Antineutrophil Cytoplasmic Antibodies and Organ-Specific Manifestations in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a rare and often severe systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). EGPA can affect multiple organ systems, but the relationships between ANCA status and the organ-specific manifestations of EGPA in previous reports were inconsistent. OBJECTIVE: To investigate the association of the ANCA status with organ-specific manifestations in EGPA. METHODS: We performed a systematic review of studies published before March 16, 2020, in the PubMed, Embase, Web of Science, and Cochrane Library databases. The primary outcome was the association of ANCA status with organ-specific involvements of EGPA. Odds ratios (ORs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 24 cross-sectional studies with 2527 patients with EGPA, including 921 ANCA-positive patients and 1606 ANCA-negative patients, were included in the meta-analysis. The significant results of pooled analyses revealed that compared with patients with EGPA with negative ANCA status, patients with EGPA with positive ANCA status had higher risks of peripheral neuropathy (OR, 1.701), renal involvement (OR, 5.097), and cutaneous purpura (OR, 1.746) and lower risks of pulmonary infiltrates (OR, 0.589) and cardiac involvement (OR, 0.427). The pooled analysis also revealed no significant association of ANCA status with asthma and involvements of the central nervous system, gastrointestinal tract, or skin. CONCLUSIONS: This study provides more evidence that patients with EGPA may exhibit different features of disease based on their ANCA status.

The Effects of Different Dynamic Culture Systems on Cell Proliferation and Osteogenic Differentiation in Human Mesenchymal Stem Cells.

The culture environment plays an important role for stem cells' cultivation. Static or dynamic culture preserve differential potentials to affect human mesenchymal stem cells' (hMSCs) proliferation and differentiation. In this study, hMSCs were seeded on fiber disks and cultured in a bidirectional-flow bioreactor or spinner-flask bioreactor with a supplement of osteogenic medium. The hMSCs' proliferation, osteogenic differentiation, and extracellular matrix deposition of mineralization were demonstrated. The results showed that the spinner flask improved cell viability at the first two weeks while the bidirectional-flow reactor increased the cell proliferation of hMSCs through the four-week culture period. Despite the flow reactor having a higher cell number, a lower lactose/glucose ratio was noted, revealing that the bidirectional-flow bioreactor provides better oxygen accessibility to the cultured cells/disk construct. The changes of calcium ions in the medium, the depositions of Ca2+ in the cells/disk constructs, and alkaline phosphate/osteocalcin activities showed the static culture of hMSCs caused cells to mineralize faster than the other two bioreactors but without cell proliferation. Otherwise, cells were distributed uniformly with abundant extracellular matrix productions using the flow reactor. This reveals that the static and dynamic cultivations regulated the osteogenic process differently in hMSCs. The bidirectional-flow bioreactor can be used in the mass production and cultivation of hMSCs for applications in bone regenerative medicine.

The efficacy of ablation-based combination therapy for vitiligo: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: This study aimed to compare the efficacy of vitiligo treatments with and without ablation therapy. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis of literature published before September 15, 2017. Comparative studies of vitiligo patients treated with and without ablation therapy were included. The primary outcome was ≥ 50 % repigmentation. Secondary outcomes were ≥ 75 % repigmentation and patient scores on a subjective visual analogue scale. RESULTS: Fifteen studies with a total of 401 participants were included. The ablation-based combination therapy group had significantly superior results to the control group (odds ratio [OR] for ≥ 50 % repigmentation: 10.490, 95 % confidence interval [CI]: 4.632-23.757; OR for ≥ 75 % repigmentation: 5.812, 95 % CI: 2.194-15.393). Patients receiving ablation-based combination therapy were significantly more satisfied with the efficacy than the control group (standardized mean difference: 1.073, 95 % CI: 0.528-1.619). Subgroup analysis showed that the erbium laser group, CO2 laser group and fractional CO2 laser group achieved significantly better repigmentation than the control groups. CONCLUSIONS: According to objective and subjective evaluations, treatments for vitiligo are more effective when combined with ablation therapy than when used alone.

Pyoderma gangrenosum preceding the onset of extranodal natural killer/T-cell lymphoma: A case report.

INTRODUCTION: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that may be associated with systemic diseases. The association of PG with lymphoid malignancies has rarely been reported. Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive entity with a poor prognosis. Here, we report the case of a patient who had idiopathic PG refractory to systemic steroids and subsequently developed ENKTL. CASE REPORT: A 70-year-old man presented with a 2-month history of intermittent fever and multifocal painful papules, plaques, and ulcerations on his extremities. The histological and culture results of the lesions were consistent with those of PG. A thorough work-up was performed and did not demonstrate any underlying systemic diseases including malignancy. The PG lesions were refractory to systemic steroid therapy. An enlarging nodule was observed over his right infraorbital area 4 months after the onset of the skin eruptions. The nodule was later biopsied and diagnosed as ENKTL by using histopathological and immunohistochemical studies. Fludeoxyglucose positron emission tomography/computed tomography revealed multiple intense fludeoxyglucose-avid masses in the bones and lungs, suggesting multiorgan metastases. The patient rejected chemotherapy and died 4 weeks after the diagnosis. CONCLUSION: The present case indicates that in any patient with idiopathic PG refractory to conventional therapy, the presence of any underlying disease or malignancy must be thoroughly evaluated. The present case serves as a reminder that when assessing patients with PG, clinicians should increase their awareness regarding the delayed association with malignancy, even in the absence of a concomitant systemic disease at presentation. Furthermore, the prompt evaluation of any suspicious lesions in the context of PG for the possibility of a malignant nature can improve the prognosis, particularly in cases of aggressive malignancy. Understanding the cutaneous spectrum of ENKTL is crucial because of its variable clinical appearance and aggressive nature. Our case demonstrates that PG can be a presenting sign of ENKTL.

Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages.

BACKGROUND: Propionibacterium acnes (P. acnes), a gram-positive anaerobic bacterium, plays a critical role in the development of inflammatory lesion as a result of cytokines production by keratinocytes and macrophages activation. However, effect of P. acnes on iNOS/NO and COX-2/PGE2 production in macrophages is still uninvestigated. OBJECTIVE: This study aimed at determining the reactive oxygen species (ROS), inducible nitric oxide (NO) synthase (iNOS)/nitric oxide (NO), and cyclooxygenase (COX)-2/prostaglandin (PG)E2 produced by macrophages upon P. acnes infection, and dissecting the mechanism of P. acnes-stimulated multiplicity of infection (MOI)-dependent increases in iNOS and COX-2 protein expressions in accordance with the elevation of NO and PGE2 production by RAW264.7 macrophages. METHODS: Using an in vitro cell culture system, the effects of P. acnes on iNOS/NO, COX-2/PGE2, ROS production, ERK/JNK, and AP-1/NF-κB activation were examined via Western blotting, a flow cytometric analysis, and luciferase assay. In pharmacological studies, the ROS scavenger, N-acetyl cysteine (NAC), the NADPH oxidase inhibitor, diphenylene iodide (DPI), and mitogen-activated protein kinase (MAPK) inhibitors (U0126 and SP600125) were applied to investigate the mechanism. RESULTS: We found that P. acnes exposures increased iNOS/NO and COX-2/PGE2 expression in RAW264.7, J774A.1, and peritoneal macrophages via a MOI-dependent manner. Increased ROS production, ERK/JNK protein phosphorylation, and elevated AP-1/NF-κB luciferase activity are identified in P. acnes-induced iNOS/NO and COX-2/PGE2 production. Additionally, hispolon but not its analogs, hispolon methylether or dehydroxyhispolon, showed significant inhibition of P. acnes-induced iNOS/NO and COX-2/PGE2 production, indicating an important role of OH at C5 for hispolon's inhibition of P. acnes-induced inflammatory events in macrophages. CONCLUSION: ROS-dependent stimulation of ERK, JNK, NF-κB, and AP-1 activation contributes to P. acnes-induced iNOS/NO and COX-2/PGE2 in macrophages, and chemicals such as hispolon possessing ability to block iNOS/NO and COX-2/PGE2 production reserve potential to be further developed for treatment of the early phase of inflammation elicited by P. acnes.

Quercetin enhancement of arsenic-induced apoptosis via stimulating ROS-dependent p53 protein ubiquitination in human HaCaT keratinocytes.

In this study, QUE, but not the structurally related chemical, rutin, enhanced the cytotoxicity of arsenic trioxide (As(+3)) against the viability of normal human HaCaT keratinocytes via induction of apoptosis. QUE enhancement of As(+3)-mediated apoptosis was accompanied by increased intracellular peroxide production according to a DCFH-DA analysis, and DNA ladders induced by QUE/As(+3) were inhibited by adding the antioxidative compound, N-acetyl cysteine (NAC). A loss of the mitochondrial membrane potential by QUE/As(+3) was observed according to DiOC(6) staining in concert with increased Bax protein and cytosolic cytochrome (Cyt) c protein expression in HaCaT cells, which was prevented by the addition of NAC. A decrease in the p53 protein with increased protein ubiquitination was detected in QUE/As(+3)-treated HaCaT cells, and this was prevented by the addition of NAC. The decrease in the p53 protein by QUE/As(+3) was reversed by adding the proteasome inhibitor, MG132. L-Buthionine sulphoximine (BSO) enhanced the cytotoxicity of As(+3) against the viability of HaCaT cells with reduced p53 protein through inducing protein ubiquitination and reactive oxygen species (ROS) production, and disrupting the mitochondrial membrane potential in HaCaT cells. Additionally, QUE and BSO enhanced the cytotoxic effects of monomethylarsonous acid (MMA(+3)) but not other arsenic compounds in accordance with increased p53 protein ubiquitination in HaCaT cells. QUE plus As(+3) stimulation of apoptosis in human HaCaT keratinocytes via activating ROS-dependent p53 protein ubiquitination may offer a rationale for the use of QUE to improve the clinical efficacy of arsenics in treating psoriasis.

Clear cell fibrous papule: report of a case mimicking a balloon cell nevus.

Clear cell fibrous papule (FP) is a rare variant of FP. We report a 39-year-old female patient who presented with a dome-shaped papule on the nose. The diagnosis of clear cell FP was made based on histological and immunohistochemical studies. Interestingly, scattered S-100 cells were admixed within the lesion, a finding hitherto not reported. The S-100 positivity may be misleading and should be cautiously interpreted.