Antibacterial Conductive Collagen-Based Hydrogels for Accelerated Full-Thickness Wound Healing.

Antibacterial conductive hydrogels have been extensively utilized in tissue repair and regeneration on account of their unique electrochemical performances and advantages of anti-pathogenic bacterial infection. Here, multi-functional collagen-based hydrogels (CHLY) with adhesivity, conductivity, and antibacterial and antioxidant activities were developed by introducing cysteine-modified ε-poly(l-lysine) (ε-PL-SH) and in situ-polymerized polypyrrole (PPy) nanoparticles to induce full-thickness wound healing. CHLY hydrogels have a low swelling ratio, good compressive strength, and viscoelasticity due to chemical crosslinking, chelation, physical interaction, and nano-reinforcements in the matrix network of hydrogels. CHLY hydrogels possess excellent tissue adhesion ability, low cytotoxicity, enhanced cell migration ability, and good blood coagulation performance without causing hemolysis. Interestingly, the chemical conjugation of ε-PL-SH in the hydrogel matrix gives hydrogels an inherently robust and broad-spectrum antibacterial activity, while the introduction of PPy endows hydrogels with superior free radical scavenging capacity and good electroactivity. Significantly, CHLY hydrogels have advantages in alleviating persistent inflammatory response as well as promoting angiogenesis, epidermis regeneration, and orderly collagen deposition at the wound sites through their multi-functional synergies, thus effectively accelerating full-thickness wound healing and improving wound healing quality. Overall, our developed multi-functional collagen-based hydrogel dressing demonstrates promising application prospects in the field of tissue engineering to induce skin regeneration.

A Five-LLPS Gene Risk Score Prognostic Signature Predicts Survival in Hepatocellular Carcinoma.

Background: Primary liver cancer, dominated by hepatocellular carcinoma (HCC), is one of the most common cancer types and the third leading cause of cancer death in 2020. Previous studies have shown that liquid-liquid phase separation (LLPS) plays an important role in the occurrence and development of cancer including HCC, but its influence on the patient prognosis is still unknown. It is necessary to explore the effect of LLPS genes on prognosis to accurately forecast the prognosis of HCC patients and identify relevant targeted therapeutic sites. Methods: Using The Cancer Genome Atlas dataset and PhaSepDB dataset, we identified LLPS genes linked to the overall survival (OS) of HCC patients. We applied Least Absolute Shrinkage and Selection Operator (LASSO) Cox penalized regression analysis to choose the best genes for the risk score prognostic signature. We then analysed the validation dataset and evaluated the effectiveness of the risk score prognostic signature. Finally, we performed quantitative real-time PCR experiments to validate the genes in the prognostic signature. Results: We identified 43 differentially expressed LLPS genes that were associated with the OS of HCC patients. Five of these genes (BMX, FYN, KPNA2, PFKFB4, and SPP1) were selected to generate a prognostic risk score signature. Patients in the low-risk group were associated with better OS than those in the high-risk group in both the training dataset and the validation dataset. We found that BMX and FYN had lower expression levels in HCC tumour tissues, whereas KPNA2, PFKFB4, and SPP1 had higher expression levels in HCC tumour tissues. The validation demonstrated that the five-LLPS gene risk score signature has the capability of predicting the OS of HCC patients. Conclusion: Our study constructed a five-LLPS gene risk score signature that can be applied as an effective and convenient prognostic tool. These five genes might serve as potential targets for therapy and the treatment of HCC.

Risk factors of vestibular migraine-related brain white matter lesions.

OBJECTIVE AND PURPOSE: Migraine is related to white matter lesions (WMLs), and attack frequency and duration in migraine patients are thought to increase WMLs. However, the relationship between vestibular migraine (VM) and WMLs remains unclear. This study explored the risk factors for WMLs in VM patients and provided a basis for the prevention of WMLs in VM patients. METHODS: A large single-center cross-sectional study of patients with VM was conducted. None of the patients had comorbidities, such as hypertension and diabetes, or adverse lifestyle habits (smoking and drinking). All patients were divided into WML + and WML- groups after assessment of WMLs using magnetic resonance imaging (MRI). After collecting the patient's detailed medical history, statistical analysis was performed. RESULTS: In univariate analysis, the frequency of vertigo was statistically significant between the WML + and WML- groups. However, there was no significant difference in other clinical features. Multivariate regression analysis found that the frequency of vertigo (OR 2.399; 95% CI 1.014-5.679; p = 0.046) was an independent risk factor for WMLs. High frequency of vertigo episodes showed more pronounced risk factors (OR 9.607; 95% CI 1.061-87.014; p = 0.044). CONCLUSION: These results substantiate that vertigo frequency is an independent risk factor for WMLs in VM. A high frequency of vertigo episodes is more likely to be associated with WMLs than a low frequency. These results suggest a possible approach to the prevention of WMLs in VM patients.

Rare massive hepatic hemangioblastoma: A case report.

BACKGROUND: Hepatic hemangioblastoma is an extremely rare disease; only three cases have been reported in the literature, and its magnetic resonance imaging (MRI) findings are unreported. CASE SUMMARY: We report a case of incidental hepatic hemangioblastoma. The patient had no history of von Hippel-Lindau disease or associated clinical signs. Computed tomography and MRI showed a large tumor occupying almost half of the right side of the liver with expansive growth, well-defined borders, heterogeneous mildly progressive enhancement, and visibly enlarged blood supply vessels. Flow voids were observed on T2-weighted imaging. Both diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) map findings of the mass were predominantly inhomogeneous. Postoperative pathology indicated a diagnosis of hemangioblastoma. CONCLUSION: Enlarged peripheral blood-supplying vessels and progressive enhancement seem to be typical imaging features of hepatic hemangioblastoma. However, a solid significantly enhanced mass with a low signal on DWI and a high signal on ADC may also be helpful for the diagnosis of hepatic hemangioblastoma.

Multifunctional ß-Cyclodextrin-Poly(ethylene glycol)-Cholesterol Nanomicelle for Anticancer Drug Delivery.

Nanoparticle drug delivery systems have drawn considerable attention worldwide due to their unique characteristics and advantages in anticancer drug delivery. Herein, the curcumin (Cur) loaded nanomicelles with two-stage drug release behavior were developed. ß-Cyclodextrin (ß-CD) and cholesterol were conjugated onto both ends of the poly(ethylene glycol) (PEG) chain to obtain an amphiphilic ß-CD-PEG-Chol. The Cur was loaded into the cavities of ß-CD and nanomicelle when the ß-CD-PEG-Chol self-assembled to the Cur@ß-CD-PEG-Chol nanomicelles (Cur@CPC NMs). These Cur@CPC NMs are spherical particles with a particle size of 120.9 nm. The Cur drug loading capacity of Cur@CPC NMs are 61.6 ± 6.9 mg/g. The release behavior of Cur from Cur@CPC NMs conformed to a two-stage mode of "burst-release followed by sustained-release". The prepared Cur@CPC NMs possess high storage stability and excellent hemocompatibility. Moreover, these Cur@CPC NMs exhibit satisfactory antioxidant activity and anticancer activity, resulting in significant reduction in intracellular H2O2-induced ROS and a nearly 50% lethality rate of HepG-2 cells. Meanwhile, the Cur@CPC NMs show good anti-inflammatory activity, by which the secretion of inflammatory factors of IL-6 and TNF-α are inhibited. Overall, the developed Cur@CPC NMs show application prospects in anticancer drug delivery systems.

Gene Expression Trajectories from Normal Nonsmokers to COPD Smokers and Disease Progression Discriminant Modeling in Response to Cigarette Smoking.

