Ferulic acid nanoemulsion as a promising anti-ulcer tool: in vitro and in vivo assessment.

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Geriatric nutritional risk index and adverse medical outcomes among Egyptian patients admitted to a geriatric hospital: a prospective cohort study.

BACKGROUND: Elderly are one of the most heterogeneous and vulnerable groups who have a higher risk of nutritional problems. Malnutrition is prevalent among hospitalized elderly but underdiagnosed and almost undistinguishable from the changes in the aging process. The Geriatric Nutritional Risk Index (GNRI) is a tool created to predict nutrition-related complications in hospitalized patients. This study aims to measure the prevalence of nutritional risk using the GNRI among hospitalized elderly Egyptian inpatients and to determine the association between the GNRI and selected adverse clinical outcomes. METHODS: A hospital-based prospective cohort study was conducted among 334 elderly patients admitted to a tertiary specialized geriatric university hospital in Cairo, Egypt from August 2021 to June 2022. Within 48 hours after hospital admission, socio-demographic characteristics, blood biomarkers, anthropometric measurements, and nutritional risk assessment by the GNRI score were obtained. Patients were divided into three groups based on their GNRI: high, low, and no nutritional risk (GNRI<92, 92-98, and >98) respectively. Patients were followed up for the occurrence of adverse outcomes during hospital stay (bed sores, Healthcare-Associated Infections (HAIs), hospital Length of Stay (LOS), and hospital mortality) and three months after discharge (non-improvement medical status, appearance of new medical conditions, hospital readmission and 90-day mortality). Multivariable regression and survival analysis were conducted. RESULTS: The prevalence of high-nutritional risk was 45.5% (95% CI, 40%-51%). Patients with high risk had significantly longer LOS than those with no risk. The high-nutritional risk was significantly associated with the development of bed sores (Adjusted Odds Ratio (AOR) 4.89; 95% CI, 1.37-17.45), HAIs (AOR: 3.18; 95% CI, 1.48-6.83), and hospital mortality (AOR: 4.41; 95% CI, 1.04-18.59). The overall survival rate was significantly lower among patients with high-nutritional risk compared to those with no risk. CONCLUSION: GNRI is a simple and easily applicable objective nutritional screening tool with high prognostic value in this Egyptian sample of patients. The findings of this study signal the initiation of the application of this tool to all geriatric hospitals in Egypt.

Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept.

Oleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tract. Therefore, loading oleuropein onto chitosan nanoparticles is expected to enhance its biological efficiency. Oleuropein-loaded chitosan nanoparticles were prepared and characterized for particle size, surface charge, in vitro release, and anti-inflammatory activity. Their in vivo efficacy was assessed by measuring specific inflammatory and protective biomarkers, along with histopathological examination. The optimum oleuropein chitosan nanoparticles were cationic, had a size of 174.3 ± 2.4 nm and an entrapment efficiency of 92.81%, and released 70% of oleuropein within 8 h. They recorded a lower IC50 in comparison to oleuropein solutions for membrane stabilization of RBCs (22.6 vs. 25.6 µg/mL) and lipoxygenase inhibition (7.17 vs. 15.6 µg/mL). In an ethanol-induced gastric ulcer in vivo model, they decreased IL-1ß, TNF-α, and TBARS levels by 2.1, 1.7, and 1.3 fold, respectively, in comparison to increments caused by exposure to ethanol. Moreover, they increased prostaglandin E2 and catalase enzyme levels by 2.4 and 3.8 fold, respectively. Immunohistochemical examination showed that oleuropein chitosan nanoparticles markedly lowered the expression of IL-6 and caspase-3 in gastric tissues in comparison to oleuropein solution. Overall, oleuropein chitosan nanoparticles showed superior gastroprotective effects to oleuropein solution since comparable effects were demonstrated at a 12-fold lower drug dose, delineating that chitosan nanoparticles indeed enhanced the potency of oleuropein as a gastroprotective agent.

Pylorus ligation-induced hyperacidity: synergistic prophylactic effects of linagliptin and L-arginine via up-regulation of EP4 receptor subtype and improvement of vascular endothelial damage.

