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1.
Ann Palliat Med ; 9(5): 3453-3461, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065796

RESUMO

BACKGROUND: One of the common adverse reactions to anthracyclines, a group of chemotherapeutics, is cardiotoxicity. Cancer patients receiving anthracycline-based chemotherapeutic regimens often discontinue treatment due to cardiotoxicity. How to prevent and reduce the cardiotoxicity of anthracyclines is one of the hot topics in the field of onco-cardiology. Traditional Chinese medicine can reduce the toxic side effects of chemotherapeutics. The present study aimed to investigate the protective effect of Qishen Huanwu capsule (QSHWC) on pirarubicin (THP)-induced myocardial injury in rats and the underlying mechanisms. METHODS: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six groups: control group, THP, low-dose QSHWC, moderate-dose QSHWC, high-dose QSHWC, and LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] (n=8 each). Echocardiographic examination was performed to examine heart structure and function. Hematoxylin and eosin (HE) staining was conducted to examine histopathological changes in myocardial tissue. Immunofluorescence staining was carried out to examine the expression of the autophagosome-specific marker protein microtubule-associated protein 1 light chain 3 (LC3). Western blot was performed to analyze the expression of LC3-I, LC3-II, PI3K, phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR. RESULTS: Compared with the control group, the THP group had a higher left ventricular end-systolic diameter (LVESD), lower left ventricular ejection fraction (LVEF), lower left ventricular fractional shortening (LVFS), and inferior heart function. In addition, compared with the control group, the THP group had significantly higher LC3 protein expression, a significantly higher LC3-II/LC3-I ratio (P<0.05), and significantly lower p-PI3K, p-Akt, and p-mTOR (P<0.05). QSHWC attenuated the THP-induced decline in heart function, downregulated LC3 protein in rat myocardial tissue, decreased the LC3-II/LC3-I ratio, and increased p-PI3K, p-Akt, and p-mTOR. In the LY294002 group, the above effects of QSHWC were reversed. CONCLUSIONS: QSHWC alleviated THP-induced myocardial injury. The underlying mechanism was related to the activation of the PI3K/Akt/mTOR pathway and the mitigation of the excessive autophagy of cardiomyocytes caused by THP.

2.
Int J Mol Sci ; 21(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066038

RESUMO

Noise-induced hearing loss is one of the major causes of acquired sensorineural hearing loss in modern society. While people with excessive exposure to noise are frequently the population with a lifestyle of irregular circadian rhythms, the effects of circadian dysregulation on the auditory system are still little known. Here, we disturbed the circadian clock in the cochlea of male CBA/CaJ mice by constant light (LL) or constant dark. LL significantly repressed circadian rhythmicity of circadian clock genes Per1, Per2, Rev-erbα, Bmal1, and Clock in the cochlea, whereas the auditory brainstem response thresholds were unaffected. After exposure to low-intensity (92 dB) noise, mice under LL condition initially showed similar temporary threshold shifts to mice under normal light-dark cycle, and mice under both conditions returned to normal thresholds after 3 weeks. However, LL augmented high-intensity (106 dB) noise-induced permanent threshold shifts, particularly at 32 kHz. The loss of outer hair cells (OHCs) and the reduction of synaptic ribbons were also higher in mice under LL after noise exposure. Additionally, LL enhanced high-intensity noise-induced 4-hydroxynonenal in the OHCs. Our findings convey new insight into the deleterious effect of an irregular biological clock on the auditory system.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33067822

