RESUMO
The coastal seas of China are increasingly threatened by algal blooms, yet their comprehensive spatiotemporal mapping and understanding of underlying drivers remain challenging due to high turbidity and heterogeneous water conditions. We developed a singular value decomposition-based algorithm to map these blooms using two decades of MODIS-Aqua satellite data, spanning from 2003 to 2022. Our findings indicate significant algal activity along the Chinese coastline, impacting an average annual area of approximately 1.8 × 105 km2. The blooms exhibit peak intensity in August, while the maximum affected area occurs in September, featuring multifrequency outbreaks in spring, and pronounced large-scale events in summer and autumn. Notably, our analysis demonstrates a robust 67% increase in bloom occurrences over the study period. This expansion is primarily attributed to increased nutrient inflow from terrestrial sources linked to human activity and precipitation, compounded by rising global sea surface temperatures. These spatiotemporal insights are critical for devising effective management strategies and policies to mitigate the impacts of algal blooms.
Assuntos
Eutrofização , China , Oceanos e Mares , Monitoramento Ambiental , Estações do Ano , Análise Espaço-TemporalRESUMO
Homoyessotoxin (homo-YTX) and nitrite (NO2-N), released during harmful dinoflagellate cell lysis adversely affect abalones. However, their toxicity mechanisms in shellfish remain unclear. This study investigated the economic abalone species Haliotis discus hannai exposed to varying concentrations of homo-YTX (0, 2, 5, and 10 µg L-1) and NO2-N (0, 3, and 6 mg L-1) on the basis of their 12 h LC50 values (5.05 µg L-1 and 4.25 mg L-1, respectively) and the environmentally relevant dissolved concentrations during severe dinoflagellate blooms, including mixtures. The test abalones were exposed to homo-YTX and NO2-N for 12 h. The mortality rate (D), reactive oxygen species (ROS) levels, antioxidant defense capabilities, and expression levels of antioxidant-related, Hsp-related, and apoptosis-related genes in abalone gills were assessed. Results showed that the combined exposure to homo-YTX and NO2-N increased the D and ROS levels and upregulated B-cell lymphoma-2 (BCL2)-associated X (BAX) and caspase3 (CASP3) expression levels while reducing glutathione peroxidase (GPx) activity and GPx, CuZnSOD, and BCL2 expression levels. High concentrations of homo-YTX (10 µg L-1) and NO2-N (6 mg L-1) solutions and the combinations of these toxicants inhibited the activities of superoxide dismutase (SOD) and catalase (CAT) and downregulated the expression levels of MnSOD, CAT, Hsp70, and Hsp90. The ROS levels were negatively correlated with the activities of SOD, CAT, and GPx and the expression levels of MnSOD, CuZnSOD, CAT, GPx, Hsp70, Hsp90, and BCL2. These results suggest that homo-YTX, in conjunction with NO2-N, induces oxidative stress, disrupts antioxidant defense systems, and triggers caspase-dependent apoptosis in the gills of abalone. ROS-mediated antioxidative and heat-shock responses and apoptosis emerge as potential toxicity mechanisms affecting the survival of H. discus hannai due to homo-YTX and NO2-N exposure.
Assuntos
Antioxidantes , Gastrópodes , Animais , Antioxidantes/metabolismo , Nitritos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Nitrogênio , Superóxido Dismutase/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Gastrópodes/genética , Gastrópodes/metabolismoRESUMO
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF) have been associated with sarcopenia. However, modifiers of this association have been less studied. METHODS: This study used data from the NHANES database 2011-2014 of the USA. Adults aged 18 years or older, had complete information of handgrip strength test and NAFLD and AHF status were eligible for inclusion. NAFLD was defined using the Fatty Liver Index (FLI). AHF was defined using the NAFLD fibrosis score (NFS). Univariate and multivariate logistic regression were performed to determine the associations between the study variables and prevalent NAFLD and AHF. RESULTS: A total of 19 931 participants were selected from the 2011-2014 NHANES database. The multivariate analysis showed that stronger grip strength was significantly and independently associated with decreased odds for NAFLD (tertile 2: adjusted odd ratio [aOR]: 0.41, 95% confidence interval [CI]: 0.29-0.59; tertile 3: aOR: 0.11, 95% CI: 0.05-0.24) and AHF (tertile 2: aOR: 0.66, 95% CI: 0.46-0.94; tertile 3: aOR: 0.28, 95% CI: 0.12-0.63). In stratified analyses, strongest grip strength was significantly associated with reduced odds for NAFLD regardless of age, body mass index, and having diabetes or not. Strongest grip strength was associated with reduced odds for NAFLD in individuals who had moderate to ideal physical activity (aOR: 0.31). CONCLUSIONS: Grip strength has an inverse association with prevalent NAFLD and AHF in the US population, which appears to be modified by physical activity level. Future prospective cohort studies are needed to clarify the role of physical activity in modifying the risks.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Inquéritos Nutricionais , Força da Mão , Estudos Transversais , Prevalência , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicaçõesRESUMO
The harmful dinoflagellate Karenia mikimotoi is responsible for the mortality of aquatic animals. However, the mechanism behind these toxic effects has not been fully determined. Herein, the toxic effects of K. mikimotoi on the growth performance, antioxidative responses, physiological activities, and energetic substance contents of rotifer Brachionus plicatilis were assessed. Rotifers were exposed to Nannochloropsis salina (Eustigmatophyceae), K. mikimotoi, and a mixture of N. salina and K. mikimotoi with biomass ratio proportions of 3:1, 1:1, and 1:3, respectively. Results indicated that K. mikimotoi negatively affected the population growth, survival, and specific growth rates of rotifers within 24 h. The level of reactive oxygen species (ROS), the content of malondialdehyde, and the activity of amylase increased. However, the total antioxidant capacity level, pepsase, cellulase, alkaline phosphatase, xanthine oxidase, and lactate dehydrogenase activities, and glycogen and protein contents decreased with increasing proportions of K. mikimotoi. The mixture of 50% N. salina and 50% K. mikimotoi promoted the increase in glutamic-pyruvic transaminase activity and triglyceride content. These findings underscore ROS-mediated antioxidative responses, physiological responses, and energetic substance content changes in B. plicatilis work together to affect population dynamics inhibition of rotifers by K. mikimotoi.
Assuntos
Artrópodes , Dinoflagellida , Rotíferos , Animais , Antioxidantes , Espécies Reativas de Oxigênio , Fosfatase AlcalinaRESUMO
In August 2022, melon (Cucumis melo), cucumber (Cucumis sativus) and luffa (Luffa aegyptiaca) plants showed virus-like symptoms characteristic of geminiviruses (yellowish green, mosaic patterns and severe curling of leaves, short internodes, and stunting) in 10 greenhouses in Fengxian district and 20 greenhoues in Jiading district of Shanghai, China. Fifty symptomatic leaf samples were randomly collected: 28 from melon, 17 from cucumber, and 5 from luffa. To investigate the etiology of the observed disease, total DNA and RNA was extracted via a DNA extraction kit (Tiangen, Not: DP350) and TRIzol reagent (Sigma-Aldrich, Not: T9424), respectively. Healthy melon plants grown in a growth chamber served as negative control. The DNA and RNA samples were screened for the presence of