Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway.

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Association of physical functional activity impairment with severity of sarcopenic obesity: findings from National Health and Nutrition Examination Survey.

We aim to clarify the relationship between low skeletal muscle mass and varying levels of adiposity and to identify the types of physical function impairments associated with sarcopenic obesity (SO). This study examined cross-sectional data from the National Health and Nutrition Examination Survey with whole-body dual-energy X-ray absorptiometry (DXA) scans. The data included age, gender, DXA-assessed body composition, and physical functional activity with performing daily tasks by questionnaire. We subdivided the data by body composition into a non-SO group and a SO group (ASMI 0-49.99% and FMI of 50-100%), after which the SO data were subdivided into three classes. A higher class indicated higher adiposity and lower muscle mass. The physical function impairment of the two groups was compared. Our study examined 7161 individuals, of which 4907 did not have SO and 2254 had SO, and their data were further divided into three classes (i.e., class I, 826 individuals; class II, 1300 individuals; and class III, 128 individuals). Significant differences in demographics and DXA parameters were identified between the non-SO and SO groups (P < 0.001); the individuals with SO were older, included more women, and exhibited high adiposity and less lean muscle mass. The individuals with class III SO exhibited greater differences and reported more difficulty in performing daily activities. The individuals with class III SO exhibited the most severe physical function impairment. Our study highlights the considerable difficulties encountered by individuals with SO in performing daily activities. Given this finding, customized rehabilitation strategies should be implemented to improve the quality of life of individuals with SO.

Pb(NO3 )2 induces cell apoptosis through triggering of reactive oxygen species accumulation and disruption of mitochondrial function via SIRT3/SOD2 pathways.

Lead (Pb) is nonbiodegradable and toxic to the lungs. To investigate the potential mechanisms of Pb-induced reactive oxygen species (ROS) accumulation and cell death in the lungs, human non-small lung carcinoma H460 cells were stimulated with Pb(NO3 )2 in this study. The results showed that Pb(NO3 )2 stimulation increased cell death by inducing cell apoptosis which showed a reduced Bcl-2 expression and an enhanced caspase 3 activation. Pb(NO3 )2 also caused the production of H2 O2 in H460 cells that triggering the buildup of ROS and mitochondrial membrane potential loss. We found that Pb(NO3 )2 modulates oxidoreductive activity through reduced the glutathione-disulfide reductase and glutathione levels in Pb(NO3 )2 -exposed H460 cells. Furthermore, the superoxide dismutase (SOD) upstream molecule sirtuin 3 (SIRT3) was increased with Pb(NO3 )2 dose. Collectively, these results demonstrate that Pb(NO3 )2 promotes lung cell death through SIRT3/SOD-mediated ROS accumulation and mitochondrial dysfunction.

The protective effects of beta-mangostin against sodium iodate-induced retinal ROS-mediated apoptosis through MEK/ERK and p53 signaling pathways.

Previous studies have indicated that NaIO3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens. The influence of BM on NaIO3-induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO3-induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO3; it was mediated by significantly reduced NaIO3-upregulated ROS, cellular H2O2 production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO3-induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO3 from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO3 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO3-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.

The association between tyrosine kinase inhibitors and fatal arrhythmia in patients with non-small cell lung cancer in Taiwan.

Objective: As a standard therapy, tyrosine kinase inhibitors (TKIs) improved survival in patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation. However, treatment-related cardiotoxicity, particularly arrhythmia, cannot be ignored. With the prevalence of EGFR mutations in Asian populations, the risk of arrhythmia among patients with NSCLC remains unclear. Methods: Using data from the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified patients with NSCLC from 2001 to 2014. Using Cox proportional hazards models, we analyzed outcomes of death and arrhythmia, including ventricular arrhythmia (VA), sudden cardiac death (SCD), and atrial fibrillation (AF). The follow-up duration was three years. Results: In total, 3876 patients with NSCLC treated with TKIs were matched to 3876 patients treated with platinum analogues. After adjusting for age, sex, comorbidities, and anticancer and cardiovascular therapies, patients receiving TKIs had a significantly lower risk of death (adjusted HR: 0.767; CI: 0.729-0.807, p < 0.001) than those receiving platinum analogues. Given that approximately 80% of the studied population reached the endpoint of mortality, we also adjusted for mortality as a competing risk. Notably, we observed significantly increased risks of both VA (adjusted sHR: 2.328; CI: 1.592-3.404, p < 0.001) and SCD (adjusted sHR: 1.316; CI: 1.041-1.663, p = 0.022) among TKI users compared with platinum analogue users. Conversely, the risk of AF was similar between the two groups. In the subgroup analysis, the increasing risk of VA/SCD persisted regardless of sex and most cardiovascular comorbidities. Conclusions: Collectively, we highlighted a higher risk of VA/SCD in TKI users than in patients receiving platinum analogues. Further research is needed to validate these findings.

