Predictive Value of Serum Markers SFRP1 and CC16 in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) patients are particularly vulnerable to acute exacerbation, resulting in a huge socioeconomic burden. Objective: In this study, we evaluated the value of serum secreted frizzled-related protein 1 (SFRP1) and Clara cell-secreted protein (CC16) in predicting the risk of acute exacerbations in patients with COPD. Methods: The study included 123 COPD patients admitted to our hospital from May 2020 to June 2021, including 65 patients in stable stage (STCOPD group), 58 patients in acute exacerbation stage (AECOPD group), and 60 healthy volunteers (control group). Serum SFRP1 and CC16 levels were detected by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristics curve (ROC) analysis was performed to evaluate the sensitivity and specificity of serum SFRP1 and CC16 for predicting the risk of acute exacerbation in COPD patients. Results: The age among groups is significantly different, but there is no difference in the gender and body mass index (BMI). The level of serum SFRP1 in the AECOPD group was significantly higher than that in the STCOPD group and the control group, and the level of serum CC16 was lower than that in the STCOPD group and the control group. Serum SFRP1 was negatively correlated with forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (r = -0.473, P < 0.001). Serum CC16 was positively correlated with FEV1/FVC (r = 0.457, P < 0.001). The area under the curve (AUC), sensitivity, and specificity of SFRP1 for predicting the risk of exacerbation was 0.847 (95% CI: 0.775 to 0.920), 86.20%, and 80.00%. The AUC, sensitivity, and specificity of CC16 for predicting the risk of exacerbation were 0.795 (95% CI: 0.711 to 0.879), 74.10%, and 86.20%. Conclusions: These findings suggest that SFRP1 and CC16 may be useful serum markers for predicting the risk of exacerbation in COPD patients.

The Beneficial Effect of an Intra-articular Injection of Losartan on Microfracture-Mediated Cartilage Repair Is Dose Dependent.

BACKGROUND: A previous publication demonstrated that the oral intake of losartan promoted microfracture-mediated hyaline-like cartilage repair in osteochondral defects of a rabbit knee model. However, an intra-articular (IA) injection of losartan may have direct beneficial effects on cartilage repair and has not been studied. PURPOSE: To determine the dosage and beneficial effects of an IA injection of losartan on microfracture-mediated cartilage repair and normal cartilage homeostasis. STUDY DESIGN: Controlled laboratory study. METHODS: Rabbits were divided into 5 groups (n = 6 each): a microfracture group (MFX group) and 4 different losartan treatment groups that received varying doses of IA losartan (0.1, 1, 10, and 100 mg per knee). An osteochondral defect (5 mm) was created in the trochlear groove cartilage of 1 limb in each rabbit, and 5 microfracture perforations were made in the osteochondral defect. Both the injured and the contralateral knee joints were injected with IA losartan immediately after microfracture and at 2 and 4 weeks after surgery. Rabbits were sacrificed at 6 weeks after surgery for analysis including gross observation, micro-computed tomography, histology, and reverse transcription quantitative polymerase chain reaction. RESULTS: Micro-computed tomography and gross observation demonstrated comparable subchondral bone healing and hyaline-like cartilage morphology in the 0.1-, 1-, and 10-mg losartan groups relative to the MFX group. Conversely, the 100-mg losartan group showed neither bony defect healing nor cartilage repair. Histology revealed higher O'Driscoll scores and hyaline-like cartilage regeneration in the 1-mg losartan group compared with the MFX group. In contrast, the 100-mg losartan group showed the lowest histology score and no cartilage repair. An IA injection of losartan at the doses of 0.1, 1, and 10 mg did not cause adverse effects on uninjured cartilage, while the 100-mg dose induced cartilage damage. Quantitative polymerase chain reaction results showed downregulation of the transforming growth factor ß (TGF-ß) signaling pathway after IA losartan injection. CONCLUSION: An IA injection of losartan at the dose of 1 mg was most effective for the enhancement of microfracture-mediated cartilage repair without adversely affecting uninjured cartilage. Conversely, a high dose (100 mg) IA injection of losartan inhibited cartilage repair in the osteochondral defect and was chondrotoxic to normal articular cartilage. CLINICAL RELEVANCE: An IA injection of losartan at an optimal dosage represents a novel microfracture enhancement therapy and warrants a clinical trial for future clinical applications.

Polysaccharide-based recoverable double-network hydrogel with high strength and self-healing properties.

Polysaccharide-based hydrogels (PSBHs) have received significant attention for numerous bio-applications due to their biocompatibility and non-immunogenic performance. However, the construction of PSBH with superior mechanical properties by a simple method is rarely adequately researched. This study focuses on the construction of a novel PSBH with superior mechanical and recoverable properties by integrating the synergistic and complementary interactions of covalent bond-associated oxidized sodium alginate (SA-CHO) gel and hydrogen bond-associated agarose (Aga) gel. With the synergy and complementarity of the SA-CHO and Aga networks, the hydrogel exhibited 17 and 15 times (20 and 9 times) greater compressive stress and modulus, respectively, compared with the SA-CHO gel (Aga gel). The hydrogel also displayed excellent fatigue resistance, recurrent shapeability, acid resistance and recovery ability, as well as self-healing ability. This study provides a unique perspective for enhancing the mechanical properties of PSBH through the synergy and complementarity of different kinds of polysaccharides without sacrificing the functionality of the PSBH.

