Periodontitis increases the risk of gastrointestinal dysfunction: an update on the plausible pathogenic molecular mechanisms.

Periodontitis is an immuno-inflammatory disease of the soft tissues surrounding the teeth. Periodontitis is linked to many communicable and non-communicable diseases such as diabetes, cardiovascular disease, rheumatoid arthritis, and cancers. The oral-systemic link between periodontal disease and systemic diseases is attributed to the spread of inflammation, microbial products and microbes to distant organ systems. Oral bacteria reach the gut via swallowed saliva, whereby they induce gut dysbiosis and gastrointestinal dysfunctions. Some periodontal pathogens like Porphyromonas. gingivalis, Klebsiella, Helicobacter. Pylori, Streptococcus, Veillonella, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus, Haemophilus, Aggregatibacter actinomycetomcommitans and Streptococcus mutans can withstand the unfavorable acidic, survive in the gut and result in gut dysbiosis. Gut dysbiosis increases gut inflammation, and induce dysplastic changes that lead to gut dysfunction. Various studies have linked oral bacteria, and oral-gut axis to various GIT disorders like inflammatory bowel disease, liver diseases, hepatocellular and pancreatic ductal carcinoma, ulcerative colitis, and Crohn's disease. Although the correlation between periodontitis and GIT disorders is well established, the intricate molecular mechanisms by which oral microflora induce these changes have not been discussed extensively. This review comprehensively discusses the intricate and unique molecular and immunological mechanisms by which periodontal pathogens can induce gut dysbiosis and dysfunction.

Can Duvelisib and Eganelisib work for both cancer and COVID-19? Molecular-level insights from MD simulations and enhanced samplings.

SARS-CoV-2 has caused severe illness and anxiety worldwide, evolving into more dreadful variants capable of evading the host's immunity. Cytokine storms, led by PI3Kγ, are common in cancer and SARS-CoV-2. Naturally, there is a yearning to see whether any drugs could alleviate cytokine storms for both. Upon investigation, we identified two anticancer drugs, Duvelisib and Eganelisib, that could also work against SARS-CoV-2. This report is the first to decipher their synergic therapeutic effectiveness against COVID-19 and cancer with molecular insights from atomistic simulations. In addition to PI3Kγ, these drugs exhibit specificity for the main protease among all SARS-CoV-2 targets, with significant negative binding free energies and small time-dependent conformational changes of the complexes. Complexation makes active sites and secondary structures highly mechanically stiff, with barely any deformation. Replica simulations estimated large pulling forces in enhanced sampling to dissociate the drugs from Mpro's active site. Furthermore, the radial distribution function (RDF) demonstrated that the therapeutic molecules were closest to the His41 and Cys145 catalytic dyad residues. Finally, analyses implied Duvelisib and Eganelisib as promising dual-purposed anti-COVID and anticancer drugs, potentially targeting Mpro and PI3Kγ to stop virus replication and cytokine storms concomitantly. We also distinguished hotspot residues imparting significant interactions.

Bacteriophages: the dawn of a new era in periodontal microbiology?

The oral microbiome, populated by a diverse range of species, plays a critical role in the initiation and progression of periodontal disease. The most dominant yet little-discussed players in the microbiome, the bacteriophages, influence the health and disease of the host in various ways. They, not only contribute to periodontal health by preventing the colonization of pathogens and disrupting biofilms but also play a role in periodontal disease by upregulating the virulence of periodontal pathogens through the transfer of antibiotic resistance and virulence factors. Since bacteriophages selectively infect only bacterial cells, they have an enormous scope to be used as a therapeutic strategy; recently, phage therapy has been successfully used to treat antibiotic-resistant systemic infections. Their ability to disrupt biofilms widens the scope against periodontal pathogens and dental plaque biofilms in periodontitis. Future research focussing on the oral phageome and phage therapy's effectiveness and safety could pave way for new avenues in periodontal therapy. This review explores our current understanding of bacteriophages, their interactions in the oral microbiome, and their therapeutic potential in periodontal disease.

