Smartphone-Integrated Photoacoustic Analytical Device for Point-of-Care Testing of Food Contaminant Azodicarbonamide.

Azodicarbonamide (ADA) is widely used as a flour additive due to its oxidizing and bleaching properties, but it reacts with wet flour during heat processing and is easily decomposed into semicarbazide with genotoxicity and carcinogenicity. In order to improve the efficiency of food safety supervision and expand the scope of food safety control, it is of great significance to develop a facile method for point-of-care testing (POCT) of ADA. Herein, a field-portable and universal smartphone-based photoacoustic (PA) integration device is constructed for quantitative POCT of ADA in flour. The recognition probe Prussian blue with favorable stability is loaded on a flexible substrate for fabricating a portable test strip. In the presence of target ADA, the PA signal changes driven by a modulated 808 nm laser beam can be conveniently collected through the recording application (Audio Lab) of the smartphone. By combining the economic test strip and portable PA device with smartphone readout, it not only greatly simplifies the operation steps but also dramatically reduces the size and cost of the instrument. There is a favorable linear relationship between the PA signal and ADA concentration in the range of 10-200 µmol L-1 (R2 = 0.9928), and a detection limit of 5 µmol L-1 obtained is much lower than the maximum allowable ADA level in the extract of flour (388 µmol L-1). The present miniature PA device with strong POCT ability holds enormous public health significance and economic value in the field of food safety, especially in resource-limited settings.

Molecular and Supramolecular Approach to Highly Photocytotoxic Phthalocyanines with Dual Cell Uptake Pathways and Albumin-Enhanced Tumor Targeting.

Phototherapy for non-invasive cancer treatment has been extensively studied. An urgent challenge in phototherapy application is to fabricate appropriate targeted agents to achieve efficient therapeutic effect. Herein, a molecular and supramolecular approach for targeting phototherapy was reasonably designed and realized through the axial sulfonate modification of silicon(IV) phthalocyanines (Pcs), followed by supramolecular interaction with albumin. This approach can not only improve the photoactivities (e.g., fluorescence emission and reactive oxygen species production) of the Pcs but also enhance their tumor targeting. Most importantly, one of the deigned Pcs (4) can target HepG2 cells through dual cell pathways, leading to an extremely high phototoxicity with an EC50 (i.e., concentration of Pcs to kill 50% of cells under light irradiation) value of 2.0 nM. This finding presents a feasible strategy to realize efficient targeting phototherapy.

The Risk Stratification for Cervical Cancer and Precursors of Domestic HPV Testing With HPV 16/18 Genotyping in Women With NILM Cytology in CentralChina: A Cohort Study.

OBJECTIVE: To evaluate the clinical performance and utility for risk stratification of DH3 HPV assay in women (≥30 years) with NILM cytology. METHODS: A prospective cohort was established in Central China between November 8 to December 14, 2016 which consisted of 2180 women aging 30-64 years with NILM cytology. At baseline, all women were screened using DH3 HPV assay. HPV 16/18 positive women would be assigned to colposcopy and biopsied if necessary. Then, hr-HPV positive women without CIN2+ lesions would be followed up by cytology every 12 months for two years. In the 3rd year of follow up, all women that were not biopsy proven CIN2+ would be called back and screened by cytology again. In follow-up period, women with ASC-US and above were referred to colposcopy and biopsied if clinically indicated. CIN2+ was the primary endpoint in analysis. The clinical performance and utility for risk stratification of DH3 HPV assay were assessed by SPSS 22.0 and SAS 9.4. RESULTS: Of 2180 qualified women, the prevalence of hr-HPV was 8.5% (185/2180), 45(2.1%) were HPV 16/18 positive. The clinical performance for HPV16/18 was 91.7% for sensitivity, 98.4% for specificity, respectively against CIN2+ detection at baseline. In four years of study, the corresponding rates of HPV 16/18 were 51.5% and 98.7%, respectively. The cumulative absolute risk for the development of CIN2+ was as high as 37.8% for HPV 16/18 positive women, followed by hr-HPV positive (14.6%), other hr-HPV positive (11.0%) and HPV negative (0.3%) in three years. The relative risk was 125.6 and 3.4 for HPV 16/18 positive group when compared with HPV negative and other hr-HPV positive group, respectively. CONCLUSIONS: DH3 HPV assay demonstrated excellent clinical performance against CIN2+ detection in cervical cancer screening and utility of risk stratification by genotyping to promote scientific management of women with NILM cytology.

