The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial.

BACKGROUND: Poor diet quality is an important risk factor for increased asthma prevalence and poor asthma control. To address the question of whether adults with asthma can benefit from following a healthy diet, this trial will test the efficacy and mechanisms of action of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with sodium reduction among patients with uncontrolled asthma. METHODS: In this 2-arm randomized clinical trial, 320 racially/ethnically and socioeconomically diverse adults with uncontrolled asthma on standard controller therapy will be randomized to either a control or an intervention group and assessed at baseline, 3, 6 and 12 months. Control and intervention participants will receive education on lung health, asthma, and other general health topics; additionally, the intervention group will receive DASH behavioral counseling over 12 months. The primary hypothesis is that the DASH behavioral intervention, compared with the education-only control, will lead to significantly more participants with minimum clinically important improvement (responders) in asthma-specific quality of life at 12 months. Secondary hypotheses will test the intervention effects on other asthma (e.g., asthma control, lung function) and non-asthma outcomes (e.g., quality of life). Additionally, therapeutic (e.g., short chain fatty acids, cytokines) and nutritional biomarkers (e.g., dietary inflammatory index, carotenoids) will be assessed to understand the mechanisms of the intervention effect. CONCLUSION: This trial can substantially advance asthma care by providing rigorous evidence on the benefits of a behavioral dietary intervention and mechanistic insights into the role of diet quality in asthma. CLINICALTRIALS: gov #: NCT05251402.

Ferroptosis in neurodegenerative diseases: inhibitors as promising candidate mitigators.

OBJECTIVE: Ferroptosis is a new form of iron-dependent programmed cell death, characterized by intracellular iron overload and lipid peroxidation. Several studies have revealed that ferroptosis is associated with the occurrence and development of various neurodegenerative diseases (NDs). Therefore, this paper reviews the mechanism and related genes of ferroptosis, focusing on the research of antiferroptosis drugs in NDs to provide theoretical support for future experimental research and clinical application. MATERIALS AND METHODS: This work focuses on ferroptosis, and the authors searched the literature on PubMed related to ferroptosis using the keywords "neurodegenerative diseases" and "neurons". All articles were from August 2022 and earlier, excluding irrelevant or retracted articles, and articles from the last five years were used as the main inclusion criteria. RESULTS: After collection and summary, it was found that ferroptosis in NDs was not only related to iron metabolism, lipid metabolism, and amino acid metabolism but also related to genes such as Nrf2, FSP1, VDACs, and p53. We also summarized drugs that inhibited ferroptosis in NDs and classified them according to their mechanism of action. CONCLUSIONS: Ferroptosis was involved in the progression of NDs through its production mechanism and related genes. Targeting ferroptosis might be a new strategy for treating NDs.

Performance of rupture-related morphological parameters in posterior communicating artery aneurysms with fetal-type variant.

BACKGROUND: The aim of the study was to investigate the impact of fetal-type posterior cerebral artery (fPCA) variant on morphological parameters of posterior communicating artery (PComA) aneurysms for rupture risk assessment. MATERIALS AND METHODS: A total of 98 PComA aneurysms (62 ruptured and 36 unruptured) in 98 consecutive patients were reviewed. Morphological parameters were calculated including aneurysm size, aspect ratio (AR), size ratio (SR), dome-to-neck ratio, bottleneck factor and inflow angle. Performances of morphological parameters to discriminate rupture status were compared between aneurysms with or without fPCA. RESULTS: Fetal-type posterior cerebral artery variant was determined in 39 (39.8%, 25 ruptured and 14 unruptured) lesions. The ruptured group revealed a significantly larger size (p = 0.004), AR (p = 0.003), SR (p = 0.001), and inflow angle (p < 0.001). For the aneurysms without fPCA, all morphological parameters were significantly different between ruptured and unruptured aneurysms (p < 0.05); for the aneurysms with fPCA, only inflow angle (p = 0.001) was significantly related with the rupture status. Multivariate analysis showed that SR (p = 0.035 and p = 0.011) and inflow angle (p = 0.001 and p = 0.028) were independent rupture risk factors for the total cohort and the aneurysms without fPCA; while only inflow angle (p = 0.004) revealed to be independently related with rupture status of aneurysms without fPCA. CONCLUSIONS: The performances of morphological parameters to discriminate rupture status were different between PComA aneurysms with and without fPCA variants. Inflow angle might be a reliable predictor for rupture risk of PComA aneurysms.

