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1.
J Nanosci Nanotechnol ; 20(10): 6561-6567, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32385014

RESUMO

Objective: This study aimed to determine the effects of dimer captosuccinic acid-coated Fe3O4 (super paramagnetic) nanoparticles (NP) on 2-deoxy-d-glucose in targeted cancer cells with high rates of glucose metabolism. Methods: We prepared Fe3O4@DMSA NP and 2-DG-conjugated Fe3O4@DMSA NP, γ-FE, O, and @DMSA-DG NP. Glucose consumption in MDA-MB-231 and MCF-7 breast cancer cells was determined using γ-Fe2O3@DMSA NP or Fe3O4@DMSA-DG NP, and absorption was tested using Prussian blue staining, ultraviolet colorimetry, and magnetic resonance imaging. Results: Glucose consumption was the highest in MDA-MB-231, and the lowest in human mammary epithelial cells (HMEPiC). The significant uptake of Fe2O3@DMSA-DG NP by MDA-MB-231 and MCF-7 cells within two hours was inhibited by glucose. The uptake of Fe3O4@DMSA-DG NP was significantly higher in MDA-MB-231 than in MCF-7 cells, whereas Fe3O4@DMSA NP was not obviously uptaken by either cell line. Absorption was also not evident in HMEPiC incubated with Fe3O4@DMSA-DG NP and Fe3O4@DMSA NP. Conclusions: The tumor targeting efficacy of 2-DG coated Fe3O4@DMSA NP was improved over Fe3O4,@DMSA NP in cancer cells with high rates of glucose metabolism.

2.
Theranostics ; 10(12): 5384-5397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373219

RESUMO

Rationale: The existence of primary and acquired drug resistance is the main obstacle for the effect of multi-kinase inhibitor sorafenib and regorafenib in advanced hepatocellular carcinoma (HCC). However, plenty of patients did not significantly benefit from sorafenib treatment and little is known about the mechanism of drug resistance. Methods: Laser capture microdissection was used to acquire matched normal liver and tumor tissues on formalin-fixed paraffin-embedded specimens collected before sorafenib therapy from the first surgery of 119 HCC patients. Ultra-deep sequencing (~1000×) targeting whole exons of 440 genes in microdissected specimens and siRNA screen in 7 cell lines were performed to find mutations associated with differential responses to sorafenib. Patient-derived xenograft models were employed to determine the role of TP53 in response to sorafenib. Lentiviruses harboring wild-type and c.G52C-mutant OCT4 were applied to explore the function of OCT4 in resistance to sorafenib. ChIP-PCR assay for analysis of OCT4 transcriptional activity was performed to explore the affinity with the KITLG promoter. Statistical analyses were used to associate levels of p53 and OCT4 with tumor features and patient outcomes. Results: Total 1,050 somatic mutations and 26 significant driver genes were identified. SiRNA screening in 7 HCC cell lines was further performed to identify mutations associated with differential responses to sorafenib. A recurrent nonsynonymous mutation c.G52C in OCT4 (OCT4 mut) was strongly associated with good response to sorafenib, whereas the stop-gain mutation in TP53 showed the opposite outcome both in vitro and in vivo. OCT4 wt-induced stem cell factor (encoded by KITLG gene, SCF) expression and cross-activation of c-KIT/FLT3-BRAF signals were identified indispensably for sorafenib resistance, which could be reversed by the combination of c-KIT tyrosine kinase inhibitors or neutralizing antibody against SCF. Mechanistically, an OCT4 binding site in upstream of KITLG promoter was identified with a higher affinity to wildtype of OCT4 rather than G52C-mutant form, which is indispensable for OCT4-induced expression of KITLG and sorafenib resistance. Conclusion: Our study reported a novel somatic mutation in OCT4 (c.G52C) responsible for the sorafenib effect, and also shed new light on the treatment of HCC through the combination of specific tyrosine kinase inhibitors according to individual genetic patterns.

