Nitazoxanide, Vit.D, other) may improve the treatment of patients with HCV-4. The IL28B CC polymorphism may be associated with sustained virological response.

Angiotensin-converting enzyme (ACE) serum levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus.

OBJECTIVES: To investigate the association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE level among Egyptian SLE patients and its relation to disease activity parameters. SUBJECTS AND METHODS: We enrolled 50 Egyptian female systemic lupus erythematosus (SLE) patients and 29 healthy controls. Measurement of serum ACE level was done using ELISA, and the ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. RESULTS: A significant difference was found in ACE genotypes between SLE patients and controls (χ(2 )= 7.84, p = 0.02). The frequency of ACE DD versus (DI and II) genotypes was significantly higher in SLE patients compared with controls (χ(2 )= 5.57, p = 0.018 and OR for risk of SLE was 3.1 with 95% confidence interval: 1.198.06). Mean serum ACE level was significantly higher in the SLE group compared with controls (p = 0.006). Subjects with DD genotype had a significantly higher mean level than those with DI (p = 0.015) and II genotypes (p = 0.02). Lupus nephritis patients had a significantly higher frequency of DD versus DI and II genotypes compared with lupus patients without nephritis (Fisher's exact test, p = 0.025) and controls (χ (2) =8.74, p = 0.003). SLE patients with vasculopathy had a significantly higher frequency of DD versus DI/II genotypes compared with SLE patients without vasculopathy (Fisher's exact test, p = 0.04) and controls (χ(2 )= 9.84 and p = 0.002). Mean serum ACE level was significantly higher in the lupus nephritis and SLE patients with vasculopathy compared with controls (p = 0.008, p = 0.001, respectively). Significant positive correlations were found between serum ACE level and serum creatinine and 24 h proteinuria (p = 0.03, 0.009, respectively). SLE patients with DD genotype had a statistically significant higher mean SLEDAI score than those with (DI/II) genotypes (p = 0.02). Significant positive correlation was found between serum ACE levels and SLEDAI scores (p = 0.04). CONCLUSION: ACE genotype and subsequently serum ACE level could be associated with the disease activity of Egyptian SLE patients; in addition, ACE deletion polymorphism might be used as one of the predictive factors for the activity of SLE. Further studies on a larger number of patients should be done to determine the exact prevalence of ACE gene polymorphism among Egyptian SLE patients.

Protective effect of dietary flavonoid quercetin against lipemic-oxidative hepatic injury in hypercholesterolemic rats.

CONTEXT: Quercetin, a dietary-derived flavonoid, is ubiquitous in fruits and vegetables and plays important roles in human health by virtue of its antioxidant activity. OBJECTIVE: This study was conducted to investigate the possible modulatory effect of quercetin against hepatic lipemic-oxidative injury in rats fed with a high cholesterol diet (HCD), and to highlight the underlying mechanisms of such effect. MATERIALS AND METHODS: Different groups of male Sprague-Dawley rats were used; one group was treated by gavage with HCD cocktail (1 mL/100 g) whereas another group was orally administered HCD-enriched with quercetin (15 mg/kg). Corresponding control animals were also used. RESULTS: Quercetin administration significantly decreased liver triglycerides (24%), liver total cholesterol (TC) (22%), serum TC (20%), serum low-density lipoprotein cholesterol (31%), and duplicated serum high-density lipoprotein cholesterol (HDL-C). This study also revealed that quercetin administration significantly reduced the activity of serum alanine aminotransferase (41%), aspartate aminotransferase (51%), and γ-glutamyl transpeptidase (G-GT) (35%). Significant inhibition of thiobarbituric acid-reacting substances (40%), together with a valuable enhancement of reduced glutathione (GSH) content (53%) in the liver homogenates, was observed. In addition, quercetin-treated hypercholesterolemic animals exhibited a reasonable improvement of hepatic antioxidant enzymes. Moreover, serum and liver content of nitric oxide (NO) were markedly decreased in this model (26 and 25%, respectively), and were almost normalized following quercetin administration. DISCUSSION AND CONCLUSION: These data revealed that quercetin has the ability to ameliorate HCD-induced lipemic-oxidative injury in rat liver possibly through its antioxidant potential and/or increased NO bioavailability.

A long-term study of liver-related events in Caucasian hepatitis B patients with normal ALT values and high viremia.

Background and study aims: There is ongoing debate whether antiviral therapy should be initiated in hepatitis B e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels but high HBV DNA levels >2,000 IU/mL. Since the need for antiviral therapy might be different between Asian and Caucasian patients, we studied the long-term disease outcome in Caucasian patients living in Western Europe. Patients and methods: One hundred sixteen patients with high HBV DNA levels (>2,000 IU/mL) at diagnosis were included in the high viremia group, while those with HBV DNA <2,000 IU/mL were used as controls (n = 327). All patients were Caucasian, HBeAg negative, had normal ALT levels and had no significant liver disease at diagnosis. Results: Median follow-up was 7 + 9.8 years in the high viremia group and this was 10 + 12.5 years in controls. The cumulative probability of a liver-related event over 10 years was 4.8% vs 0.0% in the control group (p=.008). In multivariable analysis, high viremia group was associated with the occurrence of a liver-related event (hazards ratio (HR) 95% confidence interval (CI): 1.20-11.98, p=.023). In this subgroup, older age at diagnosis (HR 95% CI: 1.01-1.16, p=.023) predicted a higher risk of liver-related event. In the high viremia group, liver-related mortality was 0.9% and none of the patients developed hepatocellular carcinoma. Conclusions: HBV DNA >2,000 IU/mL influences the long-term disease outcome in Caucasian HBeAg-negative patients living in Western Europe. Nevertheless, the risk of liver-related events is low.

Ergothioneine mitigates cisplatin-evoked nephrotoxicity via targeting Nrf2, NF-κB, and apoptotic signaling and inhibiting γ-glutamyl transpeptidase.

AIM: Cisplatin is a potent chemotherapeutic agent whose therapeutic application is hindered by the associated nephrotoxicity. Cisplatin-evoked nephrotoxicity has been largely attributed to the induction of oxidative stress and inflammatory responses. The current study aimed at investigating the ability of ergothioneine to mitigate cisplatin-evoked nephrotoxicity and to elucidate the underlining molecular mechanisms. MAIN METHODS: Wistar rats were treated with a daily dose of ergothioneine (70 mg/kg, po) for fourteen days and a single dose of cisplatin (5 mg/kg, ip) on day ten. On day fifteen, kidneys and blood specimens were collected and subjected to Western blotting, ELISA, histopathological, and spectrophotometric analysis. KEY FINDINGS: Ergothioneine significantly enhanced renal function in cisplatin-treated rats as manifested by increased GFR and decreased serum creatinine and blood urea nitrogen. Ergothioneine effectively reduced the cisplatin-induced oxidative stress and mitigated apoptosis and the histopathological changes. Mechanistically, ergothioneine induced the expression of the antioxidant transcription factor Nrf2 and up-regulated its downstream targets NQO1 and HO-1. Equally important, ergothioneine inhibited γ-glutamyl transpeptidase that plays crucial roles in biotransformation of cisplatin into a toxic metabolite. Additionally, it reduced the pro-apoptotic protein p53 and the inflammatory transcription factor NF-κB along with its downstream pro-inflammatory cytokines TNF-α and IL-1ß. SIGNIFICANCE: The results of the current work shed the light on the ameliorating effect of ergothioneine on cisplatin-evoked nephrotoxicity that is potentially mediated through modulation of Nrf2, p53, and NF-κB signaling and inhibition of γ-glutamyl transpeptidase. This findings support the potential application of ergothioneine in controlling cisplatin-associated nephrotoxicity although clinical investigations are warranted.