Transcriptomic profiling of recessive dystrophic epidermolysis bullosa wounded skin highlights drug repurposing opportunities to improve wound healing

xlomafota13 shared this article with you from Inoreader Transcriptomic profiling of recessive dystrophic epidermolysis bullosa wounded skin highlights drug repurposing opportunities to improve wound healing Via Experimental Dermatology Abstract Chronic wounds present a major disease burden in people with recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering skin disorder caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils at the dermal-epidermal junction. Treatment of RDEB wounds is mostly symptomatic and there is considerable unmet need in trying to improve and accelerate wound healing. In this study, we defined transcriptomic profiles and gene pathways in RDEB wounds and compared these to intact skin in RDEB and healthy control subjects. We then used a reverse transcriptomics approach to discover drugs or compounds which might restore RDEB wound profiles towards intact skin. Differential expression analysis identified >2000 differences between RDEB wounds and intact skin, with RDEB wounds displaying aberrant cytokine-cytokine interactions, Toll-like receptor signalling, and JAK-STAT signalling pathways. In silico prediction for compoun ds that reverse gene expression signatures highlighted methotrexate as a leading candidate. Overall, this study provides insight into the molecular profiles of RDEB wounds and underscores the possible clinical value of reverse transcriptomics data analysis in RDEB, and the potential of this approach in discovering or repurposing drugs for other diseases. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Investigation of miR‐126‐3p loaded on adipose stem cell‐derived exosomes for wound healing of full‐thickness skin defects

xlomafota13 shared this article with you from Inoreader Investigation of miR‐126‐3p loaded on adipose stem cell‐derived exosomes for wound healing of full‐thickness skin defects Via Experimental Dermatology Abstract Objective To investigate the function of miR-126-3p loaded on adipose stem cell (ADSC)-derived exosomes (ADSC-Exos) in wound healing of full-thickness skin defects. Methods ADSCs transfected with miR-126-3p mimic, miR-126-3p inhibitor or pcDNA3.1-PIK3R2, or PKH26-marked ADSC-Exos were cultured with fibroblasts or human umbilical vein endothelial cells (HUVECs). The proliferation and migration rates of fibroblasts and angiogenesis of HUVECs were measured. Rats with full-thickness skin defects were injected with ADSC-Exos or exosomes extracted from ADSCs transfected with miR-126-3p inhibitor and the wound healing rates were measured. The wound bed, collagen deposition and angiogenesis in injured rats were assessed. Results ADSC-Exos could be ingested by fibroblasts and HUVECs. Co-incubation with ADSCs or ADSC-Exos promoted the proliferation and migration of fibroblasts and angiogenesis of HUVECs, which was further enhanced by miR-126-3p overexpression. Inhibition of ADSC-Exos or miR-126-3p or PIK3R2 overexpression suppressed the proliferation and migration of fibroblasts and angiogenesis of HUVECs. ADSC-derived exosomal miR-126-3p increased wound healing rate, collagen deposition and newly formed vessels in injured rats. Conclusion ADSC-derived exosomal miR-126-3p promotes wound healing of full-thickness skin defects by targeting PIK3R2. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Oral Kaposi sarcoma development is associated with HIV viral load, CD4+ count and CD4+/CD8+ ratio

xlomafota13 shared this article with you from Inoreader Oral Kaposi sarcoma development is associated with HIV viral load, CD4+ count and CD4+/CD8+ ratio Via pubmed: "med oral patol oral... Med Oral Patol Oral Cir Bucal. 2021 Oct 27:24708. doi: 10.4317/medoral.24708. Online ahead of print. ABSTRACT BACKGROUND: Kaposi's sarcoma (KS) is an uncommon, multifocal and angioproliferative lesion, which demonstrates a poor prognosis. The aim of the present research was to explore the association of HIV viral load, CD4+ and CD8+ counts and the CD4+/CD8+ ratio on the risk of oral Kaposi's sarcoma (KS) development. MATERIAL AND METHODS: A total of 62 patients were retrieved from March 2008 to October 2020 from the files of two oral pathology centres. Clinical, laboratory and follow-up data were retrieved from their medical files. Poisson regression was used to explore the role of history of immunosuppression and its association with oral KS development. A P-value <0.05 was considered significant. RESULTS: Sixty-two patients were included in the present study (32 with oral KS and 30 with no presentation of lesions anywh ere on the body). Patients with oral KS presented a mean age of 32.6 years, and male patients were more affected. The hard palate (15 cases; 46.8%) was the main anatomical site affected. The lesions were mostly presented as swellings (13 cases; 40.6%) and nodules (12 cases; 37.5%). Systemic manifestations were also observed, including candidiasis (4 cases; 12.5%), bacterial infection (3 cases; 9.3%), tuberculosis (3 cases; 9.3%), herpes simplex (3 cases; 9.3%) and pneumonia (3 cases; 9.3%). A significant correlation was observed between HIV viral load, CD4+ count and the CD4+/CD8+ ratio with oral KS development. CONCLUSIONS: HIV viral load, CD4+ count and the CD4+/CD8+ ratio are associated with oral KS development. PMID:347 04977 | DOI:10.4317/medoral.24708 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Is periapical surgery follow-up with only two-dimensional radiographs reliable? A retrospective cohort type sensitivity study

xlomafota13 shared this article with you from Inoreader Is periapical surgery follow-up with only two-dimensional radiographs reliable? A retrospective cohort type sensitivity study Via pubmed: "med oral patol oral... Med Oral Patol Oral Cir Bucal. 2021 Oct 27:24447. doi: 10.4317/medoral.24447. Online ahead of print. ABSTRACT BACKGROUND: Two-dimensional (2D) radiographic techniques are commonly used for assessing lesion prognosis after endodontic surgery. The present retrospective cohort study analyzes the sensitivity and ability of different radiographic techniques in obtaining area and volume measurements of periapical lesions. MATERIAL AND METHODS: Preoperative and follow-up (6-48 months) periapical and panoramic radiographs (index test) and cone-beam computed tomography (CBCT) images (reference standard) were selected from an endodontic microsurgery database. Sensitivity was analyzed independently by two examiners. The areas of the 2D radiographic images and CBCT volumes were studied using Itk-Snap software and Romexis viewer. RESULTS: The sample comprised 105 patients and 105 teeth, with a mean follow-up of 21 months (range 6-48). P reoperatively, CBCT detected all the periapical areas, periapical radiography detected 67, and panoramic radiography detected 60. Postoperatively, of the 52 cases in which CBCT detected remains of the periapical area, periapical radiography detected 22, and panoramic radiography detected 17. The measurements of the areas obtained by the 2D methods, and the volumes obtained by CBCT, had to be transformed into linear measures for comparison purposes. The measurements were found to be significantly different in both the preoperative and the follow-up images. CONCLUSIONS: Periapical radiography showed greater sensitivity than panoramic radiography, both preoperatively and at follow-up. The lesions measured with CBCT were larger, with significant differences than as evidenced by the periapical and panoramic radiographs. PMID:34704982 | DOI:10.4317/medoral.24447 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study

xlomafota13 shared this article with you from Inoreader Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study Via pubmed: "med oral patol oral... Med Oral Patol Oral Cir Bucal. 2021 Oct 27:24511. doi: 10.4317/medoral.24511. Online ahead of print. ABSTRACT BACKGROUND: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia. MATERIAL AND METHODS: We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64 oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were performed to evaluate predictive factors for malignant transformation (MT). RESULTS: We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than in low grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki- 67 score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, the binary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation-free survival (MTFS) as well as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression of BubR1 and Mad2 when combined showed an increased risk for malignant transformation (P=0.013; HR of 4.6, 95% CI of 1.4-15.1). CONCLUSIONS: Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant transformation independently of histological grade and could be potential and useful predictive risk markers of malignant transformation in oral leukoplakias. PMID:34704983 | DOI:10.4317/medoral.24511 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Thyroid function post laryngectomy and hemithyroidectomy ‐ do all laryngectomy patients need thyroid replacement?

xlomafota13 shared this article with you from Inoreader Thyroid function post laryngectomy and hemithyroidectomy ‐ do all laryngectomy patients need thyroid replacement? Via Clinical Otolaryngology Abstract Hypothyroidism is a common complication following laryngectomy with hemithyroidectomy, with a varying incidence between 44-89% amongst this group of patients 1–7. It is often underrecognized due to the insidious onset of thyroid dysfunction and relatively non-specific nature of hypothyroid symptoms. Hypothyroidism may be detrimental to wound healing and be associated with an increased risk of fistula formation, particularly in salvage cases 4,6 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lnc‐MEG3 inhibits invasion, migration, and epithelial– mesenchymal transition of nasopharyngeal carcinoma cells by regulating sequestosome 1

xlomafota13 shared this article with you from Inoreader Lnc‐MEG3 inhibits invasion, migration, and epithelial– mesenchymal transition of nasopharyngeal carcinoma cells by regulating sequestosome 1 Via Head & Neck Abstract Background Long non-coding RNAs regulate malignant behaviors of nasopharyngeal carcinoma (NPC). We aim to investigate the roles and mechanisms of long non-coding RNA maternally expressed gene 3 (lnc-MEG3) in NPC. Methods The expression levels of lnc-MEG3 and sequestosome 1 (SQSTM1) in NPC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell invasion and migration abilities were evaluated using transwell and wound healing assays, respectively. Results Downregulated lnc-MEG3 expression and upregulated SQSTM1 expression were found in NPC tissues and cells. Overexpression of lnc-MEG3 inhibited invasion, migration, and epithelial–mesenchymal transition in NPC cells. Overexpression of lnc-MEG3 reduced the expression level of SQSTM1, and SQSTM1 expression was inversely correlated with lnc-MEG3 level in NPC tissues. Besides, overexpression of SQSTM1 reversed the effects of lnc-MEG3 overexpression. Moreover, knockdown of lnc-MEG3 enhanced NPC progression while its effects were eased by SQSTM1 silence. Conclusion Lnc-MEG3 inhibits malignant behaviors by regulating SQSTM1 expression. It may serve as a therapeutic target to treat NPC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Adenoid Cystic Carcinoma of the Gingiva: A Case Report and Literature Review

xlomafota13 shared this article with you from Inoreader Adenoid Cystic Carcinoma of the Gingiva: A Case Report and Literature Review Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Oct 27:34894211055591. doi: 10.1177/00034894211055591. Online ahead of print. ABSTRACT OBJECTIVES: Adenoid cystic carcinoma (ACC) is a commonly encountered salivary gland malignancy. However, it rarely occurs in the gingiva, an area generally thought to be devoid of minor salivary glands. We present a case occurring in this unusual site and review other reported cases. METHODS: A 56 year-old male presented with a right-sided mandibular to othache for 1 year and underwent dental extraction. Due to persistent pain, follow up examination revealed a large gingival lesion. A biopsy was positive for adenoid cystic carcinoma. RESULTS: The patient underwent a complete right segmental mandibulectomy and was reconstructed with a fibular osteocutaneous free flap. Three months postoperatively, during the planning for adjuvant radiation therapy, the patient developed pain in the left mandible. Imaging revealed extensive involvement of the left native mandible. Deep bone biopsies in several areas of the left mandible revealed ACC. He then underwent a complete left hemi-mandibulectomy and reconstruction with a fibular osteocutaneous free flap. Tensor fascia lata suspension slings were placed due to concern for an open mouth deformity attributable to disruption of bilateral masticator slings. He will undergo adjuvant radiation therapy. Our review of the literature revealed 50 cases of gingival ACC published since 1972. Disease recurrence and distant metastases were noted in several patients, occurring at the latest after 30 years follow-up. CONCLUSIONS: Given its indolent behavior, high proclivity for late recurrence and metastasis, and overall infrequency, ACC represents a pathology that requires early diagnosis and comprehensive long-term surveillance. While ACC is well described in oral cavity sites with high densities of minor salivary glands, it is not commonly seen in the gingiva. As such, gingival ACC may display a unique biological and/or clinical character. We offer the first literature review of this rare entity. PMID:34706573 | DOI:10.1177/00034894211055591 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperbaric Oxygen Therapy for Sudden Sensorineural Hearing Loss

xlomafota13 shared this article with you from Inoreader Hyperbaric Oxygen Therapy for Sudden Sensorineural Hearing Loss Via JAMA Otolaryngology–Head & Neck Surgery Online First The treatment of idiopathic sudden sensorineural hearing loss (SSNHL) continues to be a substantial clinical challenge, in part because of the heterogeneity of the patient population and in part because of the difficulty of studying a disorder with no known causes and no defined, proven, or widely accepted course of clinical intervention. We read with interest the systematic review and meta-analysis by Joshua and colleagues on hyperbaric oxygen therapy (HBOT) for patients with SSNHL. Rhee and colleagues published a review of the same topic i n 2019; however, their conclusions were criticized for significant heterogeneity of the pooled studies, which introduced potentially unsurmountable bias. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperbaric Oxygen Therapy for Sudden Sensorineural Hearing Loss

xlomafota13 shared this article with you from Inoreader Hyperbaric Oxygen Therapy for Sudden Sensorineural Hearing Loss Via JAMA Otolaryngology–Head & Neck Surgery Online First This systematic review and meta-analysis evaluates recent evid ence on the effect of hyperbaric oxygen therapy on hearing outcomes in patients with sudden sensorineural hearing loss to determine if this treatment should be part of a combination regimen. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM2.5

xlomafota13 shared this article with you from Inoreader Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM<sub>2.5</sub> Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1435. doi: 10.3892/etm.2021.10870. Epub 2021 Oct 11. ABSTRACT Flavonoids which are extracted from citrus peel and pulp have been reported to have multiple beneficial effects on human health. Isosinensetin (ISO) is a type of flavonoid compound, which has several protective effects including anticancer, antioxidant, antiviral, anti-inflammatory and bacteriostatic. However, the molecular mechanism of its antioxidant and anti-inflammatory effects remain unclear. The present study aimed to investigate the intervention effect and possible mechanism of ISO on human bronchial epithelial cells injured by fine particular matter ≤2.5 µm in diameter (PM2.5). In the present study, the cell viability was detected by Cell Counting Kit-8 method. The levels of pro-inflammatory cytokines were analyzed by ELISA. The level of reactive oxygen species (ROS) was detected by fluorescence probe. The expression levels of proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor кΒ (NF-кB) proteins were detected by western blotting. The results revealed that ISO evidently increased the viability of 16-HBE cells and sharply decreased the levels of pro-inflammatory factors in cell culture supernatant. ISO significantly inhibited ROS release caused by PM2.5. Moreover, the expression levels of PCNA, Nrf2 and NF-кB proteins were downregulated after ISO incubation. These results indicated that ISO alleviated 16-HBE-cell injury by PM2.5 through the ROS-Nrf2/NF-кB signaling pathway. PMID:34707716 | PMC:PMC8543438 | DOI:10.3892/etm.2021.10870 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.