Theodore J Kottom, Kyle Schaefbauer, Eva M Carmona, Andrew H Limper
Pneumocystis jirovecii is a fungal pathogen that can cause life-threatening infections in individuals who are immunocompromised. Acquired via inhalation, upon entering the respiratory tract, the fungi first encounter innate immune cells such as alveolar macrophages (AMs). Relatively little is known about the AM cellular responses to the organism, and particularly transcription factor (TF) profiles leading to early host responses during infection. Utilizing the Mouse Transcription Factors RT2 Profiler™ PCR Array, we report an initial TF survey of these macrophage and Pneumocystis interactions...
May 8, 2021: Pathogens
Miguel Alejandro Lopez-Ramirez, Catherine Chinhchu Lai, Shady Ibrahim Soliman, Preston Hale, Angela Pham, Esau J Estrada, Sara McCurdy, Romuald Girard, Riya Verma, Thomas Moore, Rhonda Lightle, Nicholas Hobson, Robert Shenkar, Orit Poulsen, Gabriel G Haddad, Richard Daneman, Brendan Gongol, Hao Sun, Frederic Lagarrigue, Issam A Awad, Mark H Ginsberg
Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in one of three genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2 and KLF4-dependent elevation of eNOS in CCM endothelium...
May 27, 2021: Journal of Clinical Investigation
Anastassios Philippou, Andrea Tryfonos, Apostolos Theos, Adrianos Nezos, Antonis Halapas, Maria Maridaki, Michael Koutsilieris
Eccentric exercise has been extensively used as a model to study the contraction-induced muscle damage and its consequent processes. This study aimed at examining molecular responses associated with tissue remodelling, inflammation and angiogenesis in skeletal muscle during the recovery period after eccentric exercise in humans. Ten healthy men performed 50 maximal eccentric muscle actions with the knee extensors and muscle biopsies were collected from the vastus lateralis before and 6 h, 48 h and 120 h post eccentric exercise...
May 24, 2021: Molecular Biology Reports
Jing Zhou, Yaocheng Li, Xuejing Shi, Shulan Hao, Fupeng Zhang, Zhi Guo, Yu Gao, Hao Guo, Likun Liu
Purpose: Tumor blood vessels exhibit morphological and functional aberrancies. Its maturity and functionality are closely associated with colon cancer progression and therapeutic efficacy. The direct evidence proving whether oridonin (ORI) has vascular normalization promoting effect from which combination therapies will benefit is still lacking. Methods: We established a subcutaneous xenograft model of human colon cancer. The animals were divided into the Control and ORI-treated groups. Immunohistochemical analysis and TUNEL staining was applied to evaluate the proliferation, apoptosis and angiogenesis...
2021: Journal of Cancer
Jun-Young Shin, Jong-Gu Choi, Sungchul Shin, Sujung Yeo, Sang-Suk Lee
The gene expression of Prox-1 and Hif-1a for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs + PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs + LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Prox-1 and Hif-1a were enriched and decreased in an isolated PVs compared to LVs, respectively...
2021: Advances in Experimental Medicine and Biology
N A Diez-Calzadilla, R Noguera Salvá, P Soriano Sarrió, J M Martínez-Jabaloyas
INTRODUCTION: Renal cell carcinoma (RCC) accounts for 2-3% of all tumors being the most frequent solid lesion in the kidney. OBJECTIVE: To determine what genetic alterations and immunohistochemical (IHC) of clear cell renal carcinoma (ccRCC) are associated with prognosis and tumor aggressiveness. PATIENTS AND METHODS: Experimental analytical study with 57 patients who underwent radical and partial nephrectomy between 2005 and 2011, all with diagnosis of ccRCC and minimum post-operative follow-up of 36 months...
April 18, 2021: Cancer Treatment and Research Communications
B V Gagloev, N A Pozdeyeva, I O-H Al-Darraji
PURPOSE: To study the changes in the concentration of vascular endothelial growth factor A (VEGF-A) in the intraocular fluid (IOF) of rats with alloxan model of diabetes mellitus (DM) on insulin therapy at different time points. MATERIAL AND METHODS: The alloxan model of DM was simulated in 197 rats by a single intraperitoneal injection of 100 mg/kg alloxan hydrate. The animals were divided into 3 groups 7 days after administration of alloxan hydrate. The main group consisted of animals with alloxan model of DM, which begain receiving single daily intraperitoneal injections of insulin at a dose of 0...
2021: Vestnik Oftalmologii
Shan Xiao, Ye Yang, Yue-Tong Liu, Jun Zhu
Purpose: To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. Methods: DN rats were randomly divided into two groups ( n = 10) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues...
2021: Journal of Diabetes Research
Abdelghani El Rafei, Barry H Trachtenberg, Jessica Schultz, Ranjit John, Jerry D Estep, Raquel Araujo-Gutierrez, T Eric E Suarez, Kevin Goodwin, Rebecca Cogswell
BACKGROUND: Assess the association between digoxin use and gastrointestinal bleeding (GIB) in a multicenter continuous flow left ventricular assist device (LVAD) cohort. METHODS: Patients implanted with continuous flow LVADs with data on GIB and digoxin use from two centers were included in the analysis (n = 649). GIB events were captured up to 2 years of follow-up. Digoxin use was defined as digoxin prescribed at discharge or within the first 3 months after LVAD implantation...
March 4, 2021: Journal of Heart and Lung Transplantation
Yufei Tang, Shaoqi Zong, Hailun Zeng, Xiaofeng Ruan, Liting Yao, Susu Han, Fenggang Hou
MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20-22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways...
April 17, 2021: Cancer Cell International
Hyoungki Kim, Soonjo Kwon
Mouse clonal mesenchymal stem cells (mc-MSCs) were cultured on a Cytodex 3 microcarrier in a spinner flask for a suspension culture under hypoxia condition to increase mass productivity. The hypoxia environment was established using 4.0 mM Na2 SO3 with 10 μM or 100 µM CoCl2 for 24 h in a low glucose DMEM medium. As a result, the proliferation of mc-MSCs under hypoxic conditions was 1.56 times faster than the control group over 7 days. The gene expression of HIF-1a and VEGFA increased 4.62 fold and 2...
April 5, 2021: Bioprocess and Biosystems Engineering
Cheng-Xiang Song, Ji-Ying Chen, Na Li, Yuan Guo
Background: Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) suppresses post-apoptotic necrosis and alleviates inflammation. Defective efferocytosis induces diseases that include atherosclerosis and autoimmune diseases. C1q/TNF-related protein 9 (CTRP9), a novel adipokine, has been reported to protect against various cardiovascular disease; however, the effect of CTRP9 on efferocytosis has not been elucidated. Methods: 1. The efferocytosis of macrophages incubated with ACs with or without CTRP9 treatment was detected by flow cytometry (FCM) and immunostaining...
2021: Journal of Inflammation Research
Shraddha M Kamat, Andrew R Mendelsohn, James W Larrick
Modest modulation of oxygen intake, either by inducing mild intermittent hypoxia or hyperoxia appears to induce modest rejuvenative changes in mammals, in part, by activating key regulator hypoxia-induced factor 1a (HIF-1a). Interestingly both lower oxygen and transient higher oxygen levels induce this hypoxia regulator. Hyperbaric oxygen induces HIF-1a by the hyperoxic-hypoxic paradox that results from an overinduction of protective factors under intermittent hyperoxic conditions, leading to a state somewhat similar to that induced by hypoxia...
April 2021: Rejuvenation Research
Jia Shi, Tianxi Yu, Kai Song, Shihan Du, Simeng He, Xinxin Hu, Xiangyun Li, Haibo Li, Shuan Dong, Yuan Zhang, Zilei Xie, Cui Li, Jianbo Yu
Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed that preemptive administration of DEX (50μg/kg) alleviated lung pathologic injury, reduced oxidative stress indices (OSI), improved mitochondrial dysfunction, upregulated the expression of HIF-1α and HO-1, accompanied by shifting the dynamic course of mitochondria into fusion...
March 21, 2021: Redox Biology
Dimitrios Pavlakis, Spyridon Kampantais, Konstantinos Gkagkalidis, Victoras Gourvas, Dimitrios Memmos, Aikaterini Tsionga, Georgios Dimitriadis, Ioannis Vakalopoulos
BACKGROUND: One of the main factors in response to hypoxia in the tumor microenvironment is the hypoxia-inducible factor (HIF) pathway. Although its role in other solid tumors, particularly renal cell carcinoma, has been sufficiently elucidated, it remains elusive in prostate cancer. The aim of the present study was to investigate the expression of main proteins involved in this pathway and determine the correlation of the results with clinicopathological outcomes of patients with prostate cancer...
January 2021: Technology in Cancer Research & Treatment
Athanasios Tampakis, Benjamin Weixler, Silvan Rast, Ekaterini-Christina Tampaki, Eleonora Cremonesi, Venkatesh Kancherla, Nadia Tosti, Christoph Kettelhack, Charlotte K Y Ng, Tarik Delko, Savas D Soysal, Urs von Holzen, Evangelos Felekouras, Nikolaos Nikiteas, Martin Bolli, Luigi Tornillo, Luigi Terracciano, Serenella Eppenberger-Castori, Giulio C Spagnoli, Salvatore Piscuoglio, Markus von Flüe, Silvio Däster, Raoul A Droeser
BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset...
March 18, 2021: Acta Oncologica
Jian Wang, Xiean Ling, Min Zhou, Guanggui Ding, Bin Peng, Jun Wan
Osimertinib (OSI) resistance commonly occurs during the treatment of non-small-cell lung cancer (NSCLC). This study aims to investigate whether the thermal effects of radiofrequency ablation (RFA) can increase the sensitivity of OSI-resistant NSCLC to OSI treatment and whether OSI effectively inhibits the recurrence of OSI-resistant NSCLC following RFA treatment and improve survival of NSCLC patients. In vitro, OSI-resistant NCI-H1975 (NCI-H1975/OSIR) cells and thermotolerant NCI-H1975/OSIR (NCI-H1975/OSIR-a-h) cells were established using human NSCLC cell line NCI-H1975...
March 17, 2021: Neoplasma
Samuel C Russo, Federico Salas-Lucia, Antonio C Bianco
Deiodinases modify the biological activity of thyroid hormone (TH) molecules, i.e. they may activate thyroxine (T4) to 3,5,3'-tri-iodothyronine (T3), or inactivate T3 to 3,3'-diiodo-L-thyronine (T2) or T4 to reverse tri-iodothyronine (rT3). Although evidence of deiodination of T4 to T3 was available since the 1950s, objective evidence of TH metabolism was not established until the 1970s. The modern paradigm considers that the deiodinases not only play a role in the homeostasis of circulating T3, but they also provide dynamic control of TH signaling: cells that express the activating type 2 deiodinase (D2) have enhanced TH signaling due to intracellular build-up of T3; the opposite is seen in cells that express type 3 deiodinase (D3), the inactivating deiodinase...
March 15, 2021: Endocrinology
Shrihari T G
Innate and adaptive immune cells recruited to the tumor microenvironment by chemokines following noxious stimuli such as physical or chemical or infectious agents. Innate and adaptive immune cells release inflammatory mediators such as cytokines, chemokines, growth factors, proteolytic enzymes, activate transcription factors (NF-KB, STAT3,HIF-1a) results in tumor initiation, promotion, and progression. This article highlights about the role of innate and adaptive immune cells in tumor microenvironment.
January 2021: Gulf Journal of Oncology
Alexey Surov, Maciej Pech, Maciej Powerski, Katja Woidacki, Andreas Wienke
AIM: Our purpose was to perform a systemic literature review and meta-analysis regarding use of apparent diffusion coefficient (ADC) for prediction of histopathological features in rectal cancer (RC) and to proof if ADC can predict treatment response to neoadjivant radiochemotherapy in RC. METHODS: MEDLINE library, Cochrane and SCOPUS database were screened for associations between ADC and histopathology and/or treatment response in RC up to June 2020. Authors, year of publication, study design, number of patients, mean value and standard deviation of ADC were acquired...
March 4, 2021: Digestive Diseases
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