Search results for: tumor necrosis factor-alpha

Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.

Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis

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Authors: Santram Lodhi, Alok Pal Jain, Awesh K. Yadav, Gopal Rai

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Rhodiola rosea L. (Crassulaceae) is commonly known as golden root or rose root. It is a perennial herbaceous plant and most investigated species of the genus Rhodiola. Rhodiola rosea contains flavonoids, terpenoids, phenylpropanoid glycosides and phenylethanol derivatives in the roots of the plant. The objective of present study was to investigate the protective effect of hydroalcoholic extract from Rhodiola rosea roots in DSS induced colitis in mice. The ulcerative colitis was induced by DSS (3%, w/v) in mice and estimated weight loss and stool consistency. Various parameters including Colon length, spleen weights and ulcer index were also measured. The histological observations were observed by H&E staining. Effect of hydroalcoholic extract on various antioxidant parameter of rat colon such as tissue myeloperoxidase (MPO), reduced GSH, SOD concentrations and lipid peroxidation were determined. Pro-inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and nitric oxide (NO) were determined by ELISA. In DSS induced group, mice body weight decreased gradually as compared to the control group. Redness and edema were observed in the colons intensely and scores representing inflammation in this group. The extract treated showed with tissue levels of TNF-α, IL-6 and MPO activity were significantly (p<0.05) increased. The mice treated with higher doses of hydroalcoholic extract (300 mg/kg) significantly reduced the activity compared with standard drug sulfasalazine (100 mg/kg. B.wt). Conclusion: Results of this study were suggested that the efficacy of hydroalcoholic extract, especially at the higher dose, was similar to that of standard drug, which concerned its potential application as a natural medicine for the treatment of ulcerative colitis.

Keywords: phenylpropanoid, Rhodiola rosea, sulfasalazin, ulcerative colitis

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Yong Hwang, Kang Yeol Suh, Yundeok Jang, Tae Hoon Kim

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Introduction: Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. Acute kidney injury is a potential complication of severe rhabdomyolysis and the prognosis is substantially worse if renal failure develops. We try to identify the factors that were predictive of AKI in severe trauma patients with rhabdomyolysis. Methods: This retrospective study was conducted at the emergency department of a level Ⅰ trauma center. Patients enrolled that initial creatine phosphokinase (CPK) levels were higher than 1000 IU with acute multiple trauma, and more than 18 years older from Oct. 2012 to June 2016. We collected demographic data (age, gender, length of hospital day, and patients’ outcome), laboratory data (ABGA, lactate, hemoglobin. hematocrit, platelet, LDH, myoglobin, liver enzyme, and BUN/Cr), and clinical data (Injury Mechanism, RTS, ISS, AIS, and TRISS). The data were compared and analyzed between AKI and Non-AKI group. Statistical analyses were performed using IMB SPSS 20.0 statistics for Window. Results: Three hundred sixty-four patients were enrolled that AKI group were ninety-six and non-AKI group were two hundred sixty-eight. The base excess (HCO3), AST/ALT, LDH, and myoglobin in AKI group were significantly higher than non-AKI group from laboratory data (p ≤ 0.05). The injury severity score (ISS), revised Trauma Score (RTS), Abbreviated Injury Scale 3 and 4 (AIS 3 and 4) were showed significant results in clinical data. The patterns of CPK level were increased from first and second day, but slightly decreased from third day in both group. Seven patients had received hemodialysis treatment despite the bleeding risk and were survived in AKI group. Conclusion: We recommend that HCO3, CPK, LDH, and myoglobin should be checked and be concerned about ISS, RTS, AIS with injury mechanism at the early stage of treatment in the emergency department.

