Pachymic Acid Protects Against Bleomycin-Induced Pulmonary Fibrosis by Suppressing Fibrotic, Inflammatory, and Oxidative Stress Pathways in Mice.

Pachymic acid (PA), a natural extract from Poria cocos (Schw.) Wolf, possesses anti-inflammatory and anti-oxidative properties. However, it is still unknown whether PA can protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, we investigated the effects of PA in mice administered BLM. Our results showed that PA significantly improved lung damage and pathological manifestations. Additionally, PA reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while increasing the level of IL-10. PA also decreased the levels of hydroxyproline and malondialdehyde, and increased the activities of superoxide dismutase and glutathione peroxidase in lung tissue. Furthermore, PA inhibited the increases in pyrin domain-containing protein 3 (NLRP3), ASC, IL-1ß, P20, and TXNIP induced by BLM. In conclusion, our study demonstrated the protective effects of PA against BLM-induced PF in mice by suppressing fibrotic, inflammatory, and oxidative stress pathways.

The Association between Smoking Cessation and Depressive Symptoms: Diet Quality Plays a Mediating Role.

OBJECTIVE: This cross-sectional study aimed to explore the association between smoking cessation and depressive symptoms and investigate the mediating role of dietary quality. METHODS: We used data from the 2007-2014 National Health and Nutrition Examination Survey. Logistic regression models were applied to evaluate the associations between smoking cessation and depressive symptoms. Stratified analysis was performed according to different HEI levels. We examined the mediating role of HEI in the relationship between depressive symptoms and cessation duration using the Karlson-Holm-Breen (KHB) method. RESULTS: A total of 20,004 participants aged 20 years or older were included in the analyses. There were significant correlations between years for smoking cessation and depressive symptoms (OR: 0.985, 95% CI: 0.971~0.999) after adjusting for correlation covariables. A likelihood ratio test showed that there was an interaction between smoking cessation and diet quality (p = 0.047). In the mediation analysis, we estimated that the increase in HEI scores after quitting smoking could explain the 6.91% decline in depressive symptoms. CONCLUSION: In this cross-sectional study, smoking cessation showed a protective effect on depressive symptoms and that diet quality can influence and mediate this association.

DNMT1/miR-130a/ZEB1 Regulatory Pathway Affects the Inflammatory Response in Lipopolysaccharide-Induced Sepsis.

Sepsis is a global health care issue that affects millions of people. DNA methyltransferase I (DNMT1)-mediated DNA methylation is involved in a number of human diseases by affecting many types of cellular progression events. However, the role and underlying molecular mechanism of DNMT1 in development of sepsis remain largely unknown. Lipopolysaccharide (LPS) induced lung fibrosis in the sepsis mouse model, and DNMT1 was upregulated in lung tissues of a sepsis mouse model compared with lung tissues from control mice. Then, this study demonstrated that LPS induced the production of interleukin (IL)-7 and tumor necrosis factor (TNF)-α and promoted DNMT1 expression in primary type II alveolar epithelial cells (AECII cells). Knockdown of DNMT1 inhibited IL-7 and TNF-α secretion in AECII cells exposed to LPS. Further study demonstrated that DNMT1 repressed the expression of miR-130a in AECII cells with or without LPS exposure. Next, this study demonstrated that miR-130a inhibited ZEB1 expression in AECII cells exposed to LPS. Ultimately, this study revealed the role of the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells exposed to LPS. Overall, our data revealed that LPS induced the secretion of inflammatory factors by modulating the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells, thus providing a novel theoretical basis that might be beneficial for establishment of diagnostic and therapeutic strategies for sepsis.

Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets.

