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RATIONALE: Human infection with Angiostrongylus cantonensis is uncommon and has only been sporadically reported in the literature. Patients infected with A cantonensis usually have a delayed diagnosis and sometimes a poor prognosis. PATIENT CONCERNS: A 70-year-old woman presented to the respiratory department with complaints of headache, chest pain, myalgia, fatigue, and anorexia for 7 days. DIAGNOSES: Complete blood count showed eosinophilia. The serum was tested showing a positive finding of A cantonensis antibody. Cerebrospinal fluid was tested using high-throughput metagenomics analysis and 16 reads for A cantonensis were mapped. The patient was diagnosed with A cantonensis infection. INTERVENTIONS: The patient received a 7-day course of albendazole and 4-day course of prednisone. OUTCOMES: When discharged from the hospital, the patient still suffered from fatigue and poor memory. Aminotransferase levels were high due to albendazole's liver toxicity. In a post-discharge follow-up about 1 month later she had recovered completely both physically and mentally, and peripheral eosinophil count and aminotransferase levels were both normal. LESSONS: Because the direct identification of parasites is difficult, high-throughput metagenomics analysis may provide a reliable alternative tool for the diagnoses of infection with A cantonensis. When albendazole is prescribed, caution must be taken with respect to its liver toxicity.
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Angiostrongylus cantonensis , Meningitis , Meningoencefalitis , Insuficiencia Respiratoria , Animales , Femenino , Humanos , Anciano , Albendazol/uso terapéutico , Cuidados Posteriores , Metagenómica , Alta del Paciente , Meningoencefalitis/complicaciones , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Anticuerpos , Insuficiencia Respiratoria/complicaciones , Meningitis/diagnósticoRESUMEN
[This corrects the article on p. 8833 in vol. 13, PMID: 34539998.].
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The increased proliferation and migration of airway smooth muscle cells (ASMCs) are essential factors in the development of asthma. Long noncoding RNAs (lncRNAs) play key roles in the pathogenesis of various diseases, including asthma. A growing body of evidence indicates that lncRNA FTX regulates proliferation and migration in multiple cell types and the progression of various diseases. However, the role of FTX in asthma is still not yet fully understood. Therefore, we explored the role of FTX in the proliferation and migration of ASMCs stimulated by platelet-derived growth factor BB (PDGF-BB) in vitro, as well as the underlying molecular mechanisms. Here, it is demonstrated that the expression of FTX in ASMCs treated with PDGF-BB is significantly up-regulated, and FTX knockout effectively represses the proliferation and migration and promotes the apoptosis of ASMCs induced by PDGF-BB. Mechanistically, FTX can inhibit the proliferation and migration of ASMCs caused by PDGF-BB by targeting miR-590-5p, and FTX over-expression reverses the inhibitory effect. Furthermore, JAK2 is a direct target of the FTX/miR-590-5p signal axis, the over-expression of which reverses the inhibitory effect on the proliferation and migration and the apoptosis-inducing effect of miR-590-5p in ASMCs. Collectively, these results highlight the crucial regulatory role of the FTX/miR-590-5p/JAK2 axis in ASMC proliferation, migration, and apoptosis.
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OBJECTIVE: The pathogenesis of chronic obstructive pulmonary disease (COPD) remains elusive. Here, we assessed the correlation between CD8+ T cell frequencies and autophagy in COPD patients. METHODS: Subjects were divided into three groups (n = 30 patients/group): (1) COPD patients in the stable phase; (2) smokers with normal lung function; and (3) non-smokers with normal lung function. Flow cytometry was used to enumerate CD8+ T cell subsets (CD8+, CD8+ effector, and CD8+ memory T cells) and quantitate T-cell apoptosis. RT-PCR and western blotting were used to measure levels of LC3 and p62. RESULTS: Frequencies of CD8+ T cell subsets and expression of p62 and LC3 II/I were significantly higher in COPD patients compared with the other two groups, while the rate of apoptosis was lower. In COPD patients, LC3 II/I and p62 expression were positively correlated with CD8+ T cell subset frequencies. Moreover, a significant correlation was observed between LC3 II/I and p62 expression and T cell subset frequencies. CONCLUSION: Autophagy level is positively correlated with the frequencies of CD8+ T cells, suggesting that autophagy might be involved in COPD pathogenesis.
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Enfermedad Pulmonar Obstructiva Crónica , Fumar , Autofagia , Linfocitos T CD8-positivos , Humanos , Subgrupos de Linfocitos TRESUMEN
Metabolic disorders can lead to a scarcity or excess of certain metabolites such as glucose, lipids, proteins, purines, and metal ions, which provide the biochemical foundation and directly contribute to the etiology of metabolic diseases. Nonalcoholic fatty liver disease, obesity, and cancer are common metabolic disorders closely associated with abnormal lipid metabolism. In this review, we first describe the regulatory machinery of lipid metabolism and its deregulation in metabolic diseases. Next, we enumerate and integrate the mechanism of action of some natural compounds, including terpenoids and flavonoids, to ameliorate the development of metabolic diseases by targeting lipid metabolism. Medicinal natural products have an established history of use in health care and therapy. Natural compounds might provide a good source of potential therapeutic agents for treating or preventing metabolic diseases with lipid metabolic abnormalities.
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Metabolismo de los Lípidos/fisiología , Neoplasias/metabolismo , Obesidad/metabolismo , Animales , Humanos , Metabolismo de los Lípidos/genética , Neoplasias/inmunología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/inmunologíaRESUMEN
Ambrisentan is a highly selective endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). The analysis of the process-related impurities will help not only to optimize the process parameters but also to develop reasonable analytical methods and set the quality standard for a quality control strategy in pharmaceutical manufacturing. During the manufacture of ambrisentan, five unknown impurities were detected in pilot batches ranging from 0.05% to 0.15% by HPLC. All of these impurities were isolated and synthesized successfully and were identified and characterized by LC-MS, HRMS, ESI-MS/MS(Q-Tof), 1D-NMR (1H, 13C, DEPT) and 2D-NMR (COSY, HSQC, HMBC) techniques. The formation mechanisms that yield these impurities are discussed for the first time. Quality control strategies to deal with these impurities are developed to obtain bulk drug of ICH-grade quality.
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Antihipertensivos/análisis , Contaminación de Medicamentos , Fenilpropionatos/análisis , Piridazinas/análisis , Control de Calidad , Antihipertensivos/química , Antihipertensivos/normas , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Espectroscopía de Resonancia Magnética/métodos , Fenilpropionatos/química , Fenilpropionatos/normas , Piridazinas/química , Piridazinas/normas , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVES: In this study, we aimed to investigate the effects of anti-Fas ribozyme on the apoptosis of T lymphocytes (T cells) in mice model with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Male 6-week-old C57BL/6 mice were used to establish the COPD model by exposure to cigarette smoke. The COPD mice were sacrificed for spleen dissection and T cell isolation. T cells were randomly divided into four groups (n=10 per group). Group A was used as the control. B, C, and D groups were transfected with empty lentivirus, anti-Fas ribozyme, and an anti-Fas ribozyme mutant, respectively. The expression of Fas mRNA and protein in the T cells were evaluated using qPCR and Western blot, respectively. Flow cytometry was used to evaluate the apoptosis of CD4+ T cells and calculate the ratio of CD4+ to CD8+ T cells (CD4+/CD8+). RESULTS: Anti-Fas ribozyme significantly inhibited the expression of Fas in the T cells of COPD mice. In addition, the number of apoptotic CD4+ T cells and CD4+/CD8+ of the C and D groups were significantly lower and higher than those of group A, respectively (P<0.05). The apoptotic CD4+ T cells and CD4+ CD8+ of the C group were significantly lower and higher than those of group D, respectively (P<0.05). CONCLUSION: Anti-Fas ribozyme significantly inhibited the expression of Fas, increased CD4+/CD8+, and inhibited the apoptosis of T cells in COPD mice.
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We tested the role of the lymphocyte chemokine XCL1 in a murine model of chronic obstructive pulmonary disease (COPD). COPD was instigated in mice by a 12-week exposure to cigarette smoke. Some COPD animals additionally received intranasal injections of recombinant XCL1. We demonstrated that the expression of CD4(+) T cells diminished, while CD8(+) counts increased in the lungs of COPD mice, and that these changes were further aggravated by exogenous XCL1. The levels of XCL1 negatively correlated with CD4(+)/CD8(+) ratio (r = -0.945, p < 0.05). In addition, the levels of this chemokine negatively correlated with the levels of interleukin-2, the lymphokine that is produced by activated CD4(+). This observation further supported negative association between XCL1 and CD4(+) response in an experimental model of COPD. In conclusion, murine model of COPD is characterized by elevated levels of XCL1, increased counts of CD8(+) T cells and diminished ratio of CD4(+)/CD8(+) cells, and decreased activity of CD4(+) T cells. This indicates that XCL1 is involved in chronic inflammatory processes in COPD and may be an important pharmacological target in this disease.