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1.
Sci Total Environ ; 724: 138134, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32408437

RESUMO

PM2.5 pollution has been one of the main environmental issues of concern for the Yangtze River Delta Urban Agglomeration (YRDUA) during the recent decade. In this paper, allied with big data and wavelet analysis, spatiotemporal variations of PM2.5 and its influencing factors (air pollutants and meteorological factors) are studied based on hourly concentrations of PM2.5 from 2015 to 2018 in the YRDUA. Results showed that PM2.5 presented a step-shaped decline from northwest to southeast in space and significant multi-scale temporal variations in time. On the macroscopic level, PM2.5 concentrations decreased from 2015 to 2018, showing a U-shaped pattern within a year. On the microscopic level, it had a four-stage annual variation (January to March, April to June, July to September, October to December) and the mutation events mainly occurred in winter. There were two dominant periods of PM2.5, an annual cycle on the time scale of 250-480 d and a semi-annual cycle on the time scale of 130-220 d. In addition, PM2.5 showed time scale-dependent correlations with air pollutants and meteorological factors. Among air pollutants, the correlation between PM2.5 and CO was the most consistent, and the correlation between PM2.5 and SO2/NO2 improved with the increase of time scale, while the correlation between PM2.5 and O3 was positive at shorter time scales but negative at broader time scales. Among meteorological factors, the correlations between PM2.5 and wind speed, precipitation, temperature, air pressure and relative humidity were mainly reflected at broader time scales. These findings would be helpful to improve the accuracy of prediction model and provide references for the ongoing joint prevention and control.

2.
Sci Total Environ ; 724: 138187, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32408447

RESUMO

Chlorophenols (CPs) are important pollutants detected frequently in the environment. This study intended to detect the inhibitory effects of fourteen CPs (2-CP, 3-CP, 4-CP, 4C2AP, 4C3MP, 2.4-DCP, 2.3.4-TCP, 2.4.5-TCP, 2.4.6-TCP, 3.4.5-TCP, 2.3.4.5-TECP, 2.3.4.6-TECP, 2.3.5.6-TECP and PCP) towards human liver cytochrome P450 3A4 (CYP3A4). Throughout the tests, testosterone was used as the probe substrate and CPs were used as inhibitors. A series of experiments (enzyme activity assays, preliminary screening tests, inhibition kinetics determination) were conducted to determine the inhibition of CPs towards human liver CYP3A4. CPs with the inhibitory effect >80% were selected for the inhibition evaluation in liver microsomes from different animal species (monkey, rat, dog, pig). The results showed that 2.3.4-TCP, 3.4.5-TCP, and 2.3.4.5-TECP inhibited the activities of CYP3A4 by 80.3%, 93.4%, 91.6%, respectively. Inhibition kinetics type were non-competitive and inhibition kinetics constant (Ki) values were 26.4 µM, 13.5 µM, and 8.8 µM for the inhibition of 2.3.4-TCP, 3.4.5-TCP, and 2.3.4.5-TECP towards human CYP3A4, respectively. Inhibition kinetics type was competitive and Ki value was 4.9 µM for the inhibition of 2.3.4-TCP towards CYP3A4 in Monkey liver microsomes (MyLMs). Inhibition kinetic types were non-competitive and Ki values were 8.1 µM and 28.7 µM for the inhibition of 3.4.5-TCP and 2.3.4.5-TECP towards CYP3A4 in MyLMs. Inhibition kinetic types were non-competitive and Ki values were 13.8 µM, 0.6 µM, and 6.1 µM for the inhibition of 2.3.4-TCP, 3.4.5-TCP, and 2.3.4.5-TECP towards CYP3A4 in Dog liver microsomes (DLMs), respectively. By comparing Ki values and inhibition kinetic types, the dog was the most suitable model to assess the inhibition of 2.3.4-TCP and 2.3.4.5-TECP towards CYP3A4, and monkey was the most suitable model to assess the inhibition of 3.4.5-TCP towards CYP3A4. In conclusion, our recent study on the inhibition of CPs towards CYP3A4 and species differences was important for further toxicological studies of CPs in human bodies.

