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1.
Front Pharmacol ; 13: 842839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308239

RESUMO

In the clinical practice of traditional Chinese medicine, toxic heat and blood stasis syndrome (THBSS) is a common syndrome observed in various critical diseases. Paeoniae Radix Rubra (PRR) has known therapeutic effects on THBSS. However, its pharmacodynamic mechanisms and effective substances in the treatment of THBSS still need further elucidation. Our previous study indicated that THBSS had three stages of progression, and the abnormal biochemical indices of each stage were different. Therefore, this study aimed to elucidate the pharmacodynamic mechanisms and effective substances of PRR for the treatment of THBSS with a stage-oriented strategy. Specifically, research was performed separately in two stable stages of THBSS: the excessive heat and little blood stasis (EHLBS) and blood stasis (BS) stages. THBSS model rats, at different time periods after syndrome initiation (first 5 h for EHLBS and 24 h later for BS), were used to conduct the two-stage investigation. Targeted metabonomics analysis was performed to elucidate the pharmacodynamic mechanisms of PRR in the treatment of EHLBS or BS. Based on the relationship between the individual differences in blood drug concentrations and pharmacodynamic effects, partial least squares regression analysis was employed to screen for the effective substances from the original constituents and metabolites of PRR. We found that PRR could upregulate primary bile acid biosynthesis, glycerophospholipid metabolism, ether lipid metabolism, and five amino acid metabolic pathways (e.g., arginine and proline metabolism) to treat EHLBS. Meanwhile, PRR alleviated BS by upregulating primary bile acid biosynthesis and downregulating glycerophospholipid metabolism. But PRR had no obvious effects on ether lipid metabolism and amino acid metabolism in this stage. In total, 17 and 9 potential effective substances were found in the EHLBS and BS stages, respectively, among which there were only five common compounds between the two stages. To our knowledge, sixteen compounds were regarded as potential effective substances of PRR for the first time. Therefore, the pharmacodynamic mechanisms and effective substances of PRR in the treatment of EHLBS and BS were partly different. Overall, this stage-oriented strategy provides a new way to study the pharmacodynamic mechanisms and effective substances of traditional Chinese drugs.

2.
Int J Ophthalmol ; 15(3): 495-501, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310049

RESUMO

AIM: To explore a more accurate quantifying diagnosis method of diabetic macular edema (DME) by displaying detailed 3D morphometry beyond the gold-standard quantification indicator-central retinal thickness (CRT) and apply it in follow-up of DME patients. METHODS: Optical coherence tomography (OCT) scans of 229 eyes from 160 patients were collected. We manually annotated cystoid macular edema (CME), subretinal fluid (SRF) and fovea as ground truths. Deep convolution neural networks (DCNNs) were constructed including U-Net, sASPP, HRNetV2-W48, and HRNetV2-W48+Object-Contextual Representation (OCR) for fluid (CME+SRF) segmentation and fovea detection respectively, based on which the thickness maps of CME, SRF and retina were generated and divided by Early Treatment Diabetic Retinopathy Study (ETDRS) grid. RESULTS: In fluid segmentation, with the best DCNN constructed and loss function, the dice similarity coefficients (DSC) of segmentation reached 0.78 (CME), 0.82 (SRF), and 0.95 (retina). In fovea detection, the average deviation between the predicted fovea and the ground truth reached 145.7±117.8 µm. The generated macular edema thickness maps are able to discover center-involved DME by intuitive morphometry and fluid volume, which is ignored by the traditional definition of CRT>250 µm. Thickness maps could also help to discover fluid above or below the fovea center ignored or underestimated by a single OCT B-scan. CONCLUSION: Compared to the traditional unidimensional indicator-CRT, 3D macular edema thickness maps are able to display more intuitive morphometry and detailed statistics of DME, supporting more accurate diagnoses and follow-up of DME patients.

3.
Angew Chem Int Ed Engl ; 61(20): e202200872, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35191168

RESUMO

Exploring high-efficiency and stable halide perovskite-based photocatalysts for the selective reduction of CO2 to methane is a challenge because of the intrinsic photo- and chemical instability of halide perovskites. In this study, halide perovskites (Cs3 Bi2 Br9 and Cs2 AgBiBr6 ) were grown in situ in mesoporous TiO2 frameworks for an efficient CO2 reduction. Benchmarked CH4 production rates of 32.9 and 24.2 µmol g-1 h-1 with selectivities of 88.7 % and 84.2 %, were achieved, respectively, which are better than most reported halide perovskite photocatalysts. Focused ion-beam sliced-imaging techniques were used to directly image the hyperdispersed perovskite nanodots confined in mesopores with tunable sizes ranging from 3.8 to 9.9 nm. In situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy showed that the built-in electric field between the perovskite nanodots and mesoporous titania channels efficiently promoted photo-induced charge transfer. Density functional theory calculations indicate that the high methane selectivity was attributed to the Bi-adsorption-mediated hydrogenation of *CO to *HCO that dominates CO desorption.

4.
Zhen Ci Yan Jiu ; 47(1): 33-8, 2022 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-35128868

RESUMO

OBJECTIVE: To observe the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the motor function and the expression of glial fibrillary acidic protein (GFAP) and microtubule associated protein 2 (MAP2) in cerebral ischemic penumbra of rats with middle cerebral artery occlusion (MCAO) and explore the mechanism of taVNS in the improvement of motor function in MCAO rats. METHODS: A total of 48 male SD rats were randomized into a sham-operation group, a model group, a transcutaneous auricular non-vagus nerve stimulation (tnVNS) group and a taVNS group, with 12 rats in each group. The suture-occluded method was adopted to prepare MCAO rat model. The auricular rim was stimulated in the tnVNS group and the concha stimulated in the taVNS group, 2 mA in intensity, 10 Hz in frequency, 30 min each time, once a day, for 14 days consecutively. The nerve functional assessment was recorded in each group. The expressions of nicotinic acetylcholine receptor (α7nAchR) in the cerebral ischemic penumbra and the spleen were detected by using Western blot. With the immunofluorescence, the expressions of GFAP and MAP2 were detected. RESULTS: After modeling, compared with the sham-operation group, the nerve functional score was increased in the model group, the tnVNS group and the taVNS group (P<0.01), suggesting the success of modeling. After treatment, the score was increased in the model group (P<0.01) as compared with the sham-operation group. Compared with the model group, the neurological deficit score was reduced in the taVNS group (P<0.01). Compared with the sham-operation group, GFAP expression was increased and MAP2 expression was reduced remarkably in the cerebral ischemic penumbra in the model group (P<0.05). In comparison with the model group, GFAP expression was reduced, while MAP2 expression was increased remarkably in the cerebral ischemic penumbra in the taVNS group (P<0.05). There were no significant differences in the abovementioned indexes between the model group and tnVNS group (P>0.05). The differences in the expression of α7nAchR in the cerebral ischemic penumbra and the spleen had no statistical significance among groups (P>0.05). CONCLUSION: TaVNS is effective on neuroprotection in MCAO rats, which may be related to its function of inhibition of GFAP expression and promotion of MAP2 expression in the ischemic penumbra.


Assuntos
Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Animais , Proteína Glial Fibrilar Ácida/genética , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/terapia , Masculino , Proteínas Associadas aos Microtúbulos , Artéria Cerebral Média , Ratos , Ratos Sprague-Dawley
5.
Neoplasma ; 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35225646