Background: Cigarette smoking (CS) is considered to the predominant risk factor contributing to the etiopathogenesis of chronic obstructive pulmonary disease (COPD); meanwhile, genetic predisposition likely plays a role in determining disease susceptibility. Objectives: We aimed to investigate gene expression trajectories from normal nonsmokers to COPD smokers and disease progression discriminant modeling in response to cigarette smoking. Methods: Small airway epithelial samples of human with different smoking status using fiberoptic bronchoscopy and corresponding rat lung tissues following 0, 3, and 6 months of CS exposure were obtained. The expression of the significant overlapping genes between human and rats was confirmed in 16HBE cells, rat lung tissues, and human peripheral PBMC using qRT-PCR. Binary logistic regression analysis was carried out to establish discrimination models. Results: The integrated bioinformatic analysis of 8 human GEO datasets (293 individuals) and 9 rat transcriptome databases revealed 13 overlapping genes between humans and rats in response to smoking exposure during COPD progression. Of these, 5 genes (AKR1C3/Akr1c3, ERP27/Erp27, AHRR/Ahrr, KCNMB2/Kcnmb2, and MRC1/Mrc1) were consistently identified in both the human and rat and validated by qRT-PCR. Among them, ERP27/Erp27, KCNMB2/Kcnmb2, and MRC1/Mrc1 were newly identified. On the basis of the overlapping gene panel, discriminant models were established with the receiver operating characteristic curve (AUC) of 0.98 (AKR1C3/Akr1c3 + ERP27/Erp27) and 0.99 (AHRR/Ahrr + KCNMB2/Kcnmb2) in differentiating progressive COPD from normal nonsmokers. In addition, we also found that DEG obtained from each expression profile dataset was better than combined analysis as more genes could be identified. Conclusion: This study identified 5 DEG candidates of COPD progression in response to smoking and developed effective and convenient discriminant models that can accurately predict the disease progression.

131I-Labeled Silk Fibroin Microspheres for Radioembolic Therapy of Rat Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a promising technology in hepatocellular carcinoma (HCC) therapy, which utilizes radionuclide-labeled microspheres to achieve arterial embolization and internal irradiation. However, the therapeutic effect of liver cancer can be affected by low radionuclide labeling rate and stability, as well as poor biocompatibility, and non-biodegradability of microspheres. Here, 131I-labeled silk fibroin microspheres (131I-SFMs) were developed as radioembolization material for effective TARE therapy against HCC. Silk fibroin rich in 10.03% of tyrosine was extracted from silkworm cocoons and then emulsified and genipin-crosslinked to prepare SFMs. SFMs show a good settlement rate, biodegradability, hemocompatibility, and low cytotoxicity. Afterward, 131I-SFMs were obtained by radiolabeling 131I onto the SFMs through the chloramine-T method. 131I-SFMs possess a high 131I labeling rate of over 84% and good radioactive stability and are thus conducive to internal radiotherapy. Significantly, 131I-SFMs with diameters around 11 µm were successfully radioembolized at the hepatic artery. 131I-SFMs were diffused in the liver, indicating the favorable biodistribution and biosafety in vivo. Based on the combination of embolization and local radiotherapy, the administration of 131I-SFMs shows a favorable inhibitive effect against the progression of HCC. Overall, the newly developed 131I-SFMs as radioembolization microspheres provide a promising application for effective TARE therapy against liver cancer.

Integrated analysis of single-cell RNA-seq dataset and bulk RNA-seq dataset constructs a prognostic model for predicting survival in human glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5-year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM patients. To date, most prognostic models for predicting survival in GBM were constructed based on bulk RNA-seq dataset, which failed to accurately reflect the difference between tumor cores and peripheral regions, and thus show low predictive capability. An effective prognostic model is desperately needed in clinical practice. METHODS: We studied single-cell RNA-seq dataset and The Cancer Genome Atlas-glioblastoma multiforme (TCGA-GBM) dataset to identify differentially expressed genes (DEGs) that impact the OS of GBM patients. We then applied the least absolute shrinkage and selection operator (LASSO) Cox penalized regression analysis to determine the optimal genes to be included in our risk score prognostic model. Then, we used another dataset to test the accuracy of our risk score prognostic model. RESULTS: We identified 2128 DEGs from the single-cell RNA-seq dataset and 6461 DEGs from the bulk RNA-seq dataset. In addition, 896 DEGs associated with the OS of GBM patients were obtained. Five of these genes (LITAF, MTHFD2, NRXN3, OSMR, and RUFY2) were selected to generate a risk score prognostic model. Using training and validation datasets, we found that patients in the low-risk group showed better OS than those in the high-risk group. We validated our risk score model with the training and validating datasets and demonstrated that it can effectively predict the OS of GBM patients. CONCLUSION: We constructed a novel prognostic model to predict survival in GBM patients by integrating a scRNA-seq dataset and a bulk RNA-seq dataset. Our findings may advance the development of new therapeutic targets and improve clinical outcomes for GBM patients.

