Seeking the adsorption of tetracycline in water by Fe-modified sludge biochar at different pyrolysis temperatures.

The composite material SBC-Fe-x with sludge and Fe3+ was developed by different calcination temperatures (600, 700, and 800 °C) for the removal of tetracycline (TC). The adsorption rates of SBC-Fe-600, SBC-Fe-700, and SBC-Fe-800 were 77.5%, 89%, and 91%, respectively. Furthermore, the Langmuir model indicated that the maximum adsorption capacity of SBC-Fe-700 (157.93 mg/g) was three times greater than that of SBC-Fe-600. The conclusions were confirmed by a series of characterizations that SBC-Fe-700 showed a larger specific surface area, well-developed pore structure, rich oxygen-containing functional groups and a high degree of graphitization. The results of pH experiments indicated the broad applicability of SBC-Fe-700 for TC adsorption. In addition, SBC-Fe-700 suggested outstanding performance in different water environments. This work produced a feasible adsorbent for the removal of TC, and a new direction for sludge resource utilization was proposed.

Metal-Organic Frameworks Marry Sponge: New Opportunities for Advanced Water Treatment.

Metal-organic frameworks (MOFs) have garnered attention across various fields due to their noteworthy features like high specific surface area, substantial porosity, and adjustable performance. In the realm of water treatment, MOFs exhibit great potential for eliminating pollutants such as organics, heavy metals, and oils. Nonetheless, the inherent powder characteristics of MOFs pose challenges in terms of recycling, pipeline blockage, and even secondary pollution in practical applications. Addressing these issues, the incorporation of MOFs into sponges proves to be an effective solution. Strategies like one-pot synthesis, in situ growth, and impregnation are commonly employed for loading MOFs onto sponges. This review comprehensively explores the synthesis strategies of MOFs and sponges, along with their applications in water treatment, aiming to contribute to the ongoing advancement of MOF materials.

Novel indocyanine green-loaded photothermal nanoparticles targeting TRPV1 for thermal ablation treatment of severe murine asthma induced by ovalbumin and lipopolysaccharide.

To identify a replacement strategy for bronchial thermoplasty (BT) with non-invasive and free-of-severe side effect is urgently needed in the clinic for severe asthma treatment. In this study, PLGA-PEG@ICG@TRPV1 pAb (PIT) photothermal nanoparticles targeting bronchial TRPV1 were designed for photothermal therapy (PTT) against severe murine asthma induced by ovalbumin and lipopolysaccharide. PIT was formulated with a polyethylene glycol (PEG)-grafted poly (lactic-co-glycolic) acid (PLGA) coating as a skeleton structure to encapsulate indocyanine green (ICG) and was conjugated to the polyclonal antibody against transient receptor potential vanilloid 1 (TRPV1 pAb). The results revealed that PIT held good druggability due to its electronegativity and small diameter. PIT demonstrated great photothermal effects both in vivo and in vitro and exhibited good ability to target TRPV1 in vitro because of its selective cell uptake and specific cell toxicity toward TRPV1-overexpressing cells. The PIT treatment effectively reduced asthma symptoms in mice. This is evident from improvements in expiratory airflow limitation, significant decreases in inflammatory cell infiltration in the airways, and increases in goblet cell and columnar epithelial cell proliferation. In conclusion, PIT alleviates severe murine asthma symptoms through a combination of TRPV1 targeting and photothermal effects.

Effects of human umbilical cord blood mononuclear cells on ovalbumin-induced asthma in mice.

Background: Umbilical cord blood mononuclear cells (UCMNCs) show broad immune-modulation effects, which may be helpful for treating asthma. Effects of UCMNCs on asthma were investigated with mouse model in present study. Methods: Asthma was induced in BALB/c mice by ovalbumin (OVA) immunization and challenge. Asthmatic mice were then treated on days 7 and 20 with intravenous injections of UCMNCs in doses of 4×105, 2×106, and 107 cells per mouse for the low-dose UCMNC (UCMNCL), medium-dose UCMNC (UCMNCM), and high-dose UCMNC (UCMNCH) groups, respectively. Fetal mouse blood mononuclear cells (FMMNCs) were administered to FMMNC group at a dose of 2×106 cells per mouse as approximate allograft control. Airway hyperresponsiveness (AHR), airway inflammation indexes, and CD4/CD8 T cell subsets were measured at day 25. Results: Compared with the model group, AHR in the UCMNCL group, inflammation score of lung tissue in the UCMNCM group, interleukin (IL)-5 in bronchoalveolar lavage fluid (BALF) in UCMNCL group, IL-5 and IL-13 in BALF in UCMNCM group, and IL-17 in serum in UCMNCH group were significantly inhibited. Compared with the model group, CD4+CD8+ T cells were reduced in the UCMNCL group, while decrease of CD4-CD8- T cells and increase of CD4+CD8- T cells were further strengthened in UCMNCM group. FMMNC treatment significantly reduced the IL-13 and IL-17 in serum, decreased CD4-CD8- and CD4+CD8- T cells, and increased the CD4+CD8+ and CD4-CD8+ T cells in BALF. Conclusions: UCMNCs can modulate AHR, T-helper (Th)2 inflammation, and airway injury in experimental asthma at appropriate dose.

The impact of freezing methods on the quality, moisture distribution, microstructure, and flavor profile of hand-grabbed mutton during long-term frozen storage.

The aim of present study was to investigate the influence of conventional freezing (CF, -18 °C), low-temperaturefreezing (LF, -40 °C), and ultra-low-temperature freezing (ULF, -80 °C) on the quality, moisture distribution, microstructure, and flavor profile of hand-grabbed mutton (HGM) during frozen storage (0, 30, 60, 90, 120, 150 and 180 days). The TPC, TVB-N, and TBARS values increased significantly with prolonged storage, while the moisture content decreased (P < 0.05). Additionally, the concentrations of aldehydes, alcohols, ketones, acids, and alkenes decreased significantly as the storage duration increased. However, the concentrations of esters and heterocyclics increased (P < 0.05). Notably, at 30-180 days of storage, the TBARS and TVB-N values in ULF samples were significantly lower than those in CF and LF samples, while the moisture content was significantly higher (P < 0.05). Low field-nuclear magnetic resonance (LF-NMR) analysis showed that ULF decreased water migration and maintained the original texture characteristics of HGM during frozen storage. The ULF and LF groups had significantly higher levels of volatiles than the CF group (P < 0.05). The findings show that ULF, with its relatively rapid freezing rates, can still maintain the high quality of HGM after 180 days of frozen storage, contributing to quality control.

Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

BACKGROUND: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. METHODS: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. RESULTS: Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. CONCLUSIONS: Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells.

BACKGROUND: Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs. METHODS: Primary human ABSCs were isolated from healthy volunteers. A Flexcell FX-5000 Tension system was used to mimic the pathological airway mechanical stretch conditions of patients with CAD. ABSCs were stretched for 12, 24, or 48 h with 20% elongation. We first performed bulk RNA sequencing to identify the most predominantly changed genes and pathways. Next, apoptosis of stretched ABSCs was detected with Annexin V-FITC/PI staining and a caspase 3 activity assay. Proliferation of stretched ABSCs was assessed by measuring MKI67 mRNA expression and cell cycle dynamics. Immunofluorescence and hematoxylin-eosin staining were used to demonstrate the differentiation state of ABSCs at the air-liquid interface. RESULTS: Compared with unstretched control cells, apoptosis and caspase 3 activation of ABSCs stretched for 48 h were significantly increased (p < 0.0001; p < 0.0001, respectively), and MKI67 mRNA levels were decreased (p < 0.0001). In addition, a significant increase in the G0/G1 population (20.2%, p < 0.001) and a significant decrease in S-phase cells (21.1%, p < 0.0001) were observed. The ratio of Krt5+ ABSCs was significantly higher (32.38% vs. 48.71%, p = 0.0037) following stretching, while the ratio of Ac-tub+ cells was significantly lower (37.64% vs. 21.29%, p < 0.001). Moreover, compared with the control, the expression of NKX2-1 was upregulated significantly after stretching (14.06% vs. 39.51%, p < 0.0001). RNA sequencing showed 285 differentially expressed genes, among which 140 were upregulated and 145 were downregulated, revealing that DDIAS, BIRC5, TGFBI, and NKX2-1 may be involved in the function of primary human ABSCs during mechanical stretch. There was no apparent difference between stretching ABSCs for 24 and 48 h compared with the control. CONCLUSIONS: Pathological stretching induces apoptosis of ABSCs, inhibits their proliferation, and disrupts cilia cell differentiation. These features may be related to abnormal regeneration and repair observed after airway epithelium injury in patients with CAD.

Investigation Tracing the Origin of Tan Sheep Visceral Tissues through Mineral Elements.

