tbuckley/cabot-search huggingface dataset:
Sex Hormones and Asthma
Authors: Fernando Holguin
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Sex Hormones and AsthmaA potential causal association between changes in sex hormones and asthma incidence or severity has long been supported by several well-known epidemiological observations; for example, asthma is more prevalent and severe in male children, yet after childhood, women are more commonly affected throughout adulthood (1).Perimenstrual worsening has been reported to occur in 20-40% of patients with severe or difficult-to-control asthma, particularly among obese females (2).On the basis of this information, suppressing sex hormone fluctuations through hormonal replacement therapy (HRT) would indeed make logical sense to reduce asthma incidence or potentially improve asthma outcomes; however, this has not been consistently shown, and in fact, some longitudinal studies have shown that HRT actually increased the odds of developing this disease (3,4).Several factors such as the type and timing of HRT, the type study design, and individual characteristics (obese vs. nonobese) may potentially explain the variability in response to this treatment.It may also imply, however, that we do not fully understand how variations in sex hormone levels affect asthma, and therefore, we do not know in whom and when HRT could be useful.To this effect, in this issue of the Journal, Han and colleagues (pp.158-166) present the first large population-representative study evaluating the association between serum estradiol and serum free testosterone levels with self-referred current asthma diagnosis in men and women participating in the National Health and Nutrition Examination Survey (5).This cross-sectional analysis of 7,615 (3,953 men and 3,662 women) adults shows that women with higher serum testosterone levels have between 30% and 44% lower odds of current asthma when compared with the women with the lowest testosterone levels.Given the significant interaction found between obesity and sex hormones on asthma, the authors showed in the fully adjusted model that in obese women, higher serum estradiol and serum free testosterone were, respectively, associated with a 40% and a 40-50% reduction in the odds of current asthma.The associations in men were less impressive, as only the highest serum estradiol quartile, relative to the lowest, was associated with reduced asthma odds in nonobese subjects.Whereas prior large-scale epidemiological studies have attributed changes in asthma-related outcomes to sex hormones only by proxy (i.e., puberty or menstrual period), the results from this study, by directly measuring serum levels, significantly strengthen causality.Further, the association with testosterone, which had been largely overlooked in many prior asthma studies,
A systematic strategy for screening therapeutic constituents of Schisandra chinensis (Turcz.) Baill infiltrated blood–brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines
Authors: Yiwen Zhang, Xinyan Lv, Jiameng Qu, Xin Zhang, Mingyang Zhang, Hao Gao, Qian Zhang, Ran Liu, Huarong Xu, Qing Li, Kaishun Bi
Journal: Acta Pharmaceutica Sinica B (2019)

Schisandra chinensis, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of S. chinensis remains obscure. In this study, to explore the active constituents of S. chinensis, we compared pharmacodynamics and chemical profiles in vitro/in vivo of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components in vitro and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of S. chinensis targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of S. chinensis and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.
Cationic synthetic long peptides-loaded nanogels: An efficient therapeutic vaccine formulation for induction of T-cell responses
Authors: Neda Kordalivand, Elena Tondini, Chun Yin Jerry Lau, Tina Vermonden, Enrico Mastrobattista, Wim E. Hennink, Ferry Ossendorp, Cornelus F. van Nostrum
Journal: Journal of Controlled Release (2019)

Recent studies have shown a high potency of protein-based vaccines for cell-mediated cancer immunotherapy. However, due to their poor cellular uptake, efficient immune responses with soluble protein antigens are often not observed. As a result of superior cellular uptake, nanogels loaded with antigenic peptides were investigated in this study as carrier systems for cancer immunotherapy. Different synthetic long peptides (SLPs) containing the CTL and CD4+ T-helper (Help) epitopes were synthesized and covalently conjugated via disulfide bonds to the polymeric network of cationic dextran nanogels. Cationic nanogels with a size of 210 nm, positive zeta potential (+24 mV) and high peptide loading content (15%) showed triggered release of the loaded peptides under reducing conditions. An in vitro study demonstrated the capability of cationic nanogels to maturate dendritic cells (DCs). Importantly, covalently SLP-loaded nanogels adjuvanted with poly(I:C) showed superior CD8+ T cell responses compared to soluble peptides and nanogel formulations with physically loaded peptides both in vitro and in vivo. In conclusion, covalently SLPs-loaded cationic nanogels are a promising system to provoke immune responses for therapeutic cancer vaccination.
Circulating levels of gastrointestinal hormones in response to the most common types of bariatric surgery and predictive value for weight loss over one year: Evidence from two independent trials
Authors: Nikolaos Perakakis, Alexander Kokkinos, Natia Peradze, Nikolaos Tentolouris, Wael Ghaly, Eleni Pilitsi, Jagriti Upadhyay, Andreas Alexandrou, Christos S. Mantzoros
Journal: Metabolism (2019)
Bridging the gap or paving the way for uninvited guests?
Authors: Roy L. J. van Wanrooij, Jeanin E. van Hooft
Journal: Endoscopy (2019)

The early phase of acute pancreatitis is characterized by a systemic inflammatory response that leads to necrosis of the pancreas parenchyma and/or the pancreatic fat tissue in about 20 % of patients [1]. Acute necrotizing pancreatitis (ANP) is commonly associated with pancreatic duct leakage resulting in extensive damage of the parenchyma and duct(s) of the pancreas, which in turn is associated with disconnected duct syndrome and persistent peripancreatic fluid collections [2]; vice versa, leakage of enzymatic active pancreatic fluid into the pancreas parenchyma is also thought to aggravate damage of the pancreas [2]. After 7 – 14 days, the inflammatory response attenuates, and during this late phase the course of disease is now mostly determined by whether or not necrotic tissue becomes infected, which occurs in about 30 % of patients with ANP [3]. Mortality rates in patients with infected ANP are high (30 %), and although recent developments in treatment approaches utilizing minimal invasive drainage strategies have improved outcomes, further progress is much needed [4].
AB0034 INCREASED PRODUCTION OF HYDROGEN AND METHANE SUGGESTED BACTERIAL OVERGROWTH IN THE SMALL INTESTINE IN PATIENTS WITH AUTOIMMUNE DISEASE DETECTED BY LACTULOSE BREATH TESTS
Authors: Lili Shang, Tingting Zhang, Xiaoli Liu, Hui Wang, Chong Gao, Jinfang Zhao, LI Xiao-Feng, Huiying Gao
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Researchers have linked a species of intestinal bacteria to the onset of rheumatoid arthritis. The lactulose breath test detects small intestinal bacterial overgrowth (SIBO) can measure hydrogen and methane produced by intestinal bacteria. <h3>Objectives:</h3> To investigate the intestinal flora of patients with autoimmune diseases through a lactulose breath test. <h3>Methods:</h3> The study was conducted on 720 cases of autoimmune disease. The hydrogen value was increased by ≥20p.p.m and the methane value increased by ≥10p.p.m in 90 minutes was defined as positive for SIBO. Spearman's rank correlation analysis was used to determine the association between age and hydrogen values or methane values. <h3>Results:</h3> A total of 75% of patients had a positive breath test. Among them, the positive rate of rheumatoid arthritis (RA) patients was 69.4%, systemic lupus erythematosus (SLE) 69%, Sjogren's syndrome (SS) 79.22%, ankylosing spondylitis (AS) 89.29%, and juvenile arthritis (JIA) 73.33%. In addition, patients with AS had significantly higher hydrogen value than that with RA, SLE, and SS (p &lt;0.05) (Fig. 1). Sex was no statistically significant difference between lactulose breath test results. In female patients, age was positively correlated with hydrogen values (r = 0.151; p = 0.049) and methane values (r = 0.248; p = 0.001); in male patients, age was negatively correlated with hydrogen values (r = -0.367); p=0.006) (Fig. 2). <h3>Conclusion:</h3> Patients with autoimmune disease have positive bacterial growth in the small intestine, and hydrogen production is significantly increased in patients with AS, suggesting that hydrogen production in the small intestine may be related to inflammation. In addition, with increasing age of the female, hydrogen and methane produced in the small intestine may increase, with increasing age of the male, small intestine may reduce the production of hydrogen, suggesting a reason why there are more female patients than male in some autoimmune disease. <h3>References</h3> [1] Gislane Lelis Vilela de Oliveira, Aline Zazeri Leite, Bruna Stevanato Higuchi, Marina Ignácio Gonzaga, Vânia Sammartino Mariano.Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology. 2017Sep; 152(1): 1–12.doi: 10.1111/imm.12765 [2] Maria C. Opazo, Elizabeth M. Ortega-Rocha, Irenice Coronado-Arrázola, Laura C. Bonifaz, Helene Boudin, Michel Neunlist, Susan M. Bueno, Alexis M. Kalergis, Claudia A. Riedel. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases. Front Microbiol. 2018;9:432.doi: 10.3389/fmicb.2018.00432 <h3>Disclosure of Interests:</h3> None declared
E-Cigarettes: Unstandardized, Under-Regulated, Understudied, and Unknown Health and Cancer Risks
Authors: Ernest T. Hawk, Karen Colbert Maresso
Journal: Cancer Research (2019)

E-cigarettes have the ability to deliver nicotine in a manner that is similar to, and, theoretically, safer than, combusted tobacco. However, these devices are extremely heterogeneous and regulation has struggled to keep up with their rapid evolution. A compilation of early data suggest that e-cigarettes may contain numerous toxic substances, including known carcinogens. However, there are few data available on the short- and long-term health effects of e-cigarettes, including any potential effect on cancer risk. Until more is known, e-cigarettes should not be considered a safe alternative to combusted tobacco use.
Conditional knockout of TGF-βRII /Smad2 signals protects against acute renal injury by alleviating cell necroptosis, apoptosis and inflammation
Authors: Qin Yang, Gui-Ling Ren, Biao Wei, Juan Jin, Xiao Ru Huang, Wei Shao, Jun Li, Xiao-Ming Meng, Hui Yao Lan
Journal: Theranostics (2019)

Rationale: TGF-β/Smad signaling is the central mediator for renal fibrosis, however, its functional role in acute kidney injury (AKI) is not fully understood. We previously showed Smad2 protects against renal fibrosis by limiting Smad3 signaling, but details on its role in acute phase are unclear. Recent evidence showed that TGF-β/Smad3 may be involved in the pathogenesis of AKI, so we hypothesized that Smad2 may play certain roles in AKI due to its potential effect on programmed cell death. Methods: We established a cisplatin-induced AKI mouse model with TGF-β type II receptor or Smad2 specifically deleted from renal tubular epithelial cells (TECs). We also created stable in vitro models with either Smad2 knockdown or overexpression in human HK2 cells. Importantly, we evaluated whether Smad2 could serve as a therapeutic target in both cisplatin- and ischemic/reperfusion (I/R)-induced AKI mouse models by silencing Smad2 in vivo. Results: Results show that disruption of TGF-β type II receptor suppressed Smad2/3 activation and attenuated renal injury in cisplatin nephropathy. Furthermore, we found that conditional knockout of downstream Smad2 in TECs protected against loss of renal function, and alleviated p53-mediated cell apoptosis, RIPK-mediated necroptosis and p65 NF-κB-driven renal inflammation in cisplatin nephropathy. This was further confirmed in cisplatin-treated Smad2 knockdown and overexpression HK2 cells. Additionally, lentivirus-mediated Smad2 knockdown protected against renal injury and inflammation while restoring renal function in established nephrotoxic and ischemic AKI models. Conclusions: These findings show that unlike its protective role in renal fibrosis, Smad2 promoted AKI by inducing programmed cell death and inflammation. This may offer a novel therapeutic target for acute kidney injury.
Molecular Diversification of the Seminal Fluid Proteome in a Recently Diverged Passerine Species Pair
Authors: Melissah Rowe, Emma Whittington, Kirill Borziak, Mark Ravinet, Fabrice Eroukhmanoff, Glenn-Peter Sætre, Steve Dorus
Journal: Molecular Biology and Evolution (2019)

Seminal fluid proteins (SFPs) mediate an array of postmating reproductive processes that influence fertilization and fertility. As such, it is widely held that SFPs may contribute to postmating, prezygotic reproductive barriers between closely related taxa. We investigated seminal fluid (SF) diversification in a recently diverged passerine species pair (Passer domesticus and Passer hispaniolensis) using a combination of proteomic and comparative evolutionary genomic approaches. First, we characterized and compared the SF proteome of the two species, revealing consistencies with known aspects of SFP biology and function in other taxa, including the presence and diversification of proteins involved in immunity and sperm maturation. Second, using whole-genome resequencing data, we assessed patterns of genomic differentiation between house and Spanish sparrows. These analyses detected divergent selection on immunity-related SF genes and positive selective sweeps in regions containing a number of SF genes that also exhibited protein abundance diversification between species. Finally, we analyzed the molecular evolution of SFPs across 11 passerine species and found a significantly higher rate of positive selection in SFPs compared with the rest of the genome, as well as significant enrichments for functional pathways related to immunity in the set of positively selected SF genes. Our results suggest that selection on immunity pathways is an important determinant of passerine SF composition and evolution. Assessing the role of immunity genes in speciation in other recently diverged taxa should be prioritized given the potential role for immunity-related proteins in reproductive incompatibilities in Passer sparrows.
JAK2 Genotyping (Real-Time Allelic Discrimination) Reveals Rare JAK2 V617F-Positive Erythroid Colonies in Pediatric Patients with Essential Thrombocythemia.
Authors: Dagmar Pospisilova, Jitka Veselovska, Sona Pekova, Monika Horvathova, Renata Solna, Jana Cmejlova, Radek Cmejla, Monika Belickova, Jan Stary, Vladimir Divoky
Journal: Blood (2007)
Recurrent Stroke in a Man With a Pacemaker
Authors: Shing Ching, Raymond Chun-Kong Chan, Chiu Sun Yue
Journal: JAMA Cardiology (2019)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
Mesenchymal stem cells promote healing of nonsteroidal anti-inflammatory drug-related peptic ulcer through paracrine actions in pigs
Authors: Xianfeng Xia, Kai Fung Chan, Gerald Tsz Yau Wong, Peng Wang, Liu Liu, Baldwin Po Man Yeung, Enders Kwok Wai Ng, James Yun Wong Lau, Philip Wai Yan Chiu
Journal: Science Translational Medicine (2019)

Stem cell therapy enhances healing of NSAID-related peptic ulcer through reducing inflammation and stimulating cell proliferation and angiogenesis.
Hepatomas are exquisitely sensitive to pharmacologic ascorbate (P-AscH<sup>-</sup>)
Authors: Xuan Zhang, Tiefu Liu, Zehuan Li, Yanling Feng, Christopher Corpe, Shanshan Liu, Jingpu Zhang, Xiaomeng He, Feng Liu, Li Xu, Longqiang Shen, Shun Li, Qianlin Xia, Xiuhua Peng, Xiaohui Zhou, Weiping Chen, Xiaoyan Zhang, Jianqing Xu, Jin Wang
Journal: Theranostics (2019)

Rationale: Ascorbate is an essential micronutrient known for redox functions at normal physiologic concentrations. In recent decades, pharmacological ascorbate has been found to selectively kill tumour cells. However, the dosing frequency of pharmacologic ascorbate in humans has not yet been defined. Methods: We determined that among five hepatic cell lines, Huh-7 cells were the most sensitive to ascorbate. The effects of high-dose ascorbate on hepatoma were therefore assessed using Huh-7 cells and xenograft tumour mouse model. Results: In Huh-7 cells, ascorbate induced a significant increase in the percentage of cells in the G0/G1 phase, apoptosis and intracellular levels of ROS. High doses of ascorbate (4.0 pmol cell-1), but not low doses of ascorbate (1.0 pmol cell-1), also served as a pro-drug that killed hepatoma cells by altering mitochondrial respiration. Furthermore, in a Huh-7 cell xenograft tumour mouse model, intraperitoneal injection of ascorbate (4.0 g/kg/3 days) but not a lower dose of ascorbate (2.0 g/kg/3 days) significantly inhibited tumour growth. Gene array analysis of HCC tumour tissue from xenograft mice given IP ascorbate (4.0 g/kg/3 days) identified changes in the transcript levels of 192 genes/ncRNAs involved in insulin receptor signalling, metabolism and mitochondrial respiration. Consistent with the array data, gene expression levels of AGER, DGKK, ASB2, TCP10L2, Lnc-ALCAM-3, and Lnc-TGFBR2-1 were increased 2.05-11.35 fold in HCC tumour tissue samples from mice treated with high-dose ascorbate, and IHC staining analysis also verified that AGER/RAGE and DGKK proteins were up-regulated, which implied that AGER/RAGE and DGKK activation might be related to oxidative stress, leading to hepatoma cell death. Conclusions: Our studies identified multiple mechanisms are responsible for the anti-tumour activity of ascorbate and suggest high doses of ascorbate with less frequency will act as a novel therapeutic agent for liver cancer in vivo.
Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts
Authors: Rengaswamy Sankaranarayanan, Partha Basu, Prabhdeep Kaur, Rajesh Bhaskar, Gurinder Bir Singh, Phumzay Denzongpa, Rajesh K Grover, Paul Sebastian, Tapan Saikia, Kunal Oswal, Rishav Kanodia, Amantia Dsouza, Ravi Mehrotra, Goura Kishor Rath, Viniita Jaggi, Sundram Kashyap, Ishu Kataria, Roopa Hariprasad, Peter Sasieni, Neerja Bhatla, Preetha Rajaraman, Edward L Trimble, Soumya Swaminathan, Arnie Purushotham
Journal: The Lancet Oncology (2019)
Multiparametric magnetic resonance imaging shows promising results to assess renal transplant dysfunction with fibrosis
Authors: Octavia Bane, Stefanie J. Hectors, Sonja Gordic, Paul Kennedy, Mathilde Wagner, Amanda Weiss, Rafael Khaim, Zhengzi Yi, Weijia Zhang, Veronica Delaney, Fadi Salem, Cijiang He, Madhav C. Menon, Sara Lewis, Bachir Taouli
Journal: Kidney International (2019)
HBX-induced miR-5188 impairs FOXO1 to stimulate β-catenin nuclear translocation and promotes tumor stemness in hepatocellular carcinoma
Authors: Xian Lin, Shi Zuo, Rongcheng Luo, Yonghao Li, Guifang Yu, Yujiao Zou, Yan Zhou, Zhan Liu, Yiyi Liu, Yingying Hu, Yingying Xie, Weiyi Fang, Zhen Liu
Journal: Theranostics (2019)

Cancer stem cells (CSCs) are the key factor in determining cancer recurrence, metastasis, chemoresistance and patient prognosis in hepatocellular carcinoma (HCC).The role of miR-5188 in cancer stemness has never been documented.In this study, we investigated the clinical and biological roles of miR-5188 in HCC.Methods: MiRNA expression in HCC was analyzed by bioinformatics analysis and in situ hybridization.The biological effect of miR-5188 was demonstrated in both in vitro and in vivo studies through the ectopic expression of miR-5188.The target gene and molecular pathway of miR-5188 were characterized using bioinformatics tools, dual-luciferase reporter assays, gene knockdown, and rescue experiments.Results: MiR-5188 was shown to be upregulated and confer poor prognosis in HCC patient data from TCGA database.MiR-5188 was subsequently identified as a significant inducer of cancer stemness that promotes HCC pathogenesis.Specifically, the targeting of miR-5188 by its antagomir markedly prolonged the survival time of HCC-bearing mice and improved HCC cell chemosensitivity in vivo.Mechanistic analysis indicated that miR-5188 directly targets FOXO1, which interacts with β-catenin in the cytoplasm to reduce the nuclear translocation of β-catenin and promotes the activation of Wnt signaling and downstream tumor stemness, EMT, and c-Jun.Moreover, c-Jun transcriptionally activates miR-5188 expression, forming a positive feedback loop.Interestingly, the miR-5188-FOXO1/β-catenin-c-Jun feedback loop was induced by hepatitis X protein (HBX) through Wnt signaling and participated in the HBX-induced pathogenesis of HCC.Finally, analyses of transcriptomics data and our clinical data supported the significance of the abnormal expression of the miR-5188 pathway in HCC pathogenesis.Conclusions: These findings present the inhibition of miR-5188 as a novel strategy for the efficient elimination of CSCs to prevent tumor metastasis, recurrence and chemoresistance in patients with hepatocellular carcinoma.Our study highlights the importance of miR-5188 as a tumor stemness inducer that acts as a potential target for HCC treatment.
P1.02 Chemotherapy with VMAT (Volumetric Modulated Arc Therapy) Radiation Therapy For Poor Risk Stage IIIA-C NSCLC Patients
Authors: Y. Zhou, M. Fidler, M. Batus, E. Ritz, G. Tolekidis, P. Bonomi, G. Marwaha
Journal: Journal of Thoracic Oncology (2019)