Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with oxidative stress that causes excruciating pain, discomfort, and joint destruction. Ebselen (EB), a synthesized versatile organo-selenium compound, protects cells from reactive oxygen species (ROS)-induced injury by mimicking glutathione peroxidase (GPx) action. This study aimed to investigate the antioxidant and anti-inflammatory effects of EB in an arthritic irradiated model. This goal was achieved by subjecting adjuvant-induced arthritis (AIA) rats to fractionated whole body γ-irradiation (2 Gy/fraction once per week for 3 consecutive weeks, for a total dose of 6 Gy) and treating them with EB (20 mg/kg/day, p.o) or methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) as a reference anti-RA drug. The arthritic clinical signs, oxidative stress and antioxidant biomarkers, inflammatory response, expression of NOD-like receptor protein-3 (NLRP-3) inflammasome, receptor activator of nuclear factor κB ligand (RANKL), nuclear factor-κB (NF-κB), apoptotic indicators (caspase 1 and caspase 3), cartilage integrity marker (collagen-II), and histopathological examination of ankle joints were assessed. EB notably improved the severity of arthritic clinical signs, alleviated joint histopathological lesions, modulated oxidative stress and inflammation in serum and synovium, as well as reduced NLRP-3, RANKL, and caspase3 expression while boosting collagen-II expression in the ankle joints of arthritic and arthritic irradiated rats with comparable potency to MTX. Our findings suggest that EB, through its antioxidant and anti-inflammatory properties, has anti-arthritic and radioprotective properties in an arthritic irradiated model.

Serum sclerostin in acute kidney injury patients.

BACKGROUND: Many of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI. OBJECTIVE: We looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome. CASES AND METHODS: This is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away. RESULTS: Serum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P<0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P<0.04), had lower AST (30.5 vs. 58 units, P<0.001), had higher platelet count (206 vs 162×109/L, P<0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r=0.99, P<0.001) and group II (r=1, P<0.001). Homa IR had positive correlation with serum sclerostin (r=0.148, P=0.014) and serum FGF23 (r=0.142, P=0.018) in group I. CONCLUSION: Sclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.

A comparison between different management surgical approaches in the treatment of splenic flexure colon cancer

Background: There are many surgical approaches which described extent of resection of the colon for adequate surgicalmanagement of splenic flexure cancer, but up till now there is no established surgical procedure, this is because the presence of double lymphatic drainage of themesenteric vessels. Segmental resection of the colon for the management of splenic flexure cancer was a recently accepted surgical procedure. Objective: In the present study, we aimed to compare three surgical management techniques to clarify the best management approach of Egyptian patients with splenic flexure cancer regarding operative, clinical, and oncological outcomes: segmental resection, and extended left or right hemicolectomy,. Materials and Methods In the present study, we included 90 patients with splenic flexure cancer. Cases were divided into 3 groups. Each group included 30 patients in order to compare three surgical techniques: segmental resection, extended left hemicolectomy, and extended right hemicolectomy. Results: We have found no statistically significant differences between the three included groups regarding operative findings, postoperative complications, local recurrence, distant recurrence, disease progression, recurrence-free survival rate, progression-free survival rate, and overall survival rate. The operative time was longer, and the number of lymph nodes was higher in the extended right hemicolectomy group (p<0.001). Conclusion: We have shown that segmental resection of the splenic flexure is surgically and clinically suitable for the adequate management of operable cases of carcinoma of the splenic flexure. (AU)

Assessment of pharmacy students' knowledge, attitude, and practice toward herbal dietary supplements.

Objective: Although there has been an expanded use of herbal supplements worldwide, data concerning their consumption patterns and knowledge are limited. Consequently, the present study aimed to assess the knowledge, attitude, and practice of Lebanese pharmacy students toward herbal dietary supplements. Participants and methods: A cross-sectional observational study was conducted by administering a 23-items' survey to a convenient sample of pharmacy students. Results: Out of 355 pharmacy students assessed, 168 were using at least one dietary supplement, mainly to treat health problems. Their primary source of information was the Internet. Health benefits of Ginkgo Biloba were known by 63% while that of Glucosamine by 12%. Similarly, side effects of Ginkgo Biloba were recognized by 62% while that of St. John's Wort by only 2%. Conclusion: Despite the comprehensive coverage of herbal supplements in the pharmacy curriculum, some were weakly known namely; Glucosamine and St. John's Wort. Consequently, emphasis should be done to fill the gap.

Antiproliferative potential of moluccella laevis L. aerial parts family lamiaceae (labiatae), supported by phytochemical investigation and molecular docking study.