geminiviruses, Cucurbit chlorotic yellow virus (CCYV), Melon yellow spot virus (MYSV), Cucumber mosaic virus (CMV), Zucchini yellow mosaic virus (ZYMV) and Cucumber green mottle mosaic virus (CGMMV) through PCR or RTâPCR with geminiviruses (Deng et al. 1994), CCYV, MYSV, CMV, ZYMV and CGMMV (Zeng et al. 2011, 2019) primers. The PCR results showed that 28 melon leaves and 17 cucumber leaves were positive for geminivirus and CCYV, respectively, 5 luffa samples were infected with only geminivirus, and virus was not detected from the healthy plants. These results indicate that these two viruses are widely distributed throughout cucurbit crops in Shanghai, China. All the geminiviruses sequences (approximately 510 bp) were quite similar to each other and were most similar (99.4%) to the Tomato leaf curl New Delhi virus (ToLCNDV) sequence (GenBank Accession No. OP356207) (Li et al. 2022). To confirm the presence of geminiviruses, the segments of DNA-A and DNA-B were amplified by PCR with 4 ToLCNDV-specific primer sets (Mizutani et al. 2011) and sequenced from 10 samples (4 melon, 4 cucumber and 2 luffa). Both DNA-A and DNA-B of the ToLCNDV sequences and features were deposited in GenBank under the accession numbers OQ190939-OQ190948 (DNA-A, 2739 nt) and OQ190949-OQ190958 (DNA-B, 2693 nt). BLASTn analysis of Shanghai isolates of ToLCNDV (DNA-A and DNA-B) showed that the sequences shared nucleotide identities ranged from 99.3% to 100% among them and with values of more than 99.4% nucleotide identity with ToLCNDV isolates from tomato in China (OP356207 and OP356208) (Li et al. 2022). To confirm the virus infection, we have successfully constructed an infectious clone for 0823-1 isolate in the binary plasmid and inoculated melon with and without an infectious clone. The melon plants inoculated with ToLCNDV 15 dpi showed the high accumulation of the virus and displayed symptoms similar to viruses in greenhouse. Based on the complete sequences, results of the molecular phylogenetic analysis (Fig. 2) and infectious clone, these geminiviruses were identified as ToLCNDV. ToLCNDV has been reported to occur and spread by the whitefly (Bemisia tabaci) in many Asian countries (Sohrab et al. 2003; Sohrab et al. 2011; Aamir et al. 2020) and Europe (Juárez et al. 2014; Ruiz et al. 2015; Luigi et al. 2019). Large populations of whiteflies were also present in all our surveyed areas. However, to our knowledge, this is the first report of the occurrence of ToLCNDV in cucurbit plants in China. The presence of ToLCNDV and CCYV can cause severe losses in crop yields or even crop failure. In addition to TYLCV, ToLCNDV is another major geminivirus-induced disease threatening cucurbit and other vegetable production in China.
RESUMO
The taxonomy of the extant dinoflagellate genus Gonyaulax is challenging since its thecate morphology is rather conservative. In contrast, cysts of Gonyaulax are varied in morphology and have been related with the fossil-based genera Spiniferites and Impagidinium. To better understand the systematics of Gonyaulax species, we performed germination experiments on cysts that can be identified as S. ristingensis, an unidentified Spiniferites with petaloid processes here described as Spiniferites pseudodelicatus sp. nov. and Impagidinium variaseptum from Chinese and Portuguese waters. Despite marked differences in cyst morphology, motile cells of S. pseudodelicatus and I. variaseptum are indistinguishable from Gonyaulax baltica. Motile cells hatched from S. ristingensis are morphologically similar to G. baltica as well but differ in the presence of one pronounced antapical spine. Three new species, Gonyaulax amoyensis (cyst equivalent S. pseudodelicatus), Gonyaulax bohaiensis (cyst equivalent I. variaseptum), and Gonyaulax portimonensis (cyst equivalent S. ristingensis), were erected. In addition, a new ribotype (B) of G. baltica was reported from South Korea and a bloom of G. baltica ribotype B is reported from New Zealand. Molecular phylogeny based on LSU and SSU rRNA gene sequences revealed that Gonyaulax species with minute or short antapical spines formed a well-resolved clade, whereas species with two pronounced antapical spines or lack of antapical spines formed the sister clade. Six strains of four above species were examined for yessotoxin production by liquid chromatography coupled with tandem mass spectrometry, and very low concentrations of yessotoxin were detected for one G. bohaiensis strain.
