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Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings

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Health 2013年第3期5卷 396-401页

作者： Ritchie C. Shoemaker Dennis House James C. Ryan Center for Research on Biotoxin Associated Illnesses Pocomoke City USA proteogenomics LLC Vero Beach USA

Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illness. This illness, termed a chronic inflammatory response syndrome (CIRS-WDB), is systemic with symptoms acquired from multiple organ systems. Treatment of CIRS-WDB has progressed rapidly as a better understanding of the inflammatory pathophysiology has led to targeted, sequential therapies. The fundamental basis of uncontrolled innate immune responses, the humoral deficiency of regulatory neuropeptides melanocyte stimulating hormone (MSH) or vasoactive intestinal polypeptide (VIP), seen in over 98% of pa tients, has not consistently responded to any treatment modality. Use of replacement VIP has been attempted anecdotally;VIP replacement therapies show promise in short term studies but longer therapies have not been attempted. Here we report an open label trial of 20 patients with refractory CIRS-WDB illness who took replacement VIP in a nasal spray for at least 18 months with confirmation of durable efficacy and absence of significant side effects. These 20 patients were similar in symptoms and lab find- ings to three previously published cohorts in- volving 1829 patients and 169 controls. Dosage of VIP was titrated downwards from four to zero doses a day to determine minimum effective dose, and retitrated upwards for maximum improvement over time. The trial showed that VIP therapy safely 1) reduced refractory symptoms to equal controls;2) corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9;3) corrected estradiol, testosterone and 25-OH Vitamin D;4) returned pulmonary artery systolic pressure (PASP) during exercise to normal;and 5) enhanced quality of life in 100% of trial patients. Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.

关键词： Vasoactive Intestinal Polypeptide (VIP) Chronic Inflammatory Response Syndrome (CIRS) TGF Beta-1 C4a MSH T Regulatory Cells Water-Damaged Buildings

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Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly

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Journal of Molecular Cell Biology 2020年第8期12卷 654-665页

作者： Xu Liu Leilei Xu Junying Li Phil Y.Yao Wanjuan Wang Hazrat Ismail Haowei Wang Bryce Liao Zhihong Yang Tarsha Ward Ke Ruan Jianchun Zhang Quan Wu Ping He Xia Ding Dongmei Wang Chuanhai Fu Zhen Dou Feng Yan Wenwen Wang Xing Liu Xuebiao Yao MOE Key Laboratory for Cellular Dynamics&Anhui Key Laboratory for Chemical Biology CAS Center for Excellence in Molecular Cell ScienceHefei National Science Center for Physical Sciences at Microscale&University of Science and Technology of ChinaHefei 230027China Department of Physiology Morehouse School of MedicineAtlantaGA 30310USA School of Basic Medical Sciences Beijing University of Chinese MedicineBeijing 100029China Department of Biology Duke University DurhamNC 27708USA Institute of proteogenomics Beijing 100029China Harvard Medical School BostonMA 02115USA

Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase ***,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains *** the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric *** sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during *** real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability *** biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic *** inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the ***,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone *** findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle *** CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis.

关键词： organoids.cell division central spindle CENP-E syntelin PRC1

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