[Impact of maternal X chromosome aneuploidies on cell free DNA prenatal screening].

Objective: To investigate the impact of maternal X chromosome aneuploidies on cell free DNA (cf-DNA) prenatal screening. Methods: After genetic counseling, invasive prenatal diagnosis was provided for the 124 cases with high risk of sex chromosome aneuploidie (SCA) indicated by cf-DNA prenatal screening. For cases with discordant results of fetal prenatal diagnosis and cf-DNA prenatal screening, maternal leukocyte was collected for copy number variation sequencing (CNV-seq) to detect whether the maternal X chromosome was carrying variations. Results: Totally, 124 cases with high risks of SCA indicated by cf-DNA prenatal screening, 9 cases refused to take invasive prenatal diagnosis, while the remaining 115 cases received. Among the 115 cases, 41 cases received accordant results with cf-DNA prenatal screening while 74 cases discordant. Among the 74 cases with discordant results, 19 cases were indicated with maternal X chromosome variations by maternal leukocyte CNV-seq, which accounting for 25.7% (19/74) of the SCA false positive cases, and 15.3% (19/124) of all SCA cases. Conclusions: Pregnant women with X chromosome variations may affect the results of cf-DNA prenatal screening, resulting in false positive or false negative outcomes, it should be emphasized that the cf-DNA results may be affected by maternal X chromosome variations. In cases with discordant results of prenatal diagnosis and cf-DNA prenatal screening, maternal leukocyte CNV-seq is recommended to find the reasons of false positive or negative results. And cf-DNA prenatal screening is not recommended for pregnant women who are already known with X chromosome variations.

Simvastatin alleviates bone resorption in apical periodontitis possibly by inhibition of mitophagy-related osteoblast apoptosis.

AIM: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. METHODOLOGY: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. RESULTS: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. CONCLUSIONS: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.

Sirtuin 6 attenuates periapical lesion propagation by modulating hypoxia-induced chemokine (C-C motif) ligand 2 production in osteoblasts.

AIM: To investigate the attenuating effect of sirtuin 6 (SIRT6) on hypoxia-induced production of chemokine (C-C motif) ligand 2 (CCL2) by osteoblasts and the relevance of this action on the pathogenesis of periapical lesions. METHODOLOGY: Sirtuin 6 was overexpressed in MC3T3-E1 murine osteoblasts by lentivirus-mediated gene transfer. The relationship between the antiglycolytic/antioxidative activities of SIRT6 and its effect on hypoxia-induced CCL2 production were examined. Pathogenetic relevance of the actions of SIRT6 was assessed in a rat model of induced apical periodontitis. The data were analysed statistically using Student's t-test or one-way analysis of variance (anova) and then a Tukey's multiple comparison test. RESULTS: In cultured murine osteoblasts, 24-h hypoxic treatment significantly enhanced the generation of reactive oxygen species (P = 0.003), expression of lactate dehydrogenase A (LDHA) and production of lactate (P = 0.007). A reciprocal effect between hypoxia-induced redox imbalance and hypoxia-enhanced glycolysis was noted which in turn augmented the secretion of CCL2. Through its antiglycolytic and antioxidative effects, SIRT6 blocked the vicious cycle to suppress CCL2 production. In normal periapical tissues of rats, strong expression of SIRT6 and low levels of LDHA and 8-OHdG (a marker of oxidative DNA damage) were found in osteoblasts. In induced apical periodontitis, osteoblastic expression of SIRT6 was significantly suppressed (P = 0.001) which was associated with significantly elevated levels of LDHA (P = 0.003) and 8-OHdG (P = 0.004) and significantly enhanced recruitment of macrophages (P = 0.004). CONCLUSIONS: Sirtuin 6 has a therapeutic effect on periapical lesions through suppression of CCL2 synthesis. The anti-inflammatory action of SIRT6 is closely related to its regulatory activities in cellular metabolism and redox homoeostasis.

Effectiveness of mouth rinses against COVID-19: a systematic review and network meta-analysis.

OBJECTIVE: This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Part I), alleviating clinical symptoms or severity of disease (Part II), and decreasing the incidence of SARS-CoV-2 infection (Part III). METHODS: Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) with restrictions were searched up to 3rd March 2023. Twenty-three studies (22 RCTs and one NRCT) met the inclusion criteria for this systematic review. RESULTS: Five RCTs (454 patients and nine interventions) in Part I were eligible for NMA. The NMA results showed that, in comparison with no rinse, sodium chloride (NaCl) was the most effective mouth rinse for reducing the viral load, followed by povidone-iodine (PVP-I), ß-cyclodextrin + citrox (CDCM), hydrogen peroxide (HP), chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), placebo and hypochlorous acid (HClO). However, these results were not significant. Based on surface under the cumulative ranking curve scores, PVP-I was likely to be the most efficacious mouth rinse for reducing SARS-CoV-2 viral load, followed by CDCM, HP, NaCl, CHX, CPC, placebo, no rinse and HClO. CONCLUSION: Due to heterogeneity of the primary studies, the effectiveness of different mouth rinses to reduce viral infectivity, improve clinical symptoms or prevent SARS-CoV-2 infection remains inconclusive.

An appliance to replace prematurely lost maxillary anterior teeth using double stainless steel crowns on abutment teeth.

This paper describes an appliance to replace prematurely lost maxillary anterior teeth. The prosthesis is different from previous appliance designs, since it uses double stainless steel crowns on abutment teeth, and uses a donor cast to fabricate artificial teeth. A case is presented describing laboratory and office procedures.

Curcumin inhibits TGFß1-induced CCN2 via Src, JNK, and Smad3 in gingiva.

Transforming growth factor ß (TGFß) is a key regulator associated with the pathogenesis of gingival overgrowth (GO). Connective tissue growth factor (CTGF/CCN2) is overexpressed in GO tissues. CCN2 promotes and sustains fibrosis initiated by TGFß. Previous studies have shown that JNK and Smad3 activation is required for TGFß-induced CCN2 expressions in human gingival fibroblasts (HGFs). In this study, we have found that Src is a major signaling mediator for TGFß-induced CCN2 expressions in HGFs. Pre-treatment with 2 Src kinase inhibitors (PP2, Src inhibitor-1) significantly reduced TGFß1-induced CCN2 synthesis and JNK and Smad3 activation in HGFs. These results suggest that Src is an upstream signaling transducer of JNK and Smad3 with respect to TGFß1-stimulated CCN2 expression in HGFs. We further found that curcumin significantly abrogated the TGFß1-induced CCN2 in HGFs by inhibiting the phosphorylations of Src, JNK, and Smad3. Furthermore, curcumin inhibited TGFß1-induced HGF migration and α-SMA expression. Curcumin potentially qualifies as a useful agent for the control of GO.