RESUMO

The next-generation positron zirconium-89(89 Zr, T1/2 = 3.27 days) is a novel nuclide for immuno-PET because of its favorite longer half-life. The aim of this work is to develop optimized methods for routine production and purification of 89 Zr through Monte Carlo (MC) simulation and laboratory experiments. 89 Y(p,n)89 Zr reaction was used for 89 Zr production. Optimized thicknesses of Al degrader (0.11 cm) and 89 Y foil (0.064 cm) were simulated through MC method. 89 Zr (15.0-40.7 mCi) with an average production rate of 0.92 ± 0.12 mCi/µA·h was produced after 1-2 h bombardment at the proton beam energy 20 MeV and current 20 µA. High radio-purity 89 Zr (6.14-26.8 mCi) obtained eluted from hydroxamate resin using 1 mol/L oxalic acid solution, with the concentration of 2.7×104 mCi/L. The gamma spectrum showed that the characteristic peak of 89 Zr were 511 and 909 keV, and no impurities found. [89 Zr]Zr-DFO-trastuzumab was successfully labeled and performed good radiochemical purity (>95%) and stability that showed potential application in tumor molecular imaging.

4.
Allergy ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040337

RESUMO

BACKGROUND: The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. MEASURE: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11,766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. 63 healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. RESULTS: A combination test of NAT and serological testing for IgM antibody with discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N specific antibodies, S1 specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17d to 25d, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. CONCLUSION: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health and immunization strategies.

5.
Cell Immunol ; 358: 104221, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33035772

RESUMO

Germinal centers (GCs), which are the site of antibody diversification and affinity maturation, are vitally important for humoral immunity. GC B cell proliferation is essentially for these processes by providing enough templates for somatic hypermutation (SHM) and serving as a critical mechanism of positive selection. In the current study, we found a significant reduction of GC response in the spleens of GC B cell specific PHF14 knockout (PHF14GCB KO) mice compared with the wild-type control (PHF14GCB WT) when the mice were challenged with SRBCs or lymphocytic choriomeningitis virus. We also demonstrated that PHF14 did not affect the cell survival of GC B cells, but regulated the proliferation of GC B cells. In addition, PHF14 suppressed the expression of Cdkn1a (p21) though regulating the level of H3K4me3 to control the proliferation of GC B cells. Collectively, our data suggest that PHF14 plays an important role in the process of germinal center formation by regulating GC B cell proliferation in spleen.

6.
Medicine (Baltimore) ; 99(41): e22671, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031333

RESUMO

Epithelial-myoepithelial carcinoma (EMC) is a rare neoplasm of the salivary glands. The aim of this study is to review and evaluate clinicopathological features and treatment of EMC of salivary gland for better sensitivity and specificity of the diagnosis.The clinical and pathological data of the 10 salivary gland EMC cases from 2008 to 2017 were analyzed.Six cases of EMC were diagnosed to be originated from parotid gland and 4 cases were from the minor salivary gland including palate, tongue, and oropharynx. Seven cases were performed radical surgery and 3 cases had radiotherapy postoperation, 2 cases had a local recurrence. The follow-up period was 4 to 104 months and the survival rate was 100%. Histopathology showed the tumors had a dominant prototypical biphasic tubular structure consisting of inner, cuboidal ductal cells and an outer layer of clear, myoepithelial cells, which grew infiltratively. The immunohistochemistry (IHC) showed the marker proteins CK, S-100, CD117, and Calponin were strongly positive in most EMC.EMC is a rare and low-grade malignant tumor with good overall survival but relatively high tendency for local recurrence. Surgery is the priority choice for EMC therapy. Complete surgical excision and negative margins are necessary for good prognosis. Imaging techniques should be used to assess the neck dissection and it is unclear whether adjuvant radiotherapy is beneficial. To ensure the sensitivity and specificity of the EMC diagnosis, we should perform both pathological and IHC analysis.