Gastric hyperacidity and ulceration are chronic diseases characterized by repeated healing followed by re-exacerbation. The study aims to protect against gastric hyperacidity without interfering with gastric acid secretion. Pylorus ligation-induced hyperacidity is commonly utilized in the induction of gastric ulcers.Forty-two rats were distributed into seven groups (n = 6). Group I comprised sham-operated group. Group II served as pylorus-ligation group. Groups III-VII were given oral Linagliptin (LN; 3 and 6 mg/kg), L-arginine (LA; 150 and 300 mg/kg) and their combination (LN 3 + LA 150 mg/kg), respectively for 7 days. On the 8th day, groups II-VII were subjected to pylorus-ligation.Treatment of pylorus-ligated rats with LN, LA and their combination improved the gastric hyperacidity as exhibited by a marked reduction in the gastric juice volume, total and free acidities and pepsin contents with a noticeable increase in pH. Pre-treatment with LN, LA and their combination showed a marked alleviation in the gastric inflammatory indicators evidenced by reduction in the gastric levels of MCP-1and Il-1ß as well as elevation of eNOS levels versus the sham-operated group. A marked up-regulation in the gastric gene expression of PGE, EP4 and VEGF accompanied by an improvement of the histopathologic pictures/scores, and TNF-α and caspase-3 immuno-staining were also recorded.By estimating the combination-index, it can be concluded that combining LN with LA exhibited prophylactic synergistic effects in ameliorating pylorus ligated-induced hyperacidity, mainly via up-regulation of EP4 receptor and improvement of vascular endothelial damage through VEGF expression in gastric mucosa.

Oxidative stress, gene expression and histopathology of cultured gilthead sea bream (Sparus aurata) naturally co-infected with Ergasilus sieboldi and Vibrio alginolyticus.

BACKGROUND: Parasitic and bacterial co-infections have been associated with increasing fish mortalities and severe economic losses in aquaculture through the past three decades. The aim of this study was to evaluate the oxidative stress, histopathology, and immune gene expression profile of gilthead sea bream (Sparus aurata) co-infected with Ergasilus sieboldi and Vibrio alginolyticus. RESULTS: Vibrio alginolyticus and Ergasilus sieboldi were identified using 16 S rRNA and 28 S rRNA sequencing, respectively. The collagenase virulence gene was found in all Vibrio alginolyticus isolates, and the multiple antimicrobial resistance index ranged from 0.286 to 0.857. Oxidant-antioxidant parameters in the gills, skin, and muscles of naturally infected fish revealed increased lipid peroxidation levels and a decrease in catalase and glutathione antioxidant activities. Moreover, naturally co-infected gilthead sea bream exhibited substantial up-regulation of il-1ß, tnf-α, and cyp1a1. Ergasilus sieboldi encircled gill lamellae with its second antennae, exhibited severe gill architectural deformation with extensive eosinophilic granular cell infiltration. Vibrio alginolyticus infection caused skin and muscle necrosis in gilthead sea bream. CONCLUSION: This study described some details about the gill, skin and muscle tissue defense mechanisms of gilthead sea bream against Ergasilus sieboldi and Vibrio alginolyticus co-infections. The prevalence of co-infections was 100%, and no resistant fish were detected. These co-infections imbalance the health status of the fish by hampering the oxidant-antioxidant mechanisms and proinflammatory/inflammatory immune genes to a more detrimental side. Our results suggest that simultaneous screening for bacterial and parasitic pathogens should be considered.

Using the Health Belief Model to assess COVID-19 perceptions and behaviours among a group of Egyptian adults: a cross-sectional study.

