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1.
Food Chem ; 303: 125369, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442902

RESUMO

A well-designed yolk-shell Fe3O4@graphitic carbon (YS-Fe3O4@GC) submicroboxes with a tunable internal cavity were constructed by one-step pyrolysis strategy followed by partially etching, in which the Fe3O4 magnetic core was well confined in compartment of GC submicroboxes. The suitable internal cavity, graphitic carbon shell and large specific surface area, play great roles in improving mass transfer of analytes. Compared to its core-shell structure, the YS-Fe3O4@GC submicroboxes as dispersive magnetic solid-phase extraction (d-MSPE) materials exhibited superior enrichment performance for sulfonamides (SAs). Thus, it was applied to sensitive/simultaneous detection of trace SAs in milk and meat samples, combing with high performance liquid chromatography (HPLC). Under optimized conditions, limits of detection (LODs, 0.11-0.25 µg L-1 for milk and 0.46-2.24 µg kg-1 for meat) and recoveries (77.2-118.0%) were obtained. This work not only offers a facile strategy for the tunable fabrication of yolk-shell architecture, but also successfully affords its exploration as d-MSPE materials.


Assuntos
Análise de Alimentos , Grafite/química , Extração em Fase Sólida/métodos , Sulfonamidas/isolamento & purificação , Animais , Cromatografia Líquida de Alta Pressão , Compostos de Ferro/química , Limite de Detecção , Magnetismo , Carne/análise , Leite/química , Sulfonamidas/análise
2.
Int J Cancer ; 146(1): 248-261, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31144303

RESUMO

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.

3.
J Theor Biol ; 484: 109996, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31491497

RESUMO

BACKGROUND: Gastric cancer (GC) incidence and mortality in China remained high due to delayed diagnosis and accounted for about half of the world's GC cases and deaths. Early detection with endoscopic screening and consequent timely treatment can significantly improve survival. This study aimed to explore the long-term population impact of endoscopic screening on national GC disease burdens in China. METHODS: Most of previous studies investigated the disease burdens of cancer using Markov model or age-period-cohort (APC) model, which are difficult to estimate the population size of undiagnosed cases. In this paper, we proposed a new dynamic compartmental model based on GC natural history and calibrated model outputs to diagnosed GC cases and GC-related death counts using Markov Chain Monte Carlo methods. We investigated the impact of screening strategies with various coverage (10%, 40%, 70%) and frequency (every 1, 3, 5 years) on disease burdens. RESULTS: We estimated that 2.22 (95%CI: 1.97-2.47) million Chinese are living with GC in 2019, among which, 42.7% (40.3-45.0%) remained undiagnosed. Without systematic screening, we projected 10.46 (9.07-11.86) million incident cases and 7.35 (6.59-8.11) million GC-related deaths over the next 30 years (2019-2049). Screening with coverage rate at 10%, 40%, 70% every 3 years could prevent 0.85 (0.63-1.06), 2.32 (1.79-2.86), and 3.04 (2.38-3.70) million incident cases, and prevent 1.17 (1.01-1.32), 3.08 (2.70-3.46), and 3.93 (3.46-4.40) million deaths respectively, compared with 'no screening' scenario. Screening would substantially increase the number of diagnosed GC cases within the first three years of program initiation, but this number would quickly reduce below 'no screening' scenario. Three-yearly screening at the above coverage rates would reduce the proportion of undiagnosed GC cases to 38.8% (36.9-40.7%), 25.5% (23.4-27.6%), and 17.8% (16.0-19.6%) by 2049, respectively. Delaying implementation of the screening program would substantially reduce its effectiveness. CONCLUSIONS: Initiating national endoscopic screening programmes would likely have a major effect on reducing GC incidence and mortality in China. Health resources should be substantially increased and directed to treatment of GC to cope with the initial rise in diagnosed GC cases.

