RESUMO
To explore the common questions of acupuncture translational medicine study and the development strategy of its translational application. It is believed that the research on the individual and common mechanisms of acupuncture effects, and the common molecule of acupoint and parameter research for the effect onset of acupuncture may promote clinical translation and instrument research and development. The study of meridian theory should be fully applied to clinical practice to build a meridian diagnostic system with clinical significance. Using evidence-based medicine, the clinical research of acupuncture can be transformed into clinical guidelines to provide the effective regimens for clinical practice. The communication and cooperation should be enhanced between the basic research and clinical application in the field of acupuncture. It is suggested that the promotion of acupuncture translational medicine research is contribute to the overall development of acupuncture discipline, and to better service for the human health engineering.
Assuntos
Meridianos , Projetos de Pesquisa , Humanos , Ciência Translacional BiomédicaRESUMO
Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell development. Abnormal MHC II expression can lead to immunodeficiency, clinically termed as type II bare lymphocyte syndrome (BLS), which usually results from mutations in the MHC II transactivator (CIITA) and other coactivators. Here, we present a new paradigm for MHC II deficiency in mice that involves a spontaneous point mutation on H2-Aa. A significantly reduced population of CD4+ T cells was observed in mice obtained from the long-term homozygous breeding of autophagy-related gene microtubule-associated protein 1 light chain 3 ß (Map1lc3b, Lc3b) knockout mice; this phenotype was not attributed to the original knocked-out gene. MHC II expression was generally reduced, together with a marked deficiency of H2-Aa in the immune cells of these mice. Using cDNA and DNA sequencing, a spontaneous H2-Aa point mutation that led to false pre-mRNA splicing, deletion of eight bases in the mRNA, and protein frameshift was identified in these mice. These findings led to the discovery of a new type of spontaneous MHC II deficiency and provided a new paradigm to explain type II BLS in mice.
Assuntos
Antígenos de Histocompatibilidade Classe II , Mutação Puntual , Animais , Linfócitos T CD4-Positivos , Camundongos , Camundongos Knockout , Imunodeficiência Combinada Severa , Linfócitos TRESUMO
Lilium × formolongi is an important cut flower species that is able to flower within a year following seed propagation, with flower induction that is very sensitive to the photoperiod. Cryptochromes are blue/UV-A light receptors that regulate many important plant growth and development processes, including photoperiodic flowering. In this study, we isolated the cryptochrome 1 (CRY1) gene from L. × formolongi and analyzed its function in transgenic Arabidopsis. The predicted LfCRY1 protein was strongly homologous to other CRY1 proteins. The transcription of LfCRY1 was induced by blue light, with LfCRY1 exhibiting its highest expression and diurnal expression patterns during the flowering-induction stage under both long-day (LD) and short-day (SD) photoperiods. Overexpression of LfCRY1 in Arabidopsis promoted flowering under LDs but not SDs and inhibited hypocotyl elongation under blue light. The LfCRY1 protein was located in both the nucleus and cytoplasm. LfCRY1 interacted with the important flowering activator LfCOL9 in both yeast and onion cells. These results provide functional evidence for the role of LfCRY1 in controlling photoperiodic flowering under LDs and indicate that LfCRY1 may be a counterpart of AtCRY1. Understanding the role of LfCRY1 in photoperiodic flowering is beneficial for the molecular breeding of lilies with shorter vegetative stages.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Lilium , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Clonagem Molecular , Criptocromos/genética , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Luz , Lilium/genética , FotoperíodoRESUMO
The photoperiodic flowering pathway is essential for plant reproduction. As blue and ultraviolet-A light receptors, cryptochromes play an important role in the photoperiodic regulation of flowering. Lilium × formolongi is an important cut flower that flowers within a year after seed propagation. Floral induction is highly sensitive to photoperiod. In this study, we isolated the CRYPTOCHROME2 gene (LfCRY2) from L. × formolongi. The predicted LfCRY2 protein was highly homologous to other CRY2 proteins. The transcription of LfCRY2 was induced by blue light. LfCRY2 exhibits its highest diurnal expression during the floral induction stage under both long-day and short-day photoperiods. Overexpression of LfCRY2 in Arabidopsis thaliana promoted flowering under long days but not short days, and inhibited hypocotyl elongation under blue light. Furthermore, LfCRY2 was located in the nucleus and could interact with L. × formolongi CONSTANS-like 9 (LfCOL9) and A. thaliana CRY-interacting basic-helix-loop-helix 1 (AtCIB1) in both yeast and onion cells, which supports the hypothesis that LfCRY2 hastens the floral transition via the CIB1-CO pathway in a manner similar to AtCRY2. These results provide evidence that LfCRY2 plays a vital role in promoting flowering under long days in L. × formolongi.