Assessment of Tyrosine Kinase Inhibitors and Survival and Cardiovascular Outcomes of Patients With Non-Small Cell Lung Cancer in Taiwan.

Importance: Tyrosine kinase inhibitors (TKIs) have been recognized as the standard treatment for patients with non-small cell lung cancers (NSCLCs) and epidermal growth factor receptor (EGFR) sequence variation. Although TKIs have been reported to cause cardiotoxicity, they are widely administered owing to the high prevalence of EGFR sequence variation in Taiwan. Objective: To compare the outcomes of death and major adverse cardiac and cerebrovascular events among patients with NSCLC who use and do not use TKIs in a national cohort. Design, Setting, and Participants: Using data from the Taiwanese National Health Insurance Research Database and National Cancer Registry, patients treated for NSCLC from 2011 to 2018 were identified, and their outcomes were analyzed, including death and major adverse cardiac and cerebrovascular events (MACCEs; such as heart failure, acute myocardial infarction, and ischemic stroke) after adjusting for age, sex, cancer stage, comorbidities, anticancer therapies, and cardiovascular drugs. The median follow-up duration was 1.45 years. The analyses were performed from September 2022 to March 2023. Exposures: TKIs. Main Outcomes and Measures: Cox proportional hazards models were used to estimate death and MACCEs in patients treated with and without TKIs. Given that death may reduce the incidence of cardiovascular events, the competing risk method was used to calculate the MACCE risk after adjustment for all potential confounders. Results: Overall, 24 129 patients treated with TKIs were matched with 24 129 patients who did not receive TKIs (24 215 [50.18%] were female; and the mean [SD] age was 66.93 [12.37] years). Compared with those not receiving TKIs, the TKI group presented with a significantly lower hazard ratio (HR) of all-cause death (adjusted HR, 0.76; 95% CI, 0.75-0.78; P < .001), and the reason for death was primarily cancer. In contrast, the HR of MACCEs significantly increased (subdistribution HR, 1.22; 95% CI, 1.16-1.29; P < .001) in the TKI group. Furthermore, afatinib use was associated with a significantly reduced risk of death among patients receiving various TKIs (adjusted HR, 0.90; 95% CI, 0.85-0.94; P < .001) compared with those receiving erlotinib and gefitinib, although the outcomes of MACCEs were similar between the 2 groups. Conclusions and Relevance: In this cohort study of patients with NSCLC, TKI use was associated with reduced HRs of cancer-related death but increased HRs of MACCEs. These findings suggest the importance of close monitoring of cardiovascular problems in individuals receiving TKIs.

Association of Statin Use With Cancer- and Noncancer-Associated Survival Among Patients With Breast Cancer in Asia.