3.
J Mater Chem B ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32373848

RESUMO

Researchers developing implantable neural probes face a dilemma. Rigid neural probes facilitate direct implantation, but the brain tissue suffers from a vulnerable interface and a strong neuroinflammatory response due to mechanical mismatch between the probe and the brain tissue. Flexible neural probes offer stable interfaces and eliminate neuroinflammatory responses but require auxiliary implantation. Here, we have created a new kind of micro fiber-shaped neural probe with alterable elastic moduli before and after implantation. Carbon nanotube fibers and calcium crosslinked sodium alginate functioned as the core electrode and sheath layer, respectively. The response of calcium crosslinked sodium alginate to water will alter the probe elastic moduli from ∼10 GPa to ∼10 kPa post implantation, which is close to the elastic modulus of brain tissue. The micro fiber probes were directly implanted into mouse brains without any additional materials. After implantation, they became soft and offered dynamically adaptable interfaces with a reduced inflammatory response, benefiting long-term monitoring of neuron signals. Continuous four week monitoring of neuron signals was achieved. The simplicity of the strategy makes it suitable for versatile neuron techniques in neuron recording and modulation.

4.
J Int Med Res ; 48(5): 300060520905488, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32363966

RESUMO

Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.

5.
ChemSusChem ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367650

RESUMO

Oxygen vacancy is usually thought to be beneficial for photogenerated charge separation. In this work, the oxygen vacancy in ov-Bi 2 O 3 (Bi 2 O 3 with oxygen vacancy) is found to be able to produce 1 O 2 in the dark due to chemical adsorption. The oxygen vacancy is further found to be responsible for the results that ov-Bi 2 O 3 exhibits higher 1 O 2 generation under light irradiation with 1 O 2 as the only reactive oxygen species (ROS) than does Bi 2 O 3 with 1 O 2 , H 2 O 2 etc. as the ROS. The photocatalytic activity is checked by the selective photo-oxidation of phenyl methyl sulfide to phenyl methyl sulfoxide and phenyl alcohol to benzaldehyde. In either case, ov-Bi 2 O 3 displays better performance than does Bi 2 O 3 , suggesting the significant role of oxygen vacancy in modulating the photocatalytic oxidation properties. This work provides an alternative approach to obtain singlet oxygen, which may guide further design of photocatalysts with high efficiency and selectivity towards photocatalytic organic synthesis.

6.
BMC Plant Biol ; 20(1): 159, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293284

RESUMO

BACKGROUND: In most angiosperms, the inheritance of the mitochondria takes place in a typical maternal manner. However, very less information is available about if the existence of structural variations or not in mitochondrial genomes (mitogenomes) between maternal parents and their progenies. RESULTS: In order to find the answer, a stable rice backcross inbred line (BIL) population was derived from the crosses of Oryza glaberrima/Oryza sativa//Oryza sativa. The current study presents a comparative analysis of the mitogenomes between maternal parents and five BILs. There were recorded universal structural variations such as reversal, translocation, fusion, and fission among the BILs. The repeat-mediated recombination and non-homologous end-joining contributed virtually equal to the rearrangement of mitogenomes. Similarly, the relative order, copy-number, expression level, and RNA-editing rate of mitochondrial genes were also extensively varied among BILs. CONCLUSIONS: These novel findings unraveled an unusual mystery of the maternal inheritance and possible cause for heterogeneity of mitogenomes in rice population. The current piece of work will greatly develop our understanding of the plant nucleo-cytoplasmic interaction and their potential role in plant growth and developmental processes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32314195

RESUMO

PURPOSE: Cystic fibrosis transmembrane conductance regulator (CFTR) and adhesion G protein-coupled receptor G2 (ADGRG2) have been identified as the main pathogenic genes in congenital bilateral absence of the vas deferens (CBAVD), which is an important cause of obstructive azoospermia. This study aimed to identify the disease-causing gene in two brothers with CBAVD from a Chinese consanguineous family and reveal the intracytoplasmic sperm injection (ICSI) outcomes in these patients. METHODS: Whole-exome sequencing and Sanger sequencing were used to identify the candidate pathogenic genes. Real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to assess the expression of the mutant gene. Moreover, the ICSI results from both patients were retrospectively reviewed. RESULTS: A novel hemizygous loss-of-function mutation (c.G118T: p.Glu40*) in ADGRG2 was identified in both patients with CBAVD. This mutation is absent from the human genome databases and causes an early translational termination in the third exon of ADGRG2. Expression analyses showed that both the ADGRG2 mRNA and the corresponding protein were undetectable in the proximal epididymal tissue of ADGRG2-mutated patients. ADGRG2 expression was restricted to the apical membranes of non-ciliated epithelia in human efferent ducts, which was consistent with a previous report in mice. Both ADGRG2-mutated patients had normal spermatogenesis and had successful clinical outcomes following ICSI. CONCLUSIONS: Our study verifies the pathogenic role of ADGRG2 in X-linked CBAVD and broadens the spectrum of ADGRG2 mutations. In addition, we found positive ICSI outcomes in the two ADGRG2-mutated CBAVD patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32273695

RESUMO

Purpose: The present study aimed to develop and validate the modified patient-reported outcome scale for chronic obstructive pulmonary disease (mCOPD-PRO) for measuring the health status in COPD using both classical test theory and item response theory. Methods: A working group was initially established. The conceptual framework of COPD-PRO was modified. Subsequently, items related to COPD were gathered and selected through expert consultation, patient cognitive interviewing, classical test theory methods, as well as the item response theory method. Finally, the formed mCOPD-PRO was evaluated in terms of reliability, content validity, construct validity, criterion validity, known groups validity, and feasibility. Results: A total of 155 items were gathered in the item bank, and two rounds of expert consultation, interviews with patients and field survey were conducted. The mCOPD-PRO included 27 items in the physiological, psychological, and environmental domains. The Cronbach's alpha of the instrument was 0.954. The correlation coefficients between the scores of each item and its domain scores ranged from 0.429 to 0.902. Confirmatory factor analysis showed that the comparative fit index, incremental fit index, non-normed fit index, standardized root-mean-square residual, and root-mean-square error of approximate were 0.91, 0.91, 0.90, 0.11, and 0.16, respectively. The correlation coefficient between mCOPD-PRO total scores and COPD assessment test scores and the modified Medical Research Council dyspnea scale scores was 0.771 and 0.651, respectively. The differences in mCOPD-PRO total scores and domain scores between the mild/moderate group and severe/extremely severe group of patients with COPD were both statistically significant (P<0.01). The acceptance and completion rates of mCOPD-PRO were both 99.5%, and the median completion time was 5 min (IQR, 4-11 min). Conclusion: The 27-item mCOPD-PRO is well developed and has good reliability, validity, and feasibility. It may provide a scientific and effective instrument for the clinical evaluation of COPD.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32323121

RESUMO

BACKGROUND: Asthenoteratospermia with multiple morphological abnormalities in the sperm flagella (MMAF) is a significant cause of male infertility. WDR19 is a core component in the IFT-A complex and has a critical role in intraflagellar transport. However, the role of WDR19 mutations in male infertility has yet to be examined. METHODS AND RESULTS: We performed whole exome sequencing (WES) for 65 asthenoteratospermia individuals and identified a proband who carried a homozygous WDR19 (c.A3811G, p.K1271E) mutation from a consanguineous family. Systematic examinations, including CT scanning and retinal imaging, excluded previous ciliopathic syndromes in the proband. Moreover, semen analysis of this patient showed that the progressive rate decreased to zero, and the sperm flagella showed multiple morphological abnormalities. Scanning and transmission electron microscopy assays indicated that the ultrastructure of sperm flagella in the patient was completely destroyed, while immunofluorescence revealed that WDR19 was absent from the sperm neck and flagella. Moreover, IFT140 and IFT88, predicted to interact with WDR19 directly, were mis-allocated in the WDR19-mutated sperm. Notably, the MMAF subject harboring WDR19 variant and his partner successfully achieved clinical pregnancy through intracytoplasmic sperm injection (ICSI). CONCLUSIONS: We identified WDR19 as a novel pathogenic gene for male infertility caused by asthenoteratospermia in the absence of other ciliopathic phenotypes, and that patients carrying WDR19 variant can have favorable pregnancy outcomes following ICSI.

