Non-ablative fractionated laser skin resurfacing for the treatment of aged neck skin

Journal of Dermatological Treatment, Ahead of Print.
Source: Journal of Dermatological Treatment - Category: Dermatology Tags: article Source Type: research

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Serine-rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes. Hepatic SRSF3 expression was similarly decreased and RNA splicing dysregulated in mouse models of NAFLD and NASH...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
CONCLUSION This precision medicine approach identifies PI3K/Akt/mTOR signaling as the first pharmacologically targetable pathogenic process in IL-6 blockade–refractory iMCD. Prospective evaluation of sirolimus in treatment-refractory iMCD is planned (NCT03933904).FUNDING This study was supported by the Castleman’s Awareness &Research Effort/Castleman Disease Collaborative Network, Penn Center for Precision Medicine, University Research Foundation, Intramural NIH funding, and the National Heart Lung and Blood Institute.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Although obesity is typically associated with metabolic dysfunction and cardiometabolic diseases, some people with obesity are protected from many of the adverse metabolic effects of excess body fat and are considered “metabolically healthy.” However, there is no universally accepted definition of metabolically healthy obesity (MHO). Most studies define MHO as having either 0, 1, or 2 metabolic syndrome components, whereas many others define MHO using the homeostasis model assessment of insulin resistance (HOMA-IR). Therefore, numerous people reported as having MHO are not metabolically healthy, but simply have...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Parkinson’s disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron los...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
We report that calcium oxalate (CaOx) crystal deposition led to rapid tubule dilation, activation of PKD-associated signaling pathways, and hypertrophy in tubule segments along the affected nephrons. Blocking mTOR signaling blunted this response and inhibited efficient excretion of lodged crystals. This mechanism of “flushing out” crystals by purposefully dilating renal tubules has not to our knowledge been previously recognized. Challenging PKD rat models with CaOx crystal deposition or inducing calcium phosphate deposition by increasing dietary phosphorus intake led to increased cystogenesis and disease progr...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
In conclusion, IL-1α and IL-1β are upstream components of a signaling pathway, including IL-1R1 and downstream SPDEF and ERN2, that generate a positive feedback cycle capable of producing persistent mucus hyperconcentration and IL-1α and/or IL-1β–mediated neutrophilic inflammation in the absence of infection in CF airways. Targeting this pathway therapeutically may ameliorate mucus obstruction and inflammation-induced structural damage in young CF children.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Mucus obstruction is a hallmark of cystic fibrosis (CF) airway disease, leading to chronic infection, dysregulated inflammation, and progressive lung disease. As mucus hyperexpression is a key component in the initiation and perpetuation of airway obstruction, the triggers underlying mucin release must be identified and understood. In this issue of the JCI, Chen et al. sought to delineate the mechanisms that allow IL-1α/IL-1β to perpetuate the mucoinflammatory environment characteristic of the CF airway. The authors demonstrated that IL-1α and IL-1β stimulated non-CF human bronchial epithelial (HBE) c...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The prognostic value of immune cell infiltration within the tumor microenvironment (TME) has been extensively investigated via histological and genomic approaches. Based on the positive prognostic value of T cell infiltration, Immunoscore has been developed and validated for predicting risk of recurrence for colorectal cancer (CRC). Also, association between a consensus T helper 1 (Th-1) immune response and favorable clinical outcomes has been observed across multiple cancer types. Here, we reanalyzed public genomic data sets from The Cancer Genome Atlas (TCGA) and NCBI Gene Expression Omnibus (NCBI-GEO) and performed mult...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after p...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole-genome RNA sequencing, gene set enrichment analysis, and immunohistochemistry. Our analyses revealed 5 mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: AR-high tumors (ARPC), AR-low tumors (ARLPC), amphicrine tumors composed of cells coexpressing AR and NE genes (AMPC), doub...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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