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1.
Biomed Pharmacother ; 121: 109552, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715370

RESUMO

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.

2.
Clin Chim Acta ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31758934

RESUMO

BACKGROUND: The polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder syndrome of women in reproductive age. Metabolomic studies of the follicular fluid can reveal the potential metabolic pathways related to PCOS. The objection of this study was to explore the changes of metabolites in the follicular fluid of PCOS. METHODS: We collected follicular fluid samples of 35 patients with PCOS and 33 controls without PCOS for metabolomic analysis with UPLC Q-Exactive. The identified metabolites were annotated with KEGG and HMDB to determine the disturbances of metabolic pathways in PCOS. Based on the regression model, we conducted the ROC analysis to find the biomarker of PCOS in the follicular fluid. RESULTS: Metabolomic analysis identified 21 differential metabolites in PCOS, which revealed that the Vitamin B6 metabolism, phenylalanine metabolism and carnitine synthesis were the key changed pathways. We found that 7ß-Hydroxycholesterol was potential biomarker of PCOS based on the ROC analysis. CONCLUSION: We identified metabolic alterations and biomarker in the follicular fluid of PCOS, providing novel ways for the diagnosis and treatment of PCOS.

3.
Surg Endosc ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586253

RESUMO

BACKGROUND: Emergency endoscopic retrograde cholangiopancreatography (ERCP) for ascending acute cholangitis in patients with severe comorbidities is challenging. Here, we evaluated the efficacy and safety of one-stage ERCP in such patients by performing a retrospective study. METHODS: We included all patients with ascending acute cholangitis and undergoing ERCP between January 2017 and March 2019. In total, we recruited 212 patients: 74 and 138 with and without severe comorbidities, respectively. We collected and analyzed data related to basal characteristics, ERCP, and clinical outcomes. RESULTS: Elderly age (76.20 ± 9.99 years vs. 66.52 ± 8.16 years, P = 0.000), higher levels of leukocyte count (15.86 ± 2.47 × 109/ml vs. 13.49 ± 1.65 × 109/ml, P = 0.000), and serum bilirubin (3.11 ± 1.29 mg/dl vs. 1.94 ± 0.90 mg/dl, P = 0.000) were present in patients with severe comorbidities. A significantly higher proportion of these patients were severe cases (32.4% vs. 6.5%, P = 0.000), American Society of Anesthesiologists (ASA) stage V status (37.8% vs. 10.1%, P = 0.000) and had undergone general anesthesia (56.8% vs. 18.8%, P = 0.000). Successful biliary cannulation and complete stone clearance in one session were achieved in 207 and 202 patients, respectively. Mean length of hospital stay was 8.02 ± 2.71 days. Forty-three patients required ICU stay with the mean length of 3.26 ± 3.51 days. In-hospital mortality occurred in seven patients; all these patients had severe comorbidities. ERCP details, including urgent and early ERCP, biliary cannulation, complete stone clearance in one session, stent insertion, and complications were not significantly different between the two groups. Patients with severe comorbidities had a longer in-hospital stay (9.39 ± 3.15 days vs. 7.29 ± 2.11 days, P = 0.000), a higher proportion of ICU admission (45.9% vs. 6.5%, P = 0.000), and a longer ICU stay length (4.88 ± 4.37 days vs. 1.44 ± 0.52 days, P = 0.000). Our data also revealed that early diagnosis is an important predictor associated with clinical outcomes. CONCLUSIONS: One-stage ERCP is safe and effective for ascending acute cholangitis caused by choledocholithiasis. Early diagnosis is a significant predictor of clinical outcomes.

4.
ACS Appl Mater Interfaces ; 11(43): 40564-40574, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566943

RESUMO

The fabrication of metal-organic framework (MOF)-based macro-materials is considered as a promising strategy toward the practical applications of powdered MOF crystals. In this study, selective laser sintering (SLS), an advanced three-dimensional (3D) powder printing technique, has been employed to fabricate MOF-polymer mixed matrix films (MMFs) by using thermoplastic polyamide 12 (PA12) powder as the matrix material and five types of MOFs including ZIF-67, NH2-MIL-101(Al), MOF-801, HKUST-1, and ZIF-8 crystals as the fillers. A three-layer HKUST-1-PA12 complex with a grid pattern is fabricated to demonstrate the printability of 3D MOF-polymer structure. Single-layer MMFs with grid patterns are printed by using the five types of MOF fillers with different mass loadings to study their free-standing characteristic, thickness, specific surface area, hydrophilia, water permeate flux, and mechanical stability. The methylene blue (MB) adsorption tests are conducted using the NH2-MIL-101(Al)-PA12 MMFs with different grid patterns to exemplify the applications of the MMFs for water purification. It is confirmed that the MOF components retain their high maximum adsorption capacity, and the printed MMFs can be conveniently regenerated for cyclic utilization. This work provides an insight into the utilization of advanced 3D printing technology to manufacture macro-MOF-polymer materials for practical applications.

