Biochemical analysis of oral fluids for disease detection.

The field of diagnostics using invasive blood testing represents the majority of diagnostic tests used as part of routine health monitoring. The relatively recent introduction of salivary diagnostics has lead to a major paradigm shift in diagnostic analyses. Additionally, in this era of big data, oral fluid testing has shown promising outcomes in a number of fields, particularly the areas of genomics, microbiomics, proteomics, metabolomics, and transcriptomics. Despite the analytical challenges involved in the interpretation of large datasets generated from biochemical studies involving bodily fluids, including saliva, many studies have identified novel oral biomarkers for diagnosing oral and systemic diseases. In this regard, oral biofluids, including saliva, gingival crevicular fluid (GCF), peri-implant crevicular fluid (PICF), dentinal tubular fluid (DTF), are now attracting increasing attention due to their important attributes, such as noninvasive sampling, easy handling, low cost, and more accurate diagnosis of oral diseases. Recently, the utilization of salivary diagnostics to evaluate systemic diseases and monitor general health has increased in popularity among clinicians. Saliva contains a wide range of protein, DNA and RNA biomarkers, which assist in the diagnosis of multiple diseases and conditions, including cancer, cardiovascular diseases (CVD), auto-immune and degenerative diseases, respiratory infections, oral diseases, and microbial (viral, bacterial and fungal) diseases. Moreover, due to its noninvasive nature and ease-of-adoption by children, it is now being used in mass screening programs, oral health-related studies and clinical trials in support of the development of therapeutic agents. The recent advent of highly sensitive technologies, such as next-generation sequencing, mass spectrometry, highly sensitives ELISAs, and homogeneous immunoassays, suggests that even small quantities of salivary biomarkers are able to be assayed accurately, providing opportunities for the development of many future diagnostic applications (including emerging technologies, such as point-of-care and rapid molecular technologies). The present article explores the omics and biochemical compositions of various oral biofluids with important value in diagnostics and monitoring.

COVID-19 Pandemic and Role of Human Saliva as a Testing Biofluid in Point-of-Care Technology.

Novel coronavirus disease 2019 (COVID-19) outbreak has termed as a controllable pandemic, and the entire world has come to a standstill trying to mitigate the disease with health systems. Health care providers, around the globe, are fighting day and night. Currently, rapid testing is taking place with the help of nasopharyngeal, oropharyngeal swab, bronchoalveolar lavage, sputum, urine, and blood. All these approaches are invasive or embarrassing to the infected person. It is observed that salivary glands are hosting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) because of angiotensin-converting enzyme 2 and the detection of high viral loads in the saliva and is playing a crucial role in virus transmission, especially from individuals showing absolutely no symptoms. Saliva is proving to be a promising noninvasive sample specimen for the diagnosis of COVID-19, thus helping to monitor the infection and prevent it from further spreading by prompt isolation.

Efficacy of metformin in the management of periodontitis: A systematic review and meta-analysis.

Periodontitis is characterized by inflammation of the periodontium and leads to loss of teeth if untreated. Although a number of surgical and pharmacological options are available for the management of periodontitis, it still affects a large proportion of population. Recently, metformin (MF), an oral hypoglycemic, has been used to treat periodontitis. The aim of this review is to systematically evaluate the efficacy of MF in the treatment of periodontitis. An electronic search was carried out using the keywords 'metformin', 'periodontal' and 'periodontitis' via the PubMed/Medline, ISI Web of Science and Google Scholar databases for relevant articles published from 1949 to 2016. The addressed focused question was: 'Is metformin effective in reducing bone loss in periodontitis? Critical review and meta-analysis were conducted of the results obtained in the selected studies. Following the removal of the duplicate results, the primary search resulted in 17 articles and seven articles were excluded based on title and abstract. Hence, 10 articles were read completely for eligibility. After exclusion of four irrelevant studies, six articles were included. The topical application of MF resulted in improved histological, clinical and radiographic outcomes. Additionally, results from the meta-analysis indicated that application of metformin improved the clinical and radiographic outcomes of scaling and root-planing, but at the same time heterogeneity was evident among the results. However, because of a lack of histological and bacterial studies, in addition to short follow-up periods and risk of bias, the long-term efficacy of MF in the treatment of bony defects is not yet ascertained. Further studies are needed to envisage the long-term efficacy of MF in the management of periodontitis.

Outcomes of Dental Implant Therapy in Patients With Down Syndrome: A Systematic Review.