Importance: In addition to protective effects on the cardiovascular system, statins may reduce the risk of breast cancer recurrence owing to potential anti-inflammatory benefits. Given that patients with breast cancer in Asia are relatively younger at diagnosis and most are free from traditional cardiovascular risk factors, it is uncertain whether the use of statins can improve survival. Objective: To investigate the association of statin use with cancer- and noncancer-associated survival in patients with breast cancer. Design, Setting and Participants: This cohort study used the Taiwanese National Health Insurance Research Database and National Cancer Registry to identify patients diagnosed with breast cancer from January 2012 to December 2017. Age, cancer stage, anticancer therapies, comorbidities, socioeconomic status, and cardiovascular drugs were matched by propensity score method. Statistical analyses, including Cox proportional hazards models, were performed from June 2022 to February 2023. The mean (SD) follow-up duration was 4.10 (2.96) years. Interventions: Patients receiving statins within 6 months before the diagnosis of breast cancer were compared with those not receiving statins. Main Outcomes and Measures: Outcomes included death, heart failure, and arterial and venous events. Results: Overall, 7451 patients (mean [SD] age, 64.3 [9.4] years) treated with statins were matched with 7451 nonusers (mean [SD] age, 65.8 [10.8] years). Compared with nonusers, statin users had a significantly lower risk of all-cause death (adjusted hazard ratio [HR], 0.83; 95% CI, 0.77-0.91; P < .001). Notably, the risk reduction was mainly attributed to cancer-related death (adjusted HR, 0.83; 95% CI, 0.75-0.92; P < .001). Only a small number of patients died of cardiovascular causes, and the ratios were similar between statin users and nonusers. No significant differences were observed in cardiovascular outcomes, including heart failure and arterial and venous events, between statin users and nonusers. Using a time-dependent analysis, statin users also presented a significantly lower risk of cancer-related death (adjusted HR, 0.28; 95% CI, 0.24-0.32; P < .001) than nonusers, and notably, the risk was even lower in high-dose statin (HDS) users compared with non-HDS users (HDS users: adjusted HR, 0.84; 95% CI, 0.73-0.98; P = .002; non-HDS users: adjusted HR, 0.79; 95% CI, 0.68-0.91; P = 001). Conclusions and Relevance: In this cohort study of Asian patients with breast cancer, statin use was associated with a reduced risk of cancer-associated death rather than cardiovascular death. Our findings provide evidence to support the use of statins in patients with breast cancer; however, randomized studies are necessary.

Luteolin Reduces Aqueous Extract PM2.5-induced Metastatic Activity in H460 Lung Cancer Cells.

Fine particulate matter (PM2.5) is the critical cause of lung cancer and can further promote tumor cell migration and invasion. This study investigated the effects of luteolin, an antiangiogenic flavonoid agent, on blocking aqueous extract PM2.5-prompted cancer progression. We observed that luteolin reduced cell migration and the expression of pro-metastatic factors pro-matrix metalloproteinase (MMP)-2 and intercellular adhesion molecule (ICAM)-1 in PM2.5-exposed H460 lung cancer cells. Luteolin treatment also reduced the transduction of PM2.5-induced epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) cascade signaling. Furthermore, the reduction of MMP-2 expression and ICAM-1 production by luteolin in PM2.5-stimulated H460 cells is EGFR-PI3K-AKT pathway dependent. These results suggest that luteolin exhibits antitumor progression by inhibiting EGFR-PI3K-AKT pathway.

Particulate matter 2.5 exposure induces epithelial-mesenchymal transition via PI3K/AKT/mTOR pathway in human retinal pigment epithelial ARPE-19 cells.

Exposure to particulate matter 2.5 (PM2.5) has been linked to ocular surface diseases, yet knowledge of the molecular mechanism impacted on retina pathogenesis is limited. Therefore, the purpose of this study was to explore the effects and involved factors of PM2.5 exposure in human retinal pigment epithelial APRE-19 cells. Our data revealed a decreased cell viability and an increased migratory ability in APRE-19 cells after PM2.5 stimulation. The MMP-2 and MMP-9 protein levels were markedly increased while the MMPs regulators TIMP-1 and TIMP-2 were significantly reduced in PM2.5-exposed APRE-19 cells. PM2.5 also increased pro-MMP-2 expression in the cell culture supernatants. Additionally, PM2.5 promoted the EMT markers through the activation of PI3K/AKT/mTOR pathway. Moreover, the ICAM-1 production was also remarkably increased by PM2.5 but reduced by PI3K/AKT inhibitor LY294002 in APRE-19 cells. Taken together, these results suggest that PM2.5 promotes EMT in a PI3K/AKT/mTOR-dependent manner in the retinal pigment epithelium.

The Establishment of a Noninvasive Bioluminescence-Specific Viral Encephalitis Model by Pseudorabies Virus-Infected NF-κBp-Luciferase Mice.

Encephalitis is a rare brain inflammation that is most commonly caused by a viral infection. In this study, we first use an in vivo imaging system (IVIS) to determine whether NF-κBp-luciferase expression could be detected in the brain of pseudorabies virus (PRV)-infected NF-κBp-luciferase mice and to evaluate proinflammatory mediators in a well-described mouse model of PRV encephalitis. In in vitro studies, we used murine microglia (BV-2) cells to demonstrate the PRV-induced encephalitis model entailing the activation of microglia cells. The results indicate that PRV-induced neuroinflammation responses through the induction of IL-6, TNF-α, COX-2, and iNOS expression occurred via the regulation of NF-κB expression in BV-2 cells. In in vivo studies, compared with MOCK controls, the mice infected with neurovirulent PRV exhibited significantly elevated NF-κB transcription factor activity and luciferase protein expression only in the brain by IVIS. Mild focal necrosis was also observed in the brain. Further examination revealed biomarkers of inflammation, including inducible cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α and interleukin (IL)-6, both of which constituted proinflammatory cytokines. PRV infection stimulated inflammation and COX-2 and iNOS expression of IL-6 and TNF-α. The presented results herein suggest that PRV induces iNOS and COX-2 expression in the brain of NF-κBp-luciferase mice via NF-κB activation. In conclusion, we used NF-κBp-luciferase mice to establish a specific virus-induced encephalitis model via PRV intranasal infection. In the future, this in vivo model will provide potential targets for the development of new therapeutic strategies focusing on NF-κB inflammatory biomarkers and the development of drugs for viral inflammatory diseases.

Risks of Aromatase Inhibitor-Related Cardiotoxicity in Patients with Breast Cancer in Asia.

BACKGROUND: Despite a preferred endocrine therapy for women with estrogen and progesterone receptor-positive breast cancer, aromatase inhibitors (AIs) have been reported to increase risks of cardiovascular events. Given that breast cancer patients in Asia are younger at diagnosis, it is urgent to investigate this safety concern. METHODS: Through the Taiwanese National Cohort, we identified breast cancer patients initiating selective estrogen receptor modulators (SERMs) or AIs from 2010 to 2016. Outcomes includes major adverse cardio- and cerebrovascular events (MACCEs). The average follow-up duration was five years. RESULTS: We identified 16,730 breast cancer patients treated with SERMs and 11,728 receiving AIs. The population was older and had more comorbidities in the AI group than in the SERM group. After adjusting for age, cancer stage, cancer therapies, cardiovascular drugs and comorbidities, despite similar risks of MACCEs between AI and SERM users, the risk of HF was significantly higher in patients treated with SERMs after adjusted mortality as a competing risk. When divided by the age of 50 years, despite a similar MACCEs in the younger population, MACCEs remained significantly higher in the older population who received SERMs. CONCLUSIONS: In this Asian cohort, we found that among patients of old age or with advanced cancer stage, the use of SERMs was associated with a higher risk of cardiovascular events than the use of AIs.

Osteoporosis increases the risk of rotator cuff tears: a population-based cohort study.

INTRODUCTION: Osteoporosis has been demonstrated to be a risk factor for rotator cuff retears after surgery; however, no studies have directly investigated the association between osteoporosis and the development of rotator cuff tears. To investigate whether osteoporosis is associated with an increased risk of rotator cuff tears. MATERIALS AND METHODS: We conducted a population-based, matched-cohort study with a 7-year follow-uTwo matched cohorts (n = 3511 with osteoporosis and 17,555 without osteoporosis) were recruited from Taiwan's Longitudinal Health Insurance Dataset. Person-year data and incidence rates were evaluated. A multivariable Cox model was used to derive an adjusted hazard ratio (aHR) after controlling for age, sex, and various prespecified comorbidities. Age and sex were added in the model to test for interaction with osteoporosis. RESULTS: Women constituted 88.5% of the cohorts. During follow-up of 17,067 and 100,501 person-years for the osteoporosis and nonosteoporosis cohorts, 166 and 89 rotator cuff tears occurred, respectively. The cumulative incidence of rotator cuff tears was significantly higher in the osteoporosis cohort than in the nonosteoporosis cohort (p < 0.001, log-rank). The Cox model revealed a 1.79-fold increase in rotator cuff tears in the osteoporosis cohort, with an aHR of 1.79 (95% confidence interval, 1.55-2.05). Effect modification of sex and age on rotator cuff tears was not found in patients with osteoporosis. CONCLUSION: This population-based study supports the hypothesis that compared with individuals without osteoporosis, those with osteoporosis have a higher risk of developing rotator cuff tears.

