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1.
Environ Int ; 136: 105446, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31926437

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression. OBJECTIVES: To investigate whether PFAS exposure is associated with altered microRNA expression in serum. METHODS: We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA). RESULTS: Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer's disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3a), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPARα), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGFα). DISCUSSION: PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects.

2.
Immunogenetics ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900503

RESUMO

The function of natural killer (NK) cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is regulated by the balance between inhibitory KIRs (iKIRs) and activating KIRs (aKIRs). However, few studies have examined the subsequent expression of KIR genes unique to the donor. We defined the set of KIR genes expressed only in the donor and designed a method for measuring the expression of these KIR genes by quantitative real-time polymerase chain reaction (RT-qPCR) based on genetic cloning techniques. In this study, we evaluated the recovery pattern of KIR genes in 252 donor-recipient pairs. The expression of each KIR unique to the donor was in line with that of KIR genes shared by the donor and recipient, such as KIR2DS1, KIR3DS1, KIR2DS4, or KIR2DS3. The timing of the peak mRNA expression of aKIRs unique to the donor was inconsistent but occurred within the first 3 months posttransplantation, whereas the peak mRNA expression of iKIRs was consistently observed in the third month after transplantation. The expression of KIR2DL2 in the third month posttransplantation was significantly higher in the transplant recipients than in the donors (p = 0.01). The KIR2DL1 and KIR3DL1 levels in the transplant recipients in the second and third months posttransplantation were also obviously higher than the donor levels (p < 0.0001). Thus, these observations should be considered when attempting to predict the correlation between mRNA expression and prognosis after allo-HSCT.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31902079

RESUMO

Climate change is anticipated to raise overall temperatures in the twenty-first century and is likely to intensify population exposure to heat during the warm season and, as a result, increase the risk of heat-related illnesses and deaths. While earlier studies of heat exposure and related health impacts generally focused on the acute effects of short-term exposure indicated by high daily temperature or several days of very hot weather, recent research has suggested that small changes in seasonal average temperature over a long period of time is likely to pose significant health risk as well. Using downscaled climate projections under three Representative Concentration Pathways emission scenarios, high-spatial-resolution population data, and the latest population projections by the United Nations, we aim at projecting future changes in long-term population exposure to summer heat across China in the mid- and late-twenty-first century resulting from global climate change. As the impacts of population growth are often overlooked in projecting future changes in heat exposure, we estimated changes in population-weighted average temperature in the warmest quarter over two future 20-year time periods and compared them with changes in temperature only. Our analysis shows that, nationally, population-weighted average temperature in the warmest quarter is projected to increase by 2.2 °C relative to the current situation in the 2050s and by 2.5 °C in the 2070s, as the result of climate change and population growth. Despite the foreseeable population stabilization in China, changes in population-weighted temperature are projected to be higher than changes in temperature itself for the majority of the 33 provinces (ranging from 0.02 °C to 1.27 °C, or 1% to 126% higher in the 2050s and from 0.02 °C to 1.16 °C, or 1% to 73% higher in the 2070s), with the largest differences mainly occurring in Western China. The impact of urbanization is projected to be relatively insignificant. Our findings provide evidence of possible underestimation of future changes in long-term exposure to summer heat if the effect of population growth is not factored in.