BACKGROUND: It is crucial to study the public's perceptions and behaviour during a pandemic as this will be the driving force for practicing recommended precautions. The current study aimed to identify perceptions of a group of Egyptian adults to COVID-19 using the Health Belief Model (HBM), to measure self-reported practice of preventive behaviours and to identify influencing factors. METHODS: Cross sectional study was used, including Egyptian adults aged 18 + years. A structured anonymous online questionnaire was used including: a demographic section, the modified MERS- CoV Health Belief Model scale after addition of questions related to COVID-19 and questions on preventive behaviours to COVID-19. RESULTS: Of the 532 study participants, 28.6% were males, age ranges (18 to 74 years). There was a statistically significant positive correlation between total practice score and all COVID-19 Health Belief Model constructs total scores except for perceived barriers score showing negative correlation (P value < 0.05). Linear regression analysis showed that older age, male gender and living inside Cairo were associated with lower practice score (P value < 0.01). CONCLUSIONS: Increased perceived susceptibility, perceived benefits, cues to action and perceived self-efficacy scores were associated with higher practice score in the current study. Additionally, results revealed that social media and websites can play an important role in shaping risk perception in the community. Stressing risk perception and efficacy beliefs prevention message can drive people to practice preventive behaviors.

Synergistic effect of arginine and Lactobacillus plantarum against potassium dichromate induced-acute liver and kidney injury in rats: Role of iNOS and TLR4/NF-κB signaling pathways.

Objectives: Our study was conducted to evaluate the synergistic effect of arginine (ARG) and Lactobacillus plantarum against potassium dichromate (K2Cr2O7) induced-acute hepatic and kidney injury. Materials and Methods: Fifty male Wistar rats were divided into five groups. The control group received distilled water. The potassium dichromate group (PDC) received a single dose of PDC (20 mg/kg; SC). The arginine group (ARG) and Lactobacillus plantarum group received either daily doses of ARG (100 mg/kg, PO) or L. plantarum (109 CFU/ml, PO) for 14 days. The combination group (ARG+L. plantarum) received daily doses of ARG (100 mg/kg) with L. plantarum (109 CFU/ml), orally for 14 days, before induction of acute liver and kidney injury. Forty eight hours after the last dose of PDC, serum biochemical indices, oxidative stress biomarkers, pro-inflammatory cytokines, histopathological and immunohistochemical analysis were evaluated. Results: Combining ARG with L. plantarum restored the levels of serum hepatic & kidney enzymes, hepatic & renal oxidative stress biomarkers, and TLR 4/ NF-κB signaling pathway. Furthermore, they succeeded in decreasing the expression of iNOS and ameliorate the hepatic and renal markers of apoptosis: Caspase-3, Bax, and Bcl2. Conclusion: This study depicts that combining ARG with L. plantarum exerted a new bacteriotherapy against hepatic and renal injury caused by PDC.

Neuromodulatory role of L-arginine: nitric oxide precursor against thioacetamide-induced-hepatic encephalopathy in rats via downregulation of NF-κB-mediated apoptosis.

The aim of the present study was to investigate the impact of arginine (ARG), a nitric oxide (NO) precursor, on thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats by injection of TAA (100 mg/kg, i.p) three times per week for six consecutive weeks. TAA-injected rats were administered ARG (100 mg/kg; p.o.) concurrently with TAA for the six consecutive weeks. Blood samples were withdrawn, and rats were sacrificed; liver and brain tissues were isolated. Results of the present study demonstrated that ARG administration to TAA-injected rats revealed a restoration in the serum and brain ammonia levels as well as serum aspartate transaminase, alanine transaminase, and alkaline phosphatase and total bilirubin levels as well as behavioral alterations evidenced by restoration in locomotor activity, motor skill performance, and memory impairment. ARG showed also improvement in the hepatic and neuro-biochemical values, pro-inflammatory cytokines, and oxidative stress biomarkers. All these results were confirmed by histopathological evaluation as well as ultrastructural imaging of the cerebellum using a transmission electron microscope. Furthermore, treatment with ARG could ameliorate the immunological reactivity of nuclear factor erythroid-2-related factor 2 (Nrf2) and cleaved caspase-3 proteins in the cerebellum and hepatic tissues. From all the previous results, it can be fulfilled that ARG showed a beneficial role in modulating the adverse complications associated with TAA-induced HE in rats via reducing hyperammonemia and downregulating nuclear factor kappa B (NF-κB)-mediated apoptosis.

