Search

Abstract Introduction Cytomegalovirus generally causes self-limited, mild and asymptomatic infections in immunocompetent patients. An aggressive course in immunocompetent healthy patients is unusual. Case presentation We report the case of an immunocompetent 16-year-old Egyptian boy with encephalitis, acute renal failure, and acute hepatitis triggered by viral infection with a complete recovery following antiviral treatment. Conclusion We believe that this case adds to the understanding of the molecular biology, clinical presentation and increasing index of suspicion of many viral infections.

Objectives : This study aimed to investigate the correlation between apical sparing of longitudinal strain (LS), as measured by speckle-tracking echocardiography (STE), and the histological presence of myocardial fibrosis (MF), in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Twenty-seven HOCM patients who underwent elective Morrow procedures +/- aortic valve replacement (AVR) were included. All patients had standard echocardiography, with STE pre- and post-operatively. Intraoperative probes of the interventricular septum were sent for histological analysis. Correlation of different regional LS patterns with the histological findings of MF and with clinical outcome were analyzed. In addition, a logistic regression and ROC analysis were performed. Results: All patients underwent the Morrow procedure for HOCM, with 33.3% also undergoing AVR. A total of 74.1% showed evidence of MF in the histological analysis. Patients with MF had significantly lower GLS than patients without MF (-12.7 ± 2.7% vs. -23.0 ± 5.7%, p < 0.001). The LS in patients with MF was significantly lower at the basal regions of the LV segments and increased significantly towards the apex as compared to the patients without MF (mean basal-strain %: -10.6 ± 2.6 vs. -17.3 ± 4.6, p < 0.001; mean apical strain %: -21.8 ± 4.8 vs. -16.7 ± 5.6, p = 0.032). In the logistic regression, only the GLS remained as an independent predictor of MF with an Odds ratio of 1.07 (95%-CI: 1.05-1.09, p < 0.001). Conclusions: Our study highlights the significant correlation between GLS and MF in HOCM patients. These findings contribute to the growing understanding of MF in HOCM and may inform future approaches to patient management and risk stratification.

Aims: This study aimed to compare the changes in the left ventricle (LV) and right ventricle (RV) geometry and performance after the implantation of HeartMate II (HMII) and HeartMate 3 (HM3). In addition, we investigated whether the echocardiographic parameters LV sphericity index (LVSI) and the novel pressure-dimension index (PDI) can predict post-operative right ventricular failure (RVF)., Methods and Results: Between 2012 and 2020, 46 patients [HMII (n = 22) and HM3 (n = 24)] met the study's criteria and had echocardiography tests pre-operatively, 6 and 12 months post-operatively. The LVSI and PDI were calculated together with the standard LV and RV echocardiographic parameters. The mean follow-up was 24 ± 7 months. In both groups, the LV end-diastolic diameter (LVEDD) significantly decreased 12 months post-operatively compared with the pre-operative values (HMII: 6.4 ± 1.4 cm vs. 5.7 ± 0.9 cm, P = 0.040; HM3: 6.7 ± 1.3 cm vs. 5.5 ± 0.9 cm, P < 0.01, respectively). RV function 12 months post-operatively was better in the HM3 group than in the HMII group, as indicated by a significantly higher RV fractional area change (RVFAC) in the HM3 group than in the HMII group 12 months post-operatively (35 ± 12% vs. 26 ± 16%, P = 0.039), significantly higher tricuspid annular plane systolic excursion (TAPSE) in the HM3 group 12 months post-operatively compared with the HMII group (13.9 ± 1.9 mm vs. 12.0 ± 2.1 mm, P = 0.002), and the tissue Doppler estimated tricuspid annular systolic velocity (TASV) was also significantly higher in the HM3 group 12 months post-operatively compared with the HMII group (11.5 ± 2.7 mm/s vs. 9.9 ± 1.5 mm/s, P = 0.020). The LVSI value was significantly higher 12 months post-operatively in the HMII group than in the HM3 group (1.2 ± 0.4 vs. 0.8 ± 0.2, P = 0.001, respectively), indicating worse geometric changes. The PDI decreased 12 months post-operatively in the HM3-group compared with the baseline (3.4 ± 1.4 mmHg/cm 2 vs. 2.0 ± 0.8 mmHg/cm 2 , P < 0.001). In the univariate and multivariate analyses, only the pre-operative PDI was a predictor of post-operative RVF [odds ratio: 3.84 (95% CI: 1.53-18.16, P = 0.022)]. The area under the curve for pre-operative PDI was 0.912. The 2 year survival was significantly better in the HM3 group (log-rank, P = 0.042)., Conclusions: The design of HM3 offered better geometrical preservation of the LV and enabled normal PDI values, leading to improved RV function, as indicated by better RVFAC, TAPSE, and TASV values. The use of pre-operative PDI as an additional tool for established risk scores might offer a better pre-operative predictor of RVF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Psoriasis is an inflammatory immune-mediated skin disease that affects nearly 2-3 % of the global population. The current study aimed to develop safe and efficient anti-psoriatic nanoformulations from Artemisia monosperma essential oil (EO). EO was extracted using hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and head-space solid-phase microextraction (HS-SPME), as well as GC/ MS was used for its analysis. EO nanoemulsion (NE) was prepared using the phase inversion method, while the biodegradable polymeric film (BF) was prepared using the solvent casting technique. A.monosperma EO contains a high percentage of non-oxygenated compounds, being 90.45 (HD), 82.62 (MADH), and 95.17 (HS-SPME). Acenaphthene represents the major aromatic hydrocarbon in HD (39.14 %) and MADH (48.60 %), while sabinene as monoterpene hydrocarbon (44.2 %) is the primary compound in the case of HS-SPME. The anti-psoriatic Effect of NE and BF on the successful delivery of A.monosperma EO was studied using the imiquimod (IMQ)-induced psoriatic model in mice. Five groups (n = 6 mice) were classified into control group, IMQ group, IMQ+standard group, IMQ+NE group, and IMQ+BF group. NE and BF significantly alleviated the psoriatic skin lesions and decreased the psoriasis area severity index, Baker's score, and spleen index. Also, they reduced the expression of Ki67 and attenuated the levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 17. Additionally, NE and NF were able to downregulate the NF-κB and GSK-3β signaling pathways. Despite the healing properties of BF, NE showed a more prominent effect on treating the psoriatic model, which could be referred to as its high skin penetration ability and absorption. These results potentially contribute to documenting experimental and theoretical evidence for the clinical uses of A.monosperma EO nanoformulations for treating psoriasis., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Vaccination of healthcare workers (HCWs) is pivotal in decreasing the incidence of contagious infections in hospital settings. In this study, we assessed the knowledge, attitude, and practice regarding HCWs' recommended vaccines among medical students and interns in Egypt., Methods: A multicenter, cross-sectional study was conducted using a structured, pilot-tested, and self-administered questionnaire among Egyptian medical students and interns. We invited 1332 participants to our survey using a systematic random sampling that included participants across nine medical schools in Egypt during the 2021-2022 academic year., Results: Out of 1332 participants, 1141 completed our questionnaire with a response rate of 85.7%. Overall, 43% of the participants had intermediate knowledge (knew 2-3 HCWs' recommended vaccines). Furthermore, 36.7% had received a booster dose of at least one of the HCWs' recommended vaccines over the last 10 years, with only 6.1% having received all recommended vaccines. Hepatitis B vaccine was the most widely known (71%) and received (66.7%). Interns were more likely to know, receive, and recommend HCWs' recommended vaccines. The majority (> 90%) agreed that vaccination is beneficial and safe, with a median score of eight (interquartile range [IQR: Q25-Q75]: 7-9) out of ten for vaccine efficacy and eight (IQR: 7-8) for safety. However, the median score for hesitancy was five (IQR: 2-7). The most common influential and limiting factors for vaccination were scientific facts (60.1%) and fear of vaccine side effects (44.9%)., Conclusion: Although medical students in Egypt have good knowledge of and attitudes towards vaccination, there is a gap in their practices. Interventions are needed to improve vaccination uptake among medical students in Egypt., (© 2024. The Author(s).)

