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1.
Environ Pollut ; 292(Pt B): 118348, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637828

RESUMO

Particulate matter (PM) exposure increased the risk of hospital admission and was related to symptoms of schizophrenia (SCZ). However, there are limited studies on the relationship between PM exposure and SCZ relapse risk, and the underlying biological mechanisms remain unclear. We designed an air purification intervention study under a 16-day real air purifier scenario and another 16-day sham air purifier scenario, with a 2-day washout period. Twenty-four chronic stable male patients were recruited. The oxidative stress biomarkers were measured including serum catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and nitric oxide (NO). The relapse risk was evaluated by the early signs scale (ESS). Linear mixed effect models were fitted to establish the associations between PM exposure and ESS and oxidative stress. Mediation model was performed to explore the mediation effect of oxidative stress on the PM-ESS association. Higher concentrations of PM2.5/PM10 exposure were associated with an elevated risk of relapse of SCZ. For each 10 µg/m3 in PM2.5 concentration, the scores of ESS and subscales of incipient psychosis (ESS-IP), depression/withdrawal (ESS-N), anxiety/agitation (ESS-A), and excitability/disinhibition (ESS-D) were increased by 4.112 (95% CI: 3.174, 5.050), 1.516 (95%CI: 1.178, 1.853), 1.143 (95%CI: 0.598, 1.689), 1.176 (95%CI: 0.727, 1.625) and 0.238 (95%CI: 0.013, 0.464), while logCAT, SOD and T-AOC were reduced by 0.039 U/ml (95% CI: 0.017, 0.060), 1.258 U/ml (95% CI: 0.541, 1.975), and 0.076 mmol/l (95% CI: 0.026, 0.126). In addition, pathways of "PM2.5→T-AOC→ESS-A″ and "PM2.5→T-AOC→ESS-D″ were found, with significant T-AOC mediated effects 15.70% (P = 0.02) and 52.99% (P = 0.04). Our findings suggest that PM may increase the risk of anxiety, depression, excitability, and incipient psychosis behaviors in SCZ patients, while reducing the function of the antioxidant system. The decrease of T-AOC may medicate the PM-ESS association in SCZ.

2.
Adv Sci (Weinh) ; : e2102592, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719864

RESUMO

The accuracy of de novo protein structure prediction has been improved considerably in recent years, mostly due to the introduction of deep learning techniques. In this work, trRosettaX, an improved version of trRosetta for protein structure prediction is presented. The major improvement over trRosetta consists of two folds. The first is the application of a new multi-scale network, i.e., Res2Net, for improved prediction of inter-residue geometries, including distance and orientations. The second is an attention-based module to exploit multiple homologous templates to increase the accuracy further. Compared with trRosetta, trRosettaX improves the contact precision by 6% and 8% on the free modeling targets of CASP13 and CASP14, respectively. A preliminary version of trRosettaX is ranked as one of the top server groups in CASP14's blind test. Additional benchmark test on 161 targets from CAMEO (between Jun and Sep 2020) shows that trRosettaX achieves an average TM-score ≈0.8, outperforming the top groups in CAMEO. These data suggest the effectiveness of using the multi-scale network and the benefit of incorporating homologous templates into the network. The trRosettaX algorithm is incorporated into the trRosetta server since Nov 2020. The web server, the training and inference codes are available at: https://yanglab.nankai.edu.cn/trRosetta/.

3.
Biodivers Data J ; 9: e74295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759731

RESUMO

Background: Pleosporales is the largest order of Dothideomycetes. In recent years, systematics of Pleosporales have undergone considerable revisions. Dictyosporiaceae is one of the newly established families within this order proposed to accommodate holomorphic saprobic Dothideomycetes. Currently 18 genera are recognised in Dictyosporiaceae. New information: The new species, Jalapriyaaquaticum sp. nov. and J.apicalivaginatum sp. nov. were collected from freshwater habitats in Gansu and Yunnan Provinces, China, respectively and are introduced, based on morphology and molecular analysis of combined ITS, LSU, SSU and TEF1-α sequence data. We also recovered one fresh collection of Dictyocheirosporavinaya D'souza, Bhat & K.D. Hyde, which is a new record for China. Jalapriyaaquaticum differs from extant species of Jalapriya in rows converging at the apex and apical cells with spherical-like appendages. Jalapriyaapicalivaginatum differs from extant species of Jalapriya in having the rows of conidia mostly arranged in a plane. The phylogenetic analysis place the new collections within Dictyosporiaceae (Pleosporales). Descriptions and illustrations of Jalapriyaaquaticum, J.apicalivaginatum and Dictyocheirosporavinaya are provided. A synopsis of characters of species of Jalapriya is also provided.