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway.

Clinical manifestation of gastric ulcers is frequent, in addition to their costly drug regimens, warranting the development of novel drugs at lower costs. Although Bassia indica is well characterized for its anti-inflammatory and antioxidant potential, capacity of its ethanol extract (BIEE) to prevent stomach ulcers' progression has not been reported. A nuclear protein termed high-mobility group box 1 (HMGB1) plays a key role in the formation of stomach ulcers by triggering a number of inflammatory responses. The main purpose of the current investigation was to evaluate the in vivo anti-inflammatory and anti-ulcerogenic capabilities of BIEE against ethanol-induced gastric ulcers in rats via the HMGB1/TLR-4/NF-B signaling pathway. HMGB1 and Nuclear factor kappa (NF-B) expression, IL-1ß and Nrf2 contents showed an increase along with ulcer development, concurrent with an increase in immunohistochemical TLR-4 level. In contrast, pre-treatment with BIEE significantly reduced HMGB1 and Nuclear factor kappa (NF-B) expression levels, IL-1ß and Nrf2 contents and ulcer index value. Such protective action was further confirmed based on histological and immunohistochemical TLR-4 assays. Untargeted analysis via UPLC-ESI-Qtof-MS has allowed for the comprehensive characterization of 40 metabolites in BIEE mostly belonged to two main chemical classes, viz., flavonoids and lipids. These key metabolites, particularly flavonoids, suggesting a mediation for the anti-inflammatory and anti-ulcerogenic properties of BIEE, pose it as a promising natural drug regimen for treatment of stomach ulcers.

Effects of oleic acid and/or exercise on diet-induced thermogenesis and obesity in rats: involvement of beige adipocyte differentiation and macrophage M1 inhibition.

Background and purpose: Obesity is a public health problem and the existence of beige adipocytes has got interested as a potential therapeutic involvement for obesity and obesity-associated diseases. Adipose tissue M1 macrophage inhibition, also, has a vital role in obesity via down-regulating adipose tissue inflammation and the use of natural compounds such as oleic acid with exercise has been proposed. The present study aimed to evaluate the possible effects of oleic acid and exercise on diet-induced thermogenesis and obesity in rats. Experimental approach: Wister albino rats were categorized into six groups. Group I: normal control, group II: oleic acid group (9.8 mg/kg; orally), group III: high-fat diet (HFD), group IV: HFD plus oleic acid, group V: HFD plus exercise training, group VI: HFD plus exercise training and oleic acid. Findings/Results: Oleic acid administration and/or exercise significantly decreased body weight, TG, and cholesterol, as well as elevated HDL levels. Furthermore, oleic acid administration and/or exercise reduced serum MDA, TNF-α, and IL-6 levels, elevated the levels of GSH and irisin, increased the expression of UCP1, CD137, and CD206, and reduced CD11c expression. Conclusion and implications: Oleic acid supplementation and/or exercise could be used as therapeutic agents for treating obesity via its antioxidant and anti-inflammatory activities, stimulation of beige adipocyte differentiation, and macrophage M1 inhibition.

The Experience of Palliative Care Nurses in Qatar During the Time of COVID-19: A Qualitative Study.

BACKGROUND: The COVID-19 pandemic has been a source of significant confusion and fear for healthcare workers as they try to maintain some sense of normalcy within their daily practices. One of the many areas affected by this pandemic has been palliative care. Palliative care nurses were thrust into a world of chaos as they faced increasing numbers of patients who were in the process of dying. PURPOSE: The aim of this research was to explore the caring experiences of palliative care nurses during the COVID-19 pandemic. METHODS: A qualitative interpretive description design was used to explore the experience of nurses caring for dying patients in a palliative care unit during the COVID-19 pandemic. Twenty-two nurses working in a palliative care unit participated in this study. Data were collected during 1.5- to 2-hour focus group sessions that were guided by open-ended questions. RESULTS: The collected data were analyzed and coded into themes, including (a) transitioning to the new normal, (b) ethical dilemmas, and (c) collaboration and support for fellow colleagues. CONCLUSIONS: Although the COVID-19 pandemic has not yet ended, this study provides relevant implications for practice. These implications include (a) holding continuing education sessions to help nurses better understand the meaning of pandemic conditions and how best to respond and (b) supporting nurses to better cope with the additional burdens faced because of increased patient loads. Overall, the nurses in this study were shown to have demonstrated reliance and resilience in the face of COVID-19.

