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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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Optimization of preparation of hydrogel microspheres by using response surface methodology. • ALG/KGM/COS/Zeolite P hydrogel microspheres with pH sensitivity. • Zeolite P as a key factor to control release of hydrogel microspheres. • The great potential of ALG/KGM/COS/Zeolite P hydrogel microspheres in intestinal bacterial inhibition. Owing to their non-toxicity and non-resistance to bacteria, potassium diformate (KDF) bacterial inhibitors may act as antibacterials in the intestinal tract and are good alternatives to antibiotics; however, KDF has low intestinal utilization rate when used directly. We prepared pH-sensitive sodium alginate (ALG)/konjac glucomannan (KGM)/chitosan oligosaccharide (COS)/Zeolite P hydrogel microspheres for the slow release of KDF using a complex coalescence method to ensure better bacterial inhibition and balance of the gut flora in the intestine. We found that the hydrogen bonding interaction between ALG and KGM, chelating interaction between ALG and Ca2+, and electrostatic interaction of COS together build a three-dimensional porous network structure. Notably, Zeolite P contributes to the formation of a dense three-dimensional network structure to avoid premature release of KDF in the stomach, improve the stability of KDF and prolong its release in the intestine. In vitro bacterial inhibition experiments showed that the maximum antibacterial rates of the hydrogel microspheres were 92 ± 3%, 86 ± 4%, and 88 ± 4% against Escherichia coli , Staphylococcus aureus , and Bacillus subtilis , respectively, indicating that they can effectively inhibit bacterial growth and balance the bacterial flora. In addition, hydrogel antibacterial microspheres are biodegradable and non-cytotoxic. Thus, ALG/KGM/COS/Zeolite P hydrogel microspheres may be used for colon-targeted delivery of drugs. [ABSTRACT FROM AUTHOR]

• The pH-sensitive composite hydrogel microspheres were prepared by the complex coalescence method. • Zeolite p maintains the stability of the hydrogel of the composite hydrogel microspheres. • Anti-bacteria, release and pH sensitive performance of hydrogel antibacterial microspheres. • The kinetics of dissolution and release of composite hydrogel microspheres followed the same trend. • ALG/KGM/COS/Zeolite p composite hydrogel antibacterial microspheres have great potential for intestinal bacterial inhibition. Potassium diformate(KDF) is a non-antibiotic growth promoter. To improve the utilization of KDF in the intestinal tract, P-type zeolite molecular sieve (zeolite P) was used as the drug-binding effector of KDF and was encapsulated in sodium alginate (ALG)/konjac glucomannan (KGM)/chitosan oligosaccharide (COS) composite hydrogel microspheres to prepare environment friendly, intelligent and pH-sensitive composite hydrogel microspheres for controlling the release of KDF. The composite hydrogel microspheres were characterized using XRD, FT-IR, TGA, and SEM. In addition, the swelling behavior of the composite hydrogel microspheres in three buffered media was determined. Thus, the phase composition, structural characteristics, thermal stability, apparent morphology and swelling properties were determined. Results indicated that the composite hydrogel microspheres possessed pH sensitivity, compatibility and porous 3D network structure. Furthermore, ALG formed polyelectrolyte complexes with COS, providing the composite hydrogel microspheres a complete three-dimensional network structure. The embedded network structure of zeolite P, which limited the size of the inner capsule, assisted in improving the thermal stability, and allowed expansion and controlled release of KDF. Under a simulated gastrointestinal environment, the in vitro release conformed to a good pH-sensitive drug release pattern and prevented premature release of KDF in the gastric juice. In the in vitro antibacterial test, the maximum inhibition rate of the antibacterial agent against Escherichia coli, Staphylococcus aureus and Bacillus subtilis were 96.63%, 93.81% and 93.31%, respectively, indicating its considerable potential as an intestinal antibacterial. A pH sensitive composite hydrogel microsphere loaded with KDF was prepared to maximize the bacteriostatic effect of KDF in the intestinal tract. Notably, the strong hydrogen bonding between ALG and KGM, the polyelectrolyte layer formed by COS and ALG and Zeolite P acted as a skeletal support, all of which contributed to the controlled release of KDF. Moreover, the composite hydrogel microspheres possessed significant growth inhibitory effects on E. coli, S. aureus and Bacillus subtilis. [Display omitted] [ABSTRACT FROM AUTHOR]

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 β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]