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1.
ANZ J Surg ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34291537

RESUMO

BACKGROUND: Previous studies have reached mixed results regarding the effects of patellar denervation with electrocautery (PD) on total knee replacement (TKR). This systematic review and meta-analysis aimed to summarize all available literatures to investigate the influence of PD on postoperative anterior knee pain (AKP) and knee function after TKR. METHODS: Electronic databases, including PubMed, Cochrane Library and Embase, were searched from their inception to March 2021. Randomized controlled trials (RCT) and quasi-randomized controlled trials (quasi-RCT) comparing PD and non-patellar denervation (NPD) in TKR were selected, and the Cochrane risk of bias tool was used to assess the quality of included trials. AKP prevalence was defined as the primary outcome. RESULTS: A total of 12 RCTs and one quasi-RCT enrolled 1895 knees proved eligible. PD knees had significantly lower AKP prevalence than NPD knees (odds ratio [OR] = 0.54; 95% confidence intervals [95% CI], 0.36-0.81; p = 0.003). There was no difference between PD and NPD in terms of visual analogue scale for knee pain and range of motion, American knee society knee score, American knee society function score, patellar feller score, Oxford knee score for knee function. The results of subgroup analysis based on follow-up duration and patella resurfacing were in accordance with the results. PD knees were not associated with a higher risk of complication or revision. CONCLUSION: PD can significantly reduce the AKP prevalence following TKR without increasing the risk of complication and revision. Although the pain relief effect of PD may not be associated with improved knee function after TKR, this procedure is preferred in both patella resurfacing and patella non-resurfacing TKR.

2.
Aging (Albany NY) ; 13(undefined)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282053

RESUMO

BACKGROUND: Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown. METHODS: A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal. RESULTS: Among the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover. CONCLUSIONS: In conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

3.
J Org Chem ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264081

RESUMO

Nickel-catalyzed asymmetric hydrogenation for kinetic resolution of [2.2]paracyclophane-derived cyclic N-sulfonylimines was successfully developed. High selectivity factors were observed in most cases (s up to 89), providing the recovered materials and hydrogenation products in good yields with high levels of enantiopurity. The recovered materials and hydrogenation products are useful synthetic intermediates for the synthesis of planar chiral [2.2]paracyclophane-based compounds.

4.
Org Lett ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34283623

RESUMO

An interrupted Pummerer/palladium-catalyzed fluoro-alkylation strategy was developed for alkenyl C-H fluoroalkylthiolation. Palladium-catalyzed ring-opening fluoroalkylation via aliphatic C-S bond cleavage of the vinylsulfonium salts efficiently afforded fluoroalkylthiolated alkene derivatives from readily available alkene substrates and CsF. The protocol features broad substrate scopes and good functional group tolerance under an air atmosphere. The practicability of the synthetic method was demonstrated by transforming the multisubstituted alkene products to diverse fluoroalkylthiolated N-heterocycles.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34246549

RESUMO

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of non-alcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportion of non-alcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

6.
Front Endocrinol (Lausanne) ; 12: 611526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248834

RESUMO

Background: It has been reported that dyslipidemia is related to coronavirus-related diseases. Critical patients with coronavirus disease 2019 (COVID-19) who suffered from multiple organ dysfunctions were treated in the intensive care unit (ICU) in Wuhan, China. Whether the lipids profile was associated with the prognosis of COVID-19 in critical patients remained unclear. Methods: A retrospective study was performed in critical patients (N=48) with coronavirus disease 2019 in Leishenshan hospital between February and April 2020 in Wuhan. The parameters including lipid profiles, liver function, and renal function were collected on admission day, 2-3days after the admission, and the day before the achievement of clinical outcome. Results: Albumin value and creatine kinase (ck) value were statistically decreased at 2-3 days after admission compared with those on admission day (P<0.05). Low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), apolipoprotein A (ApoA), and apolipoprotein A (Apo B) levels were statistically decreased after admission (P<0.05). Logistic regression showed that HDL-c level both on admission day and the day before the achievement of clinical outcome were negatively associated with mortality in critical patients with COVID-19. Total cholesterol (TC) level at 2-3days after admission was related to mortality in critical patients with COVID-19. Conclusions: There were lipid metabolic disorders in the critical patients with COVID-19. Lower levels of HDL-c and TC were related to the progression of critical COVID-19.


