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During respiration, particulate matter with a diameter of 2.5 µm or less (PM 2.5 ) suspended in the atmosphere enters the terminal alveoli and blood. PM 2.5 particles can attach to toxic substances, resulting in health problems. Limited information is available regarding the effects of prenatal exposure to water-soluble PM 2.5 (WS-PM 2.5 ) and water-insoluble PM 2.5 (WI-PM 2.5 ) on male reproduction. In addition, whether exposure to these particles has transgenerational effects remains unknown. We investigated whether prenatal exposure to WS-PM 2.5 and WI-PM 2.5 disrupts sperm function in generations F1, F2, and F3 of male mice. Pregnant BALB/c mice were treated using intratracheal instillation on gestation days 7, 11, and 15 with 10 mg of a water extract or insoluble PM 2.5 . On postnatal day 105, epididymal sperm count, motility, morphology, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, the sperm chromatin DNA fragmentation index (DFI), and testicular DNA methyltransferase (Dnmt) levels were evaluated in all generations. Whole-genome bisulfite sequencing was used to analyze the DNA methylation status of generation F3. According to the results, exposure to WS-PM 2.5 affected sperm morphology, ROS production, and mean DFI in generation F1; ROS production and mean DFI in generation F2; and sperm morphology and MMP in generation F3. Similarly, exposure to WI-PM 2.5 affected sperm morphology, ROS production, mean DFI, %DFI, and Dnmt1 expression in generation F1; sperm morphology, MMP, and ROS production in generation F2; and sperm morphology, ROS, and %DFI in generation F3. Two hypermethylated genes, PRR16 and TJP2, were observed in the WS-PM 2.5 and WI-PM 2.5 groups, two hypomethylated genes, NFATC1 and APOA5, were observed in the WS-PM 2.5 group, and two hypomethylated genes, ZFP945 and GSE1, were observed in the WI-PM 2.5 group. Hence, prenatal exposure to PM 2.5 resulted in transgenerational epigenetic effects, which may explain certain phenotypic changes in male reproduction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ping-Chi Hsu reports financial support and article publishing charges were provided by National Kaohsiung University of Science and Technology. No any activities to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Female carriers with X-linked chronic granulomatous disease (XL-CGD) who have < 10% reactive oxygen species (ROS) production due to profound X-chromosome inactivation (XCI or lyonization) are more susceptible to infections. We assessed ROS production in Taiwanese female carriers with XL-CGD to investigate whether the level of ROS correlated to their clinical features of infection, autoimmunity, and autoinflammation., Methods: Clinical course, ROS production, flavocytochrome b558 (Cyto b558) expression, and genetic analysis in carriers were investigated after identifying their index cases between 2004 and 2019., Results: A total of 19 mothers (median 27 years; range 25-60 years) and three of four girls (range 4-6 years) relative to 22 male index XL-CGD cases from 19 unrelated families were enrolled. Approximately half (8/19, 42%) of the mothers had novel one-allele mutations. Twenty-two of the 23 females were carriers. One carrier with de novo [Arg290X]CYBB who suffered from refractory salmonella sepsis and chorioretinitis as an XL-CGD phenotype had extreme XCI, absent Cyto b558 expression, and only 8% ROS production. The remaining carriers had bimodal patterns of Cyto b558 expressions (median 40.2%, 26.8-52.4%) and ROS production (38.3%, range 28.2-54.2%) sufficient to prevent significant infections, although neck lymphadenitis recurred in one mother and sister who had ROS expressions of 28.2% and 38.0%, respectively. However, none of the carriers had manifestations of autoimmunity or autoinflammation (e.g., photosensitivity, aphthous stomatitis, or joint disorders), of which each was seen in approximately one-third of XL-CGD carriers from the Western world., Conclusion: One carrier had undetectable Cyto b558 expression and an extremely low ROS production, and consequently presented with an XL-CGD phenotype. One mother and her daughter experienced recurrent neck lymphadenitis despite having sufficient ROS production. Significant autoimmunity/autoinflammation did not develop in any of the carriers. Studies with a longer follow-up period are needed to validate our findings., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Salmonella Typhimurium and S. Stanley are the most prevalent serogroup B serovars to infect humans in Taiwan. The aim was to determine possible factors to influence the prevalence between S. Typhimurium and S. Stanley. Genotypes were determined by pulsed field gel electrophoresis (PFGE) analysis and the intracellular survival, phagocytosis, reactive oxygen species (ROS) production of human monocyte THP-1 cell and tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and IL-1βexpression in peripheral blood CD14 + cells after infection were analyzed. 182 S. Stanley was clonal disseminated with main pulsotypes 2 from 2004 to 2007. Overall S. Typhimurium evolved more genotypes, while S. Stanley conserved in genotypes. Human blood CD14 + monocytes expressed TNF-α, IL-6 and IL-1β differently among serovars and bacterial conditions (live vs. killed). Live S. Stanley and S. Typhimurium suppressed the TNF-α and IL-6 expression compared to killed bacteria. However, live S. Typhimurium stimulated more IL-1β expression than the killed bacteria, but S. Stanley expressed similar IL-1β levels in both conditions. Furthermore, S. Stanley and S. Typhimurium differed in intracellular survival in the THP-1 cells, an early decrease for S. Stanley, not for S. Typhimurium. Additionally, higher reactive oxygen species (ROS) production in THP-1 cells was found agsinst S. Stanley infection, not found in S. Typhimurium. However, some isolates of S. Stanley could recover from early loss to become more in the monocytes than S. Typhimurium. Difference in phagocytized number, intracellular survival, ROS production and IL-1β expression may contribute to prevalence different between two serovars., (Copyright © 2018. Published by Elsevier Ltd.)

