Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sjögren's syndrome.

OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

A new approach for vertical bone augmentation: Reconstructing bony peaks before GBR with a customized titanium mesh.

This image article presents a single patient receiving a reconstructed fibular bony peak (BP) for guided bone regeneration (GBR) with a customized titanium mesh. The patient was informed and understood the objectives and signed a written informed consent document before surgery.

Caspase-3 and gasdermin E mediate macrophage pyroptosis in periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis is a chronic inflammatory disease linked to pyroptosis, an inflammatory cell death process. Macrophages are essential for maintaining microenvironment homeostasis, which is crucial for periodontal health. This study explores the mechanisms underlying the relationship between macrophage pyroptosis and periodontitis. METHODS: Expression of the pyroptosis marker gasdermin E (GSDME) and the macrophage surface marker CD68 was examined by immunofluorescence double staining in healthy and periodontitis gingival tissues. In an in vitro pyroptosis model, RAW264.7 cells were irritated using Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) after treatment with either a nuclear factor kappa-B (NF-κB) agonist or inhibitor. The mRNA and protein levels of NF-κB, caspase-3, GSDME, and interleukin-1ß (IL-1ß) were evaluated through qRT-PCR, western blotting, and ELISA techniques. RESULTS: GSDME and CD68 were heavily elevated in inflamed gingival tissues compared to healthy tissues and co-localized in the same region. Furthermore, exposure to P. gingivalis-LPS resulted in a significant upregulation of NF-κB, caspase-3, GSDME, and IL-1ß at both the mRNA and protein levels in RAW264.7 cells. NF-κB agonist or inhibitor pretreatment enhanced or inhibited these effects. CONCLUSIONS: GSDME-mediated macrophage pyroptosis is implicated in periodontitis. Based on in vitro experiments, P. gingivalis-LPS causes pyroptosis in RAW264.7 cells through the caspase-3/GSDME pathway. Furthermore, NF-κB regulates this pyroptotic pathway.

Recent developments in two-dimensional molybdenum disulfide-based multimodal cancer theranostics.

Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS2) as a versatile platform in biomedical applications, few review articles have focused on MoS2-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS2 cancer theranostics and emerging strategies in this field. This review highlights the potential applications of 2D MoS2 in single-model imaging and therapy, including fluorescence imaging, photoacoustic imaging, photothermal therapy, and catalytic therapy. This review further classifies the potential of 2D MoS2 in multimodal imaging for diagnostic and synergistic theranostic platforms. In particular, this review underscores the progress of 2D MoS2 as an integrated drug delivery system, covering a broad spectrum of therapeutic strategies from chemotherapy and gene therapy to immunotherapy and photodynamic therapy. Finally, this review discusses the current challenges and future perspectives in meeting the diverse demands of advanced cancer diagnostic and theranostic applications.

Dimensional changes in free gingival grafts at implant sites in the reconstructed mandible: a retrospective study.

OBJECTIVE: To evaluate the dimensional changes in free gingival grafts (FGG) at implant sites in mandibular reconstruction patients. METHODS: Patients who received FGG 4 months after implant placement in the reconstructed mandible with no keratinized mucosa (KM) present were invited for re-examination after 36.7 ± 16.8 months (3.06 ± 1.4 years). Immediately after graft extraction (T0), graft width (GW), graft length (GL), graft thickness (GT), graft dimension (GD), and vertical bone height were documented. Re-examination (T1) included clinical examinations (GW, GL, GD, peri-implant probing depths, and modified Sulcus Bleeding Index), radiographic examination (marginal bone level), and medical chart review. RESULTS: Twenty patients and 62 implants (47 in fibula flaps and 15 in iliac flaps) were included. A significant decrease in GW (51.8%), GL (19.2%), and GD (60.2%), were found between T0 and T1 (p < .001). The univariate analysis showed that GW change was not significantly associated with reconstruction technique, baseline GL, baseline GT, baseline GD, implant location, or type of prosthesis. Implant survival rate of 100% was observed at follow-up. CONCLUSIONS: Within the limitations of the study, free gingival grafts at implant sites in the reconstructed mandible undergo dimensional change that result in a reduction of approximately 60% of the original graft dimension. Graft width decreased over 50%. CLINICAL RELEVANCE: FGG is the standard of care intervention for increasing the amount of KM around implants. This study was the first to evaluate the dimensional change in FGG at implant sites in mandibular reconstruction patients after a medium-term follow-up. CLINICAL TRIAL REGISTRATION: Clinical trial registration is not applicable as this study comprehends a retrospective analysis.

