Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

1. Download : Download high-res image (207KB)
2. Download : Download full-size image

     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Comparison of Foaming Properties Between the Shirasu Porous Glass Membrane Device and Tessari’s Three-way Stopcock Technique for Polidocanol and Ethanolamine Oleate Foam Production: A Benchtop Study

PurposeTo compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC).Materials and MethodsFoam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope.ResultsMedian foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50–300 s; POL entropy: at 0–60 s; EO SD: at 0–600 s; EO entropy: at 0–460 s; POL energy: at 0–40 s; POL GLCM homogeneity: at 0–250 s; EO energy: at 0–360 s; EO GLCM homogeneity: at 0–480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 μm (P < .01), respectively, in the POL foam; and 36 and 36 μm (P = .45), respectively, in the EO foam.ConclusionsPOL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.     

补肾活血方对血管性痴呆大鼠海马神经细胞自噬的影响＊

目的 探究补肾活血方对血管性痴呆（Vascular Dementia， VD）大鼠模型自噬的影响。方法 52周龄SD雄性大鼠50只，随机分为假手术组（Sham组）、模型组（VD组）、模型+补肾活血方组（BSHX组）、模型+雷帕霉素组（Rap组）和模型+3-甲基腺嘌呤组（3-MA组），每组10只大鼠。除Sham组外其余各组采用两血管阻断法（2-VO）建立VD模型。BSHX组中药灌胃治疗28天；自噬干预组于造模前30 min侧脑室给药。运用Morris水迷宫测试各组大鼠的学习记忆能力；通过尼氏染色和透射电子显微镜（Transmission electron microscope，TEM）观察大鼠海马区病理形态及自噬变化；采用蛋白免疫印迹（Western blot）法和反转录实时荧光定量PCR（RT-qPCR）检测大鼠海马Beclin-1、P62以及微管相关蛋白1轻链3（LC3）蛋白及mRNA表达情况。结果 与VD组比较，BSHX组大鼠学习记忆能力显著提升（P<0.05），镜下观察BSHX组和3-MA组的细胞形态及数量均有改善，自噬小体鲜见，Beclin-1以及LC3蛋白和mRNA表达水平显著降低（P<0.05），P62蛋白和mRNA表达水平明显升高（P<0.05）结论 补肾活血方可以降低VD大鼠海马区Beclin-1和LC3蛋白及mRNA的表达，提高P62的表达，通过抑制自噬的发生，减轻对神经细胞的损伤，改善学习记忆能力。     

黄连NRAMP3基因的克隆与生物信息学分析＊

目的 克隆黄连（Coptis chinensis Franch.）中自然抗性相关巨噬细胞蛋白（Natural Resistance-Associated Macrophage Protein，NRAMP）的编码基因，并进行生物信息学分析。方法 从黄连基因组中比对NRAMP3基因，并根据比对的基因序列设计特异性引物，经PCR扩增得到的黄连NRAMP3编码序列，进行克隆、测序和生物信息学分析，并利用qPCR技术对黄连NRAMP3基因进行时空表达分析。结果 得到黄连NRAMP3基因cDNA序列，全长1617 bp，编码538个氨基酸，通过与GenBank上的其他蛋白序列比对，将其命名为CcNRAMP3；序列分析显示，黄连NRAMP3基因编码的氨基酸序列包含一个典型的NRAMP结构域（PF01566），有12个跨膜结构域，亚细胞定位于液泡膜上，具有疏水性强的特点。二级结构中肽链构象主要包括α-螺旋与无规则卷曲两部分；三级结构模型具有葡萄球菌锰转运突变体（MntH）的晶体结构。利用系统进化关系分析推测它可能具有转运重金属元素Cd功能。对黄连NRAMP3基因的组织表达分析表明，CcNRAMP3基因在黄连叶片中表达量最高。在遭受镉胁迫时，在须根中表达量先升高后降低，该基因很可能主要在根部对镉进行响应并发挥作用。结论 本研究首次通过克隆得到黄连NRAMP3基因，并运用生物信息学方法对其理化性质、结构特征等进行了分析预测，这些结果将为黄连NRAMP3基因的功能研究以及其对镉转运的调控机制提供理论依据和基因资源。