Immunosuppressive interleukin-35 (IL-35) serum concentrations were analyzed in patients with active pulmonary Mycobacterium tuberculosis (MTB) infections (PTB), PTB patients after two months treatment (stable PTB) and healthy controls. IL-35 concentrations were highest in active PTB followed by stable PTB cases and lowest in healthy control participants (all P < 0.01). The same trents were found for supernatants of isolated blood mononuclear cells (PBMCs), with additional enhancements after MTB antigen stimulation only for PBMCs of active and stable PTB patients (P < 0.001), for EBI3 and IL-12a transcriptions in PBMCs (P < 0.001) and percentages of EBI3 expressing (CD4 + CD25 + Foxp3+) regulatory T cells (Treg) (P < 0.001). IL-35 antibody applications significantly reversed MTB antigen stimulated IL-35 and IL-10 expression in PBMCs of active and stable PTB patients, and reduced Foxp3 expression in CD4 + CD25 + cells and EBI3 expression in Treg cells, but had no effects on healthy control cells. The percentages of Th1 and Th17 cells in CD4 + cells were enhanced after MTB antigen stimulation of cells taken from active and stable PTB patients, which were partly increased only for Th1 cells after IL-35 antibody exposure. MTB antigen-driven upregulation of IL-35 may lead to reduced immune surveillance in PTB patients.

First Report of Podosphaera xanthii Causing Powdery Mildew on Melothria indica in China.

Melothria indica Lour. is a wild ornamental plant widely distributed in South China. In November 2020, powdery mildew symptoms with 100% (60 plants) incidence were observed on M. indica climbing on a fence in Zhanjiang (21.17N,110.18E), Guangdong, China. The symptoms were typical for powdery mildew with white colonies on leaf surfaces and stems. Conidiophores appeared in all symptomatic tissues. Chasmothecia were observed only during the late stage of disease. Hyphae were hyaline, branched, and septate. Conidiophores were erect, hyaline, smooth, and had a dimension of 61.5 to 185.6 µm × 8.5 to 14.5 µm (n=20) and a cylindrical, flexuous foot cell, followed by 1 to 5 (-6) shorter cells. Conidia were ellipsoid to ovoid and had a dimension of 24.5 to 38.5 µm×15.5 to 21.8 µm (n=50) with well-developed fibrosin bodies. Germ tubes were in the lateral position. Chasmothecia were gregarious or scattered, subglobose, (64.8-) 65.5 µm to 115.5 (-120.5) µm (n=20) in diameter. The appendages were few, and hyphoid. Ascus one per ascomas, clavate, or subglobose, 56.5 to 78.3 (-90) µm×52.5 to 60.5 (-72) (n=20) µm. Each ascus had eight ascospores that were broadly ellipsoid and sized 13.8 to 18.6 µm×12.5 to 16.5 µm (n=30). The morphological characteristics were consistent with the previous description of Podosphaera xanthii (Castagne) U. Braun & Shishkoff (Braun and Cook 2012). Three voucher specimens, Ms-1, Ms-2, and Ms-3, were deposited in the fungus collection at Aquatic Organisms Museum of Guangdong Ocean University, and were used for molecular analysis. Their internal transcribed spacer (ITS) regions were amplified using primers ITS1/ITS4. Amplicons were sequenced and submitted to GenBank (accession no. MW512919, MW512920, and MW512921). The sequences were identical to each other and 100% similar to two of P. xanthii (Accession No. MT472035 and MN818563). On the basis of the morphological and molecular characteristics, the fungus was identified as P. xanthii. Pathogenicity was examined through inoculation by gently pressing the naturally infected leaves onto healthy ones of three potted M. indica plants with three leaves. Healthy leaves were leaves of three further plants which served as the control. White powdery mildew colonies with an incidence of 100% were similarly observed after 7 days at 28 °C and 80% relative humidity in a greenhouse. The fungal colonies on diseased leaves were morphologically identical to the specimen, and the control plants developed no symptoms. The Koch's postulates have completed. Golovinomyces cichoracearum is known to cause powdery mildew on M. indica in China (Liu et al. 2015). P. xanthii (synonym:P. fusca p.p.) is the cause of powdery mildew on cucurbits worldwide (Braun and Cook 2000), including M. indica (synonym:M. japonica) in Korea (Kwon et al. 2015) and Japan (Takamatsu et al. 2005), but hitherto not for China. While, the teleomorph of the fungus on cucurbits is seldom found worldwide and in China only in the north (Liu et al. 2011), chasmothecia are recorded for here southern China (21.17N,110.18E).

Start-up of the anaerobic hydrolysis acidification (ANHA)- simultaneous partial nitrification, anammox and denitrification (SNAD)/enhanced biological phosphorus removal (EBPR) process for simultaneous nitrogen and phosphorus removal for domestic sewage treatment.

