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1.
BMC Pregnancy Childbirth ; 19(1): 420, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744468

RESUMO

BACKGROUND: Antenatal depression (AD) is considered as one of the major health burdens and has adverse effects on the outcome of expectant mothers and newborns. The present study aims to investigate the prevalence of antenatal depression (AD), and to explore the potential risk factors of AD among pregnant women in Chengdu, including personal background, related social factors, family factors and cognitive factors. METHODS: The prospective nested case-control study included pregnant women who were in their second pregnancy and attended prenatal care at three tertiary hospitals and one regional hospital in Chengdu, China, between March 2015 and May 2016. Self-designed questionnaires were given to participants in their second and third trimesters to collect information on clinical and demographic characteristics, and a modified edition of Edinburgh Postnatal Depression Scale (EPDS) were used to measure AD. The logistic regression was applicated in analyses. RESULTS: A total of 996 pregnant women were included in analysis. Ninety-three women suffered from AD symptoms only in their second trimester, 96 only in their third trimester, and 107 displayed persistent depression in both trimesters. In the univariate analyses, age and marital relationships were linked with AD occurrence in both second and third trimester. In addition, increasing age, full-time job, higher education level, and no gender preference of spouse were associated with reduced persistent depression. Multivariate analysis showed that gender preference and marital relationship were the potential risk factors of persistent depression. CONCLUSIONS: Age, marital relationship relationships, with parents-in-law, the negative recognition of this pregnancy and husband's gender preference were found as risk factors of AD occurrence in some specific trimester. Gender preference of husbands and marital relationships were independently associated with persistent depression. These findings suggest that stronger family support can help improve mental health of pregnant women.

2.
Int J Oncol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31746424

RESUMO

A growing body of evidence indicates that S100 calcium­binding protein A8 (S100A8) is frequently overexpressed in malignant tumor tissues and regulates tumor progression; however, the role of S100A8 in cholangiocarcinoma (CCA) remains unclear. The present study demonstrated that the protein expression of S100A8 was significantly higher in pathological tissues compared with adjacent normal tissues from patients with CCA. In addition, S100A8 expression was significantly associated with differentiation, lymph node metastasis and poor prognosis in patients following surgical resection of CCA. Furthermore, both in vitro and in vivo experiments revealed that overexpression of S100A6 promoted, while S100A8 knockdown attenuated, the migration and metastasis of CCA cells. Of note, the present results indicated that S100A8 promoted the CCA tumor cell­induced migration of vascular endothelial cells. Finally, S100A8 was demonstrated to positively regulate the expression of vascular endothelial growth factor (VEGF) in CCA cells, which was mediated by activation of the Toll­like receptor 4 (TLR4)/NF­κB pathway. In conclusion, the present study demonstrated that S100A8 had an important role in facilitating CCA cell migration and metastasis via upregulation of VEGF expression by activating the TLR4/NF­κB pathway. These findings may provide a novel target for CCA treatment.

3.
Cell Death Differ ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700144

RESUMO

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play important roles in human diseases, including cancer; however, only a few of them have been experimentally validated and functionally annotated. Here, we identify a novel lncRNA that we term HITT (HIF-1α inhibitor at translation level). HITT is commonly decreased in multiple human cancers. Decreased HITT is associated with advanced stages of colon cancer. Restoration of the expression of HITT in cancer cells inhibits angiogenesis and tumor growth in vivo in an HIF-1α-dependent manner. Further study reveals that HITT inhibits HIF-1α expression, mainly by interfering with its translation. Mechanically, HITT titrates away YB-1 from the 5'-UTR of HIF-1α mRNA via a high-stringency YB-1-binding motif. The reverse correlation between HITT and HIF-1α expression is further validated in human colon cancer tissues. Moreover, HITT is one of the most altered lncRNAs upon the hypoxic switch and HITT downregulation is required for hypoxia-induced HIF-1α expression. We further demonstrate that HITT and HIF-1α form an autoregulatory feedback loop where HIF-1α destabilizes HITT by inducing MiR-205, which directly targets HITT for degradation. Together, these results expand our understanding of the cancer-associated functions of lncRNAs, highlighting the HITT-HIF-1α axis as constituting an additional layer of regulation of angiogenesis and tumor growth, with potential implications for therapeutic targeting.

4.
Proc Natl Acad Sci U S A ; 116(42): 20938-20946, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31575748

RESUMO

Plants are vulnerable to disease through pathogen manipulation of phytohormone levels, which otherwise regulate development, abiotic, and biotic responses. Here, we show that the wheat pathogen Xanthomonas translucens pv. undulosa elevates expression of the host gene encoding 9-cis-epoxycarotenoid dioxygenase (TaNCED-5BS), which catalyzes the rate-limiting step in the biosynthesis of the phytohormone abscisic acid and a component of a major abiotic stress-response pathway, to promote disease susceptibility. Gene induction is mediated by a type III transcription activator-like effector. The induction of TaNCED-5BS results in elevated abscisic acid levels, reduced host transpiration and water loss, enhanced spread of bacteria in infected leaves, and decreased expression of the central defense gene TaNPR1 The results represent an appropriation of host physiology by a bacterial virulence effector.

5.
Eur J Gastroenterol Hepatol ; 31(11): 1313-1321, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567616

RESUMO

Monocytes originating from bone marrow play a key role in the inflammatory response. Divergent findings regarding the prognostic value of inflammatory factors like absolute monocyte count (AMC) in colorectal cancer (CRC) exist in the current literature. Thus, we sought to perform a systemic meta-analysis to comprehensively estimate whether the peripheral AMC affects the clinical outcome of CRC patients. A comprehensive literature search was performed in PubMed, Web of Science and EMBASE last updated to 23 December 2018, to identify studies reporting the prognostic value of AMC in patients with CRC. Hazard ratios and corresponding 95% confidence intervals (CIs) or P values were used as the effect size estimates for clinical outcomes including overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS) and progression-free survival (PFS) with the random-effect inverse variance weighted method. The potential heterogeneity was assessed with Q test and I statistics. Subgroup analyses with respect to some clinicopathological parameters were conducted. A total of 16 clinical studies comprising 3826 patients were included for analysis. Pooled analyses revealed that CRC patients with elevated AMC were significantly associated with worse OS (hazard ratio = 1.708, 95% CI: 1.480-1.971, P < 0.001), DFS (hazard ratio = 1.817, 95% CI: 1.289-2.560, P = 0.001), CSS (hazard ratio = 1.551, 95% CI: 1.187-2.027, P = 0.001) and PFS (hazard ratio = 1.487, 95% CI: 1.259-1.756, P < 0.001). In addition, subgroup analyses provided more information and demonstrated the prognostic effect of elevated preoperative AMC in patients with CRC. There were no significant heterogeneity and publication bias. In conclusion, elevated AMC seems to be served as an unfavorable and robust predicative indicator in CRC patients.

6.
iScience ; 20: 392-401, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31622880

RESUMO

We identify dynamic topological phenomena such as dynamic Chern numbers and dynamic quantum phase transitions in quantum quenches of the non-Hermitian Su-Schrieffer-Heeger Hamiltonian with parity-time (PT) symmetry. Their occurrences in the non-unitary dynamics are intimately connected with fixed points in the Brillouin zone, where the density matrices do not evolve in time. Based on our theoretical formalism characterizing topological properties of non-unitary dynamics, we prove the existence of fixed points for quenches between distinct static topological phases in the PT-symmetry-preserving regime, thus unveiling the interplay between dynamic topological phenomena and PT symmetry. Interestingly, non-Hermiticity of the driving Hamiltonian gives rise to rich dynamic topological phenomena which are different, either qualitatively or quantitatively, from their counterparts in unitary dynamics. Our work sheds light on dynamic topological phenomena in open systems and is readily accessible in experiments.

7.
BMC Med Genomics ; 12(1): 135, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619233

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. METHODS: In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. RESULTS: The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer-associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. CONCLUSIONS: Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.

8.
Ecotoxicology ; 28(10): 1150-1159, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31620949

RESUMO

Cadmium (Cd) exposure is harmful to amphibians in natural environments and the Cd concentration is a key parameter in water monitoring. Cd pollution has been a severe issue in the Yangtze River and its southern reaches in recent years. Acute toxicity assays were employed to determine the tolerance limits of Cd for Microhyla fissipes tadpoles and five different concentrations of Cd (0, 50, 100, 200 and 300 µg/L) were involved to detect its chronic effects on metamorphosis, growth, locomotion, genotoxicity and enzymatic activities of M. fissipes tadpoles. The results showed that the 24-h and 48-h LC50 values of Cd on M. fissipes tadpoles were 2591.3 µg/L and 1567.9 µg/L, respectively, and the presumable non-lethal concentration obtained was 172.2 µg/L. During the 70-day chronic toxicity assays, Cd showed negative impacts on survival, growth, metamorphosis and the frequency of erythrocytes nuclear abnormality of M. fissipes tadpoles. However, the Cd exposure caused the increased body size and condition of tadpoles at complete metamorphosis (GS46). The tadpoles exposed to 200 µg/L of Cd exhibited degraded locomotor performance at GS46. Weight increments of tadpoles were inhibited at Day 14 and massive deaths were observed over the next 14 days. The enzymatic activities of tadpoles experienced a shock response stage (GS30-GS35) and a complete recovery stage (GS36-GS41) in all treatments. However, the enzymatic activities (except alkaline phosphatase) of tadpoles at GS46 increased after Cd exposure, especially at high concentrations. In summary, Cd is a threat to M. fissipes tadpoles as that causes reduced fitness.

9.
Hum Mutat ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31660661

RESUMO

We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (NM_001267550.1:c.39974-11T>G), inherited in trans with a second pathogenic TTN variant. Muscle-derived RNA studies of three individuals confirmed mis-splicing induced by the c.39974-11T>G variant; in-frame exon 214 skipping or use of a cryptic 3' splice-site effecting a frameshift. Confounding interpretation of pathogenicity is the absence of exons 213-217 within the described skeletal muscle TTN N2A isoform. However, RNA-sequencing from 365 adult human gastrocnemius samples revealed 56% specimens predominantly include exons 213-217 in TTN transcripts (inclusion rate ≥ 66%). Further, RNA-sequencing of five fetal muscle samples confirms 4/5 specimens predominantly include exons 213-217 (fifth sample inclusion rate 57%). Importantly, contractures improved significantly with age for four individuals, which may be linked to decreased expression of pathogenic fetal transcripts. Our study extends emerging evidence supporting a vital developmental role for TTN isoforms containing metatranscript-only exons. This article is protected by copyright. All rights reserved.

10.
Ann Clin Transl Neurol ; 6(10): 1980-1988, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31509352

RESUMO

OBJECTIVE: To characterize the natural history and clinical features of myopathies caused by mono-allelic, dominantly acting pathogenic variants in COL12A1. METHODS: Patients with dominant COL12A1-related myopathies were characterized by history and clinical examination, muscle imaging, and genetic analysis. Pathogenicity of the variants was assessed by immunostaining patient-derived dermal fibroblast cultures for collagen XII. RESULTS: Four independent families with childhood-onset weakness due to novel, dominantly acting pathogenic variants in COL12A1 were identified. Adult patients exhibited distal-predominant weakness. Three families carried dominantly acting glycine missense variants, and one family had a heterozygous, intragenic, in-frame deletion of exon 52 of COL12A1. All pathogenic variants resulted in increased intracellular retention of collagen XII in patient-derived fibroblasts as well as loss of extracellular, fibrillar collagen XII deposition. Since haploinsufficiency for COL12A1 is largely clinically asymptomatic, we designed and evaluated small interfering RNAs (siRNAs) that specifically target the mutant allele containing the exon 52 deletion. Immunostaining of the patient fibroblasts treated with the siRNA showed a near complete correction of collagen XII staining patterns. INTERPRETATION: This study characterizes a distal myopathy phenotype in adults with dominant COL12A1 pathogenic variants, further defining the phenotypic spectrum and natural history of COL12A1-related myopathies. This work also provides proof of concept of a precision medicine treatment approach by proposing and validating allele-specific knockdown using siRNAs specifically designed to target a patient's dominant COL12A1 disease allele.