3.
Mol Cancer Ther ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404408

RESUMO

Multiple myeloma (MM) is a hematologic cancer that disrupts normal bone marrow function with multiple lines of therapeutic options but is incurable, as patients ultimately relapse. We developed a novel antibody-drug conjugate targeting CS-1, a protein that is highly expressed on MM tumor cells. The anti-CS-1 monoclonal antibody specifically bound to cells expressing CS-1 and, when conjugated to a cytotoxic pyrrolobenzodiazepine payload, reduced the viability of MM cell lines in vitro. In mouse models of MM, a single administration of the CS-1 ADC caused durable regressions in disseminated models and complete regression in a subcutaneous model. In an exploratory study in cynomolgus monkeys, the CS-1 ADC demonstrated a half-life of 3-6 days; however, no highest non-severely toxic dose was achieved, as bone marrow toxicity was dose limiting. Bone marrow from dosed monkeys showed reductions in progenitor cells as compared with normal marrow. In vitro cell killing assays demonstrated that the CS-1 ADC substantially reduced the number of progenitor cells in healthy bone marrow, leading us to identify previously unreported CS-1 expression on a small population of progenitor cells in the myeloid-erythroid lineage. This finding suggests that bone marrow toxicity is the result of both on-target and off-target killing by the ADC.

4.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(2): 147-151, 2020 Feb 29.
Artigo em Chinês | MEDLINE | ID: mdl-32376532

RESUMO

The SARS-CoV-2 epidemic starting in Wuhan in December, 2019 has spread rapidly throughout the nation. The control measures to contain the epidemic also produced influences on the transport and treatment process of patients with acute myocardial infarction (AMI), and adjustments in the management of the patients need to be made at this particular time. AMI is characterized by an acute onset with potentially fatal consequence, a short optimal treatment window, and frequent complications including respiratory infections and respiratory and circulatory failure, for which active on-site treatment is essential. To standardize the management and facilitate the diagnosis and treatment, we formulated the guidelines for the procedures and strategies for the diagnosis and treatment of AMI, which highlight 5 Key Principles, namely Nearby treatment, Safety protection, Priority of thrombolysis, Transport to designated hospitals, and Remote consultation. For AMI patients, different treatment strategies are selected based on the screening results of SARS-CoV-2, the time window of STEMI onset, and the vital signs of the patients. During this special period, the cardiologists, including the interventional physicians, should be fully aware of the indications and contraindications of thrombolysis. In the transport and treatment of AMI patients, the physicians should strictly observe the indications for patient transport with appropriate protective measurements of the medical staff.


Assuntos
Infecções por Coronavirus , Infarto do Miocárdio , Pandemias , Pneumonia Viral , Betacoronavirus , Consenso , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Consulta Remota , Terapia Trombolítica , Transporte de Pacientes
5.
J Immunol ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434942

RESUMO

Neisseria gonorrhoeae deploys a unique immune evasion strategy wherein the lacto-N-neotetraose termini of lipooligosaccharide (LOS) are "capped" by a surface LOS sialyltransferase (Lst), using extracellular host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation enhances complement resistance by recruiting factor H (FH; alternative complement pathway inhibitor) and also by limiting classical pathway activation. Sialylated LOS also engages inhibitory Siglecs on host leukocytes, dampening innate immunity. Previously, we showed that analogues of CMP-sialic acids (CMP-nonulosonates [CMP-NulOs]), such as CMP-Leg5,7Ac2 and CMP-Neu5Ac9N3, are also substrates for Lst. Incorporation of Leg5,7Ac2 and Neu5Ac9N3 into LOS results in N. gonorrhoeae being fully serum sensitive. Importantly, intravaginal administration of CMP-Leg5,7Ac2 attenuated N. gonorrhoeae colonization of mouse vaginas. In this study, we characterize and develop additional candidate therapeutic CMP-NulOs. CMP-ketodeoxynonulosonate (CMP-Kdn) and CMP-Kdn7N3, but not CMP-Neu4,5Ac2, were substrates for Lst, further elucidating gonococcal Lst specificity. Lacto-N-neotetraose LOS capped with Kdn and Kdn7N3 bound FH to levels ∼60% of that seen with Neu5Ac and enabled gonococci to resist low (3.3%) but not higher (10%) concentrations of human complement. CMP-Kdn, CMP-Neu5Ac9N3, and CMP-Leg5,7Ac2 administered intravaginally (10 µg/d) to N. gonorrhoeae-colonized mice were equally efficacious. Of the three CMP-NulOs above, CMP-Leg5,7Ac2 was the most pH and temperature stable. In addition, Leg5,7Ac2-fed human cells did not display this NulO on their surface. Moreover, CMP-Leg5,7Ac2 was efficacious against several multidrug-resistant gonococci in mice with a humanized sialome (Cmah-/- mice) or humanized complement system (FH/C4b-binding protein transgenic mice). CMP-Leg5,7Ac2 and CMP-Kdn remain viable leads as topical preventive/therapeutic agents against the global threat of multidrug-resistant N. gonorrhoeae.

