BDNF and Krox20 as Indicators of Platelet-rich Plasma-Induced Nerve Regeneration in a Neuropathic Orofacial Pain Model.

OBJECTIVE: Various growth factors contained in PRP can increase angiogenesis and cell proliferation, which plays an essential role in the process of neuroregeneration and peripheral nerve injury recovery. This study analyzed PRP effects in the neuro-regeneration of axonotmesis through brain-derived neurotrophic factor (BDNF) and Krox20 expressions. MATERIALS AND METHODS: Freeze-dried allogeneic platelet-rich plasma (PRP) were prepared from allogeneic sources. Forty-two Rattus norvegicus were divided into three groups: negative control group, positive control group (crushing infraorbital nerve) and treatment group (crushing infraorbital nerve without PRP injection). Each group was observed for fourteen and twenty-one days after injury. Infraorbital nerve tissue is isolated for indirect immunohistochemistry examination with BDNF and Krox20 antibodies. Data analysis was performed using One-Way ANOVA and Mann-Whitney tests with significant value as p < 0.05. RESULTS: The PRP group showed BDNF expression significantly higher than control positive groups, both observation days (p = 0.00). A higher Korx20 expression showed by the PRP group after 21 days than in the control positive groups (p = 0.002). CONCLUSION: PRP can potentially improve neuroregeneration of axonotmesis through increased BDNF and Krox20 expression on the twenty-one days after injury.

Potential targets of phytochemical immunomodulatory therapy in periodontitis immunopathogenesis: A narrative review.

Introduction: Periodontitis is one of the most prevalent diseases occurring worldwide, and is caused by an imbalance of host immunological defenses and microbiome profile which occurs in the oral cavity. This imbalance leads to irregularity and uncontrolled activities of immune cells, resulting in over-reactivity of periodontopathogens and tissue destruction. To alleviate periodontitis, exact targeting of specific events involving particular cells could be a potential application of immunomodulatory agents. Phytochemical drug development targeting specific immunopathogenesis events could be a promising complementary, alternative approach to periodontal therapy. Objectives: This review aimed to explore various events involving a variety of cells in the immunopathogenesis of periodontitis in order to determine potential specific immunomodulation targets for future development of effective phytochemical drugs. Results: Immunopathogenesis of periodontitis contributes significantly to the disease onset and resolution. Various events occur during the disease development, which involve a variety of immune cells and mediators. Among these, neutrophils, cytokines and lymphocytes, especially Th17 cells, were reported to be the most relevant components in the disease pathogenesis. These components affect the initial responses to periodontopathogens, inhibit oxidative stress formation, control intercellular communication to enhance inflammation, and promote effector cells' migration to induce alveolar bone resorption. Several phytochemical drugs were developed to cure periodontitis, however, the development of phytochemical immunomodulatory drugs to target specific events has not been realized. Conclusion: This review concluded that development of phytochemical immunomodulatory drugs to target particular events generated by neutrophils, pro-inflammatory cytokines and lymphocytes has tremendous potential to regulate and modulate the immunopathogenesis of periodontitis.

The Oral Lesion in the COVID-19 Patient: Is It True Oral Manifestation or Not?

Objective: Many previously reported publications mentioned that oral lesion in COVID-19 patients was varied. The term oral manifestations refer to pathognomonic features that are found consistently with a specific cause and effect. In this context, the oral manifestation of COVID-19 was inconclusive. This systematic review aimed to analyse previously reported publications related to oral lesions in COVID-19 patients to define as oral manifestations or not. The PRISMA guidelines were implemented in this review. Methods: All umbrella reviews, systematic reviews, systematic reviews and meta-analyses, comprehensive reviews, and original and non-original studies were included. Twenty-one of systematic review, 32 original studies and 68 non-original studies reported the oral lesion in COVID-19 patients. Results: Most of the publications mentioned that ulcers, macular, pseudomembranes and crusts were frequent oral lesions. The reported oral lesions in COVID-19 patients did not show any pathognomonic features and might be unrelated directly to COVID-19 infections, however, more likely due to gender, age, underlying diseases, and medication. Conclusion: The oral lesions found in previous studies do not have pathognomonic features and are inconsistent. Therefore, the reported oral lesion, in present time, cannot be defined as an oral manifestation.