Assuntos
COVID-19/mortalidade , Dislipidemias/epidemiologia , Mortalidade Hospitalar , Insuficiência de Múltiplos Órgãos/mortalidade , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , COVID-19/sangue , COVID-19/epidemiologia , China/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estado Terminal , Dislipidemias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
7.
Huan Jing Ke Xue ; 42(8): 3709-3718, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309257

RESUMO

Lake Tianmu is an important source of drinking water, and its water quality can influence ecosystem service functions. Unraveling the sources and composition of chromophoric dissolved organic matter (CDOM) that can affect water treatment processes is necessary to maintain water supply safety and ecosystem service functioning of Lake Tianmu. Samples were collected monthly in 2017 and analyzed for CDOM absorbance and fluorescent spectra using parallel factor analysis (PARAFAC) to investigate the spatial and temporal variations of CDOM sources and composition in Lake Tianmu. PARAFAC results showed that CDOM in Lake Tianmu was mainly composed of a microbial humic-like component C1 (44.2%±9.8%), followed by a tryptophan-like component C2 (29.2%±4.3%), tyrosine-like component C3 (17.2%±13.1%), and terrestrial humic-like component, C4 was the lowest (9.4%±2.4%). The CDOM abundance a(254) and fluorescence intensities of C1 and C2 were significantly higher in the river mouths than in the downstream lake regions, whereas the spectral slope S275-295 was significantly lower in the river mouths (t-test, P<0.05), indicating that allochthonous inputs cause an elevated degree of humification and relative increase in the molecular weight of CDOM in the inflowing river mouths. Seasonal differences in CDOM composition were mainly ascribed to the a(254) and fluorescence intensities of C1, C2, and C4 being significantly higher in the summer and autumn than in the winter and spring (t-test, P<0.05). Our results showed that the influences of different seasons on CDOM composition comprise differences in rainfall and runoff input, as well as water temperature, thermal stratification, phytoplankton biomass, and mineralization of CDOM by light and microbes.


Assuntos
Água Potável , Lagos , China , Ecossistema , Rios , Espectrometria de Fluorescência
8.
Huan Jing Ke Xue ; 42(8): 3719-3729, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309258

RESUMO

In the past few decades, China's rapid industrial activities and urbanization processes have greatly impacted the urban surface water ecosystem. The changes in the quality of urban surface water directly affect the supply and carbon cycling of urban waters. We collected 50 water samples from urban rivers, lakes, and reservoirs in the city of Changchun in June 2020. Three-dimensional fluorescence spectroscopy coupled with parallel factor analysis (EEMs-PARAFAC) was used to unravel the optical characteristics, composition, and sources of chromophoric dissolved organic matter (CDOM). Our results indicated that the mean concentration of DOC is significantly higher in urban rivers than in reservoirs (t-test, P<0.05), and the mean UV absorption coefficient of CDOM a254 of urban rivers is significantly larger than that of park lakes and reservoirs (t-test, P<0.05), indicating that urban rivers have the highest concentration of CDOM. The spectral slope of CDOM absorption S275-295 and the spectral slope ratio SR were shown to be higher in park lakes than in reservoirs, and even higher than in urban rivers (t-test, P<0.001). Three fluorescent components were obtained using PARAFAC, namely terrestrial human-like (C1), microbial human-like (C2) and tryptophan-like (C3) components. The mean fluorescence intensity of C1-C3 was significantly higher in urban rivers than in both the park lakes and reservoirs (t-test, P<0.005), and the mean fluorescence intensity of C1 in the reservoir water body was significantly higher than that of C2 and C3 (t-test, P<0.005), indicating that the discharge of municipal wastewater likely contributes significantly to the CDOM pool of urban rivers in Changchun, and the contribution percentages of highly bio-labile protein-like components to the CDOM pool in these waters are high. Urban wastewater treatment should be strengthened to effectively protect water quality, as well as the economic, environmental, and ecological functions of urban waters in Changchun City.