Keywords: acute kidney injury, emergencies, multiple trauma, rhabdomyolysis

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Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

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N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

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The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

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Authors: Zainab Shaikh, Yusuf Miyanji

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Pilomatrixoma is a benign neoplasm of the hair follicle matrix that is not commonly diagnosed in general practice. This is a case report of a 9-year-old boy who presented with a one-year history of a 19mm x 11 mm swelling in the left infra-orbital region. This was previously undiagnosed in Spain, where the patient resided at the time of initial presentation, due to the language barrier the patient’s family encountered. An ultrasound and magnetic resonance imaging gave useful information regarding surrounding structures for complete tumor excision and indicated that the risk of facial nerve palsy is low. The lesion was surgically excised and a definitive diagnosis was made after histopathology. Pilomatrixoma, although not rare in its occurrence, is rarely this large at the time of excision due to early presentation. This case highlights the importance of including pilomatrixoma in the differential diagnosis of dermal and subcutaneous lesions in the head and neck region, as it is often misdiagnosed due to the lack of awareness of its clinical presentation.

Keywords: pilomatrixoma, swelling, infra-orbital, facial swelling

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Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

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Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA micro array. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 Nano LabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring software analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with down-regulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38 - MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: cDNA microarray, thymoquinone, CARD16, PTPRR, CASP10

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Authors: Madhuri S. Ghate, Rahul P. Chavhan, Shriya S. Nahar

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Learning objective: •To describe Magnetic Resonance Imaging (MRI) imaging appearances of typical and atypical uterine fibroids with emphasis on differentiating it from other similar conditions. •To classify uterine fibroids according to International Federation of Gynecology and Obstetrics (FIGO) Sub-classifications system and emphasis on its clinical significance. •To show cases with atypical imaging appearances atypical fibroids Material and methods: MRI of Pelvis had been performed in symptomatic women of child bearing age group on 1.5T and 3T MRI using T1, T2, STIR, FAT SAT, DWI sequences. Contrast was administered when degeneration was suspected. Imaging appearances of Atypical fibroids and various degenerations in fibroids were studied. Fibroids were classified using FIGO Sub-classification system. Its impact on surgical decision making and clinical outcome were also studied qualitatively. Results: Intramural fibroids were most common (14 patients), subserosal 7 patients, submucosal 5 patients . 6 patients were having multiple fibroids. 7 were having atypical fibroids. (1 hyaline degeneration, 1 cystic degeneration, 1 fatty, 1 necrosis and hemorrhage, 1 red degeneration, 1 calcification, 1 unusual large bilobed growth). Fibroids were classified using FIGO system. In uterus conservative surgeries, the lesser was the degree of myometrial invasion of fibroid, better was the fertility outcome. Conclusion: Relationship of fibroid with mucosal and serosal layers is important in the management of symptomatic fibroid cases. Risk to fertility involved in uterus conservative surgeries in women of child bearing age group depends on the extent of myometrial invasion of fibroids. FIGO system provides better insight into the degree of myometrial invasion. Knowledge about the atypical appearances of fibroids is important to avoid diagnostic confusion and untoward treatment.

Keywords: degeneration, FIGO sub-classification, MRI pelvis, uterine fibroids

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Authors: Samira Bensoltane, Smina Ait Hamlet, Samti Meriem, Semmasel Asma

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Living organisms in the soil are subject to regular fluctuations of abiotic parameters, as well as a chemical contamination of the environment due to human activities. They are subject to multiple stressors they face. The aim of our work was to study the effects of insecticide: thiamethoxam (neonicotinoid), and the potential reversibility of the effects by an antioxidant: ginger on a bioindicator species in ecotoxicology, the land snail Helix aspersa. The effects were studied by a targeted cell approach of evaluating the effect of these molecules on tissue and cellular aspect of hepatopancreas through histological study. Treatment with thiamethoxam concentrations 10, 20, and 40 mg/l shows signs of inflammation even at low concentrations and from the 5th day of treatment. Histological examination of the hepatopancreas of snails treated with thiamethoxam showed significant changes from the lowest concentrations tested , note intertubular connective tissue enlargement, necrosis deferent types of cells (cells with calcium , digestive, excretory) , also damage acini, alteration of the apical membrane and lysis of the basement membrane in a dose- dependent manner. After 10 days of treatment and with 40 mg/l, the same changes were observed with a very advanced degeneration of the wall of the member that could be confused with the cell debris. For cons, the histological study of the hepatopancreas in Helix aspersa treated with ginger for a period of 15 days after stopping treatment with thiamethoxam has shown a partial regeneration of hepatopancreatic tissue snails treated with all concentrations of thiamethoxam and especially in the intertubular connective tissue of the wall and hepatopancreatic digestive tubules. Finally, we can conclude that monitoring the effect of the insecticide thiamethoxam showed significant alterations, however, treatment with ginger shows regeneration of damaged cells themselves much sharper at low concentration (10 mg/L).

Keywords: Helix aspersa, insecticides, thiamethoxam, ginger, hepatopancreas

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Authors: Aastha Agarwal, Veena Sharma

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N-nitrosopyrollidine or NPYR is a tobacco-specific nitrosamine which upon intoxicated causes abnormal production of Reactive Oxygen Species disrupt the endogenous antioxidant system. The study was designed to evaluate the histological changes in lung tissue of Mus musculus in NPYR administered lungs and effect of isolated flavonoid 3,6-dihydroxy-(3’,4’,7’-trimethoxyphenyl)-chromen-4-one-7-glucoside (ITC) from experimental plant Indigofera tinctorial. Post treatment with isolated compound significantly restored the abnormal symptoms and changes in pulmonary tissue. Transverse section of mouse lung in control animals appeared as a thin lace. Histologically, most of the lung was arranged as alveoli which were thin walled structures made up of single layered squamous epithelial cells. In the transverse section of lung at 100 X will clearly show the component of alveoli, surround by a thin layer of connective tissue and blood vessels. Smaller bronchioles were lined by cuboidal epithelial cells while larger bronchioles were lined by ciliated columnar epithelium layer while in NPYR intoxicated lungs signs of vast pulmonary damages and carcinogenesis as alveolar damage, necrosis, DADs or defused alveolar damages hyperplasia, metaplasia, dysplasia and next stage of carcinogenesis were revealed. Treatment with ITC showed the significant positive changes in the lung tissue due to the side hydroxyl and methoxy groups in its structure which help in combating oxidative injuries and give protection from the free radicals generated during the metabolism of NPYR in body. Thus, histopathological analysis confirms the development of the cancerous conditions in the lung tissue in mice model and the protective effects of ITC.

Keywords: flavonoid, histopathology, Indigofera tinctoria, lung

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Authors: Akash Soogumbur

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Tourniquets are commonly used in orthopaedic surgery to provide hemostasis during procedures on the upper and lower limbs. However, there is a risk of complications associated with tourniquet use, such as nerve damage, skin necrosis, and compartment syndrome. The British Orthopaedic Association (BOAST) guidelines recommend the use of tourniquets at a pressure of 300 mmHg or less for a maximum of 2 hours. Research Aim: The aim of this study was to evaluate the effectiveness of a tourniquet checklist in improving compliance with the BOAST guidelines. Methodology: This was a retrospective study of all orthopaedic procedures performed at a single institution over a 12-month period. The study population included patients who had a tourniquet applied during surgery. Data were collected from the patients' medical records, including the duration of tourniquet use, the pressure used, and the method of exsanguination. Findings: The results showed that the use of the tourniquet checklist significantly improved compliance with the BOAST guidelines. Prior to the introduction of the checklist, compliance with the guidelines was 83% for the duration of tourniquet use and 73% for pressure used. After the introduction of the checklist, compliance increased to 100% for both duration of tourniquet use and pressure used. Theoretical Importance: The findings of this study suggest that the use of a tourniquet checklist can be an effective way to improve compliance with the BOAST guidelines. This is important because it can help to reduce the risk of complications associated with tourniquet use. Data Collection: Data were collected from the patients' medical records. The data included the following information: Patient demographics, procedure performed, duration of tourniquet use, pressure used, method of exsanguination. Analysis Procedures: The data were analyzed using descriptive statistics. The compliance with the BOAST guidelines was calculated as the percentage of patients who met the guidelines for the duration of tourniquet use and pressure used. Question Addressed: The question addressed by this study was whether the use of a tourniquet checklist could improve compliance with the BOAST guidelines. Conclusion: The results of this study suggest that the use of a tourniquet checklist can be an effective way to improve compliance with the BOAST guidelines. This is important because it can help to reduce the risk of complications associated with tourniquet use.

Keywords: tourniquet, pressure, duration, complications, surgery

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Authors: Shangerganesh Lingeshwaran

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In this presentation, we have performed numerical simulations for a reaction-diffusion equation with various nonlinear density-dependent diffusion operators and proliferation functions. The mathematical model represented by parabolic partial differential equation is considered to study the invasion of gliomas (the most common type of brain tumors) and to describe the growth of cancer cells and response to their treatment. The unknown quantity of the given reaction-diffusion equation is the density of cancer cells and the mathematical model based on the proliferation and migration of glioma cells. A standard Galerkin finite element method is used to perform the numerical simulations of the given model. Finally, important observations on the each of nonlinear diffusion functions and proliferation functions are presented with the help of computational results.

Keywords: glioma invasion, nonlinear diffusion, reaction-diffusion, finite eleament method

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Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Through analysis of a published micro-array-based high-throughput assessment, we discovered that miR-1275 was markedly down-regulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its effect and mechanism involved in NPC development and progression. In this study, we investigated the role of miR-1275 on the development of NPC. The results indicated that miR-1275 was significantly down-regulated in primary NPC tissues, and very low levels were found in NPC cell lines. Ectopic expression of miR-1275 in NPC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of HOXB5. In addition, miR-1275 suppresses G1/S transition through inhibition of HOXB5. Further, oncogene HOXB5 was revealed to be a putative target of miR-1275, which was inversely correlated with miR-1275 expression in NPC. Collectively, our study demonstrates that as a tumor suppressor, miR-1275 played a pivotal role on NPC through inhibiting cell proliferation, and suppressing G1/S transition by targeting oncogenic HOXB5.

Keywords: microRNA-1275 (miR-1275), HOXB5, nasopharyngeal carcinoma, proliferation

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Authors: Mohamed El Moctar Abeidi

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The indazole derivatives exhibit a wide spectrum of biological activities. They are known for their anti-tumor, antiplatelet, anti-viral, anti-microbial, anti-inflammatory, anti-leishmania and even anti-spermatogen. As part of our research on the synthesis of a number of heterocycles capable of exhibiting a biological and pharmacological property, due to our ongoing interest in the development of a simple and low-cost procedure for obtaining heterocyclic compounds that may have an interest for medicinal purposes. We present in this work the synthesis of 6-nitro-indazoles derivatives, using two different methods. the first method is the alkylation of Nitroindazole by two different alkylating agents under the conditions of solid/liquid phase transfer catalysis in N, N-dimethylformamide (DMF) in the presence of potassium carbonate (K₂CO₃) as a base, and tetra-n-butylammonium bromide (BTBA) as a catalyst. While the other method is the 1,3-dipolar cycloaddition, in this case, we have undertaken the preparation of bi-heterocyclic containing the 6-nitroindazole associate with group of isoxazoline, isoxazole or 1,2,3-Triazole under normal conditions and, under the catalytic conditions of the click chemistry we were also able to determine the structures without any ambiguity by the ¹H and ¹³C NMR.

Keywords: indazole, 6-nitroindazole, isoxazole, 1, 2, 3-Triazole

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Authors: Khusboo Agrawal, S. Saraf

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Quercetin, a flavonol provides a cellular protection against UV induced oxidative damages due to its excellent free radical scavenging activity and direct pro-apoptopic effect on tumor cells. However, its topical use is limited due to its unfavorable physicochemical properties. The present study was aimed to evaluate the potential of mesoporous silica nanoparticles as topical carrier system for quercetin delivery. Complexes of quercetin with mesoporous silica was prepared with different weight ratios and characterized by thermo gravimetric analysis, X-ray diffraction, high resolution TEM, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry The protective effect of this vehicle on UV-induced degradation of the quercetin was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated by using Franz diffusion cells. The immobilization of Quercetin in mesoporous silica nanoparticles (MSNs) increased the stability without undermining the antioxidant efficacy.

Keywords: cancer, MSNs, quercetin, topical delivery

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Authors: Stefaan Carpentier, Aya Al Masri, Fabrice Leroy, Thibault Julien, Safoin Aktaou, Malorie Martin, Fouad Maaloul

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Introduction: During an 'Interventional Radiology (IR)' procedure, the patient's skin-dose may become very high for a burn, necrosis, and ulceration to appear. In order to prevent these deterministic effects, a prediction of the peak skin-dose for the patient is important in order to improve the post-operative care to be given to the patient. The objective of this study is to estimate, before the intervention, the patient dose for ‘Chronic Total Occlusion (CTO)’ procedures by selecting relevant clinical indicators. Materials and methods: 103 procedures were performed in the ‘Interventional Cardiology (IC)’ department using a Siemens Artis Zee image intensifier that provides the Air Kerma of each IC exam. Peak Skin Dose (PSD) was measured for each procedure using radiochromic films. Patient parameters such as sex, age, weight, and height were recorded. The complexity index J-CTO score, specific to each intervention, was determined by the cardiologist. A correlation method applied to these indicators allowed to specify their influence on the dose. A predictive model of the dose was created using multiple linear regressions. Results: Out of 103 patients involved in the study, 5 were excluded for clinical reasons and 2 for placement of radiochromic films outside the exposure field. 96 2D-dose maps were finally used. The influencing factors having the highest correlation with the PSD are the patient's diameter and the J-CTO score. The predictive model is based on these parameters. The comparison between estimated and measured skin doses shows an average difference of 0.85 ± 0.55 Gy for doses of less than 6 Gy. The mean difference between air-Kerma and PSD is 1.66 Gy ± 1.16 Gy. Conclusion: Using our developed method, a first estimate of the dose to the skin of the patient is available before the start of the procedure, which helps the cardiologist in carrying out its intervention. This estimation is more accurate than that provided by the Air-Kerma.

Keywords: chronic total occlusion procedures, clinical experimentation, interventional radiology, patient's peak skin dose

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Authors: Jiping Cai, Ningzhi Wangyang, Jun Shao

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Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality that leads to structural and functional damage in several parts of the brain, such as cranial nerves, optic nerve tract or other circuitry involved in vision and occipital lobe, depending on its location and severity. As a result, the function associated with vision processing and perception are significantly affected and cause blurred vision, double vision, decreased peripheral vision and blindness. Here two cases complaining of monocular vision loss (actually temporal hemianopia) due to traumatic chiasmal syndrome after frontal head injury were reported, and were compared the findings with individual case reports published in the literature. Reported cases of traumatic chiasmal syndrome appear to share some common features, such as injury to the frontal bone and fracture of the anterior skull base. The degree of bitemporal hemianopia and visual loss acuity have a variable presentation and was not necessarily related to the severity of the craniocerebral trauma. Chiasmal injury may occur even in the absence bony chip impingement. Isolated bitemporal hemianopia is rare and clinical improvement usually may not occur. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis, and secondary mechanisms such as cell death, inflammation, edema, neurogenesis impairment and axonal damage associated with TBI. Beside visual field test, MRI evaluation of optic pathways seems to the strong objective evidence to demonstrate the impairment of the integrity of visual systems following TBI. Therefore, traumatic chiasmal syndrome should be considered as a differential diagnosis by both neurosurgeons and ophthalmologists in patients presenting with visual impairment, especially bitemporal hemianopia after head injury causing frontal and anterior skull base fracture.

Keywords: bitemporal hemianopia, brain injury, optic chiasma, traumatic chiasmal syndrome.

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Authors: Amir Ghasemlouei, Alireza Khalaj

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In women, cancer of the breast is one of the most common incident cancer and cause of death from cancer .we reviewed the prevalence of obesity and its association with breast cancer. In this study, a total of 25 articles regarding the subject matter of the article have been presented in which 640 patients were examined that 320 patients with breast cancer and 320 were controls. The distribution of breast cancer patients and controls with respect to their anthropometric indices in patients with higher weight, which was statistically significant (60.2 ± 10.2 kg) compared with control group (56.1 ± 11.3 kg). The body mass index of patients was (26.06+/-3.42) and significantly higher than the control group (24.1+/-1.7). Obesity leads to increased levels of adipose tissue in the body that can be stored toxins and carcinogens to produce a continuous supply. Due to the high level of fat and the role of estrogen in a woman is endogenous estrogen of the tumor and regulate the activities of growth steroids, obesity is a risk factor for breast cancer is confirmed. Our study and other studies show that obesity is a risk factor for breast cancer. And with a weight loss intervention for breast cancer can be prevented in the future.

Keywords: breast cancer, review study, obesity, overweight

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Authors: Ahmad Rasyadan Arshad, A. Rahman A. Jamal, N. Mohamed Ibrahim, Nor Azian Abdul Murad

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Introduction: Parkinson’s disease (PD) is a complex and asymptomatic disease where patients are usually diagnosed at late stage where about 70% of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers is crucial for early diagnosis of PD. MicroRNA (miRNA) is a short nucleotide non-coding small RNA which regulates the gene expression in post-translational process. The involvement of these miRNAs in neurodegenerative diseases includes maintenance of neuronal development, necrosis, mitochondrial dysfunction and oxidative stress. Thus, miRNA could be a potential biomarkers for diagnosis of PD. Objective: This study aim to identify the miRNA involved in Late Onset PD (LOPD) and Early Onset PD (EOPD) compared to the controls. Methods: This is a case-control study involved PD patients in the Chancellor Tunku Muhriz Hospital at the UKM Medical Centre. miRNA samples were extracted using miRNeasy serum/plasma kit from Qiagen. The quality of miRNA extracted was determined using Agilent RNA 6000 Nano kit in the Bioanalyzer. miRNA expression was performed using GeneChip miRNA 4.0 chip from Affymetrix. Microarray was performed in EOPD (n= 7), LOPD (n=9) and healthy control (n=11). Expression Console and Transcriptomic Analyses Console were used to analyze the microarray data. Result: miR-129-5p was significantly downregulated in EOPD compared to LOPD with -4.2 fold change (p = <0.050. miR-301a-3p was upregulated in EOPD compared to healthy control (fold = 10.3, p = <0.05). In LOPD versus healthy control, miR-486-3p (fold = 15.28, p = <0.05), miR-29c-3p (fold = 12.21, p = <0.05) and miR-301a-3p (fold = 10.01, p =< 0.05) were upregulated. Conclusion: Several miRNA have been identified to be differentially expressed in EOPD compared to LOPD and PD versus control. These miRNAs could serve as the potential biomarkers for early diagnosis of PD. However, these miRNAs need to be validated in a larger sample size.

Keywords: early onset PD, late onset PD, microRNA (miRNA), microarray

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Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

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Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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Authors: Mohammadreza Hajialigol, Nargues Falahi Charkhabi, Fatemeh Shahryari, Saadat Sarikhani