5.
Pathol Res Pract ; 215(11): 152637, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31570278

RESUMO

Gastric cancer (GC) represents one of the most predominant malignancies with high incidence and mortality rates. Although traditional chemotherapeutics, including cisplatin are effective in the treatment of GC, patients often develop drug resistance in clinic. The present study aimed to explore the underlying mechanism of cisplatin-induced drug resistance in GC. The potential role of DNA demethylase ten-eleven translocation-2 (TET2) in modulating cisplatin resistance of GC cells was investigated. It was observed that TET2 was significantly decreased in cisplatin resistance SGC7901/DDP cells compared with non-resistant cells and TET2 overexpression markedly reduced the tolerance to cisplatin. Additionally, evidence was provided that TET2 regulated interleukin-6 levels in the tumor microenvironment through histone acetylation and therefore served an important role in the development of cisplatin resistance in GC cells. Taken together, the results suggested that TET2-mediated cisplatin resistance may represent a novel mechanism of drug resistance in GC cells and may offer novel treatment approaches.

6.
Int J Nanomedicine ; 14: 8001-8011, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632014

RESUMO

Background: The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance. Methods: In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(ß-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The pK b value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility. Results: The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX. Conclusion: All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.

7.
J Invest Surg ; : 1-8, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533485

RESUMO

Objectives: The study was aimed to investigate the safety and feasibility of avoiding urinary catheterization after surgery in patients undergoing lung cancer resection. Methods: Between 1 January 2014 and 31 December 2017, the patients with primary lung cancer who received lobectomy or segmental resection via video-assisted thoracic surgery (VATS) in our department were screened. Based on whether a urinary catheter was inserted after surgery, patients were divided into urinary catheter (UC) group or non-UC group, and rates of postoperative urinary retention (POUR), urinary catheter re-insertion and urinary tract infection (UTI) were compared. Results: There was no difference in International prostate symptom score (p = .268) between the groups, but a higher Sedation-Agitation Scale (SAS) score was found in UC group [4.0 (3.0 4.0) vs. 4.0 (2.0, 4.0); p < .001], with a higher proportion of patients with agitation (SAS score > 4; 17.3%, 317/1,835 vs. 12.9%, 86/660, p = .008). In contrast, a higher rate of POUR was observed in non-UC group (11.2%, 74/660 vs. 7.4%, 136/1,835, p = .003), whereas the rate of UTI was significantly lower in this group (5.8%, 38/660 vs. 8.3%, 153/1,835, p = .033). Multivariable analysis revealed the non-placement of UC as the independent factor for POUR (OR: 1.542, 95%CI: 1.135-2.095, p = .006) and UTI (OR: 0.664, 95%CI: 0.459-0.962, p = .031). Conclusion: This retrospective study with large sample of 2,495 patients provided evidence to the hypothesis that avoiding urinary catheterization contributed to decrease in the incidence of UTI and was safe and feasible in patients undergoing lung cancer surgery.

8.
Mol Med Rep ; 20(4): 3802-3810, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485625

RESUMO

Glial cell line­derived neurotrophic factor (GDNF) is critical for the proliferation of spermatogonial stem cells (SSCs), but the underlying mechanisms remain poorly understood. In this study, an unbiased metabolomic analysis was performed to examine the metabolic modifications in SSCs following GDNF deprivation, and 11 metabolites were observed to decrease while three increased. Of the 11 decreased metabolites identified, glycylglycine was observed to significantly rescue the proliferation of the impaired SSCs, while no such effect was observed by adding sorbitol. However, the expression of self­renewal genes, including B­cell CLL/lymphoma 6 member B, ETS variant 5, GDNF family receptor α1 and early growth response protein 4 remained unaltered following glycylglycine treatment. This finding suggests that although glycylglycine serves an important role in the proliferation of SSCs, it is not required for the self­renewal of SSCs.