Hemodynamic Changes Caused by Multiple Stenting in Vertebral Artery Fusiform Aneurysms: A Patient-Specific Computational Fluid Dynamics Study.

BACKGROUND AND PURPOSE: The multiple stent placement technique has largely improved the long-term outcomes of intracranial fusiform aneurysms, but the hemodynamic mechanisms remain unclear. In this study, we analyzed the hemodynamic changes caused by different stent-placement strategies in patient-specific models using the computational fluid dynamics technique, aiming to provide evidence for clinical decision-making. MATERIALS AND METHODS: Ten vertebral artery fusiform aneurysms were included, and their patient-specific computational fluid dynamics models were reconstructed. A fast virtual stent placement technique was used to simulate sequential multiple stent placements (from a single stent to triple stents) in the vertebral artery fusiform aneurysm models. Hemodynamic parameters, including wall shear stress, pressure, oscillatory shear index, relative residence time, and flow pattern, were calculated and compared among groups with different numbers of stents. RESULTS: Virtual stents were deployed in all 10 cases successfully, consistent with the real stent configuration. Wall shear stress decreased progressively by 7.2%, 20.6%, and 25.8% as the number of stents increased. Meanwhile, relative residence time and pressure increased on average by 11.3%, 15.4%, and 45.0% and by 15.7%, 21.5%, and 28.2%. The oscillatory shear index showed no stable variation trend. Flow patterns improved by weakening the intensity of the vortices and displacing the vortex center from the aneurysmal wall. CONCLUSIONS: Stent placement modifies hemodynamic patterns in vertebral artery fusiform aneurysms, which might favor thrombosis formation in the aneurysmal sac. This effect is amplified with the number of stents deployed. However, a potential risk of rupture or recanalization exists and should be considered when planning to use the multiple stent placement technique in vertebral artery fusiform aneurysms.

Lack of Association between SLC6A11 Genetic Polymorphisms and Drug Resistant Epilepsy in Chinese Han Population.

BACKGROUND: Epilepsy is one of the most common chronic neurological diseases. A recent study has implicated that the genetic variants of the SLC6A11 gene encoding GAT-3, an astrocytic GABA transporter, may influence the efficacy of antiepileptic drugs (AEDs) in the Korean population. METHODS: This study aims to investigate the possible associations between SLC6A11 gene and drug resistance in Chinese epilepsy patients. Genomic DNA from 240 drug resistant epilepsy (DRE) patients and 336 drug responsive epilepsy patients was tested for the polymorphisms using Illumina GoldenGate assay. RESULTS: None of the 14 tagSNP alleles and genotypes were found to be related to DRE. The frequencies of haplotype 5 was obviously lower in DRE patients than that in drug responsive epilepsy patients (1% vs. 4%, OR = 2.56 [0.107 - 0.763], p = 0.01). However, after the correction of multiple comparisons with Bonferroni's method, we found that haplotype 5 was not associated with DRE. CONCLUSIONS: Our study suggested no existing association between the 14 SNPs of SLC6A11 and AEDs efficacy in the Chinese Han population.

Effects of heme oxygenase-1 recombinant Lactococcus lactis on the intestinal barrier of hemorrhagic shock rats.

This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280-320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.

A minicircuitry comprised of microRNA-9 and SIRT1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.