Plant-Derived Exosome-like Nanoparticles for Biomedical Applications and Regenerative Therapy.

Plant-derived exosome-like nanoparticles (PDENs) comprise various bioactive biomolecules. As an alternative cell-free therapeutic approach, they have the potential to deliver nano-bioactive compounds to the human body, and thus lead to various anti-inflammatory, antioxidant, and anti-tumor benefits. Moreover, it is known that Indonesia is one of the herbal centers of the world, with an abundance of unexplored sources of PDENs. This encouraged further research in biomedical science to develop natural richness in plants as a source for human welfare. This study aims to verify the potential of PDENs for biomedical purposes, especially for regenerative therapy applications, by collecting and analyzing data from the latest relevant research and developments.

Gingival Mesenchymal Stem Cells Metabolite Decreasing TRAP, NFATc1, and Sclerostin Expression in LPS-Associated Inflammatory Osteolysis In Vivo.

OBJECTIVE: Bone is a dynamic tissue that undergoes remodeling. During bone remodeling, there are transcription factors such as nuclear factor-activated T cells-1 (NFATc1), sclerostin, and tartrate-resistant acid phosphatase (TRAP) that are released for bone resorption. Metabolite from gingival mesenchymal stem cells (GMSCs) has the ability to activate proliferation, migration, immunomodulation, and tissue regeneration of bone cells and tissues. Furthermore, the aim of this study is to investigate the metabolite of GMSCs' effect on expression of NFATc1, TRAP, and sclerostin in calvaria bone resorption of Wistar rats. MATERIALS AND METHODS: Twenty male healthy Wistar rats (Rattus norvegicus), 1 to 2 months old, 250 to 300 g body were divided into four groups, namely group 1 (G1): 100 µg phosphate-buffered saline day 1 to 7; group 2 (G2): 100 µg lipopolysaccharide (LPS) day 1 to 7; group 3 (G3): 100 µg LPS + 100 µg GMSCs metabolite day 1 to 7; and group 4 (G4): 100 µg GMSCs metabolite day 1 to 7. Escherichia coli LPS was used to induce inflammatory osteolysis on the calvaria with subcutaneous injection. GMSCs metabolite was collected after passage 4 to 5, then injected subcutaneously on the calvaria. All samples were sacrificed on the day 8 through cervical dislocation. The expression of TRAP, NFATc1, and sclerostin of osteoclast in the calvaria was observed with 1,000× magnification. STATISTICAL ANALYSIS: One-way analysis of variance and Tukey honest significant different were conducted to analyze differences between groups (p < 0.05). RESULTS: The administration of GMSCs metabolite can significantly decrease TRAP, NFATc1, and sclerostin expression (p < 0.05) in LPS-associated inflammatory osteolysis calvaria in Wistar rats (R. norvegicus). There were significantly different TRAP, NFATc1, and sclerostin expressions between groups (p < 0.05). CONCLUSION: GMSCs metabolite decrease TRAP, NFATc1, and sclerostin expression in LPS-associated osteolysis calvaria in Wistar rats (R. norvegicus) as documented immunohistochemically.

The Macrophage Responses during Diabetic Oral Ulcer Healing by Liquid Coconut Shell Smoke: An Immunohistochemical Analysis.

OBJECTIVES: Liquid coconut shell smoke (LC-SS) is used in natural food preservation for a long history. The purpose of this study was to analyze the role of LC-SS in macrophage responses during diabetic oral ulcer healing as medication. MATERIALS AND METHODS: Oral ulcers were induced in the labial lower mucosa of the research subjects using a round steel blade following diabetic induction by means of alloxan. Twenty-four diabetic Wistar rats presenting oral ulcers were divided into two groups, a test group, which was given topical treatment of LC-SS and a control group, which was given benzydamine hydrochloride (BHCl). The role of LC-SS in macrophages was assessed by means of immunohistochemistry for nuclear factor kappa B (NF-κB) and tumor necrosis factor-α (TNF-α) expression. RESULT: LC-SS increased macrophages compared with BHCl (p = 0.000). The LC-SS affected only TNF-α expression by stimulating NF-κB expression (p = 0.046) but did not macrophage numbers (p = 0.861). CONCLUSION: LC-SS has a stronger effect compared with BHCl on diabetic oral ulcer healing by increasing macrophage response to produce TNF-α while decreasing NF-κB expression.