Assuntos
Dinoflagellida , Cromatografia Líquida , Dinoflagellida/genética , Filogenia , República da Coreia , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: We aimed to develop a less invasive inguinofemoral lymphadenectomy (IFL) approach for vulvar cancer based on the investigation of the anatomic distribution of sentinel and metastatic nodes. METHODS: Patients with vulvar cancer treated by surgery between 1995 and 2019 were retrospectively reviewed. A seven-field method was adopted to assign the anatomic locations for lymph nodes removed via IFL or sentinel node biopsy. Only patients with nodal metastasis or sentinel nodes were included. RESULTS: A total of 102 patients with eligible data were analyzed. Nodal metastasis was confirmed in 118 groins undergoing IFL; sentinel node detection succeeded in 46 groins. The medial-inguinal field had the highest rate of nodal metastasis involvement (59.3%, 70/118) and sentinel nodes present (73.9%, 34/46). The inferior-femoral field was involved only in one groin with quadruple-field metastases. The lateral-inguinal field was not involved in any groin. Neither the lateral-inguinal nor the inferior-femoral field presented sentinel nodes. CONCLUSION: The lateral-inguinal and inferior-femoral fields of the groins have a low risk of developing nodal metastasis. Therefore, a modified IFL preserving these fields can be established to reduce surgical morbidity without sacrificing its therapeutic effect.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Fêmur/cirurgia , Canal Inguinal/cirurgia , Excisão de Linfonodo/métodos , Linfonodo Sentinela/cirurgia , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/secundário , Feminino , Fêmur/patologia , Seguimentos , Humanos , Canal Inguinal/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Neoplasias Vulvares/patologia , Adulto JovemRESUMO
BACKGROUND: The management for patients with vulvar cancer after sentinel lymph-node biopsy (SLNB) remains controversial. The aim of this study was to investigate the long-term outcomes of individualized management after SLNB for early stage vulvar cancer. METHODS: The medical records of patients with vulvar cancer treated by surgery involving SLNB between 2004 and 2019 were retrospectively reviewed. During this period, the inguinofemoral lymphadenectomy (IL) were performed with individualized strategy, while the postoperative intensity-modulated radiotherapy was planned with a consistent policy. RESULTS: We identified 138 patients with at least one sentinel node detected, of whom 64 underwent further IL while 74 had SLNB only. Nodal metastases (pN+) were confirmed in 22 patients with IL and 16 without. Radiotherapy was scheduled with the dose of 60-70 Gy for all pN+ patients and finally completed in 15 with IL and 15 without. The median follow-up time was 56 months (6-156 months). Recurrence was observed in 24 patients, of whom 10 were pN- at primary treatment. The 3-year overall survival (OS) was 97.2, 95.2, 68.3, and 71.8%; 3-year disease-free survival (DFS) was 94.5, 91.4, 60.2, and 59.2%, respectively, for patients with pN- and IL, pN- and SLNB, pN+ and IL, and pN+ and SLNB. Neither OS nor DFS showed significant difference between SLNB and IL in pN- (P = 0.564 for OS, P = 0.423 for DFS), or pN + patients (P = 0.920 for OS, P = 0.862 for DFS). CONCLUSIONS: With appropriate adjuvant radiotherapy, SLNB alone provided similar long-term survival compared with IL for both patients with and without sentinel node metastasis.
Assuntos
Neoplasias Vulvares , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Vulvares/radioterapia , Neoplasias Vulvares/cirurgiaRESUMO
PURPOSE: To describe a non-anatomic arthroscopic all-inside repair technique for middle-aged and older patients with medial meniscus posterior root tears (MMPRTs) and to evaluate the short- to mid-term clinical and radiologic results. The hypothesis was that this procedure would yield good clinical outcome results and structural healing in middle- and older-aged patients. METHODS: This was a retrospective study evaluating patients who had undergone MMPRT repair by suturing the meniscal root directly to the capsule, rather than by the transtibial technique, between 2013 and 2016. This all-inside repair technique was performed for patients with type II MMPRTs who were over 40 years old. Exclusion criteria included tibial osteotomy due to malalignment, concomitant multiple-ligament injuries and follow-up time less than 2 years. The Lysholm score, Tegner activity score and International Knee Documentation Committee (IKDC) score were evaluated preoperatively and at the final follow-up. Medial meniscal extrusion, the International Cartilage Repair Society (ICRS) grades of the medial compartment, and the healing status of the medial meniscus root were assessed on magnetic resonance imaging preoperatively and at the final follow-up. RESULTS: Twenty-nine patients (mean age 61.7 ± 7.9) were included; the mean follow-up duration was 46.2 ± 7.9 months. The mean Lysholm score significantly improved from 33.7 ± 20.9 preoperatively to 81.7 ± 19.9 at the final follow-up (p < 0.001), the median Tegner activity score improved from 1.0 (range 1-4) to 3.0 (range 2-4, p < 0.001), and the mean IKDC score improved from 20.1 ± 16.4 to 69.6 ± 16.2 (p < 0.001). On MRI, 9 (31%) cases had complete healing; 17 (59%) had partial healing; and 3 (10%) had failed healing (ICCs ≥ 0.92). Mean meniscal extrusion significantly increased from 2.3 ± 1.7 mm preoperatively to 3.5 ± 1.5 mm postoperatively (p < 0.001, ICCs ≥ 0.92). CONCLUSION: Non-anatomic arthroscopic all-inside repair of MMPRTs to the posterior capsule yielded good to excellent clinical results and a high rate of healing in the medial meniscus root on MRI in middle-aged and older patients at short- to mid-term follow-up, despite increased meniscal extrusion. This method is an alternative to the transtibial pullout repair technique for treating MMPRTs in middle- and older-aged patients. LEVEL OF EVIDENCE: Level IV.
