Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation.

BACKGROUND: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. METHODS: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. RESULTS: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-ß/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. CONCLUSION: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.

A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity of antibodies with the cytotoxicity of chemotherapeutic drugs to reduce adverse reactions by preferentially targeting the payload to the tumor. The structure of ADCs has also provided inspiration for the development of additional drug conjugates. In recent years, drug conjugates such as ADCs, peptide‒drug conjugates (PDCs) and radionuclide drug conjugates (RDCs) have been approved by the Food and Drug Administration (FDA). The scope and application of drug conjugates have been expanding, including combination therapy and precise drug delivery, and a variety of new conjugation technology concepts have emerged. Additionally, new conjugation technology-based drugs have been developed in industry. In addition to chemotherapy, targeted therapy and immunotherapy, drug conjugate therapy has undergone continuous development and made significant progress in treating lung cancer in recent years, offering a promising strategy for the treatment of this disease. In this review, we discuss recent advances in the use of drug conjugates for lung cancer treatment, including structure-based drug design, mechanisms of action, clinical trials, and side effects. Furthermore, challenges, potential approaches and future prospects are presented.

Comprehensive bioinformatics analysis of the solute carrier family and preliminary exploration of SLC25A29 in lung adenocarcinoma.

According to the latest epidemiological investigation, lung adenocarcinoma (LUAD) is one of the most fatal cancer among both men and women. Despite continuous advancements in treatment approaches in recent years, the prognosis for LUAD remains relatively poor. Given the crucial role of the solute carrier (SLC) family in maintaining cellular energy metabolism stability, we conducted a comprehensive analysis of the association between SLC genes and LUAD prognosis. In the present study, we identified 71 genes among the SLC family members, of which 32 were downregulated and 39 were upregulated in LUAD samples. Based on these differentially expressed genes, a prognostic risk scoring model was established that was composed of five genes (SLC16A7, SLC16A4, SLC16A3, SLC12A8, and SLC25A15) and clinical characteristics; this model could effectively predict the survival and prognosis of patients in the cohort. Notably, SLC2A1, SLC25A29, and SLC27A4 were identified as key genes associated with survival and tumor stage. Further analysis revealed that SLC25A29 was underexpressed in LUAD tissue and regulated the phenotype of endothelial cells. Endothelial cell proliferation and migration increased and apoptosis decreased with a decrease in SLC25A29 expression. Investigation of the upstream regulatory mechanisms of SLC25A29 revealed that SLC25A29 expression gradually decreased as the lactate concentration increased. This phenomenon suggested that the expression of SLC25A29 may be related to lactylation modification. ChIP-qPCR experiments confirmed the critical regulatory role played by H3K14la and H3K18la modifications in the promoter region of SLC25A29. In conclusion, this study confirmed the role of SLC family genes in LUAD prognosis and revealed the role of SLC25A29 in regulating endothelial cell phenotypes. These study results provided important clues to further understand LUAD pathogenesis and develop appropriate therapeutic strategies.

Effects of microwave ablation on serum Golgi protein 73 in patients with primary liver cancer.

BACKGROUND: Microwave ablation (MWA) is an effective treatment option for patients with primary liver cancer. However, it has been reported that the MWA procedure induces a hepatic inflammatory response and injury, which may negatively affect the efficacy of MWA. As such, the discovery of reliable markers to monitor the patient's response to MWA is needed. Golgi protein 73 (GP73) has been shown to be associated with chronic liver disease. To date, the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear. AIM: To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer. METHODS: A total of 150 primary liver cancer patients with a single small lesion (≤ 3 cm in diameter) were retrospectively enrolled spanning the period between January 2016 and October 2018. All of the patients received MWA for the treatment of primary liver cancer. Serum GP73, alpha-fetoprotein (AFP), and widely used liver biochemical indicators [serum albumin, total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared before MWA and at different time points, including 1, 2, and 4 wk following the ablation procedure. RESULTS: Complete tumor ablation was achieved in 95.33% of the patients at 1 mo after MWA. The 1-, 2-, and 3-year disease-free survival rates were 74.67%, 59.33%, and 54.00%, respectively. The serum AFP levels were significantly decreased at 1, 2, and 4 wk after MWA; they returned to the normal range at 12 wk after MWA; and they remained stable thereafter during follow-up in those cases without recurrence. In contrast, the serum GP73 levels were significantly increased at 1 and 2 wk after MWA. The serum GP73 levels reached the peak at 2 wk after MWA, started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione, and returned to the pretreatment levels at 12 and 24 wk after MWA. Notably, the changes of serum GP73 in response to MWA were similar to those of TBIL, ALT, and AST. CONCLUSION: Serum GP73 is markedly increased in response to MWA of liver cancer. Thus, serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.

