Publications by authors named "Walid D Fakhouri"

Previous studies implicate immune dysregulation in the metabolic changes accompanying obesity and type 2 diabetes. This study investigated the interplay between metabolic and immunological parameters during the progression of type 2 diabetes in an obese Mexican American cohort from Starr County, Texas. Individuals matched for age, gender, and BMI were stratified into five categories: diabetes-free, isolated impaired glucose tolerance, combined glucose impairment (fasting or post-load), type 2 diabetes without complications, and type 2 diabetes with lower extremity complications.

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Objective: To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren's syndrome biopsies.

Design: We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.

Results: In Irf6-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates.

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: An individual's genetic makeup influences their organ development, orofacial structures, and overall health. Though many studies have been conducted to determine the inheritance of oral diseases and conditions, there is a lack of comprehensive research classifying these disorders based on the genetic and environmental etiology. : This systematic review aimed to analyze the existing body of literature using the PubMed and Cochrane databases and answer the following question: "What evidence exists supporting the role of genetic factors in oral conditions?" This systematic-narrative review methodically categorizes oral diseases and conditions based on their genetic or environmental linkages.

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  • In Finland, isolated cleft palate (CP) occurs more frequently than cleft lip with or without cleft palate (CL/P), which is the opposite trend seen in other European countries.
  • A genome-wide association study revealed a specific single nucleotide polymorphism (rs570516915) strongly linked to CP in the Finnish population, showing significant statistical results and confirmed in other cohorts.
  • The risk allele for rs570516915 disrupts a binding site for the IRF6 transcription factor, leading to decreased IRF6 expression, indicating that this genetic alteration may be a key factor in the mechanism causing CP.
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  • In Finland, isolated cleft palate (CP) occurs more frequently than cleft lip with or without cleft palate (CL/P), which is the opposite trend seen in other European nations.
  • A genome-wide association study identified a specific SNP (rs570516915) that is strongly linked to CP in the Finnish and Estonian populations.
  • This SNP disrupts a binding site for the transcription factor IRF6, leading to decreased enhancer activity and impaired autoregulation, which may contribute to the increased risk of CP.
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  • Disease risk prediction can be enhanced by analyzing genomic sequences and transcriptional profiles, though identifying harmful non-coding DNA variations remains challenging for common diseases.
  • This study explores the interactions between P53 and cMYC proteins in regulation of target genes, revealing co-occupancy patterns in DNA regions that are conserved through evolution.
  • Results indicate that doxorubicin treatment leads to changes in protein levels and gene expression, suggesting a method to connect non-coding variations to gene regulation and disease risk screening.
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  • * Rats treated with TC showed increased testosterone levels in both plasma and saliva but did not experience changes in salivary flow, pH, or buffering capacity; however, certain proteins and minerals in saliva decreased.
  • * The results indicate that TC may harm the parotid and submandibular glands, which could pose risks to oral and overall health for individuals who misuse anabolic steroids.
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Objective: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters.

Materials And Methods: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg).

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TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis.

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Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats.

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  • * The study focused on the co-occupancy and competitive interactions between the transcription factors P53 and cMYC in regulating gene expression, identifying that approximately 344-366 genomic regions were co-occupied by both factors in human and mouse embryonic stem cells.
  • * Treatment with doxorubicin altered protein levels of P53 and cMYC in certain cell types and resulted in significant changes in the expression of nearby genes, indicating that variations in non-coding DNA influence the binding affinity of these transcription factors, which in turn affects gene regulation
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Objective: This study aimed to analyze the salivary flow rate, biochemical composition, and redox status in orchiectomized spontaneously hypertensive rats (SHR) compared to normotensive Wistar rats.

Design: Thirty-two young adult male SHR and Wistar (3-months-old) rats were randomly distributed into four groups; either castrated bilaterally (ORX) or underwent fictitious surgery (SHAM) as Wistar-SHAM, Wistar-ORX, SHR-SHAM, and SHR-ORX. Two months beyond castration, pilocarpine-induced salivary secretion was collected from 5-month-old rats to analyze salivary flow rate, pH, buffer capacity, total protein, amylase, calcium, phosphate, sodium, potassium, chloride, thiobarbituric acid reactive substances (TBARs), carbonyl protein, nitrite, and total antioxidant capacity.

