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Holocene paleoclimate reconstructions and comparisons largely rely on accurate age-depth modeling. However, uncertainties in chronology, such as those caused by sparse radiocarbon dates, will hamper inter-core comparisons and correlations, and might result in misleading “cause and consequence” conclusions. This study aimed to find a solution to increase the comparability and minimize the uncertainty of wetland chronology as much as possible. Sediment cores were recovered and radiocarbon dated from the Lianhuachi wetland located in Southeastern China. Humification degree and loss-on-ignition (LOI) were determined using colorimetric and combustion methods respectively. Our data were compared with previously published datasets obtained in the same wetland. The results show that independent humification profiles from the Lianhuachi wetland displayed high similarities. This high similarity between the humification profiles allowed us to transfer radiocarbon ages from one core to another using sequence slotting correlation. Applying the humification-based chronology refinement method to all sediment cores resulted in an improvement in the correlation coefficients between the same but independently measured proxy sequences from the wetland, which suggests both the inter- and intra-core comparability was improved. Because determining peat humification degree is easy, inexpensive, and time-saving, we suggest that humification can serve as a tool that can be used to correlate different cores and to transfer published radiocarbon ages within the same wetland (peatland) or in a comparable geological setting, to establish a more robust chronology of these comparable cores. The degree of peat humification can thus serve as a relative dating technique to refine the chronology of wetland (including peatland) records.

Purpose Preoperative fibrinogen levels are associated with the development, recurrence and metastasis of malignant tumors. This study was designed to investigate the clinical value of preoperative fibrinogen/lymphocyte count ratio (FLR) index in hepatocellular carcinoma (HCC). Patients and methods The clinical data of 479 patients with HCC who underwent radical resection were retrospectively analyzed. The correlation between FLR and clinicopathological features was analyzed by chi-square test or non-parametric test. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method. Results The optimal cut-off value of FLR was determined as 1.6 according to the receiver operating characteristic curve (ROC) analysis, in order to predict prognosis for HCC patients after radical resection. It was further found that FLR level was correlated with tumor size, TNM stage, microvascular invasion and prognosis. Multivariate Cox regression analyses found that FLR was an independent predictor for postoperative OS (overall survival) (p = 0.002) and PFS (progression-free survival) (p = 0.001) in patients with HCC; and the 1-, 3- and 5-year OS and PFS of HCC patients in the FLR ≤1.6 level group were significantly higher than those in the FLR >1.6 level group. Conclusion Preoperative FLR level is a novel and effective predictor of prognosis in patients with HCC, and elevated FLR level is associated with poor prognosis in patients with HCC.

Background The purpose of this retrospective study was to investigate the relationship between serum iron levels and the prognosis and risk of recurrence in patients with hepatocellular carcinoma (HCC). Methods A total of 253 HCC patients who underwent radical resection were involved in this study. Results According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for preoperative serum iron in the assessment of HCC postoperative prognosis was 94 ug/dL. The overall survival (OS) of patients in the high iron group was significantly better than that in the low iron group (p 5 cm (χ 2 = 11.590, p 5 cm, and microvascular invasion were independent predictors for shorter OS and DFS in HCC patients after operation, while recurrence was for shorter OS. Conclusion Patients with low preoperative serum iron level had worse postoperative survival and higher recurrence rate in HCC. Preoperative serum iron is an independent predictor of HCC patients. For HCC patients with low iron levels, prognosis of patients may be improved if appropriate iron is supplemented.

