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1.
Sci Rep ; 11(1): 19493, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593910

RESUMO

Increasing evidence has indicated that senescent cells are associated with the glioma development. Thus, we aimed to explore the relationship between the cellular senescence gene profile and the clinical prognosis of diffuse glioma. In total, 699 gliomas from The Cancer Genome Atlas (TCGA) dataset were used as the training cohort and 693 gliomas from the Chinese Glioma Genome Atlas (CGGA) dataset were used as the validation cohort. Bioinformatics statistical methods are used to develop the risk signature and to study the prognostic value of the risk signature. We identified a 14-gene risk signature and its risk score was an independent prognostic factor (P < 0.001) in the validation dataset. The risk signature had better prognostic value than traditional factors for the 3- and 5-year survival rate. Importantly, the risk signature could further stratify gliomas in specific subgroups of World Health Organization (WHO) classification by the survival rate. Furthermore, the mRNA levels of genes involved in the cell cycle, cell division and other processes were significantly correlated with the risk score. Our study highlighted a 14-gene risk signature for further stratifying the outcomes of patients with gliomas with definite WHO subgroups. These results indicate the potential clinical implications of cell aging-related genes in gliomas.

2.
J Chem Theory Comput ; 17(10): 6483-6490, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34516136

RESUMO

SARS-CoV-2 that caused COVID-19 has spread since the end of 2019. Its major effects resulted in over four million deaths around the whole world by August 2021. Therefore, understanding virulence mechanisms is important to prevent future outbreaks and for COVID-19 drug development. The envelope (E) protein is an important structural protein, affecting virus assembly and budding. The E protein pentamer is a viroporin, serving as an ion transferring channel in cells. In this work, we applied molecular dynamic simulations and topological and electrostatic analyses to study the effects of palmitoylation on the E protein pentamer. The results indicate that the cation transferring direction is more from the lumen to the cytosol. The structure of the palmitoylated E protein pentamer is more stable while the loss of palmitoylation caused the pore radius to reduce and even collapse. The electrostatic forces on the two sides of the palmitoylated E protein pentamer are more beneficial to attract cations in the lumen and to release cations into the cytosol. The results indicate the importance of palmitoylation, which can help the drug design for the treatment of COVID-19.


Assuntos
Proteínas do Envelope de Coronavírus/química , Lipoilação , Antivirais/química , Antivirais/farmacologia , Cátions/química , Biologia Computacional , Citosol/química , Desenho de Fármacos , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , Análise de Componente Principal , Prótons , Eletricidade Estática
3.
Biosci Trends ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588390

RESUMO

Both cytomegalovirus (CMV) viremia and disseminated nontuberculous mycobacterial (NTM) disease are common opportunistic infections in AIDS patients. Whether concurrent CMV viremia is associated with mortality in patients with AIDS and disseminated NTM disease is unknown. Subjects were patients with AIDS and disseminated NTM disease seen at a single center from January 2015 to April 2021. Data were retrospectively collected. Differences in demographics and clinical characteristics and hospitalization survival rates were compared between patients with disseminated NTM and with CMV viremia or not. Subjects were 113 AIDS patients with disseminated NTM who were seen at this Hospital from January 2015 to April 2021. Twenty-six of the patients had CMV viremia and 87 did not. The median age was 36 years (interquartile range [IQR] 29-42) and 108 patients were male (96%). The median CD4 count was 7 cells/µL (IQR 3-17). The median plasma CMV viral load was 9,245 IU/mL (IQR 3147-45725). The serum albumin of patients with CMV viremia was significantly lower than that of patients without CMV viremia (P = 0.03). Compared to patients without CMV viremia (81.6%), patients with CMV viremia had a significantly poorer prognosis (P = 0.01). Cox regression analysis indicated that the risk of a poor prognosis in patients with CMV viremia was 4.7 times higher than that in patients without CMV viremia (P = 0.003), and patients with CD8 more than 250/µL had a better prognosis (P = 0.02). CMV viremia increases the risk of a poor prognosis in patients with AIDS and a disseminated NTM infection. A routine CMV DNA test should be performed on patients with AIDS and disseminated NTM disease in order to reduce the risk of death.

