Abstract Objective Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). Methodology HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. Results Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1β, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. Conclusion These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways. W W5401 nonpeptide non peptide CaR C aR CaRA aRA (C5aRA antiinflammatory anti models However elucidated this LPStreated LPS treated . (HGFs) CCK transcriptionPCR transcription RTPCR RT (RT-PCR (LPS according S1 S S3. S3 S3) NFκB/MAPK NFκBMAPK NF κB/MAPK κB RTquantitative quantitative RTqPCR qPCR (RT-qPCR FSP1 FSP 1 FSP- LPSstimulated stimulated pp65. pp65 pp p p65. p65 p-p65 IL1β, IL1β ILβ IL 1β, 1β β IL-1β IL6, IL6 6, 6 IL-6 TNFα, TNFα TNF α, α TNF-α pp65, p65, pIκBα, pIκBα IκBα, IκBα p-IκBα pJNK, pJNK JNK, JNK p-JNK pcJUN, pcJUN c JUN, JUN p-c-JUN TLR LPSinduced induced NFκB W540 (HGFs κBMAPK pp6 p6 p-p6 IL- W54 p-p W5

Abstract Background Subarachnoid hemorrhage (SAH) is an uncommon and serious subtype of stroke, which leads to the loss of the patient’s ability to produce and live for many years. Objective To investigate the clinical effect of nimodipine in the treatment of SAH. Methods Electronic databases including China National Knowledge Infrastructure (CNKI), VIP, SinoMed, China Master’s Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed and Embase were searched from 2010 and 2021. All randomized controlled trials evaluating the efficacy of nimodipine in the treatment of SAH were included in our meta-analysis. The patients were divided into control group and treatment group. Meta-analysis was performed with Stata16.0 software. Results A total of 10 studies were included. Compared with the control group, the treatment group had higher effective rate (OR = 3.21, 95% CI: 2.25, 4.58; p < 0.001), and lower incidence of adverse reactions (OR = 0.35, 95% CI: 0.19, 0.67; p = 0.001). Before treatment, no significant differences were identified in middle cerebral artery blood flow velocity and Glasgow coma scale (GCS) score between the two groups. However, after treatment, the middle cerebral artery blood flow velocity (SMD = — 1.36, 95% CI: —2.28, —0.49; p = 0.002) and GCS score (SMD = 1.24, 95% CI: 0.58, 1.89; p < 0.001) in the treatment group were significantly better than those in the control group. Conclusions Nimodipine is effective in the treatment of SAH, lowering incidence of adverse reactions and therefore improving the prognosis of patients. (SAH stroke patient s years CNKI, CNKI , (CNKI) VIP SinoMed Masters Master Fulltext Full text CMFD, CMFD (CMFD) CDFD, CDFD (CDFD) Library 201 2021 metaanalysis. metaanalysis meta analysis. analysis meta-analysis Metaanalysis Meta Stata160 Stata Stata16 0 Stata16. software 1 OR 321 3 21 3.21 95 CI 225 2 25 2.25 4.58 458 4 58 0.001, 0001 0.001 001 035 35 0.35 019 19 0.19 0.67 067 67 0.001. . (GCS groups However SMD 136 36 1.36 2.28, 228 28 —2.28 0.49 049 49 —0.49 0.002 0002 002 124 24 1.24 058 0.58 1.89 189 89 (CNKI (CMFD (CDFD 20 202 Stata1 32 3.2 9 22 2.2 4.5 45 5 000 0.00 00 03 0.3 01 0.1 0.6 06 6 13 1.3 2.28 —2.2 0.4 04 —0.4 12 1.2 05 0.5 1.8 18 8 3. 2. 4. 0.0 0. 1. —2. —0. —2 —0