The current biologically guided study aimed the in vitro investigation of cytotoxic activity, identification of the phytochemical content of Moluccella laevis L. aerial parts and supporting this activity by a molecular docking study. Aqueous fraction demonstrated the most potent cytotoxic effect against CACO-2 with IC50 = 0.067 ± 0.01 µg/mL. Furthermore, EtOAc fraction showed a remarkable cytotoxic activity against MCF-7 cell line with IC50 = 0.35 ± 0.02 µg/mL. Consequently, total ethanolic extract (TEE) and its fractions were subjected to LC-HR-ESI-MS metabolic profiling to discover the constituents that possibly underlie their cytotoxicity. Twenty compounds were tentatively identified from metabolic analysis. Furthermore, eight compounds were isolated. In silico docking study revealed that stachydrine is more likely to account for the antiproliferative activity of both EtOAc and aqueous fractions, probably via its moderate inhibition of receptor tyrosine kinases. [Formula: see text].

Assessment of Conventional Solvent Extraction vs. Supercritical Fluid Extraction of Khella (Ammi visnaga L.) Furanochromones and Their Cytotoxicity.

BACKGROUND: Khella (Ammi visnaga Lam.) fruits (Apiaceae) are rich in furanochromones, mainly khellin and visnagin, and are thus incorporated in several pharmaceutical products used mainly for treatment of renal stones. METHODS: The objective of this study was to compare the yield of khellin and visnagin obtained using different conventional solvents and supercritical fluid extraction (SCFE) with carbon dioxide (containing 5% methanol as co-solvent). Water, acetone and ethanol (30% and 95%) were selected as conventional solvents. RESULTS: Highest extract yield was obtained from 30% ethanol (15.44%), while SCFE gave the lowest yield (4.50%). However, the percentage of furanochromones were highest in SCFE (30.1%), and lowest in boiling water extract (5.95%). HPLC analysis of conventional solvent extracts showed other coumarins that did not appear in supercritical fluid extraction chromatogram due to non-selectivity of solvent extraction. Ammi visnaga extracts as well as standard khellin and visnagin were tested for their cytotoxic activity using sulforhodamine B assay on breast cancer (MCF-7) and hepatocellular carcinoma (Hep G2) cell lines. Results revealed a strong cytotoxic activity (IC50 < 20 µg/mL) for the SCFE and standard compounds (khellin and visnagin) (IC50 ranging between 12.54 ± 0.57 and 17.53 ± 1.03 µg/mL). However, ethanol and acetone extracts had moderate cytotoxic activity (IC50 20-90 µg/mL) and aqueous extract had a weak activity (IC50 > 90 µg/mL). CONCLUSIONS: Thus, supercritical fluid extraction is an efficient, relatively safe, and cheap technique that yielded a more selective purified extract with better cytotoxic activity.

Indomethacin Analogs: Synthesis, Anti-inflammatory and Analgesic Activities of Indoline Derivatives.

BACKGROUND: Microwave assisted reactions offer a considerable advantages over conventional method reactions because the former results in substantial rate enhancement in a wide range of organic reactions. OBJECTIVE: we interested herein to prepare new anti-inflammatory and analgesic agents analogues to Indomethacin in short reaction time by using microwaves irradiation. METHOD: Synthesis of new hydrazonoindolines having thiazole moiety under microwave irradiation were achieved via the reaction of hydrazonoyl chlorides or halogenated active methylene derivatives with thiosemicarbazone derivatives. Also, the utility of the versatile indoline-2,3-dione derivatives in the design of new multifunctional building blocks using condensation with hydrazine derivatives was demonstrated. RESULTS: All products were formed in short reaction time and high yield. The information derived from the spectral data of the formed compounds was confirmed their structures. Also, the analgesic and antiinflammatory activities of the designed derivatives were screened and the results obtained indicated that six derivatives 4g, 9b, 4c, 10b, 4d and 11a revealed the highest anti-inflammatory and analgesic effects. CONCLUSION: we succeeded in this context to design and synthesis of new anti-inflammatory and analgesic agents analogues to Indomethacin in short reaction time and with high yield.

Bio-energy generation in an affordable, single-chamber microbial fuel cell integrated with adsorption hybrid system: effects of temperature and comparison study.

A microbial fuel cell (MFC) integrated with adsorption system (MFC-AHS) is tested under various operating temperatures with palm oil mill effluent as the substrate. The optimum operating temperature for such system is found to be at ∼35°C with current, power density, internal resistance (Rin), Coulombic efficiency (CE) and maximum chemical oxygen demand (COD) removal of 2.51 ± 0.2 mA, 74 ± 6 mW m-3, 25.4 Ω, 10.65 ± 0.5% and 93.57 ± 1.2%, respectively. Maximum current density increases linearly with temperature at a rate of 0.1772 mA m-2 °C-1, whereas maximum power density was in a polynomial function. The temperature coefficient (Q10) is found to be 1.20 between 15°C and 35°C. Present studies have demonstrated better CE performance when compared to other MFC-AHSs. Generally, MFC-AHS has demonstrated higher COD removals when compared to standalone MFC regardless of operating temperatures. ABBREVIATIONS: ACFF: activated carbon fiber felt; APHA: American Public Health Association; CE: Coulombic efficiency; COD: chemical oxygen demand; ECG: electrocardiogram; GAC: granular activated carbon; GFB: graphite fiber brush; MFC: microbial fuel cell; MFC-AHS: microbial fuel cell integrated with adsorption hybrid system; MFC-GG: microbial fuel cell integrated with graphite granules; POME: palm oil mill effluent; PTFE: polytetrafluoroethylene; SEM: scanning electron microscope.

Performance evaluation of a hybrid system for efficient palm oil mill effluent treatment via an air-cathode, tubular upflow microbial fuel cell coupled with a granular activated carbon adsorption.

An air-cathode MFC-adsorption hybrid system, made from earthen pot was designed and tested for simultaneous wastewater treatment and energy recovery. Such design had demonstrated superior characteristics of low internal resistance (29.3Ω) and favor to low-cost, efficient wastewater treatment and power generation (55mW/m(3)) with average current of 2.13±0.4mA. The performance between MFC-adsorption hybrid system was compared to the standalone adsorption system and results had demonstrated great pollutants removals of the integrated system especially for chemical oxygen demand (COD), biochemical oxygen demand (BOD3), total organic carbon (TOC), total volatile solids (TVS), ammoniacal nitrogen (NH3-N) and total nitrogen (TN) because such system combines the advantages of each individual unit. Besides the typical biological and electrochemical processes that happened in an MFC system, an additional physicochemical process from the activated carbon took place simultaneously in the MFC-adsorption hybrid system which would further improved on the wastewater quality.

Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of insulin and adiponectine receptors, Tyrosine kinase, PI3K, glucose transporters, sRAGE and visfatin in insulin resistant/diabetic rats.

UNLABELLED: As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in several models of diabetes and/or insulin resistance (IR); however, its exact mechanisms have not been profoundly explicated. Hence, the objective of this work is to verify some of the possible mechanisms that underlie its therapeutic efficacy. Moreover, the study aimed to assess the potential modulatory effect of CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2 diabetic model was adopted, in which rats were fed high fat/high fructose diet (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin (35 mg/kg, i.p.). At the end of the 7(th) week animals were treated with CoQ10 (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone opposed the HFFD effect and increased the hepatic/muscular content/activity of tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin receptors. Conversely, it decreased the content/activity of insulin receptor isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA index, improved the serum lipid panel and elevated the levels of glutathione, sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that of glimepiride in almost all the assessed parameters, except for glucose, fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the effect of the latter on the aforementioned parameters. CONCLUSION: These results provided a new insight into the possible mechanisms by which CoQ10 improves insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms involve modulation of insulin and adiponectin receptors, as well as TK, PI3K, glucose transporters, besides improving lipid profile, redox system, sRAGE, and adipocytokines. The study also points to the potential positive effect of CoQ10 as an adds- on to conventional antidiabetic therapies.

Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol-chitosan hydrogel containing honey bee venom in diabetic rats.

Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze-thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same previous composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities.

Complementary medicine use in patients with head and neck cancer in Ireland.

The objectives of the study were: first, to determine the prevalence of traditional medicine (TM) and complementary and alternative medicine (CAM) use in head and neck cancer patients in Ireland; second, to educate ourselves on the plethora of CAM/TM options available to patients outside the dominion of conventional medicine. The study design consisted of a cross-sectional survey carried out in three head and neck cancer centres. Self-administered questionnaires were distributed to 110 head and neck cancer patients attending the three cancer centres and data were collected for statistical analysis. A total of 106 patients completed the questionnaire; 21.7% of the participants used CAM/TM since their diagnosis with head and neck cancer. CAM/TM usage was higher in female (34.3%) than in male patients (16.2%). CAM/TM use was more common in the 41-50-year age group, in patients with higher educational levels and those holding strong religious beliefs, and also in married than single patients. The most common types of CAM/TM used were spiritual and laying on of hands. The most common reasons reported for using CAM/TM were to counteract the ill effects of treatment and increase the body's ability to fight cancer. Sources of information on CAM/TM were friends (65%), family (48%) and media (21%). This survey reveals a high prevalence of CAM/TM use in head and neck cancer patients, hence emphasising the need for otolaryngologists to educate themselves on the various therapies available to be able to provide informative advice. There is an urgent need for evidence-based investigation of various CAM/TM therapies currently offered to patients.