Search

The ameliorating effects of four exogenous effectors were investigated in germinating pea seeds exposed to copper excess. The results showed that the application of IAA, GA3, Ca or citric acid alleviated Cu-induced inhibition of growth and simultaneously reduced the oxidative stress injury, particularly contents of hydrogen peroxide, malondialdehyde and carbonyl groups. The improving effects can probably be mediated by the decreases in lipoperoxidation and protein oxidation as evidenced by changes in antioxidant enzyme activities. In addition, the efficiency of this recovery was compared within two types of treatments. Obtained results demonstrated that the stress abruption by the addition of effectors after three days of Cu application (treatment of type II) seems to be more effective than the simultaneous application of ‘Cu + effectors’ at the beginning of germination (treatment of type I). Data could provide some clues to physiological and biochemical mechanisms of the response of germinating seeds to the addition of chemicals under heavy metal stress.

Background: The rise of virtual healthcare underscores the transformative influence of digital technologies in reshaping the healthcare landscape. As technology advances and the global demand for accessible and convenient healthcare services escalates, the virtual healthcare sector is gaining unprecedented momentum. Saudi Arabia, with its ambitious Vision 2030 initiative, is actively embracing digital innovation in the healthcare sector. Methods: In this narrative review, we discussed the key drivers and prospects of virtual healthcare in Saudi Arabia, highlighting its potential to enhance healthcare accessibility, quality, and patient outcomes. We also summarized the role of the COVID-19 pandemic in the digital transformation of healthcare in the country. Healthcare services provided by Seha Virtual Hospital in Saudi Arabia, the world's largest and Middle East's first virtual hospital, were also described. Finally, we proposed a roadmap for the future development of virtual health in the country. Results and conclusions: The integration of virtual healthcare into the existing healthcare system can enhance patient experiences, improve outcomes, and contribute to the overall well-being of the population. However, careful planning, collaboration, and investment are essential to overcome the challenges and ensure the successful implementation and sustainability of virtual healthcare in the country.

This study explores the integration of parallel compression and a two-phase ejector in transcritical CO 2 refrigeration systems, aiming to improve efficiency and performance. This innovative approach bridges the gap between conventional approaches and explores new energy-saving potential. The study uses thermodynamic modeling, mathematical simulation, and in-depth analysis to look at energy and exergy performance in a new configuration for applications in the retail sector at medium evaporation temperatures. The work investigates thermodynamic phenomena in a novel cycle with steady-state conditions, low pressure differentials, and adiabatic efficiency. The model is validated against experimental and theoretical published data, revealing component-specific exergy destruction and key parameters. The novel cycle efficiently extracts heat at higher temperatures, outperforming conventional and parallel cycles. Exergetic efficiency surpasses the standard cycle, with gas cooler pressure and temperature dependence enhancing efficiency by 40%-45%. The distribution of exergy destruction percentages reveals efficiency determinants, emphasizing heat exchange optimization and ejector responsiveness in energy dissipation dynamics. The study investigates the coefficient of performance (COP) dependence on gas cooler pressure and temperature, revealing superior performance compared to conventional cycles. COP increases by 50% at 80 bars, indicating enhanced efficiency. The new cycle offers exceptional efficiency gains, with a COP enhancement of over 75% for evaporator temperature transitions. Comparative analysis shows a COP superiority of up to 53% for lower evaporator temperatures and 20% for higher evaporator temperatures, demonstrating substantial energy savings and improved performance across various operating conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Colon cancer (CC) is one of the most common malignancies worldwide. Characterization of new prognostic biomarkers for right-sided CC (RCC) and left-sided CC (LCC) may contribute to improving early detection. An association of human leukocyte antigens class II (HLA-II) with the predisposition to CC was suggested., Aim of the Study: We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC., Patients and Methods: Our study comprised 93 CC patients and 100 healthy controls. Genotyping of HLA class II alleles were performed by the Polymerase Chain Reaction Sequence-Specific Primers (PCR-SSP)., Results: DRB1*03 was positively associated with CC. In contrast, DRB1*11, DRB1*13, DQB1*03, and DQB1*05 were negatively linked to CC. Haplotype analysis revealed that DRB1*04-DQB1*04 and DRB1*09-DQB1*02 were positive, while DRB1*01-DQB1*05, DRB1*04-DQB1*03, DRB1*07-DQB1*02, DRB1*11-DQB1*03, DRB1*11-DQB1*05, and DRB1*13-DQB1*06 were negatively associated with CC. For sigmoid CC, DRB1*13, DRB1*11, and DQB1*05 were negative, while DRB1*04-DQB1*02, and DRB1*07-DQB1*03 were positively associated. DRB1*03 and DRB1*04-DQB1*04 were positive, while DRB1*11 and DQB1*03 were negatively linked to RCC. According to the LCC, DRB1*07, DRB1*11, DQB1*03, DQB1*05, and DRB1*07-DQB1*02 were negative. In contrast, DRB1*09-DQB1*02 was positively associated with LCC. Stratified analysis revealed that DRB1*11 is associated with higher risk of metastasis in CC and sigmoid CC, and tolerance to treatment in RCC. DQB1*03 was associated with lymph-node invasion in CC., Conclusion: DRB1 and DQB1 polymorphisms could be used as future biomarkers for the early detection of subjects at a higher risk of developing RCC and LCC, metastasis in sigmoid CC, and tolerance to treatment in RCC., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2 mg/kg) or CPF and GSE (20 mg/kg) for 1 week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rigid ryegrass ( Lolium rigidum Gaud.) is one of the most troublesome weeds in Moroccan and Tunisian cereal crop fields. In total, 19 rigid ryegrass field populations were randomly selected in northern wheat crop areas of Morocco and Tunisia to examine the patterns of herbicide resistance to acetolactate synthase (ALS)- and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. Greenhouse experiments confirmed reduced sensitivity to ALS- and/or ACCase-inhibiting herbicides in all L. rigidum populations. The occurrence of target-site resistance (TSR) was tested using high-throughput genotyping. The advent of next-generation sequencing (NGS) has enabled easy identification of causal mutations and confirmed the presence of ALS and ACCase mutations at specific codons conferring TSR. Thirteen populations showed resistance to ALS-inhibiting herbicides associated with point mutations in positions Pro-197-Thr, Pro-197-Ser, Pro-197-Leu, Pro-197-Gln and Trp-574-Leu, while resistance to ACCase-inhibiting herbicides was detected in 18 populations in positions Asp-2078-Val, Trp-2027-Cys, Ile-1781-Leu, Gly-2096-Ala, and Ile-2041-Asn of the enzymes conferring TSR. Additionally, dose-response experiments with pyroxsulam applied after the inhibition of cytochrome P450 monooxygenase by malathion showed an increase in sensitivity in two out of seven highly resistant (HR) rigid ryegrass populations. This demonstrates the presence of non-target-site resistance (NTSR) in some ryegrass populations. Further evidence of NTSR was investigated in dose-response experiments with pyroxsulam, following pretreatment with the glutathione S -transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl), which partially reversed resistance in only a few individuals of two L. rigidum populations. Hence, our study confirms the existence of multiple and cross-resistance to ALS- and ACCase-inhibiting herbicides in L. rigidum from Morocco and Tunisia with both TSR and NTSR mechanisms. These results emphasize local resistance management as an important tool to detect and mitigate gene flow from rigid ryegrass populations where resistance has evolved., Competing Interests: Author AE is employed by Maghreb Phytotest SARL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 El-Mastouri, Košnarová, Hamouzová, Alimi and Soukup.)

