Knockdown of ABHD11­AS1 prevents the procession of TNBC by upregulating miR­199a­5p.

Breast cancer (BC) has become a threat to women's health. In addition, patients with triple-negative BC (TNBC) have the worst prognosis among all patients with BC. Furthermore, long non-coding RNA ABHD11-AS1 is aberrantly highly expressed in TNBC, suggesting that RNA ABHD11-AS1 may serve as an important role in the progression of TNBC. However, the detailed function of ABHD11-AS1 in TNBC remains largely unknown. The levels of ABHD11-AS1 in MDA-MB-231 cells were assessed by reverse transcription-quantitative PCR. To investigate the effect of ABHD11-AS1 on the progression of TNBC, a xenograft animal model was established. Knockdown of ABHD11-AS1 inhibited the epithelial-mesenchymal transition and migration of TNBC cells. In addition, ABHD11-AS1 promoted the viability and migration of TNBC cells by upregulating microRNA (miR)-199a-5p. Furthermore, knockdown of ABHD11-AS1 suppressed TNBC tumor growth in vivo by upregulating miR-199a-5p. In conclusion, knockdown of ABHD11-AS1 suppressed the progression of TNBC via upregulation of miR-199a-5p. The data of the present study may provide novel directions and a theoretical basis for TNBC treatment.

Objectively quantifying facial erythema in rosacea aided by the ImageJ analysis of VISIA red images.

BACKGROUND: Facial erythema, a prominent characteristic of rosacea, causes concern to both the patient and doctor. In clinical practice, commonly used erythema severity subjective assessment tools lack objectivity and are less comprehensive. Even with images taken by the VISIA® system, diffused erythema is difficult to segment and evaluate fully due to the automatic threshold segmentation method. This study aimed to explore a more objective and scientific erythema quantification tool with the aid of the ImageJ software analysis of the red area images taken by the VISIA® system. MATERIALS AND METHODS: Patients with rosacea were enrolled and assessed for the clinical severity of their illness using various stools-the standard grading systems (SGS) for rosacea, investigator's global assessment (IGA), and clinician's erythema assessment (CEA). Facial images in the red area mode of the VISIA® system were further analyzed by the ImageJ for the relative intensity of redness and percentage of erythema area; the correlation with the scores of the subjective grading systems was evaluated. RESULTS: This study included 201 patients (195 females and 6 males). The relative intensity of redness was positively correlated to the SGS, IGA, and CEA scores (0.688, 0.725, and 0.718, respectively) (p < 0.001). The percentage of erythema area was positively correlated to the SGS, IGA, and CEA scores (0.615, 0.666, and 0.656, respectively) (p < 0.001). CONCLUSION: We demonstrated a more objective and precise method of assessing the severity of facial erythema rosacea, which could comprehensively assess the severity by both the area and intensity of facial erythema.

Mast cell stabilization: new mechanism underlying the therapeutic effect of intense pulsed light on rosacea.

BACKGROUND: Rosacea, a chronic inflammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL). OBJECTIVE: To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment. METHODS: Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like inflammation induced by intradermal injection of 320 µM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37-stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR. RESULTS: Profound infiltration of inflammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and inflammatory cytokines was higher in lesional areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated inflammation in mice with rosacea-like inflammation, as demonstrated by the significantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of inflammatory cytokines and inhibiting rosacea-like inflammatory reactions. CONCLUSION: The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate inflammatory reactions.

A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages.

Background: Rosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration. Objective: To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment. Methods: Skin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-α, and IL-1ß) evaluation. An in vivo murine rosacea-like inflammation model was established by LL-37 intradermal injection with or without carvedilol gavage-based pretreatment. Erythema proportion (Image J) and skin redness (L*a*b colorimetry) were quantified. Murine skin samples underwent pathological examination for inflammatory status and immunofluorescence staining. Murine skin and lipopolysaccharide-stimulated RAW 264.7 cells with or without carvedilol pretreatment were evaluated by quantitative reverse transcription-polymerase chain reaction and western blotting. Clinical facial images of patients were obtained using the VISIA skin analysis system before, 4, and 6 months following oral carvedilol administration. Results: Rosacea skin lesions exhibited more pronounced inflammatory cell infiltration than peripheral areas, with profound macrophage infiltration and inflammatory cytokines (TLR2, kallikrein 5, cathelicidin, TNF-α, and IL-1ß). In vivo, carvedilol alleviated inflammation in LL-37 mice, down-regulating TLR2, KLK5, and cathelicidin expression. In vitro, carvedilol decreased TLR2 expression in RAW 264.7 cells, further reducing KLK5 secretion and LL-37 expression and ultimately inhibiting rosacea-like inflammatory reactions. Clinical manifestations and facial redness obviously improved during 6-month follow-up with systemic carvedilol administration. Conclusion: Carvedilol is effective against rosacea, with inhibition of macrophage TLR2 expression as a novel anti-inflammatory mechanism.

Paeoniflorin inhibits the macrophage-related rosacea-like inflammatory reaction through the suppressor of cytokine signaling 3-apoptosis signal-regulating kinase 1-p38 pathway.

ABSTRACT: Rosacea is a facial chronic inflammatory skin disease with immune and vascular system dysfunction. Paeoniflorin (PF) is a traditional Chinese medicine with anti-inflammatory properties. However, its effects on rosacea remain unknown. Here, we investigated the mechanisms through which PF inhibits the macrophage-related rosacea-like inflammatory response. Immunohistochemical methods were used to detect differences in the inflammatory response and degree of macrophage infiltration in granulomatous rosacea lesions and their peripheral areas. Cell Counting Kit-8 was used to determine the cytotoxicity of PF towards RAW 264.7 cells. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure the influence of PF on mRNA and protein expression levels of suppressor of cytokine signaling 3 (SOCS3), apoptosis signal-regulating kinase 1 (ASK1)-p38, Toll-like receptor 2, and cathelicidin antimicrobial peptide ( or LL37) in the lipopolysaccharide (LPS)-induced macrophage-related rosacea-like inflammatory response of RAW 264.7 cells. Inflammatory cell infiltration was more pronounced in granulomatous rosacea lesions than in peripheral areas. LL37 expression increased significantly, and the infiltration of a large number of CD68+ macrophages was observed in the lesions. PF promoted SOCS3 expression in RAW 264.7 cells and inhibited the LPS-induced increase in toll-like receptor 2 and LL37 expression through the ASK1-p38 cascade, thereby alleviating the macrophage-related rosacea-like inflammatory response. These changes could be abrogated by SOCS3 siRNA in vitro.In conclusion, the pathogenesis of rosacea involves abnormal macrophage infiltration within the lesions. PF inhibits the macrophage-related rosacea-like inflammatory response through the SOCS3-ASK1-p38 pathway, demonstrating its potential application as a novel drug for rosacea therapy.

Association between rosacea and cardiovascular disease: A systematic review and meta-analysis.

BACKGROUND: Rosacea and cardiovascular diseases (CVD) are chronic inflammatory disorders. While CVD is the leading cause of mortality globally, increasing evidence indicates that CVD prevalence could be higher among patients with rosacea. AIMS: This review aimed to determine the association between the prevalence of CVD and rosacea. PATIENTS/METHODS: A systematic review of observational studies with controls available in MEDLINE, EMBASE, PubMed, Cochrane, and Web of Science databases was conducted. We performed a pooled meta-analysis using random-effects weighting. Overall, 11 studies met the inclusion criteria, which indicated increased odds for at least one risk factor of CVD, including diabetes, high blood pressure, or dyslipidemia. RESULTS: The pooled meta-analysis indicated an association of rosacea with higher odds of insulin resistance or diabetes (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.97-1.45), high systolic blood pressure (OR, 1.96; 95% CI, 1.35-2.84), dyslipidemia (OR, 1.50; 95% CI, 1.19-1.88), and CVD (OR, 6.65; 95% CI, 2.80-15.76). No publication bias was detected. The effect of confounding factors due to overlapping symptoms and lack of individual-level data were limitations of this review. CONCLUSION: Patients with rosacea have a high risk of CVD. However, further studies are warranted to confirm the association between rosacea and CVD.

Phospholipid Scramblase 1 Interacts with Midkine and Regulates Hepatic Cancer Cell Proliferation and Migration.

BACKGROUND: Mounting evidence indicates that nuclear targeting by growth factors plays an indispensable role on their biological activities. Midkine (MK) is a multifunctional growth factor and has been discovered to play important roles in carcinogenesis. MK has been reported to localize to the nucleus and nucleolus of HepG2 cells and is involved in cell proliferation and apoptosis. METHODS: The interaction was reconfirmed by in vitro pull down and in vivo coimmunoprecipitation (Co-IP), also by the colocalization in the HepG2 cells. The proliferation and migration was determined by MTT and trans-well assay. RESULTS: PLSCR1 was identified as a novel MK-interacting protein. Notably, PLSCR1 interacted with MK in the cell nucleus and regulated hepatic carcinoma cell proliferation and migration. CONCLUSIONS: This study suggests that PLSCR1 positively regulates hepatic carcinoma cell proliferation and migration through interacting with MK, thus deepening our understanding on the regulation of midkine during hepatic carcinoma growth and metastasis.