An In Vitro Study to Evaluate the Antimicrobial Activity of a Zinc Citrate, Sodium Fluoride, Alum and Xylitol-Based Toothpaste Formulation.

INTRODUCTION: Periodontitis is a prevalent condition significantly affecting oral health. Comorbid conditions, such as diabetes, can heighten the severity of periodontal disease and overall oral health. Therefore, to enhance oral health and manage comorbid conditions, comprehensive periodontal care is essential. This approach could involve using toothpaste containing antimicrobial ingredients in routine oral care. This paper presents the results of an in vitro study analysing the antimicrobial properties of the test formulation containing zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste (Stolin-R). These ingredients work together to help in providing comprehensive oral care by controlling growth of bacteria majorly responsible for periodontal disease and thus maintaining optimal oral hygiene. AIM: To determine the antimicrobial properties of zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste formulation against key periodontal pathogens through in vitro analyses. MATERIALS AND METHODS: The antimicrobial efficacy of test formulation is evaluated through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-dependent antibacterial assessment against key periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Prevotella intermedia, Streptococcus mutans, and Bacteroides fragilis. RESULTS: The test formulation demonstrated potent antimicrobial effectiveness against Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Streptococcus mutans, and Tannerella forsythia, by exhibiting low MIC and MBC. Additionally, significant bacterial reduction, exceeding 99.99%, was observed within five minutes, emphasising its potential as an effective adjunct in combating periodontal infection. CONCLUSION: Zinc citrate, alum, sodium fluoride, and xylitol-based toothpaste formulation demonstrates significant antimicrobial activity against key periodontal pathogens, suggesting its potential as an effective agent for maintaining oral health and combating gingival infection.

Prospective Evaluation of Dental Practitioners' Knowledge, Attitude, and Practice Toward Adult Dental Pain Management: A Cross-Sectional Multicenter Study.

Background Dental pain among adults is a prevalent concern impacting oral health and quality of life. Dental pain management presents a significant challenge for dental practitioners in effectively alleviating patient discomfort. Among the medications available, non-steroidal anti-inflammatory drugs (NSAIDs) are considered the most effective analgesics in dental care. While numerous studies have been conducted to assess the role of antibiotics in dental practice, there is a scarcity of studies specifically examining the prescription patterns of analgesics. The primary aim of this study was to evaluate the knowledge, attitudes, and practices of dental practitioners (DPs) in India concerning the management of adult dental pain. Method This survey utilized a computer-aided questionnaire-based approach. A total of 110 dentists, including 16 from metropolitan areas and 84 from non-metropolitan cities practicing at dental healthcare setups, clinics, and hospitals, were interviewed as part of the survey. The participants comprised dental professionals specializing in prosthodontics, endodontics, orthodontics, periodontics, oral surgery, pedodontics, and oral medicine. The study was conducted between September 2022 and January 2023. Results The primary reason patients seek dental consultation, as reported by 95% of dentists, is tooth cavities, followed by tooth sensitivity, post-root canal treatment, and pulpitis. All surveyed dentists prescribed NSAIDs to their patients for managing dental pain. Local anesthesia (LA) was the second choice for 75% of dentists, prescribed to 23% of their patients. The primary use of NSAIDs was for patients experiencing severe pain and to manage post-procedure pain. Eighty percent of DPs recognized ketorolac as a fast-acting molecule, providing immediate relief within 10-15 minutes. Overall, analysis indicated that 98% of DPs are satisfied and 67% are extremely satisfied with ketorolac among monotherapies for dental pain management due to its quick onset of action, fast pain relief, and usefulness in post-surgical pain management. Conclusion NSAIDs like ketorolac, diclofenac, and aceclofenac were the preferred prescriptions for overall dental pain management. Dental practitioners associated ketorolac with fast pain relief, quick onset of action, and effectiveness in post-surgical pain management, emphasizing its lasting effects. The insights from the study contribute to enhancing dental pain management strategies.

Functional role of circular RNAs in cancer development and progression.

Circular RNAs (circRNAs) are a large class of endogenously expressed non-coding RNAs formed by covalently closed loops through back-splicing. High throughput sequencing technologies have identified thousands of circRNAs with high sequence conservation and cell type specific expression in eukaryotes. CircRNAs play multiple important roles in cellular physiology functioning as miRNA sponges, transcriptional regulators, RBP binding molecules, templates for protein translation, and immune regulators. In a clinical context, circRNAs expression is correlated with patient's clinicopathological features in cancers including breast, liver, gastric, colorectal, and lung cancer. Additionally, distinct properties of circRNAs, such as high stability, exonuclease resistance, and existence in body fluids, show promising role for circRNAs as molecular biomarkers for tumor diagnosis, non-invasive monitoring, prognosis, and therapeutic intervention. Therefore, it is critical to further understand the molecular mechanism underlying circRNAs interaction in tumors and the recent progress of this RNA species in cancer development. In this review, we provide a detailed description of biological functions, molecular role of circRNAs in different cancers, and its potential role as biomarkers in a clinical context.

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone.

Crosstalk between growth factors (GFs) and steroid hormones recurs in embryogenesis and is co-opted in pathology, but underlying mechanisms remain elusive. Our data from mammary cells imply that the crosstalk between the epidermal GF and glucocorticoids (GCs) involves transcription factors like p53 and NF-κB, along with reduced pausing and traveling of RNA polymerase II (RNAPII) at both promoters and bodies of GF-inducible genes. Essentially, GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal inhibitory loops. As expected, no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, but forced demethylation of regulatory regions broadened the repertoire of GF-inducible genes. We report that enhancers, like some promoters, are poised for activation by GFs and GCs. In addition, within the cooperative interface of the crosstalk, GFs enhance binding of the GC receptor to DNA and, in synergy with GCs, promote productive RNAPII elongation. Reciprocally, within the antagonistic interface GFs hyper-acetylate chromatin at unmethylated promoters and enhancers of genes involved in motility, but GCs hypoacetylate the corresponding regions. In conclusion, unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie the crosstalk between GFs and a steroid hormone.

MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer.

Nuclear Factor kappa B (NF-κB) signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative (ER-) breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. We focused on mechanisms of NF-κB regulation by microRNAs (miRNAs), which regulate eukaryotic gene expression at the post-transcriptional level. In a previous genome-wide miRNA screen, we had identified miR-30c-2-3p as one of the strongest negative regulators of NF-κB signaling. Here we have uncovered the underlying molecular mechanisms and its consequences in breast cancer. In vitro results show that miR-30c-2-3p directly targets both TNFRSF1A-associated via death domain (TRADD), an adaptor protein of the TNFR/NF-κB signaling pathway, and the cell cycle protein Cyclin E1 (CCNE1). Ectopic expression of miR-30c-2-3p downregulated essential cytokines IL8, IL6, CXCL1, and reduced cell proliferation as well as invasion in MDA-MB-231 breast cancer cells. RNA interference (RNAi) induced silencing of TRADD phenocopied the effects on invasion and cytokine expression caused by miR-30c-2-3p, while inhibition of CCNE1 phenocopied the effects on cell proliferation. We further confirmed the tumor suppressive role of this miRNA using a dataset of 781 breast tumors, where higher expression was associated with better survival in breast cancer patients. In summary we have elucidated the mechanism by which miR-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression in breast cancer.

Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer.

Amplified HER2, which encodes a member of the epidermal growth factor receptor (EGFR) family, is a target of effective therapies against breast cancer. In search for similarly targetable genomic aberrations, we identified copy number gains in SYNJ2, which encodes the 5'-inositol lipid phosphatase synaptojanin 2, as well as overexpression in a small fraction of human breast tumors. Copy gain and overexpression correlated with shorter patient survival and a low abundance of the tumor suppressor microRNA miR-31. SYNJ2 promoted cell migration and invasion in culture and lung metastasis of breast tumor xenografts in mice. Knocking down SYNJ2 impaired the endocytic recycling of EGFR and the formation of cellular lamellipodia and invadopodia. Screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration but did not affect the related neural protein SYNJ1, suggesting that SYNJ2 is a potentially druggable target to block cancer cell migration.

MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer.

Tamoxifen is an endocrine therapy which is administered to up to 70% of all breast cancer patients with oestrogen receptor alpha (ERα) expression. Despite the initial response, most patients eventually acquire resistance to the drug. MicroRNAs (miRNAs) are a class of small non-coding RNAs which have the ability to post-transcriptionally regulate genes. Although the role of a few miRNAs has been described in tamoxifen resistance at the single gene/target level, little is known about how concerted actions of miRNAs targeting biological networks contribute to resistance. Here we identified the miRNA cluster, C19MC, which harbours around 50 mature miRNAs, to be up-regulated in resistant cells, with miRNA-519a being the most highly up-regulated. We could demonstrate that miRNA-519a regulates tamoxifen resistance using gain- and loss-of-function testing. By combining functional enrichment analysis and prediction algorithms, we identified three central tumour-suppressor genes (TSGs) in PI3K signalling and the cell cycle network as direct target genes of miR-519a. Combined expression of these target genes correlated with disease-specific survival in a cohort of tamoxifen-treated patients. We identified miRNA-519a as a novel oncomir in ER+ breast cancer cells as it increased cell viability and cell cycle progression as well as resistance to tamoxifen-induced apoptosis. Finally, we could show that elevated miRNA-519a levels were inversely correlated with the target genes' expression and that higher expression of this miRNA correlated with poorer survival in ER+ breast cancer patients. Hence we have identified miRNA-519a as a novel oncomir, co-regulating a network of TSGs in breast cancer and conferring resistance to tamoxifen. Using inhibitors of such miRNAs may serve as a novel therapeutic approach to combat resistance to therapy as well as proliferation and evasion of apoptosis in breast cancer.

Adjuvant effect of aqueous extract of Rhodiola imbricata rhizome on the immune responses to tetanus toxoid and ovalbumin in rats.

In the present study we have evaluated the immunopotentiating activity of Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The dynamic changes in humoral and cell-mediated immune response were measured. The results indicated that the TT specific immunoglobulin levels were significantly enhanced by RAE and were at par with complete Freund's adjuvant (CFA). The level of OVA induced antibody response was also enhanced by RAE. It was observed that TT and OVA in combination with CFA or RAE could evoke a significant delayed type hypersensitivity (DTH) response, confirming its potential to generate strong cell-mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress the swelling response. Therefore, this study suggests that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-mediated immune response against strong antigen like TT and weak antigen like OVA.