Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.

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1. The purpose of the present study was to investigate the association between the single nucleotide polymorphism (SNP) 45T/G and plasma adiponectin levels and the prevalence of Type 2 diabetes mellitus (T2DM) in Uygurs of the Xinjiang region, China. 2. We performed a cross-sectional survey in a representative sample of 151 Uygur adults aged 24-80 years. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP45 T/G polymorphism (exon 2) in the adiponectin gene. An ELISA was used to determine plasma adiponectin levels. Logistic regression was used to screen risk factors for T2DM. 3. Compared with the normal glucose tolerance (NGT) group, the T2DM group exhibited a higher distribution of the TG + GG genotype, G allele frequency and lower plasma adiponectin concentrations in TG + GG genotype carriers compared with those with the TT genotype. Compared with SNP45 T carriers, in the NGT group, G carriers had higher levels of systolic and diastolic blood pressure, low density lipoprotein (P < 0.05) and total cholesterol (P < 0.005). In the T2DM group, G carriers had lower levels of homeostasis model assessment (HOMA) of insulin sensitivity (P < 0.05) and higher levels of HOMA of insulin resistance (P < 0.05). 4. Adiponectin SNP 45 is positively correlated with the prevalence of T2DM in Uygurs of Xinjiang. The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.

The gut microbiome may have an important influence on the development of diabetes mellitus type 2 (DM2). To better understand the DM2 pandemic in ethnic minority groups in China, we investigated and compared the composition and richness of the gut microbiota of healthy, normal glucose tolerant (NGT) individuals and DM2 patients from two ethnic minority groups in Xinjiang, northwest China, the Uygurs and Kazaks. The conserved V6 region of the 16S rRNA gene was amplified by PCR from the isolated DNA. The amplified DNA was sequenced and analyzed. An average of 4047 high quality reads of unique tag sequences were obtained from the 40 Uygurs and Kazaks. The 3 most dominant bacterial families among all participants, both healthy and DM2 patients, were the Ruminococcaceae, Lachnospiraceae, and Enterobacteriaceae. Significant differences in intestinal microbiota were found between the NGT individuals and DM2 patients, as well as between the two ethnic groups. Our findings shed new light on the gut microbiome in relation to DM2. The differentiated microbiota data may be used for potential biomarkers for DM2 diagnosis and prevention.

This study was designed to evaluate the epidemiology of type 2 diabetes and hypertension in Uygur and Kazak ethnic populations. A three-step stratified sampling method was used. Questionnaires, blood pressure, anthropometric measurement, and fasting blood glucose were monitored. In total, 1,571 Uygur and 2,913 Kazak subjects were randomly enrolled. The prevalence of type 2 diabetes and glucose intolerance was 5.55-and 1.90-fold higher, respectively, in Uygur than in the Kazak population (8.16 vs. 1.47%, P \ 0.001 and 3.29 vs. 1.73%, P \ 0.001). However, the prevalence of hypertension and obesity was significantly higher in the Kazak than in the Uygur population (hypertension: 43.52 vs. 31.98%, P \ 0.001; obesity: 25.0 vs. 14.5%, P \ 0.001, respectively). Our data suggest a significantly different prevalence in hypertension, hyperlipidemia, and type 2 diabetes between the two ethnic groups. The prevalence of type 2 diabetes was much lower, while the prevalence of hypertension was much higher associated with a higher incidence of obesity in the Kazak population. Individuals with a greater BMI and blood pressure were more prone to development of type 2 diabetes. Our data revealed that waist circumference of Kazak ethnics was greater than that of Uygur, even at the same BMI level. Serum fasting glucose was associated with different factors in Uygur and Kazak.

Eight new germacrane-type sesquiterpenoids, volvalerenals A-E (2-6) and volvalerenic acids A-C (7-9), along with four known compounds, were isolated from a chloroform extract of the roots of Valeriana officinalis var. latifolia. The structures and relative configurations of 2-9 were elucidated on the basis of spectroscopic data interpretation. The effects of all compounds isolated on acetylcholinesterase were evaluated.