Preparation of ZnO Nanoparticles with High Dispersibility Based on Oriented Attachment (OA) Process.

Understanding nanoparticle growth mechanisms is crucial for the synthesis of nanocrystals with desired biological and chemical properties. Growth of nanocrystals by oriented attachment (OA) is frequently reported as a method supplementary to the classical growth by Ostwald ripening (OR) process. In this work, ZnO nanoparticles (NPs) were prepared by wet chemical method. Size/shape evolution of ZnO NPs in ethanol solution was systematically studied using transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray diffraction (XRD). In addition, a detailed process of the nanoparticle growth-based OA mechanism is discussed. Results revealed that reaction conditions affect size/shape of NPs and change their surface structure: prior to OA, the surface of adjacent particles transformed into their "rough" states. We proved that stability of the solution was significantly improved in this state. Such a state is important to design nanoparticles with high stability and as nano-suspensions with special physical and/or chemical properties. This state is a critical step in enhancing OA process.

Gentianella turkestanerum Showed Protective Effects on Hepatic Injury by Modulating the Endoplasmic Reticulum Stress and NF-κB Signaling Pathway.

OBJECTIVE: To investigate the protective effects of Gentianella turkestanerum extraction by butanol (designated as GBA) on hepatic cell line L02 injury induced by carbon tetrachloride (CCl4) and hydrogen peroxide (H2O2). METHODS: L02 cells were incubated with 5 µg/mL, 10 µg/mL, 20 µg/mL, 40 µg/mL, 60 µg/mL, 80 µg/mL and 100 µg/mL GBA for 24 hours, and then MTT assay was used to screen the cytotoxicity for GBA. Cells were divided into blank control group, CCl4/H2O2 model group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L); silymarin+CCl4/H2O2 group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L) and 5 µg/mL silymarin; GBA+CCl4/H2O2 group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L) and GBA (5 µg/mL, 10 µg/mL and 20 µg/mL). MTT assay was performed to determine the cellular activity. Malondialdehyde (MDA) content was determined using a commercial kit. The alanine transaminase (ALT), aspartate transaminase (AST) in the supernatant was determined. PE-Annexin V/7-ADD method was utilized to determine the apoptosis of cells. RT-PCR was used to evaluate the expression of endoplasmic reticulum stressrelated genes (CHOP, PERK, IRE1 and ATF6) mRNA. Western blot analysis was performed to determine the expression of CHOP, Caspase 12 and NF-κB protein. RESULTS: Cellular survival after GBA (5 µg/mL, 10 µg/mL and 20 µg/mL) incubation was ≥ 75%. After GBA incubation, levels of ALT and AST showed a significant decrease (P < 0.05), while that of the MDA showed a significant decrease (P < 0.05). The apoptosis in the CCl4 or H2O2 group showed a significant increase compared to the control group (P < 0.05). In contrast, GBA-preincubation could attenuate the cellular apoptosis compared to the CCl4 or H2O2 group, which displayed a dose-dependent manner (P < 0.05). The expression of CHOP, PERK, IRE1 and ATF6 mRNA was significantly up-regulated in the presence of CCl4 or H2O2 (P < 0.05). Whereas, GBA induced a significant decrease in these mRNA thereafter (P < 0.05), together with a decrease in CHOP and Caspase 12 proteins (P < 0.05). Besides, it could attenuate the expression of NF-κB p65 in nuclear protein. CONCLUSION: G. turkestanerum could inhibit the lipid peroxidation and increase the antioxidant activity. Also, it could inhibit the cellular apoptosis through down-regulating the transcriptional level of ERS related genes and proteins. This process was associated with the nuclear translocation of NF-κB p65 protein.

Toxicity of zearalenone on the intestines of pregnant sows and their offspring and alleviation with modified halloysite nanotubes.

BACKGROUND: The objective of this study was to examine the effects of maternal exposure to zearalenone (ZEN) on the intestines of pregnant sows and offspring on postnatal days (PD) 1, 21 and 188. Eighteen pregnant sows (six per treatment) were fed a control diet (ZEN, 0.03 mg kg-1 ), ZEN diet (ZEN, 2.77 mg kg-1 ) and ZEN + 1% modified halloysite nanotube (MHNT) diet (ZEN, 2.76 mg kg-1 ) respectively from gestation days (GD) 35 to 70. At the end of the experiment, three sows of each group on GD70 and the offspring on PD1, PD21 and PD188 were killed to analyze the changes of intestines. RESULTS: The results showed that ZEN caused oxidative stress, an inflammatory response, changes in the structure of jejunum and alterations of the bacterial numbers in cecal digesta in pregnant sows and PD1 and PD21 piglets. On PD188, bacterial numbers were also altered. MHNTs supplementation reduced the amount of ZEN in the intestine and reversed to a large extent the effects induced by ZEN on the intestines of pregnant sows and offspring. CONCLUSION: The results obtained from this study indicated that MHNTs treatment was beneficial for the adsorption of ZEN in the intestine of sows. © 2017 Society of Chemical Industry.

