Effect of dapagliflozin against NAFLD and dyslipidemia in type 2 diabetic albino rats: possible underlying mechanisms.

OBJECTIVE: The aim was to investigate the effect of dapagliflozin on non-alcoholic fatty liver disease and dyslipidemia in type 2 diabetic rats by studying the histopathological structure of the liver and detecting possible underlying mechanisms for this impact by evaluating the potential anti-inflammatory action of dapagliflozin. MATERIALS AND METHODS: 100 albino rats were used in this work and divided into five equal groups: group I (Control group), group II (Control diabetic group), group III (was administered dapagliflozin, 0.75 mg/kg, p.o.), group IV (was administered dapagliflozin, 1.5 mg/kg, p.o.), and group V (was administered dapagliflozin, 3 mg/kg, p.o.). RESULTS: In our study, the total body weight, liver weight, liver index, blood glucose level, insulin level, insulin resistance, total cholesterol, triglycerides, liver enzymes, IL-1 ß, and MDA were significantly higher in the control diabetic group than the normal group. The dapagliflozin reduced all the above variables significantly in a dose-dependent manner compared to the control diabetic group (p-value = 0.001 for all). CONCLUSIONS: Dapagliflozin may be a promising novel treatment strategy for treating T2DM-related non-alcoholic fatty liver disease (NAFLD), and dyslipidemia where it possesses anti-oxidative, anti-inflammatory and anti-dyslipidemic effects.

The regulation of HBP1, SIRT1, and SREBP-1c genes and the related microRNAs in non-alcoholic fatty liver rats: The association with the folic acid anti-steatosis.

Folic acid is one of the vital micronutrients that contribute to the genetic stability and other biological activities. In addition, microRNAs regulate gene expression through a multittude of pathways. Our current work aimd to explore the possible ameliorative potency of folic acid and its association with the hepatic miR-21, -34a, and -122 expression as well as their targeted genes, HBP1, SIRT1, and SREBP-1c in rats with non-alcoholic fatty liver disease (NAFL). A total of 50 Wistar rats were randomly divided into two groups, a control group (n = 10) and NAFL group (n = 40). Rats in NAFL group were fed a high-fat diet (HFD) containing 20% fats for 14 weeks. The NAFL group was further subdivided into four groups (n = 10/group), one untreated and three orally folic acid-treated groups (25, 50, and 75 µg/Kg b.wt). NAFL characteristics was evaluated in rats in addition to the miR-21, -34a, and -122 profile as well as the transcriptional levels of HBP1, SIRT1, and SREBP-1c genes. NAFL rats exhibited the classic traits of fatty liver disease profile and dysregulation in the pattern of miR-21, -34a, and -122 expression as well as their targeted genes (HBP1, SIRT1, and SREBP-1c, respectively) in the liver. Additionally, NAFL rats had altered levels of TNF-α and adiponectin. These alterations were significantly ameliorated in a dose-dependent pattern following the folic acid treatments. In conclusions, the anti-steatotic, insulin-sensitizing, glucose-lowering and lipotropic potencies of folic acid in NAFL rats may be linked to the epigenetic modulation of the hepatic microRNAs (miR-21, -34a, and -122) and the expression of their target genes (HBP1, SIRT1, and SREBP-1c).

Contrasting alien effects on native diversity along biotic and abiotic gradients in an arid protected area.

Alien impact on native diversity could be a function of both the relatedness of alien species to native community and resources availability. Here, we investigated whether alien plants expand or decrease the functional and phylogenetic space of native plant communities, and how this is affected by alien relatedness to natives and by resources availability. We used a trait-environment dataset of 33 alien and 130 native plants in 83 pairs of invaded and non-invaded plots, covering a gradient of soil resources (organic matter-nitrogen) in Saint-Katherine-Protectorate, Egypt. First, we compared the changes in native composition and calculated alien relatedness to natives within each pair of plots. Second, we tested the effects of resources availability and relatedness on the magnitude of alien impact (defined as a change in native diversity). We found that native composition was phylogenetically less but functionally more diverse in invaded plots compared to non-invaded ones. Moreover, in resources-rich plots, dissimilar aliens to natives significantly increased native diversity, while in resource-limited ones, similar aliens to natives declined native diversity. These results suggest that the assessment of alien impacts in arid-regions is significantly linked to resources-availability and relatedness to natives. Hence, future studies should test the generality of our findings in different environments.

Preliminary study on the possible impact of Thalassodendron ciliatum (Forss.) den Hartog acidic polysaccharide fractions against TAA induced liver failure.

