Chromatographic evaluation and application of nitrogenous heterocyclic ring-bonded stationary phase in hydrophilic interaction liquid chromatography.

Hydrophilic interaction liquid chromatography (HILIC) based on polar stationary phases has vital research significance in the separation of polar compounds. Numerous HILIC stationary phases with different structures have been developed, which do not have universal properties and broad selectivity, making it a challenge to select the suitable column based on the properties of the samples. Consequently, it is particularly important to develop a bonded phase capable of separating a wide variety of samples, while having enhanced retention, improved selectivity, symmetric peak shape and good stability. Herein, a novel nitrogen-containing heterocyclic bonded phase with multiple functionalities, such as thioether, amino and hydroxyl groups (named AMTA) was employed as HILIC stationary phase. Detailed chromatographic evaluations were carried out, and the results showed that it was superior to other hydrophilic chromatographic columns in terms of selectivity, peak shapes and practical sample separation. Lastly, it has been verified that AMTA exhibited high orthogonality with the XBridge C18 column of reversed-phase liquid chromatography (RPLC) mode. In summary, we anticipate our assay to be instructive to other researchers in developing the HILIC stationary phase.

Application of the molecular dynamics simulation GROMACS in food science.

Food comprises proteins, lipids, sugars and various other molecules that constitute a multicomponent biological system. It is challenging to investigate microscopic changes in food systems solely by performing conventional experiments. Molecular dynamics (MD) simulation serves as a crucial bridge in addressing this research gap. The Groningen Machine for Chemical Simulations (GROMACS) is an open-source, high-performing molecular dynamics simulation software that plays a significant role in food science research owing to its high flexibility and powerful functionality; it has been used to explore the molecular conformations and the mechanisms of interaction between food molecules at the microcosmic level and to analyze their properties and functions. This review presents the workflow of the GROMACS software and emphasizes the recent developments and achievements in its applications in food science research, thus providing important theoretical guidance and technical support for obtaining an in-depth understanding of the properties and functions of food.

SERUM TRANSACTIVE RESPONSE DNA BINDING PROTEIN 43 ASSOCIATES WITH POOR SHORT-TERM NEUROLOGIC OUTCOME AFTER RETURN OF SPONTANEOUS CIRCULATION FOLLOWING CARDIAC ARREST.

ABSTRACT: Objective : To explore the association of serum transactive response DNA binding protein 43 (TDP-43) with 28-day poor neurologic outcome in patients with return of spontaneous circulation (ROSC) after cardiac arrest. Methods : We performed a study between January and December 2023. Eligible patients with ROSC following cardiac arrest were enrolled. Their baseline characteristics were collected, and serum levels of TDP-43, tumor necrosis factor-α, interleukin-6 and 10, C-reactive protein, and neuron-specific enolase (NSE) at 24 h after ROSC were measured. The neurologic function was assessed by the cerebral performance category scores on day 28 after ROSC. Results : A total of 92 patients were included, with 51 and 41 patients in the good and poor neurologic outcome groups, respectively. Serum TDP-43 was significantly higher in the poor than the good neurologic outcome group ( P < 0.05). Univariate and multivariate logistic regression analyses showed that TDP-43, Witnessed CA, IL-6, and NSE were associated with poor 28-day neurologic outcome (all P < 0.05). Restricted cubic spline analysis revealed that TDP-43 at the serum level of 11.64 pg/mL might be an ideal cutoff value for distinguishing between good and poor neurologic outcomes. Area under curve of serum TDP-43 (AUC = 0.78) was close to that of serum NSE (AUC = 0.82). A dynamic nomogram prediction model that combined TDP-43, Witnessed CA, IL-6, and NSE was constructed and validated. Conclusion : Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest.

A nitrogenous heterocyclic ring-bonded stationary phase for separating alkaloids in supercritical fluid chromatography.

A novel silica stationary phase was designed and prepared through thiol-epoxy click chemistry for supercritical fluid chromatography (SFC). The developed stationary phase was characterized by elemental analysis, Fourier transform infrared spectrometry and solid-state 13C/CP MAS NMR spectroscopy. In order to evaluate the chromatographic performance and retention mechanisms of the prepared column, a variety of alkaloids were used, including indoles, isoquinolines, pyrrolidines, piperidines, quinolizidines and organic amines. The stationary phase showed more symmetrical peak shapes and better performance for these compounds compared to the conventional SFC stationary phases. The investigations on the effects of pressure and temperature on retention provided information that the selectivity of the compounds can be improved by changing the density of the supercritical fluids. Moreover, it shows improved separation efficiency of three natural products with alkaloids as the main components at high sample loading. In conclusion, the developed stationary phase could offer flexible selectivity toward alkaloids and complex samples.

Ordered mesoporous silica microspheres for supercritical fluid chromatography.