OBJECTIVE: The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML. PATIENTS AND METHODS: Expression of miR-9 and SIRT1 in AE-positive AML patients, healthy donors and AML cell lines were detected by qPCR. Relevance between miR-9 and SIRT1 was assessed by plasmid transfection, Western blot and correlation analysis. Luciferase assay was used to confirm the target gene of miR-9. Knockdown of SIRT1 in different cell lines was achieved by shRNA transfection and CCK-8 assay was used to investigate the effects on cell proliferation. RESULTS: The miR-9 expression was lower in AE-positive cell lines compared to that in other AE-negative AML cell lines, while expression of SIRT1 was higher in AE-positive cell lines. Expression of miR-9 was also downregulated in adult primary t(8;21) AML patients compared to healthy donors. The over-expression of miR-9 decreased luciferase activity of wild-type SIRT1, which was recovered after transfection with mutant SIRT1. The miR-9 directly targets SIRT1 by binding to its 3'-untranslated region and reducing its protein levels. Importantly, miR-9 and SIRT1 mRNA levels were inversely correlated in AE-positive AML cell lines and t(8;21) AML primary leukemia cells. Knockdown of SIRT1 levels using shSIRT1 inhibited cell proliferation in AE-positive AML cell lines. CONCLUSIONS: SIRT1 is the target gene of miR-9 and the signaling pathway connecting miR-9 and SIRT1 is a therapeutic target for t(8;21) AML.

Change in serum TSH levels within the reference range was associated with variation of future blood pressure: a 5-year follow-up study.

Controversy exists on the relationship between serum thyrotropin (TSH) and blood pressure, and only a few prospective studies are available up to now. The study aimed to investigate the association between serum TSH within the reference range and blood pressure through a 5-year follow-up study. A total of 623 subjects with normal TSH were followed up for 5 years, including the measurement of demographic data, blood pressure, height, weight and serum TSH. Finally, 531 subjects were included in this prospective study. Body mass index (BMI), prevalence of hypertension, and systolic and diastolic blood pressure were all higher at follow-up than at baseline. Adjusted for age, gender, smoking status, BMI and homoeostasis model assessment of insulin resistance (HOMA-IR) at baseline, multiple linear regression analyses found no relationship between serum TSH at baseline and levels of blood pressure at follow-up, but the changes in serum TSH levels during follow-up was positively associated with the changes in systolic blood pressure (B=2.134, P<0.05), which became more significant in women but not significant in men. The change of systolic blood pressure in group of TSH increase >0.5 mIU l-1 was significantly higher than in group of TSH decrease >0.5 mIU l-1 within reference, after adjusting for age, gender, smoking status, BMI and HOMA-IR at baseline. This result became more significant in women, but no statistical significance was observed in men. Co-variation with serum TSH levels and blood pressure was observed during 5-year follow-up among people with normal TSH.

Effects of heme oxygenase-1 recombinant Lactococcus lactis on the intestinal barrier of hemorrhagic shock rats

This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280–320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.

Relationships and redundancies of selected hemodynamic and structural parameters for characterizing virtual treatment of cerebral aneurysms with flow diverter devices.

BACKGROUND AND PURPOSE: To quantify the relationship and to demonstrate redundancies between hemodynamic and structural parameters before and after virtual treatment with a flow diverter device (FDD) in cerebral aneurysms. METHODS: Steady computational fluid dynamics (CFD) simulations were performed for 10 cerebral aneurysms where FDD treatment with the SILK device was simulated by virtually reducing the porosity at the aneurysm ostium. Velocity and pressure values proximal and distal to and at the aneurysm ostium as well as inside the aneurysm were quantified. In addition, dome-to-neck ratios and size ratios were determined. Multiple correlation analysis (MCA) and hierarchical cluster analysis (HCA) were conducted to demonstrate dependencies between both structural and hemodynamic parameters. RESULTS: Velocities in the aneurysm were reduced by 0.14m/s on average and correlated significantly (p<0.05) with velocity values in the parent artery (average correlation coefficient: 0.70). Pressure changes in the aneurysm correlated significantly with pressure values in the parent artery and aneurysm (average correlation coefficient: 0.87). MCA found statistically significant correlations between velocity values and between pressure values, respectively. HCA sorted velocity parameters, pressure parameters and structural parameters into different hierarchical clusters. HCA of aneurysms based on the parameter values yielded similar results by either including all (n=22) or only non-redundant parameters (n=2, 3 and 4). CONCLUSION: Hemodynamic and structural parameters before and after virtual FDD treatment show strong inter-correlations. Redundancy of parameters was demonstrated with hierarchical cluster analysis.

High-sensitivity C-reactive protein predicts adverse cardiovascular events in patients with Takayasu arteritis with coronary artery involvement.

The study aimed to assess the association of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) to major adverse cardiovascular events (MACE) in Takayasu arteritis (TA) patients with coronary artery disease (CAD). Data on 60 TA patients with CAD and 60 age- and severity-matched patients with CAD hospitalized in Fuwai Hospital from 2005 to August 2014 were assessed. The clinical features, laboratory data, coronary angiographic findings, treatment, and follow-up outcomes were summarized retrospectively. MACE were defined as death from cardiac causes, myocardial infarction, nonfatal target vessel revascularization, or rehospitalization due to unstable or progressive angina. CAD patients had more atherogenic lipid and lipoprotein profiles such as lower levels of high-density lipoprotein cholesterol (HDL-C) (1.0 ± 0.2 vs. 1.3 ± 0.3 mmol/L, p = 0.01) and higher levels of low-density lipoprotein cholesterol (LDL-C) (2.5 ± 0.9 vs. 2.2 ± 1.1 mmol/L, p = 0.04) in contrast with TA-CAD patients. During a mean follow-up period of 3.2 years, 31 patients with Takayasu coronary arteritis reached the endpoint. Multivariate Cox proportional hazards model demonstrated that log(hsCRP) (HR = 5.3, 95 % CI = 1.1-27.8, p = 0.04) was a significant and independent predictor of MACE in patients with Takayasu coronary arteritis. Elevated baseline levels of hsCRP predict cardiovascular events, independent of other prognostic markers in TA-related CAD patients.

Intra-aneurysmal microcatheter looping technique for stent-assisted embolization of complex intracranial aneurysms.

The endovascular treatment of wide-necked, large and giant aneurysms remains challenging. This retrospective study investigated the feasibility and safety of an intra-aneurysmal microcatheter looping technique for stent-assisted embolization of complicated intracranial aneurysms.This technique was used for 31 patients with complicated cerebral aneurysms from January 2007 to November 2013. The clinical and angiographic results were retrospectively evaluated.The target aneurysms were successfully treated in all cases (100%). A flow diverter was used in seven procedures. There were no aneurysmal perforations or ischemic complications, except for a microguidewire perforation of the distal vessel in one case. Among the 24 cases with conventional stent-assisted embolization, complete embolization or neck residual was obtained in 21 cases. Partial occlusion occurred in three cases.In conclusion, the intra-aneurysmal microcatheter looping technique is a safe and feasible alternative treatment of complicated intracranial aneurysms. This approach is a reasonable choice for patients and leads to successful outcomes.

[MiR-128, a key regulator of oncogenic properties].

MicroRNAs (miRNA) are small noncoding RNAs that are critical regulators of gene function. In the recent years, miRNAs have been increasingly noted for their capacity to regulate key malignant properties of tumor cells. MicroRNA-128 (miR-128) is a brain-enriched miRNA that is normally involved in the development of the nervous system and in the maintenance of neural physiological functions. In tumorcells, miR-128 expression is dysregulated through a variety of genetic and epigenetic events. Dysregulation: of miR-128 has profound effects on tumorigenesis and maintenance of tumor cells through alterations in cellular proliferation, differentiation, metabolism, and apoptosis. This article will review the latest advances in our understanding of miR-128, specifically in the context of clinical and fundamental cancer biology. Further characterization of miR-128 will likely identify its new roles in cancer biology. The use of miR-128 as a diagnostic and/or therapeutic tool may result in improvements in diagnosis, prognosis, and treatment of numerous cancers.

Association of abnormal lipid spectrum with the disease activity of Takayasu arteritis.

Our study aimed to determine whether proatherogenic lipid profiles exist in patients with active Takayasu arteritis (TA) and assess the relationship between different lipid profiles and disease activity in TA. A total of 132 premenopausal female patients with TA and 100 sex-, age-, and body mass index-matched healthy controls were included in our study. The clinical data were collected in detail from all participants. Patients with active TA had significantly lower levels of apolipoprotein A1 (apoA1) (1.47 ± 0.30 vs. 1.99 ± 0.33 mmol/L, p < 0.001) and lower levels of high-density lipoprotein cholesterol (HDL-C) (1.23 ± 0.33 vs. 1.68 ± 0.38 mmol/L, p < 0.001) than patients with inactive TA. However, they had higher ratios of apolipoprotein B (apoB)/apoA1 (0.74 ± 0.27 vs. 0.48 ± 0.14, p < 0.001) compared with patients with inactive TA. Multiple linear regression analysis demonstrated that the apoB/apoA1 ratio was independently associated with TA activity (ß = 0.38, p = 0.04). In addition, multivariate stepwise forward regression analysis showed that the apoB/apoA1 ratio was the major determinant for high-sensitivity C-reactive protein (ß = 0.58, p = 0.002). Our findings indicate that patients with active TA had proatherogenic lipid profiles. In addition, the ratio of apoB to apoA1 could be used as a marker for monitoring and targeting patients with TA.

