Role of CD19+ CD5+ CD1d+ Bregs in maintaining the Th17/Treg balance in mice with systemic lupus erythematosus complicated with atherosclerosis.

OBJECTIVE: In this study, we aimed to investigate Bregs, their regulatory effects on Th17/Treg cell balance, and the release of downstream inflammatory factors in a mouse model of low-density lipoprotein receptor (LDLr)-/- + Pristane. METHODS: After the establishment of the mouse model of systemic lupus erythematosus (SLE) complicated with atherosclerosis (AS), 8-week-old LDLr-/- + Pristane mice (n = 10) were included in the SLE + AS group. Furthermore, 8-week-old MRL/lpr and C57 mice were used as the SLE and normal control groups, respectively (n = 10 per group). After feeding the mice a high-fat diet for 14 weeks, peripheral blood and spleen of mice were collected, and Bregs, Th17, and Treg cells and related inflammatory factors were detected by flow cytometry, enzyme-linked immunosorbent assay, and reverse-transcription polymerase chain reaction. RESULTS: The number of Bregs and Tregs in spleen lymphocytes of SLE + AS mice significantly decreased compared with the C57 group (p < .05), whereas the number of Th17 cells significantly increased (p = .000). Furthermore, the proportion of Bregs showed a negative correlation with the Th17/Treg ratio (p = .03). Mice in the SLE + AS group showed higher serum interleukin (IL)-10, IL-17, and tumor necrosis factor-α levels than those in the SLE and C57 groups (p < .05). Furthermore, IL-35 and transforming growth factor (TGF)-ß expression was reduced in the SLE + AS group compared with the C57 group (p < .05). CONCLUSIONS: The proportion of Breg decreases was negatively associated with increased Th17/Treg which was increased in SLE + AS mice, indicating that Bregs may regulate Th17/Treg cell homeostasis and cytokine release via IL-35 and TGF-ß production.

Transbronchial lung cryobiopsy for connective tissue disease-related interstitial lung disease and interstitial pneumonia with autoimmune features: a single center retrospective case series.

OBJECTIVE: Transbronchial lung cryobiopsy (TBLC) has been recently introduced for diagnosing interstitial lung diseases. We aimed to assess the effectiveness and safety of TBLC by identifying the specific patterns of histology in the diagnosis of connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF). METHODS: The clinical-radiological-pathological data from the Affiliated Hospital of Guilin Medical University between July 1, 2017, and October 31, 2020, of patients whose clinical-radiological or clinical-radiological-pathological diagnosis was CTD-ILD or IPAF and who underwent TBLC, transbronchial lung biopsy (TBLB), or surgical lung biopsy were retrospectively analyzed and summarized with review. The size of biopsy samples, complications, and diagnostic yield were compared. RESULTS: Fourteen patients met the inclusion criteria, of whom 12 underwent TBLC, 1 underwent TBLB, and 1 underwent each procedure at different times. Compared to the size of TBLB specimens (5.625 ± 0.479 mm2), the size of TBLC specimens (12.00 (12.00, 15.00) mm2) was much larger (Z = - 3.262, P = 0.001). The diagnostic yields of TBLC and TBLB were 100.00% (13/13) and 0.00% (2/2), respectively (P = 0.0095). The most frequent complication was mild bleeding. The risk of bleeding between TBLB (1/2, 50.00%) and TBLC (10/13, 76.92%) did not differ significantly (P = 0.469). CONCLUSION: TBLC can add extra diagnostic value by effectively identifying specific types of histology for patients with suspected CTD-ILD or IPAF, with a procedure that is safe from adverse events. Key Points • Transbronchial lung cryobiopsy has been introduced recently for diagnosing interstitial lung disease. • Transbronchial lung cryobiopsy was found to be effective and safe in the diagnosis for patients with suspected interstitial lung disease. It can be used as a preferred method for biopsy when the clinical-radiological diagnosis is uncertain.

Evodiamine induces apoptosis and enhances apoptotic effects of erlotinib in wild-type EGFR NSCLC cells via S6K1-mediated Mcl-1 inhibition.

Erlotinib is effective in NSCLC patients with known drug-sensitizing EGFR mutations, but its clinical efficacy in patients with wild-type EGFR or acquired resistance to erlotinib remains modest. Evodiamine is a chemical extracted from the Evodia rutaecarpa (Juss.) Benth, we showed that evodiamine could induce anti-proliferation and apoptosis in four wild-type EGFR NSCLC cell lines, and combining evodiamine with erlotinib might successfully inhibit cell proliferation and survival in wild-type EGFR NSCLC cells, characterized as erlotinib-resistant. In addition, evodiamine plus erlotinib significantly increased the apoptotic rate of NSCLC cells, as compared to single agent treatment alone. Further investigation of the mechanism underlying these effects revealed that evodiamine plus erlotinib might downregulate Mcl-1 expression through the mTOR/S6K1 control of its translation. Thus, our study has revealed evodiamine as a pertinent sensitizer to erlotinib and the strategy of combining erlotinib with evodiamine appears to be an attractive option for reversing resistance to erlotinib.

Novel microbiosensors prepared utilizing biomimetic silicification method.

We demonstrate fabrication of microbiosensors utilizing a simple, rapid biomimetic silicification method catalyzed by poly-L-lysine at ambient temperature to provide a mild and efficient method for entrapment of the enzymes required for a range of analytes. To obtain a robust poly-L-lysine layer for precipitating silica onto the Pt surface, a Pt microelectrode was first functionalized with abundant carboxyl groups by electrochemical deposition of poly(pyrrole-1-propanoic acid). By means of zero length cross-linking reagents N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide sodium salt (NHSS), poly-L-lysine was covalently immobilized onto microelectrode surface. Under mild chemical conditions, three enzymes including adenosine deaminase (AD, EC 3.5.4.4), nucleoside phosphorylase (NP, EC 2.4.2.1) and xanthine oxidase (XO, EC 1.1.3.22) could then be simultaneously entrapped into a continuous silicate layer formed on top of Pt microelectrode from a mixture of enzymes and hydrolyzed silanes in Tris buffer (0.1M, pH 7.2) via the catalytic action of the attached poly-L-lysine. The fabricated adenosine biosensors exhibited good analytical performance with a sensitivity of 153.0+/-2.4 microA mM(-1)cm(-2) (n=4, R.S.D.=2.1%), a lower detection limit of 40 nM and a favourable response time (estimated as 10-90% response rise time) of 25+/-2s (n=4). The good selectivity of the adenosine microbiosensor against coexisting interfering substances such as ascorbic acid, urate and 5-HT was achieved through formation of a screening barrier from electrodeposited poly(diaminobenzene) following the biomimetic deposition process. We found that our methods were adaptable for other enzymes and analytes allowing fabrication of l-glutamate and lactate biosensors.