Assuntos
Criptocromos/fisiologia , Flores/fisiologia , Lilium/genética , Fotoperíodo , Sequência de Aminoácidos , Arabidopsis , Ritmo Circadiano , Criptocromos/química , Filogenia , Plantas Geneticamente ModificadasRESUMO
Here, we aimed to build a nomogram model to estimate the probability of nasogastric tube-associated pressure injuries (NTAPIs) in intensive care unit(ICU)patients. This prospective cohort study included 219ICU patients with nasogastric tube between September 2019 and January 2020.Univariate and multivariate logistic regression analyses were used to develop the nomogram model. The resulting nomogram was tested for calibration, discrimination, and clinical usefulness. Of the included patients, 58 developed NTAPIs, representing an incidence rate of 26.5%. Binary logistic regression analysis revealed that the prediction nomogram included C-reactive protein, vasopressor use, albumin level, nasogastric tube duration, and Sequential Organ Failure Assessment score. The value of these predictors was again confirmed using theLasso regression analysis. Internal validation presented a good discrimination of the nomogram, with an area under the curve value of 0.850, and good calibration (Hosmer-Lemeshow test, P = 0.177). The decision curve analysis also demonstrated preferable net benefit along with the threshold probability in the prediction nomogram. The nomogram model can accurately predict the risk factors for NTAPIs, to formulate intervention strategies as early as possible to reduce NTAPI incidence.
Assuntos
Intubação Gastrointestinal/efeitos adversos , Nomogramas , Úlcera por Pressão/etiologia , Adulto , Idoso , Área Sob a Curva , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Gastrointestinal/métodos , Intubação Gastrointestinal/normas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Úlcera por Pressão/fisiopatologia , Desenvolvimento de Programas/métodos , Estudos Prospectivos , Curva ROC , Fatores de RiscoRESUMO
The knowledge, attitude, and practice of nurses in intensive care units (ICUs) are determinants for the efficacy of preventing the medical device-related pressure injury (MDRPI). The aim of this study was to determine the level and factors of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI in western China. An annual cross-sectional study was conducted in hospitals of western China from May 2020 to September 2020. Nurses' knowledge and attitudes were assessed using Clinical Nurses Prevention MDRPI of Critically Ill Patients for the Knowledge, Attitude, Practice Assessment Scale. SPSS software version 25.0 and independent t-test, Chi-square, Fisher exact, one-way analysis of variance, and multiple linear regression tests were used for data analysis. A total of 1002 nurses in ICUs from 37 hospitals in Gansu Province, China, participated in this study. The scores of overall KAP, knowledge, attitudes, and practice were 149.17 ± 24.62, 53.83 ± 12.23, 37.24 ± 6.35 and 58.10 ± 9.83, respectively. There was a positive and significant relationship between three variables. Findings revealed that nurses' knowledge score in the Tertiary hospital was higher than scores of other hospitals as 3.840 units. Moreover, the knowledge score and practice score of nurses with bachelor's degree or above were higher than other nurses and are 0.978 and 1.106 units, respectively. Based on the findings, practice of nurses increased by 0.992 units, with a 1-year increase in work experience of nurses in the ICU. The levels of knowledge, attitude, and practice of nurse in ICUs on preventing MDRPI were acceptable. The findings of the study highlight that a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI, as well as improving the quality of care for critically ill patients.
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Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Enfermeiras e Enfermeiros , Úlcera por Pressão/prevenção & controle , China , Estudos Transversais , Humanos , Unidades de Terapia Intensiva , Inquéritos e QuestionáriosRESUMO
Chronic pain is a significant public health problem with emotional and disabling factors, which may not completely respond to current medical treatments such as opioids. The systematic review and meta-analysis aimed to examine the effectiveness and safety of MBCT for patients with chronic pain. Database searches of PubMed, Medline, EMBASE, the Cochrane Library, PsycINFO, Web of Science, Scopus and CINAHL up to 15 October 2019. Included studies assessed with the Cochrane risk-of-bias tool. Eight RCTs involved 433 patients, including chronic low back pain, fibromyalgia, migraine, rheumatoid arthritis and mix etiology. MBCT intervention demonstrated a short-term improvement on depression mood [standardized mean difference -0.72; 95% confidence interval = -1.22 to -0.22, p = 0.005] compared with usual care and was associated with short-term improvement in mindfulness compared with non-MBCT [SMD 0.51; 95% CI = 0.01 to 1.01, p = 0.04]. Between-group differences in pain intensity, pain inference and pain acceptance were not signiï¬cant at short- or long-term follow-up. Compared to active treatments, MBCT intervention not found significant differences in either short- or long-term outcomes. MBCT showed short-term efficacious on depressed mood and mindfulness of chronic pain patients. Longer follow-ups, large sample and rigorous RCTs that can be best understand remaining uncertainties needed.