OBJECTIVES: Patients with Down syndrome (DS) require an earlier and more frequent tooth replacement than rest of the population. The objective of this systematic review is to critically analyze and summarize studies to ascertain the outcomes and survival of dental implants placed in jaws of DS patients. METHODS: Using the key words "dental implants," "Down syndrome," and "prosthodontics," an electronic search was conducted via PubMed/MEDLINE, ISI Web of Science, Google Scholar, Embase, and Central Register of Controlled Trials (CENTRAL) databases by 2 authors, S.N. and Z.K., independently. Retrieved studies were screened against the predefined exclusion and inclusion criteria. To estimate the risk of bias, quality assessment of included studies was carried using the 'Case Reports (CARE) guidelines'. RESULTS: Primary search resulted in 156 studies. Eight studies met the inclusion criteria and reporting a total of 81 dental implants placed in 36 DS patients. The type of implant loading ranged from immediate to a delay of 1 year after placement of the implant. Implant diameter ranged from 3.3 to 4.5 mm, and height ranged from 8.5 to 18 mm. The follow-up ranged from 1 to 6 years. Of 81 implants placed, 21 implants (26%) were reported as failed. CONCLUSIONS: Patients with DS have a higher risk of implant failure. However, the reason for the failure is not very well understood. Although case reports and case series suggest that implant survival is diminished in DS patients, large-scale randomized controlled trials are required to determine the exact mechanism associated with risks of implant failure.

Chitosan Biomaterials for Current and Potential Dental Applications.

Chitosan (CHS) is a very versatile natural biomaterial that has been explored for a range of bio-dental applications. CHS has numerous favourable properties such as biocompatibility, hydrophilicity, biodegradability, and a broad antibacterial spectrum (covering gram-negative and gram-positive bacteria as well as fungi). In addition, the molecular structure boasts reactive functional groups that provide numerous reaction sites and opportunities for forging electrochemical relationships at the cellular and molecular levels. The unique properties of CHS have attracted materials scientists around the globe to explore it for bio-dental applications. This review aims to highlight and discuss the hype around the development of novel chitosan biomaterials. Utilizing chitosan as a critical additive for the modification and improvement of existing dental materials has also been discussed.

Efficacy of Enamel Matrix Derivative in Vital Pulp Therapy: A Review of Literature.

INTRODUCTION: Vital pulp therapy (VPT) aims to preserve the health and maintain life of the tooth pulp which has been compromised by caries, trauma or restorative procedures. Recently, enamel matrix derivative (EMD) has been introduced as a material for vital pulp therapy. The aim of this review is to critically analyze and summarize the available literature on EMD for VPT. METHODS AND MATERIALS: Online databases (PubMED/MEDLINE, Google Scholar, ISI Web of Science, and Wiley-Online) were searched by using the following keywords in various combinations: Enamel Matrix Derivative, Emdogain, 'Vital Pulp Therapy, 'Apexogenisis', Apexification, Pulp Capping, Endodontics, Dentine and Pulpotomy for studies indexed from January 1949 to April 2016. We used an English-limited search in Google.co.uk for the missing grey literature. All studies fulfilling the selection criteria were carefully reviewed for the focused question: "Does using EMD in VPT, compared with other materials, result in better clinical, radiographic and histological outcomes?". RESULTS: The primary search resulted in 18 articles of which, 14 articles (including 6 animal studies and 6 clinical trials and 2 case reports) met the inclusion criteria for this review and hence were included. The number of teeth tested in the animal studies ranged from 8 to 144 including pigs, rats and dogs teeth. A number of studies used EMD in the experimental group in comparison with calcium hydroxide, propylene glycol alginate (PGA) and MTA as a control. The observation period ranged from 1 to 2 months and 4 out of 6 animal trials reported more favorable outcomes with EMD while two studies reported comparable outcomes. CONCLUSION: Although EMD has potential for various applications in endodontics, studies conducted to date have failed to demonstrate any significant advantage of EMD over conventional VPT materials. Additionally, the 5-year and 10-year survival rate of EMD-treated teeth is not yet known. Hence, studies with a longer follow-up periods are required to deduce the long-term viability of teeth treated with EMD.

Histatin peptides: Pharmacological functions and their applications in dentistry.

