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1.
J Cell Physiol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603257

RESUMO

Non-small-cell lung cancer (NSCLC) is the most common malignancy along with high mortality rate worldwide. Recently, nucleolar and spindle-associated protein 1 (NUSAP1) has been reported to be involved in the malignant progression of several cancers. However, in NSCLC, the biological function of NUSAP1 and its molecular mechanism have not been reported. Here, our findings indicated that the NUSAP1 messenger RNA expression level was remarkably upregulated in NSCLC tissues compared with that of adjacent normal tissues. We also found that NUSAP1 gene expression was notably upregulated in NSCLC cell lines (A549, 95-D, H358, and H1299) compared with that of normal human bronchial epithelial cell line (16HBE). Subsequently, the biological function of NUSAP1 was investigated in A549 and H358 cells transfected with NUSAP1 small interfering RNA (siRNA), respectively. Results showed that NUSAP1 knockdown inhibited NSCLC cell proliferation, and promoted cell apoptosis. Furthermore, the number of cell migration and invasion was significantly suppressed by NUSAP1 knockdown. In addition, our results indicated that NUSAP1 knockdown increased the gene expression of B-cell translocation gene 2 (BTG2), but decreased the expression levels of phosphoinositide 3-kinase (PI3K) and phosphorylated serine/threonine kinase (p-AKT). BTG2 siRNA partly abrogates the effect of NUSAP1 knockdown on BTG2 gene expression. Fumonisin B1 (FB1), a AKT activator, reversed the effect of NUSAP1 knockdown on the biological function in NSCLC. Taken together, NUSAP1 knockdown promotes NSCLC cell apoptosis, and inhibits cell proliferation, cell migration, and invasion, which is associated with regulating BTG2/PI3K/Akt signal pathway. Our findings suggest that NUSAP1 is a promising molecular target for NSCLC treatment.

2.
Cell Death Dis ; 10(9): 669, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511495

RESUMO

The fundamental roles for the Salvador-Warts-Hippo (SWH) pathway are widely characterized in growth regulation and organ size control. However, the function of SWH pathway is less known in cell fate determination. Here we uncover a novel role of the SWH signaling pathway in determination of cell fate during neural precursor (sensory organ precursor, SOP) development. Inactivation of the SWH pathway in SOP of the wing imaginal discs affects caspase-dependent bristle patterning in an apoptosis-independent process. Such nonapoptotic functions of caspases have been implicated in inflammation, proliferation, cellular remodeling, and cell fate determination. Our data indicate an effect on the Wingless (Wg)/Wnt pathway. Previously, caspases were proposed to cleave and activate a negative regulator of Wg/Wnt signaling, Shaggy (Sgg)/GSK3ß. Surprisingly, we found that a noncleavable form of Sgg encoded from the endogenous locus after CRISPR-Cas9 modification supported almost normal bristle patterning, indicating that Sgg might not be the main target of the caspase-dependent nonapoptotic process. Collectively, our results outline a new function of SWH signaling that crosstalks to caspase-dependent nonapoptotic signaling and Wg/Wnt signaling in neural precursor development, which might be implicated in neuronal pathogenesis.

3.
Exp Cell Res ; : 111624, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31539530

RESUMO

ADP-ribosylation factor 3 (ARF3) is a member of the KRAS proto-oncogene, GTPase(Ras) super-family of guanine nucleotide-binding proteins that mediates Golgi-related mitosis, but its role in malignant cells is unclear. In the present study, we found that mRNA and protein expression of ARF3 is up-regulated in breast cancer cells. Immunohistochemical analysis of 167 paraffin-embedded archived breast cancer tissues showed that ARF3 expression was localized primarily in the cytoplasm and was significantly up-regulated in malignant specimens compared to benign specimens. There were strong associations between ARF3 expression and clinicopathological characteristics in breast cancer. We also found that overexpressing ARF3 promoted, while silencing endogenous ARF3 inhibited, the proliferation of breast cancer cells by regulating cell cycle G1-S transition. Moreover, the pro-proliferative effect of ARF3 on breast cancer cells was associated with inactivation of the forkhead box O1 (FOXO1) transcription factor. ARF3 promotes breast cancer cell proliferation through the participation of FOXO1 and represents as a novel prognostic marker and therapeutic target for breast cancer.