Effect of Occupational Extremely Low-Frequency Electromagnetic Field Exposure on the Thyroid Gland of Workers: A Prospective Study.

OBJECTIVE: The aim of this study was to investigate the biological effects of occupational extremely low-frequency electromagnetic field (ELF-EMF) exposure on the thyroid gland. METHODS: We conducted a prospective analysis of 85 workers (exposure group) exposed to an ELF-EMF (100 µT, 10-100 Hz) produced by the electromagnetic aircraft launch system and followed up on thyroid function indices, immunological indices, and color Doppler images for 3 years. Additionally, 116 healthy volunteers were randomly selected as controls (control group), the thyroid function of whom was compared to the exposure group. RESULTS: No significant difference was observed in thyroid function between the exposure and control groups. During the follow-up of the exposure group, the serum free triiodothyronine (FT3) level was found to slowly decrease and free thyroxine (FT4) level slowly increase with increasing exposure time. However, no significant difference was found in thyroid-stimulating hormone (TSH) over the three years, and no significant difference was observed in the FT3, FT4 and TSH levels between different exposure subgroups. Furthermore, no significant changes were observed in thyroid autoantibody levels and ultrasound images between subgroups or over time. CONCLUSION: Long-term exposure to ELF-EMF may promote thyroid secretion of T4 and inhibit deiodination of T4 to T3. ELF-EMF has no significant effect on thyroid immune function and morphology.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Tailoring Multifunctional Small Molecular Photosensitizers to In Vivo Self-Assemble with Albumin to Boost Tumor-Preferential Accumulation, NIR Imaging, and Photodynamic/Photothermal/Immunotherapy.

Cancer immunotherapy has great potential in tumor eradication and metastasis suppression. However, systemic administration of immune adjuvants and inadequate specificity in cancer treatment, lead to restricted therapeutic benefits and potential immune-related side effects in clinical settings. In this report, the synthesis of various lengths of heptamethine cyanine small molecules to act as multifunctional photosensitizers (PS) for tumor-specific accumulation, near-infrared (NIR) fluorescent imaging, and photodynamic/photothermal/immunotherapy is optimized. In particular, it is demonstrated that C8, which contains eight carbons on two N-alkyl side chains, efficiently self-assembles with albumin to form nanosized dye-albumin complexes. This feature facilitates C8 in vivo self-assembly to remarkably improve its water-solubility, NIR fluorescent emission, long-term blood circulation, as well as tumor-specific accumulation. More importantly, C8 not only exhibits a superior phototherapeutic effect on primary tumors, but also elicits secretion of damage associated molecular patterns, cytokine secretion, dendritic cell maturation, and cytotoxic T lymphocytes activation, ultimately triggering a sufficient antitumor immune response to suppress growths of distant and metastatic tumors. Hence, this multifunctional small molecular PS is characterized with excellent tumor-preferential accumulation, imaging-guided laser irradiation, and phototherapy-induced in situ antitumor immune response, providing a prospective future of its use in tumor-targeting immunotherapy.

Long Noncoding RNAs and Circular RNAs in the Metabolic Reprogramming of Lung Cancer: Functions, Mechanisms, and Clinical Potential.

As key regulators of gene function, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are generally accepted to be involved in lung cancer pathogenesis and progression. Recent research has clarified the phenomenon of metabolic reprogramming in lung cancer because of its significant role in tumor proliferation, migration, invasion, metastasis, and other malignant biological behaviors. Emerging evidence has also shown a relationship between the aberrant expression of lncRNAs and circRNAs and metabolic reprogramming in lung cancer tumorigenesis. This review provides insight regarding the roles of different lncRNAs and circRNAs in lung cancer metabolic reprogramming, by how they target transporter proteins and key enzymes in glucose, lipid, and glutamine metabolic signaling pathways. The clinical potential of lncRNAs and circRNAs as early diagnostic biomarkers and components of therapeutic strategies in lung cancer is further discussed, including current challenges in their utilization from the bench to the bedside and how to adopt a proper delivery system for their therapeutic use.

Establishment of a Prognostic Model of Lung Adenocarcinoma Based on Tumor Heterogeneity.

