Correlation between tumor necrosis factor-α and interleukin-1β in exhaled breath condensate and pulmonary function in chronic obstructive pulmonary disease / 中国热带医学

@#Abstract: Objective To explore the correlation between lung function in patients with chronic obstructive pulmonary disease (COPD) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels in exhaled breath condensate (EBC), and to provide a convenient methodological basis for the diagnosis and treatment of COPD and the determination of its efficacy. Methods A total of 81 COPD patients and 40 healthy controls were selected from the respiratory department of the Fourth Affiliated Hospital of Guangzhou Medical University from August 2020 to February 2022 as the research subjects. The COPD patients were divided into 41 cases in the acute exacerbation group and 40 cases in the remission group according to their status. All participants underwent lung function detection, venous blood and EBC collection, and the levels of TNF-α and IL-1β in EBC and venous blood were analyzed by enzyme-linked immunosorbent assay (ELISA), and correlation analysis was performed by Pearson correlation analysis method. Results The levels of TNF-α and IL-1β in EBC of in the acute exacerbation group, the healthy control group, the remission group were (5.16±0.18) pg/μL and (7.75±0.27) pg/μL, (2.66±0.31) pg/μL and (2.41±0.24） pg/μL, (3.61±0.29) pg/μL and (3.17±0.38) pg/μL, respectively. Compared with the healthy control group, the levels of TNF-α and IL-1β in EBC in the COPD acute exacerbation group were significantly higher than those in the healthy control group and the COPD remission group (F=9.451, 8.217, P<0.001). Serum tests were consistent with this result. Correlation analysis showed that the levels of TNF-α and IL-1β in EBC were significantly positively correlated with the level of serum inflammation levels (P<0.001), while significantly negatively correlated with lung function (P<0.001).  Conclusions TNF-α and IL-1β in EBC are potential biomarkers of inflammation in patients with COPD, and their detection can be used to effectively assess lung function in patients with COPD. 

An Investigation of Employees' Intention to Comply with Information Security System-A Mixed Approach Based on Regression Analysis and fsQCA.

Employee security compliance behavior has become an important safeguard to protect the security of corporate information assets. Focusing on human factors, this paper discusses how to regulate and guide employees' compliance with information security systems through effective methods. Based on protection motivation theory (PMT), a model of employees' intention to comply with the information security system was constructed. A questionnaire survey was adopted to obtain 224 valid data points, and SPSS 26.0 was applied to verify the hypotheses underlying the research model. Then, based on the results of a regression analysis, fuzzy set qualitative comparative analysis (fsQCA) was used to explore the conditional configurations that affect employees' intention to comply with the information security system from a holistic perspective. The empirical results demonstrated that perceived severity, perceived vulnerability, response efficacy, and self-efficacy all positively influenced the employees' intention to comply with the information security system; while rewards and response costs had a negative effect. Threat appraisal had a greater effect on employees' intention to comply with the information security system compared to response appraisal. The fsQCA results showed that individual antecedent conditions are not necessary to influence employees' intention to comply with an information security system. Seven pathways exist that influence an employees' intention to comply with an information security system, with reward, self-efficacy, and response cost being the core conditions having the highest probability of occurring in each configuration of pathways, and with perceived severity and self-efficacy appearing in the core conditions of configurations with an original coverage greater than 40%. Theoretically, this study discusses the influence of the elements of PMT on employees' intention to comply with an information security system, reveals the mechanism of influence of the combination of the influencing factors on the outcome variables, and identifies the core factors and auxiliary factors in the condition configurations, providing a new broader perspective for the study of information security compliance behavior and providing some theoretical support for strengthening enterprise security management. Practically, targeted suggestions are proposed based on the research results, to increase the intention of enterprise employees to comply with information security systems, thereby improving the effectiveness of enterprise information security management and the degree of information security in enterprises.

Correction to: Platelet-derived growth factor-BB induces pulmonary venous smooth muscle cells proliferation by upregulating calcium sensing receptor under hypoxic conditions.

[This corrects the article DOI: 10.1007/s10616-021-00456-5.].

Chronic hypoxia promoted pulmonary arterial smooth muscle cells proliferation through upregulated calcium-sensing receptorcanonical transient receptor potential 1/6 pathway.

