Network Pharmacology and Molecular Docking Reveal the Mechanism of Corydalis saxicola Bunting Total Alkaloids in Treating Radiation-Induced Oral Mucositis.

The study aims to explore the effect and mechanism of total alkaloids of Corydalis saxicola Bunting (CSBTA) in the treatment of radiation induced oral mucositis (RIOM) through network pharmacology and molecular docking. The components and corresponding targets of Corydalis saxicola Bunting were screened by literature review. RIOM related targets were obtained in GeneCards. Cytoscape software was used to construct the component-target-pathway network. Protein-Protein Interaction (PPI) networks was constructed by String database. GO and KEGG enrichment analyses were performed by Metascape. AutoDock Vina 4.2 software was used for molecular docking. There were 26 components of CSBTA targeting 61 genes related to RIOM. Through Cytoscape and PPI analysis, 15 core target genes of CSBTA for treating RIOM were identified. GO functional analysis indicated that CSBTA might play a role through kinase binding and protein kinase activation. KEGG pathway analysis showed that the core targets of CSBTA were mainly focused on cancer and reactive oxygen species (ROS) pathway. The results of molecular docking showed that CSBTA had strong binding energy with target protein including SRC, AKT and EGFR. The study demonstrates that CSBTA may treat RIOM by affecting SRC, AKT and EGFR through ROS pathway.

Inhibitory Effects of Corydalis saxicola Bunting Total Alkaloids on Macrophage Pyroptosis.

This study investigated the effect of Corydalis saxicola Bunting total alkaloids (CSBTA) on pyroptosis in macrophages (Mϕ). In the Mϕ pyroptosis model, an inverted fluorescence microscope was used to assess cell pyroptosis, while a scanning electron microscope was used to observe morphological changes in Mϕ. NLR family pyrin domain-containing 3 (NLRP3), caspase-1, and gasdermin D (GSDMD) expression levels were detected by polymerase chain reaction and western blotting, whereas interleukin-1 (IL-1) and interleukin-18 (IL-18) expression levels were measured by an enzyme-linked immunosorbent assay. After pretreatment with CSBTA or the caspase-1 inhibitor, acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone (Ac-YVAD-cmk), it was discovered that NLRP3, caspase-1, and GSDMD expressions were significantly reduced at both the mRNA and protein levels, as were IL-1 and IL-18 levels. The inhibitory effects of CSBTA and Ac-YVAD-cmk did not differ significantly. These findings indicate that CSBTA blocks Porphyromonas gingivalis-lipopolysaccharide-induced Mϕ pyroptosis.

The over-expression of miRNA-206 in peripheral blood of patients with burning mouth syndrome and its relationship with anxiety and depression.

BACKGROUND: Burning mouth syndrome (BMS) is characterised by persisting burning pain of the oral mucosa, and its etiopathogenesis remains poorly understood. OBJECTIVES: Our study aimed to detect the expression of miRNA-206 in the blood and clarify the relationship among miRNA-206, pain, anxiety and depression of BMS patients. METHODS: Thirty patients with BMS and 30 healthy individuals were enrolled in the experimental and control groups, respectively. Data on medical history and clinical oral examination for all participants were collected. Simultaneously, scores of Visual Analogous Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were administered. The expression level of miRNA-206 in plasma were determined by RT-(q)PCR. Finally, the relationship of miRNA-206 expression with the VAS score, SAS score, and SDS score was analysed. Chi-square test and t-test were used for statistical analysis of the data, and p < .05 was considered statistically significant. RESULTS: The majority of the patients with BMS identified the tongue as the main pain area, and showed dry mouth and poor sleep quality. The SAS and SDS scores of patients with BMS were higher than those of healthy controls (p < .05) and were positively correlated with VAS pain score. In addition, miRNA-206 expression was higher in patients with BMS than in healthy individuals (p < .05), and was positively correlated with the VAS and SDS scores (p < .05). CONCLUSIONS: Patients with BMS suffer from pain and tend to be more anxious and depressed than healthy controls. miRNA-206 expression in the peripheral blood of patients with BMS is positively correlated with pain and depression, which may be involved in the pathogenesis of BMS.

The efficacy of subgingival air polishing and subgingival debridement in periodontal support therapy: a meta-analysis.

OBJECTIVE: To assess whether there is sufficient evidence of a difference in efficacy between subgingival air polishing (SubAP) and subgingival debridement as periodontal support treatment. The systematic review protocol was registered in the PROSPERO database under no. CRD42020213042. METHODS: A comprehensive search was conducted using eight online databases to develop straightforward clinical questions and search strategies, from their inception to 27 January 2023. The references of identified reports were also retrieved for inclusion in the analysis. The risk-of-bias of the included studies was evaluated using the Revised Cochrane Risk-of-Bias tool (RoB 2). A meta-analysis was performed on five clinical indicators using the Stata 16 software. RESULTS: Twelve randomized controlled trials were ultimately included, and most included studies had varying degrees of risk-of-bias. The results of the meta-analysis indicated that there was no significant difference between SubAP and subgingival scaling in terms of improving probing depth (PD), clinical attachment loss (CAL), plaque index (PLI), and bleeding on probing% (BOP%). The results of the visual analogue scale score analysis indicated that SubAP produced less discomfort than did subgingival scaling. DISCUSSION: SubAP can provide better treatment comfort than subgingival debridement. There was no significant difference in the efficacy of the two modalities in improving PD, CAL, and BOP% in supportive periodontal therapy. CONCLUSION: Currently, evidence for assessing the difference in the efficacy of SubAP and subgingival debridement in improving the PLI is insufficient, and further high-quality clinical studies are needed.

The oral histopathological and immunological characteristics of a xenogeneic mouse chronic graft-versus-host disease model.

BACKGROUND: Oral lesions are important clinical manifestations of chronic graft-verse-host disease (cGVHD). However, the oral characteristics of cGVHD mouse model are not yet clear. This study aims to demonstrate oral histopathological and immunological characteristics of a xenogeneic cGVHD mouse model. MATERIALS AND METHODS: 2.5 × 106 , 5.0 × 106 , 7.5 × 106 , and 10.0 × 106  human peripheral blood mononuclear cells (hPBMCs) were intravenously transplanted into NCG mice to induce cGVHD. After transplantation, clinical observations were recorded. Tissue samples from salivary glands and oral mucosa were stained with H&E, Masson Trichrome, and immunofluorescence, and the histopathology of oral tissues was scored according to our modified criteria. RESULTS: NCG mice showed signs of cGVHD onset after transplantation. The oral histopathological lesion incidences in each group were 37.50%, 50.00%, 62.50%, and 75.00%, respectively. Oral histopathological lesion incidence and histopathological scores were positively correlated with the amount of infused hPBMCs. Epithelial atrophy, epithelial cells vacuolar degeneration, and basal cells liquefaction denaturation were observed in oral mucosa, and acinar destruction and collagen deposition were observed in the salivary glands. Human CD45+ , CD4+ , CD8+ , IL-17+ , and FoxP3+ cells infiltrated into oral tissues. In the 5.0 × 106  hPBMCs group, oral histopathological changes mainly began between days 30 and 45 post-transplantation, and became more severe after day 45. The oral histopathological scores also gradually increased. CONCLUSION: Inflammation in oral mucosa epithelium and salivary glands, and CD4+ and CD8+ T cells dominating infiltration are the main oral features in the xenogeneic cGVHD mouse model. The severity of oral histopathological lesions shows a dose and time correlation. These may be helpful to oral cGVHD research.

Effect of probiotics on gingival inflammation and oral microbiota: A meta-analysis.

To evaluate the effect of probiotics on gingival inflammation and oral microbiota in patients suffering from plaque-induced gingivitis. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were electronically searched until December 2020. The quality of included studies was assessed with the Cochrane Collaboration's Risk of Bias tool. The differences were expressed as weighted mean differences (WMD) and 95% of confidence interval (95% CI). I2 test was performed to evaluate the heterogeneity of the studies. All analyses were performed using Review Manager (version 5.3). Eleven randomized and controlled trials were included, enrolling 554 patients. All comparisons displayed that oral probiotics had no significant improvement in the Gingival Index (GI), Plaque Index (PI), and bleeding on probing (BOP) of patients with plaque-induced gingivitis. In terms of microecology, no significant difference in the volumes of gingival crevicular fluid (GCF), the concentration of IL-1ß, and the counts of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), and Fusobacterium nucleatum (Fn) were found between the probiotic group and the placebo group. There exists no clear evidence that oral probiotics have positive effect on gingival inflammation and oral microecological environment of patients with plaque-induced gingivitis.

