Follow-up value of serum AFP and aminotransferases in chronic hepatitis B progression.

Introduction: Chronic viral hepatitis (CH) is a stage prior to cirrhosis and primary cancer. Standard protocols for CH assessment during the long follow-up period are of great importance for precise treatment and living quality improvement. In this study, we aimed to analyze multiple serum indexes in chronic hepatitis B (CHB)-infected patients and to discuss their combined values in clinical applications. Methods: Total 503 lines of laboratory data from 2012 to 2021 were extracted from103 CHB patients who were followed-up in our hospital. They were divided into the remission group and the progression group according to their complete clinical information and laboratory data. A series of models of serum indexes were analyzed to illustrate the fluctuation trend of @ach index in a time-dependent manner. Results: The models revealed that abundant serum alpha-fetoprotein (AFP) in the remission group was characteristically associated with hepatocyte destruction markers aspartate aminotransferase (AST) and alanine aminotransferase and favored a much longer progression-free period (P 0.0001). A model-derived equation consisting of serum AFP and AST values showed a good performance (83% reliability) to distinguish the two groups. Discussion: This study clearly demonstrates the intrinsic quantitative relationship between serum AFP and liver aminotransferases involving antivirus treatment response. The model-based equation compensates for serum hepatitis B virus DNA detection during outpatient follow-up and it may serve as a useful laboratory tool for CHB progression assessment.

Right time to detect urine iodine during papillary thyroid carcinoma diagnosis and treatment: A case report.

BACKGROUND: This is the first documentation of a spontaneous and nonspecific chemical reaction of an iodinated contrast media with ammonium persulfate used in As3+-Ce4+ catalytic spectrophotometry for urine iodine concentration (UIC) detection. CASE SUMMARY: We herein report an incidental case who had a dual source computed tomography examination for papillary thyroid carcinoma diagnosis. Serial spot urine specimens were collected during her hospitalization and were measured by As3+-Ce4+ catalytic spectrophotometry on a Beckman Coulter AU5800. The reacted solutions were "brownish", and the results showed extremely high iodine concentrations despite serial dilutions. The patient claimed no dietary habit of iodized salt or iodine-containing medical history, which strongly pointed to iodinated contrast media (ICM) via intravenous injection. Even with 0.01% ICM, its interruption is still profound on the desired urine iodine reaction with ammonium persulfate, leading to inaccurate UIC and possibly inappropriate treatment. CONCLUSION: The following laboratory suggestions should be considered: (1) As3+-Ce4+ catalytic spectrophotometry is only suitable for UIC measurement after confirmed ICM renal clearance; (2) A mass spectrometry-based method can be applied as an alternative during the ICM clearance period; and (3) The UIC baseline can be confirmed after ICM injection by consecutive detection for at least 2 mo.

Current Understanding and Management of Plasma Cell Mastitis: Can We Benefit from What We Know?

Background: Plasma cell mastitis (PCM), also known as mammary duct ectasia, is a chronic nonbacterial breast inflammation characterized by duct expansion and plasma cell infiltration. The severe and intense clinical manifestations profoundly affect the quality of life of female patients. Although the pathological process of PCM is known to include four stages (duct dilatation, inflammation, abscess and fistula), there is still lack of imaging techniques and serum markers with high specificity in clinical practice. Due to recurrent acute attacks and the prolonged healing process of the disease, most patients choose to accept mastectomy. Summary: We searched for studies, reports and reviews referring to PCM in the past 20 years; more than half of the results were related to animal studies, and little attention has been paid to human beings, which may explain the frequent misdiagnosis of PCM as breast cancer and the limited treatment options. This review focuses on the current diagnostic methods and markers for PCM and hierarchically discusses the typical clinical features, etiological causes and relevant molecular mechanisms of PCM. Key Messages: We herein highlight the urgent need to develop more specific and sensitive biomarkers in the clinical laboratory. It will help to establish a standardized flowchart for the diagnosis and treatment of PCM in order to improve recovery for female patients.

microRNA, a Subtle Indicator of Human Cytomegalovirus against Host Immune Cells.