BACKGROUND The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL AND METHODS Using a web-based platform, all CRC-causing genes were identified using a database of gene-disease associations (DisGeNET), and all well-known genes of CC identified using the databases of prediction of protein targets of small molecules (Swiss Target Prediction), drug classification, and target prediction (SuperPred). The carefully selected genes of CRC and CC were concurrently constructed by using a database of functional protein association networks (STRING), and use of software for visualizing complex networks (Cytoscape), characterized with production of protein-protein interaction (PPI) network of CC against CRC. The important biological targets of CC against CRC were identified through topological analysis, then the biological processes and molecular pathways of CC against CRC were further revealed for testing these important biotargets by enrichment assays. RESULTS We found that the key predictive targets of CC against CRC were estrogen receptor 2 (ESR2), ATP-binding cassette sub-family G member 2 (ABCG2), breast cancer type 1 susceptibility protein (BRCA1), estrogen receptor 1 (ESR1), cytochrome p450 19A1 (CYP19A1), and epidermal growth factor receptor (EGFR). Visual analysis revealed that the biological processes of CC against CRC were positively linked to hormonal metabolism, regulation of genes, transport, cell communication, and signal transduction. Further, the interrelated molecular pathways were chiefly related to endogenous nuclear estrogen receptor alpha network, forkhead box protein A1 (FOXA1) transcription factor network, activating transcription factor 2 (ATF2) transcription factor network, regulation of telomerase, plasma membrane estrogen receptor signaling, estrogen biosynthesis, androgen receptor, FOXA transcription factor networks, estrogen biosynthesis, and phosphorylation of repair proteins. CONCLUSIONS Use of system pharmacology revealed the biotargets, biological processes, and pharmacological pathways of CC against CRC. Intriguingly, the identifiable predictive biomolecules are likely potential targets for effectively treating CRC.

Background Obesity increases the risk of developing diabetes mellitus. Clinical studies suggest that risk factors like palmitic acid (PA) and lipopolysaccharide (LPS) exist simultaneously in diabetes with obesity. Combination of PA and LPS even at low concentration can induce strong inflammatory reaction. Monocyte chemoattractant protein-1 (MCP-1) is an important inflammatory chemokine related to insulin resistance and type II diabetes. Our previous study using PCR array revealed that LPS and PA synergistically induce MCP-1 mRNA expression in macrophage cells RAW264.7, while the protein expression of MCP-1 in this case was not investigated. Moreover, the underling mechanism in the synergistic effect of MCP-1 expression or production induced by treatment of LPS and PA combination remains unclear. Methods Protein secretion of MCP-1 was measured by the enzyme-linked immunosorbent assay (ELISA) and mRNA levels of MCP-1 and Toll-like receptor 4 (TLR4) were measured by real-time PCR. Statistical analysis was conducted using SPSS software. Results LPS could increase MCP-1 transcription as well as secretion in RAW264.7, and PA amplified this effect obviously. Meanwhile, combination of LPS with PA increased TLR4 mRNA expression while LPS alone or PA alone could not, TLR4 knockdown inhibited MCP-1 transcription/secretion induced by LPS plus PA. Moreover, not NF-κB inhibitor but inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK were found to block MCP-1 generation stimulated by LPS plus PA. Conclusion LPS and PA synergistically induced MCP-1 secretion in RAW264.7 macrophage cells, in which MCP-1 transcription mediated by MAPK/TLR4 signaling pathways was involved. Combined treatment of PA and LPS in RAW264.7 cells mimics the situation of diabetes with obesity that has higher level of PA and LPS, MAPK/TLR4/ MCP-1 might be potential therapeutic targets for diabetes with obesity.

Siming Li,1,* Wentao Xu,1,* Minjun Liao,1,2,* Yuanping Zhou,2 Jun Weng,1 Liying Ren,1 Junxiong Yu,1,3 Weijia Liao,1 Zhaoquan Huang1,4 1Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China; 2Department of Infectious Diseases, Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 3Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China; 4Department of Pathology, Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijia LiaoLaboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of ChinaEmail liaoweijia288@163.comZhaoquan HuangDepartment of Pathology, Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of ChinaEmail 191990449@qq.comBackground: Currently, there is still a lack of effective biomarkers for the recurrence monitoring and survival prognosis assessment of hepatocellular carcinoma (HCC) patients with alpha-fetoprotein (AFP)-negative (≤ 20 ng/mL) after radical resection.Methods: The clinicopathological data of 606 patients (303 in the AFP-negative group and 303 in the AFP-positive group) who underwent radical resection of HCC were analyzed retrospectively.Results: The gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) of patients in the AFP-negative group was lower than that in the AFP-positive group (p < 0.001). The GLR level of the early-recurrence group was higher than that of the non-early-recurrence group (p =0.003). GLR had fair accuracy in predicting the early-recurrence of HCC patients [c-index=0.654 (95% CI=0.606– 0.702); AUC=0.681 (95% CI=0.625– 0.733)]. Univariate analysis showed that patients with tumor size < 5 cm, no microvascular invasion, single tumor, no metastasis, BCLC stage 0–A, no recurrence, and GLR ≤ 45.0 had longer disease-free survival (DFS) and overall survival (OS) among AFP-negative HCC patients. In addition, multivariate Cox proportional hazards regression analysis showed that tumor size < 5 cm (p =0.003), no recurrence (p < 0.001), and GLR < 45.0 (p < 0.001) were independent predictors of longer OS.Conclusion: GLR may be a potential indicator for early recurrence monitoring and prognosis evaluation in HCC patients with AFP-negative after radical resection.Keywords: hepatocellular carcinoma, AFP-negative, GLR, prognosis, early-recurrence

