Construction of pH-sensitive sodium alginates/sodium carboxymethyl cellulose/zeolite P composite hydrogel microspheres loaded with potassium diformate.

As a substitute for feed antibiotics, potassium diformate (KDF) can effectively inhibit bacterial overgrowth in the gastrointestinal tract. To avoid the sudden release of KDF in the stomach, this article proposes a new controlled drug delivery system for controlled drug release. In this system, P-type zeolite molecular sieve (Zeolite P) and drug KDF are combined and embedded into the hydrogel microspheres of sodium alginate (ALG) and sodium carboxymethyl cellulose (CMC). In addition, ALG/CMC/Zeolite P composite hydrogel microspheres were prepared with Ca2+ as the crosslinking agent. The structure, composition, morphology, and thermal stability of the hydrogel microspheres were systematically characterized. The effect of the composition ratio of ALG and CMC on the swelling properties of the hydrogel microspheres was also investigated. The results revealed that ALG and CMC form a hydrogen bond and chelate with Ca2+ to form a double crosslinked network structure. Thus, Zeolite P can be effectively encapsulated in the hydrogel microspheres to form a dense three-dimensional network structure. Particularly, Zeolite P helps in improving the thermal stability of microspheres, balance the swelling properties, and control the release of KDF. The drug release results and release kinetics reveal that the ALG/CMC/Zeolite P composite hydrogel has higher drug release in an environment with pH 7.4. The release kinetics follow the Ritger-Peppas model and the first-order kinetic model, which indicates that the composite hydrogel has good specific pH sensitivity. In vitro antibacterial experiments revealed that the composite hydrogel microspheres have broad-spectrum antibacterial activity, and certain inhibitory effects on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis.

ZNF561-AS1 Regulates Cell Proliferation and Apoptosis in Myocardial Infarction Through miR-223-3p/NLRP3 Axis.

Long non-coding RNAs (lncRNAs) have been widely recognized as important regulators in myocardial infarction (MI) and other heart diseases. Our study aimed to investigate the mechanism and biological function of an unknown lncRNA zinc finger protein 561 antisense RNA 1 (ZNF561-AS1) in MI. After confirming the MI model was successful, we applied reverse transcription quantitative polymerase chain reaction and Western blot (WB) and found that the expression of NLR family pyrin domain containing 3 (NLRP3), interleukin (IL)-1ß, and IL-18 was substantially increased in infarct and border zones of MI mice heart at 24 h and 72 h compared with that in sham-operated models. Moreover, we found that NLRP3 expression was promoted in hypoxia human cardiomyocytes (HCMs). Through cell function assays including CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, and TdT-mediated dUTP Nick-End Labeling (TUNEL), supported by WB analysis, we verified that silencing of NLRP3 facilitated proliferation but impeded apoptosis of hypoxia-induced myocardial cell. Moreover, Ago2-RIP and RNA pull-down assays displayed that NLRP3 could combine with miR-223-3p. Luciferase reporter assays further confirmed that NLRP3 was directly targeted by miR-223-3p. Simultaneously, we found that miR-223-3p was the downstream gene of ZNF561-AS1. In addition, we conducted a series of rescue experiments to affirm that ZNF561-AS1 regulated cell proliferation and apoptosis in MI through miR-223-3p/NLRP3 axis.

Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression.

BACKGROUND/AIMS: Lung cancer continues to be the leading cause of cancer related deaths worldwide due to its high incidence, malignant behavior and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. METHODS: We first evaluated the IL-35 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by realtime PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs were assessed. RESULTS: IL-35 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The down-regulation of IL-35 was significantly correlated with the results of American Joint Committee on Cancer stage, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-35 in NSCLC cells suppressed cell migration, invasion, proliferation, colony formation through suppressing ß-catenin. IL-35 inhibited NSCLC formation in the mice model and sensitize the cancer cells to chemotherapy drugs. CONCLUSION: Our results showed that IL-35 plays an inhibitory role in NSCLC development and function as a novel prognostic indicator and a potential therapeutic target.

Do Wet-Dry Ratio and Fe-Mn System Affect Oxidation-Reduction Potential Nonlinearly in the Subsurface Wastewater Infiltration Systems?

To understand characteristics of on-line oxidation-reduction potential (ORP) in a subsurface wastewater infiltration system (SWIS) under different intermittent influent conditions, ORP among five matrix depths at wet-dry ratios (Rwds) of 2:1, 1:1 and 1:2 with a hydraulic load of 0.10 m³·(m²·d)-1 were monitored. Results showed that the optimal Rwd for the SWIS was 1:1. In that case, ORP at 40 and 65 cm depths changed significantly, by 529 mV and 261 mV, respectively, from the inflow period to the dry period, which was conducive to the recovery of the oxidation environment. It was concluded that ORP varied nonlinearly in strongly aerobic and hypoxic environment. Wastewater was fed into the SWIS at 80 cm and dissolved oxygen diffused at the initial period of one cycle. As a consequence, ORP at 65 cm increased with water content increasing. However, ORP at 40 and 95 cm displayed inverse trends. Moreover, results showed that ORP decreased with Fe2+ and Mn2+ increasing under aerobic conditions (p < 0.05) because Fe2+ and Mn2+ moved with wastewater flow. Effluent met reuse requirements and no clogging was found in the SWIS during the operation.

Astragalus Polysaccharides Attenuate Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats.

Astragalus polysaccharides (APS) have been shown to possess a variety of biological activities including anti-oxidant and anti-inflammation functions in a number of diseases. However, their function in pulmonary arterial hypertension (PAH) is still unknown. Rats received APS (200[Formula: see text]mg/kg once two days) for 2 weeks after being injected with monocrotaline (MCT; 60[Formula: see text]mg/kg). The pulmonary hemodynamic index, right ventricular hypertrophy, and lung morphological features of the rat models were examined, as well as the NO/eNOS ratio of wet lung and dry lung weight and MPO. A qRT-PCR and p-I[Formula: see text]B was used to assess IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] and WB was used to detect the total I[Formula: see text]B. Based on these measurements, it was found that APS reversed the MCT-induced increase in mean pulmonary arterial pressure (mPAP) (from 32.731[Formula: see text]mmHg to 26.707[Formula: see text]mmHg), decreased pulmonary vascular resistance (PVR) (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text] min/L to 246.351[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L), and reduced right ventricular hypertrophy (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L to 246.351 mmHg[Formula: see text][Formula: see text][Formula: see text]min/L) ([Formula: see text]0.05). In terms of pulmonary artery remodeling, the WT% and WA% decreased with the addition of APS. In addition, it was found that APS promoted the synthesis of eNOS and the secretion of NO, promoting vasodilation and APS decreased the MCT-induced elevation of MPO, IL-1[Formula: see text], IL-6 and TNF-[Formula: see text], reducing inflammation. Furthermore, APS was able to inhibit the activation of pho-I[Formula: see text]B[Formula: see text]. In couclusion, APS ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via eNOS/NO and NF-[Formula: see text]B signaling pathways.

Serum carcinoembryonic antigen, neuron-specific enolase as biomarkers for diagnosis of nonsmall cell lung cancer.

OBJECTIVE: To investigate the clinical efficacy of serum carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) as biomarkers for diagnosis of nonsmall cell lung cancer (NSCLC). MATERIAL AND METHODS: Forty-six cytology or pathology confirmed nonsmall cell lung patients and 33 cases of benign lung disease (BLD) were retrospective reviewed in our hospital from February 2013 to January 2016. The serum concentrations of CEA and NSE were measured by chemiluminescent assay. The sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (area under the curve) of serum CEA and NSE as biomarkers for diagnosis of lung cancer were analyzed by SPSS version 17.0 software. RESULTS: The serum CEA and NSE concentration were 30.69 ± 14.11 ng/mL, 52.36 ± 49.68 ng/mL for NSCLC patients and 12.69 ± 8.87 ng/mL, 5.32 ± 4.66 for BLD patients, respectively with statistical difference (P < 0.05); the diagnostic sensitivity and specificity were 58.66% and 76.48% for serum CEA at the cutoff value of 5.74 ng/mL and 66.67% and 78.69% for serum NSE at the cutoff value of 19.35 ng/mL; the diagnostic area under the ROC curve was 0.81 and 0.76 for CEA and NSE, respectively as biomarkers for diagnosis of NSCLC. CONCLUSION: Serum CEA and NSE are potential biomarker for NSCLC diagnosis.

Downregulation of leptin inhibits growth and induces apoptosis of lung cancer cells via the Notch and JAK/STAT3 signaling pathways.

Previous studies have documented that leptin is involved in the pathogenesis of many human cancer types by regulation of numerous signal transduction pathways. The aim of this study was to investigate the biological roles of leptin and the mechanisms attributed to its action in non-small cell lung cancer (NSCLC) cell lines. The expression of leptin was measured by quantitative real-time PCR and western blot in seven NSCLC cell lines. Proliferation and apoptosis of NSCLC cells in response to leptin knockdown were determined by MTT assay and flow cytometry, respectively. The effect of leptin knockdown on the Notch and JAK/STAT3 signaling pathways was further examined by western blot. Leptin expression was significantly increased in NSCLC cell lines compared with normal human bronchial epithelial cell HBE. Leptin knockdown inhibited cell proliferation and induced apoptosis in NSCLC cell lines through inactivation of the Notch and JAK/STAT3 signaling pathways. Furthermore, gene silencing of Notch signaling with Notch-1 siRNA or inhibition of JAK/STAT3 signaling by JSI-124, an inhibitor of STAT3, resulted in proliferation inhibition and apoptosis induction in NSCLC A549 cells. Our findings suggested that leptin knockdown could become a new approach for the prevention of lung cancer progression, which is likely to be mediated at least partially by inactivation of the Notch and JAK/STAT3 signaling pathways.