Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid.

PURPOSE: Oral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. MATERIALS AND METHODS: Gallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel. UV-visible (UV) spectrophotometry verified Zn-GANP synthesis. TEM, DLS, and FTIR were utilized to investigate ZnO-NPs' characteristics. Rats were orally exposed to DEN for 8 weeks at 20 mg/kg five times per week, followed by intraperitoneal injection of Zn-GANPs at 20 mg/kg for 5 weeks. Using oxidative stress, anti-inflammatory, liver function, histologic, apoptotic, and cell cycle parameters for evaluating Zn-GANPs treatment. RESULTS: DEN exposure elevated inflammatory markers (AFP and NF-κB p65), transaminases (AST, ALT), γ-GT, globulin, and total bilirubin, with reduced protein and albumin levels. It also increased MDA levels, oxidative liver cell damage, and Bcl-2, while decreasing caspase-3 and antioxidants like GSH, and CAT. Zn-GANPs significantly mitigated these effects and lowered lipid peroxidation, AST, ALT, and γ-GT levels, significantly increased CAT and GSH levels (p<0.05). Zn-GANPs caused S and G2/M cell cycle arrest and G0/G1 apoptosis. These results were associated with higher caspase-3 levels and lower Bcl-2 and TGF-ß1 levels. Zn-GANPs enhance and restore the histology and ultrastructure of the liver in DEN-induced rats. CONCLUSION: The data imply that Zn-GANPs may prevent and treat DEN-induced liver damage and carcinogenesis.

Natural angiotensin converting enzyme inhibitors: A safeguard against hypertension, respiratory distress syndrome, and chronic kidney diseases.

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.

Comparative effects of minimally invasive approaches vs. conventional for obese patients undergoing aortic valve replacement: a systematic review and network meta-analysis.

BACKGROUND: Minimally invasive approaches like mini-thoracotomy and mini-sternotomy for Aortic Valve Replacement (AVR) showed impressive outcomes. However, their advantages for obese patients are questionable. We aimed in this network meta-analysis to compare three surgical approaches: Full sternotomy (FS), Mini-sternotomy (MS), and Mini-thoracotomy (MT) for obese patients undergoing AVR. METHODS: We followed the PRISMA extension for this network meta-analysis. PubMed/Medline, Scopus, Web of Science, and Cochrane searched through March 2023 for relevant articles. The analysis was performed using R version 4.2.3. RESULTS: Out of 344, 8 articles met the criteria with 1392 patients. The main outcomes assessed were perioperative mortality, re-exploration, atrial fibrillation, renal failure, ICU stay, hospital stay, cross-clamp time, and bypass time. In favor of MS, the length of ICU stay and hospital stay was significantly lower than for FS [MD -0.84, 95%CI (-1.26; -0.43)], and [MD -2.56, 95%CI (-3.90; -1.22)], respectively. Regarding peri-operative mortality, FS showed a significantly higher risk compared to MS [RR 2.28, 95%CI (1.01;5.16)]. Also, patients who underwent minimally invasive approaches; MT and MS, required less need of re-exploration compared to FS [RR 0.10, 95%CI (0.02;0.45)], and [RR 0.33, 95%CI (0.14;0.79)], respectively. However, Intraoperative timings; including aortic cross-clamp, and cardiopulmonary bypass time, were significantly lower with FS than for MS [MD -9.16, 95%CI (-1.88; -16.45)], [MD -9.61, 95%CI (-18.64; -0.59)], respectively. CONCLUSION: Our network meta-analysis shows that minimally invasive approaches offer some advantages for obese patients undergoing AVR over full sternotomy. Suggesting that these approaches might be considered more beneficial alternatives for obese patients undergoing AVR.

Design and optimization of silymarin loaded in lyophilized fast melt tablets to attenuate lung toxicity induced via HgCl2 in rats.

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 32 factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q10). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q10 of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl2 in a manner comparable to free SM at the same dosage.

Design and optimization of cranberry extract loaded bile salt augmented liposomes for targeting of MCP-1/STAT3/VEGF signaling pathway in DMN-intoxicated liver in rats.

Cranberry extract (CBE) is a major source of the antioxidant polyphenolics but suffers from limited bioavailability. The goal of this research was to encapsulate the nutraceutical (CBE), into bile salt augmented liposomes (BSALs) as a promising oral delivery system to potentiate its hepatoprotective impact against dimethylnitrosamine (DMN) induced liver injury in rats. The inclusion of bile salt in the liposomal structure can enhance their stability within the gastrointestinal tract and promote CBE permeability. CBE loaded BSALs formulations were fabricated utilizing a (23) factorial design to explore the impact of phospholipid type (X1), phospholipid amount (X2), and sodium glycocholate (SGC) amount (X3) on BSALs properties, namely; entrapment efficiency percent, (EE%); vesicle size, (VS); polydispersity index; (PDI); zeta potential, (ZP); and release efficiency percent, (RE%). The optimum formulation (F1) exhibited spherical vesicles with EE% of 71.27 ± 0.32%, VS; 148.60 ± 6.46 nm, PDI; 0.38 ± 0.02, ZP; -18.27 ± 0.67 mV and RE%; 61.96 ± 1.07%. Compared to CBE solution, F1 had attenuated DMN-induced hepatic injury, as evidenced by the significant decrease in serum level of ALT, AST, ALP, MDA, and elevation of GSH level, as well as SOD and GPX activities. Furthermore, F1 exhibited an anti-inflammatory character by suppressing TNF-α, MCP-1, and IL-6, as well as downregulation of VEGF-C, STAT-3, and IFN-γ mRNA levels. This study verified that when CBE was integrated into BSALs, F1, its hepatoprotective effect was significantly potentiated to protect the liver against DMN-induced damage. Therefore, F1 could be deliberated as an antioxidant, antiproliferative, and antifibrotic therapy to slow down the progression of hepatic damage.

The Potential Synergistic Activity of Zolmitriptan Combined in New Self-Nanoemulsifying Drug Delivery Systems: ATR-FTIR Real-Time Fast Dissolution Monitoring and Pharmacodynamic Assessment.

PURPOSE: The current work aimed to overcome the poor permeability and undesirable adverse effects of Zolmitriptan (ZMT) and to increase its efficacy in the treatment of acute migraine by exploiting the synergistic effect of the essential oil, lavender, to fabricate ZMT self-nanoemulsifying drug delivery systems (ZMT-SNEDDS). METHODS: ZMT-SNEDDS were fabricated based on full factorial design (32) to statistically assess the impact of oil and surfactant concentrations on the nanoemulsion globule size, zeta potential and percentage drug dissolution efficiency. An ATR-FTIR method was developed and validated for continuous real-time monitoring of ZMT dissolution and permeation. The dose of the optimized ZMT-SNEDDS used in the efficacy study was selected according to the acute toxicity study. The efficacy study was performed on migraineous rats induced by nitroglycerin and was evaluated by the activity cage and thermal tests, electroencephalogram, electroconvulsive stimulation, and biochemical analysis of brain tissue. Finally, histopathological and immunohistochemical examinations of the cerebra were carried out. RESULTS: Upon dilution, the optimized ZMT-SNEDDS (F5) exhibited nanosized spherical droplets of 19.59±0.17 nm with narrow size distribution, zeta potential (-23.5±1.17mV) and rapid emulsification characteristics. ATR-FTIR spectra elucidated the complete time course of dissolution and permeation, confirming F5 superior performance. Moreover, ZMT-SNEDDS (F5) showed safety in an acute toxicity study. ZMT concentration in rat brain tissues derived from F5 was lower compared to that of ZMT solution, yet its effect was better on the psychological state, algesia, as well as maintaining normal brain electrical activity and delayed convulsions. It counteracted the cerebral biochemical alternations induced by nitroglycerin, which was confirmed by histopathological examination. CONCLUSION: In a nutshell, these findings corroborated the remarkable synergistic efficacy and the high potency of lavender oil-based ZMT-SNEDDS in migraine management compared to the traditional zolmitriptan solution.

Correction to: Role of Enhanced Recovery Program for Colorectal Cancer Patients: National Cancer Institute Experience.

[This corrects the article DOI: 10.1007/s13193-021-01278-9.].

Role of Enhanced Recovery Program for Colorectal Cancer Patients: National Cancer Institute Experience.

Enhanced recovery program (ERP) was introduced in patients scheduled for colorectal surgical procedures to enhance gastrointestinal recovery and shorten their hospital stay. This study aims to evaluate the role of ERP in colorectal cancer patients. A prospective cohort study performed at National Cancer Institute-Cairo University including 50 patients with colorectal cancer treated between October 2016 and May 2017. They were divided in 2 equal groups: study group (ERP group) and control group (conventional protocol group). Incidence of postoperative morbidity was greater in the control group compared to the study group. Only the incidence of paralytic ileus was greater in the study group. The study group had a statistically significant hospital stay length compared to the control group. ERP was associated with lower incidence of postoperative morbidity excluding incidence of paralytic ileus; also, it was associated with a shorter hospital stay.

Contralateral Coupling During Extracorporeal Shockwave Lithotripsy for Stones in Ectopic Kidney: Is It Feasible?

Purpose: Extracorporeal shockwave lithotripsy (SWL) results in a lower stone-free rate (SFR) for ectopic kidneys when using the standard technique, directing the shock wave from the same side of the stone; however, this may not be the optimal approach when the ectopic kidney is located more medial and anterior than the normally positioned kidney. Thus, contralateral coupling where waves come from the opposite direction may result in a better outcome. We tested the feasibility and outcome of contralateral coupling during SWL for stone in ectopic kidney. Materials and Methods: We prospectively recruited 20 patients with simple renal ectopia, who presented with renal stones that were amenable for SWL in the period between 2014 and 2018 at outpatient clinic of urology department, Minia University. Patients received SWL in Private Nile SWL Center were included to benefit from the ability of the electromagnetic SWL lithotripter. We did SWL in a supine position, and then contralateral coupling was performed from the opposite side of the affected kidney, rather than using the standard ipsilateral coupling approach. The SFR and various pre-, intra-, and postprocedural SWL variables were assessed, including stone characteristics, body habitus, shock wave numbers, and auxiliary measures. Count and percentages were calculated. Results: The mean stone radius was 14.7 mm with a mean S.T.O.N.E. (size, topography, obstructions, number of stones, and evaluation of HUs) of 9.6 points. Effective SWL was achieved in 80% of cases, 65% of them were stone free with effective single SWL session in 56% of cases. Hematuria, infection, and obstruction occurred in 50%, 20%, and 15% cases, respectively. One case required ureteral stent insertion. Conclusions: SWL applied through contralateral coupling is feasible, with comparable safety profile to the standard ipsilateral approach. Better SFR was achieved with the contralateral approach, in fewer sessions. However, the recruitment of more cases is necessary.

Retinal thickness as a potential biomarker of neurodegeneration and a predictor of early cognitive impairment in patients with multiple sclerosis.

OBJECTIVES: The purpose of this research is to predict the cognitive impairment and to determine its correlation with retinal thickness, mainly (RFNL and GCIPL) in cases of multiple sclerosis. METHODS: 60 multiple sclerosis patients and 30 age and sex-matched healthy controls were included in this study. Cognitive functions were evaluated in all study participants by the Montreal Cognitive Assessment (MoCA). OCT imaging was done to determine the thickness. The correlation between the cognitive domains of MoCA and the thickness of the retinal nerve fiber layers was analyzed by Spearman correlation. ROC curve was constructed to determine the cut-off points for retinal thickness, and a binary logistic regression was performed to determine the independent predictive capacity of established cut-off points. RESULTS: Impaired cognition was found in 26 MS patients (43.3%). Cognitively impaired patients were significantly older (P < 0.05), had significantly longer disease duration (P < 0.05), had higher average EDSS scores (4.3 ± 1.22 vs 3.1 ± 1.45, P < 0.001), and occurred more in progressive types of MS (P < 0.001). A significant positive correlation was found between cognitive function and RNFL thickness and GCIPL (P < 0.001). The retinal thickness (RNFL and GCIPL) cut-off points established for the prediction of cognitive impairment in MS patients were 79 µm and 76 µm, respectively. CONCLUSION: The clear correlation between cognitive impairment and atrophy of inner retinal layers (RNFL and GCIPL) proposes that OCT is valuable in evaluating the neurodegeneration and prediction of early cognitive impairment in MS. ABBREVIATIONS: EDSS: Expanded Disability Status Scale; HCs: Healthy controls; GCIPL: Ganglion cell-inner plexiform layer; ILM: Internal limiting membrane; INL:  Inner nuclear layer; MoCA: Montreal Cognitive Assessment; MS: Multiple sclerosis; PPMS: Primary progressive multiple sclerosis; RNFL:  Retinal nerve fiber layer; RRMS: Relapsing-remitting multiple sclerosis; SD: Standard deviations; SPMS: Secondary progressive multiple sclerosis; SPSS: Statistical Package for the Social Sciences.

Functional and anatomical evaluation of the effect of nepafenac in prevention of macular edema after phacoemulsification in diabetic patients.

AIM: To evaluate the effect of prophylactic administration of nepafenac in prevention of macular edema occurring in diabetic patients after phacoemulsification and to investigate the correlation between optical coherence tomography (OCT) foveal thickness and multifocal electroretinogram (MF-ERG) parameters. METHODS: The study included two groups. Group 1 included 50 diabetic patients with senile cataract (50 eyes, 30 females, 20 males, aged 55±7y) received nepafenac 0.1% eye drop. Group 2 included another 50 diabetic patients with senile cataract (50 eyes, 22 female, 28 males, aged 53.8±8y) did not receive nepafenac. All patients were followed up for 3mo postoperatively. OCT and MF-ERG were done preoperative and at 1wk, 1, 2 and 3mo. RESULTS: The mean foveal thickness was statistically significantly lower in Group 1. Five eyes in Group 2 developed clinical cystoid macular oedema (CMO) (10%), and no patients in Group 1 developed central macular thickening more than 50 µm. There were insignificant differences in MF-ERG amplitudes and latencies between the two groups except in the five eyes that developed CMO, there statistically significant reduction of MF-ERG amplitude with increase in foveal thickness. CONCLUSION: Perioperative nepafenac reduces the incidence of CMO following uncomplicated phacoemulsification significantly. Nepafenac has no side effects.

Effect of Transcranial Direct Current Stimulation of the Motor Cortex on Visceral Pain in Patients with Hepatocellular Carcinoma.

Objective: Hepatocellular carcinoma (HCC) is frequently associated with visceral pain. Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain; however, its effectiveness in malignant visceral pain is unknown. This study aimed to investigate the effects of tDCS in patients with visceral pain due to HCC. Design: This is a randomized, sham-controlled, double-blind, prospective study. Forty patients with visceral pain due to HCC were enrolled and randomly assigned into two groups: a real and a sham group; tDCS was applied over the primary motor area (M1) for 10 consecutive days (2 mA, 30 minutes). Patient's pain was evaluated by visual analog scale (VAS) and verbal descriptor scale (VDS) and for depression by Hamilton rating scale (HAM-D). Evaluation was done at prestimulation, after the first, fifth, and 10th sessions, and one month after the end of stimulation sessions. Results: Real tDCS showed a reduction of VDS (P = 0.001, F = 4.01) and VAS (P = 0.001, F = 6.817) for HAM-D (P = 0.012, F = 5,077); the effect started from the fifth session and continued to one month after stimulation, while in the sham group the effect persisted for five days only. Percentage reduction in all scales in the real group after the 10th session was as follows: VDS P = 0.008, VAS P = 0.001, HAM-D = 0.001; for one month after the end of stimulation, it was as follows: VDS P = 0.001, VAS P = 0.037, HAM-D = 0.002. Conclusions: tDCS proved to be an effective and clinically relevant therapeutic strategy for visceral pain due to HCC.