Overexpression of pyrroline-5-carboxylate reductase 1 (PYCR1) has been associated with the development of certain cancers; however, no studies have specifically examined the role of PYCR1 in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas expression array and meta-analysis conducted using the Gene Expression Omnibus database, we determined that PYCR1 was upregulated in HCC compared to adjacent nontumor tissues (P < 0.05). These data were verified using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry analysis. Additionally, patients with low PYCR1 expression showed a higher overall survival rate than patients with high PYCR1 expression. Furthermore, PYCR1 overexpression was associated with the female sex, higher levels of alpha-fetoprotein, advanced clinical stages (III and IV), and a younger age (< 45 years old). Silencing of PYCR1 inhibited cell proliferation, invasive migration, epithelial-mesenchymal transition, and metastatic properties in HCC in vitro and in vivo. Using RNA sequencing and bioinformatics tools for data-dependent network analysis, we found binary relationships among PYCR1 and its interacting proteins in defined pathway modules. These findings indicated that PYCR1 played a multifunctional role in coordinating a variety of biological pathways involved in cell communication, cell proliferation and growth, cell migration, a mitogen-activated protein kinase cascade, ion binding, etc. The structural characteristics of key pathway components and PYCR1-interacting proteins were evaluated by molecular docking, and hotspot analysis showed that better affinities between PYCR1 and its interacting molecules were associated with the presence of arginine in the binding site. Finally, a candidate regulatory microRNA, miR-2355-5p, for PYCR1 mRNA was discovered in HCC. Overall, our study suggests that PYCR1 plays a vital role in HCC pathogenesis and may potentially serve as a molecular target for HCC treatment.

Suspended particulate organic carbon (POC) and sedimentary total organic carbon (TOC) in coastal areas play critical roles in the global carbon cycle, yet sources and dynamics of coastal POC and TOC have been affected by various anthropogenic activities such as aquaculture, sewage discharge, dam construction and land reclamation. To better understand the anthropogenic impacts on coastal organic carbon, this study was carried out in a representative semi-enclosed bay, Dongshan Bay, Southeast China. Through analyses of stable isotopic compositions of both POC (δ13CPOC and δ15NPN) and TOC (δ13CTOC and δ15NTN), the ratio of total organic carbon vs. total nitrogen (C/N), grain size, Chl-a concentrations and hydrological parameters, our study led to the following main findings: 1) During flood season, the distribution of δ13CPOC, δ13CTOC, δ15NPN and δ15NTN values within the bay did not follow the conventional land-sea transition pattern. This distribution pattern indicated more terrestrial organic matter input seaward, which contrasts with the conventional organic matter distribution along the estuarine gradient. 2) Using the organic δ13C, δ15N and C/N signatures of different endmembers, we found that the sources of organic matter deposited in the bay were strongly related to anthropogenic activities, including municipal wastewater discharge, aquaculture, land reclamation and sluice-dyke construction. Furthermore, 3) by applying the Grain Size Trend Analysis Model and the previously-estimated residual current directions, we suggested that human activities have not only altered the sources of organic matter to the semi-enclosed bays, but also significantly modified their transportation and deposition patterns, and might influence the ultimate fate of organic matter into and out of Dongshan Bay. The conclusions of this study should be applicable to similar coastal bays around the world.