The simultaneous partial nitrification, anammox and denitrification (SNAD) process has been widely used in domestic sewage biological denitrification technology because of its high efficiency and low consumption. However, the simultaneous removal of another important pollution element, phosphorus, has been difficult, and its C/N ratio limitation of the influent is strict. The start-up of the anaerobic hydrolysis acidification (ANHA)- simultaneous partial nitrification, anammox and denitrification (SNAD)/enhanced biological phosphorus removal (EBPR) coupling process achieves the treatment of urban sewage for carbon, nitrogen and phosphorus removal. Under optimal conditions, the final total nitrogen and total phosphorus removal rates reached 91.59% and 89.10%, respectively. High-throughput sequencing technology showed that the ANHA reactor was mainly Lactococcus. At the same time, the main bacteria in the SNAD/EBPR process were anammox bacteria (AnAOB, Candidatus_Kuenenia, Candidatus_Brocadia) primarily existing in biofilms, while the ammonium oxidizing bacteria (AOB, Nitrosomonas), denitrifying polyphosphate-accumulating organisms (DPAOs, Pseudomonas, Flavobacterium, Bdellovibrio) and Denitrifying bacteria (DNB, Thauera, Denitratisoma, Rhodobacteraceae).were mainly found in the suspended sludge. These conclusions provide valuable information for the full-scale treatment of domestic sewage.

Design, preparation, characterization, and application of MnxCu1-xOy/γ-Al2O3 catalysts in ozonation to achieve simultaneous organic carbon and nitrogen removal in pyridine wastewater.

In the process of treating high-concentration pyridine wastewater, problems such as low treatment efficiency and total nitrogen (TN) residues are always encountered. Catalytic ozonation can degrade pyridine wastewater well, and it also has the potential to remove TN. However, limited research has been conducted on the development of ozonation catalysts that can simultaneously remove the total organic carbon (TOC) and TN. Density functional theory (DFT) technology can determine the number of active components on the catalyst based on its composition; therefore, it can be used to guide the research and development of such catalysts. Here, we presented a strategy to guide the preparation of two-component Mn and Cu catalysts using DFT technology. By characterising and applying the prepared MnxCu1-xOy/γ-Al2O3 catalysts, it was confirmed that the DFT accurately predicted the changes in the active site content. The selected catalyst also achieved strong TOC and TN removal rates during the catalytic ozonation of high-concentration pyridine wastewater. A Box-Behnken design and response surface methodology was used to optimise the process conditions of catalytic ozonation and verify its stability. Under the optimal reaction conditions, the TOC and TN removal efficiencies from a 500 mg/L pyridine solution were 99.8% and 45.8%, respectively. This work indicated that the use of DFT for the design of catalytic materials was an effective method, which can provide a theoretical basis for material design and reduce the time for material screening.

Resveratrol inhibits cell apoptosis by suppressing long noncoding RNA (lncRNA) XLOC_014869 during lipopolysaccharide-induced acute lung injury in rats.

BACKGROUND: Acute lung injury (ALI) is a common clinical complication with a high mortality rate. Resveratrol (Res) has been shown to protect against ALI, but the role of long noncoding RNAs (lncRNAs) in this process is still unclear. METHODS: Male rats (n=20) aged 7-8 weeks were randomly divided into four groups: control, lipopolysaccharide (LPS), LPS + Res, and LPS + dexamethasone (Dexa). Intragastric administration of Res (0.5 mg/kg) or Dexa (1.5 mg/kg) was performed 1 h before intraperitoneal injection of LPS (5 mg/kg). Lung tissue, serum, and bronchoalveolar lavage fluid were sampled 6 h after LPS treatment for inflammatory factor detection, pathological detection, lncRNA sequencing and bioinformatical analysis, and TdT-mediated dUTP Nick-End Labeling. Quantitative real time polymerase chain reaction and western blotting were used to verify the sequencing results. LPS, Res, and RNA interference were used in rat alveolar epithelial cells experiments to confirm the protective of Res/lncRNA against ALI. RESULTS: Res pretreatment inhibited lung injury and the increase of inflammatory cytokines induced by LPS. The differentially expressed lncRNAs and mRNAs (P<0.05 and |fold change| >2) were mainly involved in the signaling pathway of immunity, infection, signaling molecules and interactions. Among the lncRNAs and mRNAs, 26 mRNAs and 23 lncRNAs had high levels in lungs treated with LPS but decreased with Res, and 17 mRNAs and 27 lncRNAs were at lower levels in lungs treated with LPS but increased with Res. lncRNA and adjacent mRNA analysis showed that lncRNAs XLOC_014869 and the adjacent gene Fos, and the possible downstream genes Jun and Faslg were increased by LPS, but these changes were attenuated by Res. Pretreatment with Res reduced LPS-induced lung tissue apoptosis. Similarly, Res treatment and knockdown of lncRNA XLOC_014869 reduced LPS-induced apoptosis and the levels of Fos, c-Jun, and Fas-L. CONCLUSIONS: Res can inhibit the increase of lncRNAs XLOC_014869 caused by LPS stimulation and inhibit lung cell apoptosis. These effects may be due to lncRNA XLOC_014869 mediation of the pro-apoptotic factors (Fos, c-Jun, and Fas-L).

