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1.
Zhongguo Gu Shang ; 33(6): 566-71, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32573165

RESUMO

OBJECTIVE: To investigate the therapeutic effects of vacuum sealing drainage (VSD) combined with antibiotics in treating acute periprosthetic joint infection (PJI). METHODS: From March 2012 to December 2018, there were 11 patients with acute PJI underwent debridement, VSD, antibiotics and retention of implant, including 7 males and 4 females, with an average age of 72.5 years old (ranged, 58 to 88 years old). There were 8 hips and 3 knees. Three patients had sinus tract. RESULTS: There were 2 patients with negative culture result and 9 patients with positive culture result, including 5 cases of methicillin sensitive staphylococcus aureus, 2 cases of methicillin-resistant staphylococcus aureus (MRSA), 2 cases of staphylococcus epidermidis. The mean follow up duration was 28 months (ranged from 8 to 52 months). One case of infection around hip prosthesis failed to be debrided. The time of debridement and replacement of the calcar joint was 84 days. Debridement was successful in 10 cases. At the latest follow up, Harris score of patients with successful debridement of hip periprosthetic infection ranged from 74 to 93, with an average score of 84.1;Knee Society scores of patients with periprosthetic infection were 84, 84, 89. CONCLUSION: For acute infection around the prosthesis within 1 month after knee replacement and 6 weeks after hip replacement, and for bleeding around the prosthesis with acute infection caused by anticoagulant drugs, satisfactory results can be obtained by debridement, VSD and sensitive antibiotics.

2.
Biomed Environ Sci ; 33(5): 350-358, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32553079

RESUMO

Objective: Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. Methods: A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion: MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.

3.
Brain Behav ; : e01720, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32558355

RESUMO

BACKGROUND: Visual deprivation can lead to abnormal and plastic changes in the brain's visual system and other systems. Although the secondary changes of gray matter in patients have been well studied, the study of white matter is rare. In fact, subtle changes in white matter may be revealed by diffusion tensor imaging, and tract-based spatial statistics can be used to analyze DTI image data. PURPOSE: In the present study, diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) were used to investigate abnormal structural changes in the white matter (WM) of patients with monocular blindness (MB). METHODS: We recruited 16 healthy controls (HC) (fourteen males and two females) and 16 patients (fifteen males and one female) with right-eye blindness (without differences in left-eye vision). All patients were of similar age. Data acquisition was performed using magnetic resonance imaging (MRI) and DTI. Voxel-based whole brain comparisons of fractional anisotropy (FA) and radial diffusivity (RD) of WM fibers in patients and HC were performed using the TBSS method. The mean FA and RD values for altered brain regions in MB patients were analyzed via the receiver operating characteristic (ROC) curve. Correlation analysis was performed to investigate the relationships between the average FA (RD) value of the whole brain and anxiety score, depression score, and visual function questionnaire score in MB patients. RESULTS: In MB patients, the mean FA of the whole brain was decreased versus HC. Moreover, the FA values of the corpus callosum, the corona radiata, the posterior thalamic radiation, and the right retrolenticular part of internal capsule were significantly decreased. In addition, the average RD value of the whole brain in MB patients was higher than that observed in HC. The mean FA and RD values of brain regions were analyzed using the ROC curve, and the results showed that the area under the ROC curve was more accurate. Furthermore, the average FA and RD values of the whole brain were significantly correlated with anxiety score, depression score, and visual function-related quality of life score. CONCLUSION: DTI and TBSS may be useful in examining abnormal spontaneous alterations in the WM of MB patients. The observed changes in FA and RD values may imply the larvaceous neurological mechanism involved in MB.

4.
mSphere ; 5(3)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493723

RESUMO

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the Aedes species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the presence of bone lesions and erosive arthritis in the joints of CHIKV-infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow-derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs leads to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. For the first time to our knowledge, we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed decreased gene expression of the major regulator of osteogenic differentiation, RUNX2, in CHIKV-infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells, i.e., decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization, were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs, indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection.IMPORTANCE Presently, no vaccines or treatment options are available for CHIKV infection. Joint pain is one of the major concerns. Although studies have shown an association between bone pathology and infection, the molecular pathogenesis in the context of bone pathology is poorly defined. Here, we demonstrate for the first time that BMSCs and BMSC-derived osteogenic cells are susceptible to CHIKV infection, and that infection likely alters the function of osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.

5.
World J Gastroenterol ; 26(21): 2877-2888, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32550762

RESUMO

BACKGROUND: Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer. Neoadjuvant chemoradiotherapy (NCRT) can effectively reduce the postoperative recurrence rate; thus, NCRT with total mesorectal excision (TME) is the most widely accepted standard of care for rectal cancer. The addition of lateral lymph node dissection (LLND) after NCRT remains a controversial topic. AIM: To investigate the surgical outcomes of TME plus LLND, and the possible risk factors for lateral lymph node metastasis after NCRT. METHODS: This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018. In the NCRT group, TME plus LLND was performed in patients with short axis (SA) of the lateral lymph node greater than 5 mm. In the non-NCRT group, TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm. Data regarding patient demographics, clinical workup, surgical procedure, complications, and outcomes were collected. Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients. RESULTS: LLN metastasis was pathologically confirmed in 35 patients (39.3%): 26 (41.3%) in the NCRT group and 9 (34.6%) in the non-NCRT group. The most common site of metastasis was around the obturator nerve (21/35) followed by the internal iliac artery region (12/35). In the NCRT patients, 46% of patients with SA of LLN greater than 7 mm were positive. The postoperative 30-d mortality rate was 0%. Two (2.2%) patients suffered from lateral local recurrence in the 2-year follow up. Multivariate analysis showed that cT4 stage (odds ratio [OR] = 5.124, 95% confidence interval [CI]: 1.419-18.508; P = 0.013), poor differentiation type (OR = 4.014, 95%CI: 1.038-15.520; P = 0.044), and SA ≥ 7 mm (OR = 7.539, 95%CI: 1.487-38.214; P = 0.015) were statistically significant risk factors associated with LLN metastasis. CONCLUSION: NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter, poorer histological differentiation, or advanced T stage. Selective LLND for NCRT patients can have a favorable oncological outcome.

6.
Oncogene ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546724

RESUMO

Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) in colorectal cancer (CRC), which is evidenced from human CRC specimens, animal models, and cancer cell lines. TMA samples from randomly selected 60 CRC specimens firstly identified the clinical correlation between high SphK2 and increased DPD (p < 0.001). Then the regulatory mechanism was explored in CRC models of villin-SphK2 Tg mice, SphK2-/-mice, and human CRC cells xenografted nude mice. Assays of ChIP-Seq and luciferase reporter gene demonstrated that high SphK2 upregulated DPD through promoting the HDAC1-mediated H3K56ac, leading to the degradation of intracellular 5-FU into inactive α-fluoro-ß-alanine (FBAL). Lastly, inhibition of SphK2 by SLR080811 exhibited excellent inhibition on DPD expression and potently reversed 5-FU resistance in colorectal tumors of villin-SphK2 Tg mice. Overall, this study manifests that SphK2high conferred 5-FU resistance through upregulating tumoral DPD, which highlights the strategies of blocking SphK2 to overcome 5-FU resistance in CRC.

7.
Plant Cell ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32487564

RESUMO

The switch from dark- to light-mediated development is critical for the survival and growth of seedlings, but the underlying regulatory mechanisms are incomplete. Here, we show that the steroids phytohormone brassinosteroids play crucial roles during this developmental transition by regulating chlorophyll biosynthesis to promote greening of etiolated seedlings upon light exposure. Etiolated seedlings of the brassinosteroids-deficient det2-1 (de-etiolated2) mutant accumulated excess protochlorophyllide, resulting in photo-oxidative damage upon exposure to light. Conversely, the gain-of-function mutant bzr1-1D (brassinazole-resistant 1-1D) suppressed the protochlorophyllide accumulation of det2-1, thereby promoting greening of etiolated seedlings. Genetic analysis indicated that phytochrome-interacting factors (PIFs) were required for BZR1-mediated seedling greening. Furthermore, we reveal that GROWTH REGULATING FACTOR 7 (GRF7) and GRF8 are induced by BZR1 and PIF4 to repress chlorophyll biosynthesis and promote seedling greening. Suppression of GRFs function by overexpressing microRNA396a caused an accumulation of photochlorophyllide in the dark and severe photobleaching upon light exposure. Additionally, BZR1, PIF4 and GRF7 interact with each other and precisely regulate the expression of chlorophyll biosynthetic genes. Our findings reveal an essential role for BRs in promoting seedling development and survival during the initial emergence of seedlings from subterranean darkness into sunlight.