4.
MycoKeys ; 84: 141-162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815729

RESUMO

Ganodermadianzhongense sp. nov. and G.esculentum sp. nov. are proposed as two new species based on both phenotypic and genotypic evidences. Ganodermadianzhongense is characterized by the stipitate basidiomata, laccate and oxblood red pileus, gray white pore surface, duplex context and broadly ellipsoid basidiospores (9.0-12.5 × 6.5-9.0 µm) with coarse interwall pillars. Ganodermaesculentum is characterized by its basidiomata with slender stipe, white pore surface, homogeneous pileus context, and slightly truncate, narrow basidiospores (8.0-12.5 × 5.0-8.0 µm). Phylogenetic analyses were carried out based on the internal transcribed spacer (ITS), translation elongation factor 1-α (TEF1-α) and the second subunit of RNA polymerase II (RPB2) sequence data. The illustrations and descriptions for the new taxa are provided.

5.
PLoS One ; 16(11): e0260188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34793556

RESUMO

Chronic inflammation can cause oviduct mucosal damage and immune dysfunction, leading to infertility, early pregnancy loss, ectopic pregnancy, tumors, and a decrease in reproductive capacities in female animals. Estrogen can suppress immune responses in different tissues and oviducts, and regulate the oviduct immune balance; however, the underlying mechanisms remain unclear. The objective of this study was to explore the mechanism of estrogen-regulated oviduct mucosal immunity and discover new estrogen targets for regulating oviduct mucosal immune homeostasis. Sheep oviduct epithelial cells (SOECs) were treated with 17-ß estradiol (E2). Transcriptome sequencing and analysis showed differentially expressed S100 calcium-binding protein A (S100A) genes that may participate in the oviduct mucosa immunoregulation of estrogen. Quantitative polymerase chain reaction and immunocytochemistry analysis showed that S100A8 expression changed dynamically in E2-treated SOECs and peaked after 7 h of treatment. Estrogen nuclear receptors and G protein-coupled membrane receptors promoted E2-dependent S100A8 upregulation. The S100A8 gene was disrupted using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 method. Levels of inflammatory factors interleukin (IL)-1ß and IL-4 were significantly upregulated in S100A8-knockdown SOECs, whereas those of the anti-inflammatory factor IL-10 was downregulated. Following S100A8 knockdown in SOECs treated with E2 for 7 h, IL-10 levels increased significantly. Estrogen affected oviduct mucosa immune function and dynamically regulated S100A8 in SOECs. S100A8 knockdown caused an excessive immune response, indicating that S100A8 is beneficial for maintaining immune homeostasis in the oviduct mucosa. Moreover, estrogen can compensate for the effect of S100A8 knockdown by upregulating IL-10.

6.
Adv Nutr ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792092

RESUMO

Milk contains a number of bone-beneficial nutrients. However, milk, due to D-galactose contents, might have unfavorable effects on bone health. A meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effects of milk supplementation on bone mineral density (BMD), bone turnover markers (N-terminal telopeptide of type I collagen [NTx], C-terminal telopeptide of type 1 collagen [CTx], osteocalcin, bone alkaline phosphatase [BALP], and procollagen type 1 N-propeptide [P1NP]), and hormonal indices related to bone metabolism (parathyroid hormone [PTH], 25-hydroxyvitamin D [25(OH)D], and insulin-like growth factor 1 [IGF-1]) in adults. The PubMed and Web of Science databases were searched. A random-effects model was used to estimate the pooled effect sizes. A total of 20 RCTs were included. The trial duration was ranged from 1 month to 36 months. Milk supplementation resulted in a small but significant increase in BMD at the hip (+0.004 g/cm2; n = 9 RCTs) and lumbar spine (+0.025 g/cm2; n = 7), but did not significantly affect whole body BMD (n = 3) and femoral neck BMD (n = 7). Milk supplementation reduced the levels of P1NP (-5.20 ng/ml; n = 9), CTx (-0.16 ng/ml; n = 9), and NTx (-8.66 nmol bone collagen equivalents/mmol creatinine; n = 3). The levels of osteocalcin (n = 9) and BALP (n = 3) were not affected by milk supplementation. Reduced parathyroid hormone PTH (-1.01 pg/ml; n = 13) levels and increased of IGF-1 (+1.79 nmol/l; n = 4) levels were observed with milk supplementation. 25(OH)D (3.73 ng/ml; n = 11) levels were increased with vitamin-D fortified milk supplementation. The addition of milk to the diet may potentially increase the likelihood of preventing bone loss by restoring bone homeostasis through the modulation of calcium-vitamin D-PTH axis, bone remodeling rate, and growth hormone/IGF-1 axis.