Cell Junctions in Periodontal Health and Disease: An Insight.

Cells are the building blocks of all living organisms. The presence of cell junctions such as tight junctions, gap junctions, and anchoring junctions between cells play a role in cell-to-cell communication in periodontal health and disease. A literature search was done in Scopus, PubMed, and Web of Science to gather information about the effect of cell junctions on periodontal health and disease. The presence of tight junction in the oral cavity helps in cell-to-cell adhesiveness and assists in the barrier function. The gap junctions help in controlling growth and development and in the cell signaling process. The presence of desmosomes and hemidesmosomes as anchoring junctions aid in mechanical strength and tissue integrity. Periodontitis is a biofilm-induced disease leading to the destruction of the supporting structures of the tooth. The structures of the periodontium possess multiple cell junctions that play a significant role in periodontal health and disease as well as periodontal tissue healing. This review article provides an insight into the role of cell junctions in periodontal disease and health, and offers concepts for development of therapeutic strategies through manipulation of cell junctions.

Unmasking an Allosteric Binding Site of the Papain-like Protease in SARS-CoV-2: Molecular Dynamics Simulations of Corticosteroids.

To date, mechanistic insights into many clinical drugs against COVID-19 remain unexplored. Dexamethasone, a corticosteroid, is one of them. While treating the entire corticosteroid database, including vitamins D2 and D3, with cutting-edge computational techniques, several intriguing results are unfolded. From the top-notch candidates, dexamethasone is likely to inhibit the viral main protease (Mpro), with vitamin D3 exhibiting multitarget [Mpro, papain-like protease (PLpro), and nucleocapsid protein (N-pro)] roles and ciclesonide's dynamic flipping disinterring a cryptic allosteric site in the PLpro enzyme. The results rationalize why these drugs improve the health of COVID-19 patients. Understanding an enzyme's secret binding site is essential to understanding how the enzyme works and how to inhibit its function. Ciclesonide's allosteric inhibition could not only jeopardize PLpro's catalytic role in polyprotein processing but also make it less vulnerable to the host body's defense machinery. Hotspot residues in the identified allosteric site could be considered for effective therapeutic designs against PLpro.

Gene therapy as a treatment of oral cancer: An insight.

Oral cancer or oral squamous cell carcinoma comprises more than three-fourth of all the malignant neoplasms of the oral cavity. Worldwide, it is the 18th most common malignancy. The patients suffering from cancer usually remains immune to the standard therapies such as surgical resection of tumours, radiotherapy and chemotherapy; however, there can be probabilities of chronic and acute toxicities and secondary malignancies as well. Recently, gene therapy has been introduced in the arena of biomedicine to improve the treatment modality for oral malignant and potentially malignant disorders. It replaces the defective gene followed by repairing by a therapeutic gene. Gene therapy can attack cancerous cells without causing harmful effect to the normal tissue. It is useful to cope with the relapse of diseases and as a synergetic treatment. The present article reviewed the types of gene therapy, modes of delivery of the therapeutic genes and different techniques used along with pros and cons of gene therapy.

Effect of ozone irrigation and powered toothbrushing on dental plaque, gingival inflammation, and microbial status in institutionalized mentally challenged individuals: A double-blinded, randomized, controlled clinical trial.

Aim: This study compares and evaluates the efficacy of ozonated water irrigation (OZI) and powered toothbrushing on the oral health and microbial status of mentally challenged individuals. Materials and Methods: Thirty individuals of age range 15-30 years with a mild-to-moderate level of mental retardation (MR) and gingival inflammation participated in this double-blind randomized controlled clinical trial. Total duration of the study was 45 days consisting of two clinical phases (phase I, i.e., aided) and phase II, i.e. unaided) of the duration of 21 days in each phase, with a washout period of 3 days between the two phases. With a split-mouth design, sites from each subject were randomly allocated into two treatment groups: Powered Toothbrushing (PB) and OZI were randomly done for each half side of the mouth of each subject. Subgingival plaque samples were collected from sites of both the treatment groups and sent for microbial analysis. Clinical and microbial parameters were measured before and after the treatment. Results: Significant improvement of the clinical and microbial parameters was found in both treatment groups. However, intergroup differences in the parameters were statistically nonsignificant. Conclusion: OZI could serve as an alternative or adjunct to powered toothbrushes for people with MR.