The traceability of quality mineral fingerprints in the viscera of Tan sheep from northwest China was studied. Twenty-five mineral elements in the heart and liver samples of Tan sheep were determined using an inductively coupled plasma mass spectrometer (ICP-MS), and the characteristics of the mineral elements in the visceral tissues of the Tan sheep were further analyzed in combination with a principal component analysis (PCA), hierarchical cluster analysis (HCA), and linear discriminant analysis (LDA) to establish a discriminant model and verify it. The results show that 11 elements (137Ba, 43Ca, 63Cu, 56Fe, 39K, 31P, 60Ni, 78Se, 118Sn, 125Te, and 66Zn) in the Tan sheep heart samples had significant differences among different regions (p < 0.05), and the results of the LDA show that the accuracy rate of the return-generation examination was 85.70%, and the accuracy rate of the hand-over-fork examination was 87.50%; 10 elements (111Cd, 59Co, 52Cr, 56Fe, 39K, 55Mn, 95Mo, 23Na, 121Sb, and 78Se) in the Tan sheep liver samples had significant differences among different regions (p < 0.05), and the results of the LDA showed that the accuracy rate of the return-generation examination was 96.30%, and the accuracy rate of the hand-over-fork examination was 86.25%. This indicates that the multi-element analysis has potential for determining the origin of Tan sheep viscera in certain regions.

Cuprous Oxide-Based Cationic Hydrogel by the Integration of Enrichment and Immobilization of Radioiodine (I-, IO3-) in Aqueous Solution.

The efficient capture and immobilization of radioiodine (I-, IO3-) is of great importance in radioactive waste management. Here, a Cu2O-loaded three-dimensional bulk cationic hydrogel composite (Cu2O@CH) was successfully prepared by simple redox reactions and UV photopolymerization, which realized the rapid enrichment and efficient immobilization of I- and IO3-. The adsorption experiments showed that the maximum adsorption capacity of Cu2O@CH for I- in the solution at pH = 3 reached 416.5 mg/g, and the adsorption capacity of IO3- in the solution at pH = 6 could reach 313.4 mg/g. It exhibited extremely fast adsorption kinetics for I- and IO3-. In addition, Cu2O@CH also exhibited efficient I- and IO3- removal from simulated high-level liquid waste. The rapid capture and effective immobilization of radioiodine (I-, IO3-) were realized by the electrostatic interaction of -N+(CH3)3 groups in Cu2O@CH with I- and IO3-, as well as the chemical reactions between Cu2O and I-. The bulk cationic hydrogel composite explored the multifunctional role toward fast, high adsorption capability and easy handling, highlighting its superiority compared to the powder adsorbent, which renders it a potential adsorbent for the removal of radioactive iodine (I-, IO3-) in nuclear wastewater treatment.

High freezing rate improves flavor fidelity effect of hand grab mutton after short-term frozen storage.

Taking the eutectic point as the final freezing temperature, the differences of flavor substances of in hand grab mutton (HGM) frozen at three rates of 0. 26 cm/h (-18°C), 0.56 cm/h (-40°C) and 2.00 cm/h (-80°C) were determined and analyzed. The results showed that the flavor of HGM decreased significantly after freezing. With the increase of freezing rate, the contents of aldehydes, alcohols, ketones, acids, esters, others, free amino acids and 5'-nucleotides were higher, and the content of specific substances was also generally increased. All samples from unfrozen and frozen HGM could be divided into four groups using an electronic nose based on different flavor characteristics. Seven common key aroma components were determined by relative odor activity value (ROAV), including hexanal, heptanal, octanal, nonanal, (E)-oct-2-enal, (2E,4E)-deca-2,4-dienal and oct-1-en-3-ol. The higher the freezing rate, the greater the ROAVs. Taste activity values calculated by all taste substances were far <1, and the direct contribution of the substances to the taste of HGM was not significant. The equivalent umami concentration of HGM frozen at -80°C was the highest. These findings indicated that higher freezing rate was more conducive to the retention of flavor substances in HGM, and the flavor fidelity effect of freezing at -80°C was particularly remarkable.

Effect of dietary probiotics supplementation on meat quality, volatile flavor compounds, muscle fiber characteristics, and antioxidant capacity in lambs.

