IFI16 Positively Regulates RIG-I-Mediated Type I Interferon Production in a STING-Independent Manner.

Previous studies have shown that interferon gene-stimulating protein (STING) is essential for IFN-γ-inducible protein 16 (IFI16) as the DNA sensor and RNA sensor to induce transcription of type I interferon (IFN-I) and is essential for IFI16 to synergize with DNA sensor GMP-AMP (cGAMP) synthase (cGAS) in induction of IFN-I transcription. While other and our previous studies have shown that IFI16 enhanced retinoic acid-inducible gene I (RIG-I)-, which was an RNA sensor, and mitochondrial antiviral signaling (MAVS)-, which was the adaptor protein of RIG-I, induced production of IFN-I, so we wonder whether IFI16 regulates the signal pathway of RNA-RIG-I-MAVS-IFN-I in a STING-dependent manner. We used HEK 293T cells, which did not express endogenous STING and were unable to mount an innate immune response upon DNA transfection and found that IFI16 could enhance RIG-I- and MAVS-mediated induction of IFN-I in a STING-independent way. Furthermore, we found that upregulation of the expression of NF-kappa-B essential modulator (NEMO) by IFI16 was not the mechanism that IFI16 regulated the induction of IFN-I. In conclusion, we found that IFI16 regulated the signal pathway of RNA-RIG-I-MAVS-IFN-I in a STING-independent manner.

Anatomical and Functional Discrepancy in Diabetic Patients With Intermediate Coronary Lesions　- An Intravascular Ultrasound and Quantitative Flow Ratio Study.

BACKGROUND: Data regarding the performance of computational fractional flow reserve in patients with diabetes mellitus (DM) remain scarce. This study sought to explore the impact of DM on quantitative flow ratio (QFR) and its association with intravascular ultrasound (IVUS)-derived anatomical references.Methods and Results: IVUS and QFR were retrospectively analyzed in 237 non-diabetic and 93 diabetic patients with 250 and 102 intermediate lesions, respectively. Diabetics were further categorized based on adequate (HbA1c <7.0%: 47 patients with 53 lesions) or poor (HbA1c ≥7.0%: 46 patients with 49 lesions) glycemic control. Lesions with QFR ≤0.8 or minimum lumen area (MLA) ≤4.0 mm2and plaque burden (PB, %) ≥70 were considered functionally or anatomically significant, respectively. PB increased, and MLA decreased stepwise across non-diabetics, diabetics with adequate glycemic control and those with poor glycemic control. In contrast, QFR was similar among the 3 groups. PB correlated significantly with the QFR for lesions in non-diabetics, but not for lesions in diabetics. DM was independently correlated with the functionally non-significant lesions (QFR >0.8) with high-risk IVUS features (MLA ≤4.0 mm2and PB ≥70; OR 2.053, 95% CI: 1.137-3.707, P=0.017). When considering the effect of glycemic control, HbA1c was an independent predictor of anatomical-functional discordance (OR 1.347, 95% CI: 1.089-1.667, P=0.006). CONCLUSIONS: Anatomical-functional discordance of intermediate coronary lesions assessed by IVUS and QFR is exacerbated in patients with diabetes, especially when glycemia is poorly controlled.

Novel strategy for reusing agricultural mulch film residual by iron modification for arsenic removal in gold-smelting wastewater.

In gold-smelting wastewater after the original treatment process of flocculation and precipitation using mainly lime, a mixture of As, Cu, Pb, Mn, Zn, Al, Ni, and Fe existed with an arsenic concentration of 813.07 mg/L and other ions' concentration at ug/L levels. In this work, a new clean process of mainly adsorption with self-made adsorbent Fe-PE, which was synthesized by loading ferric lignin on agricultural mulch film residual, was investigated to purify and remove arsenic from gold-smelting wastewater. A batch of column experiments was investigated to explore the reaction behavior between wastewater and adsorbent Fe-PE. The results showed while operating the adsorption columns at a pilot scale for 68 days, the arsenic concentration in the effluent was below 0.5 mg/L, and there was no significant change in the concentration of co-existing metal ions, indicating that Fe-PE had a good selective adsorption performance for arsenic in wastewater. Furthermore, Fe-PE did not dissolve and release Fe ions in wastewater, and the whole process could not produce sludge. This work first suggested an efficient and potential application for the purification and removal of arsenic from gold-smelting wastewater with agricultural mulch film residual after chemical modification, which will provide a novel strategy for reusing the agricultural mulch film residual.