Migraine, a debilitating neurological condition, significantly affects patients' quality of life. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist approved for managing dyslipidemia, has shown promise in treating neurological disorders. Therefore, this study aims to investigate the protective effects of fenofibrate against nitroglycerin (NTG)-induced chronic migraine in rats. Migraine was induced in rats by administering five intermittent doses of NTG (10 mg/kg, i. p.) on days 1, 3, 5, 7, and 9. Rats were treated with either topiramate (80 mg/kg/day, p. o.), a standard drug, or fenofibrate (100 mg/kg/day, p. o.) from day 1-10. Fenofibrate significantly improved mechanical and thermal hypersensitivity, photophobia, and head grooming compared to topiramate. These effects were associated with reduced serum levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP), and pituitary adenylate cyclase-activating polypeptide (PACAP). Furthermore, fenofibrate down-regulated c-Fos expression in the medulla and medullary pro-inflammatory cytokine contents. Additionally, fenofibrate attenuated NTG-induced histopathological changes in the trigeminal ganglia and trigeminal nucleus caudalis. These effects were associated with the inhibition of CGRP/p-CREB/purinergic 2X receptor 3 (P2X3) and nerve growth factor (NGF)/protein kinase C (PKC)/acid-sensing ion channel 3 (ASIC3) signaling pathways. This study demonstrates that fenofibrate attenuated NTG-induced migraine-like signs in rats. These effects were partially mediated through the inhibition of CGRP/p-CREB/P2X3 and NGF/PKC/ASIC3 signaling pathways. The present study supports the idea that fenofibrate could be an effective candidate for treating migraine headache without significant adverse effects. Future studies should explore its clinical applicability., 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: Considering the controversial benefits of video-assisted thoracoscopic surgery (VATS), we intended to evaluate the impact of surgical approach on cardiac function after lung resection using myocardial work analysis., Methods: Echocardiographic data of 48 patients (25 thoracotomy vs. 23 VATS) were retrospectively analyzed. All patients underwent transthoracic echocardiography (TTE) within 2 weeks before and after surgery, including two-dimensional speckle tracking and tissue Doppler imaging., Results: No notable changes in left ventricular (LV) function, assessed mainly using the LV global longitudinal strain (GLS), global myocardial work index (GMWI), and global work efficiency (GWE), were observed. Right ventricular (RV) TTE values, including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV), right ventricular global longitudinal strain (RVGLS), and RV free-wall GLS (RVFWGLS), indicated greater RV function impairment in the thoracotomy group than in the VATS group [TAPSE(mm) 17.90 ± 3.80 vs. 21.00 ± 3.48, p = 0.006; d = 0.84; TASV(cm/s): 12.40 ± 2.90 vs. 14.70 ± 2.40, p = 0.004, d = 0.86; RVGLS(%): - 16.00 ± 4.50 vs. - 19.40 ± 2.30, p = 0.012, d = 0.20; RVFWGLS(%): - 11.50 ± 8.50 vs. - 18.31 ± 5.40, p = 0.009, d = 0.59; respectively]., Conclusions: Unlike RV function, LV function remained preserved after lung resection. The thoracotomy group exhibited greater RV function impairment than did the VATS group. Further studies should evaluate the long-term impact of surgical approach on cardiac function., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Thermoresponsive drug delivery systems have been used to treat diseases that cause hyperthermia or elevated body tissue temperatures, viz., rheumatoid arthritis and different cancers. The aim of the study was to enhance berberine (BER) release using thermosensitive nanostructured lipid carriers (TNLCs) through intra-articular administration for the management of arthritis. TNLCs were prepared using binary mixtures of stearic acid and decanoic acid as solid and liquid lipids, respectively. Lipid mixtures with an optimum melting point were assessed using differential scanning calorimetry studies. In vitro characterization of the BER TNLCs included particle size, zeta potential, entrapment efficiency, and drug release at 37 °C and 41 °C. Joint diameter measurement, real-time polymerase chain reaction (RT-PC) analysis, enzyme-linked immunosorbent assay (ELISA) for inflammatory markers, and histological evaluation of the dissected joints were all performed in vivo on rats with adjuvant-induced arthritis. In vitro characterization revealed negatively charged BER-loaded TNLCs with a spherical shape, particle size less than 500 nm, BER entrapment efficiency up to 79%, and a high drug release rate at an elevated temperature of 41 °C. In silico studies revealed the affinity of BER to different formula components and to the measured biomarkers. In vivo assessment of the optimum TNLCs showed that BER TNLCs were superior to the BER solution suspension regarding their effect on inflammatory biomarkers, joint diameter, and histological studies.

Background: Studies exploring the effect of COVID-19 on male reproductive system suggest a detrimental association, however with conflicting results. The aim of this study was to assess the association between COVID-19 infection and male reproductive potential including hormone profiles and semen parameters., Methods: This prospective cohort study included 48 patients with confirmed COVID-19 infection. Patients were subdivided into an asymptomatic group ( n  = 30) and a group with COVID-19 symptoms ( n  = 18). Serum hormone levels including testosterone, LH, FSH and estradiol were collected during active infection (baseline, time 0), and at 3 and 6 months following COVID-19 infection. Semen samples (basic semen analysis and oxidation reduction potential) were examined at 3 and 6 months following infection. Student and paired-t tests were used to compare continuous variables between the study groups and across the studied time intervals, respectively. Multivariate binary logistic regression analysis was performed to explore predictors for COVID-19 symptoms during active infection., Results: Patients with COVID-19 symptoms were significantly older ( p  = 0.02) and had significantly lower serum testosterone levels ( p  = 0.01) and significantly higher LH: testosterone ratio ( p  = 0.01) than asymptomatic patients. Multivariate analysis revealed older age (OR =  1.18, p  = 0.03) and lower serum testosterone level (OR = 0.8, p  = 0.03) as independent predictors of symptomatic COVID-19 infection. Significant increase in testosterone ( p  < 0.001 for both) and decrease in LH ( p  = 0.02, p  = 0.007) and LH: testosterone ( p  = 0.02, p  = 0.005) levels were observed at 3 and 6 months in patients with COVID-19 symptoms. Asymptomatic patients demonstrated significant increase in testosterone ( p  = 0.02) and decrease in LH: testosterone ( p  = 0.04) levels only at 3 months following COVID-19 infection. No significant differences were observed between the two study groups with regards to the semen analysis results obtained at 3 or 6 months following COVID-19 infection., Conclusion: Significantly lower testosterone values are associated with worse disease severity among men with COVID-19 infection. This association appears to be temporary as a significant increase in testosterone levels are witnessed as early as 3 months following recovery. No significant detrimental effect for COVID-19 infection on testicular sperm production is found in this patient population., 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., (© 2024 Majzoub, Khalafalla, Arafa, El Ansari, Nair, Al Bishawi, Saleh, Khair Ella, ElBardisi, Khattab and AlRumaihi.)

Purpose: Laser corneal reshaping is a common eye surgery utilized to overcome many vision disorders. Different UV laser wavelengths can be effective in the treatment. However, the ArF excimer laser (193 nm) is the most commonly used due to its high absorption in the cornea. In the current study, we investigate the efficacy of applying a solid-state laser (Nd:YAG fourth harmonic at 266 nm) for the corneal reshaping procedure., Methods: The utilized laser is generated using an optical setup based on a BBO nonlinear crystal which converts the Q-switched laser (532 nm) to its fourth harmonic (266 nm). Different pulse energies were applied with the same number of the shoots on ex vivo rabbit corneas, and the histological effect is studied. Moreover, the possible thermal damage on the treated corneal tissues was inspected via electron microscope. Additionally, the DNA damage on the corneal cells due to the application of the proposed laser was examined and compared with the existing technology (ArF Excimer laser at 193 nm) using the comet assay., Results: The histological examination revealed an appropriate ablation result with the minimum thermal effect at 1.5 mJ and 2.0 mJ. The overall results show that applying 50-shoots of the 1.5-mJ pulse energy using the proposed 266-nm solid-state laser produces the optimum ablation effect with the minimum thermal damage, and almost the same DNA damage occurred using the commercial 193-nm ArF excimer laser., Conclusion: Solid-state laser at 266 nm could be a good alternative to the common 193-nm excimer laser for corneal reshaping procedures., (© 2023. The Author(s).)

The goal of this study was the development and evaluation of semisolid caffeine (CAF) loaded nanostructured lipid carriers (NLCs) for topical treatment of cellulite. CAF-loaded NLC formulations were prepared via high-speed homogenization followed by ultrasonication. A 3 2 full factorial design was employed for formulation optimization. The total lipid content (%) and the liquid lipid content per total lipids (%) were chosen as factors, whereas particle size (PS), polydispersity index (PDI), zeta potential (|ZP|) and viscosity (VIS) were selected as responses. The design suggested CAF-NLC3 as the optimum formulation consisting of a total lipid content of 15% w/w (palmitic acid and soft paraffin/isopropyl myristate, 7:3 w/w) and a surfactant content of 10% w/w (Tween 80/lecithin, 8:1.2 w/w). CAF-NLC3 revealed PS, PDI, ZP, VIS and CAF content values of 318.8 nm, 0.253, -41.1 mV, 18.0 Pa.s and 97.57%, respectively. It showed a pseudoplastic rheological behavior, acceptable pH value (5.25), good spreadability (1.12 mm 2 /g) and spherical shape employing transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction demonstrated the amorphization of CAF in CAF-NLC3. CAF-NLC3 remained stable for 3 months at room and refrigeration conditions. A single topical application of CAF-NLC3 on shaved abdominal skins of Wistar rats revealed enhanced skin retention of CAF by 2-fold and 1.4-fold after 4 h when compared with plain CAF gel (CAF-P) and marketed CAF gel (CAF-M), respectively. Furthermore, CAF-NLC3 exhibited a superior anti-cellulite activity in comparison with CAF-P and CAF-M through elevating extracellular matrix components (collagen 1, elastin and hyaluronic acid) and stimulating the brown adipose tissue thermogenesis via up-regulating UCP1 and PPAR-γ expression. In addition, CAF-NLC3 prominently increased lipolysis through HSL activity and decreased pro-inflammatory cytokines such as ICAM-1 and VCAM-1 after 30 days of treatment on a high fat diet-induced cellulite rat model. These findings were further confirmed by histopathological examination supported by morphometric analysis. Therefore, incorporation of CAF in a semisolid NLC formulation would be a promising cosmetic approach for the topical treatment of cellulite., 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 © 2023 Elsevier B.V. All rights reserved.)

Phthalates are common plasticizers present in medical-grade plastics and other everyday products. Di-ethylhexyl phthalate (DEHP) has been noted as a causative risk factor for the initiation and augmentation of cardiovascular functional disorders. G-CSF is a glycoprotein found in numerous tissues throughout the body and is currently applied in clinical practice and has been tested in congestive heart failure. We aimed to examine in depth the effect of DEHP on the histological and biochemical structure of the cardiac muscle in adult male albino rats and the mechanisms underlying the possible ameliorative effect of G-CSF. Forty-eight adult male albino rats were divided into control group, DEHP group, DEHP+ G-CSF group and DEHP-recovery group. We measured serum levels of aspartate aminotransferase (AST), creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Left ventricular sections were processed for light and electron microscope examination, and immunohistochemical staining of Desmin, activated Caspase-3 and CD34. DEHP significantly increased enzyme levels, markedly distorted the normal architecture of cardiac muscle fibers, downregulated Desmin protein levels and enhanced fibrosis, and apoptosis. G-CSF treatment significantly decreased the enzyme levels compared to DEHP group. It enhanced CD34 positive stem cells recruitment to injured cardiac muscle, therefore improved the ultrastructural features of most cardiac muscle fibers via anti-fibrotic and anti-apoptotic effects in addition to increased Desmin protein expression levels. The recovery group showed partial improvement due to persistent DEHP effect. In conclusion, administration of G-CSF effectively corrected the histopathological, immunohistochemical and biochemical alterations in the cardiac muscle after DEHP administration by stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms., (© 2023. The Author(s).)

Genus Quercus is a well-known source for its polyphenolic content and important biological activity. Plants belonging to the Quercus genus were traditionally used in asthma, inflammatory diseases, wound healing, acute diarrhea, and hemorrhoid. Our work intended to study the polyphenolic profile of the Q. coccinea (QC) leaves and to assess the protective activity of its 80% aqueous methanol extract (AME) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Together, the potential molecular mechanism was investigated. Nineteen polyphenolic compounds (1-18), including tannins, flavone, and flavonol glycosides. Phenolic acids and aglycones were purified and identified from the AME of QC leaves. Treatment with AME of QC showed an anti-inflammatory effect evidenced by a remarkable decline in the count of white blood cells and neutrophils which was in harmony with decreasing the levels of high mobility group box-1, nuclear factor kappa B, tumor necrosis factor-α, and interleukin 1 beta. In addition, the antioxidant activity of QC was documented through the significant reduction in malondialdehyde level and elevation of reduced glutathione level and superoxide dismutase activity. Furthermore, the mechanism involved in the pulmonary protective effect of QC involved the downregulation of the TLR4/MyD88 pathway. The AME of QC showed a protective effect against LPS-induced ALI through the powerful anti-inflammatory and antioxidant activities which are linked to its abundancy with polyphenols., 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 © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study was performed to explore in detail the toxic effects of Tributyltin Chloride (TBT) on the pituitary-testicular axis and the possible amelioration with Hesperidin. Seventy-two adult male albino rats were divided into four groups: Control group (I), TBT-treated group (II), TBT+Hesperidin group (III), and Recovery group (IV). Body and testicular weights were measured. Blood samples were taken to estimate serum levels of testosterone, FSH and LH hormones by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) level was measured in testes homogenates. Tissue samples from the pituitary glands and testes were processed for light, electron microscope examination, and immunohistochemical detection of anti-FSH, and Ki67 proteins. Results showed a statistically significant decrease in testicular weight, serum testosterone, FSH and LH levels and a significant increase in tissue MDA in the TBT group when compared to the control group. TBT treatment caused severe histopathological changes with decreased area percent of PAS-stained basophils, and anti FSH immuno-stained gonadotrophs in the pituitary gland. The testes of group II also showed marked tissue damage, cell loss with decreased epithelial height and decreased number of proliferating spermatogenic cells. Hesperidin supplementation with TBT proved significant amelioration of the previously mentioned parameters in both glands which could improve male fertility. In conclusion: The flavonoid Hesperidin has the potential to protect against the reproductive damage induced by TBT in susceptible individuals.

Caffeine (CAF) is a challenging natural bioactive compound with proven antiaging efficacy. However, being hydrophilic hampers its permeation through the skin. Our aim is to develop a novel CAF-loaded nano-cosmeceutical tool counteracting skin photoaging via improving CAF skin permeation using a bioactive nanocarrier. Caffeinated hyalurosomes are novel biocompatible antiaging nanoplatforms designed by immobilization of phospholipid vesicles with a hyaluronan polymer. Physicochemical properties of the selected hyalurosomes formulation showed nano-sized vesicles (210.10 ± 1.87 nm), with high zeta potential (-31.30 ± 1.19 mv), and high encapsulation efficiency (84.60 ± 1.05%). In vitro release results showed outstanding sustained release profile from caffeinated hyalurosomes compared to the CAF-loaded in conventional gel over 24 h. The in-vivo study revealed a photoprotective effect of caffeinated hyalurosomes, reflected from the intact and wrinkling-free skin. Results of biochemical analyses of oxidative stress, pro-inflammatory mediators, and anti-wrinkling markers further confirmed the efficacy of the prepared hyalurosomes compared to the CAF conventional gel. Finally, histopathological examination demonstrated normal histological structures of epidermal layers with minimal inflammatory cell infiltrates in the caffeinated hyalurosomes group compared to the positive control group. Conclusively, caffeinated hyalurosomes successfully achieved enhanced CAF loading and penetration into the skin besides the hydration effect of hyaluronan. Consequently, the developed delivery system presents a promising skin protection nano-platforms via the double effects of both hyaluronan and CAF, hence it guards against skin photodamage., Competing Interests: The authors declare that they have neither conflict of interest nor competing financial interests that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

It is unclear whether direct-acting antiviral drugs (DAAs) result in the complete eradication of HCV infection or whether some quantities of the virus may persist after achieving a sustained virologic response (SVR). Aim The aim of this work was to study the possibility of the persistence of HCV RNA in peripheral blood mononuclear cells (PBMCs) after achieving SVR following DAA treatment. This study included 100 patients infected with HCV genotype 4, who were candidates for receiving DAAs and who achieved SVR during follow-up, as determined at 12 and/or 24 weeks following the end of treatment. All patients were subjected to demographic, biochemical and hematological assessments. Detection of HCV RNA in the serum and PBMCs and determination of the HCV genotype were performed with real-time PCR. We detected HCV RNA in the PBMCs of 20 out of 100 (20%) patients infected with HCV genotype 4, who achieved SVR. However, the persistent viral load in the PBMCs was very low (range: 400-900 U/mL; mean ± SD: 645.45 ± 153 U/mL). Multiple logistic regression analysis showed that only the higher posttreatment levels of aspartate transaminase (AST) were significantly predictive of HCV RNA persistence in the PBMCs (OR: 1.29; 95% CI: 1.08-1.55). Additionally, according to the Cox proportional hazard model, liver cirrhosis was the only significant risk factor for the persistence of HCV infection in PBMCs (HR: 5.8; 95% CI: 1.3-26.1; P < 0.02). Our results indicated the persistence of HCV RNA in some HCV patients who achieved SVR after treatment with DAAs., (© 2022. The Author(s).)

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes., Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05., Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% ( n = 66). The primary outcome was not statistically different (87.5% ( n = 35) in anakinra group vs. 92.5% ( n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy., Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy., Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678., Competing Interests: All 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 © 2023 Elmekaty, Maklad, Abouelhassan, Munir, Ibrahim, Nair, Alibrahim, Iqbal, Al Bishawi, Abdelmajid, Aboukamar, Hadi, Khattab, Al Soub and Al Maslamani.)

Purpose: COVID-19 frequently affects the kidneys with symptoms ranging from mild proteinuria to progressive acute kidney injury. This prospective study aimed to assess the short- and long-term impact of asymptomatic and mild COVID-19 on the renal function of healthy young adults, and to determine the correlation between viral load and kidney function among these patients., Methods: This was a prospective cohort study conducted over a period of 6 months. Patients were followed-up at baseline, and then after 3 and 6 months, respectively. Real-time PCR cycle threshold (CT) was used to determine the viral load and disease activity. Patients were classified into two groups with either asymptomatic COVID-19 or mild pneumonia. The assessment parameters were variables that could directly or indirectly relate to the renal function., Results: A total of 48 patients were included and evaluated. The majority of patients (62.5%) had asymptomatic COVID-19 disease. Patients with mild pneumonia had significantly higher serum creatinine (SCr) at the time of COVID-19 diagnosis (beta = 12.836, 95% CI = 2.405-23.268, P = 0.019), after 3 months (beta = 14.345, 95% CI = 1.149-27.542, P = 0.035), and after 6 months (beta = 14.100, 95% CI = 0.730-27.470, P = 0.040) compared to asymptomatic patients. Mild pneumonia was also significantly associated with lower serum albumin level at the time of COVID-19 diagnosis (beta = - 6.317, 95% CI = - 9.448-- 3.185, P < 0.001)., Conclusion: Mild COVID-19 is associated with mild renal involvement without AKI. Changes in the renal function appear to be related to reduced creatinine clearance and possible albumin leakage in the acute phase of the disease. The reduction in creatinine clearance is not predicted by viral load, and it appears to be a long-term effect of the disease that can last for at least 6 months., (© 2022. The Author(s).)

Rationale: Alteration of the NAD + metabolic pathway is proposed to be implicated in lipopolysaccharide (LPS)-induced neurotoxicity and mitochondrial dysfunction in neurodegenerative diseases. Apigenin, a naturally-occurring flavonoid, has been reported to maintain NAD + levels and to preserve various metabolic functions., Objectives: This study aimed to explore the effect of apigenin on mitochondrial SIRT3 activity as a mediator through which it could modulate mitochondrial quality control and to protect against intracerebrovascular ICV/LPS-induced neurotoxicity., Methods: Mice received apigenin (40 mg/kg; p.o) for 7 consecutive days. One hour after the last dose, LPS (12 µg/kg, icv) was administered., Results: Apigenin robustly guarded against neuronal degenerative changes and maintained a normal count of intact neurons in mice hippocampi. Consequently, it inhibited the deleterious effect of LPS on cognitive functions. Apigenin was effective in preserving the NAD + /NADH ratio to boost mitochondrial sirtuin-3 (SIRT3), activity, and ATP production. It conserved normal mitochondrial features via induction of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α), along with mitochondrial transcription factor A (TFAM) and the fusion proteins, mitofusin 2 (MFN2), and optic atrophy-1 (OPA1). Furthermore, it increased phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and parkin expression as well as the microtubule-associated protein 1 light chain 3 II/I ratio (LC3II/I) to induce degradation of unhealthy mitochondria via mitophagy., Conclusions: These observations reveal the marked neuroprotective potential of apigenin against LPS-induced neurotoxicity through inhibition of NAD + depletion and activation of SIRT3 to maintain adequate mitochondrial homeostasis and function., (© 2022. The Author(s).)

Balancing microglia M1/M2 polarization has been shown as a prospective therapeutic strategy for Parkinson's disease (PD). Various vital signaling pathways are likely to govern the microglial phenotype. The implication of 5HT1A receptors in neurodegenerative disorders has raised interest in exploring the repositioning of flibanserin (Flib), a 5HT1A agonist, as an effective neuroprotective agent for PD. Therefore, this study was designed to assess the ability of Flib to modulate microglia phenotype switching from M1 to M2 via PI3K/AKT downstream targets in a rotenone model of PD. Rats received rotenone (1.5 mg/kg) every other day and were concurrently treated with Flib (40 mg/kg/day) with or without wortmannin (15 μg/kg/day), a PI3K inhibitor, for 21 days. Flib improved the motor perturbations induced by rotenone, as confirmed by the reversion of histopathological damage and tyrosine hydroxylase immunohistochemical alterations in both the striata and substantia nigra. The molecular signaling of Flib was elaborated by inducing striatal AKT phosphorylation and the expression of its substantial target, KLF4. Flib induced STAT6 phosphorylation to promote M2 polarization as demonstrated by the increased CD163 ++ microglial count with striatal arginase activity. In parallel, it markedly inhibited M1 activation as evidenced by the reduction in CD86 ++ microglia count with striatal proinflammatory mediators, IL-1β and iNOS. The pre-administration of wortmannin mostly negated Flib's neuroprotective effects. In conclusion, Flib AKT/ KLF4-dependently amended M1/M2 microglial imbalance to exert a promising neuroprotective effect, highlighting its potential as a revolutionary candidate for conquering PD., 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 © 2022 Elsevier B.V. All rights reserved.)

The purpose of the present study was to investigate the effects of ERK1/2 inhibition on both the amygdala and hippocampal structures, and to investigate its role in regulating memory for sexual information. This study utilized a cerebral ischemia reperfusion (IR) model to produce a stressful brain condition that highlights the possible involvement of a hippocampal GC/pERK1/2/BDNF pathway in the resulting sexual consequences of this ailment. Male Wistar rats were divided into four groups: (1) sham; (2) IR: subjected to 45 min of ischemia followed by 48 h of reperfusion; (3) PD98059: received PD98059 at 0.3 mg/kg, i.p.; (4) IR + PD98059. This study provides new evidence for cerebral IR-induced amygdala injury and the sexual impairments that are associated with motor and cognitive deficits in rats. These findings were correlated with histopathological changes that are defined by extensive neuronal loss in both the hippocampus and the amygdala. The current study postulated that the ERK inhibitor PD98059 could reverse IR-induced injury in the amygdala as well as reversing IR-induced sexual impairments. This hypothesis is supported by the ability of PD98059 to: (1) restore luteinizing hormone and testosterone levels; (2) increase sexual arousal and copulatory performance (as evidenced by modulating mount, intromission, ejaculation latencies, and post-ejaculatory intervals); (3) improve the histological profile in the amygdala that is associated with reduced glutamate levels, c-Fos expression, and elevated gamma aminobutyric acid levels. In conclusion, the present findings introduce pERK1/2 inhibition as a possible strategy for enhancing sexual activity in survivors of IR., 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 © 2022 Elsevier B.V. All rights reserved.)

The vast socio-economic impact of Alzheimer's disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol O -glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, β-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste.