Purpose Preoperative fibrinogen levels are associated with the development, recurrence and metastasis of malignant tumors. This study was designed to investigate the clinical value of preoperative fibrinogen/lymphocyte count ratio (FLR) index in hepatocellular carcinoma (HCC). Patients and Methods The clinical data of 479 patients with HCC who underwent radical resection were retrospectively analyzed. The correlation between FLR and clinicopathological features was analyzed by chi-square test or non-parametric test. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan–Meier method. Results The optimal cut-off value of FLR was determined as 1.6 according to the receiver operating characteristic curve (ROC) analysis, in order to predict prognosis for HCC patients after radical resection. It was further found that FLR level was correlated with tumor size, TNM stage, microvascular invasion and prognosis. Multivariate Cox regression analyses found that FLR was an independent predictor for postoperative OS (overall survival) (p = 0.002) and PFS (progression-free survival) (p = 0.001) in patients with HCC; and the 1-, 3- and 5-year OS and PFS of HCC patients in the FLR ≤1.6 level group were significantly higher than those in the FLR >1.6 level group. Conclusion Preoperative FLR level is a novel and effective predictor of prognosis in patients with HCC, and elevated FLR level is associated with poor prognosis in patients with HCC.

Background Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment. Methods From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients. Results The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p 5 cm, HCC combined with MVI and GLR > 56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS). Conclusion GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI.

Vat photopolymerization (VP) technology is a popular manufacturing technology for ceramic parts with complex shapes and high dimensional accuracy. However, there is still a lack of systematic research on how to design suitable monomer formulations for ceramic powder with different characteristics. In this study, the effect of monomers with different functionalities on the stability, rheology, and curing behavior of different ceramic suspensions was investigated intensively. The results showed that the high-functionality monomer facilitates improved stability and cure depth. Whereas, it has a negative impact on viscosity and excess width. For ceramic powders with a low refractive index and light absorbance, a relatively high cure depth can be obtained by using a monomer with low functionality. Moreover, the cure depth and viscosity of aluminum nitride (AlN) suspensions with different monomer combinations were also studied. Finally, the alumina (Al2O3), zirconia (ZrO2), AlN, and silicon nitride (Si3N4) parts were successfully fabricated.

Purpose: Microvascular invasion (MVI) is an independent risk factor for poor prognosis of hepatocellular Carcinoma (HCC), However, there is still a lack of preoperative markers to predict MVI of HCC. This study intends to explore the potential application value of gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) in predicting MVI of HCC, and provide guidance of clinical diagnosis and treatment.Patients and methods: From March 2010 to December 2015, 230 HCC patients underwent surgical treatment in Affiliated Hospitals of Guilin Medical University were selected. Clinicopathological parameters between MVI group (n = 115) and non-MVI group (n = 115) were comparative analyzed. Gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) was used as the key risk factor of HCC with MVI and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. Kaplan-meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analysis were used to establish independent predictors affecting postoperative HCC patients.Results: The level of GLR in the MVI group and non-MVI group was 84.83 ± 61.84 and 38.42 ± 33.52 (p < 0.001) respectively. According to the ROC curve analysis, the optimal cut-off value of GLR was 56, and the area under ROC curve (AUC) was 0.781 (95%CI, 0.719 - 0.833) for risk prediction in HCC patients with MVI. Multivariate analysis results showed that the tumor size > 5 cm, HCC combined with MVI and GLR > 56 are independent risk factors for poor prognosis of HCC patients. In addition, compared with non-MVI group, patients with MVI had shorter progression-free survival (PFS) rates and overall survival (OS).Conclusion: GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC patients combined with MVI.

For postmenopausal cardiovascular disease, long-term estrogen therapy may increase the risk of breast cancer. To reduce this risk, estrogen may be replaced with the phytoestrogen formononetin, but how formononetin acts on vascular endothelial cells (ECs) and breast cancer cells is unclear. Here, we show that low concentrations of formononetin induced proliferation and inhibited apoptosis more strongly in cultured human umbilical vein endothelial cells (HUVECs) than in breast cancer cells expressing estrogen receptor α (ERα) (MCF-7, BT474) or not (MDA-MB-231), and that this differential stimulation was associated with miR-375 up-regulation in HUVECs. For the first time, we demonstrate the presence of a feedback loop involving miR-375, ras dexamethasone-induced 1 (RASD1), and ERα in normal HUVECs, and we show that formononetin stimulated this feedback loop in HUVECs but not in MCF-7 or BT474 cells. In all three cell lines, formononetin increased Akt phosphorylation and Bcl-2 expression. Inhibiting miR-375 blocked these changes and increased proliferation in HUVECs, but not in MCF-7 or BT474 cells. In ovariectomized rats, formononetin increased uterine weight and caused similar changes in levels of miR-375, RASD1, ERα, and Bcl-2 in aortic ECs as in cultured HUVECs. In mice bearing MCF-7 xenografts, tumor growth was stimulated by 17β-estradiol but not by formononetin. These results suggest selective action of formononetin in ECs (proliferation stimulation and apoptosis inhibition) relative to breast cancer cells, possibly via a feedback loop involving miR-375, RASD1, and ERα. This differential effect may explain why formononetin may not increase the risk of postmenopausal breast cancer.

// Rong Li 1, * , Chao Guo 2, * , Xinmou Wu 4 , Zhaoquan Huang 1, 3 and Jian Chen 1 1 Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guangxi, Guilin 541004, PR China 2 Department of Pharmacy, Guigang City People’s Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, PR China 3 Department of Pathology, Affiliated Hospital of Guilin Medical University, Guangxi, Guilin 541004, PR China 4 Department of Pharmacy, Guangxi Medical University, Guangxi, Nanning 530021, PR China * These authors share senior authorship Correspondence to: Jian Chen, email: chjian80726@163.com Zhaoquan Huang, email: hospital_huang@126.com Keywords: acetaminophen, liver impairment, biomarker, FGF21 Received: January 25, 2017 Accepted: May 06, 2017 Published: May 18, 2017 ABSTRACT Acetaminophen (APAP) is a common medication that induces hepatocellular damage in a time- or dose-dependent manner. Fibroblast growth factor 21 (FGF21) exerts a series of biological effects, including cellular repair. Compared to clinical diagnosis parameters, we aimed to evaluate whether FGF21 can serve as a sensitive biomarker for APAP-induced liver impairment. In the present study, we discussed comparable data from APAP-treated patients and parallelly established APAP-exposed mice for investigation. The resulting human serological data showed that APAP-treated patients have a visible reduction of FGF21 expression in undetected liver impairment of clinical diagnosis. In the animal study, APAP-exposed livers exhibited normal metabolic functions and liver functions, as revealed by biochemical test and histopathological examination. Endogenous FGF21 concentrations in APAP-treated mice were decreased in sera and liver cells. Moreover, comparable immunoassay data showed that hepatocellular FGF21 expression was reduced in a time-dependent manner. Taken together, these findings elucidate the involvement of abnormal FGF21 expression in early APAP-induced liver impairment. Interestingly, FGF21 may be a promising biomarker of APAP-exposed livers.

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is a newly identified cytosolic DNA sensor, but its function in lung epithelial cells is relatively unknown. In the present study, the effects of lipopolysaccharide (LPS) on the expression and function of cGAS in the A549 lung epithelial cell line was investigated. The cells were treated with LPS at different concentrations (e.g., 100, 200, 400 and 800 ng/ml), and the cGAS expression levels were examined via western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The cells were pretreated with LPS, followed by E. coli DNA transfection using Lipofectamine(®) 3000. After 24 h, interferon (IFN)-β production was measured using ELISA and the expression of the autophagic markers, microtubule-associated proteins 1A/1B light chain 3 and sequestosome-1, were determined using western blot analysis. The cells were also pretreated with either a toll-like receptor (TLR) 4 inhibitor, a serine/threonine-protein kinase TBK1 (TBK1) inhibitor or an nuclear factor (NF)-κB inhibitor, followed by LPS treatment, and the cGAS expression levels were examined via western blot analysis and RT-qPCR. The result showed that LPS treatment upregulated cGAS expression in a dose-dependent manner. E. coli DNA treatment could induce IFN-β production and autophagy via cGAS, which was enhanced by LPS pretreatment. The effect of LPS on cGAS expression was suppressed by treatment with a TLR4 inhibitor, a TBK1 inhibitor and an NF-κB inhibitor. In conclusion, LPS enhances DNA-induced IFN-β production and autophagy by upregulating cGAS expression through the myeloid differentiation primary response protein MyD88-independent TLR4 signaling pathway in A549 cells.