Assuntos
Ecossistema , Rios , China , Humanos , Lagos , Espectrometria de Fluorescência , Qualidade da Água
9.
Nano Lett ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061554

RESUMO

Oxide semiconductors are widely used in the photocatalytic fields, and introducing oxygen vacancies is an effective strategy to improve their photocatalytic efficiency. However, oxygen vacancies in the bulk often act as the recombination centers of electron-hole pairs, which accelerates the recombination of electron-hole pairs. In this paper, we propose a strategy of electric field treatment and apply it to a TiO2 film with oxygen vacancies to promote the photocatalytic efficiency. After treatment by an electric field, the conductive channels consisting of oxygen vacancies are formed in the TiO2 film, which greatly decreases the resistance by almost 6 × 103 times. The yield of CO can reach up to 1.729 mmol gcat-1 h-1, which is one of the best performances among the reported TiO2-based catalysts. This work provides an effective and feasible way for enhancing photocatalytic activity through an electric field, and this method is promising for wide use in the field of catalysis.

11.
Nat Biomed Eng ; 5(6): 533-545, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34131321

RESUMO

Regular screening for the early detection of common chronic diseases might benefit from the use of deep-learning approaches, particularly in resource-poor or remote settings. Here we show that deep-learning models can be used to identify chronic kidney disease and type 2 diabetes solely from fundus images or in combination with clinical metadata (age, sex, height, weight, body-mass index and blood pressure) with areas under the receiver operating characteristic curve of 0.85-0.93. The models were trained and validated with a total of 115,344 retinal fundus photographs from 57,672 patients and can also be used to predict estimated glomerulal filtration rates and blood-glucose levels, with mean absolute errors of 11.1-13.4 ml min-1 per 1.73 m2 and 0.65-1.1 mmol l-1, and to stratify patients according to disease-progression risk. We evaluated the generalizability of the models for the identification of chronic kidney disease and type 2 diabetes with population-based external validation cohorts and via a prospective study with fundus images captured with smartphones, and assessed the feasibility of predicting disease progression in a longitudinal cohort.

12.
Inorg Chem ; 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34152761

RESUMO

The efficient synthesis of quantum materials is becoming a research hotspot as it determines their successful application in the fields of biomedicine, illumination, energy, sensors, information, and communication. Among the quantum materials, it is still a challenge to synthesize quantum wires (QWs) with surfactants due to the inevitable radial growth of QWs in the soft template method. In this paper, amphipathic graphene oxide (GO) was adopted as a macromolecular surfactant to limit the radial growth instead of the commonly used surfactant. GO could roll up under its electrostatic interaction with a cuprous oxide (Cu2O) quantum dot (QD) and then form a tubular template for the growth of the Cu2O QW, which was named herein as the nanoparticle-induced graphene oxide rolling (NIGOR) procedure. The NIGOR procedure was confirmed by the molecular dynamics results by simulating systems consisting of GO and Cu2O nanoparticles. An intermediate with a necklace morphology corresponding to the simulation result was also observed experimentally during the formation of the QW. Meanwhile, the formation mechanism of the QW was demonstrated rationally. Furthermore, increasing the dosage of the reactant, reaction time, and temperature altered the diameter of the QW from 2 to 4 nm and also changed the morphology of the final products from a QD to a QW and then to a bundle of QWs. This was attributed to the aggregation of materials for the lowest surface energy in the system. Additionally, the universality of NIGOR was manifested via the synthesis of other metal oxides as well. The NIGOR strategy provided an alternative, convenient, and mass production method for synthesizing QWs.

13.
Mol Cell Endocrinol ; 534: 111373, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34174367

RESUMO

Fracture healing is a complicated process affected by many factors, such as inflammatory responses and angiogenesis. Omentin-1 is an adipokine with anti-inflammatory properties, but whether omentin-1 affects the fracture healing process is still unknown. Here, by using global omentin-1 knockout (omentin-1-/-) mice, we demonstrated that omentin-1 deficiency resulted in delayed fracture healing in mice, accompanied by increased inflammation and osteoclast formation, and decreased production of platelet-derived growth factor-BB (PDGF-BB) and osteogenesis-promoting vessels that are strongly positive for CD31 and Endomucin (CD31hiEmcnhi) in the fracture area. In vitro, omentin-1 treatment suppressed the ability of the tumor necrosis factor-α (TNF-α)-activated macrophages to stimulate multi-nuclear osteoclast formation, resulting in a significant increase in the generation of mono-nuclear preosteoclasts and PDGF-BB, a pro-angiogenic protein that is abundantly secreted by preosteoclasts. PDGF-BB significantly augmented endothelial cell proliferation, tube formation and migration, whereas direct treatment with omentin-1 did not induce obvious effects on angiogenesis activities of endothelial cells. Our study suggests a positive role of omentin-1 in fracture healing, which may be associated with the inhibition of inflammation and stimulation of preosteoclast PDGF-BB-mediated promotion of CD31hiEmcnhi vessel formation.

14.
Biochem Pharmacol ; 190: 114642, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34077739

RESUMO

We performed additional mechanistic analyses to redefine neratinib biology and determined the mechanisms by which the multi-kinase inhibitor neratinib interacted with the thymidylate synthase inhibitor pemetrexed to kill NSCLC cells expressing either mutant KRAS (G12S; Q61H; G12A; G12C) or mutant NRAS (Q61K) or mutant ERBB1 (L858R; L858R T790M; exon 19 deletion). Neratinib rapidly reduced KRASG12V and RAC1G12V nanoclustering which was followed by KRASG12V, but not RAC1G12V, being extensively mislocalized away from the plasma membrane. This correlated with reduced levels of, and reorganized membrane localization of phosphatidylserine and cholesterol. Reduced nanoclustering was not associated with inactivation of ERBB1, Merlin or Ezrin. The drug combination killed cells expressing mutant KRAS, NRAS or mutant ERBB1 proteins. Afatinib or osimertinib resistant cells were killed with a similar efficacy to non-resistant cells. Compared to osimertinib-resistant cells, sensitive cells had less ERBB2 Y1248 phosphorylation. In osimertinib resistant H1975 cells, the drug combination was less capable of inactivating AKT, mTOR, STAT3, STAT5, ERK1/2 whereas it gained the ability to inactivate ERBB3. In resistant H1650 cells, the drug combination was less capable of inactivating JAK2 and STAT5. Sensitive cells exhibited elevated basal phosphorylation of YAP and TAZ. In resistant cells, portions of YAP and TAZ were localized in the nucleus. [Neratinib + pemetrexed] increased phosphorylation of YAP and TAZ, caused their nuclear exit, and enhanced ERBB2 degradation. Thus, neratinib targets an unidentified protein whose functional inhibition directly results in RAS inactivation and tumor cell killing. Our data prove that, albeit indirectly, oncogenic RAS proteins are druggable by neratinib.

15.
Mol Plant ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34171480

RESUMO

Rice (Oryza sativa), a major staple throughout the world and a model system for plant genomics and breeding, was the first crop genome sequenced almost two decades ago. However, reference genomes for all higher organisms to date contain gaps and missing sequences. Here, we report the assembly and analysis of gap-free reference genome sequences for two elite O. sativa xian/indica rice varieties, Zhenshan 97 and Minghui 63, which are being used as a model system for studying heterosis and yield. Gap-free reference genomes provide the opportunity for a global view of the structure and function of centromeres. We show that all rice centromeric regions share conserved centromere-specific satellite motifs with different copy numbers and structures. In addition, the similarity of CentO repeats in the same chromosome is higher than across chromosomes, supporting a model of local expansion and homogenization. Both genomes have over 395 non-TE genes located in centromere regions, of which ∼41% are actively transcribed. Two large structural variants at the end of chromosome 11 affect the copy number of resistance genes between the two genomes. The availability of the two gap-free genomes lays a solid foundation for further understanding genome structure and function in plants and breeding climate-resilient varieties.

