Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 742
Filtrar
1.
Orthop Surg ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33951305

RESUMO

Oblique lateral lumbar interbody fusion (OLIF) has been extensively used, with satisfactory outcomes for the treatment of degenerative lumbar disease. This article aims to demonstrate a modified lateral approach, also known as the anteroinferior psoas (AIP) technique for OLIF, which is expected to enhance security by operating under direct vision. The core procedures of our technique are as follows. First, a minimal skin incision is recommended 2 cm backward compared with the normal incision of OLIF, facilitating the oblique placement of the working channel and the orthogonal maneuver for the cage placement. Second, two special custom-made retractors, as an alternative to the index finger, are used to pull the psoas muscle to the dorsal side and pull the abdominal organs together with extraperitoneal fate to the ventral side under direct visualization, making the exposure of the working channel convenient and safe and avoiding radiation exposure. Third, the anterior border of the psoas is bluntly dissected and retracted backwards, obviously enlarging the retroperitoneal anatomic corridor and then expanding clinical indications of OLIF. The benefits of this technique include that it has a short learning curve, satisfactory clinical outcomes, and low risk of perioperative complications.

2.
Virus Res ; : 198440, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33940002

RESUMO

Globally, ovarian cancer is the seventh most common cancer and the eighth-most common cause of cancer death among women with a five-year survival rate of less than 45%. Although reovirus is known to be effective for treating ovarian cancer, some types of tumor cells still exhibit resistance to reovirus. In order to solve this resistance problem in the treatment of ovarian cancer, we selected the reovirus-resistant OV-90 ovarian cancer cells to study reovirus oncolytic effects. We found that the viability of OV-90 cells decreased after reovirus double-stranded RNA (dsRNA) genome transfection. Interestingly, we observed that chemical blockage of the Toll-like receptor 3 (TLR3)-dsRNA binding complex in OV-90 cells and the inhibition of downstream TLR3 signaling disrupted OV-90 apoptosis triggered by reovirus dsRNA. Together, these results demonstrate that reovirus dsRNA induces reovirus-resistant tumor cell apoptosis through the TLR3 signaling pathway.

3.
J Transl Med ; 19(1): 185, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933132

RESUMO

BACKGROUND: Cetuximab has been approved for use for first-line treatment of patients with wild-type KRAS metastatic colorectal cancer (CRC). However, treatment with cetuximab has shown limited efficacy as a CRC monotherapy. In addition, natural killer (NK) cell function is known to be severely attenuated in cancer patients. The goal of this study was to develop a new strategy to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells, in combination with cetuximab against CRC cells. METHODS: Ex vivo expanded NK cells were stimulated with reovirus, and reovirus-activated NK cells mediated ADCC assay were performed on CRC cells in combination with cetuximab. The synergistic antitumor effects of reovirus-activated NK cells and cetuximab were tested on DLD-1 tumor-bearing mice. Finally, Toll-like receptor 3 (TLR3) knockdown in NK cells, along with chemical blockade of TLR3/dsRNA complex, and inhibition of the TLR3 downstream signaling pathway, were performed to explore the mechanisms by which reovirus enhances NK cell cytotoxicity. RESULTS: We first confirmed that exposure of NK cells to reovirus enhanced their cytotoxicity in a dose-dependent manner.We then investigated whether reovirus-activated NK cells exposed to cetuximab-bound CRC cells exhibited greater anti-tumor efficacy than either monotherapy. Co-culture of CRC cell lines with reovirus-activated NK cells indicated that NK cytotoxicity was significantly higher in combination with cetuximab, regardless of KRAS mutation status or EGFR expression level. We also found that reovirus activation of NK cells, in conjunction with cetuximab, resulted in significantly stronger anti-tumor efficacy.Finally, TLR3 knockdown, inhibition of TLR3/dsRNA complex or TBK1/IKKε demonstrated that activation of NK cells by reovirus was dependent on TLR3 and its downstream signaling pathway. CONCLUSIONS: This study demonstrated that combination treatment of reovirus-activated NK cells with cetuximab synergistically enhances their anti-tumor cytotoxicity, suggesting a strong candidate strategy for clinical treatment of CRC.