Human cytomegalovirus (HCMV) is a double-stranded DNA virus that belongs to the ß-herpesvirus family and infects 40-90% of the adult population worldwide. HCMV infection is usually asymptomatic in healthy individuals but causes serious problems in immunocompromised people. We restricted this narrative review (PubMed, January 2022) to demonstrate the interaction and molecular mechanisms between the virus and host immune cells with a focus on HCMV-encoded miRNAs. We found a series of HCMV-encoded miRNAs (e.g., miR-UL112 and miR-UL148D) are explicitly involved in the regulation of viral DNA replication, immune evasion, as well as host cell fate. MiRNA-targeted therapies have been explored for the treatment of atherosclerosis, cardiovascular disease, cancer, diabetes, and hepatitis C virus infection. It is feasible to develop an alternative vaccine to restart peripheral immunity or to inhibit HCMV activity, which may contribute to the antiviral intervention for serious HCMV-related diseases.

Serum miR-27a is a biomarker for the prognosis of non-small cell lung cancer patients receiving chemotherapy.

BACKGROUND: Lung cancer has a high incidence and a 5-year survival rate of less than 15%. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Chemotherapy and immunotherapy are the most frequently used alternative treatments for patients with advanced-stage NSCLC in whom surgery failed. Previous studies have suggested that miR-27a is involved in cancer development and progression. The purpose of this study was to investigate the clinical value of miR-27a in the prognosis of NSCLC patients after chemotherapy. METHODS: Flow cytometry was used to detect the apoptosis rate of SPC-A1 cells treated with optical cisplatin at different times. Simultaneously, the expression of miR-27a in supernatants and cells was detected. Fifty-two newly diagnosed NSCLC patients were recruited. All patients received gemcitabine and cisplatin as first-line chemotherapy and docetaxel as second-line chemotherapy. At the end of every chemotherapy cycle, a therapeutic evaluation was performed according to the RECIST criteria. The expression of serum miR-27a was detected in each cycle. RESULTS: After treatment with 2.5 µg/mL cisplatin, the apoptosis rates of SPC-A1 cells were significantly greater than those of the paired untreated control groups at 12, 24, 48 and 72 h. The expression of miR-27a in supernatants and cells was also consistent with the apoptosis rate and changed a time-dependent manner. The chi-square test showed that an increase in miR-27a after chemotherapy was more common in patients who achieved partial response (PR) than in those who achieved no response (NR) (61.5% vs. 30.8%, P=0.026). Kaplan-Meier survival analysis indicated that patients with decreased miR-27a levels had poorer outcomes than those with increased miR-27a levels (P<0.05). Furthermore, dynamic changes in serum miR-27a with a gradual increasing trend during chemotherapy predicted a good prognosis. CONCLUSIONS: Collectively, our results suggest that miR-27a is involved in the apoptosis of lung cancer cells and that serum miR-27a levels are related to the prognosis of NSCLC patients. The expression levels of miR-27a in the serum may be an independent predictor for the prognosis of NSCLC.

Hypomethylation of the DAZ3 promoter in idiopathic asthenospermia: a screening tool for liquid biopsy.