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Dor Crônica/terapia , Terapia Cognitivo-Comportamental/métodos , Atenção Plena , Dor Crônica/psicologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Ferroptosis is a novel form of regulated cell death which is dependent on iron and reactive oxygen species (ROS) and associated with the accumulation of lipid peroxides. It is obviously different from other cell death types in terms of morphology, biochemistry, genetics, etc. Also, it is related to the production of iron catalyzed lipid peroxides which is triggered by non-enzymatic or enzymatic reactions. Ferroptosis has been proved to be involved in hematological diseases, cardio-cerebrovascular diseases, liver and kidney diseases. This paper will review the definition, mechanism, inducers of ferroptosis, as well as the function of ferroptosis in respiratory system. We expect to present a new concept for respiratory research and suggest potential targets for clinical prevention and treatment of respiratory diseases.
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Ferroptose , Transtornos Respiratórios , Morte Celular , Humanos , Ferro , Espécies Reativas de OxigênioRESUMO
Corona virus disease 2019 (COVID-19) is a new type of coronavirus pneumonia, which is caused by infection of a novel coronavirus, SARS-CoV-2. The virus infects lung cells by binding angiotensin-converting enzyme 2 (ACE2) of cell surface, which leads to leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung, causing respiratory symptoms. The aggravation of local inflammation causes cytokine storm, resulting in systemic inflammatory response syndrome. In December 2019, a number of new pneumonia cases were reported by Wuhan Municipal Health Commission, after then a novel coronavirus was isolated and identified as SARS-CoV-2. To the date of Sep. 13th, 2020, COVID-19 is affecting 216 countries or regions, causing 28 637 952 cases, 917 417 deaths, and the mortality rate is 3.20%. This review will summarize the structure of SARS-CoV-2 and the pharmaceutical treatment of COVID-19, and their potential relationships.
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Infecções por Coronavirus , Pandemias , Pneumonia Viral , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Betacoronavirus , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine. METHODS: We searched Pubmed, Embase, Web of Science, Cochrane database library, CINAHL, and PsycINFO for relevant publications. A random-effects model was used to pool the estimates of the prevalence of SI and SA, which were also stratified by the geographical location of the research institutions from the studies included in this meta-analysis. RESULTS: Fifteen studies involving 2,247,648 participants with migraine were selected. Pooled prevalence estimates of SI and SA were 15.5% [95% confidence interval (CI) 10.4-21.3%] and 3.9% (95% CI 0.9-8.8%), respectively, and the prevalence of SI was higher in Asian countries (21.5%, 95%CI 16.8-26.6%) compared with non-Asian countries (11.0%, 95%CI 6.1-17.2%). Measures of heterogeneity between studies were high for all outcomes (I2 = 89-100%), indicating that the substantial between-study heterogeneity in estimated proportions was not attributed to sampling error. The leave-one-out analysis showed that no single study significantly affected the final pooled results. CONCLUSIONS: This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.
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Transtornos de Enxaqueca , Tentativa de Suicídio , Ásia , Humanos , Transtornos de Enxaqueca/epidemiologia , Prevalência , Ideação SuicidaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lychee seed, the seed of Litchi chinensis Sonn. is one of the commonly used in traditional Chinese medicine (TCM). It possesses many pharmacological effects such as blood glucose and lipid-lowering effects, liver protection, and antioxidation. Our preliminary studies have proven that an active fraction derived from lychee seed (LSF) can significantly decrease the blood glucose level, inhibit amyloid-ß (Aß) fibril formation and Tau hyperphosphorylation, and improve the cognitive function and behavior of Alzheimer's disease (AD) model rats. AIM OF THE STUDY: The aim of this study was to identify the main active components in LSF that can inhibit the hyperphosphorylation of Tau through improving insulin resistance (IR) in dexamethasone (DXM)-induced HepG2 and HT22 cells. MATERIALS AND METHODS: The isolation was guided by the bioactivity evaluation of the improvement effect of IR in HepG2 and HT22 cells. The mRNA and protein expressions of IRS-1, PI3K, Akt, GSK-3ß, and Tau were measured by RT-PCR, Western blotting, and immunofluorescence methods, respectively. RESULTS: After extraction, isolation, and elucidation using chromatography and spectrum technologies, three polyphenols including catechin, procyanidin A1 and procyanidin A2 were identified from fractions 3, 5, and 9 derived from LSF. These polyphenols inhibit hyperphosphorylated Tau via the up-regulation of IRS-1/PI3K/Akt and down-regulation of GSK-3ß. Molecular docking result further demonstrate that these polyphenols exhibit good binding property with insulin receptor. CONCLUSIONS: catechin, procyanidin A1, and procyanidin A2 are the main components in LSF that inhibit Tau hyperphosphorylation through improving IR via the IRS-1/PI3K/Akt/GSK-3ß pathway. Therefore, the findings in the current study provide novel insight into the anti-AD mechanism of the components in LSF derived from lychee seed, which is valuable for the further development of a novel drug or nutrient supplement for the prevention and treatment of AD.
Assuntos
Resistência à Insulina , Litchi , Polifenóis/farmacologia , Proteínas tau/antagonistas & inibidores , Doença de Alzheimer , Animais , Linhagem Celular , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sementes , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
BACKGROUND: Tacrolimus, a calcineurin inhibitor, is recommended by the recent guidelines from the Kidney Disease Improving Global Outcomes Group as the first-line treatment for steroid-resistant nephrotic syndrome (SRNS), but its clinical application in China is still limited. We investigated the efficacy and safety of tacrolimus combined with low-dose corticosteroids in a population of Chinese children with SRNS. METHODS: In this prospective non-randomized, non-controlled study, Chinese children with SRNS who failed the previous full-dose prednisone treatment were given tacrolimus (0.1 mg/kg/day) and low-dose prednisone (0.25-0.50 mg/kg/day). We compared the overall remission rate (ORR) and adverse events in the follow-up period with this therapeutic regimen. RESULTS: A total of 76 children were enrolled into the study with an average follow-up period of 18 ± 6 months (maximum 36 months). ORR achieved by the first, third, and sixth months was 94.7%, 94.7%, and 96.0%, respectively. All patients who attained an initial tacrolimus trough concentration (FK506C0) > 6 ng/mL (60.3%) achieved remission. The relative risk of relapse at FK506C0 < 3 ng/mL compared to 3-6 ng/mL, 6-9 ng/mL, and 9-12 ng/mL was 2.3, 3.2, and 16.9, respectively. During the follow-up period, adverse effects that had been previously reported were rare. CONCLUSIONS: Combination of tacrolimus and low-dose prednisone was safe and effective for the treatment of children with SRNS, with high remission rates observed as early as the first month. Relapses were infrequent, but tended to increase significantly with decreases in FK506C0.
Assuntos
Inibidores de Calcineurina/uso terapêutico , Glucocorticoides/administração & dosagem , Síndrome Nefrótica/tratamento farmacológico , Prednisona/administração & dosagem , Tacrolimo/uso terapêutico , Adolescente , Inibidores de Calcineurina/efeitos adversos , Criança , Pré-Escolar , China , Resistência a Medicamentos , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Prednisona/efeitos adversos , Estudos Prospectivos , Tacrolimo/efeitos adversos , Resultado do TratamentoRESUMO
Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg-1, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg-1·d-1. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process.