Cytokine modulation by etanercept ameliorates metabolic syndrome and its related complications induced in rats administered a high-fat high-fructose diet.

The aim of the present study was to investigate the effect of etanercept (ETA)-an anti-tumor necrosis factor α (TNF-α) monoclonal antibody-on metabolic disorders such as obesity, hypertension, dyslipidemia, and insulin resistance associated with the metabolic syndrome (MS). MS was induced in rats via high-fat high-fructose (HFHF) administration for 8 weeks. Rats were divided into three groups: negative control, HFHF model, and ETA-treated groups [HFHF + ETA (0.8 mg/kg/twice weekly, subcutaneously) administered in the last 4 weeks]. ETA effectively diminished the prominent features of MS via a significant reduction in the percent body weight gain along with the modulation of adipokine levels, resulting in a significant elevation of serum adiponectin consistent with TNF-α and serum leptin level normalization. Moreover, ETA enhanced dyslipidemia and the elevated blood pressure. ETA managed the prominent features of MS and its associated complications via the downregulation of the hepatic inflammatory pathway that induces nonalcoholic steatohepatitis (NASH)-from the expression of Toll-like receptor 4, nuclear factor kappa B, and TNF-α until that of transforming growth factor-in addition to significant improvements in glucose utilization, insulin sensitivity, and liver function parameter activity and histopathological examination. ETA was effective for the treatment of all prominent features of MS and its associated complications, such as type II diabetes mellitus and NASH.

Modulatory effect of dietary probiotic and prebiotic supplementation on growth, immuno-biochemical alterations, DNA damage, and pathological changes in E. coli-infected broiler chicks.

Avian pathogenic Escherichia coli is one of the principal causes of heavy economic losses to the poultry industry. Little is known about the underlying mechanisms, particularly the potential role of immunoglobulin A and the DNA damage, involving the beneficial effects of dietary supplementation of probiotics and prebiotics in avian colibacillosis. The current study investigated the potential effects of probiotic and prebiotic dietary supplementation on E. coli-infected broiler chicks. A total of 120 1-day-old unsexed Hubbard chicks were divided into six groups: Group 1 was considered as a negative control; Group 2 was supplemented with 1 g/kg feed of Lactobacillus plantarum; Group 3 was supplemented with amylase enzyme; Group 4 served as a positive control infected orally by E. coli O78; Group 5 was supplemented with L. plantarum from 1-day-old chicken and then infected orally with E. coli O78; and Group 6 was supplemented with amylase enzyme from 1-day old chicken and then infected orally with E. coli O78. For all examined groups, the experimental period lasted for 42 days. The E. coli-infected group revealed a decrease in body performance parameters with a significant increase in the liver enzymes and renal function tests. The same group recorded a significant decrease in serum total proteins, albumins, and globulins, and the alteration of immunological parameters, antioxidant enzymes, oxidative stress parameters, and comet assay revealed highly damaged DNA in the liver and the intestine. By histopathological examination, a series of histopathological changes in the liver, the kidney, and the intestine were observed. The infected chick pretreated with probiotics or prebiotics demonstrated an improvement in body performance parameters besides a significant decrease in the hepatic enzymes and renal function tests. We noticed that, in treated groups, there was a significant increase in serum total proteins in the serum albumin and globulin levels, immunological parameters, and antioxidant enzymes. Furthermore, DNA damage and histopathological changes within hepatic, renal, and intestinal tissues were markedly diminished in the treated groups compared with the infected group. We concluded that the adverse effects of E. coli could be modulated through the chemopreventive administration of probiotics and prebiotics.

