Effects of toothpaste containing inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and dental plaque microbiota.

Plaque-induced gingivitis is an inflammatory response in gingival tissues resulting from bacterial plaque accumulation at the gingival margin. Postbiotics can promote the proliferation of beneficial bacteria and optimise the state of microbiota in the oral cavity. In this study, we investigated the effect of inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and the dental plaque microbiota. A total of 32 healthy gingival participants (Group N, using blank toothpaste for 3 months) and 60 patients with plaque-induced gingivitis (30 in Group F, using inactivated Probio-01 toothpaste for 3 months, and 30 in Group B, using blank toothpaste for 3 months, respectively) were recruited. Clinical indices, which included bleeding on probing (BOP), gingival index (GI), and plaque index (PI), were used to assess the severity of gingivitis. Furthermore, 16SrDNA amplicon sequencing was used to explore changes in the gingival state and dental plaque microbiota in patients with plaque-induced gingivitis. The results showed that inactivated Probio-01 significantly reduced clinical indices of gingivitis, including BOP, GI, and PI, in participants with plaque-induced gingivitis and effectively relieved gingival inflammation, compared with that observed in the control group (group B). Inactivated Probio-01 did not significantly influence the diversity of dental plaque microbiota, but increased the relative abundance of dental plaque core bacteria, such as Leptotrichia and Fusobacterium (P < 0.05). Strong correlations were observed between the indices and abundance of dental plaque microbiota. Overall, the inactivated Probio-01 significantly reduced the clinical indices of gingivitis and effectively improved gingival inflammation in patients with plaque-induced gingivitis. The activity of inactivated Probio-01 against plaque-induced gingivitis was possibly mediated by its ability to regulate the dental plaque microbiota, as indicated by the close correlation between the plaque microbiota and clinical indices of gingivitis.

Brønsted Acid-Catalyzed Intramolecular Tandem Double Cyclization of γ-Hydroxy Acetylenic Ketones with Alkynes into Naphtho[1,2-b]furan-3-ones.

A metal-free and atom-economic route for the synthesis of naphtho[1,2-b]furan-3-ones has been realized via p-TsOH·H2O-catalyzed intramolecular tandem double cyclization of γ-hydroxy acetylenic ketones with alkynes in formic acid. The benzene-linked furanonyl-ynes are the key intermediates obtained by the scission/recombination of C-O double bonds. Further, the structural modifications of the representative product were implemented by reduction, demethylation, substitution, and [5 + 2]-cycloaddition.

Dual Proton/Silver-Catalyzed Serial (5 + 2)-Cycloaddition and Nazarov Cyclization of (E)-2-Arylidene-3-hydroxyindanones with Conjugated Eneynes: Synthesis of Indanone-Fused Benzo[cd]azulenes.

A one-pot step-economic tandem process involving (5 + 2)-cycloaddition and Nazarov cyclization reactions has been reported for the facile synthesis of indanone-fused benzo[cd]azulenes from (E)-2-arylidene-3-hydroxyindanones and conjugated eneynes. This highly regio- and stereoselective bisannulation reaction is enabled by dual silver and Brønsted acid catalysis and opens up a new avenue for the construction of important bicyclo[5.3.0]decane skeletons.

Prognostic prediction of subjective cognitive decline in major depressive disorder based on immune biomarkers: a prospective observational study.

