Despite the advances in detection of and therapies for various tumors, high rates of treatment failure and mortality still exist throughout the world. These high rates are mainly due to the powerful capability of tumor cells to proliferate and migrate. Recent studies regarding the transient receptor potential (TRP) have indicated that TRP channels are associated with tumors and that TRP channels might represent potential targets for cancer treatment. TRP channels are important calcium-selective ion channels in many different tissues and cell types in mammals and are crucial regulators of calcium and sodium. TRP were first discovered in the photoreceptors of Drosophila with gene defects or mutations. TRP channels can be divided into seven subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), TRPA (ankyrin transmembrane protein), and TRPN (NomPC-like). TRPC proteins are conserved across organisms since they are most homologous to Drosophila TRP. TRP superfamilies have been linked to many physiological and pathological functions, including cell differentiation, proliferation, apoptosis, and ion homeostasis. This review focuses on the properties of TRP in oncogenesis, cancer proliferation, and cell migration.
Preoperative chemoradiotherapy (CRT) combined with surgery has become a standard treatment strategy for patients with locally advanced rectal cancer (LARC). The pathological response is an important prognostic factor for LARC. The variety of tumor responses has increased the need to find a useful predictive model for the response to CRT to identify patients who will really benefit from this multimodal treatment. Magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), serum carcinoembryogenic antigen (CEA), molecular biomarkers analyzed by immunohistochemistry and gene expression profiling are the most used predictive models in LARC. The majority of predictors have yielded encouraging results, but there is still controversy. Diffusion-weighted MRI may be the best model to detect the dynamic changes of rectal cancer and predict the response at an early stage. Gene expression profiling and single nucleotide polymorphisms hold considerable promise to unveil the underlying complex genetics of response to CRT. Because each parameter has its own inherent shortcomings, combined models may be the future trend to predict the response.
T-antigen (Galβ1-3GalNAcα-1-Ser/Thr) is an oncofetal antigen that is commonly expressed as a carbohydrate determinant in many adenocarcinomas. Since it is associated with tumor progression and metastasis, production of recombinant antibodies specific for T-antigen could lead to the development of cancer diagnostics and therapeutics. Previously, we isolated and characterized 11 anti-T-antigen phage clones from a phage library displaying human single-chain antibodies (scFvs) and purified one scFv protein, 1G11. More recently, we purified and characterized 1E8 scFv protein using a Drosophila S2 expression system. In the current study, four anti-T-antigen scFv genes belonging to Groups 1-4 were purified from inclusion bodies expressed in Escherichia coli cells. Inclusion bodies isolated from E. coli cells were denatured in 3.5 M Gdn-HCl. Solubilized His-tagged scFv proteins were purified using Ni2+-Sepharose column chromatography in the presence of 3.5 M Gdn-HCl. Purified scFv proteins were refolded according to a previously published method of step-wise dialysis. Two anti-T-antigen scFv proteins, 1E6 and 1E8 that belong to Groups 1 and 2, respectively, were produced in sufficient amounts, thus allowing further characterization of their binding activity with T-antigen. Specificity and affinity constants determined using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR), respectively, provided evidence that both 1E8 and 1E6 scFv proteins are T-antigen specific and suggested that 1E8 scFv protein has a higher affinity for T-antigen than 1E6 scFv protein.
The present study is designed to search for the serum cytokine biomarker for liver injury induced by Dioscorea bulbifera L., which is a traditionally used herbal medicine in China. Mice were orally given various doses of ethyl acetate extract (EF) isolated from D. bulbifera for 12 days. The activity of serum alanine/aspartate transaminases (ALT/AST) was increased in EF (400 mg/kg)-treated mice. Histological assessment further confirmed EF (400 mg/kg)-induced liver injury. Results of a cytokine-antibody array demonstrated that there were 10 cytokines up-regulated and 1 cytokine down-regulated in EF (400 mg/kg)-treated mice. Enzyme-linked immunosorbent assay (ELISA) further confirmed the increased level of CD30 ligand (CD30L) and decreased level of interlukin-3 (IL-3) in EF-treated mice. In conclusion, our results demonstrate that the altered expression of CD30L and IL-3 may be potential biomarkers for hepatotoxicity induced by D. bulbifera.
The skin of Bufo bufo gargarizans Cantor has long been used for the treatment of hepatitis B in China and supercritical carbon dioxide extraction (SC-CO2) is widely used in extracting active ingredients from natural products. The aim of present study was to assess the anti-hepatitis B virus (HBV) effect of the supercritical CO2 extract from the skin of Bufo bufo gargarizans Cantor (SCE-BC). Cytotoxicity of SCE-BC was analyzed using an MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] assay in HepG2.2.15 cells. The hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core-related antigen (HBcrAg) concentrations in cell culture medium were determined by chemiluminescent enzyme immunoassay. HBV mRNA in cells was determined using real-time polymerase chain reaction. SCE-BC concentrations below 10-2 μg/mL had no significant toxicity to HepG2.2.15 cells. SCE-BC at 10-4 μg/mL effectively inhibited the secretion of HBeAg by 23.36% on day 6. It was more potent than the positive control lamivudine (100 μg/mL) in terms of the inhibition of HBeAg and HBcrAg secretion on day 6. Consistent with the HBV antigen reduction, HBV mRNA expression was markedly inhibited in comparison to the control when HepG2.2.15 cells were treated with SCE-BC. Moreover, SCE-BC had greater inhibitory activity with respect to HBeAg than to HBsAg. Since HBeAg promotes immune tolerance and persistent infection during HBV infection, the present results suggest that immune tolerance induced by HBeAg might be overcome by SCE-BC. Therefore, SCE-BC warrants further investigation.
This study sought to investigate the protective effect of an alternative medicine, Shufeng Jiedu Capsule, in acute lung injury and inflammation signaling pathways related to that action. Hematoxylin and eosin (HE) staining was used to observe pathological changes in rat lung tissue, arterial blood was subjected to blood gas analysis and lactic acid levels were determined, immunofluorescent staining for interleukin-1β (IL-1β) was performed, enzyme linked immunosorbent assay (ELISA) was used to detect biomarkers of the nuclear factor-κB (NF-κB) inflammation pathway including IL-1β and tumor necrosis factor α (TNF-α), biomarkers of the mitogen-activated protein kinase (MAPK) signal pathway including P-selectin, transforming growth factor β (TGF-β), keratinocyte-derived chemokine (KC), and C-Jun/AP-1 were measured, and real-time PCR was used to detect NF-κB mRNA. Results in rats with lipopolysaccharide-induced acute lung injury suggested that Shufeng Jiedu Capsule may increase the partial pressure of oxygen in lung tissue, decrease lactic acid levels, inhibit inflammatory factors such as IL-1β and TNF-α, and suppress the levels of P-selectin, TGF-β, KC, C-Jun/AP-1, and NF-κB mRNA. Thus, Shufeng Jiedu Capsule is a traditional medicine that may alleviate acute lung injury by suppressing the MAPK/NF-κB signaling pathway.
This study retrospectively analyzed Chinese publicly reported data on Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS). The HIV/AIDS morbidity (1/100,000) and mortality (1/100,000) rates in China continually increased from 0.23 and 0.06 in 2004 to 1.53 and 0.69 in 2011, respectively. The AIDS case fatality rate decreased yearly from 53.57% in 2008 to 45.11% in 2011, and the fatality rate in rural areas (0.25-0.42%) was higher than that in cities (0.13-0.22%). The number of HIV/AIDS patients discharged from city-level hospitals increased from 329 in 2004 to 7,266 in 2011, and this number was higher than the number of similar patients discharged from county-level (rural) hospitals (the number of HIV/AIDS patients increased from 252 in 2004 to 5,957 in 2011). The factors contributing to these trends include: enhanced physician HIV/AIDS education regarding diagnosis, intervention, monitoring, testing, and treatment; improved safety of blood collection and use; and improved management of HIV/AIDS patients. Therefore, HIV/AIDS prevention and control in rural areas of China is the key to reducing HIV transmission and mortality in China.
The purpose of this study was to investigate the ability of stroke volume variation (SVV) to predict fluid responsiveness in patients undergoing pulmonary lobectomy with one lung ventilation (OLV). Thirty patients intubated with double-lumen tube were scheduled for a pulmonary lobectomy requiring OLV for at least 1 hour under general anesthesia. Hemodynamic variables including heart rate, mean arterial pressure, cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP) and SVV were measured before and after volume expansion (VE) (8 mL/kg of 6% hydroxyethyl starch). Fluid responsiveness was defined as an increase in CI ≥ 10% after VE. Of the 30 patients, 16 (53%) were responders and 14 (47%) were nonresponders to intravascular VE. There were significant increases of CI, SVI in responders after VE (p < 0.01), but there were no significant changes in SVV in responders and nonresponders (p > 0.05). The baseline value of SVV, CVP, CI and SVI did not correlate significantly with ΔCI (p > 0.05). The area under the Receiver Operating Characteristic (ROC) curve were 0.507 for SVV (95% confidence interval, 0.294-0.720) and 0.556 for CVP (95% confidence interval, 0.339-0.773), neither was able to predict fluid responsiveness with sufficient statistical power. SVV measured by the Vigileo-FloTrac system was not able to predict fluid responsiveness in patients undergoing pulmonary lobectomy with OLV after thoractomy.
Psoriasis and psoriatic arthritis are chronic inflammatory diseases of the skin and joints, but the relationship between them has not been fully understood. Since the delay of treatment for psoriatic arthritis can result in the severe deformities, it is important to identify the pathological triggers of the arthritis. On the other hand, many reports suggest that the changes of immune balance during pre/postpartum period are associated with the state of autoimmune diseases. Here, we report a female case with psoriasis whose arthritis may be triggered by the delivery. Our report suggests that immune tolerance may diminish in the postpartum period, which may alter the susceptibility to arthritis. Female patients should be followed-up carefully during postpartum period against the development of arthritis.