Lung cancer is one of the main cancer types due to its persistently high incidence and mortality, yet a simple and effective prognostic model is still lacking. This study aimed to identify independent prognostic genes related to the heterogeneity of lung adenocarcinoma (LUAD), generate a prognostic risk score model, and construct a nomogram in combination with other pathological characteristics to predict patients' overall survival (OS). A significant amount of data pertaining to single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and somatic mutation were used for data mining. After statistical analyses, a risk scoring model was established based on eight independent prognostic genes, and the OS of high-risk patients was significantly lower than that of low-risk patients. Interestingly, high-risk patients were more sensitive and effective to immune checkpoint blocking therapy. In addition, it was noteworthy that CCL20 not only affected prognosis and differentiation of LUAD but also led to poor histologic grade of tumor cells. Ultimately, combining risk score, clinicopathological information, and CCL20 mutation status, a nomogram with good predictive performance and high accuracy was established. In short, our research established a prognostic model that could be used to guide clinical practice based on the constantly updated big multi-omics data. Finally, this analysis revealed that CCL20 may become a potential therapeutic target for LUAD.

Novel phosphanegold(I) thiolate complexes suppress de novo lipid synthesis in human lung cancer.

The upregulation of lipid metabolism is considered one of the most common characteristic changes in tumor cells. In this study, the effects of phosphanegold(I) thiolate complexes on the regulation of lipid metabolism in lung cancer cells were investigated. Six novel phosphanegold(I) thiolate complexes capable of inhibiting lung cancer cell growth both in vitro and in vivo were synthesized and characterized. These complexes significantly inhibited the activity of thioredoxin reductases and impaired the normal structure and function of mitochondria, leading to an accumulation of internal reactive oxygen species. In addition, they markedly inhibited key enzymes involved in de novo lipid synthesis, including sterol regulatory element-binding proteins, fatty acid synthase, and adenosine triphosphate citrate lyase, thus reducing endogenous fatty acid and phospholipid synthesis. Both approaches suppressed lipid droplets storage and ultimately induced apoptosis in lung cancer cells. Interestingly, pretreatment with N-acetyl-l-cysteine and free fatty acids partially reversed the inhibitory effect of phosphanegold(I) thiolate complexes on lung cancer cells. These results are the first to indicated that gold(I) complexes are promising candidates for targeting lipid metabolism in lung cancer treatment strategies.

Necroptosis in Pulmonary Diseases: A New Therapeutic Target.

In the past decades, apoptosis has been the most well-studied regulated cell death (RCD) that has essential functions in tissue homeostasis throughout life. However, a novel form of RCD called necroptosis, which requires receptor-interacting protein kinase-3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), has recently been receiving increasing scientific attention. The phosphorylation of RIPK3 enables the recruitment and phosphorylation of MLKL, which oligomerizes and translocates to the plasma membranes, ultimately leading to plasma membrane rupture and cell death. Although apoptosis elicits no inflammatory responses, necroptosis triggers inflammation or causes an innate immune response to protect the body through the release of damage-associated molecular patterns (DAMPs). Increasing evidence now suggests that necroptosis is implicated in the pathogenesis of several human diseases such as systemic inflammation, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, neurological diseases, and cancer. This review summarizes the emerging insights of necroptosis and its contribution toward the pathogenesis of lung diseases.

Gold Compounds and the Anticancer Immune Response.

Gold compounds are not only well-explored for cytotoxic effects on tumors, but are also known to interact with the cancer immune system. The immune system deploys innate and adaptive mechanisms to protect against pathogens and prevent malignant transformation. The combined action of gold compounds with the activated immune system has shown promising results in cancer therapy through in vivo and in vitro experiments. Gold compounds are known to induce innate immune responses; however, these responses may contribute to adaptive immune responses. Gold compounds play the role of a major hapten that acts synergistically in innate immunity. Gold compounds support cancer cell antigenicity and promote anti-tumor immune response by inducing the release of CRT, ATP, HMGB1, HSP, and NKG2D to enhance immunogenicity. Gold compounds affect various immune cells (including suppressor regulatory T cells), inhibit myeloid derived suppressor cells, and enhance the function and number of dendritic cells. Gold nanoparticles (AuNPs) have potential for improving the effect of immunotherapy and reducing the toxicity and side effects of the treatment process. Thus, AuNPs provide an ideal opportunity for exploring the combination of anticancer gold compounds and immunotherapeutic interventions.

Recent Advances of Gold Compounds in Anticancer Immunity.

In recent years, gold compounds have gained more and more attentions in the design of new metal anticancer drugs. Numerous researches have reported that gold compounds, in addition to their widely studied cytotoxic antitumor effects, also reverse tumor immune escape and directly facilitate the functions of immune cells, leading to enhanced anticancer effects. This review mainly summarizes our current understandings of antitumor effects of gold drugs and their relationships with various aspects of antitumor immunity, including innate immunity, adaptive immunity, immunogenic cell death, and immune checkpoints, as well as their roles in adverse effects. Some recent examples of anticancer gold compounds are highlighted. The property of gold compounds is expected to combine with anticancer immunotherapy, such as immune checkpoint inhibitors, to develop new anticancer therapeutic strategies.

IL-6 and CD8+ T cell counts combined are an early predictor of in-hospital mortality of patients with COVID-19.

BACKGROUNDFatal cases of COVID-19 are increasing globally. We retrospectively investigated the potential of immunologic parameters as early predictors of COVID-19.METHODSA total of 1018 patients with confirmed COVID-19 were enrolled in our 2-center retrospective study. Clinical feature, laboratory test, immunological test, radiological findings, and outcomes data were collected. Univariate and multivariable logistic regression analyses were performed to evaluate factors associated with in-hospital mortality. Receiver operator characteristic (ROC) curves and survival curves were plotted to evaluate their clinical utility.RESULTSThe counts of all T lymphocyte subsets were markedly lower in nonsurvivors than in survivors, especially CD8+ T cells. Among all tested cytokines, IL-6 was elevated most significantly, with an upward trend of more than 10-fold. Using multivariate logistic regression analysis, IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/µL were found to be associated with in-hospital mortality after adjusting for confounding factors. Groups with IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/µL had a higher percentage of older and male patients as well as a higher proportion of patients with comorbidities, ventilation, intensive care unit admission, shock, and death. Furthermore, the receiver operating curve of the model combining IL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/µL) displayed a more favorable discrimination than that of the CURB-65 score. The Hosmer-Lemeshow test showed a good fit of the model, with no statistical significance.CONCLUSIONIL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/µL) are 2 reliable prognostic indicators that accurately stratify patients into risk categories and predict COVID-19 mortality.FundingThis work was supported by funding from the National Natural Science Foundation of China (no. 81772477 and 81201848).

Hospitalization Due to Asthma Exacerbation: A China Asthma Research Network (CARN) Retrospective Study in 29 Provinces Across Mainland China.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.

Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease.

BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ±â€Š6.60 vs. 41.27 ±â€Š4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

Long non-coding RNA JPX correlates with poor prognosis and tumor progression in non-small-cell lung cancer by interacting with miR-145-5p and CCND2.

Emerging studies have shown that the aberrant expression and function of long non-coding RNAs (lncRNAs) are involved in carcinogenesis and the development of various cancers. The long noncoding RNA JPX (lncRNA JPX) on the X chromosome is an activator of X-inactive-specific transcript (XIST) and is a molecular switch for X-chromosome inactivation. However, the exact mechanism by which JPX acts in non-small-cell lung cancer (NSCLC) is not well studied. Here, through integrating clinical data and a series of functional experiments, we found that lncRNA JPX expression is significantly upregulated in NSCLC tissues compared with that in paired adjacent normal tissues from two independent datasets and significantly associated with a poor survival and other malignant phenotypes (tumor stage, tumor volume) of NSCLC. Furthermore, we elucidated that JPX functions as an oncogene in NSCLC-promoting cell proliferation and cell migration by affecting cell-cycle progression. Mechanistically, JPX upregulates cyclin D2 (CCND2) expression in a competing endogenous RNA mechanism by interacting with miR-145-5p, thus provoking the development and progression of NSCLC. These findings reveal the mechanism of X-chromosome lncRNA JPX and its core regulatory circuitry JPX/miR-145-5p/CCND2 in the development and progression of NSCLC, which bring us closer to an understanding of the molecular drivers of NSCLC.

Distinct prognostic values of mRNA expression of glutathione peroxidases in non-small cell lung cancer.

INTRODUCTION: Glutathione peroxidases (GPxs) constitutes an enzyme family which has the ability to reduce free hydrogen peroxide to water and lipid hydroperoxides to their corresponding alcohols, and its main biological roles are to protect organisms from oxidative stress-induced damage. GPxs include eight members in different tissues of the body, and they play essential roles in carcinogenesis. However, the prognostic value of individual GPx in non-small cell lung cancer (NSCLC) remains elusive. MATERIALS AND METHODS: In the current study, we investigated the prognostic value of GPxs in NSCLC patients through the "Kaplan-Meier plotter" database, wherein updated gene expression data and survival information from a total of 1,926 NSCLC patients are included. RESULTS: High expression of GPx1 mRNA was correlated with worse overall survival (OS) in adenocarcinoma patients. High expression of GPx2 mRNA was correlated with worse OS for all NSCLC patients. In contrast, high expression of GPx3 mRNA was associated with better OS for all NSCLC patients. High expression of GPx4 mRNA was significantly correlated with worsening adenocarcinoma in these patients. GPx5 mRNA high expression correlated with worsening OS for all NSCLC patients. DISCUSSION: The current findings of prognostic values of individual mRNA expression of GPxs in NSCLC patients indicate some GPxs may have prognostic value in NSCLC patients, and this needs further study.