4.
Nanotoxicology ; : 1-15, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31561730

RESUMO

The spread of antibiotic resistance genes (ARGs) has become a global environmental issue; it has been found that nanoparticles (NPs) can promote the transfer of ARGs between bacteria. However, it remains unclear whether NPs can affect this kind of conjugation in Streptomyces, which mainly conjugate with other bacteria via spores. In the present study, we demonstrated that Al2O3 NPs significantly promote the conjugative transfer of ARGs from Escherichia coli (E. coli) ET12567 to Streptomyces coelicolor (S. coelicolor) M145 without the use of heat shock method. The number of transconjugants induced by Al2O3 particles was associated with the size and concentration of Al2O3 particles, exposure time, and the ratio of E. coli and spores. When nanoparticle size was 30 nm at a concentration of 10 mg/L, the conjugation efficiency reached a peak value of 182 cfu/108 spores, which was more than 60-fold higher than that of the control. Compared with nanomaterials, bulk particles exhibited no significant effect on conjugation efficiency. We also explored the mechanisms by which NPs promote conjugative transfer. After the addition of NPs, the intracellular ROS content increased and the expression of the classical porin gene ompC was stimulated. In addition, ROS enhanced the mRNA expression levels of conjugative genes by inhibiting global regulation genes. Meanwhile, expression of the conjugation-related gene intA was also stimulated, ultimately increasing the number of transconjugants. Our results indicated that Al2O3 NPs significantly promoted the conjugative transfer of ARGs from bacteria to spores and aggravated the diffusion of resistance genes in the environment.

5.
Chem Commun (Camb) ; 55(80): 12056-12059, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31536062

RESUMO

CoPcCl is used as a catalytic electrolyte additive for lithium sulfur batteries under the guidance of theoretical calculations. The electrolyte additive strategy is easier to realize and more effective compared with the fabrication of catalytic host materials. Adding CoPcCl in the electrolyte enhanced the sulfur utilization remarkably.

6.
Am J Hypertens ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31504137

RESUMO

BACKGROUND: While sex differences characterize susceptibility and severity of idiopathic pulmonary arterial hypertension (IPAH), our understanding of the relationship between levels of gonadotropins and sex hormones in fertile women and the disease is limited. We aimed to investigate whether gonadotropin and sex hormone levels in women of reproductive age were associated with risk and mortality of IPAH. METHODS: We did a matched case-control study. Cases were reproductive female patients with idiopathic pulmonary arterial hypertension admitted in Shanghai Pulmonary Hospital (Tongji University School of Medicine, Shanghai, China) during 2008 to 2014. Healthy controls were matched on age and body mass index. We also did a prospective cohort study to assess the effects of hormone levels on mortality in IPAH fertile female patients. RESULTS: 164 cases and 133 controls were included. After adjustment for age and body mass index, the odds ratios of having IPAH for follicle stimulating hormone, testosterone, and progesterone as expressed on natural log scale were 1.51 (95%CI 1.06, 2.16), 0.42 (0.31-0.57), and 0.52(0.43-0.63), respectively. In the cohort study with a median follow up of 77-months, the hazard ratios for dying after adjustment for baseline characteristics and treatments among IPAH patients were 2.01 (95% CI: 1.22-3.30) and 0.78 (95% CI: 0.62-0.98) for follicle stimulating hormone and progesterone in natural log scale, respectively. CONCLUSIONS: In reproductive women with IPAH, high follicle stimulating hormone and low progesterone tended to be associated with high risk of IPAH and mortality among patients.

7.
Cell Transplant ; : 963689719874769, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31512502

RESUMO

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.

8.
Complement Ther Clin Pract ; 37: 58-67, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31487580

RESUMO

BACKGROUND: and purpose: Complementary and Alternative Medicine(CAM) has been greatly used in cancer patients. This research aimed to explore the research priorities of CAM for cancer patient's treatment. METHODS: Web of Science(WoS), HistCite, BibExcel, GunnMap and VOSviewer were used to extract and visualize information. RESULTS: 2768 articles published in 789 journals were indexed in the WoS from 1989 to 2018. The USA(n = 1009) and Technion-Israel Institute Technology(n = 58) were the most prolific country and institution, respectively. Keywords co-occurrence analysis indicated that the research hotspots around the world formed five clusters, so did the author co-citation analysis. The research priorities of the top-five countries, the top-three prolific authors and the co-citation core authors were also discussed, which reveals the differences and similarities among them. CONCLUSION: This study delineates a framework for better understanding the situational use of CAM in cancer patients, which could help health care workers to prioritize and organize future research.

9.
Nano Lett ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31398289

RESUMO

Terahertz (THz) modulators are always realized by dynamically manipulating the conversion between different resonant modes within a single unit cell of an active metasurface. In this Letter, to achieve real high-speed THz modulation, we present a staggered netlike two-dimensional electron gas (2DEG) nanostructure composite metasurface that has two states: a collective state with massive surface resonant characteristics and an individual state with meta-atom resonant characteristics. By controlling the electron transport of the nanoscale 2DEG with an electrical grid, collective-individual state conversion can be realized in this composite metasurface. Unlike traditional resonant mode conversion confined in meta-units, this state conversion enables the resonant modes to be flexibly distributed throughout the metasurface, leading to a frequency shift of nearly 99% in both the simulated and experimental transmission spectra. Moreover, such a mechanism can effectively suppress parasitic modes and significantly reduce the capacitance of the metasurface. Thereby, this composite metasurface can efficiently control the transmission characteristics of THz waves with high-speed modulations. As a result, 93% modulation depth is observed in the static experiment and modulated sinusoidal signals up to 3 GHz are achieved in the dynamic experiment, while the -3 dB bandwidth can reach up to 1 GHz. This tunable collective-individual state conversion may have great application potential in wireless communication and coded imaging.

10.
Small ; : e1903173, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31441228

RESUMO

Introducing ferromagnetism in transition metal dichalcogenides has attracted lots of attention due to the possible applications in spintronics devices. Generally, single magnetic element doping is used to introduce magnetism. However, mostly, weak ferromagnetism is observed. In this work, codoping of two kinds of transition metals (Nb and Co) into WSe2 is used to study its magnetic properties. In detail, single crystal WSe2 is codoped with 4 at% Co and various concentrations of Nb by employing the physical ion implantation method. Raman, X-ray diffraction and X-ray photoelectron spectroscopy results reveal the effective substitutional doping of implanted elements (Co and Nb). Magnetic measurements illustrate that both un-doped and 4 at% Co doped WSe2 show weak ferromagnetism whereas magnetization is strongly enhanced when Co and Nb are codoped into WSe2 . The magnetization is comparable with a ferromagnet, which may be attributed to Co, Nb doping and defects. In addition, a large coercivity of ≈1.2 kOe is observed in the 1 at% Nb-4 at% Co codoped WSe2 sample, which may be ascribed to the combined effect of doping-induced stress, defect-dictated pinning and anisotropy of NbSe bond owing to the charge transfer between Nb and Se ions.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31456413

RESUMO

AIM: It is known that mitochondrial reactive oxygen species generation ([ROS]m) causes the release of Ca2+ via ryanodine receptor-2 (RyR2) on the sarcoplasmic reticulum (SR) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). In this study, we sought to determine whether hypoxia-induced, RyR2-mediated Ca2+ release may in turn promote [ROS]m in PASMCs and the underlying signaling mechanism. RESULTS: Our data reveal that application of caffeine or norepinephrine to induce Ca2+ release increased [ROS]m in PASMCs. Likewise, exogenous Ca2+ augmented ROS generation in isolated mitochondria and at complex III from PASMCs. Inhibition of mitochondrial Ca2+ uptake (MCU) with Ru360 attenuated agonist-induced [ROS]m. Ru360 produced a similar inhibitory effect on hypoxia-induced [ROS]m. Rieske iron-sulfur protein (RISP) gene knockdown inhibited Ca2+- and caffeine-induced [ROS]m. Inhibition of RyR2 by tetracaine or RyR2 gene knockout suppressed hypoxia-induced [ROS]m as well. INNOVATION: In this article, we present convincing evidence that Ca2+ release following hypoxia or RyR simulation causes a significant increase in MCU, and the increased MCU subsequently RISP-dependent [ROS]m, which provides a positive feedback mechanism to enhance hypoxia-initiated [ROS]m in PASMCs. CONCLUSION: Our findings demonstrate that hypoxia-induced mitochondrial ROS-dependent SR RyR2-mediated Ca2+ release increases MCU and then RISP-dependent [ROS]m in PASMCs, which may make significant contributions to HPV and associated pulmonary hypertension.

