Hepatic insulin resistance and related obesity: highlighting the ameliorative role of nutraceuticals, dietary intervention, and pharmaceuticals.

Insulin resistance (IR) is the unifying denominator of all obesity-related metabolic abnormalities. It possesses a definite higher risk of developing type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). NAFLD is intimately linked to an accumulation of detrimental oxidative intermediates, which in turn promote insulin receptor substrates serine/threonine phosphorylation and ultimately block hepatic insulin signalling, and hepatic IR. The causal relationship between hepatic IR and NAFLD is bidirectional, and hepatic IR itself is "selective" in terms of resisting only insulin's suppressive effects on glucose production while keeping those enhancing hepatic lipogenesis intact. The present Research Topic aims to highlight the effect of natural compounds, dietary intervention, and synthetic drugs on hepatic IR and disorders related to obesity

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 μg/mL, compared to celecoxib drug (IC50 value 251.2 μg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1β. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 μg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.the Faculty of Science, Port Said University and Suez Canal University, EgyptPrincess Nourah bint Abdulrahman University, Riyadh, Saudi Arabiathe Faculty of Medicine, Al-Azhar University, EgyptPeer Reviewe

Desert palm date seeds as a biodiesel feedstock:Extraction, characterization, and engine testing

The development of alternative fuels is increasingly important in order to maintain ongoing global economic and technological progress in the face of fossil fuel depletion and increasing environmental damage. Desert palm date seeds have clear potential as feedstock for biodiesel production given their high oil content and availability as food waste that requires no further cultivation. In this study we investigated the optimum production processes and conditions for date seed oil biodiesel, including characterizing the intermediate product and correcting its composition to meet international fuel standards. Four biodiesel blends were prepared (B5, B10, B15, and B20) and tested in a compression ignition engine at engine speeds from 1600 to 3600 rpm (200 rpm increments) and three engine loads (50%, 75%, and 100%). The highest oil yield and biodiesel conversion achieved were 10.74 wt.% and 92%, respectively. The biodiesel properties conformed well with the standards; the values for brake power, brake thermal efficiency, and brake specific fuel consumption were comparable with petrol diesel, though the latter was slightly superior. All blends produced lower levels of CO2, CO, and HC but higher levels of NOx emissions. These results demonstrate the fundamental suitability of date seeds as biodiesel feedstock, deserving of further research

Effects of Ketosis and Hypocalcemia on The Biochemical Parameters and Subsequent Postpartum Reproductive Performance in Buffaloes

Water buffaloes (Bubalus bubalis) are mainly distributed in tropical and subtropical countries that include the Indian sub-continent and some Mediterranean countries such as Egypt. The transition period is the most stressful period for buffaloes, and it is considered as a turning point in the productive cycle from one lactation to the next and includes different metabolic, physiological, and nutritional changes. Metabolic disorders are common causes of lower productivity in buffaloes. Of these metabolic disorders, ketosis and hypocalcemia are most prevalent. This study aimed to study the ketosis- and hypocalcemia-related biochemical changes during the transition period and their impacts on the postpartum reproductive fertility in Buffaloes. Out of 120 total number of examined buffaloes, 40 buffaloes were used in this study; control group (n=10), hypocalcemia-affected (n=15), and ketosis-affected group (n=15). All buffaloes were subjected to thorough clinical and gynecological examination. Both urine and blood samples were collected from all groups. The amounts of ketone bodies were detected in urine. Biochemical parameters were evaluated including concentrations of glucose, triglycerides, cholesterol, non-esterified fatty acids (NEFA), calcium, phosphorus, sodium, potassium, albumin, total protein, urea and progesterone hormone (P4) in blood the following time-points (2-weeks prepartum, 1-week prepartum, partum, 1-week postpartum, and 2-weeks postpartum). Both hypocalcemia- and ketosis affected buffaloes had lower glucose, phosphorus, sodium and albumin and higher NEFA than control group. Hypocalcemia-affected buffaloes showed lower calcium and higher total protein than control group, while, ketosis-affected buffaloes showed lower cholesterol and total protein than control group. Moreover, metabolic disorders negatively affected the reproductive performance. Both ketosis and hypocalcemia significantly prolonged the duration to first estrus, increased both the number of days-open and the number of services per conceptio

Hydatid cyst of the quadrigeminal cistern: A case report for unusual location with literature review

Intracranial hydatid cyst involves supratentorial area and mainly affecting the middle cerebral artery territory with the predilection of the partial lobe. It can be single - which is the most common - or multiple up to 35 cysts. They tend to be huge at the time of symptomatic presentation especially when they are presented as a solitary lesion with a slow growth rate around 1.5 cm/year, however, it is variable and it can be up to 10 cm/year. Surgical treatment is mandatory for all patients once the correct diagnosis is made, except for patients with multiple organ involvement in poor general conditions and deep-located cysts. The existence of hydatidosis in the cisternal spaces must not be neglected given the capacity of E. granulosus larvae to disseminate via the CSF. In this case report; two and half years’ male child presented with a history of 2 attacks of generalized seizure for the last 72 hours with the head circumference at the upper normal limit for his age. This paper presents the first case report demonstrating a primary single hydatid cyst located in the quadrigeminal cistern in a child. We concluded that in spite of the feasibility of the imaging and the high suspension of cerebral hydatid cyst, still, the reports show more locations which can be described as unusual although for a head to toe suspected distribution of hydatid disease is already understood. An eminent medical and surgical (if indicated) treatment of the primary cerebral hydatid cyst are always effective and recommended

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC