10 research outputs found
Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation
Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations
Clinical-Epidemiological Characteristics of Hidradenitis Suppurativa: A Retrospective Cohort Study from a Tertiary Care Centre in Northern Israel
Background: Hidradenitis suppurativa (HS) is characterised by inflamed lesions that typically appear in apocrine-rich flexural areas. Although studies have reported clinical and epidemiological data from western countries, data from the Middle East are scarce. The aim of this study is to characterise the differences in the clinical characteristics of patients with HS of Arab and Jewish ancestry and review the clinical characteristics, the course of the disease, the comorbidities, and the response to treatment. Methods: This is a retrospective study. We collected clinical and demographic data from patient files between 2015â2018 at the Rambam Healthcare Campus dermatology clinicâa tertiary hospital located in the north of Israel. Our results were compared to those of a previously published Israeli control group registered in Clalit Health Services. Results: Of the 164 patients with HS, 96 (58.5%) were men and 68 (41.5%) were women. The average age at diagnosis was 27.5 years and the average latency between the onset and diagnosis of the disease was 4 years. We found a higher adjusted prevalence of HS in Arab patients (56%) than in their Jewish counterparts (44%). Gender, smoking, and obesity, as well as axilla and buttock lesions, were risk factors for severe HS, with no differences between ethnicities. No differences were documented in comorbidities and in response to adalimumab, with a high overall response rate of 83%. Conclusions: Our findings revealed differences between Arab and Jewish patients with HS in terms of incidence and gender predominance, while no differences were documented in comorbidities and response to adalimumab
Management of Melasma: Laser and Other TherapiesâReview Study
Melasma is a commonly occurring pigmented skin condition that can significantly affect oneâs appearance, described as symmetric hyperpigmentation that presents as irregular brown to gray-brown macules on various facial areas, such as the cheeks, forehead, nasal bridge, and upper lip, along with the mandible and upper arms. Due to its complex pathogenesis and recurrent nature, melasma management is challenging and the outcomes following treatment are not always deemed satisfactory. Solely treating hyperpigmentation may prove ineffective unless paired with regenerative techniques and photoprotection, since one of the main reasons for recurrence is sun exposure. Hence, the treatment protocol starts with addressing risk factors, implementing stringent UV protection, and then treatment using different strategies, like applying topical treatments, employing chemical peels, laser and light therapies, microneedling, and systemic therapy. This review aims to provide a summary of the effectiveness and safety of the frequently employed laser and light therapies for treating melasma, focusing on laser therapy as a treatment for melasma
miR-184 represses ÎČ-catenin and behaves as a skin tumor suppressor
Abstract miR-184-knockout mice display perturbed epidermal stem cell differentiation. However, the potential role of miR-184 in skin pathology is unclear. Here, we report that miR-184 controls epidermal stem cell dynamics and that miR-184 ablation enhances skin carcinogenesis in mice. In agreement, repression of miR-184 in human squamous cell carcinoma (SCC) enhances neoplastic hallmarks of human SCC cells in vitro and tumor development in vivo. Characterization of miR-184-regulatory network, suggests that miR-184 inhibits pro-oncogenic pathways, cell proliferation, and epithelial to mesenchymal transformation. Of note, depletion of miR-184 enhances the levels of ÎČ-catenin under homeostasis and following experimental skin carcinogenesis. Finally, the repression of ÎČ-catenin by miR-184, inhibits the neoplastic phenotype of SCC cells. Taken together, miR-184 behaves as an epidermal tumor suppressor, and may provide a potentially useful target for skin SCC therapy
Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5â/â mice
Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. Mice lacking the ubiquitin ligase RNF5 exhibit attenuated activation of the unfolded protein response (UPR) components, which coincides with increased expression of inflammasome components, recruitment and activation of dendritic cells and reduced expression of antimicrobial peptides in intestinal epithelial cells. Reduced UPR expression is also seen in murine and human melanoma tumor specimens that responded to immune checkpoint therapy. Co-housing of Rnf5â/â and WT mice abolishes the anti-tumor immunity and tumor inhibition phenotype, whereas transfer of 11 bacterial strains, including B. rodentium, enriched in Rnf5â/â mice, establishes anti-tumor immunity and restricts melanoma growth in germ-free WT mice. Altered UPR signaling, exemplified in Rnf5â/â mice, coincides with altered gut microbiota composition and anti-tumor immunity to control melanoma growth
Sequence variation in PPP1R13L results in a novel form of cardioâcutaneous syndrome
Dilated cardiomyopathy (DCM) is a lifeâthreatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4â30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patientsâ fibroblasts and PPP1R13Lâknocked down human fibroblasts presented higher expression levels of proâinflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13lâknocked down murine cardiomyocytes and hearts of Ppp1r13lâdeficient mice. The hypersensitivity to lipopolysaccharide was NFâÎșBâdependent, and its inducible binding activity to promoters of proâinflammatory cytokine genes was elevated in patientsâ fibroblasts. RNA sequencing of Ppp1r13lâknocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13lâdeficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomalârecessive cardioâcutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors
Prolidase deficiency associated with systemic lupus erythematosus (SLE): single site experience and literature review
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Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5-/- mice.
Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. Mice lacking the ubiquitin ligase RNF5 exhibit attenuated activation of the unfolded protein response (UPR) components, which coincides with increased expression of inflammasome components, recruitment and activation of dendritic cells and reduced expression of antimicrobial peptides in intestinal epithelial cells. Reduced UPR expression is also seen in murine and human melanoma tumor specimens that responded to immune checkpoint therapy. Co-housing of Rnf5-/- and WT mice abolishes the anti-tumor immunity and tumor inhibition phenotype, whereas transfer of 11 bacterial strains, including B. rodentium, enriched in Rnf5-/- mice, establishes anti-tumor immunity and restricts melanoma growth in germ-free WT mice. Altered UPR signaling, exemplified in Rnf5-/- mice, coincides with altered gut microbiota composition and anti-tumor immunity to control melanoma growth
BoletĂn Oficial de la Provincia de Guadalajara: NĂșmero de la Victoria - 1939 agosto 25
RNF5Â is a ubiquitin ligase regulating ER stress response. Here the authors show that Rnf5 deficiency potentiates immune response against melanoma via altered microbiota, and isolate bacterial strains that confer the same phenotype to wild type mice