Introduction: Solitary plasmacytoma is a rare, localized malignancy. Bone localizations are the most common. Extramedullary plasmacytomas are much rarer. They are most often in the upper respiratory tract and can be complicated by amyloidosis. Here is an original report of a mediastinal extramedullary plasmacytoma revealed by type AA renal amyloidosis., Case Presentation: We present the case of a 52-year-old patient with mediastinal extramedullary plasmocytoma diagnosed by renal failure due to type AA renal amyloidosis. Treatment was based on surgery with chemotherapy based on prednisone and melphalan. The patient presented end-stage renal failure that required hemodialysis at discharge., Conclusion: Extramedullary plasmacytoma is a rare tumour that may be associated with amyloidosis, usually type AL. To our knowledge, its association with AA amyloidosis has not been reported in the literature. Treatment is based on surgery combined with radiotherapy or chemotherapy.

The ability to accurately predict long-term kidney transplant survival can assist nephrologists in making therapeutic decisions. However, predicting kidney transplantation (KT) outcomes is challenging due to the complexity of the factors involved. Artificial intelligence (AI) has become an increasingly important tool in the prediction of medical outcomes. Our goal was to utilize both conventional and AI-based methods to predict long-term kidney transplant survival. Our study included 407 KTs divided into two groups (group A: with a graft lifespan greater than 5 years and group B: with poor graft survival). We first performed a traditional statistical analysis and then developed predictive models using machine learning (ML) techniques. Donors in group A were significantly younger. The use of Mycophenolate Mofetil (MMF) was the only immunosuppressive drug that was significantly associated with improved graft survival. The average estimated glomerular filtration rate (eGFR) in the 3rd month post-KT was significantly higher in group A. The number of hospital readmissions during the 1st year post-KT was a predictor of graft survival. In terms of early post-transplant complications, delayed graft function (DGF), acute kidney injury (AKI), and acute rejection (AR) were significantly associated with poor graft survival. Among the 35 AI models developed, the best model had an AUC of 89.7% (Se: 91.9%; Sp: 87.5%). It was based on ten variables selected by an ML algorithm, with the most important being hypertension and a history of red-blood-cell transfusion. The use of AI provided us with a robust model enabling fast and precise prediction of 5-year graft survival using early and easily collectible variables. Our model can be used as a decision-support tool to early detect graft status., (© 2023. The Author(s).)

Objective: The aim of the present study was to investigate the effects of Grape seed extract (GSE) and exercise training on Doxorubicin (Doxo)-induced cardio, hepato and myo toxicities in healthy rats., Methods: Thirty male Wistar rats were randomly divided into five groups and daily treated by intraperitoneal route during two months either with ethanol 10% (Control); Doxo (1.5 mg/kg); Doxo + exercise (1.5 mg/kg + swimming exercise for 30 min twice a week); Doxo + GSE (1.5 mg/kg + GSE 2.5 g/kg); Doxo + GSE + exercise (1.5 mg/kg + GSE 2.5 g/kg + swimming exercise for 30 min twice a week). At the end of the treatment, tissues were collected and processed for the determination of oxidative stress (OS), intracellular mediators, energy fuelling biomarkers, carbohydrate metabolism parameters and muscle histopathology., Results: Doxo provoked OS characterised by an increased lipoperoxidation (LPO) and protein carbonylation and decreased antioxidant enzyme activities. Doxo also affected intracellular mediators, disturbed carbohydrate metabolism and energy fuelling in skeletal muscle as assessed by down-regulated Electron Transport Chain (ETC) complex activities leading in fine to altered skeletal muscle structure and function., Conclusion: Almost all Doxo-induced disturbances were partially corrected with GSE and exercise on their own and more efficiently with the combined treatment (GSE + exercise).

Quaternary tungstates with the composition Li 3 Ba 2 Gd 3 (WO 4 ) 8 doped with different concentrations of Dy 3+ (from 0.5 to 10 at%) were prepared by the solid-state reaction method at 900 °C. Their structural, spectroscopic and optical properties were studied systematically in this work. X-ray diffraction analysis confirmed the crystallization of Li 3 Ba 2 Gd 3 (WO 4 ) 8 to have a monoclinic structure (sp. gr. C 2/ c ); the lattice constants for 1 at% doping concentration of Dy 3+ are a = 5.2126(2) Å, b = 12.7382(1) Å, c = 19.1884(3) Å, V calc = 1273,40(4) Å 3 and β = a × c = 91.890(9)°. The first principles calculations for the undoped crystal revealed a direct bandgap of 2.45 eV, which is very close to the experimental one. The identified broad, and strong excitation peak at 450 nm indicates that Li 3 Ba 2 Gd 3 (WO 4 ) 8 :Dy 3+ phosphors are suitable to be pumped by a blue laser diode (LD). Under excitation at 445 nm, the phosphor showed a stronger luminescence peak at 575 nm which corresponds to the Dy 3+ : 4 F 9/2 → 6 H 13/2 transition, and three weaker emissions peaks at 477, 661, and 750 nm. Meanwhile, the effect of different Dy 3+ contents on the luminescence properties was investigated. The optimum concentration to minimize the quenching effect was 4 at% and the critical distance is 31.209 Å. The phosphor emitted strong greenish-yellow light situated at (0.425, 0.472) in CIE coordinates with a color temperature of 3652 K. All the measured luminescence lifetime curves exhibited a single-exponential nature. Excellent thermal stability was found for this tungstate phosphor (the activation energy is 0.352 ± 0.01 eV). The measured absolute photoluminescence quantum yield was around 10.5%. The results presented in this work show that Li 3 Ba 2 Gd 3 (WO 4 ) 8 :Dy 3+ phosphors with strong yellow emission are promising candidates for white-light emitting LED (wLED) applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