16.
Immunol Lett ; 237: 17-26, 2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34192561

RESUMO

OBJECTIVE: To understand the characteristics of DNA methyltransferase 3a (DNMT3a) in thymoma associated Myasthenia Gravis reveal its transcriptional regulator network as while as analyze the effect of DNMT3a on Rel/ nuclear factor-kappaB family (RelA/RelB) and its downstream autoimmune regulatory factor (Aire). METHODS: Tissues of 30 patients with thymoma, with or without myasthenia gravis (MG), were collected and the DNMT3a protein expression were evaluated through immunohistochemistry. We performed mRNA expression profiling microarray detection and analysis, and integrated the analysis by constructing protein-protein interaction networks and the integration with other database. We identified molecular difference between low and high DNMT3a in the thymoma by heatmap. We also performed PCR validation in thymoma tissues. The DNMT3a-shRNA plasmid was transfected into TEC cells, and these cells were treated with 5-aza-2-deoxycytidine, a blocker of DNMT3a. After the down-regulation of DNMT3a in TEC cells, the transcript and protein levels of RelA, RelB, Aire, and CHRNA3 were evaluated by western blotting. In addition, changes in gene expression profiles were screened through microarray technology. We performed differential gene analysis in the thymoma cohort by heatmap with R (v.4.3.0) software. RESULTS: In 30 matched tissue specimens, the expression of DNMT3a protein in thymoma with MG was lower than that in thymoma. Through mRNA expression profiling analysis, we constructed a co-expression network of DNMT3a and found direct interaction between IKZF1 and DNMT3a, and this co-expression relationship was overlappted with Cistrome DB database. We found up-regulation of 149 mRNAs and repression of 177 mRNAs in thymoma with MG compared with thymoma. Gene ontology and pathway analysis show the involvement of a multitude of genes in the mis-regulation of MG-related pathways. RNA interference significantly reduced the level of mRNA of DNMT3a, which proved that plasmid DNMT3a was effective. In comparison to the control group, the levels of DNMT3a, Aire, and CHRNA3 mRNA and protein in TEC cells transfected with DNMT3a-shRNA interference plasmid were significantly decreased, while the expression level of RelA and RelA/RelB was significantly increased. CONCLUSIONS: Our study reveals the DNMT3a-NF-κB pathway has a major effect on MG, and can be used as a marker for diagnosis as well as a target for MG treatment.

17.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 1044-1054, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34110382

RESUMO

Growing evidence has indicated that the long noncoding RNA (lncRNA) CYTOR is involved in the initiation and progression of malignancies, including gastric cancer. Nevertheless, the mechanisms of CYTOR in gastric cancer development are not fully understood. In the present study, we aimed to clarify the association of CYTOR, miR-103, and RAB10 in gastric cancer progression. We found that CYTOR expression was increased in metastatic gastric cancer biopsies compared with that in primary samples. CYTOR expression was significantly positively correlated with the invasiveness, lymph node metastasis, and advanced stages of gastric cancer. In addition, downregulation of CYTOR expression hampered cell proliferation and migration but induced cell apoptosis. Furthermore, CYTOR sponged miR-103 and diminished miR-103 expression, thus rescuing oncogene RAB10 expression. Knockdown of CYTOR suppressed tumor growth in human BGC823 mouse models. These findings suggest that the CYTOR/miR-103/RAB10 axis is a novel signaling pathway that facilitates gastric cancer progression. CYTOR-targeted interventions provide a rationale to improve therapies targeting gastric cancer progression.

18.
Int J Pharm ; 606: 120825, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34171430

RESUMO

D-Limonene (D-Lim), a volatile oil extracted from citrus fruits, has therapeutic effects on lung inflammation and cancer, whilst the deep delivery of D-Lim was challenging due to its physical instability for a long period of time. To prevent the volatilization of D-Lim and achieve efficient pulmonary delivery, herein, D-Lim was loaded into biodegradable γ-cyclodextrin metal-organic framework (γ-CD-MOF) with optimal loading efficiency achieving 13.79 ± 0.01% (molar ratio of D-Lim and γ-CD-MOF was 1.6:1), which possessed cubic shape with controllable particle size (1-5 µm). The experimental results indicated that γ-CD-MOF could improve the stability of D-Lim. A series of characterizations and molecular docking were used to reveal the interaction between D-Lim and γ-CD-MOF. The solidification of D-Lim by γ-CD-MOF played a crucial role in the exploitation of its inhalable dosage form, dry powder inhaler (DPI). Specifically, the aerosolization of D-Lim@γ-CD-MOF for inhalation was satisfactory with a fine particle fraction (FPF) of 33.12 ± 1.50% at 65 L/min of flow rate. Furthermore, in vivo study had shown a 2.23-fold increase in bioavailability of D-Lim solidified by γ-CD-MOF for inhalation compared to D-Lim for oral administration. Therefore, it is considered that γ-CD-MOF could be an excellent carrier for pulmonary drug delivery to realize solidification and lung therapeutic effects of volatile oils.