Sulphur-based autotrophic denitrification of wastewater obtained following graphite production: Long-term performance, microbial communities involved, and functional gene analysis.

Sulphur-based autotrophic denitrification is an energy-efficient NO3--N removal process; it does not require carbon and may potentially replace traditional denitrification processes. This process was used to treat graphite production-derived wastewater and achieved almost complete removal of NO3--N (concentration in effluent: 5.2 mg/L; concentration in influent: 606 mg/L) at a salinity of 15 g/L with a 30 h hydraulic retention time. A unique microbial community was established, in which the abundance of Thiobacillus increased with the increase of the NO3--N concentration and salinity. Metagenomic analysis revealed that the denitrification metabolic pathway in the bioreactor was active. It also revealed the increased activation of nhaH, a gene encoding Na+/H+ antiporters; proA, proB, and proC, genes encoding proline; and Trk and Kdp systems during the treatment of graphite production-derived wastewater to maintain cell function, providing valuable information about utilizing the sulphur-based autotrophic denitrification process to treat graphite production-derived wastewater.

Nano ferrites (AFe2O4, A = Zn, Co, Mn, Cu) as efficient catalysts for catalytic ozonation of toluene.

Nano ferrites (AFe2O4, A = Zn, Co, Mn, Cu) were supported on the surface of γ-Al2O3 support by hydrothermal synthesis to prepare a series of novel composite catalysts (AFe2O4/γ-Al2O3) for catalytic ozonation for elimination of high concentration toluene at ambient temperature. The characterization results showed that the high-purity nano-AFe2O4 particles were uniformly loaded on mesoporous γ-Al2O3. Further, it was confirmed that among the several catalysts prepared, the amount of oxygen vacancies (Ovs), Lewis acid sites (LAS), and Brønsted acid sites (BAS) of the ZnFe2O4/γ-Al2O3 catalyst were the highest. This meant that the ZnFe2O4/γ-Al2O3 catalyst had a strong adsorption capacity for toluene and ozone (O3), and had a strong catalytic activity. When the temperature was 293 K and the space velocity was 1500 h-1, the mol ratio of O3 to toluene was 6, the degradation rate of toluene (600 mg m-3) can reach an optimum of 99.8%. The results of electron paramagnetic resonance (EPR) and Fourier infrared (FT-IR) proved superoxide radicals and hydroxyl radicals by catalytic ozonation. Moreover, the GC-MS analysis results indicated that the toluene degradation began with the oxidation of methyl groups on the benzene ring, eventually producing CO2 and H2O. After repeated experiments, the toluene degradation rate remained stable, and the residual content of O3 in each litre of produced gas was less than 1 mg L-1, thereby indicating that the ZnFe2O4/γ-Al2O3 catalyst had excellent reusability and showed great potential for the treatment of toluene waste gas.

Intramyocardial injection of a fully synthetic hydrogel attenuates left ventricular remodeling post myocardial infarction.