Resumo Antecedentes Hemorragia subaracnóidea (SAH) é um subtipo raro e grave de acidente vascular cerebral (AVC), o que leva à perda da capacidade do paciente de produzir e viver por muitos anos. Objetivo Investigar o efeito clínico da nimodipina no tratamento da SAH. Métodos As bases de dados eletrônicas, incluindo a China National Knowledge Infrastructure (CNKI), VIP, SinoMed, Masters Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed e Embase foram pesquisadas no período de 2010 a 2021. Todos os ensaios controlados aleatorizados que avaliam a eficácia da nimodipina no tratamento da SAH foram incluídos na nossa meta-análise. Os pacientes foram divididos em grupo controle e grupo de tratamento. Meta-análise foi realizada com o software Stata 16.0. Resultados Foram incluídos um total de dez estudos. Em comparação com o grupo controle, o grupo de tratamento tinha uma taxa mais elevada (OR = 3,21, 95% CI: 2,25, 4,58; p < 0,001), e menor incidência de reações adversas (OR = 0,35, 95% CI: 0,19, 0,67; p = 0,001). Antes do tratamento, não foram identificadas diferenças significativas na velocidade média do fluxo sanguíneo da artéria cerebral e na pontuação de Glasgow coma scale (GCS) entre os dois grupos. No entanto, após o tratamento, a velocidade média do fluxo sanguíneo da artéria cerebral (SMD = −1,36, 95% CI: −2,28, 0,49; p = 0,002) e a pontuação do GCS (SMD = 1,24, 95% CI: 0,58, 1,89; p < 0,001) no grupo de tratamento foram significativamente melhores do que os do grupo controle. Conclusões A nimodipina é eficaz no tratamento da SAH, diminuindo a incidência de reações adversas e, consequentemente, melhorando o prognóstico dos doentes. (SAH AVC, AVC , (AVC) anos eletrônicas CNKI, CNKI (CNKI) VIP SinoMed Fulltext Full text CMFD, CMFD (CMFD) CDFD, CDFD (CDFD) Library 201 2021 metaanálise. metaanálise meta análise. análise meta-análise Metaanálise Meta 160 16 0 16.0 estudos OR 321 3 21 3,21 95 CI 225 2 25 2,25 4,58 458 4 58 0,001, 0001 0,001 001 035 35 0,35 019 19 0,19 0,67 067 67 0,001. . (GCS grupos entanto SMD 136 1 36 −1,36 228 28 −2,28 0,49 049 49 0,002 0002 002 124 24 1,24 058 0,58 1,89 189 89 consequentemente doentes (AVC (CNKI (CMFD (CDFD 20 202 16. 32 3,2 9 22 2,2 4,5 45 5 000 0,00 00 03 0,3 01 0,1 0,6 06 6 13 −1,3 −2,2 0,4 04 12 1,2 05 0,5 1,8 18 8 3, 2, 4, 0,0 0, −1, −2, 1, −1 −2 −

Abstract Background: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. Results: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (lECs) to investigate the communication between MCs and lECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into lECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. Conclusions: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.

Abstract Background: Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells. Methods: In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine. Results: Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3. Conclusions: Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.

ABSTRACT Hydroxydihydrobovolide (HDB) was for the first time isolated from Portulaca oleracea L. and then its cytotoxicity against SH-SYTY cells was studied. Moreover, a rapid and sensitive ultra-high performance liquid chromatographic (UHPLC) method with bergapten as internal standard (IS) was developed and validated to investigate the pharmacokinetics of HDB in rats after intravenous and oral administrations of extract (POE). The UHPLC analysis was performed on a Diamonsil C18 analytical column, using acetonitrile-water (35:65, v/v) as the mobile phase with UV detection at 220 nm. The calibration curve was linear over the range of 0.2-25 µg/mL in rat plasma. The average extraction recovery was from 90.1 to 98.9%, and the relative standard deviations (RSDs) of the intra- and inter-day precisions were less than 4.7 and 4.1%, respectively. The results showed that 50 µM HDB had significant cytotoxicity on the SH-SY5Y cells, which was rapidly distributed with a Tmax of 11 min after oral administration and presented a low absolute bioavailability, 4.12%.