RESUMO

Long non-coding RNA brain cytoplasmic RNA 1 (LncRNA BCYRN1) has been proved to participate in the cancer cell metastasis process, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms involved in the BCYRN1-mediated function remain largely unknown. The qRT-PCR analysis was carried out to examine the relative expressions of BCYRN1, microRNA-30b-3p (miR-30b-3p), and Rho-associated coiled-coil protein kinase 1 (ROCK-1). ROCK1 protein level was detected via western blot assay. The migrative and invasive abilities of H520 and A549 cells were evaluated via Transwell assay. The relationships between BCYRN1 and miR-30b-3p or ROCK-1 and miR-30b-3p were examined by luciferase reporter assay. The expression levels of BCYRN1 and ROCK1 were upregulated in NSCLC tissues and cells, while miR-30b-3p was downregulated. Higher BCYRN1 expression indicated lymph node metastasis and advanced tumor-node-metastasis (TNM) stage of NSCLC patients. Loss of BCYRN1 suppressed cell migration and invasion. More importantly, miR-30b-3p possessed the binding sites with BCYRN1. Besides, BCYRN1 negatively regulated the expression level of miR-30b-3p. Meanwhile, ROCK-1 was proven to be directly targeted by miR-30b-3p. In addition, the silencing of miR-30b-3p also weakened the effect of BCYRN1 knockdown on cell migration and invasion. In vivo, BCYRN1 silencing reduced the growth of A549 cells. LncRNA BCYRN1 was involved in the metastasis of NSCLC through modulating the miR-30b-3p/ROCK1 axis.

6.
Environ Res ; 209: 112786, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35077713

RESUMO

BACKGROUND: Women are vulnerable to depression during postpartum period. While several studies have shown associations between ambient air pollution exposure and depression in general population, there was few studies focused on the effect of various air pollutants on postpartum depression (PPD). OBJECTIVE: This study is designed to explore the association between prenatal exposure to air pollutants and PPD, and to reveal the potential vulnerable exposure time point. METHODS: The study enrolled 10,209 pregnant women who delivered between October 2019 and February 2021 in 5 participating hospitals from 3 cities in China. Edinburgh Postnatal Depression Scale (EPDS) was administered at 6 weeks postpartum to identify PPD symptoms. Associations between PPD symptoms and exposure levels in PM2.5, PM10, SO2, CO, NO2, and O3 averaged over the whole pregnancy and each trimester were estimated using logistic regression models after adjusting for potential confounding factors. Distributed lag models (DLMs) were used to determine the relevant associations in each gestational week. RESULTS: The risk for developing PPD symptoms was significant following a 10 µg/m3 increase in PM10 (aOR = 1.47, 95%CI:1.36-1.59), NO2 (aOR = 1.63, 95%CI:1.44-1.85), and 0.1 mg/m3 increase in CO (aOR = 2.31, 95%CI: 1.99-2.69) during the whole pregnancy. Similar results were also found in exposure during each trimester of pregnancy. Besides, SO2 exposure during the second trimester was a major risk factor for developing PPD symptoms (aOR = 1.10, 95%CI:1.03-1.18). Consistent effects were also observed in DLMs, except for PM2.5 and O3, which showed no significant sensitive windows throughout pregnancy period. CONCLUSION: Exposure to PM10, CO, NO2, and SO2 in pregnancy is associated with increased risks of developing depression at 6 weeks postpartum. Our findings reveal the importance of air pollution control for preventing maternal mental health disorders among the public.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Efeitos Tardios da Exposição Pré-Natal , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Cidades/epidemiologia , Estudos de Coortes , Depressão , Feminino , Humanos , Material Particulado/análise , Material Particulado/toxicidade , Período Pós-Parto , Gravidez
7.
Plant Physiol ; 188(3): 1496-1506, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34893909

RESUMO

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.


Assuntos
Dioxigenases/genética , Dioxigenases/metabolismo , Diterpenos/metabolismo , Furanos/metabolismo , Plantas Medicinais/metabolismo , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Vias Biossintéticas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Raízes de Plantas/metabolismo
8.
J Dev Orig Health Dis ; 13(2): 187-196, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947503

RESUMO

Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4-6 months, 7-12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.


Assuntos
Complicações na Gravidez , Nascimento Prematuro , Peso ao Nascer , Criopreservação , Transferência Embrionária/efeitos adversos , Feminino , Fertilização In Vitro , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/etiologia , Estudos Retrospectivos
9.
Sci Adv ; 7(50): eabl3594, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34878842

RESUMO

Coenzyme Q (CoQ) is an electron transporter in the mitochondrial respiratory chain, yet the biosynthetic pathway in eukaryotes remains only partially resolved. C6-hydroxylation completes the benzoquinone ring full substitution, a hallmark of CoQ. Here, we show that plants use a unique flavin-dependent monooxygenase (CoqF), instead of di-iron enzyme (Coq7) operating in animals and fungi, as a C6-hydroxylase. CoqF evolved early in eukaryotes and became widely distributed in photosynthetic and related organisms ranging from plants, algae, apicomplexans, and euglenids. Independent alternative gene losses in different groups and lateral gene transfer have ramified CoqF across the eukaryotic tree with predominance in green lineages. The exclusive presence of CoqF in Streptophyta hints at an association of the flavoenzyme with photoautotrophy in terrestrial environments. CoqF provides a phylogenetic marker distinguishing eukaryotes and represents a previously unknown target for drug design against parasitic protists.

10.
Pestic Biochem Physiol ; 179: 104969, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802519

RESUMO

Carboxylesterases (CarEs) usually play critical roles in the detoxification of toxic chemicals and therefore may be involved in insecticide resistance in agricultural pests. Previous work has shown that CarE 001C from Helicoverpa armigera was able to metabolize the isomers of cypermethrin and fenvalerate. In this study, seven mutants of CarE 001C with single amino acid substitution were produced and expressed in the Escherichia coli. Enzyme kinetic analysis indicated that all seven mutations dramatically reduced enzymatic activities toward the generic substrate α-naphthyl acetate, but in vitro metabolism assay showed that two of the mutations, H423I and R322L, significantly improved hydrolase activities toward fenvalerate, with their recorded specific activities being 3.5 and 5.1 nM·s-1·mg -1 proteins, respectively. Further, thermostability assay showed that the stability of one mutant enzyme was enhanced. This study will help us better understand the potential of CarEs in insecticide detoxification and resistance in H. armigera.


Assuntos
Inseticidas , Mariposas , Piretrinas , Animais , Carboxilesterase/genética , Carboxilesterase/metabolismo , Hidrolases de Éster Carboxílico/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Cinética , Mariposas/genética , Mariposas/metabolismo , Mutação , Nitrilas
11.
Front Neurol ; 12: 740136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795628

RESUMO

Background: We found a positive correlation between the prior stroke history and recurrent stroke in patients who underwent percutaneous coronary intervention (PCI) in our previous study, which indicated the close interaction of stroke and cardiovascular diseases. However, it is unclear whether prior stroke is still associated with worse prognosis at a longer follow-up period. Methods: A total of 10,724 coronary heart disease (CHD) patients who received PCI from January to December 2013 were prospectively enrolled and were subsequently divided into the prior stroke (n = 1,150) and non-prior stroke (n = 9,574) groups according to their history. Baseline characteristics and 5-year outcomes were recorded. Results: Patients with prior stroke had more clinical risk factors, as well as more extensive coronary artery lesions. Although in-hospital outcomes were similar between patients from the two groups, the 5-year follow-up result revealed that patients with prior stroke experienced higher incidence of stroke, major adverse cardiac and cerebrovascular events (MACCEs), all-cause death, and cardiac death (7.0 vs. 3.0%, p < 0.001; 25.9 vs. 20.3%, p < 0.001; 5.3 vs. 3.5%, p = 0.002; 3.1 vs. 2.1%, p = 0.032, respectively). After the propensity score matching, the 5-year stroke rate was still higher in the prior stroke group (6.8 vs. 3.4%, p = 0.001). The multivariable regression analysis also identified the prior stroke as a risk predictor of the 5-year stroke (HR = 2.011, 95% CI: 1.322-3.059, p = 0.001). Conclusions: Coronary heart disease patients with prior stroke who received PCI had a higher incidence of 5-year long-term adverse cardiovascular and cerebrovascular events, especially recurrent stroke. Prior stroke was a strong risk predictor of future stroke events.

12.
Metab Eng ; 68: 86-93, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555495

RESUMO

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.


Assuntos
Lycopersicon esculentum , Ubiquinona , Carotenoides/metabolismo , Frutas/metabolismo , Humanos , Lycopersicon esculentum/genética , Mitocôndrias , Ubiquinona/genética
13.
Front Cardiovasc Med ; 8: 715539, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458340

RESUMO

Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS). Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c. Results: Subjects were divided into quartiles according to baseline DB (µmol/L): Q1 (0-1.6), Q2 (1.61-2.20), Q3 (2.21-2.80), and Q4 (>2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate-high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p < 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829-1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001-1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063-1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction. Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.

14.
Aging (Albany NY) ; 13(10): 14001-14014, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030135

RESUMO

Vascular dementia (VaD) is the second most common type of dementia worldwide. Although there are five FDA-approved drugs for the treatment of Alzheimer's disease (AD), none of them have been applied to treat VaD. Adalimumab is a TNF-α inhibitor that is used for the treatment of autoimmune diseases such as rheumatoid arthritis. In a recent retrospective case-control study, the application of adalimumab for rheumatoid or psoriasis was shown to decrease the risk of AD. However, whether adalimumab can be used for the treatment of VaD is not clear. In this study, we used 2VO surgery to generate a VaD rat model and treated the rats with adalimumab or vehicle. We demonstrated that VaD rats treated with adalimumab exhibited significant improvements in memory. In addition, adalimumab treatment significantly alleviated neuronal loss in the hippocampi of VaD rats. Moreover, adalimumab significantly reduced microglial activation and reversed M1/M2 polarization in VaD rats. Furthermore, adalimumab treatment suppressed the activity of NF-κB, an important neuroinflammatory transcription factor. Finally, adalimumab displayed a protective role against oxidative stress in VaD rats. Our results indicate that adalimumab may be applied for the treatment of human patients with VaD.


Assuntos
Adalimumab/uso terapêutico , Encéfalo/patologia , Circulação Cerebrovascular/fisiologia , Inflamação/patologia , Transtornos da Memória/tratamento farmacológico , Adalimumab/farmacologia , Animais , Biomarcadores/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Doença Crônica , Transtornos da Memória/fisiopatologia , Microglia/efeitos dos fármacos , Microglia/patologia , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(2): 199-204, 2021 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-33966698

RESUMO

Objective To investigate the risk factors for patients using intraoperative vasopressor infusions during carotid body tumor(CBT)excision.Patients' mean arterial pressure(MAP)and heart rate(HR)fluctuations as well as their requirements for vasoactive agents during surgery were assessed. Methods The patients receiving CBT excision in Peking Union Medical College Hospital from May 1,2013 to July 31,2017 were included for a retrospective cohort study.The potential factors of intraoperative requirement for vasopressor infusions were investigated using univariate analysis and Logistic multivariate analysis.Furthermore,the relationships of Shamblin types of CBT with intraoperative MAP/HR fluctuations and requirements for vasoactive agents were analyzed. Results A total of 108 patients with 116 CBTs were included.Univariate analysis revealed that maximum tumor diameter >4 cm,intraoperative internal carotid artery injury,internal carotid artery reconstruction,malignant pathology,advanced Shamblin types(type Ⅱ and Ⅲ),estimated blood loss ≥400 ml,and operation duration >4 hours were associated with intraoperative requirements for vasopressor infusions.Logistic analysis showed that Shamblin type Ⅲ(OR=2.286,95% CI=1.324-14.926,P=0.016)and operation duration >4 hours(OR=3.874,95% CI=1.020-14.623,P=0.046)were risk factors for intraoperative requirements for vasopressor infusions during CBT surgery.In addition,Shamblin type Ⅲ was associated with intraoperative abnormal HR elevation and requirements for vasopressors.Conclusions Shamblin type Ⅲ and operation duration>4 hours are risk factors for intraoperative requirements of patients for using vasopressor infusions during CBT surgery.Shamblin type Ⅲ is associated with intraoperative abnormal HR elevation and requirements for vasopressors.