The in vitro and in vivo antioxidant activities and its potential to protect against amyloid-P toxicity of essential oils from Zelkova serrata (Thunb.) Makino were investigated in the model organism Caenorhabditis elegans. The results revealed that the essential oil of Z serrata heartwood exhibited great radical scavenging activities and high total phenolic content. In vivo assays showed significant inhibition of oxidative damage in wild-type C. elegans under juglone- indueed oxidative stress and heat shock. Based on results from both in vitro and in vivo assays, the major compound in essential oil of heartwood, (-)-(S, 4S)- 7-hydroxycalamenene (IS, 4S-7HC), may contribute significantly to the observed antioxidant activity. Further evidence showed that IS, 4S-7HC significantly delayed the paralysis phenotype in amyloid beta-expressing transgenic C. elegans. These findings suggest that IS, 4S-7HC from the essential oil of Z serrata heartwood has potential as a source for antioxidant or Alzheimer's disease treatment.

This study reports on a cytotoxic toxin derived from the venom of the crown-of-thorns starfish Acanthaster planci (CAV). The protein toxin was isolated through both ion-exchange and gel-filtration chromatography, and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrum analyzes. The CAV was identified as plancitoxin I protein. The mechanistic role of the CAV toxin was explored in human malignant melanoma A375.S2 cell death. The results indicated that after incubation with CAV toxin, cells significantly decreased in A375.S2 cell viability and increased in the lactate dehydrogenase (LDH) level in a dose-dependent manner. The assays indicated that CAV toxin promoted reactive oxygen species (ROS) production, induced nitric oxide (NO) formation, lost mitochondrial membrane potential (ΔΨm) and induced inter-nucleosomal DNA fragmentation in A375.S2 cells. The molecular cytotoxicity of the CAV toxin was tested through evaluation of the apoptosis/necrosis ratio by double staining with annexin V-FITC and a propidium iodide (PI) assay. The results suggested that CAV toxin induced a cytotoxic effect in A375.S2 cells via the apoptotic procedure, and may be associated with the regulation of the p38 pathways., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: The phytochemical composition of aqueous and ethanol extracts from Gynura bicolor DC., a vegetable, was determined. Human umbilical vein endothelial (HUVE) cells were used to examine the antioxidative and anti-inflammatory potentials of these extracts at 1, 2 or 4% (v/v) against high-glucose-induced injury., Results: Both aqueous and ethanol extracts contained phenolic acids, flavonoids, carotenoids and anthocyanins in the ranges 1428-1569, 1934-2175, 921-1007 and 2135-2407 mg per 100 g dry weight respectively. Both extracts were rich in quercetin, lutein, malvidin and pelargonidin. Addition of these extracts at test doses decreased reactive oxygen species formation, preserved glutathione content and retained glutathione peroxide and catalase activities in high-glucose-treated HUVE cells (P < 0.05). Treatments with these extracts at 2 and 4% lowered interleukin-6, tumor necrosis factor-alpha and prostaglandin E2 production and reduced cyclooxygenase-2 activity (P < 0.05)., Conclusion: These findings suggest that this vegetable could be considered as a functional food and might provide antioxidative and anti-inflammatory protection., (© 2014 Society of Chemical Industry.)

