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1.
BMC Nephrol ; 21(1): 95, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160882

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication among human immunodeficiency virus (HIV)-infected patients resulting in increased morbidity and mortality. Continuous renal replacement therapy (CRRT) is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in Intensive Care Unit (ICU) and explore the influence factors correlated with CRRT and their prognosis. METHODS: We performed a retrospective case-control study in the ICU of the Beijing Ditan Hospital Capital Medical University. From June 1, 2005 to May 31, 2017, 225 cases were enrolled in this clinical study. RESULTS: 122 (54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1, 2 and 3 were 38 (31.1%), 21(17.2%) and 63(51.7%), respectively. 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By univariate logistics analysis, it showed that higher likelihood of diagnosis for respiratory failure (OR = 7.333,95% CI 1.467-36.664, p = 0.015), higher likelihood of diagnosis for septic shock (OR = 1.005,95% CI 1.001-1.01, p = 0.018), and higher likelihood to use vasoactive agents (OR = 10.667,95% CI 1.743-65.271, p = 0.001), longer mechanical ventilation duration (OR = 1.011,95% CI 1.002-1.019, p = 0.011), higher likelihood for diagnosis for PCP (OR = 7.50,95% CI 1.288-43.687, p = 0.025), higher SOFA score at ICU admission (OR = 1.183,95% CI 1.012-1.383, p = 0.035), longer duration of CRRT (OR = 1.014,95% CI 1.001-1.028, p = 0.034) contributed to a higher mortality at ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p = 0.595). CONCLUSIONS: There is a high incidence of AKI in HIV-infected patients admitted in our ICU. Patients with severe AKI were more prone to be admitted for CRRT and have a consequent poor prognosis.

2.
J Phys Chem B ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32155068

RESUMO

Ultraviolet radiation induced damage to DNA/RNA can lead to chemical modifications to the nucleosides, and understanding the excited states involved is the key to reveal the mechanism of those reactions. 5-Halogen cytidines are metabolized DNA/RNA nucleoside byproducts that exhibit very important biological functions in the process of nucleic acid methylation as well as DNA/RNA damage repairing. However, despite the accumulation of knowledge about their biological functions, the effects of halogen substitution on the excited states of canonical nucleoside have not received much attention. In this work, the excited-state dynamics of 5-fluorocytidine, 5-chlorocytidine, and 5-bromocytidine is investigated. Excitation at 295 nm results in a bifurcation event that leads to sub-picosecond decay to ground state and population of intramolecular charge transfer states which have several to tens of picosecond lifetimes. The results elucidate the general excited-state relaxation pathways in 5-halogen cytidines, and the intrinsic charge transfer state may affect the halogen bonding that stabilizes DNA and protein structures when 5-halogen cytidines are excited.

3.
Plant Sci ; 292: 110387, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005392

RESUMO

The cyclic electron flow (CEF) around photosystem I (PSI) plays a crucial role in photosynthesis and also functions in plant tolerance of abiotic environmental stress. However, the role of PGR5/PGRL1- and NDH-dependent CEF in tomato under hightemperature (HT) is poorly understood. Here, we assessed the photoprotective effect of these pathways in tomato leaves under HT by using antimycin A (AA) and rotenone (R), which are chemical inhibitors of PGR5/PGRL1- and NDH-dependent CEF, respectively. The results showed that AA treatment caused significantly greater inhibition of CEF under HT compared to R treatment. Moreover, AA treatment caused a greater decrease in maximal photochemistry efficiency (Fv/Fm) and increased damage to the donor and acceptor side of photosystem II (PSII); however, the limitation of the acceptor side in PSI [Y(NA)] was significantly increased. In addition, thylakoid membrane integrity was compromised and reactive oxygen species, proton gradient (ΔpH), antioxidant enzyme activity, and the expression of photosystem core subunit genes were significantly decreased under AA treatment. These findings indicate that PGR5/PGRL1-dependent CEF protects PSII and PSI from photooxidative damage through the formation of ΔpH while maintaining thylakoid membrane integrity and normal gene expression levels of core photosystem components. This study demonstrates that PGR5/PGRL1-dependent CEF plays a major role in HT response in tomato.

4.
Biosens Bioelectron ; 154: 112073, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056968

RESUMO

With the function of mediating intercellular communication between cells, extracellular vesicles (EVs) have been intently studied for their physiopathology and clinical application values. However, efficient EV isolation from biological fluids remains a significant challenge. To address this, this work constructs a new microvortex chip that can isolate EVs efficiently by integrating the lipid nanoprobe modified Morpho Menelaus (M. Menelaus) butterfly wing into microfluidic chip. M. Menelaus wing is well known for its orderly arranged periodic nanostructures and can generate microvortex when liquid passes through it, leading to increased interaction between EVs and M. Menelaus wing. In addition, the nanoprobe containing lipid tails can be inserted into EVs through their lipid bilayer membrane structure. Based on the described properties, high-throughput enrichment of EVs with over 70% isolation efficiency was realized. Moreover, it was demonstrated that the nanoprobe system based on M. Menelaus wing enabled downstream biological analysis of nucleic acids and proteins in EVs. Microvortex chips showed potential application value in efficient EV isolation for biomedical research and cancer diagnosis.

5.
Microvasc Res ; 130: 103990, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088162

RESUMO

BACKGROUND: Assessment of the coronary microcirculation remains challenging. OBJECTIVE: we explored the feasibility of evaluating the coronary microvasculature in rats with myocardial infarction (MI) using a three-dimensional visualization technique. METHODS: Animals were divided into the sham operation group (S), MI 45 min group (M45), and MI 180 min group (M180). Opened microvessels were labelled with the fluorescent dye DiI (1, 1'-dioctadecyl-3, 3, 3'3'-tetramethylindo carbocyanine perchlorate) using a heart perfusion method. The microvascular distribution and opening status were observed under laser scanning confocal microscopy, which was adjusted to facilitate evaluation of subjects around 6 to 20 µm. RESULTS: Microvascular vessels (6-20 µm) were successfully labelled by DiI. Intact and clear three-dimensional microvascular structures were observed in myocardium of sham rats and remote non-infarct myocardial tissue of MI rats, while there was almost no microvascular structure in the infarct area of the M45 group, and only a small amount of microvascular visualization was visualized in the infarct area of the M180 group. The microvascular area and microvascular density in M45 group and M180 group in the infarct border zone were significantly lower than corresponding area in S group. CONCLUSION: Three-dimensional visualization of opened coronary microvascular vessels is feasible in DiI-labelled myocardium in this rat MI model. This novel technique might be useful for defining the underlying mechanisms of coronary microvascular diseases and observe the efficacy of various therapy strategies on coronary microvessels.

6.
Aging (Albany NY) ; 12(4): 3298-3311, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32062612

RESUMO

BACKGROUND: Berberine (BBR) has gained considerable attention because of its anti-tumor activity. BBR can induce apoptosis of acute lymphoblastic leukemia (ALL) cells through the MDM2/p53 pathway. However, the effects of BBR on those ALL patients with p53 deficiency remain unclear. RESULTS: We found that BBR reduced ALL cell viability and induced apoptosis in p53-null EU-4 and p53-mutant EU-6 cells by downregulating X-linked inhibitor of apoptosis protein (XIAP), which is increased in ALL tissues and cells. BBR-induced cell apoptosis was attenuated by inhibition of XIAP that was controlled by PIM-2. Mechanistic studies showed that BBR treatment induced an enhancement of miR-24-3p. PIM-2 is a direct target of miR-24-3p. Blockade of PIM-2 or miR-24-3p reversed BBR-induced cell apoptosis. In vivo studies, BBR remarkably alleviated leukemia conditions in a EU4 xenograft mouse model, whereas inhibition of miR-24-3p significantly reversed the effects of BBR in the leukemia condition. CONCLUSIONS: miR-24-3p/PIM-2/XIAP signaling contributes to BBR-mediated leukemia mitigation in p53-defect ALL, which should be further developed as a treatment strategy in ALL patients with p53 deficiency. METHODS: Cell viability and apoptosis were determined using CCK-8 and TUNEL assays, respectively. The dual-luciferase reporter gene system was used to determine the interaction between miR-24-3p and 3'-untranslated regions (UTRs) of PIM-2.

7.
J Cancer Res Clin Oncol ; 146(2): 367-379, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31953613

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) play crucial roles in the regulation and treatment of multiple myeloma (MM). The objective of this research was to study the functional mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in MM. METHODS: MALAT1, microRNA-1271-5p (miR-1271-5p), and SRY-Box 13 (SOX13) levels were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, and invasion were respectively assayed using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), flow cytometry, and transwell assay. Glycolysis was evaluated by glucose consumption, lactate production, ATP/ADP ratio, and the detection of related enzymes. Associated proteins were measured using Western blot. Target relation was verified via dual-luciferase reporter assay. Xenograft tumor assay was implemented to study the influence of MALAT1 on MM in vivo. RESULTS: The up-regulation of MALAT1 and the down-regulation of miR-1271-5p were found in MM serums and cells. MALAT1 knockdown suppressed cell viability, invasion, and glycolysis while expedited cell apoptosis in MM cells. MALAT1 directly targeted miR-1271-5p and miR-1271-5p depression reverted the effects of MALAT1 knockdown on MM cells. SOX13 was a target of miR-1271-5p and SOX13 overexpression weakened the effects of miR-1271-5p on MM. MALAT1 indirectly modulated SOX13 expression through targeting miR-1271-5p. MALAT1 down-regulation inhibited MM growth by miR-1271-5p/SOX13 axis in vivo. CONCLUSION: LncRNA MALAT1 expedited MM tumorigenesis, invasion, and glycolysis via miR-1271-5p/SOX13 axis. MALAT1 might contribute to the therapy of MM as a promising indicator.


Assuntos
Autoantígenos/metabolismo , MicroRNAs/metabolismo , Mieloma Múltiplo/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição SOXD/metabolismo , Animais , Autoantígenos/genética , Carcinogênese , Estudos de Casos e Controles , Linhagem Celular Tumoral , Glicólise , Xenoenxertos , Humanos , Camundongos , MicroRNAs/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Invasividade Neoplásica , RNA Longo não Codificante/genética , Fatores de Transcrição SOXD/genética
8.
Cell Biochem Funct ; 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31930546

RESUMO

Chemotherapy resistance has become a hold back and major clinical challenge in osteosarcoma cancer. The alteration and subcellular distribution of apurinic/apyrimidinic endonuclease 1 (APE1) has been reported to be involved in chemotherapy resistance in many cancers. Here, we report that the cytoplasmic distribution of APE1 plays a key role in the sensitivity of combination platinum chemotherapy in osteosarcoma. Interestingly, the prevalence of cisplatin-induced DNA damage and apoptosis in low cytoplasmic APE1 osteosarcoma cell lines was higher than in high expression of cytoplasmic APE1 cell lines. Overexpression of cytoplasmic APE1 protected the osteosarcoma cells from CDDP-induced apoptosis. In addition, clinical data also show that the level of cytoplasmic APE1 was negatively associated with sensitivity to combination chemotherapy of cisplatin in osteosarcoma patients. Our findings suggest that cytoplasmic APE1 plays a significant role in chemotherapy resistance. This role is a supplement to the extranuclear function of APE1, and cytoplasmic APE1 expression level could be a promising predictor of platinum treatment prognosis for osteosarcoma patients.

9.
Clin Cancer Res ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911545

RESUMO

BACKGROUND: Tumor genomic features have been of particular interest because of their potential impact on the tumor immune microenvironment and response to immunotherapy. Due to the substantial heterogeneity, an integrative approach incorporating diverse molecular features is needed to characterize immunological features underlying primary resistance to immunotherapy and for the establishment of novel predictive biomarkers. METHODS: We developed a pan-cancer deep machine-learning model integrating tumor mutation burden, microsatellite instability and somatic copy number alterations to classify tumors of different types into different genomic clusters, assessed the immune microenvironment in each genomic cluster and the association of each genomic cluster with response to immunotherapy. RESULTS: Our model grouped 8,646 tumors of 29 cancer types from the Cancer Genome Atlas into four genomic clusters. Analysis of RNA-sequencing data revealed distinct immune microenvironment in tumors of each genomic class. Furthermore, applying this model to tumors from two melanoma immunotherapy clinical cohorts demonstrated that patients with melanoma of different genomic classes achieved different benefit from immunotherapy. Interestingly, tumors in cluster 4 demonstrated a cold immune microenvironment and lack of benefit from immunotherapy despite high microsatellite instability burden. CONCLUSION: Our study provides a proof-for-principle that deep learning modeling may have the potential to discover intrinsic statistical cross-modality correlations of multifactorial input data to dissect the molecular mechanisms underlying primary resistance to immunotherapy, which likely involves multiple factors from both the tumor and host at different molecular levels.

10.
Cell Signal ; 69: 109543, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31958511

RESUMO

The gene trim7 encodes at least four isoforms Glycogenin-interacting protein 1 (GNIP1), GNIP2, GNIP3 and Tripartite motif containing 7 (TRIM7). GNIP1, the longest isoform, has been reported acting as an oncogene. However, it is very interesting that TRIM7, the shortest isoform, only 15 amino acids different from GNIP1 in C-terminal, acts in a completely different way from that of GNIP1 in our present study. TRIM7 expression was decreased in tumor compared with adjacent normal tissues, and the level of TRIM7 was negatively correlated with clinical stage of 94 patients with lung cancer. In vitro, TRIM7 dramatically inhibited the proliferation and migration of tumor cells, and promoted cell apoptosis. Further study showed that TRIM7 interacted with p65 via its C-terminal which is different from GNIP1. The interaction between TRIM7 and p65 promoted the ubiquitination of p65 and finally accelerated the degradation of p65 via 26S proteasome. In vivo, the tumor volume and weight were decreased by TRIM7 stable expression. Meanwhile, Ki67 was down-regulated, thyroid transcription factor 1 (TTF-1) and Caspase 3 were up-regulated in TRIM7 overexpression group in xenograft model. It is very impressive that TRIM7t (a truncated TRIM7 without C-terminal sequence that different with GNIP1) had little effect on the tumor growth in vivo. These findings highlight a curious mechanism for negative regulation of NF-kappa B signaling pathway by TRIM7 and demonstrate that TRIM7 would be a potential therapeutic target for lung cancer.

11.
J Exp Bot ; 71(1): 435-449, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31616940

RESUMO

Soluble carbohydrates not only directly affect plant growth and development but also act as signal molecules in processes that enhance tolerance to cold stress. Raffinose family oligosaccharides (RFOs) are an example and play an important role in abiotic stress tolerance. This study aimed to determine whether galactinol, a key limiting factor in RFO biosynthesis, functions as a signal molecule in triggering cold tolerance. Exposure to low temperatures induces the expression of galactinol synthase (AnGolS1) in Ammopiptanthus nanus, a desert plant that survives temperatures between -30 °C to 47 °C. AnGolS1 has a greater catalytic activity than tomato galactinol synthase (SlGolS2). Moreover, SlGolS2 is expressed only at low levels. Expression of AnGolS1 in tomato enhanced cold tolerance and led to changes in the sugar composition of the seeds and seedlings. AnGolS1 transgenic tomato lines exhibited an enhanced capacity for ethylene (ET) signaling. The application of galactinol abolished the repression of the ET signaling pathway by 1-methylcyclopropene during seed germination. In addition, the expression of ERF transcription factors was increased. Galactinol may therefore act as a signal molecule affecting the ET pathway.