There are many human oral antimicrobial peptides responsible for playing important roles including maintenance, repairing of oral tissues (hard or soft) and defense against oral microbes. In this review we have highlighted the biochemistry, physiology and proteomics of human oral histatin peptides, secreted from parotid and submandibular salivary glands in human. The significance of these peptides includes capability for ionic binding that can kill fungal Candida albicans. They have histidine rich amino acid sequences (7-12 family members; corresponding to residues 12-24, 13-24, 12-25, 13-25, 5-11, and 5-12, respectively) for Histatin-3. However, Histatin-3 can be synthesized proteolytically from histatin 5 or 6. Due to their fungicidal response and high biocompatibility (little or no toxicity), these peptides can be considered as therapeutic agents with most probable applications for example, artificial saliva for denture wearers and salivary gland dysfunction conditions. The objectives of current article are to explore the human histatin peptides for its types, chemical and biological aspects. In addition, the potential for therapeutic bio-dental applications has been elaborated.

Influence of uncontrolled diabetes mellitus on periodontal tissues during orthodontic tooth movement: a systematic review of animal studies.

Diabetes mellitus (DM) may adversely affect periodontal tissues during orthodontic tooth movement (OTM). The aim of this review is to systematically analyze and review animal studies investigating the effect of DM on periodontal tissues during OTM. An electronic search was conducted via PubMed/Medline, Google Scholar, Embase, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials (CONTROL) using the keywords "diabetes," "orthodontics," and "tooth movement" for studies published between January 2000 and August 2016. After elimination of duplicate items, the primary search resulted in 89 articles. After exclusion of irrelevant articles on the basis of abstract and title, full texts of 25 articles were read to exclude additional irrelevant studies. Seven animal studies were included in this review for qualitative analysis. When compared to healthy animals, more bone resorption and diminished bone remodeling were observed in diabetic animals in all studies. Furthermore, DM decreased the rate of OTM in one study, but in another study, DM accelerated OTM. DM may adversely affect bone remodeling and tooth movement during application of orthodontic forces. However, a number of potential sources of bias and deficiencies in methodology are present in studies investigating the association between OTM and DM. Hence, more long-term and well-designed studies are required before the exact mechanism and impact of DM on outcomes of orthodontic treatment is understood.

Effect of bisphosphonates on root resorption after tooth replantation - a systematic review.

BACKGROUND/AIM: Replantation of avulsed teeth may lead to root resorption. Bisphosphonates (BPs), a class of drugs of used to treat resorptive diseases of the bone such as osteoporosis and Paget's disease, have been observed to exert an antiresorptive effect on periodontal bone as well. The antiresorptive properties of BPs could prove them useful in preventing root resorption of replanted avulsed teeth. The aim of this systematic review was to analyze and summarize the currently available literature concerning the use of BPs in preventing root resorption of avulsed teeth. MATERIALS AND METHODS: PubMed/MEDLINE, Google Scholar, ISI Web of Knowledge, and Embase databases were searched using keywords 'bisphosphonate', 'replantation', and 'tooth'. Quality assessment of each study was carried out. In addition, general characteristics and outcomes of each study were summarized. RESULTS: After exclusion of 116 irrelevant articles, 10 animal studies were included in this review. The majority of the studies suggest that surface application of zoledronate or alendronate reduces root resorption of replanted teeth in animal models. Surface treatment with etidronate had no significant effect on root resorption, and intracanal etidronate accelerated resorption. CONCLUSION: Surface application of zoledronate and alendronate reduces root resorption of replanted teeth in animal models. However, the efficacy of intracanal usage of BPs is still debatable.

Propolis: A natural biomaterial for dental and oral healthcare.

The field of health has always emphasised on the use of natural products for curing diseases. There are varieties of natural products (such as silk, herbal tea, chitosan) used today in the biomedical application in treating a large array of systemic diseases. The natural product "Propolis" is a non-toxic resinous material having beneficial properties such as antimicrobial, anticancer, antifungal, antiviral and anti-inflammatory; hence gain the attention of researchers for its potential for bio-dental applications. The study aims to explore the properties and chemistry of propolis concerning biomedical and dental applications. In addition, status and scope of propolis for current and potential future in bio-dental applications have been discussed. This review gives an insight to the reader about the possible use of propolis in modern-day dentistry.

Bisphosphonate releasing dental implant surface coatings and osseointegration: A systematic review.