With its robust ability to integrate and learn from large sets of clinical data, artificial intelligence (AI) can now play a role in diagnosis, clinical decision making, and personalized medicine. It is probably the natural progression of traditional statistical techniques. Currently, there are many unmet needs in nephrology and, more particularly, in the kidney transplantation (KT) field. The complexity and increase in the amount of data, and the multitude of nephrology registries worldwide have enabled the explosive use of AI within the field. Nephrologists in many countries are already at the center of experiments and advances in this cutting-edge technology and our aim is to generalize the use of AI among nephrologists worldwide. In this paper, we provide an overview of AI from a medical perspective. We cover the core concepts of AI relevant to the practicing nephrologist in a consistent and simple way to help them get started, and we discuss the technical challenges. Finally, we focus on the KT field: the unmet needs and the potential role that AI can play to fill these gaps, then we summarize the published KT-related studies, including predictive factors used in each study, which will allow researchers to quickly focus on the most relevant issues., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Aims: This study aimed to determine the antibacterial and antileishmanial potential of Micromeria nervosa extracts. The identification of the antileishmanial compound and the study of its molecular mechanism of action have also been undertaken., Methods and Results: Ethanol extract showed high polyphenol content and diethyl ether extract exhibited high DPPH scavenging and low beta-carotene bleaching activity (IC50 = 13.04 ± 0.99 and 200.18 ± 3.32 μg mL-1, respectively). However, diethyl ether extract displayed high antibacterial activity against Gram-positive strains including methicillin-resistant Staphylococcus aureus (MIC = 31.25 μg mL-1), Staph. aureus ATCC6538 (MIC = 62.5 μg mL-1), and Listeria monocytogenes ATCC 19115 (MIC = 125 μg mL-1), as well as high antileishmanial activity against the promastigote forms of L. infantum and L. major (IC50 = 11.45 and 14.53 μg mL-1, respectively). The active compound was purified using bioassay-guided fractionation and thin layer chromatography, and identified as ursolic acid using high-performance liquid chromatography coupled with a photodiode array and mass spectrometry. The purified compound was strongly inhibitory against the promastigote and amastigote forms of L. infantum and L. major (IC50 = 5.87 and 6.95 μg mL-1 versus 9.56 and 10. 68 μg mL-1, respectively) without overt cytotoxicity against Raw 264.7 macrophage cells (SI = 13.53 and 11.43, respectively). The commercial compound (ursolic acid) showed similar activity against amastigotes and promastigotes forms of L. infantum and L. major. Moreover, its molecular mode of action against leishmaniasis seems to involve the expression of the ODC and SPS genes involved in thiol pathway., Conclusion: Extracts of M. nervosa can be considered as a potential alternative to antimicrobial and antileishmanial drugs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Threatened species are frequently patchily distributed across small wild populations, ex situ populations managed with varying levels of intensity and reintroduced populations. Best practice advocates for integrated management across in situ and ex situ populations. Wild addax ( Addax nasomaculatus ) now number fewer than 100 individuals, yet 1000 of addax remain in ex situ populations, which can provide addax for reintroductions, as has been the case in Tunisia since the mid-1980s. However, integrated management requires genetic data to ascertain the relationships between wild and ex situ populations that have incomplete knowledge of founder origins, management histories, and pedigrees. We undertook a global assessment of genetic diversity across wild, ex situ and reintroduced populations in Tunisia to assist conservation planning for this Critically Endangered species. We show that the remnant wild populations retain more mitochondrial haplotypes that are more diverse than the entirety of the ex situ populations across Europe, North America and the United Arab Emirates, and the reintroduced Tunisian population. Additionally, 1704 SNPs revealed that whilst population structure within the ex situ population is minimal, each population carries unique diversity. Finally, we show that careful selection of founders and subsequent genetic management is vital to ensure genetic diversity is provided to, and minimize drift and inbreeding within reintroductions. Our results highlight a vital need to conserve the last remaining wild addax population, and we provide a genetic foundation for determining integrated conservation strategies to prevent extinction and optimize future reintroductions., Competing Interests: The authors declare that they have no competing interests in relation to this manuscript., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Introduction: Chronic kidney disease (CKD) is a worldwide public health concern characterised by a progressive alteration of renal function, and obesity, diabetes and hypertension are major risk factors. Oxidative stress is commonly observed in CKD patients resulting from an imbalance between overproduction of reactive oxygen species (ROS) and impairment of defense mechanisms. Therefore, strategies that alleviate oxidative stress may have major clinical implications towards improving vascular health and reducing the burden of CKD. Also, CKD worsens the quality of life of patients, therefore it is fundamental to implement new therapeutic strategies aimed at slowing down its progression., Materials and Methods: This interventional study is a randomised placebo-controlled clinical trial consisting at the daily oral supplementation with high dosing grape seed flour (GSF ≈ 1 g/kg) for experimental (n = 30) or starch for placebo (n = 10) to patients suffering from CKD of various stages and aetiologies. Blood and urine samples were collected at baseline and after a six-month-long supplementation period to follow up the disease evolution through the determination of renal function biomarkers, as well as antioxidant, anti-inflammatory and blood parameters., Results: Supplementation with high dosing GSF was safe and well tolerated during the entire period of investigation. GSF clearly improved the main renal function biomarkers as GFR, proteinuria, blood pressure, oxidative stress and inflammation as well as the overall patient welfare as indicated by several blood parameters., Conclusion: Most importantly high dosing GSF specifically halted and even reversed the progression of diabetic nephropathy a major cause of CKD and end stage renal disease.

The COVID-19 pandemic has transformed the health landscape by hampering the management of patients with chronic diseases. Providing optimal healthcare has become a critical issue, especially for patients with end-stage renal disease (ESRD) receiving in-center dialysis. Peritoneal Dialysis (PD) has the advantage of being a home-based therapy. Several papers about COVID-19 in the chronic kidney disease (CKD) population have been published, but few studies focused on the PD population, with limited case series. In this paper, we share our strategy for managing PD patients during the pandemic and describe the characteristics of 24 episodes of COVID-19 that occurred in our PD patients. Also, we report the impact of the pandemic on different outcomes and discuss the challenges of renal replacement therapy (RRT) in the time of COVID-19 and the advantages of PD. During the period from December 2019 to September 2021, 127 patients received PD in our center. Among them, we recorded 24 episodes of COVID-19 that occurred in 20 patients, corresponding to an incidence of 8.4 per 1000 patient-months. None of the 20 patients with COVID-19 were vaccinated and there was a significant male gender predominance in the COVID-19 group compared to the non-COVID-19 group. The prevalence of diabetic nephropathy and primary glomerulonephritis were also significantly higher in the COVID-19 group. The revealing symptoms were asthenia, dry cough, and the deterioration of general conditions in 100%, 75%, and 63% of the patients, respectively. A biological inflammatory syndrome was found in 30% of the patients. Chest computed tomography (CT) scan, performed in 5 patients, showed features of COVID pneumonia with an average extent of damage of 55%. The rate of patients starting PD during the study period was comparable to that before the pandemic. Furthermore, we did not find a significant difference between the infected and the non-infected groups regarding the incidence of peritonitis, PD technique failure, and mortality (6.1 [0-1.46] vs 3.9 [0.15-0.64] deaths per 1000 patient-months. COVID-19 does not seem to have influenced the outcomes of our patients treated with PD even before the launch of mass immunization in our country. Thus, PD can be a great option for RRT in the era of the COVID-19 pandemic since many issues could be managed remotely to avoid regular hospital visits and contribute to maintaining social distancing, which is the cornerstone of breaking the chain of transmission of the novel virus., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Catheter-related infections (CRI) are a major cause of morbidity and mortality in chronic hemodialysis (HD) patients. In this paper, we share our experience with CRI in HD patients. We recorded 49 cases of CRI among 167 patients during a period of 40 months (January 2018-April 2021). The incidence of CRI was 3.7 per 1000 catheter-days. The revealing symptoms were dominated by fever or chills (90%). Inflammatory signs were observed in 74% of cases with respectively concurrent exit-site (51%) and tunnel infection (6%). The biological inflammatory syndrome was found in 74% of patients (average CRP level = 198.9 mg/l). Blood cultures were performed in all cases and were positive in 65% of cases. Thirteen patients have been diagnosed with Infection complications, which were respectively infective endocarditis in 7 cases, septic arthritis in 3 cases, infective myositis in one case, cerebral thrombophlebitis in 1 case and mediastinitis in 1 case. The death occurred in eleven patients, it was due to septic shock in 9 cases, pulmonary embolism in one case and neurologic alterations related to cerebral thrombophlebitis. The mean seniority in HD was 16.5 months in the group with CRI and 3.7 months in the group without CRI (p < 0.04). We did not notice significant difference in mortality between tunnelled and non-tunnelled catheters. CRI does not seem to be more severe in patients with diabetes. Duration of use of the HD catheter (p < 0.007) and ferritin level (p < 0.0001) were independent factors that predispose to CRI in our population., (© 2022. The Author(s).)

Introduction: The rate of hospitalization represents a morbidity indicator in HD patients. The study aimed to evaluate hospitalization patterns in a large HD cohort., Methods: All DaVita-KSA HD patients from October 2014 to December 2019 were included. Demographical and clinical characteristics and hospitalization data were recorded. Less than 24 h admission was excluded. Overall and cause-specific hospitalization rates were calculated., Results: During the follow-up period, 3982 patients with a mean age of 52.5 ± 16.8 years, 2667 hospitalizations were recorded in 34.1% of the patients and 45.6% had repeated admissions. Infectious causes accounted for 26.6% of all recorded causes vs. 15.6% for cardiovascular complications. The median hospital stay length was 11 days, while the overall annual hospitalization rate of 34.9% and the annual duration of 3.7 days per patient. Hospitalized patients had a higher risk of mortality (p < 0.001)., Conclusion: Infectious complications were the leading cause of hospitalization and had the longest hospital stay., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

Background: The characterization of reinfection with SARS-CoV-2 has been a subject of concern and controversy, especially with the surge of infections with highly transmissible variants worldwide., Methods: This retrospective national study used comorbidities, vaccination status, SARS-CoV-2 variants of concern, and demographics data to profile participants who were reinfected with SARS-CoV-2, defined as having two reverse transcriptase-polymerase chain reaction-positive SARS-CoV-2 tests within at least 90 days apart. A multivariate logistic regression model assessed the risk factors associated with reinfection . Two control groups were selected: nonreinfected participants reporting a positive test (control group one) and those reporting a negative test (control group two)., Results: Between March 2020 and December 2021, 4454 reinfected participants were identified in Saudi Arabia (0.8%, 95% confidence interval [CI] 0.7-0.8). The majority (67.3%) were unvaccinated (95% CI 65.9-68.7) and 0.8% (95% CI 0.6-1.1) had severe or fatal SARS-CoV-2 disease. COVID-19 vaccines were 100% effective against mortality in reinfected individuals who received at least one dose, whereas it conferred 61% (odds ratio [OR] 0.4, 95% CI 0.1-1.0) additional protection against severe disease after the first dose and 100% after the second dose. In the risk factor analysis, reinfection was highly associated with comorbidities, such as HIV (OR 2.5, 95% CI 1.3-5.2; P = 0.009), obesity (OR 2.3, 95% CI 1.3-3.9; P = 0.003), pregnancy (OR 3.2, 95% CI 1.4-7.4; P = 0.005), and working in health care facilities (OR 6.1, 95% CI 3.1-12.9; P <0.0001). The delta variant (B.1.617.2) was the most frequent variant of concern among the reinfected cohort., Conclusion: This in-depth study of the reinfection profile identified risk factors and highlighted the associated SARS-CoV-2 variants. Results showed that naturally acquired immunity to SARS-CoV-2 through multiple reinfections together with vaccine-induced immunity provided substantial protection against severe SARS-CoV-2 disease and mortality., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Multiple sclerosis (MS), a multifactorial autoimmune disease of the central nervous system (CNS), is characterized by demyelination and chronic inflammation, as well as axonal and neuronal loss. There is no cure for MS, and despite a significant improvement in the therapeutic management of patients during the last 20 years, some symptoms are still resistant to treatment, and the evolution of the disease to progressive form seems still ineluctable. The etiology of MS is complex and still not fully understood. However, inflammation is a major driver of physiopathology and oxidative stress contributes to CNS lesions and promotes existing inflammatory response. Plant polyphenols are endowed with many therapeutic benefits through alleviating oxidative stress and inflammation, thus providing neuroprotection in MS. We presently evaluated the curative effect of grape seed extract (GSE) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS., Experimental Approach: Six-week-old C57Bl/6J females were subjected to the EAE paradigm (using myelin oligodendrocyte glycoprotein peptide fragment (35-55), complete Freund's adjuvant, and pertussis toxin) and then chronically treated with GSE from day 10 to day 30 post-induction. Clinical score and body weight were monitored daily, while evaluation of sensitive, motor, cognitive, and anxiety-related behaviors was performed weekly. Then, the GSE effect was evaluated on whole brain and spinal cord samples through the evaluation of oxidative stress damage, antioxidant capacities, myelin alteration, astroglial and microglial proliferation, and sirtuin expression., Key Results: Grape seed extract curative chronic treatment corrected the clinical course of EAE, as well as the mechanical hypersensitivity, and avoided the development of EAE mouse thermal cold allodynia. The neuropathological evaluation showed that GSE reduced oxidative stress in the brain and spinal cord by decreasing the lipid and protein oxidation through correction of the three main antioxidant enzyme activities, namely, superoxide dismutase, catalase, and glutathione peroxidase, as well as restoring normal myelin protein expression and correcting microglial and astroglial protein overexpression and sirtuin downregulation., Conclusion and Implications: These data strongly support GSE as an effective therapeutic approach in MS treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mabrouk, El Ayed, Démosthènes, Aissouni, Aouani, Daulhac-Terrail, Mokni and Bégou.)

