Sulfated Galactofucan from Sargassum Thunbergii Attenuates Atherosclerosis by Suppressing Inflammation Via the TLR4/MyD88/NF-κB Signaling Pathway.

PURPOSE: Sulfated galactofucan (SWZ-4), which was extracted from Sargassum thunbergii, has recently been reported to show anti-inflammatory and anticancer properties. The present study aimed to evaluate whether SWZ-4 attenuates atherosclerosis in apolipoprotein E-knockout (ApoE-KO) mice by suppressing the inflammatory response through the TLR4/MyD88/NF-κB signaling pathway. METHODS: Male ApoE-KO mice were fed with a high-fat diet for 16 weeks and intraperitoneally injected with SWZ-4. RAW246.7 cells were treated with lipopolysaccharide (LPS) and SWZ-4. Atherosclerotic lesions were measured by Sudan IV and oil red O staining. Serum lipid profiles, inflammatory cytokines, and mRNA and protein expression levels were evaluated. RESULTS: SWZ-4 decreased serum TNF-α, IL-6 and IL-1 levels, but did not reduce blood lipid profiles. SWZ-4 downregulated the mRNA and protein expression of TLR4 and MyD88, reduced the phosphorylation of p65, and attenuated atherosclerosis in the ApoE-KO mice (p < 0.01). In LPS-stimulated RAW 264.7 cells, SWZ-4 inhibited proinflammatory cytokine production and the mRNA expression of TLR4, MyD88, and p65 and reduced the protein expression of TLR4 and MyD88 and the phosphorylation of p65 (p < 0.01). CONCLUSION: These results suggest that SWZ-4 may exert an anti-inflammatory effect on ApoE-KO atherosclerotic mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway in macrophages and therefore may be a treatment for atherosclerosis.

The effectiveness of balneotherapy and aquatic exercise on bone metabolism: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness of balneotherapy and/or aquatic exercise on bone metabolism. DESIGN: A systematic literature search was conducted from inception to January 4, 2021. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model according to study heterogeneity. RESULTS: Seven articles involving 467 participants were selected. Three balneotherapy studies were qualitatively integrated. The results showed that bone resorption slowed down with or without stimulation of bone formation. A pooled meta-analysis of four studies on aquatic exercise showed significant evidence for a reduction in parathyroid hormone (PTH; SMD = -0.71; 95% CI, -1.04 to -0.38; P < 0.001), and a significant increase in osteocalcin (OC; SMD = 0.60; 95% CI, 0.16 to 1.03; P = 0.007) after aquatic exercise. CONCLUSION: Balneotherapy and aquatic exercise had significant effects on bone metabolism, reducing bone resorption and/or increasing bone formation. This study highlights the importance of balneotherapy and aquatic exercise for bone health.

Sulfated galactofucan from Sargassum thunbergii induces senescence in human lung cancer A549 cells.

Isolated compounds from Sargassum thunbergii (S. thunbergii) have shown to exhibit diverse biological activities, including anti-cancer activity. In this study, we examined the effect of sulfated galactofucan (SWZ-4-H), which was successfully isolated from S. thunbergii, and its underlying mechanism on human lung cancer (LC) A549 cell growth in vitro and in vivo. In vitro experiment indicated that SWZ-4-H decreased cell growth and number in a dose-dependent manner (P < 0.05 vs. control). Besides, cells treated with SWZ-4-H had irregular morphology, including increased cell volumes, and large nuclei, which suggested senescence-like changes. Moreover, SWZ-4-H increased senescence-related ß-galactosidase (SA-ß-Gal) staining in a dose-dependent manner; however, while lower (1 mg mL-1) concentration induced mainly senescence without causing cell death, higher dosage (3 mg mL-1) induced both senescence and cell death. The effect of SWZ-4-H was further confirmed by analyzing the expression of p53, p21, p16, and Rb (p-RB); SWZ-4-H significantly increased the expression of p53, p21, and p16 and decreased phosphorylated Rb (p-RB) in a dose-dependent manner. Moreover, in vivo experiment showed that SWZ-4-H significantly reduced the tumor volume without affecting the body weight. To sum up, our data indicated that SWZ-4-H could induce lung cancer senescence by regulating p53, p21, p16, and p-Rb, thus providing a novel perspective on anti-cancer mechanisms of SWZ-4-H in human lung cancer A549 cells.

Efficacy of a novel chelator BPCBG for removing uranium and protecting against uranium-induced renal cell damage in rats and HK-2 cells.

Chelation therapy is a known effective method to increase the excretion of U(VI) from the body. Until now, no any uranium chelator has been approved for emergency medical use worldwide. The present study aimed to evaluate the efficacy of new ligand BPCBG containing two catechol groups and two aminocarboxylic acid groups in decorporation of U(VI) and protection against acute U(VI) nephrotoxicity in rats, and further explored the detoxification mechanism of BPCBG for U(VI)-induced nephrotoxicity in HK-2 cells with comparison to DTPA-CaNa3. Chelating agents were administered at various times before or after injections of U(VI) in rats. The U(VI) levels in urine, kidneys and femurs were measured 24 h after U(VI) injections. Histopathological changes in the kidney and serum urea and creatinine and urine protein were examined. After treatment of U(VI)-exposed HK-2 cells with chelating agent, the intracellular U(VI) contents, formation of micronuclei, lactate dehydrogenase (LDH) activity and production of reactive oxygen species (ROS) were assessed. It was found that prompt, advanced or delayed injections of BPCBG effectively increased 24 h-urinary U(VI) excretion and decreased the levels of U(VI) in kidney and bone. Meanwhile, BPCBG injection obviously reduced the severity of the U(VI)-induced histological alterations in the kidney, which was in parallel with the amelioration noted in serum indicators, urea and creatinine, and urine protein of U(VI) nephrotoxicity. In U(VI)-exposed HK-2 cells, immediate and delayed treatment with BPCBG significantly decreased the formation of micronuclei and LDH release by inhibiting the cellular U(VI) intake, promoting the intracellular U(VI) release and inhibiting the production of intracellular ROS. Our data suggest that BPCBG is a novel bi-functional U(VI) decorporation agent with a better efficacy than DTPA-CaNa3.

Comparison of cellular damage response to low-dose-rate 125I seed irradiation and high-dose-rate gamma irradiation in human lung cancer cells.

PURPOSE: To investigate the difference of cellular response between low-dose-rate (LDR) 125I seed irradiation and high-dose-rate (HDR) γ-irradiation in human lung cancer cells. METHODS AND MATERIALS: A549 and NCI-H446 cells with or without wortmannin (WM) treatment were exposed to 125I seeds and γ-rays, respectively. Cell survival, micronuclei (MN) formation, and the expressions of Ku70/Ku80 proteins were measured. RESULTS: There was a strong negative correlation between survival and MN formation for both irradiations, and the MN inductions of NCI-H446 were about twofolds of those of A549, and the survival of NCI-H446 was lower than that of A549, indicating the radiosensitivity of NCI-H446 cells was greater than that of A549 cells. Interestingly, at 4-Gy radiation, NCI-H446 cells were more sensitive to LDR irradiation than HDR irradiation. WM treatment enhanced the radiosensitivity of A549 cells evenly to (125I seed and γ-irradiation, but this treatment led NCI-H446 cells to be more sensitive to LDR 125I. Further results revealed that the expression of phosphorylated Ku80 protein was enhanced in irradiated A549, but in contrast, it was markedly decreased in NCI-H446 cells after 4-Gy LDR 125I irradiation as that compared with γ-irradiated and nonirradiated cells. CONCLUSION: NCI-H446 cells were more sensitive to LDR 125I irradiation than HDR irradiation, and this sensitivity could be further enhanced by WM treatment. But no obvious differences of cellular response to both irradiations were observed in A549. Ku as molecular markers together with cell proliferation rate can be used to predict the radiosensitivity of tumor cells to LDR 125I seed irradiation.

[Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro].

This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.