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1.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38612453

RESUMO

The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.


Assuntos
Flavonas , Hepatite A , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Criança , Clostridiales , Flavonóis
2.
Biol Res ; 56(1): 66, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057829

RESUMO

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Ratos , Humanos , Animais , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Proliferação de Células , Miócitos de Músculo Liso/metabolismo , Glicólise , Células Cultivadas
3.
J Pharmacol Exp Ther ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38135510

RESUMO

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619 were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. Significance Statement This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.

4.
Children (Basel) ; 10(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38002910

RESUMO

Early-term neonates (with a gestational age (GA) of 37 and 0/7 weeks to 38 and 6/7 weeks) face higher morbidities, including respiratory and neurodevelopmental issues, than full-term (39 and 0/7 weeks to 40 and 6/7 weeks) infants. This study explores whether hyperbilirubinemia necessitating phototherapy also differs between these groups. A retrospective study was conducted on neonates born from January 2021-June 2022, excluding those with specific conditions. Evaluated factors included GA, birth weight, bilirubin levels, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and feeding type, with phototherapy given as per AAP guidelines. Of 1085 neonates, 356 met the criteria. When stratifying the neonates based on the need for phototherapy, a higher proportion of early-term neonates required phototherapy compared to full-term (p < 0.05). After factoring in various risks (GA; birth weight; gender; feeding type; G6PD deficiency; transcutaneous bilirubin levels at 24 h and 24-48 h postpartum; maternal diabetes; and the presence of caput succedaneum or cephalohematoma), early-term neonates were more likely to need phototherapy than full-term babies (OR: 2.15, 95% CI: 1.21 to 3.80). The optimal cut-off for transcutaneous bilirubin levels 24-48 h postpartum that were used to predict phototherapy need was 9.85 mg/dl. In conclusion, early-term neonates are at a greater risk for developing jaundice and requiring phototherapy than full-term neonates. Monitoring bilirubin 24-48 h postpartum enhances early prediction and intervention.

6.
BMC Pregnancy Childbirth ; 23(1): 539, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495968

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) are known risk factors for postpartum diabetes mellitus (DM) and hypertension, respectively. This study aimed to examine the association between the co-occurrence of GDM and PIH and the subsequent development of diabetes mellitus (DM), hypertension, and metabolic syndrome. METHODS: A cohort study was conducted using data from the Taiwan National Health Insurance Research Database (TNHIRD). The study population included 2,297,613 pregnant women with no history of certain medical conditions who gave birth between 2004 and 2015. The women were classified into four cohorts based on their medical history: GDM cohort, PIH cohort, both GDM and PIH cohort, and normal cohort (without GDM and PIH). RESULTS: The GDM cohort had a higher risk of developing DM, hypertension, and metabolic syndrome than the normal cohort, with hazard ratios of 7.07, 1.54, and 2.51, respectively. The PIH cohort also had an increased risk for these conditions compared with the normal cohort, with hazard ratios of 3.41, 7.26, and 2.68, respectively. The cohort with both GDM and PIH had the highest risk of developing postpartum DM, hypertension, and metabolic syndrome, with hazard ratios of 21.47, 8.02, and 5.04, respectively, compared with the normal cohort. CONCLUSION: The cohort of patients with both GDM and PIH had the highest impact on developing postpartum DM compared with either condition alone cohort. Furthermore, the co-occurrence of both conditions increases the risk, with a higher likelihood of developing postpartum DM than hypertension or metabolic syndrome.


Assuntos
Diabetes Gestacional , Hipertensão Induzida pela Gravidez , Síndrome Metabólica , Gravidez em Diabéticas , Humanos , Feminino , Gravidez , Diabetes Gestacional/epidemiologia , Estudos de Coortes , Hipertensão Induzida pela Gravidez/epidemiologia , Fatores de Risco
7.
Front Cell Infect Microbiol ; 13: 1200617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457965

RESUMO

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.


Assuntos
COVID-19 , Doenças Transmissíveis , Influenza Humana , Infecções Respiratórias , Humanos , Criança , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Pandemias/prevenção & controle , Influenza Humana/epidemiologia
8.
J Formos Med Assoc ; 122(10): 1001-1007, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37142476

RESUMO

BACKGROUND: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. METHODS: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. RESULTS: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD. CONCLUSION: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months.


