Differential Impact of the Ubiquitin-Proteasome System on Clear Cell Carcinoma and High-Grade Serous Ovarian Cancer

                                               http://austinpublishinggroup.com/biochemistry/

Ovariancancer is particularly deadly and difficult to target because of its aggressive nature. With high mortality rates, current studies are focused on improving early detection and prevention methods as well as developing new treatments. To successfully develop these therapeutic options, researchers first need to understand how the cancer forms, spreads, and functions. Since ovarian cancer is composed of many heterogeneous subtypes, such as high-grade serous ovarian cancer and clear cell epithelial ovarian cancer, the nuances of each type need also be examined and understood in order to target each individually. It has been determined that each subtype has a unique relationship with the tumor suppressor, p53. Understanding how each subtype interacts with p53 can lead to specialized treatment mechanisms that target these interactions. MDM2 and ADRM1, over expressed in clear cell carcinoma and high grade serous ovarian cancer respectfully, are key components of these interactions within ovarian cancer. MDM2 is a negative regulator of p53, while ADRM1 aids in protein degradation. The overexpression of each molecule acts specifically to aid ovarian cancer in survival. In this review, recent advances in studying ovarian cancer subtypes will be covered, as well as how these subtypes relate to the ubiquitin-proteasome system and the key tumor suppressor in human cells, p53.

DUBs: Deubiquitinating Enzymes; HGSC: High-Grade Serous Ovarian Cancer; CCC: Clear Cell Carcinoma; MDM2: Murine Double Minute 2; UPS: Ubiquitin-Proteasome System; ROCA: Risk Of Ovarian Cancer Algorithm; CIC: Cancer Initiating Cell; BRCA: Breast Cancer Gene; ADRM1: Adhesion Regulating Molecule 1; CA-125: Serum Cancer Antigen-125.

Ovariancancer, one of the deadliest and most aggressive gynecological malignancies, is the fifth most common cause of cancer death in women. As recently as 2017, the annual ovarian cancer mortality was approximately 65% of the incidence rate due to low predictive value in screening procedures for women without increased risk factors. As a result, only 15% of patients are diagnosed with localized disease and many patients are diagnosed in stage III or IV. The four main histological subtypes within epithelial ovarian cancer are serous, clear cell, endometrioid, and mucinous adenocarcinomas. Each subtype has its own unique abnormalities, making diagnosis and treatment of ovarian cancer difficult. While all women are susceptible to ovarian cancer, increased risk factors include familial history, nulliparity, lack of breast feeding, and infertility. About 20% of ovarian cancers are familial, linked mostly to Breast Cancer Alleles 1 and 2, (BRCA1 or BRCA2), though other gene mutations have been implicated as well.

Serum Immunoglobulin Levels in Nigerian Patients with Sickle Cell Anaemia in Bone Pain Crisis and Steady State

                                       http://austinpublishinggroup.com/blood-disorders/

SickleCell Disease (SCD) is a group of haemoglobin disorder resulting from the inheritance of the sickle β-globin gene. The homozygous state (Hb SS or sickle cell anaemia) is the most common form of the disease, however the interaction of the abnormal haemoglobin S (HbS) with thalassemia and other haemoglobin variants also result in sickling.

SCDis a major public health problem and the most common genetic disease disorder that affect mankind. The disease has a global distribution, but certain regions of the world have high prevalence for the sickle cell gene including Equatorial Africa, Sicily in Southern Italy, Middle East and Central India.

In Nigeria, the magnitude of the problem is much more pronounced given that 25% of the population carry the sickle cell gene. The World Health Organization (WHO) estimates the prevalence of SCA to be 20 per 1000 live birth annually which translate to about 150,000 children born annually with SCA in Nigeria, thus making Nigeria the country with the highest disease burden globally.

The common and most distressing clinical manifestation of SCA is the episodic and unpredictable sickle cell vaso-occlusive crisis (VOC). The crisis occurs unpredictably over a life-time and account for most common cause of emergency room visits and hospitalization. The most common acute VOC is the Bone Pain Crisis (BPC). BPC is defined as painful episodes involving one or more sites of bones in the absence of preceding trauma or obvious infection. The most common sites are the long bones of the limbs, lumbar spine, and thoracic cage.

Malaria bacterial and viral infection, are the most common precipitating factors for VOC and leading cause of mortality in SCD. SCA patients are prone to infection because of a defect in the alternative pathway of complement activation and opsonisation reduced ability of neutrophils to kill pathogens and functional 

The Association between Vitamin D and Rejection in Adult Renal Transplant Recipients: A Meta-Analysis