Assuntos
Tumor do Corpo Carotídeo , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares
16.
BMC Pregnancy Childbirth ; 21(1): 341, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926401

RESUMO

BACKGROUND: Previous studies have focused on pregnancy outcomes after frozen embryo transfer (FET) performed using different endometrial preparation protocols. Few studies have evaluated the effect of endometrial preparation on pregnancy-related complications. This study was designed to explore the association between different endometrial preparation protocols and adverse obstetric and perinatal complications after FET. METHODS: We retrospectively included all FET cycles (n = 12,950) in our hospital between 2010 and 2017, and categorized them into three groups, natural cycles (NC), hormone replacement therapy (HRT) and ovarian stimulation (OS) protocols. Pregnancy-related complications and subsequent neonatal outcomes were compared among groups. RESULTS: Among all 12,950 FET cycles, the live birth rate was slightly lower for HRT cycles than for NC (HRT vs. NC: 28.15% vs. 31.16%, p < 0.001). The pregnancy loss rate was significantly higher in OS or HRT cycles than in NC (HRT vs. NC: 17.14% vs. 10.89%, p < 0.001; OS vs. NC: 16.44% vs. 10.89%, p = 0.001). Among 3864 women with live birth, preparing the endometrium using OS or HRT protocols increased the risk of preeclampsia, and intrahepatic cholestasis of pregnancy (ICP) in both singleton and multiple deliveries. Additionally, OS and HRT protocols increased the risk of low birth weight (LBW) and small for gestational age (SGA) in both singletons and multiples after FET. CONCLUSION: Compared with HRT or OS protocols, preparing the endometrium with NC was associated with the decreased risk of pregnancy-related complications, as well as the decreased risk of LBW and SGA after FET.


Assuntos
Transferência Embrionária/efeitos adversos , Endométrio/fisiologia , Terapia de Reposição Hormonal/efeitos adversos , Indução da Ovulação/métodos , Complicações na Gravidez/etiologia , Adulto , China , Colestase Intra-Hepática/etiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Nascido Vivo , Modelos Logísticos , Pré-Eclâmpsia/etiologia , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Retrospectivos
17.
Vet Microbiol ; 257: 109080, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33915344

RESUMO

Pseudorabies virus (PRV) is related to alphaherpesvirus and varicellovirus. pUL16 is a conserved protein in all herpesviruses, and studies have shown that UL16 can interact with the viral proteins pUL11, pUL49, pUL21, gD, and gE. In this study, we found that pUL16 interacted with the viral capsid protein VP26, which could not translocate into the nucleus itself but did appear in the nucleus. We further determined whether pUL16 assists the translocation of VP26 into the nucleus. We found that pUL16 interacted with VP26 with or without viral proteins, and since VP26 itself did not contain a nuclear location signal, we concluded that pUL16 assisted the translocation of VP26 into the nucleus. Deletion of UL16 and UL35 significantly reduced the 50 % tissue culture infective dose, virulence, attachment, and internalization of PRV in cells. These results show that the interaction between pUL16 and VP26 influences the growth and virulence of pseudorabies virus. Our research is the first study to show that pUL16 interacts with VP26, which may explain the targeting site of UL16 and viral capsids. It is also the first to show that UL16 assists the transport of other viral proteins to organelles. Previous researches on pUL16 usually emphasized its interaction with pUL11, pUL21, and gE, and sometimes commented on pUL49 and gD. Our research focuses on the novel interaction between pUL16 and VP26, thereby enriching the studies on herpesviruses and possibly providing different directions for researchers.