Herein, silica microspheres with ordered mesopores are synthesized and applied as a stationary phase for supercritical fluid chromatography (SFC). The excellent particle monodispersity and pore orderliness coupled with the rapid analytes diffusion of the supercritical fluid lead to an ultra-high column efficiency of 340 000 plate per m.

[Development progress of stationary phase for supercritical fluid chromatography and related application in natural products].

Supercritical fluid chromatography (SFC) is an environment-friendly and efficient column chromatography technology that was developed to expand the application range of high performance liquid chromatography (HPLC) using a supercritical fluid as the mobile phase. A supercritical fluid has a temperature and pressure that are above the critical values as well as relatively dynamic characteristics that are between those of a gas and liquid. Supercritical fluids combine the advantages of high solubility and diffusion, as their diffusion and viscosity coefficients are equivalent to those of a gas, while maintaining a density that is comparable with that of a liquid. Owing to the remarkable compressibility of supercritical fluids, analyte retention in SFC is significantly influenced by the density of the mobile phase. Thus, the column temperature and back pressure are crucial variables that regulate analyte retention in SFC. Increasing the back pressure can increase the density and solubility of the mobile phase, leading to reductions in retention time. The column temperature can affect selectivity and retention, and the degree to which different analytes are affected by this property varies. On the one hand, increasing the temperature reduces the density of the mobile phase, thereby extending the retention time of the analytes; on the other hand, it can also increase the energy of molecules, leading to a shorter retention time of the analyte on the stationary phase. CO2, the most widely employed supercritical fluid to date, presents moderate critical conditions and, more importantly, is miscible with a variety of polar organic solvents, including small quantities of water. In comparison with the mobile phases used in normal-phase liquid chromatography (NPLC) and reversed-phase liquid chromatography (RPLC), the mobile phase for SFC has a polarity that can be extended over a wide range on account of its extensive miscibility. The compatibility of the mobile phase determines the diversity of the stationary phase. Nearly all stationary phases for HPLC, including the nonpolar stationary phases commonly used for RPLC and the polar stationary phases commonly used for NPLC, can be applied to SFC. Because all stationary phases can use the same mobile-phase composition, chromatographic columns with completely different polarities can be employed in SFC. The selectivity of SFC has been effectively expanded, and the technique can be used for the separation of diverse analytes ranging from lipid compounds to polar compounds such as flavonoids, saponins, and peptides. The choice of stationary phase has a great impact on the separation effect of analytes in SFC. As new stationary phases for HPLC are constantly investigated, specialized stationary phases for SFC have also been continuously developed. Researchers have discovered that polar stationary phases containing nitrogen heterocycles such as 2-EP and PIC are highly suitable for SFC because they can effectively manage the peak shape of alkaline compounds and provide good selectivity in separating acidic and neutral compounds.The development of various stationary phases has promoted the applications of SFC in numerous fields such as pharmaceuticals, food production, environmental protection, and natural products. In particular, natural products have specific active skeletons, multiple active groups, and excellent biological activity; hence, these materials can provide many new opportunities for the discovery of novel drugs. According to reports, compounds related to natural products account for 80% of all commercial drugs. However, natural products are among the most challenging compounds to separate because of their complex composition and low concentration of active ingredients. Thus, superior chromatographic methods are required to enable the qualitative and quantitative analysis of natural products. Thanks to technological improvements and a good theoretical framework, the benefits of SFC are gradually becoming more apparent, and its use in separating natural products is expanding. Indeed, in the past 50 years, SFC has developed into a widely used and efficient separation technology. This article provides a brief overview of the characteristics, advantages, and development process of SFC; reviews the available SFC stationary phases and their applications in natural products over the last decade; and discusses prospects on the future development of SFC.

Multi-effective components and their target mechanism of Ziziphi Spinosae Semen in the treatment of insomnia.

Insomnia is a common and refractory disease. Since more than 2000 years ago, people have been using Ziziphi Spinosae Semen (ZSS). However, there are lack of molecular mechanisms of sleep promotion effects of ZSS. The purpose of this study is to clarify the active ingredients in ZSS that are used to treat insomnia. Using a method called cellular label-free integrative pharmacology (CLIP), we established five insomnia-related target models, including serotonin (5HT2A and 5HT1A), melatonin (MT1), dopamine (D2) and epinephrine (ß2) receptors. The one-dimensional (1D) fractions of ZSS extract were prepared on a RZC18 column and assayed on five models. Subsequently, the active fraction was further analyzed, fractionated and quantified using a two-dimensional (2D) liquid phase method coupled with a charged aerosol detector (CAD), This CAD-coupled 2D-LC method requires micro-fractions from the 1D separation and thus it greatly saves sample amounts and corresponding preparation time, and quickly conduct activity screening. The composition of the active 2D fractions was then determined using three-dimensional (3D) HPLC-MS, and molecular docking was separately carried out for the described compounds on the targets for activity prediction. Seven compounds were predicted to be active on 5HT2A, and two compounds on D2. We experimentally verified the prediction and found that vitexin exhibited D2 agonistic activity, and nuciferine exhibited 5HT2A antagonistic activity. This study revealed the effective components and their targets of ZSS in the treatment of insomnia, also highlighted the potential of the CLIP technique and bioactivity guided multi-dimensional HPLC-MS in molecular mechanism elucidation for traditional Chinese medicines.