Quantitative comparison of hemodynamic parameters from steady and transient CFD simulations in cerebral aneurysms with focus on the aneurysm ostium.

OBJECTIVE: To quantitatively compare hemodynamics simulated with steady-state and transient computational fluid dynamics (CFD) simulations in cerebral aneurysms with single inflow, with focus at the aneurysm ostium. METHODS: Transient and steady-state CFD simulations were performed in 10 cerebral aneurysms. Distributions and average values for pressure, helicity, vorticity, and velocity were qualitatively compared at proximal and distal parent artery locations, at the ostium plane, and in the aneurysm, and scaling factors between the two kinds of simulations were determined. Relative inflow and outflow areas at the ostium were compared, as were average inflow and outflow velocities. In addition, values for the pressure-loss coefficient (PLC), a recently introduced parameter to assess aneurysm rupture risk, were compared for both kinds of simulation. RESULTS: Distributions of hemodynamic parameters had a similar shape but were lower for transient than for steady-state simulations. Averaged scaling factors over cases and anatomical locations showed differences for hemodynamic parameters (0.485 ± 0.01 for pressure, 0.33 ± 0.02 for helicity, 0.58 ± 0.06 for vorticity and 0.56 ± 0.04 for velocity). Good agreement between ratios of inflow and outflow areas at the aneurysm ostium was obtained (Pearson correlation coefficient >0.97, p<0.001) and for the PLC (linear regression slope 0.73 ± 0.14, R(2)=0.75). CONCLUSIONS: Steady-state simulations are a quick alternative to transient simulation for visualizing and quantifying inflow and outflow areas at the aneurysm ostium, potentially of value when planning flow diverter treatment and for quantifying the PLC, a potential indicator of aneurysm rupture.

Hepatitis B virus X protein upregulates Lin28A/Lin28B through Sp-1/c-Myc to enhance the proliferation of hepatoma cells.

Hepatitis B virus X protein (HBx) plays critical roles in the pathogenesis of hepatocellular carcinoma (HCC). Here, we were interested in knowing whether the oncogene Lin28A and its homolog Lin28B are involved in the hepatocarcinogenesis mediated by HBx. We showed that the expression levels of Lin28A and Lin28B were increased in clinical HCC tissues, HepG2.2.15 cell line and liver tissues of p21-HBx transgenic mice. Interestingly, the expression levels of HBx were positively associated with those of Lin28A/Lin28B in clinical HCC tissues. Moreover, the overexpression of HBx resulted in the upregulation of Lin28A/Lin28B in hepatoma HepG2/H7402 cell lines by transient transfection, suggesting that HBx was able to upregulate Lin28A and Lin28B. Then, we examined the mechanism by which HBx upregulated Lin28A and Lin28B. We identified that the promoter region of Lin28A regulated by HBx was located at nt -235/-66 that contained Sp-1 binding element. Co-immunoprecipitation showed that HBx was able to interact with Sp-1 in HepG2-X cells. Moreover, chromatin immunoprecipitation (ChIP) demonstrated that HBx could bind to the promoter of Lin28A, which failed to work when Sp-1 was silenced. Electrophoretic mobility shift assay (EMSA) further identified that HBx was able to interact with Sp-1 element in Lin28A promoter via transcription factor Sp-1. In addition, we found that c-Myc was involved in the activation of Lin28B mediated by HBx. In function, Lin28A/Lin28B played important roles in HBx-enhanced proliferation of hepatoma cells in vitro and in vivo. In conclusion, HBx activates Lin28A/Lin28B through Sp-1/c-Myc in hepatoma cells. Lin28A/Lin28B serves as key driver genes in HBx-induced hepatocarcinogenesis.