[Photobiomodulation in the prevention and the management of side effects of cancer treatments: Bases, results and perspectives]. / Photobiomodulation dans la prévention et la prise en charge des effets secondaires des traitements anticancéreux : bases, bilan et perspectives.

BACKGROUND: Assess the current and potential indications of photobiomodulation (PBM) therapy and their level of evidence in the prevention or treatment of side effects related to oncology treatments (radiation therapy, and to a minimal extent favored and hematopoietic stem cell transplants). And report on the recommended modalities (parameters and doses) of PBM therapy. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that evaluated PBM in the prevention or management side effects related to cancer treatments. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "dysgeusia"; "hyposalivation"; "lockjaw"; "bone necrosis"; "osteoradionecrosis"; "radiation induced fibrosis"; "voice and speech alterations"; "palmar-plantar erythrodysesthesia"; "graft versus host disease"; "peripheral neuropathy"; "chemotherapy induced alopecia". Prospective studies were included, while retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has been shown to be effective in randomized controlled trials in the prevention and management of certain complications related to radiotherapy, in particular acute mucositis, epitheliitis and upper limb lymphedema. The level of evidence associated with PBM was heterogeneous, but overall remained moderate. The main limitations were the diversity and the lack of precision of the treatment protocols which could compromise the efficiency and the reproducibility of the results of the PBM. For other effects related to chemo/radiation therapy (dysgeusia, osteonecrosis, peripheral neuropathy, alopecia, palmar-plantar erythrodysaesthesia) and haematopoietic stem cell transplantation (graft versus host disease), treatment with PBM suffers from a lack of studies or limited studies at the origin of a weakened level of proof. However, based on these results, it was possible to establish safe practice parameters and doses of PBM. CONCLUSION: Published data suggest that PBM could therefore be considered as supportive care in its own right for patients treated with radiation, chemotherapy, immunotherapy, hormone therapy or targeted therapies, whether in clinical practice or clinical trials. therapies. However, until solid data have been published on its long-term safety, the use of PBM should be considered with caution and within the recommended parameters and doses, particularly when practiced in areas of known or possible tumours. In this case, the patient should be informed of the theoretical benefits and risks of PBM in order to obtain informed consent before treatment.

Dual-Scan Photoacoustic Tomography for the Imaging of Vascular Structure on Foot.

Chronic leg ulcers are affecting approximately 6.5 million Americans, and they are associated with significant mortality, reduced quality of life, and high treatment costs. Since many chronic ulcers have underlying vascular insufficiency, accurate assessment of tissue perfusion is critical to treatment planning and monitoring. This study introduces a dual-scan photoacoustic (PA) tomography (PAT) system that can simultaneously image the dorsal and plantar sides of the foot to reduce imaging time. To account for the unique shape of the foot, the system employs height-adjustable and articulating baseball stages that can scan along the foot's contour. In vivo results from healthy volunteers demonstrate the system's ability to acquire clear images of foot vasculature, and results from patients indicate that the system can image patients with various ulcer conditions. We also investigated various PA features and examined their correlation with the foot condition. Our preliminary results indicate that vessel sharpness, occupancy, intensity, and density could all be used to assess tissue perfusion. This research demonstrated the potential of PAT for routine clinical tissue perfusion assessment.

Medication-Related Osteonecrosis of the Jaw: Successful Medical Management of Complex Maxillary Alveolus with Sinus Involvement.

Medication-related osteonecrosis of the jaw (MRONJ) in cancer patients presents a considerable challenge in management. Current management is primarily based on interventions in a limited number of cases assessing a single approach. Medical management typically is reported to include antimicrobial therapy with or without surgery. Advances in the understanding of pathogenesis have led to the investigation of additional medical interventions for early-stage necrosis. We present 3 patients with advanced-stage MRONJ of the maxilla using combined medical modalities including antimicrobial therapy, photobiomodulation therapy, pentoxifylline, vitamin E, and synthetic parathyroid hormone. All patients had a good outcome and avoided surgical intervention. We also report biological and functional imaging that may assist in more effective diagnosis and management of MRONJ. The 3 patients reported suggest that combined medical management should be considered in all cases of MRONJ (including stage III) prior to determining if surgical intervention is required. Functional imaging with a technetium bone scan or positron emission tomography scan correlated with diagnosis and confirmed resolution in patients. We present 3 challenging MRONJ patients that were effectively managed with a combined medical and nonsurgical therapy that demonstrated good clinical outcomes avoiding surgical interventions.