Given the role of the deleted in azoospermia gene in male infertility, whether the somatic deleted in azoospermia methylation status is associated with idiopathic asthenospermia should be determined. To investigate the methylation levels of the deleted in azoospermia promoter in peripheral white blood cells from idiopathic asthenospermia patients relative to those in normozoospermia controls, 61 ethylene diamine tetraacetic acid anticoagulant blood samples were drawn from all participants for DNA isolation. The deleted in azoospermia promoter methylation ratio was detected by MassARRAY-based methylation quantification and confirmed by quantitative methylation-specific polymerase chain reaction. A MassARRAY-based methylation analysis showed that the deleted in azoospermia 3 promoter (0 to - 2 kbp) was significantly hypomethylated in peripheral white blood cells from idiopathic asthenospermia males, specifically one CpG site (- 246 to - 247). Quantitative methylation-specific polymerase chain reaction data further confirmed that the methylation level of the deleted in azoospermia 3 promoter region in idiopathic asthenospermia patients was significantly lower than that in normozoospermia males. The area under the receiver operating characteristic curve determined by quantitative methylation-specific polymerase chain reaction was 0.737 (95% confidence interval: 0.552 to 0.924), with a sensitivity of 53.9% and a specificity of 88.2% at a cut-off level of 74.7%. Therefore, our results suggested that methylation ratio detection of the deleted in azoospermia 3 promoter region by real-time polymerase chain reaction assay is a promising and feasible tool for liquid biopsy in the clinical laboratories. The methylation status of other reported infertility-related genes should also be investigated in peripheral white blood cells.

High expression of squamous cell carcinoma antigen in poorly differentiated adenocarcinoma of the stomach: A case report.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) is regarded as a specific indicator of epithelial malignancies and is widely used in the diagnosis of squamous cell carcinoma (SCC). However, the expression of SCCA in gastric adenocarcinoma has not been studied in detail. CASE SUMMARY: A 52-year-old man was admitted to our hospital for a 2.5 cm × 2.5 cm ulcer at the antrum-body junction with dull pain and fullness in the upper abdomen for 2 mo. His pre-surgery serological testing results showed 0.51 ng/mL SCCA (reference interval, < 1.5 ng/mL) and 9.9 ng/mL carcinoembryonic antigen (reference range, < 4.7 ng/mL). He underwent radical distal gastrectomy and Roux-en Y anastomosis and was diagnosed with poorly differentiated mucinous adenocarcinoma (Lauren classification: Diffuse) by pathological examination of the resected lesion. Immunohistochemistry showed that SCCA was highly expressed in the cytoplasm of cancer cells. After surgery, the patient received an S-1 adjuvant chemotherapy regimen for six cycles containing tegafur, gimeracil, and oteracil potassium. He showed no sign of recurrence or metastasis within 24-mo follow-up. CONCLUSION: This is a frontal report of SCCA overexpression in poorly differentiated adenocarcinoma of the stomach.

MAb NJ001 inhibits lung adenocarcinoma invasiveness by directly regulating TIMP-3 promoter activity via FOXP1 binding sites.

BACKGROUND: Previously, we developed a monoclonal antibody (mAb) NJ001 that binds to the antigen SP70 in human non-small cell lung cancer (NSCLC) cells and showed it could inhibit lung adenocarcinoma (AD) growth. Here, we investigated the effect and mechanisms of NJ001 in lung AD metastasis. METHODS: Human lung AD cells (SPC-A1 and A549) were treated with different concentrations of mAb NJ001, and the effects of NJ001 on cell migration and invasive activity were investigated using wound-healing and Matrigel assays, respectively. The molecular mechanism of this inhibition was explored by microarrays, qRT-PCR, western blot, luciferase assays and electrophoretic mobility shift assays (EMSA). RESULTS: MAb NJ001 markedly suppressed lung AD cell migration; and the invasiveness of SPC-A1 and A549 cells treated with mAb NJ001 was diminished by 65%. Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) was highly expressed in SPC-A1 cells treated with mAb NJ001, whereas knockdown of TIMP-3 by shRNA significantly increased SPC-A1 and A549 invasiveness. MAb NJ001 affects lung AD by inhibiting TIMP-3 through direct transcriptional regulation of FOXP1 binding sites in the TIMP-3 promoter region, as shown in luciferase assays and EMSA. CONCLUSIONS: MAb NJ001 inhibits invasiveness and metastasis in lung AD through the FOXP1 binding sites in the TIMP-3 promoter region. It may have clinical applications in preventing and treating metastatic lung AD.

