The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report.

A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report

SUMMARY A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

In-situ electronic structure redistribution tuning of single-atom Mn/g-C3N4 catalyst to trap atomic-scale lead(II) for highly stable and accurate electroanalysis.

Constructing catalysts with simple structures, uniform effective sites, and excellent performance is crucial for understanding the reaction mechanism of target pollutants. Herein, the single-atom catalyst of Mn-intercalated graphitic carbon nitride (Mn/g-C3N4) was prepared. It was found that the intercalated Mn atoms acted as strong electron donors to effectively tune the electronic structure distribution of the in-situ N atoms, providing a large number of negative potential atomic-scale sites for catalytic reactions. In the detection, the in-situ N atom established an electron bridge for the transient electrostatic trapping of free Pb(II), which induced Pb-N-Mn coordination bonding. Even in g-C3N4-loaded Mn nanoparticles, the N atom was again confirmed to be the interaction site for coupling with Pb. And the MnII-N4-C/MnIV-N4-C cycle actively participated in the electrocatalysis of Pb(II) was confirmed. Moreover, Mn/g-C3N4 achieved highly stable and accurate detection for Pb(II) with a sensitivity of 2714.47 µA·µM-1·cm-2. And excellent reproducibility and specific detection of real water samples made the electrode practical. This study contributes to understanding the changes in the electronic structure of chemically inert substrates after single-atom intercalation and the interaction between contaminants and the microstructure of sensitive materials, providing a guiding strategy for designing highly active electrocatalytic interfaces for accurate electroanalysis.

HbSnRK2.6 Functions in ABA-Regulated Cold Stress Response by Promoting HbICE2 Transcriptional Activity in Hevea brasiliensis.

Low temperature remarkably limits rubber tree (Hevea brasiliensis Muell. Arg.) growth, latex production, and geographical distribution, but the underlying mechanisms of Hevea brasiliensis cold stress response remain elusive. Here, we identified HbSnRK2.6 as a key component in ABA signaling functions in phytohormone abscisic acid (ABA)-regulated cold stress response in Hevea brasiliensis. Exogenous application of ABA enhances Hevea brasiliensis cold tolerance. Cold-regulated (COR) genes in the CBF pathway are upregulated by ABA. Transcript levels of all five HbSnRK2.6 members are significantly induced by cold, while HbSnRK2.6A, HbSnRK2.6B, and HbSnRK2.6C can be further activated by ABA under cold conditions. Additionally, HbSnRK2.6s are localized in the cytoplasm and nucleus, and can physically interact with HbICE2, a crucial positive regulator in the cold signaling pathway. Overexpression of HbSnRK2.6A or HbSnRK2.6B in Arabidopsis extensively enhances plant responses to ABA and expression of COR genes, leading to increased cold stress tolerance. Furthermore, HbSnRK2.6A and HbSnRK2.6B can promote transcriptional activity of HbICE2, thus, increasing the expression of HbCBF1. Taken together, we demonstrate that HbSnRK2.6s are involved in ABA-regulated cold stress response in Hevea brasiliensis by regulating transcriptional activity of HbICE2.

Lapiferin protects against H1N1 virus-induced pulmonary inflammation by negatively regulating NF-kB signaling.

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.

The use of high-resolution MRI to detect thrombosis and lipid-rich carotid artery plaques in a patient with homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia is a rarely agentic disorder of the lipoprotein metabolism intimately related to premature atherosclerotic cardiovascular disease that can lead to high disability and mortality. Homozygous familial hypercholesterolemia typically affects not only the aortic root, compromising the coronary ostia, but also affects other territories such as the carotid, descending aorta, and renal arteries. Multi-contrast high-resolution magnetic resonance imaging (MRI) provides a validated and useful method to characterize carotid artery atherosclerotic plaques quantitatively. However, very few studies have been done on assessing plaque composition in patients with Homozygous familial hypercholesterolemia using high-resolution MRI. This report is to evaluate the value of MRI in accessing carotid artery disease in patients with Homozygous familial hypercholesterolemia. We describe a 28-year-old patient from Beijing, China, who presented to the Neurology Clinic with intermittent blurred vision of the right eye, headache, nausea, and vomiting for eight years without obvious causes. Familial hypercholesterolemia was suspected based on medical history and laboratory examination. Carotid Doppler ultrasound showed bilateral common carotid artery, internal carotid artery, and external carotid artery wall thickening with hyperechoic signals. Subsequently, high-resolution multi-contrast MRI of the carotid showed calcification with hypo-intense areas located at the middle layer of the plaque, with moderate stenosis. The plaque located at the right bifurcation of the common carotid artery extended to the internal carotid artery, causing lumen stenosis close to occlusion. The patient was treated with right carotid artery endarterectomy. At a 6-month follow-up, there had been no recurrence of the patient's symptoms.

The use of high-resolution MRI to detect thrombosis and lipid-rich carotid artery plaques in a patient with homozygous familial hypercholesterolemia

SUMMARY Homozygous familial hypercholesterolemia is a rarely agentic disorder of the lipoprotein metabolism intimately related to premature atherosclerotic cardiovascular disease that can lead to high disability and mortality. Homozygous familial hypercholesterolemia typically affects not only the aortic root, compromising the coronary ostia, but also affects other territories such as the carotid, descending aorta, and renal arteries. Multi-contrast high-resolution magnetic resonance imaging (MRI) provides a validated and useful method to characterize carotid artery atherosclerotic plaques quantitatively. However, very few studies have been done on assessing plaque composition in patients with Homozygous familial hypercholesterolemia using high-resolution MRI. This report is to evaluate the value of MRI in accessing carotid artery disease in patients with Homozygous familial hypercholesterolemia. We describe a 28-year-old patient from Beijing, China, who presented to the Neurology Clinic with intermittent blurred vision of the right eye, headache, nausea, and vomiting for eight years without obvious causes. Familial hypercholesterolemia was suspected based on medical history and laboratory examination. Carotid Doppler ultrasound showed bilateral common carotid artery, internal carotid artery, and external carotid artery wall thickening with hyperechoic signals. Subsequently, high-resolution multi-contrast MRI of the carotid showed calcification with hypo-intense areas located at the middle layer of the plaque, with moderate stenosis. The plaque located at the right bifurcation of the common carotid artery extended to the internal carotid artery, causing lumen stenosis close to occlusion. The patient was treated with right carotid artery endarterectomy. At a 6-month follow-up, there had been no recurrence of the patient's symptoms.

RESUMO A hipercolesterolemia familiar homozigótica, uma doença patogênica rara do metabolismo da lipoproteína intimamente relacionada com a doença cardiovascular aterosclerótica prematura, pode conduzir a uma elevada deficiência e mortalidade. A hipercolesterolemia familiar homozigótica afeta tipicamente não só a raiz aórtica, comprometendo os óstios coronários, mas também outros territórios, como a carótida, a aorta descendente e as artérias renais. Imagens de ressonância magnética multicontraste de alta resolução (RM) fornecem um método validado e útil para caracterizar quantitativamente as placas de aterosclerose da artéria carótida. No entanto, muito poucos estudos foram feitos sobre a avaliação da composição da placa em doentes com hipercolesterolemia familiar homozigótica utilizando ressonância magnética de alta resolução. Este trabalho deve avaliar o valor da ressonância magnética no acesso à doença da artéria carótida em doentes com hipercolesterolemia familiar homozigótica. Descrevemos um paciente de 28 anos de Pequim, China, que se apresentou à clínica neurológica com visão turva intermitente do olho direito, dor de cabeça, náuseas e vômitos por oito anos sem causas aparentes. Suspeitava-se de hipercolesterolemia familiar com base no histórico médico e no exame laboratorial. O ultrassom Doppler carotídeo mostrou uma artéria carótida bilateral comum, artéria carótida interna e parede da carótida externa espessando-se com sinais hiperecoicos. Posteriormente, a ressonância multicontraste de alta resolução da carótida mostrou calcificação com áreas hipointensas localizadas na camada média da placa, com estenose moderada. A placa localizada na bifurcação direita da artéria carótida comum estendia-se até a artéria carótida interna, causando estenose do lúmen próxima à oclusão. O paciente foi tratado com endarterectomia da artéria carótida direita. Em seis meses de acompanhamento, não houve recorrência dos sintomas do paciente.

Lapiferin protects against H1N1 virus-induced pulmonary inflammation by negatively regulating NF-kB signaling

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.

Clinical Characteristics and Adverse Events in Acute Coronary Syndrome Patients with a History of Peripheral Arterial Disease.

BACKGROUND: In clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored. OBJECTIVE: This study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD). METHODS: A total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant. RESULTS: The age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events. CONCLUSION: A history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

Clinical Characteristics and Adverse Events in Acute Coronary Syndrome Patients with a History of Peripheral Arterial Disease / Características Clínicas e Eventos Adversos em Pacientes com Síndrome Coronariana Aguda e História de Doença Arterial Periférica

Abstract Background: In clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored. Objective: This study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD). Methods: A total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant. Results: The age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events. Conclusion: A history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

Resumo Fundamento: Na observação clínica, os pacientes com síndrome coronariana aguda com doença arterial periférica têm prognóstico ruim, portanto, a relação entre as doenças e as características clínicas precisa ser mais explorada. Objetivos: Este estudo tem o objetivo de investigar características clínicas e fatores de risco independentes para eventos adversos hospitalares em pacientes com síndrome coronariana aguda e história de doença arterial periférica (DAP). Métodos: Foram incluídos no estudo 5682 pacientes com síndrome coronariana aguda. Os pacientes foram divididos em dois grupos de acordo com a presença ou ausência de DAP prévia: grupo DAP (n = 188) e grupo sem DAP (n = 5494, grupo controle). Em seguida, foram analisadas características clínicas e a incidência de eventos adversos hospitalares nesses grupos; um p < 0,05 foi considerado estatisticamente significativo. Resultados: A idade dos pacientes com DAP foi maior que a idade do grupo controle (65,5 ± 10,3 anos vs. 58,6 ± 11 anos, p < 0,001), e a proporção de pacientes com história de diabetes ou acidente vascular cerebral foi maior no grupo DAP que no grupo controle [73 (39%) vs. 1472 (26,8%), p = 0,018; 36 (19,3%) vs. 396 (7,2%), p < 0,001). A análise de regressão logística multivariada para eventos adversos hospitalares mostrou que história de DAP (OR = 1,791, p = 0,01), história de diabetes (OR = 1,223, p = 0,001), e idade >65 anos de idade (OR = 4,670, p < 0,001) foram fatores de risco independentes para eventos adversos hospitalares. Conclusão: DAP prévia, idade avançada, e história de diabetes são fatores de risco independentes para eventos adversos hospitalares em pacientes com síndrome coronariana aguda.

Identification of an antifungal metabolite produced by a potential biocontrol Actinomyces strain A01.

Actinomyces strain A01 was isolated from soil of a vegetable field in the suburb of Beijing, China. According to the morphological, cultural, physiological and biochemical characteristics, and 16S rDNA sequence analysis, strain A01 was identified as Streptomyces lydicus. In the antimicrobial spectrum test strain A01 presented a stable and strong inhibitory activity against several plant pathogenic fungi such as Fusarium oxysporum, Botrytis cinerea, Monilinia laxa, etc. However, no antibacterial activity was found. In pot experiments in greenhouse, the development of tomato gray mold was markedly suppressed by treatment with the fermentation broth of the strain A01, and the control efficacy was higher than those of Pyrimethanil and Polyoxin. A main antifungal compound (purity 99.503%) was obtained from the fermentation broth of strain A01 using column chromatography and HPLC. The chemical structural analysis with U V, IR, MS, and NMR confirmed that the compound produced by the strain A01 is natamycin, a polyene antibiotic produced by S. chattanovgensis, S. natalensis, and S. gilvosporeus, widely used as a natural biological preservative for food according to previous reports. The present study revealed a new producing strain of natamycin and its potential application as a biological control agent for fungal plant diseases.

Immune responses induced by a Leishmania (Leishmania) amazonensis recombinant antigen in mice and lymphocytes from vaccinated subjects

A resposta imune induzida por uma proteina recombinante de Leishmania (Leishmania) amazonensis de 33 kD (Larp33) foi avaliada em linfocitos de individuos vacinados com a Leishvacin e em camundongos atraves de vacinacao. Larp33 foi expressa em Escherichia coli apos clonagem de um fragmento genomico de L. (L.) amazonensis de 2,2 kb no vetor pDS56-6His. Larp33 foi reconhecida por anticorpos IgG presentes no soro de individuos vacinados com Leishvacin e induziu proliferacao em linfocitos desses individuos em niveis comparaveis ao antigeno total de Leishmania...