Negative conversion of autoantibody profile in chronic hepatitis B: A case report.

BACKGROUND: Autoimmune antibodies are detected in many diseases. Viral infections are accompanied by several immunopathological manifestations. Some autoimmune antibodies have been associated with the immune response induced by virus or drugs. Thus, a comprehensive diagnosis of chronic hepatitis B combined with autoimmune hepatitis is required, and immunosuppressant or antiviral therapy should be carefully considered. CASE SUMMARY: We present a case of a patient who had negative transformation of autoimmune antibodies during chronic active hepatitis B. A 50-year-old female who had a history of asymptomatic hepatitis B virus carriers for more than 10 years presented to the hospital with the complaint of weakness for 1 wk. Blood tests revealed elevated liver enzymes; the detection of autoantibodies was positive. Hepatitis B viral load was 72100000 IU/mL. The patient started tenofovir alafenamide fumigate 25 mg daily. Liver biopsy was performed, which was consistent with chronic active hepatitis B. The final diagnosis of the case was chronic active hepatitis B. The autoimmune antibodies turned negative after 4 wk of antiviral therapy. The patient recovered and was discharged with normal liver function. There was no appearance of autoantibodies, and liver function was normal at regular follow-ups. CONCLUSION: Autoimmune antibodies may appear in patients with chronic active hepatitis. It is necessary to differentiate the diagnosis with autoimmune hepatitis.

Microtubule Stabilization Promotes Microcirculation Reconstruction After Spinal Cord Injury.

Spinal cord microcirculation plays an important role in maintaining the function of spinal cord neurons and other cells. Previous studies have largely focused on the ability of microtubule stabilization to inhibit the fibroblast migration and promote axon regeneration after spinal cord injury (SCI). However, the effect of microtubule stabilization treatment on microcirculation reconstruction after SCI remains unclear. By using immunofluorescence, we found that microtubule stabilization treatment improved microcirculation reconstruction via increasing the number of microvessels, pericytes, and the perfused microvessels after SCI. To clarify the underlying mechanisms, rat brain microvascular endothelial cells and pericytes were subjected to glucose oxygen deprivation. By using flow cytometry and western blotting, we found that microtubule stabilization treatment inhibited apoptosis and migration of endothelial cells and pericytes but promoted proliferation and survival of endothelial cells and pericytes through upregulated expression of vascular endothelial growth factor A (VEGFA), VEGF receptor 2, platelet-derived growth factor-B (PDGFB), PDGF receptor ß, and angiopoietin-1 after SCI. Taken together, this study provides evidence for the mechanisms underlying the promotion of microcirculation reconstruction after SCI by microtubule stabilization treatment. Importantly, this study suggests the potential of microtubule stabilization as a therapeutic target to reduce microcirculation dysfunction after SCI in the clinic.

The Potential Benefits of HPV E6/E7 mRNA Test in Cervical Cancer Screening in China.

This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7-96.4) and 95.7% (95%CI: 91.3-97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0-97.7], 96.3% [95%CI: 92.1-98.3]), but higher than LBC (80.4% [95%CI: 74.5-85.2] and 88.8% [95%CI: 83.0-92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2-83.0]) and CIN3+ (70.5% [95%CI: 65.7-74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9-75.7], 62.8% [95%CI: 57.8-67.5]), but lower than LBC (84.5% [95%CI: 80.1-88.0] 79.8% [95%CI: 75.4-83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.

MALAT1 is involved in the pathophysiological process of PCOS by modulating TGFß signaling in granulosa cells.

Polycystic ovary syndrome (PCOS) is an endocrine disorder, the etiology of which is complex and unclear. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a conserved long non-coding RNA which has been found to play a role in the pathophysiological process of reproductive system diseases, such as endometriosis and pregnancy loss. However, the role of MALAT1 in PCOS is still unknown. In this study, reduced MALAT1 expression was found in granulosa cells (GCs) from 68 patients with PCOS and 30 healthy controls, which relates to upregulated cell proliferation and downregulated apoptosis. Using phosphorylation pathway profiling array, MALAT1 reduction was identified to contribute to the repression of transforming growth factor beta (TGFß) signaling in GCs. Subsequently, MALAT1 was confirmed to function as a competing endogenous RNA (ceRNA), interacting with miR-125b and miR-203a. Meanwhile, miR-125b and miR-203a was identified as two novel TGFß signaling negative regulators by targeting TGFBR1 and TGFBR2. Finally, MALAT1 knockdown was found to induce the upregulation of miR-125b and miR-203a, which further repressed TGFß signaling, changed some downstream gene expression, and resulted in a disordered cell cycle. In conclusion, MALAT1 reduction was identified in GCs, which may contribute to the pathophysiological processes of PCOS by regulating TGFß signaling through sponging miR-125b and miR-203a.