Background: Obesity is a worldwide health problem and a significant risk factor for diabetes and cardiovascular diseases. Gut microbiota (GM) plays an essential role in obesity, and prebiotics such as polyphenols could be one way to improve microbial dysbiosis-induced obesity., Objective: This study was designed to assess the effectiveness of grape seed and skin extract (GSSE), and/or orlistat on obese rats fed with high fat diet by targeting GM modulations. The impact of treatments was also studied in non-obese rats., Material and Methods: Rats were rendered obese or kept with a standard diet for three months. Then they were treated either with GSSE or orlistat or with the combined treatment (GSOR) during three months and then sacrificed. Adipose tissues, blood and faeces were collected and analyzed., Results: In obese rats and to a lesser extent in non-obese rats, treatments decreased the weight of various adipose tissues and the serum levels of cholesterol, LDL, triglycerides, lipase, and CRP and increased HDL and adiponectin. GSOR treatment was even more efficient that orlistat. Obese rats had less GM diversity than non-obese rats and orlistat reduced it even more. However, diversity was restored with GSSE and GSOR treatments. Potential pathogenic Streptococcus alactolyticus/gallolyticus species were greatly increased in obese rats and drastically reduced with the treatments, as wells as other potential pathobionts., Conclusions: GSSE exerts beneficial effects in obese rats and restores, at least partially, the observed dysbiosis. GSOR induced the highest beneficial effect. Moreover, the various treatments could also enhance physiological and GM modifications in non obese rats., (© 2022. The Author(s).)

Context: Chronic rheumatic diseases seem to be associated with a higher risk of developing cardiovascular diseases. The link between cytokines and lipid profile in spondyloarthritis is not well elucidated., Aims: We aimed to assess the relationship between cytokines and obesity, lipid profile and atherogenic indexes in spondyloarthritis., Methods and Material: We conducted a cross-sectional study including 45 patients with axial radiographic spondyloarthritis. For each patient, we measured the following pro-inflammatory cytokines: interleukin (IL-) 1, IL-8, IL-6, IL-17, IL-23 and tumor necrosis factor a (TNFa), and anti-inflammatory cytokines: IL-10. We also measured total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc). We calculated the following ratios: TC/HDLc, TG/HDLc, LDLc/HDLc and Log[TG/HDLc]., Statistical Analysis Used: SPSS., Results: The mean age was 46 ± 11.9 years. IL-8 levels were increased in obese patients (P = 0.003). IL-8 and IL-22 levels were significantly higher in patients with abdominal obesity (P = 0.024 and P = 0.042, respectively). IL-6 levels were lower in patients with hypercholesterolemia (P = 0.009). IL-1 levels correlated to TG (r = 0.413; P = 0.005). IL-1 and IL-6 were correlated to TG/HDLc (IL-1: r = 0.484, P = 0.001; IL-6; r = 0.700, P = 0.012) and Log[TG/HDLc] (IL-1: r = 0.354; P = 0.012; IL-6: r = 0.309, P = 0.041). IL-10 level was correlated to TC/HDLc (r = 0.333, P = 0.027) and LDLc/HDLc (r = 0.342, P = 0.023)., Conclusions: IL-8 and IL-22 were higher in patients with abdominal obesity, highlighting the contribution of the adipocytes to the secretion of pro-inflammatory cytokines. The correlation between cytokines and atherogenic indexes suggests the role of these cytokines in the occurrence of cardiovascular diseases in spondyloarthritis., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Endocrinology and Metabolism.)

The severity of COVID-19 is largely determined by the inflammatory response, a "Cytokine storm," that involves both pro- and anti-inflammatory cytokines. In the current study we investigated the balance of pro- and anti-inflammatory status as represented by the levels of IL-6/IL-10 in severe to critical COVID-19 patients. 66 confirmed COVID-19 patients admitted to the ICU were categorized into groups according to the mortality and respiratory failure. Data were collected retrospectively in ICU, including a peripheral immune cells and infection-related biomarker CRP. The measurements of cytokine levels were performed by Immulite analyzer for IL-6 and ELISA sandwich for IL-10. In addition, longitudinal measurement of IL-6 was performed during 5 days post admission. Longitudinal assays showed that IL-6 was sustained at a medium level within 5 days post admission in severe cases who survived or not requiring mechanical ventilation, whereas it was sustained at high levels throughout the disease course in either deceased cases or who developed respiratory failure. The ratio of IL-6/lymphocytes was positively correlated with the risk of mortality, while IL-10/lymphocytes ratio could predict respiratory failure in ICU. IL-6/IL-10 profiling revealed that deceased patients have different magnitudes of both IL-6 and IL-10 cytokine release. Notably, excessive levels of IL-6 concomitant with high levels of IL-10 were more common in diseased COVID-19 patients. Taking into account the IL-6/IL-10 profiling may help clinicians to identify the right time of anti-inflammation treatment and select patients who will respond to anti-cytokine therapies and maintain an adequate inflammatory response for SARS-CoV-2 clearance., (Copyright © 2022. Published by Elsevier GmbH.)

According to the free-radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout life span leads to impairment of the main biological macromolecules as DNA, lipids, and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains a high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anticarcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong life span of Wistar rats when administered from early life (1-month-old animals) till their natural death. Data clearly show that high-dose GSF extends organism longevity and health span by improving multi-organ damages, systemic fueling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation is currently under investigation., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features., Methods: Study subjects comprised 120 patients infected with HCV-1b, and treated with Peg-IFN/RBV. Genotyping of six IL-10 promoter variants in the intron region (rs1878672, rs1554286, rs1518111) and promotor region (rs1800872, rs1800871, rs1800896) were done by real-time PCR., Results: Compared to G/G, carriage of IL-10 rs1800896 (-1082A/G) A/A genotype was more frequent in patients with sustained virological response (SVR). The decline in viral load over the first 12weeks of treatment was more pronounced in rs1800896 A/A genotype carriers, compared to G/G genotype carriers, and was irrespective of the treatment dosage. Carriage of rs1800896 A/A genotype was positively associated with improvement in viral load decline, which was simultaneous, with and without carriage of the common favourable IL-28B variant. Carriage of both IL-10 rs1800896 G/G and IL-28B non-favourable genotype was associated with twice the risk of getting slow decline of viral load during treatment. Haploview analysis identified ACGCTA and CCGCTG haplotypes to be linked with excellent PegIFN/RBV cure rate, and complete HCV eradication. On the other hand, ACGCTG and CCGCTA haplotypes were associated with resistance to PegIFN/RBV treatment., Conclusion: IL-10 rs1800896 variant markedly influences the clinical outcome of HCV infection, and is a determinant of the response to HCV treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cyclic lipopeptides produced by Bacillus species exhibit interesting therapeutic potential. However, their clinical use remains limited due to their low stability, undesirable interactions with host macromolecules, and their potential toxicity to mammalian cells. The present work aims to develop suitable lipopeptide-loaded chitosan nanoparticles with improved biological properties and reduced toxicity. Surfactin and bacillomycin D lipopeptides produced by Bacillus amyloliquefaciens B84 strain were loaded onto chitosan nanoparticles by ionotropic gelation process. Nanoformulated lipopeptides exhibit an average size of 569 nm, a zeta potential range of 38.8 mV, and encapsulation efficiency (EE) of 85.58%. Treatment of Candida (C.) albicans cells with encapsulated lipopeptides induced anti-adhesive activity of 81.17% and decreased cell surface hydrophobicity (CSH) by 25.53% at 2000 µg/mL. Nanoformulated lipopeptides also induced antileishmanial activity against Leishmania (L.) major promastigote and amastigote forms at respective IC 50 values of 14.37 µg/mL and 22.45 µg/mL. Nanoencapsulated lipopeptides exerted low cytotoxicity towards human erythrocytes and Raw 264.7 macrophage cell line with respective HC 50 and LC 50 values of 770 µg/mL and 234.56 µg/mL. Nanoencapsulated lipopeptides could be used as a potential delivery system of lipopeptides to improve their anti-adhesive effect against C. albicans cells colonizing medical devices and their anti-infectious activity against leishmania., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Allium sativum (As), commonly known as garlic, has been used for a long time, for its therapeutic effects. Recent studies showed the ability of As to modulate vascular activity. The present study aimed to investigate the vasomodulatory effects of aqueous extract of As and to analyse the molecular nature of the active components. Experiments were performed on chick chorioallantoic membrane. Fractions of garlic were directly injected using micropipette on a high vessel density area. Our results clearly indicated that garlic increased permeability and induced vasodilatation of blood vessels and capillaries. These effects were dose-dependent and had been observed just few minutes after the onset of treatment. The active component responsible of these effects, which had a low molecular weight seems to be of peptide nature and appeared different from Dially Sulfide (DAS) and Dially Disulfide (DADS).

Ischemic stroke is a major health concern and a leading cause of mortality worldwide. Oxidative stress is an early event in the course of stroke inducing neuro-inflammation and cell death. Grape seed extract (GSE) is a natural phytochemical mixture exhibiting antioxidant, anti-inflammatory and neuroprotective properties. Orlistat (ORL) is an anti-obesity agent and a gastro-intestinal lipase inhibitor which showed recently beneficial effects on brain lipotoxicity. Recent studies reported the increase of lipase activity upon stroke which led us to investigate the neuroprotective effect of ORL on rat brain I/R injury as well as the putative synergism with GSE. I/R insult infarcted the brain parenchyma as assessed by TTC staining, induced an oxidative stress as revealed by increased lipoperoxidation along with alteration of antioxidant enzymes activities which was corrected using the cotreatment of ORL + GSE. I/R also disturbed the main metabolic pathways involved in brain fueling as glycolysis, neoglucogenesis, glycogenolysis, TCA cycle and electron transfer chain (ETC) complexes. These disturbances were also corrected with the cotreatment ORL + GSE which maintained energetic activities near to the control level. I/R also disrupted transition metals distribution, along with associated enzymes as tyrosinase, LDH or glutamine synthetase activities and induced hippocampal inflammation as revealed by glycogen depletion from dentate gyrus area along with depressed anti-inflammatory IL1β cytokine and increased pro-inflammatory CD68 antigen. Interestingly almost all I/R-induced disturbances were corrected either partially upon ORL and GSE on their own and the best neuroprotection was obtained in the presence of both drugs (ORL + GSE) enabling robust neuroprotection of the sub granular zone within hippocampal dentate gyrus area., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several cytokines have been implicated in its pathogenesis and onset. Our objective was to determine the profile of pro and anti-inflammatory cytokines, including IL-1β, IL-6, IL-8, IL-23, IFN-, TNF-α, IL-10 in autoimmune hepatitis and their association with HLA gene polymorphisms. Serum cytokine levels were determined in 50 autoimmune hepatitis patients and one hundred fifty controls using chemiluminescence and ELISA techniques and HLA genotyping performed by PCR SSP. The levels of IL-6 (12 pg/mL vs. 5.5 pg/mL, p = 0.017), IL-8 (24.1 pg/mL vs. 7.8 pg/mL, p = 0.006), and TNF-α (61.1 pg/mL vs. <4.00 pg/mL, p = 0.002) were significantly higher in AIH patients in pretreatment phase compared to levels after remission and in controls. HLA*DRB15 was significantly associated with higher levels of IL-8. IL-6, IL-8, and TNF-α may be biomarkers of AIH activity. HLA gene expression may play a role in higher cytokine production and could allow an earlier diagnosis and better management of the disease.

Ischemic stroke is a leading cause of mortality worldwide that occurs following the reduction or interruption of blood brain supply, characterized by a cascade of early events as oxidative stress and ensuing neuro-inflammation, energy failure and the burst of intracellular Ca++ resulting in activation of phospholipases and large increase in FFA including arachidonic acid, ultimately leading to nervous cell death. Grape Seed Flour (GSF) is a complex polyphenolic mixture harboring antioxidant, anti-inflammatory and neuroprotective properties. Orlistat (Xenical ™,Xe) is a gastro-intestinal lipase inhibitor and an anti-obesity agent. In an earlier study we reported the higher efficiency in neuroprotection against HFD-induced brain lipotoxicity when combining the two drugs (GSF + Xe). As a result repurposing Xe as an adjunct to GSF therapy against stroke appeared relevant and worthy of investigation. I/R insult disrupted the blood brain barrier (BBB) as assessed by EB dye extravasation, increased water and Na + within the brain. Ultrastructurally I/R altered the brain blood capillaries at the vicinity of hippocampus dentate gyrus area as assessed by transmission and scanning electron microscopy. I/R altered lipid metabolism as revealed by LDL/HDL ratio, lipase activity, and FFA profiles. Moreover, I/R induced neuro-inflammation as assessed by down-regulation of anti-inflammatory CD 56 and up-regulation of pro-inflammatory CD 68 antigen. Importantly almost all I/R-induced disturbances were retrieved partially upon Xe or GSF on their own, and optimally when combining the two drugs. Xe per se is protective against I/R injury and the best neuroprotection was obtained when associating low dosage Xe with high dosage GSF, enabling neuroprevention and cell survival within hippocampus dentate gyrus area as revealed by increased staining of Ki 67 proliferation biomarker., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the phospholipid profile in total plasma, non-high-density lipoprotein (HDL), and HDL fractions. We tried to correlate the phospholipid profile to low-density lipoprotein (LDL) size, as reflected by cholesterol content in each LDL subclass., Methods: We measured small dense LDL-C levels after heparin-magnesium precipitation and measured high-density lipoprotein phospholipid (HDL-P) levels using a colorimetric enzymatic method., Results: The correlation of the phospholipid profile to small dense LDL-C (sdLDL-C) in patients with coronary problems showed a negative association between small dense low-density lipoprotein (sdLDL) and HDL-P (r = -0.73; P = .02). Moreover, a strong positive correlation was detected between TG and the ratio HDL-P/HDL-C (r = 0.83; P <.001)., Conclusions: HDL phospholipid has an antiatherogenic effect in coronary artery disease with or without diabetes. Further, large LDL modulation seems to be associated with diabetes rather than coronaropathy., (© American Society for Clinical Pathology 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Stroke is a worldwide concern. Many studies pointed out relevant preventive effect of grape seed powder (GSP) against deleterious brain ischemia/reperfusion (I/R) injury, but curative effect has been scarcely approached. The present work aimed at studying the preventive and curative effect of GSP against stroke using in-vitro and in-vivo models. Primary neuron-astrocyte cocultures were used to evaluate in-vitro GSP protective and curative effect on oxygen-glucose-deprivation (OGD). A murine I/R model, in which GSP was administered as delayed post stroke drug, to evaluate its potential clinically translatable therapy was used and behavioral tests were conducted after 15 days. Ultra-structure of hippocampus dentate gyrus using Transmission Electron Microscopy (TEM) was also undertaken. GSP prevented OGD-induced toxicity and cell death in a dose dependent manner and was neuroprotective as assessed by sustained cell viability (70 % ±1 for OGD + GSP and 37 % ±2 for OGD) and modulated cytokines and brain derived neurotrophic factor (BDNF) expression. GSP also promoted behavioral outcomes by increasing step-down inhibitory time from 17s±4 to 50s±11 and rat overall activities by improving scores in open field test to near control level. Furthermore, GSP protected hippocampus dentate gyrus area from I/R-induced drastic alterations as assessed by reduced autophagic vacuoles., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The effect of gamma-irradiation and ionizing radiation (high-energy electrons beam) on the physicochemical properties of metoprolol tartrate at the solid phase and aqueous solution, has been investigated in the present study to model some properties affected by absorbed doses and to reveal some interesting mutual causal correlation. The proposed some interesting models can be adapted to other experimental conditions, and the newly obtained values of the adjustable parameters could be an excellent criterion of the state quality of the metoprolol tartrate or for other additional interpretations. The peculiar behaviour of variation of physicochemical properties against dose leads us to confirm the suggested optimized doses mentioned in previous work, for sterilization and safe medical uses.