Recombinant human interleukin 17A enhances the anti-Candida effect of human oral mucosal epithelial cells by inhibiting Candida albicans growth and inducing antimicrobial peptides secretion.

BACKGROUND: Candida albicans (C albicans) is the most common fungal pathogen causing opportunistic infections. IL17 (IL17A) is a vital mediator of antifungal immunity. The aim of the study was to investigate the effect of recombinant human interleukin 17A (rhIL17A) on human oral mucosal epithelial cells (hOMECs) defending against C albicans infection. METHODS: Human oral mucosal epithelial cells were divided into four groups: C albicans+ (MOI = 0.1), rhIL17A+ (100 µg/L), rhIL17A + C albicans+ (MOI = 0.1, rhIL17A:100 µg/L) and blank control. Then, C albicans growth was observed after 24 hours. Human beta-2 defensin (hBD-2), S100A8 and LL-37 in supernatants and their mRNAs in cells were measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. RESULTS: In C albicans+ group, C albicans hyphae formation and the death of infected hOMECs were observed. However, in the rhIL17A + C albicans+ group, IL17 inhibited both hypha formation, and C albicans from infecting hOMECs and its further growth. There was no statistical significance in adhesion rates of C albicans to hOMECs. Compared with the control group, the level of hBD-2 mRNA has increased, while hBD-2 and hBD-2 mRNA levels in the rhIL17A + C albicans+ group were the highest. Both hBD-2 and hBD-2 mRNA levels were higher in the rhIL17A+ group than in the C albicans+ group. S100A8 and LL-37 mRNAs have similar trend, and both upregulated after treatment with rhIL17A; however, protein levels were undetectable. CONCLUSION: Recombinant human interleukin 17A may inhibit C albicans from infecting hOMECs by affecting the growth and reproduction of C albicans as well as the formation of hyphae. Besides, rhIL17A might induce hBD-2, S100A8 and LL-37 secretion from hOMECs to strengthen their anti-infective ability.

Regulatory effect of 17ß-estradiol on the expression of ß-defensin-2 and proinflammatory cytokines in human oral epithelial cells.

BACKGROUND: Although estrogen deficiency has been proposed as a risk factor for oral mucosal inflammatory diseases in post-menopausal women, the mechanisms involved remain unclear. This study aimed to investigate the effect of 17ß-estradiol (E2) on the inflammatory response stimulated by interleukin-1 beta (IL-1ß) in human oral mucosal epithelial cells (hOMECs) and its possible mechanism. METHODS: Primary hOMECs were obtained from female infants and cultured in keratinocyte growth medium. The hOMECs at second passage were collected and stimulated by 10-7  mol/L ICI182,780 or 10-7  mol/L G1 for 1 hour, E2 (10-7  mol/L, 10-8  mol/L, 10-9  mol/L) for 36 hour, 100 ng/mL IL-1ß for 12 hours, respectively. Human beta-2 defensin (hBD-2), tumor necrosis factor-alpha (TNF)-α, IL-6, IL-8, estrogen receptor-alpha (ERα), estrogen receptor-beta (ERß), and G protein-coupled receptor 30 (GPR30) mRNA levels and protein levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western Blot (WB), respectively. RESULTS: Expression of hBD-2 and inflammatory cytokines increased after IL-1ß stimulation, which was down-regulated by E2 pre-treatment. With ICI182,780, the suppression of E2 on hBD-2 mRNA was attenuated. With G1, the mRNA expression and protein expression of hBD-2 were reduced. CONCLUSION: Pre-treatment of hOMECs with E2 at physiological concentrations inhibited the IL-1ß-induced expression of hBD-2 and inflammatory cytokines. The protective effects of E2 suggest its potential use treating oral inflammatory diseases in clinical practice.