Glycyrrhizin improved autophagy flux via HMGB1-dependent Akt/mTOR signaling pathway to prevent Doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is one of the most effective and irreplaceable chemotherapeutic agents but its clinical use is limited due to its cardiotoxicity. Glycyrrhizin(GL) has been applied to liver disorders for long. However, little is known that if GL could be meaningful in attenuating cardiotoxicity. The aim of this study is to investigate the cardioprotective effects of GL in DOX-induced cardiotoxicity (DIC) and the underlying mechanism. Here, H9c2 cardiomyoblasts, Neonatal rat cardiomyocytes (NRCMs), and Rats were introduced as test models. A single dose of 20 mg/kg DOX (i.p.) was applied to induce acute cardiotoxicity in vivo, as reflected by growth inhibition, increased levels of AST and CK-MB, and reduction of SOD activity, while GL (25 or 50 mg/kg/d, 14 d, i.p.) could counteract these effects. Moreover, pre-incubation with GL (0.8 mM for 12 h) in H9c2 cells protected against DOX-induced cytotoxicity, oxidative stress and depolarization of mitochondrial membrane potential (MMP). Besides, Western blot analysis showed that DOX upregulated the expression of LC3 II and p62 whereas GL reversed that both in vitro and in vivo and improved the obstructed autophagy flux in DOX-treated H9c2 cells with an autophagy inhibitor Bafilomycin A1 (Baf A1, 50 nM, 2 h). It has been previously documented that High-mobility group box 1 (HMGB1) was involved in DIC. In our work, knockdown of HMGB1 significantly increased cell viability and LC3 II level in H9c2, suggesting HMGB1 was crucial in DOX-induced autophagy-triggering cell death. Intriguingly, GL is a direct inhibitor of HMGB1. We found that GL downregulated Akt/mTOR autophagy signaling pathway in DOX-treated H9c2 cells. More importantly, in non-silencing H9c2 cells (transfected with negative control siRNA) cells, the expression of phospho-Akt, phospho-mTOR, p62, and LC3 II was significantly decreased with GL pretreament compared to DOX alone. However, in H9c2/HMGB1－(transfected with HMGB1 siRNA) cells exposed to DOX, the expression of p-Akt, p-mTOR, p62, LC3 II had no statistical difference with or without GL, revealing that HMGB1 mediated the cardioprotective action of GL in DIC. Taken together, our findings demonstrate that improved autophagy flux via HMGB1-dependent Akt/mTOR signaling pathway might contribute to attenuate DIC and go a novel insight into the underlying mechanisms of GL's cardioprotective action. GL could be a potential candidate for the prevention of DIC.

Development and validation of a prediction model for microvascular invasion in hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma (HCC) patients after hepatectomy and liver transplantation, but it can be determined only in surgical specimens. Accurate preoperative prediction of MVI is conducive to clinical decisions. AIM: To develop and validate a preoperative prediction model for MVI in patients with HCC. METHODS: Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected. Then, the patients were nonrandomly split into a training cohort and a validation cohort. Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram. We evaluated the discrimination and calibration ability of the nomogram by using R software. RESULTS: MVI was confirmed in 209 (46.0%) patients by a pathological examination. Multivariate logistic regression analysis identified four risk factors independently associated with MVI: Tumor size [odds ratio (OR) = 1.195; 95% confidence interval (CI): 1.107-1.290; P < 0.001], number of tumors (OR = 4.441; 95%CI: 2.112-9.341; P < 0.001), neutrophils (OR = 1.714; 95%CI: 1.036-2.836; P = 0.036), and serum α-fetoprotein (20-400 ng/mL, OR = 1.955; 95%CI: 1.055-3.624; P = 0.033; >400 ng/mL, OR = 3.476; 95%CI: 1.950-6.195; P < 0.001). The concordance index was 0.79 (95%CI: 0.74-0.84) and 0.81 (95%CI: 0.74-0.89) in the training and validation cohorts, respectively. The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes. CONCLUSION: We have developed and validated a preoperative prediction model for MVI in patients with HCC. The model could aid physicians in clinical treatment decision making.