                                               http://austinpublishinggroup.com/biometrics/

The problem has been discussed a lot, but the results remain controversial. Since no consensus had been reached yet for whether vitamin D insufficient is a major contributor for rejection in renal transplant patients, we performed a meta-analysis of the association between them. Pub Med, Medline, web of science, Ovid and Springer databases were searched for observational studies linked with vitamin D and rejection in adult renal transplant recipients. A meta-analysis was conducted by pooling data from relevant cohort and case control studies. The Q statistic and I2 were used to measure heterogeneity. Subgroup analysis and meta-regression were conducted to detect the source of heterogeneity. When significant heterogeneity was observed statistically, a random-effect model can be used to estimate the odds ratio. And sensitivity analysis was conducted to make sure whether the results were stable. The analysis consisted of seven studies including five cohort studies and two case control studies, with a total of 2731 participants. These studies contained different vitamin D doses with a varying degree of intervention duration. Pooled odds ratio was 1.07, 95% confidence interval: [0.50-2.28], with significant heterogeneity among these studies (I2=82%, P<0.01). Vitamin D has no association with rejection in adult renal transplant recipients. There is a necessity that future investigations are encouraged to reveal the underlying mechanisms and the risk factors for rejection.

Chronic Kidney Diseases (CKD) is highly prevalent in the general population, which have become a worldwide epidemic with an occurrence rate of approximately 5%-15%. When the CKD is developing to End-Stage Renal Disease (ESRD), kidney transplantation is a preferred treatment for the increasing number of patients. Renal transplant recipients usually have low vitamin D levels, especially in the early post-transplantation period. Vitamin D is an important hormone which closely correlated with many immune disorders. It not only maintains the basic metabolism of calcium and phosphorus, but also affects immune functions of the body. More and more people have realized that vitamin D is one of the largest modifiable risk factors for health.

Since the kidney is an active organ of vitamin D, it is also increasingly appreciated that there may be an association between vitamin D and allograft outcomes in renal transplant recipients. Some retrospective cohort studies stated that vitamin D can improve the prognosis of graft, reduce graft loss and prevent rejection by inhibiting allograft rejection.

Vertebral Artery Dissection Associated with Bathing: A Case Report

                                           http://austinpublishinggroup.com/biomarkers/

VertebralArtery Dissection (VAD) is often associated with trauma or occurs spontaneously, inevitably causing some neurological deficits. We herein report the case of a 49-year-old female patient presented with sudden onset of severe posterior neck pain with occipital headache, vertigo and vomiting when she was bathing. Dissection of the right vertebral artery at the level of V4 segment was confirmed by use of Magnetic Resonance Imaging (MRI) and CT Angiography (CTA), and Digital Subtraction Angiography (DSA). The patient was started with clopidogrel (75mg/d) and low molecular weight heparin calcium injection (Fraxiparine, 0.4ml: 4100AXaIU/bid, subcutaneous injection). Recovery of neurologic function was excellent, and she was discharged after 21 days. However, reexamine CTA showed an abnormal intracranial segment of the right vertebral artery. The patient still continued treatment with Clopidogrel (75mg/d). We suggest that patients with symptoms of neck pain or headache and even disturbances of posterior circulation after manipulation and stretching of the neck, VAD has to be taken into consideration.

Spontaneousdissection of the intracranial vertebral artery is an increasingly recognized cause of stroke. The annual incidence of spontaneous Vertebral Artery Dissection (VAD) is 1-1.5 per 100,000. Usually, a history of drug treatment, generalized convulsive seizure, minor blunt trauma or activity associated with rotation or hyperextension of the neck, such as tooth-brushing, aerobics, yoga, painting of the ceiling and spinal manipulations can cause VAD, and it is generally labeled as spontaneous dissection. The purpose of this case report is to describe a female patient who presented with posterior neck and occipital pain and was undergoing a vertebral artery dissection when she was standing in a shower and washing her hair. The VAD caused embolic complications: pontine and cerebellar infarctions.

A49-year-old female patient presented with sudden onset of severe posterior neck pain with occipital headache, vertigo and vomiting when she was bathing two hours ago. When she was admitted to our department, she appeared tired and distressed. She stated that she had burning, sharp pain worse than she had ever experienced before. She was healthy previously, and denied any head or neck trauma and chiropractic manipulation. She has no personal or family history of systemic illnesses, connective tissue diseases, myocardial infarctions or cerebrovascular insults. On physical examination, her temperature was 37.6⁰C, pulse 72 beats/min, and blood pressure 132/78 mmHg. No remarkable positive signs were detected by the lung, cardiac, and abdominal examinations.

Characterization and Utilization of Podoviridae Phages for Controlling Pathogenic Escherichia coli Serovar O168 from Ducklings in Egypt

                                               http://austinpublishinggroup.com/bacteriology/

This study was carried out to isolate and characterize lytic bacteriophages against the multidrug resistant and pathogenic Escherichia coli serotype O168 isolated from ducklings in Egypt; and also to study efficacy of single phage and cocktail phages on In vitro inactivation of E. coli O168. One hundred and fifteen samples from ducklings, including caecal contents, skin, minced breast, gizzard, swabs from mouth, cloacae and inner surface of liver, were collected, pre-enriched in peptone water and streaked MacConkey agar, and Eosin-Methylene Blue agar. The presumptive isolates of E. coli were subjected for biochemical and serological identifications. Antimicrobial susceptibility testing was performed by the disk diffusion method. Phages against E. coli serotype O168 were isolated from sewage samples using plaque assay test. An evaluation of phages efficacy was achieved separately and in cocktail to control the most multidrug resistant serotype E. coli O168. Three different single plaques with different plaque morphologies and diameters designated as ECa1, ECb1, and ECc1 were picked and chosen for further purification, amplification and characterization. The recovered phages were belonged to the family Podoviridae. The use ofcocktail phages (ECa1/ECb1/ECc1) was significantly effective (reductions of 7.4 log CFU/ml 12hrs post treatment) than the use single phage suspensions. This study confirmed the higher efficacy of phage cocktails in controlling the infection of ducklings with multidrug resistant E. coli O168. These phages will reduce mortality in ducklings, and also protect human health from adverse side effects of antibiotic residues.

Duckmeat is the most popular type of food in Egypt and various parts of the world. Ducks are excellent sources of animal-derived high quality proteins that contain essential and nonessential amino acids. Pathogenic Escherichia coli infecting poultry is the causative agent of colibacillosis, one of the most important causes of economic losses in industry of poultry worldwide. In Egypt, five serotypes of E. coli (O86, O127, O114, O26 and O78) were identified from gizzard, heart, spleen and muscles of ducks. Some bacterial diseases such as salmonellosis, colibacillosis, and pasteurelliosis infect a variety of organ systems with involving the alimentary tract. Escherichia coli is a food borne pathogen, and has a public health concern. Recently, there has been attention that some multidrug resistant E. coli have represented a worldwide multiple food borne disease disorders related to the contaminated food consumption. Also, the misuse of antimicrobial agents in poultry production for growth promotion and treatment purposes increases the major interest for the multidrug resistance that are frequently seen among serovars of E. coli and Salmonella. Antimicrobial-resistant food borne pathogens is recognized as an essential public health in the developing countries and this resistance reduces the therapeutic options for treatment of human salmonellosis.

Investigation of Bismuth Nanoparticles Antimicrobial Activity against High Pathogen Microorganisms

                         http://austinpublishinggroup.com/bioterrorism-biosecurity-biodefense/

Despite of the common efforts in biodefense around the world the problem of high dangerous pathogens distribution, especially under the threat of terrorist attacks, is still urgent. Among the biotoxins that could be used for dispersion, leading experts identify large number of high pathogen microorganisms of category A and B, such as well-known pathogens: Bacillus anthracis, Salmonella, Escherichia etc. The most important problem in the struggle against biohazard is high effective defense of civil population. Such effective defense can be provided using safe drugs, which are effective against wide range of biotoxins.

Modern antimicrobial preparations and vaccines don’t possess by wide range of activity against different classes of pathogens. So, the search and development of new high effective antimicrobial substances with high effectiveness against wide spectra of high pathogen microorganisms - causative agents of most dangerous human and animals’ diseases is topical problem today. Metal nanoparticles are possessed by high potential in this area.

The main goal of presented work was antimicrobial activity investigation of the synthesized bismuth nanoparticles against wide spectra of pathogen microorganisms - potential causative agents of high dangerous human and animals’ diseases. Spherical Bismuth Nanoparticles (BiNP) have been synthesized by the method of chemical condensation in water medium. The concentration of obtained BiNP was 77.5 mg/ml by metal. The shape and size of synthesized BiNP have been defined by the method of Transmission Electron Microscopy.

Hormones and Feed Intake Regulation: Ruminant and Rat Models

                                  http://austinpublishinggroup.com/biotechnology-bioengineering/

Theobjective of this mini review article was to illuminate hormones-mediated feed intake regulation in ruminant and rat models. This was to help formulate nutritional strategies to optimize metabolism and performance in food-producing animals and to improve human physiology and health. Nutrient partitioning is mediated by a variety of hormones. Hormones are involved in both short-term and long-term regulation of feed intake. The greatest fluctuations in body metabolism, nutrient partitioning, and feed intake usually occur around calving in large ruminants when levels of metabolic and reproductive hormones are highly variable in periparturient cows.

Estrogen depresses feed intake by acting primarily on the paraventricular nucleus of the hypothalamus. Insulin is another important hormone possessing both long-term and short-term effects on ruminant nutrient partitioning and feed intake. The long-term roles of insulin in feed intake control relate to pregnancy and lactation. This occurs mainly during mid- and late-lactation when the cow tends to gain weight. Insulin is involved in both up- and down-regulation of feed intake in mammals. When compared to prepartum levels, insulin secretion drops substantively shortly after parturition. Without the postpartum drop in insulin secretion rate, the cow would be unable to use body reserves and deal with insufficient Dry Matter Intake (DMI). The low postpartum insulin will additionally enable the cow to gradually increase DMI.

Theshort-term insulin effects on nutrient metabolism and partitioning, which are more relevant to the findings of dairy cattle studies, initiate upon or even shortly before feeding or nutrient ingestion. Seeing the fresh feed can cause a surge in insulin secretion in sheep and cattle. The higher postprandial insulin surge leads to greater glucose uptake by peripheral tissues.