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B Antonioli, M Galuzzi
First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function...
March 2018: European Review for Medical and Pharmacological Sciences
Y-X Cao, Z-Q Wang, J-X Kang, K Liu, C-F Zhao, Y-X Guo, B-H Jiao
OBJECTIVE: It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells. MATERIALS AND METHODS: PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1...
March 2018: European Review for Medical and Pharmacological Sciences
Liyuan Mao, Qiongyun Chen, Ke Gong, Xiaolin Xu, Yurou Xie, Wenqing Zhang, Hanwei Cao, Tianhui Hu, Xiaoting Hong, Yan-Yan Zhan
Hyperactivated glucose uptake and glycolytic metabolism are considered as a hallmark of cancer. Berberine, a natural alkaloid with tumor‑selective anticancer effects, has been shown to promote glucose uptake in metabolic tissues and cells. However, whether and how berberine regulates the glucose metabolism of cancer cells are still poorly understood. In the present study, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines as assessed by RT‑qPCR...
May 2018: Oncology Reports
Guangbao Yang, Ligeng Xu, Jun Xu, Rui Zhang, Guosheng Song, Yu Chao, Liangzhu Feng, Fengxuan Han, Ziliang Dong, Bin Li, Zhuang Liu
Photodynamic therapy (PDT) is an oxygen-dependent light-triggered non-invasive therapeutic method showing many promising aspects in cancer treatment. For effective PDT, nanoscale carriers are often needed to realize tumor-targeted delivery of photosensitizers, which ideally should further target specific cell organelles that are most vulnerable to reactive oxygen species (ROS). Secondly, as oxygen is critical for PDT-induced cancer destruction, overcoming hypoxia existing in majority of solid tumors is important for optimizing PDT efficacy...
March 22, 2018: Nano Letters
Andrea Becerra-Calixto, Rafael Posada-Duque, Gloria Patricia Cardona-Gómez
Astrocytes play metabolic and structural support roles and contribute to the integrity of the blood-brain barrier (BBB), linking communication between neurons and the endothelium. Cyclin-dependent kinase 5 (CDK5) likely exerts a dual effect on the endothelium and astrocytes due to its involvement in migration and angiogenesis; the overactivation of CDK5 is associated with dysfunction in glutamate recapture and hypoxia. Recently, we proposed that CDK5-targeted astrocytes facilitate the recovery of neurological and motor function in transplanted ischemic rats...
March 22, 2018: Molecular Neurobiology
Abigail L Lind, Fang Yun Lim, Alexandra A Soukup, Nancy P Keller, Antonis Rokas
Biosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. In Aspergillus molds, asexual development is regulated by the BrlA > AbaA > WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of Δ brlA , Δ abaA , and Δ wetA mutant and wild-type strains of the human pathogen Aspergillus fumigatus ...
March 2018: MSphere
Leonardo J Magnoni, Ep Eding, Isabelle Leguen, Patrick Prunet, Inge Geurden, Rodrigo O A Ozório, Johan W Schrama
Oxygen limitation and dietary imbalances are key aspects influencing feed intake (FI) and growth performance in cultured fish. This study investigated the combined effects of hypoxia and dietary electrolyte balance on the growth performance, body composition and nutrient utilization in a rainbow trout (Oncorhynchus mykiss) isogenic line. Fish were fed ad libitum two experimental diets: electrolyte-balanced or -imbalanced diets (DEB 200 or 700 mEq kg-1 , respectively) and exposed to normoxia or hypoxia (7.9 or 4...
March 21, 2018: Scientific Reports
Paulo Afonso Medeiros Kanda, Aline de Almeida Xavier Aguiar, Jose Lucivan Miranda, Alexandre Loverde Falcao, Claudia Suenia Andrade, Luigi Neves Dos Santos Reis, Ellen White R Bacelar Almeida, Yanes Brum Bello, Arthur Monfredinho, Rafael Guimaraes Kanda
Microcephaly (MC), previously considered rare, is now a health emergency of international concern because of the devastating Zika virus pandemic outbreak of 2015. The authors describe the electroencephalogram (EEG) findings in sleep EEG of epileptic children who were born with microcephaly in areas of Brazil with active Zika virus transmission between 2014 and 2017. The authors reviewed EEGs from 23 children. Nine were females (39.2%), and the age distribution varied from 4 to 48 months. MC was associated with mother positive serology to toxoplasmosis (toxo), rubella (rub), herpes, and dengue (1 case); toxo (1 case); chikungunya virus (CHIKV) (1 case); syphilis (1 case); and Zika virus (ZIKV) (10 cases)...
2018: Neurodiagnostic Journal
Marianne S Joerger-Messerli, Byron Oppliger, Marialuigia Spinelli, Gierin Thomi, Ivana di Salvo, Philipp Schneider, Andreina Schoeberlein
Hypoxic-ischemic (HI) insult in the perinatal phase harbors a high risk of encephalopathy in the neonate. Brain cells undergo apoptosis, initiating neurodegeneration. So far, therapeutic approaches such as cooling remain limited. Transplantation of mesenchymal stem cells (MSCs) exhibits therapeutic success despite the short-time survival in the host brain, providing strong evidence that their beneficial effects are largely based on secreted factors, including extracellular vesicles (EVs). The aim of this study was to investigate the effects of human Wharton's jelly MSC (hWJ-MSC)-derived EVs on neuroprotection and neuroregeneration, using an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) mimicking HI injury in the mouse neuroblastoma cell line neuro2a (N2a)...
January 2018: Cell Transplantation
Jing Zhang, Qing Zhang
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc...
March 19, 2018: Biomedicines
Ewelina Bratek, Apolonia Ziembowicz, Elzbieta Salinska
Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible experimental therapies, the induction of ischemic tolerance is promising. Recent investigations have shown that activation of group II metabotropic glutamate receptors (mGluR2/3) can provide neuroprotection against H-I, but the mechanism of this effect is not clear...
March 17, 2018: Brain Sciences
Yun Wang, Qing-Jiang Pang, Jiang-Tao Liu, Hai-Hao Wu, Dong-Ying Tao
MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Zhijuan Chen, Lingbao Ai, Mam Y Mboge, Robert McKenna, Christopher J Frost, Coy D Heldermon, Susan C Frost
Human cell lines are an important resource for research, and are often used as in vitro models of human diseases. In response to the mandate that all cells should be authenticated, we discovered that the MDA-MB-231 cells that were in use in our lab, did not validate based on the alleles of 9 different markers (STR Profile). We had been using this line as a model of triple negative breast cancer (TNBC) that has the ability to form tumors in immuno-compromised mice. Based on marker analysis, these cells most closely resembled the MCF10A line, which are a near diploid and normal mammary epithelial line...
March 21, 2018: Cancer Biology & Therapy
Kimberley Jae Botting, Xin Yee Loke, Song Zhang, Johnnie B Andersen, Jens Randel Nyengaard, Janna L Morrison
Intrauterine growth restriction (IUGR) increases the risk of ischaemic heart disease in adulthood. Studies in rats suggest cardiac vulnerability is more pronounced in males and in offspring that were exposed to hypoxia in utero. Therefore, we aimed to test the hypotheses that 1) IUGR adolescent males, but not females, have fewer cardiomyocytes and altered expression of cardiometabolic genes compared to Controls and 2) IUGR due to hypoxia has a greater effect on these parameters compared to IUGR due to nutrient restriction...
March 21, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Thomas W L Scheeren, Jannis N Wicke, Jean-Louis Teboul
PURPOSE OF REVIEW: The current review attempts to demonstrate the value of several forms of carbon dioxide (CO2) gaps in resuscitation of the critically ill patient as monitor for the adequacy of the circulation, as target for fluid resuscitation and also as predictor for outcome. RECENT FINDINGS: Fluid resuscitation is one of the key treatments in many intensive care patients. It remains a challenge in daily practice as both a shortage and an overload in intravascular volume are potentially harmful...
March 20, 2018: Current Opinion in Critical Care
Hunter G Moss, Truman R Brown, Donald B Wiest, Dorothea D Jenkins
Persistent oxidative stress depletes reduced glutathione (GSH), an intracellular antioxidant and an important determinant of CNS injury after hypoxia ischemia. We used standard, short echo time Stimulated Echo Acquisition Mode (STEAM) to detect GSH by magnetic resonance spectroscopy (MRS) in 24 term neonates with hypoxic-ischemic encephalopathy (HIE), on day of life 5-6, after rewarming from therapeutic hypothermia. MRS demonstrated reliable, consistent GSH of 1·64 ± 0·20 mM in the basal ganglia immediately before intravenous infusion of N-acetylcysteine...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Barbara J Morgan, Nicole Schrimpf, Morgan Rothman, Ann Mitzey, Mark S Brownfield, Robert C Speth, John M Dopp
Chronic intermittent hypoxia (CIH) increases basal sympathetic nervous system activity, augments chemoreflex-induced sympathoexcitation, and raises blood pressure. All effects are attenuated by systemic or intracerebroventricular administration of angiotensin II type 1 receptor (AT1 R) antagonists. This study aimed to quantify the effects of CIH on AT1 R- and AT2 R-like immunoreactivity in the rostroventrolateral medulla (RVLM) and paraventricular nucleus of the hypothalamus (PVN), central regions that are important components of the extended chemoreflex pathway...
March 21, 2018: Clinical and Experimental Hypertension: CHE
Alina L Bendinger, Christin Glowa, Jörg Peter, Christian P Karger
A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions...
March 2018: Journal of Biomedical Optics
Shaolin Ma, Sunila Pradeep, Wei Hu, Dikai Zhang, Robert Coleman, Anil Sood
Anti-angiogenic therapy has been demonstrated to increase progression-free survival in patients with many different solid cancers. Unfortunately, the benefit in overall survival is modest and the rapid emergence of drug resistance is a significant clinical problem. Over the last decade, several mechanisms have been identified to decipher the emergence of resistance. There is a multitude of changes within the tumor microenvironment (TME) in response to anti-angiogenic therapy that offers new therapeutic opportunities...
2018: F1000Research
Hadas Pahima, Simona Reina, Noa Tadmor, Daniella Dadon-Klein, Anna Shteinfer-Kuzmine, Nathalie M Mazure, Vito De Pinto, Varda Shoshan-Barmatz
The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca2+ and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity...
February 27, 2018: Oncotarget
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