11.
PLoS Genet ; 15(9): e1008272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31513573

RESUMO

Newly emerged wheat blast disease is a serious threat to global wheat production. Wheat blast is caused by a distinct, exceptionally diverse lineage of the fungus causing rice blast disease. Through sequencing a recent field isolate, we report a reference genome that includes seven core chromosomes and mini-chromosome sequences that harbor effector genes normally found on ends of core chromosomes in other strains. No mini-chromosomes were observed in an early field strain, and at least two from another isolate each contain different effector genes and core chromosome end sequences. The mini-chromosome is enriched in transposons occurring most frequently at core chromosome ends. Additionally, transposons in mini-chromosomes lack the characteristic signature for inactivation by repeat-induced point (RIP) mutation genome defenses. Our results, collectively, indicate that dispensable mini-chromosomes and core chromosomes undergo divergent evolutionary trajectories, and mini-chromosomes and core chromosome ends are coupled as a mobile, fast-evolving effector compartment in the wheat pathogen genome.

12.
Mol Immunol ; 114: 629-642, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31542608

RESUMO

Neutrophils are essential to the pathogenesis of many inflammatory diseases. In the autoantibody-mediated K/BxN model of inflammatory arthritis, the alternative pathway (AP) of complement and Fc gamma receptors (FcγRs) are required for disease development while the classical pathway is dispensable. The reason for this differential requirement is unknown. We show that within minutes of K/BxN serum injection complement activation (CA) is detected on circulating neutrophils, as evidenced by cell surface C3 fragment deposition. CA requires the AP factor B and FcγRs but not C4, implying that engagement of FcγRs by autoantibody or immune complexes directly triggers AP C3 convertase assembly. The absence of C5 does not prevent CA on neutrophils but diminishes the upregulation of adhesion molecules. In vivo two-photon microscopy reveals that CA on neutrophils is critical for neutrophil extravasation and generation of C5a at the site of inflammation. C5a stimulates the release of neutrophil proteases, which contribute to the degradation of VE-cadherin, an adherens junction protein that regulates endothelial barrier integrity. C5a receptor antagonism blocks the extracellular release of neutrophil proteases, suppressing VE-cadherin degradation and neutrophil transendothelial migration in vivo. These results elucidate the AP-dependent intravascular neutrophil-endothelial interactions that initiate the inflammatory cascade in this disease model but may be generalizable to neutrophil extravasation in other inflammatory processes.

13.
Stem Cell Res Ther ; 10(1): 279, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470890

RESUMO

OBJECTIVE: Autograft microskin transplantation has been widely used as a skin graft therapy in full-thickness skin defect. However, skin grafting failure can lead to a pathological delay wound healing due to a poor vascularization bed. Considering the active role of adipose-derived stem cell (ADSC) in promoting angiogenesis, we intend to investigate the efficacy of autograft microskin combined with ADSC transplantation for facilitating wound healing in a full-thickness skin defect mouse model. MATERIAL AND METHODS: An in vivo full-thickness skin defect mouse model was used to evaluate the contribution of transplantation microskin and ADSC in wound healing. The angiogenesis was detected by immunohistochemistry staining. In vitro paracrine signaling pathway was evaluated by protein array and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. RESULTS: Co-transplantation of microskin and ADSC potentiated the wound healing with better epithelization, smaller scar thickness, and higher angiogenesis (CD31) in the subcutaneous layer. We found both EGF and VEGF cytokines were secreted by microskin in vitro. Additionally, secretome proteomic analysis in a co-culture system of microskin and ADSC revealed that ADSC could secrete a wide range of important molecules to form a reacting network with microskin, including VEGF, IL-6, EGF, uPAR, MCP-3, G-CSF, and Tie-2, which most likely supported the angiogenesis effect as observed. CONCLUSION: Overall, we concluded that the use of ADSC partially modulates microskin function and enhances wound healing by promoting angiogenesis in a full-thickness skin defect mouse model.

14.
Biofactors ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518024

RESUMO

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.

15.
Molecules ; 24(19)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546621

RESUMO

The state of the art ion mobility quadrupole time of flight (IM-QTOF) mass spectrometer coupled with ultra-high performance liquid chromatography (UHPLC) can offer four-dimensional information supporting the comprehensive multicomponent characterization of traditional Chinese medicine (TCM). Compound Xueshuantong Capsule (CXC) is a four-component Chinese patent medicine prescribed to treat ophthalmic disease and angina. However, research systematically elucidating its chemical composition is not available. An approach was established by integrating reversed-phase UHPLC separation, IM-QTOF-MS operating in both the negative and positive electrospray ionization modes, and a "Component Knockout" strategy. An in-house ginsenoside library and the incorporated TCM library of UNIFITM drove automated peak annotation. With the aid of 85 reference compounds, we could separate and characterize 230 components from CXC, including 155 ginsenosides, six astragalosides, 16 phenolic acids, 16 tanshinones, 13 flavonoids, six iridoids, ten phenylpropanoid, and eight others. Major components of CXC were from the monarch drug, Notoginseng Radix et Rhizoma. This study first clarifies the chemical complexity of CXC and the results obtained can assist to unveil the bioactive components and improve its quality control.