12.
J Clin Pharm Ther ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31468568

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear. CASE DESCRIPTION: A 57-year-old woman with refractory depression whose symptoms did not improve after 20-seconds intravenous injection of 0.5 mg/kg ketamine went into remission following eight, 1-minute intravenous injections of 1 mg/kg ketamine delivered over a 4-week period. By 6-month follow-up, no significant adverse events had occurred and cognitive function had improved. WHAT IS NEW AND CONCLUSION: High-dose intravenous injections of ketamine may stably improve depressive symptoms and cognitive function in patients with refractory depression who do not respond to rapid intravenous injection of standard-dose ketamine. The high-dose treatment appears to be associated with only mild side effects.

13.
BMC Nephrol ; 20(1): 291, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375084

RESUMO

BACKGROUND: Neutrophil gelatinase-assoicated lipocalin (NGAL) appears to be a promising proximal tubular injury biomarker for early prediction of delayed graft function (DGF) in kidney transplant recipients. However, its predictive values in urine and blood were varied among different studies. Here, we performed the meta-analysis to compare the predictive values of urine NGAL (uNGAL) and blood NGAL (bNGAL) for DGF in adult kidney transplant recipients. METHODS: We systematically searched Medline, Cochrane library and Embase for relevant studies from inception to May 2018. The summary receiver operating characteristic (SROC) curves, the pooled sensitivity, specificity and diagnostic odds ratio (DOR) were used to evaluate the prognostic performance of uNGAL and bNGAL for the identification of DGF. RESULTS: A total of 1036 patients from 14 eligible studies were included in the analysis. 8 studies focused on NGAL in urine and 6 reported NGAL in serum or plasma. The composite area under the ROC (AUC) for 24 h uNGAL was 0.91 (95% CI, 0.89-0.94) and the overall DOR for 24 h uNGAL was 24.17(95% CI, 9.94-58.75) with a sensitivity of 0.88 (95% CI, 0.75-0.94) and a specificity of 0.81 (95% CI, 0.68-0.89). The composite AUC for 24 h bNGAL was 0.95 (95% CI, 0.93-0.97) and the overall DOR for 24 h bNGAL was 43.11 (95% CI, 16.43-113.12) with a sensitivity of 0.91 (95% CI, 0.81-0.96) and a specificity of 0.86 (95% CI, 0.78-0.92). CONCLUSIONS: Urine and serum/plasma NGAL were valuable biomarkers for early identification of DGF in kidney transplantation. In addition, the bNGAL was superior to uNGAL in early prediction of DGF.

14.
Mol Autism ; 10: 32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367295

RESUMO

Background: Lower gestational age may increase autism spectrum disorder (ASD) vulnerability; however, the incidence of ASD diagnosis through a direct assessment on every very preterm birth child on the population base remains unclear. Moreover, the behavioral characteristics of preterm birth ASD are unknown. Methods: Every very preterm birth child (gestational age < 32 weeks; birth weight < 1500 g) who was discharged from neonatal intensive care units in Southern Taiwan and prospectively followed to 5 years of age was evaluated using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). The term birth (gestational age > 37 weeks) ASD children characterized by ADOS and ADI-R were group matched to the preterm birth ASD by age at examination for comparison. ADOS severity scores were calculated by the Mann-Whitney U test and ADI-R by multivariate analysis of variance and canonical discriminant analysis. Results: Two hundred forty-six (87%) of the 283 very preterm survivors were followed prospectively to 5 years of age. Nineteen (7.7%) of the 246 children fulfilled the diagnostic criteria of ASD. After excluding 1 patient with cerebral palsy and profound mental disability, 18 preterm ASD children were compared with 44 term birth ASD children. The two ASD groups were comparable for age at examination, gender, and intelligence quotient. The two groups showed comparable ADOS severity scores in social affect deficits, restricted repetitive behaviors, and total score, but had differences in qualitative abnormalities in reciprocal social interaction (Wilks lambda F value = 6.2, P < 0.001) of ADI-R. Compared to term birth ASD children, preterm birth ASD children exhibited worse nonverbal behaviors that regulate social interaction (OR 2.59, 95% CI 1.41-4.73, P = 0.002) but more favorable peer relationships (OR 0.58, 95% CI 0.38-0.90, P = 0.01) and socioemotional reciprocity (OR 0.55, 95% CI 0.33-0.92, P = 0.02). In contrast to the heterogeneous severity of social reciprocity in the term ASD group, the behavioral characteristics of the preterm ASD group showed a homogeneous reciprocal social interaction pattern. Conclusions: The 5-year incidence rate of ASD was high in very preterm birth children. Preterm birth ASD exhibited a specific behavioral phenotype of reciprocal social interaction.

15.
Sci Rep ; 9(1): 11253, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375702

RESUMO

In this research, antibiotic-producing bacteria, Streptomyces coelicolor (S. coelicolor) M145, was exposed to copper oxide (CuO) particles to investigate the effects of nano-particles (NPs) on antibiotic production. Results showed that a higher yield of antibiotics was obtained with smaller particle sizes of CuO NPs. When exposed to 10 mg/L of 40 nm CuO NPs, the maximum amount of actinorhodin (ACT) obtained was 2.6 mg/L after 144 h, which was 2.0-fold greater than that of control. However, the process was inhibited when the concentration of CuO NPs was increased to higher than 20 mg/L. Transcriptome analysis showed that all the genes involved in the ACT cluster were significantly up-regulated after exposure to 10 mg/L NPs, which could be the direct cause of the increase of ACT production. Additionally, some genes related to the generation of acetyl-coA were up-regulated. In this way, CuO NPs led to an increase of secondary metabolites. The mechanism related to these changes indicated that nano-particle‒induced ROS and Cu2+ played synergetic roles in promoting ACT biosynthesis. This is a first report suggesting that CuO NPs had a significant effect on antibiotic production, which will be helpful in understanding the mechanism of antibiotic production in nature.

16.
Plant Cell Rep ; 38(10): 1347-1360, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414199

RESUMO

KEY MESSAGE: VqERF114 regulates stilbene synthesis by interacting with VqMYB35. Resveratrol is a stilbene, an important class of secondary metabolites that accumulates in some plant species, including grapevine. In the plant, these are involved in the response to attack by plant pathogens and, as a component of the human diet, they offer a range of significant health benefits. Stilbene synthase (STS), the key enzyme responsible for resveratrol synthesis, has been characterised in a small number of plant species. However, the regulatory mechanisms for stilbene synthesis are uncertain. Here, an ERF family transcription factor from Chinese wild Vitis quinquangularis, VqERF114, was characterised as an indirect regulator of stilbene synthesis. A transient overexpression assay of VqERF114 in grapevine leaves led to increased STS expression and stilbene accumulation. However, VqERF114 did not bind to the promoters of VqSTSs but the MYB transcription factor, VqMYB35, did interact with VqERF114. This interaction was confirmed by a yeast two-hybrid assay and bimolecular fluorescence complementation. Furthermore, VqMYB35 showed activation effects on the expressions of VqSTS15, VqSTS28, VqSTS42 and VqSTS46 by binding directly to the MBS elements in their promoters. Co-overexpression of VqERF114 and VqMYB35 resulted in higher VqSTSs expression and more stilbene synthesis. These results demonstrate that VqERF114 regulates stilbene synthesis by interacting with VqMYB35.