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

Recently, glycerol dialkyl glycerol tetraethers (GDGTs) have been successfully used to identify different sources for organic-matter in the offshore and open ocean areas, while their applicability in the coastal areas remains unclear. This study was carried out to investigate the behavior of GDGTs and their applicability as indicators for organic-matter sources in a small subtropical river-estuary system, the Jiulong River-Estuary system (JRES), southeastern China. In 2018, three groups of samples including riverbank soils, riverbed surface sediments, and estuarine surface sediments were collected and analyzed. The results supported three main findings: 1) The abundances of GDGTs and crenarchaeol, and the ratios of iGDGTs/bGDGTs, GDGT-0/crenarchaeol (GDGT-0/cren), crenarchaeol isomer / (crenarchaeol + crenarchaeol isomer) and the IIIa/IIa, were good indicators for organic-matter sources; 2) At the middle and lower reaches of West River, the abnormally high values of GDGT-0/cren ratio and bGDGT abundance might indicate anthropogenic-induced water eutrophication; and 3) The branched and isoprenoid tetraether index (BIT) was especially sensitive in indicating of the soil- vs marine-organic matter contribution to the total organic matter of estuarine sediments. The high BIT values at the estuary turbidity maximum zone (TMZ) and the mid estuary suggested that TMZ filtering effect, preservation conditions and extra sources of soils have impacted the organic-matter distribution. Understanding the behavior and application of GDGTs in such a system helps to improve research on organic carbon cycling in the coastal system.

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (≥4cm), alpha-fetoprotein (≥100ng/ml), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041- 2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01- 2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.

Background: Calycosin and genistein are the two main components of isoflavones. Previously, we reported that these compounds display antitumor activities in the breast cancer cell lines MCF-7 and T47D. In the present study, we investigated the mechanism of action of calycosin and genistein, and their respective efficacies as potential therapies for the treatment of breast carcinoma in the clinic. Methods: MCF-7 cells were treated with calycosin or genistein. Cell proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The expression level of phosphorylated Akt protein was determined by western blotting. Expression level of HOTAIR was quantified by real-time PCR. Results: Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF-7 breast cancer cells, especially after treatment with calycosin. Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. Conclusion: Calycosin is more effective in inhibiting breast cancer growth in comparison with genistein, through its regulation of Akt signaling pathways and HOTAIR expression.

Our previous study revealed that serum deprivation upregulated human alkaline ceramidase 2 (haCER2) activity and mRNA in HeLa cells, but the mechanism remains unknown. In the present study, serum deprivation also upregulated haCER2 activity in HepG2 human hepatoma cell line cells due to an increase in haCER2 mRNA, in which mRNA transcription, not mRNA stability, is involved. Furthermore, p38 mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathway is involved in haCER2 mRNA upregulation by serum deprivation, and this mechanism may explain why haCER2 is upregulated in human liver cancer. In conclusion, p38 MAPK, AP-1 or haCER2 may be used as targets in liver cancer therapy.

Rhodium (II) complex with 2-benzoylpyridine (Rh(L)2Cl2) is a new, synthetic, active metal-complex, which is produced by the reaction of 2-benzoylpyridine (L) with rhodium chloride hydrate (RhCl3·nH2O). The crystal structure was determined by X-ray diffraction which is mono-nuclear. In order to explore the biological properties of the novel complex, a series of studies were performed. The results showed that Rh(L)2Cl2 had the anti-tumor activity in HepG2 and other cell lines and has been shown to induce G1 cell cycle arrest and apoptosis in HepG2 cells. The anti-cancer effect of Rh(L)2Cl2 is regulated by increased expression of caspase-3 and PARP via the mitochondrial and the death receptor pathways. Bcl-2 family proteins might play an important role in the Rh(L)2Cl2-induced changes in these two pathways. Further studies indicated that Rh(L)2Cl2 increased the level of reactive oxygen species (ROS), but that Rh(L)2Cl2-induced apoptosis was ROS-independent. In conclusion, Rh(L)2Cl2 is a potential new anti-tumor drug, which induces HepG2 cell death via the mitochondrial and death receptor pathways and has no obvious toxicity to normal liver cell.