Quality assessment of PBM protocols for oral complications in head and neck cancer patients: part 2.

PURPOSE: To investigate the role of photobiomodulation (PBM) in patients undergoing head and neck cancer (HNC) treatment. We focused on the consequences of the main complications, such as quality of life (QoL), analgesia, functional impairment, and nutritional status, as well as on the impact on survival/ recurrences, radiotherapy (RT) interruption, adherence, cost-effectiveness, safety, feasibility, and tolerability. METHODS: An electronic search in PubMed and Scopus databases was performed. Full texts were carefully assessed, and data were assimilated into a tabular form for discussion and consensus among the expert panel. RESULTS: A total of 22 papers were included. Overall, a beneficial effect of PBM was evidenced in the amelioration of QoL, nutritional status, the reduction of pain, and functional impairment. Preventive PBM may reduce the incidence and duration of RT interruptions, potentially contributing to improved cancer treatment outcomes. PBM treatments are safe and recommended for routine use, with the caveat of avoiding direct tumor exposures where feasible. However, it does not appear to impact cancer survivorship/recurrences directly. Despite additional clinical efforts involving routine PBM use, the individual and public health benefits will positively impact oncology care. CONCLUSIONS: Quality of life, pain and functional impairment, nutritional status, and survival may be effectively improved with PBM. Given its established efficacy also in reducing RT interruptions and its safety, feasibility, and tolerability, PBM should be included in the field of supportive cancer care in HNC patients. Improved understanding of PBM mechanisms and precise dose parameters is enabling the generation of more robust, safe, and reproducible protocols; thus, it is imperative to support further clinical implementation as well as both applied and basic science research in this novel field.

Use of either transcranial or whole-body photobiomodulation treatments improves COVID-19 brain fog.

There is increasing recognition of post-COVID-19 sequelae involving chronic fatigue and brain fog, for which photobiomodulation (PBM) therapy has been utilized. This open-label, pilot, human clinical study examined the efficacy of two PBM devices, for example, a helmet (1070 nm) for transcranial (tPBM) and a light bed (660 and 850 nm) for whole body (wbPBM), over a 4-week period, with 12 treatments for two separate groups (n = 7 per group). Subjects were evaluated with a neuropsychological test battery, including the Montreal Cognitive Assessment (MoCA), the digit symbol substitution test (DSST), the trail-making tests A and B, the physical reaction time (PRT), and a quantitative electroencephalography system (WAVi), both pre- and post- the treatment series. Each device for PBM delivery was associated with significant improvements in cognitive tests (p < 0.05 and beyond). Changes in WAVi supported the findings. This study outlines the benefits of utilizing PBM therapy (transcranial or whole-body) to help treat long-COVID brain fog.

Photobiomodulation therapy mitigates cardiovascular aging and improves survival.

BACKGROUND: Photobiomodulation (PBM) therapy, a form of low-dose light therapy, has been noted to be effective in several age-associated chronic diseases such as hypertension and atherosclerosis. Here, we examined the effects of PBM therapy on age-associated cardiovascular changes in a mouse model of accelerated cardiac aging. METHODS: Fourteen months old Adenylyl cyclase type VIII (AC8) overexpressing transgenic mice (n = 8) and their wild-type (WT) littermates (n = 8) were treated with daily exposure to Near-Infrared Light (850 nm) at 25 mW/cm2 for 2 min each weekday for a total dose of 1 Einstein (4.5 p.J/cm2 or fluence 3 J/cm2 ) and compared to untreated controls over an 8-month period. PBM therapy was administered for 3.5 months (Early Treatment period), paused, due to Covid-19 restrictions for the following 3 months, and restarted again for 1.5 months. Serial echocardiography and gait analyses were performed at monthly intervals, and serum TGF-ß1 levels were assessed following sacrifice. RESULTS: During the Early Treatment period PBM treatments: reduced the age-associated increases in left ventricular (LV) mass in both genotypes (p = 0.0003), reduced the LV end-diastolic volume (EDV) in AC8 (p = 0.04); and reduced the left atrial dimension in both genotypes (p = 0.02). PBM treatments substantially increased the LV ejection fraction (p = 0.03), reduced the aortic wall stiffness (p = 0.001), and improved gait symmetry, an index of neuro-muscular coordination (p = 0.005). The effects of PBM treatments, measured following the pause, persisted. Total TGF-ß1 levels were significantly increased in circulation (serum) in AC8 following PBM treatments (p = 0.01). We observed a striking increase in cumulative survival in PBM-treated AC8 mice (100%; p = 0.01) compared to untreated AC8 mice (43%). CONCLUSION: PBM treatment mitigated age-associated cardiovascular remodeling and reduced cardiac function, improved neuromuscular coordination, and increased longevity in an experimental animal model. These responses correlate with increased TGF-ß1 in circulation. Future mechanistic and dose optimization studies are necessary to assess these anti-aging effects of PBM, and validation in future controlled human studies is required for effective clinical translation.