Stroke is one of the leading causes of long-lasting disability in human and oxidative stress an important underlying cause. Molecular insights into pathophysiology of ischemic stroke are still obscure, and the present study investigated the protective effect of high dosage Grape Seed Extract (GSE 2.5 g/kg) on brain ischemia-reperfusion (I/R) injury using a proteomic approach. Ischemia was realized by occlusion of the common carotid arteries for 30 min followed by 1 h reperfusion on control or GSE pre-treated rats, and a label-free quantification followed by mass spectrometry analysis used to evaluate I/R induced alterations in protein abundance and metabolic pathways as well as the protection afforded by GSE. I/R-induced whole brain ionogram dyshomeostasis, ultrastructural alterations, as well as inflammation into hippocampal dentate gyrus area, which were evaluated using ICP-OES, transmission electron microscopy and immuno-histochemistry respectively. I/R altered the whole brain proteome abundance among which 108 proteins were significantly modified (35 up and 73 down-regulated proteins). Eighty-four proteins were protected upon GSE treatment among which 27 were up and 57 down-regulated proteins, suggesting a potent protective effect of GSE close to 78%of the disturbed proteome. Furthermore, GSE efficiently prevented the brain from I/R-induced ion dyshomeostasis, ultrastructural alterations, inflammatory biomarkers as CD56 or CD68 and calcium burst within the hippocampus. To conclude, a potent protective effect of GSE on brain ischemia is evidenced and clinical trials using high dosage GSE should be envisaged on people at high risk for stroke.

Background/aim: We investigated the association of three IL-10 promoter single-nucleotide polymorphisms and altered IL-10 plasma levels with the risk of head and neck cancer (HNC)., Materials and Methods: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA)., Results: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA)., Conclusion: Our results demonstrate that IL-10-1082, IL-10-819, and IL-10-592 variants, and haplotypes GC and GT constitute biomarkers for early detection of HNC, especially NPC subtype. IL-10 -819T/C and TA haplotype may be used as biomarkers for early detection of LC.

Vitis vinifera grape is a highly cultivated crop and solid wastes generated by the wine industry are largely under exploited. Plentiful studies have intended analyzing the polyphenolic content of grape seeds but characterization of non phenolic compounds is rather scarce. The present study aimed at the selective extraction of lipid, phenolic and aqueous phases from grape seed powder (GSP) in order to establish their intimate composition, as well as their antioxidant and chelating properties underlying partly their biological effects. Major non phenolic compounds identified in the lipid phase were glyceryl-monostearate and 2-monostearin whereas fructofuranose and sucrose were the most abundant in the aqueous phase. Among the most abundant compounds detected in the various phases, the polyphenol quercetin exhibited the best affinity and free binding energy towards the active site of the calcium-dependent protease calpain. Polyphenols likely constitute the bioactive part of GSP that should be exploited as safe modulators of intracellular signaling which is likely at the basis of their health beneficial effects. Nevertheless other compounds as lipids or sugars should be valorized along with polyphenols to improve their bioavailability into highly protected organs as brain or eye., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Previous studies have highlighted the importance of polymorphisms of toll-like receptors (TLRs) in the pathogenesis of certain cancers, including head and neck cancers (HNC)., Aim of the Study: The aim of this study was to evaluate the association of TLR2 (-196 to -174 ins/del) and TLR3 (1377 C>T) as potential risk factors for HNC in Tunisians., Material and Methods: A case-control study including 246 HNC patients (174 nasopharyngeal carcinoma - NPC and 72 laryngeal cancer - LC) and 250 healthy controls. Genotyping was done by using PCR and PCR-RFLP methods., Results: Higher minor allele frequencies of TLR2 (-196 to -174 ins/del) and TLR3 1377 C>T polymorphisms were seen in HNC, NPC, and LC compared to controls. In addition, higher increased HNC, NPC, and LC risk was associated with TLR2 ins/del and TLR2 del/del genotypes (p < 0.0001). Positive association with HNC, NPC, and LC risk was seen with TLR2 del-containing genotypes (ins/del + del/del) (p < 0.0001). The T/T genotype of TLR3 is associated with HNC, NPC, and LC susceptibility (p < 0.0001). Positive association with HNC and NPC risk was seen with TLR3 T allele carriers (C/T + T/T) (p < 0.0001). Increased frequency of T-ins, C-del, and T-del haplotypes was revealed in HNC and NPC cases than healthy controls; however, T-del was significantly higher in LC cases., Conclusions: Our results demonstrate an increased risk of HNC, NPC, and LC with TLR2 ins/del, TLR2 del/del, and TLR3 T/T genotypes. And positive association with T-ins, C-del, and T-del haplotypes with HNC and NPC and T-del haplotype with LC., Competing Interests: The authors declare no conflict of interest.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, which usually manifests in adulthood. It is characterized by the development of multiple cysts in the kidneys and many other extrarenal manifestations. We aimed to determine the factors that contribute to the progression of ADPKD to end-stage renal disease (ESRD). In a retrospective multicentric study, we reviewed the records of 569 patients with ADPKD, hospitalized at a nephrology department or followed up at the outpatient department of university and regional hospitals, covering the north and center of the country, during the period 1969-2016. The mean age of the study patients was 48.54 ± 13.68 years and 14% were young adults (<40 years). There were 272 female and 297 male patients (sex ratio: male/female = 1.09). A family history of ADPKD was found in 43.7% of cases. Renal symptoms were dominated by loin pain, renal failure, hypertension, and hematuria, seen in, respectively, 51.9%, 48.2%, 29.1%, and 24.6% of the patients. The median serum creatinine level was 459 μmol/L (range: 47-2454), and hypertension had preceded the onset of ADPKD in 28.8% of cases. Extrarenal manifestations consisted of urologic complications (54.6%), liver cysts (43.5%), cardiac involvement (31.9%), cerebral aneurysms (12.9%), and gastrointestinal involvement (9.4%). ESRD occurred in 43.1% after a mean follow-up of 47 months (range: 0-384). Risk factors for poor renal prognosis were age >40 years (P = 0.009), hematuria (P = 0.034), hemoglobin >14 g/dL (P = 0.0013), high uric acid level (P = 0.001), and leukocyturia (P = 0.02). Death occurred in 59 cases (10.3%), mostly caused by infections (44.1%). In our study, ADPKD was lately diagnosed in most cases. Family screening is important, which will enable early detection and management of the complications associated with ADPKD.