Assuntos
Vacina BCG , Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Piúria , Criança , Humanos , Lactente , Vacina BCG/efeitos adversos , Cicatriz/complicações , Cicatriz/tratamento farmacológico , Doença da Artéria Coronariana/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Piúria/complicações , Piúria/tratamento farmacológico , Estudos Retrospectivos
9.
Clin Microbiol Infect ; 29(2): 257.e1-257.e5, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36191846

RESUMO

OBJECTIVES: SARS coronavirus 2 (SARS-CoV-2)-associated multi-system inflammatory syndrome in children indicates that viruses can trigger a Kawasaki disease (KD)-like hyperinflammation. A plausible hypothesis was that coronavirus-specific 'holes' in humoral immunity could cause both diseases. METHODS: To determine whether SARS-CoV-2-naïve patients with KD have inferior humoral immunity for the novel coronavirus, sera of children with KD and control children from year 2015 to 2021 were subjected to ELISA, microwestern, and neutralization assays to evaluate the capabilities in recognizing the receptor-binding domain of SARS-CoV-2, spotting spike proteins of three respiratory syndromic coronaviruses, and blocking SARS-CoV-2 from binding to angiotensin-converting enzyme 2 receptors in vitro, respectively. RESULTS: 29 patients with KD before 2019, 74 patients with KD in 2019 or 2020, 54 non-febrile controls, and 24 febrile controls were included in the study. SARS-CoV-2 was recognized on ELISA for both patients with KD in 2016 and those with KD in 2020. Microwestern demonstrated cross-reactive IgG in an all-or-none manner towards three spike proteins of syndromic coronaviruses regardless of sample year or KD status. The ratio between the sera that recognized all spike proteins and those that recognized none (51 vs. 47) was significantly higher from patients with KD than from non-febrile controls (17 vs. 32; p 0.047) but not from febrile controls (13 vs. 11; p 0.85). Most positive sera (12 of 17 controls, 5 of 8 patients with KD before 2019, and 28 of 33 patients with KD in 2019 or 2020) offered protection comparable to low-titre sera from the WHO reference panel. DISCUSSION: Humoral immunity of SARS-CoV-2-naïve children with KD was not inferior to that of controls in offering cross-protection against the novel coronavirus.


Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Humanos , Criança , SARS-CoV-2 , Imunidade Humoral , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais
10.
Front Cardiovasc Med ; 9: 1041082, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523363

RESUMO

Background: Cardiac auscultation is a traditional method that is most frequently used for identifying congenital heart disease (CHD). Failure to diagnose CHD may occur in patients with faint murmurs or obesity. We aimed to develop an intelligent diagnostic method of detecting heart murmurs in patients with ventricular septal defects (VSDs) and atrial septal defects (ASDs). Materials and methods: Digital recordings of heart sounds and phonocardiograms of 184 participants were obtained. All participants underwent echocardiography by pediatric cardiologists to determine the type of CHD. The phonocardiogram data were classified as normal, ASD, or VSD. Then, the phonocardiogram signal was used to extract features to construct diagnostic models for disease classification using an advanced optical coherence tomography network (AOCT-NET). Cardiologists were asked to distinguish normal heart sounds from ASD/VSD murmurs after listening to the electronic sound recordings. Comparisons of the cardiologists' assessment and AOCT-NET performance were performed. Results: Echocardiography results revealed 88 healthy participants, 50 with ASDs, and 46 with VSDs. The AOCT-NET had no advantage in detecting VSD compared with cardiologist assessment. However, AOCT-NET performance was better than that of cardiologists in detecting ASD (sensitivity, 76.4 vs. 27.8%, respectively; specificity, 90 vs. 98.5%, respectively). Conclusion: The proposed method has the potential to improve the ASD detection rate and could be an important screening tool for patients without symptoms.

12.
Front Cell Dev Biol ; 10: 1036809, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268515

RESUMO

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system, which has a highly invasive growth pattern, which creates poor prospects for patient survival. Chemotherapy and tumor surgery are limited by anticancer drug resistance and tumor invasion. Evidence suggests that combinations of treatments may be more effective than single drugs alone. Natural polyphenolic compounds have potential as drugs for the treatment of glioblastoma and are considered as potential anticancer drugs. Although these beneficial effects are promising, the efficacy of natural polyphenolic compounds in GBM is limited by their bioavailability and blood-brain barrier permeability. Many of them have a significant effect on reducing the progression of glioblastoma through mechanisms such as reduced migration and cell invasion or chemosensitization. Various chemical formulations have been proposed to improve their pharmacological properties. This review summarizes natural polyphenolic compounds and their physiological effects in glioblastoma models by modulating signaling pathways involved in angiogenesis, apoptosis, chemoresistance, and cell invasion. Polyphenolic compounds are emerging as promising agents for combating the progression of glioblastoma. However, clinical trials are still needed to confirm the properties of these compounds in vitro and in vivo.

13.
Front Neurol ; 13: 1001829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212657

RESUMO

Background: Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients. Objective: The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear. Methods: All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered via an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed. Results: No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months. Conclusion: These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.

14.
Brain Sci ; 12(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36138874

RESUMO

BACKGROUND: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. METHODS: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A's role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. RESULTS: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. CONCLUSION: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.

15.
Acta Cardiol Sin ; 38(5): 601-611, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36176364

RESUMO

Background: Epicardial adipose tissue (EAT) is increased in adolescents with obesity and may play a role in early cardiovascular pathophysiological changes. There is a lack of evidence focusing on the association between EAT and cardiac function in adolescents. This study explored associations between EAT, left ventricle (LV) geometric, and LV functional changes in adolescents. Methods: Adolescent volunteers between 10 and 20 years of age were included. Body mass index (BMI) was presented as age- and sex-specific BMI z-scores. Blood samples for glucose metabolism, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were obtained. EAT thickness, LV hypertrophy, and LV diastolic function were measured by echocardiography. Results: The mean age of the 276 adolescents was 13.51 ± 2.44 years. BMI z-score was strongly associated with EAT thickness (r = 0.77; p < 0.001). Multivariable analysis revealed that age, insulin resistance, total cholesterol to high-density lipoprotein cholesterol ratio, and hs-CRP were independent predictors of increased EAT thickness. After adjusting for sex, age, and BMI z-score by multivariable analysis, EAT thickness was a strong predictor of higher LV mass indexed to height2.7, higher relative wall thickness, lower mitral annulus e'/a', and higher E/e' of the mitral annulus. There was no association between EAT and LV ejection fraction. Conclusions: EAT was highly associated with LV hypertrophy and reduction in LV diastolic function, independent of BMI z-score in the enrolled adolescents. Of note, the negative impacts of EAT on LV geometry and diastolic function occurred as early as in adolescence. This highlights the importance of preventing obesity and EAT deposition early in life.

16.
Plant Signal Behav ; 17(1): 2094618, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35786356

RESUMO

Microspore transfers the developmental fate into embryogenesis in vitro regulated by determinant factors of stress-induced. However, the key regulators of microspore embryogenesis (ME) are still largely undiscovered to reveal the mechanism of cell fate transition. Here, we report that Phospholipase C (PLC) is involved at the early stages of ME in Nicotiana tabacum. NtPLC2/3/4 are expressed at the initial stages of ME. The expression levels of NtPLC2/3 are transient activated after 3 days in culture, while the expression level of NtPLC4 maintains relatively stable. Inhibition of PLCs induces the decrease in NtPLC2/3/4 expression level and decline of ME yield. We confirm that lipids in microspore are degraded and then re-accumulate at first embryonic division stage. Inhibition of PLCs suppresses the lipids metabolism at the early stages of ME. Thus, we propose that PLCs-mediated lipid metabolism is a novel regulator at the early stages of ME.


Assuntos
Nicotiana , Fosfolipases Tipo C , Diferenciação Celular , Desenvolvimento Embrionário , Lipídeos , Nicotiana/genética , Fosfolipases Tipo C/genética
17.
Front Pharmacol ; 13: 757398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295329

RESUMO

Background: The substitution of generic drugs can effectively alleviate the rapid growth of drug costs; however, the clinical effectiveness and medical costs of originator products and generics were barely studied in China. Objectives: To compare the effectiveness of antihypertensive drugs and hypertension-related medical costs between originator and generic initiators in Yinzhou, China. Methods: We conducted a population-based retrospective cohort study using the Chinese Electronic Health Records Research in Yinzhou (CHERRY), from July 1, 2011, to December 31, 2018. Hypertension patients initiating with originator products were compared with patients initiating with generic counterparts. We used 1:1 propensity score matching to pair the two groups based on sociodemographic, clinical, and health service utilization variables. Cox proportional regression was adopted to compare the rate of hospitalization for hypertension-related cardiovascular disease between matched originator and generic initiators. Wilcoxon matched-pairs signed-rank test was used to compare annual hypertension-related medical costs. Results: Matched pairs (10,535) of patients were included in the comparative study of originator products and generics, corresponding to seven antihypertensive drugs including amlodipine, felodipine, nifedipine, irbesartan, losartan, valsartan, and metoprolol. The average age of patients included in the analysis was around 60 years (originator vs. generics initiators: from 59.0 vs. 59.1 years in losartan to 62.9 vs. 63.6 years in nifedipine). Higher hospitalization rates among originator initiators were observed for three calcium channel blockers (hazard ratio[95% CI]: amlodipine, 3.18[1.43, 7.11]; felodipine, 3.60[1.63, 7.98]; and nifedipine, 3.86[1.26, 11.81]; respectively). The remaining four out of seven drugs of the clinical endpoint estimates showed comparable outcomes between originator products and generics (hazard ratio[95% CI]: irbesartan, 1.19[0.50, 2.84]; losartan, 1.84[0.84, 4.07]; valsartan, 2.04[0.72, 5.78]; and metoprolol, 1.25[0.56, 2.80]; respectively). Higher median annual hypertension-related medical costs were observed in originator initiators (all p < 0.001), except for metoprolol (p = 0.646). Conclusion: We observed comparable or even better clinical outcomes and less medical cost associated with the use of antihypertensive generics compared to originator counterparts. This could help increase patient and provider confidence in the efficacy of generic medicines to manage hypertension diseases.