4.
Chin J Integr Med ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31903532

RESUMO

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

5.
Plant Cell Physiol ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904850

RESUMO

Autopolyploids often show growth advantages over their diploid progenitors because of their increased photosynthetic activity; however, the underlying molecular basis of such mechanism remains elusive. Here, we aimed to characterize autotetraploid pak choi (Brassica rapa ssp. chinensis) at the physiological, cellular, and molecular levels. Autotetraploid pak choi has thicker leaves than its diploid counterparts, with relatively larger intercellular spaces and cell size and greater grana thylakoid height. Photosynthetic data showed that the relative electron transport rate (rETR) was markedly higher in autotetraploid than in diploid pak choi. Transcriptomic data revealed that the expressions of genes involved in 'photosynthesis' biological process and 'thylakoids' cellular component were mainly regulated in autotetraploids. Overall, our findings suggested that the increased rETR in the thylakoids contributed to the increased photosynthetic capacity of autotetraploid leaves. Furthermore, we found that the enhanced rETR is associated with increased BrPetC expression, which is likely altered by histone modification. The ectopic expression of BrPetC in Arabidopsis thaliana led to increased rETR and biomass, which were decreased in BrPetC-silenced pak choi. Autotetraploid pak choi also show altered hormone levels, which was likely responsible for the increased drought resistance and impaired powdery mildew resistance of this lineage. Our findings further our understanding on how autotetraploidy provides growth advantages to plants.

6.
Alzheimers Dement ; 16(1): 178-191, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914229

RESUMO

INTRODUCTION: The PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations. METHODS: In total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network. PSENs/APP mutations and APOE frequencies were determined. RESULTS: In total, 13.12% of pedigrees carried PSENs/APP missense mutations, 3.71% carried PSENs/APP synonymous/untranslated region variants, and 83.17% did not carry PSENs/APP mutations. Eleven missense mutations were first identified. In patients without PSENs/APP mutations, 44.31% carried one APOEε4 allele, and 14.85% two APOEε4 alleles. DISCUSSION: The new PSENs/APP mutations indicate heterogeneity in AD pathogenesis between Chinese and other ethnic groups. The low mutation rate suggests the involvement of other genes/factors in Chinese FAD. APOEε4 might be a major gene for some FAD without PSENs/APP mutations.

7.
Eur J Prev Cardiol ; : 2047487319894685, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914807

RESUMO

AIMS: The role of tea consumption in the primary prevention of atherosclerotic cardiovascular disease remains unclear in cohort studies. This prospective cohort study aimed to investigate the associations of tea consumption with the risk of atherosclerotic cardiovascular disease and all-cause mortality. METHODS: We included 100,902 general Chinese adults from the project of Prediction for ASCVD Risk in China (China-PAR) in 15 provinces across China since 1998. Information on tea consumption was collected through standardized questionnaires. Outcomes were identified by interviewing study participants or their proxies, and checking hospital records and/or death certificates. Cox proportional hazard regression models were used to calculate hazard ratios and their corresponding 95% confidence intervals related to tea consumption. RESULTS: During a median follow-up of 7.3 years, 3683 atherosclerotic cardiovascular disease events, 1477 atherosclerotic cardiovascular disease deaths, and 5479 all-cause deaths were recorded. Compared with never or non-habitual tea drinkers, the hazard ratio and 95% confidence interval among habitual tea drinkers was 0.80 (0.75-0.87), 0.78 (0.69-0.88), and 0.85 (0.79-0.90) for atherosclerotic cardiovascular disease incidence, atherosclerotic cardiovascular disease mortality, and all-cause mortality, respectively. Habitual tea drinkers had 1.41 years longer of atherosclerotic cardiovascular disease-free years and 1.26 years longer of life expectancy at the index age of 50 years. The observed inverse associations were strengthened among participants who kept the habit during the follow-up period. CONCLUSION: Tea consumption was associated with reduced risks of atherosclerotic cardiovascular disease and all-cause mortality, especially among those consistent habitual tea drinkers.

8.
Ultrasound Med Biol ; 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31917043

RESUMO

We aimed to evaluate whether subcapsular injection of ultrasonic contrast agent (UCA) can distinguish between benign and malignant lymph node (LN) lesions exhibiting homogeneous enhancement in intravenous contrast-enhanced ultrasound (CEUS) images. From November 2012 to July 2015, 32 patients with superficial lymphadenopathy exhibiting homogeneous enhancement after intravenous CEUS were enrolled. A small amount of UCA was injected into LNs using a subcapsular approach, and perfusion characteristics were recorded. Using the pathology identified via core needle biopsy as the gold standard, we calculated the sensitivity, specificity and accuracy of the technique in terms of distinguishing between benign and malignant LN lesions. Pathology revealed 23 cases of true benign and 9 cases of true malignant LN lesions; the former included 2 cases of tuberculosis and 21 cases of reactive hyperplasia, and the latter included 7 lymphomas and 2 metastases. Subcapsular CEUS diagnosed 24 benign and 8 malignant LN lesions. Most lymphomas (6 of 7, 85.7%) exhibited heterogeneous perfusion, with lymphatic tract distortion in the absence of interruption. Reactive hyperplasia LNs manifested as diffuse homogeneous or brush-like perfusion from the subcapsular region to the center, without lymphatic tract distortion. Metastatic LNs had lymphatic tract interruptions. The sensitivity, specificity, consistency and positive and negative predictive values were 77.8%, 95.6%, 90.6%, 87.5% and 91.7%, respectively. For LNs exhibiting uniform enhancement in intravenous CEUS imaging, subcapsular CEUS may help to distinguish between benign and malignant lesions. In particular, lymphatic distortion without interruption may specifically indicate a lymphoma.

10.
Phytochem Anal ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31908072

RESUMO

INTRODUCTION: The herbs Notopterygium incisum (NI) and N. franchetii (NF) are referred to as "Qianghuo" in the Chinese Pharmacopeia and are popular for treatment of certain conditions, including headaches, rheumatoid arthritis and the common cold. Recently, several adulterations of NI and NF have been found in the Chinese herbal market. OBJECTIVE: The aim of this study was to rapidly identify the unique characteristic compounds of NI and NF, to discriminate Qianghuo from its adulterations. METHODOLOGY: Twenty-four batches of NI and NF samples with different origins were collected and extracted with methanol. The extracts were analysed using ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). Principal component analysis (PCA) and orthogonal partial squared discriminant analysis (OPLS-DA) were then used to distinguish between NI and NF and to identify their potential characteristic markers. RESULTS: Fifty compounds were identified or tentatively characterised according to the retention time, m/z value and MS/MS fragment analysis. Six compounds were selected as potential markers of NI and NF by PCA and OPLS-DA. They were successfully applied to authenticate 17 kinds of Chinese patent medicines containing Qianghuo. The markers could not be detected in three of the Chinese patent medicines, indicating that they were counterfeit products. CONCLUSION: The UHPLC-QTOF-MS/MS coupled with the multivariate analysis method could discriminate NI and NF from their adulterations. Moreover, the data clearly demonstrated significant differences in the chemical compositions of NI and NF. Further research is needed to examine the relationship between therapeutic efficacy and the chemical constituents of NI and NF.

11.
Free Radic Res ; : 1-15, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909644

RESUMO

Dexmedetomidine (Dex), a sedative and analgesic agent, is known to have a cardioprotective effect against ischaemia/reperfusion (I/R) injury via regulation of antioxidant and anti-inflammatory signals. In contrast, Se shows a cardioprotective effect against I/R injury, because it is a key component of selenoproteins, most of which are antioxidant enzymes such as GPxs and TrxRs. This study aimed to determine whether the protective effects on myocardial cells against I/R injury were further improved when treatment with Dex and Se in combination. H9C2 cells were treated with Dex and Na2SeO3, alone or in combination, before oxygen glucose deprivation/reoxygenation (OGD/R). OGD/R-induced myocardial cell injury was evaluated using cell viability, apoptosis rate, the release of LDH, and intracellular ROS levels. Both Dex and Na2SeO3 improved cell viability and reduced the apoptosis rate, LDH release, and intracellular ROS. This cytoprotection was higher with Dex and Na2SeO3 cotreatment than their individual treatments. Treatment with Dex increased the SOD1, SOD2, GPx1, and GPx2 expression in H9C2 cells in OGD/R, while Na2SeO3 increased the GPx1-4 and TrxR1-3 mRNA levels. Notably, cotreatment with Dex and Na2SeO3 increased the mRNA expression of all these antioxidant enzymes. Dex treatment attenuated the activation of JNK, p65 (NF-κB), Camk1, and NLRP3 signals. Na2SeO3 enhanced the inhibitory effect of Dex on phosphorylated (p)-p65, p65, and NLRP3 in OGD/R. However, TrxR1 knockdown attenuated the positive effect of Na2SeO3 on Dex-mediated anti-inflammatory effects. In summary, cotreatments with Dex and Na2SeO3 further improved antioxidant and anti-inflammatory protection of myocardial cells from I/R injury compared to their individual treatments.

