Identification of the Microbial Transformation Products of Secoisolariciresinol Using an Untargeted Metabolomics Approach and Evaluation of the Osteogenic Activities of the Metabolites.

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

Efficacy and safety of percutaneous endoscopic decompression via transforaminal and interlaminar approaches for lumbar spine stenosis: Protocol for a systematic review and meta-analysis.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common and frequently-occurring disease in the elderly. Percutaneous endoscopic decompression (PED) has become the first choice for the treatment of LSS because of its small wound, mild pain and rapid recovery. The surgical approaches are mainly divided into percutaneous interlaminar approach and transforaminal approach. However, these two surgical approaches have their own advantages, disadvantages and indications. Hence, the present study aims to synthesize the available direct and indirect evidence of transforaminal approach and interlaminar approach to prove their respective advantages and disadvantages. METHODS: The following databases will be searched: Cochrane Library, PubMed, Web of Science, Embase, CNKI, Wanfang data, and China Biomedical Literature Database (CBM). The search dates will be set from the inception to November 2019. Two researchers independently screened the literature, extracted the data and assessed the risk of bias in the included studies. The efficacy outcomes including: Back and Leg Visual Analog Scale (VAS) score, the MacNab criteria, the Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) score. The safety outcomes including: incidence of complications (dura tear, incomplete decompression, reoperation, etc.). The meta-analysis will be conducted using Stata 12.0 software. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess evidence quality. RESULTS: The results of this meta-analysis will be published in a peer-reviewed journal. CONCLUSION: The meta-analysis will provide a comprehensive summary of the evidence for 2 approaches to PED in patients with LSS. PROTOCOL REGISTRATION NUMBER: CRD42019128080.

N-Heterocyclic carbene-catalyzed formal cross-coupling reaction of α-haloenals with thiols: organocatalytic construction of sp2 carbon-sulfur bonds.

A novel N-heterocyclic carbene (NHC)-catalyzed formal cross-coupling reaction between α-haloenals and thiols was developed. In the presence of 5 mol% NHC precursors and 1.6 equiv. potassium carbonate, various thiols coupled with α-haloenals to produce α-thioenals in 53% to 91% yield and excellent Z-selectivity.

[Effect of inhibiting the expression of hSMG-1 on chemosensitivity of human non-small cell lung cancer H1299 cells].

OBJECTIVE: To investigate the effect of inhibiting the expression of human suppressor of morphogenesis in genitalia-1 (hSMG-1) on chemosensitivity in human lung cancer H1299 cells. METHODS: Specialized small interference RNAs (siRNAs) of hSMG-1 were transfected into H1299 cells. The knockdown effect was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. After the administration of anti-cancer drugs, the cell viable rate was determined by cell counting kit (CCK-8) and apoptotic rate was measured by Annexin V-FITC PI double staining on flow cytometry. The apoptotic related activated caspase 3 and caspase 9 were determined by colorimetric assay. RESULTS: The expression of hSMG-1 mRNA was significantly inhibited by hSMG-1 siRNA. And the inhibition rate of (73.8 ± 10.3)% was obtained (P < 0.01). The knockdown effect was further confirmed by immunofluorescence. The inhibition of hSMG-1 enhanced the sensitivity of H1299 cells to gemcitabine and cisplatin. The survival rates significantly decreased when the hSMG-1 siRNA transfected cells were treated with 10.0 mg/L gemcitabine and 10.0 mg/L cisplatin for 48 h respectively (0.51 ± 0.02 vs 0.69 ± 0.01, P < 0.01 and 0.34 ± 0.03 vs 0.48 ± 0.01, P < 0.01;all compared with control siRNA group). Annexin V-FITC PI double staining showed that, under the treatment of anti-cancer drugs, the apoptotic rate of H1299 cells was significantly increased by hSMG-1 knockdown [gemcitabine, (20.9 ± 3.4)% vs (12.0 ± 2.7)%, P < 0.05; cisplatin, (10.2 ± 1.8)% vs (4.5 ± 2.0)%, P < 0.05; all compared with control siRNA group]. Further study showed the inhibition of hSMG-1 up-regulated the activated caspase 3 and caspase 9 in the treated H1299 cells (gemcitabine, 0.1 mg/L, 48 h, caspase 3: 14.4 ± 3.8 vs 2.3 ± 0.4, P < 0.01; caspase 9: 15.5 ± 2.4 vs 4.2 ± 0.9, P < 0.01; cisplatin, 1.0 mg/L, 48 h, caspase 3: 18.8 ± 3.0 vs 6.5 ± 1.5, P < 0.01; caspase 9: 20.3 ± 4.2 vs 8.1 ± 2.0, P < 0.05; all compared with control siRNA group). CONCLUSION: The inhibition of hSMG-1 significantly enhances the sensitivity of human lung cancer H1299 cells to gemcitabine and cisplatin through an induction of more apoptotic cells. And the activation of mitochondrial apoptotic pathway is involved.