6.
Inflamm Res ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32435966

RESUMO

INTRODUCTION: Neuroinflammation is a key aspect of various injuries and diseases of the central nervous system and brain, including stroke, Alzheimer's, Parkinson's, multiple sclerosis, etc. Phoenixin-14 is a naturally occurring pleiotropic peptide involved in reproduction, anxiety, pain, and other functions. MATERIALS AND METHODS: Primary astrocytes were isolated from new-born pups of c57bl/6 mice. The gene expression of GPR173, CHOP, and GADD34 was measured by real-time PCR. Protein expression was assessed by western blot analysis. Secretions of IL-1ß and IL-18 were determined by ELISA. RESULTS: Phoenixin-14 (PNX-14) is a ligand for the G protein-coupled receptor GPR173, which we demonstrate to be expressed in astrocytes and suppressed by exposure to lipopolysaccharide (LPS). Endoplasmic reticulum (ER) stress resulting from injury or disease leads to the unfolded protein response, which is mediated by the activation of transcription factors including eIF-2α, ATF4, and CHOP, and regulated by GADD34. ER stress also leads to a robust neuroinflammatory response, which is mediated by HMGB1-induced activation of the NLRP3 inflammasome and subsequent production of IL-1ß and IL-18. In the present study, we demonstrate that PNX-14 could attenuate LPS-induced ER stress response and NLRP3 inflammasome activation in mouse cerebral astrocytes. Our findings show that PNX-14 could suppress the production of ROS as well as the decrease in SOD induced by LPS. PNX-14 also inhibited HMGB1-mediated NLRP3 inflammasome activation and production of IL-1ß and IL-18. Through a GPR173 siRNA knockdown experiment, we further demonstrate that GPR173 knockdown abolished the effects of PNX-14 on LPS-induced NLRP3 expression and IL-18 production. CONCLUSION: These findings suggest that PNX-14 may have potential in the treatment of neuroinflammation.

7.
Technol Cancer Res Treat ; 19: 1533033819898729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301392

RESUMO

OBJECTIVE: The aim of the present research is to study the roles of miR-203a-3p on cell proliferation, migration, invasion, and epithelial-mesenchymal transition in pancreatic cancer. METHODS: Transcription profiles were acquired from Gene Expression Omnibus database, which was used to screen out the differentially expressed microRNAs and messenger RNAs in pancreatic cancer. Pancreatic cancer tissues were used to verify the bioinformatics results by quantitative real-time polymerase chain reaction. The relationship between miR-203a-3p and SLUG was examined by TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation. The Cell Counting Kit-8, wound healing, and transwell assays were conducted to investigate the proliferation, migration, and invasion capability of pancreatic cancer cells, respectively. The expression of epithelial-mesenchymal transition-related proteins was determined by the Western blot assay. Xenograft assay was performed to verify findings from in vitro assays. RESULTS: Bioinformatic analysis found that a total of 113 microRNAs and 1749 messenger RNAs expressed differentially in pancreatic cancer tissues. Among these microRNAs, the expression of miR-203a-3p was significantly decreased in both pancreatic cancer tissues and cells. On the other hand, the SLUG expression was remarkably upregulated in pancreatic cancer tissues and cells in comparison with normal tissues and cells. Moreover, TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation revealed that SLUG was a target of miR-203a-3p. The upregulation of miR-203a-3p expression inhibited the proliferation, migration, and invasion ability of pancreatic cancer cells by suppressing the epithelial-mesenchymal transition process via sponging SLUG. CONCLUSION: These findings indicate that downregulation of miR-203a-3p in pancreatic cancer cells leads to high expression of SLUG, which promotes epithelial-mesenchymal transition process and induces cancer progression.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32343612

