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Exosomes (exos) are primarily responsible for the process of mesenchymal stem cells (MSCs) treatment for acute lung injury (ALI), but the mechanism remains unclear, particularly in altered microenvironment. Therefore, this study aimed to investigate the potential mechanism of exos derived from human umbilical cord mesenchymal stem cells (hucMSCs) primed with interferon-gamma (IFN-γ) on ALI and to propose a promising and cell-free strategy. This study extracted exos from hucMSCs supernatant primed and unprimed with IFN-γ marked with IFN-γ-exos and CON-exos, which were identified and traced. IFN-γ-exos administration to ALI models suppressed the NF-κB signaling pathway compared to CON-exos, which were quantified through western blot and immunohistochemical staining. Reverse transcription-quantitative polymerase chain reaction validated miR-199b-5p expression in the IFN-γ-exos and CON-exos treatment groups. Data analysis, a dual-luciferase reporter assay, and cell transfection were conducted to investigate the target binding between miR-199b-5p and Aftiphilin (AFTPH), with AFTPH expression analyzed via cell immunofluorescence and western blot. Co-immunoprecipitation was conducted for the interaction between AFTPH and NF-κB p65. The result revealed that miR-199b-5p was down-regulated in the IFN-γ-exos treatment group, which had a target binding site with AFTPH, and an interaction with NF-κB p65. Consequently, IFN-γ-exos inhibited the NF-κB signaling pathway in ALI in vitro and in vivo through the miR-199b-5p/AFTPH axis. Our results demonstrated new directions of novel and targeted treatment for ALI. [ABSTRACT FROM AUTHOR]

The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure (CXL 118, CXL121, and CXL122) is described in this report. The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity. Notably, these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the presentation and management of hypertension secondary to Takayasu arteritis (TA) in a large cohort, single center in China. We retrospectively analyzed 381 TA patients with hypertension hospitalized in Fuwai hospital between Jan. 2004 and Feb. 2014. Diagnosis of hypertension was according to clinic blood pressure or the central blood pressure measured during angiography. Renal artery stenosis was the most common cause (264, 69.3%), followed by the thoracic descending aorta stenosis (98, 25.7%), abdominal aorta stenosis (78, 20.5%), and severe aortic regurgitation (45, 11.8%). More than two kinds of pathologies were found in 98 (25.7%) patients. The mean age of hypertension onset was 25.0 ± 14.3 years. The mean blood pressure of upper extremity in patients without bilateral subclavian artery stenosis (321, 84.3%) was 176.0 ± 29.4 mmHg/97.2 ± 23.0 mmHg, while in 60 (15.7%) patients with bilateral subclavian artery stenosis, the mean central blood pressure was 192.7 ± 30.8 mmHg/102.4 ± 121.1 mmHg. A total of 305 were followed for 38.4 ± 36.7 months, and the rate of blood pressure control, improvement, and failure was 50.8, 41.0, and 8.2%, respectively. Immunosuppressive therapy (OR 2.402, 95% confidence interval 1.253-4.603, P = 0.008) and the pathogenesis of hypertension (P = 0.010) were associated with prognosis of hypertension. The pathogenesis of hypertension due to TA is very complex and multifactorial. Renal artery stenosis is most frequently observed, followed by stenosis of the thoracic descending aorta, abdominal aorta, and severe aortic regurgitation. Immunosuppressive therapy and identifying the pathogenesis of hypertension is of great importance in patients with TA. [ABSTRACT FROM AUTHOR]

Neonatal diabetes mellitus (NDM) is a rare monogenic disorder presenting as uncontrolled hyperglycemia during the first 6 months of life. Hyperglycemic hyperosmolar state (HHS) is quite rare in NDM patients, and reported experience with this condition is limited. Continuous renal replacement therapy (CRRT) is frequently used as a mode of dialytic treatment in critically ill patients with acute renal failure, but has seldom been used in patients with diabetic ketoacidosis (DKA) and HHS. We report the case of a 2-month-old infant admitted to our hospital presenting with dyspnea and lethargy. Blood gas showed severe hyperosmotic DKA. After 21 h of fluid and insulin therapy, the baby presented with increased drowsiness and irregular respiration, which suggested cerebral edema. Moreover, the DKA and HHS were exacerbated. After 18 h of CRRT, the patient gradually recovered from DKA and HHS. The gene analysis revealed a de novo mutation (c.602G > A (p.R201H)) of the KCNJ11 gene, and oral glibenclamide successfully replaced insulin treatment in the patient. [ABSTRACT FROM AUTHOR]