16.
J Neuromuscul Dis ; 6(4): 475-483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31498126

RESUMO

Calpainopathy, also known as limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) or LGMD R1 Calpain3-related, is one of the most common genetically characterized forms of limb-girdle muscular dystrophy with a wide range of phenotypic severity. We evaluated a consanguineous family with a clinical phenotype consistent with calpainopathy in whom conventional sequencing did not detect any mutations in the CAPN3 gene. Using whole exome sequencing paired with haplotype analysis, we identified a homozygous deep intronic single base pair deletion in CAPN3 (c.946-29delT). Familial segregation studies were consistent with recessive inheritance. Immunoblotting of muscle tissue from the patient showed complete absence of calpain 3. In silico analysis predicted the deletion to disrupt the branch point and subsequently alter splicing of exon 7. Studies of patient fibroblasts and muscle tissue confirmed altered splicing, resulting in an inclusion of a 389-bp intronic sequence upstream of exon 7, originating from a cryptic splice acceptor site in intron 6. This out-of-frame insertion results in a premature stop codon, leading to an apparent absence of protein likely due to degradation of the transcript via nonsense-mediated decay. We then designed phosphorodiamidate morpholino oligomers (PMOs) as splice modulators to block the new splice acceptor site. This approach successfully prevented the aberrant splicing - reverting the majority of the splice to the wildtype transcript. These results confirm the pathogenicity of this novel deep intronic mutation and provide a mutation-specific therapeutic strategy. Thus, deep intronic mutations in CAPN3 may be pathogenic and should be considered in the appropriate clinical setting. The identification of mutations which may be missed by traditional Sanger sequencing is essential as they may be excellent targets for individualized therapeutic strategies using RNA-directed splice modulation.

17.
J Cancer Res Ther ; 15(4): 921-926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436253

RESUMO

Aims: ATP-binding cassette subfamily C member 3 (ABCC3) is involved in multidrug resistance and is overexpressed in some solid tumors. Recent work revealed an increase in circulating anti-ABCC3 antibodies in lung and esophageal cancers. This in vitro study was undertaken to investigate the effects of the natural IgG antibody against the ABCC3-derived peptide antigen on proliferation of oral squamous cell carcinoma (OSCC) cells and augment the development of efficient and effective treatments in patients with OSCC. Subjects and Methods: An in-house enzyme-linked immunosorbent assay was applied to detect anti-ABCC3 IgG antibody in human plasma. Two OSCC cell lines, CAL27 and SCC15, were cultured with 20% plasma either positive or negative for anti-ABCC3 IgG. Cell proliferation was quantified by the CCK-8 method, and cell apoptosis and cell cycle distribution were analyzed by flow cytometry. The expression of the ABCC3 gene in the cell lines was analyzed by reverse transcriptase quantitative real-time polymerase chain reaction. Results: The results showed that plasma anti-ABCC3 IgG significantly inhibited the proliferation of CAL27 cells but not SCC15 cells, although ABCC3 was expressed in both cell lines. The proportion of apoptotic cells was significantly higher in CAL27 cells treated with anti-ABCC3 IgG-positive plasma than in those treated with IgG-negative plasma. Cell cycle progression was arrested in CAL27 cells treated with anti-ABCC3 IgG-positive plasma. Conclusions: Our data suggest that human plasma anti-ABCC3 IgG may be a promising agent in anti-OSCC therapy, although further studies are needed to arrive at a definitive conclusion.