7.
Br J Clin Pharmacol ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010043

RESUMO

AIMS: Voriconazole is a broad-spectrum antifungal agent for the treatment of invasive fungal infections. There is limited information about the pharmacokinetics and appropriate dosage of voriconazole in patients with liver dysfunction. This study aimed to explore the relationship between voriconazole trough concentration (Ctrough ) and toxicity, identify the factors significantly associated with voriconazole pharmacokinetic parameters and propose an optimised voriconazole dosing regimen for patients with liver dysfunction. METHODS: The study prospectively enrolled 51 patients with 272 voriconazole concentrations. Receiver operating characteristic (ROC) curves were used to explore the relationship between voriconazole Ctrough and toxicity. The pharmacokinetic data was analysed with nonlinear mixed-effects method. Dosing simulations stratified by total bilirubin (TBIL, TBIL-1: TBIL < 51 µmol/L; TBIL-2: 51 µmol/L ≤ TBIL < 171 µmol/L; TBIL-3: TBIL ≥ 171 µmol/L) were performed. RESULTS: ROC curve analysis revealed that voriconazole Ctrough of ≤ 5.1 mg/L were associated with significantly lower the incidence of adverse events. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Population pharmacokinetic parameters of clearance (CL), the volume of distribution (V) and oral bioavailability (F) were 0.88 L/h, 148.8 L and 88.4%, respectively. Voriconazole CL was significantly associated with TBIL and platelet count. The V increased with body weight. Patients with TBIL-1 could be treated with a loading dose of 400 mg every 12 hours (q12h) for first day, followed by a maintenance dose of 100 mg q12h administered orally or intravenously. TBIL-2 and TBIL-3 patients could be treated with a loading dose of 200 mg q12h and maintenance doses of 50 mg q12h or 100 mg once daily (qd) and 50 mg qd orally or intravenously, respectively. CONCLUSIONS: Lower doses and longer dosing intervals should be considered for patients with liver dysfunction. TBIL-based dosing regimens provide a practical strategy for achieving voriconazole therapeutic range and therefore maximizing treatment outcomes.

8.
Sci Adv ; 6(40)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33008901

RESUMO

Aging is the dominant risk factor for most chronic diseases. Development of antiaging interventions offers the promise of preventing many such illnesses simultaneously. Cellular stress resistance is an evolutionarily conserved feature of longevity. Here, we identify compounds that induced resistance to the superoxide generator paraquat (PQ), the heavy metal cadmium (Cd), and the DNA alkylator methyl methanesulfonate (MMS). Some rescue compounds conferred resistance to a single stressor, while others provoked multiplex resistance. Induction of stress resistance in fibroblasts was predictive of longevity extension in a published large-scale longevity screen in Caenorhabditis elegans, although not in testing performed in worms and flies with a more restricted set of compounds. Transcriptomic analysis and genetic studies implicated Nrf2/SKN-1 signaling in stress resistance provided by two protective compounds, cardamonin and AEG 3482. Small molecules identified in this work may represent attractive tools to elucidate mechanisms of stress resistance in mammalian cells.

9.
Mol Ther ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-33002420

RESUMO

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33006657

RESUMO

INTRODUCTION: Over the last decades, multiple peptide receptors were recognized as potential diagnostic and therapeutic targets in nuclear medicine. 68Ga-NT-20.3 radiopharmaceutical has been developed for diagnosis of neurotensin receptors. High neurotensin receptor expression has been observed in pancreatic ductal adenocarcinoma as well as various malignancies. Until now, 68Ga-labelled NT ligand was successfully applied in in vitro as well as in animal model. Our study is the first in-human study on safety and tolerability of 68Ga-NT-20.3. METHODS: Subjects were intravenously injected with 2.5 MBq of 68Ga-DOTA-NT-20.3 per kilogramme of body weight, and series of PET images were acquired at 5-25 min, 25-45 min, 45-65 min, and 65-85 min after 68Ga-NT-20.3 injection. Vital parameters are as follows: systolic and diastolic blood pressure (mmHg), heart rate (heart beat/min), respiratory rate (number of breaths/min), ECG, and body temperature (°C) were checked before, immediately after, and 3 h after 68Ga-NT-20.3 injection. The organ-absorbed doses were calculated for the self-dose and cross-dose from each organ region using the OLINDA/EXM version 2.1 software. RESULTS AND CONCLUSION: The results from this small trial demonstrate that PET radiopharmaceutical 68Ga-NT-20.3 is safe and well tolerated.