19.
Oxid Med Cell Longev ; 2021: 8865813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968299

RESUMO

Cassiae Semen is a widely used herbal medicine and a popular edible variety in many dietary or health beverage. Emerging evidence disclosed that improper administration of Cassiae Semen could induce obvious liver injury, which is possibly attributed to emodin, one of the bioactive anthraquinone compounds in Cassiae Semen, which caused hepatotoxicity, but the underlying mechanisms are not completely understood. Hence, the present study firstly explored the possible role of oxidative stress-mediated mitochondrial dysfunction and ER stress in emodin-cause apoptosis of L02 cells, aiming to elaborate possible toxic mechanisms involved in emodin-induced hepatotoxicity. Our results showed that emodin-induced ROS activated ER stress and the UPR via the BiP/IRE1α/CHOP signaling pathway, followed by ER Ca2+ release and cytoplasmic Ca2+ overloading. At the same time, emodin-caused redox imbalance increased mtROS while decreased MMP and mitochondrial function, resulting in the leaks of mitochondrial-related proapoptotic factors. Interestingly, blocking Ca2+ release from ER by 2-APB could inhibit emodin-induced apoptosis of L02, but the restored mitochondrial function did not reduce the apoptosis rates of emodin-treated cells. Besides, tunicamycin (TM) and doxorubicin (DOX) were used to activate ER stress and mitochondrial injury at a dosage where obvious apoptosis was not observed, respectively. We found that cotreatment with TM and DOX significantly induced apoptosis of L02 cells. Thus, all the results indicated that emodin-induced excessive ROS generation and redox imbalance promoted apoptosis, which was mainly associated with BiP/IRE1α/CHOP signaling-mediated ER stress and would be enhanced by oxidative stress-mediated mitochondrial dysfunction. Altogether, this finding has implicated that redox imbalance-mediated ER stress could be an alternative target for the treatment of Cassiae Semen or other medicine-food homologous varieties containing emodin-induced liver injury.


Assuntos
Emodina/uso terapêutico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Apoptose , Linhagem Celular Tumoral , Emodina/farmacologia , Humanos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Smegmamorpha
20.
Urolithiasis ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34050772

RESUMO

Calcium oxalate (CaOx) is a major contributor to urolithiasis, one of the most common urological diseases. Our previous study has shown that Klotho rs3752472 polymorphism correlates with an increased risk of CaOx-related urolithiasis in human cohorts. This study aims to identify the effect of Klotho rs3752472 polymorphism on the renal epithelium injury caused by CaOx. A rat urolithiasis model was established and validated. Renal function was assessed, and histological examination was performed. The distribution and expression of Klotho in the rat model were detected by immunohistochemical staining and western blotting analysis. A renal epithelial cell line (HK2) was used and intervened by COM crystals with several concentrations and time points. Expression of Klotho and key mediators in Wnt/ß-catenin pathway were assessed by Western blotting analysis. Wide-type and mutated plasmids of Klotho rs3752472 were added in the cell culture, and the activation of Wnt/ß-catenin signaling was tested. Finally, Wide-type and mutated plasmids of Klotho rs3752472 were adoptively transferred to the rat model, and the expression of Klotho was verified. In the rat model, Klotho was mainly distributed in the renal tubular area, which significantly declined in the urolithiasis group. In vitro, COM crystals significantly inhibited the expression of Klotho and induced remarkable renal epithelial cell injury. The mutation of Klotho rs3752472 can notably enhance the expression of Klotho, as well as the protection from renal epithelial cell injury and the inhibition of Wnt/ß-catenin signaling pathway. After adoptively transferred to the rat urolithiasis model, similar results were observed for the mutation of Klotho rs3752472. Klotho was significantly correlated with the renal epithelial cell injury induced by CaOx crystals. Furthermore, the mutation of Klotho rs3752472 can remarkably enhance the expression of Klotho in renal tissues and cells, and subsequently protect the renal epithelial cell from the formation of CaOx crystals through the inhibition of Wnt/ß-catenin signaling pathway.

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