4.
Drug Discov Ther ; 15(4): 225-226, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34334555

RESUMO

Combined antiretroviral therapy (cART) has significantly reduced human immunodeficiency virus (HIV) associated morbidity and mortality and turned HIV infection into a manageable chronic condition. However, lifelong cART is still required. Two-drug regimens could reduce the number of HIV agents and lower the adverse events caused by lifelong medication. A new two-drug regimen, DEVATO, consisting of dolutegravir and lamivudine has durable efficacy, is well-tolerated, and has a high barrier to viral resistance, which is why it is recommended as a new first-line treatment option for people living with HIV infection.

5.
Proc Natl Acad Sci U S A ; 118(28)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34260376

RESUMO

A significant unmet need for new contraceptive options for both women and men remains due to side-effect profiles, medical concerns, and the inconvenience of many currently available contraceptive products. Unfortunately, the development of novel nonsteroidal female contraceptive medicine has been stalled in the last couple of decades due to the lack of effective screening platforms. Drosophila utilizes conserved signaling pathways for follicle rupture, a final step in ovulation that is essential for female reproduction. Therefore, we explored the potential to use Drosophila as a model to screen compounds that could inhibit follicle rupture and be nonsteroidal contraceptive candidates. Using our ex vivo follicle rupture assay, we screened 1,172 Food and Drug Administration (FDA)-approved drugs and identified six drugs that could inhibit Drosophila follicle rupture in a dose-dependent manner. In addition, we characterized the molecular actions of these drugs in the inhibition of adrenergic signaling and follicle rupture. Furthermore, we validated that three of the four drugs consistently inhibited mouse follicle rupture in vitro and that two of them did not affect progesterone production. Finally, we showed that chlorpromazine, one of the candidate drugs, can significantly inhibit mouse follicle rupture in vivo. Our work suggests that Drosophila ovulation is a valuable platform for identifying lead compounds for nonsteroidal contraceptive development and highlights the potential of these FDA-approved drugs as novel nonsteroidal contraceptive agents.

6.
Cells ; 10(7)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209120

RESUMO

As a major effector of the ESX-1 secretion system, EsxA is essential for the virulence of pathogenic mycobacteria, such as Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). EsxA possesses an acidic pH-dependent membrane permeabilizing activity and plays an essential role by mediating mycobacterial escape from the phagosome and translocation to the cytosol for intracellular replication. Moreover, EsxA regulates host immune responses as a potent T-cell antigen and a strong immunoregulator. EsxA interacts with multiple cellular proteins and stimulates several signal pathways, such as necrosis, apoptosis, autophagy, and antigen presentation. Interestingly, there is a co-dependency in the expression and secretion of EsxA and other mycobacterial factors, which greatly increases the complexity of dissecting the precise roles of EsxA and other factors in mycobacterium-host interaction. In this review, we summarize the current understandings of the roles and functions of EsxA in mycobacterial infection and discuss the challenges and future directions.

7.
J Infect Chemother ; 27(10): 1459-1464, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34158238

RESUMO

Introduction Lymphoma is the most common cancer in HIV/AIDS patients. Chemotherapy regiments recommended for lymphomas in HIV-negative patients are also used for lymphomas in HIV/AIDS patients. Little is known about the infections among HIV/AIDS patients with lymphoma undergoing chemotherapy. Methods This retrospective study investigated the incidence, spectrum of and risk factors for infections during chemotherapy in 164 HIV/AIDS patients with lymphoma admitted to Shanghai Public Health Clinical Center from July 2013 to December 2020. Results The median age of the patients was 43 years old; 90.9% (149/164) were male. A total of 112 (68.3%) patients had a CD4 count < 200 cells/µL at lymphoma diagnosis. Diffuse large B-cell lymphoma (56%, 91/164) and Burkitt lymphoma (28%, 46/164) were the two most common subtypes of lymphoma. Among the 137 patients who underwent chemotherapy (total cycles = 749), 58.4% (80/137) of patients experienced a total of 153 episodes of infection, with an incidence rate of 20.4% (153/749). The most commonly seen infections were lung infection (29.2%, 40/137) and febrile neutropenia (27.0%, 37/137). Multivariate analysis showed that grade 4 neutropenia during chemotherapy (OR = 7.128, 95% CI 3.051-16.654, p < 0.001) and duration of antiretroviral treatment at lymphoma diagnosis <6 months (OR = 3.520, 95% CI 1.432-8.653, p = 0.006) were independent risk factors for infection during chemotherapy. Conclusions A large proportion of HIV/AIDS patients with lymphoma may be at risk of infection during chemotherapy. Effective measures should be taken for patients with high risk factors to prevent the occurrence of infection.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Linfoma Relacionado a AIDS , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , China/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Incidência , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/epidemiologia , Masculino , Estudos Retrospectivos
8.
BMC Infect Dis ; 21(1): 514, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074256

RESUMO

BACKGROUND: Talaromyces marneffei (TM) bloodstream infection is common in Acquired Immunodeficiency Syndrome (AIDS) patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyzed the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determined the outcomes of hospitalization after diagnosis in our hospital over the past 5 years. METHODS: From January 2015 to July 2020, 87 cases of TM detected by blood culture in patients admitted to our center were collected. The admission complaints, blood cells, biochemistry, CD4 and CD8 cell counts and 1,3-ß-D-glucan (BDG), procalcitonin (PCT), CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis (60 cases). Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM turnaround in blood culture. The difference was statistically significant when the P value was < 0.05. RESULTS: A total of 87 patients were collected, with a median age of 34 years, a median hemoglobin of 94 g/L and CD4 count of 7/µl. The rate of TM bloodstream infection among all in-hospital patients increased from 0.99% in 2015 to 2.09% in 2020(half year). Patients with TM bloodstream infection with CD8 count < 200/µl had a 12.6-fold higher risk of poor prognosis than those with CD8 count > 200/µl (p = 0.04), and those with BDG < 100 pg/mL had a 34.9-fold higher risk of poor prognosis than those with BDG > 100 pg/mL (p = 0.01). CONCLUSIONS: TM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/µl is with an increased risk of poor prognosis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fungemia/epidemiologia , Micoses/epidemiologia , Talaromyces/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , China/epidemiologia , Feminino , Fungemia/diagnóstico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
Neurosurg Rev ; 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33988802

RESUMO

Multiple factors, such as tumor size, lateralization, tumor location, accompanying syringomyelia, and regional spinal cord atrophy, may affect the resectability and clinical prognosis of intramedullary spinal cord ependymomas. However, whether long-segmental involvement of the spinal cord may impair functional outcomes remains unclear. This study was aimed to compare perioperative neurological functions and long-term surgical outcomes between multisegmental ependymomas and their monosegmental counterparts. A total of 62 patients with intramedullary spinal cord ependymoma (WHO grade II) were enrolled, and all of them underwent surgical resection. The patients were classified into the multisegmental group (n = 43) and the monosegmental group (n = 19). Perioperative and long-term (average follow-up period, 47.3 ± 21.4 months) neurological functions were evaluated using the modified McCormick (mMC) scale and the modified Japanese Orthopaedic Association (mJOA) scoring system. Preoperative neurological functions in the multisegmental group were significantly worse than those in the monosegmental group (P < 0.05). However, postoperative short-term neurological functions, as well as long-term functional outcomes, were similar between the two groups (P > 0.05). Logistic regression analysis showed that preoperative mMC and mJOA scores were significantly correlated with neurological improvement during the follow-up period (P < 0.05). Multisegmental involvement of the spinal cord is associated with worse neurological functions in patients with intramedullary spinal cord ependymoma, while the long-term prognosis is not affected. The preoperative neurological status of the patient is the only predictor of long-term functional improvement.

10.
Anal Chim Acta ; 1164: 338521, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992217

RESUMO

Conventional UV/Vis absorption spectroscopy is an economical and user-friendly technique for online monitoring, however, by which some electroactive chemicals are hardly determined in the presence of fluctuating background due to the formation of colored chemicals. Here, we propose an electrochemical difference absorption spectroscopy (EDAS) to accurately quantify colorless chemicals based on visible color change via electrolysis with strong variation in the background. EDAS is realized by twin spectroelectrochemical flow cells system, replacing the two cuvette cells of a dual beam spectrophotometer. Each cell consists of a three-electrode system, quartz windows and a thin flow channel. Flowing of analyte from one cell (reference cell) to the other (sample cell) can eliminate the influence of colored interferents even while their concentrations are changing. When different potentials are applied on the sample and reference cells respectively, electrolysis occurs and colored products flowing through quartz windows can absorb the incident light, resulting in difference absorption spectra induced from potential difference. We find that steady-state difference absorbance (ΔA) at characteristic wavelength is linearly changed with sample concentrations. EDAS is firstly verified by Fe(CN)64- at different potentials and flow rates, in good agreements with a simplified theory that describes linear relationship between ΔA and analyte concentration. Then EDAS is used to determine Cu(I) in Cu(I)-Cu(II) mixed solutions and tetramethylbenzidine in its partially oxidized solutions to illustrate the powerful ability to detect colorless chemicals with varied background, implying its promising potential applications in the chemical industry.

11.
Anal Chem ; 93(22): 7843-7850, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029050

RESUMO

Frequently calibrating electrochemical biosensors (ECBs) to obtain acceptable accuracy can be cumbersome for the users. Thus, the achievement of calibration-free operation would effectively lead to commercial applications for ECBs in the real world. Herein, we fabricated a temperature-alternated electrochemical aptamer-based (TAEAB) sensor, producing a cycle of "enhanced-responsive and ∼nonresponsive" state at rapidly alternated interface temperatures (5 and 30 °C, respectively). The ratio of peak currents collected at two temperatures overcomes sensor-to-sensor fabrication variations, obviating sensor calibration prior to use due to its good reproducibility. We then demonstrated the capability of TAEAB sensors for improved, sensitive, and calibration-free measurement of different targets within 7 min, which respectively achieved a detection limit of 0.5 µM procaine in undiluted urine and 1.0 µM adenosine triphosphate in undiluted serum. This generalizable approach ameliorates sensitivity without the complicated amplification step, thus simplifying the operation procedure and reducing the detection time, which will effectively improve the clinical utility of biosensors.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Calibragem , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Temperatura
12.
Int J Infect Dis ; 107: 139-144, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33892189

RESUMO

OBJECTIVES: To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system (CNS) infection in people living with human immunodeficiency virus (PLWH) in a real-world situation. METHODS: Cerebrospinal fluid (CSF) was sent for mNGS for PLWH who tested negative on all conventional tests but were still suspected to have CNS infection. A retrospective analysis was undertaken of the results and the clinical effect of mNGS on this cohort. The final diagnosis was adjudicated by a panel discussion following hospital discharge when the results of all tests and patients' responses to the empiric therapy were available. RESULTS: Eighty-eight eligible PLWH, including 51 (58%) patients suspected of encephalitis and 34 (46.7%) patients suspected of meningitis, were included in the analysis. Sixty-eight (77.3%) patients were diagnosed with CNS infection, of which 50 were based on the pathogens identified by mNGS. The most common disease missed by mNGS was clinically suspected tuberculous meningitis, followed by clinically suspected non-tuberculous mycobacterial meningitis. The results from mNGS led to modification of treatment in 21 (23.9%) patients, and increased confidence in continuation of original therapy in 30 (34.1%) patients. During hospitalization, two (2.3%) patients died and 66 (75%) patients improved. CONCLUSIONS: mNGS of CSF is a useful tool for the diagnosis of CNS infection among PLWH. Further investigations are warranted to improve its sensitivity.


Assuntos
Infecções do Sistema Nervoso Central/complicações , Infecções do Sistema Nervoso Central/diagnóstico , Infecções por HIV/complicações , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Cell Biol Int ; 45(8): 1654-1665, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33760331

RESUMO

TET1 mediates demethylation in tumors, but its role in diabetic nephropathy (DN), a prevalent diabetic complication, is unclear. We attempted to probe the possible mechanism of TET1 in DN. A DN rat model was established and verified by marker detection and histopathological observation. The in vitro model was established on human mesangial cells (HMCs) induced by high glucose (HG), and verified by evaluation of fibrosis and inflammation. The differentially expressed mRNA was screened out by microarray analysis. The most differentially expressed mRNA (TET1) was reduced in DN rats and HG-HMCs. The upstream and downstream factors of TET1 were verified, and their roles in DN were analyzed by gain- and loss-function assays. TET1 was decreased in DN rats and HG-HMCs. High expression of TET1 decreased biochemical indexes and renal injury of DN rats and hampered the activity, fibrosis, and inflammation of HG-HMCs. Ap1 lowered TET1 expression, and enhanced inflammation in HG-HMCs, and accentuated renal injury in DN rats. TET1 overexpression inhibited the effect of Ap1 on DN. TET1 promoted the transcription of Nrf2. The Ap1/TET1 axis mediated the Nrf2/ARE pathway activity. Overall, TET1 overexpression weakened the inhibitory effect of Ap1 on the Nrf2/ARE pathway, thus alleviating inflammation and renal injury in DN.

14.
Int J Hematol ; 113(6): 903-909, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33594656

RESUMO

We investigated the clinical characteristics and outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma (AIDS-BL). A single-center retrospective study was performed of 78 cases over a 10-year period. The baseline characteristics of enrolled patients included the following: median age, 46 years; median CD4+ T lymphocyte count, 156 cells/µL; advanced stage, 74.3%; > 1 extranodal site, 55.1%; international prognostic index (IPI) > 1, 85.9%; and elevated serum lactate dehydrogenase, 82.1%. The 1-year and 2-year overall survival (OS) rates were 52.2 ± 5.9% and 42.7 ± 6.2%, respectively. A prognostic analysis of 65 patients who had undergone chemotherapy showed that B symptoms (with vs. without fever, night sweat or weight loss), number of extranodal sites (0, 1 vs. > 1), level of serum albumin (≥ 35 g/L vs. < 35 g/L), hemoglobin (≥ 110 g/L vs. < 110 g/L), and IPI score (≤ 2 vs. > 1) were all associated with OS. However, only B symptoms (HR = 4.036, 95% CI 1.821-8.948, p = 0.001), serum albumin level < 35 g/L (HR = 2.131, 95% CI 1.013-4.483, p = 0.046), and chemotherapy without rituximab (HR = 2.286, 95% CI 1.108-4.714, p = 0.025) were independent predictors of OS after multivariate adjustment. Patients with AIDS-BL were likely to present with high-risk features, and their clinical outcomes were relatively poor, especially those with B symptoms and lower serum albumin levels.


Assuntos
Síndrome de Imunodeficiência Adquirida , Linfoma de Burkitt , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/mortalidade , Adulto , Idoso , Linfoma de Burkitt/sangue , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/etiologia , Linfoma de Burkitt/mortalidade , Contagem de Linfócito CD4 , Intervalo Livre de Doença , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana/metabolismo , Taxa de Sobrevida
15.
Med Hypotheses ; 149: 110540, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33618246

RESUMO

Hypoparathyroidism is one of the most common postoperative complications of thyroid surgery, and organoid transplantation is a frontier field expected to treat hypoparathyroidism. Organoids are three-dimensional cell aggregates derived from embryonic stem cells, pluripotent stem cells, or tissue precursor cells, possessing similar structures and functions to organs. Thus they can replace diseased organs to play a role. Adipose-derived stem cells (ASCs) are a population of postnatal stem cells residing in the fat tissue, capable of differentiating into parathyroid-like cells with parathyroid hormone secretion function. Additionally, we have prepared cartilaginous organoids by intelligent porous hydrogel and differentiated ASCs via "bottom-up" strategy in vitro. Therefore, we speculate that parathyroid organoids can be achieved by the biomaterial-assisted assembly of differentiated adipose stem cells and it is a promising treatment for hypoparathyroidism.


Assuntos
Hipoparatireoidismo , Células-Tronco Pluripotentes , Adipócitos , Tecido Adiposo , Humanos , Hipoparatireoidismo/terapia , Organoides
17.
J Neurosci ; 41(2): 307-319, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33203745

RESUMO

There has been considerable research showing populations of neurons encoding for different aspects of space in the brain. Recently, several studies using two-photon calcium imaging and virtual navigation have identified "spatially" modulated neurons in the posterior cortex. We enquire here whether the presence of such spatial representations may be a cortex-wide phenomenon and, if so, whether these representations can be organized in the absence of the hippocampus. To this end, we imaged the dorsal cortex of mice running on a treadmill populated with tactile cues. A high percentage (40-80%) of the detected neurons exhibited sparse, spatially localized activity, with activity fields uniformly localized over the track. The development of this location specificity was impaired by hippocampal damage. Thus, there is a substantial population of neurons distributed widely over the cortex that collectively form a continuous representation of the explored environment, and hippocampal outflow is necessary to organize this phenomenon.SIGNIFICANCE STATEMENT Increasing evidence points to the role of the neocortex in encoding spatial information. Whether this feature is linked to hippocampal functions is largely unknown. Here, we systematically surveyed multiple regions in the dorsal cortex of the same animal for the presence of signals encoding for spatial position. We described populations of cortical neurons expressing sequential patterns of activity localized in space in primary, secondary, and associational areas. Furthermore, we showed that the formation of these spatial representations was impacted by hippocampal lesion. Our results indicate that hippocampal inputs are necessary to maintain a precise cortical representation of space.


Assuntos
Hipocampo/fisiologia , Neocórtex/fisiologia , Percepção Espacial/fisiologia , Algoritmos , Animais , Sinais (Psicologia) , Hipocampo/citologia , Camundongos , Camundongos Transgênicos , Neocórtex/citologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Desempenho Psicomotor/fisiologia , Tato
19.
Virulence ; 12(1): 312-328, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33356823

RESUMO

Current genetic studies (e.g. gene knockout) have suggested that EsxA and EsxB function as secreted virulence factors that are essential for Mycobaterium tuberculosis (Mtb) intracellular survival, specifically in mediating phagosome rupture and translocation of Mtb to the cytosol of host cells, which further facilitates Mtb intracellular replicating and cell-to-cell spreading. The EsxA-mediated intracellular survival is presumably achieved by its pH-dependent membrane-permeabilizing activity (MPA). However, the data from other studies have generated a discrepancy regarding the role of EsxA MPA in mycobacterial intracellular survival, which has raised a concern that genetic manipulations, such as deletion of esxB-esxA operon or RD-1 locus, may affect other codependently secreted factors that could be also directly involved cytosolic translocation, or stimulate extended disturbance on other genes' expression. To avoid the drawbacks of gene knockout, we first engineered a Mycobacterium marinum (Mm) strain, in which a DAS4+ tag was fused to the C-terminus of EsxB to allow inducible knockdown of EsxB (also EsxA) at the post-translational level. We also engineered an Mm strain by fusing a SpyTag (ST) to the C-terminus of EsxA, which allowed inhibition of EsxA-ST MPA at the post-secretional level through a covalent linkage to SpyCatcher-GFP. Both post-translational knockdown and functional inhibition of EsxA resulted in attenuation of Mm intracellular survival in lung epithelial cells or macrophages, which unambiguously confirms the direct role of EsxA MPA in mycobacterial intracellular survival.


Assuntos
Proteínas de Bactérias/genética , Permeabilidade da Membrana Celular , Macrófagos/microbiologia , Mycobacterium marinum/genética , Processamento de Proteína Pós-Traducional/genética , Fatores de Virulência/genética , Células A549 , Células Epiteliais/microbiologia , Humanos , Pulmão/citologia , Células THP-1 , Virulência
20.
J Clin Pharm Ther ; 46(3): 688-697, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33325109

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Subcutaneous administration of low-molecular-weight heparin (LMWH) may cause complications such as haematoma, bruising and pain at different injection sites. Several studies have been carried out to investigate whether bruising and pain depend on injection sites; however, the results have been conflicting, and a clear consistent conclusion has not been reached. The purpose of this systematic review and meta-analysis was to assess the incidence and severity of bruising and pain after subcutaneous injection of LMWH in different sites. METHODS: Two reviewers independently searched the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI) databases for randomized controlled and self-controlled trials reporting side-effects from LMWH with different subcutaneous injection sites. Cochrane bias risk assessment tools and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the randomized controlled and self-controlled trials, respectively. Rev Man 5.3 software was used to analyse the data that were extracted after quality assessment to determine the incidence and severity of side-effects at different subcutaneous injection sites. RESULTS AND DISCUSSION: A total of eleven studies were included in this analysis. The meta-analysis provided evidence that subcutaneous injection in the abdominal area had a lower incidence of bruising than that in the arm area (risk ratios: 0.76; 95% confidence interval: 0.64-0.90; I2  = 52%, p < .05), but the difference in the bruising size between the two injection sites was marginally significant (standardized mean difference: 0.08; 95% confidence interval: -0.45 to 0.62; I2  = 85%, p > .05). There was also no significant difference in the bruising size between subcutaneous injection in the abdominal area and subcutaneous injection in the thigh area (standardized mean difference: -0.16; 95% confidence interval: -0.34 to 0.22; I2  = 32%, p > .05). Subcutaneous injections in the abdominal area had a lower severity of pain than injections in the arm area (risk ratios: 0.57; 95% confidence interval: 0.48-0.67; I2  = 81%; p < .05), but no statistically significant difference was shown between the pain intensity in the abdominal and arm area (mean difference: -1.64; 95% confidence interval: -4.36 to 1.08; I2  = 99%; p > .05). WHAT IS NEW AND CONCLUSION: Subcutaneous injection of LMWH in the abdominal area could reduce the incidence of side-effects at the injection site and reduce patient discomfort. The abdomen is proposed as the first choice of injection site for LMWH. The findings provide useful information to nurses in clinical practice when choosing the subcutaneous injection site for LMWH.

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