IL28B Genetic Variation Is Associated with Spontaneous Clearance of Hepatitis C Virus, Treatment Response, Serum IL-28B Levels in Chinese Population

<p><b>Background:</b> The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients.</p> <p><b>Methods:</b> We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR.</p> <p><b>Results:</b> We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97–0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous.</p> <p><b>Conclusions:</b> Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.</p&gt

ssDNA Aptamer Specifically Targets and Selectively Delivers Cytotoxic Drug Doxorubicin to HepG2 Cells.

Hepatocellular carcinoma (HCC) is the third leading cause of death due to cancer worldwide with over 500,000 people affected annually. Although chemotherapy has been widely used to treat patients with HCC, alternate modalities to specifically deliver therapeutic cargos to cancer cells have been sought in recent years due to the severe side effects of chemotherapy. In this respect, aptamer-based tumor targeted drug delivery has emerged as a promising approach to increase the efficacy of chemotherapy and reduce or eliminate drug toxicity. In this study, we developed a new HepG2-specific aptamer (HCA#3) by a procedure known as systematic evolution of ligands by exponential enrichment (SELEX) and exploited its role as a targeting ligand to deliver doxorubicin (Dox) to HepG2 cells in vitro. The selected 76-base nucleotide aptamer preferentially bound to HepG2 hepatocellular carcinoma cells but not to control cells. The aptamer HCA#3 was modified with paired CG repeats at the 5'-end to carry and deliver a high payload of intercalated Dox molecules at the CG sites. Four Dox molecules (mol/mol) were fully intercalated in each conjugate aptamer-Dox (ApDC) molecule. Biostability analysis showed that the ApDC molecules are stable in serum. Functional analysis showed that ApDC specifically targeted and released Dox within HepG2 cells but not in control cells, and treatment with HCA#3 ApDC induced HepG2 cell apoptosis but had minimal effect on control cells. Our study demonstrated that HCA#3 ApDC is a promising aptamer-targeted therapeutic that can specifically deliver and release a high doxorubicin payload in HCC cells

Retrospective validation of bone risk stratification criteria for men with de novo metastatic hormone-naive prostate cancer in China

Background Bone metastasis has been suggested to be a significant impactor on the prognosis of newly diagnosed de novo metastatic hormone-sensitive prostate cancer (mHSPC), and some risk stratification models have been proposed on the basis of this hypothesis. However, the effectiveness of these risk stratification criteria has not been fully evaluated in China. This study aimed to evaluate the effectiveness of the risk stratification models in China. Methods A total of 140 patients who were newly diagnosed with metastatic prostate cancer followed by primary androgen deprivation-based therapy from January 2008 to June 2021 at our institution were enrolled in this study. The patients were divided into different groups on the basis of high- and low-volume disease (H/LVD) criteria, high-and low-risk disease (H/LRD) criteria, extremity bone metastasis criteria (EBM), and extent of disease (EOD) criteria. The area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA) were used to compare the validity and net benefit of these models. Using the Cox proportional hazards model, we performed univariable and multivariable analyses of the factors influencing overall survival (OS) and the time of progression to metastatic castration-resistant prostate cancer (CRPC). Results The median patient age was 72 years. Most patients had a Gleason score ≥8 (102 cases, 72.9%) and clinical T stage >2 (75 cases, 53.6%). The median follow-up time was 25 months (range, 2–95 months). Ninety-two patients progressed to CRPC and fifty-seven patients died during the follow-up. The AUC of OS and CRPC showed that the EOD model had higher validity than the other risk stratification models. DCA shows that the net benefit of the EOD model on OS was better than that of the other risk stratification models. As for CRPC, the net benefit of the EOD model was second only to that of the H/LRD model when the threshold was 0.5, the EOD model outperformed the other models. The effectiveness of EOD as an independent prognostic variable was verified through univariable and multivariable analyses. Conclusion The EOD model yields reasonable risk stratification for use in Chinese mHSPC patients, providing further evidence supporting its role in clinical decision-making

Twin-resonance-coupling and high sensitivity sensing characteristics of a selectively fluid-filled microstructured optical fiber

A twin-resonance-coupling phenomenon and the sensing characteristics of a selectively fluid-filled microstructured optical fiber (SFMOF) are proposed and demonstrated. The SFMOF is realized by selectively infiltrating refractive index fluid into a single air hole located at the second ring near the core of the MOF. Twin-resonance dips are observed in the transmission spectrum. Theoretical and experimental investigations reveal that the twin-resonance dips both result from the coupling between LPC01 silica core mode and LPL01 liquid rod mode. Their sensitivities strongly depend on the dispersion curves of the silica and fluid material. Sensitivities of 290 nm/°C (739,796 nm/RIU) and 591.84 nm/N (701.2 pm/µɛ) are achieved, which are the highest for a SFMOF-based device to date, to our best knowledge. Furthermore, the twin-resonance dips appear to shift in the opposite directions with changes in temperature or axial strain, providing a method to achieve two- or multi-parameter measurement in such a compact structure.Published versio

Control and design of fiber birefringence characteristics based on selective-filled hybrid photonic crystal fibers

We demonstrated a kind of birefringence-controllable hybrid photonic crystal fibers (HPCFs) by selectively infiltrating air holes of PCFs with index-tunable liquids processing higher index than silica background. Detailed theoretical investigations on mode couplings from fundamental core mode to high-index-liquid-rod modes and birefringence properties of several HPCFs were presented. Strong wavelength dependence of phase and group birefringence was found, and HPCFs with different arrangements of high index liquid rods possess distinct birefringence characteristics. Then, the Sagnac interferometers (SIs) based on two typical HPCFs with different liquid-rod arrangements were theoretically and experimentally studied. The results indicated the SIs exhibit different transmission spectra and temperature responses due to the distinct birefringence features of HPCFs. A temperature sensitivity of −45.8 nm/°C at 56.5 °C was achieved using one HPCF, and a sensitivity of −11.6 nm/°C from 65 °C to 85 °C was achieved using the other HPCF. The thermal tunable HPCFs with birefringence-controllable properties will provide great potential for a variety of tunable optical devices and sensors.Published versio

Binding assay and biostability assay of HCA#3.

<p>(a) Binding assay of HCA#3 with HepG2 and control cells. Fluorescence imaging of cells bound to aptamer HCA#3 labeled with Cy3. (b) Biostability of aptamers; HCA#3 aptamers recovered from incubation with complete medium containing 0, 1, 5, or 10% FBS were visualized on 3% agarose gel.</p

ApDC specifically delivered Dox into HepG2 cells.

<p>(a) Cytotoxicity assays of Dox and ApDC. The HepG2 and the SK-HEP-1 cells were treated with aptamer, free Dox (2 μM), or ApDC (final equivalent concentration of aptamer was 0.5 μM and DOX was 2 μM). After incubation for 48 h, cell viability was evaluated by the annexin V apoptosis assay (mean ± SD, n = 3). The star indicates a statistically significant difference between Dox and the ApDC groups (p<0.05). (b) HepG2, SK-HEP-1, and PANC-28 cells were treated with increasing concentrations of Dox and ApDC, and cell apoptosis was measured after 48 h. (c) HepG2 and SK-HEP-1 cells were treated with aptamer, free Dox (2 μM), or ApDC (final equivalent concentration of aptamer was 0.5 μM and DOX was 2 μM). After incubation for 48 h, Western blotting analysis was performed on HepG2 and SK-HEP-1 cells using antibodies specific for cleaved-PARP and cleaved-caspase-3. β-Actin was used as a loading control.</p