Performance of Different Combination Models of High-Risk HPV Genotyping in Triaging Chinese Women With Atypical Squamous Cells of Undetermined Significance.

Objective: The purpose of this study was to evaluate the effect of different combination models of high-risk human papilloma viruses (HPV) genotyping in triaging Chinese women with atypical squamous cells of undetermined significance (ASCUS). Methods: We established a screening cohort of 3,997 Chinese women who underwent cervical cytology and HPV genotyping test. Women with ASCUS cytology underwent punch biopsy under colposcopy/endocervical curettage. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different combination models of HR-HPV genotyping calculated that cervical intraepithelial neoplasia 2 or higher (CIN2+) on histology were endpoints. Results: Of the full sample, 393 women had ASCUS. Among ASCUS women with a CIN2 lesion, the prevalence for HPV were 40.0% (type 16), 10.0% (type 18), 0.0% (type 33), 30.0% (type 52), 40.0% (type 58), and 30.0% (other nine types). For ASCUS women with a CIN3 lesion, the prevalence for HPV were 68.4% (type 16), 15.8% (type 18), 10.5% (type 33), 31.6% (type 52), 15.8% (type 58), and 36.8% (other nine types). Combination model including HPV16/18/33/52/58 for predicting CIN2+ lesion in women with ASCUS had relatively higher sensitivity [93.1% (78.0, 98.1)], specificity [75.8% (71.2, 79.9)], PPV [23.5% (16.7, 32.0)], and NPV [99.3% (97.4, 99.8)] than other combination models. Moreover, the referral rate of HPV16/18/33/52/58 (29.3%) was lower than HR-HPV (36.1%). Conclusions: The study demonstrates that specific HR-HPV types HPV16/18/33/52/58 may be an effective strategy in ASCUS triage. This improves the subsequent selection of ASCUS patients.

Targeting PAK1 with the Small Molecule Drug AK963/40708899 Suppresses Gastric Cancer Cell Proliferation and Invasion by Downregulation of PAK1 Activity and PAK1-Related Signaling Pathways.

PAK1 (p21-activated kinase 1) is a serine/threonine protein kinase which has been initially identified as downstream effector of the Rho GTPase family. In previous research, PAK1 has been involved in the regulation of diverse cellular processes, such as cell motility, cell proliferation, gene transcription, cytoskeletal rearrangement, and cell invasion. Hyper-activation of PAK1 was constantly observed in a variety of human cancer which make it a potential target of novel anti-tumor drugs. To date, a great number of attentions focus on identifying the PAK1 inhibitors in medical and pharmaceutical fields. In this article, we found that a novel and potent PAK1 inhibitor, AK963/40708899, suppressed the proliferation of human gastric cancer cells significantly by downregulation of PAK1-NF-κB-cyclinB1 pathway. In addition, AK963/40708899 inhibited the formation of filopodia and promoted cell adhesion which in turn inhibited invasive potential of gastric cells by negatively regulating PAK1-LIMKl-cofilin and PAK1-ERK-FAK pathways. Considering our result, AK963/40708899 would be a possible candidate for PAK1 targeted anti-tumor drug. Anat Rec, 302:1571-1579, 2019. © 2019 American Association for Anatomy.

Evaluation of p16/Ki-67 dual staining in the detection of cervical precancer and cancer in China.

Background This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining in the detection of cervical intraepithelial neoplasia grade 2 or 3 or worse (CIN2+/CIN3+) in Chinese women. Methods Cervical exfoliated cells were collected from 537 eligible women and were used for liquid-based cytology (LBC), p16/Ki-67 dual staining, and human papillomavirus (HPV) DNA testing. All women received colposcopy with biopsies taken at abnormal sites. Histopathological diagnoses were used as the gold standard. Results p16/Ki-67 staining had a positivity rate of 43.58% overall; the rate increased significantly with histological severity (p <0.001). The sensitivities of p16/ki-67 for detecting CIN2+ and CIN3+ were 88.10% and 91.30%, respectively. Compared with high-risk HPV (HR-HPV), sensitivity of p16/Ki-67 was lower for detecting CIN2+ (88.10% versus 95.71%), but similar for detecting CIN3+ (91.30% versus 96.27%). Specificities of p16/Ki-67 were 85.02% for detecting CIN2+ and 76.86% for detecting CIN3+, values similar to those for LBC (84.71% for CIN2+, 80.05% for CIN3+) but higher than those for HR-HPV (62.77% for CIN2+, 71.25% for CIN3+). All the tests performed better in women>30 years. With respect to the performance of triage for women with ASC-US, sensitivities of p16/Ki-67 were 86.36% for detecting CIN2+ and 83.33% for detecting CIN3+, values similar to those of HR-HPV. However, specificities of p16/Ki-67 were both higher than those of HR-HPV (85.96% versus 67.54% for CIN2+, 79.84% versus 62.90% for CIN3+). Conclusion P16/Ki-67 dual staining could probably provide an optional method for China's national cervical cancer screening, and could also be considered as an efficient method of triage for managing women with ASC-US.

Functionalized Asymmetric Bola-Type Amphiphiles for Efficient Gene and Drug Delivery.

The studies of bolaamphiphile-based nanoparticles as delivery vectors are still rudimentary and under development. In this study, several asymmetric bolaamphiphiles containing lysine and another moiety with special functions, such as pH-sensitive or cell-targeting property, were designed and synthesized. The potentials of these bolaamphiphile-based nanoparticles as versatile vectors for both nucleic acids and chemical drugs were studied. With the presence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), these amphiphiles could be prepared into bolasomes, which showed good DNA binding ability and could condense plasmid DNA into nanoparticles with appropriate size and surface potential. Lys-His, which has a pH-sensitive histidine on one head, exhibited higher transfection efficiency than the symmetric counterpart and comparable efficiency to commercially available transfection reagent. Mechanism studies confirmed that the bolaplexes formed from Lys-His might induce the highest cellular uptake and the best endosomal escape ability. On the other hand, these bolaamphiphiles also exhibited good drug loading ability. The self-assembly vesicles could efficiently encapsulate the hydrophobic anti-cancer drug doxorubicin (DOX) in aqueous solution with high drug loading content and encapsulation efficiency. Confocal laser scanning microscopy (CLSM) experiment and cell viability assay exhibited a controlled release of the drug with the assistance of bolasomes. It was shown that such bolaamphiphiles have great potential as nano-vectors for both drug and gene or their co-delivery.

The synergistic effect of esophageal squamous cell carcinoma KYSE150 cells and M2 macrophages on lymphatic endothelial cells.

Objective: This study aimed to investigate whether tumor-associated macrophages (TAMs) and esophageal squamous cell carcinoma (ESCC) cells could synergistically influence the generation of lymphatic vessels via the VEGF-C/VEGFR-3 signaling pathway and to address its mechanism. Methods: M2 macrophages were sorted with immunomagnetic beads and induced in vitro. VEGF-C siRNA plasmids were constructed and transfected into M2 macrophages and the ESCC cell line KYSE150. Different conditioned culture media before and after transfection were collected and classified into different groups for culturing ESCC-associated lymphatic endothelial cells (ESCC-LECs). Using the CCK-8 assay, Transwell cell migration assay and Matrigel three-dimensional culture, the proliferation, migration and ring forming abilities of ESCC-LECs before and after transfection were compared, respectively. With ELISA, western blot and q(RT)-PCR, VEGF-C concentrations in conditioned culture media and the protein and mRNA expression levels of VEGFR-3 in LECs before and after transfection were compared, respectively. Results: Before transfection, ESCC-LECs in the group with mixed culture medium had stronger proliferation, migration and ring forming abilities than the other groups. The VEGF-C concentration and VEGFR-3 protein and mRNA expression levels were higher in the mixed culture medium group than in the other groups. After transfection, all indices were the lowest in the mixed culture medium group. Conclusions: M2 macrophages can enhance the proliferation, migration and ring forming abilities of ESCC-LECs. ESCC cells and M2 macrophages have synergistic effects on the proliferation, migration and ring forming abilities of ESCC-LECs. VEGF-C siRNA can inhibit the proliferation, migration and ring forming abilities of ESCC-LECs by silencing the expression of VEGF-C and its receptor VEGFR-3 in KYSE150 cells and M2 macrophages.

LC-0882 targets PAK4 and inhibits PAK4-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells.

