ALDH2 Deficiency Aggravates Lung Fibrosis through Mitochondrial Dysfunction and Aging in Fibroblasts.

Idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, is characterized by fibroblast activation and aberrant extracellular matrix (ECM) accumulation. Effective therapeutic development is limited due to incomplete understanding of the mechanisms by which fibroblasts become aberrantly activated. Here we show acetaldehyde dehydrogenase 2 (ALDH2) in fibroblasts as a potential therapeutic target for pulmonary fibrosis. A decrease in ALDH2 expression was observed in IPF patients and bleomycin-treated mice. ALDH2 deficiency spontaneously induces collagen accumulation in the lungs of aged mice. Furthermore, Young ALDH2 knockout mice exhibited exacerbated bleomycin-induced pulmonary fibrosis and increased mortality compared with that in control mice. Mechanistic studies revealed that transforming growth factor (TGF)-ß1 induction and ALDH2 depletion constitute a positive feedback loop that exacerbates fibroblast activation. TGF-ß1 downregulated ALDH2 through a TGF-ß receptor 1/Smad3-dependent mechanism. The subsequent deficiency in ALDH2 resulted in fibroblast dysfunction that manifested as impaired mitochondrial autophagy and senescence, leading to fibroblast activation and ECM production. ALDH2 overexpression markedly suppressed fibroblast activation and this effect was abrogated by PTEN-induced putative kinase 1 (PINK1) knockdown, indicating that the pro-fibrotic effects of ALDH2 are PINK1-dependent. Furthermore, Alda-1-induced ALDH2 activation reversed the established pulmonary fibrosis in both young and aged mice. In conclusions, ALDH2 expression inhibits the pathogenesis of pulmonary fibrosis. Strategies to upregulate or activate ALDH2 expression could be potential therapies for pulmonary fibrosis.

Effects of hydraulic retention time and influent nitrate concentration on solid-phase denitrification system using wheat husk as carbon source.

Solid-phase denitrification shows promise for removing nitrate (NO3--N) from water. Biological denitrification uses external carbon sources to remove nitrogen from wastewater, among which agriculture waste is considered the most promising source due to its economic and efficiency advantages. Hydraulic retention time (HRT) and influent nitrate concentration (INC) are the main factors influencing biological denitrification. This study explored the effects of HRT and INC on solid-phase denitrification using wheat husk (WH) as a carbon source. A solid-phase denitrification system with WH carbon source was constructed to explore denitrification performance with differing HRT and INC. The optimal HRT and INC of the wheat husk-denitrification reactor (WH-DR) were 32 h and 50 mg/L, respectively. Under these conditions, NO3--N and total nitrogen removal rates were 97.37 ± 2.68% and 94.08 ± 4.01%, respectively. High-throughput sequencing revealed that the dominant phyla in the WH-DR operation were Proteobacteria, Bacteroidetes, and Campilobacterota. Among the dominant genera, Diaphorobacter (0.85%), Ideonella (0.38%), Thiobacillus (4.22%), and Sulfurifustis (0.60%) have denitrification functions; Spirochaeta (0.47%) is mainly involved in the degradation of WH; and Acidovorax (0.37%) and Azospira (0.86%) can both denitrify and degrade WH. This study determined the optimal HRT and INC for WH-DR and provides a reference for the development and application of WH as a novel, slow-release carbon source in treating aquaculture wastewater.

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization.

Pulmonary fibrosis is characteristic of several human lung diseases that arise from various causes. Given that treatment options are fairly limited, mouse models continue to be an important tool for developing new anti-fibrotic strategies. In this study, intrapulmonary administration of bleomycin (BLM) is carried out by nasal nebulization to create a mouse model of pulmonary fibrosis that closely mimics clinical disease characteristics. C57BL/6 mice received BLM (7 U/mL, 30 min/day) by nasal nebulization for 3 consecutive days and were sacrificed on day 9, 16, or 23 to observe inflammatory and fibrotic changes in lung tissue. Nasal aerosolized BLM directly targeted the lungs, resulting in widespread and uniform lung inflammation and fibrosis. Thus, we successfully generated an experimental mouse model of typical human pulmonary fibrosis. This method could easily be used to study the effects of the administration of various nasal aerosols on lung pathophysiology and validate new anti-inflammatory and anti-fibrotic treatments.