This study investigated the effects of probiotics on growth performance, meat quality, muscle fiber characteristics, volatile compounds, and antioxidant capacity in lambs. A total of 24 Sunit lambs were randomly allocated into two groups, each consisting of three replicates of four lambs. Throughout the experiment period, the lambs were fed with based diet (CON) and 10 g probiotics/d supplemented diet (PRO). Compared with the CON group, the number of lactic acid bacteria in fecal samples of PRO group was significantly increased (p < .05) and the coliforms were significantly decreased (p < .05). Dietary probiotics supplementation decreased pH24h, L*, and shear force (p < .05). The muscle fibers were switched from type IIB to type I, with a decrease in the mean cross-sectional area (CSA) (p < .05) of longissimus thoracis (LT) muscle. Also, probiotics altered the composition of meat volatile flavor compounds, such as nonanal, undecanal, 1-pentanol, 1-hexanol, and 2,3-octanedione. In addition, probiotics increased the total antioxidative capacity (T-AOC) and catalase (CAT) activity of LT muscle, while it decreased superoxide dismutase (SOD) activity (p < .05). Overall, these results indicated that probiotics could be used as an effective feed additive by improving meat tenderness and flavor.

Dietary α-lipoic acid supplementation improves postmortem color stability of the lamb muscles through changing muscle fiber types and antioxidative status.

This study investigated the effect of dietary α-lipoic acid (600 mg/kg) supplementation on the postmortem color stability of the biceps femoris from lambs. The results showed that dietary α-lipoic acid supplementation increased a* and decreased b* and metmyoglobin (MMb) percentage of the biceps femoris with the time of storage (P < 0.05). The content of malondialdehyde (MDA) reduced with the time of storage after treatment with α-lipoic acid (P < 0.05). α-lipoic acid increased the myoglobin (Mb) content, and myosin heavy chain I (MyHC I) gene expression but decreased glycogen content, lactate dehydrogenase (LDH) activity, and MyHC IIb gene expression (P < 0.05). The T-AOC value, catalase (CAT) activity, and expression of SOD and CAT gene expression increased after α-lipoic acid treatment (P < 0.05). Therefore, dietary α-lipoic acid supplementation improved the meat color by regulating muscle fiber types and inhibited glycolysis. Moreover, α-lipoic acid maintained meat color stability by effectively inhibiting muscle oxidation via enhancing the antioxidant capacity.

Impact of dietary Lactobacillus supplementation on intramuscular fat deposition and meat quality of Sunit sheep.

To investigate the impacts of dietary Lactobacillus supplementation on meat quality such as edible quality and nutritional value of Sunit sheep, a 90-day feeding experiment (Lactobacillus dietary group, R group; non-Lactobacillus dietary group, C group) using twelve 3-month-old Sunit sheep was conducted. The deposition of intramuscular fat (IMF) was increased (p < .05) while the share force and cooking loss were decreased (p < .05) in the R group compared with the C group. The proportions of seven kinds of fatty acids (FAs) have changed significantly (p < .05), especially with higher functional FAs and lower trans-FA in the R group. Metabonomics analysis showed that the metabolites and pathway-related lipid syntheses, such as carnitine cycle, tricarboxylic acid cycle, and glycerophosphocholine metabolic pathway, have significantly changed in the R group. The Lactobacillus dietary supplements impacted the variation of IMF deposition and FAs composition by altering the lipid metabolism pathways of Sunit sheep and then changed the edible quality and nutritional value. PRACTICAL APPLICATIONS: It is well known that the intramuscular fat (IMF) and fatty acids composition in livestock is positively correlated with various aspects of meat quality such as edible quality and nutritional value, which are related to consumer preference. The present study analyzed the effects of Lactobacillus supplement on the intramuscular fat deposition and meat quality of Sunit sheep, which resulted in the increase of IMF, and the differences of fatty acids composition, especially the functional fatty acids. It was explored the mechanism of Lactobacillus affect the variation of lipid metabolism pathways and key metabolites in sheep, which suggested that altering the feeding regimen could improve the meat quality of agri-animals.

Integrated Metabolomics and Transcriptome Revealed the Effect of Fermented Lycium barbarum Residue Promoting Ovis aries Immunity.