Systemic treatments for rheumatoid arthritis are associated with many side effects. This study aimed to minimize the side effects associated with the systemic administration of leflunomide (LEF) by formulating LEF-loaded emulsomes (EMLs) for intra-articular administration. Additionally, EMLs were loaded with supramagnetic nanoparticles (SPIONs) to enhance joint localization, where a magnet was placed on the joint area after intra-articular administration. Full in vitro characterization, including colloidal characteristics, entrapment efficiency, and in vitro release were conducted besides the in vivo evaluation in rats with adjuvant-induced arthritis. In vivo study included joint diameter measurement, X-ray radiographic analysis, RT-PCR analysis, Western blotting, ELISA for inflammatory markers, and histopathological examination of dissected joints. The particle size and entrapment efficiency of the selected LEF SPION EMLs were 198.2 nm and 83.7%, respectively. The EMLs exhibited sustained release for 24 h. Moreover, in vivo evaluation revealed LEF SPION EMLs to be superior to the LEF suspension, likely due to the increase in LEF solubility by nanoencapsulation that improved the pharmacological effects and the use of SPION that ensured the localization of EMLs in the intra-articular cavity upon administration.

Living donors are healthy individuals who are exposed to a major surgical procedure during which a major part of their liver is resected. Data on the long-term consequences of living liver donation are scarce. This study examined clinical, laboratory, and long-term health-related quality of life (HRQoL) in 237 living liver donors and 239 matched controls during 48-168 months of postdonation follow-up. We used the 36-item short-form health survey (SF-36), version 1. The scores for the four following subscales were higher in nondonors than in donors: physical functioning (p = 0.009), role limitations due to physical health (p = 0.002), energy/fatigue (p < 0.001), and bodily pain (p < 0.001). The scores on the eight subscales of the SF-36 were higher in donors with living recipients than in donors whose recipients died (p < 0.001). Our results suggest that living donor right hepatectomy is safe and results in a postdonation HRQoL similar to that of nondonors in those donors whose recipients are healthy, whereas donors whose recipients die have a lower HRQoL that is significantly negatively correlated with the time since recipient death and improves over time., (© 2022 American Association for the Study of Liver Diseases.)

Background: The World Health Organization declared the coronavirus disease-2019 (COVID-19) a pandemic in December 2019. COVID-19 can affect most organs of the body but predominantly affects the lungs. Chest infection is associated with hyponatremia primarily due to inappropriate ectopic secretion of antidiuretic hormone. We conducted a six-month retrospective observational study to evaluate the relationship between chest X-ray (CXR) radiological findings and serum sodium levels. Our secondary goal was to assess the relationship between CXR findings and patient outcomes., Aim of the Study: To assess the relationship between the initial CXR findings, hyponatremia severity, and outcome in COVID-19 infected patients., Materials and Methods: We conducted a retrospective review of CXR findings of COVID-19 patients aged > 18 years. The patients were healthy and had no history of hyponatremia before COVID-19 infection. All recruited patients were admitted to one of four hospitals in Qatar (Hazm Mebaireek General Hospital, Communicable Disease Center, and all affiliated quarantine centers managed under the Communicable Disease Centre, Mesaieed Hospital, and Ras Laffan Hospital) between March and June 2020. We excluded patients with factors that contributed to hyponatremia. Three score grades were established to describe the CXR findings. Patients were divided into three groups by the principal researcher according to their serum sodium levels. A radiologist evaluated the CXR findings with the patient and group information obscured. The principal researcher collected the X-ray scores for analysis with the serum sodium levels. We used SPSS for Windows, Version 15.0. (SPSS Inc., Chicago, IL, USA) and STATA Package Version 12.0 (StataCorp, College Station, TX, USA) to analyze the data. A p -value ≤  0.05 was considered significant., Results: A total of 414 CXR patients with COVID-19 were recruited; 275 patients had hyponatremia and 139 had normal sodium levels and were used as the control group. Patients with normal serum sodium and hyponatremia were classified into three categories based on the CXR findings. Grade 0 (95), Grade 1 (43), and Grade 2 (137) hyponatremic patients were reported. The mean sodium levels were 133.6, 131.3, and 127.2 mmol/L for Grades 0, 1, and 2, respectively ( p  < 0.001). More than 95% of the patients who developed hyponatremia were >30 years. Moderate and severe hyponatremia was more prevalent in patients with Grade 1 or Grade 2 CXR findings and were >30 years., Conclusion: Serum sodium levels in COVID-19 patients correlated well with the severity of the CXR findings observed at the early disease stage. Furthermore, simple CXR scores can be used to identify COVID-19 patients at a higher risk of hyponatremia, length of hospital stay, medical care support type, and mortality., (© 2022 Habas, Said, Ramzee, Ghazouani, Fino, Abu Khattab, Al Masalamani, Nair, licensee HBKU Press.)

Deverra tortuosa (Desf.) DC. and Deverra. triradiata Hochst. ex Bioss are perennial desert shrubs widely used traditionally for many purposes and they are characteristic for their essential oil. The objective of the present study was to investigate the in vivo wound healing activity of the essential oil (EO) of D. tortuosa and D. triradiata through their encapsulation into nanoemulsion. EO nanoemulsion was prepared using an aqueous phase titration method, and nanoemulsion zones were identified through the construction of phase diagrams. The EO was prepared by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and supercritical fluid extraction (SFE) and analyzed using GC/MS. D. tortuosa oil is rich in the non-oxygenated compound, representing 74.54, 73.02, and 41.19% in HD, MADH, and SFE, respectively, and sabinene represents the major monoterpene hydrocarbons. Moreover, D. triradiata is rich in oxygenated compounds being 69.77, 52.87, and 61.69% in HD, MADH, and SFE, respectively, with elemicin and myristicin as major phenylpropanoids. Topical application of the nanoemulsion of D. tortuosa and D. triradiata (1% or 2%) exhibited nearly 100% wound contraction and complete healing at day 16. Moreover, they exhibit significant antioxidant and anti-inflammatory effects and a significant increase in growth factors and hydroxyproline levels. Histopathological examination exhibited complete re-epithelialization accompanied by activated hair follicles and abundant collagen fibers, especially at a concentration of 2%. Therefore, the incorporation of the two Deverra species into nanoemulsion could professionally endorse different stages of wound healing., 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 Kamel, Teiama, El-Hagrassi, Elgayed, Khattab, El-Sayed, Ibrahim, Mady and Moharram.)

Ethnopharmacological Relevance: Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed., Aim of the Study: The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. rugulosa leaves in relevance to their flavonoid content using an appropriate in vivo model., Materials and Methods: The aqueous methanol extract of M. rugulosa leaves was administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for seven days prior to the initiation of liver-injury induced by paracetamol (3 g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum samples. The oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), were assessed in liver homogenate. The results were supported by histopathological and immuno-histochemical studies. The phytochemical investigation of the flavonoid-rich fraction of the aqueous methanol extract was accomplished using different chromatographic and spectroscopic techniques., Results: The aqueous methanol extract of M. rugulosa leaves showed a powerful hepatoprotective activity evidenced by the significant reduction of MDA and NO levels, as well as increasing GSH and catalase activity. Moreover, the extract exhibited anti-inflammatory and antiapoptotic activities witnessed by decreasing TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract showed a significant decrease in liver weight/body weight (LW/BW) ratio, and total bilirubin induced by paracetamol. On the other hand, the chromatographic separation of the flavonoid-rich fraction afforded twenty known flavonoids namely; iso-orientin (1), orientin (2), isovitexin (3), vitexin (4), quercetin-3-O-β-D-glucuronid methyl ether (5), quercetin-3-O-β-D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), kaempferol-3-O-β-D-mannuronopyranoside (9), kaempferol-7-O-methyl ether-3-O-β-D-glucopyranoside (10), guaijaverin (11), avicularin (12), kaempferide-3-O-β-D-glucopyranoside (13), astragalin (14), afzelin (15), luteolin (16), apigenin (17), quercetin (18), kaempferol (19), and catechin (20)., Conclusion: The aqueous methanol extract of M. rugulosa leaves showed potential hepatoprotective, antioxidant, and anti-inflammatory activities against paracetamol-induced liver inflammation which is correlated at least in part to its considerable phenolic content., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bariatric surgery is increasingly performed over the past decade for the treatment of morbid obesity. It has beneficial effects on weight reduction, along with diabetes remission. Conflicting results have been reported to evaluate the effect of ethics differences on the outcomes of bariatric surgery. We conducted this meta-analysis to outline the effects of ethnic differences on the outcomes of bariatric surgery, including weight reduction, biochemical variables, diabetes, and hypertension remission. A comprehensive literature search was conducted, using PubMed, Web of Science (ISI), Google Scholar, Popline, Global Health Library (GHL), Virtual Health Library (VHL) including Cochrane database, New York Academy of Medicine (NYAM), and System for Information on Grey Literature in Europe (SIGLE) for studies reporting body mass index (BMI), percentage of excess weight loss (%EWL), waist circumference, hypertension, lipid profile, and diabetes variables. We used the National Heart, Lung, and Blood Institute (NHLBI) tool (Bethesda, MD: NHLBI, National Institutes of Health {NIH}) for quality assessment. Comprehensive Meta-Analysis version 2 software (Englewood, NJ: Biostat, Inc.) was applied to perform the meta-analysis of the variables of interest. We included 23 studies of 71,679 subjects, who underwent bariatric surgery. The majority of the included cases were Whites 55,030 (77%), while 705 (1%) were Asians. The percentages of Blacks, African Americans, Hispanics, and Non-Hispanics were 9.3%, 1.3%, 10.4%, and 1%, respectively. BMI showed no significant difference between Whites vs African American and Hispanic vs Non-Hispanic groups (MD: 0.858; 95% CI: 3.408-1.691; p = 0.509 and MD: 0.455; 95% CI: 2.444-1.554; p = 0.663, respectively). The same result was reported for %EWL, comparing Whites vs African Americans. Lipid biochemical variables, diabetes remission, and hypertension control were significantly more seen among the Asian population. In conclusion, we reported a significant ethnic diversity and reduction in waist circumference, hyperlipidemia, and the associated morbidity one year after bariatric surgery in the Asian population. Further, high-quality prospective studies should focus on the social and psychological ethnic differences associated with obesity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Khattab et al.)

Background: Minimally invasive surgery for left ventricular assist device implantation may have advantages over conventional sternotomy (CS). Additionally, ultra-fast-track anesthesia has been linked to better outcomes after cardiac surgery. This study summarizes our early experience of combining minimally invasive surgery with ultra-fast-track anesthesia (MIFTA) in patients receiving HeartMate 3 devices and compares the outcomes between MIFTA and CS., Methods: From October 2015 to January 2019, 18 of 49 patients with Interagency Registry for Mechanically Assisted Circulatory Support profiles >1 underwent MIFTA for HeartMate 3 implantation. For bias reduction, propensity scores were calculated and used as a covariate in a regression model to analyze outcomes. Weighted parametric survival analysis was performed., Results: In the MIFTA group, intensive care unit stays were shorter (mean difference, 8 days [95% CI, 4-13]; P <0.001), and the incidences of pneumonia and right heart failure were lower than those in the CS group (odds ratio, 1.36 [95% CI, 1.01-1.75]; P =0.016, respectively). At 6 and 12 hours postoperatively, MIFTA patients had a better hemodynamic performance with lower pulmonary wedge pressure (mean difference, 2.23 mm Hg [95% CI, 0.41-4.06]; P =0.028) and a higher right ventricular stroke work index (mean difference, -1.49 g·m/m 2 per beat [95% CI, -2.95 to -0.02]; P =0.031). CS patients had a worse right heart failure-free survival rate (hazard ratio, 2.35 [95% CI, 0.96-5.72]; P <0.01)., Conclusions: Compared with CS, MIFTA is a beneficial approach for non-Interagency Registry for Mechanically Assisted Circulatory Support 1 HeartMate 3 patients with lower adverse event incidences, better hemodynamic performance, and preserved right heart function. Future large multicentric investigations are required to verify MIFTA's effects on outcomes.

SARS-CoV-2 is the causative agent of coronavirus disease started in 2019 (COVID-19). IL-6 gene is located on chromosome 7. A considerable number of polymorphisms was identified in the IL-6 gene. Polymorphism in IL-6-174C allele is associated with a higher level of IL-6 production and this may lead to severity of in COVID-19 patients. We intended to investigate the role of polymorphism in the promotor region of IL-6 gene as a predictor for disease severity in COVID-19 patients. Fifty patients diagnosed with COVID-19 and classified into moderate and severe groups and twenty apparently healthy controls were enrolled in the study. Genotyping for IL-6 gene (-174G/C) was done by using TaqMan SNP genotyping assay for all studied groups. The distribution of different IL-6-174G/C genotypes among COVID-19 patients was 76% for GG genotype, 22% for GC genotype and 2% for CC genotype. Whereas the distribution of genotypes among the control group was 80% for GG genotype, 20% for GC genotype and 0.0% for CC genotype. The G allele distribution was 87% and 90% in the patients and control groups, respectively, while the C allele was 13% and 10% in the patients and control groups, respectively. There was no significant statistical association between different genotypes, severity and treatment outcome in the patients group. In conclusion, this study showed no relation between -174G/C IL-6 gene polymorphism and disease, in COVID-19 patients. Keywords: Interleukin-6, Promotor region, Polymorphism, COVID-19, Severity., (Copyright© by the Egyptian Association of Immunologists.)

Computed tomography (CT) is a common modality for liver diagnosis, treatment, and follow-up process. Providing accurate liver segmentation using CT images is a crucial step towards those tasks. In this paper, we propose a stacked 2-U-Nets model with three different types of skip connections. The proposed connections work to recover the loss of high-level features on the convolutional path of the first U-Net due to the pooling and the loss of low-level features during the upsampling path of the first U-Net. The skip connections concatenate all the features that are generated at the same level from the previous paths to the inputs of the convolutional layers in both paths of the second U-Net in a densely connected manner. We implement two versions of the model with different number of filters at each level of each U-Net by maximising the Dice similarity between the predicted liver region and that of the ground truth. The proposed models were trained with 3Dircadb public dataset that were released for Sliver and 3D liver and tumour segmentation challenges during MICCAI 2007-2008 challenge. The experimental results show that the proposed model outperformed the original U-Net and 2-U-Nets variants, and is comparable to the state-of-the-art mU-Net, DC U-Net, and Cascaded UNET., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Mahmoud Abdelazim Khattab et al.)

Background: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others., Main Body of the Abstract: Certain miRNAs (non-coding RNA sequences) are involved in the pathogenesis in viral myocarditis, and those miRNAs are interestingly upregulated in severe COVID-19. We hypothesize that the use of mRNA-based vaccines may be triggering the release of host miRNAs or that trigger the occurrence of myocarditis. This is based on the finding of altered host miRNA expression promoting virus-induced myocarditis., Short Conclusion: In conclusion, miRNAs are likely implicated in myocarditis associated with mRNA vaccines. Our hypothesis suggests the use of miRNA as a biomarker for the diagnosis of mRNA vaccine-induced myocarditis. Additionally, the interplay between viral miRNA and the host immune system could alter inflammatory profiles, hence suggesting the use of therapeutic inhibition to prevent such complications., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