11.
Adv Mater ; : e2004142, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051904

RESUMO

Heteroepitaxial modification of nanomaterials has become a powerful means to create novel functionalities for various applications. One of the most elementary factors in heteroepitaxial nanostructures is the misfit strain arising from mismatched lattices of the constituent parts. Misfit strain not only dictates epitaxy kinetics for diversifying nanocrystal morphologies but also provides rational control over materials properties. In recent years, advances in chemical synthesis along with the rapid development of electron microscopy and X-ray diffraction techniques have enabled a substantial understanding of strain-related processes, which offers theoretical foundation and experimental guidance for researchers to refine heteroepitaxial nanostructures and their properties. Herein, recent investigations on heterogeneous core-shell nanocrystals containing misfit strains are summarized, with a focus on the mechanistic understanding of strain and strain-induced effects such as tuning the epitaxial habit, modulating the optical emission, and enhancing the catalytic activity and magnetic coercivity.

12.
Life Sci ; 259: 118379, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32890604

RESUMO

With the increasing application of medical imaging contrast materials, contrast-induced nephropathy has become one of the leading causes of iatrogenic renal insufficiency. The underlying mechanism is associated with renal medullary hypoxia, direct toxicity of contrast agents, oxidative stress, apoptosis, immune/inflammation and epigenetic regulation in contrast-induced nephropathy. Up to date, there is no effective therapy for contrast-induced nephropathy, and thus risk predication and effective preventive strategies are keys to reduce the occurrence of contrast-induced nephropathy. It was found that the proper use of contrast medium, personalized hydration, and high-dose statins may reduce the occurrence of contrast-induced nephropathy, while antioxidants have not shown significant therapeutic benefits. Additionally, the role of remote ischemia preconditioning and vasodilators in the prevention of contrast-induced nephropathy needs further study. This review aims to discuss the incidence, pathogenesis, risk prediction, and preventive strategies for contrast-induced nephropathy.


Assuntos
Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Humanos , Rim/efeitos dos fármacos , Nefropatias/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos
13.
J Biomed Nanotechnol ; 16(5): 626-639, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919483

RESUMO

Glial cell line derived neurotropic factor (GDNF) plays a crucial role in the development and maintenance of glial cells, serotonergic and dopaminergic neurons. A positively therapeutic effect has been demonstrated on some animal neurodegenerative diseases. However, the inability to deliver the protein across blood brain barrier (BBB) into damaged brain region limits its clinical application. Here, we developed GDNF-loaded microbubbles (MBs) and achieved a local and precise delivery of GDNF into the brain through MRI-guided focused ultrasound-induced BBB disruption. To demonstrate the therapeutic effect, rat depression model was developed by chronic mild stress treatment. Typical depression behaviors were confirmed. MRI-guided focused ultrasound was used to irradiate the GDNF-loaded MBs. Obvious BBB opening was observed in the treated rat brains and a significant higher GDNF concentration was detected in the ultrasound-treated brain tissues. Behavioral tests demonstrated the increased GDNF could reverse the depressive-like behaviors induced by chronic mild stress, improve the expression of 5-HT 1B receptor and the protein p11, and increase the number of 5-HT or TPH2 immunoreactive neurons. In conclusion, our study provided an effective approach to deliver GDNF proteins into brain to treat rat depression through MRI-guided focused ultrasound-induced destruction of blood-brain barrier.

14.
Inorg Chem ; 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32921054

RESUMO

Cyclometalated organoplatinum(II) complexes have aroused tremendous interests due to their square-planar geometry and intriguing photophysics. To access multiplatinum systems with more than three cyclometalated organoplatinum(II) units, the traditional covalent synthetic approach suffers from tedious multistep reactions with low overall yield. In comparison, supramolecular assembly can be regarded as an effective strategy toward multiplatinum(II) architectures. Despite the progresses achieved, it is still challenging to fabricate well-ordered supramolecular assemblies with precise numbers of organoplatinum(II) units. Herein, self-complementary dimerized molecular tweezers with four cyclometalated platinum(II) units have been successfully constructed by taking advantage of dual roles of the incorporated 2,2':6',2''-terpyridine unit (serving as the rigid spacer and encapsulated guest). Furthermore, addition of electron-rich carbazoles leads to conversion of the self-complementary structure to molecular tweezer/guest complexes. Such a structural transformation gives rise to the concomitant luminescent color change. The unique guest-induced fluorochromic phenomena, which are seldom reported in the previous host-guest systems, would be promising as tunable luminescent and ratiometric sensing materials.

15.
Int J Occup Saf Ergon ; : 1-13, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900280

RESUMO

Background. Trade-offs are common behaviors of resilient systems, when the systems adapt to changing situations to meet multiple goals. Objective. In the context of the Beijing taxi service system (BTSS), this work investigates the sharp-end taxi drivers' trade-offs between work safety and business profitability, demonstrates their resilience in balancing these two goals and identifies factors that contribute to the trade-offs. Methods. An empirical framework incorporating questionnaire surveys, semi-structured interviews, field observation, data screening and categorization was adopted. Data were collected from a random sample of 70 taxi drivers. Results. In the drivers' decisions we found a slight bias in favor of profitability rather than safety (regardless of their finances), and a high level of resilience that the drivers had developed in making strategies for the trade-offs. Trip distance, possibility of traffic congestion, redundant consumption, weather conditions, road features and real-time broadcast information were identified as determinants of the drivers' decision-making. Conclusion. The findings inform BTSS organizational layers and regulators about the sharp-end drivers' needs for productive safety, and provide an evidence base for making more definitive recommendations about support provision and resource re-allocation in an effective and proactive manner.

16.
Plant Physiol ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900982

RESUMO

The large sunflower family, Asteraceae, is characterized by compressed, flower-like inflorescences that may bear phenotypically distinct flower types. The CYCLOIDEA/TEOSINTE BRANCHED1 (CYC/TB1)-like transcription factors (TFs) belonging to the TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) protein family are known to regulate bilateral symmetry in single flowers. In Asteraceae, they function at the inflorescence level, and were recruited to define differential flower type identities. Here, we identified upstream regulators of GhCYC3, a gene that specifies ray flower identity at the flower head margin in the model plant Gerbera hybrida. We discovered a previously unidentified expression domain and functional role for the paralogous CINCINNATA-like (CIN) TCP proteins. They function upstream of GhCYC3 and affect the developmental delay of marginal ray primordia during their early ontogeny. At the level of single flowers, the Asteraceae CYC genes show a unique function in regulating the elongation of showy ventral ligules that play a major role in pollinator attraction. We discovered that during ligule development, the E class MADS-box TF GRCD5 activates GhCYC3 expression. We propose that the C class MADS-box TF GAGA1 contributes to stamen development upstream of GhCYC3. Our data demonstrate how interactions among and between the conserved floral regulators, TCP and MADS-box TFs, contribute to the evolution of the elaborate inflorescence architecture of Asteraceae.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32902096

RESUMO

The first total synthesis of a hexacyclic ent -kaurane diterpenoid alkaloid, liangshanone, has been completed. Its intricate cage-like framework was assembled through several key transformations including an oxidative dearomatization/Diels-Alder (OD/DA) cycloaddition sequence, a tandem alkene cleavage/ Mannich cyclization, a Robinson-type annulation, and an intramolecular aldol reaction. Notably, an organocatalytic enantio-selective α-hydroxymethylation process allowed the preparation of the enantioenriched tricycle 15a that should enable asymmetric access to the target natural product.