Chamaecyparis obtusa Siebold & Zucc. f.formosana Hayata (Cupressaceae) is one of the treasured conifers in Taiwan. In this study, the wood essential oil of the species was extracted and its anti-inflammatory bioactivities analyzed. The composition analysis of the essential oil yielded a total of 57 compounds with alpha-terpineol (19.4%), tau-muurolol (16.9%), borneol (16%), and alpha-cadinol (10.9%) predominating. The anti-inflammatory assays of the essential oil suggest that C obtusa f. formnosana wood oil has no cytotoxicity, and was capable of inhibiting the expressions of tumor necrosis factor (TNF-alpha), IL-6, IL-1, pro IL-1beta, NO, iNOS, and NLRP3 in murine macrophage cells. It was unable, however, to inhibit the expression of COX-2. Further investigation of the effect of the essential oil on the cellular signal transduction indicated that it was capable of inhibiting ERKI/2, JNKI/2 and p38; it also showed excellent inhibition against ROS. Thus, the overall results indicated that C. obtusa f.formnosana wood oil had very good anti-inflammatory efficacies.

Oral squamous cell carcinoma (OSCC) accounts for 5.8% of all malignancies in Taiwan and the incidence of OSCC is on the rise. OSCC is also a common malignancy worldwide and the five-year survival rate remains poor. Therefore, new and effective treatments are needed to control OSCC. In the present study we have investigated the efficacy and associated mechanisms of polyenylpyrroles and their analogs in both in vitro cell culture and in vivo nude mice xenografts. Auxarconjugatin B (compound 1a) resulted in cell cycle arrest in the G2/M phase and caspase-dependent apoptosis in OEC-M1 and HSC-3 cells by activating DNA damage and mitochondria dysfunction through the loss of mitochondrial membrane potential, release of cytochrome c, increase in B-cell lymphoma-2-associated X protein level, and decrease in B-cell lymphoma-2 level. Compound 1a-induced generation of intracellular reactive oxygen species through cytochrome P450 1A1 was identified as a major mechanism of its effect for DNA damage, mitochondria dysfunction and apoptosis, which was reversed by antioxidant N-acetylcysteine as well as cytochrome P450 1A1 inhibitor and specific siRNA. Furthermore, compound 1a-treated nude mice showed a reduction in the OEC-M1 xenograft tumor growth and an increase in the caspase-3 activation in xenograft tissue. These results provide promising insights as to how compound 1a mediates cytotoxicity and may prove to be a molecular rationale for its translation into a potential therapeutic against OSCC.