Assuntos
Bupleurum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Proteína HMGB1/metabolismo , Polissacarídeos/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Animais , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/metabolismo , Inflamação/prevenção & controle , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Raízes de Plantas/química , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade , Fator de Transcrição RelA/metabolismoRESUMO
OBJECTIVE: Systematic tracking of microRNA (miRNA) targets remains a challenge. In our work, we aimed to use TargetScore to investigate the potential targets of miRNA203 and miRNA-146a in psoriasis by integrating miRNA overexpression information and sequence data, and to further uncover the functions of miRNA203 and miRNA-146a in psoriasis. METHODS: This was a case-control bioinformatics analysis using already published microarray data of psoriasis. We calculated targetScores by combining log fold-change and sequence scores obtained from TargetScan context score, probabilities of conserved targeting, and derived the distribution of targetScores. The scoring cutoff was chosen based on the different targetScore distributions for the nonvalidated and validated targets. The potential target genes for miRNA-203 and miRNA-146a were predicted based on the targetScore threshold. To reveal the functions of miRNA-203 and miRNA-146a, we implemented pathway enrichment analyses for the targets of miRNA-203 and miRNA-146a. RESULTS: TargetScore >0.4 was selected as the threshold to filter out less confidence targets because we observed little overlap between the 2 distribution at targetScoreâ=â0.4. Based on the targetScore >0.4, 49 target genes for miRNA-203 and 17 targets for miRNA-146a were identified. Pathway enrichment results showed that the target genes of miRNA-203 (including KIR2DL1, HLA-DQA1, KIR3DL1) only participated in antigen processing and presentation. The target genes of miRNA-146a (covering ADORA3, CYSLTR2, HRH4) were only involved in neuroactive ligand-receptor interaction. CONCLUSION: MiRNA203 and miRNA-146a played important roles in psoriasis progression, partially through regulating the pathways of antigen processing and presentation, and neuroactive ligand-receptor interaction, respectively.
Assuntos
MicroRNAs/biossíntese , Psoríase/genética , Teorema de Bayes , Estudos de Casos e Controles , Expressão Gênica , Humanos , MicroRNAs/genética , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Amyloid-ß (Aß) is commonly recognized as the most important factor that results in neuronal cell death and accelerates the progression of Alzheimer's disease (AD). Increasing evidence suggests that microglia activated by Aß release an amount of neurotoxic inflammatory cytokines that contribute to neuron death and aggravate AD pathology. In our previous studies, we found that lychee seed fraction (LSF), an active fraction derived from the lychee seed, could significantly improve the cognitive function of AD rats and inhibit Aß-induced neuroinflammation in vitro, and decrease neuronal injuries in vivo and in vitro. In the current study, we aimed to isolate and identify the specific components in LSF that were responsible for the anti-neuroinflammation effect using preparative high performance liquid chromatography (pre-HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) methods. To this end, we confirmed two polyphenols including catechin and procyanidin A2 that could improve the morphological status of BV-2 cells and suppress the release, mRNA levels, and protein expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) through downregulating the nuclear factor-κB (NF-κB) signaling pathway using ELISA, RT-PCR, and Western blotting methods. Furthermore, catechin and procyanidin A2 could inhibit Aß-induced apoptosis in BV-2 cells by upregulating Bcl-2 and downregulating Bax protein expression. Therefore, the current study illustrated the active substances in lychee seed, and first reported that catechin and procyanidin A2 could suppress neuroinflammation in Aß-induced BV-2 cells, which provides detailed insights into the molecular mechanism of catechin and procyanidin A2 in the neuroprotective effect, and their further validations of anti-neuroinflammation in vivo is also essential in future research.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Inflamação/tratamento farmacológico , Litchi/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Polifenóis/química , Polifenóis/uso terapêutico , Sementes/química , Animais , Apoptose/efeitos dos fármacos , Catequina/metabolismo , Linhagem Celular , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , NF-kappa B/metabolismo , Neurônios/imunologia , Proantocianidinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Neglected tropical diseases (NTDs) are closely related to poverty and affect over a billion people in developing countries. The unmet treatment needs cause high mortality and disability thereby imposing a huge burden with severe social and economic consequences. Although coordinated by the World Health Organization, various philanthropic organizations, national governments and the pharmaceutical industry have been making efforts in improving the situation, the control of NTDs is still inadequate and extremely difficult today. The lack of safe, effective and affordable medicines is a key contributing factor. This paper reviews the recent advances and some of the challenges that we are facing in the fight against NTDs. MAIN BODY: In recent years, a number of innovations have demonstrated propensity to promote drug discovery and development for NTDs. Implementation of multilateral collaborations leads to continued efforts and plays a crucial role in drug discovery. Proactive approaches and advanced technologies are urgently needed in drug innovation for NTDs. However, the control and elimination of NTDs remain a formidable task as it requires persistent international cooperation to make sustainable progresses for a long period of time. Some currently employed strategies were proposed and verified to be successful, which involve both mechanisms of 'Push' which aims at cutting the cost of research and development for industry and 'Pull' which aims at increasing market attractiveness. Coupled to this effort should be the exercise of shared responsibility globally to reduce risks, overcome obstacles and maximize benefits. Since NTDs are closely associated with poverty, it is absolutely essential that the stakeholders take concerted and long-term measures to meet multifaceted challenges by alleviating extreme poverty, strengthening social intervention, adapting climate changes, providing effective monitoring and ensuring timely delivery. CONCLUSIONS: The ongoing endeavor at the global scale will ultimately benefit the patients, the countries they are living and, hopefully, the manufacturers who provide new preventive, diagnostic and therapeutic products.
Assuntos
Descoberta de Drogas , Doenças Negligenciadas , Medicina Tropical , Humanos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/prevenção & controleRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) represents the most commonly occurring inflammatory type of arthritis and is a major cause of disability. Reports have placed emphasis on the potential of, granzyme B (GZMB) as a potentially valuable prognostic marker in early RA, the mechanism of which still remains largely unclear. Thus, the aim of the current study was to investigate the effects GZMB gene silencing influences synovial tissue hyperplasia and articular cartilage tissue injury of RA through the regulation of the MAPK signaling pathway. METHODS: Following the successful establishment of the collagen-induced animal model of RA in rats, a five-grade scoring method was applied to evaluate the swelling degree measurement of the rats for model identification. The various rat responses to GZMB shRNA and U-46619 (activator of the MAPK signaling pathway) were subsequently detected. The general status of rats was observed and recorded, with their weight and ankle diameter kept accurate record of. ELISA was employed to detect the levels of inflammatory cytokines, while RT-qPCR and Western blotting techniques were applied to determine the expressions of GZMB and pathway-related genes and proteins. RESULTS: GZMB gene silencing was observed to aid in the maintenance of rat weight increases, while acting to reduce the degree of ankle swelling, while hypertrophy of the synovial tissue and the injury of the articular cartilage tissue were not obvious. GZMB gene silencing was shown to decrease inflammatory cytokine levels, as well as decreased bcl-2, Cyclin D1, VEGF and bFGF while increasing caspase 3. Notably, GZMB gene silencing suppressed the activation of the MAPK signaling pathway by reducing the phosphorylation extent of ERK and MEK. CONCLUSION: Taken together, the key findings of the present study ultimately suggest that GZMB gene silencing acts to inhibit MAPK signaling pathway through regulating the expressions of inflammatory factors, factors correlated with apoptosis (bcl-2 and caspase), as well as factors associated with angiogenesis (VEGF and bFGF), thus relieving synovial tissue hyperplasia and articular cartilage tissue injury brought about by RA. The GZMB gene could well be a new therapeutic target for RA treatment.
Assuntos
Artrite Experimental/enzimologia , Cartilagem Articular/enzimologia , Granzimas/metabolismo , Hiperplasia/enzimologia , Sistema de Sinalização das MAP Quinases/fisiologia , Membrana Sinovial/enzimologia , Animais , Artrite Experimental/genética , Artrite Experimental/patologia , Cartilagem Articular/lesões , Inativação Gênica/fisiologia , Granzimas/antagonistas & inibidores , Granzimas/genética , Hiperplasia/genética , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Ratos , Ratos Wistar , Membrana Sinovial/patologiaRESUMO
OBJECTIVE: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China. STUDY DESIGN: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA). RESULTS: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group. CONCLUSIONS: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.
Assuntos
Cesárea/estatística & dados numéricos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Pequim/epidemiologia , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Incidência , Recém-Nascido , Modelos Logísticos , Razão de Chances , Gravidez , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
The CatSper channel is known as one of the most important Ca²âº channels on the cell membrane of mammalian sperm and plays a key role in the motility, hyperactivation and fertilization function of sperm. The CatSper protein, expressed exclusively in the principal piece of the sperm tail, is composed of CatSper1-4 and 5 auxiliary unitsß,γ,δ and ε, and has an essential part in the functional and structural domains of Ca²âºas well as in the spatiotemporal regulation of the P-Tyr protein, sperm hyperactivation, efficient sperm migration in the oviduct, egg penetration, and normal fertility. Recent studies show that functional deficiency of CatSper seriously affects sperm function,and the loss of any one of its 9 subunits may lead to male reproductive dysfunction. This paper outlines recent advances in the studies of the CatSperprotein, focusing on its expression, location, structure, and regulation,as well as itsinfluence on sperm hyperactivation and male reproduction.