Recurrence of Local Kyphosis After Percutaneous Kyphoplasty: The Neglected Injury of the Disc-Endplate Complex.

Background: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures. Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors. Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81±8.60° postoperatively to 25.13±8.91° at the final follow-up which showed a statistically significant difference (p<0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p<0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc-endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p<0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis. Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc-endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.

In vitro and in vivo evaluation of a modified porcine acellular dermal matrix for soft tissue augmentation.

OBJECTIVES: To evaluate the effects of a modified porcine acellular dermal matrix (P-ADM), subepithelial connective tissue graft (SCTG) and other commercial bovine acellular dermal matrix membrane materials (B-ADM) on gingival soft tissue augmentation in the oral esthetic zone. MATERIAL AND METHODS: The characteristics of P-ADM were observed by scanning electron microscope (SEM), Hematoxylin and eosin (H&E) and Masson's trichrome staining (Masson staining). The biocompatibility of P-ADM was verified by CCK8, phalloidin and living/dead cell staining. Beagle dog models were constructed and the thickness of gingiva was analyzed by the intraoral scanner. The morphology was observed by H&E and Masson staining. RESULTS: Scanning electron microscopy, H&E and Masson staining showed that the P-ADM was mainly composed of collagen fibers, with no component of nuclear. The results of CCK8, phalloidin and living/dead cell staining indicated that the P-ADM had good cytocompatibility and no cytotoxicity. Human gingival fibroblasts were able to adhere and stretch on the surface of the material with pseudopodia. The SCTG group outperformed the B-ADM and P-ADM groups in terms of effectiveness, according to the analysis of digital oral scanning data at various time points following incremental soft tissue surgery. Compared with the B-ADM group, the effect of soft tissue increment was better in the P-ADM group. CONCLUSIONS: P-ADM, as a biocompatible biomaterial, can be used as an alternative biomaterial for oral soft tissue thickening. However, the results of this study need to be verified by more clinical trials.

In vitro and in vivo evaluation of antiviral activity of a phenylpropanoid derivative against spring viraemia of carp virus.

Phenylpropanoids, common natural compounds, possess many different biological activities such as antioxidant, anti-inflammatory and antiviral. Spring viraemia of carp virus (SVCV) can cause a high mortality in common carp (Cyprinus carpio). However, there are currently no licenced drugs that effectively cure this disease. In this study, we designed and synthesized a phenylpropanoid derivative 4-(4-methoxyphenyl)-3,4-dihydro-2H-chromeno[4,3-d]pyrimidine-2,5(1 H)-dione (E2), and explored the antiviral effect against SVCV in vitro and in vivo. Up to 25 mg/L of E2 significantly inhibited the expression levels of SVCV protein genes in the epithelioma papulosum cyprini (EPC) cell line by a maximum inhibitory rate of >90%. As expected, E2 remarkably declined the apoptotic of SVCV-infected cells and suppressed potential enhancement of the mitochondrial membrane potential (ΔΨm), these data implied that E2 could protect mitochondria from structural damage in response to SVCV. Meanwhile, E2 was added to EPC cells under four different conditions: time-of-addition, time-of-removal, pre-treatment of viruses and pre-treatment of cells indicated that E2 may block the post-entry transport process of the virus. Additionally, the up-regulation of six interferon (IFN)-related genes also demonstrated that E2 indirectly activated IFNs for the clearance of SVCV in common carp. Drug cure effect showed that treatment with E2 at 0.5 d post infection (dpi) is more effective than at 0, 1 or 2 dpi. Most importantly, intraperitoneal therapy of E2 markedly improved common carp survival rate and reduced virus copies in body. Therefore, the E2 has potential to be developed into a novel anti-SVCV agent.

Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo.

Spring viremia of carp virus (SVCV) causes devastating losses in aquaculture. Coumarin has an advantageous structure for the design of novel antiviral agents with high affinity and specificity. In this study, we evaluated a hydroxycoumarin medicine, i.e., 7-(6-benzimidazole) coumarin (C10), regarding its anti-SVCV effects in vitro and in vivo. Results showed that up to 12.5 mg/L C10 significantly inhibited SVCV replication in the epithelioma papulosum cyprini (EPC) cell line, with a maximum inhibitory rate of >97%. Furthermore, C10 significantly reduced cell death and relieved cellular morphological damage in SVCV-infected cells. Decreased mitochondrial membrane potential (ΔΨm) also suggested that C10 not only protected mitochondria, but also reduced apoptosis in SVCV-infected cells. For in vivo studies, intraperitoneal injection of C10 resulted in an anti-SVCV effect and substantially enhanced the survival rate of virus-infected zebrafish. Furthermore, C10 significantly enhanced antioxidant enzyme activities and decreased reactive oxygen species (ROS) to maintain antioxidant-oxidant balance within the host, thereby contributing to inhibition of SVCV replication. The up-regulation of six interferon (IFN)-related genes also demonstrated that C10 indirectly activated IFNs for the clearance of SVCV in zebrafish. This was beneficial for the continuous maintenance of antiviral effects because of the low viral loads in fish. Thus, C10 is suggested as a therapeutic agent with great potential against SVCV infection in aquaculture.

Inhibition of a novel coumarin on an aquatic rhabdovirus by targeting the early stage of viral infection demonstrates potential application in aquaculture.

Spring viremia of carp virus (SVCV) is one of the most serious pathogens in aquaculture, resulting in devastating damage in cyprinid. In this study, we designed and synthesized a novel coumarin derivative (C3007) for evaluating its in vitro and in vivo anti-SVCV effects. Here, we determined that up to 25 mg/L C3007 significantly decreased SVCV protein gene expression levels in EPC cells by a maximum inhibitory rate of >95%. When C3007 was preincubated with SVCV, infectivity was significantly inhibited in vitro in a time-dependent manner, with complete inhibition at 25 mg/L. For in vivo studies, C3007 exhibited an anti-SVCV effect by substantially enhancing the survival rate of virus-infected fish via intraperitoneal injection. Although the horizontal transmission of SVCV was hindered by C3007 in a static cohabitation challenge model, it was not completely blocked, showing that the viral loads in recipient fish were obviously reduced. Thus, C3007 could potentially be used as a therapeutic agent with great potential in aquatic systems and may also be suitable for applications in pond aquaculture settings against viral transmission. Additionally, the C3007-preincubated virus induced an antiviral immune response with high levels of IFN expression, suggesting that C3007 pre-treatment could be used in vaccine development.

PMA-triggered PKCε activity enhances Nrf2-mediated antiviral response on fish rhabdovirus infection.

Viral infection is often accompanied with alteration of intracellular redox state, especially an imbalance between reactive oxygen species (ROS) production and antioxidant cellular defenses. The previous studies showed that an antioxidant cellular defense system, the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), played an important role against spring viraemia of carp virus (SVCV) infection in fish. To further reveal the mediated mechanism that Nrf2 active state was affected by protein kinase C (PKC), here we evaluated SVCV replication in host cells by treated with a strong activator of PKC phorbol-12-myristate-13-acetate (PMA) and an inhibitor staurosporine. Our results showed that PMA significantly repressed SVCV replication and viral-induced apoptosis in Epithelioma papulosum cyprini (EPC) cell, suggesting that PKC may exhibit an anti-SVCV effect. Likewise, PMA resulted in a higher phosphorylation levels of PKCε rather than PKCα/ß to participate in the activation of Nrf2, mainly involved in the activation of Nrf2 phosphorylation of Ser40 to favor Nrf2 translocation to nucleus. Furthermore, the data revealed that PMA up-regulated an antiviral response heme oxygenase-1 (HO1) gene expression that was confirmed as the key player against SVCV infection by HO1 specific siRNA. Overall, this study provided a new therapeutic target for the treatment of SVCV infection, and modulating PKC activity could be used for the prevention and treatment of SVCV.

Protein biochip-based semiquantitative detection for plasma leptin.

PURPOSE: Plasma leptin is secreted from adipose tissues and plays pivotal roles in human physiological and pathological processes. Here, we aimed at conducting a protein biochip-based sandwich-like approach for detection of plasma leptin among healthy individuals, obesity, and diabetes patients. EXPERIMENTAL DESIGN: Totally, 96 plasma samples, including 45 healthy individuals with standard body mass index (BMI), 28 obesity and 23 diabetes patients, were recruited in the study. Plasma leptin was detected by a well-established protein biochip. Meanwhile an ELISA was also performed for assessment of the leptin detection by the protein biochip. RESULTS: We found that the plasma leptin level in the obesity and diabetes patients was significantly higher than that in healthy individuals with standard body mass index (p < 0.001). The limit detection concentration of leptin was as low as 0.006 µg/mL. The plasma leptin could be semiquantitatively detected by the protein biochip. The compatibility of the biochip-based detection approach seemed acceptable in comparison with the ELISA assay (R2 = 0.948). CONCLUSIONS: We provided a protein biochip-based approach for plasma detection. This approach would be a potential substitution for the ELISA assay.

Polymorphisms in the CHIT1 gene: Associations with colorectal cancer.

Colorectal cancer (CRC) is one of the most common solid tumors worldwide, often associated with inflammation. The microbes in the human intestine have a key role in inflammations and CRC. Chitotriose renders growth advantage to some bacteria, especially some pathogens, and thus has a role in inflammations. The enzyme chitotriosidase, encoded by the CHIT1 gene of the host, may degrade chitotriose with different efficiencies depending on the alleles. We sequenced the CHIT1 gene for 320 Chinese Han CRC patients and 404 normal controls, and focused on variations rs61745299 and rs35920428 within the CHIT1 gene for their possible roles in CRC. Statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). Multiple sequence alignment was conducted using the Vector NTI, and protein expression levels were analyzed by western blotting. The two variations, rs61745299 and rs35920428 within the CDS region of CHIT1 gene, were associated with the risk of CRC (both with P values < 0.001). Western blotting analysis showed that the variations increased the expression levels of the CHIT1 and C-reaction protein genes in the cancer tissue. We conclude that the two variations of CHIT1, rs61745299 and rs35920428, increase expression of the gene and are associated with CRC in Chinese Han populations.