The water-soluble acidic polysaccharide from Thalassodendron ciliatum (Forss.) den Hartog was successfully extracted, fractionated and purified. The phytochemical profile of the two water-soluble fractions (F1 and F2), were detected using different analytic techniques. GC-MS analysis revealed the presence of 22 saccharide. Acidic polysaccharide, galacturonic and glucuronic acid were the most abundant. Moreover, paper chromatography and electrophoresis also performed as a preliminary chemical characterization of the polymer. The hepatoprotective activity of the fractions against thioacetamide (TAA) induced liver failure; antioxidant potential and preliminary immunomodulatory activity were assigned in-vivo. The results revealed a potent competence to improve the liver function profile (ALT, AST, total bilirubin, total glyceride, etc.) and a remarkable improvement in liver architecture in comparison to the challenged intoxicated groups. Moreover, they showed high anti-oxidative properties and a promising immunomodulatory influence via Il6. These findings provide new insight into the possible role of polysaccharide purified two fractions in the treatment of acute liver injury.

Real world analysis of high-cut-off (HCO) hemodialysis with bortezomib-based backbone therapy in patients with multiple myeloma and acute kidney injury.

BACKGROUND: In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. METHODS: Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. RESULTS: The median number of HCO hemodialysis sessions was 11 (range 1-42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. CONCLUSION: The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.

Maturation of Atriplex halimus L. leaves involves changes in the molecular regulation of stomatal conductance under high evaporative demand and high but not low soil water content.

MAIN CONCLUSION: Under high water availability, the maximum gas exchange was observed at noon in the expanding and expanded leaves. The expanded leaves showed lower gas exchange capacity due to the regulation of stomatal-movement genes. Under well-watered condition, stomatal conductance (gs) and photosynthetic rate (A) of expanding and expanded leaves of Atriplex halimus peaked at noon despite the midday decline in the leaf relative water content, suggesting deviation from typical isohydric behaviour. However, the expanding leaves had higher gs and A than the expanded ones. When light intensity was temporarily increased, A and gs were enhanced in both types of leaves though to a higher level in the expanding leaves. In well-watered expanded leaves: (1) A was mainly dependent on gs rather than photosynthetic capacity; gs was controlled by internal factors, thereby limiting water loss via transpiration (E); (2) the accumulation of total soluble sugars (TSS) along with increased Rubisco protein could be a subsidiary factor limiting A; (3) TSS and ABA seem to act in co-ordination to up-regulate ABA-dependent genes controlling gs and (4) the significant induction of DREBs suggests a role in maintaining high relative water content in these leaves compared to the expanding ones. In expanding leaves of well-watered plants, high A along with Rubisco down-regulation and elevated TSS suggests that A was regulated by signals coordinating carbon and nitrogen balance and the elevated ABA could be involved in regulating the hydraulic activity to enhance cell expansion and facilitate leaf growth. Both expanded and expanding leaves behaved in typical isohydric manner under water stress, which did not involve the accumulation of ABA suggesting that stomatal closure was primarily stimulated by hydraulic rather than chemical signals.

Rats' urinary metabolomes reveal the potential roles of functional foods and exercise in obesity management.

The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).

Colonic Atresia: Association with Other Anomalies.

BACKGROUND: Colonic atresia (CA) is a rare form of congenital intestinal atresia. Although CA may be isolated, it is more commonly reported in literature in association with other congenital anomalies. MATERIALS AND METHODS: This study is a review of prospectively collected data of all the patients with colonic atresia presented to our center (Ain Shams University) during 2008 to 2016. RESULTS: Twelve patients were enrolled in this study. The atresia was of type I in one case, type II in four cases, type IIIa in six cases, type IV in one case. These cases accounted for 4.9 % of intestinal atresias managed in our center during the same period. Five cases were isolated CA, while the other seven cases had associated abdominal congenital anomalies (exomphalos, Hirschsprung's disease, imperforate anus, closing gastroschisis, colonic duplication, and multiple small bowel atresia in two cases). The management in ten cases was by staged procedure with creation of a temporary stoma initially, while primary anastomosis was established in two cases. We had two cases with delayed presentations, one missed diagnosis, and three mortalities in this series. CONCLUSIONS: The low incidence of CA may result in delay in the diagnosis and management. Hirschsprung's disease should be excluded in every case of colonic atresia. Early diagnosis and proper surgical management is essential for good prognosis.

New polyhydroxylated sterols from Palythoa tuberculosa and their apoptotic activity in cancer cells.

