CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

HPLC-MS法鉴定广西产拳卷地钱中5种黄酮类成分

目的采用HPLC-MS鉴定广西产拳卷地钱75%乙醇提取物中黄酮类成分。方法采用色谱柱:ACQUITY UPLC HSS T3 C18(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)-乙腈(B),梯度洗脱,质谱使用电喷雾电离源(ESI)正负离子模式。结果分析得出拳卷地钱含有黄酮类成分5个,分别是Apigenin7,4’-diglucuronide、Apigenin7-glucuronide、芹菜素、木犀草素、金圣草黄素。结论该方法稳定、准确性好,可用于广西产拳卷地钱成分鉴定及质量控制。     

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).     

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC.