ABSTRACT
BACKGROUND: Adjuvant Xuebijing therapy exhibited a protective effect on severe community-acquired pneumonia (SCAP) in previous studies. Blood inflammatory biomarkers related to the disease subtype and severity of SCAP might be associated with the effects of Xuebijing on clinical outcomes of SCAP. PURPOSE: To investigate whether neutrophils or lymphocytes are a useful biomarker of the therapeutic effect of Xuebijing on mortality and inflammation damage index. STUDY DESIGN: A post hoc analysis of a randomized, placebo-controlled and double-blinded clinical trial of Xuebijing in patients with SCAP (Clinical Trial Registration: ChiCTR-TRC-13003534). METHODS: We compared 28-day mortality (primary outcome) and four clinical scores (secondary outcome), including pneumonia severity index (PSI) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, and systemic inflammatory response syndrome (SIRS) score, according to the baseline strata of neutrophil count and lymphocyte count. RESULTS: A total of 675 patients were included in the analyses, of which 334 received Xuebijing and 341 received the placebo. Xuebijing was more effective in SCAP patients with higher lymphocyte counts and lower neutrophil counts. In the lymphocyte-dominated inflammation (LDI) subgroup, defined as neutrophil count <13 × 109 cells/l and lymphocyte count ≥0.65 × 109 cells/l, Xuebijing reduced 28-day mortality by 15% while mortality of the neutrophil-dominated inflammation (NDI) subgroup decreased by 4.7% (p = 0.050). There was also greater improvement in the PSI, SOFA, APACHE II, and SIRS scores following Xuebijing treatment in the LDI subgroup compared with the NDI subgroup. CONCLUSIONS: Xuebijing treatment shows stronger protective effects in SCAP patients with higher lymphocyte and lower neutrophil counts. Our findings may facilitate the selection of the most appropriate treatments for individual patients with SCAP, including who will receive Xuebijing injections.
Subject(s)
Neutrophils , Pneumonia , Humans , Pneumonia/drug therapy , Lymphocyte Count , Systemic Inflammatory Response Syndrome , Adjuvants, Immunologic/therapeutic use , Adjuvants, Pharmaceutic/therapeutic useABSTRACT
In biomaterials and drug delivery, the development of polymeric therapies capable of the synchronized release of several therapeutic agents remains an important challenge. In this article, we describe the development of polymeric nanoparticles (PNPs) with precise molar ratios of Curcumin (CUR) and Methotrexate (MEX). The highly symmetric synthetic approach allows for the development of novel NPs-based combination therapeutic strategies for colorectal cancer. The fabricated CUR/MEX@PNPs were confirmed by transmission microscopy (TEM) and the size and polydispersity index were assessed through the dynamic light scattering (DLS). CUR and MEX were released slowly from the drug delivery without any burst impact. Furthermore, CUR/MEX@PNPs exhibited dose-responsive cytotoxic effects in CL40 and SW1417 cells, with a greater cell death ratio than that of free drugs. The drugs-loaded polymeric nanomaterials were more easily taken up by cancer cells in vitro, according to the cellular uptake analysis. The apoptotic features were confirmed by various fluorescence staining assay. The results of the fluorescent assay reveal that the nanomaterials remarkably induce apoptosis in colorectal cancer cells. Further, the apoptosis cell death mechanism was displayed that these nanomaterials significantly induce apoptosis in the targeted cancer cells. Overall, the current investigation confirmed that CUR/MEX@PNPs could be used to successfully combat colorectal cancers in the immediate future.HighlightsWe have developed the Curcumin (CUR) and Methotrexate (MEX) encapsulated polymeric nanoparticles (CUR/MEX@PNPs).CUR/MEX@PNPs confirmed by the various analytical methods.CUR/MEX@PNPs enhanced the in vitro proliferation against the colorectal cancer cells.Biochemical analysis results reveals that CUR/MEX@PNPs induce apoptosis.The apoptosis was confirmed by Annexin-V-FITC and PI for flow cytometry.
Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Curcumin , Nanoparticles , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Curcumin/pharmacology , Drug Carriers , Drug Delivery Systems , Humans , Particle SizeABSTRACT
The loss regularity of nitrogen (N), phosphorus (P), and chemical oxygen demand (CODMn) of runoff under different rainfall intensity and different management practices in Phyllostachys praecox cv. prevernalis forest land was studied. The total nitrogen (TN) and CODMn concentration in runoff were significantly correlated with the rainfall intensity under the three management modes named as control, fertilization, and cover. Moreover, N mainly lost in the form of nitrate (NO3--N). Generally, the relationship between total and dissolved phosphorus (TP and DP) loss in the three management modes was estimated in following orders: coverage > fertilization > control. The loss of P was mainly in the granular state, and the loss of DP only accounted negligible amount of the TP loss. The loss of CODMn was closely related to the magnitude of rainfall intensity. Results revealed that CODMn concentration in runoff under fertilization and cover management was significantly correlated with the rain fall intensity.
Subject(s)
Water Movements , Water Pollutants, Chemical , China , Environmental Monitoring , Forests , Nitrogen/analysis , Nutrients , Phosphorus/analysis , Rain , Water Pollutants, Chemical/analysisABSTRACT
Nowadays, it is highly desired to develop dual-modal fluorescence and magnetic resonance imaging (FI/MRI) probes in medical imaging because it unites the respective advantages of each imaging modality: high sensitivity of FI and superior spatial resolution of MRI. In this study, a facile strategy to fabricate a new bimodal imaging nanoprobe (Gd-CQDs@N-Fe3O4) was reported by integrating the fluorescence ability of carbon quantum dots (CQDs) and T1 and T2 contrast-enhancing functionality of Gd(III) ions and Fe3O4 nanoparticles into a single hybrid nanostructure. The hybrid composites were investigated by FT-IR, XRD, TEM, XPS, VSM, and so on, which confirmed that Gd-CQDs@N-Fe3O4 nanoparticles were successfully obtained and exhibited superparamagnetic property at room temperature. The derived nanoprobes presented an excitation wavelength-independent emission behavior. In addition, r1 and r2 relaxivities of the synthesized imaging nanoprobes were measured to be 5.16 and 115.6 mM-1 s-1, which nominated Gd-CQDs@N-Fe3O4 nanocomposites as a suitable T1-T2 contrast agent. The Gd-CQDs@N-Fe3O4 nanoparticles combining two synergetic imaging modalities showed great potential in FI/MRI dual-modal imaging for a more complementary and accurate detection.
Subject(s)
Carbon/chemistry , Gadolinium/chemistry , Magnetic Resonance Imaging , Magnetite Nanoparticles/chemistry , Quantum Dots/chemistry , Contrast Media , Fluorescence , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
Hepatocellular carcinoma (HCC) is one of the most malignant types of human primary tumor and has a poor prognosis, therefore, the development of novel therapeutic modalities is necessary. Fatsioside A is a novel baccharanetype triterpenoid glycoside, which is extracted from the fruits of Fatsia japonica. Previous data has revealed that fatsioside A can exert growth inhibition, cell cycle arrest and induce apoptosis in human glioma cells. However, no detailed investigations have been performed to determine its action on human hepatocellular cells, and the exact mechanisms underlying the induction of apoptosis remain to be elucidated. The aim of the present study was to investigate the anticancer effect of fatsioside A in the HepG2 human HCC cell line, and to investigate the underlying mechanisms by focusing on the AMPactivated protein kinase (AMPK) signaling cascade. The results of the present study demonstrated that fatsioside A induced apoptotic death of the human HepG2 HCC cells, which was associated with a marked activation of AMPK and increased expression of the downstream acetylCoA carboxylase carboxylase. Inhibition of AMPK by RNA interference or by its inhibitor, compound C, suppressed fatsioside Ainduced caspase3 cleavage and apoptosis in the HepG2 cells, while AICAR, the AMPK activator, elicited marked cytotoxic effects. Together, these results suggested that fatsioside Ainduced apoptotic death requires AMPK activation in HepG2 cells.
Subject(s)
AMP-Activated Protein Kinases/genetics , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Araliaceae/chemistry , Gene Expression Regulation, Neoplastic , Saponins/pharmacology , AMP-Activated Protein Kinases/antagonists & inhibitors , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/genetics , Acetyl-CoA Carboxylase/metabolism , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Caspase 3/genetics , Caspase 3/metabolism , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Hep G2 Cells , Humans , Plant Extracts/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Ribonucleotides/pharmacology , Saponins/isolation & purification , Signal TransductionABSTRACT
The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish the NAFLD model, then were given oxymatrine treatment (40, 80, and 160 mg/kg, respectively) for another 8 weeks. Body weight gain, liver index, serum and liver lipids, and histopathological evaluation were measured. Enzymatic activity and gene expression of the key enzymes involved in the lipogenesis and fatty acid oxidation were assayed. The results showed that oxymatrine treatment reduced body weight gain, liver weight, liver index, dyslipidemia, and liver triglyceride level in a dose dependant manner. Importantly, the histopathological examination of liver confirmed that oxymatrine could decrease the liver lipid accumulation. The treatment also decreased the fatty acid synthase (FAS) enzymatic activity and increased the carnitine palmitoyltransferase 1A (CPT1A) enzymatic activity. Besides, oxymatrine treatment decreased the mRNA expression of sterol regulatory element binding transcription factor 1(Srebf1), fatty acid synthase (Fasn), and acetyl CoA carboxylase (Acc), and increased the mRNA expression of peroxisome proliferator activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), and acyl CoA oxidase (Acox1) in high fructose diet induced NAFLD rats. These results suggested that the therapeutic effect of oxymatrine on the hepatic steatosis in high fructose diet induced fatty liver rats is partly due to down-regulating Srebf1 and up-regulating Pparα mediated metabolic pathways simultaneously.
Subject(s)
Alkaloids/pharmacology , Diet/adverse effects , Fatty Liver/drug therapy , Fructose/adverse effects , PPAR alpha/metabolism , Quinolizines/pharmacology , Sterol Regulatory Element Binding Protein 1/antagonists & inhibitors , Alkaloids/therapeutic use , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Dyslipidemias/complications , Dyslipidemias/drug therapy , Energy Intake/drug effects , Fatty Acids/metabolism , Fatty Liver/genetics , Fatty Liver/metabolism , Fatty Liver/pathology , Gene Expression Regulation/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Non-alcoholic Fatty Liver Disease , Oxidation-Reduction/drug effects , PPAR alpha/genetics , Quinolizines/therapeutic use , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Signal Transduction/drug effects , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolismABSTRACT
ß-Casomorphin-7 (ß-CM-7) is regarded as the most representative milk-derived bioactive peptide. The present work studies the efficacy of ß-CM-7 against myocardial injury in streptozotocin-induced diabetic rats, focusing on the following assays: (1) the level of blood glucose and advanced glycosylation end product (AGE), the activity of lactate dehydrogenase (LDH) in serum; (2) the level of hydrogen peroxide (H2O2), the activity of Na(+)K(+)-ATPase, Ca(2+)Mg(2+)-ATPase and enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in myocardial tissue; (3) the protein expression of glucose transporter-4 (GLUT-4) in myocardial tissue. It showed that with the influence of ß-CM-7, the levels of blood glucose of ß-CM-7 treatment group decreased markedly compared with model group (P<0.01) accompanied with their alleviated symptoms of diabetes. In the antioxidant and oxidant levels, ß-CM-7 treatment group signified a remarkable increase in the activity of GSH-Px, SOD and CAT of the anti-oxidation system and meanwhile demonstrated a considerable reduction in H2O2 content (all P<0.05) in comparison with model group. We also found both the content of AGE and the activity of LDH of ß-CM-7 treated group considerably reduced while the content of GLUT-4 and the activity of Na(+)K(+)-ATPase and Ca(2+)Mg(2+)-ATPase of ß-CM-7 treated group increased obviously (P<0.05). Meanwhile the cardiac indexes were significantly lessened. Thus our assay validates that the remedy employing ß-CM-7 may treat diabetic cardiomyopathy with high efficacy predominantly associated with the mechanism that ß-CM-7 ameliorates myocardial energy metabolism and abates free-radical-mediated oxidative stress in blood and myocardium.