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Background: Rosacea is a chronic inflammatory skin disorder. Inflammation and oxidative stress are involved in the etiopathogenesis of rosacea and chronic kidney disease (CKD). This study aimed to investigate the association between rosacea and CKD. Methods: This population-based cohort study identified 277 patients with rosacea in the Taiwan National Health Insurance Research Database during 2001–2005. These patients were matched for age, sex, and comorbidities with 2216 patients without rosacea. All subjects were individually followed-up for 8–12 years to identify those who subsequently developed CKD Results: The incidence rates of CKD per 1000 person-years were 16.02 in patients with rosacea and 10.63 in the non-rosacea reference population. After adjusting for other covariates and considering the competing risk of mortality, patients with rosacea remained at increased risk of CKD (adjusted sub-distribution hazard ratio (aSD-HR) 2.00; 95% confidence interval (CI) 1.05–3.82). The aSD-HRs (95% CI) for CKD were 1.82 (0.83–4.00) and 2.53 (1.11–5.75) for patients with mild and moderate-to-severe rosacea, respectively. Conclusions: Rosacea is an independent risk factor for CKD. High rosacea severity and old age further increased CKD risk in patients with rosacea. Careful monitoring for CKD development should be included as part of integrated care for patients with rosacea. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic cancer is one of the most lethal types of cancer with a 5-year survival rate of ~5%. Histone deacetylases (HDACs) participate in many cellular processes, including carcinogenesis, and pharmacological inhibition of HDACs has emerged as a potential therapeutic strategy. In this study, we explored antitumor activity of the novel HDAC inhibitor AR-42 in pancreatic cancer. Methods: Human pancreatic cancer cell lines BxPC-3 and PANC-1 were used in this study. Real-time PCR, RT-PCR, and western blotting were employed to investigate expression of specific genes and proteins, respectively. Translocation of apoptosis-inducing factor was investigated by immunofluorescence and subcellular fractionation. The number of apoptotic cells, cell cycle stages, and reactive oxygen species (ROS) generation levels were determined by flow cytometry. Cell invasiveness was examined by the Matrigel invasion assay. Efficacy of AR-42 in vivo was evaluated by utilizing BxPC-3 xenograft mouse model. Results: AR-42 inhibited pancreatic cancer cell proliferation by causing G2/M cell cycle arrest via regulating expression levels of genes and proteins involved in cell cycle. AR-42 also induced ROS generation and DNA damage, triggering apoptosis of pancreatic cancer cells via both caspase-3-dependent and caspase-3-independent pathways. In addition, AR-42 increased expression levels of negative regulators of p53 (miR-125b, miR-30d, and miR33), which could contribute to lower expression level of mutant p53 in pancreatic cancer cells. Cell invasion assay showed that AR-42 reduced cancer cell aggressiveness and significantly diminished BxPC-3 xenograft tumor growth in vivo. Conclusion: AR-42, a novel HDAC inhibitor, inhibited pancreatic cancer cells by regulating p53 expression, inducing cell cycle arrest, particularly at the G2/M stage, and activating multiple apoptosis pathways. Additionally, AR-42 inhibited cell invasiveness and potently suppressed pancreatic cancer tumors in vivo. We conclude that by virtue of its multiple mechanisms of action, AR-42 possesses a considerable potential as an antitumor agent in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Mitochondria play a pivotal role in most eukaryotic cells, as they are responsible for the generation of energy and diverse metabolic intermediates for many cellular events. During endosymbiosis, approximately 99% of the genes encoded by the mitochondrial genome were transferred into the host nucleus, and mitochondria import more than 1000 nuclear-encoded proteins from the cytosol to maintain structural integrity and fundamental functions, including DNA replication, mRNA transcription and RNA metabolism of dozens of mitochondrial genes. In metazoans, a family of nuclear-encoded proteins called the mitochondrial transcription termination factors (mTERFs) regulates mitochondrial transcription, including transcriptional termination and initiation, via their DNA-binding activities, and the dysfunction of individual mTERF members causes severe developmental defects. Arabidopsis thaliana and Oryza sativa contain 35 and 48 mTERFs, respectively, but the biological functions of only a few of these proteins have been explored. Here, we investigated the biological role and molecular mechanism of Arabidopsis mTERF15 in plant organelle metabolism using molecular genetics, cytological and biochemical approaches. The null homozygous T-DNA mutant of mTERF15, mterf15, was found to result in substantial retardation of both vegetative and reproductive development, which was fully complemented by the wild-type genomic sequence. Surprisingly, mitochondria-localized mTERF15 lacks obvious DNA-binding activity but processes mitochondrial nad2 intron 3 splicing through its RNA-binding ability. Impairment of this splicing event not only disrupted mitochondrial structure but also abolished the activity of mitochondrial respiratory chain complex I. These effects are in agreement with the severe phenotype of the mterf15 homozygous mutant. Our study suggests that Arabidopsis mTERF15 functions as a splicing factor for nad2 intron 3 splicing in mitochondria, which is essential for normal plant growth and development. [ABSTRACT FROM AUTHOR]

Introduction: Lower urinary tract symptoms (LUTS), which encompass storage, voiding, and postmicturition symptoms, are highly prevalent and recognized globally. Based on a nationwide population-based database, this study tests the hypothesis that medical attendance for LUTS is associated with a subsequent increase in the number of outpatient visits and hospitalizations, with differences among medical specialties and age groups. Methods: Participants were selected from a random population sample of approximately one million people as a representative cohort of National Health Insurance (NHI) enrollees in Taiwan. Participants had at least three outpatient service claims with a coding of LUTS during the recruitment period 2001–2004. Both the LUTS group and non-LUTS control group were monitored for subsequent outpatient visits and hospitalizations, excluding LUTS-related healthcare services, for 2 years following the index date. The results were categorized based on medical specialty and age group. Results: The outpatient visit rates (no. per person-year) and adjusted incidence rate ratios (IRRs) (95% confidence interval (CI) were significantly higher in urology (4.51, 95%CI 4.15–4.91) and gynecology (1.82, 95%CI 1.76–1.89) for the LUTS group. They were also significantly high in other departments, including internal medicine (1.25), general practice (1.13), Chinese medicine (1.77), family medicine (1.19), surgery (1.38), and psychiatry (1.98). Similarly, the hospitalization rate (no. per 1000 person-year) and adjusted IRRs (95% CI) were significantly higher in urology (5.50, 95% CI = 4.60–6.50) and gynecology (1.60, 95% CI = 1.35–1.90), as well as in internal medicine (1.55) and surgery (1.56), but not in psychiatry (1.12). Furthermore, the IRRs differed among 3 age groups. Conclusions: A significantly higher number of outpatient visits and hospitalizations were observed for individuals with LUTS, compared to the control group, and the effects differed with the advancement of age. This study broadens understanding of LUTS by viewing their impact on healthcare services with multiple and overlapping systems, rather than considering them exclusively as symptoms of traditional diseases of the bladder and urethra. [ABSTRACT FROM AUTHOR]