Demyelinating processes in aging and stroke in the central nervous system and the prospect of treatment strategy

Demyelination occurs in response to brain injury and is observed in many neurodegenerative diseases. Myelin is synthesized from oligodendrocytes in the central nervous system, and oligodendrocyte death‐induced demyelination is one of the mechanisms involved in white matter damage after stroke and neurodegeneration. Oligodendrocyte precursor cells (OPCs) exist in the brain of normal adults, and their differentiation into mature oligodendrocytes play a central role in remyelination. Although the differentiation and maturity of OPCs drive endogenous efforts for remyelination, the failure of axons to remyelinate is still the biggest obstacle to brain repair after injury or diseases. In recent years, studies have made attempts to promote remyelination after brain injury and disease, but its cellular or molecular mechanism is not yet fully understood. In this review, we discuss recent studies examining the demyelination process and potential therapeutic strategies for remyelination in aging and stroke. Based on our current understanding of the cellular and molecular mechanisms underlying remyelination, we hypothesize that myelin and oligodendrocytes are viable therapeutic targets to mitigate brain injury and to treat demyelinating‐related neurodegeneration diseases.     

Industrial Production of Organophosphate Flame Retardants (OPFRs): Big Knowledge Gaps Need to Be Filled?

Bulletin of Environmental Contamination and Toxicology - Since the phase-out of traditional halogenated flame retardants (HFRs), interests of research are gradually being shifted to organophosphate...     

Quantification evaluation of 99mTc-MDP concentration in the lumbar spine with SPECT/CT: compare with bone mineral density

Annals of Nuclear Medicine - Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the...     

The NEDD4-1 E3 ubiquitin ligase: A potential molecular target for bortezomib sensitivity in multiple myeloma

E3 ubiquitin ligases primarily determine the substrate specificity of the ubiquitin-proteasome system and play an essential role in the resistance to bortezomib in multiple myeloma (MM). Neural precursor cell-expressed developmentally downregulated gene 4-1 (NEDD4-1, also known as NEDD4) is a founding member of the NEDD4 family of E3 ligases and is involved in the proliferation, migration, invasion and drug sensitivity of cancer cells. In the present study, we investigated the role of NEDD4-1 in MM cells and explored its underlying mechanism. Clinically, low NEDD4-1 expression has been linked to poor prognosis in patients with MM. Functionally, NEDD4-1 knockdown (KD) resulted in bortezomib resistance in MM cells in vitro and in vivo. The overexpression (OE) of NEDD4-1, but not an enzyme-dead NEDD4-1-C867S mutant, had the opposite effect. Furthermore, the overexpression of NEDD4-1 in NEDD4-1 KD cells resensitized the cells to bortezomib in an add-back rescue experiment. Mechanistically, pAkt-Ser473 levels and Akt signaling were elevated and decreased by NEDD4-1 KD and OE, respectively. NEDD4-1 ubiquitinated Akt and targeted pAkt-Ser473 for proteasomal degradation. More importantly, the NEDD4-1 KD-induced upregulation of Akt expression sensitized MM cells to growth inhibition after treatment with an Akt inhibitor. Collectively, our results suggest that high NEDD4-1 levels may be a potential new therapeutic target in MM.     

ROC曲线评价彩色多普勒超声血流成像S/D值在鉴别卵巢良恶性肿瘤中的价值

目的：探讨ROC曲线评价彩色多普勒超声血流成像(CDFI)收缩期与舒张末期流速比(S/D)值在鉴别卵巢良恶性肿瘤中的价值,以为临床诊断提供依据。方法：选取2015年12月至2018年12月我院确诊治疗的卵巢癌患者96例作为癌症组,同期选取卵巢良性病变患者96例作为对照组,所有患者均给予CDFI检查并测定血流分级、S/D值,以病理学检查为标准,采用ROC 曲线评估S/D值鉴别卵巢良恶性肿瘤的效能。结果：癌症组血流分级、S/D值明显高于对照组,差异有统计学意义(P<0.05)；在鉴别卵巢良恶性肿瘤敏感度、特异度、准确度中,血流分级以≥Ⅱ级为临界值时分别为81.25%、83.33%、82.29%,ROC曲线显示S/D值以≥2.20为临界值时分别为87.50%、81.25%、84.38%,两者联合时分别为95.83%、93.75%、94.79%,两者联合时明显高于两者单独时,差异有统计学意义(P<0.05),但两者单独时基本相同,差异无统计学意义(P>0.05)。结论：血流分级及ROC曲线评价S/D值对鉴别卵巢良恶性肿瘤具有良好的效能,联合应用时可进一步提高其鉴别效能。     

破裂前交通动脉瘤术后患者认知功能及预后的临床研究

目的研究破裂前交通动脉瘤手术治疗后患者的认知功能及预后情况。 方法回顾性分析山西医科大学第一医院神经外科自2015年3月至2017年6月连续收治的94例破裂前交通动脉瘤患者的临床资料，应用认知功能电话问卷修订版及工具性日常生活能力量表、改良Rankin量表评价术后患者的认知功能及预后。采用单因素分析及多因素Logistic回归分析术后患者认知功能与预后的影响因素。 结果67例患者完成了术后认知功能及预后的随访评价。单因素分析：Hunt-Hess分级、文化程度是术后患者认知功能的影响因素（P<0.05）；Hunt-Hess分级、Fisher分级、年龄、文化程度是患者预后的影响因素（P<0.05）。进一步行多因素分析，高文化程度是术后患者认知功能的独立影响因素（OR=0.073，95%CI：0.008~0.638，P=0.018）。 结论高文化程度是术后患者认知功能的独立影响因素，且是保护因素。     

Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: −23.6% (spine) and −13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11–1.92) and incident (OR 1.55; 95% CI, 1.03–2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38–0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).