pH-Sensitive nanoparticles based on amphiphilic imidazole/cholesterol modified hydroxyethyl starch for tumor chemotherapy.

pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.

The Effect of Plug Rotation Speed on Micro-Structure of Nugget Zone of Friction Plug Repair Welding Joint for 6082 Aluminum Alloy.

This paper carried out the friction plug repair welding of 6082 aluminum alloy keyhole defects by using the method of friction heating between shaft shoulder and base material. In addition, a well-formed friction plug welding joint was obtained at different plug rotation speeds. In order to study the influence mechanism of plug rotation speeds on the microstructure of the weld nugget zone, EBSD technology was used to analyze the grain morphology, grain size and grain boundary characteristics of the weld nugget zone under different rotation speeds of the plug rod. The results show that in the nugget zone, the grain was fine and equated crystals refinement, and there was a preferred orientation. The deformation texture components in the welded nugget zone increased with the plug rotation speed from 1600 to 2000 rpm. However, the grain size first decreased and then increased, while the components in the High-Angle Boundary first increased and then decreased.

LncRNA Nqo1-AS1 Attenuates Cigarette Smoke-Induced Oxidative Stress by Upregulating its Natural Antisense Transcript Nqo1.

Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3'UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.

Functionalization of an Electroactive Self-Healing Polypyrrole-Grafted Gelatin-Based Hydrogel by Incorporating a Polydopamine@AgNP Nanocomposite.

Hydrogels are considered a promising wound dressing owing to their ability to absorb wound exudates and their moist network structure for skin regeneration. It is of great significance to give added multiple functions to hydrogels for wound healing. In this paper, we present a gelatin-based hydrogel with self-healing ability, conductivity, and antibacterial and antioxidant activities. Dopamine was added into an alkaline solution to polymerize into polydopamine (PDA), which was used to reduce AgNO3 into Ag nanoparticles (AgNPs) to gain a PDA@AgNP composite. Polypyrrole-grafted gelatin (PPyGel) was dissolved in a PDA@AgNP solution and ferric ions were used as a cross-linking agent to form PDA@AgNPs-PPyGel-Fe hydrogels. The as-prepared hydrogels are soft and ductile and exhibit porous structures with pore sizes from 20 to 50 µm. The hydrogels have high water absorption ability, indicating the potential to absorb wound exudates. PPy and Fe3+ endow the hydrogels with slightly higher conductivity than that of skin tissue, indicating the ability to effectively transmit bioelectric signals for skin regeneration. The ionic interactions and hydrogen bonding in hydrogels make them possess self-healing ability, and the self-healing process can be completed in 30 min. PDA confers hydrogels with effective antioxidant activities, while AgNPs endow hydrogels with good antibacterial activities. Moreover, the hydrogels possess good blood compatibility and cytocompatibility. In sum, the developed hydrogel has potential applications as wound dressings.

High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study.

BACKGROUND: Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear. METHODS: This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed. RESULTS: After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: - 2.07, 6.66), (RERI) = 2.98, 95% CI: - 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk. CONCLUSIONS: This research indicates that high Mn exposure was negatively related to high TG risk in workers.

Occupational exposure to manganese and risk of creatine kinase and creatine kinase-MB elevation among ferromanganese refinery workers.

BACKGROUND: Elevated exposure to manganese (Mn) could induce cardiovascular dysfunction. However, limited research is available on the effects of occupational Mn exposure on myocardial enzymes. We aimed to evaluate the relationships between Mn exposure and myocardial enzyme elevation among Mn-exposed workers. METHODS: Data were from a follow-up investigation of a Mn-exposed workers healthy cohort in 2017. A total of 744 workers were divided into low-exposure and high-exposure groups according to Mn time-weighted average (Mn-TWA) of less than or equal to 0.15 mg/m3 or greater than 0.15 mg/m3 , respectively. Serum levels of myocardial enzymes, including creatine kinase (CK) and creatine kinase-MB (CK-MB), lactic dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate transaminase, were assessed, as well as airborne Mn exposure levels. RESULTS: After adjustment for sex, body mass index, seniority, education, current smoking status, current drinking status, and hypertension, Mn-TWA levels were positively associated with the risk of CK elevation (odds ratio [OR] = 1.47 (95% confidence interval [CI]: 1.18-1.83) per interquartile range [IQR] increase), and risk of CK-MB elevation [OR = 1.57 (95% CI: 1.03-2.38) per IQR increase]. In a stratified analysis, Mn-TWA levels were positively correlated with CK elevation in workers of seniority greater than 19 years, male workers, current smokers, and drinkers. CONCLUSION: Our results suggest that occupational exposure to Mn is associated with increased risk of CK and CK-MB elevation. The potential mechanisms of the associations between airborne exposure to Mn and increased risk of these myocardial enzyme elevations warrant further investigation.

pH-Responsive nanoparticles based on cholesterol/imidazole modified oxidized-starch for targeted anticancer drug delivery.

Various nanoparticles have been developed for tumor-targeted drug delivery. However, nanoparticles with effective targeting and intelligent release capacity are still deficient. Herein, we present new pH-responsive and neutral charged nanoparticles for tumor-targeted anticancer drug delivery. Oxidized starch was synthesized and simultaneously modified by cholesterol and imidazole to obtain amphiphilic cholesterol/imidazole modified oxidized-starch (Cho-Imi-OS). Cho-Imi-OS easily self-assembled into nanoparticles by dialysis. Curcumin was selected as model drug to be encapsulated into the hydrophobic core of nanoparticles. The results showed that curcumin would effectively accumulate in cancer cells by encapsulating into the nanoparticles owing to the nano-sized structure and near neutral charged property of nanoparticles. Curcumin was released faster at pH 5.5 than that at pH 7.4 from the curcumin-loaded nanoparticles (Cur-NPs), indicating the pH-triggered release capacity of Cur-NPs after endocytosis by endosomes since the pH is low to 5.0∼6.0 in endosomes. Naturally, Cur-NPs showed significantly strong inhibitory effect on cancer cells.

Sodium tanshinone IIA sulfonate protects against acute exacerbation of cigarette smoke-induced chronic obstructive pulmonary disease in mice.

Exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by acute airway inflammation and mucus hypersecretion, which is by far the most costly aspect of its management. Thus, it is essential to develop therapeutics with low side effects for CODP exacerbation. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component of Chinese herbal medicine Danshen. Although it possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, it remains unknown whether STS protects against COPD exacerbation. In this study, we challenged cigarette smoke (CS)-exposed mice with lipopolysaccharide (LPS), and then treated these mice with STS. We found that STS significantly ameliorated pulmonary inflammatory responses, mucus hypersecretion and lung function decline in CS-exposed mice challenged with LPS. STS treatment also significantly attenuated increased IL-6 and IL-8 releases from cigarette smoke extract (CSE)-treated human bronchial epithelial cells (16HBE) challenged with LPS. Mechanistically, STS reduced activation of ERK1/2 and NF-κB in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD.

Hydrogen sulfide inhibits cigarette smoke-induced inflammation and injury in alveolar epithelial cells by suppressing PHD2/HIF-1α/MAPK signaling pathway.

Chronic obstructive pulmonary fibrosis (COPD) is a chronic and fatal lung disease with few treatment options. Sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S), was found to alleviate cigarette smoke (CS)-induced emphysema in mice, however, the underlying mechanisms have not yet been clarified. In this study, we investigated its effects on COPD in a CS-induced mouse model in vivo and in cigarette smoke extract (CSE)-stimulated alveolar epithelial A549 cells in vitro. The results showed that NaHS not only relieved emphysema, but also improved pulmonary function in CS-exposed mice. NaHS significantly increased the expressions of tight junction proteins (i.e., ZO-1, Occludin and claudin-1), and reduced apoptosis and secretion of pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1ß) in CS-exposed mouse lungs and CSE-incubated A549 cells, indicating H2S inhibits CS-induced inflammation, injury and apoptosis in alveolar epithelial cells. NaHS also upregulated prolyl hydroxylase (PHD)2, and suppressed hypoxia-inducible factor (HIF)-1α expression in vivo and in vitro, suggesting H2S inhibits CS-induced activation of PHD2/HIF-1α axis. Moreover, NaHS inhibited CS-induced phosphorylation of ERK, JNK and p38 MAPK in vivo and in vitro, and treatment with their inhibitors reversed CSE-induced ZO-1 expression and inflammation in A549 cells. These results suggest that NaHS may prevent emphysema via the suppression of PHD2/HIF-1α/MAPK signaling pathway, and subsequently inhibition of inflammation, epithelial cell injury and apoptosis, and may be a novel strategy for the treatment of COPD.

Association between long-term occupational manganese exposure and bone quality among retired workers.

Despite well documents for manganese-induced neurological deficits, limited researches are available for effects of manganese (Mn) exposure on the bone. Here we aimed to explore the associations between long-term occupational Mn exposure and bone quality among retired workers. We conducted a cross-sectional study of 304 exposed subjects (n, male = 161 and female = 143) and 277 control retired workers (n, male = 65 and female = 212) recruited from a ferromanganese refinery. Self-reported occupation types were used as exposure classification confirmed by expert consultation. Bone quality was measured by quantitative ultrasound (QUS). In sex-stratified analyses throughout, stiffness index (SI) and T-score levels of the participants in the highest exposed group [tertile 3 of Mn cumulative exposure index (Mn-CEI)] were significantly lower as compared with the control group among female workers (SI, mean, 61.60 vs. 68.17; T-score, mean, -3.01 vs. -2.34, both P < 0.05). In addition, SI and T-score were found to be negatively associated with Mn-CEI only in the highest exposure group as compared with the female controls (both P = 0.01). However, we did not find the significant difference for SI or T-score among the male subjects in exposure models and the male controls (P > 0.05). Our results suggest that female retired workers in the highest Mn-exposed model (tertile 3 of Mn-CEI) potentially experience a higher risk of developing osteoporosis compared with the female controls. Further investigations on possible mechanisms on bone quality alteration are needed in the future.

Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway.

Airway remodeling is one of the characteristics for chronic obstructive pulmonary disease (COPD). The mechanism underlying airway remodeling is associated with epithelial-mesenchymal transition (EMT) in the small airways of smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to reduce oxidative stress, and to modulate EMT. Here, we investigated the effects and mechanisms of hydrogen sulfide (H2S) on pulmonary EMT in vitro and in vivo. We found that H2S donor NaHS inhibited cigarette smoke (CS)-induced airway remodeling, EMT and collagen deposition in mouse lungs. In human bronchial epithelial 16HBE cells, NaHS treatment also reduced CS extract (CSE)-induced EMT, collagen deposition and oxidative stress. Mechanistically, NaHS upregulated SIRT1 expression, but inhibited activation of TGF-ß1/Smad3 signaling in vivo and in vitro. SIRT1 inhibition by a specific inhibitor EX527 significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress. SIRT1 inhibition also abolished the protection of NaHS against CSE-induced EMT. Moreover, SIRT1 activation attenuated CSE-induced EMT by modifying TGF-ß1-mediated Smad3 transactivation. In conclusion, H2S prevented CS-induced airway remodeling in mice by reversing oxidative stress and EMT, which was partially ameliorated by SIRT1 activation. These findings suggest that H2S may have therapeutic potential for the prevention and treatment of COPD.

Author Correction: Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model.

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