Ameliorative effect of chitosan nanoparticles against carbon tetrachloride-induced nephrotoxicity in Wistar rats.

CONTEXT: Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications. OBJECTIVE: This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats. MATERIALS AND METHODS: Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl4-induced nephrotoxicity (untreated), and two groups receiving CCl4 + chitosan NPs (10 and 20 mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-κB and COX-2 in renal tissues. RESULTS: Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20 mg/kg) concurrently with CCl4 for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20 mg/kg) revealed a significant (p ˂ 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-α (33.6%), interleukin-1ß (31.1%), and caspase-3 (36.6%). CONCLUSIONS: Chitosan nanoparticles afforded significant protection and amelioration against CCl4-induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications.

Doxorubicin-induced hepatic toxicity in rats: Mechanistic protective role of Omega-3 fatty acids through Nrf2/HO-1 activation and PI3K/Akt/GSK-3ß axis modulation.

Doxorubicin (DOX), a common antibiotic used to treat a variety of tumors, has several substantial adverse effects that limit its clinical use. As a result, finding effective protective agents to combat DOX-induced organ damage is a necessity. The current study was set to delineate the hepatoprotective role of omega-3 fatty acids (ω-3FA) against DOX-mediated acute liver damage in rats and the underlined mechanism of GSK-3ß inhibition. Five groups of rats were orally received either saline (groups 1 & 2) or ω-3FA (25, 50 and 100 mg/kg/day; groups 3, 4 & 5, respectively) for 28 consecutive days. Single DOX intraperitoneal injection (20 mg/kg) was used to induce hepatic toxicity in all groups except group 1 (negative control). Blood samples and liver tissues were collected 48-hr after injection. Our results revealed that pre-administration of ω-3FA (25, 50 and 100 mg/kg) to DOX-induced hepatic injured rats showed a significant reduction in serum hepatic injury biomarkers (ALT, AST, total and direct bilirubin) as well as hepatic contents of MDA, GSH, Nrf2 and HO-1. Additionally, hepatic PI3K, pAkt and GSK-3ß have been restored significantly in a dose-dependent manner. Furthermore, all the hepatic histopathological features have been retained upon ω-3FA treatment together with the immunostaining intensity of tumor necrosis factor-α and caspase-3. These results suggest that ω-3FA have shown a marked activation of the Nrf2/HO-1 signaling pathway and modulation of the PI3K/pAkt/GSK-3ß axis against DOX-induced hepatotoxicity.

Pharmacological and metabolomic profiles of Musa acuminata wastes as a new potential source of anti-ulcerative colitis agents.

Musa acuminata (MA) is a popular fruit peels in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic approaches were found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS2 fragmentation and NMR spectroscopy. These include: cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside; gallic acid and flavonoids; quercetin, quercetin-3-O-ß-D-glucoside, luteolin-7-O-ß-D-glucopyranoside. GC/MS analysis of MA peels essential oil led to identification of 37 compounds. The leaves, pseudostem and fruit peels extracts were tested for their safety and their anti-ulcerative colitis efficacy in rats. Rats were classified into: normal, positive, prednisolone reference group, MA extracts pretreated groups (250-500 mg/kg) for 2 weeks followed by induction of ulcerative colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examinations were done. Inflammatory markers (ANCA, CRP and Ilß6) were measured in sera. The butanol extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of ulcerative colitis and lowered the inflammatory markers compared to untreated group. MA wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-ulcerative colitis food supplements.

Evaluating Pain Management Practices for Cancer Patients among Health Professionals: A Global Survey.

Background: Cancer incidence in the world is predicted to increase in the next decade. While progress has been in diagnosis and treatment, much still remains to be done to improve cancer pain therapy, mainly in underserved communities in low-income countries. Objective: To determine knowledge, beliefs, and barriers regarding pain management in both high- and low-income countries (according to the WHO classification); and to learn about ways to improve the current state of affairs. Design: Descriptive survey. Setting/Subjects: Fifty-six countries worldwide; convenience sample of 1639 consisted of 36.8% physicians; 45.1% nurses, and 4.5% pharmacists employed in varied settings. Results: Improved pain management services are key elements. Top barriers include religion factors, lack of appropriate education and training at all levels, nonadherence to guidelines, patients' reluctance to report on pains, over regulation associated with prescribing and access to opioid analgesics, fear of addiction to opioids, and lack of discussions around prognosis and treatment planning. Conclusion: The majority of patients with cancer in low-income countries are undertreated for their pain. Promoting cancer pain accredited program of training and education on pain management for physicians and nurses is crucial, as well as advocating policymakers and the public at large.

Curcumin nanoemulsion ameliorates brain injury in diabetic rats.

Diabetes mellitus has been implicated in the exacerbation of cerebral ischemic injuries. Among the most promising therapeutic approaches is the combination of nutraceuticals and nanotechnology. Curcumin has been termed "the magic molecule", and it was proven to exert several therapeutic actions. Therefore, the aim of the presented work was to investigate the therapeutic effects of curcumin nanoemulsion (NC) administered orally on the middle cerebral artery occlusion and reperfusion (MCAO/Re)-induced cerebral damage in rats with streptozotocin-induced diabetes. The cerebral injury was induced in rats by MCAO/Re 6 weeks after single intraperitoneal STZ injection (50 mg/kg; i.p.). MCAO/Re diabetic rats were then treated with NC (50 and 100 mg/kg; bw; p.o.) for two consecutive weeks. The results of the present study showed that oral treatment of MCAO/Re diabetic rats with NC was associated with a marked attenuation of the neurological deficit score as well as the brain imbalance of the redox homeostasis. NC treatment was also associated with decline in the brain expression of tumor necrosis factor, interleukin-1ß, COX-2, cleaved caspase-3, and nuclear factor kappa B. In addition, the expression of glucose transporter 1 proteins upon treatment was restored. PRACTICAL APPLICATIONS: From all these results, it can be concluded that oral supplementation of curcumin nanoemulsion (NC) in diabetic rats reduced the brain injury via augmentation of the expression of glucose transporter 1, as well as its antioxidant and anti-inflammatory properties. Therefore, NC could be delineated as a promising treatment option for cerebral ischemia in diabetic patients.

Iron supplementation ameliorates aloin-induced iron deficiency anemia in rats.

Aloin, an anthraquinone glycoside, is one of other C-glycosides found in the leaf exudate of Aloe plant. Aloin possesses several biologic activities, including antitumor activity in vitro and in vivo. However, aloin treatment has shown iron deficiency anemia and erythropoiesis in vivo. The present study was undertaken to verify if iron supplementation could alleviate these perturbations, compared to doxorubicin, an anthracycline analog. Oral iron supplementation (20.56 mg elemental Fe/kg bw) to aloin-treated rats normalized red blood corpuscles count, hemoglobin concentration, and serum levels of total iron binding capacity and saturated transferrin, as well as hepatic iron content, hepcidin level, and mRNA expression of ferritin heavy chain (Ferr-H) and transferrin receptor-1 (TfR-1) genes. Although, serum hyperferremia, and leukocytosis were maintained, yet the spleen iron overload was substantially modulated. However, combined aloin and iron treatment increased iron storage levels in the heart and bone marrow, compared to aloin treatment per se. On other hand, oral iron supplementation to rats treated with doxorubicin (15 mg/kg bw) lessened the increase in the spleen iron content concomitantly with hepatic hepcidin level, rebound hepatic iron content to normal level, and by contrast augmented serum levels of iron and transferrin saturation. Also, activated Ferr-H mRNA expression and repressed TfR-1 mRNA expression were recorded, compared to doxorubicin treatment per se. Histopathological examination of the major body iron stores in rats supplemented with iron along with aloin or doxorubicin showed an increase in extramedullary hematopoiesis. In conclusion, iron supplementation restores the disturbances in iron homeostasis and erythropoiesis induced by aloin treatment.