COVID-19 pandemic has changed the world dramatically since was first reported in Wuhan city, China [1]. Not only as a respiratory illness that could lead to fatal respiratory failure, but also some evidences suggest that it can propagate as a chronic disease associated with a variety of persistent post COVID-19 pathologies that affect patients' life [2,3]. Pulmonary hypertension (PH) is one of the challenging diseases that may develop as a consequence of SARS-COV-2 infection in some COVID-19 survivors [4,5]. The vasopressor, proliferative, proinflammatory, and prothrombotic actions of endothelin [6] may be encountered in the COVID-19-induced PH pathology. And so, endothelin blockers may have an important role to restrict the development of serious PH outcomes with special precautions considering patients with significant hypoxemia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Backgrounds: Modern dietary habits have been associated with Nonalcoholic Steatohepatitis (NASH). Curcumin is a natural herbal found to suppress cellular oxidative states and could be beneficial in NASH. This study investigates the effect of curcumin in an animal model of NASH., Materials and Methods: Fifty rats were allocated into five groups. Control, High Fat Diet (HFD), curcumin prophylactic (CP) and therapeutic (CT) groups. HFD regimen was given for 16 weeks. Curcumin was given along with HFD (prophylactic) or after establishment of the model for two weeks (therapeutic). Livers and blood samples were harvested for histological, biochemical, and molecular studies., Key Findings: Livers from HFD groups showed vascular, inflammatory, cellular degenerative and fibrotic changes. The hepatic damage was reflected by the increased serum liver enzymes. HFD groups showed excessive fibrotic change. Interestingly, curcumin administration as prophylactic or therapeutic significantly preserved and/or restored liver structure. This was evidenced by the normalization of the liver enzymes, preservation and/or reversibility of cellular changes and the decrease of the stage of fibrosis. Nuclear factor E2-related factor 2 gene (Nrf2) expression showed no changes in the HFD groups, however it showed upregulation in curcumin treated groups. Thus, the protective and therapeutic effect of curcumin could be induced through upregulation of the Nrf2 gene. Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers., Significance: Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Atorvastatin Calcium (At-Ca) has pleiotropic effect as anti-inflammatory drug beside its main antihyperlipidemic action. Our study was conducted to modulate the anti-inflammatory effect of At-Ca to be efficiently sustained for longer time. Single oil-water emulsion solvent evaporation technique was used to fabricate At-Ca into polymeric nanoparticles (NPs). In vitro optimization survey was performed on Poly(lactide-co-glycolide) (PLGA) loaded with At-Ca regrading to particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (% EE), surface morphology and in vitro release pattern. In vitro drug-polymers interactions were fully scanned using Fourier-Transform Infrared Spectroscopy (FTIR) and Differential Scanning calorimetry (DSC) proving that the method of fabrication is an optimal strategy maintaining the drug structure with no interaction with polymeric matrix. The optimized formula with particle size (248.2 ± 15.13 nm), PDI (0.126 ± 0.048), zeta potential (-12.41 ± 4.80 mV), % EE (87.63 ± 3.21%), initial burst (39.78 ± 6.74%) and percent cumulative release (83.63 ± 3.71%) was orally administered in Male Sprague-Dawley rats to study the sustained anti-inflammatory effect of At-Ca PLGA NPs after carrageenan induced inflammation. In vivo results demonstrate that AT-Ca NPs has a sustained effect extending for approximately three days. Additionally, the histological examination revealed that the epidermal/dermal layers restore their typical normal cellular alignment with healthy architecture.

Alzheimer's disease (AD) is a neurodegenerative disease where oxidative stress plays a major role as a key pathologic factor. The study aims to develop resveratrol (RES)-loaded bilosomes for oral use, aiming to enhance RES bioavailability. RES-loaded bilosomes were prepared using the thin-film hydration technique. The effect of different formulation variables viz . the number of extrusion cycles, drug concentration and the effect of pH of the medium and cholesterol addition on the physicochemical properties of the prepared bilosomes was investigated. Results revealed the successful entrapment of RES into bilosomes. An optimized formula was selected, showing the lowest particle size (189 ± 2.14), acceptable PDI (0.116) and entrapment efficiency (76.2 ± 1.36). In vivo studies on a streptozotocin-induced animal model of AD showed the preeminence of bilosomes over traditional drug suspension to enhance mice memory via Y-maze and Morris water maze tests. Moreover, mice treated with the optimized formula exhibited decreased COX2, IL-6, amyloid-beta peptide and Tau protein levels compared to the drug suspension. Immuno-histochemical analysis revealed a significant decrease of glial fibrillary acidic protein values and microglial cell count in mice treated with bilosomes. Finally, it could be advocated that RES-loaded bilosomes could be a promising drug delivery system to control AD.

This study determined the ovarian, uterine, and luteal hemodynamic variations using Doppler between pregnant and non-pregnant pluriparous buffalos in relation to their anatomical and histological basics during the first 31 days after natural mating. Adult healthy cyclic Egyptian buffalo (n = 10) were selected and categorized into two groups; group 1 (n = 5) was mated naturally by a fertile bull during the late estrus phase, and group 2 (n = 5) was not mated. Animals were subjected to Doppler ultrasonography to evaluate luteal, ovarian, and uterine blood flows from day 7 until day 31 post-mating. Besides, three pregnant (one month) and other non-pregnant uterus (n = 6) were obtained from a local abattoir to study the anatomical and histological features. Our results revealed that the luteal, ovarian, and uterine arteries cross-sectional diameters/mm increased (P < 0.05) from day 7 till day 31. Resistance (RI) and pulsatility indices (PI) decreased linearly (P < 0.05) in pregnant buffalos till day 31, but the peak systolic, end diastolic velocities and flow volume of those arteries were increased. Additionally, luteal colored areas away and toward CL were increased (P < 0.05) in the pregnant group compared to non-pregnant ones. There was a significant (P < 0.05) increase in the lumen diameter of luteal, ovarian, and uterine artery sections in pregnant buffalos compared to those of non-pregnant ones. While the mean value of tunica media's thickness of both luteal and uterine artery was significantly higher in non-pregnant buffalos than pregnant ones, except for that of the ovarian artery. Additionally, the ovarian and uterine artery tunica muscularis relative area % was (P < 0.05) higher in pregnant buffalos than in non-pregnant ones, except for that of the luteal artery. It was concluded that in pregnant buffalos, ovarian, uterine, and luteal blood flows were improved from the first week until 31 days post-mating via a decline in both Doppler indices with an increase in Doppler velocities and blood flow volume in relation to their histological changes based on their anatomical architecture in comparison to non-pregnant one., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mycotoxins are toxic secondary metabolites produced by different strains of fungi, such as aspergillus, fusarium, and penicillium that can contaminate feed ingredients or the entire feed of poultry and animals. Mycotoxins can cause many serious complications to both humans and animals due to carcinogenic, mutagenic, and immunosuppressive disorders. Therefore, the present experiment aims to investigate the effect of broiler chickens' diets supplemented with different levels of nanosilica (NS) as an adsorbent agent of mycotoxins on their growth performance and hepatic histopathology. Detectable levels of toxins were present in the feed before feeding, and all levels of mycotoxins were above the normal limit. A total of 180 one-day-old male Arbor Acres broiler chickens were allocated randomly to six treatment groups with three replicates per group, including ten chickens per replicate. The experiment lasted for five weeks, and dietary treatments included control diet and diets with four levels of nanosilica as 0.05%, 0.10%, 0.15%, and 0.20% as well as 0.50% bentonite (fixfin ® Dry) diet. Bodyweight, body weight gain, average daily feed intake, and feed conversion ratio were measured weekly. At the end of the fifth week, six chickens per treatment were sacrificed to investigate the effects of NS and bentonite on carcass characteristics and hepatic histopathology. The results showed that providing broiler chickens' diets with an adsorbent agent, such as NS or bentonite, can reduce the side effects of mycotoxins and enhance their growth performance. The best record was achieved with NS at 0.20%, compared with the control group and other dietary treatment groups. Accordingly, 0.20% of NS could be used in broiler chickens' diets to minimize the harmful effects of mycotoxins.

MAIT cells have been shown to be activated upon several viral infections in a TCR-independent manner by responding to inflammatory cytokines secreted by antigen-presenting cells. Recently, a few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. In this study, we investigate the effect of SARS-CoV-2 infection on the frequency and phenotype of MAIT cells by flow cytometry, and we test in vitro stimulation conditions on the capacity to enhance or rescue the antiviral function of MAIT cells from patients with coronavirus disease 2019 (COVID-19). Our study, in agreement with recently published studies, confirmed the decline in MAIT cell frequency of hospitalized donors in comparison to healthy donors. MAIT cells of COVID-19 patients also had lower expression levels of TNF-alpha, perforin and granzyme B upon stimulation with IL-12 + IL-18. 24 h' incubation with IL-7 successfully restored perforin expression levels in COVID-19 patients. Combined, our findings support the growing evidence that SARS-CoV-2 is dysregulating MAIT cells and that IL-7 treatment might improve their function, rendering them more effective in protecting the body against the virus.

Objectives: This study aimed to determine the role of ONSD measurement by US for diagnosis of high ICP in TBI patients., Methods: ONSD measurement by US was performed in adult TBI patients within 1 h of planned CT brain, while CT signs of high ICP were determined. Invasive ICP measurement was performed simultaneously in patients who had intraventricular device in situ. High ICP was determined as ICP > 22 mmHg., Results: A total of 48 patients were enrolled. Twenty-eight patients had positive CT criteria for high ICP, while 20 patients were negative. The mean value of ONSD was 0.63 ± 0.06 cm in positive group compared with 0.55 ± 0.07 cm in negative one with significant difference (p < 0.001). A total of 22 patients had intraventricular device. Thirteen patients had high ICP, while 9 patients had normal ICP. The mean value of ONSD was 0.66 ± 0.05 cm in high ICP group compared with 0.58 ± 0.08 cm in normal one with significant difference (p = 0.004). ONSD with cut-off value > 0.61 cm predicted high ICP with sensitivity of 84.62% and specificity of 66.67% with significant AUC of 0.85 (p = 0.006)., Conclusion: ONSD measurement by ultrasound is a good screening tool for high ICP in traumatic brain injury patients.

Background: Hydroxychloroquine (HC) ± azithromycin (AZ) is widely used for Covid-19. The Qatar Prospective RCT of Expediting Coronavirus Tapering (Q-PROTECT) aimed to assess virologic cure rates of HC±AZ in cases of low-acuity Covid-19., Methods: Q-PROTECT employed a prospective, placebo-controlled design with blinded randomization to three parallel arms: placebo, oral HC (600 mg daily for one week), or oral HC plus oral AZ (500 mg day one, 250 mg daily on days two through five). At enrollment, non-hospitalized participants had mild or no symptoms and were within a day of Covid-19 positivity by polymerase chain reaction (PCR). After six days, intent-to-treat (ITT) analysis of the primary endpoint of virologic cure was assessed using binomial exact 95% confidence intervals (CIs) and χ 2 testing. (ClinicalTrials.gov NCT04349592, trial status closed to new participants.)., Findings: The study enrolled 456 participants (152 in each of three groups: HC+AZ, HC, placebo) between 13 April and 1 August 2020. HC+AZ, HC, and placebo groups had 6 (3·9%), 7 (4·6%), and 9 (5·9%) participants go off study medications before completing the medication course ( p  = 0·716). Day six PCR results were available for all 152 HC+AZ participants, 149/152 (98·0%) HC participants, and 147/152 (96·7%) placebo participants. Day six ITT analysis found no difference ( p  = 0·821) in groups' proportions achieving virologic cure: HC+AZ 16/152 (10·5%), HC 19/149 (12·8%), placebo 18/147 (12·2%). Day 14 assessment also showed no association ( p  = 0·072) between study group and viral cure: HC+AZ 30/149 (20·1%,), HC 42/146 (28·8%), placebo 45/143 (31·5%). There were no serious adverse events., Interpretation: HC±AZ does not facilitate virologic cure in patients with mild or asymptomatic Covid-19., Funding: The study was supported by internal institutional funds of the Hamad Medical Corporation (government health service of the State of Qatar)., Competing Interests: The authors have no financial or personal relationships with other people or organizations that could represent a conflict of interest., (© 2020 The Authors.)

Background: There is a scarcity of data regarding the effect of Type 2 diabetes mellitus (T2DM) and associated comorbidities on the clinical presentation and outcome of symptomatic patients with -COVID-19 infection in comparison with non-diabetic patients., Aim of the Study: We described and compared the clinical presentation and radiological and hematological data of a cohort of symptomatic COVID19 positive T2DM diabetic patients (n = 59) versus another cohort of non-diabetic symptomatic COVID19 positive patients (n =244) diagnosed at the same time from January 2020 to May 2020. Associated comorbidities were -assessed, and the Charlson Comorbidity Index was calculated. The outcomes including duration of hospitalization, duration of Intensive Care Unit (ICU) stay, duration of mechanical ventilation, and duration of O2 -supplementation were assessed., Results: Prevalence of T2DM in symptomatic COVID19 positive patients was 59/303 (=19.5%).  Diabetic patients had higher prevalence of hypertension, chronic kidney disease (CKD) and cardiac dysfunction [coronary heart disease (CHD)], and congestive heart failure (CHF). Charlson Comorbidity score was significantly higher in the T2DM patients (2.4± 1.6) versus the non-diabetic -patients (0.28 ± 0.8; p: < 0.001). Clinically and radiologically, T2DM patients had significantly higher percentage of pneumonia, severe pneumonia and ARDS versus the non-diabetic patients. Hematologically, diabetic patients had significantly higher C-reactive protein (CRP), higher absolute neutrophilic count (ANC) and lower counts of lymphocytes and eosinophils compared to non-diabetic patients. They had significantly higher systolic and diastolic blood pressures, longer duration of hospitalization, ICU stay, mechanical ventilation and oxygen therapy. CRP was correlated significantly with the duration of stay in the ICU and the duration for oxygen supplementation (r = 0.37 and 0.42 respectively; p: <0.01)., Conclusions: T2DM patients showed higher inflammatory response to COVID 19 with higher absolute neutrophilic count (ANC) and CRP with lower lymphocytic and eosinophilic counts. Diabetic patients had more comorbidities and more aggressive course of the disease with higher rate of ICU admission and longer need for hospitalization and oxygen use.

Direct intra-articular delivery of drugs to osteoarthritic joints offers the possibility of delivering high drug concentrations at the site of action as well as decreasing long term associated side effects after oral drug delivery. So in the current work, we aimed to improve the osteoarthritic therapeutic efficacy of the non-steroidal anti-inflammatory drug; celecoxib, through the formulation of drug loaded hyaluronan nanocapsules. The proposed formulation aimed to combine the beneficial viscosupplemental properties of hyaluronic acid with the pharmacological, anti-inflammatory, effect of celecoxib in a novel drug carrier for intra-articular delivery. The proposed nanocapsules were prepared by the nanoprecipitation method. Several formulation variables were studied aiming at optimizing the nanocapsules' size, polydispersity index and celecoxib entrapment efficiency %. The optimized hyaluronan nanocapsules formulation showed a size of 254.9 ± 3.06 nm, which is appropriate for the intra-articular delivery of celecoxib, high entrapment efficiency% of 97.98% ± 0.19, and prolonged celecoxib release for almost one week. The transmission electron microscope images revealed spherical shape of the nanocapsules with distinct shell and core structure. The in-vivo evaluation of the anti-osteoarthritic activity of the optimized hyaluronan nanocapsules formulation showed the superiority of the prepared celecoxib nanocapsules compared to celecoxib suspension in a Monoiodoacetate induced osteoarthritic rat model, regarding histological, swelling and immunohistochemical parameters of osteoarthritis., 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 B.V. All rights reserved.)

Nitrites are found in several forms; they are widely found in water resources and used as additives and preservatives for food and as a color source. We investigated the hazardous effects of exposing rats to different doses of nitrites. Moreover, we examined such impacts, after acute ingestion, on liver and renal tissues in rats and to what extent this affects the organs' functions. Animals were divided into five groups: one control group 1 (group C) and four sodium nitrite (NaNO 2 )-treated group (8 rats per group). The four NaNO 2 -treated groups include group 2 (N20), group 3 (N40), group 4 (N60), and group 5 (N75). NaNO 2 was dissolved in distilled water, and single acute dose was orally given by gavage at 20, 40, 60, and 75 mg/kg body weight, respectively. Our results revealed significant increase of liver enzymes activity-aspartate transaminase (AST), alanine aminotransferase (ALT), and creatinine between different groups with increasing doses of nitrite ingestion. The results of hepatic and renal oxidative stress showed significant increase in the malondialdehyde (MDA) levels and significant decrease in the antioxidant parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as the dose of nitrite increases. Further, the methemoglobin percent showed significant increase with increasing nitrite doses. Abnormal morphological alterations in the liver and kidney tissues were obviously proportional to the administered nitrite doses. The expression of caspase 3 and Bax level showed enhanced induction of immunoexpression, especially in the high doses of nitrites. On the other hand, the maximal immunoexpression level of anti-apoptotic marker Bcl 2 was found in lower doses of nitrites, whereas marked decrease of Bcl 2 levels was observed in the higher doses. In conclusion, administration of sodium nitrite in a dose-dependent manner is capable of inducing cellular and genetic toxicities and causes disturbance in biochemical analysis, oxidative and anti-oxidative balance, and methemoglobinemia. It also makes histopathological alterations and leads to the activation of apoptosis-related Bax, Bcl 2 , and caspase 3 genes of liver and kidney tissues in rats.

Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H 2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra . Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF- α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources., Competing Interests: The authors declare that they have no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)