RESUMO

Mitochondrial injury in granulosa cells is associated with the pathogenesis of polycystic ovary syndrome (PCOS). However, the protective effects of melatonin against mitochondrial injury in the granulosa cells of PCOS remain unclear. In this study, decreased mitochondrial membrane potential and mtDNA content, increased number of autophagosomes were found in the granulosa cells of PCOS patients and the DHT-treated KGN cells, with decreased protein level of the autophagy substrate P62 and increased levels of the cellular autophagy markers Beclin-1 and LC3B-II, while the protein levels of PINK1 and Parkin were increased and the level of SIRT1 was decreased. DHT-induced PCOS-like mice also showed enhanced mitophagy and decreased SIRT1 mRNA expression. Melatonin treatment significantly increased the protein level of SIRT1 and decreased the levels of PINK1/Parkin, while ameliorated the mitochondrial dysfunction and PCOS phenotype in vitro and in vivo. However, when the KGN cells were treated with SIRT1 siRNA to knock down SIRT1 expression, melatonin treatment failed to repress the excessive mitophagy. In conclusion, melatonin protects against mitochondrial injury in granulosa cells of PCOS by enhancing SIRT1 expression to inhibit excessive PINK1/Parkin-mediated mitophagy.

9.
New Microbiol ; 43(2)2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32310297

RESUMO

Up to now, the UL16-17 region of human cytomegalovirus (HCMV) has not been well characterized at the level of mRNA and protein, especially for the Han strain, the first clinical HCMV strain in China. In previous studies, three transcripts were detected from the UL16-17 region by northern blot analysis for Merlin strain. Transcriptions of UL16 and UL17 were also studied by 5' rapid amplification of cDNA ends (5'RACE) and deep sequencing for AD169 and Towne strains, respectively. However, details of 3' end of UL16 and UL17 transcripts have never been confirmed by 3'RACE. The expressing phage of the UL16-17 region needs further research by northern blot, too. In the present study, cDNA library screening, northern blot and RACE were used to identify the transcription characteristics of the UL16-17 region. Mainly, 3 clusters of transcripts with the same 3' end were found to be expressed from the UL16-17 region in both Han and AD169 strains. The lengths of the core transcripts among the 3 clusters were 1,254nt, 718nt and 468nt, respectively. The corresponding 5' ends are at nt23119, nt23655, nt23905 in the HCMV Han genome. The consistent 3' end is located at nt24372 in the Han genome. The 1,254nt and 468nt transcripts are transcribed in early and late phases, and the 718nt transcript is transcribed only in the late phase.

10.
PLoS One ; 15(4): e0231078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32339170

RESUMO

BACKGROUND: Certain cosmetic habits may trigger or aggravate rosacea, while there is little published epidemiologic evidence to support this point. PURPOSE: To examine if daily skin care habits have an effect on the development of rosacea in Chinese population. METHODS: A multi-center retrospective case-control survey of 1,245 rosacea cases and 1,538 skin-healthy controls was conducted in China. Participants completed the questionnaire comprised of demographic characteristics, socioeconomic data and daily skin care habits. Data were collected retrospectively and analyzed using the chi-square test and t-test. Multivariate logistic regression analyses were used to predict rosacea. RESULTS: The multivariate logistic regression analysis highlighted some results: Dry, oily or mixed skin (OR = 6.3-6.9, P< .001), the usage of foaming cleanser (OR = 1.45, 95%CI 1.115-1.886, P = .01), make up more than 6 times a week (OR = 2.839, 95%CI 1.962-4.108, P< .001), using facial mask more than 4 times a week (OR = 2.56-3.069, P< .001), facial treatments at beauty salon more than once a week (OR = 4.946, 95%CI 2.005-12.198, P = .0018) and using beauty salon products (OR = 2.334, 95%CI 1.435-3.976, P = .0018) are positively correlated with the development of rosacea. Using of moisturizing products (OR = 0.602, 95%CI 0.386-0.983, P = .035) and sunscreen cream (OR = 0.303-0.507, P< .001 or P = .0167 for different frequency) presented significantly negative correlations with rosacea. Frequency of cleansing showed a nonlinear association with rosacea: using facial cleansers 1~3 times per week (OR = 0.647, 95%CI 0.429-0.975, P = .038) showed beneficial effects while using facial cleanser excessively (twice or more daily) (OR = 2.131, 95%CI 1.394-3.256, P< .001) positively correlated to rosacea strongly. CONCLUSIONS: Excessive use of facial cleanser (twice or more a day) and facial mask (more than 4 times a week), frequent makeup (more than 6 times a week), regular skin care in beauty salon (more than once a week), and using beauty salon products were closely correlated to the development of rosacea in Chinese population.