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BACKGROUND AND OBJECTIVES Iran is the third producer of Persian walnut worldwide. However, its walnut trees have been under threat from decline during last decade. Walnut canker caused by B. nigrifluens and B. rubrifaciens was recorded in multiple regions of Iran. Furthermore, Brenneria rosae subsp. rosae and Gibbsiella quercinecans were recently recognized as responsible for walnut decline in northwestern Iran. This study aimed to identify the causal agent of walnut decline in Kermanshah and Isfahan. MATERIAL AND METHODS Symptomatic samples were collected from affected walnut trees of Kermanshah and Isfahan provinces. The pathogenicity of strains was proved on immature walnut fruits cv. ‘Hartley’ and young green twigs of two-year-old walnut seedling cv. ‘Chandler’. Pathogenic strains were subjected to conventional phenotypic tests. 16S rRNA, gyrB, and infB genes were partially amplified and sequenced. RESULTS Irregular longitudinal cankers and dark lesions were observed in the outer and inner bark, respectively. Twenty-four strains were isolated on EMB-agar media. Fourteen strains were able to cause necrosis and a dark-colored region in the mesocarp and on young green twigs around the inoculation site 14 and 30 days post-inoculation, respectively. Strains were able to hydrolyze Tween 20, Tween 80, gelatin and esculin, however, did not produce indole or urease. Pairwise comparison, the 16S rRNA gene nucleotide sequences of strain I2 were 100% identical with those of Rahnella victoriana FRB 225T. Moreover, a phylogenetic tree reconstructed based on the concatenated sequences of two housekeeping gene fragments, gyrB (601 bp) and infB (615 bp), revealed that the strains I2, I5, and KE6 were clustered with R. victoriana FRB 225T. CONCLUSION To the best of our knowledge, this is the first report of R. victoriana in association with walnut decline. This result is necessary to find resistant genotypes.

Keywords: emerging pathogens, Iran, juglans regia, MLSA

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Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

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Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Yuping Liu, Li Tao, Yin Lu

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Accumulating evidence has been shown that diallyl trisulfide (DATS) from garlic may reduce the risk of developing several types of cancer. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we demonstrate the effectiveness of DATS on the metastatic behaviors of MDA-MB-435s human breast cancer cell line co-incubated with activated platelets. Indeed, our data identified that DATS significantly blocked platelets fouction induced by PAF, followed by the decreased production of TXB2. DATS was found to dose-dependently suppressed MDA-MB-435s cell migration and invasion in presence of activated platelets by PAF in vitro. Furthermore, the expression, secretion and enzymatic activity of matrix metalloproteinase (MMP)-2/9, as well as the luciferase activity of upstream regulator NF-κB in MDA-MB-435s, were obviously diminished by DATS. In parallel, DATS blocked upstream NF-κB activation signaling complexes composed of extracellular signal-related kinase (ERK) as assessed by measuring the levels of the phosphorylated forms.

Keywords: DATS, ERK, metastasis, MMPs, NF-κB, platelet

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Authors: Jose Carlos Tavares Carvalho, Hady Keita, Giovanna Rocha Santana, Igor Victor Ferreira Dos Santos, Jesus Rafael Rodriguez Amado, Ariadna Lafourcade Prada, Adriana Maciel Ferreira, Helison Oliveira

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Summary: As animal model, zebrafish can be a good opportunity to establish a profile of tissue alteration caused by Bothrops alternatus venom and to screen new anti-venom drugs. Objective: To establish tissue biomarkers from zebrafish injected by snake venom and elucidate the use of glucocorticoids in ophidic accidents. Materials and Methods: The Danio rerio fish were randomly divided into four groups: control group, venom group, Dexamethasone1h before venom injected group and Dexamethasone 1 h after venom injected group. The concentration of Bothrops alternatus venom was 0.13 mg/ml and the fish received 20µl/Fish. The Body weight measurement and histological characteristics of gills, kidneys, liver, and intestine were determinate. Results: Physical analysis shows necrosis accompanied by inflammation in animals receiving the Bothrops alternatus venom. Significant difference was observed in the variation of weight between the control group, and the groups received the venom (t student test, p < 0.05). The average histological alterations index of gill, liver, kidney or intestine was statistically higher in animals received the venom (t Student test, p < 0.05). The alterations were lower in the groups that received Dexamethasone 1h before and after venom injected compared to the group that received only the venom. Dexamethasone 1h before venom injected group had minor histopathological alterations. Conclusion: The organs of zebrafish may be a tissue biomarker of alterations from Bothrops alternatus venom and dexamethasone reduced the damage caused by this venom in the organs studied, which may suggest the use of zebrafish as animal model for research related to screening new drug against snake venom.

Keywords: zebrafish, snake venom, biomarker, drugs

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