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Bone metabolism and repair are directly regulated by arachidonic acid metabolites. At present, we analyzed the dose-response effects of a selective cysteinyl leukotriene receptor type-1 antagonist during bone repair after tooth extraction and on non-injured skeleton. Sixty-three 129 Sv/Ev male mice composed the groups: C-Control (saline solution); MTK2-2 mg/Kg of Montelukast (MTK) and MTK4-4 mg/Kg of MTK, daily administered by mouth throughout all experimental periods set at 7, 14, and 21 days post-operative.

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(1) Background: Several studies showed a sustained temperature of 47 °C or 50 °C for one minute resulted in vascular stasis and bone resorption with only limited bone regrowth over a 3-4-week healing period. The purpose of the present study was to evaluate the temperature changes (ΔΤ) that occur during the preparation of dental implant osteotomies using MIS straight drills versus Densah burs in a clockwise (cutting) drilling protocol. (2) Methods: Two hundred forty (240) osteotomies of two different systems' drills were prepared at 6 mm depth at 800, 1000, and 1200 revolutions per minute (RPM), in fresh, unembalmed tibiae, obtained by a female cadaver.

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Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons and glial cells. We have previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation.

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Oral ulcers are lesions that occur due to disruption of epithelial integrity of the mucosa of the oral cavity. Intraoral ulcers are often associated with pain, redness, symptoms of discomfort, and blood hemorrhage. The etiology for many oral ulcers is local trauma, systemic health conditions, or medication; for other ulcers the cause is less clear.

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This study investigated the role 5-lypoxigenase (5-LO) on alveolar socket healing in aged female mice treated with zoledronic acid (ZL). Forty 129/Sv female mice (64-68 weeks old), 20 wild type (WT) and 20 5-LO knockout (5LOKO) were equally distributed according to ZL treatment: WT Control, WT ZL, 5LOKO Control, and 5LOKO ZL. ZL groups were treated with an intraperitoneal injection of 250 µg/Kg of ZL, while controls were treated with saline.

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Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others.

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Pericoronitis is inflammation of the operculum associated with a partially erupted third molar. It is a highly prevalent infection of the oral cavity and presents as a painful sensation of the soft tissue encompassing the crown of the involved tooth. Though pericoronitis is common, there is no evidence-based standard-of-care for treatment of emergency patients with acute pericoronitis.

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In recent years, the knowledge generated by decoding the human genome has allowed groundbreaking genetic research to better understand genomic architecture and heritability in healthy and disease states. The vast amount of data generated over time and yet to be generated provides the basis for translational research towards the development of preventive and therapeutic strategies for many conditions. In this special issue, we highlight the discoveries of disease-associated and protective DNA variations in common human diseases and developmental disorders.

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Treatment with cumulative dosages of zoledronic acid (ZA) in elderly patients is a risk factor for the development of medication-related osteonecrosis of the jaws (MRONJ), mainly related to surgical triggers such as tooth extraction. However, animal models for the investigation and understanding of MRONJ pathophysiology in senescent and postmenopausal stages remains to be developed and characterized. The aim of this study was to analyze MRONJ development in senescent female mice treated with cumulative dosages of ZA.

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Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes in humans. However, Tfap2a and Grhl3 are also required for neurulation in mice. Here, we found that homeostasis of Irf6 is also required for development of the neural tube and associated structures.

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Background: Interferon regulatory factor 6 (IRF6) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in IRF6 are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown.

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Article Synopsis
  • Mandibular disorders are a prevalent birth defect in humans, often leading to secondary issues like airway obstruction and feeding difficulties that can impact quality of life.
  • The study aims to uncover hormonal and genetic factors linked to nonsyndromic mandibular disorders, identifying significant interactions in the FGF and BMP signaling pathways.
  • Findings suggest that certain genes related to skeletal formation may play a crucial role as genetic risk factors for common mandibular disorders, indicating a need for further research into their implications.
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Dental implants provide a predictable treatment option for partial and complete edentulism via the placement of a fixed permanent artificial root to support prosthetic dental crowns. Despite the high survival rates, long-term dental implant failures are still reported, leading to implant removals and additional financial and health burdens. While extrinsic factors that improve the success rate of implants have been well explored, the impact of genetic factors on this matter is poorly understood.

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