10.
Int J Cardiovasc Imaging ; 36(6): 1157-1166, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32146608

RESUMO

To evaluate the accuracy of compressed sensing (CS) cardiovascular magnetic resonance imaging (CMR) in the classifications of heart failure (HF). One hundred and fifty-four patients underwent 3 T CMR using CS single-breath-hold cine (SBH-cine) after a standard multiple-breath-hold cine (MBH-cine). The image quality of the two methods was compared. Cardiac function parameters were quantitatively analyzed. The patients were divided into different HF types based on diagnostic criteria using two sequences. The scan time for CS SBH-cine was reduced by 88% compared with that of standard MBH-cine. In the non-atrial-fibrillation (NAF) group (n = 121), the image quality score of CS SBH-cine was slightly decreased compared with standard MBH-cine (4.5 ± 0.6 for the CS SBH-cine vs. 4.7 ± 0.5 for the standard MBH-cine, T = 5.038, p < 0.05). In the atrial fibrillation (AF) group (n = 33), the CS SBH-cine image quality score was slightly higher than that of the standard MBH-cine (3.8 ± 0.7 for the CS SBH-cine vs. 3.3 ± 0.5 for the standard MBH-cine, T = - 4.503, p < 0.05). The left ventricular (LV) end diastolic volume, LV end systolic volume, LV ejection fraction, and LV mass index calculated by CS SBH-cine had no significant differences from those calculated by standard MBH-cine. The agreement on HF classifications of both the standard MBH-cine and the CS SBH-cine was excellent (kappa = 0.934, p < 0.05). The result showed that HF could be classified accurately using CS SBH-cine.

11.
J Pharm Biomed Anal ; 185: 113244, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32193041

RESUMO

Currently, controllable linker cleavage at the target site will facilitate the clinical treatment of cancer. Dual-functional prodrugs in combination of carbohydrate as targeting group and pH-sensitive cleavable linker are desired in clinical development. Here, a qualified structure of N-phenylcarbamate-d-gluconhydroximo-1,5-lactam was employed and proved to be a potential candidate prodrug in the drug design. To proof this concept, the possible mechanism of Beckmann rearrangement and the degraded products were confirmed by HPLC and LC-MS under the acid condition mimic lysosome. Hence, the strategy of d-gluconhydroximo-1,5-lactam as a prodrug carrier fabricated with interested drugs will provide a great potential approach for chemotherapy.

12.
J Assist Reprod Genet ; 37(4): 829-840, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124190

RESUMO

PURPOSE: To investigate the relation between mutations in ciliopathy-related SPAG6 and RSPH3 and male infertility with severe asthenoteratospermia characterized by multiple flagellar malformations and reveal the intracytoplasmic sperm injection (ICSI) outcomes of those primary ciliary dyskinesia (PCD) patients. METHODS: Whole-exome sequencing was applied to identify the pathogenic genes for the five PCD patients. The ICSI outcomes of those patients were compared with eight DNAH1-mutated patients and 215 oligo-asthenospermia (OAT) patients. RESULTS: We identified, for the first time, the compound heterozygous SPAG6 mutations (c.143_145del: p.48_49del, c.585delA: p.Lys196Serfs*6) in a sporadic PCD patient. Further, a novel homozygous nonsynonymous RSPH3 mutation (c.C799T: p.Arg267Cys) was identified in another PCD patient with consanguineous parents. The pathogenicity of these mutations in the assembly of sperm flagella was confirmed by flagellar ultrastructure analysis, immunofluorescence, and quantitative real-time PCR. All five patients underwent six ICSI cycles. The fertilization rate, blastocyst development rate, and clinical pregnancy rate were 69.3%, 50.0%, and 66.7%, respectively. Four of the five couples, including the subjects carrying mutations in SPAG6 or RSPH3, got healthy children born after ICSI. Additionally, the ICSI outcomes of the five PCD couples were statistically comparable with those of the eight DNAH1-mutated couples and the 215 OAT couples. CONCLUSIONS: Mutations in ciliopathy-related SPAG6 and RSPH3 cause severe asthenoteratospermia characterized by multiple flagellar malformations, resulting in sterility. ICSI is an optimal management with a positive pregnancy outcome.