4.
J Mater Chem B ; 9(13): 3047-3054, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885666

RESUMO

Prenatal diagnostics holds great significance for pregnant women desiring healthy babies. Fetal nucleated red blood cells (fNRBCs), bearing the complete genome of the fetus, have been regarded as an important biomarker for noninvasive prenatal diagnostics (NIPD). The high-performance detection and enrichment of fNRBCs from maternal blood, especially during early pregnancy, is urgently needed for NIPD, which, unfortunately, remains a big challenge for early-pregnancy fNRBC isolation. In this study, we developed an innovative platform based on silica microbeads for fNRBC isolation and release in early pregnancy. Microbeads were coated with self-assembled MnO2 nanoparticles (SiO2@MnO2) and then modified with a specific antibody. Benefiting from the three-dimensional nanostructure of the MnO2 nanoparticles, the isolation efficiency of the fNRBCs was enhanced. Subsequently, fNRBCs were released via dissolving the MnO2-nanoparticle coating using oxalic acid. We successfully isolated fNRBCs from the maternal peripheral blood samples of 20 pregnant women in the early pregnancy period, ranging from 41 to 62 gestational days. More importantly, the fetal origin of isolated cells was confirmed via fluorescent in situ hybridization and short tandem repeat analysis. This platform based on SiO2@MnO2 microbeads has verified the existence of fNRBCs in early-pregnancy maternal blood and is a promising approach for NIPD in early pregnancy.

5.
Environ Res ; 197: 111174, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33894235

RESUMO

BACKGROUND: Dyslipidemia is a crucial risk factor for cardiovascular diseases. Previous studies have suggested that air pollution is associated with blood lipids. However, little evidence exists in low- and middle-income regions. We aimed to investigate the association between air pollution and blood lipids in southwestern China. METHODS: We included 67,305 participants aged 30-79 years from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Three-year average concentrations of particles with diameters ≤1 µm (PM1), particles with diameters ≤ 2.5 µm (PM2.5), particles with diameters ≤ 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using satellite-based spatiotemporal models. Individual serum lipids, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were measured. Linear, logistic, and quantile regression models were used to evaluate the association between ambient air pollution and blood lipids. RESULTS: All five air pollutants in our study were associated with lipid levels. Increased air pollution exposure was associated with a high risk of dyslipidemia. Each 10 µg/m3 increase in PM2.5 was associated with 0.92% (95% confidence interval (CI): 0.64%, 1.20%), 2.23% (95% CI: 1.44%, 3.02%), and 3.04% (95% CI: 2.61%, 3.47%) increases in TC, TG, and LDL-C levels, respectively, and a 2.03% (95% CI: 1.69%, 2.37%) decrease in HDL-C levels, and high risks of dyslipidemia (OR = 1.14, 95% CI: 1.10, 1.18). Stronger associations of air pollution with blood lipids were found in participants with high lipid levels than in those with low lipid levels. CONCLUSION: Long-term exposure to air pollutants was associated with blood lipid levels and the risk of dyslipidemia. People with high lipid levels were more susceptible to air pollution. Therefore, air pollution prevention and control may help reduce the incidence of dyslipidemia and the burden of CVDs.

6.
Plant Biol (Stuttg) ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811408

RESUMO

14-3-3 proteins bind to and modulate the activity of phosphorylated proteins that regulate a variety of metabolic processes in plants. Over the past decade, interest in the plant 14-3-3 field has increased dramatically, mainly due to the vast number of mechanisms by which 14-3-3 proteins regulate metabolism. As this field develops, it is essential to understand the role of these proteins in metabolic and stress responses. This review summarizes the current knowledge about 14-3-3 proteins in plants, including their molecular structure and function, regulatory mechanism, and roles in carbon and nitrogen metabolism and stress responses. We begin with a molecular structural analysis of 14-3-3 proteins, which describes the basic principles of 14-3-3 function, and then discuss the regulatory mechanisms and roles in carbon and nitrogen metabolism of 14-3-3 proteins. We conclude with a summary of the 14-3-3 response to biotic stress and abiotic stress.

