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Immunomodulatory oligonucleotide ImT504:Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

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World Journal of Stem Cells 2017年第3期9卷 45-67页

作者： Jorge Zorzopulos steven m opal Andrés Hernando-Insúa Juan m Rodriguez Fernanda Elías Juan Fló Ricardo A López Norma A Chasseing Victoria A Lux-Lantos maria F Coronel Raul Franco Alejandro D montaner David L Horn Immunotech S.A. Ciudad de Buenos Aires C1440FFXArgentina Infectious Disease Division Memorial Hospital of Rhode Island and Alpert Medical SchoolProvidenceRI 02905United States Fundación Pablo Cassara Ciudad Autonoma de Buenos Aires C1440FFXArgentina Instituto de Biología y medicina Experimental(IBYmE-CONICET) Ciudad Autónoma de Buenos Aires C1428ADNArgentina Instituto de Ciencia y Tecnolog'DR.Cesar milstein” Fundación Pablo CassaráCiudad Autonoma de Buenos Aires C1440FFXArgentina David Horn LLC DoylestownPA 18902United States

The immune responses of humans and animals to insults(i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged proinflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. mesenchymal stem cell(mSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. mSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted mSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to mSC transplant, a synthetic drug with the capacity to boost endogenous mSC expansion and/or activation may also be effective. Regarding this, ImT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of mSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. ImT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, ImT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of ImT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

关键词： Immunohomeostasis Immunoprotection Immunoregeneration Inflammation mesenchymal stem cells ImT504

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Common sense and other writings

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作者： Thomas Paine edited by J. m. opal.

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Transport model for shale gas well leakage through the surrounding fractured zones of a longwall mine

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International Journal of mining Science and Technology 2020年第5期30卷 635-641页

作者： Kayode m.Ajayi steven J.Schatzel Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthPittsburghPA 15236USA

The environmental risks associated with casing deformation in unconventional(shale)gas wells positioned in abutment pillars of longwall mines is a concern to many in the mining and gas well *** the recent interest in shale exploration and the proximity to longwall mining in Southwestern Pennsylvania,the risk to mine workers could be catastrophic as fractures in surrounding strata create pathways for transport of leaked ***,this research by the National Institute for Occupational Safety and Health(NIOSH)presents an analytical model of the gas transport through fractures in a low permeable *** derived equations are used to conduct parametric studies of specific transport conditions to understand the influence of stratum geology,fracture lengths,and the leaked gas properties on subsurface *** results indicated that the prediction that the subsurface gas flux decreases with an increase in fracture length is specifically for a non-gassy *** sub-transport trend could be significantly impacted by the stratum gas generation rate within specific fracture lengths,which emphasized the importance of the stratum *** findings provide new insights for improved understanding of subsurface gas transport to ensure mine safety.

关键词： Subsurface gas transport Longwall mining Shale gas well Analytical modeling Environmental risk Shale gas casing failure

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Assessing the reproductive health of men with occupational exposures

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Asian Journal of Andrology 2014年第1期16卷 23-30页

作者： steven m Schrader Katherine L marlow Centers for Disease Control and Prevention National Institute for Occupational Safety and Health Division of Applied Research and Technology Cincinnati OH USA.

The earliest report linking environmental （occupational） exposure to adverse human male reproductive effects dates back to1775 when an English physician, Percival Pott, reported a high incidence of scrotal cancer in chimney sweeps. This observation led to safety regulations in the form of bathing requirements for these workers. The fact that male-mediated reproductive harm in humans may be a result of toxicant exposures did not become firmly established until relatively recently, when Lancranjan studied lead-exposed workers in Romania in 1975, and later in 1977, when Whorton examined the effects of dibromochloropropane （DBCP） on male workers in California. Since these discoveries, several additional human reproductive toxicants have been identified through the convergence of laboratory and observational findings. many research gaps remain, as the pool of potential human exposures with undetermined effects on male reproduction is vast. This review provides an overview of methods used to study the effects of exposures on male reproduction and their reproductive health, with a primary emphasis on the implementation and interpretation of human studies. Emphasis will be on occupational exposures, although much of the information is also useful in assessing environmental studies, occupational exposures are usually much higher and better defined.

关键词： accessory glands endocrine epidemiology semen sexual function sperm testis toxicology

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Strigolactones redefine plant hormones

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Science China(Life Sciences) 2016年第10期59卷 1083-1085页

作者： Lu Wang steven m.Smith School of Biological Sciences University of Tasmania Institute of Genetics and Developmental Biology Chinese Academy of sciences

A commonly accepted view of plant growth hormones is that their interaction with the cognate receptor protein is reversible, so that each hormone molecule can potentially interact multiple times with a receptor and so either amplify the hormone signal or maintain it over an extended period of time. The signal can be ＇cancelled＇ by degrading the hormone. Strigolactones present us with a potentially new paradigm. The receptor is a serine hydrolase-type protein which attacks the strigolactone resulting in covalent modi- fication of the receptor, while at the same time destroying the hormone. Strigolactone is apparently a one-use ＇dispos- able＇ hormone.

关键词：植物激素受体蛋白定义植物生长激素相互作用激素信号酸水解

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Determinants of the Specif icity of Protein Targeting to Chloroplasts or mitochondria

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molecular Plant 2019年第7期12卷 893-895页

作者： Lucas mcKinnon steven m.Theg Department of Plant Biology University of California Davis Davis CA USA

Chloroplasts and mitochondria are both thought to have arisen through primary endosymbiosis (Kutschera and Niklas, 2005). As each organelle evolved, most of its genome was transferred to the host nucleus resulting in the vast majority of its proteome being nuclear encoded and synthesized on cytosolic ribosomes (Shi and Theg, 2013).