OBJECTIVE: Subjective cognitive decline (SCD) is highlighted in patients with major depressive disorder (MDD), which impairs objective cognitive performance and worsens the clinical outcomes. Immune dysregulation is supposed to be the potential mechanism of cognitive impairment. However, the peripheral immune biomarkers in patients troubled with MDD and SCD are not conventionally described. METHODS: A prospective-observational study was conducted for 8 weeks. Subjective cognitive function was measured using the Chinese version of the 20-item perceived deficits questionnaire-depression (PDQ-D) and depression symptoms were evaluated with Hamilton Depression Rating Scale-17 (HDRS-17). Luminex assays were used to measure 48 immune cytokines in plasma at baseline. Integrating these results and clinicopathological features, a logistic regression model was used to develop a prognostic prediction. RESULTS: Totally, 114 patients were enrolled in this study. Among the patients who completed follow-up, 56% (N = 50) had residual subjective cognitive decline, and 44% (N = 50) did not. The plasma levels of FGF basic, INF-γ, IL-1ß, MCP-1, M-CSF and SCF were increased and the levels of IL-9, RANTES and PDGF-BB were decreased in the SCD group. Additionally, Basic FGF, IFN-γ, IL-1ß, and SCF were positively correlated and IL-9, RANTES, and PDGF-BB were negatively correlated with the PDQ-D scores after treatment. Notably, combinations of cytokines (SCF and PDGF-BB) and PDQ-D scores at baseline showed good performance (The area under the receiver operating characteristic curve = 0.818) in the prediction of subjective cognitive decline. CONCLUSION: A prognostic model based on protein concentrations of SCF, PDGF-BB, and scores of PDQ-D showed considerable accuracy in predicting residual subjective cognitive decline in depression.

Metal-Free Intramolecular [3+2] Cycloaddition of γ-Hydroxy Acetylenic Ketones with Alkynes for the Synthesis of Naphtho[1,2-c]furan-5-ones and Its Derivatization via a Selective C(sp2)-H Deuteration Reaction.

A metal-free intramolecular [3+2] cycloaddtion has been achieved by treating benzene-linked propynol-ynes with AcOH/H2O in a one-pot manner. The reaction provides greener, 100% atom-economic, highly regioselective, and more practical access to functionalized naphtho[1,2-c]furan-5-ones with valuable and versatile applications. The regioselective α-deuteration of naphtho[1,2-c]furan-5-ones has been also presented with excellent deuterium incorporation and chemical yields. Moreover, the fluorescent properties of naphtho[1,2-c]furan-5-one products have been investigated in solution.

Dental visit experience and dental care barriers among Hong Kong preschool children with special education needs.

BACKGROUND: Children with special education needs (SEN) require additional supports in education settings, as well as extra supports in healthcare services. AIM: To investigate dental visit experience and dental care barriers among Hong Kong preschoolers with SEN. DESIGN: This was designed as a cross-sectional study. A structured questionnaire was employed to investigate dental attendance and dental care barriers among Hong Kong preschoolers with SEN. Binary logistic regression and multi-factor ANOVA were performed to identify factors associated with children's dental visit experience. RESULTS: A total of 383 children were included in the final analysis. The average age of the recruited children was 3.87 ± 0.95 years. 72.5% parents reported that dental visits were a challenging task for their children. Among children with caries, 70.7% had never visited a dentist. Regression models indicated that (a) children over 3 years or children whose parents received tertiary education were more likely to visit a dentist; (b) the existence of dental care barriers was associated with children's primary diagnosis, practical skills, conceptual skills, and parents' education attainment; and (c) children with low conceptual skills (95%CI:0.71 to 2.40, P < .001), or children from low-income families (95%CI:1.21 to -0.06, P = .031) had more dental care barriers than their counterparts. CONCLUSION: Unmet dental treatment needs and dental care barriers existed among pre-schoolers with SEN. Dental care barriers were associated with children's developmental profile, parents' education attainment, and household income.

Toothbrush deterioration and parents' suggestions to improve the design of toothbrushes used by children with special care needs.