7.
Atherosclerosis ; 325: 24-29, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33887530

RESUMO

BACKGROUND AND AIMS: Serum calcium abnormality is associated with adverse cardiovascular outcomes, but the effects of serum calcium level on stroke outcomes remain unknown. We aimed to assess the relationship between serum calcium level and 1-year outcomes in patients with acute ischemic stroke and transient ischemic attack. METHODS: We included 9375 stroke patients from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to albumin corrected-calcium quartiles. Composite end point comprised recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Multivariable Cox or logistic regression was used to evaluate the independent association of albumin corrected-calcium with all-cause mortality, recurrent stroke, composite end point, and poor functional outcome (modified Rankin Scale score ≥3). RESULTS: Compared with the lowest calcium quartile (<2.16 mmol/L), the adjusted hazard ratio (95% CI) of the top quartile (≥2.31 mmol/L) was 1.56 (1.11-2.18) for all-cause mortality, 1.06 (0.87-1.28) for recurrent stroke and 1.08 (0.90-1.01) for composite end point, and the adjusted odds ratio for poor functional outcome was 1.18 (0.96-1.44). The addition of serum calcium to conventional risk factors improved risk prediction of all-cause mortality, leading to a small but significant increase in C-statistics and reclassification with non-significant integrated discrimination improvement (C-statistics, p = 0.02; net reclassification index 11.8%, p = 0.038; integrated discrimination improvement 0.08%, p = 0.42). CONCLUSIONS: High serum calcium levels at baseline were associated with all-cause mortality at 1-year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke.

8.
9.
Cell Metab ; 33(3): 455-456, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33657385

RESUMO

Many of the gut-microbiome-derived signatures for liver cirrhosis, especially the important ones, were likely under the influence of proton pump inhibitors (PPIs). Wu et al. suggest that drug usage is a confounding factor in metagenomics analysis that should be controlled for.

10.
Acta Pharmacol Sin ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782541

RESUMO

PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. In this study, we described a novel PI3Kδ inhibitor SAF-248, which exhibited high selectivity for PI3Kδ (IC50 = 30.6 nM) over other PI3K isoforms at both molecular and cellular levels, while sparing most of the other human protein kinases in the kinome profiling. SAF-248 exhibited superior antiproliferative activity against 27 human lymphoma and leukemia cell lines compared with the approved PI3Kδ inhibitor idelalisib. In particular, SAF-248 potently inhibited the proliferation of a panel of seven DLBCL cell lines (with GI50 values < 1 µM in 5 DLBCL cell lines). We demonstrated that SAF-248 concentration-dependently blocked PI3K signaling followed by inducing G1 phase arrest and apoptosis in DLBCL KARPAS-422, Pfeiffer and TMD8 cells. Its activity against the DLBCL cells was negatively correlated to the protein level of PI3Kα. Oral administration of SAF-248 dose-dependently inhibited the growth of xenografts derived from Pfeiffer and TMD8 cells. Activation of mTORC1, MYC and JAK/STAT signaling was observed upon prolonged treatment and co-targeting these pathways would potentiate the activity of SAF-248. Taken together, SAF-248 is a promising selective PI3Kδ inhibitor for the treatment of DLBCL and rational drug combination would further improve its efficacy.

11.
BMC Public Health ; 21(1): 591, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765991

RESUMO

OBJECTIVE: Sleep plays an important role in the health and well-being of middle aged and elderly people, and social capital may be one of the important factors for sleep disorders. This study aimed to understand the relationship between social capital and sleep disorders in a unique region of China -Tibet that generally has the disadvantaged economic status compared to other parts of China. METHODS: The study was based on Tibetan data from The China Multi-Ethnic Cohort (CMEC) and was conducted from May 2018 to September 2019. A total of 3194 Tibetans aged > 50 were selected from the community population by multi-stage stratified cluster sampling. Social capital was measured using two validated health-related social capital scales, family/community and society.. Sleep disorders were measured as the presence of disorders of initiating and maintaining sleep, early morning awakening, or daytime dysfunction. Logistic regression models were applied to examine the association between social capital and sleep disorders. RESULTS: 39.9% (1271/3194) of the participants had sleep disorders. In addition, after controlling for all potential variables, family social capital was significantly negatively associated with sleep disorders (OR = 0.95, P < 0.05), while community and society social capital was not associated with sleep disorders. Then, when we did all the sex-stratified analyses, the significant association between social capital and sleep disorders was found only in women (OR = 0.94, P < 0.05), while no association was found in males; neither males nor females showed any association with community and society social capital. CONCLUSION: Our study would help to better understand the extent of health inequality in China, and guide future interventions, strategies and policies to promote sleep quality in low-income areas, taking into account both the role of Tibetan specific cultural traditions, lifestyles and religious beliefs in social capital and the gender differences in social capital.