Intramyocardial hydrogel injection is an innovative and promising treatment for myocardial infarction (MI) and has recently entered clinical trials. By providing mechanical support to the ventricular wall, hydrogel injectate may act to preserve cardiac function and slow the remodeling process that leads to heart failure. However, improved outcomes will likely depend on the use of hydrogels specifically designed for this unique application, and better understanding of the mechanisms affected by the intervention. In this work, we present the first large animal study achieving functional and geometrical improvements in treating MI using a relatively stiff, fully synthetic hydrogel designed for intramyocardial injection. In addition, the renin-angiotensin system coincided with the mechanical effects of hydrogel injection and attenuated left ventricular remodeling, even after significant hydrogel degradation had occurred in vivo. These results may inspire further optimization of hydrogel materials used in intramyocardial hydrogel injection therapy and a better description of physiologic pathways affected by its implementation to facilitate successful clinical translation.

Injectable, porous, biohybrid hydrogels incorporating decellularized tissue components for soft tissue applications.

Biodegradable injectable hydrogels have been extensively studied and evaluated in various medical applications such as for bulking agents, drug delivery reservoirs, temporary barriers, adhesives, and cell delivery matrices. Where injectable hydrogels are intended to facilitate a healing response, it may be desirable to encourage rapid cellular infiltration into the hydrogel volume from the tissue surrounding the injection site. In this study, we developed a platform technique to rapidly form pores in a thermally responsive injectable hydrogel, poly(NIPAAm-co-VP-co-MAPLA) by using mannitol particles as porogens. In a rat hindlimb muscle injection model, hydrogels incorporating porosity had significantly accelerated cellular infiltration. To influence the inflammatory response to the injected hydrogel, enzymatically digested urinary bladder matrix (UBM) was mixed with the solubilized hydrogel. The presence of UBM was associated with greater polarization of the recruited macrophage population to the M2 phenotype, indicating a more constructive foreign body response. The hybrid hydrogel positively affected the wound healing outcomes of defects in rabbit adipose tissue with negligible inflammation and fibrosis, whereas scar formation and chronic inflammation were observed with autotransplantation and in saline injected groups. These results demonstrate the value of combining the effects of promoting cell infiltration and mediating the foreign body response for improved biomaterials options soft tissue defect filling applications. STATEMENT OF SIGNIFICANCE: Our objective was to develop a fabrication process to create porous injectable hydrogels incorporating decellularized tissue digest material. This new hydrogel material was expected to exhibit faster cellular infiltration and a greater extent of pro-M2 macrophage polarization compared to control groups not incorporating each of the functional components. Poly(NIPAAm-co-VP-co-MAPLA) was chosen as the representative thermoresponsive hydrogel, and mannitol particles and digested urinary bladder matrix (UBM) were selected as the porogen and the bioactive decellularized material components respectively. In rat hindlimb intramuscular injection models, this new hydrogel material induced more rapid cellular infiltration and a greater extent of M2 macrophage polarization compared to control groups not incorporating all of the functional components. The hybrid hydrogel positively affected the wound healing outcomes of defects in rabbit adipose tissue with negligible inflammation and fibrosis, whereas scar formation and chronic inflammation were observed with autotransplantation and in saline injected groups. The methodology of this report provides a straightforward and convenient mechanism to promote cell infiltration and mediate foreign body response in injectable hydrogels for soft tissue applications. We believe that the readership of Acta Biomaterialia will find the work of interest both for its specific results and general translatability of the findings.

Nitro-Oleic Acid (NO2-OA) Release Enhances Regional Angiogenesis in a Rat Abdominal Wall Defect Model.