Assuntos
Meniscos Tibiais , Lesões do Menisco Tibial , Adulto , Idoso , Artroscopia , Humanos , Articulação do Joelho , Imageamento por Ressonância Magnética , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/cirurgiaRESUMO
Animal-mediated indirect interactions play a significant role in maintaining the biodiversity of plant communities. Less known is whether interspecific synchrony of seed rain can alter the indirect interactions of sympatric tree species. We assessed the seed dispersal success by tracking the fates of 21 600 tagged seeds from six paired sympatric tree species in both monospecific and mixed plots across 4 successive years in a subtropical forest. We found that apparent mutualism was associated with the interspecific synchrony of seed rain both seasonally and yearly, whereas apparent competition or apparent predation was associated with interspecific asynchrony of seed rain either seasonally or yearly. We did not find consistent associations of indirect interactions with seed traits. Our study suggests that the interspecific synchrony of seed rain plays a key role in the formation of animal-mediated indirect interactions, which, in turn, may alter the seasonal or yearly seed rain schedules of sympatric tree species.
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Dispersão de Sementes , Árvores , Animais , Comportamento Alimentar , Florestas , Roedores , SementesRESUMO
OBJECTIVES: To determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to July 30, 2019, for studies concerning SLNB with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator for evaluation. RESULTS: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0.77 (95% CI 0.66-0.85) with high heterogeneity (I2 = 69.73%). Two representative sectioning protocols for FSE were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected) and latitudinal (L-protocol, SLN was cut at intervals). Meta-regression showed that FSE protocol was the only source of heterogeneity (p < 0.001). The pooled sensitivity was 0.86 (95% CI 0.79-0.91, I2 = 0%) and 0.59 (0.46-0.72, I2 = 58.47%) for FSE using L- (13 studies, 650 patients) and E- (13 studies, 1047 patients) protocol, respectively. Among the available data, marcometastases (>2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0.97 (95% CI 0.89-0.99) if only marcometastases were considered. These findings were robust to sensitivity analyses. CONCLUSION: The sectioning protocol determines the accuracy of FSE in SLNB. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements.
Assuntos
Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Neoplasias do Colo do Útero/patologia , Feminino , Secções Congeladas/métodos , Humanos , Período Intraoperatório , Metástase Linfática , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Sentinel lymph node (SLN) biopsy is an attractive technique that is widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. METHODS: Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered successful. Patients' clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. RESULTS: Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in the obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion, and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed a significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P < 0.001) and lymph node metastasis (40.9% versus 3.8%, P < 0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also have a high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected. CONCLUSIONS: In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection. The risk of having undetected metastasis is high when SLN is positive; therefore, further lymphadenectomy may be necessary for these patients.
Assuntos
Excisão de Linfonodo/métodos , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Estudos Prospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
Oligodendrocytes (OLs) are the myelinating glia of the central nervous system. Injury to OLs causes myelin loss. In demyelinating diseases, such as multiple sclerosis, the remyelination is hindered principally due to a failure of the oligodendrocyte precursor cells (OPCs) to differentiate into mature OLs. To identify inducers of OPC to OL differentiation, a high-throughput screening based on myelin basic protein expression using neural progenitor cells-derived OPCs has been performed and, PD0325901-an MEK (MAPK kinase) inhibitor-is found to significantly enhance OPC to OL differentiation in a dose- and time-dependent manner. Other MEK inhibitors also display similar effect, indicating blockade of MAPK-ERK signaling is sufficient to induce OPC differentiation into OLs. PD0325901 facilitates the formation of myelin sheaths in OPC-neuron co-culture in vitro. And in experimental autoimmune encephalomyelitis model and cuprizone-induced demyelination model, PD0325901 displays significant therapeutic effect by promoting myelin regeneration. Our results suggest that targeting the MAPK-ERK pathway might be an intriguing way to develop new therapies for demyelinating diseases.