Assuntos
Proteínas do Capsídeo/metabolismo , Núcleo Celular/metabolismo , Herpesvirus Suídeo 1/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteínas Virais/genética , Proteínas Virais/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Proteínas do Capsídeo/genética , Linhagem Celular , Chlorocebus aethiops , Feminino , Deleção de Genes , Células HEK293 , Herpesvirus Suídeo 1/genética , Humanos , Camundongos Endogâmicos BALB C , Suínos , Células Vero , Replicação Viral
18.
Parasitol Res ; 120(5): 1627-1636, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33792812

RESUMO

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.


Assuntos
Pulmão/parasitologia , Paragonimíase/patologia , Paragonimus/embriologia , Paragonimus/crescimento & desenvolvimento , Animais , Braquiúros/parasitologia , China , Perfilação da Expressão Gênica , Humanos , Estágios do Ciclo de Vida , Metacercárias/crescimento & desenvolvimento , Paragonimíase/parasitologia , Paragonimus/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Transcriptoma/genética
19.
Environ Pollut ; 276: 116756, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33662814

RESUMO

While the effects of ambient pollutants on adverse perinatal outcomes have been studied, most studies have focused on preterm birth, stillbirth, and low birthweight. Few studies have examined the effects of ambient pollutants on prelabor rupture of membranes (PROM). This study was designed to explore the acute effects of ambient pollutants on both term PROM (TPROM) and preterm PROM (PPROM). We enrolled pregnant women receiving antenatal care between October 2013 and December 2019 at the International Peace Maternity and Child Health Hospital (IPMCHH). The effects of ambient pollutants (including PM2.5, PM10, SO2, CO, NO2, and 8-h O3) on TPROM and PPROM were estimated using generalized additive models (GAMs). Exposure-response relationship curves were also evaluated using GAMs after adjustment for confounding factors. Potential lagged effects were examined using various lag models. The data of 100,200 pregnant women who delivered at IPMCHH were analyzed. The fitted spline curves for PPROM were similar to the temporal trends of PM2.5, PM10, SO2, CO and NO2 but not O3, while those for TPROM were different from the temporal trends of all six air pollutants. An increased risk of PPROM was associated with increased concentrations of PM2.5, PM10, SO2 and CO on lag days 2 and 3, while no association was found between PPROM and daily concentration of O3. After adjustment for confounding factors, there was a shift in the exposure-response curves, indicating associations between PPROM and PM2.5, PM10, SO2, and CO on lag days 2-3. Interaction effects of PM2.5, PM10, SO2, and CO were also found to increase the risk of PPROM. In conclusion, acute exposures to six critical air pollutants were not associated with an increased risk of TPROM; however, PM2.5, PM10, SO2, and CO were found to interact, increasing the risk for PPROM on lag days 2 and 3.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Nascimento Prematuro , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , China/epidemiologia , Exposição Ambiental , Feminino , Humanos , Recém-Nascido , Material Particulado/análise , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia
20.
J Agric Food Chem ; 69(7): 2168-2178, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33566615

RESUMO

Amorpha-4,11-diene synthase (ADS) is the first committed enzyme in the biosynthesis of artemisinin. Artemisinin production by biobased fermentation is considered a reliable alternative pathway. Heterologously expressed ADS has been established to generate several minor products, including structural analogues of amorpha-4,11-diene, but their fate in fermentation is still unknown. Here, using chiral analysis, we found that ADS produces one of the analogues, amorpha-4-en-11-ol, as a pair of epimers. Labeling experiments revealed that ADS mutants yielded amorphene-type sesquiterpenes, indicating the co-occurrence of initial 1,6 and 1,10 cyclization of farnesyl diphosphate in a single enzyme. Interestingly, the immediate downstream oxidase CYP71AV1 had very low affinity to the side products of the recombinant ADS, including amorpha-4-en-7-ol, which is structurally similar to amorpha-4,11-diene. Our data uncover the complex catalytic mechanism of recombinant ADS and reveal a potential negative effect of the side products of recombinant ADS on the production of the artemisinin precursor in microbes.


Assuntos
Alquil e Aril Transferases , Artemisininas , Fabaceae , Sesquiterpenos , Alquil e Aril Transferases/genética , Oxirredutases
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