12.
Plant Sci ; 305: 110829, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33691963

RESUMO

Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the photorespiration pathway in higher plants. Our previous study showed that AtSHMT1 controls the assimilation of HCHO to sugars in Arabidopsis. The expression of SHMT1 was induced in Arabidopsis but was inhibited in tobacco under HCHO stress. To investigate whether the function of AtSHMT1 in the HCHO assimilation could be exerted in tobacco, AtSHMT1 was overexpressed alone (S5) or co-overexpressed (SF6) with Arabidopsis formate dehydrogenase (AtFDH) in leaves using a light-inducible promoter in this study. 13C NMR analyses showed that the 13C-metabolic flux from H13CHO was introduced to sugar synthesis in SF6 leaves but not in S5 leaves. The increase in the production of metabolites via the original pathways was particularly greater in SF6 leaves than in S5 leaves, suggesting that co-overexpression of AtSHMT1 and AtFDH is more effective than overexpression of AtSHMT1 alone in the enhancement of HCHO metabolism in tobacco leaves. Consequently, the increase in HCHO uptake and resistance was greater in SF6 leaves than in S5 leaves. The mechanism underlying the role of overexpressed AtSHMT1 and AtFDH was discussed based on changes in photosynthetic parameters, chlorophyll content, antioxidant enzyme activity and the oxidative level in leaves.

13.
Global Spine J ; : 2192568221992098, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33685261

RESUMO

STUDY DESIGN: A retrospective study of prospectively collected radiographic and clinical data. OBJECTIVE: This study aims to investigate the relationship between endplate morphology parameters and the incidence of cage subsidence in patients with mini-open single-level oblique lateral lumbar interbody fusion (OLIF). METHODS: We included 119 inpatients who underwent OLIF from February 2015 to December 2017. A total of 119 patients with single treatment level of OLIF were included. Plain anteroposterior and lateral radiograph were taken preoperatively, postoperatively, and during follow-up. The correlation between disc height, endplate concave angle/depth, cage position and cage subsidence were investigated. Functional rating index (Visual Analogue Scale for pain, and Roland Morris Disability Questionnaire) were employed to assess clinical outcomes. RESULTS: Cage subsidence was more commonly seen at the superior endplates (42/119, 35.29%) than at the inferior endplates (6/119, 5.04%) (p < 0.01). More importantly, cage subsidence was significantly less in patients with superior endplates that were without concave angle (3/20, 15%) than with concave angle (37/99, 37.37%) (p < 0.05). Cage subsidence correlated negatively with preoperative anterior disc height (r = -0.21, p < 0.05), but positively with disc distraction rate (r = 0.27, p < 0.01). Lastly, the distance of cage to the anterior edges of the vertebral body showed a positive correlation (r = 0.26, p < 0.01). CONCLUSIONS: This study for the first time demonstrated that endplate morphology correlates with cage subsidence after OLIF. Since relatively flat endplates with smaller concave angle significantly diminish the incidence of subsidence, the morphology of cage surface should be taken into consideration when designing the next generation of cage. In addition, precise measurement of the disc height to avoid over-distraction, and more anteriorly placement of the cage is suggested to reduce subsidence.