7.
MycoKeys ; 84: 79-101, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790026

RESUMO

During investigations into freshwater fungi from the Great Mekong Subregion, four Distoseptispora taxa were collected from China and Thailand. Based on morphological characteristics, and phylogenetic analyses of combined LSU, ITS, SSU, TEF1-α, and RPB2 sequence data, two new species Distoseptisporabangkokensis and D.lancangjiangensis are introduced, and two known species D.clematidis and D.thysanolaenae were first reported in freshwater habitat. Illustrations and descriptions of these taxa are provided, along with comparisons with extant taxa in the genus.

8.
Phys Rev Lett ; 127(18): 180501, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34767433

RESUMO

Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2-3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor [Nature 574, 505 (2019)NATUAS0028-083610.1038/s41586-019-1666-5. We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.

9.
Nat Protoc ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759384

RESUMO

The trRosetta (transform-restrained Rosetta) server is a web-based platform for fast and accurate protein structure prediction, powered by deep learning and Rosetta. With the input of a protein's amino acid sequence, a deep neural network is first used to predict the inter-residue geometries, including distance and orientations. The predicted geometries are then transformed as restraints to guide the structure prediction on the basis of direct energy minimization, which is implemented under the framework of Rosetta. The trRosetta server distinguishes itself from other similar structure prediction servers in terms of rapid and accurate de novo structure prediction. As an illustration, trRosetta was applied to two Pfam families with unknown structures, for which the predicted de novo models were estimated to have high accuracy. Nevertheless, to take advantage of homology modeling, homologous templates are used as additional inputs to the network automatically. In general, it takes ~1 h to predict the final structure for a typical protein with ~300 amino acids, using a maximum of 10 CPU cores in parallel in our cluster system. To enable large-scale structure modeling, a downloadable package of trRosetta with open-source codes is available as well. A detailed guidance for using the package is also available in this protocol. The server and the package are available at https://yanglab.nankai.edu.cn/trRosetta/ and https://yanglab.nankai.edu.cn/trRosetta/download/ , respectively.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34718439

RESUMO

OBJECTIVE: To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with systemic lupus erythematosus (SLE) susceptibility, glucocorticoids (GCs) efficacy, and prognosis. METHODS: Our study was done in two stages. First, we performed the whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and glucocorticoids efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. RESULTS: In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all P  BH<0.05). We confirmed that T16362C was related to GCs efficacy (P  BH=0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (P  BH<0.05). In the prognosis study, variants A4833G (P  BH=0.003) and G14569A (P  BH=9.744 × 1 0 -4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (P  BH<0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (P  BH=0.001) and prognosis (P  BH=0.013). Moreover, mtDNA variants-environment interactions were observed. CONCLUSION: We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GCs efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GCs efficacy. Our findings provide important information for future understanding the occurrence and development of SLE.

11.
Chin Med J (Engl) ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34711717

RESUMO

BACKGROUND: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC), thus this study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC. METHODS: The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN). RESULTS: A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (28.80% in DM vs. 19.30% in non-DM, P = 0.026) and N3b status (18.70% in DM vs. 12.80% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P = 0.011) and N3b status (OR = 1.752, P = 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (ß = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1-2: 2.17% vs. 4.85%, T3: 29.03% vs. 20.27%, T4a: 38.89% vs. 25.84%, T4b: 50.00% vs. 36.64%; ELN16-29: 8.57% vs. 10.36%, ELN30-44: 27.87% vs. 20.45%, ELN≥45: 37.74% vs. 25.25%), N3b status (DM vs. non-DM, T1-2: 0.00% vs. 1.67%, T3: 16.13% vs. 5.14%, T4a: 27.78% vs. 19.10%, T4b: 44.00% vs. 28.00%; ELN16-29: 8.57% vs. 7.89%, ELN30-44: 18.03% vs. 11.79%, ELN≥45: 26.42% vs. 17.33%), and the number of MLN (DM vs. non-DM, T1-2: 0.40 vs. 1.05, T3: 8.58 vs. 5.16, T4a: 9.65 vs. 8.64, T4b: 17.00 vs. 12.75; ELN16-29: 3.63 vs. 4.61, ELN30-44: 5.75 vs. 5.45, ELN≥45: 11.96 vs. 7.65) of DM group increased with the advancement of primary tumor depth stage and raising of ELN. CONCLUSIONS: DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34713403

RESUMO

With the increasing frequency of extreme events caused by global climate change, the association between extreme precipitation (EP) and disease has aroused concern currently. However, no study has examined the relationship between EP and schizophrenia. Our study aimed to explore the relationship between EP and schizophrenia, and to further examine the difference between urban and rural areas. This study used quasi-Poisson generalized linear regression model combined with distributed lag non-linear model (DLNM) to estimate the association between EP (≥ 95th percentile) and hospitalization for schizophrenia from 2010 to 2019 in the city of Lu'an, China. EP could significantly increase the risk of hospitalization for schizophrenia. The effect firstly appeared at lag1 [relative risk (RR): 1.056, 95% confidence interval (95%CI): 1.003-1.110] and continued until lag17 (RR: 1.039, 95%CI: 1.004-1.075). Our research showed that EP had a significant effect on the hospitalization for schizophrenia in both urban and rural areas, and no significant difference was found (p>0.05). EP exerted more acute effects on schizophrenia living in rural areas than those in urban areas in the cold season. Further studies on the burden of schizophrenia found that patients who are male, aged ≤ 39 years or less, and living in urban areas are a priority for future warnings. We should pay more attention to the impact of EP on burden of schizophrenia, especially during the cold season, targeting those vulnerable groups, thereby implementing more accurate and timely preventive measures.

13.
Environ Res ; : 112078, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34599899

RESUMO

OBJECTIVES: Evidence of childhood asthma hospitalizations associated with temperature variability (TV) and the attributable risk are limited in China. We aim to use a comprehensive index that reflected both intra- and inter-day TV to assess the TV-childhood asthma relationship and disease burden, further to identify seasonality vulnerable populations, and to explore the effect modification of PM2.5. METHODS: A quasi-distributed lagged nonlinear model (DLNM) combined with a linear threshold function was applied to estimate the association between TV and childhood asthma hospitalizations during 2013-2016 in Hefei, China. Subgroup analysis was conducted by age and sex. Disease burden is reflected by the attributable fraction and attributable number. Besides, modifications of PM2.5 were tested by introducing the cross-basis of TV and binary PM2.5 as an interaction term. RESULTS: The risk estimates peaked at TV0-3 and TV0-4 in the cool and the warm season separately, with RR of 1.051 (95%CI: 1.021-1.081) and 1.072 (95%CI: 1.008-1.125), and the effects lasted longer in the cool season. The school-age children in the warm season and all subgroups except pre-school children in the cool season were vulnerable to TV. It is estimated that the disease burden related to TV account for 6.2% (95% CI: 2.7%-9.4%) and 4% (95% CI: 0.6%-7.1%) during the cool and warm seasons in TV0-3. In addition, the risks of TV were higher under the high PM2.5 level compared with the low PM2.5 level in the cool season, although no significant differences between them. CONCLUSIONS: TV exposure significantly increases the risk and disease burden of childhood asthma hospitalizations, especially in the cool season. More medical resources should be allocated to school-age children. Giving priority to pay attention to TV in the cool season in practice could obtain the greatest public health benefits and those days with high TV and high PM2.5 need more attention.

14.
Mol Neurobiol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34635980

RESUMO

Spinal cord injury (SCI), a devastating neurological impairment, usually imposes a long-term psychological stress and high socioeconomic burden for the sufferers and their family. Recent researchers have paid arousing attention to white matter injury and the underlying mechanism following SCI. Ferroptosis has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improving functional recovery after traumatic brain injury (TBI) and SCI. However, the role of ferroptosis in white matter injury and the therapeutic effect of ferrostatin-1 on SCI are still unknown. Here, our results indicated that ferroptosis played a pivotal role in the secondary white matter injury, and ferrostatin-1 could reduce iron and reactive oxygen species (ROS) accumulation and downregulate the ferroptosis-related genes and its products of IREB2 and PTGS2 to further inhibit ferroptosis in oligodendrocyte, finally reducing white matter injury and promoting functional recovery following SCI in rats. Meanwhile, the results demonstrated that ferrostatin-1 held the potential of inhibiting the activation of reactive astrocyte and microglia. Mechanically, the present study deciphers the potential mechanism of white matter damage, which enlarges the therapeutic effects of ferrostatin-1 on SCI and even in other central nervous system (CNS) diseases existing ferroptosis.

15.
Cell Transplant ; 30: 9636897211017829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665040

RESUMO

Human pluripotent stem cells (hPSCs) are sources of several somatic cell types for human developmental studies, in vitro disease modeling, and cell transplantation therapy. Improving strategies of derivation of high-purity specific neural and glial lineages from hPSCs is critical for application to the study and therapy of the nervous system. Here, we will focus on the principles behind establishment of neuron and glia differentiation methods according to developmental studies. We will also highlight the limitations and challenges associated with the differentiation of several "difficult" neural lineages and delay in neuronal maturation and functional integration. To overcome these challenges, we will introduce strategies and novel technologies aimed at improving the differentiation of various neural lineages to expand the application potential of hPSCs to the study of the nervous system.

16.
Cells ; 10(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34685720

RESUMO

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

17.
Cells ; 10(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34685754

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive nervous system disease that causes motor neuron (MN) degeneration and results in patient death within a few years. To recapitulate the cytopathies of ALS patients' MNs, SOD1G85R mutant and corrected SOD1G85G isogenic-induced pluripotent stem cell (iPSC) lines were established. Two SOD1 mutant ALS (SOD1G85R and SOD1D90A), two SOD1 mutant corrected (SOD1G85G and SOD1D90D), and one sporadic ALS iPSC lines were directed toward MNs. After receiving ~90% purity for MNs, we first demonstrated that SOD1G85R mutant ALS MNs recapitulated ALS-specific nerve fiber aggregates, similar to SOD1D90A ALS MNs in a previous study. Moreover, we found that both SOD1 mutant MNs showed ALS-specific neurite degenerations and neurotransmitter-induced calcium hyperresponsiveness. In a small compound test using these MNs, we demonstrated that gastrodin, a major ingredient of Gastrodia elata, showed therapeutic effects that decreased nerve fiber cytopathies and reverse neurotransmitter-induced hyperresponsiveness. The therapeutic effects of gastrodin applied not only to SOD1 ALS MNs but also to sporadic ALS MNs and SOD1G93A ALS mice. Moreover, we found that coactivation of the GSK3ß and IGF-1 pathways was a mechanism involved in the therapeutic effects of gastrodin. Thus, the coordination of compounds that activate these two mechanisms could reduce nerve fiber cytopathies in SOD1 ALS MNs. Interestingly, the therapeutic role of GSK3ß activation on SOD1 ALS MNs in the present study was in contrast to the role previously reported in research using cell line- or transgenic animal-based models. In conclusion, we identified in vitro ALS-specific nerve fiber and neurofunctional markers in MNs, which will be useful for drug screening, and we used an iPSC-based model to reveal novel therapeutic mechanisms (including GSK3ß and IGF-1 activation) that may serve as potential targets for ALS therapy.

18.
Front Pharmacol ; 12: 755140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690786

RESUMO

As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from Chrysanthemum indicum L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKß, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.

19.
J Affect Disord ; 297: 156-168, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34687781

RESUMO

BACKGROUND: Hospital workers have been under intense psychological pressure since the COVID-19 outbreak. We analyzed the psychological status of hospital staff in the late period of the COVID-19 to provide a basis for the construction of global health care after the COVID-19 outbreak. METHODS: We used online surveys to assess participants' self-reported symptoms at the late stage of the outbreak. This study collected data on sociodemographic characteristics, epidemic-related factors, psychological status (PHQ-9, GAD-7, and PHQ-15), psychological assistance needs, perceived stress and support, PTSD symptoms (PCL-C) and suicidal and self-injurious ideation (SSI). Participants were hospital workers in all positions from 46 hospitals. Chi-square tests to compare the scales and logistic regression analysis were used to identify risk factors for PTSD and SSI. RESULTS: Among the 33,706 participants, the prevalences of depression, anxiety, somatic symptoms, PTSD symptoms, and SSI were 35.8%, 24.4%, 49.7%, 5.0%, and 1.3%, respectively. Logistic regression analysis showed that work in a general ward, attention to the epidemic, high education, work in non-first-line departments, insufficient social support, and anxiety and somatization symptoms were influencing factors of PTSD (P<0.05). The independent risk factors for SSI were female gender; psychological assistance needs; contact with severe COVID-19 patients; high stress at work; single or divorced marital status; insufficient social support; and depression, anxiety or PTSD symptoms (P<0.05). LIMITATIONS: This cross-sectional study could not reveal causality, and voluntary participation may have led to selection bias. The longer longitudinal studies are needed to determine the long-term psychological impact. CONCLUSION: This COVID-19 pandemic had a sustained, strong psychological impact on hospital workers, and hospital workers with PTSD symptoms were a high-risk group for SSI in the later period of the epidemic. Continuous attention and positive psychological intervention are of great significance for specific populations.

20.
Biomed Pharmacother ; 143: 112141, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34509822

RESUMO

AIM: Modified Suanzaoren Decoction (MSZRD) is obtained by improving Suanzaoren Decoction (SZRT), a traditional Chinese herbal prescription that has been used to treat insomnia for more than thousands of years. Our previous study showed that MSZRD can improve the gastrointestinal discomfort related insomnia by regulating Orexin-A. This study is the first study to evaluate the effects and possible mechanisms of MSZRD in mice with insomnia caused by p-chlorophenylalanine (PCPA) combined with multifactor random stimulation. METHODS: After 14 days of multifactor stimulation to ICR mice, a PCPA suspension (30 mg/mL) was injected intraperitoneally for two consecutive days to establish an insomnia model. Three different doses of MSZRD (3.6, 7.2, and 14.4 g/kg/day) were given to ICR mice for 24 days. The food intake and back temperature were measured, and behavioral tests and pentobarbital sodium-induced sleep tests were conducted. The levels of Orexin-A, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and adrenocortical hormones (CORT) in the serum and 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in hypothalamus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) were measured by high-performance liquid chromatography (HPLC). The expression of 5HT1A receptor (5-HTRIA) and orexin receptor 2 antibody (OX2R) was measured by Western blot (WB) and immunohistochemical staining (ICH). Hematoxylin and eosin (H&E) staining and Nissl staining were used to assess the histological changes in hypothalamus tissue. RESULTS: Of note, MSZRD can shorten the sleep latency of insomnia mice (P < 0.05, 0.01), prolonged the sleep duration of mice (P < 0.05, 0.01), and improve the circadian rhythm disorder relative to placebo-treated animals. Furthermore, MSZRD effectively increased the content of 5-HT and 5-HTR1A protein in the hypothalamus of insomnia mice (P < 0.05, 0.01), while downregulated the content of DA and NE (P < 0.05, 0.01). Importantly, serum GABA concentration was increased by treatment with MSZRD (P < 0.05), as reflected by a decreased Glu/GABA ratio (P < 0.05). Moreover, MSZRD decreased the levels of CORT, ACTH, and CRH related hormones in HPA axis (P < 0.05, 0.01). At the same time, MSZRD significantly downregulated the serum Orexin-A content in insomnia mice (P < 0.05), as well as hypothalamic OX2R expression (P < 0.05). In addition, MSZRD also improved the histopathological changes in hypothalamus in insomnia mice. CONCLUSION: MSZRD has sleep-improvement effect in mice model of insomnia. The mechanism may be that regulating the expression of Orexin-A affects the homeostasis of HPA axis and the release of related neurotransmitters in mice with insomnia.

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