Organochlorine pesticides (OCPs) are ubiquitous contaminants with high bioaccumulation and persistence in the environment; they can have adverse effects in humans and animals. This study examined ...residual concentrations in water, sediments, and fishes as well as the association between the health risks of OCPs and fish consumption in the Taiwanese population. Various water and sediment samples from Taiwanese aquaculture and fish samples from different sources were collected and analyzed through gas chromatography tandem mass spectrometry to determine the concentrations of 20 OCPs, namely, aldrin;
cis
-chlordane;
trans
-chlordane; dieldrin; endrin; alpha-endosulfan; beta-endosulfan; heptachlor; hexachlorobenzene; alpha-hexachlorocyclohexane; beta-hexachlorocyclohexane; lindane; mirex; pentachlorobenzene;
o,p′
-dichlorodiphenyltrichloroethane (DDT);
p,p′
-DDT; and DDT metabolites (
o,p’
-dichlorodiphenyldichloroethane DDD;
p,p’
-DDD;
o,p’
-dichlorodiphenyldichloroethylene DDE; and
p,p’
-DDE). None of the analyzed samples was positive for OCP contamination, suggesting no new input pollution from the land through washing into Taiwanese aquaculture environments. However, OCP residues were detected in fishes caught along the coast, namely, skipjack tuna and bigeye barracuda, and in imported fishes, such as codfish and salmon. DDT was the predominant pesticide. The contamination pattern of persistent organic pollutants was as follows: dieldrin >
cis
-chlordane > hexachlorobenzene, with average concentrations ranging from 0.09 to 2.74 ng/g. The risk was assessed in terms of the estimated daily intake (EDI) for potential adverse indices; the EDI of OCP residues was lower than 1% of the acceptable daily intake established by the Food and Agriculture Organization of the United Nations and World Health Organization. The assessed risk was negligible and considered to be at a safe level, suggesting no association between fish consumption and risks to human health in Taiwan. However, a continuous monitoring program for OCP residues in fishes is necessary to further assess the possible effects on human health.
Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from
, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant ...properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (
) and inducible nitric oxide synthase (
)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid-binding protein 4 (
) and sterol regulatory element-binding protein 1 (
) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.
Seafood safety is a crucial public health concern for consumers. In this study, we applied a validated method to analyze the residue of banned veterinary drugs in shellfish, namely chloramphenicol, ...malachite green, leucomalachite green, and nitrofuran metabolites; additionally, the QuEChERS method was employed to detect 76 herbicides by LC/MS/MS and GC/MS/MS. In total, 42 shellfish samples, which included hard clams, freshwater clams, and oysters, were collected from aquafarms and production areas in Taiwan during 2012. Our results revealed 3.8ng/g of chloramphenicol in one hard clam, 19.9–32.1ng/g of ametryn in two hard clams, 16.1–60.1ng/g of pendimethalin in four hard clams, and 17.0ng/g of mefenacet in one oyster, indicating that 19.1% of the samples contained residues from banned veterinary drugs and pesticides. These data can be used to monitor the residue of veterinary drugs and pesticides in aquatic organisms and as a reference for food safety.
•A certified method was employed for analyzing residues of banned veterinary drugs and herbicides in shellfish samples.•The trace levels of chloramphenicol, ametryn, pendimethalin were detected in hard clam samples.•For ensuring food safety, continual monitoring of aquatic products is necessary.
Antrodia camphorata (AC) exhibits potential for engendering cell‐cycle arrest as well as prompting apoptosis and metastasis inhibition in triple‐negative breast cancer (TNBC) cells. We performed the ...current study to explore the anti‐epithelial‐to‐mesenchymal transition (EMT) properties of fermented AC broth in TNBC cells. Our results illustrated that noncytotoxic concentrations of AC (20–60 μg/ml) reversed the morphological changes (fibroblastic‐to‐epithelial phenotype) as well as the EMT by upregulating the observed E‐cadherin expression. Furthermore, we discovered treatment with AC substantially inhibit the Twist expression in human TNBC (MDA‐MB‐231) cells as well as in those that were transfected with Twist. In addition, we determined AC to decrease the observed Wnt/β‐catenin nuclear translocation through a pathway determined to be dependent on GSK3β. Notably, AC treatment consistently inhibited the EMT by downregulating mesenchymal marker proteins like N‐cadherin, vimentin, Snail, ZEB‐1, and fibronectin; at that same time upregulating epithelial marker proteins like occludin and ZO‐1. Bioluminescence imaging that was executed in vivo demonstrated AC substantially suppressed breast cancer metastasis to the lungs. Notably, we found that western blot analysis confirmed that AC decreased lung metastasis as demonstrated by upregulation of E‐cadherin expression in biopsied lung tissue. Together with our results support the anti‐EMT activity of AC, indicating AC as having the potential for acting as an anticancer agent for the treatment of human TNBC treatment.
Antrodia camphorata inhibits epithelial–mesenchymal transition, resulting in the apoptosis and metastasis inhibition of triple‐negative breasts cancer cells.