Purpose: Currently, almost all adrenal venous sampling (AVS) procedures are performed by femoral vein access. The purpose of this study was to establish the technique of AVS via an antecubital approach and evaluate its safety and feasibility.Materials and Methods: From January 2012 to June 2015, 194 consecutive patients diagnosed as primary aldosteronism underwent AVS via an antecubital approach without ACTH simulation. Catheters used for bilateral adrenal cannulations were recorded. The success rate of bilateral adrenal sampling, operation time, fluoroscopy time, dosage of contrast, and incidence of complications were calculated.Results: A 5F MPA1 catheter was first used to attempt right adrenal cannulation in all patients. Cannulation of the right adrenal vein was successfully performed in 164 (84.5%) patients. The 5F JR5, Cobra2, and TIG catheters were the ultimate catheters for right adrenal cannulation in 16 (8.2%), 5 (2.6%), and 9 (4.6%) patients, respectively. For left adrenal cannulation, JR5 and Cobra2 catheters were used in 19 (9.8%) and 10 (5.2%) patients, respectively, while only TIG catheters were used in the remaining 165 (85.1%) patients. The rate of successful adrenal sampling on the right, left, and bilateral sides was 91.8%, 93.3%, and 87.6%, respectively. The mean time of operation was (16.3 ± 4.3) minutes, mean fluoroscopy time was (4.7 ± 1.3) minutes, and the mean use of contrast was (14.3 ± 4.7) ml. The incidence of adrenal hematoma was 1.0%.Conclusions: This study showed that AVS via an antecubital approach was safe and feasible, with a high rate of successful sampling. [ABSTRACT FROM AUTHOR]

Different choices of control variables in variational assimilation can bring about different influences on the analyzed atmospheric state. Based on the WRF model's three-dimensional variational assimilation system, this study compares the behavior of two momentum control variable options-streamfunction velocity potential ( ψ-χ) and horizontal wind components ( U-V)-in radar wind data assimilation for a squall line case that occurred in Jiangsu Province on 24 August 2014. The wind increment from the single observation test shows that the ψ-χ control variable scheme produces negative increments in the neighborhood around the observation point because streamfunction and velocity potential preserve integrals of velocity. On the contrary, the U-V control variable scheme objectively reflects the information of the observation itself. Furthermore, radial velocity data from 17 Doppler radars in eastern China are assimilated. As compared to the impact of conventional observation, the assimilation of radar radial velocity based on the U-V control variable scheme significantly improves the mesoscale dynamic field in the initial condition. The enhanced low-level jet stream, water vapor convergence and low-level wind shear result in better squall line forecasting. However, the ψ-χ control variable scheme generates a discontinuous wind field and unrealistic convergence/divergence in the analyzed field, which lead to a degraded precipitation forecast. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic and metabolic bone disease. New drugs with good curative effect, fewer side effects, and high safety need to be developed urgently. Recently, simvastatin has been used to treat osteoporosis more frequently; however, its clinical effect and treatment mechanism are still unknown. With the use of animal models, the treatment effectiveness of simvastatin on experimental osteoporosis was investigated and the functional mechanism was preliminarily explored. The results show that simvastatin significantly increased the mechanical parameters such as maximum load, stiffness, and energy-absorbing capacity, and improved the microarchitecture. They indicated that the antiosteoporosis activity of simvastatin may be due to the promotion of proliferation and differentiation of osteoblasts. Simvastatin was effective in treating experimental osteoporosis. This study provides necessary experimental evidence for the clinical application of simvastatin in osteoporosis treatment. [ABSTRACT FROM AUTHOR]

Bevacizumab (Bev), a monoclonal antibody against vascular endothelial growth factor, when combined with standard first-line chemotherapy, shows impressive clinical benefit in advanced non-squamous non-small cell lung cancer (ns-NSCLC). Our study aims to investigate whether the addition of Bev to pemetrexed improves progression-free survival (PFS) in advanced ns-NSCLC patients after the failure of at least one prior chemotherapy regimens. Patients with locally advanced, recurrent, or metastatic ns-NSCLC, after failure of platinum-based therapy, with a performance status 0 to 2, were eligible. Patients received 500 mg/m of pemetrexed intravenously (IV) day 1 with vitamin B12, folic acid, and dexamethasone and Bev 7.5 mg/kg IV day 1 of a 21-day cycle until unacceptable toxicity, disease progression or the patient requested therapy discontinuation. The primary end point was PFS. Between December 2011 and October 2013, 33 patients were enrolled, with median age of 55 years and 36.4 % men. Twenty-three patients (69.7 %) had received two or more prior regimens, and 28 patients (84.8 %) had received chemotherapy containing pemetrexed. The median number of the protocol regimens was 4. Median PFS was 4.37 months (95 % CI 2.64-6.09 months). Median overall survival (OS) was 15.83 months (95 % CI 10.52-21.15 months). Overall response rates were 6.45 %. Disease control rate was 54.84 %. No new safety signals were detected. No patient experienced drug-related deaths. The combination of Bev and pemetrexed every 21 days is effective in ns-NSCLC patients who failed of prior therapies with improved PFS. Toxicities are similar with historical data of these two agents and are tolerable. Our results may provide more a regimen containing Bev and pemetrexed for Chinese clinical practice in previously treated ns-NSCLC. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy is frequently caused by pressure overload (i.e., high blood pressure or hypertension) and can lead to heart failure. The major objective of the present study was to investigate the proteomic changes in response to the development of left ventricular hypertrophy (LVH) induced by abdominal aortic banding (AB) and its prevention by antihypertensive treatment with angiotensin II receptor blocker (ARB) telmisartan. One week after AB and Sham surgery, rats were assigned into three groups: SHAM-control, aortic banding without treatment (AB-Ctrl) and aortic banding with telmisartan treatment (AB-Telmi; 5mg/kg/day for 8 weeks). Echocardiography, hemodynamics, and pathology were performed to assess LVH. Left ventricular myocardium was sampled. The analysis of proteomic proteins from myocardium was performed by two-dimensional gel electrophoresis and MALDI-TOF-MS. In AB-Ctrl, heart rate, systolic arterial blood pressure, diastolic blood pressure, left ventricular end systolic pressure, interventricular septal thickness at diastole, posterior wall thickness in diastole, heart weight (HW) and HW/body weight (BW) were increased, indicating that both hypertension and LVH developed. Telmisartan prevented hypertension and LVH. Concurrently, among numerous proteins, there were 17 that were differentially expressed among hypertrophic hearts, normal hearts, and the hearts where hypertrophic response was suppressed by ARB treatment. Primarily, proteins involved in cell structure, metabolism, stress and signal transduction exhibited up-regulations in LVH, providing cellular and molecular mechanism for hypertrophic development. These changes were prevented or greatly attenuated by telmisartan regimen. Interestingly, antioxidative-related heat shock protein 2 was detected neither in SHAM-Ctrl nor in AB-Ctrl, but in AB-Telmi. LVH is accompanied by series changes of protein expression. Both LVH and proteomic changes can be prevented by blockade of renin-angiotensin system with telmisartan. These protein alterations may constitute mechanistic pathways leading to hypertrophy development and experimental targets for novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

Genetically modified (GM) crops have brought various economic benefits but may also have adversely affected soil microorganisms. To examine whether transgenic high-methionine soybean ZD91 alters the bacterial community structure in the rhizosphere, we performed a 2-year follow-up study using the transgenic high-methionine soybean cultivar ZD91 and wild type cultivar ZD. The community composition and the relative abundance of bacteria in rhizosphere soil were determined by sequencing of the 16S rRNA amplicon. Our results indicated that transgenic soybean ZD91 had no significantly effects on rhizosphere bacterial communities. Instead, the plant growth stage and year appeared to have a stronger effect on bacterial communities. Our findings therefore provided reliable scientific evidence for potential commercial cultivation of cultivar ZD91. [ABSTRACT FROM AUTHOR]