18.
Am J Physiol Cell Physiol ; 317(5): C910-C921, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411917

RESUMO

Activation of calpain 1 (CPN1) and calpain 2 (CPN2) contributes to cardiac injury during ischemia (ISC) and reperfusion (REP). Complex I activity is decreased in heart mitochondria following ISC-REP. CPN1 and CPN2 are ubiquitous calpains that exist in both cytosol (cs)-CPN1 and 2 and mitochondria (mit)-CPN1 and 2. Recent work shows that the complex I subunit (NDUFS7) is a potential substrate of the mit-CPN1. We asked whether ISC-REP led to decreased complex I activity via proteolysis of the NDUFS7 subunit via activation of mit-CPN1 and -2. Activation of cs-CPN1 and -2 decreases mitophagy in hepatocytes following ISC-REP. We asked whether activation of cs-CPN1 and -2 impaired mitophagy in the heart following ISC-REP. Buffer-perfused rat hearts underwent 25 min of global ISC and 30 min of REP. MDL-28170 (MDL; 10 µM) was used to inhibit CPN1 and -2. Cytosol, subsarcolemmal mitochondria (SSM), and interfibrillar mitochondria (IFM) were isolated at the end of heart perfusion. Cardiac ISC-REP led to decreased complex I activity with a decrease in the content of NDUFS7 in both SSM and IFM. ISC-REP also resulted in a decrease in cytosolic beclin-1 content, a key component of the autophagy pathway required to form autophagosomes. MDL treatment protected the contents of cytosolic beclin-1 and mitochondrial NDUFS7 in hearts following ISC-REP. These results support that activation of both cytosolic and mitochondrial calpains impairs mitochondria during cardiac ISC-REP. Mitochondria-localized calpains impair complex I via cleavage of a key subunit. Activation of cytosolic calpains contributes to mitochondrial dysfunction by impairing removal of the impaired mitochondria through depletion of a key component of the mitophagy process.

19.
Nanoscale ; 11(35): 16476-16487, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31453622

RESUMO

Pancreatic cancer is a highly malignant carcinoma with limited effective treatment options, resulting in a poor patient survival rate of less than 5%. In this study, cationic albumin nanoparticles were assembled with negatively charged hyaluronic acid (HA) to achieve a hierarchical nanostructure and efficient delivery of small molecule drugs to the tumor site in the pancreas. A combination of chemotherapy with indoleamine-2,3-dioxygenase (IDO) inhibition was explored to enhance the chemotherapeutic efficacy in vivo. Hydrophobic celastrol (CLT) and hydrophilic 1-methyltryptophan (MT) were concurrently loaded in HA coated cationic albumin nanoparticles (HNPs) with an average size of ∼300 nm. The size of HNPs was reduced in the presence of hyaluronidase to facilitate penetration into deep tumor tissues. Also, the biodistribution study in the C57BL/6 mice xenograft model showed enhanced tumor accumulation and prolonged circulation of HNPs. Compared with CLT solution, the combination of CLT with MT showed significantly enhanced tumor inhibition in both xenograft and orthotopic pancreatic cancer mice models via downregulating the immunosuppressive tumor microenvironment. Taken together, the combination of CLT with MT administered via HNPs represents a highly promising strategy for targeted pancreatic cancer therapy.

20.
Food Res Int ; 124: 86-92, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466654

RESUMO

This study aimed at producing isomaltooligosaccharides in juice blends using orange juice and malt extract and assessing their acceptability. Different blend formulations were prepared and fermented, varying the concentration of orange juice, sucrose and malt extract. Dextransucrase from Weissella cibaria 10 M was used to enzymatically synthesize α(1-6) linked glucan-oligosaccharides by transglycosylation reactions, with maltose as acceptor carbohydrate and sucrose as donor. The optimal yield of oligosaccharides was after 24 h, producing 19.4 g/L of oligosaccharides (degree of polymerization 3) from 36 g/L maltose and 19 g/L sucrose. All the blend proved to be good alternatives for synthesizing isomalto-oligosaccharides with different degrees of polymerization. Sensory analysis showed good average acceptability compared to natural orange juice, achieving scores of around 6 on a 9-point hedonic scale. In a comprehensive analysis, juice blends containing orange juice and malt extract with Weissella cibaria to produce oligosaccharides exhibited good sensory indicators as an innovative prebiotic beverage. A prebiotic oligosaccharide beverage can be produced by enzymatic synthesis of oligosaccharides with different degrees of polymerization.

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