Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity.

Understanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery, tissue engineering, therapeutics, etc. GO has been shown to accumulate in the liver after entering the body, and thus, understanding the GO-liver interaction will facilitate the development of safer bio-applications. In this study, the hepatic clearance of two types of PEGylated GOs with different lateral sizes (s-GOs: ~70 nm and l-GOs: ~300 nm) was carefully investigated. We found that GO sheets across the hepatic sinusoidal endothelium, which then may be taken up by the hepatocytes via the Disse space. The hepatocytes may degrade GO into dot-like particles, which may be excreted via the hepatobiliary route. In combination with ICP-MS, LA-ICP-MS, and synchrotron radiation FTIR techniques, we found that more s-GO sheets in the liver were prone to be cleared via hepatobiliary excretion than l-GO sheets. A Raman imaging analysis of ID/IG ratios further indicated that both s-GO and l-GO generated more defects in the liver. The liver microsomes may contribute to GO biotransformation into O-containing functional groups, which plays an important role in GO degradation and excretion. In particular, more small-sized GO sheets in the liver were more likely to be cleared via hepatobiliary excretion than l-GO sheets, and a greater clearance of s-GO will mitigate their hepatotoxicity. These results provide a better understanding of the hepatic clearance of soft NMs, which is important in the safer-by-design of GO.

A Dual-Function Hemicyanine Material with Highly Efficient Photothermal and Photodynamic Effect Used for Tumor Therapy.

Small molecular organic optical agents with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), hold credible promise for anti-tumor therapy by overcoming individual drawbacks and enhancing photon utilization efficiency. However, developing effective dual-function PTT-PDT photosensitizers (PSs) for efficient synergistic phototherapy remains challenging. Here, a benz[c,d]indolium-substituted hemicyanine named Rh-BI, which possesses a high photothermal conversion efficiency of 41.67% by exhaustively suppressing fluorescence emission, is presented. Meanwhile, the rotating phenyl group at meso-site induces charge recombination to enhance the molar extinction coefficient up to 13.58 × 104 M-1cm-1, thereby potentiating the photodynamic effect. Under 808 nm irradiation, Rh-BI exhibits significant phototoxicity in several cancer cell types in vitro with IC50 values as low as ≈0.5 µM. Moreover, treatment of 4T1 tumor-bearing mice with Rh-BI under laser irradiation successfully inhibits tumor growth. In a word, an effective strategy is developed to build PTT-PDT dual-functional optical materials based on hemicyanine backbone for tumor therapy by modulating conjugation system interaction to adjust the energy consumption pathway.

Design, synthesis, and biological evaluation of ocotillol derivatives fused with 2-aminothiazole via A-ring as modulators of P-glycoprotein-mediated multidrug resistance.

Overexpression of P-glycoprotein (P-gp) plays a key role in the development of multidrug resistance (MDR), the major reason for the failure of chemotherapy in clinics. Ocotillol and its derivatives had been reported with good P-gp-mediated tumor MDR reversal activity in vitro. Herein, a series of ocotillol derivatives fused with 2-aminothiazole (2-AT) via A-ring were designed and synthesized to further improve the tumor MDR reversal potency. These compounds were evaluated for their MDR reversal activity against the KBV cells by MTT assay. Among them, the most promising derivative against P-gp-mediated MDR was compound 12 with 2-AT and glycine in the A-ring. Rhodamine123 (Rh123) accumulation assay, Western blot assay, and P-gp-Glo™ assay showed that compound 12 efficiently inhibited the efflux function of P-gp by stimulating P-gp ATPase rather than downregulating its expression. Moreover, compound 12 sensitized KBV cells to paclitaxel arrested cells in the G2/M phase and induced cell apoptosis. Importantly, compound 12 significantly inhibited the growth of KBV cell-derived xenograft tumors in nude mice by increasing the sensitivity of paclitaxel in vivo. Finally, the structure-activity relationships (SARs) of ocotillol derivatives were further investigated. In summary, compound 12 has the potential to overcome MDR in cancer caused by P-gp.

Effect of a 21-day balneotherapy program on blood cell counts, ponogen levels, and blood biochemical indexes in servicemen in sub-health condition.

[Purpose] The aim of our study was to explore the changes in the blood of servicemen in sub-health conditions during a 21-day balneotherapy program. [Subjects and Methods] For this study, 129 servicemen in sub-health condition were recruited. The subjects were randomly divided into either the balneotherapy group (70) or the control group (59). Subjects in the balneotherapy group received whole-body immersion bath therapy in thermomineral water (30 min daily) for 21 days. Their blood samples were examined 1 day before and after balneotherapy. The parameters studied included mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC), lactic acid (LAC), alanine aminotransferase (ALT), glucose (GLU), and triglycerides (TG) levels. [Results] After 21 days of balneotherapy, MCH levels and MCHC increased significantly and WBC counts increased significantly. LAC levels decreased significantly. ALT, GLU, and TG levels decreased significantly. In the control group, there were no statistical differences before and after tap water baths following the same procedure. [Conclusion] A 21-day balneotherapy program significantly improved blood cell counts and blood biochemical indexes and reduced ponogen levels in servicemen in sub-health condition.