The physiopathology of autoimmune hepatitis (AIH) is complex and still not fully elucidated. The genes localized outside the histocompatibility complex involved in regulation and signal transduction of the immune system SH2B3, TGFβ1, STAT4 and PTPN22 could be associated to the susceptibility and hepatocyte lysis mechanism of this lethal autoimmune disorder., Patients and Methods: We investigated four polymorphic sites in SH2B3 (rs3184504), TGFβ1 (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150 healthy controls from Tunisia using real-time PCR., Results: Significant associations were found for SH2B3 T allele (OR = 1.861; p = 0.015, pc = 0.366) and PTPN22 A allele (OR = 7.070; p = 0.026; pc = 1.00) and AIH with opposite homozygous being protective against the disease (CC genotype with OR = 0.420, p = 0.025; GG genotype with OR = 0.136, p = 0.025, respectively). No statistically significant associations were found for the TGFβ1 and STAT4 polymorphisms with AIH susceptibility., Conclusion: Our work enlarges information on non-HLA genes that are associated with AIH by focusing in a region of the world that was poorly molecularly characterized for this disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Grape seed powder (GSP) contains high amount of bioactive polyphenols usually used as nutritional supplement or food preservatives due to their antioxidant and scavenging properties. The purpose of the present work was to evaluate the safety of increasing dosage GSP (w/w) of 0.5%, 5%, 10% and 20% corresponding to 0.4, 4, 8 and 16 g/kg bw respectively, when administered sub-chronically to Wistar rats in a 2 month-repeated dosing oral toxicity trial. Overally GSP had no effect on food intake, decreased body weight gain without affecting brain, liver, heart or kidney relative weight. GSP did not alter haematology except an increase in platelets, slightly decreased plasma transaminases, creatinine, urea and xanthine oxidase activity, without affecting uricemia, glycemia, triglyceridemia and cholesterolemia. GSP did not affect intracellular mediators as calcium, free iron or H 2 O 2 , but exerted real anti-oxidative properties in the four selected organs as assessed by lower lipoperoxidation and carbonylation, higher non protein thiols and antioxidant enzyme activities as CAT, GPx and SOD. Besides GSP exerted anti-inflammatory properties as supported by lower plasma IL17 A and CRP and higher IL10 and adiponectin. Histopathologically GSP provoked the dilation of heart and kidney arterioles and increased the size of the hippocampal dentate gyrus reflecting higher neurogenesis as assessed by Ki-67 labeling. Under the experimental conditions of the current study, GSP appeared as highly safe even when administered at very high dosage and could find potential applications in a variety of biotic or abiotic stresses-induced multi-organ dysfunction., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Spleen is the largest lymphoid organ and obesity is related to an elevated risk of immunity dysfunction. The mechanism whereby fat adversely affects the spleen is poorly understood. This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and orlistat (Xenical, Xe) on high-fat diet (HFD)-induced spleen lipotoxicity. Obese rats were treated either with GSSE (4 g/kg body weight) or Xe (2 mg/kg body weight) or GSSE+Xe and monitored for weight loss for 3 months. Animals were then sacrificed and their spleen used for the evaluation of lipotoxicity-induced oxidative stress and inflammation as well as the putative protection afforded by GSSE and Xe treatment. HFD induced body weight gain and glycogen accumulation into the spleen; ectopic deposition of cholesterol and triglycerides and an oxidative stress characterized by increased lipoperoxidation and carbonylation; inhibition of antioxidant enzyme activities, such as catalase, glutathione peroxidase, and superoxide dismutase; depletion of zinc and copper; and a concomitant increase in calcium. HFD also increased plasma pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17A, tumour necrosis factor alpha, and C-reactive protein, and decreased plasma IL-10 and adiponectin. Importantly, GSSE counteracted all the deleterious effects of HFD on spleen (i.e., lipotoxicity, oxidative stress, and inflammation) and the best protection was obtained when combining Xe+GSSE. Combining GSSE with Xe prevented against fat-induced spleen lipotoxicity, oxidative stress, and inflammation; this combination may be beneficial in other diseases related to the spleen.

Background: Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function., Objective: We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE)., Methods: We started by characterizing the GSSE and its composition using gas chromatography coupled to mass spectrometry (GC-MS). We used a rat model of high-fat-diet and we evaluated the effect of GSSE on oxidative stress and energetic disturbances induced by HFD. We analyzed the effect of HFD on lung oxidative status by assessing lipid oxidation level, non-protein thiols (NPSH) and superoxide anion level… We also evaluated the effect of HFD on creatine kinase (CK), malate dehydrogenase (MDH) and mitochondrial complex IV., Results: HFD induced body weight gain, increased lung weight and lipid content without affecting insulinemia and dropped adiponectemia. HFD also provoked on lung oxidative stress characterized by increased carbonylation (+ 95%; p = 0.0045), decreased of NPSH (- 32%; p = 0.0291) and inhibition of antioxidant enzyme activities such as glutathione peroxidase (- 25%; p = 0.0074). HFD also altered lung intracellular mediators as superoxide anion O 2 ¯ (+ 59%; p = 0.0027) and increased lung xanthine oxidase activity (+ 27%; p = 0.0122). HFD induced copper depletion (- 24%; p = 0.0498) and lead (- 51%: p = 0.0490) from the lung. Correlatively HFD decreased the copper associated enzyme tyrosinase (- 29%; p = 0.0500) and decreased glutamine synthetase activity (- 31%; p = 0.0027). HFD altered also lung energy metabolism by increasing CK activity (+ 22%; p = 0.0108) and decreasing MDH and mitochondrial complex IV activities (- 28%; p = 0.0120, - 31%; p = 0.0086 respectively). Importantly all these alterations were efficiently corrected with GSSE treatment., Conclusion: In conclusion, GSSE has the potential to alleviate the deleterious lipotoxic effect of HFD on lung and it could find potential application in the protection against HFD-induced lung complications.