13.
J Asian Nat Prod Res ; 22(6): 521-530, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32186415

RESUMO

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1-3), with four known compounds (4-7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.[Formula: see text].


Assuntos
Hypericum , Células Hep G2 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Floroglucinol
14.
Water Res ; 175: 115673, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32171097

RESUMO

Due to the increase of emerging contaminants in water, how to use new treatment technology to make up for the defects of traditional wastewater treatment method has become one of the research hotspots at present. Intimate coupling of photocatalysis and biodegradation (ICPB) as a novel wastewater treatment method, which combines the advantages of biological treatment and photocatalytic reactions, has shown a great potential as a low-cost, environmental friendly and sustainable treatment technology. The system mainly consists of photocatalytic materials, porous carriers and biofilm. The key principle of ICPB is to transform bio-recalcitrant pollutants into biodegradable products by photocatalysis on the surface of porous carriers. The biodegradable products were mineralized simultaneously through the biofilm inside the carriers. Because of the protection of the carriers, the microorganism can remain active even under the UV-light, the mechanical force of water flow or the attack of free radicals. ICPB breaks the traditional concept that photocatalytic reaction and biodegradation must be separated in different reactors, improves the purification capacity of sewage and saves the cost. This review summarizes the recent advances of ICPB photocatalysts, carriers and biofilm being applied, and focuses on the mechanisms and reactor configurations which is particularly novel. Furthermore, the possible ongoing researches on ICPB are also put forward. This review will provide a valuable insight into the design and application of ICPB in environment and energy field.


Assuntos
Titânio , Águas Residuárias , Biodegradação Ambiental , Biofilmes , Esgotos
15.
Environ Sci Technol ; 54(7): 3940-3950, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32182045

RESUMO

In flooded paddy soils, inorganic and methylated thioarsenates contribute substantially to arsenic speciation besides the much-better-investigated oxyarsenic species, and thioarsenate uptake into rice plants has recently been shown. To better understand their fate when soil redox conditions change, that is, from flooding to drainage to reflooding, batch incubations and unplanted microcosm experiments were conducted with two paddy soils covering redox potentials from EH -260 to +200 mV. Further, occurrence of thioarsenates in the oxygenated rice rhizosphere was investigated using planted rhizobox experiments. Soil flooding resulted in rapid formation of inorganic thioarsenates with a dominance of trithioarsenate. Maximum thiolation of inorganic oxyarsenic species was 57% at EH -130 mV and oxidation caused nearly complete dethiolation. Only monothioarsenate formed again upon reflooding and was the major inorganic thioarsenate detected in the rhizosphere. Maximum thiolation of mono- and dimethylated oxyarsenates was about 70% and 100%, respectively, below EH 0 mV. Dithiolated species dominated over monothiolated species below EH -100 mV. Among all thioarsenates, dimethylated monothioarsenate showed the least transformation upon prolonged oxidation. It also was the major thiolated arsenic species in the rhizosphere with concentrations comparable to its precursor dimethylated oxyarsenate, which is especially critical since dimethylated monothioarsenate is highly carcinogenic.