12.
Biosci Trends ; 13(6): 469-475, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31866615

RESUMO

Significant advances in our understanding of neutrophil biology were made in the past several years. A newly discovered mechanism was discovered, the formation of neutrophils extracellular traps (NETs). The structure of NETs is composed of the DNA strand and neutrophil granule proteins. NETs were found to have an association with tumor progression. This review highlights the latest knowledge about the controversial effect on tumors of NETs. Pro-tumor and anti-tumor effects are described respectively. The probable mechanisms of the anti-tumor effect are related to its direct killing of cancer cells or stimulation of the immune system to fight against the tumor. The pro-tumor effect has a correlation with matrix metalloproteinase 9 (MMP-9), cathepsin G, and neutrophil elastase (NE). Moreover, the structure of the NETs makes it able to catch the circulating tumor cells, which could lead to metastasis. This review summarizes our knowledge about the proven roles of NETs in the progression of cancer with particular focus on the components of the NETs, and considers NETs as a potential target for cancer therapy.

13.
Life Sci ; 242: 117228, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881227

RESUMO

AIMS: Berberine (BBR) is reported to induce apoptosis and inhibit migration of leukemic cells, but the underlying pharmacological mechanisms have not been fully revealed. This study aims to investigate the possible mechanisms from the perspective of autophagy. MAIN METHODS: P-53-null leukemic cell lines Jurkat and U937 were used for the in vitro study. MDC staining was used for observation of autophagy in leukemic cells, and Western blot analysis was for determination of the expression levels of autophagy-associated proteins. Apoptosis of the leukemic cells was detected by flow cytometry. Cellular location of MDM2 was observed with immunofluorescence staining. Ubiquitination of MDM2 was assessed by immunoprecipitation. Male 6-8-week-old NOD/SCID mice were used for evaluating the effect of BBR on chemotherapy sensitivity in vivo. KEY FINDINGS: BBR induced autophagy in p53-null leukemic cells, which was inhibited by autophagy inhibitors 3-methyladenine. 3-methyladenine also inhibited BBR-induced apoptosis in leukemic cells. In addition, BBR not only decreased MDM2 mRNA expression, but also enhanced MDM2 self-ubiquitination in leukemic cells. Forced overexpression of MDM2 reversed the effect of BBR on autophagy and apoptosis. Furthermore, BBR promoted doxorubicin-induced autophagy and cell death in the leukemic cells and overexpression of MDM2 suppressed these effects. In vivo, BBR combined with doxorubicin achieved better therapeutic effect than doxorubicin alone. SIGNIFICANCE: MDM2 inhibits autophagy and apoptosis in leukemic cells in a p53-independent manner. BBR induces autophagy in p53-null leukemic cells through downregulating MDM2 expression at both transcriptional and post-transcriptional levels, which may contribute to the anti-cancer effect of BBR in leukemia.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Berberina/farmacologia , Células Jurkat/efeitos dos fármacos , Leucemia Experimental/tratamento farmacológico , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Células U937/efeitos dos fármacos , Animais , Western Blotting , Citometria de Fluxo , Imunofluorescência , Humanos , Células Jurkat/metabolismo , Leucemia Experimental/metabolismo , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Células U937/metabolismo , Ubiquitinação
14.
Mater Sci Eng C Mater Biol Appl ; 106: 110156, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753375

RESUMO

The silver contained coatings on cast Cobalt Chrome (CoCr) alloys were prepared by vacuum plasma spraying technique. The Scanning Electron Microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray Diffraction (XRD), energy dispersive spectrometry (EDS), properties of corrosion resistance, wear resistance and effect of vitro antibacterial on the surface of silver contained coating were investigated. The cytotoxicity of the coatings was performed with L-929 fibroblasts by MTT assay. SEM showed that the surfaces of the coatings were dense, smooth, no obvious cracks except only a few pores. XRD analysis indicated that the contents of the surface were mainly Ag and Cr except a small amount of Ag2O, Cr2O3. EDS analysis indicated that the distributions of Cr and Ag were uniform without any large-scale clustering. The wear resistance of silver coatings is similar to that of CoCr alloys, and the corrosion resistance is slightly better than that of CoCr alloys. The Ag coating had no significant effect on the proliferation of L929 cells. The antibacterial results indicated that the number of S. mutans and C. albicans were significantly reduced on the surface of silver contained coating than that of CoCr alloys. All the results indicated that the silver contained coatings can be achieved by vacuum plasma spraying technique with good surface characteristic and antibacterial properties and have promising applications in biomedical area.

15.
J Am Chem Soc ; 141(51): 20424-20433, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31791120

RESUMO

The development of catalysts based on earth abundant metals in place of noble metals is becoming a central topic of catalysis. We herein report a cobalt/tetraphosphine complex-catalyzed homogeneous hydrogenation of polar unsaturated compounds using an air- and moisture-stable and scalable precatalyst. By activation with potassium hydroxide, this cobalt system shows both high efficiency (up to 24 000 TON and 12 000 h-1 TOF) and excellent chemoselectivities with various aldehydes, ketones, imines, and even N-heteroarenes. The preference for 1,2-reduction over 1,4-reduction makes this method an efficient way to prepare allylic alcohols and amines. Meanwhile, efficient hydrogenation of the challenging N-heteroarenes is also furnished with excellent functional group tolerance. Mechanistic studies and control experiments demonstrated that a CoIH complex functions as a strong hydride donor in the catalytic cycle. Each cobalt intermediate on the catalytic cycle was characterized, and a plausible outer-sphere mechanism was proposed. Noteworthy, external inorganic base plays multiple roles in this reaction and functions in almost every step of the catalytic cycle.

16.
J Nutr Sci Vitaminol (Tokyo) ; 65(5): 390-398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666475

RESUMO

Vitamin D deficiency (VDD) is common in tuberculosis (TB) and may be implicated in the etiology of the disease and in its clinical course. The aim of this study was to investigate the association between leptin, inflammatory markers and VD status in TB patients, stratified for presence or absence of diabetes mellitus (DM). Two hundred ninety-nine TB patients were recruited from October 2015 to August 2016. Also, 91 normal controls were included. The information including socio-demographics, dietary intake and living habits was obtained by face-to-face interview. Serum concentrations of leptin and TNF-α, CRP and IL-6 were compared between TB patients with and without severe VDD (SVDD). Pearson's correlation was used to analyze the association between TNF-α, leptin and 25-hydroxyvitamin D (25(OH)D). A significantly higher prevalence of VDD and SVDD was observed in TB patients compared with normal controls (93.0% vs 70.3%, 65.9% vs 3.3% respectively). Concentration of leptin was significantly lower, while TNF-α higher in TB patients with SVDD compared to those without (p<0.05). After adjustment for confounders, leptin was positively associated with 25(OH)D (r=0.210, p=0.002) with similar correlation in TB patients with DM (r=0.240, p=0.020). A negative association between TNF-α and 25(OH)D was observed (r=-0.197, p=0.003), which was significant only in the subgroup without DM (r=-0.304, p=0.001). Our findings indicate that a higher VD status in TB patients may be related to higher immune activity and less serious tissue damage, and that this relation is different according to presence or absence of DM co-morbidity.