Yoga as an Integrated Holistic Approach to Oral Health: A Review.

Objectives: The association between various systemic diseases and periodontitis has been explored extensively. A sedentary lifestyle plays a significant role in systemic and periodontal disease progression. Therefore, lifestyle modification has been considered a component of therapeutic aspects for periodontal disease and systemic disease. This review focuses on how yoga may reduce chronic gingival inflammation by improving the body's defense, which can act more efficiently on periodontal bacteria and help maintain healthy gingiva. Materials and Methods: A literature search was performed in PubMed/MEDLINE CINAHL, Web of Science, and Google Scholar for all the published articles related to yoga and its systemic benefits and potential role in reducing periodontal breakdown, and the findings were summarized. Results: The practice of yoga therapy has been proven to show several benefits, such as reduced stress levels, anxiety and depression, increased antioxidant levels, reduced insulin resistance, and improved respiratory function. It also helps to improve the immune system. Conclusion: Yoga can be used as a potential treatment modality adjunct to conventional periodontal therapy as it has been shown to have a potential benefit in controlling systemic risk factors.

Oleogel-based drug delivery for the treatment of periodontitis: current strategies and future perspectives.

Periodontitis is the chronic inflammation of tooth-supporting tissues that leads to loss of tooth support if untreated. Conventional therapy for periodontitis (mechanical removal of microbial biofilm and oral hygiene enforcement) is augmented by anti-microbial and anti-inflammatory drugs. These drugs are frequently delivered locally into the periodontal pocket for maximum efficiency and minimum adverse effects. The potential of oleogels for periodontal drug delivery has been discussed and further, the future scope of oleogel-based drug delivery systems in dentistry. An oleogel-based local drug delivery system offers several advantages over other systems. Superior mechanical properties (firmness and compressibility), muco-adhesion, shear thinning, thixotropy, controlled drug release and the ability to incorporate water-insoluble drugs clearly distinguish and highlight the potential of oleogels as periodontal local drug delivery systems. Bigels can combine the qualities of both hydrogels and oleogels to provide a more promising option for drug delivery. However, there is limited evidence concerning oleogels as local drug delivery agents in periodontics. Further studies are needed to discern the clinical efficacy of oleogel-based drug delivery systems.

Development and validation of a structured questionnaire to assess the Knowledge, Attitude and Practice (KAP) regarding the effect of yoga on periodontal health among Indian adults.

Background: Periodontal disease is a chronic inflammatory disease of structures surrounding the teeth. Its etiology is multifactorial. The primary etiological factor is the microbial component; the other factors are systemic, behavioral, environmental, and psychological. Conventional management includes routine periodontal therapy involving prophylactic and surgical management. In developing countries like India, complementary medicine and alternative medicines like yoga are gaining popularity for improving systemic health. Hence this pilot study was designed to assess the psychometric properties of a structured questionnaire that can assess knowledge, attitude, and practice (KAP) regarding the impact of yoga on oral and periodontal health in Indian population. Methods: The KAP questionnaire was developed (Stage One) using a deductive approach, and a psychometric evaluation of the questionnaire was performed to evaluate it's reliability and validity (Stage Two). Initial content validation and test re-test reliability were assessed using kappa statistics with binary responses. An intraclass correlation coefficient (ICC) was used to assess the questions in the practice and attitude category with categorical variables. Further assessment of psychometric properties of the questionnaire was done using item response theory. The developed questionnaire had four principal sections: demography of participants; knowledge regarding yoga and oral health; attitude towards yoga and oral health; and practice towards implementing yoga for oral health. Results: The ICC for all the assessed questions was greater than 0.60 suggesting satisfactory stability. Internal consistency measured using Cronbach's alpha for knowledge, attitude, and practice items were reported to be 0.632, 0.923, and 0.591 respectively and that of the KAP total was 0.632. Conclusions: The findings of this study showed that the questionnaire had an acceptable psychometric property for measuring KAP regarding yoga and it's role in oral and periodontal health among Indian adults. The analysis of participant responses revealed that they had a medium level of knowledge regarding yoga and periodontal disease.

Comparison of Ozonated Olive Oil and Chlorhexidine Gel as an Adjunct to Nonsurgical Periodontal Therapy for the Treatment of Chronic Periodontitis: A Randomized Controlled Clinical Trial.

Objectives: Complete elimination of the pathogenic microorganisms from the gingival sulcus area is the ultimate goal of any periodontal therapy. Certain factors such as anatomical variation of teeth, deep periodontal pocket, and tissue-invading ability of some bacteria decrease the effectiveness of conventional nonsurgical periodontal therapy, i.e., scaling and root planing (SRP). Hence, antimicrobial agents could be used as an adjunct to SRP, in order to increase the efficacy of it. Although Chlorhexidine (CHX) is the gold standard as an antiplaque agent, it has several drawbacks. Recently, ozone therapy is being tried for the treatment of several diseases in the field of dentistry. Therefore, the purpose of this study was to evaluate and compare the efficacy of local application of CHX and ozonated olive oil as adjunctive to SRP for the treatment of chronic periodontitis. Materials and Methods: Thirty individuals who fulfilled the eligibility criteria were selected for this split-mouth randomized controlled trial. The treatment sites from each individual were randomly allocated into two groups. Along with SRP, the local application of CHX and ozonated olive oil was done for the control and test sites, respectively. Pocket probing depth, relative attachment loss, and sulcus bleeding index were measured before and 3 months after the treatment. Intragroup and intergroup differences in the clinical parameters were analyzed by Wilcoxon signed-rank test and Mann-Whitney U test, respectively. Results: Three months' posttreatment, all the parameters showed significant improvement in both the groups. However, the intergroup comparison failed to be significant statistically. Conclusion: Ozonated olive oil could enhance the outcomes of SRP for the treatment of periodontal diseases.

Comparison of Chlorhexidine and Hydrogen Peroxide as Preprocedural Mouthrinse during Ultrasonic Scaling: A Triple-Blinded Randomized Controlled Clinical Trial.

Background: Every year, around 2 million people suffer from hospital-acquired infections worldwide. Aerosols are produced while performing ultrasonic scaling. They are potential source of infection and cross contamination. It can result in spread of several infections including hepatitis, HIV, SARS CoV 2, etc. Preprocedural rinse before scaling is considered an effective measure to reduce the microbial load in aerosols. Materials and Methods: This study was a triple-blinded randomized controlled trial performed on 90 participants diagnosed with chronic periodontitis. Random allocation of participants into three groups, i.e., Group-1, Group-2, and Group-3, was done, wherein 0.12% chlorhexidine (CHX), 1.5% hydrogen peroxide (HP), and distilled water (DW) were used, respectively, as preprocedural mouthrinse. The participants of each group were instructed to perform mouthrinse for 60 s before the start of ultrasonic scaling sessions. Blood agar plates were kept at three locations, i.e., operator's chest area, patient's chest area, and assistant's chest area for aerosol collection after scaling. Colony-forming units (CFUs) were counted for microbiological analysis. Results: Least number of CFUs was found in the CHX group, followed by HP and DW groups. Location wise, the patient's chest area had the highest CFU count and the least was at the assistant's chest area. CFU count between the groups was statistically significant. Conclusion: Preprocedural rinse using HP can effectively be used as a method to reduce dental aerosols generated during ultrasonic scaling.

Clinico-microbiological Efficacy of Indocyanine Green as a Novel Photosensitizer for Photodynamic Therapy among Patients with Chronic Periodontitis: A Split-mouth Randomized Controlled Clinical Trial.

