Nephroprotective Role of Combined Sitagliptin and Oleuropein in Cisplatin-Induced Acute Kidney Injury: Regulation of SDF-1α/Nrf2/ HO-1 Axis and Autophagy

Background: Accumulating evidence proves that cisplatin, a widely used anticancer, causes acute kidney injury (AKI). Sitagliptin (Sita), a dipeptidyl peptidase-4 (DPP4) inhibitor, is a hypoglycemic agent that can promote tissue angiogenesis and cell survival. However, little is known about the nephroprotective effect of Sita in cisplatin-induced AKI especially its effect on SDF-1α, usually degraded by DPP4. Meanwhile, the olive oil component oleuropein (Ole) activates Nrf2/heme oxygenase-1 (HO-1) axis, which ultimately leads to SDF-1α activation. Herein, we studied the nephroprotective effects of combined Sita and Ole on oxidative stress and autophagy through SDF-1α/Nrf2/ HO-1 axis in cisplatin-induced AKI in rats. Methods: AKI was induced in vivo through single IP injection of cisplatin (7 mg/kg), while Sita (10 mg/kg) and Ole (16 mg/kg) were given separately and in combination for 7 days prior and 5 days after cisplatin injection. AKI was assessed through histopathological examination, measurement of serum creatinine and urea. Also, serum GLP-1, serum and kidney SDF-1α levels were measured by ELISA. LC3-II, P62, HO-1, Nrf2, and caspase-3 were investigated by western blotting. Results: Sita and Ole monotherapy and in combination accelerated kidney recovery as they suppress serum SDF-1α, serum BUN, creatinine and renal histopathological features. Each of Sita and Ole enhanced Nrf2/HO-1axis in renal tissues while only Sita enhanced renal SDF-1α. Sita and Ole monotherapy showed incompetent autophagy where the late steps of autophagy were incomplete. Combined treatment enhanced SDF-1α in kidney tissue which showed recovery through autophagy process. Conclusion: Sita and Ole show promising nephroprotective effects in cisplatin-induced AK

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome

: The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.Fil: Ravindranath, Vijayalakshmi. Indian Institute of Science; IndiaFil: Dang, Hoang Minh. Vietnam National University; VietnamFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Mansour, Hader. University of Pittsburgh; Estados Unidos. Mansoura University; EgiptoFil: Nimgaonkar, Vishwajit L.. University of Pittsburgh; Estados UnidosFil: Russell, Vivienne Ann. University of Cape Town; SudáfricaFil: Xin, Yu. Peking University; Chin

The karyotype of the forensically important flesh flies (Diptera: Sarcophagidae), Mini Review

Maggots of flesh flies were known as one of the main players in the depletion of earthily decomposed remains. They colonized the carrion few minutes after death, and were known as the initial colonizers in several research papers. In consequence, they could be used in the minimum post-mortem intervals (PMImini) estimation. Also, some sarcophagid species proved capable of detecting several toxins/ drugs in carcasses in the entomotoxicological research. The difficulty to identify sarcophagid females and larvae hindered their role as entomological evidence. Cytogenetics would aid in the identification of the immatures and their sex; the differentiation between adult species; and/ or the categorization of the taxa. Sarcophagidae received little attention concerning their karyotype measurements, especially in Egypt where there is only one unpublished thesis (El-Bassiony 2001). This mini review listed the previous studies and findings on sarcophagid’s karyotypes, especially the solitary data from Egypt

Liposuction and port site nipple sparing mastectomy: an alternative method for the operative treatment of gynecomastia at Alexandria main university hospital

Abstract Background Gynecomastia is characterized by unusually large masses that radiate concentrically from the base of the nipple and is caused by abnormal growth of the glandular tissue of the male breast. An alternative strategy for the surgical treatment of gynecomastia was used in this experimental study, which aims to use liposuction and port site nipple sparing mastectomy. Methods The study was conducted in the surgical oncology unit at Alexandria Main University Hospital included 103 patients with a mean age of 27 and no medical history. 100 patients had bilateral gynecomastia, and three patients had unilateral gynecomastia,with two having it on the right side and one on the left. Results Among the 103 participants, 83 had grade II gynecomastia and 20 had grade I. Only one of the three patients who participated in the study had an expanding hematoma on one side that needed to be surgically evacuated in the operating room. None of our patients experienced an infection or seroma following surgery. Furthermore, only three of our patients experienced nipple areolar complicated superficial epidermolysis, which need regular dressings until recovery. Of the 103 patients, 97 (94.17%) were pleased with the outcomes. Conclusion Liposuction and port site nipple sparing mastectomy are viable options for treating grade I to II gynecomastia, particularly if the patient prefers a more aesthetically pleasing chest contour; no scars equals better patient satisfaction. Trial registration retrospectively registered

Comparison of sucrose intake and production of elimination spots among adult Musca domestica, Musca autumnalis, Phormia regina and Protophormia terraenovae

Objective: To compare the differences in intake and excretion between Musca domestica and other three species from families Muscidae and Calliphoridae which may help explaining the significance of house fly in the transmission of pathogens. Methods: The four adult species were supplied with two concentrations of sucrose via modified capillary feeder assay system. The two sucrose concentrations were applied to one adult male/each experiment and the elimination spots were counted. Using 0.25 mol/L sucrose + 0.25% bromophenol blue, one active non-starved male/cup was observed carefully for 1 h to record its behavior. As a growing medium used in bacterial transmission experiments, undiluted trypticase soy broth was used to feed 3-day-old females and males of Musca domestica following two different diets upon emergence and the frequency of elimination spots was estimated. Results: The two Musca species have half the weight of the two Phormia species. Comparing the volume of intake per hour, house fly took as much as the other species, all of which were larger. House fly produced twice, or more, the number of elimination spots/h than the other three species. Feeding the flies a sugar liquid diet resulted in producing more fecal spots than regurgitation spots. The male house flies produced less elimination spots/h when fed with trypticase soy broth than with the two sucrose solutions. Conclusions: House flies eliminated more than the other examined fly species and most of these elimination events were defecation which implicates the fecal route for pathogen transmission by this important vector

Combustion Characteristics and Emissions of a Direct-Injection Diesel Engine Fueled with GTL Fuel Blends

Gas to Liquids (GTL) is one of clean alternative fuels which loosely defined terms that is generally used to describe the chemical conversion of natural gas to some type of liquid products. As such, it excludes the production of liquefied natural gas (LNG), but includes the conversion of gas to methanol, liquid fuels, and petrochemicals, being the most common applications. In other words, Gas to liquids (GTL) technology is used to convert a carbon containing feedstock such as natural gas, to synthetic diesel fuels and further developed by oil companies. Fewer studies investigated the use of GTL diesel with the existing diesel engines to study the effect of using this new alternative fuel on the efficiency and emissions in these engines. Hence, the objectives of this study are to investigate the behavior of the GTL - diesel fuel blends in context of different combustion characteristics, engine performance and emissions. It is expected that the outcomes of this study will shed further light on GTL diesel fuel as a clean alternative fuel.qscienc