Automation in Dentistry with Mechanical Drills and Lasers for Implant Osteotomy: A Narrative-Scoping Review.

The popularity of implants is increasing with the aging population requiring oral-dental rehabilitation. There are several critical steps in the implant workflow, including case selection, implant design, surgical procedure, biological tissue responses, and functional restoration. Among these steps, surgical osteotomy procedures are a crucial determinant of clinical success. This brief review was aimed at outlining the current state of the field in automation-assisted implant surgical osteotomy technologies. A broad search of the literature was performed to identify current literature. The results are outlined in three broad categories: semi-automated static (image-guided) or dynamic (navigation-assisted) systems, and fully-automated robotic systems. As well as the current mechanical rotary approaches, the literature supporting the use of lasers in further refinement of these approaches is reviewed. The advantages and limitations of adopting autonomous technologies in practical clinical dental practices are discussed. In summary, advances in clinical technologies enable improved precision and efficacious clinical outcomes with implant dentistry. Hard-tissue lasers offer further advancements in precision, improved biological responses, and favorable clinical outcomes that require further investigation.

Quality Assessment of PBM Protocols for Oral Complications in Head and Neck Cancer Patients: Part 1.

Background: Radiotherapy and chemotherapy are frequently employed in head and neck cancer (HNC) patients causing significant side effects that impair life quality and prognosis. Photobiomodulation (PBM) has become a growing approach to managing such oral complications. Despite its proven efficacy and absence of contraindications, there is still a lack of universally accepted disease-specific PBM protocols. Objective: A narrative review was conducted to identify the current proposals relating to the use of PBM to treat complications of oncological treatments in HNC patients. Methods: An electronic search in PubMed and Scopus databases was performed with the following keywords: ("photobiomodulation" OR "PBM" OR "laser therapy" OR "LLLT" OR "laser") AND ("head and neck cancer" OR "oral cancer") AND ("mucositis" OR "oral mucositis" OR "dysgeusia" OR "oedema" OR "xerostomia" OR "dermatitis" OR "trismus") until October 2021. Results: A total of 35 papers were included in the narrative review. Oral mucositis was the most studied complication, and advisable protocols are conceivable. Although there is a growing interest in PBM to manage of xerostomia, radiodermatitis, pain, and trismus, literature is still scarce to propose a universally feasible protocol. Conclusions: PBM therapy could significantly prevent or reduce the severity of many side effects related to cancer therapies. More research is needed to obtain recommendations over the preferable parameters.

Redox signaling induces laminin receptor ribosomal protein-SA expression to improve cell adhesion following radiofrequency glow discharge treatments.