11.
Fish Shellfish Immunol ; 101: 58-65, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32224279

RESUMO

Desiccation is a commonly stressful situation experienced by sea cucumber during transportation without/less water. The present study was conducted to investigate the effects of aerial exposure on the survival, oxidative damage, antioxidant capacity, immune-related response and gene expression of Apostichopus japonicus at different low temperatures. After acclimation, sea cucumbers were randomly divided into 3 groups, which were exposed to 5 °C, 10 °C and 15 °C in the closed laboratory condition, respectively. Each group has three parallel replicates. During the experiment, coelomic fluid and respiratory tree of A. japonicus were sampled at the time points of 0, 3, 6, 12, 24 and 48 h post-desiccation for further analysis. The results showed that the survival rates of sea cucumber significantly decreased as time prolonged, and those of 5 °C at 6-48 h of desiccation were significantly higher than 15 °C. Most oxidative damage parameters (e.g., O2- production, MDA, LPO and PC contents) significant increased after 6-12 h of desiccation. Antioxidant enzyme activities and T-AOC in coelomic fluid firstly increased and then decreased during aerial exposure, indicating that sea cucumber could adjust antioxidant defense to reduce the concentrations of ROS and MDA as a strategy for protecting organisms from oxidative damage in the early stage (0-6 h) of desiccation. The relative expression levels of Hsp90 and Hsp70 mRNA in respiratory tree of sea cucumber exhibited similar rise-fall trends with antioxidant parameters, while immune enzyme activities of ACP, AKP, LSZ and T-NOS, and gene expression of TLR, Rel and p105 all significantly decreased as time prolonged. Overall, low temperature postponed the process of ROS formation and the depression of antioxidant and non-specific immune responses of sea cucumber within a certain extent, which implied that it might play a positive role in improvement of desiccation tolerance. This study not only contribute to better understand the adaption mechanisms of A. japonicus to desiccation stress, but also provide valuable information for sea cucumber culture and transportation.

12.
Crit Rev Oncol Hematol ; 149: 102922, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32244162

RESUMO

We compared the Multinational Association of Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for identifying serious complications in febrile neutropenia patients. We searched MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews from inception to March 19, 2019. Two reviewers independently screened citations, extracted data, and assessed quality. We included 26 studies, totalling 6617 patients. Pooled sensitivity and specificity for MASCC < 21 was 55.6 % (95 % CI: 46.2 %-64.5%) and 86.0 % (95 % CI: 81.3 %-89.7 %), respectively. Pooled sensitivity and specificity for CISNE ≥ 3 was 78.9 % (95 % CI: 65.3 %-88.1 %) and 64.9 % (95 % CI: 49.6 %-77.7 %), respectively. Pooled sensitivity and specificity for CISNE ≥ 1 was 96.7 % (95 % CI: 93.6 %-98.3 %) and 22.2 % (95 % CI: 15.6 %-30.4 %), respectively. The CISNE score had higher sensitivity and may be more useful than the MASCC score in the acute setting.


Assuntos
Antineoplásicos/efeitos adversos , Neutropenia Febril/induzido quimicamente , Febre/complicações , Neoplasias/tratamento farmacológico , Adulto , Antineoplásicos/uso terapêutico , Neutropenia Febril/diagnóstico , Febre/etiologia , Humanos , Neoplasias/complicações , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento
13.
J Am Chem Soc ; 142(13): 6304-6311, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32168449

RESUMO

Herein we report an unprecedented chiral induction of anion-coordination-driven tetrahedra (A4L6-type) by peripheral guests, S-, R-α-methylcholine and S-, R-ß-methylcholine, which are bound along the tetrahedral edges in a highly site-specific fashion. This "peripheral templation", which has proven indispensable for the formation of tetrahedral structure, is also an effective approach to encoding chiral information to the tetrahedron. Moreover, the site-selective binding of chiral choline derivatives to the anion cage with induced one-handedness may imply applications of such metal-free, labile systems in the study of biological processes such as selective recognition of structurally similar molecules.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32195574