17.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(4): 619-626, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31441263

RESUMO

Aiming at the problem of the influence of preloading force on its mechanical response in soft tissue compression experiments, an elimination method of preloading force based on linear loading region is proposed. Unconfined compression experiments under a variety of different preloading forces are performed. The influence of the preloading force on the parameters of constitutive model is analyzed. In the preload phase, the mechanical response of the soft tissue is taken as a linear model. The preloading force is eliminated by taking the preloading phase into account throughout the response process. According to five different preloading forces of the unconfined compression experiments, the elimination method is validated with two different constitutive models of soft tissue, and the error between the models obtained by the preloading force elimination method and the traditional method with the experimental results is compared. The results show that the error obtained by preloading force elimination method is significantly smaller than the traditional method. The preloading force elimination method can eliminate the influence of preloading force on mechanical response to a certain extent, and constitutive model parameters which are closer to the true properties of soft tissue can be obtained.


Assuntos
Modelos Biológicos , Pressão , Elasticidade , Modelos Lineares , Estresse Mecânico
18.
Transfusion ; 59(10): 3177-3185, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31393615

RESUMO

BACKGROUND: A serum alanine aminotransferase (ALT) test is currently demanded for blood donation in China. One of the major reasons to include such a test is possible etiology of known or unknown hepatotropic viruses. However, this hypothesis has never been examined convincingly. STUDY DESIGN AND METHODS: The study recruited 90 Chinese blood donors that were divided into three groups based on their ALT values. Serum virome from these donors was explored using a metagenomics approach with enhanced sensitivity resolved at single sequencing reads. RESULTS: Anellovirus and pegivirus C (GBV-C) were detected among these donors. None of them were found solely in donors with abnormal liver enzyme. Anellovirus was highly prevalent (93.3%) and the co-infection with multiple genera (alpha, beta, and gammatorquevirus) were more common in the donors with normal ALT values in comparison to those with elevated ALT (single/double/triple Anellovirus genera, 1/3/24 vs. 7/7/14 or 6/7/13, p = 0.009). For unmapped reads that accounted for 15 ± 14.9% of the data, similarity-based (BLASTN, BLASTP, and HMMER3) and similarity-independent (k-mer frequency) analysis identified several circular rep encoding ssDNA (CRESS-DNA) genomes. Direct PCR testing indicated these genomes were likely reagent contaminants. CONCLUSION: Viral etiology is not responsible for elevated ALT levels in Chinese blood donors. The ALT test, if not abandoned, should be adjusted for its cutoff in response to donor shortage in China.

19.
Nat Biomed Eng ; 3(9): 706-716, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31384008

RESUMO

Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases.

20.
Int Immunopharmacol ; 75: 105803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401383

RESUMO

Infection remains a major cause of morbidity and mortality after kidney transplantation (KT). Reliable biomarkers to predict post-transplant infection are lacking. We investigated the predictive performance of pre- and post-transplant levels of T-cell immunoglobulin and mucin domain-3 (Tim-3) and Galectin-9 (Gal-9), two pleiotropic immunomodulatory molecules, in early identification of infection. Serum Tim-3 and Gal-9 were paired measured before and 30 days after transplantation (PTD 30) in 95 KT recipients (KTRs). The decline rates of Tim-3 and Gal-9 were calculated relative to pre-transplant levels. KTRs with infection history had significantly higher levels of PTD 30 Tim-3 and Gal-9, and slower decrease rates of Gal-9 compared to non-infected recipients, while no difference was observed between two groups regarding pre-transplant levels. The AUCs for predicting 1-year post-transplant infection were 0.653 and 0.711 for post-transplant Tim-3 and Gal-9, 0.664 and 0.670 for relative Tim-3 and Gal-9, respectively. After adjusting for potential confounders, PTD 30 Tim-3, Gal-9 and relative Gal-9 remained as independent risk factors for post-transplant infection. Our results suggested that PTD 30 Tim-3 and Gal-9 and relative decrease of Gal-9 were promising predictors for identifying KTRs with high risk of infection, while pre-transplant Tim-3 and Gal-9 showed no predictive power to infection.

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