The objectives of this investigation were to examine whether airborne particles induce DNA damaging and estrogen-disrupting effects and to explore the relationships between them. In this study, airborne particulate was collected at an urban, a suburban, and a rural site in central Taiwan. The organic solvent extracts of airborne particulate were examined in human MCF-7 and T47D-KBluc breast cancer cells. We observed significant increases in reactive oxygen species (ROS) generation in MCF-7 cells after treatment with the particulate extracts whereas aryl hydrocarbon receptor (AhR) antagonist blocked the particulate-induced ROS generation in cells. Further, induction of CYP1A1 protein expression was confirmed by immunoblots in cells treated with airborne particles, suggesting the roles of AhR status in mediating the particulate-induced toxicity. In addition, we observed that at non-cytotoxic concentration (∼0.01 m(3) air equivalent), airborne particles induced decreases in intracellular NAD(P)H and NAD(+) in MCF-7 cells. These decreases were completely blocked by three types of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. Moreover, we demonstrated increases in the number of DNA strand breaks in MCF-7 cells exposed to airborne particles as measured by the single-cell gel electrophoresis (Comet) assay. Overall, this evidence confirms that airborne particles induce decreases in intracellular NAD(P)H and NAD(+) through PARP-1 activation mediated by formation of DNA strand breaks. Furthermore, we confirmed that with series dilution airborne particles (∼10(-7)-10(-2) m(3) air equivalent) possess both estrogenic and anti-estrogenic activities as determined by the ERα-mediated reporter gene assay in human T47D-KBluc breast cancer cells. In conclusions, we confirmed that the DNA-damaging activity and estrogenicity of airborne particles varied considerably with concentration (air equivalent). Our findings add further support to the theme that ROS formation is a significant determinant factor in mediating the induction of oxidative DNA damage and repair in human breast cancer cells exposed to airborne particles and that oxidative stress and the subsequent induction of DNA damage may, in part, contribute to airborne particle-induced carcinogenesis.

This study was designed to determine the relevance between the levels of reactive oxygen species (ROS) in microenvironment (follicular fluid or culture media) and the embryo development in IVF/ICSI cycles. A total of 466 follicles from 174 IVF/ICSI cycles were collected for this study. The ROS levels in monofollicular fluid and spent culture media were evaluated by chemiluminescence assay with luminol as a probe. The results demonstrated that it is in ICSI cycles that elevated ROS levels in follicular fluid were associated with day 3 poor embryo quality. The ROS levels in spent culture media were correlated with advanced degree of fragmentation. In addition, ROS levels in culture media, instead of in follicular fluid, were negatively correlated with implantation potential of embryos. The ROS levels in culture media may be viewed as an embryo metabolic marker and function as an adjuvant criterion for embryo selection.

