Suppression of proliferation, migration and invasion in non-small cell lung cancer cells via profilin 2 inhibition by microRNA-194

Purpose: To investigate the anti-tumor effect of microRNA-194 (miR-194) and possible relationship with profilin 2.Methods: The expressions of miR-194 and profilin 2 were investigated via  bioinformatic analysis and were further verified using quantitative real-time  polymerase chain reaction (qRT-PCR) in both normal and non-small cell lung cancer (NSCLC) cells. Dual luciferase reporter assay, together with transfection, was  applied to determine the effect of miR-194 and profilin 2 on proliferation, migration and invasion, and its underlying mechanisms.Results: Relatively low expression of miR-194 and high expression of profilin 2 in cancerous lung tissue were found through bioinformatic analysis and further confirmed by qRT-PCR on normal and NSCLC cell lines. Profilin 2 was the direct target of miR-194. Also, miR-194 overexpression inhibited the proliferation,  migration and invasion of NSCLC cells, and this suppressive effect was partially  reversed by transfection of pcDNA3.1-PFN2 plasmid.Conclusion: The results show that miR-194 plays a tumor suppressor role in NSCLC development. It inhibits the proliferation, migration and invasion of NSCLC cells via profilin 2 suppression. Interventions targeting the miR-194/profilin 2 axis may  therefore serve as a clinical strategy for the prevention and treatment of NSCLC metastases.Keywords: Non-small cell lung cancer, MicroRNA-194, Profilin 2, Proliferation, Migration, Invasio

Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy

AbstractNewcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2) could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients.Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0–24 h).Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0–24 h nor normalized AUCss, 0–24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = −0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0–24 h (r = −0.414, p = 0.049). Patients with AUCss, 0–24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0–24 h < 50 mg·h/L or patients with AUCss, 0–24 h 50–100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose.Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023

Mental Health Disorders of Home Care Elders in the United States: A Secondary Analysis of the Outcome and Assessment Information Set (OASIS)

Home care has been the fastest growing sector in the U.S. healthcare system for over three decades. In 2012, there were over 4.7 million home care patients in the United States. Most of these patients were elders (4 million); and this number is expected to increase as the U.S. population continues to age. One major health concern in this elderly home care population is mental health disorders (MHDs), which have been noted with increasing rates and substantial consequences in local data. However, much of our knowledge on this topic was generated from local studies that had a number of methodological limitations. These include over reliance on local and outdated data, a lack of theoretical foundation, and a lack of statistical justification, which may well account for the high variability across findings. To date, no national investigation has been conducted on this topic, supporting the need for a large-scale study which employs recent data to better understand the prevalence, risk factors and impact of MHDs among home care elders in the U.S. This dissertation study addressed these gaps by using the de-identified national home care dataset, Outcome and Assessment Information Set (OASIS), to: 1) examine the national prevalence of MHDs and MHD-caused medical events in the U.S. elderly home care population, and 2) identify factors associated with MHDs and MHD-caused medical events in this population. The 5% random sample used in this study was consisted of 28,475 elderly home care patients: their average age was 79.41; patients were mostly female, white, Medicare beneficiaries, referred from short-stay acute hospitals, and living with others at home. Approximately 38% of this sample had MHDs, mostly depression (28.0%) and anxiety (18.9%). Compared with other patients, those with MHDs were younger, more likely to be female, smokers, frail, living alone, referred from psychiatric hospitals, cognitively or sensually impaired, in poorer general health, had a recent history of falls or multiple hospitalizations, and evidenced insufficient social support. Among patients identified with MHDs, less than one third (31.8%) received mental health services, including psychiatric nursing services (n=317) and depression interventions (n=4,459). During the 60-day home care episode, 16.95% of the sample had subsequent hospitalizations and 12.72% had subsequent emergent care events; 0.45% of these medical events were directly caused by MHDs. In addition, depression intervention was the strongest risk factor for these subsequent medical events, associated with an approximate two-fold risk for all-cause hospitalizations (HR: 1.943) and emergent care events (HR: 1.974). However, 61.61% (n=2,747) of these high-risk depression intervention recipients did not screen positive for depression at admission. Findings in this dissertation study revealed the high national prevalence of MHDs in the elderly U.S. home care population, and the strong association between these disorders and subsequent all-cause medical events. However, these MHDs were largely under-detected and under-managed in this population, highlighting the need for closer monitoring and targeted intervention through enhanced psychiatric training among front-line home care nurses. Recommendations for further work are made, including the development of an electronic algorithm of identified MHD correlates and risk factors as useful in the development of a nationwide monitoring system for geriatric MHDs in the home care setting

Technological Innovations and Data-Driven Support for Older Adults

Entering a new digital era where novel devices and emerging technologies, including artificial intelligence, are playing an incredible role with significant impact on health and health care delivery, JMIR Aging commits to supporting the community of patients and families, clinicians, and scientists to improve the efficiency, equity, and effectiveness of older adult care through the dissemination of cutting-edge evidence