4.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165578, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672550

RESUMO

Atherosclerosis is an inflammatory disease of the arterial wall, which involves endothelial cells and immune cells. Endothelial dysfunction has been considered an important step in the initiation of the disease. TIPE1 is a newly identified protein of the TIPE family, and plays a vital role in inflammation and tumorigenesis. However, its role in atherogenesis remains unclear. In this study, we demonstrated that TIPE1 promoted atherogenesis by inducing endothelial dysfunction. When human umbilical vein endothelial cells (HUVECs) were exposed to oxidative stress, the level of TIPE1 was significantly up-regulated, and the ROS generation markedly increased in TIPE1 over-expressing HUVECs. As a result, the growth of HUVECs was inhibited, and the apoptosis was enhanced. However, the cell contact ability between HUVECs and THP-1 cells were augmented due to the up-regulation of adhesion molecules such as E-selectin and ICAM-1 induced by TIPE1 overexpression. Importantly, ApoE-/- mice injected with TIPE1 recombinant lentivirus developed significantly severe atherosclerosis accompanied by hyperglycemia, hypercholesterolemia and increased white blood count. These findings indicated that excessive ROS induced by the overexpression of TIPE1 in endothelial cells accelerated the process of atherogenesis.

5.
J Cell Physiol ; 235(2): 1674-1688, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31432509

RESUMO

Renal interstitial fibrosis is a key factor in the development of chronic renal diseases, possibly leading to uremia. The present study conducted aimed to assess the hypothesis whether keratin 1 (KRT1) silencing could suppress kidney interstitial fibrosis and glomerular sclerosis via the Notch pathway to alleviate uremic symptoms. Differentially expressed genes associated with uremia were identified using the gene expression omnibus (GEO) database. Uremic rat models were established, in which short hairpin-RNA against KRT1, activators, and inhibitors of the Notch pathway were transfected. To further validate the mechanism of KRT1 in uremia, KRT1 expression, cell apoptosis, glomerular area (GA), and glomerular capillary volume (GV), the score of glomerular sclerosis, and tubulointerstitial injury were assayed and investigated. GEO database revealed that KRT1 was upregulated in uremia and regulated the Notch pathway. GA, GV, cell apoptosis, glomerular sclerosis, and tubulointerstitial injury were typically located in more elevated levels of uremia in rats. KRT1 silencing and Notch pathway inhibition decreased the expression of Jagged1, Notch1, NICD1, Hey1, Hes1, α-SMA, and FN, which further resulted in decreased cell apoptosis, GA, GV, the score of glomerular sclerosis, and tubulointerstitial injury. Subsequently, the effect of KRT1 silencing on uremia was no longer evident once the Notch pathway was activated. The co-localization of high expression KRT1 and Notch1 was found in uremia. In summary, the results identified KRT1 as a key regulator in uremia progression, and KRT1 silencing can suppress glomerular sclerosis and tubulointerstitial injury via inactivation of the Notch pathway in uremic rats.

6.
J Hazard Mater ; 382: 121026, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446355

RESUMO

In this work, 3D hierarchical Cu2SnS3@SnS2 flower assembled from nanopetals with sandwich-like Cu2SnS3-SnS2-Cu2SnS3 double interfacial heterojunction was successfully designed and synthesized on fluoride doped tin oxide (FTO) for photoelectrochemical (PEC) sensor by in situ electrodeposition p-type Cu2SnS3 nanoparticles on both inner and outer surfaces of n-type SnS2 nanopetals. The unique double interfacial heterojunction simultaneously combines 3D flower-like architectures to drastically increase the light trapping and absorption in visible-near infrared range (Vis-NIR), and dramatically inhibites the charge carrier recombination, which is crucial for boosting the PEC activity. Benefitting from the shape and compositional merits, the Cu2SnS3@SnS2 heterojunction possess dual-mode signal by controlling the electrodeposition time to manipulate the composition ratio of Cu2SnS3 and SnS2. The Cu2SnS3@SnS2/FTO electrode not only exhibits excellent photoeletro-reduction capacity for ultra-sensitive sensing trace persistent organic pollutant (nitrobenzene, NB), but also presents photoeletro-oxidization activity for high selective detection of L-cysteine (L-Cys) without any auxiliary enzyme under the light illumination. Dual mode sensor displayed superb performance for the detection of NB/L-Cys, showing a wide linear range from 100 pM to 300 µM/10 nM to 100 µM and a low detection limit (3S/N) of 68 pM/8.5 nM, respectively. Such a tunable double interfacial heterojunction design opened up new avenue for constructing multifunction PEC sensing platform.

7.
Chemosphere ; 239: 124811, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726522

RESUMO

China has been suffering from endemic fluorosis for the past 30 years. This study investigated fluoride concentrations in 10 districts of Tianjin, China, to illustrate their spatial distribution characteristics and potential human health risks. The results showed fluoride concentration of 0.01-6.30 mg L-1 with a mean value of 0.99 mg L-1, and 78.82% of water fluoride reaches the standard for drinking water (1.5 mg L-1). Higher fluoride levels were recorded in deep well pumps supply zones, and more potential changes in fluoride occurred was positively correlated with pH in groundwater. Mean value of fluoride in drinking water in 10 districts followed the order of WQ > BC > JZ > NH > BD > BH > JN > JH > DL > XQ. Estimations of non-carcinogenic risk for drinking water indicated that mean hazard quotient values of fluoride for combined pathways (i.e., oral ingestion and dermal absorption) were >1.0 for all age groups of WQ and BC. The results also showed that the estimated risk primarily came from the ingestion pathway. Risk levels for children varied obviously, generally in the order of 1-4y > 4-7y > 7-9y (years old). In the central tendency center and reasonable maximum exposure conditions, estimated risks were 1.25, 1.12, 0.771 and 3.66, 3.29, 2.27, respectively. The results supply material information for health authorities in fluorosis areas to put forward more efficient policies to control the endemic diseases. Attention should be paid to the formulation of health promotion strategies and measures to reduce fluoride intake in order to protect the health of residents.

8.
Cell Signal ; 65: 109460, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678253

RESUMO

BACKGROUND: Although gankyrin has been identified as a vital regulator of tumorigenesis, its role and regulatory mechanism in osteosarcoma (OS) remain unclear. METHODS: QRT-PCR, western blot and IHC staining were conducted to detect the expression of gankyrin in OS. Pearson's χ² test was adopted to examine the associations between gankyrin expression and clinicopathologic characteristics. Kaplan-Meier method was used to investigate the relationship between gankyrin expression and overall survival of patients with OS. Next, a series of in vitro and in vivo assays were performed to determine the positive feedback loop between gankyrin and YAP in OS. RESULTS: We first reported that gankyrin is upregulated in human OS specimens and cell lines and predicts OS progression and poor prognosis. Furthermore, we demonstrated that gankyrin protects miR-200a-mediated yes-associated protein (YAP) downregulation through p53 and establishes a positive feedback loop to regulate YAP signaling in U2OS and MG63 cells. Intriguingly, gankyrin interacts with YAP to promote OS cell growth in vitro. In addition, our results showed that gankyrin promotes OS tumor growth and regulates YAP levels in vivo. Notably, we also observed a positive correlation between gankyrin and YAP expression in human OS tissues, and co-upregulation of gankyrin and YAP indicated a poor prognosis. CONCLUSIONS: Our results identify that gankyrin acts as an oncogene in OS by forming a positive feedback loop with YAP, and disrupting the gankyrin-YAP regulation may be beneficial for controlling OS tumorigenesis.

9.
Anal Chim Acta ; 1094: 130-135, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761039

RESUMO

Quantification of plasma membrane proteins (PMPs) is crucial for understanding the fundamentals of cellular signaling systems and their related diseases. In this work, a super-quadruplex scaffold was designed to regulate assembly of oligonucleotide-grafted AIEgens for detection of PMPs. The nonfluorescence oligonucleotide-grafted AIEgen (Oligo-AIEgen) was firstly synthesized by attaching the AIEgen to 3'-terminus of the oligonucleotide through click chemistry. Meanwhile, the tetramolecular hairpin-conjugated super-quadruplex (THP-G4) as cleavage element and signal enhancement scaffold composited of three elements: a substrate sequence of DNAzyme in the loop region, partial hybridization region in the stem, and six guanine nucleotides to form G-quadruplex. Once the DNAzyme was anchored on the specific PMPs through aptamer-protein recognition, the substrate sequence on the loop of THP-G4 was cleaved by DNAzyme with the aid of cofactor MnII, resulting in the conformation switch of THP-G4 to the activated G-quadruplex scaffold. The latter could assemble Oligo-AIEgens to generate aggregation-induced emission (AIE) enhancement, resulting in a simple and sensitive strategy for detection of membrane proteins. Moreover, the DNAzyme continuously cut the next THP-G4 to achieve recycling amplification. Under the optimized conditions, this AIE-based strategy exhibited good linear relationship with the logarithm of MUC1 concentration from 0.01 to 10 µg mL-1 with the limit of detection down to 4.3 ng mL-1. The G4-assembled AIEgens provides a universal platform for detecting various biomolecules and a proof-of concept for AIE biosensing.

10.
Chemosphere ; 241: 125101, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31683431

RESUMO

Source diverted blackwater collected from toilets can be anaerobically digested to recover energy. The anaerobically digested blackwater (ADB) contains high levels of ammonium and low carbon to nitrogen (C/N) ratio. In the present study, ADB was treated by a two-stage nitritation-denitrification/anammox process in an integrated fixed film activated sludge-continuous flow reactor (IFAS-CFR). NH4+-N, NO2--N, total nitrogen (TN), and chemical oxygen demand (COD) removal efficiencies were 80%, 82%, 76%, and 78%, respectively. Anaerobic ammonium oxidation (anammox) and denitrification contributed to 44-48%, and 52-56% of total nitrogen removal, respectively. Both of the protein- and humic acid-like matters were removed during the process. An increase in feed load promoted the sustained growth of anammox bacteria-Candidatus Brocadia in the biofilm, as well as an increase of denitrifiers (Pseudomonas, Thermotonus, Phodanobacter, Caulobacter) in both biofilm and suspended biomass, which remained higher in the suspended biomass than in biofilm. Overall, biofilm had higher nitrogen removal efficiency than suspended biomass, while suspended biomass had a higher COD removal efficiency than biofilm.

11.
Opt Express ; 27(22): 31874-31888, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684411

RESUMO

A dual-optimized adaptive Kalman filtering (DO-AKF) algorithm based on back propagation (BP) neural network and variance compensation was developed for high-sensitivity trace gas detection in laser spectroscopy. The BP neural network was used to optimize the Kalman filter (KF) parameters. Variance compensation was introduced to track the state of the system and to eliminate the variations in the parameters of dynamic systems. The proposed DO-AKF algorithm showed the best performance compared with the traditional multi-signal average, extended KF, unscented KF, KF optimized by BP neural network (BP-KF) and KF optimized by variance compensation (VC-KF). The optimized DO-AKF algorithm was applied to a QCL-based gas sensor system for an exhaled CO analysis. The experimental results revealed a sensitivity enhancement factor of 23. The proposed algorithm can be widely used in the fields of environmental pollutant monitoring, industrial process control, and breath gas diagnosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31685422

RESUMO

Colorimetric sensor array is a sensitive, rapid, and inexpensive detection technology which simulates human olfaction system based on various organic dyes. In this work, a sensor array based on acid-sensitive CdTe QDs coupled with chemometrics method was developed and proved to be a rapid, accurate and sensitive method for identification of 32 kinds of Chinese traditional cereal vinegars (CTCV). The specificity of identification of this method was mainly depends on the organic acids and melanoidins of CTCV. Among them, organic acids can quench the fluorescence of QDs through enhancing their electron transfer (hydrogen bond) and resonance energy transfer, and the fluorescence intensity of melanoidin was closely related to the brewing technology and aging year of CTCV. The types and aging time of 32 CTCV can be 100% identified at a dilution of 1000 by partial least squares discriminant analysis, when the latent variables were 4. And only one kind of QDs is needed instead of various organic dyes to this kind of colorimetric sensor array. Except for vinegar, this method can also be used in the identification of other food which rich in organic acid.