SP70-Targeted Imaging for the Early Detection of Lung Adenocarcinoma.

NJ001 is a monoclonal antibody that can specifically recognize the SP70 antigen on lung adenocarcinoma cells. The goal of this study was to explore its utility in targeted imaging. Subcutaneous xenograft and orthotopic lung tumor implantation BALB/c mouse models were established. Near-infrared fluorescent CF750-labeled NJ001 was injected into two tumor mouse models. Mice that received orthotopic lung tumor implantation were also injected with NJ001-conjugated nanomagnetic beads intravenously, and then underwent micro-CT scanning. Meanwhile, mice with lung tumor were intravenously injected with normal saline and bare nanomagnetic beads as a control. Fluorescence could be monitored in the mice detected by anti-SP70 fluorescence imaging, which was consistent with tumor burden. Signal intensities detected with SP70-targeted micro-CT scans were greater than those in control mice. More importantly, orthotopic tumor lesions could be found on the fourth week with SP70-targeted imaging, which was 2 weeks earlier than detection in the control. Our results suggest that SP70 is a promising target for molecular imaging, and molecularly targeted imaging with an NJ001-labeled probe could be applied for the early detection of lung adenocarcinoma.

Umbilical cord-matrix stem cells induce the functional restoration of vascular endothelial cells and enhance skin wound healing in diabetic mice via the polarized macrophages.

BACKGROUND: Chronic nonhealing wounds represent one of the most common complications of diabetes and require advanced treatment strategies. Increasing evidence supports the important role of mesenchymal stem cells in diabetic wound healing; however, the underlying mechanism remains unclear. Here, we explored the effects of umbilical cord-matrix stem cells (UCMSCs) on diabetic wound healing and the underlying mechanism. METHODS: UCMSCs or conditioned medium (UCMSC-CM) were injected into the cutaneous wounds of streptozotocin-induced diabetic mice. The effects of this treatment on macrophages and diabetic vascular endothelial cells were investigated in vivo and in vitro. RESULTS: Our results reveal that UCMSCs or UCMSC-CM accelerated wound healing by enhancing angiogenesis. The number of host macrophages recruited to the wound tissue by local infusion of UCMSCs was greater than that recruited by fibroblast transplantation or control. The frequency of M2 macrophages was increased by UCMSC transplantation or UCMSC-CM injection, which promoted the expression of cytokines derived from M2 macrophages. Furthermore, when cocultured with UCMSCs or UCMSC-CM, lipopolysaccharide-induced macrophages acquired an anti-inflammatory M2 phenotype characterized by the increased secretion of the cytokines interleukin (IL)-10 and vascular endothelial growth factor and the suppressed production of tumor necrosis factor-α and IL-6. UCMSC-CM-activated macrophages significantly enhanced diabetic vascular endothelial cell functions, including angiogenesis, migration, and chemotaxis. Moreover, the action of UCMSC-CM on macrophages or vascular endothelial cells was abrogated by the administration of neutralizing antibodies against prostaglandin E2 (PGE2) or by the inhibition of PGE2 secretion from UCMSCs. CONCLUSIONS: Our findings demonstrate that UCMSCs can induce the functional restoration of vascular endothelial cells via the remodeling of macrophage phenotypes, which might contribute to the marked acceleration of wound healing in diabetic mice.

Liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients.

BACKGROUND: Hepatitis B is a major public health problem in China. Accurate liver injury assessment is essential for clinical evidence-based treatment. Liver biopsy is considered the gold standard method to stage liver disease, but it is not widely used in resource-limited settings. Therefore, non-invasive liquid biopsy tests are needed. AIM: To assess liver injury in hepatitis B patients using quantified cell free DNA combined with other serum biomarker as a liquid biopsy-based method. METHODS: A cohort of 663 subjects including 313 hepatitis B patients and 350 healthy controls were enrolled. Ultrasound-guided liver biopsies followed by histopathological assessments were performed for the 263 chronic hepatitis B patients to determine the degree of liver injury. Cell-free DNA was quantified using a novel duplex real-time polymerase chain reaction assay. RESULTS: Compared with healthy controls, patients with hepatitis B virus (HBV) infection had significantly higher plasma DNA, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and HBV DNA levels (P < 0.01). Serum ALT, AST, bilirubin, and plasma DNA levels of patients with marked-severe inflammation were significantly higher than those with mild-moderate inflammation (P < 0.01). There was a statistically significant correlation between hepatocyte inflammation severity and serum bilirubin (R 2 = 0.673, P < 0.01) or plasma DNA (R 2 = 0.597, P < 0.01) levels. The areas under the curves of serum ALT, bilirubin, plasma DNA, and their combination to distinguish between patients with mild-moderate and marked-severe inflammation were 0.8059, 0.7910, 0.7921, and 0.9564, respectively. CONCLUSION: The combination of plasma DNA, serum ALT, and bilirubin could be a candidate liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients.

Lithiated NiCo2O4 Nanorods Anchored on 3D Nickel Foam Enable Homogeneous Li Plating/Stripping for High-Power Dendrite-Free Lithium Metal Anode.

Lithium (Li) metal is one of the promising anode materials in the next-generation high-energy batteries, but Li dendrite growth and a big volume change during cycling result in low Coulombic efficiency (CE), short lifespan, and safety hazards, thereby impeding practical implementation of Li in rechargeable batteries. Herein, we report a highly stable and dendrite-free Li metal anode based on a three-dimensional (3D) conductive and lithiophilic scaffold comprising lithiated NiCo2O4 nanorods grown on nickel foam (LNCO/Ni). The nanorods grown on 3D Ni foam with a large surface area effectively reduce the averaged electrical current in the electrode, and the conformal Li2O coating produced in situ on the lithiated NiCo2O4 nanorods provides the surface lithiophilicity enabling stable Li plating/stripping without Li dendrite growth even at a high current density of 5 mA cm-2. The LNCO/Ni-Li anode shows a low voltage hysteresis of 16 mV, high CE of 98.7%, and stable cycling without obvious voltage fluctuation for over 500 cycles (1000 h) at a current density of 1 mA cm-2. Specifically, for a scalable Li loading of 20 mA h cm-2 on LNCO/Ni, no growth of Li dendrite and electrode thickness fluctuations are observed. The full cell consisting of the LNCO/Ni-Li anode and the LiFePO4 cathode exhibits a high rate capability and CE as high as 99.6% for more than 160 cycles. Our study reveals a new strategy to develop stable Li-metal anodes for high-energy batteries.

Human Papillomavirus Type 16 Disables the Increased Natural Killer Cells in Early Lesions of the Cervix.

The mechanism for pathogenesis of human papillomavirus (HPV) in the cervix has been investigated intensively. However, detailed differences in the distribution and function of innate immune cells between high-risk HPV types, especially during the chronic inflammation phase, have not been described fully. In this study, histologic pathology results of 245 women with HPV type 16 only (HPV16+) or type 18 only (HPV18+) were analyzed retrospectively from January 2015 to November 2016. More severe lesions of the cervix were observed in HPV16+ women compared with those in HPV18+ women. In total, 212 cervical brush specimens were collected from women suffering from chronic inflammation, HPV16+, or HPV18+ from December 2016 to December 2018. Flow cytometry analysis showed that abundant NK cells along with aberrant Treg cells were found in the HPV16-infected cervix. Quantitative real-time PCR demonstrated that higher expression levels of IFN-γ but muted IL-2 and KLRG-1 expression was detected in the cervix of patients with HPV16+ compared to HPV18+, which were further confirmed using 20 paraffin sections of cervical conization tissue. The ex vivo cytotoxicity experiment showed that the cytotoxicity of NK cells was significantly decreased in the cervix of HPV16+ patients compared with that of HPV18+ patients. Collectively, our results suggested that HPV16 disables the increased NK cells in the early lesion of the cervix, indicating that the local immune system of the cervix is hyporesponsive to HPV16 infection and this may explain its bias for malignant transformation.