Gastric cancer is the most common malignant tumor and globally the third leading cause of cancer-related deaths. Therefore, there exists an urgent need to identify new effective gastric cancer treatments. Given the important roles in tumorigenesis and progression, p21-activated kinase 4 (PAK4) has been regarded as an attractive high-value druggable target. In this study, we examined the effects and molecular mechanisms of action of the small molecular compound LC-0882 on gastric cancer cells in vitro. LC-0882 was found to significantly inhibit the proliferation of human gastric cancer cells by repressing phospho-PAK4/cyclin D1 and CDK4/6 expression. In addition, LC-0882 was found to attenuate cell invasion by blocking the PAK4/LIMK1/cofilin signaling pathway. Finally, analysis of immunofluorescence revealed that LC-0882 exposure decreased filopodia formation and induced cell elongation in BGC823 and SGC7901 gastric cancer cells. These findings suggest that targeting PAK4 with the novel compound LC-0882 may provide a new chemotherapeutic approach in gastric cancer treatment.

The association of three promoter polymorphisms in interleukin-10 gene with the risk for colorectal cancer and hepatocellular carcinoma: A meta-analysis.

Mounting evidence supports a potent inhibitory role of interleukin-10 (IL-10) in tumor carcinogenesis, angiogenesis and metastasis. This meta-analysis was designed to examine the association of three promoter polymorphisms (-592C > A, -819C > T and -1082G > A) in IL-10 gene with the risk for colorectal cancer and hepatocellular carcinoma. Qualification assessment and data collection were completed by two authors independently. The random-effects model using the DerSimonian and Laird method was fitted by the STATA software. Twenty-five articles involving 5933 cases and 9724 controls were meta-analyzed. Overall comparisons of the mutant alleles (-592A, -819T and -1082A) of three promoter polymorphisms with alternative wild alleles failed to reveal any statistical significance for both colorectal cancer and hepatocellular carcinoma (P > 0.05), and the likelihood of heterogeneity was low (I(2) < 50%). For -592C > A polymorphism, a significant risk for colorectal cancer was identified when analysis was restricted to East Asians (odds ratio or OR = 1.41, 95% confidence interval or CI: 1.18-1.68, P < 0.001) and retrospective studies (OR = 1.23, 95% CI: 1.09-1.39, P = 0.001). As weighed by the Egger's test and the fill-and-trim method, there was a low probability of publication bias for all studied polymorphisms. Our findings collectively suggest that the -592C > A polymorphism in IL-10 gene might be a susceptibility locus for colorectal cancer in East Asians.

The association of six non-synonymous variants in three DNA repair genes with hepatocellular carcinoma risk: a meta-analysis.

Hepatocellular carcinoma is a complex polygenic disease. Despite the huge advances in genetic epidemiology, it still remains a challenge to unveil the genetic architecture of hepatocellular carcinoma. We, therefore, decided to meta-analytically assess the association of six non-synonymous coding variants from XRCC1, XRCC3 and XPD genes with hepatocellular carcinoma risk by pooling the results of 20 English articles. This meta-analysis was conducted according to the PRISMA statement, and data collection was independently completed in duplicate. In overall analyses, the minor alleles of four variants, Arg280His (odds ratio, 95% confidence interval, P: 1.37, 1.13-1.66, 0.001), Thr241Met (1.93, 1.17-3.20, 0.011), Asp312Asn (1.22, 1.08-1.38, 0.001) and Lys751Gln (1.42, 1.02-1.97, 0.038), were associated with the significant risk for hepatocellular carcinoma. There were low probabilities of publication bias for all variants. Subgroup analyses revealed significant association of XRCC1 gene Arg399Gln with hepatocellular carcinoma in Chinese especially from south China (odds ratio, 95% confidence interval, P: 1.57, 1.16-2.14, 0.004), in larger studies (1.48, 1.11-1.98, 0.007) and in studies with population-based controls (1.33, 1.06-1.68, 0.016). Taken together, our findings demonstrated that XPD gene Asp312Asn and XRCC1 gene Arg399Gln might be candidate susceptibility loci for hepatocellular carcinoma. Considering the ubiquity of genetic heterogeneity, further validation in a broad range of ethnic populations is warranted.

Discovery of a new series of imidazo[1,2-a]pyridine compounds as selective c-Met inhibitors.