Spatial heterogeneity characteristics of soil-epikarst thickness in a typical karst dolomite small watershed

Objective The thickness of soilepikarst is an important index affecting the hydrological process of critical zones. The spatial heterogeneity is critical understanding the structural evolution mechanism of the key zones of the Earth and the water conservation function of the key zones of the Earth. Methods Based on the 1.4 km2 area of the Mulian catchment in Huanjiang, Guangxi, the 1 731 soil-epikarst thickness samples were obtained through electrical resistivity tomography (ERT) with 45 sampling lines.The spatial distribution pattern of soil and epikarst thickness and its influencing factors were investigated. The results showed that the average thickness of soil and epikarst was 1.15 m and 6.44 m with strong and medium variance, respectively. Results The results of geostatistical analysis indicated that the spherical model and exponential model could reflect the spatial structure characteristics of soil and epikarst thickness, respectively. Soil thickness showed moderate spatial autocorrelation, a long range and good spatial continuity. However, the epikarst presented strong spatial autocorrelation and spatial dependence with a short range. Soil thickness was affected by multiple environmental factors (topographic wetness index, vertical curvature, curvature, aspect, slope, elevation, coverage, outcrop ratio and NDVI), while the thickness of epikarst was more affected by soil thickness and vegetation type. Conclusion These results are helpful for understanding the evolution of the soil-epikarst zone and provide a scientific basis for the spatial prediction of soil-epikarst thickness in karst areas

Preferential Flow in Different Soil Architectures of a Small Karst Catchment

In karst regions, soil architecture varies along topographical locations, resulting in marked differences in infiltration rates. However, the relationship between soil architecture and preferential flow (PF) is still unclear. In this study, dye tracing was used to investigate PF and the dominant effects of five types of soil architecture in a small karst catchment. These soil architectures included deep clay soil in farmland (CSF) and deep clay soil in shrubland (CSS) in the depression; shallow clay soil with minimally weathered, slanted bedrock on downslope locations (CSWD); shallow sandy loam soil with highly weathered bedrock on midslope locations (SLSM); and sandy loam soil with rock fragments on upslope locations (SLSU). The results showed that macropores and cracks were the major channels that resulted in a high degree of PF in depressions and downslope locations. Preferential flow also continued along the rock–soil interface in the downslope locations. Finger flow mainly appeared in mid- and upslope locations, and cracks mainly appeared in the surface soil layer. However, down- and upslope locations showed lower PF. We observed that PF might not contribute to the different infiltration rates in different topographical locations. Tillage in depressions damages macropores, thereby minimizing vertical percolation. The high saturated hydraulic conductivity () of the soil matrix covered the development of PF in the mid- and upslope locations, and the decrease in weakened the formation of PF as a result of heterogeneity of soil properties. These findings demonstrate that infiltration-excess runoff may occur in depressions and downslope locations and that saturation-excess runoff may occur in mid- and upslope locations

The ongoing role of serum uric acid in blood pressure

Positive association between blood pressure (BP) and uric acid is evident, but specific effect size of serum uric acid (SUA) at different levels on BP is unclear, and interaction effect of SUA with other metabolic factors on BP was rarely reported. A cross-sectional study was conducted by making use of data from an epidemic investigation. A total of 3658 subjects were enrolled in our data analysis. In male subjects, for each 1 mg/dL increase in the SUA level, systolic blood pressure (SBP) and diastolic blood pressure (DBP) increased by 1.339 mmHg [95% CI: 0.552–2.126] and 0.515 mmHg [95% CI: 0.013–1.016], respectively, after adjusting for age, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), estimated-glomerular filtration rate (eGFR), body mass index (BMI), drinking, smoking, and waist–hip ratio (WHR). And in female subjects, for each 1 mg/dL increase in the SUA level, SBP and DBP increased by 1.180 mmHg [95% CI: 0.401–1.959] and 0.549 mmHg [95% CI: 0.086–1.011], respectively, after adjusting the same factors. In males, in subjects with SUA < 6 mg/dL, SBP increased by 0.585 mmHg [95% CI: −0.976 to 2.146] for each 1 mg/dL increase in the SUA level, while in subjects with SUA ≥ 6 mg/dL, SBP increased by 3.271 mmHg [95% CI: 1.244–5.297] (p interaction = 0.0369), after adjusting age, BMI, smoking, drinking, TG, TC, FPG, eGFR, and WHR. This difference was not observed in DBP and females. Interaction effects between SUA and BMI, TG, FPG on BP were discovered. In conclusion, higher level of SUA has a stronger effect on BP and other metabolic factors: FPG, TG, and BMI could strengthen the effect of SUA on BP