Current biomaterials effectively replace biological structures but are limited by infections and long-term material failures. This study examined the molecular mechanisms of radio frequency glow discharge treatments (RFGDT) in mediating the disinfection of biomaterial surfaces and concurrently promoting cell attachment and proliferation. Dental biomaterials were subjected to RFGDT, and viability of oral microbial species, namely Streptococcus mutants (SM), Streptococcus gordonii (SG), Moraxella catarrhalis (MC), and Porphyromonas gingivalis (PG), were assessed. Cell attachment and survival of a pre-odontoblast cell line, MDPC-23, was examined. Finally, mechanistic investigations into redox generation and biological signaling were investigated. Based on their compositions, dental biomaterials induced reactive oxygen species (ROS) following dose-dependent RFGDT. Reduced microbial viability was evident following RFGDT in the catalase-negative (SM and SG) species more prominently than catalase-positive (MC and PG) species. Cell adhesion assays noted improved MDPC-23 attachment and survival. Pretreatments with N-acetylcysteine (NAC) and catalase abrogated these responses. Immunoassays noted redox-induced downstream expression of a laminin receptor, Ribosomal Protein SA, following RFGDT. Thus, RFGDT-induced redox mediates antimicrobial and improves cell responses such as adhesion and proliferation. These observations together provide a mechanistic rationale for the clinical utility of RFGDT with dental biomaterials for regenerative clinical applications.

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues.

The major difference between tissue healing and regeneration is the extent of instructional cues available to precisely direct the biological response. A classic example is reparative or osteodentin that is seen in response to physicochemical injury to the pulp-dentin complex. Dentin regeneration can direct the differentiation of dental stem cells using concerted actions of both soluble (biomolecules, agonists, and antagonists) and insoluble (matrix topology) cues. The major purpose of this study was to examine the synergistic combination of two discrete biomaterial approaches by utilizing nanofiber scaffolds in discrete configurations (aligned or random) with incorporated polymeric microspheres capable of controlled release of growth factors. Further, to ensure appropriate disinfection for clinical use, Radio-Frequency Glow Discharge (RFGD) treatments were utilized, followed by seeding with a mesenchymal stem cell (MSC) line. SEM analysis revealed electrospinning generated controlled architectural features that significantly improved MSC adhesion and proliferation on the aligned nanofiber scaffolds compared to randomly oriented scaffolds. These responses were further enhanced by RFGD pre-treatments. These enhanced cell adhesion and proliferative responses could be attributed to matrix-induced Wnt signaling that was abrogated by pre-treatments with anti-Wnt3a neutralizing antibodies. Next, we incorporated controlled-release microspheres within these electrospun scaffolds with either TGF-ß1 or BMP4. We observed that these scaffolds could selectively induce dentinogenic or osteogenic markers (DSPP, Runx2, and BSP) and mineralization. This work demonstrates the utility of a novel, modular combinatorial scaffold system capable of lineage-restricted differentiation into bone or dentin. Future validation of this scaffold system in vivo as a pulp capping agent represents an innovative dentin regenerative approach capable of preserving tooth pulp vitality.

Thermodynamic basis for comparative photobiomodulation dosing with multiple wavelengths to direct odontoblast differentiation.

Multiple wavelength devices are now available for photobiomodulation (PBM) treatments, but their dosimetry for individual or combinatorial use remains unclear. The present work investigated the effects of 447, 532, 658, 810, 980 and 1064 nm wavelengths on odontoblast differentiation at 10 mW/cm2 using either equal treatment time for conventional fluence (300 seconds for 3 J/cm2 ) or varying times to adjust for individual wavelength photon fluence (4.6 p.J/cm2 ). Both 447 and 810 nm significantly increased alkaline phosphatase (ALP) activity, while 1064 nm showed reduced ALP activity at 3 J/cm2 . However, ALP induction was significantly improved when equivalent photon fluence dosing was used. Other wavelengths did not show significant changes compared to untreated controls. The data suggest that accounting for wavelength-specific photon energy transfer during PBM dosing could improve clinical safety and efficacy.

Enhancing osteoblast differentiation through small molecule-incorporated engineered nanofibrous scaffold.

OBJECTIVE: This study aimed to investigate the effect of small molecules incorporated into the engineered nanofibrous scaffold to enhance the osteoblast differentiation MATERIALS AND METHODS: Poly-ε-caprolactone (PCL) nanofiber matrices with lithium chloride (LiCl) were fabricated using the electrospinning technique. Scaffolds were characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). Scaffolds were seeded with MC3T3-E1 cells and assessed using Western blots (ß-catenin), alamarBlue assay (proliferation), qPCR (osteoblast differentiation), and mineralization (Alizarin Red staining). RESULTS: We observed LiCl nanofiber scaffolds induced concentration-dependent cell proliferation that correlated with an increased ß-catenin expression indicating sustained Wnt signaling. Next, we examined osteoblast differentiation markers such as osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) and noted increased expression in LiCl nanofiber scaffolds. We also noted increased bone morphogenetic protein (BMP-2, 4, and 7) expressions suggesting activated Wnt can promote cures to further osteogenic differentiation. Finally, Alizarin Red staining demonstrated increased mineral deposition in LiCl-incorporated nanofiber scaffolds. CONCLUSIONS: Together, these results indicated that LiCl-incorporated nanofiber scaffolds enhance osteoblast differentiation. CLINICAL RELEVANCE: Small molecule-incorporated nanofibrous scaffolds are an innovative clinical tool for bone tissue engineering.

Photobiomodulation-Activated Latent Transforming Growth Factor-ß1: A Critical Clinical Therapeutic Pathway and an Endogenous Optogenetic Tool for Discovery.

Objective: The central role of the TGF-ß pathway in embryonic development, immune responses, tissue healing, and malignancies is well established. Prior attempts with small molecules, peptides, and regulatory RNAs have failed mainly due to off-target effects in clinical studies. This review outlines the evidence for selectively activating the endogenous, latent transforming growth factor (TGF)-ß1 with photobiomodulation (PBM) treatments. Background: Light treatments play a central role in current-directed energy therapeutics in medicine. Therapeutic use of low-dose light treatments has been noted since the 1960s. However, the breadth of treatments and inconsistencies with clinical outcomes have led to much skepticism. This can be primarily attributed to a lack of understanding of the fundamental light-tissue interactions and optimization of clinical treatment protocols. Methods: Recent advances in molecular mechanisms and improved biophotonic device technologies have led to a resurgence of interest in this field. Results: Over the past two decades, our work has focused on outlining a direct molecular mechanism involving PBM-generated redox-mediated activation of endogenous latent TGF-ß1. Conclusions: Despite its critical roles in these processes, the complexity and cross talk in this potent growth factor signaling network have prevented the development of directed targeted therapeutics. PBM treatments offer a novel therapeutic and discovery tool in this aspect, especially with the growing evidence for its roles in cancer immunotherapy and stem cell biology.

Virtual Planning and Rapid 3D Prototyping Surgical Guide for Anterior Crown Lengthening Surgery: A Clinical Case Report.

Progress with additive 3D printing is revolutionizing biomaterial manufacturing, including clinical dentistry and prosthodontics. Among the several 3D additive printing technologies, stereolithography is very popular as it utilizes light-activated resin for precise resolution. A simplified digital technique was used to fabricate two designs of a surgical guide for crown lengthening. Two cases are presented that utilized digital imaging and communications in medicine (DICOM) files obtained with computed tomography (CT) imaging and processed using four CAD software (Blue Sky Plan, Exocad, Meshmixer and 3D Slicer). The final models were converted to standard tessellation (STL) files and the guides were 3D printed with an additive stereolithography (SLA) printer. The first case was fabricated with a bone model from cone beam computed tomography (CBCT) data, and the second case was generated with intraoral and wax-up scans alone. Both methods appear to be equally effective compared to using a conventional method of guide frabication. However, proximal bone reduction was a concern with both designs. Digitally fabricated 3D printed surgical guide for crown lengthening has merit and a practical design is needed for future clinical validation.

Effects of Near-Infrared Light on Well-Being and Health in Human Subjects with Mild Sleep-Related Complaints: A Double-Blind, Randomized, Placebo-Controlled Study.

Modern urban human activities are largely restricted to the indoors, deprived of direct sunlight containing visible and near-infrared (NIR) wavelengths at high irradiance levels. Therapeutic exposure to doses of red and NIR, known as photobiomodulation (PBM), has been effective for a broad range of conditions. In a double-blind, randomized, placebo-controlled study, we aimed to assess the effects of a PBM home set-up on various aspects of well-being, health, sleep, and circadian rhythms in healthy human subjects with mild sleep complaints. The effects of three NIR light (850 nm) doses (1, 4, or 6.5 J·cm-2) were examined against the placebo. Exposure was presented five days per week between 9:30 am and 12:30 pm for four consecutive weeks. The study was conducted in both summer and winter to include seasonal variation. The results showed PBM treatment only at 6.5 J·cm-2 to have consistent positive benefits on well-being and health, specifically improving mood, reducing drowsiness, reducing IFN-γ, and resting heart rate. This was only observed in winter. No significant effects on sleep or circadian rhythms were noted. This study provides further evidence that adequate exposure to NIR, especially during low sunlight conditions, such as in the winter, can be beneficial for human health and wellness.