OBJECTIVES: Bisphosphonates (BPs) are a class of drugs that are used to treat osteoporosis. It has been suggested that BP coatings on dental implants have a positive effect on new bone formation. The purpose of this review is to analyse the currently available data concerning the clinical and experimental efficacy of BP-releasing titanium implants such that their potential in clinical oral implant dentistry may be ascertained. METHODS: Based on a literature review, a focused research question was constructed: what is the effect of a BP-releasing coating on the osseointegration of titanium dental implant? The databases of PubMED/MEDLINE; ISI Web of Knowledge; Embase and Google Scholar were searched electronically using the keywords 'dental implant'; 'bisphosphonate' and 'titanium.' The quality; general characteristics and outcomes of each study were summarized and analysed systematically. RESULTS: A total of eleven articles fulfilled the criteria to be included in this review. Eight studies were experimental; two studies were clinical; and one study was experimental and clinical. In nine studies (82%), BP-coated implants resulted in higher osseointegration, as indicated by higher resonance frequency values, removal torque, bone-implant contact and new bone formation. In two studies (18%), there was no difference between the osseointegration of BP-coated implants and controls. CONCLUSIONS: Bisphosphonates-loaded implants may have a positive effect on osseointegration. However, more well-designed clinical studies are required to demonstrate their osseoconductive effects.

Management of recurrent aphthous ulcers using low-level lasers: A systematic review.

BACKGROUND AND OBJECTIVE: The exact etiology of recurrent aphthous ulcers (RAS) is unknown. The management of RAS is not always straightforward. The aim of this review is to critically analyze and summarize the clinical literature focusing on the management of aphthous ulcers using low-level lasers. MATERIALS AND METHODS: The Medline (PubMed), Web of Knowledge (ISI), Cochrane Central Register of Controlled Trials (CENTRAL) and Embase databases were searched electronically for studies published in last 20 years (1995-2015) using the keywords "recurrent aphthous stomatitis," "aphthous ulcers," and "laser." RESULTS: A total of 85 articles were found during the initial search; 76 studies were excluded for not fulfilling the criteria whereas nine studies were deemed suitable for this review. Among the included studies, two articles were case reports and seven were randomized clinical trials. Study design, sample size, type of intervention and control of each study were critically analyzed and summarized according to the CONSORT protocol. In majority of the patients, immediate pain relief and accelerated ulcer healing was observed following irradiation with lasers. CONCLUSIONS: Although various types of lasers have succeeded in providing immediate pain relief to patients, carbon dioxide (CO2) lasers have the unique advantage of requiring a short exposure time (5-10s). In order to ascertain the efficacy of laser for treating ulcers in the clinical setting, more clinical trials are required.

The Role of Nutrition in Periodontal Health: An Update.

Periodontal health is influenced by a number of factors such as oral hygiene, genetic and epigenetic factors, systemic health, and nutrition. Many studies have observed that a balanced diet has an essential role in maintaining periodontal health. Additionally, the influences of nutritional supplements and dietary components have been known to affect healing after periodontal surgery. Studies have attempted to find a correlation between tooth loss, periodontal health, and nutrition. Moreover, bone formation and periodontal regeneration are also affected by numerous vitamins, minerals, and trace elements. The aim of this review is to critically appraise the currently available data on diet and maintenance of periodontal health and periodontal healing. The effects of nutritional intervention studies to improve the quality of life and well-being of patients with periodontal disease have been discussed.

Therapeutic potential of melatonin in oral medicine and periodontology.

Melatonin (N-acetyl-5-methoxy tryptamine) is a substance secreted by multiple organs in vertebrates. In addition to playing a part in the circadian cycle of the body, melatonin is known to have antioxidant, antiinflammatory, and antioncotic effects on human tissues. Oral cavity is affected by a number of conditions such as periodontitis, mucositis, cancers, and cytotoxicity from various drugs or biomaterials. Research has suggested that melatonin is effective in treating the aforementioned pathologies. Furthermore, melatonin has been observed to enhance osseointegration and bone regeneration. The aim of this review is to critically analyze and summarize the research focusing on the potential of melatonin in the field of oral medicine. Topical administration of melatonin has a positive effect on periodontal health and osseointegration. Furthermore, melatonin is particularly effective in improving the periodontal parameters of diabetic patients with periodontitis. Melatonin exerts a regenerative effect on periodontal bone and may be incorporated into of periodontal scaffolds. The cytotoxic effect of various drugs and dental materials may be countered by the antioxidant properties of melatonin. Topical administration of melatonin promotes the healing of tooth extraction sockets and may also impede the progression of oral cancer. Although, there are a number of current and potential applications of melatonin, further long term clinical and animal studies are needed to assess its efficacy. Moreover, the role of melatonin supplements in the management of periodontitis should also be assessed.

Green Tea (Camellia Sinensis): Chemistry and Oral Health.