Lycium barbarum residue contains abundant bioactive nutrients which can be used as feed supplement. The fermentation treatment of plant residue can promote the utilization of nutrients, rumen digestion, and the growth and immunity of animals. Based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics and in-depth transcriptome analysis, the study tested the mechanisms of Lycium barbarum residue (RW) and fermented Lycium barbarum residue (RFW) on meat quality and immunity of sheep. Fifty-four Tan sheep were randomly divided into control, RFW or RW treatments. Data showed that RFW and RW increased the carcass weight, fat content, ash content and reduced the cooking loss of lamb. RFW performed more significant effects on activating immune-related genes than those of RW. The expression of chemokines and immune-related pathways, such as signaling pathways of interleukin-17 signaling pathway and NOD-like receptor signaling pathway, were elevated in sheep fed RFW. RW increased the diversity in rumen metabolites, especially compositions of lipids, organic acids and organ heterocyclic compounds. RFW affected numerous compounds which are closely correlated with the activation of immune genes. In conclusion, RFW could represent a valuable strategy to improve growth performance and immunity of sheep.

Predict the role of lncRNA in kidney aging based on RNA sequencing.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in physiological and pathological processes. However, no studies have been conducted on the relationship between lncRNAs and renal aging. RESULTS: First, we evaluated the histopathology of young (3-month-old) and old (24-month-old) C57BL/6J mouse kidneys. Masson trichrome staining and PAS staining showed interstitial collagen deposition and fibrosis, mesangial matrix expansion, a thicker basement membrane and renal interstitial fibrosis in old mouse kidneys. Senescence-associated ß-galactosidase (SA-ß-gal)-positive areas in the kidneys of old mice were significantly elevated compared to those of young mice. Then, we analyzed the differential expression of lncRNAs and mRNAs in the kidneys of young and old mouse kidneys by RNA-seq analysis. 42 known and 179 novel differentially expressed lncRNAs and 702 differential mRNAs were detected in the mouse kidney. Next, we focused on the differentially expressed mRNAs and lncRNAs by RNA-seq. GO and KEGG analyses were performed based on differentially expressed mRNAs between young and old mouse kidneys. Transregulation based on RIsearch and the correlation coefficient of mRNA-lncRNA were also calculated. The mRNA-lncRNA network was constructed by choosing a Spearman correlation coefficient > 0.9 or <-0.9. GO and KEGG pathway enrichment analyses revealed that differentially expressed mRNAs participated in aging-related pathways. A total of 10 lncRNAs and trans-regulated mRNAs were constructed. Finally, we validated the role of lncRNA Gm43360 by CCK-8, flow cytometry, western blot and SA-ß-gal staining. The expression level of Adra1a was positively correlated and Csnk1a1 was negatively correlated with lncRNA Gm43360. The cell counting kit-8 (CCK-8) results showed that lncRNA Gm43360 promoted cell viability. LncRNA Gm43360 increased the percentage of S phase cells and decreased the percentage of G1 phase cells compared with the negative control. LncRNA Gm43360 decreased the expression of p53, p21 and SA-ß-gal. CONCLUSIONS: LncRNA Gm43360 may play a protective role in kidney aging.

Expression of serum autophagy-related protein P62 in patients with severe pancreatitis and its correlation with prognosis.

OBJECTIVE: This study was designed to investigate the expression of serum autophagy-related protein P62 in patients with severe acute pancreatitis (AP) and its correlation with prognosis. METHODS: Eighty patients with AP treated in the First Affiliated Hospital of Gannan Medical University from January 2020 to January 2021 were enrolled as study subjects in this retrospective analysis, and they were placed into the mild AP group (n=52) or the severe AP group (n=28). According to clinical outcomes, these 80 patients were divided into a good prognosis group (GP group, n=51, surviving without serious complications such as organ failure) and a poor prognosis group (PP group, n=29, death or developing organ failure). The differences in C-reactive protein (CRP), P62 and the Acute Physiology and Chronic Health Evaluation II (APACHE-II) were compared upon admission. The changes of CRP, P62 and APACHE-II within 1-7 h after admission were dynamically analyzed in the two groups. Spearman correlation analysis was performed to explore the correlation between P62 and APACHE-II scores, and the receiver operating characteristic (ROC) curve of P62 related to poor AP outcome was plotted. RESULTS: CRP, P62 and APACHE-II in the mild AP group were significantly higher than those in the severe AP group, and these in the PP group were also significantly higher than those in the GP group (P<0.05). Dynamic monitoring showed that within 1-7 h after admission, CRP, P62, and APACHE-II in the severe AP group were significantly higher than those in the mild AP group (P<0.05), and these in the PP group were significantly higher than those in the GP group (P<0.05). Spearman correlation analysis showed that P62 level was significantly positively correlated with both CRP and APACHE-II (r=0.9331, r=0.9500, P<0.0001). ROC curve showed that AUC of P62 was 0.9570 in AP patients with poor prognosis (95% CI=0.8939-1.000, P<0.0001). CONCLUSION: Serum autophagy-related protein P62 was closely related to the condition and prognosis of AP patients, and P62 could be used as a potential indicator to assess the condition and prognosis of AP patients.

CoQ10 enhances the efficacy of airway basal stem cell transplantation on bleomycin-induced idiopathic pulmonary fibrosis in mice.

BACKGROUND: Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment. METHODS: The protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after 2 weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mouse lung tissues. RESULTS: CoQ10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1 mM, 6 h) in vitro. IPF mouse model was constructed through bleomycin (5 mg/kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects. CONCLUSION: CoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation against bleomycin-induced IPF in mice.

Nestin promotes pulmonary fibrosis via facilitating recycling of TGF-ß receptor I.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that is characterised by aberrant proliferation of activated myofibroblasts and pathological remodelling of the extracellular matrix. Previous studies have revealed that the intermediate filament protein nestin plays key roles in tissue regeneration and wound healing in different organs. Whether nestin plays a critical role in the pathogenesis of IPF needs to be clarified. METHODS: Nestin expression in lung tissues from bleomycin-treated mice and IPF patients was determined. Transfection with nestin short hairpin RNA vectors in vitro that regulated transcription growth factor (TGF)-ß/Smad signalling was conducted. Biotinylation assays to observe plasma membrane TßRI, TßRI endocytosis and TßRI recycling after nestin knockdown were performed. Adeno-associated virus serotype (AAV)6-mediated nestin knockdown was assessed in vivo. RESULTS: We found that nestin expression was increased in a murine pulmonary fibrosis model and IPF patients, and that the upregulated protein primarily localised in lung α-smooth muscle actin-positive myofibroblasts. Mechanistically, we determined that nestin knockdown inhibited TGF-ß signalling by suppressing recycling of TßRI to the cell surface and that Rab11 was required for the ability of nestin to promote TßRI recycling. In vivo, we found that intratracheal administration of AAV6-mediated nestin knockdown significantly alleviated pulmonary fibrosis in multiple experimental mice models. CONCLUSION: Our findings reveal a pro-fibrotic function of nestin partially through facilitating Rab11-dependent recycling of TßRI and shed new light on pulmonary fibrosis treatment.

A clinical and canine experimental study in small-airway response to bronchial thermoplasty: Role of the neuronal effect.

BACKGROUND: The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. METHODS: We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs' lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. RESULTS: Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)-positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. CONCLUSIONS: BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.

Enhanced secretion of hepatocyte growth factor in human umbilical cord mesenchymal stem cells ameliorates pulmonary fibrosis induced by bleomycin in rats.

Umbilical cord mesenchymal stem cells (UCMSCs) are a reportedly promising choice in the treatment of irreversible pulmonary fibrosis and lethal interstitial lung disease with limited drug treatment options. In this study, we investigated the therapeutic efficacy of UCMSCs overexpressing hepatocyte growth factor (HGF), which is considered one of the main anti-fibrotic factors secreted by MSCs. Adenovirus vector carrying the HGF gene was transfected into UCMSCs to produce HGF-modified UCMSCs (HGF-UCMSCs). Transfection promoted the proliferation of UCMSCs and did not change the morphology, and differentiation ability, or biomarkers. Rats were injected with HGF-UCMSCs on days 7 and 11 after intratracheal administration of bleomycin (10 mg/kg). We performed an analysis of histopathology and lung function to evaluate the anti-fibrotic effect. The results showed that HGF-UCMSCs decreased the Ashcroft scores in hematoxylin and eosin-stained sections, the percentage positive area in Masson trichrome-stained sections, and the hydroxyproline level in lungs. Forced expiratory volume in the first 300 m/forced vital capacity was also improved by HGF-UCMSCs. To explore the possible therapeutic mechanism of HGF-UCMSCs, we detected inflammatory factors in the lungs and performed mRNA sequencing in UCMSCs and HGF-UCMSCs. The data indicated that inhibition of interleukin-17 in the lung may be related to the anti-fibrosis of HGF-UCMSCs, and overexpressed HGF probably played a primary role in the treatment. Collectively, our study findings suggested that the overexpression of HGF may improve the anti-fibrotic effect of UCMSCs through directly or indirectly interacting with interleukin-17-producing cells in fibrotic lungs.