18.
Theranostics ; 10(22): 10326-10340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32929351

RESUMO

Although dyslipidemia commonly occurs in patients with acute promyelocytic leukemia (APL) in response to anti-APL therapy, the underlying mechanism and the lipid statuses of patients with newly diagnosed APL remain to be addressed. Methods: We conducted a retrospective study to investigate the lipid profiles of APL patients. PML-RARα transgenic mice and APL cells-transplanted mice were used to assess the effects of APL cells on the blood/liver lipid levels. Subsequently, gene set enrichment analysis, western blot and dual luciferase reporter assay were performed to examine the role and mechanism of PML-RARα and TRIB3 in lipid metabolism regulation in APL patients at pretreatment and after induction therapy. Results: APL patients exhibited a higher prevalence of dyslipidemia before anti-APL therapy based on a retrospective study. Furthermore, APL cells caused secretion of triglycerides, cholesterol, and PCSK9 from hepatocytes and degradation of low-density lipoprotein receptors in hepatocytes, which elevated the lipid levels in APL cell-transplanted mice and Pml-Rarα transgenic mice. Mechanistically, pseudokinase TRIB3 interacted with PML-RARα to inhibit PPARγ activity by interfering with the interaction of PPARγ and RXR and promoting PPARγ degradation. Thus, reduced PPARγ activity in APL cells decreased leptin but increased resistin expression, causing lipid metabolism disorder in hepatocytes and subsequent dyslipidemia in mice. Although arsenic/ATRA therapy degraded PML-RARα and restored PPARγ expression, it exacerbated dyslipidemia in APL patients. The elevated TRIB3 expression in response to arsenic/ATRA therapy suppressed PPARγ activity by disrupting the PPARγ/RXR dimer, which resulted in dyslipidemia in APL patients undergoing therapy. Indeed, the PPAR activator not only enhanced the anti-APL effects of arsenic/ATRA by suppressing TRIB3 expression but also reduced therapy-induced dyslipidemia in APL patients. Conclusion: Our work reveals the critical role of the PML-RARα/PPARγ/TRIB3 axis in the development of dyslipidemia in APL patients, potentially conferring a rationale for combining ATRA/arsenic with the PPAR activator for APL treatment.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32969968

RESUMO

OBJECTIVE: The purpose of this study was to examine the intervention effect of radial extracorporeal shock wave combined with ultrashort wave diathermy on immobilization-induced fibrosis and contracture of muscle. DESIGN: The groups included male rabbits for the group (C). To cause joint contracture, rabbits underwent plaster fixation of a left knee joint at full extension. After immobilization for 4 weeks, all rabbits were randomly divided into 4 groups: model group (M), natural recovery group (NR), radial extracorporeal shock wave treatment group (R), ultrashort wave diathermy group (U), radial extracorporeal shock wave combined with ultrashort wave diathermy group (RU). All intervention effects were assessed by evaluating the cross sectional area and the collagen deposition of muscle, the knee-joint range of motion and the protein levels for TGF-ß1 and HIF-1α. RESULTS: The combined treatment group (RU) got the best recovery of the knee-joint function. The combined treatment was more effective than radial extracorporeal shock wave or ultrashort wave diathermy alone against the fibrosis and contracture of muscle, and the over-expression of TGF-ß1and HIF-1α. CONCLUSIONS: Radial extracorporeal shock wave combined with ultrashort wave diathermy was effective in alleviating immobilization-induced contracture and fibrosis of muscle, and reducing the molecular manifestations of muscle fibrosis.

20.
Oncol Rep ; 44(4): 1596-1604, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945475

RESUMO

The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)­mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U­118 MG cells was detected by flow cytometry (FCM). A 630­nm semiconductor laser and 1­MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit­8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U­118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U­118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS­mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl­xL, increased cleaved ­caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl­xL and in the levels of cleaved­caspase 3 were partly reversed by N­acetyl­L­cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS­mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.

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