AIM: Aberrant c-Met activation plays a critical role in cancer formation, progression and dissemination, as well as in development of resistance to anticancer drugs. Therefore, c-Met has emerged as an attractive target for cancer therapy. The aim of this study was to develop new c-Met inhibitors and elaborate the structure-activity relationships of identified inhibitors. METHODS: Based on the predicted binding modes of Compounds 5 and 14 in docking studies, a new series of c-Met inhibitor-harboring 3-((1H-pyrrolo[3,2-c]pyridin-1-yl)sulfonyl)imidazo[1,2-a]pyridine scaffolds was discovered. Potent inhibitors were identified through extensive optimizations combined with enzymatic and cellular assays. A promising compound was further investigated in regard to its selectivity, its effects on c-Met signaling, cell proliferation and cell scattering in vitro. RESULTS: The most potent Compound 31 inhibited c-Met kinase activity with an IC50 value of 12.8 nmol/L, which was >78-fold higher than those of a panel of 16 different tyrosine kinases. Compound 31 (8, 40, 200 nmol/L) dose-dependently inhibited the phosphorylation of c-Met and its key downstream Akt and ERK signaling cascades in c-Met aberrant human EBC-1 cancer cells. In 12 human cancer cell lines harboring different background levels of c-Met expression/activation, Compound 31 potently inhibited c-Met-driven cell proliferation. Furthermore, Compound 31 dose-dependently impaired c-Met-mediated cell scattering of MDCK cells. CONCLUSION: This series of c-Met inhibitors is a promising lead for development of novel anticancer drugs.

GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways.

Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4) has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer.

Silicon(IV) phthalocyanines substituted axially with different nucleoside moieties. Effects of nucleoside type on the photosensitizing efficiencies and in vitro photodynamic activities.

A series of new silicon(IV) phthalocyanines (SiPcs) di-substituted axially with different nucleoside moieties have been synthesized and evaluated for their singlet oxygen quantum yields (ΦΔ) and in vitro photodynamic activities. The adenosine-substituted SiPc shows a lower photosensitizing efficiency (ΦΔ=0.35) than the uridine- and cytidine-substituted analogs (ΦΔ=0.42-0.44), while the guanosine-substituted SiPc exhibits a weakest singlet oxygen generation efficiency with a ΦΔ value down to 0.03. On the other hand, replacing axial adenosines with chloro-modified adenosines and purines can result in the increase of photogenerating singlet oxygen efficiencies of SiPcs. The formed SiPcs 1 and 2, which contain monochloro-modified adenosines and dichloro-modified purines respectively, appear as efficient photosensitizers with ΦΔ of 0.42-0.44. Both compounds 1 and 2 present high photocytotoxicities against HepG2 and BGC823 cancer cells with IC50 values ranging from 9nM to 33nM. The photocytotoxicities of these two compounds are remarkably higher than the well-known anticancer photosensitizer, chlorin e6 (IC50=752nM against HepG2 cells) in the same condition. As revealed by confocal microscopy, for both cell lines, compound 1 can essentially bind to mitochondria, while compound 2 is just partially localized in mitochondria. In addition, the two compounds induce cell death of HepG2 cells likely through apoptosis.

Predict esophageal varices via routine trans-abdominal ultrasound: A design of classification analysis model.

BACKGROUND AND AIMS: Upper gastrointestinal endoscopy remains the gold standard for diagnosis of esophageal varices. Trans-abdominal ultrasound, as a noninvasive routine examination for the follow-up of cirrhosis patient, is safe, cheap, easy to perform, and plays an important role. In this study, we attempt to design a practical classification analysis model to predict esophageal varices via ultrasound. METHODS: Compared with endoscopy, the ultrasound qualitative signs (lower esophageal Doppler signals, left gastric vein hepatofugal flow, and paraumbilical vein recanalization) and quantitative parameters (spleen diameter, spleen vein diameter, portal vein diameter, and portal vein velocity) have been evaluated in 286 cirrhosis patients. RESULTS: The classification analysis model is designed as that: the patients are defined with esophageal varices high risk, who with any ultrasound qualitative signs or who with spleen diameter greater than 162 mm without qualitative parameters. The sensitivity for detecting esophageal varices is 97.5% and the specificity is 82.6%, while the positive predictive value is 96.7%, negative predictive value is 83.4%, and the omission diagnostic rate is 2.5%. CONCLUSIONS: This classification analysis model design includes ultrasound qualitative signs and spleen diameter, which can be detected easily via routine ultrasound without other auxiliary. The classification analysis model is useful in detecting esophageal varices, which may be a supplement for predicting of esophageal varices, and reducing the frequency of endoscopy in the follow-up of cirrhosis patients.

Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Leaves of Perilla frutescens.

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia.