Lipoic acid alters the microRNA signature in breast cancer cells.

BACKGROUND: Breast cancer, the deadliest disease affecting women globally, exhibits heterogeneity with distinct molecular subtypes. Despite advances in cancer therapy, the persistence of high mortality rates due to chemotherapy resistance remains a major challenge. Lipoic acid (LA), a natural antioxidant, has proven potent anticancer properties. Yet, the impact of LA on microRNA (miRNA) expression profile in breast cancer remains unexplored. AIM: The aim of this study was to unravel the effect of LA on miRNA expression profiles in different breast cancer cell lines. METHODS: The MiRCURY LNA miRNA miRNome qPCR Panel was used to compare the miRNA signature in MDA-MB-231 and MCF-7 cells treated or not with LA. RESULTS: We identified six upregulated and six downregulated miRNAs in LA-treated MDA-MB-231 cells and 14 upregulated and four downregulated miRNAs in LA-treated MCF-7 cells compared to control cells. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis revealed that the deregulated miRNAs could alter different signaling cascades including FoxO, P53 and Hippo pathways. CONCLUSION: The outcome of this study provides further insights into the molecular mechanisms underlying the therapeutic benefit of LA. This in turn could assist the amelioration of LA-based anticancer therapies.

Characterization of circulating leptin-receptor levels following acute sleep restriction: A pilot study on healthy adult females.

BACKGROUND: Insufficient sleep adversely affects energy homeostasis by decreasing leptin levels. The underlying physiological mechanisms; however, remain unclear. Circulating leptin is well described to be regulated by its soluble receptor (sOB-R). Intriguingly, the impact of short sleep duration on sOB-R levels has never been characterized. AIM: In this study, we investigated, for the first time, the variation of sOB-R levels and its temporal relationship with circulating leptin upon acute sleep restriction. METHODS: Five adult females were maintained on an 8-hour sleep schedule (bedtime at 00:00) for 1 week before restricting their sleep to 4.5 h (bedtime at 03:30) on 2 consecutive nights. Balanced meals were scheduled to specific hours and sleep was objectively measured. Four-hour blood samples were regularly collected during waking hours between 08:00 and 00:00. RESULTS: Sleep restriction resulted in lower leptin (20.9 ± 1.7 vs 25.7 ± 1.7 ng/ml) and higher sOB-R concentrations (24.4 ± 1.2 vs 19.8 ± 1.6 ng/ml). Neither the discordant temporal relationship nor the pattern of leptin and sOB-R were altered in response to sleep restriction. CONCLUSION: Our results suggest that sleep restriction may modulate circulating leptin levels and possibly metabolism via upregulating its soluble receptor. This observation may have valuable therapeutic implications when considering sOB-R as a potential target during the management of metabolic disturbances.

Circulating microRNA profile in response to remdesivir treatment in coronavirus disease 2019 (COVID-19) patients.

Coronavirus disease 2019 (COVID-19), a serious infectious disease caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health crisis. Although no specific antiviral drugs have been proven to be fully effective against COVID-19, remdesivir (GS-5734), a nucleoside analogue prodrug, has shown beneficial effects when used to treat severe hospitalized COVID-19 cases. The molecular mechanism underlying this beneficial therapeutic effect is still vaguely understood. In this study, we assessed the effect of remdesivir treatment on the pattern of circulating miRNAs in the plasma of COVID-19 patients, which was analyzed using MiRCURY LNA miRNA miRNome qPCR Panels and confirmed by quantitative real-time RT-PCR (qRT-PCR). The results revealed that remdesivir treatment can restore the levels of miRNAs that are upregulated in COVID-19 patients to the range observed in healthy subjects. Bioinformatics analysis revealed that these miRNAs are involved in diverse biological processes, including the transforming growth factor beta (TGF-ß), hippo, P53, mucin-type O-glycan biosynthesis, and glycosaminoglycan biosynthesis signaling pathways. On the other hand, three miRNAs (hsa-miR-7-5p, hsa-miR-10b-5p, and hsa-miR-130b-3p) were found to be upregulated in patients receiving remdesivir treatment and in patients who experienced natural remission. These upregulated miRNAs could serve as biomarkers of COVID-19 remission. This study highlights that the therapeutic potential of remdesivir involves alteration of certain miRNA-regulated biological processes. Targeting of these miRNAs should therefore be considered for future COVID-19 treatment strategies.

Human CD4+CD25+CD127lowFOXP3+ regulatory T lymphocytes and CD4+CD25-FOXP3- conventional T lymphocytes: a differential transcriptome profile.

CD4+CD25+ FOXP3+ regulatory T cells (Tregs) represent a subpopulation of CD4+ T cells central for the suppression of physiological and pathological immune reactions. Although distinct cell surface antigens are expressed in regulatory T cells, those components are also present on the surface of activated CD4+CD25- FOXP3-T cells, thus making the discrimination between Tregs and conventional CD4+ T difficult and isolation of Tregs complex. Yet, the molecular components driving Tregs' function are still not fully characterized. Aiming at unraveling molecular components specifically marking Tregs, and upon using quantitative real-time PCR (qRT-PCR) followed by bioinformatics analysis, we identified, in this study, differential transcriptional profiles, in peripheral blood CD4 + CD25 + CD127low FOXP3+ Tregs versus CD4 + CD25-FOXP3- conventional T cells, for set of genes with distinct immunological roles. In conclusion, this study identifies some novel genes that appeared to be differentially transcribed in CD4+ Tregs versus conventional T cells. The identified genes could serve as novel molecular targets relevant to Tregs' function and isolation.

Effect of Ultraviolet Radiation and Benzo[a]pyrene Co-Exposure on Skin Biology: Autophagy as a Potential Target.

The skin is the outermost protective barrier of the human body. Its role is to protect against different physical, chemical, biological and environmental stressors. The vast majority of studies have focused on investigating the effects of single environmental stressors on skin homeostasis and the induction of several skin disorders, such as cancer or ageing. On the other hand, much fewer studies have explored the consequences of the co-exposure of skin cells to two or more stressors simultaneously, which is much more realistic. In the present study, we investigated, using mass-spectrometry-based proteomic analysis, the dysregulated biological functions in skin explants after their co-exposure to ultraviolet radiation (UV) and benzo[a]pyrene (BaP). We observed that several biological processes were dysregulated, among which autophagy appeared to be significantly downregulated. Furthermore, immunohistochemistry analysis was carried out to validate the downregulation of the autophagy process further. Altogether, the output of this study provides an insight into the biological responses of skin to combined exposure to UV + BaP and highlights autophagy as a potential target that might be considered in the future as a novel candidate for pharmacological intervention under such stress conditions.

Glutamine transport as a possible regulator of nitrogen catabolite repression in Saccharomyces cerevisiae.

Nitrogen catabolite repression (NCR) is a major transcriptional control pathway governing nitrogen use in yeast, with several hundred of target genes identified to date. Early and extensive studies on NCR led to the identification of the 4 GATA zinc finger transcription factors, but the primary mechanism initiating NCR is still unclear up till now. To identify novel players of NCR, we have undertaken a genetic screen in an NCR-relieved gdh1Δ mutant, which led to the identification of four genes directly linked to protein ubiquitylation. Ubiquitylation is an important way of regulating amino acid transporters and our observations being specifically observed in glutamine-containing media, we hypothesized that glutamine transport could be involved in establishing NCR. Stabilization of Gap1 at the plasma membrane restored NCR in gdh1Δ cells and AGP1 (but not GAP1) deletion could relieve repression in the ubiquitylation mutants isolated during the screen. Altogether, our results suggest that deregulated glutamine transporter function in all three weak nitrogen derepressed (wnd) mutants restores the repression of NCR-sensitive genes consecutive to GDH1 deletion.

The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings.