Oral innate immunity in HIV infection in HAART era.

Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces not only provide a physical barrier but also produce different antimicrobial peptides, including human ß-defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co-infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection, contributed to a global reduction of HIV-associated oral lesions. However, prolonged use of HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: (i) What are the roles of oral innate immunity in health and disease?, (ii) What are the effects of HIV infection on oral innate immunity?, (iii) What are the roles of oral innate immunity against other co-infections?, (iv) What are the effects of HAART on oral innate immunity?, and (v) Is oral innate immunity enhanced by HAART?

Dynamics of T-cell subsets and their relationship with oral and systemic opportunistic infections in HIV/AIDS patients during the first year of HAART in Guangxi, China.

To analyze the dynamic changes in Th1, Th2, Tc1, and Tc2 of HIV/AIDS patients during the first year of highly active antiretroviral therapy (HAART) and to explore their relationship with oral and systemic opportunistic infections, a cohort study was carried out among HIV/AIDS patients in Guangxi, China. Ninety HIV/AIDS patients and 30 healthy controls (HC) were included. The enrolled HIV/AIDS patients were examined at baseline and after 3, 6, and 12 months of HAART. On each visit, oral and systemic opportunistic infections were recorded, oral Candida load and plasma viral load (VL) were counted, differential T-cell counts and flow cytometric analysis of T-cell subsets were performed. During the first year of HAART, the total number of opportunistic infections decreased steadily with the change in oral candidiasis (OC) most representatively. A significant Th1→Th2 switch (Th1/Th2 ratio 0.23 ± 0.12, HC 1.45 ± 0.38) and slight Tc1→Tc2 shift (Tc1/Tc2 ratio 0.93 ± 0.29, HC 1.13 ± 0.33) were found at baseline, and both received slow mitigation after HAART. LgCFU and clinical OC were correlated positively with both LgVL and clinical stage (P < 0.05) at baseline. LgCFU was also correlated positively with clinical stage at all four time points (P < 0.05). In multiple factor analysis, Th1 was confirmed to be correlated negatively with LgVL (Std.B = -0.295, P = 0.025) and LgCFU (Std.B = -0.227, P < 0.001) at baseline. After HAART, LgCFU and clinical stage were only correlated negatively with CD4 when all factors were included. These results suggest that oral candidiasis and oral Candida load could be useful clinical markers in the evaluation of HIV/AIDS patients. Th1 may play an important role against oral and systemic opportunistic infections. Tc1 and Tc2 both showed positive roles in the control of viremia without HAART. J. Med. Virol. 87:1158-1167, 2015. © 2015 Wiley Periodicals, Inc.

Dynamic analysis of oral Candida carriage, distribution, and antifungal susceptibility in HIV-infected patients during the first year of highly active antiretroviral therapy in Guangxi, China.

BACKGROUND: Highly active antiretroviral therapy (HAART) as an effective therapy for immune reconstruction among patients with HIV/AIDS might have influence on oral Candida status. We investigated oral Candida carriage, distribution, and antifungal susceptibility dynamically during the first year of HAART among adult HIV-infected patients in Guangxi, China. METHODS: Forty-five adult HIV-infected patients who received their first year HAART in the AIDS clinic of the Guangxi Center for Disease Control (CDC) and 31 healthy individuals were recruited. Clinical information and oral examinations were obtained. Oral rinses taken from patients at baseline, 3, 6, 12 months during HAART, respectively, were cultured, and Candida species were identified following standard microbiological techniques. In vitro antifungal susceptibilities were tested by the broth microdilution method. RESULTS: The oral Candida load decreased gradually in the 45 patients with HIV/AIDS during the first year of HAART (P < 0.050). Among 176 Candida isolates, Candida albicans (114/176) was the predominant species, and Candida parapsilosis (23/62) was the most common non-albicans species. We found the frequency of resistance to fluconazole and itraconazole of Candida isolated from our samples increased (P < 0.05) after 12 months of HAART. In addition, the frequency of C. albicans isolates resistant to fluconazole and itraconazole was on the rise (P < 0.05). CONCLUSIONS: The Candida load decreased with increased CD4(+) T cell counts, and C. albicans was still the prevailing species. Further, a trend toward more frequent in vitro resistance to fluconazole and itraconazole was observed. Our results provide reference for treatment and prevention of oral candidiasis among this population.

Antibacterial activity of corydalis saxicola bunting total alkaloids against Porphyromonas gingivalis in vitro.

Aim: To investigate the antibacterial effects of Corydalis Saxicola bunting total alkaloid (CSBTA) on Porphyromonas gingivalis. Methods: SEM, chemical staining, RT-qPCR and ELISA were used to detect effects of CSBTA on P. gingivalis. Results: CSBTA treatment caused shrinkage and rupture of P. gingivalis morphology, decreased biofilm density and live bacteria in biofilm, as well as reduced mRNA expression of virulence genes hagA, hagB, kgp, rgpA and rgpB of P. gingivalis. Furthermore, NOK cells induced by CSBTA-treated P. gingivalis exhibited lower IL-6 and TNF-α expression levels. Conclusion: CSBTA is able to kill free P. gingivalis, disrupt the biofilm and weaken the pathogenicity of P. gingivalis. It has the potential to be developed as a drug against P. gingivalis infection.

[Box: see text].

Dynamic changes of Th1/Th2/Th17 cytokines and hBD-2/3 in erosive oral lichen planus patients saliva before and after prednisone acetate treatment.

Objective: This study aimed to investigate the expression of T helper 1 (Th1)/Th2/Th17- related cytokines and human beta defensins 2 and 3 (hBD-2 and -3) in the saliva of patients with erosive oral lichen planus (EOLP) and to explore their role in the pathogenesis of EOLP and the effects of glucocorticoids on EOLP. Methods: A total of 30 patients with EOLP and 20 age- and sex-matched healthy individuals were included in this study. The patients were treated with prednisone at a dose of 0.4 mg/(kg·d) for 1 week and examined before and after treatment. Unstimulated whole saliva samples were collected to determine the levels of cytokines (interleukin 1 beta [IL-1ß], tumour necrosis factor alpha [TNF]-α, interferon gamma [IFN-γ], IL-4, IL-6, IL-10 and IL-17) by cytometric bead array and those of hBD-2 and -3 b y enzyme-linked immunosorbent assay. In addition, oral rinse samples were collected to detect Candida load. Results: The levels of salivary IL-1ß, IL-6, hBD-2 and hBD-3 were higher and the IFN-γ/IL-4 and IL-1ß/IL-6 ratios were lower in patients with EOLP than in healthy individuals. In patients with EOLP, hBD-2 levels were positively correlated with IFN-γ levels and negatively correlated with IL-17 levels, whereas hBD-3 levels were negatively correlated with IL-17 and IL-10 levels. In addition, the prevalence of EOLP was positively correlated with IL-6 levels and negatively correlated with the IFN-γ/IL-4 ratio. The levels of IL-1ß, TNF-α, IFN-γ, IL-6, hBD-2 and hBD-3 and the IFN-γ/IL-4 ratio decreased after treatment with prednisone for 1 week. The levels of IL-6, hBD-2 and hBD-3 were significantly higher in EOLP patients than in healthy individuals; while TNF-α levels and the IFN-γ/IL-4 ratio were significantly lower in EOLP patients than in healthy individuals. Furthermore, the oral counts of Candida spp. (colony forming unit [CFU]) were negatively correlated with TNF-α levels. Numerical Rating Scale(NRS) and Sign scores decreased in EOLP patients after treatment. Approximately 80 % of patients were effectively treated. Salivary TNF-α levels were significantly higher in the treatment-ineffective group than in the treatment-effective group before treatment with prednisone, and differences in salivary IL-6 levels before and after treatment were significantly higher in the treatment-effective group than in the treatment-ineffective group. Conclusions: High expression of IL-1ß, IL-6, hBD-2 and Th1/Th2 imbalance in saliva may be associated with the pathogenesis of EOLP. IFN-γ/IL-4 balance may serve as a protective factor for EOLP. Glucocorticoids significantly alleviate the symptoms of EOLP and inhibit the expression of Th1/Th2 cytokines.

Corydalis saxicolaBunting total alkaloid eliminates Porphyromonas gingivalis strain 33277 internalized into macrophages by inhibition of TLR2.

OBJECTIVE: This study aimed to investigate the impact of Corydalis Saxicola Bunting Total Alkaloid (CSBTA) on Porphyromonas gingivalis internalization within macrophages and explore the potential role of Toll-Like Receptor 2 (TLR2) in this process. METHODS: We established a P. gingivalis internalization model in macrophages by treating P. gingivalis-infected macrophages (MOI=100:1) with 200 µg/mL metronidazole and 300 µg/mL gentamicin for 1 h. Subsequently, the model was exposed to CSBTA at concentrations of 0.02 g/L or 1 µg/mL Pam3CSK4. After a 6 h treatment, cell lysis was performed with sterile water to quantify bacterial colonies. The mRNA expressions of TLR2 and interleukin-8 (IL-8) in macrophages were analyzed using RT-qPCR, while their protein levels were assessed via Western blot and ELISA respectively. RESULTS: P. gingivalis could internalize into macrophages and enhance the expression of TLR2 and IL-8. Activation of TLR2 by Pam3CSK4 contributed to P. gingivalis survival within macrophages and increased TLR2 and IL-8 expression. Conversely, 0.02 g/L CSBTA effectively cleared intracellular P. gingivalis, achieving a 90 % clearance rate after 6 h. Moreover, it downregulated the expression of TLR2 and IL-8 induced by P. gingivalis. However, the inhibitory effect of CSBTA on the internalized P. gingivalis model was attenuated by Pam3CSK4. CONCLUSION: CSBTA exhibited the ability to reduce the presence of live intracellular P. gingivalis and lower IL-8 expression in macrophages, possibly by modulating TLR2 activity.

Differential expression of miRNA-769-5p and Smad2 in patients with or without oral cGVHD.

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.

[Relationship between pre-exposure prophylaxis and HIV infection: a meta-analysis].

OBJECTIVE: To evaluate the effect on pre-exposure prophylaxis (PrEP) to prevent HIV infection in high risk populations. METHODS: A computerized literature searching had been carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wanfang, Tsinghua Tongfang database and related websites to collect relevant papers (from establishment to June 2012) with the key words of pre-exposure prophylaxis, HIV, AIDS, high risk populations, relative risk, reduction. All randomized controlled trials (RCT) papers about using single or compound antiretroviral drugs (ARVs) orally or topically before HIV exposure or during HIV exposure in high risk populations were enrolled. Meta-analysis was conducted using Stata 10.0 to calculate the pooled RR value (95%CI). Consistency test was performed and publication bias was evaluated. RESULTS: Finally 5 RCT papers were enrolled, including 10 271 persons who were at high risk of HIV infection. The number of the experimental group was 5929, among which 116(1.96%) became infected. The number of the control group was 4342, among which 201(4.63%) became infected. Meta-analysis showed that the pooled relative risk (RR) and 95%CI was 0.49 (0.39 - 0.61), P < 0.05, indicating that the persons in experimental group had a 0.49 times lower risk of HIV infected, as compared with the control group. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 825. CONCLUSION: PrEP was an effective and safe protection measure to reduce HIV infection in high risk populations.

Analysis of subgingival micro-organisms based on multi-omics and Treg/Th17 balance in type 2 diabetes with/without periodontitis.

Type 2 diabetes mellitus (T2DM) and periodontitis are common and interrelated diseases, resulting in altered host response microbiota. The subgingival micro-organisms play a key role in periodontitis pathogenesis. To assess the shift of subgingival microbiome and metabolome in T2DM, we performed an analysis of the subgingival microbiome in patients with T2DM (n = 20) compared with non-diabetes (ND) subjects (n = 21). Furthermore, patients were subdivided into 10 T2DM with periodontitis (DP), 10 T2DM without periodontitis (DNP), 10 periodontitis (P), and 11 healthy control (H) groups. 16SrRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in all participants. T lymphocyte immunity was analyzed by flow cytometry. Furthermore, the network relationship among subgingival micro-organisms, metabolites, blood glucose level, and T lymphocyte immunity were analyzed. The results showed that the difference of the subgingival microbiome from healthy to periodontitis status was less prominent in T2DM compared with ND, though the clinical signs of disease were similar. The bacteria Eubacterium nodatum group, Filifactor, Fretibacterium, Peptostreptococcus, and Desulfovibrio, amongst others, may be important in the pathopoiesia of periodontitis in the T2DM state. In addition, some dominant bacteria showed network relationships. The Treg/Th17 ratio was lower in the DP and DNP groups than in the P and H groups-though that of P was lower than for H. The percentage of CD4+/CD8+ PD1 and CD8+ PDL1 was higher in the DP and DNP groups than in the H group; the percentage of CD8+ PDL1 was higher in the DP than P groups. Subgingival micro-organisms in periodontitis had a significant metabolic shift in terms of their signature metabolites. Butyrate metabolism and phenylalanine metabolism may play a role in the pathogenesis of periodontitis with/without T2DM. Specifically, biphenyl degradation, tryptophan metabolism, and the two-component system may play important roles in periodontitis with T2DM. Lastly, the network relationship among subgingival micro-organisms, metabolites, blood glucose level, and T lymphocyte immunity were unbalanced. This study identified the changes in the subgingival microbiome associated with periodontitis in T2DM, as well as the associated network between bacterial flora, metabolism dysbiosis, and immune regulation.

PD-L1-Mediated Immunosuppression in Oral Squamous Cell Carcinoma: Relationship With Macrophage Infiltration and Epithelial to Mesenchymal Transition Markers.

To date, immune check-point inhibitors (ICIs), particularly inhibitors of programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) have become prominent in cancer treatment and also improved life expectancy of cancer patients. As key regulators of PD-1/PD-L1 axis, the recruitment of tumor-associated macrophages (TAMs) enhances aggressive and invasive properties of tumors in immunosuppressive tumor microenvironment (TME) and promotes epithelial-mesenchymal transition (EMT). The aims of the study were first to characterize the critical links among PD-L1, TME and EMT process and, further, to explore the sensitivity of different chemical agents to different PD-L1 expression groups. Bioinformatical analysis revealed that PD-L1 was highly expressed in OSCC and higher PD-L1 expression correlated with worse survival in patients. Notably, PD-L1 was positively correlated with macrophages infiltration and EMT markers gene expression. Moreover, patients in the PD-L1high group were at a significant chance of benefiting from ICI treatment and they also showed higher sensitivity to the chemical drugs (olaparib, paclitaxel, docetaxel, and pazopanib). These findings implicate PD-L1 could serve as a novel target for prognostic and therapeutic approaches in OSCC patients; PD-L1-mediated immune evasion might be attributable to the infiltration of macrophages, resulting EMT progress; Chemical agents in combination with PD-L1 inhibitor could be served as personalized treatment plan for OSCC patients so as to maximize patient benefit.

P16-positive secondary tongue squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: A case report and literature review.

As a method to improve the survival rate of patients with hematological malignancies, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increasingly been used for treatment. However, some potentially serious complications after allo-HSCT, including graft-versus-host disease, graft failure, infection, end-organ toxicity, and secondary malignancies, will determine the success of hematopoietic reconstitution. Here, we describe a case of a patient with p16-positive tongue squamous cell carcinoma (TSCC) following allo-HSCT. A 62-year-old man who had previously received allo-HSCT due to acute lymphocytic leukemia (AML) presented with erosions on the back of the tongue surrounded by multiple white patches, which were compatible with oral chronic graft-versus-host disease (cGVHD). During follow-up, a circular-like erosive lesion appeared on the right dorsal surface of the tongue. Biopsy of this lesion confirmed early invasive TSCC (T2N0M0). Partial glossectomy and tongue reconstruction were performed after cessation of immunosuppressants. Immunohistochemical (IHC) staining was positive for p16 and ki-67, suggesting a probable active human papillomavirus (HPV) infection. Six months after surgery, the patient showed no signs of metastasis or recurrence nor progression of oral GVHD.