14.
Eur J Med Chem ; 218: 113388, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33784603

RESUMO

Diabetic kidney disease (DKD) is a major feature of the final stage of nearly all cause types of diabetes mellitus (DM). To date, few safe and effective drugs are available to treat. Peroxisome proliferator-activated receptors (PPARs), comprised of three members: PPAR-α, PPAR-δ and PPAR-γ, play a protective role in the DKD through glycemic control and lipid metabolism, whereas systemic activation of PPAR-γ causes serious side-effects in clinical trials. GFT505 is a dual PPAR-α/δ agonist, and the selectivity against PPAR-γ is still to be improved. Sulfuretin has been shown to suppress the expression of PPAR-γ and improve the pathogenesis of diabetic complications. In this study, by hybridizing the carboxylic acid of GFT505 and the parent nucleus of sulfuretin, we pioneeringly designed and synthetized a series of novel dual PPAR-α/δ agonists, expecting to provide a better benefit/risk ratio for PPARs. Of all the synthesized compounds, compound 12 was identified with highly activity on PPAR-α/δ and higher selectivity against PPAR-γ than that of GFT505 (EC50: hPPAR-α: 0.26 µM vs.0.76 µM; hPPAR-δ: 0.50 µM vs.0.73 µM; hPPAR-γ: 4.22 µM vs.2.79 µM). The molecular docking studies also depicted good binding affinity of compound 12 for PPAR-α and PPAR-δ compared to GFT505. Furthermore, compound 12 exhibited an evidently renoprotective effect on the DKD through inhibiting inflammatory process, which might at least partly via JNK/NF-κB pathways in vivo and in vitro. Overall, compound 12 hold therapeutic promise for DKD.

15.
BMC Nephrol ; 22(1): 83, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691640

RESUMO

BACKGROUND: Primary hyperoxaluria(PH)is a rare autosomal recessive genetic disease that contains three subtypes (PH1, PH2 and PH3). Approximately 80% of PH patients has been reported as subtype PH1, this subtype of PH has been related to a higher risk of renal failure at any age. Several genetic studies indicate that the variants in gene AGXT are responsible for the occurrence of PH1. However, the population heterogeneity of the variants in AGXT makes the genetic diagnosis of PH1 more challenging as it is hard to locate each specific variant. It is valuable to have a complete spectrum of AGXT variants from different population for early diagnosis and clinical treatments of PH1. CASE PRESENTATION: In this study, We performed high-throughput sequencing and genetic analysis of a 6-year-old male PH1 patient from a Chinese family. Two variants (c.346G > A: p.Gly116Arg; c.864G > A: p.Trp288X) of the gene AGXT were identified. We found a nonsense variant (c.864G > A: p.Trp288X) that comes from the proband's mother and has never been reported previously. The other missense variant (c.346G > A: p.Gly116Arg) was inherited from his father and has been found previously in a domain of aminotransferase, which plays an important role in the function of AGT protein. Furthermore, we searched 110 pathogenic variants of AGXT that have been reported worldwide in healthy local Chinese population, none of these pathogenic variants was detected in the local genomes. CONCLUSIONS: Our research provides an important diagnosis basis for PH1 on the genetic level by updating the genotype of PH1 and also develops a better understanding of the variants in AGXT by broadening the variation database of AGXT according to the Chinese reference genome.

16.
Stroke ; 52(4): 1253-1258, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33588598

RESUMO

BACKGROUND AND PURPOSE: A variety of definitions for minor stroke have been proposed. We aimed to compare the clinical characteristics and outcomes of minor stroke defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 versus ≤3. METHODS: We retrieved acute ischemic stroke patients with NIHSS score ≤5 in the CSCA study (China Stroke Center Alliance) between August 2015 and 2019. In-hospital clinical outcomes including all-cause mortality, stroke, and myocardial infarction were compared between the NIHSS score ≤5 and NIHSS score ≤3 groups using absolute standardized differences (ASD). RESULTS: A total of 1 006 798 patients were registered in the CSCA program from 1476 hospitals, 472 352 patients had NIHSS score ≤5, of whom 356 314 patients had NIHSS score ≤3. The in-hospital composite events of death, myocardial infarction, or recurrent stroke were not significantly different between the NIHSS score ≤5 and NIHSS score ≤3 groups (5.6% [26 346/472 352] versus 5.2% [18 682/356 314]; ASD, 1.8). The in-hospital all-cause mortality (0.1% [443/472 352] versus 0.1% [255/356 314]; ASD, <0.01), recurrent ischemic stroke (5.3% [25 026/472 352] versus 5.0% [17 777/356 314]; ASD, 1.4), and hemorrhagic stroke (0.5% [2151/472 352] versus 0.4% [1475/356 314]; ASD, 1.5) were not significantly different between both the NIHSS score ≤5 and NIHSS score ≤3 groups. CONCLUSIONS: Our large-scale study identified that minor stroke using NIHSS scores ≤5 and ≤3 as the definition was comparable with each other regarding in-hospital all-cause mortality, recurrent stroke, and hemorrhagic stroke. This observation may be useful for future comparison studies and clinical trial design.