BACKGROUND: Biting objects was a parafunctional oral habit among children with special care needs. Chewing or biting toothbrushes could expedite the process of toothbrush wear. However, few studies evaluated the deterioration levels of toothbrushes used by children with special needs. This study aimed to assess the deterioration level of toothbrushes used by children with special care needs, and collect parents' feedbacks to improve the design of children's toothbrushes. METHODS: The cross-sectional study recruited 277 children who had special care needs. Children's toothbrushing behaviors, background information, and parents' comments on toothbrushes were obtained. Toothbrush deterioration was assessed by bristle wear and bite mark scores. Higher scores indicated severe deterioration. RESULTS: Three hundred twenty-one toothbrushes were collected. Children who used 2 to 6 toothbrushes in a 3-month period showed higher toothbrush deterioration scores than children who used a single toothbrush. Over 40% children's toothbrushes presented excessive wear. Excessive wear was associated with social skills and parents' education background. Distinct bite marks tended to exist on toothbrushes which had been used by children who showed challenging behaviors during toothbrushing (OR = 1.96, 95%CI1.15-3.32, p < 0.05). Approximately 27% parents reported that children's toothbrushes should be modified. Parents recommended that the size of toothbrush heads, the angle of handles, and the texture/length/distribution/diameter of bristles should be adjusted. Besides, ideal toothbrushes should be able to provide verbal or visual instructions to children, motivate children to brush teeth, simplify toothbrushing procedure, and protect children who had toothbrush-biting habits. CONCLUSIONS: Excessive wear and distinct bite marks can be found on toothbrushes that had been used by children with special care needs. Toothbrush deterioration was associated with children's social skills, toothbrushing behaviors, and parents' educational attainment. The commercially available toothbrushes should be modified to meet the additional needs of young children.

Insufficient PINX1 expression stimulates telomerase activation by direct inhibition of EBV LMP1-NF-κB axis during nasopharyngeal carcinoma development.

OBJECTIVE: Early malignant transformation of nasopharyngeal carcinoma(NPC) is associated with Epstein-Barr virus(EBV) infection and telomerase activation. The EBV latent membrane protein 1(LMP1) regulates expression of various genes by triggering NF-κB signaling pathway. PINX1 is a well-identified tumor suppressor gene by inhibiting telomerase activity and cancer cell growth. However, whether and how EBV inhibit PINX1 expression and activate telomerase in NPC is still incompletely elucidated. METHODS: Immunohistochemistry, real-time PCR and Western blotting were utilized to explore the expression of PINX1. Chromatin immunoprecipitation(ChIP) and Dual-luciferase reporter assay were used to elucidate the regulatory mechanism between NF-κB and PINX1. TRAP-SYBR Green assay and Southern blotting were utilized to detect telomerase activity and telomere length. CCK8 and EdU tests were conducted to measure proliferation ability. RESULTS: We demonstrated that PINX1 is down-regulated in NPC for the first time. Mechanistically, we found that LMP1 could inhibit the transcriptional activity of PINX1 by promoting the binding of p65 to three specific sites in PINX1 promoter, significantly, two(-1698/-1689, tgcaatttcc; -206/-197, cgggctttac) of which have not been reported. In addition, we also observed that LMP1 overexpression resulted in increased telomerase activity, prolonged telomere length and enhanced proliferation. CONCLUSION: We first discovered EBV led to reduced PINX1 expression through LMP1-NF-κB-PINX1 axis, which up-regulated telomerase activity in NPC. And hence, the tumor cells acquired the ability to proliferate more exuberantly. This signaling pathway illustrates the relationship between EBV latent infection and telomerase activation, and further provides new thinking for early diagnosis and treatment in NPC.

Brønsted-Acid-Catalyzed Synthesis of 3-Alkoxy and 3-Sulfamido Indanones via a Tandem Cyclization.

Brønsted-acid-catalyzed allylic substitution reactions of the in situ generated 3-hydroxy indanones with alcohols and sulfamides were investigated, which provided a facile route for the synthesis of a large variety of 3-alkoxy and 3-sulfamido indanones. The key intermediates, 3-hydroxy indanones, were obtained through the intramolecular Meyer-Schuster rearrangement of o-propargyl alcohol benzaldehydes. The resulting 3-benzyloxy indanone could be selectively modified by allylic sulfonamidation and reduction reactions.

Oral health and associated factors among preschool children with special healthcare needs.

