Autophagy-Related Gene Expression Changes Are Found in Pancreatic Cancer and Neurodegenerative Diseases

Genetic alterations can cause cancer, including pancreatic cancer (PC) as well as certain neurodegenerative diseases. Our lab has recently identified genes that are modulated during pancreatic cancer liver metastasis, and some are known to have a role in neurobiology or neurodegenerative diseases. Autophagy or self-eating portrays the lysosomal-dependent degradation and recycling of protein aggregates and defective organisms in eukaryotic cells. Deregulation of autophagy as a cellular mechanism is common in neurodegenerative diseases as well as cancer and may represent a platform by which some genes can affect both disorders. This is exemplified for optineurin, which is an autophagy receptor that was found among genes with intensive modulation of expression in PC liver metastasis. Our results on this autophagy receptor draw the attention to the expression status of this and other autophagy genes in pancreatic cancer progression

A Study of Adiponectin in Children with Diabetes Mellitus

Objectives: Adiponectin is a hormone produced by adipose tissue. It is secreted exclusively by adipocytes and appears to play a role in the pathophysiology of obesity, diabetes mellitus (DM), and its comorbidities. The aim of this study was to assess adiponectin levels in diabetic children with type 1 DM (T1DM) and type 2 DM (T2DM), and to detect its prognostic role in them. Methods: This study was undertaken from April to July 2011 at Minia University Children’s Hospital, Egypt, and included 314 children aged 2–18 years divided into two patient groups. Group I consisted of 164 pre-diagnosed diabetic patients, further subdivided into Group Ia which included 142 patients with T1DM and Group Ib, 22 patients with T2DM; Group 2 included 150 apparently healthy children as a controls; they were age- and sex-matched to the diseased group. Patients were subjected to a thorough history taking, clinical examination, and laboratory investigations including assessment of HbA1c percentages, fasting C-peptide levels, lipid profiles and fasting serum adiponectin levels. Results: Adiponectin levels did not differ significantly between patients with T1DM and T2DM, but it was significantly higher in diabetic patients than in the controls. In T1DM, adiponectin had positive significant correlations with the duration of the disease and waist circumference, while in T2DM, it had a positive significant correlation with the dose of insulin given and negative significant associations with diastolic blood pressure, cholesterol, and C-peptide levels. Conclusion: The results of the study suggest that adiponectin can play a protective role against the metabolic complications of DM

Optineurin downregulation induces endoplasmic reticulum stress, chaperone-mediated autophagy, and apoptosis in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) shows a high level of basal autophagy. Here we investigated the role of optineurin (OPTN) in PDAC cell lines, which is a prominent member of the autophagy system. To that purpose, mining of publically available databases showed that OPTN is highly expressed in PDAC and that high levels of expression are related to reduced survival. Therefore, the role of OPTN on proliferation, migration, and colony formation was investigated by transient knockdown in Miapaca, BXPC3, and Suit2-007 human PDAC cells. Furthermore, gene expression modulation in response to OPTN knockdown was assessed by microarray. The influence on cell cycle distribution and cell death signaling cascades was followed by FACS, assays for apoptosis, RT-PCR, and western blot. Finally, autophagy and ROS induction were screened by acridine orange and DCFH-DA fluorescent staining respectively. OPTN knockdown caused significant inhibition of colony formation, increased migration and no significant effect on proliferation in Miapaca, BXPC3 and Suit2-007 cells. The microarray showed modulation of 293 genes in Miapaca versus 302 in Suit2-007 cells, of which 52 genes overlapped. Activated common pathways included the ER stress response and chaperone-mediated autophagy, which was confirmed at mRNA and protein levels. Apoptosis was activated as shown by increased levels of cleaved PARP, Annexin V binding and nuclear fragmentation. OPTN knockdown caused no increased vacuole formation as assessed by acridine orange. Also, there was only marginally increased ROS production. Combination of OPTN knockdown with the autophagy inducer erufosine or LY294002, an inhibitor of autophagy, showed additive effects, which led us to hypothesize that they address different pathways. In conclusion, OPTN knockdown was related to activation of ER stress response and chaperone-mediated autophagy, which tend to confine the damage caused by OPTN knockdown and thus question its value for PDAC therapy

Structural Characterization, thermal studies, fluorescence and optical properties of metal carbonyl derivatives of N2O2 Schiff Base

A series of four binuclear complexes [Cr2(CO)2L2] (1), [Mo2O4(L)2] (2), and [W2O4(L)2] (3) [Mo2O5(CO)L].H2O (4) were synthesized from the reaction of [M(CO)6] (M = Cr, Mo and W) with 6,6'-(([1,1'-biphenyl]-4,4' diylbis(azaneylylidene)) bis(methaneylylidene)) bis(2,4-dichlorophenol) H2L in THF. The structures of the ligand and its complexes were characterized using elemental studies, IR, mass, UV-vis and 1H NMR spectroscopy. Magnetic measurements showed diamagnetic properties for molybdenum and tungsten complexes and paramagnetic character for chromium complex. The thermal analyses for all metal complexes were also determined by the thermogravimetry technique. The thermodynamics parameters of complexes were calculated. Spectroscopic data revealed that H2L was coordinated as a tetradentate ligand through two imine nitrogen and two deprotonated phenolic oxygen atoms. The Schiff base ligand (H2L) and its complexes displayed fluorescence properties and can potentially serve as photoactive materials. The values of optical band gap energy (Eg) of the prepared complexes suggested that these compounds could be used as semiconductors

Practice of intercropping and its impact on legume productivity in Egypt

In Egypt, conserving irrigation water and raising crop output are significant concerns. Egypt's climate ranges from semi-arid and arid to desert. The number of summer legumes cultivated on a per-capita basis is declining. Excessively applied nitrogen (N) mineral fertilization and irrigation water are widespread agricultural techniques that harm the quality of the soil and the surrounding environment. It should be possible to increase overall agricultural yield while working with scarce agricultural resources through intercropping. In developing countries, intercropping is the most common farming system for increasing and maintaining agricultural production. As a widely spaced crop, maize provides ample opportunity for the practice of intercropping. Legumes are well-known for their effectiveness as intercropping companions. In light of this information, an investigation into the possibility of intercropping maize with legumes, specifically groundnut and green gram, was carried out. Seeds for groundnuts and green grams were sown between rows of paired row maize. The results demonstrated that the intercropping system had no considerable impact on maize grain and straw yields. However, there was a substantial disparity in total biomass production between the experiments; maize and groundnut (2:3) recorded the highest yield, followed by groundnut (2:2) and green gram (2:3). The land equivalent ratio (LER) unequivocally demonstrated the benefits of intercropping, and the highest LER was achieved by growing maize and groundnut (2:1)

Dietary clenbuterol modifies the expression of genes involved in the regulation of lipid metabolism and growth in the liver, skeletal muscle, and adipose tissue of Nile tilapia (Oreochromis niloticus)

The current study aimed to evaluate whether clenbuterol, a β2-adrenergic agonist, supplementation in Nile tilapia (Oreochromis niloticus) diets can influence growth and blood parameters. Besides, assessment of adipogenic genes as fatty acid synthase (FAS) and lipoprotein lipase (LPL) which is a key enzyme in the regulation of the flux of fatty acids in liver, muscle, and adipose tissue as well as muscle growth-regulating genes as myostatin (MYO) in muscle and insulin-like growth factor-1 (IGF-1) in liver. The fish were allocated into three equal groups; control group that fed basal diet only and the other two groups fed a basal diet containing clenbuterol at two doses 5 ppm and 10 ppm/kg diet for 30 consecutive days. Results revealed that clenbuterol supplementation significantly increased body weight, decreased liver, spleen and abdominal fat weights, and decreased total circulatory cholesterol and triacylglycerol levels. Moreover, clenbuterol inhibits lipogenesis by downregulation of FAS gene expression by dose and time-dependent manner in the liver while enhanced lipolysis in both the liver and in the adipose tissue. Moreover, lipolysis was reduced in muscle by dose 10 ppm on day 30. Furthermore, clenbuterol presented higher gene expression of MYO and IGF-1 in muscle and liver respectively by dose 5 ppm at day 15 on the other hand, these findings were reversed by day 30 compared with control. In conclusion, clenbuterol efficacy was apparent in a dose and time response pattern to boost growth and reduce fat deposition rates, indicating for the first time that clenbuterol has a profitable growth impact on Nile tilapia

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

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study

BackgroundDiabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.ObjectiveThis study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.Materials and methodsForty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.ResultsMT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.ConclusionCollectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020