关键词： Chloroplasts mitochondria

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KAI2-and mAX2-mediated Responses to Karrikins and Strigolactones Are Largely Independent of HY5 in Arabidopsis Seedlings

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molecular Plant 2013年第1期6卷 63-75页

作者： mark T. Waters steven m. Smitht Plant Energy Biology University of Western Australia Crawley Western Australia 6009 Australia School of Chemistry and Biochemistry University of Western Australia Crawley Western Australia 6009 Australia

Karrikins are butenolide compounds released from burning vegetation that stimulate seed germination and enhance seedling photomorphogenesis. Strigolactones are structurally similar plant hormones that regulate shoot and root development, and promote the germination of parasitic weed seeds. In Arabidopsis, the F-box protein mAX2 is required for responses to karrikins and strigolactones, and the a/~ hydrolase KAI2 is necessary for responses to karrikins. Both mAX2 and KAI2 are essential for normal light-dependent seedling development. The bZIP transcription factor HY5 acts downstream of multiple photoreceptors and promotes photomorphogenesis, but its relationship with mAX2 and KAI2 in terms of seedling development and responses to karrikins and strigolactones is poorly defined. Here, we dem- onstrate that HY5 action is genetically separable from that of mAX2 and KAI2. While by5 mutants have weak hypoco- tyl elongation responses to karrikins and the artificial strigolactone GR24, they have normal transcriptional responses, suggesting that HY5 is not involved in perception or action of karrikins or strigolactones. Furthermore, we show that overexpression of KAI2 is sufficient to enhance responses to both karrikins and GR24 in wild-type seedlings, and that KAI2 overexpression partially suppresses the hy5 long hypocotyl phenotype. These results suggest that KAI2 and mAX2 define a regulatory pathway that largely operates independently of HY5 to mediate seedling responses to abiotic signals such as smoke and light.

关键词： smoke karrikin strigolactone KAI2 HY5 photomorphogenesis.

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Schwann cell extracellular vesicles:judging a book by its cover

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Neural Regeneration Research 2023年第2期18卷 325-326页

作者： steven L.Gonias Wendy m.Campana Department of Pathology University of CaliforniaSan DiegoCAUSA Department of Anesthesiology Program in NeurosciencesUniversity of California The Veterans Administration San Diego Healthcare System San DiegoCAUSA

Schwann cells(SCs)are essential in the development of the peripheral nervous system(PNS),in PNS inj ury,and the aging *** comprise greater than 90%of the nucleated cells in peripheral nerves(Campana,2007).myelinating SCs insulate large-diameter axons,forming a 1:1relationship and promoting saltatory conduction of axonal action ***-myelinating SCs ensheathe clusters of smaller diameter axons in Remak *** types of SCs provide essential metabolic and trophic support to axons,which is essential for maintaining axon integrity in healthy peripheral nerves.

关键词： nerves conduction Schwann

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Trends and seasonality in hospitalizations for acute alcohol-related and biliary pancreatitis in the USA

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Hepatobiliary & Pancreatic Diseases International 2021年第2期20卷 173-181页

作者： Artem Shmelev Anne m Sill Tiffany Horrigan steven C Cunningham Department of Surgery Saint Agnes HealthcareBaltimoreMDUSA

Background:The incidence of acute pancreatitis(AP)is characterized by circannual and geographical *** aim of this study was to describe seasonal variation and trends in hospitalizations for AP in the USA with respect to AP ***:The Nationwide Inpatient Sample data(2000–2016)from the Healthcare Cost and Utilization Project were *** study population included all primary hospitalizations for *** AP(BAP)and alcohol-induced AP(AAP)were distinguished by diagnostic and procedural ICD *** trend decomposition was ***:There was a linear increase in annual incidence(per 100000 population)of AAP in the USA(from 17.0 in 2000 to 22.9 in 2016),while incidence of BAP,equaled 19.9 in 2000,peaked at 22.1 in 2006 and decreased to 17.4 in *** incidence demonstrated 18%annual incidence amplitude with summer peak and winter trough,more prominent in *** 2016,within AAP,the highest incidence(per 100000 population)was noted among African-Americans(up to 50.4),followed by males aged 56–70 years(26.5)and Asians of low income(25.5);within BAP,above the average incidence was observed in Hispanic(up to 25.8)and Asian(up to 25.0)*** most consistent and rapid increase in AP incidence was noted in males aged 56–70 years with an alcoholic etiology(average 6%annual incidence growth).Conclusions:The incidence and annual trends of AP vary significantly among demographic and socioeconomic groups and this knowledge may be useful for the planning of healthcare resources and identification of at-risk populations.

关键词： Pancreatitis Alcoholic pancreatitis Incidence Seasonal variation

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Hereditary diffuse gastric cancer: One family's story

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World Journal of Clinical Cases 2018年第1期6卷 1-5页

作者： Haley m Zylberberg Keith Sultan steven Rubin Donald and Barbara Zucker School of medicine at Hofstra/Northwell Division of Gastroenterology Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

Hereditary diffuse gastric cancer(HDGC) is an inherited form of gastric cancer that carries a poor prognosis. most HDGCs are caused by an autosomal dominant genetic mutation in the CDH1 gene, which carries a 70%-80% lifetime risk of gastric cancer. Given its submucosal origin, endoscopic surveillance is an unreliable means of early detection, and prophylactic gastrectomy is recommended for CDH1 positive individuals older than age 20 years. We describe the case of a male with recurrent gastric cancer who was diagnosed with HDGC secondary to the CDH1 mutation, and we also describe the patient's pedigree and outcomes of recommended genetic testing.

关键词： Hereditary diffuse gastric cancer Genetic testing Genetic diseases Gastric cancer Lobular breast cancer Inheritable diseases

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