13.
Molecules ; 24(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718071

RESUMO

Psoralen (P) and isopsoralen (IP) are the main active ingredients in the dried fruit of Psoralen corylifolia L. (PC), with a wide range of pharmacology activities. The intestinal bacteria biotransformation plays a central role in the metabolism of the complex ingredients in traditional Chinese medicine (TCM). Our study aimed to investigated the metabolic profile of P and IP in the intestinal condition, co-cultured with human fecal bacteria anaerobically. Four bio-transforming products were obtained, including 6,7-furano-hydrocoumaric acid (P-1) and 6,7-furano-hydro- coumaric acid methyl ester (P-2), which transformed from P, and 5,6-furano-hydrocoumaric acid (IP-1) and 5,6-furano-hydrocoumaric acid methyl ester (IP-2), which were transformed from IP. It is worth mentioning that IP-2 is a new compound that has not been published. Their structures were analyzed based on their spectroscopic data. Moreover, a highly sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was used to characterize the metabolic pathways of P, IP, and their bio-transforming products in the reaction samples. In addition, the dampening effects against the oxidative stress of P, IP, and their bio-transforming products by human intestinal flora were estimated in vitro via the human colorectal cells (HCT116) and heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell lines. The results showed that the metabolites have stronger activity than P and IP, which possibly provides a basis for elucidating the treating mechanisms of PC extract against inflammatory bowel disease.

14.
Inorg Chem ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710468

RESUMO

The first open hollow Sn13-oxo cluster family has been successfully prepared and characterized. These Sn13 clusters contain a {Sn7} moiety that is similar to the basic structure unit of rutile SnO2. Interestingly, the Sn13 clusters show labile coordination sites on the edge, which could be functionalized by different ligands. With the different decorated types of functionalized ligands, the open hollow Sn13 clusters present different structural details and framework diameters. The presented results provide a new open hollow structural motif of tin-oxo clusters and also a good platform for their ligand functionalization.

15.
Scand J Immunol ; : e12848, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31713248

RESUMO

The study aimed to retrospectively investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in antinuclear antibodies (ANAs) test samples of western China. Between January 2016 and November 2018, the laboratory data and clinical details of patients with positive anti-RR antibodies were collected and analyzed. The results showed that total of 197227 patients tested, 109453 patients presented with positive ANAs (55.50%), but only 107 patients with positive anti-RR antibodies (0.10%),including 51 females and 56 males. Diagnose were established in 51 of 107 patients: 25 were hepatopathy (HCV 8/25 and HBV 12/25); 13 were autoimmune diseases (AID); and 7 were renal insufficiency; 6 were chronic obstructive pulmonary disease (COPD). We make the conclusions that anti-RR antibodies have a low prevalence, and there is no gender difference. Anti-RR antibodies exist other diseases besides hepatitis C, such as HBV, some autoimmune diseases,renal insufficiency and COPD, which we need further investigation.

16.
J Mater Chem B ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714572

RESUMO

Microneedles are primarily designed for enhancing transdermal drug delivery in a minimally invasive manner. In particular, coated microneedles have attracted increasing attention due to the resulting mode of rapid and highly efficient drug administration. In this study, we developed a novel gelatin/sucrose film-coated poly(ethylene glycol)diacrylate (PEGDA) microneedle patch, which can effectively improve the skin permeability of therapeutic drugs and realize convenient and efficient drug administration. A simple and reliable technique was proposed to produce uniform film coatings on microneedles at room temperature. After introducing a prepolymer solution into the mold cavity, a film-coated microneedle patch was fabricated via a photo-induced polymerization process. Four categories of molecular models, including rhodamine B (RhB), bovine serum albumin (BSA), doxorubicin (DOX) and indocyanine green (ICG), were encapsulated into the gelatin/sucrose film to evaluate their transdermal delivery and therapeutic effects both in vitro and in vivo. The presented methodology represents a facile technique for rapid formation of film-coated microneedles for efficient transdermal delivery of small molecular drugs and large proteins.