Ganoderma formosanum Exopolysaccharides Inhibit Tumor Growth via Immunomodulation.

Ganoderma formosanum (GF) is a medicinal mushroom endemic to Taiwan. Previous research established the optimal culture conditions to produce exopolysaccharide rich in ß-glucan (GF-EPS) from submerged fermentation of GF. The present study investigated the antitumor effects of GF-EPS in a Lewis lung carcinoma cell (LLC1) tumor-bearing mice model. In the preventive model, GF-EPS was orally administered to mice before LLC1 injection. In the therapeutic model, GF-EPS oral administration was initiated five days after tumor cell injection. The tumor size and body weight of the mice were recorded. After sacrifice, the lymphocyte subpopulation was analyzed using flow cytometry. Spleen tissues were used to analyze cytokine mRNA expression. The results showed that GF-EPS (80 mg/kg) effectively suppressed LLC1 tumor growth in both the preventive and therapeutic models. GF-EPS administration increased the proportion of natural killer cells in the spleen and activated gene expression of several cytokines. Our results provide evidence that GF-EPS promotes tumor inhibition through immunomodulation in tumor-bearing mice.

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan.

AIMS: In contrast to Western patients with breast cancer, Asian patients are relatively younger at diagnosis, and most are free from traditional cardiovascular risk factors. Despite trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) being reported, its incidence and predictors remain unknown in Taiwan. METHODS AND RESULTS: Through a three-hospital retrospective cohort study, we analysed the incidence of MACCE in 386 breast cancer patients' exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13 502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab non-users, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4 and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67 and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246-1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than non-users. CONCLUSIONS: From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.

Effect of aspirin treatment duration on clinical outcomes in acute coronary syndrome patients with early aspirin discontinuation and received P2Y12 inhibitor monotherapy.

Recent clinical trials showed that short aspirin duration (1 or 3 months) in dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduced the risk of bleeding and did not increase the ischemic risk compared to 12-month DAPT in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, it is unclear about the optimal duration of aspirin in P2Y12 inhibitor monotherapy. The purpose of this study was to evaluate the influence of aspirin treatment duration on clinical outcomes in a cohort of ACS patients with early aspirin interruption and received P2Y12 inhibitor monotherapy. From January 1, 2014 to December 31, 2018, we included 498 ACS patients (age 70.18 ± 12.84 years, 71.3% men) with aspirin stopped for various reasons before 6 months after PCI and received P2Y12 inhibitor monotherapy. The clinical outcomes between those with aspirin treatment ≤ 1 month and > 1 month were compared in 12-month follow up after PCI. Inverse probability of treatment weighting was used to balance the covariates between groups. The mean duration of aspirin treatment was 7.52 ± 8.10 days vs. 98.05 ± 56.70 days in the 2 groups (p<0.001). The primary composite endpoint of all-cause mortality, recurrent ACS or unplanned revascularization and stroke occurred in 12.6% and 14.4% in the 2 groups (adjusted HR 1.19, 95% CI 0.85-1.68). The safety outcome of BARC 3 or 5 bleeding was also similar (adjusted HR 0.69, 95% CI 0.34-1.40) between the 2 groups. In conclusion, patients with ≤ 1 month aspirin treatment had similar clinical outcomes to those with treatment > 1 month. Our results indicated that ≤ 1-month aspirin may be enough in P2Y12 inhibitor monotherapy strategy for ACS patients undergoing PCI.

Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation.

