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1.
Proc Natl Acad Sci U S A ; 120(13): e2210791120, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36947519

RESUMO

Adaptive changes in crops contribute to the diversity of agronomic traits, which directly or indirectly affect yield. The change of pubescence form from appressed to erect is a notable feature during soybean domestication. However, the biological significance and regulatory mechanism underlying this transformation remain largely unknown. Here, we identified a major-effect locus, PUBESCENCE FORM 1 (PF1), the upstream region of Mao1, that regulates pubescence form in soybean. The insertion of a Ty3/Gypsy retrotransposon in PF1 can recruit the transcription factor GAGA-binding protein to a GA-rich region, which up-regulates Mao1 expression, underpinning soybean pubescence evolution. Interestingly, the proportion of improved cultivars with erect pubescence increases gradually with increasing latitude, and erect-pubescence cultivars have a higher yield possibly through a higher photosynthetic rate and photosynthetic stability. These findings open an avenue for molecular breeding through either natural introgression or genome editing toward yield improvement and productivity.


Assuntos
Glycine max , Retroelementos , Retroelementos/genética , Glycine max/genética , Fenótipo , Regiões Promotoras Genéticas/genética
2.
Plant Physiol ; 194(4): 2549-2563, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38235827

RESUMO

Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.


Assuntos
Genes myb , Glycine max , Glycine max/genética , Antocianinas/genética , Duplicação Gênica , Família Multigênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Mol Pharm ; 21(2): 373-392, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38252032

RESUMO

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Qualidade de Vida , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular
4.
Chin J Traumatol ; 27(1): 42-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37953130

RESUMO

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS: Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.


Assuntos
Edema Encefálico , Células-Tronco Neurais , Humanos , Animais , Manitol/farmacologia , Células-Tronco Neurais/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/farmacologia , Proliferação de Células
5.
Chin J Traumatol ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637176

RESUMO

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

6.
Inorg Chem ; 62(44): 18128-18135, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37881839

RESUMO

Materials with enzyme-like activity have received a lot of attention in the field of tumor catalytic therapy. Here, biocompatible core-shell MOF CSMnP with two valence states of Mn ion, which could process chemodynamic therapy (CDT), was designed and synthesized. Besides, it could also promote a series of catalytic processes in the tumor microenvironment (TME). CSMnP catalyzed endogenous hydrogen peroxide (H2O2) to oxygen (O2) via catalase-like activity and then combined with the outer layer Mn(II)-PBC to convert O2 into superoxide radicals (•O2-), exhibiting oxidase-like activity. Besides, intracellular glutathione (GSH) could be effectively consumed through the glutathione oxidase-like activity of Mn3+. The occurrence of the cascade reactions effectively amplified the enzymatic production to enhance CDT. Furthermore, the therapeutic effect of CSMnP was improved through the loading of cationic drug DOX. The loading capacity was 11.10 wt %, which was 2.2 times that of Mn(III)-PBC (4.95 wt %), and the release of DOX showed a characteristic response. Therefore, the core-shell MOF with enzyme-like activity had a potential application for tumor combination therapy.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Humanos , Catálise , Glutationa , Oxigênio , Neoplasias/tratamento farmacológico , Microambiente Tumoral
7.
Inorg Chem ; 62(51): 21299-21308, 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38069807

RESUMO

Microflora within cancer cells plays a pivotal role in promoting metastasis of cancer. However, contemporary anticancer research often overlooks the potential benefits of combining anticancer and antibacterial agents. Consequently, a metal-organic framework Cu-Cip with cuproptosis and antibacterial properties was synthesized for cancer therapy. To enhance the anticancer effect of the material, Mn2+ was loaded into Cu-Cip, yielding Mn@Cu-Cip. The fabricated material was characterized using single-crystal X-ray diffraction, PXRD, and FT-IR. By interacting with overexpressed H2O2 to produce ROS and accumulating Cu ions in cancer cells, MOFs exhibited excellent anticancer performance. Moreover, the material displayed the function of damaging Staphylococcus aureus and Escherichia coli, revealing the admirable antibacterial properties of the material. In addition, the antibacterial ability could inhibit tumor cell migration. The Cu-based MOF revealed promising applications in the field of tumor treatment.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Peróxido de Hidrogênio , Antibacterianos/farmacologia , Antibacterianos/química , Cristalografia por Raios X , Neoplasias/tratamento farmacológico
8.
Mol Breed ; 43(6): 43, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313220