Aim of the Study: San-huang-xie-xin-tang (SHXXT) is a traditional Chinese medicine and it has been shown to have an anti-inflammatory effect. Since inflammation is one of the major mechanisms of atherosclerosis, we aimed to investigate anti-atherosclerotic effect of SHXXT in human aortic smooth muscle cells (HASMCs)., Materials and Methods: Human aortic smooth muscle cells (HASMCs) were used in the present study, and rendered atherosclerosis by adding lipopolysaccharides. We first tested the effects of SHXXT on HASMC migration and proliferation as they present the major morphological change of atherosclerosis. We also examined whether SHXXT can influence the production of several biomarkers of inflammation and atherosclerosis including reactive oxygen species (ROS), COX-2, ERK1/2, IL-1β, IL-6, IL-8 and MCP-1., Results: Using the dimethyl-thiazol-diphenyltetrazoliumbromide (MTT) and wound repair assay, SHXXT was shown to significantly reduce HASMC proliferation and migration, respectively. From the fluorometric assay, SHXXT significantly reduced ROS production. SHXXT down regulated mRNA and protein levels for the COX-2 gene. In addition, phosphorylated ERK1/2 levels were suppressed by SHXXT suggesting HASMC division can be inhibited under pro-inflammatory condition. SHXXT significantly inhibited the production of IL-1β, IL-6, IL-8 and MCP-1 after LPS stimulation., Conclusions: Our results indicated that SHXXT can influence several mechanisms involved in atherosclerosis, which suggests that SHXXT may have a therapeutic potential for cardiovascular disease associated with atherosclerosis., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Cellular defenses against allergens and reactive oxygen species (ROS) exposure are critical in the pathogenesis of asthma. CD14 is a receptor for various bacterial products, such as lipopolysaccharides (LPS), and is also a mediator of inflammatory processes. Manganese superoxide dismutase (MnSOD) is an ROS scavenger, and myeloperoxidase (MPO) can convert hydrogen peroxide into hypochlorous acid; thus, they are considered to be involved in inflammatory defense. The authors conducted a case-control study to evaluate the susceptibility to childhood asthma based on CD14, MnSOD, and MPO genes., Methods: The CD14 -260, MnSOD -9, and MPO -463 genotypes were identified by polymerase chain reactions for 116 asthmatic children and 232 healthy controls. Questionnaires were administered to obtain demographic characteristics. Allergen testing used common Taiwanese aeroallergens., Results: A higher level of parental education, family history of asthma, incense burning at home, allergen-test positive, and the MnSOD Val-Ala/Ala-Ala genotypes (matched relative risk = 2.0; 95% confidence interval = 1.0-4.2) were significantly associated with childhood asthma. Interactions between CD14, MnSOD, MPO genotypes and allergy status were significantly associated with asthma risk in these children (all p <.001). Furthermore, atopic cases with MnSOD Val-Ala/Ala-Ala (log eosinophil 2.66/mm(3), log total serum immunoglobulin E [IgE] 2.48 IU/ml) or Val-Val (log eosinophil 2.61/mm(3), log total serum IgE 2.63 IU/ml) genotypes had elevated eosinophil counts and total serum IgE levels as compared to nonatopic cases with MnSOD Val-Val genotype (log eosinophil 2.27/mm(3), log total serum IgE 1.83 IU/ml)., Conclusions: Susceptible MnSOD genotypes might modulate the development of asthma in Taiwanese children.

Background: Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA., Results: Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% vs. 31.5%), 8-C (35.3% vs. 43.2%), and 9-10C (24.5% vs. 22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences., Conclusion: Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.

We constructed a probabilistic risk-based framework to assess the human oxidative stress (OS) risk from diesel exhaust particle (DEP)-induced reactive oxygen species. A human respiratory tract model was used to estimate DEP concentration and cumulative doses in lung regions for three occupational groupings (driver, homeworker and student) in northern, central, and southern Taiwan. Dose-response profiles were reconstructed in terms of the specific ratio of the reduced and oxidized forms of glutathione (GSH/GSSG ratio) for the human macrophage cell (THP-1) and human bronchial epithelial cell (BEAS-2B). The highest estimated median daily cumulative dose of DEP with 95% CI was for driver in northern Taiwan (DEP(2.5): 0.716 (0.443-1.197) mg and DEP(0.18): 0.584 (0.417-0.822) mg), significantly higher than that of the other settings. The driver in northern Taiwan setting had the highest cumulative dose-response calculated over a 2-year exposure period: 0.57 (0.41-0.76) and 0.70 (0.53-0.87) for DEP(2.5) and 0.40 (0.25-0.70) and 0.47 (0.34-0.80) for DEP(0.18), respectively, in THP-1 and BEAS-2B cells. Our results implicate that potential risks of OS from above-critical exposure to DEP(2.5) in all settings are found, whereas from DEP(0.18) in the driver in northern Taiwan setting is also alarming.

Two new neolignans, piperkadsin A (1) and piperkadsin B (2), as well as 11 known neolignans, three known alkaloids, the highly oxygenated compound (+)-crotepoxide, and stigmasterol were isolated from the stems of Piper kadsura. The anti-inflammatory activities of these compounds were evaluated. Compounds 1, 2, futoquinol (3), piperlactam S (4), and N-p-coumaroyl tyramine (5) showed potent inhibition of PMA-induced ROS production in human polymorphonuclear neutrophils with IC(50) values 4.3 +/-1.0, 12.2 +/- 3.2, 13.1 +/- 5.3, 7.0 +/- 1.9, and 8.4 +/- 1.3 microM, respectively.