18.
World Neurosurg ; 160: e250-e255, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34999010

RESUMO

BACKGROUND: Spinal meningiomas are the common benign tumors in intradural extramedullary spinal tumors. Simpson grade I resection is recommended to avoid tumor recurrence. However, the dura reconstruction increases a risk of cerebrospinal fluid leakage after this surgical resection. To address this concern, the inner dura layer resection and long-term surgical outcomes of this technique were designed and examined after total tumor resection to preserve the outer dura layer. METHODS: This study included 40 spinal meningioma patients undergoing the outer dura layer resection between 2002 and 2019. Clinical characteristics, radiologic features, preoperative and postoperative functional states, tumor recurrence, and perioperative complications were described and evaluated. RESULTS: A total of 40 spinal meningioma cases with the median age of 63 years (36-81 years) were enrolled in this study. The median postoperative follow-up period of all 40 cases was 96 months (34-193 months). About 82.5% of cases were located in the thoracic spine, while 16.5% of cases were located in the cervical spine. Of the symptomatic cases, 87.5% of cases follow with satisfactory outcomes and 12.5% of cases follow with unexpected outcomes. The local spinal meningioma recurrence rate was 2.5% (1 of 40 cases). No postoperative cerebrospinal fluid leak occurred in the 40 spinal meningioma cases. CONCLUSIONS: A long-term postoperative follow-up indicated that this modified spinal dura preservation technique caused good neurologic improvement with rare recurrence. Therefore we recommend this improved technique may be an alternative surgical option for total resection of spinal meningiomas with favorable prognosis.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Coluna Vertebral , Vértebras Cervicais/cirurgia , Dura-Máter/patologia , Dura-Máter/cirurgia , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Meningioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento
19.
Am J Cancer Res ; 11(4): 1185-1205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33948353

RESUMO

This study aimed to investigate the interaction of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, and their effects on regulating glioblastoma multiforme (GBM) malignant behaviors. AKIP1 expression was modified by pcDNA and pGPH1 vectors in U-87 MG and U-251 MG cells. Subsequently, multiple compensative experiments were conducted via adding CXCL1, CXCL2 and CXCL8 in the pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells, respectively. Furthermore, AKIP1, CXCL1/2/8 expressions in 10 GBM and 10 low-grade glioma (LGG) tumor samples were detected. AKIP1 was elevated in various GBM cell lines compared to normal human astrocytes. AKIP1 overexpression promoted U-87 MG and U-251 MG cell proliferation and invasion while inhibited apoptosis; and it enhanced chemoresistance to temozolomide (but not cisplatin) and radiation resistance; then AKIP1 knockdown showed the opposite effects. Meanwhile, AKIP1 positively regulated CXCL1/2/8, NF-κB pathway, AKT pathway and PD-L1 expression. Further multiple compensative experiments uncovered that CXCL1 and CXCL8 promoted proliferation, invasion, chemoradiation resistance, NF-κB pathway, AKT pathway and PD-L1 expression in U-87 MG and U-251 MG cells, also in pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells; although CXCL2 exhibited similar treads, but its effect was much weaker. Besides, NF-κB pathway inhibitor and AKT pathway inhibitor attenuated the effect of CXCL1&CXCL8 on promoting GBM cell malignant behaviors. Clinically AKIP1 and CXCL1/8 were elevated in GBM compared to LGG tumor samples, and they were inter-correlated. AKIP1 promotes GBM viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways.

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