Tegafur deteriorates established cardiovascular atherosclerosis in colon cancer: A case report and review of the literature.

BACKGROUND: Cardiac toxic effect of tegafur (S-1) is extremely rare, and there has been no report on this issue so far. CASE SUMMARY: We herein report a typical case of single S-1 administration after radical operation for colon cancer. The patient had no background or medical history of acute coronary syndrome (ACS), and only aortic and coronary atherosclerosis was revealed by computed tomography (CT) before surgery. He complained of sternum pain during the fifth cycle of S-1 treatment. Electrocardiogram (ECG) and serum cardiac marker cardiac troponin T (cTnT) strongly suggested ACS, which was possibly caused by S-1 cardiotoxicity. CONCLUSION: Monitoring protocols based on ECG, CT, and cTnT should be performed in real time to evaluate cardiac function during S-1 administration.

Serum SP70 is a sensitive predictor of chemotherapy response in patients with advanced nonsmall cell lung cancer.

SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression-free survival (PFS) were analyzed. Serum SP70 levels were significantly decreased after chemotherapy in the partial remission (PR) group (P < .001) and increased in the progressive disease (PD) group (P < .001), but not significantly changed in the stable disease (SD) group (P = .114). Although similar changes were observed on CEA and CYFRA21-1 levels but not NSE, ROC analysis demonstrated that SP70 is superior to the others. Additionally, patients with EGFR mutation had higher serum SP70 levels and tissue SP70 expression than patients without EGFR mutation (P = .014 and P = .002, respectively). The median PFS of patients with decreased SP70 levels after chemotherapy was longer than that of patients with stable or increased serum SP70 level (24 months vs 12 months vs 2 months, P < .001), and the differences of all other 3 tumor markers were not obvious. Serum SP70 is a sensitive and real-time indicator of chemotherapeutic efficacy in patients with advanced NSCLC and related to PFS.

Superior performance of co-cultured mesenchymal stem cells and hepatocytes in poly(lactic acid-glycolic acid) scaffolds for the treatment of acute liver failure.

Recently, cell-based therapies have attracted attention as promising treatments for acute liver failure (ALF). Bone marrow-derived mesenchymal stem cells (MSCs) are potential candidates for co-culture with hepatocytes in poly(lactic acid-glycolic acid) (PLGA) scaffolds to support hepatocellular function. However, the mechanism of culturing protocol using PLGA scaffolds for MSC differentiation into hepatocyte-like cells as well as the therapeutic effect of cell seeded PLGA scaffolds on ALF remain unsatisfactory in clinical application. Here, MSCs and hepatocytes were co-cultured at ratios of 1:2.5 (MSCs: Hep), 1:5 and 1:10, respectively. The proliferation abilities of these co-cultured cells were detected by CCK8, MTT, EdU and by scanning electron microscopy (SEM), and the ability of MSCs to differentiate into hepatocytes was detected by PCR, western blot and immunofluorescence staining. Therapeutic trials of cell seeded PLGA scaffolds were conducted through mouse abdominal cavity transplantation. Results showed that the 1:5 group showed significantly higher cellular proliferation than the 1:2.5 and 1:10 groups, supernatant albumin and urea nitrogen levels were also significantly higher in the 1:5 group than in other two groups. Similarly, the 1:5 group demonstrated better DNA transcription and liver-specific protein (albumin, CK18 and P450) production. Meanwhile, the GalN-stimulated levels of ALT, AST and TBil in mouse serum were down-regulated significantly more by (MSC + Hep)-PLGA scaffold treatment than MSC-PLGA or Hep-PLGA scaffold treatments. Furthermore, the (MSC + Hep)-PLGA scaffold-treated ALF mice showed a lower immunogenic response level than the other two groups. These data suggested that the ratio of 1:5 (MSC:Hep) co-cultures was the optimal ratio for MSCs to support hepatocellular metabolism and function in PLGA scaffolds in vitro, the (MSC + Hep)-PLGA scaffold treatment could perform better restoration for damaged liver function and could give ALF mice a greater survival rate than the monocell seeded PLGA scaffold treatment.