Assuntos
Doenças Desmielinizantes/enzimologia , Encefalomielite Autoimune Experimental/enzimologia , Sistema de Sinalização das MAP Quinases/fisiologia , Oligodendroglia/enzimologia , Recuperação de Função Fisiológica/fisiologia , Remielinização/fisiologia , Animais , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Técnicas de Cocultura , Cuprizona/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Oligodendroglia/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Remielinização/efeitos dos fármacosRESUMO
BACKGROUND: The strategy of radical surgery for stage 2 endometrial cancer (EC) remains controversial. This meta-analysis aimed to investigate the impact of radical hysterectomy (RH) versus simple hysterectomy (SH) on survival of patients with stage 2 EC. METHODS: A systematic review was conducted to identify studies comparing survival between RH and SH in International Federation of Gynecology and Obstetrics (FIGO) stage 2 EC patients by searching several databases to July 2018. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival and progression-free survival were pooled using Stata V.12.0. RESULTS: The study included 10 retrospective cohort studies enrolling 2866 patients. Patients who received RH did not show a significant survival benefit for either overall survival (pooled HR 0.92; 95% CI 0.72-1.16; P = 0.484) or progression-free survival (pooled HR 0.75; 95% CI 0.39-1.42; P = 0.378). The result remained consistent after it was balanced with possible impact from adjuvant radiotherapy (pooled HR 0.85; 95% CI 0.62-1.16; P = 0.300). In earlier studies that staged patients according to FIGO 1988, RH showed a 27% survival benefit (pooled HR 0.73; 95% CI 0.53-1.00; P = 0.050), whereas in newly published studies based on FIGO 2009 staging, it reversely showed increased risk of death (pooled HR 1.24; 95% CI 0.86-1.77; P = 0.245). However, no statistical significance was reached under either staging criterion. CONCLUSIONS: Based on the results of this meta-analysis, RH does not significantly improve survival in stage 2 EC. The choice of RH remains controversial and should be considered carefully in clinical practice. More qualified studies are needed to determine the best treatment strategy for stage 2 EC.
Assuntos
Neoplasias do Endométrio/mortalidade , Histerectomia/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/classificação , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Revisões Sistemáticas como AssuntoRESUMO
See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52.
Assuntos
Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Mutação/genética , Receptores Acoplados a Proteínas G/deficiência , Fatores Etários , Animais , Benzamidas/uso terapêutico , Corpo Estriado/metabolismo , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Comportamento Exploratório/fisiologia , Marcha/fisiologia , Células HEK293 , Humanos , Doença de Huntington/tratamento farmacológico , Doença de Huntington/fisiopatologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Camundongos Transgênicos , Neurônios/patologia , Fenótipo , Quinoxalinas/uso terapêutico , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Tiofenos/uso terapêutico , Caminhada/fisiologiaRESUMO
PURPOSE: The purpose of this study was to introduce a modified arthroscopic treatment technique for popliteal cyst and hypothesize that this modified technique would provide good clinical efficacy and low recurrence rate. METHODS: From January 2013 to January 2017, 34 patients with symptomatic popliteal cysts were treated with our technique. A figure-of-four position and double posteromedial portals were used to achieve adequate enlargement of the posteromedial valvular opening between the cyst and the joint cavity and complete excision of the cyst wall. MRI was used to detect the recurrence of the popliteal cyst, and the Rauschning and Lindgren score was recorded to evaluate the clinical outcome. RESULTS: All patients were followed up with a mean period of 14.8 months (range, 12 to 36 months). Associated intra-articular lesions were found and treated in all cases. Degenerative cartilage damage was the most common pathology, which affected 23 (67.6%) of the cases. The Rauschning and Lindgren score improved significantly after surgery, and no evidence of recurrence was found from MRI in any case. CONCLUSIONS: Our modified arthroscopic treatment technique, using a figure-of-four position and double posteromedial portals, is effective and safe for treating popliteal cyst.
Assuntos
Cisto Popliteal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroscopia/métodos , Criança , Feminino , Nível de Saúde , Humanos , Hipertrofia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Cisto Popliteal/diagnóstico por imagem , Resultado do Tratamento , Adulto JovemRESUMO
The genus Gymnodinium includes many morphologically similar species, but molecular phylogenies show that it is polyphyletic. Eight strains of Gymnodinium impudicum, Gymnodinium dorsalisulcum and a novel Gymnodinium-like species from Chinese and Malaysian waters and the Mediterranean Sea were established. All of these strains were examined with light microscopy, scanning electron microscopy and transmission electron microscopy. SSU, LSU and internal transcribed spacers rDNA sequences were obtained. A new genus, Wangodinium, was erected to incorporate strains with a loop-shaped apical structure complex (ASC) comprising two rows of amphiesmal vesicles, here referred to as a new type of ASC. The chloroplasts of Wangodinium sinense are enveloped by two membranes. Pigment analysis shows that peridinin is the main accessory pigment in W. sinense. Wangodinium differs from other genera mainly in its unique ASC, and additionally differs from Gymnodinium in the absence of nuclear chambers, and from Lepidodinium in the absence of Chl b and nuclear chambers. New morphological information was provided for G. dorsalisulcum and G. impudicum, e.g., a short sulcal intrusion in G. dorsalisulcum; nuclear chambers in G. impudicum and G. dorsalisulcum; and a chloroplast enveloped by two membranes in G. impudicum. Molecular phylogeny was inferred using maximum likelihood and Bayesian inference with independent SSU and LSU rDNA sequences. Our results support the classification of Wangodinium within the Gymnodiniales sensu stricto clade and it is close to Lepidodinium. Our results also support the close relationship among G. dorsalisulcum, G. impudicum, and Barrufeta. Further research is needed to assign these Gymnodinium species to Barrufeta or to erect new genera.
Assuntos
Dinoflagellida/citologia , Dinoflagellida/genética , Filogenia , China , Cloroplastos/ultraestrutura , DNA de Algas/análise , DNA de Protozoário/análise , DNA Ribossômico/análise , Dinoflagellida/classificação , Dinoflagellida/ultraestrutura , França , Malásia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de TransmissãoRESUMO
We investigate the cyst-theca relationship of Impagidinium caspienense. Through an incubation experiment, we succeeded in examining the motile stage. Additional molecular analysis of single-cyst PCR (LSU and SSU rDNA) reveal that the cyst is related to the species Gonyaulax baltica Ellegaard et al. (). The ability of this species to belong to two types of cyst-based genera (spiniferate and impagidinioid) suggests that environmental (particularly salinity) and not genetic factors explain the formation of both morphotypes by G. baltica, which provides evidence for heterospory in this species. The affiliation to G. baltica demonstrates that I. caspienense is not endemic to the Caspian Sea. The phylogenetic position of several other gonyaulacoid species is also documented: Impagidinium pallidum, Ataxiodinium choane, Pyxidinopsis psilata, Spiniferites belerius, and Spiniferites ramosus. The LSU and SSU rDNA based phylogenies suggest that the genera Impagidinium and Spiniferites are not monophyletic, and that P. psilata and A. choane are close to Gonyaulax verior and Gonyaulax polygramma, respectively. In addition, this study accentuates the importance of cyst morphology in the classification of the Gonyaulacales.
Assuntos
Dinoflagellida/classificação , Dinoflagellida/isolamento & purificação , Sedimentos Geológicos/parasitologia , Análise por Conglomerados , DNA de Protozoário/química , DNA de Protozoário/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dinoflagellida/genética , Dinoflagellida/fisiologia , Locomoção , Microscopia , Oceanos e Mares , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico/genética , RNA Ribossômico 18S/genética , Análise de Sequência de DNARESUMO
The resting cysts of the benthic dinoflagellate Prorocentrum leve from a natural reservoir in Gujan-Mestras (Gironde, France) were described in this study. The incubated urn-shaped cysts gave rise to cells of P. leve. Morphological observations through light microscopy and scanning electron microscopy, particularly of the periflagellar platelets, combined with large subunit ribosomal DNA sequences obtained through single-cell analysis confirm their affinity to the species P. leve. The cysts were characterized by a specific shape and the presence of an anterior plug. This is the first conclusive evidence for fossilizable resting stages within the Prorocentrales, one of the major orders within the Dinophyceae. Palynological treatments show that the cysts and endospores withstand hydrochloric and hydrofluoric acids. Micro-Fourier transform infrared analysis on single specimens suggests that the composition of the endospore is cellulosic and the cyst wall a more robust, noncellulosic ß-glucan. The spectra overall are similar to other published spectra of resting cysts from autotrophic, planktonic dinoflagellates.