RESUMO

Plasmonic color generation has attracted much research interest because of the unique optical properties of plasmonic nanocrystals that are promising for chromatic applications, such as flat-panel displays, smart windows, and wearable devices. Low-cost, monodisperse plasmonic nanocrystals supporting strong localized surface plasmon resonances are favorable for the generation of plasmonic colors. However, many implementations so far have either a single static state or complexities in the particle alignment and switching mechanism for generating multiple displaying states. Herein, we report on a facile and robust approach for realizing the electrochemical switching of plasmonic colors out of colloidal plasmonic nanocrystals. The metal nanocrystals are coated with a layer of polyaniline, whose refractive index and optical absorption are reversibly switched through the variation of an applied electrochemical potential. The change in refractive index and optical absorption results in the modulation of the plasmonic scattering intensity with a depth of 11 dB. The electrochemical switching process is fast (∼5 ms) and stable (over 1000 switching cycles). A device configuration is further demonstrated for switching plasmonic color patterns in a transparent electrochemical device, which is made from indium tin oxide electrodes and a polyvinyl alcohol solid electrolyte. Our control of plasmonic colors provides a favorable platform for engineering low-cost and high-performance miniaturized optical devices.

15.
Theranostics ; 10(7): 2965-2981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194849

RESUMO

Magnetic fluid hyperthermia (MFH) treatment makes use of a suspension of superparamagnetic iron oxide nanoparticles, administered systemically or locally, in combination with an externally applied alternating magnetic field, to ablate target tissue by generating heat through a process called induction. The heat generated above the mammalian euthermic temperature of 37°C induces apoptotic cell death and/or enhances the susceptibility of the target tissue to other therapies such as radiation and chemotherapy. While most hyperthermia techniques currently in development are targeted towards cancer treatment, hyperthermia is also used to treat restenosis, to remove plaques, to ablate nerves and to alleviate pain by increasing regional blood flow. While RF hyperthermia can be directed invasively towards the site of treatment, non-invasive localization of heat through induction is challenging. In this review, we discuss recent progress in the field of RF magnetic fluid hyperthermia and introduce a new diagnostic imaging modality called magnetic particle imaging that allows for a focused theranostic approach encompassing treatment planning, treatment monitoring and spatially localized inductive heating.

16.
Biosci Rep ; 40(3)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32110802

RESUMO

Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment.

17.
Cancer Imaging ; 20(1): 13, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000862

RESUMO

PURPOSE: To evaluate the method and effectiveness of transcatheter arterial chemoembolization (TACE) combined with simultaneous DynaCT-guided Microwave ablation (MWA) for the treatment of small hepatocellular carcinoma (SHCC). MATERIALS AND METHODS: From June 2015 to May 2017, a total of 28 consecutive patients with SHCC received single treatment of TACE and 23 subjects received a combination treatment of TACE with simultaneous DynaCT-guided MWA. Following 1 month of treatment, the tumor response was assessed using the mRECIST criteria and the outcomes were analyzed including intervention-associated complications, changes in liver function, imaging response, and progression-free survival (PFS). RESULTS: The technical success rate was 100%. The rates of CR (65%) in the combined TACE and MWA group were higher than those of the TACE group (46%). The rate of common adverse events, such as liver abscess, spontaneous bacterial peritonitis and liver dysfunction, in the combined TACE and MWA group (56%) was comparable to the corresponding rate of the TACE group (P > 0.411). The median and mean PFS of the TACE group were significantly lower than those of the combined TACE and MWA group (19.00 months vs. 29.00 months, 21.076 months vs. 24.693 months, p = 0.019, log-rank test). CONCLUSION: Stereotactic DynaCT-guided MWA is a safe and effective method for the treatment of SHCC, which usually provides an effective tumor puncture path, notably for lesions that cannot be detected following TACE. Overall, the data suggested that this treatment method could improve the clinical outcome of patients with SHCC.

18.
Genome Biol ; 21(1): 46, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093779

RESUMO

Following publication of the original paper [1], the authors reported an error in the affiliation of Xin-Tian Hu, who is also affiliated with "Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China".

