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Subhendu Mukherjee, Wei Sheng, Alexander Michkov, Krishna Sriarm, Rui Sun, Anna Dvorkin-Gheva, Paul A Insel, Luke J Janssen
We have shown that calcium (Ca2+ ) oscillations in human pulmonary fibroblasts (HPFs) contribute to pro-fibrotic effects of TGFβ and that disruption of these oscillations blunts features of pulmonary fibrosis. Prostaglandin E2 (PGE2 ) exerts anti-fibrotic effects in the lung but the mechanisms for this action are not well defined. We thus sought to explore interactions between PGE2 and the pro-fibrotic agent transforming growth factor beta (TGFβ) in pulmonary fibroblasts (PFs) isolated from patients with or without idiopathic pulmonary fibrosis (IPF)...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ping Fan, Nan Hu, Xiuyuan Feng, Yining Sun, Dan Pu, Xiaohong Lv, Zhiming Hao, Yang Li, Wujun Xue, Lan He
BACKGROUND: Osteoporosis (OP) is a systemic osteopathy with increased bone fragility and increased risk of fracture. Osteoclasts (OC) are the key target cells in the treatment of osteoporosis. We aimed to research the role of L-type calcium channel protein Cav1.3 in OC differentiation in this study. METHODS: OP rat model was established to detect the expression level of Cav1.3. Tartrate-resistant acid phosphatase assay was used to measure the differentiation of osteoclast during receptor activator of nuclear factor κ-Β ligand (RANKL)-induced osteoclasts formation...
February 11, 2019: Journal of Cellular Physiology
Kai Li, Wen Li, Hongqiang Yin, Yuen-Ki Cheong, Guogang Ren, Zhuo Yang
Chronic hypoxic damage is one of the most common pathogenic factors that can cause neurodegenerative disorder in most cases. Etidronate (Eti) is one of the best-known earlier-generations of bisphosphonate derivatives for the treatment of bone-loss related diseases. Building on the preceding study of our laboratory, we found that Eti showed neuroprotective effects against 2-vessel occlusion induced vascular dementia (VD) in rats. Therefore, in this study, we attempted to elucidate the mechanism of action, which Eti protected cells from chronic hypoxic damage caused by CoCl2 in SH-SY5Y cells in vitro...
December 11, 2018: Neurochemical Research
Shiyao Hua, Bing Wang, Rong Chen, Yuanbin Zhang, Yiwei Zhang, Tingting Li, Lin Dong, Xueyan Fu
BACKGROUND: Piper nigrum L. and Piper longum L. consist a classic formula in traditional Chinese Hui medicine and are widely used in treatment of stroke. To examine the therapeutic effect of neuron injury after apoplexy, we used a permanent middle cerebral artery occlusion model in rats to investigate the effects of dichloromethane fraction (DF) of Piper nigrum L. and Piper longum L. MATERIALS AND METHODS: After subjecting the rats to permanent middle cerebral artery occlusion, DF (100 and 200 mg/kg) were administered for 14 days...
December 7, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Jung-Hoon Pyun, Hyun-Ji Kim, Myong-Ho Jeong, Byeong-Yun Ahn, Tuan Anh Vuong, Dong I Lee, Seri Choi, Seung-Hoi Koo, Hana Cho, Jong-Sun Kang
Dysregulation of Ca2+ /calmodulin-dependent protein kinase (CaMK)II is closely linked with myocardial hypertrophy and heart failure. However, the mechanisms that regulate CaMKII activity are incompletely understood. Here we show that protein arginine methyltransferase 1 (PRMT1) is essential for preventing cardiac CaMKII hyperactivation. Mice null for cardiac PRMT1 exhibit a rapid progression to dilated cardiomyopathy and heart failure within 2 months, accompanied by cardiomyocyte hypertrophy and fibrosis. Consistently, PRMT1 is downregulated in heart failure patients...
November 30, 2018: Nature Communications
Sofia Fortalezas, Dorinda Marques-da-Silva, Carlos Gutierrez-Merino
The activation of L-type calcium channels (LTCCs) prevents cerebellar granule neurons (CGNs) from entering low-K⁺-induced apoptosis. In previous works, we showed that LTCCs are largely associated with caveolin-1-rich lipid rafts in the CGN plasma membrane. In this work, we show that protein kinase A (PKA) and calmodulin-dependent protein kinase II (CaMK-II) are associated with caveolin-1-rich lipid rafts of mature CGNs, and we further show that treatment with the cholesterol-trapping and lipid raft-disrupting agent methyl-β-cyclodextrin decreases the phosphorylation level of the LTCC β₂ subunit and the steady-state calcium concentration in neuronal somas ([Ca2+ ]i ) to values close to those measured in 5 mM KCl proapoptotic conditions...
November 20, 2018: International Journal of Molecular Sciences
Li-Li Li, Mei-Fang Jin, Hong Ni
The role of leptin in the pathogenesis of epilepsy is getting more and more attention in clinical and basic research. Although there are data indicating neuroprotective effects of elevated serum/brain leptin levels following acute seizures, no study to date has dealt with the impact of chronic leptin treatment on long-term brain injury following developmental seizures. The aim of this study was to evaluate whether chronic leptin treatment may have neuroprotective effects on cognitive and hippocampal mossy fiber sprouting following flurothyl-induced recurrent neonatal seizures and whether these effects are mediated by the zinc/CaMKII-associated mitophagy signaling pathway...
2018: Frontiers in Neurology
Jun Zhou, Yu Wang, Yiming Liu, Hanjiang Zeng, Hanshi Xu, Fan Lian
OBJECTIVE: We aim to explore the effect of adipose derived mesenchymal stem cells (ADMSCs) on a knee osteoarthritis rat model and analyze how ADMSCs affect chondrocyte apoptosis. MATERIALS AND METHODS: A surgically induced rat knee osteoarthritis (OA) model was constructed. ADMSCs were engrafted into the right knee cavity. Hematoxylin and eosin (H&E), Masson, and Safranin O were used to compare the histopathology of synovial membrane and cartilage. Immunohistochemical (IHC) was used to measure MMP-13, Collagen 2 (Col-2), Caspase-3 (Cas-3), PARP, p62, LC3b, DDR-2, FGFR-1, Wnt, P-AKT/AKT, p-CAMKII/CAMKII, and p-Smad1/Smad1 expression in the articular cartilage...
October 13, 2018: Journal of Cellular Biochemistry
Chao Liang, Fang Du, Jiaxing Wang, Jing Cang, Zhanggang Xue
BACKGROUND: Propofol can cause degeneration of developing brain cells and subsequent long-term learning or memory impairment. However, at the early stage of embryonic development, the molecular mechanism of propofol-induced inhibition in neural stem cells (NSCs) neurogenesis is still unclear. The aim of this study was to determine the role of propofol in NSCs neurogenesis and, more importantly, to explore the underlying mechanism. METHODS: First, a single intraperitoneal injection of propofol was performed in pregnant mice, and 6 hours after administration of propofol, the hippocampus RNA and the protein of the embryos' brains was extracted to analyze the expression of neuron-specific markers...
October 9, 2018: Anesthesia and Analgesia
Lili Sun, Hongmei Jia, Liyan Ma, Meng Yu, Yong Yang, Yang Liu, Hongwu Zhang, Zhongmei Zou
BACKGROUND: Xin-Ke-Shu (XKS), a patent medicine consisting of five commonly used traditional Chinese herbs, is used for the treatment of coronary heart diseases. A previous study showed that XKS has protective effects for ameliorating myocardial ischemia/reperfusion (I/R) injury. PURPOSE: This study was aimed to deeply understand the mechanisms and compatible principle of XKS against hypoxia/reoxygenation (H/R) injury and the contribution of each single herb to the efficacy of XKS...
October 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Li-Li Li, Ya-Chao Li, Dong-Jing Zhao, Mei-Fang Jin, Hong Ni
Metabolic disorders play an important role in the pathogenesis of many neurological diseases. Recent evidence suggests that leptin levels in peripheral blood and brain are lower in patients with epilepsy. Leptin is an energy-regulating hormone that plays a neuroprotective role in neurodegenerative diseases and brain trauma. However, little is known about the effects and molecular mechanisms of leptin treatment on long-term neurobehavioral impairment caused by developmental seizures. The present study evaluated whether chronic leptin treatment protected against neurobehavioral impairments induced by recurrent seizures in newborns treated with flurothyl...
October 2018: Epilepsy Research
Peter Petschner, Viola Tamasi, Csaba Adori, Eszter Kirilly, Romeo D Ando, Laszlo Tothfalusi, Gyorgy Bagdy
BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used entactogenic drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions frequently described in otherwise healthy MDMA users. Meanwhile, in post-traumatic stress disorder (PTSD) patients seem to benefit from therapeutic application of the drug, where damage in hippocampal cue extinction may play a role...
August 2, 2018: BMC Genomics
Lin Zeng, Jing Liu
OBJECTIVE: To investigate the changes in mitochondrial calcium and extracellular sodium concentrations in the masseter muscle of rats with occlusal interference and the regulatory mechanism of mitochondrial Ca2+ overload by calmodulin kinase II (CaMK II). METHODS: SD rat models of occlusal interference were established by placing a stainless steel segments (0.8 mm in diameter) to raise the occlusal surface of the upper right first molar. At 3, 7, 14, and 21 days after occlusal interference and at 3 days after removal of occlusal interference, HE staining was used to observe the histomorphological changes of the masseter muscle...
June 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Keisuke Imoto, Muneyoshi Okada, Hideyuki Yamawaki
Pulmonary arterial hypertension (PAH), which is characterized by an elevation of pulmonary arterial resistance, leads to a lethal right heart failure. It is an urgent issue to clarify the pathogenesis of PAH-induced right heart failure. The present study aimed to elucidate the characteristics of cardiac fibroblasts (CFs) isolated from hypertrophied right ventricles of monocrotaline (MCT)-induced PAH model rats. CFs were isolated from the right ventricles of MCT-injected rats (MCT-CFs) and saline-injected control rats (CONT-CFs)...
September 2018: Pflügers Archiv: European Journal of Physiology
Ling Zhang, Zheng-Wen Chen, Shu-Fen Yang, Muyasi Shaer, Ying Wang, Jun-Jie Dong, Beili Jiapaer
OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%-95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA-219 (miR-219) on inhibition of long-term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DM mice through the N-methyl-d-aspartate receptor (NMDAR) signaling pathway regulation. METHODS: The T2DM mouse models were established, after which LTP in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured...
May 27, 2018: CNS Neuroscience & Therapeutics
T Qin, N Li, X-F Tan, J-H Zheng, R Tao, M-H Chen
OBJECTIVE: To investigate the effects of hyperkalemia on the brain after I/R in h transient middle cerebral artery occlusion (tMCAO) model. MATERIALS AND METHODS: A total of 120 adult male SD rats were randomly assigned to four groups: (1) hyperkalemia 80 µg/g (HK80) group; (2) hyperkalemia 40 µg/g (HK40) group; (3) normal saline (NS) group; (4) sham (SH) group. The concentration of serum K+ was elevated in HK80 and HK40 groups. The transient middle cerebral artery occlusion (tMCAO) model was used to assess the effect of hyperkalemia on the brain after I/R...
May 2018: European Review for Medical and Pharmacological Sciences
Dayong Ren, Fanrui Zhao, Chunlei Liu, Ji Wang, Yong Guo, Jingsheng Liu, Weihong Min
BACKGROUND: Walnut protein, which is obtained as a by-product of oil expression, has not been used efficiently. Although walnuts are beneficial for cognitive functioning, the potential of their protein composition in strengthening learning and memory functions remains unknown. In this study, the inhibition of memory impairment by the Manchurian walnut hydrolyzed peptide (MWHP) was evaluated. RESULTS: Small-molecular-weight MWHP (<3 kDa) achieved the optimal antioxidative activity...
October 2018: Journal of the Science of Food and Agriculture
Leonardo Vinícius Monteiro de Assis, Maria Nathalia Moraes, Keila Karoline Magalhães-Marques, Ana Maria de Lauro Castrucci
The mammalian skin has a photosensitive system comprised by several opsins, including rhodopsin (OPN2) and melanopsin (OPN4). Recently, our group showed that UVA (4.4 kJ/m2 ) leads to immediate pigment darkening (IPD) in murine normal and malignant melanocytes. We show the role of OPN2 and OPN4 as UVA sensors: UVA-induced IPD was fully abolished when OPN4 was pharmacologically inhibited by AA9253 or when OPN2 and OPN4 were knocked down by siRNA in both cell lines. Our data, however, demonstrate that phospholipase C/protein kinase C pathway, a classical OPN4 pathway, is not involved in UVA-induced IPD in either cell line...
April 2018: European Journal of Cell Biology
Mozibur Rahman, Rui Sun, Subhendu Mukherjee, Bernd Nilius, Luke J Janssen
We previously described several ionic conductances in human pulmonary fibroblasts, including one activated by two structurally distinct TRPV4 (transient receptor potential, vanilloid-type, subtype 4)-channel agonists: 4αPDD (4α-phorbol-12,13-didecanoate) and GSK1016790A. However, the TRPV4-activated current exhibited peculiar properties: it developed slowly over many minutes, exhibited reversal potentials that could vary by tens of millivolts even within a given cell, and was not easily reversed by subsequent addition of two distinct TRPV4-selective blockers (RN-1734 and HC-067047)...
July 2018: American Journal of Respiratory Cell and Molecular Biology
Cui-Ping Guo, Zhen Wei, Fang Huang, Min Qin, Xing Li, Yu-Man Wang, Qun Wang, Jian-Zhi Wang, Rong Liu, Bin Zhang, Hong-Lian Li, Xiao-Chuan Wang
Although increasing evidences suggest a relationship between hypertension and brain function for years, it is still unclear whether hypertension constitutes a risk factor for cognitive decline and its underlying mechanism. In the present study, an experimental animal model of hypertension simply by feeding rats with high salt diet was employed. We found that long-term high salt intake caused a marked increase of systolic blood pressure linked to a declined regional cerebral blood flow. Fear conditioning and morris water maze behavioral test revealed that high salt diet induced hippocampal dependent spatial reference memory deficits, while a decreased synaptogenesis without neuronal loss in hippocampus was observed in high salt treated rats...
November 10, 2017: Oncotarget
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