Loading ferric lignin on polyethylene film and its influence on arsenic-polluted soil and growth of romaine lettuce plant.

This work developed a composite (Pe-FeLs) which loaded ferric lignin on polyethylene film (PE film) by chemical modification and physico-chemically characterized by Microscope, FESEM with elemental mapping analysis, and XRD. Microscope pictures showed that chemical modification did not destroy the appearance of PE film. The FESEM images of Pe-FeLs showed the well-distributed clusters could be clearly seen and most of the particles were spherical morphology. Elemental mapping of individual element on Pe-FeLs clearly indicated the existing of iron. The XRD pattern showed the amorphous hydroxides of iron on Pe-FeLs. In arsenic solution, the total arsenic adsorption capacity of Pe-FeLs was much higher than that of ferric lignin and PE, which showed Pe-FeLs had the ability to adsorb arsenic. For making Pe-FeLs work well in the soil, a Pe-FeLs system was set up with plastic grid plate, PE film with holes, Pe-FeLs, PE film, and plastic grid plate from the upper to bottom in order. With applying Pe-FeLs system under the soil, arsenic was significantly reduced by 25.5 ~ 53.4% in heavily, moderately, and lower arsenic-polluted soils, the biomass of the romaine lettuce increased and arsenic accumulation in the romaine lettuce decreased.

Minimally invasive direct coronary artery bypass after percutaneous coronary intervention.

OBJECTIVES: Minimally invasive direct coronary artery bypass (MIDCAB) with the left internal thoracic artery (LITA) provides excellent long-term results for isolated left anterior descending coronary artery (LAD) disease. We tried to evaluate the impact of the previous percutaneous coronary intervention (p-PCI) for LAD on the clinical outcomes of MIDCAB in this study. METHODS: A total of 197 patients with isolated LAD disease underwent MIDCAB in our center from February 2009 to May 2020. 51 patients had the p-PCI for LAD and 146 patients did not. The primary outcome was the major adverse cardiovascular event (MACE). RESULTS: The incidences of the perioperative outcomes were comparable between the two groups (p > .05). The median follow-up time was 48.0 months (interquartile range, 25.9-85.5 months). The incidences of MACE (p < .001) and myocardial infarction or recurrent angina (p < .001) were significantly higher in the p-PCI group than those in the non-PCI group. The estimated 5-year freedom from MACE in the p-PCI group was significantly lower (56.1%, 95% confidence interval [CI]: 41.2%-71.0% vs. 83.4%, 95% CI: 76.7%-90.1%, p < .001). The previous LAD-PCI (hazard ratio [HR]: 2.664, 95% CI: 1.471-4.822, p = .001) and the history of peripheral arterial disease (HR: 3.145, 95% CI: 1.085-9.113, p = .035) were the independent predictors of MACE. The p-PCI group had a higher diseased graft rate than the non-PCI group (10.9% vs. 2.3%, p = .046). CONCLUSIONS: The previous LAD-PCI may deteriorate the outcomes of MIDCAB in patients with isolated LAD disease.

miR-541-3p Promoted Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) Replication by Targeting Interferon Regulatory Factor 7.

Porcine reproductive and respiratory syndrome (PRRS) is a disease caused by PRRS virus (PRRSV), which seriously harms the pig industry. Revealing the mechanism by which PRRSV inhibits immune response will help prevent and control PRRS. Here, we found that PRRSV-2 may hijack host miR-541-3p to inhibit host innate immune response. Firstly, this work showed that miR-541-3p mimics could facilitate the replication of PRRSV-2 and the results of the quantitative real time polymerase chain reaction (qRT-PCR) showed that PRRSV-2 could up-regulate the expression of miR-541-3p in MARC-145 cells. Since previous studies have shown that type I interferon could effectively inhibit the replication of PRRSV-2, the present work explored whether miR-541-3p regulated the expression of type I interferon and found that miR-541-3p could negatively regulate the transcription of type I interferon by targeting interferon regulatory factor 7 (IRF7). More importantly, PRRSV-2 infection could down-regulate the expression of IRF7 and over-expression of IRF7 could down-regulate the replication of PRRSV-2 in MARC-145 cells. In conclusion, PRRSV-2 infection up-regulated the expression of miR-541-3p to promote its replication in MARC-145 cells, since miR-541-3p can negatively regulate the transcription of type I interferon by targeting IRF7.

The expression of myeloperoxidase in thrombi is associated with reduced heme oxygenase-1 induction and worse left ventricular remodeling in patients with acute ST-elevation myocardial infarction.

BACKGROUND: Myeloperoxidase (MPO) secreted by neutrophils is the enzyme that kills bacteria and other pathogens. Acute myocardial infarction (AMI) is usually caused by thrombosis in response to vulnerable plaque rupture. Circulating MPO was found to be associated with increased mortality in AMI patients. However, the relationship between MPO in thrombi and the prognosis of AMI patients remains unknown. HYPOTHESIS: MPO expression in thrombi is associated with the prognosis of patients who underwent primary percutaneous coronary intervention (PCI) after AMI. METHODS: This study included 41 consecutive patients with acute ST-elevation myocardial infarction, who successfully underwent primary PCI, during which we collected thrombi remaining in the culprit artery using aspiration catheters. These thrombus samples were fixed, and immunohistochemical staining against MPO and heme oxygenase-1 (HO-1) was conducted. Enrolled patients were divided into two groups based on the induction of thrombotic MPO, which was quantified using Image J software. METHODS: We observed that increased MPO was associated with lower left ventricular ejection fraction (LVEF) and worse LV remodeling in AMI patients. Instead, patients with decreased thrombotic MPO induction had a considerable improvement in LVEF 1 month after discharge (54.4 ± 2.0% vs. 61.1 ± 2.3%, p < 0.01). In the MPO group, a reduction in the thrombotic HO-1 level contributed to the development of adverse LV remodeling. Logistic regression showed that MPO was a considerable risk factor for adverse LV remodeling (adjusted OR 3.70, p < 0.05). CONCLUSION: MPO expression in thrombi is associated with reduced LVEF and deteriorated LV remodeling in AMI patients, which may be due to HO-1 suppression in thrombi.

miR-382-5p promotes porcine reproductive and respiratory syndrome virus (PRRSV) replication by negatively regulating the induction of type I interferon.

Previous studies have indicated that inhibition of type I interferon production may be an important reason for porcine reproductive and respiratory syndrome virus (PRRSV) to achieve immune escape, revealing the mechanism of inhibiting the production of type I interferon will help design novel strategies for controlling PRRS. Here, we found that PRRSV infection upregulated the expression of miR-382-5p, which in turn inhibited polyI:C-induced the production of type I interferon by targeting heat shock protein 60 (HSP60), thus facilitating PRRSV replication in MARC-145 cells. Furthermore, we found that HSP60 could interact with mitochondrial antiviral signaling protein (MAVS), an important signal transduction protein for inducing production of type I interferon, and promote polyI:C-mediated the production of type I interferon in a MAVS-dependent manner. Finally, we also found that HSP60 could inhibit PRRSV replication in a MAVS-dependent manner, which indicated that HSP60 was a novel antiviral protein against PRRSV replication. In conclusion, the study demonstrated that miR-382-5p was upregulated during PRRSV infection and may promote PRRSV replication by negatively regulating the production of type I interferon, which also indicated that miR-382-5p and HSP60 might be the potential therapeutic targets for anti-PRRSV.

Identification of a linear B-cell epitope on glycoprotein (GP) 2a of porcine reproductive and respiratory syndrome virus (PRRSV).

Glycoprotein (GP) 2a was a minor structural protein of porcine reproductive and respiratory syndrome virus (PRRSV) and was one of crucial proteins for PRRSV to bind cell receptor, which indicated that there were neutralizing epitopes on GP2a. In the present work, we used mouse anti-GP2a41-208aa serum and one GP2a41-208aa specific monoclonal antibody (McAb) to identify B-cell epitopes of GP2a by peptide-based ELISA. A liner B-cell epitope F194PTPGSRPKLHDFQQ208 was identified. However, the results of virus neutralization experiment showed that the McAb could not reduce the titers of PRRSV, which indicated that the identified epitope was not the neutralizing epitope of PRRSV. While the amino acid sequence of this epitope was conserved in North American (type 2) PRRSV, which suggested that this epitope might be diagnostic potential for type 2 PRRSV strains. In conclusion, our present work identified a new epitope on GP2a and this epitope might be diagnostic potential for type 2 PRRSV strains.

IFI16 Inhibits Porcine Reproductive and Respiratory Syndrome Virus 2 Replication in a MAVS-Dependent Manner in MARC-145 Cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded positive-sense RNA virus, and the current strategies for controlling PRRSV are limited. Interferon gamma-inducible protein 16 (IFI16) has been reported to have a broader role in the regulation of the type I interferons (IFNs) response to RNA and DNA viruses. However, the function of IFI16 in PRRSV infection is unclear. Here, we revealed that IFI16 acts as a novel antiviral protein against PRRSV-2. IFI16 could be induced by interferon-beta (IFN-ß). Overexpression of IFI16 could significantly suppress PRRSV-2 replication, and silencing the expression of endogenous IFI16 by small interfering RNAs led to the promotion of PRRSV-2 replication in MARC-145 cells. Additionally, IFI16 could promote mitochondrial antiviral signaling protein (MAVS)-mediated production of type I interferon and interact with MAVS. More importantly, IFI16 exerted anti-PRRSV effects in a MAVS-dependent manner. In conclusion, our data demonstrated that IFI16 has an inhibitory effect on PRRSV-2, and these findings contribute to understanding the role of cellular proteins in regulating PRRSV replication and may have implications for the future antiviral strategies.

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction.

MicroRNAs (miRNAs) play an important role in the regulation of immune responses. Previous studies have indicated that dysregulating the miRNAs leads to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it is not clear how PRRSV regulates the expression of host miRNA, which may lead to immune escape or promote the replication of the virus. The present work suggests that PRRSV upregulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells. Furthermore, this work demonstrated that miR-373 promoted the replication of PRRSV, since miR-373 was a novel negative miRNA for the production of beta interferon (IFN-ß) by targeting nuclear factor IA (NFIA), NFIB, interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1 (IRF1). We also found that both NFIA and NFIB were novel proteins for inducing the production of IFN-ß, and both of them could inhibit the replication of PRRSV. In conclusion, PRRSV upregulated the expression of miR-373 by elevating the expression of Sp1 and hijacked the host miR-373 to promote the replication of PRRSV by negatively regulating the production of IFN-ß. IMPORTANCE: PRRSV causes one of the most economically devastating diseases of swine, and there is no effective method for controlling PRRSV. It is not clear how PRRSV inhibits the host's immune response and induces persistent infection. Previous studies have shown that PRRSV inhibited the production of type I IFN, and the treatment of type I IFN could efficiently inhibit the replication of PRRSV, so it will be helpful to design new methods of controlling PRRSV by understanding the molecular mechanism by which PRRSV modulated the production of IFN. The current work shows that miR-373, upregulated by PRRSV, promotes PRRSV replication, since miR-373 impaired the production of IFN-ß by targeting NFIA, NFIB, IRAK1, IRAK4, and IRF1, and both NFIA and NFIB were antiviral proteins to PRRSV. In conclusion, this paper revealed a novel mechanism of PRRSV that impaired the production of type I IFN by upregulating miR-373 expression in MARC-145 cells.

Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) promotes PRRSV infection in MARC-145 cells.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) induces one of most important devastating disease of swine worldwide, and the current methods poorly control it. Previous studies have indicated that the nonstructural protein 11 (nsp11) of PRRSV may be an important protein for the immune escape of PRRSV. RESULTS: Here, we firstly explored the effect of over-expression of nsp11 on PRRSV infection and found that over-expression of nsp11 enhanced the PRRSV titers while the small interfering RNA (siRNAs) specifically targeting nsp11 could reduce the PRRSV titers in MARC-145 cells. CONCLUSION: In conclusion, PRRSV nsp11 promotes PRRSV infection in MARC-145 cells and siRNAs targeting nsp11 may be a potential therapeutic strategy to control PRRSV in future.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host's immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process.

The Endoribonuclease Activity Essential for the Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus to Inhibit NLRP3 Inflammasome-Mediated IL-1ß Induction.

NLRP3 inflammasome, which is multiprotein complex that induces the maturity and secretion of proinflammatory interleukin-1ß (IL-1ß), takes a bridge between the innate and adaptive immune responses to the invading pathogens. It has been shown that porcine reproductive and respiratory syndrome virus (PRRSV) could activate the NLRP3 inflammasome but induce the host's immunosuppression. This study aims to explore whether PRRSV could encode the component to antagonize the NLRP3 inflammasome. The obtained results showed that PRRSV could induce the expression and secretion of IL-1ß in early infection through the pathway of NLRP3 inflammasome in porcine alveolar macrophages (PAMs), but the levels of pro-IL-1ß mRNA and IL-1ß protein decreased to a degree that was similar to the level of the mock-infected group in later infection. This work also found that PRRSV nonstructural protein (nsp) 11 could inhibit the expression of pro-IL-1ß mRNA induced by lipopolysaccharide (LPS) and the secretion of IL-1ß induced by LPS plus nigericin in PAMs. Furthermore, the mutation studies showed that the endoribonuclease activity was essential for nsp11 to inhibit the secretion of IL-1ß. Therefore, it could be indicated that PRRSV could induce the activation of NLRP3 inflammasome, but the virus encoded nsp11 to inhibit this action.

Small interfering RNA targeting nonstructural protein1 α (nsp1α) of porcine reproductive and respiratory syndrome virus (PRRSV) can reduce the replication of PRRSV in MARC-145 cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically devastating and pandemic diseases of swine, which is poorly controlled by current methods. The inhibition of specific genes by small interfering RNA (siRNA) has been proven to be a potential therapeutic strategy against viral infection. Previous studies have indicated that the nonstructural protein 1α (nsp1α) of PRRSV may take an important role in virulence of PRRSV. The present work was involved to explore the effect of siRNA targeting nsp1α on the replication of PRRSV in MARC-145 cells, and the results showed that over-expression of nsp1α enhanced the replication of PRRSV and that siRNAs specifically targeting nsp1α significantly inhibited the replication of PRRSV in MARC-145 cells. In conclusion, this work indicated that nsp1α may be a viral pathogenicity factor of PRRSV and that siRNAs specifically targeting nsp1α may be a new strategy to control PRRSV in the future.

Antibody-dependent enhancement of PRRSV infection down-modulates TNF-α and IFN-ß transcription in macrophages.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease, resulting in important economic losses in pig farming. Previous studies have shown that Fcγ receptor (FcγR)-mediated entry of infectious PRRSV immune complexes into macrophages plays a pivotal role in the pathogenesis of the disease. This study demonstrates that PRRSV was able to suppress the transcription of key antiviral genes tumor necrosis factor-α (TNF-α) and interferon-ß (IFN-ß), when infection was via the ADE pathway. Investigation of this infection pathway found that PRRSV suppresses the antiviral genes by disrupting the transcription of the genes coding for the associated transcription factors interferon regulatory factor-1 (IRF-1), interferon regulatory factor-3 (IRF-3) and nuclear factor kappa B (NF-κB). The ADE pathway of infection allows PRRSV to specifically target antiviral genes and alters the innate intracellular immune responses in macrophages. The ADE mechanism described in this study furthers our understanding of pathogenesis following PRRSV infection and is of general relevance to virally induced disease and in relation to antiviral vaccination strategies.

The zinc-finger domain was essential for porcine reproductive and respiratory syndrome virus nonstructural protein-1α to inhibit the production of interferon-ß.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused one of the most economically devastating and pandemic diseases of swine. Previous studies have documented that PRRSV nonstructural protein-1α (nsp1α) was an interferon antagonist, but the mechanism by which nsp1α inhibited the interferon (IFN)-ß production was unclear. Here, by site-directed mutagenesis of the predicted zinc-coordinating residues of the zinc-finger (ZF) domain of nsp1α or by deletion of the ZF domain of nsp1α, we explored whether the ZF domain was required for nsp1α to disrupt the IFN-ß production. The results showed that both mutagenesis of the predicted zinc-coordinating residues of the ZF domain and deletion of the ZF domain made nsp1α lose its interferon antagonism activity. In conclusion, our present work indicated that the ZF domain of nsp1α was necessary for nsp1α to inhibit the IFN-ß induction.

Amino acid at position 176 was essential for porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein 1α (nsp1α) as an inhibitor to the induction of IFN-ß.

Previous studies have shown that porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1α (nsp1α) was the interferon (IFN) antagonist. However, the mechanism was unclear. In the present study, deletion of the carboxyl-terminal extension (CTE) (167-180 amino acid (aa)) made nsp1α lose its inhibitory ability to the induction of IFN-ß. And a series of C-terminal truncated mutants for nsp1α showed that 1-176 aa of nsp1α was able to inhibit the induction of IFN-ß and deleting or mutating the amino acid F176 made nsp1α not inhibit the induction of IFN-ß. In conclusion, the CTE and the amino acid F176 were critical for nsp1α as the IFN antagonist and the region representing 167-176 was the minimal subunit of the CTE for nsp1α to retain its suppressive activity to the induction of IFN-ß.

Development of an immunochromatographic strip for rapid detection of antibodies against classical swine fever virus.

The genes encoding the Erns and E2 antigen epitopes of classical swine fever virus (CSFV) were expressed as a chimeric protein in Escherichia coli BL21 by pET expression system. The antigenicity of the expressed protein CnC2 was identified by indirect enzyme-linked immunoabsorbant assay (ELISA) and immunoblot with anti-CSFV antibodies. Based on the CnC2 protein, an immunochromatographic strip was developed to evaluate the antibody titer of serum samples from swine vaccinated with CSFV vaccine rapidly. The chimeric protein used as a detector was labeled with colloidal gold. Staphylococcal protein A (SPA) and anti-CnC2 monoclonal antibodies (mAbs) were blotted onto the nitrocellulose membrane as the test and control lines, respectively. The strip assay could be performed within 5min, which did not require any special equipment or skills. Through testing sera against various strains of CSFV, the sensitivity of the strip was determined to be 97.0% (65/67) and the specificity was 100% (98/98). The strip results were consistent with those of the existing commercial ELISA kit, and their correlation coefficient was 0.935. In conclusion, the immunochromatographic strip was an acceptable method for surveying CSFV-antibody titers in pigs.

Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy.