Since the ban of tributyltin in antifouling paints, many alternative biocides have been introduced to prevent settlement and growth of marine organisms on ship hulls. Zinc pyrithione (ZnPT) is one of ...the most frequently used alternative biocides in antifouling paints. This paper reviewed the overall chemical properties, toxicological characteristics, and environmental fates of ZnPT, as well as the analytical challenges of studying pertinent processes. ZnPT is generally toxic to a wide range of marine organisms, including algae, bivalves, sea urchins, polychaetes, crustaceans, and fish, typically at μg/L levels. ZnPT can be transchelated into other compounds in the presence of metal ions, and photodegrades when exposed to UV light. ZnPT is also reported to be biodegraded or hydrolyzed forming several metabolites of their own toxicity and stability. However, ZnPT accumulates in the water column or sediment, if it does not degrade at certain environmental conditions. To determine potential risks caused by ZnPT in the marine environment, studies have evaluated the environmental distribution of ZnPT with various chromatographic or voltammetry methods. Unfortunately, rapid transchelation and degradation of ZnPT in both the marine environment and laboratory interfered with most of the methods employed, making it difficult to evaluate its environmental distribution. More robust and sensitive analytical methods need to be developed to reliably describe the environmental release and distribution of ZnPT. To comprehensively understand the risk posed by the input of ZnPT into the marine environment, total degradation processes and its potential products also need to be adequately addressed.
Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the ...management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m
. Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m
and for Korean patients with BMI ≥30 kg/m
who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.
ABSTRACTMitophagy has been implicated in mitochondrial quality control and in various human diseases. However, the study of in vivo mitophagy remains limited. We previously explored in vivo mitophagy ...using a transgenic mouse expressing the mitochondria‐targeted fluorescent protein Keima (mt‐Keima). Here, we generated mt‐Keima Drosophila to extend our efforts to study mitophagy in vivo. A series of experiments confirmed that mitophagy can be faithfully and quantitatively measured in mt‐Keima Drosophila. We also showed that alterations in mitophagy upon environmental and genetic perturbation can be measured in mt‐Keima Drosophila. Analysis of different tissues revealed a variation in basal mitophagy levels in Drosophila tissues. In addition, we found a significant increase in mitophagy levels during Drosophila embryogenesis. Importantly, loss‐of‐function genetic analysis demonstrated that the phosphatase and tensin homolog‐induced putative kinase 1 (PINK1)‐Parkin pathway is essential for the induction of mitophagy in vivo in response to hypoxic exposure and rotenone treatment. These studies showed that the mt‐Keima Drosophila system is a useful tool for understanding the role and molecular mechanism of mitophagy in vivo. In addition, we demonstrated the essential role of the PINK1‐Parkin pathway in mitophagy induction in response to mitochondrial dysfunction.—Kim, Y. Y., Um, J.‐H., Yoon, J.‐H., Kim, H., Lee, D.‐Y., Lee, Y. J., Jee, H. J., Kim, Y. M., Jang, J. S., Jang, Y.‐G., Chung, J., Park, H. T., Finkel, T., Koh, H., Yun, J. Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo. FASEB J. 33, 9742–9751 (2019). www.fasebj.org
Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity ...contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines.
Although the introduction of human epidermal growth factor receptor (HER)2‐directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T‐DM1) in the treatment of ...HER2‐positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2‐positive mBC will eventually progress. Poziotinib is an oral pan‐HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open‐label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2‐positive mBC who had progressed from more than two HER2‐directed therapies. Patients received 12 mg poziotinib once daily on a 14‐day on/7‐day off schedule. Progression‐free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30–76) and had received a median of four prior therapies including two HER2‐directed therapies for advanced or metastatic cancers. The median follow‐up duration was 12 months. The median PFS was 4.04 months (95% confidence interval CI, 2.94–4.40 months), and median overall survival has not been reached. The most common treatment‐related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2‐positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases.
What's new?
Targeting human epidermal growth factor receptor 2 (HER2) has revolutionized treatment of HER2‐positive cancers but rapid resistance development causes significant clinical problems. In this phase II study, the authors tested poziotinib, a new oral pan‐HER inhibitor, in patients with metastatic breast cancer after two prior HER2‐directed therapies. Treatment with poziotinib achieved on average a progression‐free survival of ~4 months with relatively mild side effects (skin rash and diarrhoea), an encouraging result for patients with repeated treatment failure.
Background
There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric ...cancer (GC).
Methods
In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO) in tumors and the densities of immune cells CD3(+), CD4(+), CD8(+), or PD-1(+) cells within the tumor microenvironment were measured using immunohistochemical analysis.
Results
Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (
P
< 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC PD-L1(+) vs. PD-L1(−) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (
P
values <0.05). Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells 5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (
P
values <0.05). In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables.
Conclusions
GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.
Cellular senescence acts as an important barrier to tumorigenesis by eliminating precancerous cells. Previous studies have shown an essential role of the tumor suppressor p53 in cellular senescence, ...but how p53 induces cellular senescence is not fully understood. We found that p53 promoted the formation of highly interconnected and elongated mitochondria prior to the onset of cellular senescence. The inhibition of mitochondrial elongation upon p53 expression suppressed cellular senescence, suggesting that mitochondrial elongation is required for the induction of p53‐dependent senescence. p53‐induced mitochondrial elongation resulted in mitochondrial dysfunction and subsequent increases in intracellular reactive oxygen species (ROS) levels, an important mediator of cellular senescence. Mechanistically, the inhibitory phosphorylation of Drp1 Ser637 increased upon p53 expression, suppressing the translocation of Drp1 into mitochondria. The transcriptional function of p53 was crucial for controlling the inhibitory phosphorylation of Drp1, whereas p21 was nonessential. Protein kinase A (PKA) activity was responsible for p53‐mediated Drp1 Ser637 phosphorylation and mitochondrial dysfunction. Taken together, these results suggest that p53 regulates mitochondrial dynamics through the PKA‐Drp1 pathway to induce cellular senescence.
An increase in the use of ROVs for in-water hull cleaning (IWC) has led to the need to understand the risks to the marine environment posed by the release of IWC effluents. The primary objective of ...this research is to investigate the characteristics of wastewater generated during IWC, specifically concerning suspended solids (SS) and metal concentrations, and their release rates and total load to the environment. The IWC effluents contain substantial amounts of SS and metals, with Cu and Zn being the most prevalent. These metals are predominantly associated with fine antifouling paint particles, posing a potential risk of secondary pollution upon release into the marine environment. While the treatment systems demonstrated effectiveness in reducing SS and particulate metals, achieving complete removal of dissolved and particulate metals below ambient levels proved to be challenging. To mitigate environmental risks, this study proposes, based on the particle size analysis, the implementation of multistage filtration systems with an optimal filtration pore size for the effluent treatment. In conclusion, we highlight the potential environmental risks of IWC activities. As most metals have a strong affinity towards particles in wastewater, effective removal of particles is essential to alleviate environmental stress at IWC sites.
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•In-water cleaning effluent was highly contaminated with suspended solids and metals.•Cu and Zn were the most abundant in both dissolved and particulate phases.•Most metals exist in association with fine antifouling paint particles.•Release rate of metal and SS was presented and used to estimate environmental load.•Appropriate treatment of the effluent is essential to reduce environmental stress.
Sorption of organic pollutants on microplastics can be an alternative uptake route for organic pollutants in aquatic organisms. To assess the combined effects of microplastics and organic pollutants, ...we employed phenotypic and transcriptomic analyses to the responses of the marine rotifer Brachionus koreanus to environmentally relevant concentrations of nano-sized microplastic (0.05 µm), water-accommodated fractions of crude oil, and binary mixtures thereof. Our multigenerational in vivo experiments revealed more than additive effects on population growth of B. koreanus in response to combined exposure, while a single exposure to nano-sized microplastic did not induce observable adverse effects. Synergistic transcriptome deregulation was consistently associated with dramatically higher numbers of differentially expressed genes, and increased gene expression was associated with combined exposure. The majority of synergistic transcriptional alteration was related to metabolism and transcription, with impaired reproduction resulting from energetic reallocation toward adaptation. As further supported by chemistry analysis for polycyclic aromatic hydrocarbons sorption on microplastic, our findings imply that nano-sized microplastics can synergistically mediate the effects of organic pollutants in aquatic organisms.
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•Adsorption of PAHs on nano-sized MP was verified by chemistry analysis.•Synergistic effects were observed by combined exposure of nano-sized MP and WAF.•Multigenerational adverse effects were shown by combined exposure.•Combined exposure altered transcriptome related to metabolism and transcription.
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•Hull cleaning effluent was highly contaminated with metals from antifouling paint.•Cu and Zn in the effluents were at levels lethal to almost all marine organisms.•Model simulated ...environmental concentration was higher than no-effect concentration.•Untreated discharge of the effluents will pose risk to the marine environment.•Ship’s hull cleaning should be appropriately managed to protect marine ecosystem.
Hydroblasting is used to remove biofouling and exhausted antifouling paints from ship hulls. Effluents generated from this process contain paint particles, metals, and booster biocides that may have toxic effects on organisms. To understand the potential risks of effluent discharge on marine environments, we analyzed the concentrations of metals in effluents collected during the dry-dock cleaning of ship hulls by hydroblasting. Copper and zinc were the principal metals, with concentrations ranging from 1440 to 9110 μg/L and 1800 to 22,600 μg/L, respectively. These concentrations are sufficiently high to cause harmful effects to most marine organisms. Model predictions suggested that the effluent discharge from hydroblasting posed risks to the wider marine environment of a hull-cleaning site, depending on the scale of the hull-cleaning operations and the size of the receiving environment, as well as various hydrodynamic factors. These effluents are inevitably hazardous, and their environmental release should be managed and regulated on the basis of site-specific risk assessments.
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