RESUMO

Seed oil content is one of the most important quantitative traits in soybean (Glycine max) breeding. Here, we constructed a high-density single nucleotide polymorphism linkage map using two genetically similar parents, Heinong 84 and Kenfeng 17, that differ dramatically in their seed oil contents, and performed quantitative trait loci (QTL) mapping of seed oil content in a recombinant inbred line (RIL) population derived from their cross. We detected five QTL related to seed oil content distributed on five chromosomes. The QTL for seed oil content explained over 10% of the phenotypic variation over two years. This QTL was mapped to an interval containing 20 candidate genes, including a previously reported gene, soybean RING Finger 1a (RNF1a) encoding an E3 ubiquitin ligase. Notably, two short sequences were inserted in the GmRNF1a coding region of KF 17 compared to that of HN 84, resulting in a longer protein variant in KF 17. Our results thus provide information for uncovering the genetic mechanisms determining seed oil content in soybean, as well as identifying an additional QTL and highlighting GmRNF1a as candidate gene for modulating seed oil content in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01384-2.

9.
Int Wound J ; 20(7): 2718-2725, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36950772

RESUMO

The study aimed to assess the functional and aesthetic outcomes of abdominal full-thickness skin grafts (FTSGs) in paediatric postburn digital and palmar flexion contractures. The digital and palmar functions and aesthetics of 50 children who met the criteria were evaluated at pre-operation, the 3rd- and 12th-month post-operation, respectively. In the evaluation, the Vancouver Scar Scale (VSS), total active movement (TAM), and Jebsen-Taylor Hand Function Test (JHFT) were used. The contralateral, unaffected hand served as the criteria for functional recovery. The complications of donor sites were observed, and the take rate of skin grafts was calculated. The VSS scores at the 3rd and 12th months post-operation were lower than those before the operation. The TAM of each finger was improved at the 3rd and 12th months post-operation, compared with that before the operation. There was a significant difference in the time to complete the JHFT between the affected hand and the unaffected at the 3rd month post-operation, but no significant difference between them at the 12th month post-operation. The excellent and good take rate of the skin grafts was 90.00%.No donor site complications were observed. The abdominal FTSGs are effective in repairing paediatric digital and palmar scar contractures, with satisfying functional and aesthetic results, especially in large defects after scar release and resection.


Assuntos
Queimaduras , Contratura , Criança , Humanos , Transplante de Pele/métodos , Cicatriz/cirurgia , Cicatriz/complicações , Queimaduras/complicações , Queimaduras/cirurgia , Contratura/cirurgia , Contratura/complicações , Estética
10.
Lab Invest ; 102(12): 1377-1388, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35851856

RESUMO

In recent years, CC chemokine receptor 2 (CCR2) has been found to be involved in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis, and immune escape. CCR2 overexpression was first identified as a poor prognostic predictor in diffuse large B-cell lymphoma (DLBCL) in our published article, but the mechanisms involved remain unknown. In this work, we collected data from another 138 patients with DLBCL data and verified the CCR2 expression level and its relationship to clinicopathological characteristics. Furthermore, we explored the possible mechanisms via in vitro and in vivo experiments. We showed that CCR2 overexpression was an independent prognostic marker and predicted shorter overall survival (OS) and progression-free survival (PFS) in patients with DLBCL. Blockade of CCR2 expression with a CCR2 antagonist inhibited tumor cell proliferation, migration, and anti-apoptosis ability in vitro by affecting the PI3K/Akt signaling pathway and the p38 MAPK signaling pathway. Furthermore, administration of a CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells and increased survival time in the xenograft model. Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Receptores CCR2 , Humanos , Receptores CCR2/genética , Receptores CCR2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Linfoma Difuso de Grandes Células B/metabolismo , Prognóstico , Processos Neoplásicos
11.
J Integr Plant Biol ; 64(5): 1076-1086, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35249256

RESUMO

Male-sterile plants are used in hybrid breeding to improve yield in soybean (Glycine max (L.) Merr.). Developing the capability to alter fertility under different environmental conditions could broaden germplasm resources and simplify hybrid production. However, molecular mechanisms potentially underlying such a system in soybean were unclear. Here, using positional cloning, we identified a gene, MALE STERILITY 3 (MS3), which encodes a nuclear-localized protein containing a plant homeodomain (PHD)-finger domain. A spontaneous mutation in ms3 causing premature termination of MS3 translation and partial loss of the PHD-finger. Transgenetic analysis indicated that MS3 knockout resulted in nonfunctional pollen and no self-pollinated pods, and RNA-seq analysis revealed that MS3 affects the expression of genes associated with carbohydrate metabolism. Strikingly, the fertility of mutant ms3 can restore under long-d conditions. The mutant could thus be used to create a new, more stable photoperiod-sensitive genic male sterility line for two-line hybrid seed production, with significant impact on hybrid breeding and production.


Assuntos
Glycine max , Infertilidade das Plantas , Fertilidade/genética , Proteínas de Homeodomínio , Melhoramento Vegetal , Infertilidade das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glycine max/genética , Glycine max/metabolismo
12.
Entropy (Basel) ; 24(8)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36010797

RESUMO

At present, electron optical simulator (EOS) takes a long time to solve linear FEM systems. The algebraic multigrid preconditioned conjugate gradient (AMGPCG) method can improve the efficiency of solving systems. This paper is focused on the implementation of the AMGPCG method in EOS. The aggregation-based scheme, which uses two passes of a pairwise matching algorithm and the K-cyle scheme, is adopted in the aggregation-based algebraic multigrid method. Numerical experiments show the advantages and disadvantages of the AMG algorithm in peak memory and solving efficiency. The AMGPCG is more efficient than the iterative methods used in the past and only needs one coarsening when EOS computes the particle motion trajectory.

13.
Mol Breed ; 41(2): 14, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37309478

RESUMO

As soybean plays an indispensable role in the supply of vegetable oil and protein, balancing the relationship between seed quality and yield traits according to human demand has become an important breeding goal for soybean improvement. Here, 256 intraspecific recombinant inbred lines (RILs), derived from a cross between Qi Huang No.34 (QH34) and Ji Dou No.17 (JD17), were used for quantitative trait loci (QTLs) mapping with remarkable four chemical and physical properties with a purpose for exploring the distribution of excellent alleles in germplasm resources in China. A total of 25 QTLs were detected, of which 10 QTLs inherited the alleles from the parent QH34. Pedigree research on favorable alleles on these QTLs showed the process of excellent alleles pyramided into QH34. Meta-analysis of the 25 QTLs by comparing with existed QTLs in previous study identified 17 novel QTLs. QTLs with pleiotropic effects have been detected. Furthermore, three representative elite recombinant inbred lines in different locations that have great potential in soybean breeding were selected, and finally, four seed weight-related candidate genes were identified. The discovery of these QTLs provides a new guidance for combining the diversity and rarity of germplasm resources, which can effectively increase population genetic diversity and broaden genetic basis of varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01211-6.

14.
Mol Breed ; 41(12): 72, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37309518

RESUMO

Soybean seed appearance quality greatly affects the marketability. The objective of this study was to identify the quantitative trait loci (QTLs) that control the appearance quality of soybean seeds. A total of 256 recombinant inbred lines from Qi Huang No.34 × Ji Dou No.17 were utilized for QTL mapping. We innovatively applied a machine vision system to quantify the seed appearance of each line. As a result of QTL mapping, a total of 145 QTLs for the machine vision parameters were detected across three environments. We integrated QTLs mapped overlapped and obtained 16 QTL hotspots in total. Of these hotspots, hotspot-4-1 was suggested to be a major locus controlling seed size, and hotspot-15 was identified to affect the seed color and texture. The mapping for principal components of the seed appearance also supported it. This study comprehensively dug up the QTLs for seed appearance quality of soybean cultivars while providing an efficient method for phenotyping of seed appearance. These results would contribute to dissecting the genetic bases of seed appearance quality for the improvement of soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01262-9.

15.
IUBMB Life ; 72(8): 1780-1786, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32502299

RESUMO

The present study aimed to investigate the molecular mechanism and the effect of Saponin from Tupistra chinensis Baker (STCB) on the proliferation and apoptosis of ovarian cancer cells. To investigate the inhibitory effect of STCB on the proliferation of ovarian cancer cells, SKOV3 cells were cultured and the methyl thiazolyl tetrazolium assay was used. Flow cytometry was also used to analyze the cell cycle distribution and apoptotic rate. Ki-67, cyclin D1, cleaved caspase-3, cleaved caspase-9, ß-catenin, and c-Myc protein expressions were detected by western blot. Ovarian cancer cells were treated with STCB and Wnt pathway activator lithium chloride (LiCl). These methods were also used to determine the proliferation, cell cycle distribution, and apoptosis of ovarian cancer cells. In STCB-treated group, the proliferation inhibition and apoptosis rate, the proportion of G0-G1 phase, and the expression level of cleaved caspase-3 and 9 of ovarian cancer cells were significantly increased. Similarly, the expression of Ki-67, cyclin D1, ß-catenin, and c-Myc were significantly decreased (p < .05). The results also showed that in STCB-LiCl-treated group, while the proliferation inhibition rate of ovarian cancer cells, the proportion of G0-G1 cells, the expression level of cleaved caspase-3 and 9, and the apoptosis rate (p < .05) were significantly decreased, the expression level of Ki-67, cyclin D1, ß-catenin, and c-Myc was significantly increased. STCB induced G0-G1 phase arrest, inhibited cell proliferation, and promoted apoptosis of ovarian cancer cells by inhibiting Wnt/ß-catenin pathway.


Assuntos
Asparagaceae/química , Proliferação de Células/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/química , Apoptose/efeitos dos fármacos , Caspase 3/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclina D1/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Antígeno Ki-67/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética
16.
Crit Care ; 24(1): 219, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410714

RESUMO

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Cuidados Críticos , Surtos de Doenças , Unidades de Terapia Intensiva , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Idoso , COVID-19 , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Resultado do Tratamento
17.
Neurochem Res ; 44(4): 930-946, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30661230

RESUMO

Exercise has been regarded as an effective rehabilitation strategy to facilitate motor and cognitive functional recovery after stroke, even though the complex effects associated with exercise-induced repair of cerebral ischemic injury are not fully elucidated. The enhancement of angiogenesis and neurogenesis, and the improvement of synaptic plasticity following moderate exercise are conducive to functional recovery after ischemic damage. Our previous studies have confirmed the angiogenesis and neurogenesis through the caveolin-1/VEGF pathway in MCAO rats. As an essential neurotrophic factor, BDNF has multiple effects on ischemic injury. In this study, we attempted to determine an additional mechanism of treadmill exercise-mediated motor and cognitive functional recovery through the caveolin-1/VEGF pathway associated with BDNF in the ischemic penumbra of MCAO mice. We found that mice exposed to treadmill exercise after the MCAO operation showed a significant up-regulation in expression of caveolin-1, VEGF, BDNF, synapsin I and CYFIP1 proteins, numbers of cells positive for BrdU/CD34, BDNF, BrdU/NeuN, BrdU/Synapsin I and CYFIP1 expression were increased, which support the reduction in neurological deficit and infarction volume, as well as improved synaptic morphology and spatial learning abilities, compared with the non-exercise mice. However, the caveolin-1 inhibitor, daidzein, resulted in increase in neurological deficit and infarction volume. The selective VEGFR2 inhibitor, PD173074, significantly induced larger infarction volume and neurological injury, and decreased the expression of BDNF in the ischemic penumbra. These findings indicate that exercise improves angiogenesis, neurogenesis and synaptic plasticity to ameliorate motor and cognitive impairment after stroke partially through the caveolin-1/VEGF pathway, which is associated with the coregulator factor, BDNF.


Assuntos
Isquemia Encefálica/metabolismo , Caveolina 1/biossíntese , Cognição/fisiologia , Condicionamento Físico Animal/métodos , Recuperação de Função Fisiológica/fisiologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Isquemia Encefálica/terapia , Caveolina 1/antagonistas & inibidores , Cognição/efeitos dos fármacos , Teste de Esforço/métodos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/terapia , Injeções Subcutâneas , Isoflavonas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Destreza Motora/efeitos dos fármacos , Destreza Motora/fisiologia , Pirimidinas/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
18.
Artigo em Inglês | MEDLINE | ID: mdl-30412790

RESUMO

BACKGROUND: The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. METHODS: We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1-7) (Ang-1-7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. RESULTS: Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1-7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. CONCLUSION: BML-111 could protect against acute injury via regulation RAAS.


Assuntos
Ácidos Heptanoicos/farmacologia , Receptores de Lipoxinas/agonistas , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Animais , Citoproteção/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/prevenção & controle , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Regulação para Cima/efeitos dos fármacos
19.
Arch Virol ; 164(1): 27-32, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30229302

RESUMO

Hepatitis E virus (HEV) is an emergent virus of global importance. Previous studies of HEV infection in China mainly focused on the rural areas. This work aims to study the epidemiology of HEV in a large urban environment. With a registered population of 10 million, the dense city of Wuhan presents itself as a prime opportunity to better understand this emergent virus. The epidemiological data from 2011 to 2016 were analyzed. A cross-sectional study on the seroprevalence of anti-HEV IgG was conducted among the general population (age range 0-59) in 2013. Serum and fecal samples of hepatitis E patients were collected over a period of two years: serum samples were tested for anti-HEV IgM and IgG, and fecal samples were tested for HEV-RNA. The overall seroprevalence of anti-HEV IgG was 35% in Wuhan. Among 415 hepatitis E patients, 286 cases (68.9%) were positive for HEV-IgM, 108 cases (26%) were positive for HEV-IgG alone, and 21 cases (5.1%) were negative for both IgM and IgG. Phylogenetic analysis showed that the detected genotype of HEV was genotype 4. Reported cases occurred sporadically throughout the year with the peak value appearing in the first quarter and a large proportion of male cases (2.1:1). The incidence increased with age for persons under 60 years, reaching its peak level after 60 years of age. Wuhan is endemic for HEV with its currently detected genotype being genotype 4. It is estimated that 68.9% hepatitis E cases were due to primary infection between 2012 and 2013 in Wuhan.


Assuntos
Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , China/epidemiologia , Fezes/virologia , Hepatite E/sangue , Hepatite E/virologia , Vírus da Hepatite E/genética , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Pessoa de Meia-Idade , Filogenia , Estações do Ano , Estudos Soroepidemiológicos , Adulto Jovem
20.
J Environ Manage ; 252: 109647, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31600685

RESUMO

This research built up a continuous dynamic flow filter membrane to treat diluted textile wastewater and basically investigated dynamic membrane fouling mechanism. By pre-depositing particles activated carbon (PAC) on membrane support material (MSM), a thin layer was formed on its surface, which showed excellent results in removing organic pollutants from diluted textile wastewater. Experimental data were regressed by the Langmuir, Freundlich, Temkin, Dubinin-Radushkevich (D-R) and Sips isotherm models. The three two-parameter isotherms (Temkin, D-R and Freundlich) were the models that best fitted, with respectively 0.977, 0.975 and 0.973 regression coefficients. D-R model has registered the maximum calculated adsorption capacity Qmd, cal. = 45.499 mg/g and the mean energy which was required to adsorb 1 mol of MB dye by the DM layer E = 4.249 kJ/mol; indicating the energy distribution onto heterogeneous surface of a physical adsorption process. Furthermore, kinetic models results showed that MB adsorption onto PAC at different initial concentrations follows the pseudo-second order. The obtained results also indicated that a flexible DM layer with different thickness can be formed from different amount of PAC pre-deposited on MSMs, which demonstrated that it was convenient to adjust the required DM thickness to filtrate a known initial concentration for >99% organic pollutants removal efficiency rate. However, DM fouling occurred on small pores MSMs; which resulted in an increase of the filtration pressure what have affected the filtration performance. PAC and MSMs surface morphology and texture structure, before and after filtration, were visualized respectively by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infra-Red and Attenuated Total Reflectance (FTIR/ATR). From these experimental results, a sustainable flux (>6.85 × 10-5 m/s) was established to discriminate no fouling from fouling conditions based on flux and TMP trends variance.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Humanos , Cinética , Membranas Artificiais , Têxteis , Águas Residuárias
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