8.
Infect Dis Poverty ; 9(1): 65, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513262

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is on the rise in China. This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures. METHODS: Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100 000 people. The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis (DS-TB+) were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not. RESULTS: Without any intervention changes to current conditions, the prevalence of DS-TB+ was projected to decline 67.7% by 2050, decreasing to 20 per 100 000 people, whereas that of MDR-TB was expected to triple to 58/100 000. Furthermore, 86.2% of the MDR-TB cases would be left untreated by the year of 2050. In the case where MDR-TB detection rate reaches 50% or 70% at 5% per year, the decline in prevalence of MDR-TB would be 25.9 and 36.2% respectively. In the case where treatment coverage was improved to 70% or 100% at 5% per year, MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%, respectively. If both detection rate and treatment coverage reach 70%, the prevalence of MDR-TB by 2050 would be reduced to 28/100 000 by a 51.7% reduction. CONCLUSIONS: MDR-TB, especially untreated MDR-TB, would rise rapidly under China's current MDR-TB control strategies. Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.

10.
J Food Sci ; 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506566

RESUMO

As a kind of polymer material additive, phthalic acid esters (PAEs) are widely used in food industry. However, PAEs are environmental endocrine disruptors with reproductive toxicity and teratogenic carcinogenicity, which are difficult to be degraded in the natural environment. In this paper, gas chromatography-mass spectrometer (GC-MS) methods for PAEs in polyethylene wrap film were optimized. For diisobutyl phthalate (DIBP) and dibutyl phthalate (DBP) that were mainly detected, the method had a good linearity in 1 to 500 ng/g. Then, we confirmed that the migration of DIBP and DBP from polyethylene wrap film increased with time and temperature. It is found that the migration law in different food simulations well followed the migration dynamics first-level model. The rate constant K1 and initial release rate V0 are inversely proportional to the polarity of the simulated liquid. We hope that this study can serve as a valuable reference for further research on the migration of food packing materials. PRACTICAL APPLICATION: In this paper, we present a simple example of applying migration model to evaluate the migration behaviors of PAEs in food packaging materials along with their hazardous properties. It can serve as a valuable reference for further research on the migration of food packing materials.

11.
Tree Physiol ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32542375

RESUMO

Different root zones have distinct capacities for nitrate (NO3-) uptake in Populus species, but the underlying physiological and microRNA (miRNA) regulatory mechanisms remain largely unknown. To address this question, two root zones of P. × canescens with contrasting capacities for NO3- uptake were investigated. The region of 0 to 40 mm (root zone I) to the root apex displayed net influxes, whereas the region of 40 to 80 mm (root zone II) exhibited net effluxes. Concentrations of NO3- and ammonium (NH4+) as well as nitrate reductase (NR) activity were lower in zone II than in zone I. Forty one upregulated and twenty three downregulated miRNAs, and 576 targets of these miRNAs were identified in zone II in comparison with zone I. Particularly, growth-regulating factor 4 (GRF4), a target of upregulated ptc-miR396g-5p and ptc-miR396f_L + 1R-1, was downregulated in zone II in comparison with zone I, probably contributing to lower NO3- uptake rates and assimilation in zone II. Furthermore, several miRNAs and their targets, members of C2H2 zinc finger family and APETALA2/ethylene-responsive element binding protein family, were found in root zones, which probably play important roles in regulating NO3- uptake. These results indicate that differentially expressed miRNA-target pairs play key roles in regulation of distinct NO3- uptake rates and assimilation in different root zones of poplars.

12.
Cell Death Dis ; 11(5): 335, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382041

RESUMO

Most hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage; however, the effect of systemic therapy on advanced HCC remains undetermined. Therefore, new treatment targets must be identified. We analyzed Gene Expression Omnibus datasets from two HCC patient cohorts and found that NT5DC2 was associated with vascular invasion and poor survival. In two hepatoma cell lines, NT5DC2 overexpression promoted HCC cell proliferation and clone formation in vitro and promoted tumor growth in vivo. Coimmunoprecipitation assays and liquid chromatography with tandem mass spectrometry analysis revealed that NT5DC2 bound directly to epidermal growth factor receptor (EGFR). NT5DC2 upregulated EGFR expression by downregulating EGFR ubiquitination and preventing its degradation via the ubiquitin-proteasome pathway but did not upregulate its transcription. EGFR upregulation activated downstream signal transduction, which played a critical role in the protumor effects of NT5DC2. Erlotinib, a small-molecule inhibitor of EGFR, blocked the effect of NT5DC2 in promoting HCC cell proliferation. In a cohort of 79 patients who underwent curative resection for HCC, NT5DC2 expression in the tumors was associated with larger tumors and microvascular invasion. NT5DC2 expression was also independently associated with recurrence-free survival. The present study demonstrated for the first time that NT5DC2 promotes tumor cell proliferation in HCC and may serve as a potential molecular target for treating HCC. EGFR blockage could be used to treat selected patients with NT5DC2 upregulation.