In recent decades, research on the therapeutic potential of progenitor cells has advanced considerably. Among progenitor cells, mesenchymal stromal cells (MSCs) have attracted significant interest and have proven to be a promising tool for regenerative medicine. MSCs are isolated from various anatomical sites, including bone marrow, adipose tissue, and umbilical cord. Advances in separation, culture, and expansion techniques for MSCs have enabled their large-scale therapeutic application. This progress accompanied by the rapid improvement of transplantation practices has enhanced the utilization of MSCs in regenerative medicine. During tissue healing, MSCs may exhibit several therapeutic functions to support the repair and regeneration of injured tissue. The process underlying these effects likely involves the migration and homing of MSCs, as well as their immunotropic functions. The direct differentiation of MSCs as a cell replacement therapeutic mechanism is discussed. The fate and behavior of MSCs are further regulated by their microenvironment, which may consequently influence their repair potential. A paracrine pathway based on the release of different messengers, including regulatory factors, chemokines, cytokines, growth factors, and nucleic acids that can be secreted or packaged into extracellular vesicles, is also implicated in the therapeutic properties of MSCs. In this review, we will discuss relevant outcomes regarding the properties and roles of MSCs during tissue repair and regeneration. We will critically examine the influence of the local microenvironment, especially immunological and inflammatory signals, as well as the mechanisms underlying these therapeutic effects. Importantly, we will describe the interactions of local progenitor and immune cells with MSCs and their modulation during tissue injury. We will also highlight the crucial role of paracrine pathways, including the role of extracellular vesicles, in this healing process. Moreover, we will discuss the therapeutic potential of MSCs and MSC-derived extracellular vesicles in the treatment of COVID-19 (coronavirus disease 2019) patients. Overall, this review will provide a better understanding of MSC-based therapies as a novel immunoregenerative strategy.

Circulating miRNAs: Potential diagnostic role for coronavirus disease 2019 (COVID-19).

Nowadays, the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major global health problem. Intensive efforts are being employed to better understand this pathology and develop strategies enabling its early diagnosis and efficient treatment. In this study, we compared the signature of circulating miRNAs in plasma of COVID-19 patients versus healthy donors. MiRCURY LNA miRNA miRNome qPCR Panels were performed for miRNA signature characterization. Individual quantitative real-time PCR (qRT-PCR) was carried out to validate miRNome qPCR results. Receiver-operator characteristic (ROC) curve analysis was applied to assess the diagnostic accuracy of the most significantly deregulated miRNA(s) as potential diagnostic biomarker(s). Eight miRNAs were identified to be differentially expressed with miR-17-5p and miR-142-5p being down-regulated whilst miR-15a-5p, miR-19a-3p, miR-19b-3p, miR-23a-3p, miR-92a-3p and miR-320a being up-regulated in SARS-CoV-2-infected patients. ROC curve analyses revealed an AUC (Areas Under the ROC Curve) of 0.815 (P = 0.031), 0.875 (P = 0.012), and 0.850 (P = 0.025) for miR-19a-3p, miR-19b-3p, and miR-92a-3p, respectively. Combined ROC analyses using these 3 miRNAs showed a greater AUC of 0.917 (P = 0.0001) indicating a robust diagnostic value of these 3 miRNAs. These results suggest that plasma miR-19a-3p, miR-19b-3p, and miR-92a-3p expression levels could serve as potential diagnostic biomarker and/or a putative therapeutic target during SARS-CoV-2-infection.

Isoconazole and Clemizole Hydrochloride Partially Reverse the Xeroderma Pigmentosum C Phenotype.

Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyper-photosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6-4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals.

Osteogenic potential of dental and oral derived stem cells in bone tissue engineering among animal models: An update.

Small bone defects can heal spontaneously through the bone modeling process due to their physiological environmental conditions. The bone modeling cycle preserves the reliability of the skeleton through the well-adjusted activities of its fundamental cell. Stem cells are a source of pluripotent cells with a capacity to differentiate into any tissue in the existence of a suitable medium. The concept of bone engineering is based on stem cells that can differentiate into bone cells. Mesenchymal stromal cells have been evaluated in bone tissue engineering due to their capacity to differentiate in osteoblasts. They can be isolated from bone marrow and from several adults oral and dental tissues such as permanent or deciduous teeth dental pulp, periodontal ligament, apical dental papilla, dental follicle precursor cells usually isolated from the follicle surrounding the third molar, gingival tissue, periosteum-derived cells, dental alveolar socket, and maxillary sinus Schneiderian membrane-derived cells. Therefore, a suitable animal model is a crucial step, as preclinical trials, to study the outcomes of mesenchymal cells on the healing of bone defects. We will discuss, through this paper, the use of mesenchymal stem cells obtained from several oral tissues mixed with different types of scaffolds tested in different animal models for bone tissue engineering. We will explore and link the comparisons between human and animal models and emphasized the factors that we need to take into consideration when choosing animals. The pig is considered as the animal of choice when testing large size and multiple defects for bone tissue engineering.

Comparing the osteogenic potential of schneiderian membrane and dental pulp mesenchymal stem cells: an in vitro study.

Mesenchymal stem cells, being characterized by high self-renewal capacity and multi-lineage differentiation potential, are widely used in regenerative medicine especially for repair of bone defects in patients with poor bone regenerative capacity. In this study, we aimed to compare the osteogenic potential of human maxillary schneiderian sinus membrane (hMSSM)-derived stem cells versus permanent teeth dental pulp stem cells (DPSCs). Both cells types were cultivated in osteogenic and non-osteogenic inductive media. Alkaline phosphatase (ALP) activity assay and quantitative real-time PCR analysis were carried out to assess osteogenic differentiation. We showed that ALP activity and osteoblastic markers transcription levels were more striking in hMSSM-derived stem cells than DPSCs. Our results highlight hMSSM-derived stem cells as a recommended stem cell type for usage during bone tissue regenerative therapy.

Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization.

Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms underlying their immune and trophic effects imply the secretion of various mediators rather than direct cellular contact. These mediators can be packaged in extracellular vesicles, thus paving the way to exploit therapeutic cell-free products derived from MSCs. Of importance, the function of MSCs and their secretome are significantly sensitive to their environment. Several features, such as culture conditions, delivery method, therapeutic dose and the immunobiology of MSCs, may influence their clinical outcomes. In this review, we will summarize recent findings related to MSC properties. We will also discuss the main preclinical and clinical challenges that may influence the therapeutic value of MSCs and discuss some optimization strategies.

Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage.

Xeroderma Pigmentosum C (XPC) is a multi-functional protein that is involved not only in the repair of bulky lesions, post-irradiation, via nucleotide excision repair (NER) per se but also in oxidative DNA damage mending. Since base excision repair (BER) is the primary regulator of oxidative DNA damage, we characterized, post-Ultraviolet B-rays (UVB)-irradiation, the detailed effect of three different XPC mutations in primary fibroblasts derived from XP-C patients on mRNA, protein expression and activity of different BER factors. We found that XP-C fibroblasts are characterized by downregulated expression of different BER factors including OGG1, MYH, APE1, LIG3, XRCC1, and Polß. Such a downregulation was also observed at OGG1, MYH, and APE1 protein levels. This was accompanied with an increase in DNA oxidative lesions, as evidenced by 8-oxoguanine levels, immediately post-UVB-irradiation. Unlike in normal control cells, these oxidative lesions persisted over time in XP-C cells having lower excision repair capacities. Taken together, our results indicated that an impaired BER pathway in XP-C fibroblasts leads to longer persistence and delayed repair of oxidative DNA damage. This might explain the diverse clinical phenotypes in XP-C patients suffering from cancer in both photo-protected and photo-exposed areas. Therapeutic strategies based on reinforcement of BER pathway might therefore represent an innovative path for limiting the drawbacks of NER-based diseases, as in XP-C case.

MicroRNAs in breast cancer: New maestros defining the melody.

MicroRNAs, short non-coding single-stranded RNAs, are important regulators and gatekeepers of the coding genes in the human genome. MicroRNAs are highly conserved among species and expressed in different tissues and cell types. They are involved in almost all the biological processes as apoptosis, proliferation, cell cycle arrest and differentiation. Playing all these roles, it is not surprising that the deregulation of the microRNA profile causes a number of diseases including cancer. Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Different microRNAs were shown to be up or down regulated in breast cancer. MicroRNAs can function as oncogenes or tumor suppressors according to their targets. In this review, the most common microRNAs implicated in breast cancer are fully illustrated with their targets. Besides, the review highlights the effect of exosomal microRNA on breast cancer and the effect of microRNAs on drug and therapies resistance as well as the miRNA-based therapeutic strategies used until today.

Differences in osteogenic and odontogenic differentiation potential of DPSCs and SHED.

OBJECTIVE: Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are types of human dental tissue-derived mesenchymal stem cells (MSCs) that have emerged as an interesting and promising source of stem cells in the field of tissue engineering. The aim of this work is to isolate stem cells from DPSCs and SHED, cultivate them in vitro and compare their odontogenic differentiation potential. METHODS: DPSCs and SHED were extracted from molars, premolars and canines of six healthy subjects aged 5-29 years. The cells were characterized, using flow cytometry, for mesenchymal stem cell surface markers. MTT colorimetric assay was applied to assess cell viability. Alizarin red staining, alkaline phosphatase (ALP) activity, quantitative real-time PCR (qRT-PCR) and western blot were carried out to determine DPSCs and SHED osteogenic/odontogenic differentiation. RESULTS: DPSCs express higher STRO-1 and CD44 levels compared to SHED. Moreover, the cells differentiate and acquire columnar shape with a level of calcium deposition and mineralization that is the same between DPSCs and SHED. ALP activity, ALP, COLI, DMP-1, DSPP, OC, and RUNX2 (osteogenic/odontogenic differentiation markers) expression levels were higher in DPSCs. CONCLUSIONS: DPSCs and SHED express MSCs markers. Although both cell types had calcium deposits, DPSCs presented a higher ALP activity level. In addition, DPSCs showed higher levels of osteogenic and odontogenic differentiation markers such as COLI, DSPP, OC, RUNX2, and DMP-1. These results suggest that DPSCs are closer to the phenotype of odontoblasts than SHED and may improve the efficacy of human dental tissue-derived mesenchymal stem cells therapeutic protocols. 'CLINICAL SIGNIFICANCE': DPSCs are closer than t SHED to the phenotype of odontoblasts. This would be helpful to enable better therapeutic decisions when applying MSCs-based therapy in the field of dentistry.

Immunomodulatory role for MicroRNAs: Regulation of PD-1/PD-L1 and CTLA-4 immune checkpoints expression.

The development and progression of different pathologies including, cancer, are associated with suppressed immune responses. This restrained immune activity could be associated with the activation of different immune checkpoint pathways that mediate immunosuppressive functions. Therapeutic Protocols based on abolishing the activity of immune check points provided a promising potential for treating cancer. Among the distinct known immune checkpoints, PD-1/PD-L1 and CTLA-4, are the most studied and have been the focus for development of different blocking agents. Monoclonal antibodies that can block PD-1, PD-L1 or CTLA4 have been approved for treatment of different cancers. MicroRNAs (miRNAs), short non-coding regulatory RNA molecules, could repress mRNA expression at a post-transcriptional level. Many miRNAs have been reported to modulate the expression of CTLA-4 and PD-1/PD-L1, either directly or indirectly, in multiple pathological cases, mainly cancer. In this review, after a brief introduction about T cell activation and immune checkpoints, the miRNAs regulating the expression of CTLA-4 and PD-1/PD-L1 are discussed with highlights on their role in cancer. Many of these miRNAs could serve as novel treatments in different types of cancer as detailed throughout the review.

The Effects of Intracanal Irrigants and Medicaments on Dental-Derived Stem Cells Fate in Regenerative Endodontics: An update.

Regenerative endodontics is a biologically based treatment designed for immature permanent teeth with necrotic pulp to replace dentin and root structures, as well as dental pulp cells. This procedure has become a part of novel modality in endodontics therapeutic manner, and it is considered as an alternative to apexification. In the last decade, numerous case reports, which describe this procedure, have been published. This therapeutic approach succeeded due to its lower financial cost and ease of performance. Although the clinical protocol of this procedure is not standardized and the effects of irrigants and medicaments on dental stem cells fate remain somewhat ambiguous, however when successful, it is an improvement of endodontics treatment protocols which leads to continued root development, increased dentinal wall thickness, and apical closure of immature teeth. To ensure a successful regenerative procedure, it is essential to investigate the appropriate disinfection protocols and the use of biocompatible molecules in order to control the release of growth factors and the differentiation of stem cells. This is the first review in the literature to summarize the present knowledge regarding the effect of intracanal irrigants and medicaments on the dental derived stem cells fate in regenerative endodontic procedures.

An update on human periapical cyst-mesenchymal stem cells and their potential applications in regenerative medicine.

The broad clinical applications of Mesenchymal Stem Cells (MSCs) in the regenerative medicine field is attributed to their ability to self-renew and differentiate into multiple cellular lineages. Nowadays, MSCs can be derived from a variety of adult and fetal tissues including bone marrow, adipose tissue, umbilical cord and placenta. The difficulties associated with the isolation of MSCs from certain tissues such as bone marrow promoted the search for alternative tissues which are easily accessible. Oral derived MSCs include dental pulp stem cells (DPSCs), dental follicle progenitor cells (DFPC), and periodontal ligament stem cells (PDLSC). Being abundant and easily accessible, oral derived MSCs represent an interesting alternative MSC type to be employed in regenerative medicine. Human periapical cyst-mesenchymal stem cells (hPCy-MSCs) correspond to a newly discovered and characterized MSC subtype. Interestingly, hPCy-MSCs are collected from periapical cysts, which are a biological waste, without any influence on the other healthy tissues in oral cavity. hPCy-MSCs exhibit cell surface marker profile similar to that of other oral derived MSCs, show high proliferative potency, and possess the potential to differentiate into different cell types such as osteoblasts, adipocytes and neurons-like cells. hPCy-MSCs, therefore, represent a novel promising MSCs type to be applied in regenerative medicine domain. In this review, we will compare the different types of dental derived MSCs, we will highlight the isolation technique, the characteristics, and the therapeutic potential of hPCy-MSCs.

Cytokines, Masticatory Muscle Inflammation, and Pain: an Update.

Cytokines are proteins secreted by diverse types of immune and non-immune cells and play a role in the communication between the immune and nervous systems. Cytokines include lymphokines, monokines, chemokines, interleukins, interferons, colony stimulating factors, and growth factors. They can be both pro- and anti-inflammatory and have autocrine, paracrine, and endocrine activities. These proteins are involved in initiation and persistence of pain, and the progress of hyperalgesia and allodynia, upon stimulating nociceptive sensory neurons, and inducing central sensitization. The objective of this review is to discuss several types of pro- and anti-inflammatory mediators and their relation with inflammatory pain in masticatory muscles.

Healing of Bone Defects in Pig's Femur Using Mesenchymal Cells Originated from the Sinus Membrane with Different Scaffolds.

OBJECTIVE: Repairing bone defects, especially in older individuals with limited regenerative capacity, is still a big challenge. The use of biomimetic materials that can enhance the restoration of bone structure represents a promising clinical approach. In this study, we evaluated ectopic bone formation after the transplantation of human maxillary Schneiderian sinus membrane- (hMSSM-) derived cells embedded within various scaffolds in the femur of pigs. METHODS: The scaffolds used were collagen, gelatin, and hydroxyapatite/tricalcium phosphate (HA/ßTCP) where fibrin/thrombin was used as a control. Histological analysis was performed for the new bone formation. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to assess mRNA and protein levels of specific osteoblastic markers, respectively. RESULTS: Histological analysis showed that the three scaffolds we used can support new bone formation with a more pronounced effect observed in the case of the gelatin scaffold. In addition, mRNA levels of the different tested osteoblastic markers Runt-Related Transcription Factor 2 (RUNX-2), osteonectin (ON), osteocalcin (OCN), osteopontin (OPN), alkaline phosphatase (ALP), and type 1 collagen (COL1) were higher, after 2 and 4 weeks, in cell-embedded scaffolds than in control cells seeded within the fibrin/thrombin scaffold. Moreover, there was a very clear and differential expression of RUNX-2, OCN, and vimentin in osteocytes, osteoblasts, hMSSM-derived cells, and bone matrix. Interestingly, the osteogenic markers were more abundant, at both time points, in cell-embedded gelatin scaffold than in other scaffolds (collagen, HA/ßTCP, fibrin/thrombin). CONCLUSIONS: These results hold promise for the development of successful bone regeneration techniques using different scaffolds embedded with hMSSM-derived cells. This trial is registered with NCT02676921.