9.
Sci Total Environ ; 692: 1267-1275, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539958

RESUMO

Humans are exposed to disinfection by-products (DBPs) mainly through drinking water ingestion and dermal contact. As an emerging class of nitrogenous DBPs (N-DBPs), haloacetamides (HAcAms) have been found to have significantly higher cytotoxicity than regulated DBPs. In this study, we investigated the cytotoxicity of HAcAms on two exposure pathway-related cell lines: human gastric epithelial GES-1 cells and immortalized keratinocytes HaCaT. Our results showed that the ranking order of cytotoxicity of 13 HAcAms was different between HaCaT and GES-1 cells. In addition, the 50% inhibitive concentration in HaCaT was 1.01-3.29 times that in GES-1. Further comparison among GES-1, HaCaT and CHO cell lines confirmed that different cell lines exhibited different sensitivity to the same compound. Importantly, HAcAms showed 5.83-7.13 × 104 times higher toxicity than the well-clarified DBP chloroform, clearly demonstrating the increased toxicity of HAcAms. Finally, using a novel high-content screening (HCS) analysis, we found that 39.29% of chlorinated HAcAms, 42.86% of brominated HAcAms and 16.07% of iodinated HAcAms significantly affected at least one of the cell-health parameters, such as nuclear size, membrane permeability, mitochondrial membrane potential, or cytochrome c release, in GES-1 or HaCaT cells. Thus, brominated HAcAms appear to have stronger effects under the sublethal exposure dose, possibly causing cytotoxicity via apoptosis. Together, our study provides new insights to the toxicity of HAcAms and a comprehensive toxicology dataset for health risk assessment.


Assuntos
Acetamidas/toxicidade , Desinfetantes/toxicidade , Poluentes Químicos da Água/toxicidade , Linhagem Celular , Desinfecção , Humanos , Testes de Toxicidade
10.
Chem Commun (Camb) ; 55(79): 11916-11919, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528945

RESUMO

Supermolecule ß-cyclodextrin was used to assist CsPbBr3 film fabrication. In situ growth of nanocrystals was effectively confined through strong interactions between perovskite Pb2+ ions and ß-CD hydroxyl groups, producing a compact and smooth film. The quantum efficiency achieved was 85.3% with a moisture resistance over months, exceeding the record of perovskite films.

11.
Chem Asian J ; 14(19): 3279-3282, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486264

RESUMO

Compound [Ag42 S5 (StBu)25 (CF3 COO)4 (CO3 )](CO3 )0.5 ⋅CH2 Cl2 ⋅4CH3 OH⋅9DMF (1) has been obtained and well defined. It consists of a multi-shell structure involving two Ag centres, one Ag5 S5 pentagram, two Ag5 S5 pentagons and one Ag25 S15 shell. Compound 1 has been characterized by XPS, FT-IR, PXRD, TGA, NMR, MS, UV/Vis spectrum, TEM and cyclic voltammetry. Temperature-sensitive luminescent property of 1 has also been investigated.

12.
Chem Asian J ; 14(19): 3424-3430, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31502402

RESUMO

To increase the conductivity of polyoxometalate-based metal-organic frameworks (POMOFs) and promote their applications in the field of energy storage, herein, a simple approach was employed to improve their overall electrochemical performances by introducing a functionalized single-walled carbon nanotubes (SWNT-COOH). A new POMOF compound, [Cu18 (trz)12 Cl3 (H2 O)2 ][PW12 O40 ] (CuPW), was successfully synthesized, then the size-matched functionalized SWNT-COOH was introduced to fabricate CuPW/SWNT-COOH composite (PMNT-COOH) by employing a simple sonication-driven periodic functionalization strategy. When the PMNT-COOH nanocomposite was used as the anode material for Lithium-ion batteries (LIBs), PMNT-COOH(3) (CuPWNC:SWNT-COOH=3:1) showed superior behavior of energy storage, a high reversible capacity of 885 mA h g-1 up to a cycle life of 170 cycles. The electrochemical results indicate that the uniform packing of SWNT-COOH provided a favored contact between the electrolyte and the electrode, resulting in enhanced specific capacity during lithium insertion/extraction process. This fabrication of PMNT-COOH nanocomposite opens new avenues for the design and synthesis of new generation electrode materials for LIBs.

