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Background/Objective: Hematoma expansion (HE) predicts poor outcome and is an appealing treatment target in spontaneous intracerebral hemorrhage (ICH). Clinical evidence has shown an association of HE with peripheral white blood cells (WBC) count, but the individual contributions of leukocyte subtypes between literatures are described inconsistently. Our aim was to determine the relationship between admission absolute and differential leukocyte counts and HE by using different growth definitions. Methods: We analyzed spontaneous ICH patients who underwent baseline cranial computed tomography and blood sampling within 6 h of stroke onset in our institution between September 2013 and August 2018. Hematoma volume was calculated using a semiautomated 3-dimensional reconstruction algorithm. According to commonly used absolute or relative growth definitions (>6 mL, >12.5 mL, or >33%), we defined 5 types of HE. A propensity score-matching analysis was performed to evaluate the influence of complete blood count components on HE across the various growth definitions. The receiver operating characteristic analysis assessed the predictive ability of leukocyte counts for HE. Results: A total of 1,066 patients were included, of whom 11-21% met the 5 HE definitions. After propensity score-matching, except using the definition of >12.5 mL growth or its combination with >33% growth, both WBC and neutrophil count were independently associated with reduced risk of HE (odds ratio [OR] for 103 cells increase; OR, 0.86-0.99; all p < 0.05) after adjusting confounders in multivariate analyses. However, monocyte count was correlated with increased risk of HE under the usage of >12.5 mL expansion definition only (OR, 1.43; p = 0.024). There was no association between lymphocyte count and HE (all p > 0.05). Regardless of the growth definition, admission eosinophil count was directly associated with the risk of HE (OR, 6.92-31.60; all p < 0.05), and was the best predictive subtype with area under the curve 0.64, sensitivity 69.5%, and specificity 58.9% at the optimal cut-off value of 45 cells/µL. Conclusions: Growth definition affects the relationship of HE with leukocyte subtypes counting. Eosinophil count robustly predicts HE, and may be a surrogate when using an inflammatory marker to help select acute ICH patients with high expansion risk for hemostasis treatment in clinical trial and practice.
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Basic fibroblast growth factor (bFGF) has shown great therapeutic effects for diabetic nephropathy (DN). However, its clinical applications are limited due to its short half-life, low stability and poor penetration. Herein, a bFGF-loaded liposome (bFGF-lip) was constructed and combined with ultrasound-targeted microbubble destruction (UTMD) to overcome these drawbacks. bFGF-lip exhibited spherical morphology with a diameter of 171.1 ± 14.2 nm and a negative zeta potential of -5.15 ± 2.08 mV, exhibiting a sustained-release profile of bFGF. DN rat models were successfully induced by streptozotocin. After treatment with bFGF-lip + UTMD, the concentration of bFGF in kidney of DN rats was significantly enhanced in comparison with free bFGF treatment. Additionally, the morphology and the function of the kidneys were obviously recovered after bFGF-lip + UTMD treatment as shown by ultrasonography and histological analyse. The molecular mechanism was associated with the inhibition of renal inflammation. After treatment with bFGF-lip + UTMD, the activation of NF-κB was obviously reduced in the renal tissues, and downstream inflammatory mediators including TGF-ß1, MCP-1, IL-6 and IL-1ß were also down regulated. In addition, inflammation-induced cellular apoptosis of renal tubular cells was also significantly inhibited by detecting Bax, caspase-3 and Bcl-2. Therefore, bFGF-lip in combination with UTMD might be a potential strategy to reverse the progression of early DN.
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Nefropatías Diabéticas/prevención & control , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/farmacología , Riñón/metabolismo , Microburbujas , Ondas Ultrasónicas , Animales , Caspasa 3/metabolismo , Quimiocina CCL2/metabolismo , Nefropatías Diabéticas/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Inflamación/tratamiento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Liposomas , Masculino , Proteínas de la Membrana/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN. CoQ10-lip exhibited a good round morphology with a diameter of 183±1.7nm and a negative zeta potential of -25.3mV, which was capable of prolonging the release of the encapsulated CoQ10. The early DN rat models were induced by streptozotocin (STZ) and confirmed by contrast-enhanced ultrasound (CEUS) and 24-h urinary albumin. After the administration of CoQ10-lip combined with the UTMD technique to rats with early DN, the morphology and function of the kidney were evaluated by ultrasonography, histological and molecular analyses. The renal hemodynamics were significantly improved, moreover, 24-h urinary protein, and oxidative stress indexes were modulated after treatment with CoQ10-lip+UTMD indicating recovery of renal function. An elevated level of Nphs2 protein and reduced caspase 3 level indicated the preservation of podocytes and inhibition of cell apoptosis after CoQ10-lip+UTMD treatment. The molecular mechanism was associated with the upregulation of Bcl-2 and the downregulation of Bax. Moreover, the combination of CoQ10-lip and ultrasound microbubbles demonstrated a better protective effect on the damaged kidney than the other groups (free CoQ10 or CoQ10-lip+/- UTMD). Conclusively, CoQ10-lip in combination with ultrasound microbubbles might be a potential strategy to reverse the progress of early DN.
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Liposomas/química , Microburbujas/uso terapéutico , Nanomedicina Teranóstica , Ubiquinona/análogos & derivados , Animales , Antioxidantes/uso terapéutico , Diabetes Mellitus Experimental , Masculino , Ratas , Ratas Sprague-Dawley , Ubiquinona/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the protective effect and mechanism of curcumin derivatives B06 on myocardium from type 2 diabetic rats. METHODS: Thirty-five male SD rats were randomly divided into 5 groups, normal control group (NC group), high fat group (HF group), high fat treatment group (FT group), diabetes mellitus group (DM group) and diabetes treatment group (DT group) (n = 7). The late four groups were fed with high fat food, after four weeks of high fat feeding, the rats from DM group and DT group were injected with low dosage of streptozocin intraperitoneally to induce diabetes mellitus, FT group and DT group were gavaged with curcumin derivatives B06 at the dosage of 0.2 mg/kg x d. The blood glucose and lipid were detected biochemically, blood insulin was assayed by ELISA and the insulin resistance index was calculated, the morphology of myocardium was observed by light and transmission electron microscopy, the protein expression of AMP-activated protein kinase alpha (AMPKalpha) and phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) in myocardium were tested by Western blot. RESULTS: The level of blood glucose, lipid, insulin and the insulin resistance index were increased in HF group and DM group, but they were decreased after the treatment with B06. The expression of AMPKalpha and p-AMPKalpha were decreased, but they became increased after the treatment of B06. There were increased collagen fibers in interstitium and expansion of mitochondria in cytoplasm of myocardium from DM group, but they were ameliorated in B06 treatment group. CONCLUSION: It is suggested that B06 may relieve the damage of myocardium from type 2 diabetic rats and the increased expression of AMPKalpha and p-AMPKalpha may be involved in it.