The chemical study on the total extract of the zoanthid Palythoa tuberculosa, collected from the Red Sea, resulted in the isolation of seven polyhydroxylated sterols (1-7), six of which, palysterols A-F (2-7), are new. Their chemical structures were elucidated on the basis of extensive analysis of their 1-, 2D NMR and MS spectroscopic data. This is the first chemical investigation on the species collected from Red Sea. We studied the cytotoxic effects of the total extract and some of the new polyhydroxylated sterols in three human cancer cell lines (MCF-7, HeLa, and HT-29) and one non-cancerous human cell line (KMST-6). Palysterol F (7), in particular, was able to selectively induce high levels of apoptosis (>75%) in breast adenocarcinoma (MCF-7) cells but not HeLa, HT-29 and KMST-6 cells.

Management of intrahepatic stones: the role of subcutaneous hepaticojejunal access loop. A prospective cohort study.

BACKGROUND: Patients with intrahepatic stones usually present with recurrent cholangitis, biliary sepsis and intrahepatic abscesses, may develop liver atrophy and may progress to cholangiocarcinoma. Treatment of intrahepatic stones is difficult and the disease progresses in most patients even after adequate treatment. Surgical removal of stones has been the standard management but residual stones and stone recurrence occur frequently whatever the technique. Because of the need for repeated biliary instrumentation, long-term access routes involving percutaneous transhepatic cholangioscopic lithotripsy (PTCSL), hepaticocutaneousjejunostomy (HCJ) and subparietal hepaticojejunal access loop to permit stone retrieval or stricture dilatation have been developed. PURPOSE: The aim of this work was to evaluate the outcome of subcutaneous hepaticojejunal access loop in the management of intrahepatic stones. PATIENTS AND METHODS: Between January 2009 and January 2013, 42 patients with intrahepatic stones underwent surgical treatment at the Gastrointestinal Surgery Unit, Main Alexandria University Hospital. Demographic data, details of operative findings, follow up details, and treatment of recurrent stones were analyzed. After approval of local ethics committee, all patients included in the study were informed well about the procedure and an informed written consent was obtained from every patient before carrying the procedure. RESULTS: Forty-two patients (17 males and 25 females) with intrahepatic stones underwent surgery with construction of a subcutaneous hepaticojejunal access loop. Stones were confined to the left lobe in 25 patients, the right lobe in 3 patients and bilobar in 14 patients. Associated extrahepatic stones were found in 33 patients. Twenty-two patients had associated intrahepatic duct strictures. Five patients with atrophy of segments II and III underwent hepatic resection at the time of access loop formation. The mean operation time was 4.9 h and mean blood loss was 440 mL. Mean postoperative hospital stay was 10 days. Wound infection was the commonest complication, occurring in 5 (12%) patients. There were no specific complications attributable to the construction of the access loop. The subcutaneous access loop was used to gain access to the biliary tree in 28 patients with residual or recurrent stones. A total of 55 procedures (range 1-5) were attempted with successful access achieved in all cases and successful stone clearance in 21 of the 28 patients, and all of them were symptom free for at least 12 months after the last procedure. Partial stone clearance was achieved in the remaining seven patients. These seven patients had different degrees of biliary strictures. CONCLUSION: The subcutaneous access loop offers the advantage of permanent access for the successful management of retained or re-formed intrahepatic stones with minimal morbidity since it permitted easy access to intrahepatic ducts using the conventional forward-viewing endoscope or the choledochoscope, without the additional morbidity of a biliary-cutaneous fistula or transhepatic access.

Anti-influenza A virus activity of a new dihydrochalcone diglycoside isolated from the Egyptian seagrass Thalassodendron ciliatum (Forsk.) den Hartog.

One new dihydrochalcone diglycoside has been isolated from the EtOAc fraction of the Egyptian seagrass Thalassodendrin ciliatum (Forsk.) den Hartog, and was identified as 6'-O-rhamnosyl-(1‴ → 6″)-glucopyranosyl asebogenin for which a trivial name Thalassodendrone was established. Furthermore, five known phenolics were isolated and identified as asebotin, quercetin 3,7-diglucoside, protocatechuic acid, ferulic acid and p-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and high-resolution-mass spectrometer. High-resolution electrospray ionization mass spectra (HR-ESI-MS) were obtained using a JEOL JMS-T100TD spectrometer (JEOL Ltd., Tokyo, Japan). The anti-influenza A virus activity of the isolated new compound and asebotin was evaluated, and the obtained results revealed that the inhibition dose concentration of asebotin was more than that of Thalassodendrone with IC50 = 2.00 and 1.96 µg/mL, respectively, and with cytotoxic concentration (CC50) of 3.36 and 3.14 µg/mL, respectively.