18.
Medicine (Baltimore) ; 100(7): e24810, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607845

RESUMO

BACKGROUND: Infertility is a kind of global disease. Fallopian tubal obstruction is one of the most important causes of female infertility. Complementary and alternative therapies are effective in treating tubal obstructive infertility, but there is no study on a comprehensive comparison among them. So, the purpose of this paper is to evaluate the efficacy and safety of different complementary and alternative therapies for tubal obstructive infertility. METHODS: We will search for randomized controlled trials (RCTs) from the following databases: PubMed, Cochrane Library, EMBASE, Web of Science, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database. We will assess the risk of bias of the included studies with the Cochrane tool, and the strength of evidence with the GRADE approach. Both pairwise meta-analyses and network meta-analyses will be performed to examine the relative efficacy and safety of complementary and alternative therapies in the treatment of tubal obstructive infertility. CONCLUSION: Our findings will provide clear evidence based on current available studies, which may lead to some proposals for both patients and researchers. INPLASY REGISTRATION NUMBER: INPLASY202110076.


Assuntos
Terapias Complementares/métodos , Doenças das Tubas Uterinas/complicações , Infertilidade/etiologia , Infertilidade/terapia , Terapias Complementares/estatística & dados numéricos , Gerenciamento de Dados , Doenças das Tubas Uterinas/diagnóstico , Feminino , Humanos , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/estatística & dados numéricos , Metanálise em Rede , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
19.
Int Immunopharmacol ; 94: 107437, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33571747

RESUMO

Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the therapeutic efficacy is modest, and most commonly manifests as relapse from remission. Thus, improving long-term AML survival is a crucial clinical challenge. In recent years, oncolytic virotherapy has provided an alternative approach for AML treatment. The use of oncolytic reoviruses has been explored in more than 30 clinical trials for safety and feasibility issues. However, like other oncolytic viruses, neutralizing antibodies (NAbs) reduce therapeutic efficacy. To tackle this problem, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used to deliver reovirus using in vitro and in vivo models. Human UC-MSCs were successfully loaded with reovirus, without impairing biological function.We also observed in vitro protective effects of hUC-MSCs on reovirus in the presence of NAbs. In the immunocompromised AML mouse model, hUC-MSCs effectively carried reoviruses to tumor lesions and significantly prolonged the survival of AML xenografts in mice in the presence of a high titer anti-reovirus antibody (p = 0.001). However, reovirus-induced activation of AKT, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and NF-κB signaling led to the maintenance of intrinsic migratory properties and secretion of pro-inflammatory cytokines from hUC-MSCs, particularly CXCL10. In immuno-competent AML mice, MSCs carrying reovirus triggered immune responses, and eventually inhibited tumor growth. Therefore, these results suggest that MSCs as carriers of oncolytic reoviruses can enhance the antitumor efficacy of virotherapy.

20.
Anaerobe ; 69: 102349, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610765

RESUMO

Strictly anaerobic bacteria are important to both human health and industrial usage. These bacteria are sensitive to oxygen, therefore, it is preferable to manipulate these microbes in an anaerobic chamber. However, commercial anaerobic chambers (CACs) are expensive, making them less accessible to scientists with a limited budget, especially to those in developing countries. The high price of commercial chambers has hindered, at least partially, the progress of research on anaerobes in developing countries. In the research presented here, we developed an inexpensive and reliable anaerobic chamber and successfully achieved routine maintenance of eleven strictly anaerobic bacterial strains. Furthermore, genetic manipulation examples have been set for both Clostridioidesdifficile 630 and Clostridiumbeijerinckii NCIMB 8052 strains to validate that the chamber could applied to advanced genetic engineering of strictly anaerobes. C. difficile and C. beijerinckii were both genetically manipulated in this chamber, showing it's utility for the genetic engineering of anaerobes. Most importantly, the anaerobic chamber was 76% - 88% less expensive than a CACs and has similar functionality with regards to the cultivation and manipulation of strictly anaerobic bacteria. The anaerobic chamber described in this study will promote the research of anaerobes in developing counties and scientists who have limited research budgets.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...