Emerging Insights Into the Role of the Hippo Pathway in Multiple Myeloma and Associated Bone Disease

Multiple myeloma (MM) is an incurable plasma-cell dyscrasia with numerous treatment options currently available; however, drug resistance is usually inevitable, so there is a constant need for novel treatment approaches. The Hippo pathway has emerged as an important mediator of oncogenesis in solid tumors. More recently, its key role in regulating apoptosis and mediating resistance in MM and other hematologic malignancies has been demonstrated in preclinical studies, which provides a strong basis for further clinical investigation. The Hippo pathway is also implicated in the pathogenesis of MM-induced bone disease, as it regulates both osteoblast and osteoclast function. We provide an overview of the available data regarding the role of the Hippo signaling components in the pathophysiology of MM. A better understanding of the underlying interactions at the molecular and cellular levels will lead to novel and promising treatment approaches.     

Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum β-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.     

桑枝多糖基于YAP/ TAZ信号通路调控db/db小鼠肾纤维化作用的研究

目的研究桑枝多糖基于YAP/TAZ信号通路调控db/db小鼠肾纤维化作用的影响。方法将40只24周龄自发型2型糖尿病db/db小鼠随机分为模型组、缬沙坦组(20mg/kg)、桑枝多糖低剂量组(600mg/kg)、桑枝多糖高剂量组(1200mg/kg),每组10只,日常进行高脂饮食喂养,连续灌胃相应药物60天,每天1次。另将10只db/m小鼠为空白组,日常进行普通饲料喂养,模型组与空白组小鼠灌胃等体积生理盐水60天。给药第60天采集小鼠尿液,测量尿量及终点法测24h尿白蛋白(UP)含量。全自动生化分析仪测定小鼠血清肌酐(Scr)、尿素氮(BUN)含量。末次给药后,小鼠禁食不禁水12h,测其空腹血糖(FBG)。HE染色观察小鼠肾组织病理学变化。采用ELISA法检测肾组织纤维化指标TGF-β1、纤连蛋白(FN)、结缔组织生长因子(CTGF)、胶原Ⅰ型(CollagenⅠ)含量及炎症因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、趋化因子单核细胞趋化蛋白-1(MCP-1)含量。Western blot法检测肾组织Yes相关蛋白(YAP)、TAZ蛋白表达。结果与模型组比较,桑枝多糖低、高剂量组小鼠Scr[(0.39±0.09)mg/dL、(0.32±0.07)mg/dL比(0.62±012)mg/dL]、BUN[(25.75±4.75)mg/dL、(20.62±3.68)mg/dL比(39.18±4.63)mg/dL]、UP[(3.45±0.42)mg/24h、(2.76±0.47)mg/24h比(6.38±2.03)mg/24h]含量显著降低(P均0.05);纤维化指标TGF-β1[(3.76±0.52)ng/mL、(2.53±0.38)ng/mL比(4.98±1.17)ng/mL]、FN [(5.29±1.13)ng/mL、(4.47±1.02)ng/mL比(6.13±1.07)ng/mL]、CTGF [(14.52±1.22)ng/mL、(11.24±0.87)ng/mL比(17.52±1.26)ng/mL]、CollagenⅠ[(10.93±0.85)ng/mL、(8.14±0.76)ng/mL比(14.81±1.34)ng/mL]及炎症因子TNF-α[(87.25±7.81)ng/L、(78.66±6.36)ng/L比(134.82±8.90)ng/L]、IL-6 [(34.72±3.35)ng/L、(21.16±2.51)ng/L比(58.65±5.71)ng/mL]、MCP-1[(0.38±0.04)ng/L、(0.29±0.06)ng/L比(0.51±0.05)ng/L]含量明显减少(P均0.05),YAP[(0.48±0.06)、(0.31±0.05)比(0.53±0.11)]、TAZ[(0.31±0.04)、(0.21±0.03)比(0.37±0.05)]蛋白表达显著降低(P均0.05)。结论桑枝多糖对db/db小鼠糖尿病肾病的肾纤维化有一定的保护作用,其作用机制可能与调节YAP/TAZ信号通路,降低肾脏组织纤维化因子形成及减少炎症因子含量有关。     

Stochastic non-enzymatic modification of long-lived macromolecules - A missing hallmark of aging

Damage accumulation in long-living macromolecules (especially extracellular matrix (ECM) proteins, nuclear pore complex (NPC) proteins, and histones) is a missing hallmark of aging. Stochastic non-enzymatic modifications of ECM trigger cellular senescence as well as many other hallmarks of aging affect organ barriers integrity and drive tissue fibrosis. The importance of it for aging makes it a key target for interventions. The most promising of them can be AGE inhibitors (chelators, O-acetyl group or transglycating activity compounds, amadorins and amadoriases), glucosepane breakers, stimulators of elastogenesis, and RAGE antagonists.     

Hippo信号通路与肾病

Hippo信号通路是近年来备受关注的一条调节器官生长和组织大小的重要信号通路,其已被证实在肿瘤的发生、发展中发挥重要作用.目前Hippo信号通路与肾病的相关性研究仍处于起步阶段.在急性肾损伤(acute renal injury,AKI)方面,Hippo信号通路可能参与小管上皮细胞的凋亡、上皮-间质转化(epithelial-mesenchymal transition,EMT)以及AKI进展至慢性肾脏病(chronic kidney disease,CKD)等多个环节.此外,Hippo信号通路还参与多种慢性肾脏病,包括局灶节段性肾小球硬化症、糖尿病肾病、多囊肾等的发生和疾病进展.