Development of two electronic bladder diaries: a patient and healthcare professionals pilot study.

AIMS: Assess patients' preferences in a pilot crossover study of two different electronic voiding diaries against a standard paper diary. Assess urological health professional (HP) opinions on the electronic bladder diary reporting system. METHODS: Two different electronic diaries were developed: (1) electronically read diary-a card with predefined slots read by a card reader and (2) e-diary-a handheld touch screen device. Data uploaded from either electronic diary produced an electronic report. We recruited 22 patients split into two cohorts for each electronic diary, 11 completed each type of electronic diary for 3 days either preceded or followed by a standard paper diary for 3 days. Both diaries were completed on the 7th day. Patients' perceptions of both diaries were recorded using a standardized questionnaire. A HP study recruited 22 urologists who were given the paper diary and the electronic reports. Time taken for analysis was recorded along with accuracy and HP preferences. RESULTS: The majority of patients (82%) preferred the e-diary and only 1/11 found it difficult to use. Patients had the same preference for the electronically read diary as the paper diary. The paper diary took 66% longer to analyze than the electronic report (P < 0.001) and was analyzed with an accuracy of 58% compared to 100%. Slightly more HP (9%) preferred the electronic report to the paper diary. CONCLUSIONS: This proposed e-diary with its intuitive interface has overcome previous deficiencies in electronic diaries with most patients finding the format user-friendly. Electronic reports make analysis and interpretation by HP quicker and more accurate.

Solvation effects on self-association and segregation processes in tert-butanol-aprotic solvent binary mixtures.

The present study reveals that the fully miscible binary mixtures consisting of tert-butanol with aprotic solvents form well-defined ordered supermolecular structures, which have been characterized on different length scales. Three different types of microstructures have been determined. They are separated by distinct crossovers that appear as a function of the dilution rate, going from "correlated clusters" to "diluted clusters" and "diluted monomer" microstructures. These observations have been made possible by the combination of Raman vibration spectroscopy, (1)H NMR, and neutron diffraction that probe, respectively, the cluster formation (self-association) and the intercluster correlations (cluster segregation). The solvation effects on both the cluster formation and the intercluster correlations have been assessed by tuning the alcohol-solvent interaction, i.e., changing the chemical nature of the diluting solvent from a purely inert alkane to a weakly interacting aromatic system.

Bioactive terpenoids from the Red Sea soft coral Sinularia polydactyla.

Chemical investigation of an ethyl acetate soluble fraction of Sinularia polydactyla (Ehrenberg) led to the isolation of three known terpenoides, two of them sterols, 24-methylcholestane-3ß,5α,6ß,25-tetrol 25-monoacetate (1), 24-methylcholestane-5-en-3ß,25-diol (2), in addition to a cembranoid diterpene, durumolide C (3), for the first time. The cytotoxicity and antimicrobial activities of the ethyl acetate extract and the isolated compounds 1-3 were evaluated in vitro. Durumolide C (3) showed selective cytotoxicity against HepG2 (IC50 1.0 µg/mL), whereas 24-methylcholestane-3ß,5α,6ß,25-tetrol 25-monoacetate (1) showed IC50 of 6.1 and 8.2 µg/mL against Hep2 and HCT human cancer cell lines, respectively.

Colonic endolumenal stenting devices and elective surgery versus emergency subtotal/total colectomy in the management of malignant obstructed left colon carcinoma.

BACKGROUND: Traditionally, left-sided acute bowel obstruction is treated by a staged procedure because immediate resection and anastomosis in a massive distended and unprepared colon carries a high complication rate. Total abdominal colectomy is a one-stage procedure that will remove synchronous proximal neoplasms, reduce the risk of subsequent metachronous tumor, and avoid stoma. Colorectal stents are being used for palliation and as a bridge to surgery in obstructing colorectal carcinoma, making elective surgery straightforward, enabling easily mobilization and resection of the colon with a possible trend toward reduction in postoperative complication rates compared to emergency surgery. The purpose of this work was to compare the procedures of endoscopic stenting followed by elective colectomy versus total abdominal colectomy and ileorectal anastomosis in the management of acute obstructed carcinoma of the left colon as regards feasibility, safety, and clinical outcomes METHODS: From January 2009 through May 2012, 60 patients were randomized to either emergency stenting followed by elective resection (ESER group) or total abdominal colectomy and ileorectal anastomosis (TACIR group). RESULTS: Twenty nine patients (96.7 %) had successful stenting and underwent elective surgery 7-10 days later (ESER group). Postoperative complications were encountered in four patients in the ESER group compared to 15 patients in the TACIR group (p = 0.012). Anastomotic leakage was encountered in one patient (3.3 %) in the TACIR group. There were no operative mortalities in the present study. Within the first three postoperative months, the TACIR group patients had significantly more frequent bowel motions per day compared to the ESER group patients although (p = 0.013). In both study groups, the follow-up duration ranged from 6 to 40 months with a median of 18 months. Recurrent disease was encountered in five patients (17.2 %) in the ESER group compared to four patients (13.3 %) in the TACIR group (p = 0.228). CONCLUSION: Both techniques are feasible, safe, and produce comparable oncological outcomes. However, endoscopic stenting followed by elective resection was associated with significantly less postoperative complications and bowel motions per day.

Bioactive phenolic compounds from the Egyptian Red Sea seagrass Thalassodendron ciliatum.

Five flavonoids (rutin, asebotin, 3-hydroxyasebotin, quercetin-3-O-beta-D-xylopyranoside, and a racemic mixture of catechin) and caffeic acid were isolated and identified for the first time from seagrass, Thalassodendron ciliatum, collected from the Hurghada region in Egypt. The crude extract and the isolated pure compounds were evaluated for their cytotoxic activities against HCT-116, HEPG, MCF-7, and HeLa human cancer cell lines, for their antiviral activity against Herpes Simplex and hepatitis A viruses, and for their antioxidant activity.

Cross-section measurements and nuclear model calculation for proton induced nuclear reaction on zirconium.

Proton induced nuclear reactions were measured with stacked-foil technique on natural zirconium targets up to 16.7MeV. Excitation functions were measured for the production of (90,92m,95m,95g,96)Nb and (88)Y. Cumulative cross-section, thick target yields and activation functions were deduced and compared with the available experimental data, as well as with the nuclear models codes; ALICE-IPPE, EMPIRE and TALYS. The integral yields for thick targets were deduced from the measured excitation function of the produced radionuclides.

The protective effects of fish oil and artichoke on hepatocellular carcinoma in rats.

BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the effect of fish oil and Artichoke (Cynara scolymus I.) against diethylnitrosamine (DEN) induced hepatocellular carcinoma in rats. MATERIALS AND METHODS: Animals were divided into 8 groups. Group 1, control rats. Group 2: rats injected with single dose of DEN (100 mg/kg body weight). Groups 3-8 supplemented with different concentrations of either fish oil or artichoke for 25 days before DEN injection. RESULTS: DEN treatment revealed a significant decrease in tissue xanthine oxidase (XO), glutathione, glutathione-s-transferase (GST), and a marked increase in malondialdehyde (MDA) and nitric oxide (NO) levels. Vascular endothelial growth factor (VEGF), alpha-fetoprotein (AFP), and ferritin levels showed a significant increase. A significant increase in serum aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin levels were found. A significant decrease in tissue total proteins and serum albumin was observed. The administration of DEN affected the liver cell through occurrence of hepatic cellular degeneration and necrosis. Treatment with fish oil (5%, 10%) or artichoke heads or leaves (0.5, 1 g) for 25 days led to significant amelioration of DEN-induced changes in the biochemical parameters. An almost normal histological architecture of the liver, in treated groups, was showed as compared to the controls. CONCLUSIONS: The results pointed that 10% fish oil and 1 g% leaves of artichoke succeeded to protect from hepatocellular carcinoma to a certain degree. In addition, they may be considered as protective foods against angiogenesis.

Genetic differences between strains of Biomphalaria glabrata (Planorbidae) that are susceptible and unsusceptible to schistosomiasis.

Despite the implementation control programs, schistosomiasis continues to spread throughout the world. Among modern control strategies, vector control is currently being emphasized. Within this context, analysis of the genetic variability of intermediate host snails (Biomphalaria spp) is important because it allows identification of specific sequences of the genome of this mollusk related to susceptibility/resistance to Schistosoma mansoni infection. We investigated Brazilian albino (non-pigmented) and pigmented (wild type) strains of Biomphalaria glabrata; these strains differ in their susceptibility to S. mansoni infection. Genetic variability was studied by RAPD-PCR using different random primers. The electrophoretic patterns resulting from amplification showed specific polymorphic markers for the albino and pigmented strains of B. glabrata. This information will help in the identification and isolation of genes specifically related to susceptibility, demonstrating that RAPD-PCR is an appropriate and efficient methodological approach for analysis of the genetic variability of schistosomiasis vectors.