OBJECTIVES: Although both calcium-sensing receptor (CaSR) and canonical transient receptor potential (TRPC) proteins contribute to chronic hypoxia (CH)-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, the relationship between CaSR and TRPC in hypoxic PASMCs proliferation remains poorly understood. The goal of this study was to identify that CH promotes PASMCs proliferation through CaSR-TRPC pathway. METHODS: Rat PASMCs were isolated and treated with CH. Cell proliferation was assessed by cell counting, CCK-8 assay, and EdU incorporation. CaSR and TRPC expressions were determined by qPCR and Western blotting. Store-operated Ca2+ entry (SOCE) was assessed by extracellular Ca2+ restoration. RESULTS: In PASMCs, CH enhanced the cell number, cell viability and DNA synthesis, which is accompanied by upregulated expression of CaSR, TRPC1 and TRPC6. Negative CaSR modulators (NPS2143, NPS2390) inhibited, whereas positive modulators (spermine, R568) enhanced, the CH-induced increases in cell number, cell viability and DNA synthesis in PASMCs. Knockdown of CaSR by siRNA inhibited the CH-induced upregulation of TRPC1 and TRPC6 and enhancement of SOCE and attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. However, neither siTRPC1 nor siTRPC6 had an effect on the CH-induced CaSR upregulation, although both significantly attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. CONCLUSION: These results demonstrate that upregulated CaSR-TRPC1/6 pathway mediating PASMCs proliferation is an important pathogenic mechanism under hypoxic conditions.

Platelet-derived growth factor-BB induces pulmonary venous smooth muscle cells proliferation by upregulating calcium sensing receptor under hypoxic conditions.

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which exists in both pulmonary arteries and pulmonary veins. Pulmonary vascular remodeling stems from excessive proliferation of pulmonary vascular myocytes. Platelet-derived growth factor-BB (PDGF-BB) is a vital vascular regulator whose level increases in PH human lungs. Although the mechanisms by which pulmonary arterial smooth muscle cells respond to PDGF-BB have been studied extensively, the effects of PDGF-BB on pulmonary venous smooth muscle cells (PVSMCs) remain unknown. We herein examined the involvement of calcium sensing receptor (CaSR) in PDGF-BB-induced PVSMCs proliferation under hypoxic conditions. In PVSMCs isolated from rat intrapulmonary veins, PDGF-BB increased the cell number and DNA synthesis under normoxic and hypoxic conditions, which was accompanied by upregulated CaSR expression. The influences of PDGF-BB on proliferation and CaSR expression in hypoxic PVSMCs were greater than that in normoxic PVSMCs. In hypoxic PVSMCs superfused with Ca2+-free solution, restoration of extracellular Ca2+ induced an increase of [Ca2+]i, which was significantly smaller than that in PDGF-BB-treated hypoxic PVSMCs. The positive CaSR modulator spermine enhanced, whereas the negative CaSR modulator NPS2143 attenuated, the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs. Furthermore, the spermine enhanced, whereas the NPS2143 inhibited, PDGF-BB-induced proliferation in hypoxic PVSMCs. Silencing CaSR with siRNA attenuated the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs and inhibited PDGF-BB-induced proliferation in hypoxic PVSMCs. In conclusion, these results demonstrated that CaSR mediating PDGF-BB-induced excessive PVSMCs proliferation is an important mechanism involved in the initiation and progression of PVSMCs proliferation under hypoxic conditions.

A novel function of calcium sensing receptor in chronic hypoxia-induced pulmonary venous smooth muscle cells proliferation.