OBJECTIVE: Conventional nonsurgical periodontal therapy, i.e., scaling and root planing (SRP), is not sufficient to completely eradicate the microorganisms present in dental plaque biofilm due to the incapability of instruments to reach the inaccessible areas of a tooth with anatomical variations. Hence, to increase the effectiveness of SRP, many adjunctive treatment strategies are proposed, including photodynamic therapy (PDT). Therefore, the purpose of this study was to determine the clinical and microbiological efficacy of PDT using Indocyanine green (ICG) as a novel photosensitizer for the treatment of chronic periodontitis. MATERIALS AND METHODS: Twenty individuals who fulfilled the eligibility criteria were enrolled for this randomized controlled clinical trial using split-mouth design. Treatment sites from each individual were randomly allocated into two groups: SRP was done for the sites of the control group and an additional session of PDT using ICG was performed for the sites of the test group. Subgingival plaque samples were collected from both the sites and sent for quantitative analysis of Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia using real-time polymerase chain reaction (RT-PCR) technique. Probing pocket depth (PD), clinical attachment loss (CAL), and count of all the three microorganisms were assessed at baseline and after 3 months. RESULTS: After 3 months, PD and CAL showed statistically significant improvement in the test sites (P < 0.001) compared to the control sites. However, the differences in the microbiological parameters were statistically nonsignificant between the groups. CONCLUSION: ICG as a photosensitizer may enhance the outcomes of SRP and can be used for PDT for the nonsurgical management of periodontal diseases.

Influence of a Low-Carbohydrate and Rich in Omega-3 Fatty Acids, Ascorbic Acid, Antioxidants, and Fiber Diet on Clinical Outcomes in Patients with Chronic Gingivitis: A Randomized Controlled Trial.

BACKGROUND: Nutrition has a significant impact on the pathophysiology of periodontal disease. Both micro- and macronutrients have an impact on periodontal health. This study aimed at the evaluation of the effects of a diet low in carbohydrate and rich in omega-3 fatty acids, ascorbic acid, antioxidants, and fiber on clinical outcomes in patients with gingival inflammation for four weeks. MATERIALS AND METHODS: Overall, 54 systemically healthy subjects were enrolled in this study. The clinical trial consisted of two groups: Group A (test group) (n = 27) was instructed to consume a diet comprising low carbohydrates, rich in omega-3 fatty acids, ascorbic acid, antioxidants, and fibers for the next four weeks; in Group B (control group) (n = 27), no alteration in dietary behavior was done, and these subjects were instructed to have their daily routine diet. Clinical parameters measured were plaque index (PI), gingival bleeding index (GI), probing depths (PD), clinical attachment level (CAL), and bleeding on probing (BOP) at one week without any dietary changes (baseline) for both the groups, followed by a one-week adaptation period; then, the parameters were checked on a weekly basis for the next four weeks. RESULTS: Primary clinical outcome BOP and secondary outcome GI showed significant changes in the test group compared with the control group (P < 0.05). However, no significant changes were seen in the plaque scores in the test group (P > 0.05). The degree of diet compliance on the clinical parameters (PI, GI, and BOP) was assessed by using regression analysis. CONCLUSION: Dietary recommendations can be beneficial in managing gingival and periodontal inflammation. Nutritional interventional studies as monotherapy are required to evaluate the clinical significance of diet in periodontal therapy.

Periodontitis and oral Cancer-A striking link.

Oral squamous cell carcinoma (OSCC) has become a major public health problem in the worldwide for its increasing incidence and mortality, especially in younger trends. Risk factors for OSCC apart from alcohol and tobacco use, include poor oral hygiene, inflammation caused by inadequately fitting dentures and other rough teeth surfaces, poor nutrition and some chronic infections caused by fungi, bacteria or viruses. Several studies have also found that the risk of developing OSCC may increase with periodontal disease (PD). In addition to reduce harm caused by tobacco, alcohol and betel quid it seems prudent to take measures to improve oral hygiene in periodontally compromised patients to minimize OSCC risks. This further intensifies the need for oral health education programs and large cohurt studies to edify individuals about the importance of regular oral health maintenance and routine dental care towards the prevention of oral diseases including OSCC.