Green tea is a widely consumed beverage worldwide. Numerous studies have suggested about the beneficial effects of green tea on oral conditions such as dental caries, periodontal diseases and halitosis. However, to date there have not been many review articles published that focus on beneficial effects of green tea on oral disease. The aim of this publication is to summarize the research conducted on the effects of green tea on oral cavity. Green tea might help reduce the bacterial activity in the oral cavity that in turn, can reduce the aforementioned oral afflictions. Furthermore, the antioxidant effect of the tea may reduce the chances of oral cancer. However, more clinical data is required to ascertain the possible benefits of green tea consumption on oral health.

Modifications in Glass Ionomer Cements: Nano-Sized Fillers and Bioactive Nanoceramics.

Glass ionomer cements (GICs) are being used for a wide range of applications in dentistry. In order to overcome the poor mechanical properties of glass ionomers, several modifications have been introduced to the conventional GICs. Nanotechnology involves the use of systems, modifications or materials the size of which is in the range of 1-100 nm. Nano-modification of conventional GICs and resin modified GICs (RMGICs) can be achieved by incorporation of nano-sized fillers to RMGICs, reducing the size of the glass particles, and introducing nano-sized bioceramics to the glass powder. Studies suggest that the commercially available nano-filled RMGIC does not hold any significant advantage over conventional RMGICs as far as the mechanical and bonding properties are concerned. Conversely, incorporation of nano-sized apatite crystals not only increases the mechanical properties of conventional GICs, but also can enhance fluoride release and bioactivity. By increasing the crystallinity of the set matrix, apatites can make the set cement chemically more stable, insoluble, and improve the bond strength with tooth structure. Increased fluoride release can also reduce and arrest secondary caries. However, due to a lack of long-term clinical studies, the use of nano-modified glass ionomers is still limited in daily clinical dentistry. In addition to the in vitro and in vivo studies, more randomized clinical trials are required to justify the use of these promising materials. The aim of this paper is to review the modification performed in GIC-based materials to improve their physicochemical properties.

Human Saliva Collection Devices for Proteomics: An Update.

There has been a rapid growth in the interest and adaptation of saliva as a diagnostic specimen over the last decade, and in the last few years in particular, there have been major developments involving the application of saliva as a clinically relevant specimen. Saliva provides a "window" into the oral and systemic health of an individual, and like other bodily fluids, saliva can be analyzed and studied to diagnose diseases. With the advent of new, more sensitive technologies to detect smaller concentrations of analytes in saliva relative to blood levels, there have been a number of critical developments in the field that we will describe. In particular, recent advances in standardized saliva collection devices that were not available three to four years ago, have made it easy for safe, simple, and non-invasive collection of samples to be carried out from patients. With the availability of these new technologies, we believe that in the next decade salivary proteomics will make it possible to predict and diagnose oral as well as systemic diseases, cancer, and infectious diseases, among others. The aim of this article is to review recent developments and advances in the area of saliva specimen collection devices and applications that will advance the field of proteomics.

Advances of Proteomic Sciences in Dentistry.

Applications of proteomics tools revolutionized various biomedical disciplines such as genetics, molecular biology, medicine, and dentistry. The aim of this review is to highlight the major milestones in proteomics in dentistry during the last fifteen years. Human oral cavity contains hard and soft tissues and various biofluids including saliva and crevicular fluid. Proteomics has brought revolution in dentistry by helping in the early diagnosis of various diseases identified by the detection of numerous biomarkers present in the oral fluids. This paper covers the role of proteomics tools for the analysis of oral tissues. In addition, dental materials proteomics and their future directions are discussed.

Potential of Electrospun Nanofibers for Biomedical and Dental Applications.

Electrospinning is a versatile technique that has gained popularity for various biomedical applications in recent years. Electrospinning is being used for fabricating nanofibers for various biomedical and dental applications such as tooth regeneration, wound healing and prevention of dental caries. Electrospun materials have the benefits of unique properties for instance, high surface area to volume ratio, enhanced cellular interactions, protein absorption to facilitate binding sites for cell receptors. Extensive research has been conducted to explore the potential of electrospun nanofibers for repair and regeneration of various dental and oral tissues including dental pulp, dentin, periodontal tissues, oral mucosa and skeletal tissues. However, there are a few limitations of electrospinning hindering the progress of these materials to practical or clinical applications. In terms of biomaterials aspects, the better understanding of controlled fabrication, properties and functioning of electrospun materials is required to overcome the limitations. More in vivo studies are definitely required to evaluate the biocompatibility of electrospun scaffolds. Furthermore, mechanical properties of such scaffolds should be enhanced so that they resist mechanical stresses during tissue regeneration applications. The objective of this article is to review the current progress of electrospun nanofibers for biomedical and dental applications. In addition, various aspects of electrospun materials in relation to potential dental applications have been discussed.