Safety and efficacy of citric acid-upconverting nanoparticles for multimodal biological imaging in BALB/c mice.

There has been significant progress with rare-earth coated upconversion nanoparticles (UCNPs) representing a promising new generation of contrast agents for biomedical applications. However, in vivo biological safety remains poorly investigated. This work examined citric acid-UCNP (NaYF4:Yb3+/Gd3+, ∼ 5 nm, Cit-UCNP) generated as contrast agents for multimodal imaging with concurrent magnetic resonance (MRI) and X-ray computed tomography (CT). We first examined the in vitro cytotoxicity and efficacy of Cit-UCNPs as a contrast agent. We then performed a systematic investigation of their in vivo biodistribution and biocompatibility. Our results noted that Cit-UCNPs have minimal toxicity and demonstrated significant potential as contrast agents for multimodal biomedical imaging. This study indicates Cit-UCNPs could be a valuable addition to enhance long-term targeted diagnostic and prognostic multimodal clinical imaging approaches.

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-ß1.

The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-ß1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-ß signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-ß dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-ß1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-ß1/ß3 knock-in (TGF-ß1Lß3/Lß3) mice. PBM treatments failed to activate the chimeric TGF-ß1Lß3/Lß3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-ß1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.

Additive 3-dimensional printing as a novel tool for pre- and postsurgical evaluation and patient education: A clinical case series.

BACKGROUND AND OVERVIEW: In contrast to subtractive 3-dimensional (3D) techniques synonymous with computer-aided design and computer-aided manufacturing, rapid progress in additive 3D printing, especially fused filament fabrication or fused deposition modeling, can change the practice of dentistry. CASE DESCRIPTION: In this article, the authors outline the digital workflow for fused filament fabrication and fused deposition modeling 3D printing that involves converting a Digital Imaging and Communications in Medicine file (scan or radiograph) to a printable Standard Triangle Language file that can be modified (additions or manipulations) using a readily accessible software for 3D printing. The authors also present a clinical case series showing various applications for this technique, including clinician and patient education, treatment planning, and posttreatment evaluations. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The low cost and simple workflow of additive 3D printing has potential to improve precision and efficiency in clinical dentistry for both academic and private practices.

Role of programmed cell death 4 in myofibroblast differentiation in oral submucous fibrosis.

Background: Fibrosis is an uncontrolled healing process, led by persistent differentiation of fibroblast to alpha-smooth muscle actin (αSMA) positive activated fibroblast or myofibroblast. Oral submucous fibrosis (OSMF) is one such condition that is associated with areca nut use. Recently, Programmed Cell Death 4 (PDCD4), a pro-apoptotic marker, has been shown to modulate fibroblast differentiation in various organ fibrosis. The present study aimed to evaluate the role of PDCD4 in the regulation of fibroblast differentiation in OSMF. Materials and Methods: Paraffin-embedded tissue sections from 45 cases of the normal oral mucosa, early OSMF and advanced OSMF were examined for PDCD4 and αSMA expression by immunostaining. Co-expression of PDCD4 and αSMA in fibroblasts was examined using Spearman's correlation test. Results: The stromal fibroblasts showed minimal expression of αSMA in the normal mucosa and early OSMF, while advanced OSMF groups demonstrated a higher frequency of αSMA myofibroblasts. The PDCD4 expression was noted in the normal stromal fibroblasts. However, this expression appeared to progressively reduce with an increasing grade of OSMF. Thus, a negative correlation was noted between stromal PDCD4 and αSMA expression with progressive OSMF. Conclusion: This study demonstrated a putative role for PDCD4 in oral fibrosis consistent with its role in other tissues. The lack of PDCD4 expression with increasing myofibroblast expression in OSMF suggests that targeting its dysregulation may be an attractive translational therapeutic target.