17.
Environ Toxicol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714664

RESUMO

Colorectal cancer (CRC) is a major health problem and third most common deaths in western world. Dietary interventions together with modified dietary style can prevent the CRC in humans. Xanthohumol (XHA), a polyphenol isolated from Humulus lupulus L. contains many beneficial effects. The aim of the study is to analyze the effect of XHA on Azoxymethane (AOM)-induced experimental CRC in rats. Levels of MDA were increased and enzymic antioxidants levels were decreased in AOM-induced rats. However, these levels were reversed upon XHA treatment. Further, the mRNA expressions of iNOS and COX-2 were also downregulated in XHA treated rats compared to AOM-induced rats. Further, we found that administration of XHA suppressed the wnt/ß-catenin signaling together with modulation of apoptotic proteins Bax, Bcl-2, and caspase 3. We conclude that XHA can able to quench the free radicals, inhibits cell proliferation and induces apoptosis, thus it can be a chemopreventive/therapeutic agent against CRC.

18.
Cell Death Differ ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666685

RESUMO

The retrosplenial cortex (Rsp) is a transitional cortex located between the neocortex and archicortex, but the molecular mechanism specifying Rsp from the archicortex remains elusive. We here report that the transcription factor Satb2 is required for specifying Rsp identity during its morphogenesis. In Satb2 CKO mice, the boundary between the Rsp and archicortex [i.e., subiculum (SubC)] disappears as early as E17.5, and Rsp efferent projection is aberrant. Rsp-specific genes are lost, whereas SubC-specific genes are ectopically expressed in Rsp of Satb2 CKO mice. Furthermore, cell-autonomous role of Satb2 in maintaining Rsp neuron identity is revealed by inactivation of Satb2 in Rsp neurons. Finally, Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development.

19.
Cell Death Differ ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685978

RESUMO

Cancer cells reprogram their energy metabolic system from the mitochondrial oxidative phosphorylation (OXPHOS) pathway to a glucose-dependent aerobic glycolysis pathway. This metabolic reprogramming phenomenon is known as the Warburg effect, a significant hallmark of cancer. However, the detailed mechanisms underlying this event or triggering this reprogramming remain largely unclear. Here, we found that histone H2B monoubiquitination (H2Bub1) negatively regulates the Warburg effect and tumorigenesis in human lung cancer cells (H1299 and A549 cell lines) likely through controlling the expression of multiple mitochondrial respiratory genes, which are essential for OXPHOS. Moreover, our work also suggested that pyruvate kinase M2 (PKM2), the rate-limiting enzyme of glycolysis, can directly interact with H2B in vivo and in vitro and negatively regulate the level of H2Bub1. The inhibition of cell proliferation and nude mice xenograft of human lung cancer cells induced by PKM2 knockdown can be partially rescued through lowering H2Bub1 levels, which indicates that the oncogenic function of PKM2 is achieved, at least partially, through the control of H2Bub1. Furthermore, PKM2 and H2Bub1 levels are negatively correlated in cancer specimens. Therefore, these findings not only provide a novel mechanism triggering the Warburg effect that is mediated through an epigenetic pathway (H2Bub1) but also reveal a novel metabolic regulator (PKM2) for the epigenetic mark H2Bub1. Thus, the PKM2-H2Bub1 axis may become a promising cancer therapeutic target.

20.
Org Lett ; 21(22): 9014-9018, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31687828

RESUMO

Eight-membered cyclic and [5,5]-bicyclic sulfides were synthesized via a domino reaction between thioaurone analogues and arynes. Density functional theory calculations were performed to elucidate the reaction mechanism, which involves the elementary steps of the [3 + 2] cycloaddition, 1,2-hydrogen shift, and C(sp2)-S bond cleavage as well as the substituent effect.

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