Effectiveness of agricultural waste in the enhancement of biological denitrification of aquaculture wastewater.

Nitrogen pollution in aquaculture wastewater can pose a significant health and environmental risk if not removed before wastewater is discharged. Biological denitrification uses external carbon sources to remove nitrogen from wastewater; however, these carbon sources are often expensive and require significant energy. In this study, we investigated how six types of agricultural waste can be used as solid carbon sources in biological denitrification. Banana stalk (BS), loofah sponge (LS), sorghum stalk (SS), sweet potato stalk (SPS), watermelon skins (WS) and wheat husk (WH) were studied to determine their capacity to release carbon and improve denitrification efficiency. The results of batch experiments showed that all six agricultural wastes had excellent carbon release capacities, with cumulative chemical oxygen demands of 37.74-535.68 mg/g. During the 168-h reaction, the carbon release process followed the second-order kinetic equation and Ritger-Peppas equation, while carbon release occurred via diffusion. The kinetic equation fitting, scanning electron microscopy, and Fourier transform infrared spectroscopy results showed that LS had the lowest cm and the maximum t1/2 values and only suffered a moderate degree of hydrolysis. It also had the lowest pollutant release rate and cumulative chemical oxygen demand, as well as the most efficient removal of total phosphorous (TP) and total nitrogen (TN). Therefore, we concluded that LS has the lowest potential risk of excess carbon release and capacity for long-lasting and stable carbon release. The WS leachate had the highest TN contents, while the SPS leachate had the highest TP content. In the 181-h denitrification reaction, all six agricultural wastes completely removed nitrate and nitrite; however, SS had the highest denitrification rate, followed by LS, WH, BS, SPS, and WS (2.16, 1.35, 1.35, 1.34, 1.34, and 1.01 mg/(L·h), respectively). The denitrification process followed a zero-order and first-order kinetic equation. These results provide theoretical guidance for effectively selecting agricultural waste as a solid carbon source and improving the denitrification efficiency of aquaculture wastewater treatment.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.

Bioinformatics analysis to screen key genes in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and its incidence has been on the increase in recent years. However, the molecular mechanism of PTC is unclear and misdiagnosis remains a major issue. Therefore, the present study aimed to investigate this mechanism, and to identify key prognostic biomarkers. Integrated analysis was used to explore differentially expressed genes (DEGs) between PTC and healthy thyroid tissue. To investigate the functions and pathways associated with DEGs, Gene Ontology, pathway and protein-protein interaction (PPI) network analyses were performed. The predictive accuracy of DEGs was evaluated using the receiver operating characteristic (ROC) curve. Based on the four microarray datasets obtained from the Gene Expression Omnibus database, namely GSE33630, GSE27155, GSE3467 and GSE3678, a total of 153 DEGs were identified, including 66 upregulated and 87 downregulated DEGs in PTC compared with controls. These DEGs were significantly enriched in cancer-related pathways and the phosphoinositide 3-kinase-AKT signaling pathway. PPI network analysis screened out key genes, including acetyl-CoA carboxylase beta, cyclin D1, BCL2, and serpin peptidase inhibitor clade A member 1, which may serve important roles in PTC pathogenesis. ROC analysis revealed that these DEGs had excellent predictive performance, thus verifying their potential for clinical diagnosis. Taken together, the findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.

NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018.

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.

Prospective cohort study of cancer patients diagnosed with incidental venous thromboembolism on routine computed tomography scans.

PURPOSE: Venous thromboembolism (VTE) is a major complication of cancer with recent increasing reports of incidental VTE. The objectives are to estimate the prevalence of incidental VTE in cancer patients on staging CT scans, identify common symptoms, and determine VTE recurrence in a prospective study. PATIENTS AND METHODS: One thousand ninety patients were studied. Adult cancer patients scheduled for outpatient staging CT scans were eligible. VTE cases were followed for 6 months. Fisher's exact test for group comparisons of categorical variables and generalized linear modeling to estimate the prevalence of incidental VTE was used. RESULTS: The mean age was 58 years (range 18-87 years); 50% were male. The prevalence of incidental VTE was 1.8% (CI 1.15-2.87%). Significant symptoms in patients with VTE included fatigue (p = 0.004), stress (p = 0.0195), depression (p = 0.019), poorer quality of life (p = 0.0194), and poorer physical well-being (p = 0.0007). All the patients with VTE had at least one comorbidity (p = 0.03). No patient had recurrence within 6 months. CONCLUSION: The prevalence of incidental VTE on staging CT scans is lower than previously reported. Symptoms were associated with VTE; however, further work is needed to understand whether these are clinically relevant. No VTE recurrences were noted following 6 months.

Cancer-Associated Venous Thromboembolic Disease, Version 1.2015.

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

Venous thromboembolic disease.

Venous thromboembolism (VTE) remains a common and life-threatening complication among patients with cancer. Thromboprophylaxis can be used to prevent the occurrence of VTE in patients with cancer who are considered at high risk for developing this complication. Therefore, it is critical to recognize the various risk factors for VTE in patients with cancer. Risk assessment tools are available to help identify patients for whom discussions regarding the potential benefits and risks of thromboprophylaxis would be appropriate. The NCCN Clinical Practice Guidelines in Oncology for VTE provide recommendations on risk evaluation, diagnosis, prevention, and treatment of VTE in patients with cancer.

Venous thromboembolism and malignancy.

The association between venous thromboembolism (VTE) and malignancy was first recognized more than 135 years ago. Since then, a markedly increased incidence of VTE has been found in patients with malignant disease. Numerous clinical studies have demonstrated that malignancy or its treatment are major risk factors for VTE. Recent developments in moleculobiological studies have indicated that the high risk of VTE in malignancy is attributed to the hypercoagulable state caused by the disease and its treatments. Diagnostic approaches to clinically suspected VTE continue to evolve, making the diagnosis easier and more accurate. Recent advances in clinical studies have refined the management strategies for the prophylaxis and treatment of VTE in patients with or without cancer. In this paper, recent clinical studies will be reviewed, current understanding of the pathogenesis of thrombosis in malignancy described, and clinical implications discussed.

[The effect of Ca2+ channel blocker on insulin secretion in rat pancreatic islet cells].

OBJECTIVE: To study the effect and mechanism of Ca2+ channel blocker on the insulin secretion in islet beta cells of rats. METHODS: The cells were divided into two groups: the low sugar concentration and high sugar concentration groups. These cells were examined with radioimmunoassay and fluorescence method and the effects of nifedipine (NIF), verapamil (VER), and diltiazem (DIL) on the contents of Ca2+ in the islet cells and the secretion volume of insulin at different concentrations were observed. RESULTS: In the low sugar concentration group, NIF, VER and DIL at concentration of 25, 50 and 100 microg/L respectively showed no effect on the contents of Ca2+ in islet cells and the insulin secretion (no statistical significance, P > 0.05). In the high sugar concentration group, these drugs had no inhibitory effect on insulin secretion at concentration of 25 microg/L. However, there was remarkable reduction in Ca2+ contents and insulin secretion when NIF was at the concentration of 50 and 100 microg/L, showing a relationship with dosage (P > 0.05, P > 0.01). VER, when given at 50 microg/L, showed a tendency of reduction in insulin secretion and there was a remarkable reduction at a dosage of 100 microg/L as compared with the control group (P > 0.05). When DIL was given at 100 microg/L, there was a noticeable difference in reduction of insulin secretion as compared with the control group (P > 0.05). CONCLUSION: High dosage of NIF, VER and DIL has an inhibitory effect on the entrance of extracellular Ca2+ into islet cells and thus reduces insulin secretion.