12.
Anat Rec (Hoboken) ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909895

RESUMO

Patients with multidrug-resistant tuberculosis (MDR-TB) tend to have a long course of anti-TB treatment and severe side effects. Traditional Chinese Medicine (TCM) has a synergistic effect in attenuation of MDR-TB. However, the lack of objective biological standards to classify and diagnose MDR-TB TCM syndromes could result in less effective TCM treatment. Therefore, in this study, we identified differentially expressed proteins (DEPs) in serum of individuals with MDR-TB TCM syndromes by applying isobaric tags for relative and absolute quantification coupled with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) method and bioinformatics analysis. The functional analysis of DEPs was also performed. Additionally, DEPs among three different TCM syndromes of MDR-TB were validated by enzyme-linked immunosorbent assay (ELISA). Finally, a receiver operating characteristic (ROC) curve was performed to estimate the diagnostic ability of DEPs. A total of 71 DEPs were identified in the three different MDR-TB TCM syndrome groups such as the pulmonary Yin deficiency (PYD) syndrome group, the Hyperactivity of Fire due to Yin deficiency (HFYD) syndrome group, and the deficiency of Qi and Yin (DQY) syndrome group. The results showed that the expression level of transforming growth factor-beta-induced protein ig-h3 (TGFBI) was lower in the PYD syndrome group (p = .002), the proprotein convertase subtilisin/kexin type 9 (PCSK9) was overexpressed in the HFYD syndrome group (p < .0001), and the C-C motif chemokine ligand 14 (CCL14) expression level was reduced in the DQY syndrome group (p = .004). Our study demonstrated that serum TGFBI, PCSK9, and CCL14 may serve as potential novel biomarkers for PYD syndrome, HFYD syndrome and DQY syndrome of MDR-TB, respectively. The study provides a biological basis for MDR-TB TCM syndromes classification and can be of great significance for the treatment of different TCM syndromes.

13.
Anatol J Cardiol ; 23(1): 41-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31911565

RESUMO

OBJECTIVE: Using three-dimensional speckle-tracking echocardiography (3D-STE), we aimed to evaluate left ventricular (LV) function in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In total, 97 T2DM patients were categorized into three groups based on hepatic ultrasonography: group A (those without NAFLD, n=30), group B (those with mild NAFLD, n=32), and group C (those with moderate-to-severe NAFLD, n=35). Our conventional echocardiographic parameters included transmitral peak early and late diastolic velocity (E and A), septal and lateral early (e') mitral annular diastolic tissue velocities, and left atrial maximum volume index (LAVImax). LV end-diastolic and -systolic volume, LV mass index (LVMI), and LV ejection fraction were measured using real-time three-dimensional echocardiography. The 3D-STE parameters included LV global radial strain (GRS), global longitudinal strain (GLS), global area strain (GAS), and global circumferential strain (GCS). RESULTS: Our results showed that in group C, GCS, GRS, GLS, GAS, and septal and lateral e' velocity decreased, whereas average E/e' and LAVImax increased compared to groups B and A (p<0.05). Multiple linear regression analysis showed that NAFLD is independently associated with 3D-STE parameters, and glycosylated hemoglobin also has negative impacts on all LV 3D strains. CONCLUSION: When combined with conventional echocardiography, 3D-STE can assess LV function effectively in T2DM patients with NAFLD. Additionally, the severity of LV dysfunction in the moderate-to-severe NAFLD group (group C) was worse than the mild and absent NAFLD groups (groups A and B).

14.
Chin J Integr Med ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31919749

RESUMO

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

15.
Mol Med Rep ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31922227

RESUMO

Following the publication of this article, an interested reader drew to our attention that, in the Materials and methods section of the paper, on p. 2608 in the Immunofluorescence subsection, the authors had included a catalog number (cat no. 6487) that belonged to α­actinin, not α­smooth muscle actin (α­SMA). After having investigated this matter with the authors, they were able to confirm that, although both α­SMA and α­actinin antibodies were employed in this study to investigate purification of the cardiomyocytes, the catalog number for α­SMA should have been referenced as ab5694 from Abcam, and the catalog number for α­actinin from Cell Signaling Technology is #6487. The authors were also able to confirm that staining with α­SMA was presented in Fig. 1 of their article, and therefore the relevant catalogue number should have been listed on p. 2608 as ab5694 (Abcam) for α­SMA, not #6487. The authors express their gratitude towards the reader who identified this error, and regret any inconvenience that this mistake has caused. [the original article was published in Molecular Medicine Reports 14: 2607­2613, 2016; DOI: 10.3892/mmr.2016.5544].

16.
Anat Rec (Hoboken) ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922655

RESUMO

Yin-deficiency-heat (YDH) syndrome is a very common subhealth status in Traditional Chinese Medicine. However, currently, there is no unified standard for diagnosing YDH syndrome. We applied the iTRAQ-2D LC-MS/MS method to explore the potential of serum protein profiles as biomarker for YDH syndrome. A total of 120 differentially expressed proteins (79 downregulated and 41 upregulated) were identified by the proteomic profiling. The results of KEGG pathway analysis showed that the functions of the differentially expressed proteins were mainly involved in complement and coagulation cascades. The clinical data showed that YDH syndrome was closely related to inflammation and coagulation, compared with the healthy controls. The ELISA validation results indicated that the expression levels of ALB, CFI, and KLKB1 were downregulated in the YDH syndrome group (p < .05). Moreover, we established a decision tree model based on the combination of these three proteins and achieved a sensitivity of 87.5%, a specificity of 84.4%, and AUC of 0.891. The results indicated that the combination of ALB, CFI, and KLKB1 may serve as potential biomarkers for diagnosing YDH syndrome. Our study can provide a new method for YDH syndrome diagnosis, and may also provide an experimental basis to understand the molecular mechanism of YDH syndrome.

17.
Reprod Sci ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925770

RESUMO

Premature ovarian insufficiency (POI) is a highly heterogeneous ovarian disorder. Genetic factors account for the cause of POI. We aimed to analyze the genetic alterations in two affected sisters diagnosed with POI and their parents from a highly consanguineous Chinese Han family. Whole-exome sequencing was performed, and bioinformatics analysis was used to determine the potential genetic cause of POI in this family. A SYCE1 deletion was verified by Sanger sequencing. A homozygous deletion in SYCE1 was harbored by the proband and her affected sister, whereas both parents had heterozygous deletions. There were distinct differences in the amino acid sequences between wild-type and SYCE1 deletion. Domain analysis and 3D structural analysis of the SYCE1 deletion was also performed to evaluate the potential impact and pathogenicity of POI. The SYCE1 domain structure was truncated. Additionally, the 3D structure showed that the SYCE1 deletion changed the shape of the protein compared with that of wild-type SYCE1. This study revealed a novel SYCE1 deletion. This SYCE1 deletion may be the cause of POI. Genetic counseling for POI is helpful for researchers and clinicians to identify the mode of genetic inheritance for SYCE1 deletion in POI pathology.

18.
Anticancer Drugs ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31917701

RESUMO

PURPOSE: Our retrospective study assessed the efficacy and safety of irinotecan plus raltitrexed in esophageal squamous cell cancer (ESCC) patients who were previously treated with multiple systemic therapies. METHODS: Between January 2016 and December 2018, records of 38 ESCC patients who underwent irinotecan plus raltitrexed chemotherapy after at least one line of chemotherapy were reviewed. Efficacy assessment was performed every two cycles according to the RECIST version 1.1. RESULTS: A total of 95 cycles of chemotherapy were administered, and the median course was 3 (range 2-6). There was no treatment-related death. Nine patients had partial response, 21 had stable disease and eight had progressive disease. The overall objective response rate was 23.68% (9/38) and the disease control rate was78.94% (30/38). After a median follow-up of 18.5 months, the median progression-free survival and overall survival were 105 and 221 days, respectively. There were five patients (13.15%) with grade 3/4 leukopenia, three patients (7.89%) with grade 3/4 neutropenia and one patient (2.63%) with grade 3/4 diarrhea. CONCLUSION: The combination of irinotecan plus raltitrexed was effective for pretreated ESCC patients. Further studies are needed to determine the optimal dose of the two drugs.

19.
J Refract Surg ; 36(1): 42-48, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917850

RESUMO

PURPOSE: To compare the safety of the minimum ophthalmic viscosurgical device (OVD) technique with the standard procedure in phakic Visian Implantable Collamer Lens (ICL) (STAAR Surgical AG, Nidau, Switzerland) implantation. METHODS: This retrospective cohort study evaluated a total of 147 eyes of 74 patients who underwent ICL implantation with the minimum OVD technique (minimum OVD group) and 154 eyes of 77 patients with the standard procedure (standard OVD group). Intraoperative and postoperative complications were recorded. Preoperative and postoperative visual acuity, intraocular pressure (IOP), aqueous depth (AQD), and central corneal endothelial cell density (ECD) were collected and analyzed over the 12-month follow-up. Lens vault and occurrence of paracentesis after surgery were also recorded. RESULTS: No intraocular complications were observed. No difference was found in visual outcomes, lens vault, and AQD at all time points between the two groups (P > .05). The minimum OVD group had significantly lower IOP than the standard OVD group at 2 hours (17.04 ± 4.21 vs 19.40 ± 6.78 mm Hg, P < .001) and 3 hours (15.12 ± 3.38 vs 17.15 ± 5.09 mm Hg, P < .001) postoperatively. The IOP gradually returned to the preoperative level after 24 hours postoperatively. The occurrence rate of paracentesis was significantly less in the minimum OVD group compared with the standard group (0.68% [1 of 147] vs 3.2% [5 of 154], P < .001). ECD was not significantly different between groups at all time points (P > .05). CONCLUSIONS: The minimum OVD technique could achieve visual and structural outcomes comparable to the standard procedure without additional damage to the corneal endothelial cells, while reducing the IOP fluctuations after surgery. [J Refract Surg. 2020;36(1):42-48.].

20.
Ecotoxicol Environ Saf ; 190: 110158, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31918257

RESUMO

Copper (Cu) is an essential trace element for most organisms. However, excessive Cu can be highly toxic. The purpose of this study was to elucidate the mechanism underlying Cu toxicity in the kidneys of rats after treatment with CuCl2 (15 [control], 30, 60, or 120 mg/kg in the diet) for 180 days. Histological and ultrastructural changes, antioxidant enzyme activity, and the mRNA and protein levels of apoptosis and autophagy-related genes were measured. The results showed that Cu exposure led to significant accumulation of copper in kidneys and disorganized kidney morphology. The activities of total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) in the kidneys decreased significantly, while the malondialdehyde (MDA) content increased. Furthermore, excessive Cu markedly upregulated the expression of autophagy and apoptosis-related genes (LC3A, LC3B, ATG-5, Beclin-1, Caspase3, CytC, P53, Bax), but downregulated the expression of P62, mTOR and BCL-2. Moreover, the LC3B/LC3A, ATG-5, Beclin-1, P53, Caspase3 proteins were up-regulated while P62 was down-regulated in the kidney tissues of the treatment groups. Overall, these findings provide strong evidence that excess Cu can trigger autophagy and apoptosis via the mitochondrial pathway by inducing oxidative stress in rat kidneys.

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