13.
Int Immunopharmacol ; 85: 106632, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32470880

RESUMO

Isolating and purifying liver immune cells are crucial for observing the changes in intrahepatic immune responses during the development of liver diseases and exploring the potential immunological mechanisms. Therefore, the aim of this study was to provide an optimal protocol for isolating immune cells with a high yield and less damage. We compared mechanical dissection and collagenase digestion, and the results were represented by the proportion of lymphocytes, Kupffer cells and neutrophils. The apoptosis rates of liver immune cells resulted by different isolation protocols were compared by Annexin V-staining using flow cytometric analysis. Our data indicated that the enzymatic digestion in vitro was more efficient than the mechanical dissection in vitro with a suitable collagenase IV concentration of 0.01%, and the purification of liver immune cells by a one-step density gradient centrifugation in 33% Percoll had the definite advantage of a higher proportion of the target cells. We also provided evidence that enzymatic digestion in vitro method was superior to collagenase digestion in situ for liver T lymphocytes, NK cells and NKT cells isolation and purification. This protocol was also validated in human liver samples. In conclusion, we developed an optimal protocol for isolating and purifying immune cells from mouse and human liver samples in vitro by 0.01% collagenase IV and 33% Percoll density gradient centrifugation with the advantages of higher cell yields and viability. This method provides a basis for further studying liver immune cells and liver immunity with a wide range of applications.

14.
Dis Aquat Organ ; 139: 25-33, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32351234

RESUMO

The major antigenic protein of infectious hematopoietic necrosis virus (IHNV) is the surface glycoprotein G, which contains neutralizing epitopes that induce the production of immune neutralizing antibodies. In this study, the IHNV G gene sequence was truncated according to bioinformatics principles and then recombinantly expressed via an E. coli expression system. We then assessed the specific antibody immunoglobin M (IgM) levels of rainbow trout immunized with recombinant truncated G protein (emulsified with Freund's incomplete adjuvant), and showed that antibody IgM levels of immunized fish were significantly higher than in the control group (p < 0.01). The mRNA expression levels of interferon 1 (IFN1) and interleukin-8 (IL-8) were also up-regulated significantly (p < 0.01) in head kidneys and spleens of rainbow trout immunized with recombinant truncated G protein. Also, after challenge with wild-type IHNV HLJ-09 virus on Day 28, rainbow trout immunized with recombinant truncated G protein showed cumulative survival rates of 60%. These results indicate that the truncated G protein of IHNV expressed by the E. coli prokaryotic expression system can be used as a candidate immunogen for an IHNV subunit vaccine, which lays a theoretical foundation for the study of further potential IHNV subunit vaccines.

15.
QJM ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369592
16.
Oncol Rep ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32468018

RESUMO

TAZ (transcriptional coactivator with PDZ­binding motif), which is also known as WW domain­containing transcription regulator 1 (WWTR1), a downstream effector of the Hippo pathway, has been reported to regulate cancer cell proliferation, migration and apoptosis by acting as a transcriptional coactivator. However, the function of TAZ in prostate cancer cells has not been investigated. In the present study, TAZ expression in prostate cancer (PCa) and benign prostatic hyperplasia tissues, PCa cell lines, and normal prostate epithelial cells was determined with the use of immunohistochemistry. TAZ was knocked down by shRNA in the PC3 cells, a prostate cancer cell line, and cell viability and migration assays were performed to determine the biological functions of TAZ. A mouse subcutaneous xenograft model was used to determine the in vivo effects of TAZ knockdown on tumor growth. We demonstrated that TAZ is overexpressed in PCa tissues, and the expression levels were found to be positively correlated with the Gleason scores of cancer grade. Moreover, TAZ knockdown inhibited PC3 cell proliferation, reduced cell migration, and induced apoptosis. Further experiments demonstrated that TAZ knockdown may lead to PC3 cell apoptosis through the exogenous apoptotic pathway by inducing the expression and cleavage of caspase­4 and ­7. In the tumor xenograft model, TAZ knockdown led to a decreased tumor growth rate. Taken together, the experimental results indicate that TAZ plays a significant role in the proliferation, migration and apoptosis of prostate cancer cells. TAZ could be a useful biomarker for PCa diagnosis/prognosis, and it could be a potential target for the treatment of prostate cancers.

17.
Int J Mol Med ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32468069

RESUMO

Nav1.7 is closely associated with neuropathic pain. Hydrogen sulfide (H2S) has recently been reported to be involved in numerous biological functions, and it has been shown that H2S can enhance the sodium current density, and inhibiting the endogenous production of H2S mediated by cystathionine ß­synthetase (CBS) using O­(carboxymethyl)hydroxylamine hemihydrochloride (AOAA) can significantly reduce the expression of Nav1.7 and thus the sodium current density in rat dorsal root ganglion (DRG) neurons. In the present study, it was shown that the fluorescence intensity of H2S was increased in a spared nerve injury (SNI) model and AOAA inhibited this increase. Nav1.7 is expressed in DRG neurons, and the expression of CBS and Nav1.7 were increased in DRG neurons 7, 14 and 21 days post­operation. AOAA inhibited the increase in the expression of CBS, phosphorylated (p)­MEK1/2, p­ERK1/2 and Nav1.7 induced by SNI, and U0126 (a MEK blocker) was able to inhibit the increase in p­MEK1/2, p­ERK1/2 and Nav1.7 expression. However, PF­04856264 did not inhibit the increase in CBS, p­MEK1/2, p­ERK1/2 or Nav1.7 expression induced by SNI surgery. The current density of Nav1.7 was significantly increased in the SNI model and administration of AOAA and U0126 both significantly decreased the density. In addition, AOAA, U0126 and PF­04856264 inhibited the decrease in rheobase, and the increase in action potential induced by SNI in DRG neurons. There was no significant difference in thermal withdrawal latency among each group. However, the time the animals spent with their paw lifted increased significantly following SNI, and the time the animals spent with their paw lifted decreased significantly following the administration of AOAA, U0126 and PF­04856264. In conclusion, these data show that Nav1.7 expression in DRG neurons is upregulated by CBS­derived endogenous H2S in an SNI model, contributing to the maintenance of neuropathic pain.

18.
Science ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376603

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 µg or 6 µg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.

19.
Biofabrication ; 12(3): 035020, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32369796

RESUMO

Functional reconstruction of craniomaxillofacial defects is challenging, especially for the patients who suffer from traumatic injury, cranioplasty, and oncologic surgery. Three-dimensional (3D) printing/bioprinting technologies provide a promising tool to fabricate bone tissue engineering constructs with complex architectures and bioactive components. In this study, we implemented multi-material 3D printing to fabricate 3D printed PCL/hydrogel composite scaffolds loaded with dual bioactive small molecules (i.e. resveratrol and strontium ranelate). The incorporated small molecules are expected to target several types of bone cells. We systematically studied the scaffold morphologies and small molecule release profiles. We then investigated the effects of the released small molecules from the drug loaded scaffolds on the behavior and differentiation of mesenchymal stem cells (MSCs), monocyte-derived osteoclasts, and endothelial cells. The 3D printed scaffolds, with and without small molecules, were further implanted into a rat model with a critical-sized mandibular bone defect. We found that the bone scaffolds containing the dual small molecules had combinational advantages in enhancing angiogenesis and inhibiting osteoclast activities, and they synergistically promoted MSC osteogenic differentiation. The dual drug loaded scaffolds also significantly promoted in vivo mandibular bone formation after 8 week implantation. This work presents a 3D printing strategy to fabricate engineered bone constructs, which can likely be used as off-the-shelf products to promote craniomaxillofacial regeneration.

20.
Chem Commun (Camb) ; 56(47): 6344-6347, 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32391532

RESUMO

The hydroxyl radical (˙OH) in the endoplasmic reticulum has not been studied thoroughly due to the lack of proper methods. Here, an endoplasmic reticulum-targeting fluorescent probe for detecting ˙OH is reported. With this probe, the action of ˙OH in the endoplasmic reticulum has been imaged in living cells.

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