Deep learning in the diagnosis of maxillary sinus diseases: a systematic review.

OBJECTIVES: To assess the performance of deep learning (DL) in the detection, classification, and segmentation of maxillary sinus diseases. METHODS: An electronic search was conducted by two reviewers on databases including PubMed, Scopus, Cochrane, and IEEE. All English papers published no later than February 7, 2024, were evaluated. Studies related to DL for diagnosing maxillary sinus diseases were also searched in journals manually. RESULTS: Fourteen of 1167 studies were eligible according to the inclusion criteria. All studies trained DL models based on radiographic images. Six studies applied to detection tasks, one focused on classification, two segmented lesions, and five studies made a combination of two types of DL models. The accuracy of the DL algorithms ranged from 75.7% to 99.7%, and the area under curves (AUC) varied between 0.7 and 0.997. CONCLUSION: DL can accurately deal with the tasks of diagnosing maxillary sinus diseases. Students, residents, and dentists could be assisted by DL algorithms to diagnose and make rational decisions on implant treatment related to maxillary sinuses.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Oncolytic Virus-Driven Biotherapies from Bench to Bedside.

With advances in cancer biology and an ever-deepening understanding of molecular virology, oncolytic virus (OV)-driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent. In contrast, integrated approaches, such as using immunotherapy, chemotherapy, or radiotherapy, alongside OVT have demonstrated considerable efficacy. The challenges of OVT in clinical efficacy include the restricted scope of intratumoral injections and poor targeting of intravenous administration. Further optimization of OVT delivery is needed before OVs become a viable therapy for tumor treatment. In this review, the development process and antitumor mechanisms of OVs are introduced. The advances in OVT delivery routes to provide perspectives and directions for the improvement of OVT delivery are highlighted. This review also discusses the advantages and limitations of OVT monotherapy and combination therapy through the lens of recent clinical trials and aims to chart a course toward safer and more effective OVT strategies.

Clinical efficacy of computer-assisted zygomatic implant surgery: A systematic scoping review.

STATEMENT OF PROBLEM: Digital technology can improve the success of zygomatic implant (ZI) surgery. However, the reliability and efficacy of computer-assisted zygomatic implant surgery (CAZIS) need further analysis. PURPOSE: The purpose of this scoping review was to provide an overview of the placement accuracy, implant survival, and complications of CAZIS. MATERIAL AND METHODS: A systematic search of English and Mandarin Chinese publications up to May 2023 was conducted in PubMed, Web of Science, Embase, and Wanfang database. The nonpeer-reviewed literature was searched in the trial register (clinicaltrials.gov). Clinical studies and cadaver studies on CAZIS were included. After data extraction and collection, the findings were critically reviewed, analyzed, interpreted, and discussed. RESULTS: Forty-one studies met the inclusion criteria. After excluding publications with duplicate data, retaining the most recent, 28 articles were included in this scoping review. Of these, 18 were on static computer-assisted zygomatic implant surgery (sCAZIS), 8 on dynamic computer-assisted zygomatic implant surgery (dCAZIS), and 2 on robot-assisted zygomatic implant surgery (rAZIS). Excluding the outliers, the mean deviations of ZIs in the sCAZIS group (with 8 articles reporting implant placement accuracy, 183 ZIs involved) were: 1.15 ±1.37 mm (coronal deviation), 2.29 ±1.95 mm (apical deviation), and 3.32 ±3.36 degrees (angular deviation). The mean deviations of dCAZIS (3 articles, 251 ZIs) were: 1.60 ±0.74 mm (coronal), 2.27 ±1.05 mm (apical), and 2.89 ±1.69 degrees (angular). The mean deviations of rAZIS (2 articles, 5 ZIs) were: 0.82 ±0.21 mm (coronal), 1.25 ±0.52 mm (apical), and 1.46 ±0.35 degrees (angular). Among the CAZIS reported in the literature, the implant survival rate was high (96.3% for sCAZIS, 98.2% for dCAZIS, and 100% for rAZIS, specified in 14 of 21 clinical studies). The incidence of complications was low, but, because of the few relevant studies (4/21 specified), valid conclusions regarding complications could not be drawn. CONCLUSIONS: CAZIS has demonstrated clinical efficacy with high implant survival rates and placement accuracy. Of the 3 guided approaches, rAZIS showed the smallest 3-dimensional deviation.

Sex Difference in Primary Sjögren Syndrome: A Medical Records Review Study.

OBJECTIVES: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS. METHODS: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test. RESULTS: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05). CONCLUSIONS: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.

Factors associated with secondary immune thrombocytopenia in patients with primary Sjögren's syndrome: a retrospective study of 639 cases.

OBJECTIVES: To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS). METHODS: Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS. RESULTS: 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS. CONCLUSIONS: Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

Research on primary Sjögren's syndrome in 2004-2021: a Web of Science-based cross-sectional bibliometric analysis.

The extent, range, and nature of available research in the field of primary Sjögren's syndrome (pSS) have not been understood fully. This study aimed to map the literature available on pSS, and identify global hotspots and trends in the research. Papers on pSS published between 2004 and 2021 were searched from Web of Science Core Collection. The quantity and citations of publications, and the research hotspots and trends in the field of pSS were analyzed and presented visually by Microsoft Excel and Citespace software. A total of 3606 papers mainly from 526 institutions in 83 countries/regions were included for analysis. The number of publications presented an overall upward trend in the field of pSS from 2004 to 2021. The USA ranked first in the number of publications (n = 661), followed by China (n = 491), Italy (n = 405), France (n = 351), and Japan (n = 292). Moreover, seven of the top ten countries by the number of publications on pSS were from Europe. The University of Groningen (n = 661), Xavier Mariette (n = 95), and Clinical and Experimental Rheumatology (n = 184) were the most prolific affiliation, author, and journal, respectively. Vitali C (n = 2009) and Arthritis and Rheumatism (n = 3918) held the record for the most cited papers by an author and journal, respectively. At present, the hot keywords in the field of pSS include disease activity, ultrasonography, management, consensus, and data-driven. Lymphoid organization, clinical phenotypes outcome, salivary gland ultrasonography, and Toll-like receptor are the emerging research trends in pSS. Research on pSS is flourishing. Current research of pSS mainly focuses on disease activity, ultrasonography, and management. While, the emerging research trends in pSS are lymphoid organization, clinical phenotypes outcome, salivary gland ultrasonography, and Toll-like receptor.

EFFECTS OF POST-EXTRACTION ALVEOLAR RIDGE PRESERVATION VERSUS IMMEDIATE IMPLANT PLACEMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: This systematic review aimed to compare the clinical data including success rates, tissue preservation, esthetic results, and patient-reported outcomes between delayed implant placement after alveolar ridge preservation (ARP) and immediate implant placement (IIP). MATERIAL AND METHODS: Both electronic and manual searches were performed for randomized controlled trials and cohort studies consisting of at least 10 cases per group and a follow-up of at least 1-year in duration. The primary outcome was the implant success rate and secondary outcomes were changes in marginal bone level (MBL), pink esthetic score (PES) and patient reported outcomes consisting of complications and satisfaction. RESULTS: A total of 12 studies were included (8 randomized controlled trials and 4 cohort studies). This review contained 456 implants placed after ARP and 459 implants placed through IIP. The results from this meta-analysis showed that the success rates of implants placed through ARP protocol (98.68%) was significantly higher than that of implants placed through IIP protocol (95.21%) (RR = 1.03; 95% CI [1.01; 1.06]; P = .008; I2 = 0%). CONCLUSION: The results from this meta-analysis and systematic review showed that implants placed through ARP protocol may demonstrate higher success rates compared to implants placed through IIP.

Co-carrying an object by robot in cooperation with humans using visual and force sensing.

Human-robot collaboration poses many challenges where humans and robots work inside a shared workspace. Robots collaborating with humans indirectly bring difficulties for accomplishing co-carrying tasks. In our work, we focus on co-carrying an object by robots in cooperation with humans using visual and force sensing. A framework using visual and force sensing is proposed for human-robot co-carrying tasks, enabling robots to actively cooperate with humans and reduce human efforts. Visual sensing for perceiving human motion is involved in admittance-based force control, and a hybrid controller combining visual servoing with force feedback is proposed which generates refined robot motion. The proposed framework is validated by a co-carrying task in experiments. There exist two phases in experimental processes: in Phase 1, the human hand holds one side of the box object, and the robot gripper of the Baxter robot automatically approaches to the other side of the box object and finally holds it; in Phase 2, the human and the Baxter robot co-carry the box object over a distance to different target positions. This article is part of the theme issue 'Towards symbiotic autonomous systems'.

Comparison of the efficacy of different periodic periodontal scaling protocols for oral hygiene in adolescents with fixed orthodontic appliances: A prospective cohort study.

INTRODUCTION: The purpose of this reseach was to compare the effects of different periodic periodontal scaling protocols on the periodontal health of adolescents with fixed orthodontic appliances by assessing the aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels in gingival crevicular fluid and periodontal clinical indexes in a prospective cohort study. METHODS: Forty-eight adolescents were divided into 3 groups according to the interval of periodontal scaling (group A: once a month; group B: once every 3 months; group C: once every 6 months). The AST and ALP levels in the gingival crevicular fluid were measured before orthodontic treatment (T0) and at 1 (T1), 3 (T2), 6 (T3), and 9 (T4) months during orthodontic treatment. Periodontal clinical indexes (plaque index [PI], gingival index [GI], and probing depth) were also assessed. RESULTS: At T2, significantly lower AST and ALP levels were observed in group A than in groups B and C (P <0.05). At T3 and T4, lower AST and ALP levels were detected in groups A and B than in group C (P <0.05), and there was no significant difference between the A and B groups at T4 (P >0.05). At T2, the PI and GI were increased in groups B and C compared with group A, and at T3 and T4, significantly lower PI and GI values were observed in groups A and B than in group C (P <0.05). CONCLUSIONS: Periodontal scaling promotes the oral hygiene of adolescents undergoing fixed orthodontic treatment, and periodontal scaling protocols administered monthly and once every 3 months are better for controlling periodontal health than treatments administered once every 6 months.

Identification of Peritrophins and Antiviral Effect of Bm01504 against BmNPV in the Silkworm, Bombyx mori.

The insect midgut secretes a semi-permeable, acellular peritrophic membrane (PM) that maintains intestinal structure, promotes digestion, and protects the midgut from food particles and pathogenic microorganisms. Peritrophin is an important PM protein (PMP) in the PM. Here, we identified 11 peritrophins with 1-16 chitin binding domains (CBDs) comprising 50-56 amino acid residues. Multiple CBDs in the same peritrophin clustered together, rather than by species. The CBD contained six highly conserved cysteine residues, with the key feature of amino acids between them being CX11-15CX5CX9-14CX11-12CX6-7C. Peritrophins with 2 and 4 CBDs (Bm09641 and Bm01504, respectively), and with 1, 8, and 16 CBDs (Bm11851, Bm00185, and Bm01491, respectively) were mainly expressed in the anterior midgut, and throughout the midgut, respectively. Survival rates of transgenic silkworms with Bm01504 overexpression (Bm01504-OE) and knockout (Bm01504-KO) infected with B. morinucleopolyhedrovirus (BmNPV) were significantly higher and lower, whereas expression of the key viral gene, p10, were lower and higher, respectively, compared with wild type (WT). Therefore, Bm01504-OE and Bm01504-KO transgenic silkworms were more and less resistant, respectively, to BmNPV. Bm01504 plays important roles in resisting BmNPV invasion. We provide a new perspective for studying PM function, and reveal how the silkworm midgut resists invasive exogenous pathogenic microorganisms.

[Testicular injection of lipopolysaccharide: An effective method for establishing the mouse model of orchitis].

OBJECTIVE: To search for a method of establishing a reliable mouse model of orchitis and investigate the association of orchitis with the activation of the inflammasome. METHODS: We equally randomized 40 adult male KM mice into groups A (sham operation), B (intraperitoneal injection of lipopolysaccharide ï¼»LPSï¼½), C (unilateral testicular injection of glacial acetic acid ï¼»GAAï¼½), and D (unilateral testicular injection of LPS). At 3 weeks after modeling, we measured the sperm concentration and percentage of progressively motile sperm (PMS) in the epididymis by computer-assisted semen analysis, observed the pathological changes in the testis tissue by HE staining, and determined the expressions of the Caspase-1 and interleukin (IL)-1ß proteins by Western blot. RESULTS: The sperm concentration in the epididymis was significantly decreased in groups B (ï¼»25.74 ± 3.19ï¼½ ×106/ml), C (ï¼»17.16 ± 4.41ï¼½ ×106/ml) and D (ï¼»16.92 ± 7.13ï¼½ ×106/ml) as compared with that in group A (ï¼»28.20 ± 1.63ï¼½ ×106/ml) (all P < 0.05), even more significantly in B than in C and D (P < 0.01), and so was PMS in groups B (ï¼»29.57 ± 2.16ï¼½%), C (ï¼»18.10 ± 2.38ï¼½%) and D (ï¼»7.34 ± 1.63ï¼½%) in comparison with group A (ï¼»59.34 ± 1.10ï¼½%) (P < 0.01), even more significantly in B and C than in D (P < 0.01). Light microscopy revealed different degrees of pathological changes in the testis tissue, most significant in group D, followed by C and B. Both the expressions of Caspase-1 and IL-1ß were remarkably up-regulated in groups B, C and D compared with those in group A (P < 0.01), even more markedly in D than in B and C (P < 0.05). CONCLUSIONS: Unilateral testicular injection of LPS is a more efficient method than either unilateral testicular injection of GAA or intraperitoneal injection of LPS for establishing the mouse model of orchitis. Orchitis may be pathologically associated with the activation of the NLRP3 inflammasome.

miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6.

It has been suggested that microRNAs (miRs) are involved in the immune regulation of periodontitis. However, it is unclear whether and how miRs regulate the function of B cells in the context of periodontitis. This study is to explore the role of miR-146a on the inflammatory cytokine production of B cells challenged by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). Primary B cells were harvested from mouse spleen. Quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of inflammatory cytokines in B cells in the presence or absence of P. gingivalis LPS and/or miR-146a. Bioinformatics, luciferase reporter assay and overexpression assay were used to explore the binding target of miR-146a. Our results showed that miR-146a level in B cells was elevated by P. gingivalis LPS stimulation, and the mRNA expressions of interleukin (IL)-1ß, 6 and 10, and IL-1 receptor associated kinase-1 (IRAK1), but not TNF receptor associated factor 6 (TRAF6), were also upregulated. The expression levels of IL-1ß, 6, 10 and IRAK1 were reduced in the presence of miR-146a mimic, but were elevated by the addition of miR-146a inhibitor. MiR-146a could bind with IRAK1 3' untranslated region (UTR) but not TRAF6 3'-UTR. Overexpression of IRAK1 reversed the inhibitory effects of miR-146a on IL-1ß, 6 and 10. In summary, miR-146a inhibits inflammatory cytokine production in B cells through directly targeting IRAK1, suggesting a regulatory role of miR-146a in B cell-mediated periodontal inflammation.

The anti-inflammatory effect of BML-111 on COPD may be mediated by regulating NLRP3 inflammasome activation and ROS production.

The aim of this study is to investigate whether the lipoxin receptor agonist BML-111 exerts a protective effect against inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) by regulating NLRP3 inflammasome activation and reactive oxygen species (ROS) production. In this study, mice were randomly divided into the following five groups: control group (Control), COPD model group (Model), BML-111 low-dose group (Low-BML), BML-111 high-dose group (High-BML) and Dexamethasone group (Dex). NLRP3 involvement and oxidative stress were evaluated. Differential cell counts in the BALF were calculated to obtain a reliable enumeration of each cell type, and the levels of TGF-ß, TNF-α, IL-1ß, and IL-10 in BALF were evaluated using ELISA. We found that the white blood cell and lymphocyte numbers in the BALF were significantly lower in the High-BML group than in the Model group. ELISA of the BALF showed that BML-111 reduced TGF-ß and IL-1ß levels to some extent. HE staining showed various degrees of reduction in inflammatory cell infiltration in the bronchopulmonary tissue and blood vessels of the Low-BML, High-BML and Dex groups. Measurement of oxidative stress showed that SOD activity was significantly upregulated and that the increase in MDA content was prevented in the High-BML and Dex groups. According to the Western blotting analysis, the levels of NLRP3, Cleaved-IL-1ß and Cleaved-caspase-1 were decreased and Nrf-2 was increased to various extents in the Low-BML, High-BML and Dex groups. Based on these findings, BML-111 may prevent NLRP3 inflammasome activation and inhibit ROS production via upregulation of Nrf-2, thereby exerting an anti-inflammatory effect on COPD model mice.

IL-21/anti-Tim1/CD40 ligand promotes B10 activity in vitro and alleviates bone loss in experimental periodontitis in vivo.

IL-10-expressing regulatory B cells (B10) play an essential role in immune system balance by suppressing excessive inflammatory responses. In this study, we investigated induction of B 10 cell's IL-10 competency in vitro and its effect on ligature-induced experimental periodontitis in vivo. Spleen B cells were isolated from C57BL/6J mice and cultured for 48h under the following conditions: control, CD40L, IL-21, anti-Tim1, CD40L+IL-21, CD40L+anti-Tim1, CD40L+IL-21+anti-Tim1. Silk ligatures were tied around both maxillary second molars of C57BL/6J mice for two weeks. Optimized combination of CD40L, IL-21 and anti-Tim1 and vehicle were injected into contralateral side of palatal gingiva on days 3, 6 and 9. The palatal gingival tissues and maxillary bone were collected on day 14 to determine expressions of IL-10 and periodontal bone resorption respectively. Our results demonstrated that IL-10 expressions of cultured spleen B cells were significantly increased in the presence of CD40L, IL-21 and anti-Tim1 combination when compared with control groups. Gingival IL-10 mRNA and protein expressions were significantly increased after injection of CD40L, IL-21 and anti-Tim1 combination, when compared to the control side. The gingival RANKL expression and periodontal bone loss were significantly decreased on the combination treatment side, as compared to the control side. These results suggest that combination of IL-21, anti-Tim1 and CD40L treatment induced B10 cell's IL-10 competency in vitro and inhibited periodontal bone loss in ligature-induced experimental periodontitis.