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Nuclear Factor Kappa B

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https://www.readbyqxmd.com/read/30516019/pharmacodynamic-models-of-differential-bortezomib-signaling-across-several-cell-lines-of-multiple-myeloma
#1
Vidya Ramakrishnan, Donald E Mager
The heterogeneous polyclonal nature of multiple myeloma complicates the identification of protein biomarkers predictive of drug response. In this study, a pharmacodynamic systems modeling approach was used to link in vitro bortezomib exposure and myeloma cell death. The exposure-response was integrated through a network of important protein biomarker dynamics activated by bortezomib in four myeloma cell lines. The pharmacodynamic models reasonably characterized the protein and myeloma cell dynamics simultaneously following bortezomib (20 nM) treatment...
December 4, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/30515812/diosmetin-inhibits-osteoclast-formation-and-differentiation-and-prevents-lps-induced-osteolysis-in-mice
#2
Siyuan Shao, Fangsheng Fu, Ziyi Wang, Fangming Song, Chen Li, Zuo-Xing Wu, Jiaxing Ding, Kai Li, Yu Xiao, Yiji Su, Xixi Lin, Guixin Yuan, Jinmin Zhao, Qian Liu, Jiake Xu
Osteolytic bone diseases are closely linked to the over-activation of osteoclasts and enhancement of bone resorption. It has become a major health issue in orthopedic practice worldwide. Inhibition of osteoclasts is proposed to be the main treatment for osteolytic disorders. Diosmetin (DIO) is a natural flavonoid with properties of antioxidant, anti-infection, and antishock. The effect of DIO on osteoclast differentiation is poorly understood. In this study project, we found that DIO could inhibit osteoclastic formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in a dose-dependent manner...
December 4, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30514262/the-asamet-trial-a-randomized-phase-ii-double-blind-placebo-controlled-multicenter-2-%C3%A3-2-factorial-biomarker-study-of-tertiary-prevention-with-low-dose-aspirin-and-metformin-in-stage-i-iii-colorectal-cancer-patients
#3
Marilena Petrera, Laura Paleari, Matteo Clavarezza, Matteo Puntoni, Silvia Caviglia, Irene Maria Briata, Massimo Oppezzi, Eva Mihajlovic Mislej, Borut Stabuc, Michael Gnant, Thomas Bachleitner-Hofmann, Wilfried Roth, Dominique Scherer, Walter-E Haefeli, Cornelia M Ulrich, Andrea DeCensi
BACKGROUND: Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin can reduce colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin has also been associated with decreased colon adenoma recurrence in clinical trials and lower CRC incidence and mortality in epidemiological studies in diabetics. While both drugs have been tested as single agents, their combination has not been tested in cancer prevention trials...
December 4, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30513637/%C3%AE-melanocyte-stimulating-hormone-attenuates-neovascularization-by-inducing-nitric-oxide-deficiency-via-mc-rs-pka-nf-%C3%AE%C2%BAb-signaling
#4
Wen-Tsan Weng, Chieh-Shan Wu, Feng-Sheng Wang, Chang-Yi Wu, Yi-Ling Ma, Hoi-Hung Chan, Den-Chiung Wu, Jian-Ching Wu, Tian-Huei Chu, Shih-Chung Huang, Ming-Hong Tai
α-melanocyte-stimulating hormone (α-MSH) has been characterized as a novel angiogenesis inhibitor. The homeostasis of nitric oxide (NO) plays an important role in neovascularization. However, it remains unclear whether α-MSH mitigates angiogenesis through modulation of NO and its signaling pathway. The present study elucidated the function and mechanism of NO signaling in α-MSH-induced angiogenesis inhibition using cultured human umbilical vein endothelial cells (HUVECs), rat aorta rings, and transgenic zebrafish...
November 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30511399/dihydroartemisinin-ameliorates-balloon-injury-induced-neointimal-formation-in-rats
#5
Yang He, Bei Sun, Gang Chen, Renping Huang
OBJECTIVES: This study aims to evaluate the effects of dihydroartemisinin (DHA) on the balloon injury-induced neointimal formation in rats and to investigate the underlying mechanism. METHODS: The balloon-induced carotid artery injury model was established in male Sprague-Dawley rats, immediately after which the DHA solution was injected into the tail vein of rats. In in vitro assays, primary rat vascular smooth muscle cells (VSMCs) were pretreated with DHA and then coincubated with LPS...
December 3, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30510777/the-roles-of-prostaglandin-f-2-in-regulating-the-expression-of-matrix-metalloproteinase-12-via-an-insulin-growth-factor-2-dependent-mechanism-in-sheared-chondrocytes
#6
Pei-Pei Guan, Wei-Yan Ding, Pu Wang
Osteoarthritis (OA) was recently identified as being regulated by the induction of cyclooxygenase-2 (COX-2) in response to high fluid shear stress. Although the metabolic products of COX-2, including prostaglandin (PG)E2 , 15-deoxy-Δ12,14 -PGJ2 (15d-PGJ2 ), and PGF2α , have been reported to be effective in regulating the occurrence and development of OA by activating matrix metalloproteinases (MMPs), the roles of PGF2α in OA are largely overlooked. Thus, we showed that high fluid shear stress induced the mRNA expression of MMP-12 via cyclic (c)AMP- and PGF2α -dependent signaling pathways...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/30510451/12-hete-facilitates-cell-survival-by-activating-the-integrin-linked-kinase-nf-%C3%AE%C2%BAb-pathway-in-ovarian-cancer
#7
Qian Liu, Wenhua Tan, Jianhua Che, Dandan Yuan, Liying Zhang, Yuhong Sun, Xiaolong Yue, Lei Xiao, Yuxia Jin
Background: The dysfunction of cell apoptosis is an important event in the progression of cancer, and the growth of cancer cells is negatively regulated by cell apoptosis. In different types of cancers, inhibition of cellular apoptosis is often observed in the cancerous tissue, and increased resistance to apoptosis is a hallmark of cancer. Although previous studies have shown that 12-lipoxygenase (12-LOX)/12-hydroxyeicosatetraenoic acid (12-HETE) is activated and upregulated in different types of cancers, the consequences of 12-LOX/12-HETE upregulation and its precise roles in the survival of ovarian carcinoma cells are still unknown...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30505663/cembrane-type-diterpenoids-from-the-south-china-sea-soft-coral-sarcophyton-mililatensis
#8
Songwei Li, Fei Ye, Zhengdan Zhu, Hui Huang, Shuichun Mao, Yuewei Guo
Eight cembrane-type diterpenoids, namely, (+)-(6 R )-6-hydroxyisosarcophytoxide ( 1 ), (+)-(6 R )-6-acetoxyisosarcophytoxide ( 2 ), (+)-17-hydroxyisosarcophytoxide ( 3 ), sarcomililatins A-D ( 4 - 7 ), and sarcomililatol ( 8 ), were isolated from the soft coral Sarcophyton mililatensis collected from Weizhou Island, Guangxi Autonomous Region, together with 2 known related analogues, (+)-isosarcophytoxide ( 9 ) and (+)-isosarcophine ( 10 ). The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data...
October 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30504696/notoginsenoside-r1-protects-huvec-against-oxidized-low-density-lipoprotein-ox-ldl-induced-atherogenic-response-via-down-regulating-mir-132
#9
Changgeng Fu, Dexin Yin, Haiying Nie, Dajun Sun
BACKGROUND/AIMS: Radix notoginseng is a well-known traditional Chinese herbal medicine, has extensively pharmacological activities in cardiovascular system. Notoginsenoside R1 (NGR1) is one main active ingredient of Radix notoginseng. The purpose of this study was to evaluate the functional effects of NGR1 on atherosclerosis (AS). METHODS: Human umbilical vascular endothelial cells (HUVECs) were subjected to oxidized low density lipoprotein (ox-LDL), before which cells were preconditioned with NGR1...
November 30, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30504685/nitric-oxide-is-involved-in-activation-of-toll-like-receptor-4-signaling-through-tyrosine-nitration-of-src-homology-protein-tyrosine-phosphatase-2-in-murine-dextran-sulfate-induced-colitis
#10
Xin Tun, Keiji Yasukawa, Ken-Ichi Yamada
Ulcerative colitis is characterized by colonic mucosal bleeding and ulceration, often with repeated active and remission stages. One factor in ulcerative colitis development is increased susceptibility to commensal bacteria and lipopolysaccharide (LPS). LPS activates macrophages to release nitric oxide (NO) through Toll-like receptor 4 (TLR4) signaling. However, whether NO is beneficial or detrimental to colitis remains controversial. In this study, we investigated whether NO enhances the development of colitis in mice treated with dextran sulfate sodium (DSS) and inflammation in cells treated with low-dose LPS...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/30503830/oncolytic-adenovirus-delta-24-rgd-induces-a-widespread-glioma-proteotype-remodeling-during-autophagy
#11
Andrea González-Morales, Aintzane Zabaleta, Marc García-Moure, Marta M Alonso, Joaquín Fernández-Irigoyen, Enrique Santamaría
Adenovirus Delta-24-RGD has shown a remarkable efficacy in a phase I clinical trial for glioblastoma. Delta-24-RGD induces autophagy in glioma cells, however, the molecular derangements associated with Delta-24-RGD infection remains poorly understood. Here, proteomics was applied to characterize the glioma metabolic disturbances soon after Delta-24-RGD internalization and late in infection. Minutes post-infection, a rapid survival reprogramming of glioma cells was evidenced by an early c-Jun activation and a time-dependent dephosphorylation of multiple survival kinases...
November 29, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/30503692/increasing-hypothalamic-nucleobindin-2-levels-and-decreasing-hypothalamic-inflammation-in-obese-male-mice-via-diet-and-exercise-alleviate-obesity-associated-hypogonadism
#12
Dequan Chen, Shicheng Cao, Bo Chang, Tie Ma, Haining Gao, Yao Tong, Tao Li, Junchao Han, Xuejie Yi
To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, inhibitor kappa B kinase β (IKKβ), and nuclear factor (NF)-κB were increased in obese male mice...
November 1, 2018: Neuropeptides
https://www.readbyqxmd.com/read/30502652/luteoloside-attenuates-neuroinflammation-in-focal-cerebral-ischemia-in-rats-via-regulation-of-the-ppar%C3%AE-nrf2-nf-%C3%AE%C2%BAb-signaling-pathway
#13
Qiaoling Li, Zixia Tian, Minghui Wang, Jiejian Kou, Chunli Wang, Xuli Rong, Jing Li, Xinmei Xie, Xiaobin Pang
Luteoloside, a flavonoid compound, has been reported to have anti-inflammatory, anti-oxidative, antibacterial, antiviral, anticancer, and cardioprotective effects, among others, but its neuroprotective effects have rarely been studied. The purpose of this study was to investigate the protective effect of luteoloside on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of luteoloside on cerebral ischemia-reperfusion (I/R). Male Sprague-Dawley rats were randomly divided into six groups: sham, MCAO, luteoloside (20 mg/kg, 40 mg/kg, 80 mg/kg) and nimodipine (4 mg/kg)...
November 28, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30502599/inhibitors-of-nf-%C3%AE%C2%BAb-and-p2x7-nlrp3-caspase-1-pathway-in-microglia-novel-therapeutic-opportunities-in-neuroinflammation-induced-early-stage-alzheimer-s-disease
#14
REVIEW
Baban S Thawkar, Ginpreet Kaur
Microglial activation is a distinguished attribute in many neurodegenerative diseases of aging. Compelling evidence suggests that neuroinflammation stimulated by microglia, the resident macrophage-like immune cells in the brain, play a contributing role in the pathogenesis of Alzheimer's disease (AD). Postmortem brain tissue of individuals with AD has credibly demonstrated that neuroinflammation is likely to be a key driver of the disease. Recently, It has been found that manipulating β-amyloid directly is an impracticable approach for therapeutic intervention due to the failure of β-amyloid-lowering drugs in clinical trials...
November 20, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/30502235/proresolving-lipid-mediators-resolvin-d1-and-protectin-d1-isomer-attenuate-neointimal-hyperplasia-in-the-rat-carotid-artery-balloon-injury-model
#15
Yoshihisa Makino, Takuya Miyahara, Jun Nitta, Kazuhiro Miyahara, Akihiko Seo, Masaru Kimura, Masamitsu Suhara, Atsushi Akai, Daisuke Akagi, Kota Yamamoto, Katsuyuki Hoshina
BACKGROUND: Specialized proresolving mediators from ω-3 polyunsaturated fatty acid may control resolution of inflammation. We evaluated the influence of two specialized proresolving mediators, resolvin D1 (RvD1) and protectin D1 isomer (PD1 iso) on neointimal hyperplasia after balloon injury. MATERIALS AND METHODS: Sprague Dawley male rats at 12-14 wk of age were injured as a model of balloon angioplasty. Then, 1 μg/rat of RvD1 or PD1 iso was administered intravenously via the tail vein immediately and 2 d after angioplasty...
January 2019: Journal of Surgical Research
https://www.readbyqxmd.com/read/30500665/betamethasone-suppresses-the-inflammatory-response-in-lps-stimulated-dental-pulp-cells-through-inhibition-of-nf-%C3%AE%C2%BAb
#16
Dan Wang, Ning-Xin Zhu, Man Qin, Yuan-Yuan Wang
OBJECTIVE: This study aimed to investigate the anti-inflammatory effect of betamethasone on LPS-stimulated human dental pulp stem cells (DPSCs) and its associated mechanism. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and stem cells from human exfoliated deciduous teeth (SHED) were evaluated. DESIGN: The proliferative effect of betamethasone on DPSCs was analyzed using a cholecystokinin octapeptide assay. The anti-inflammatory effect of betamethasone was investigated using quantitative polymerase chain reaction (qPCR) and ELISA...
November 20, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/30500623/apremilast-ameliorates-carfilzomib-induced-pulmonary-inflammation-and-vascular-injuries
#17
Faisal Imam, Naif O Al-Harbi, Mohammed M Al-Harbi, Wajhul Qamar, Khaldoon Aljerian, Osamah Mohammed Belali, Sary Alsanea, Ahmed Z Alanazi, Khalid Alhazzani
Acute lung injury (ALI) due to chemotherapy occurs frequently. It presents a challenge for clinicians managing therapies for different types of cancers. Carfilzomib (Kyprolis™) is a new proteasome inhibitor that shows promise for the treatment of relapsing multiple myeloma. However, several cases of severe ALI have raised concern about the use of carfilzomib against relapsed multiple myelomas. To improve the efficacy of carfilzomib, a new anti-inflammatory drug for psoriasis treatment, apremilast (Otezla™) was investigated for its protective effects against carfilzomib-induced ALI in rats...
November 27, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30500399/mir-146a-mediates-thymosin-%C3%AE-4-induced-neurovascular-remodeling-of-diabetic-peripheral-neuropathy-in-type-ii-diabetic-mice
#18
Lei Wang, Michael Chopp, XueRong Lu, Alexandra Szalad, LongFei Jia, Xian Shuang Liu, Kuan-Han Wu, Mei Lu, Zheng Gang Zhang
Diabetes induces neurovascular dysfunction leading to peripheral neuropathy. MicroRNAs (miRNAs) affect many biological processes and the development of diabetic peripheral neuropathy. In the present study, we investigated whether thymosin-β4 (Tβ4) ameliorates diabetic peripheral neuropathy and whether miR-146a mediates the effect of Tβ4 on improved neurovascular function. Male Type II diabetic BKS.Cg-m+/+Leprdb /J (db/db) mice at age 20 weeks were treated with Tβ4 for 8 consecutive weeks, and db/db mice treated with saline were used as a control group...
November 27, 2018: Brain Research
https://www.readbyqxmd.com/read/30500344/protective-role-of-chrysin-on-thioacetamide-induced-hepatic-encephalopathy-in-rats
#19
Salma A El-Marasy, Sally A El Awdan, Reham M Abd-Elsalam
Hepatic encephalopathy (HE) is a serious neuropsychiatric syndrome due to either acute or chronic hepatic failure. This study aimed to investigate the possible neuroprotective effect of chrysin, a natural flavenoid on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. HE was induced in Wistar rats by intraperitoneal (i.p.) injection of TAA (200 mg/kg) for three alternative days...
November 27, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/30488804/drugs-of-abuse-induced-subversion-of-the-peripheral-immune-response-and-central-glial-activity-focus-on-novel-therapeutic-approaches
#20
Thea Magrone, Jirillo Emilio
Drugs of abuse affect both central nervous system (CNS) and peripheral immune function. Besides involvement of dopamine and glutamate systems, chronic exposure to drugs of abuse alters immune homeostasis, promoting a pro-inflammatory status. At the same time, impaired peripheral immunity leads to an increased susceptibility to infections in drug abusers. Effects on CNS: There is evidence that certain drugs, such as opioids, activate microglial cells and astrocytes which, in turn, provoke central neuroinflammation...
November 28, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
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