Urethane dimethacrylate (UDMA) is a dimethacrylate-based resin monomer that can react with other related monomers and inorganic particles, causing hydrophobic polymerization through cross-linking upon light activation. UDMA polymers are commonly used for the reconstruction and reinforcement of teeth and bones. UDMA can become unbound and be released from light-cured polymer resins. Thus far, no evidence exists on the toxic effects of UDMA and its related working mechanisms for macrophages. Therefore, in the present study, we investigated the cytotoxicity, mode of cell death, DNA damage, caspase activities, mitochondrial dysfunction, and reactive oxygen species (ROS) generation in RAW264.7 macrophages treated with UDMA using the lactate dehydrogenase (LDH) assay kit, Annexin V-FITC and PI assays, micronucleus formation and comet assay, caspase fluorometric assay, JC-1 assay, and 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay, respectively. Our results show that UDMA induced cytotoxicity; apoptosis and necrosis; genotoxicity, which is also called DNA damage; increased caspase-3, -8, and -9 activities; mitochondrial dysfunction; and intracellular ROS generation in a concentration-dependent manner in RAW264.7 macrophages. Thus, based on the observed inhibited concentration parallel trends, we concluded that UDMA induces toxic effects in macrophages. Furthermore, UDMA-induced intracellular ROS generation, cytotoxicity, and DNA damage were reduced by N-acetyl-L-cysteine.

Full-scale investigation of in-situ iron and alkalinity generation for efficient sulfide control.

Hydrogen sulfide induced corrosion of concrete sewer pipes is a major issue for wastewater utilities globally. One of the most commonly used methods to combat hydrogen sulfide is the addition of ferric chloride. While a reliable and effective method, ferric chloride is acidic causing OH&S concerns as well as alkalinity consumption in sewage. This study investigates, under full-scale field conditions, an alternative method for sulfide control by in-situ electrochemical generation of iron ions using sacrificial iron electrodes. This method concomitantly produces alkalinity through cathodic OH- generation, rather than consumption. The gaseous hydrogen sulfide concentrations at the discharge wet well of a real-life rising main (length: ∼1 km in, diameter: 150 mm) decreased from 173 ppm to 43 ppm (90 percentile of peak values), when a current of 0.86 A/m3 of sewage was applied. The 90 percentile peak H2S value was further reduced to 6.6 ppm when the applied current was increased to 1.14 A/m3 sewage. Moreover, methane generation was almost completely inhibited from 25.3 ±â€¯1.46 mg COD/L to 0.06 ±â€¯0.04 mg COD/L. The overall cell voltage remained constant throughout the experimental period clearly showing the stability of the process. Detailed characterization of the down-stream sewer pipe biofilm revealed the complexity of the iron chemistry as the in-situ produced iron ions undergo transformation into a variety of iron species. Overall, this study demonstrates that in-situ generation of iron and alkalinity is an effective alternative method for hydrogen sulfide control in sewers.

Autoimmune Connective Tissue Diseases and the Risk of Rotator Cuff Repair Surgery: A Population-Based Retrospective Cohort Study.

OBJECTIVES: Autoimmune connective tissue diseases (ACTDs) commonly involve the shoulder joint; however, clinical epidemiological studies investigating their association with tendons are scant. Rotator cuff (RC) tears can cause shoulder disability, and surgical intervention is usually required. The study investigated RC repair surgery risk in ACTD patients. The effect of anti-inflammatory medication on RC repair surgery risk was also investigated. METHODS: We conducted a retrospective cohort study with a 7-year longitudinal follow-up period. Patients with systemic lupus erythematosus, systemic sclerosis, sicca syndrome, dermatomyositis and polymyositis diagnoses between 2004 and 2008 were enrolled. The control cohort comprised age- and sex-matched controls. The HR and adjusted HR (aHR) were estimated for the risk of RC surgery between ACTD and control cohorts after adjustment for confounders. Furthermore, the effects of steroid and non-steroidal anti-inflammatory drug (NSAID) use on the HR and aHR of RC surgery risk were analysed. RESULTS: We enrolled 5019 ACTD patients and 25 095 controls in the ACTD and control cohorts, respectively. RC surgery incidence was 49 and 24 per 100 000 person-years in the ACTD and control cohorts, respectively. In the ACTD cohort, the crude HR for RC surgery was 2.08 (95% CI , 1.08 to 4.02, p<0.05), and the aHR was 1.97 (95% CI, 1.01 to 3.82, p<0.05). The ACTD patients who used NSAIDs had an aHR of 3.13 (95% CI, 1.21 to 8.07, p<0.05) compared with the controls, but the ACTD patients who used steroids did not have a significantly higher aHR than the controls. CONCLUSIONS: ACTD patients had an increased risk of RC repair surgery. However, no difference was found in RC surgery risk when steroids were used compared with the control cohort. This could indicate that inflammation control may be a strategy for managing subsequent RC lesions.