Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to he activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism

Positive effects of a novel non-peptidyl low molecular weight radical scavenger in renal ischemia/reperfusion: a preliminary report

Ischemia/reperfusion (I/R) is one of the most common causes of acute kidney injury. Reactive oxygen species have been recognized to be an important contributor to the pathogenesis of I/R injury. We hypothesize that a non-peptidyl low molecular weight radical scavenger (IAC) therapy may counteract this factor, ultimately providing some protection after acute phase renal I/R injury. The aim of this preliminary study was to assess the ability of IAC to reduce acute kidney injury in C57BL/6 mice after 30-minute of bilateral ischemia followed by reperfusion. The rise in serum creatinine level was higher in C57BL/6 control mice after I/R when compared to IAC (1 mg)-treated mice. Control mice showed greater body weight loss compared to IAC-treated mice, and at pathology, reduced signs of tubular necrosis were also evident in IAC-treated mice. These preliminary evidences lay the basis for more comprehensive studies on the positive effects of IAC as a complementary therapeutic approach for acute phase renal I/R injury

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.

Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies

Type of High Secondary School (Governmental Vs Private) and Type of High Secondary School Certificate (Sudanese Vs Arabian): Do They Affect Learning Style?

Background: People differ in the way they perceive, process, store, and recall what they are attempting to learn. This study aimed to assess the learning styles among preclinical 1st year medical students and the influence of the type of high secondary school (governmental vs. private) and type of high secondary school certificate (Sudanese vs. Arabian) on learning style.Materials and Methods: A cross sectional institutional-based study was conducted at Al Neelain University, Khartoum State, Sudan. First year students of Medicine, Dentistry and Physiotherapy Faculties were enrolled. The VARK (Visual, Auditory, Read and write, and Kinesthetic) learning style hard copy questionnaire, © Copyright Version 7.8 (2014) held by VARK Learn Limited, Christchurch, New Zealand was administered following permission. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 21.Results: Out of 320 students, 198 correctly completed VARK questionnaires, with mean age of 17.88 years (SD 1.52) and 74.2% were female students. About 59.6% were from governmental schools and 79.4% of the studied students had Sudanese High Secondary Certificates. About 64.1% demonstrated singular mode preference. Inferential statistics showed statistically significant difference between the learning styles and the type of secondary school whether governmental or private (P-value 0.005) while no statistically significant difference in relation to the type of high school certificate of the studied group (P-value 0.225).Conclusion: The type of secondary school whether governmental or private may affect learning style of medical students while student's gender, type of college, or type of high school certificate (whether Sudanese or Arabian) do not. More andlarger studies are encouraged.Key word: Learning modalities, VARK questionnaire, Unimodal preference, Medicaleducation, Sudan

Synthesis and Biological activity of 1,3-Thiazolylidenehydrazinylidene ethylpyridiniumbromide monohydrate, 1,3-Thiazolylidenehydraziniumbromide and 1,3-Thiazolylidenehydrazine derivatives

1,3-Thiazolylidenehydrazinylidene ethylpyridinium bromide monohydrate, 1,3-thiazolylidenehydrazinium bromide and 1,3-thiazolylidenehydrazine derivatives were synthesized by heterocyclization of 2-(1-substituted ethylidene) hydrazinecarbothioamides, characterized and screened for their anti-bacterial activities. The structures of synthesized compounds were established by spectroscopic (IR, 1H, 13C-NMR, Mass) and X-ray analyses

Egg parasitoids of the genus Trichogramma (Hymenoptera, Trichogrammatidae) in olive groves of the Mediterranean region

A survey of egg parasitoids of the genus Trichogramma (Hymenoptera, Trichogrammatidae) was carried out in olive groves in Portugal, Greece, Egypt, and Tunisia during the years 2002–2004. Parasitoids were obtained either by exposing sentinel eggs (Sitotroga cerealella Olivier or Ephestia kuehniella Zeller) on olive trees or by collecting eggs of lepidopterous olive pests. Parasitized egg samples were reared separately in the laboratory for emergence of parasitoids. These were further reared in separate lines and processed by morphological and molecular biology techniques for species characterization. The recorded fauna of Trichogramma parasitoids in olive groves was species poor and consisted of species mainly known from the Mediterranean region. Trichogramma bourarachae Pintureau and Babault was found in Tunisia and Egypt, T. cordubensis Vargas and Cabello, and T. euproctidis Girault in Egypt, Trichogramma cacoeciae Marchal in Portugal, Greece, Egypt, Tunisia and Trichogramma nerudai Pintureau and Gerding in Portugal. Apart from that, Trichogramma oleae Voegele´ and Pointel was collected in Tunisia. This species is probably not indigenous, but has established after several releases of a French strain were made in recent years. For selected strains, the sequence of the internal transcribed spacer 2 (ITS-2) region of rDNA was determined and deposited in the GenBank database. Differences in important biological attributes were found among collected strains of T. bourarachae, suggesting the existence of biotypes. The results contribute to the limited knowledge on distribution and biodiversity of the genus Trichogramma in the Mediterranean region. They can be helpful for the preservation and use of indigenous Trichogramma species in biological control of lepidopterous pests in olive and other local crops