19.
Life Sci ; 248: 117455, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088216

RESUMO

AIMS: Idiopathic scoliosis is a common deformity of the spine that has an especially high incidence rate in adolescents. Some studies have demonstrated a close relationship between idiopathic scoliosis and melatonin deficiency. Our team's previous research showed that melatonin can inhibit the proliferation of osteoblasts, but the mechanism remains unclear. This study aimed to determine the mechanism by which melatonin inhibits the proliferation of osteoblasts. MAIN METHODS: Cell viability experiment, DNA fragment detection and alkaline phosphatase (ALP) activity assays were performed to determine the effects of melatonin on the proliferation, apoptosis and differentiation of osteoblasts. We used immunofluorescence to detect the expression of STIM1 in melatonin-treated osteoblasts. STIM1 interference was achieved using a specific siRNA, and a TRPC inhibitor was used to block the influx of Ca2+. The mRNA expression was determined by RT-qPCR, and protein levels were measured by Western blot. KEY FINDINGS: In this study, we found that melatonin inhibited the proliferation, differentiation and apoptosis of osteoblasts in a concentration-dependent manner. Additional studies showed that melatonin elevated cytosolic calcium levels by upregulation of STIM1, leading to osteoblast apoptosis via the mitochondrial pathway. Finally, we demonstrated that the STIM1-mediated increase in cytosolic calcium levels induced apoptosis through the ERK pathway. SIGNIFICANCE: Melatonin induces mitochondrial apoptosis in osteoblasts by regulating the STIM1/cytosolic calcium elevation/ERK pathway. These basic findings provide a basis for further clinical studies on melatonin as a drug therapeutic for idiopathic scoliosis.


Assuntos
Antioxidantes/farmacologia , Cálcio/metabolismo , Sistema de Sinalização das MAP Quinases , Melatonina/farmacologia , Osteoblastos/efeitos dos fármacos , Molécula 1 de Interação Estromal/genética , Fosfatase Alcalina/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Transporte de Íons/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Molécula 1 de Interação Estromal/agonistas , Molécula 1 de Interação Estromal/antagonistas & inibidores , Molécula 1 de Interação Estromal/metabolismo , Canais de Cátion TRPC/antagonistas & inibidores , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo
20.
J Intensive Care Med ; : 885066619899653, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31950870

RESUMO

INTRODUCTION: Cancer is associated with significant health-care expenditure, but few studies have examined the cost of patients with cancer in the intensive care unit (ICU). We aimed to describe the costs and outcomes of patients admitted to the ICU with cancer. METHODS: We conducted a retrospective cohort study of patients admitted between 2011 and 2016 to 2 tertiary-care ICUs. We included patients with a cancer-related most responsible diagnosis using International Classification of Disease, 10th Revision, Canada codes. We compared costs and outcomes of patients having cancer with noncancer controls matched for age, sex, and Elixhauser comorbidity score. We used logistic regression to determine predictors of mortality among patients with cancer. RESULTS: There were 1022 patients with cancer during the study period. Mean age was 63.2 years and 577 (56.5%) were male. Inhospital mortality for all patients with cancer was 24.0%. Total cost per patient was higher for patients with cancer compared to noncancer patients (CAD$57 084 vs CAD$40 730; P < .001) but there were no differences in the cost per day (CAD$2868 vs CAD$2887; P = .76) or ICU cost (CAD$30 495 vs CAD$29 382; P = .42). Among patients with cancer, the cost per day was higher for nonsurvivors (CAD$3477 vs CAD$2677; P < .001). Liver disease (odds ratio [OR]: 2.96; 95% confidence interval [CI]: 1.22-7.81), mechanical ventilation (OR: 1.73; 95% CI: 1.25-2.39), hematologic malignancy (OR: 3.88; 95% CI: 2.31-6.54), and unknown primary site (OR: 2.13; 95% CI: 1.36-3.35) were independently associated with mortality in patients with cancer. CONCLUSION: Patients admitted to the ICU with cancer did not differ in cost per day, ICU cost, or mortality compared to matched noncancer controls. Among patients with cancer, nonsurvivors had significantly higher cost per day compared to survivors. Hematologic and unknown primaries, liver disease, and mechanical ventilation were independently associated with mortality in patients with cancer.

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