13.
Appl Environ Microbiol ; 85(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31492669

RESUMO

In deep-sea hydrothermal vent environments, sulfur-oxidizing bacteria belonging to the clade SUP05 are crucial symbionts of invertebrate animals. Marine viruses, as the most abundant biological entities in the ocean, play essential roles in regulating the sulfur metabolism of the SUP05 bacteria. To date, vent sponge-associated SUP05 and their phages have not been well documented. The current study analyzed microbiomes of Haplosclerida sponges from hydrothermal vents in the Okinawa Trough and recovered the dominant SUP05 genome, designated VS-SUP05. Phylogenetic analysis showed that VS-SUP05 was closely related to endosymbiotic SUP05 strains from mussels living in deep-sea hydrothermal vent fields. Homology and metabolic pathway comparisons against free-living and symbiotic SUP05 strains revealed that the VS-SUP05 genome shared many features with the deep-sea mussel symbionts. Supporting a potentially symbiotic lifestyle, the VS-SUP05 genome contained genes involved in the synthesis of essential amino acids and cofactors that are desired by the host. Analysis of sponge-associated viral sequences revealed putative VS-SUP05 phages, all of which were double-stranded viruses belonging to the families Myoviridae, Siphoviridae, Podoviridae, and Microviridae Among the phage sequences, one contig contained metabolic genes (iscR, iscS, and iscU) involved in iron-sulfur cluster formation. Interestingly, genome sequence comparison revealed horizontal transfer of the iscS gene among phages, VS-SUP05, and other symbiotic SUP05 strains, indicating an interaction between marine phages and SUP05 symbionts. Overall, our findings confirm the presence of SUP05 bacteria and their phages in sponges from deep-sea vents and imply a beneficial interaction that allows adaptation of the host sponge to the hydrothermal vent environment.IMPORTANCE Chemosynthetic SUP05 bacteria dominate the microbial communities of deep-sea hydrothermal vents around the world, SUP05 bacteria utilize reduced chemical compounds in vent fluids and commonly form symbioses with invertebrate organisms. This symbiotic relationship could be key to adapting to such unique and extreme environments. Viruses are the most abundant biological entities on the planet and have been identified in hydrothermal vent environments. However, their interactions with the symbiotic microbes of the SUP05 clade, along with their role in the symbiotic system, remain unclear. Here, using metagenomic sequence-based analyses, we determined that bacteriophages may support metabolism in SUP05 bacteria and play a role in the sponge-associated symbiosis system in hydrothermal vent environments.

14.
Toxicol Mech Methods ; : 1-9, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31364909

RESUMO

Psoralen has potential hepatotoxicity and has a certain promoting effect on the clinical liver injury of Psoralea corylifolia L (Fructus Psoraleae). This study investigated the underlying mechanisms of psoralen-induced hepatotoxicity in vitro. HepG2 cells were treated with psoralen for 6, 12, 24, or 48 h, and an endoplasmic reticulum (ER) stress-specific inhibitor, 4-PBA, was employed to investigate the mechanism of psoralen on ER stress and unfolded protein response (UPR). Cell viability was tested by MTT assay, ATP assay, and cell death by LDH. The apoptosis was reflected by the flow cytometry, caspase-8, and caspase-3 activates. The expression of ER stress-related markers was determined by RT-PCR and western blot. We found that psoralen significantly decreased cell viability, increased activities of caspase-8 and caspase-3, and upregulated expression of CHOP and BAX in a time- and dose-dependent manner. Moreover, psoralen significantly increased the expression and transcription levels of ER stress-related markers, including Grp78, PERK, eIF2α, ATF4, and ATF6, while IRE1α was not significantly affected. And 4-PBA could effectively inhibit psoralen-induced cell death and apoptosis along with the inhibition of ER stress responses. These results suggested that psoralen causes liver injury due to the induction of the ER stress-mediated apoptosis via PERK-eIF2α-ATF4-CHOP and ATF6-CHOP related pathways.

15.
J Am Chem Soc ; 141(36): 14115-14119, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31468961

RESUMO

Fe-N-C single-atom catalysts (SACs) exhibit high activity for oxygen reduction reaction (ORR). However, it remains controversial how the active center mediates catalysis, and the predicted potential deviates from experimental results, hindering development of ideal SACs. Here, using first-principles calculations, we present a microkinetic model for ORR on Fe-N-C SACs, disclosing a self-adjusting mechanism induced by its intrinsic intermediate. The modeling results show that the single-atom Fe site of the FeN4 center of Fe-N-C is covered with an intermediate OH* from 0.28 to 1.00 V. Remarkably, such OH* becomes part of the active moiety, Fe(OH)N4, and can optimize intermediate bindings on the Fe site, exhibiting a theoretical half-wave potential of ∼0.88 V. Partial current density analysis reveals the dominating associative path over the dissociative ones. In addition, ORR on Mn-N-C and Co-N-C SACs is unveiled. This work demonstrates the necessity of assessing the effect of intrinsic intermediates in single-atom catalysis and provides practical guidance for rational design of high-performance SACs.

16.
Nanoscale ; 11(43): 20554-20561, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432857

RESUMO

Color centers in silicon carbide have recently attracted broad interest as high bright single photon sources and defect spins with long coherence time at room temperature. There have been several methods to generate silicon vacancy defects with excellent spin properties in silicon carbide, such as electron irradiation and ion implantation. However, little is known about the depth distribution and nanoscale depth control of the shallow defects. Here, a method is presented to precisely control the depths of the ion implantation induced shallow silicon vacancy defects in silicon carbide by using reactive ion etching with little surface damage. After optimizing the major etching parameters, a slow and stable etching rate of about 5.5 ± 0.5 nm min-1 can be obtained. By successive nanoscale plasma etching, the shallow defects are brought close to the surface step by step. The photoluminescence spectrum and optically detected magnetic resonance spectra are measured, which confirm that there were no plasma-induced optical and spin property changes of the defects. By tracing the mean counts of the remaining defects after each etching process, the depth distribution of the defects can be obtained for various implantation conditions. Moreover, the spin coherence time T2* of the generated VSi defects is detected at different etch depths, which greatly decreases when the depth is less than 25 nm. The method of nanoscale depth control of silicon vacancies would pave the way for investigating the surface spin properties and the applications in nanoscale sensing and quantum photonics.

17.
Chemistry ; 25(59): 13472-13478, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31393035

RESUMO

A series of water-soluble cationic chalcogenoviologen-based photosensitizers for photodynamic antimicrobial therapy (PDAT) is reported. The Se-containing derivatives (SeMV2+ ) 5 b and 6 b showed good antimicrobial activities due to the presence of chalcogen atoms and a cationic scaffold. The former efficiently enhanced the generation of reactive oxygen species (ROS), and the latter facilitated the ROS delivery to bacteria, resulting in their death. Interestingly, alkyl-modified photosensitizers showed higher antimicrobial activities than commonly reported photosensitizers with quaternary ammonium (QA) groups. In particular, the SeMV2+ (6 b) with excellent antibacterial activities efficiently promoted the healing of infected wounds in mice. Simple yet novel, nontoxic and biocompatible chalcogenoviologens provided a promising strategy to develop new efficient photosensitizers for photodynamic antimicrobial therapy and skin regeneration.


Assuntos
Anti-Infecciosos/química , Cátions/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Pele/fisiopatologia , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Regeneração
18.
Basic Clin Pharmacol Toxicol ; 125(6): 527-535, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31271704

RESUMO

BACKGROUND: The main bioactive components of Fructus psoraleae, such as psoralen and isopsoralen, are known to be hepatotoxic. However, its underlying mechanism is to be elucidated. METHODS: To address this, SD rats were randomly divided into control group, 60 mg/kg psoralen group and 60 mg/kg isopsoralen group. Blood was collected to detect serum biochemical indices. RNA was extracted from liver samples, and then, cDNA gene expression profiles were analysed. RESULTS: Psoralen administration significantly up-regulated serum AST (aspartate aminotransferase) while addition of isopsoralen increased serum ALT (alanine aminotransferase), AST, TBA (total bile acid) and TG (total triglyceride) levels. A total of 172 differentially expressed genes (DEGs) were acquired between psoralen group and control group while 884 DEGs were screened between isopsoralen group and control group. Chemical Carcinogenesis and Metabolism of Xenobiotics by Cytochrome P450 were the two most significantly enriched pathways as revealed by DEGs. Liver was the most impacted organ, and endoplasmic reticulum was the most impacted organelle in subcellular level. Finally, some kinds of cancers and cytochrome p450 oxidoreductase deficiency were predicted. Taken together, psoralen and isopsoralen might cause hepatotoxicity mainly through cytochrome P450 metabolism of xenobiotics. Furthermore, Cyp1a1, Cyp1a2, Gstm1 and Akr7a3 worked as key genes in hepatotoxicity. Moreover, endoplasmic reticulum was the main target subcellular structure in hepatotoxicity induced by psoralen and isopsoralen.