// Xinhuang Chen 1, * , Yan Liao 2, * , Yaqun Yu 3 , Pengpeng Zhu 1 , Jun Li 1 , Liling Qin 1 , Weijia Liao 1, 4 and Zhaoquan Huang 4, 5 1 Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China 2 Disease Prevention and Control Center of Guilin, Guilin, Guangxi, P.R. China 3 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China 4 Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, Guangxi, P.R. China 5 Department of Pathology, Guilin Medical University, Guilin, Guangxi, P.R. China * These authors have contributed equally to this work Correspondence to: Weijia Liao, email: liaoweijia288@163.com Zhaoquan Huang, email: 191990449@qq.com Keywords: hepatocellular carcinoma, MAP17, progression, Akt/mTOR, prognosis Received: December 08, 2016 Accepted: August 28, 2017 Published: October 04, 2017 ABSTRACT MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels. High MAP17 expression was positively correlated with gender, distant metastasis, early recurrence (≤ 2 year), and serum alpha-fetoprotein (all p < 0.05). Kaplan-Meier analysis showed that the DFS ( p = 0.004) and OS ( p = 0.013) in HCC patients with elevated expression of MAP17 were much worse than that in the low expression subgroup. High level of MAP17 was also significantly associated with a high probability of HCC early recurrence after surgical resection ( p = 0.005). Cox regression analysis indicated MAP17 was an independent prognostic factor for DFS (HR, 1.710; 95% CI, 1.156-2.449, p = 0.012) and OS (HR, 1.743; 95% CI, 1.152-2.639, p = 0.009) in HCC. Silencing MAP17 significantly inhibited the proliferation, invasion and migration of HCC cells in vitro , and decreased the expression levels of Akt, p-Akt (Ser473), mTOR, p-mTOR (Ser2448) and MMP-9. Suggesting MAP17 was a novel diagnostic and prognostic biomarker for HCC patients and promoted HCC cell proliferation, invasion and migration via the Akt/mTOR pathway.

Background This study aimed to assess ethnic differences in health-related quality of life (HRQoL) among the rural elderly, and to examine the influence of ethnic culture, residential segregation and socioeconomic development on HRQoL. Methods A total of 6,511 rural elderly aged 60 years and older from 5,541 households in 116 villages across eight ethnic groups in Guangxi Zhuang Autonomous region were selected and assessed for HRQoL. The EQ-5D index values were calculated based on the Chinese Time Trade-Off values set. The EQ-5D descriptive system scores, visual analogue scale scores, and index values were described by ethnic group. The EQ-5D index was modeled against ethnic culture, residential segregation and socioeconomic development using villages as random effects. Results The median (IQR) of HRQoL among all the ethnic groups was 0.88 (0.80, 0.96). Pain/discomfort was the most prevalent problem, followed by anxiety/depression. After controlling for sociodemographic characteristics, a significant difference in HRQoL among ethnic groups persisted, but this was not true for residential segregation. Conclusion Social welfare and health policies designed to improve the health of the rural elderly should focus more on older, female, less-educated, Yao minority individuals as well as lower-income households.

Background : Ethnic health inequalities for males and females among the elderly have not yet been verified in multicultural societies in developing countries. The aim of this study was to assess the extent of disparities in health expectancy among the elderly from different ethnic groups using quality-adjusted life expectancy. Design : A cross-sectional community-based survey was conducted. A total of 6,511 rural elderly individuals aged ≥60 years were selected from eight different ethnic groups in the Guangxi Zhuang Autonomous Region of China and assessed for health-related quality of life (HRQoL). The HRQoL utility value was combined with life expectancy at age 60 years (LE60) data by using Sullivan's method to estimate quality-adjusted life expectancy at age 60 years (QALE 60 ) and loss in quality-adjusted life years (QALYs) for each group. Results : Overall, LE 60 and QALE 60 for all ethnic groups were 20.9 and 18.0 years in men, respectively, and 24.2 and 20.3 years in women. The maximum gap in QALE 60 between ethnic groups was 3.3 years in males and 4.6 years in females. The average loss in QALY was 2.9 years for men and 3.8 years for women. The correlation coefficient between LE 60 and QALY lost was −0.53 in males and 0.12 in females. Conclusion : Women live longer than men, but they suffer more; men have a shorter life expectancy, but those who live longer are healthier. Attempts should be made to reduce suffering in the female elderly and improve longevity for men. Certain ethnic groups had low levels of QALE, needing special attention to improve their lifestyle and access to health care. Keywords: gender; ethnicity; inequality in health; quality-adjusted life expectancy; rural elderly (Published: 3 November 2016) Citation: Glob Health Action 2016, 9 : 32261 - http://dx.doi.org/10.3402/gha.v9.32261 This paper is part of the Special Issue: Gender and Health Inequality - intersections with other relevant axes of oppression. More papers from this issue can be found at www.globalhealthaction.net