Chronic hypoxia (CH) causes remodeling not only in pulmonary arteries but also in pulmonary veins. Pulmonary vascular remodeling stems from increased pulmonary vascular myocyte proliferation. However, the pathogenesis of CH-induced proliferation of pulmonary venous smooth muscle cells (PVSMCs) remains unknown. The present study aimed to explore the mechanisms by which CH affects PVSMCs proliferation. PVSMCs were isolated from rat distal pulmonary veins and exposed to CH (4% O2 for 60 h). The expression of calcium sensing receptor (CaSR) was determined by immunofluorescence, real-time quantitative PCR and Western blotting. Cell proliferation was assessed by cell counting, CCK-8 assay, and BrdU incorporation. Apoptosis analysis was examined by flow cytometry. In rat distal PVSMCs, CH increased the cell number and cell viability and enhanced DNA synthesis, which is accompanied by upregulated mRNA and protein expression levels of CaSR. Two negative CaSR modulators (NPS2143, NPS2390) not only attenuated CH-induced CaSR upregulation but also inhibited CH-induced increases in cell number, cell viability and the proliferation index of PVSMCs, whereas two positive modulators (spermine, R568) not only amplified CH-induced CaSR upregulation but also intensified CH-induced increases in cell number, cell viability and the proliferation index of PVSMCs. Silencing CaSR with siRNA similarly attenuated the CH-induced enhancement of cell number, cell viability and DNA synthesis in PVSMCs. Neither CH nor downregulation of CaSR with siRNA had an effect on apoptosis in PVSMCs. These results suggest that CaSR mediating excessive proliferation is a new pathogenic mechanism involved in the initiation and progression of distal PVSMCs proliferation under CH conditions.

Isolation, culture and identification of pulmonary arterial smooth muscle cells from rat distal pulmonary arteries.

The culture of pulmonary arterial smooth muscle cells (PASMCs) is one of the most powerful tools for exploring the mechanisms of pulmonary hypertension (PH). Both pulmonary vasoconstriction and remodeling occur predominantly in distal pulmonary arteries (PA). In this study, we provide our detailed and standardized protocol for easy isolation and culture of PASMCs from rat distal PA to supply every investigator with a simple, economical and useful method in studying PH. The protocol can be divided into four stages: isolation of distal PA, isolation of cells, growth in culture and passage of cells. Rat distal PASMCs were characterized by morphological activity and by immunostaining for smooth muscle α-actin and smooth muscle myosin heavy chain, but not for CD90/Thy-1 or von Willebrand factor. Furthermore, functional assessments were performed, confirming the presence of voltage-dependent Ca2+ channels and physiological characteristic of response to hypoxia. In conclusion, we have developed a detailed and simple protocol for obtaining rat distal PASMCs. These PASMCs exhibit features consistent with vascular smooth muscle cells, and they could subsequently be used to further explore the pathophysiological mechanisms of PH.

[Study on relative bioavailability of ferulic acid of combination Radix Angelicae Sinensis and Cortex Cinnamomi in mice].

OBJECTIVE: To study the phamacokinetics and relative bioavailability of combination Radix Angelicae Sinensis and Cortex Cinnamomi. METHOD: The content of ferulic acid in plasma was determined directly by HPLC after oral administration of Cortex Cinnamomi in combination individually with Radix Angelicae Sinensis. The plasma concentration-time curve were plotted. The main pharmacokinetic parameters and relative bioavailability were obtained. RESULT: The plasma concentration-time curve of fenalic aclid conformed to one-compartment model. The relative bioavailability of Cortex Cinnamomi combined with Radix Angelicae Sinensis were 226.75%. CONCLUSION: By the statistical analysis, Cortex Cinnamomi combined with Radix Angelicae Sinensis can increase the relative bioavailability of ferulic acid.

[Study on enhancing bioavailability of paeoniflorin by combined use with Chinese herbs for inner-warming].

OBJECTIVE: To study the influence of Chinese herbs for inner-warming on the bioavailability of paeoniflorin (PF) and its mechanism. METHODS: Chinese herbs (pepper fruit, evodia fruit, cassia bark, fennel fruit and prickly-ash peel) were separately used in combination with PF for gastrogavage to mice. Reversed phase high-performance liquid chromatography was used to determine the plasma concentration of PF in mice after medication. The bioavailability of PF was calculated and compared, taking single use of red peony root for control. RESULTS: The pharmacokinetics of PF in mice was conformed to the one-compartment model, as combined use with Chinese herbs for inner-warming, the relative bioavailability of PF was 137.22% for pepper fruit, 123.62% for evodia fruit, 108.39% for cassia bark, 226.02% for fennel fruit and 116.73% for prickly-ash peel, there were difference of Cmax and AUC(0-infinity) in comparison of these data with the control group (P < 0.05), but with no difference of tmax (P > 0.05). CONCLUSION: The Chinese herbs used in this experiment in combination with red peony root could enhance the bioavailability of PF, which illustrated the scientific meaning of the recipe combination of Chinese herbs for activating blood circulation and inner-warming viewing from pharmacodynamics.