17.
Clin Infect Dis ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549147

RESUMO

BACKGROUND: The emergence of multidrug-resistant tuberculosis (MDR-TB) poses a serious obstacle to global TB control programmes. METHODS: We carried out a prospective, randomised multicenter study in China focused on the potential of shorter regimen containing clofazimine (CFZ) for the treatment of MDR-TB. 135 MDR-TB cases met eligibility requirements and were randomly stratified into control group or experimental group. Patients in the control group received 18-month treatment regimen, whereas patients in the experimental group received 12-month treatment regimen containing CFZ. RESULTS: At the completion of treatment period, the difference in sputum-culture conversion between the experimental group and the control group was not significant. Notably, by the end of the 3-month treatment, 68.7% patients receiving experimental regimen had sputum-culture conversion as compared with 55.9% of those receiving control regimen; this was a significant difference, suggesting an early sputum conversion (P=0.04). 67 adverse events were reported in 56 patients in this study, including 32 in the control group and 35 in the experimental group, respectively. No significant difference in the overall incidence of adverse events was observed between the two groups. CONCLUSION: The MDR-TB patients initiated with the shorter regimen containing CFZ have a comparable successful outcome rate when compared to those with the standard regimen. The patients assigned in the experimental group achieve more rapid sputum culture conversion, reflecting the superior antimicrobial activity against MDR-TB.

18.
Technometrics ; 61(2): 176-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485090

RESUMO

Classification problems are commonly seen in practice. In this paper, we aim to develop classifiers that can enjoy great interpretability as linear classifiers, and at the same time have model flexibility as nonlinear classifiers. We propose convex bidirectional large margin classifiers to fill the gap between linear and general nonlinear classifiers for high dimensional data. Our method provides a new data visualization tool for classification of high dimensional data. The obtained bilinear projection structure makes the proposed classifier very interpretable. Additional shrinkage to approximate variable selection is also considered. Through analysis of simulated and real data in high dimensional settings, our method is shown to have superior prediction performance and interpretability when there are potential subpopulations in the data. The computer code of the proposed method is available as supplemental materials.

19.
J Clin Invest ; 129(10): 4261-4275, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483289

RESUMO

Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum. Low amounts of MDSCs at birth predicted the development of severe pathology in preterm infants - necrotizing enterocolitis (NEC). In vitro treatment of newborn neutrophils and monocytes with LF converted these cells to MDSCs via the LRP2 receptor and activation of the NF-κB transcription factor. Decrease in the expression of LRP2 was responsible for the loss of sensitivity of adult myeloid cells to LF. LF-induced MDSCs (LF-MDSCs) were effective in the treatment of newborn mice with NEC, acting by blocking inflammation, resulting in increased survival. LF-MDSCs were more effective than treatment with LF protein alone. In addition to affecting NEC, LF-MDSCs demonstrated potent ability to control ovalbumin-induced (OVA-induced) lung inflammation, dextran sulfate sodium-induced (DSS-induced) colitis, and concanavalin A-induced (ConA-induced) hepatitis. These results suggest that cell therapy with LF-MDSCs may provide potent therapeutic benefits in infants with various pathological conditions associated with dysregulated inflammation.

20.
Cancer Manag Res ; 11: 7047-7063, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440093

RESUMO

Purpose: This study screened serum proteins to identify potential biomarkers for childhood B-cell and T-cell acute lymphoblastic leukemia (ALL). Patients and methods: Serum collected from 20 newly diagnosed B-cell ALL, 20 T-cell ALL and 20 healthy children. The peptides from these samples were subjected to iTRAQ. Differentially expressed proteins (DEPs) were further validated by ELISA in 24 B-ALL, 24 T-ALL, and 24 healthy children. Results: Bioinformatics analysis revealed several pathways, including atherosclerosis signaling, interleukin signaling and production in macrophages and clathrin-mediated endocytosis signaling, that were closely related to childhood T-cell ALL. Furthermore, four selected proteins, namely LRG1, S100A8, SPARC and sL-selectin, were verified by ELISA. These results were consistent with the results of the proteomics analysis. Conclusion: Serum S100A8 may serve as new diagnostic biomarkers in childhood B-cell ALL and T-cell ALL.

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