Dear Editor, Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are three major types of skin cancer. Among them, melanoma is the most severe form and accounts for~4% of all newly diagnosed cancers annually in the United States. It is estimated that approximately 9500 people are diagnosed with skin cancer every day, and more than 1 million Americans are living with melanoma. Melanoma treatment is still a major challenge in the clinic. Photodynamic therapy (PDT) is composed of targeted ablation and immune activation, is less invasive than other therapies and has been widely used in the treatment of various cancers. However, the limitation of light penetration is an issue in PDT for deep cancer treatment. 1 To overcome this limitation and enable PDT for deep cancer treatment, researchers have proposed X-ray-induced PDT 1 and nanoparticle self-lighting PDT, 2 and these techniques have become intensively studied topics. Recently, Chen et al. 3 invented a new sensitizer called copper-cysteamine (Cu-Cy) that can be activated by UV, 4 X-rays, 5 microwave, 6 and ultrasound 7 to generate reactive oxygen species (ROS) to destroy cancer cells as well as bacteria. 8 As ROS generation by Cu-Cy nanoparticles (NPs) is not solely activated by regular light, it is more appropriate to call it oxidative therapy (OT) rather than PDT. Cu-Cy NPs of an average size of 96 nm have been tested for skin cancer treatment. 9 It was found that these Cu-Cy NP-based X-PDT exhibited a strong antitumor effect towards SCC. However, B16F10 melanoma was resistant to these Cu-Cy NP-based X-PDT, both in vitro and in vivo. 9 Size is known to be a sensitive factor influencing nanomaterial properties and performance. To further evaluate the effect of Cu-Cy NP-based X-PDT on melanoma, we applied particles with an average size of~40 nm for the treatment of melanoma, as the 40 nm Cu-Cy NPs have a larger surface area than other NPs, thereby producing more ROS. 10 In addition, the cell uptake is higher for the 40 nm NPs. As expected, the 40 nm Cu-Cy NPs were very effective in inhibiting melanoma under X-ray stimulation. These observations confirmed that the combination of Cu-Cy and X-rays facilitated cell apoptosis and/or necrosis of B16 cells. More interestingly, this combination promoted the formation of the antitumor immune response. These results suggest that Cu-Cy NPs can simultaneously facilitate radiotherapy, oxidative therapy, and immunotherapy for melanoma treatment, as illustrated in Fig. 1a. The distribution of Cu-Cy was assessed by confocal fluorescence microscopy. As shown in Supplementary Fig. S1, the uptake of Cu-Cy NPs in the nucleus after 6 h was substantially increased compared to that after 2 and 4 h of incubation. Next, the cytotoxicity was measured to assess the efficacy of Cu-Cy on B16 cells by the CCK8 viability assay. After incubation with various amounts of Cu-Cy for 24 h, the cells were irradiated with X-rays at

Lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria serve as endotoxin to exert potent immune responses. However, the effect of LPS on adipogenesis has not been elucidated. The present study was designed to examine the effect of LPS on adipogenesis in 3T3-L1 preadipocytes and possible mechanism(s) of action involved. Our results revealed that LPS challenge significantly suppressed adipogenesis in 3T3-L1 preadipocytes mainly through downregulated expression of the late adipogenic markers PPARγ and aP2 as well as AMP-activated protein kinase (AMPK) expression and activity. As an inflammatory factor, LPS was found to lead to an overt reduction in IκBα levels compared with the time-matched controls, consolidating its pro-inflammatory property in 3T3-L1 preadipocytes. Our data also revealed that LPS retarded adipogenesis, the effect of which was partially reversed by the selective inhibitor of IKKβ. IκBα was found to be involved in the anti-adipogenic effect of LPS. In conclusion, LPS is capable of inhibiting adipogenesis in 3T3-L1 adipocytes possibly through activation of NF-κB and inhibition of AMPK. With the activation of NF-κB pathway and inhibition of AMPK, LPS suppresses C/EBP α DNA-binding activity and the expression of late adipogenic markers PPARγ and aP2.