tbuckley/cabot-search huggingface dataset:
CKII-SIRT1-SM22α loop evokes a self-limited inflammatory response in vascular smooth muscle cells
Authors: Ya-Nan Shu, Li-Hua Dong, Han Li, Qian-Qian Pei, Sui-Bing Miao, Fan Zhang, Dan-Dan Zhang, Rong Chen, Ya-Juan Yin, Yan-Ling Lin, Zhen-Ying Xue, Pin Lv, Xiao-Li Xie, Li-Li Zhao, Xi Nie, Peng Chen, Mei Han
Journal: Cardiovascular Research (2017)

Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation.The ligation injury model of Sirt1-Tg/Sm22α-/- mice displayed an increased level of the inflammatory molecules in the carotid arteries compared with Sirt1-Tg mice, accompanied with aggravating neointimal hyperplasia. In the in vitro study, on the one hand, we showed that TNF-α induced the epigenetic silencing of SM22α transcription via EZH2-mediated H3K27 methylation in the SM22α promoter region, contributing to inflammatory response. On the other hand, TNF-α simultaneously induced SIRT1 phosphorylation via CKII and thereby protected against inflammation. Phosphorylated SIRT1 interacted with and deacetylated EZH2 and, subsequently, promoted SM22α transcription by inhibiting EZH2 activity. Increased SM22α in turn facilitated the phosphorylation and activation of SIRT1 via recruitment of CKII to SIRT1, which amplified the anti-inflammatory effect of SIRT1.Our findings demonstrate that, in response to TNF-α stimulation, CKII-SIRT1-SM22α acts in a loop to reinforce the expression of SM22α, which limits the inflammatory response in VSMCs in vivo and in vitro. The anti-inflammatory effect of SIRT1 may be dependent on SM22α to some extent. Our data point to targeted activation of SIRT1 in VSMCs as a promising therapeutic avenue in preventing cardiovascular diseases.
포스터전시 : 만성 C형간염에서 Pegylated interferon alpha-2a와 Ribavirin 병합요법의 치료효과
Authors: 오인수, 이현웅, 김형준, 백은경, 김기성, 이승용, 차봉기, 오형철, 최창환, 김정욱, 도재혁, 김재규, 장세경
Journal: Clinical and Molecular Hepatology (2009)
Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder
Authors: None Hypericum Depression Trial Study Group
Journal: JAMA (2002)

ContextExtracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated.ObjectiveTo test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.Design and SettingDouble-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States.ParticipantsAdult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20.InterventionsPatients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks.Main Outcome MeasuresChange in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores.ResultsOn the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was –9.20 (0.67) (95% confidence interval [CI], –10.51 to –7.89) for placebo vs –8.68 (0.68) (95% CI, –10.01 to –7.35) for H perforatum (P = .59) and –10.53 (0.72) (95% CI, –11.94 to –9.12) for sertraline (P = .18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum–treated patients (P = .21) and 24.8% of sertraline-treated patients (P = .26). Sertraline was better than placebo on the CGI improvement scale (P = .02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo.ConclusionThis study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.
The western diet, endogenous cytotoxin and genotoxin formation, a possible cause of carcinogenesis
Authors: Owen Lee, W. Robert Bruce, Qiang Dong, Peter O'Brien
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3098 

The risk of colorectal and other epithelial cancers is associated with excessive energy consumption and increased oxidative stress, typical for individuals consuming any Western diet high in sugars, fats and meats, low in vegetables and micronutrients. Here we have shown that two factors oxidative stress and fructose together caused marked cytotoxicity towards isolated hepatocytes. During inflammation, hepatic macrophages (Kupffer cells) release cytokines and NADPH oxidase becomes activated releasing reactive oxygen species. Our hepatocyte inflammation model involves exposing hepatocytes to a H2O2 generating system at a low rate that does not affect cell viability or glutathione levels. Hepatocyte viability was also not affected by high concentrations of fructose. Fructose cytotoxicity in the presence of a H2O2 generating system was preceded by increased ROS generation, disrupted mitochondrial membrane potential (MMP), and depleted ATP levels. Interestingly, such cytotoxicity, ROS generation, and MMP disruption was significantly ameliorated by the iron chelator: desferoxamine, as well as micronutrients: ascorbic acid, pyridoxal, carnitine, and thiamine. The cytoprotection specificity of these agents was unlike that seen with cytotoxicity induced by high H2O2 concentrations alone. Fructose cytotoxicity was further increased by added iron or by depleting glutathione beforehand. Glyceraldehyde and dihydroxyacetone metabolites of fructose were several fold more cytotoxic than fructose and markedly increased cellular ROS and lipid peroxidation. Overall, the order of hepatocyte cytotoxicity found for sugar/metabolites was dihydroxyacetone > glyceraldehyde > fructose > xylitol, sorbitol > glycerol, deoxyribose, glucose > ribose. Addition of H2O2 to glyceraldehyde or dihydroxyacetone in a cell free system also caused rapid oxygen uptake and further H2O2 formation that was attributed to autoxidation. Furthermore added linoleic acid or DNA was also cooxidised to form thiobarbituric acid reactive products and 8-oxodG respectively thereby implicating carbon radicals and ROS respectively. We hypothesize that ROS formed by plasma membrane NADPH oxidase during inflammation oxidises the fructose metabolites glyceraldehyde and dihydroxyacetone to ROS and carbon radicals. These reactive species cause lipid peroxidation and DNA oxidation that contribute to cytotoxicity and carcinogenesis. The cytotoxic and genotoxic mechanism described could also explain the association of other common chronic diseases of the developed and developing world with the Western diet including non-alcoholic steatohepatitis, Type 2 diabetes, hypertension, cardiovascular disease, rheumatoid arthritis or the association of colorectal cancer risk with hyperinsulinemia and the metabolic syndrome.
TCTAP A-152 Evaluation of Safety of 1-month Dual Antiplatelet Therapy Followed by Prasugrel Monotherapy in Patients Implanted Resolute Zotarolimus-eluting Stent
Authors: Fujimoto Wataru, Takahiro Sawada, Tomofumi Takaya, Yoshinori Yasaka
Journal: Journal of the American College of Cardiology (2017)
Superficial swab versus deep-tissue biopsy for the microbiological diagnosis of local infection in advanced-stage pressure ulcers of spinal-cord-injured patients: a prospective study
Authors: S. Tedeschi, L. Negosanti, R. Sgarzani, F. Trapani, S. Pignanelli, M. Battilana, R. Capirossi, D. Brillanti Ventura, M. Giannella, M. Bartoletti, F. Tumietto, F. Cristini, P. Viale
Journal: Clinical Microbiology and Infection (2017)
WHO surgical safety checklist cuts post-surgical deaths by 22%, US study finds
Authors: Michael McCarthy
Journal: BMJ (2017)

Hospitals that completed a quality improvement programme designed to implement the World Health Organization’s surgical safety checklist saw a 22% lower 30 day post-surgery mortality than hospitals that did not complete the programme, a US study has found.1

The WHO checklist requires surgical teams to take such steps as confirming the patient’s identity, scheduled procedure, and surgical site at the outset; reviewing the procedure’s risks before incision; and completing instrument and sponge counts and discussing postoperative care before the patient leaves the operating room.23

In several research trials the checklist was …
TCTAP A-113 The Comparison of Coronary Artery Disease Severity Based on the Type of Left Ventricle Hypertrophy in Stable Angina Pectoris and Hypertension Patients: The Proof of the New Paradigm
Authors: Iman Suhartono, Johan Senihardja, Rizki Francis Pandelaki, Benny Mulyanto Setiadi, Bambang Budiono, Janry Anton Pangemanan, Agnes Lucia Panda
Journal: Journal of the American College of Cardiology (2017)
Response to Comment on Chen et al. Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study. Diabetes Care 2016;39:788–793
Authors: Mu-Hong Chen
Journal: Diabetes Care (2017)

Li and Li (1) reviewed our article (2), which was published in Diabetes Care and concerned the potential confounding effect of maternal metabolic conditions, particularly maternal diabetes and obesity, on the association between autism spectrum disorder (ASD) and type 2 diabetes risk. Li and Li (1) mentioned that a growing body of evidence supports the association of maternal diabetes and obesity with the increased risk of ASD in offspring. Intergenerational transmission of overweight …
FDA Approval of Eteplirsen for Muscular Dystrophy
Authors: Jonathan Sackner-Bernstein
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma
Authors: Nidhi Jariwala, Devaraja Rajasekaran, Rachel G. Mendoza, Xue-Ning Shen, Ayesha Siddiq, Maaged A. Akiel, Chadia L. Robertson, Mark A. Subler, Jolene J. Windle, Paul B. Fisher, Arun J. Sanyal, Devanand Sarkar
Journal: Cancer Research (2017)

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor-initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-κB signaling pathways in promoting TIC formation in Alb/SND1 mice. In human xenograft models of subcutaneous or orthotopic HCC, administration of the selective SND1 inhibitor 3', 5'-deoxythymidine bisphosphate (pdTp), inhibited tumor formation without effects on body weight or liver function. Our work establishes an oncogenic role for SND1 in promoting TIC formation and highlights pdTp as a highly selective SND1 inhibitor as a candidate therapeutic lead to treat advanced HCC. Cancer Res; 77(12); 3306-16. ©2017 AACR.
The effect of rapid privatisation on mortality in mono-industrial towns in post-Soviet Russia: a retrospective cohort study
Authors: Aytalina Azarova, Darja Irdam, Alexi Gugushvili, Mihaly Fazekas, Gábor Scheiring, Pia Horvat, Denes Stefler, Irina Kolesnikova, Vladimir Popov, Ivan Szelenyi, David Stuckler, Michael Marmot, Michael Murphy, Martin McKee, Martin Bobak, Lawrence King
Journal: The Lancet Public Health (2017)

Population-level data suggest that economic disruptions in the early 1990s increased working-age male mortality in post-Soviet countries. This study uses individual-level data, using an indirect estimation method, to test the hypothesis that fast privatisation increased mortality in Russia.In this retrospective cohort study, we surveyed surviving relatives of individuals who lived through the post-communist transition to retrieve demographic and socioeconomic characteristics of their parents, siblings, and male partners. The survey was done within the framework of the European Research Council (ERC) project PrivMort (The Impact of Privatization on the Mortality Crisis in Eastern Europe). We surveyed relatives in 20 mono-industrial towns in the European part of Russia (ie, the landmass to the west of the Urals). We compared ten fast-privatised and ten slow-privatised towns selected using propensity score matching. In the selected towns, population surveys were done in which respondents provided information about vital status, sociodemographic and socioeconomic characteristics and health-related behaviours of their parents, two eldest siblings (if eligible), and first husbands or long-term partners. We calculated indirect age-standardised mortality rates in fast and slow privatised towns and then, in multivariate analyses, calculated Poisson proportional incidence rate ratios to estimate the effect of rapid privatisation on all-cause mortality risk.Between November, 2014, and March, 2015, 21 494 households were identified in 20 towns. Overall, 13 932 valid interviews were done (with information collected for 38 339 relatives [21 634 men and 16 705 women]). Fast privatisation was strongly associated with higher working-age male mortality rates both between 1992 and 1998 (age-standardised mortality ratio in men aged 20-69 years in fast vs slow privatised towns: 1·13, SMR 0·83, 95% CI 0·77-0·88 vs 0·73, 0·69-0·77, respectively) and from 1999 to 2006 (1·15, 0·91, 0·86-0·97 vs 0·79, 0·75-0·84). After adjusting for age, marital status, material deprivation history, smoking, drinking and socioeconomic status, working-age men in fast-privatised towns experienced 13% higher mortality than in slow-privatised towns (95% CI 1-26).The rapid pace of privatisation was a significant factor in the marked increase in working-age male mortality in post-Soviet Russia. By providing compelling evidence in support of the health benefits of a slower pace of privatisation, this study can assist policy makers in making informed decisions about the speed and scope of government interventions.The European Research Council.
Human ESC/iPSC-Derived Hepatocyte-like Cells Achieve Zone-Specific Hepatic Properties by Modulation of WNT Signaling
Authors: Seiji Mitani, Kazuo Takayama, Yasuhito Nagamoto, Kazuo Imagawa, Fuminori Sakurai, Masashi Tachibana, Ryo Sumazaki, Hiroyuki Mizuguchi
Journal: Molecular Therapy (2017)

The function of hepatocytes largely depends on their position in the liver lobule. Although the method of differentiating hepatocytes from human pluripotent stem cells has been largely improved over the past decade, there remains no technique for generating hepatocyte-like cells (HLCs) with zone-specific hepatic properties. In this study, we searched for the factors that promote acquisition of zone-specific properties of HLCs. Here, we identified that WNT7B and WNT8B secreted from hepatocytes and cholangiocytes play important roles in achieving perivenous zone-specific characteristics, such as the enhancement of glutamine secretion, citric acid cycle, cytochrome P450 (CYP) 1A2 metabolism, and CYP1A2 induction capacities. We also found that WNT inhibitory factor (WIF-1) secreted from cholangiocytes was necessary for achieving periportal zone-specific characteristics, such as the enhancement of urea secretion and gluconeogenesis capacities. Therefore, WNT signal modulators secreted from hepatocytes or cholangiocytes conferred zone-specific hepatic properties onto HLCs.
Health research priorities and gaps in South Asia
Authors: Soumya Swaminathan, Huma Qureshi, Mahmood Uz Jahan, Dharma K Baskota, Sunil De Alwis, Lalit Dandona
Journal: BMJ (2017)

Soumya Swaminathan and colleagues  call for increased funding and regional collaboration to boost research relevant to disease and health priorities in South Asia
Hyperkalemic Periodic Paralysis with an Hypocalcemic Episode
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Acute Anuric Renal Failure in an 80-Year-Old Man
Authors: Keith C. Summa, Bijal Jain
Journal: JAMA (2017)

An 80-year-old man with stage 4 chronic kidney disease, 2 days of anuria, and an elevated serum κ to λ free light chain ratio had a bone marrow biopsy that stained positive for the plasma cell marker CD138. What would you do next?
Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study
Authors: Jason Grebely, Francois M J Lamoury, Behzad Hajarizadeh, Yasmin Mowat, Alison D Marshall, Sahar Bajis, Philippa Marks, Janaki Amin, Julie Smith, Michael Edwards, Carla Gorton, Nadine Ezard, David Persing, Marika Kleman, Philip Cunningham, Beth Catlett, Gregory J Dore, Tanya L Applegate
Journal: The Lancet. Gastroenterology & hepatology (2017)
Phagocytosis imprints heterogeneity in tissue-resident macrophages
Authors: Noelia A-Gonzalez, Juan A. Quintana, Susana García-Silva, Marina Mazariegos, Arturo González de la Aleja, José A. Nicolás-Ávila, Wencke Walter, Jose M. Adrover, Georgiana Crainiciuc, Vijay K. Kuchroo, Carla V. Rothlin, Héctor Peinado, Antonio Castrillo, Mercedes Ricote, Andrés Hidalgo
Journal: The Journal of Experimental Medicine (2017)

Tissue-resident macrophages display varying phenotypic and functional properties that are largely specified by their local environment. One of these functions, phagocytosis, mediates the natural disposal of billions of cells, but its mechanisms and consequences within living tissues are poorly defined. Using a parabiosis-based strategy, we identified and isolated macrophages from multiple tissues as they phagocytosed blood-borne cellular material. Phagocytosis was circadianally regulated and mediated by distinct repertoires of receptors, opsonins, and transcription factors in macrophages from each tissue. Although the tissue of residence defined the core signature of macrophages, phagocytosis imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed CD206, displayed blunted expression of Il1b, and supported tissue homeostasis. Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis.
The TCF-1 and LEF-1 Transcription Factors Have Cooperative and Opposing Roles in T Cell Development and Malignancy
Authors: Shuyang Yu, Xinyuan Zhou, Farrah C. Steinke, Chengyu Liu, Shann-Ching Chen, Oksana Zagorodna, Xuefang Jing, Yoshifumi Yokota, David K. Meyerholz, Charles G. Mullighan, C. Michael Knudson, Dong-Mei Zhao, Hai-Hui Xue
Journal: Immunity (2014)
Increased Lipid Length, Macrophage Infiltration, and Neovascularization in Coronary Atheroma From Patients With Chronic Kidney Disease
Authors: Jacobo Pena, Yuliya Vengrenyuk, Safwan Kezbor, Takahiro Yoshimura, Jason C. Kovacic, Samin K. Sharma, Usman Baber, Annapoorna S. Kini, Jagat Narula, Pedro R. Moreno
Journal: JACC. Cardiovascular imaging (2017)
Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa
Authors: Elissa Meites, D Zane
Journal: New England Journal of Medicine (2010)

corrections of gestation, without prophylactic antibiotics.On day 6, severe abdominal cramping, vomiting, and diarrhea developed.She was hospitalized the next day with hypotension, tachycardia, leukocytosis (49,000 white cells per cubic millimeter), pleural effusions, and ascites, without fever.A dilation and evacuation procedure for endometritis was performed.After repeated paracenteses, she died of sepsis with acute renal failure and disseminated intravascular coagulation.C. sordellii was cultured from a cervical swab and identified by means of immunohistochemical analysis and PCR assay of decidual tissue showing acute inflammation and necrosis.As previously reported in the Journal, Planned Parenthood Federation of America health centers changed their recommended regimen for medical abortions in the years 2006 and 2007, administering buccal rather than vaginal misoprostol and adding routine prophylactic antibiotics (doxycycline) in response to rare reports of serious infection after medical abortion. 4The effectiveness of this revised regimen in preventing C. sordellii infections and the safety of routine administration of antibiotics for this procedure remain unknown.C. sordellii toxic shock syndrome may occur in reproductive-age women regardless of pregnancy status. 5 Clinicians should be aware of common clinical features, including abdominal pain, hypotension, tachycardia, third-space fluid accumulations, hemoconcentration, and marked leukemoid response, typically without fever. 1,2In patients with this presentation, a high index of suspicion for this syndrome and early aggressive treatment are needed.