16.
Clin Rheumatol ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189150

RESUMO

OBJECTIVES: Our aim was to investigate the prevalence value of a high-avidity antinuclear antibody (ANA) of the IgG isotype (HA IgG ANA) compared with that of ANAs of other isotypes in patients with systemic lupus erythematosus (SLE) and to assess the associations of HA IgG ANA with the activity of SLE and lupus nephritis. METHODS: We retrospectively analyzed clinical and laboratory data from subjects. Blood samples were acquired from 101 SLE patients, 67 patients with other autoimmune diseases, and 65 healthy donors. The levels of HA IgG ANA and other isotype ANAs were measured by indirect immunofluorescence (IIF). The prevalence and diagnosis value of HA IgG ANA and other antibodies in SLE patient were tested. The advantage of HA IgG ANA compared with HA anti-dsDNA antibodies IgG (HA dsDNA IgG) was verified by ELISA. We monitored the relative avidity indexes (RAIs) of HA IgG ANA and HA dsDNA IgG at 3 time points after the start of treatment in the same individuals with SLE. RESULTS: The prevalence of HA IgG ANA was significantly higher in active cases than in inactive cases of SLE and LN, which is consistent with data for IgG ANAs, anti-dsDNA IgG antibodies, low C3 levels, low C4 levels, and anti-C1q antibodies. HA IgG ANA showed moderate sensitivity and specificity (80% and 81.3%) for discriminating active and inactive SLE cases. However, HA IgG ANA showed no significant differences among the different clinical manifestations of SLE. Compared with that of HA dsDNA IgG, the RAI of HA IgG ANA was positively related to SLEDAI scores after treatment at 0, 1, and 3 months (r = 0.6813, p = 0.0026; r = 0.5972, p = 0.0114; r = 0.4817, p = 0.0474). CONCLUSIONS: First, we demonstrated that HA IgG ANA was a reliable diagnostic tool in SLE patients. Furthermore, HA IgG ANA was supposed to be more appropriate for identifying the activity of SLE compared with HA dsDNA IgG. In summary, HA IgG ANA may be a new biomarker for diagnosing SLE and identifying SLE activity.Key Points• We first introduced the concept of a "high-avidity IgG ANA (HA IgG ANA)" that could distinguish between the early stage of SLE and SLE that had been active for some time.• The relative avidity indexes (RAIs) of HA IgG ANA and HA dsDNAIgG were presented and applied here to evaluate the avidities of antibodies involved in SLE.• In our study, we confirmed the value of HA IgG ANA in diagnosing SLE. In addition, HA IgG ANA was more appropriate for identifying the activity of SLE than was HA dsDNA IgG.• In conclusion, HA IgG ANA could be a potential biomarker for the assessment of the prognosis of SLE activity.

17.
Int J Mol Sci ; 21(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150824

RESUMO

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1ß were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

18.
Fitoterapia ; 142: 104535, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32145311

RESUMO

Three new homoadamantane-type polyprenylated acylphloroglucinols, hyperacmosins E-G (1-3), with seven known compounds were isolated from the air-dried aerial parts of Hypericum asmosepalum. Their structures were determined by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of these compounds were evaluated. Compounds 4 and 8 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.

19.
Bioorg Chem ; 99: 103768, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217375

RESUMO

Mitochondria as one of potential anticancer target, alternatively damaging mtDNA other than nDNA is a potential method for platinum-based anticancer drugs to overcome cisplatin resistance. We herein report that bromocoumarinplatin 1, a coumarin-Pt(IV) prodrug, targeted simultaneously mitochondria and nuclei with the contents of Pt in nDNA and mtDNA were 25.75% and 65.91%, respectively, which demonstrated mtDNA apoptosis played a key role in overcoming cisplatin resistance. Moreover, 1 promoted the expression of p53 gene and protein more effectively than cisplatin, leading to the increased anticancer activity of 1 through p53 pathway. The property of preferential accumulation in cancer cells (Snu-368 and Snu-739) compared to the matched normal cells (HL-7702 cells) demonstrated that 1 was potentially safe for clinical therapeutic use. In addition, the higher therapeutic indices of 1 for HCT-116 cells in vivo indicated that bromocoumarinplatin behaved a vital function in the treatment of colon cancer.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32015036

RESUMO

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 µg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P < 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P < 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0-12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P = 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P = 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P = 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P = 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (C min) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 µg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.

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