Identification of Host-Plant Volatiles and Characterization of Two Novel General Odorant-Binding Proteins from the Legume Pod Borer, Maruca vitrata Fabricius (Lepidoptera: Crambidae).

Chemoreception is a key feature in selection of host plant by phytophagous insects, and odorant-binding proteins (OBPs) are involved in chemical communication of both insects and vertebrates. The legume pod borer, Maruca vitrata Fabricius (Lepidoptera: Crambidae) is one of the key pest species of cowpea and widely distributed throughout tropical and subtropical regions, causing up to 80% of yield loss. In this study, we investigated the electrophysiological responses of female M. vitrata to floral volatiles from V. unguiculata. Seventeen electroantennogram-active compounds were identified from floral volatiles of V. unguiculata by coupled gas chromatography-electroantennography (GC-EAD) and gas chromatography-mass spectrometry (GC-MS). Then, we cloned two novel full-length GOBP genes (MvitGOBP1 and MvitGOBP2) from the antennae of M. vitrata using reverse transcription PCR. Protein sequence analysis indicated that they shared high sequence similarity with other Pyralididae insect GOBPs and had the typical six-cysteine signature. Real-time PCR analysis indicated that MvitGOBP1-2 mRNA was highly expressed in the antennae of female adult with several thousands-fold difference compare to other tissue. Next, the recombinant MvitGOBP1-2 was expressed in Escherichia coli and purified using Ni ion affinity chromatography. Fluorescence binding assays demonstrated that MvitGOBP1-2 had different binding affinities with 17 volatile odorant molecules including butanoic acid butyl ester, limonene, 4-ethylpropiophenone, 1H-indol-4-ol, butanoic acid octyl ester and 2-methyl-3-phenylpropanal. In the field trapping experiment, these six floral volatiles could effectively attract female moths and showed significant difference compared with the blank lure. These results suggested that MvitGOBPs and the seventeen floral volatiles are likely to function in the olfactory behavior response of female moths, which may have played crucial roles in the selection of oviposition sites. The six compounds that we have identified from the volatiles of V. unguiculata may provide useful information for exploring efficiency monitoring and integrated pest management strategies of this legume pod borer in the field.

Inhibited Wnt signaling causes age-dependent abnormalities in the bone matrix mineralization in the Apert syndrome FGFR2(S252W/+) mice.

Apert syndrome (AS) is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in internal organs. Approximately 70% of AS cases are caused by a single mutation, S252W, in fibroblast growth factor receptor 2 (FGFR2). Two groups have generated FGFR2 knock-in mice Fgfr2S252W/+ that exhibit features of AS. During the present study of AS using the Fgfr2S252W/+ mouse model, an age-related phenotype of bone homeostasis was discovered. The long bone mass was lower in 2 month old mutant mice than in age-matched controls but higher in 5 month old mutant mice. This unusual phenotype suggested that bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to maintain bone homeostasis, might be involved. BMSCs were isolated from Fgfr2S252W/+ mice and found that S252W mutation could impair osteogenic differentiation BMSCs but enhance mineralization of more mature osteoblasts. A microarray analysis revealed that Wnt pathway inhibitors SRFP1/2/4 were up-regulated in mutant BMSCs. This work provides evidence to show that the Wnt/ß-catenin pathway is inhibited in both mutant BMSCs and osteoblasts, and differentiation defects of these cells can be ameliorated by Wnt3a treatment. The present study suggested that the bone abnormalities caused by deregulation of Wnt pathway may underlie the symptoms of AS.