OBJECTIVE: To investigate the oral health status and associated factors among preschool children with special healthcare needs. SUBJECTS AND METHODS: This was designed as a cross-sectional study. Dental examination was provided to 383 children at Special Child Care Centres. Covariates of interest included children's age, developmental profile, oral health-related behaviours and family social-economic status. The association between children's dental caries experiences, dental plaque deposition and gingival health status were analysed by negative binomial regression, multiple factor ANOVA and binary logistic regression when appropriate. RESULTS: The proportion of children with caries, gingival inflammation and plaque were 30.3%, 89.6% and 95.0%, respectively. Final regression models indicated that (a) tooth decay was associated with dental visit experiences, night bottle-feeding habit, fluoridated toothpaste and monthly income; (b) plaque deposition was associated with intellectual functioning, practical skills, night bottle-feeding habit, use of toothpaste, initiation of toothbrushing habit, toothbrushing duration and additional cleaning habit; (c) gingival status was associated with children's intellectual functioning and toothbrushing frequency. CONCLUSIONS: Poor oral hygiene status existed among preschool children with special healthcare needs. Children's oral health status was associated with their developmental profile, oral health-related behaviours and social-economic status.

The Impact of Adaptive Functioning and Oral Hygiene Practices on Observed Tooth-Brushing Performance Among Preschool Children with Special Health Care Needs.

OBJECTIVES: To investigate the impact of adaptive functioning and oral hygiene practices on tooth-brushing performance among preschool children with special health care needs (SHCN). METHODS: A cross-sectional study was conducted in Special Child Care Centers. Children's tooth-brushing performance was assessed by a standardized 13-step pro forma. Information regarding children's socio-economic status, adaptive skills, and oral hygiene practices were collected. Bivariate analysis and ANCOVA were used to explore the potential factors which might be associated with children's tooth-brushing performance. RESULTS: The tooth-brushing assessment was provided to 379 children with SHCN. Approximately 3% of the recruited children performed the whole tooth-brushing procedure independently. The number of tooth-brushing steps practiced by those children was 4.47 ± 3.56. Children who had established tooth-brushing habit before age one practiced more tooth-brushing steps than children who brushed their teeth after age one (p = 0.029). When children's age, gender, and socio-economic status were adjusted, children who had established regular tooth-brushing habit or children who had high levels of adaptive skills showed better tooth-brushing performance than their peers. Children who used gauze, cotton swab, or dental floss to clean their teeth practiced fewer key tooth-brushing steps than their peers who had never used additional cleaning approaches (p = 0.038). CONCLUSIONS FOR PRACTICE: Children's tooth-brushing performance was associated with adaptive skills and oral hygiene practices. Tooth-brushing training should be provided to children with SHCN in early childhood. For children who had limitations in adaptive functioning, parental assistance or supervision is recommended to guarantee the efficacy and safety of daily tooth brushing.

A systematic review and meta-analysis of dental plaque control among children and adolescents with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (ID) typically have poorer oral health. Oral diseases have a microbiological origin, and thus, dental plaque control (DPC) is key to safeguard their oral health. METHODS: A structured search strategy was applied to screen oral health promotion initiatives for DPC among children and adolescents with ID following PRISMA statements. Qualitative and quantitative analyses were performed. RESULTS: From 1,455 citations, 22 studies informed this review. Seven studies related to mechanical interventions and 13 to chemical interventions. Qualitative analyses found conventional toothbrushes were less effective than modified toothbrushes but quantitative analyses were conflicting. Of the nine studies that compared chlorhexidine to placebos, seven reported chlorhexidine was more effective than placebos. Meta-analysis favoured chlorhexidine to placebos (p < 0.0001, 95% CI 0.34-0.63). CONCLUSIONS: Both mechanical and chemical interventions are effective for DPC. It is unclear whether they are alternative means for DPC or whether they are best employed together.

Effectiveness of a visual-verbal integration model in training parents and their preschool children with intellectual and developmental disabilities to dispense a pea-sized amount of fluoridated toothpaste.

BACKGROUND: A visual-verbal integration model (VVIM) was used to train parents and their children with intellectual and developmental disabilities (IDD) to dispense a pea-sized amount of fluoridated toothpaste, aiming to balance the occurrence of dental caries and fluorosis. METHOD: Participants were 370 pairs of IDD preschool children and their parents. A two-phase pre-post-intervention study was performed. The weight of toothpaste was calculated by a portable electronic compact balance. RESULTS: A quarter of parents and <20% children dispensed the appropriate amount at baseline. Almost 85% parents and 50% children achieved the pea-sized amount after intervention. Half of the children continued to use the recommended toothpaste amount after 6 months. Children with higher intellectual functioning and conceptual skills were more likely to dispense the pea-sized amount of toothpaste. CONCLUSIONS: Visual-verbal integration model training had a desired impact on parents' toothpaste-dispensing performance. Children with higher adaptive skills may benefit from VVIM training.

Oral health status of children and adolescents with intellectual disabilities: a systematic review and meta-analysis.

AIM: To compare the oral health status of children and adolescents affected by intellectual disabilities with their unaffected counterparts. METHOD: Citations published in English were searched from electronic databases (PubMed, Embase, Web of Science, and Scopus) from their start dates to March 2017. The whole process was conducted following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The PICO (population, intervention/interest, comparator, outcome) principle was used to formulate the topic. Studies were synthesized through qualitative summary or, whenever possible, meta-analysis. RESULTS: The initial search yielded 2393 records. Thirty-nine studies from 22 countries were identified for qualitative analysis; 26 studies were eligible for meta-analysis. Participants with intellectual disabilities had higher levels of dental plaque, worse gingival status, fewer decayed and filled permanent teeth, and similar caries experience between males and females. These findings were supported by both qualitative and quantitative analysis. Various patterns of caries experiences were indicated by qualitative analysis, but it was not substantiated by meta-analysis. INTERPRETATION: There is increasing worldwide interest in oral health status of children with intellectual disabilities. Differences in dental plaque deposition, gingival inflammation, and the number of decayed and filled permanent teeth were investigated between children and adolescents with and without intellectual disabilities. Evidence remains elusive about the pattern of caries experience among those children.

Recent developments in the group-1B-metal-catalyzed synthesis of pyrroles.

Pyrroles are important synthetic targets as a result of their occurrence in numerous biologically active molecules, their important roles in diverse living processes, and their utility as versatile intermediates. As a consequence, numerous efforts focused on the development of concise and efficient methods for the construction of pyrroles. Compared with other transition metals, the group 1B metals (Cu, Ag and Au) are probably more versatile and widely used for the synthesis of pyrroles in organic chemistry. Considering the importance of both topics in organic synthesis, here we summarize recent achievements in the synthesis of pyrroles catalyzed by monometallic systems which belong to the group 1B metals (Cu, Ag and Au).

Unmethylated-maspin DNA in maternal plasma is associated with severe preeclampsia.

INTRODUCTION: Cell-free fetal DNA in maternal plasma is associated with complications of pregnancy, including preeclampsia. Determination of levels is affected by fetal gender and genetic polymorphisms. Unmethylated maspin (u-maspin) is present in the placenta, and is placental-specific. The purpose of this study was to determine whether u-maspin DNA in maternal blood could serve as a marker of preeclampsia by measuring levels in different trimesters of normal pregnancies and in those complicated by preeclampsia. MATERIAL AND METHODS: This case-control study was set in a tertiary care hospital. The population consisted of 45 women with normal pregnancies (15 in the 1st trimester, 15 in the 2nd trimester, 15 in the 3rd trimester), 20 women with mild preeclampsia, 25 women with severe preeclampsia, and six women with gestational trophoblastic disease. Peripheral blood was collected and methylation-specific PCR and fluorescence quantitative PCR were performed to measure the content of u-maspin DNA in maternal blood. RESULTS: U-maspin DNA was 5.5-fold higher in women with severe preeclampsia than in those with a normal 3rd trimester pregnancy (p < 0.05). During normal pregnancy, u-maspin DNA in maternal plasma tended to increase with advancing gestational age (p = 0.06). U-maspin DNA was not detected in healthy non-pregnant women or those with gestational trophoblastic disease. CONCLUSION: U-maspin DNA in maternal blood is associated with severe preeclampsia.

Noncoding RNA-associated competing endogenous RNA networks in trastuzumab-induced cardiotoxicity.

Trastuzumab-induced cardiotoxicity (TIC) is a common and serious disease with abnormal cardiac function. Accumulating evidence has indicated certain non-coding RNAs (ncRNAs), functioning as competing endogenous RNAs (ceRNAs), impacting the progression of cardiovascular diseases. Nonetheless, the specific involvement of ncRNA-mediated ceRNA regulatory mechanisms in TIC remains elusive. The present research aims to comprehensively investigate changes in the expressions of all ncRNA using whole-transcriptome RNA sequencing. The sequencing analysis unveiled significant dysregulation, identifying a total of 43 circular RNAs (circRNAs), 270 long noncoding RNAs (lncRNAs), 12 microRNAs (miRNAs), and 4131 mRNAs in trastuzumab-treated mouse hearts. Subsequently, circRNA-based ceRNA networks consisting of 82 nodes and 91 edges, as well as lncRNA-based ceRNA networks comprising 111 nodes and 112 edges, were constructed. Using the CytoNCA plugin, pivotal genes-miR-31-5p and miR-644-5p-were identified within these networks, exhibiting potential relevance in TIC treatment. Additionally, KEGG and GO analyses were conducted to explore the functional pathways associated with the genes within the ceRNA networks. The outcomes of the predicted ceRNAs and bioinformatics analyses elucidated the plausible involvement of ncRNAs in TIC pathogenesis. This insight contributes to a better understanding of underlying mechanisms and aids in identifying promising targets for effective prevention and treatment strategies.

Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

Recent progress in the role of endogenous metal ions in doxorubicin-induced cardiotoxicity.

Doxorubicin is a widely used anticancer drug in clinical practice for the treatment of various human tumors. However, its administration is associated with cardiotoxicity. Administration of doxorubicin with low side effects for cancer treatment and prevention are, accordingly, urgently required. The human body harbors various endogenous metal ions that exert substantial influences. Consequently, extensive research has been conducted over several decades to investigate the potential of targeting endogenous metal ions to mitigate doxorubicin's side effects and impede tumor progression. In recent years, there has been a growing body of research indicating the potential efficacy of metal ion-associated therapeutic strategies in inhibiting doxorubicin-induced cardiotoxicity (DIC). These strategies offer a combination of favorable safety profiles and potential clinical utility. Alterations in intracellular levels of metal ions have been found to either facilitate or mitigate the development of DIC. For instance, ferroptosis, a cellular death mechanism, and metal ions such as copper, zinc, and calcium have been identified as significant contributors to DIC. This understanding can contribute to advancements in cancer treatment and provide valuable insights for mitigating the cardiotoxic effects of other therapeutic drugs. Furthermore, potential therapeutic strategies have been investigated to alleviate DIC in clinical settings. The ultimate goal is to improve the efficacy and safety of Dox and offer valuable insights for future research in this field.

NPM1 promotes nasopharyngeal carcinoma metastasis and stemness by recruiting Mdm2 to induce the ubiquitination-mediated degradation of p53.

Nasopharyngeal carcinoma (NPC) is clinically challenging due to the development of distant metastasis following initial therapy. Therefore, it is necessary to elucidate the mechanisms underlying metastases to develop novel therapeutic strategies. Nucleophosmin 1 (NPM1) has been directly linked to the development of human tumors and may have both tumor-suppressing and oncogenic properties. Although NPM1 is often overexpressed in solid tumors of various histopathological origins, its specific function in mediating the development of NPC is still unknown. Here, we investigated the role of NPM1 in NPC and discovered that NPM1 was elevated in clinical NPC samples and served as a predictor of the worst prognosis in NPC patients. Furthermore, the upregulation of NPM1 promoted the migration and the cancer stemness of NPC both in vitro and in vivo. Mechanistic analyses revealed that the E3 ubiquitin ligase Mdm2 was recruited by NPM1 to induce the ubiquitination-mediated proteasomal degradation of p53. Ultimately, knockdown of NPM1 suppressed the stemness and EMT signals. In summation, this study demonstrated the role and the underlying molecular mechanism of NPM1 in NPC, providing the evidence for the clinical application of NPM1 as a therapeutic target for the treatment of patients with NPC.