19.
BMC Cancer ; 19(1): 691, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307405

RESUMO

BACKGROUND: Lung cancer is the most important cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not improved. Transforming growth factor beta or TGF-ß is a polypeptide member of the transforming growth factor beta superfamily of cytokines, while far fewer clinical studies addressing the association between TGF-ß expression and the disease prognosis have been reported up to now. Therefore, our meta-analysis aims to determine the prognostic significance of TGF-ß expression in lung cancer patients. METHODS: PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literature citations. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I2 statistic were used to estimate the level of heterogeneity. The publication bias was detected by Begg's test and Egger's test. RESULTS: Eight eligible studies involving 579 patients were selected for this meta-analysis. The combined HR for the eight eligible studies was 2.17 (95% CI: 1.71-2.77, P < 0.00001) and heterogeneity of overall prognosis was relatively low (I2 = 14.2%, P = 0.319). We further undertook the subgroup analysis including assessment of the association between TGF-ß expression and pathology of the lung cancer, treatment and quantity of sample in studies. All the results revealed that a significantly high TGF-ß expression in patients was an indicator of poor survival. Neither Begg's test nor Egger's test found publication bias in any analysis. CONCLUSIONS: The present evidence indicates that TGF-ß expression can significantly predict the worse prognosis in patients with lung cancer. The findings of our meta-analysis may be confirmed in the future by the use of more updated review pooling and additional relevant investigations.

20.
Biophys Chem ; 253: 106213, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31276987

RESUMO

The interaction event between programmed death receptor-1 (PD-1) and its ligand (PD-L1) functions as an essential immune checkpoint against cytotoxic T effector cell activation. Previously, a number of small-molecule inhibitors and antibody drugs have been successfully developed to block the PD1/PDL1 signaling axis for breast cancer immunotherapy. Here, we attempt to directly disrupt the formation of PD-1/PD-L1 complex by using a self-inhibitory peptide (SIP) strategy. In the procedure, the complex crystal structure is examined systematically with energetic analysis and alanine scanning. Two double-stranded segments I and II in PD-L1 active finger are identified as hotspot regions; they directly interact with the amphipathic pocket of PD-1 to form the complex system. The segments are derived from PD-L1 to define two SIP peptides, namely, DS-I and DS-II, which are thought to have capability of rebinding at the complex interface, thus disrupting PD-1/PD-L1 interaction as a new immune checkpoint blockade. A further analysis reveals that the free linear DS-I and DS-II peptides are highly flexible without protein context support, which would incur a large entropy penalty (unfavorable indirect readout effect) when rebinding to PD-1. Next, intramolecular cyclization is applied to constraining the intrinsically disordered conformation of free DS-II peptide into native ordered double-stranded configuration, which can be substantiated by molecular dynamics simulation and circular dichroism spectroscopy. Several cyclized counterparts of linear DS-II peptide are designed and their affinities to PD-1 are determined using fluorescence polarization assays. As might be expected, three designed cyclic peptides DS-II[c111-127], ΔDS-II[c111-127] and ΔDS-II[c110-128] exhibit considerably increased potency (Kd = 28.0 ±â€¯4.2, 17.5 ±â€¯3.1 and 11.6 ±â€¯2.3 µM, respectively) relative to linear DS-II peptide (Kd = 109 ±â€¯15 µM).


Assuntos
Antígeno B7-H1/imunologia , Neoplasias da Mama/terapia , Imunoterapia , Peptídeos/imunologia , Receptor de Morte Celular Programada 1/imunologia , Antígeno B7-H1/química , Neoplasias da Mama/imunologia , Dicroísmo Circular , Ciclização , Feminino , Humanos , Simulação de Dinâmica Molecular , Peptídeos/síntese química , Peptídeos/química , Receptor de Morte Celular Programada 1/química , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Linfócitos T Citotóxicos/imunologia
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