Preparation and evaluation of microemulsion­based transdermal delivery of Cistanche tubulosa phenylethanoid glycosides.

The primary aim of the present study was to develop a novel microemulsion (ME) formulation to deliver phenylethanoid glycoside (PG) for use in skin lighteners and sunscreens. The oil phase was selected on the basis of drug solubility, while the surfactant and cosurfactant were screened and selected on the basis of their solubilizing capacity and the efficiency with which they formed MEs. Pseudoternary phase diagrams were constructed to evaluate ME regions and five formulations of oil­in­water MEs were selected as vehicles. In vitro skin permeation experiments were performed to optimize the ME formulation and to evaluate its permeability in comparison to that of saline solution. The physicochemical properties of the optimized ME and the permeating ability of PG delivered by this ME were also investigated. The optimized ME formulation was composed of isopropyl myristate (7%, w/w), Cremorphor EL (21%, w/w), propylene glycol (7%, w/w) and water (65%, w/w). The cumulative amount of PG that permeated through excised mouse skin when carried by ME was ~1.68 times that when PG was carried by saline solution only. The cumulative amount of PG in the microemulsion (4149.650±37.3 µg·cm­2) was significantly greater than that of PG in the saline solution (2288.63±20.9 µg·cm­2). Furthermore, the permeability coefficient indicated that optimized microemulsion was a more efficient carrier for transdermal delivery of PG than the control solution (8.87±0.49 cm/hx10­3 vs. 5.41±0.12 cm/hx10­3). Taken together, the permeating ability of ME­carried PG was significantly increased compared with saline solution.

Identification and Characterization of the Major Chemical Constituents in Fructus Akebiae by High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time-of-Flight Mass Spectrometry.

Fructus Akebiae (FA), the dry fruit of Akebia quinata (THUNB.) DECNE., possesses potent antidepressant properties. Owing to the structural complexity, high polarity and thermal lability in plants, it is difficult and time-consuming to analyze the major chemical constituents by traditional strategies that involve extraction, isolation, purification and identification by chemical manipulations and spectroscopic methods. In this study, a high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS-MS) method was established for quickly identifying the chemical constituents in the extract of Fructus Akebiae. The main saponin components in the extract of Fructus Akebiae were detected with the HPLC-ESI-Q-TOF-MS-MS in negative-ion mode. These components were further analyzed by MS(2) spectra, and compared with the corresponding reference substances and literature data. Nineteen saponins in the extract of Fructus Akebiae were well separated in one run. The new method is accurate and rapid. It can be used to identify the main chemical constituents in the extract of Fructus Akebiae and can be suitable for the quality control of Fructus Akebiae.

A role of Yueju in fast-onset antidepressant action on major depressive disorder and serum BDNF expression: a randomly double-blind, fluoxetine-adjunct, placebo-controlled, pilot clinical study.

INTRODUCTION: Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD). METHODS: Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7. RESULTS: In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not. CONCLUSION: Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment.

The virus-induced signaling adaptor molecule enhances DNA-raised immune protection against H5N1 influenza virus infection in mice.

As an adaptor molecule in the retinoic acid-inducible gene-I (RIG-I) signaling pathway, the virus-induced signaling adaptor (VISA) molecule activates NF-κB and IRF3 and thereby leads to the production of type I interferons (IFNs). To explore the potential of VISA as a genetic adjuvant for DNA vaccines, a eukaryotic expression plasmid, pVISA, was generated by cloning the VISA gene into the pVAX1vector. For comparison, the pTRIF plasmid was similarly constructed, encoding the known genetic adjuvant TRIF (TIR-domain-containing adapter-inducing interferon-ß), an adapter in the Toll-like receptor (TLR) signaling pathway. Mice were immunized with the chimeric DNA vaccine pHA/NP(147-155), which encodes the HA (hemagglutinin) fused with NP (nucleoprotein) CTL epitope (NP(147-155)) of H5N1 influenza virus, either alone or in combination with pVISA or pTRIF. Antigen-specific immune responses were examined in immunized mice. Our results demonstrate that co-immunization of the pHA/NP(147-155) plasmid with the VISA adjuvant augmented DNA-raised cellular immune responses and provided protection against H5N1 influenza virus challenge in mice. In addition, our data suggest that VISA acts as a stronger adjuvant for DNA immunization than TRIF. We conclude that co-inoculation with a vector expressing the adaptor molecule VISA enhanced the protective immunity against H5N1 infection induced by pHA/NP(147-155) and that VISA could be developed as a novel genetic adjuvant for DNA vaccines.