Ventral hernia is often addressed surgically by the placement of prosthetic materials, either synthetic or from allogeneic and xenogeneic biologic sources. Despite advances in surgical approaches and device design, a number of postsurgical limitations remain, including hernia recurrence, mesh encapsulation, and reduced vascularity of the implanted volume. The in situ controlled release of angiogenic factors from a scaffold facilitating abdominal wall repair might address some of these issues associated with suboptimal tissue reconstruction. Furthermore, a biocomposite material that combines the favorable mechanical properties achievable with synthetic materials and the bioactivity associated with xenogeneic tissue sources would be desirable. In this report, an abdominal wall repair scaffold has been designed based on a microfibrous, elastomeric poly(ester carbonate)urethane urea matrix integrated with a hydrogel derived from decellularized porcine dermis (extracellular matrix [ECM] gel) and poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nitro-oleic acid (NO2-OA). NO2-OA is an electrophilic fatty acid nitro-alkene derivative that, under hypoxic conditions, induces angiogenesis. This scaffold was utilized to repair a rat abdominal wall partial thickness defect, hypothesizing that the nitro-fatty acid release would facilitate increased angiogenesis at the 8-week endpoint. The quantification of neovascularization was conducted by novel methodologies to assess vessel morphology and spatial distribution. The repaired abdominal wall defects were evaluated by histopathologic methods, including quantification of the foreign body response and cellular ingrowth. The results showed that NO2-OA release was associated with significantly improved regional angiogenesis. The combined biohybrid scaffold and NO2-OA-controlled release strategy also reduced scaffold encapsulation, increased wall thickness, and enhanced cellular infiltration. More broadly, the three components of the composite scaffold design (ECM gel, polymeric fibers, and PLGA microparticles) enable the tuning of performance characteristics, including scaffold bioactivity, degradation, mechanics, and drug release profile, all decisive factors to better address current limitations in abdominal wall repair or other soft tissue augmentation procedures.

Decreased expression of perforin in CD8+ T lymphocytes in patients with Mycobacterium tuberculosis infection and its potential value as a marker for efficacy of treatment.

BACKGROUND: Cytolytic activity against mycobacteria tuberculosis (MTB) within the infected macrophage is a crucial step in the immunity against TB infection, as MTB is an intracellular bacterium. Cytotoxic molecules such as perforin and granzymes produced by cytolytic T cells directly participate in this process. In this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (IFN-γ), perforin and granzyme B in CD8+ T cells from patients with active pulmonary TB (PTB), stable PTB and healthy controls, and explored whether MTB antigen (MTB Ag)-stimulated cytotoxic molecules would be useful for monitoring responses to anti-TB treatment. METHODS: Intracellular IFN-γ, perforin, and granzyme B were measured by flow cytometry in CD8+ T lymphocyte populations from peripheral blood mononuclear cells before and after stimulation with ESAT-6 and CFP-10 peptides for 72 hours. A total of 38 healthy controls, 52 PTB patients after treatment for 2 months and 58 patients with active PTB were enrolled. RESULTS: The positive rate of IFN-γ+ CD8+ T cells was expressed higher in active PTB patients and stable PTB compared to healthy controls. Expression of perforin in CD8+ T lymphocytes was lower in the active PTB than the stable PTB. Positive downregulation of perforin and granzyme B after stimulation with ESAT-6 and CFP-10 peptides in active PTB and stable PTB was seen. IFN-γ was upregulated after stimulation. ROC curve analysis showed that the area under the curve (AUC) of perforin and perforin + IFN-γ after stimulation were 0.766 (P=0.000), 0.802 (P=0.000), respectively. CONCLUSIONS: Our results show that expression of perforin in CD8+ T lymphocytes is downregulated in PTB infection and ESAT-6 and CFP-10 peptides might participate in the downregulation process. This finding cautiously suggests that MTB Ag-stimulated perforin downregulation and IFN-γ upregulation might be a potential index for monitoring therapy response in active PTB patients.

Evaluation of cytology in lung cancer diagnosis based on EBUS-TBNA.

AIMS: Endobronchial ultrasound (EBUS) is a relatively new modality that can be used to guide transbronchial needle aspiration (TBNA) of mediastinal lymph nodes. At present, researches on the sensitivity and specificity of cytopathology based on the EBUS-TBNA are deficient; therefore, we want to evaluate the value of cytology based on the EBUS-TBNA in this article. MATERIALS AND METHODS: We reviewed the 379 cases that underwent the EBUS-TBNA in Shanghai Pulmonary Hospital from April 2010 to May 2011. Discarding the 139 cases with insufficient cells, we analyzed the remaining 240 cases that had enough cells on the smears. STATISTICAL ANALYSIS USED: The Statistical Package for the Social Sciences version 15.0 (SPSS Inc., Chicago, IL) was used for data analysis. A P value of <0.05 was considered significant. RESULTS: We found that the cytologic diagnosis of sensitivity and specificity reached 94.52% and 95.12%, respectively. The sensitivity of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma was up to 88.24%, 100.00%, and 96.00%, respectively. The specificity of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma reached to 100.00%, 100.00%, and 99.25%, respectively. CONCLUSION: Here, we report that the cytological examination of EBUS-TBNA should be acknowledged as a simple, fast, and safe procedure that provides a reasonable sensitivity and specificity of diagnosis in lung cancer.

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy.

BACKGROUND: In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages. METHODS: A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts. RESULTS: Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model. CONCLUSIONS: A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement.

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction.

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.

Effect of transplanted adipose­derived stem cells in mice exhibiting idiopathic pulmonary fibrosis.

Stem cell­based cell therapy has provided a promising method for the treatment of pulmonary diseases, including idiopathic pulmonary fibrosis (IPF). Furthermore, adipose­derived stem cells (ADSCs) have been reported to be effective in lung repair and regeneration. In the current study, IPF was induced in mice by intratracheal instillation of bleomycin (BLM), and ADSCs were delivered systemically into the mice via the tail vein to evaluate the effects of ADSC transplantation. The ADSC engraftment rate and morphometric changes in lung tissue samples in vivo were investigated by histochemistry and immunohistochemistry, as well as by western blotting. The results indicated that ADSCs may relieve IPF and provide a significant contribution to lung repair when administered at an early stage.

Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential.

The ability to modulate the degradation properties of biomaterials such as thermally responsive hydrogels is desirable when exploring new therapeutic strategies that rely on the temporary presence of a placed scaffold or gel. Here we report a method of manipulating the absorption rate of a poly(N-isopropylacrylamide) ((poly(NIPAAm)) based hydrogel across a wide range (from 1 d to 5 mo) by small alterations in the composition. Relying upon the autocatalytic effect, the degradation of poly(NIPAAm-co-HEMA-co-MAPLA), (HEMA = 2-hydroxyethyl methacrylate; MAPLA = methacrylate-polylactide) was greatly accelerated by adding a fourth monomer methacrylic acid (MAA) at no more than 2 mol% to obtain poly(NIPAAm-co-HEMA-co-MAPLA-co-MAA) (pNHMMj) where j reflects the MAA molar % in the reactant mixture. MAA residue introduction decreased the pH inside the hydrogels and in surrounding buffered solutions. Accelerated degradation positively correlated with MAA content in pNHMMj polymers, putatively by the accelerated cleavage of MAPLA residues to raise the transition temperature of the polymer above body temperature. Physical properties including thermal transition behavior and initial mechanical strength did not vary significantly with MAA content. A rat hindlimb injection model generally reflected the in vitro observation that higher MAA content resulted in more rapid degradation and cellular infiltration. The strategy of tuning the degradation of thermally responsive hydrogels where degradation or solubilization is determined by their polyester components might be applied to other tissue engineering and regenerative medicine applications where designed biomaterial degradation behavior is needed.

Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer.

AIMS: Pyruvate kinase M2 (PKM2) and lactate dehydrogenase 5 (LDH5) are two metabolic and oncogenic markers of cancer. In this study, we sought to investigate their expression patterns and prognostic value in tongue squamous cell carcinoma (TSCC). METHODS AND RESULTS: The expression and subcellular localization of PKM2 and LDH5 in TSCC cell lines were determined by Western blot and immunofluorescence. PKM2 and LDH5 abundance was examined by immunohistochemistry in 63 TSCC tumour specimens; their association with multiple clinicopathological parameters and overall patient survival was assessed. The protein levels of PKM2 and LDH5 were both significantly higher in TSCC cells than in an immortalized oral epithelial cell line. Overexpression of PKM2 associated significantly with cervical node metastasis (P = 0.0373), while elevated LDH5 levels correlated significantly with tumour size (P = 0.0094), pathological grade (P = 0.0052), cervical node metastasis (P = 0.0023) and clinical stage (P = 0.0024). Patients with tumours showing an increase in either PKM2 or LDH5 expression displayed significantly reduced overall survival, while patients with tumours overexpressing both proteins showed the worst prognosis with lowest overall survival. Furthermore, PKM2 and LDH5 were identified as independent prognostic predictors for overall patient survival in TSCC. CONCLUSION: Our data indicate that overexpression of PKM2 and LDH5 associates with key clinicopathological features and unfavourable prognosis in TSCC.