The haskap (Lonicera caerulea L., Caprifoliaceae) berry has been widely used in traditional medicine in Kuril Islands, Russia, Japan, and China. Cyanidin-3-O-glucoside (C3G) is the most abundant ...anthocyanin in haskap berries, and C3G induces antiproliferative pharmacological activity in various cancer cells. However, no study has investigated its anti-lung large-cell carcinoma (LCC) pharmacological role. Therefore, this study determined whether C3G alone or C3G combined with 5-fluorouracil (5-FU) inhibits human lung LCC. We determined the tumor growth, apoptosis, inflammation, and metastasis in the H661 lung LCC lines xenografted into BALB/c nude mice. The mice were administered saline (control), 5-FU, C3G, or both C3G and 5-FU. Relative to the control mice, those treated with C3G alone or both C3G and 5-FU exhibited impaired tumor growth; increased tumor apoptosis; decreased inflammatory cytokine levels (e.g., IL-1β, TNF-α, C-reactive protein, and IL-6); decreased inflammation-related factors, including cyclooxygenase-2 protein and nuclear factor-κB (NF-κB) mRNA; increased inhibition of NF-κB kinase α mRNA; and downregulated metastasis-related factors, such as transforming growth factor-β, CD44, epidermal growth factor receptor, and vascular endothelial growth factor. In addition, C3G alone or combined with 5-FU affected the expression of the tumor microenvironment-related factors Ki67, CD45, PDL1, and CD73. Compared with the mice treated with 5-FU or C3G alone, those treated with both C3G and 5-FU exhibited significantly impaired tumor growth, decreased tumor sizes, and increased tumor inhibition. This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.
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•Cyanidin 3-O-glucoside, which can be derived from berries and colorful fruits, is a natural anthocyanin to be used as an anticancer agent..•Cyanidin 3-O-glucoside inhibited the growth of lung large-cell carcinoma in nude mice.•Combinatorial treatment with cyanidin 3-O-glucoside and 5-fluorouracil exerted synergistic anticancer effects on lung large-cell carcinoma.•Our results provide novel therapeutic strategies for lung large-cell carcinoma treatment.
Obesity is commonly associated with hyperglycemia and type 2 diabetes and negatively affects chromium accumulation in tissues. Exercise prevents and controls obesity and type 2 diabetes. However, ...little information is available regarding chromium changes for regulating glucose homeostasis in high-fat diet (HFD)-fed animals/humans who exercise. Therefore, this study explored the effects of exercise and whether it alters chromium distribution in obese mice. Male C57BL6/J mice aged 4 weeks were randomly divided into two groups and fed either an HFD or standard diet (SD). Each group was subgrouped into two additional groups in which one subgroup was exposed to treadmill exercise for 12 weeks and the other comprised control mice. HFD-fed mice that exercised exhibited significant lower body weight gain, food/energy intake, daily food efficiency, and serum leptin and insulin levels than did HFD-fed control mice. Moreover, exercise reduced fasting glucose and enhanced insulin sensitivity and pancreatic β-cell function, as determined by homeostasis model assessment (HOMA)-insulin resistance and HOMA-β indices, respectively. Exercise also resulted in markedly higher chromium levels within the muscle, liver, fat tissues, and kidney but lower chromium levels in the bone and bloodstream in obese mice than in control mice. However, these changes were not noteworthy in SD-fed mice that exercised. Thus, exercise prevents and controls HFD-induced obesity and may modulate chromium distribution in insulin target tissues.
Exposure to residues of antibiotics (e.g., sulfonamides) and insecticides (e.g., organophosphorus insecticides) in aquacultured food can adversely affect humans and animals and thus affect public ...health globally. Here, using a validated method, we examined the levels of residues of 12 sulfonamides as well as 18 organophosphorus insecticides in aquacultured fish in Taiwan. A total of 52 fish samples (i.e., 20 tilapia, 16 milk fish, and 16 perch samples) were obtained from Taiwanese aquafarms from June 2018 to October 2019. We detected 0.02 and 0.03 mg/kg of sulfamethazine (a sulfonamide) in one tilapia and one milk fish, respectively, and 0.02, 0.05, and 0.03 mg/kg of chlorpyrifos (an organophosphorus insecticide) in one tilapia, one milk fish, and one perch, respectively; thus, among the samples, 3.85% and 5.77% contained sulfonamides and organophosphorus insecticide residues, respectively. Furthermore, we assessed human health risk based on the estimated daily intakes (EDIs) of these residues: EDIs of sulfonamide and organophosphorus insecticide residues were <1.0% of the acceptable daily intake recommended by the Joint Food and Agriculture Organization of the United Nations/World Health Organization Expert Committee on Food Additives. The risk of exposure to sulfonamide and organophosphorus insecticide residue by consuming aquacultured fish in Taiwan was thus negligible, signifying no immediate health risk related to the consumption of fish. Our findings can constitute a reference in efforts geared toward ensuring food safety and monitoring veterinary drug and insecticide residue levels in aquacultured organisms. Residue levels in fish must be continually monitored to further determine possible effects of these residues on human health.
Rapamycin (RAPA), an immunosuprpressive drug used extensively to prevent graft rejection in transplant patients, has been reported to inhibit adipogenesis in vitro. In this study, we investigated the ...anti-obesity effects of RAPA in C57BL/6J mice on a high-fat diet (HFD). Mice treated with RAPA (2 mg/kg per week for 16 weeks) had reduced body weight and epididymal fat pads/body weight, reduced daily food efficiency, and lower serum leptin and insulin levels compared with the HFD control mice. However, RAPA-treated mice were hyperphagic, demonstrating an increase in food intake. Dissection of RAPA-treated mice revealed a marked reduction in fatty liver scores, average fat cell size, and percentage of large adipocytes of retroperitoneal and epididymal white adipose tissue (RWAT and EWAT), compared to the HFD control mice. These results suggest that RAPA prevented the effect of the high-fat diet on the rate of accretion in body weight via reducing lipid accumulation, despite greater food intake. It is likely that RAPA may serve as a potential strategy for body weight control and/or antiobesity therapy.
Supplementary Tables: available only at http://dx.doi.org/10.1254/jphs.08215FP
Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism ...underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury.
Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ ...grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.
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