Application of chromatography in purification and structural analysis of natural polysaccharides: A review.

Polysaccharides are widely distributed in natural sources from monocytic microorganisms to higher animals, and are found in a variety of biological activities in recent decades. Natural polysaccharides have the characteristics of large molecular weight, diverse composition, and complex structure, so their purification and structural analysis are difficult issues in research. Chromatography as a powerful separation technique, plays an irreplaceable role in the separation and structural analysis of natural polysaccharides, especially in the purification of polysaccharides, the separation of hydrolysates, and the analysis of monosaccharide composition. The separation mechanisms and application of different chromatographic methods in the studies of polysaccharides were summarized in this review. Moreover, the advantages and drawbacks of various chromatography methods were discussed as well.

LSD1 knockdown confers protection against osteoclast formation by reducing histone 3 lysine 9 monomethylation and dimethylation in ITGB3 promoter.

ITGB3, an osteoclast marker, is involved in osteoclast formation. Nevertheless, its related mechanism remains poorly characterized. Herein, this study examines the mechanisms affecting osteoclast formation with the involvement of ITGB3. Osteoclast formation was induced with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL), followed by measurement of the mRNA and protein expression of ITGB3 and LSD1. After gain- and loss-of-function assays, cell viability and the expression of osteoclast marker genes (NFATc1, ACP5, and CTSK) were assessed, and osteoclast formation was evaluated with TRAP staining. ChIP assays were used to examine histone 3 lysine 9 (H3K9) monomethylation (H3K9me1) and H3K9 dimethylation (H3K9me2) modifications and LSD1 protein enrichment in the ITGB3 promoter. During osteoclast formation, ITGB3 and LSD1 were gradually augmented. Knockdown of LSD1 or ITGB3 curbed cell viability, the expression of osteoclast marker genes, and osteoclast formation. Moreover, overexpression of ITGB3 nullified the suppressive impact of LSD1 knockdown on osteoclast formation. Mechanistically, LSD1 promoted ITGB3 expression by reducing H3K9 levels in the ITGB3 promoter. LSD1 enhanced ITGB3 expression by decreasing H3K9me1 and H3K9me2 levels in ITGB3 promoter to boost osteoclast formation.

Chemical profiling of Ziziphi spinosae semen using on-line comprehensive two-dimensional liquid chromatography-mass spectrometry based on a novel phthalic anhydride bonded stationary phase.

Ziziphi spinosae semen has been widely used to treat insomnia and anxiety. To profile its chemical components, an online comprehensive two-dimensional liquid chromatography-mass spectrometry was developed. In this two-dimensional liquid chromatography system, a novel phthalic anhydride-bonded stationary phase column was combined with a C18 column. As a result, this new stationary phase exhibited remarkable differences in separation selectivity from C18, achieving a good orthogonality of 83.3%. Moreover, this new stationary phase with weaker hydrophobicity than C18 realized solvent compatibility in the online configuration. Coupled with tandem MS, 154 compounds were identified, including 51 unreported compounds. Compared with one-dimensional liquid chromatography-mass spectrometry, this online two-dimensional liquid chromatography-mass spectrometry system exhibited a much higher resolving power in isomer separation. This work provided an effective separation and characterization method for the material basis of Ziziphi spinosae semen. This strategy provides ideas for the material basis research of other traditional Chinese medicines.

Decoloration and alkaloid enrichment of Dactylicapnos scandens extracts based on the use of strong anion-exchange resins in tandem with strong cation-exchange silica-based materials.

Alkaloids are natural bioactive ingredients but are usually present in low amounts in plant extracts. In addition, the dark color of plant extracts increases the difficulty in separation and identification of alkaloids. Therefore, effective decoloration and alkaloid enrichment methods are necessary for purification and further pharmacological studies of alkaloids. In this study, a simple and efficient strategy is developed for the decoloration and alkaloid enrichment of Dactylicapnos scandens (D. scandens) extracts. In feasibility experiments, we evaluated two anion-exchange resins and two cation-exchange silica-based materials with different functional groups using a standard mixture composed of alkaloids and nonalkaloids. By virtue of its high adsorbability of nonalkaloids, the strong anion-exchange resin PA408 is considered a better choice for the removal of nonalkaloids, and the strong cation-exchange silica-based material HSCX was selected for its great adsorption capacity for alkaloids. Furthermore, the optimized elution system was applied for the decoloration and alkaloid enrichment of D. scandens extracts. Nonalkaloid impurities in the extracts were removed by the use of PA408 in tandem with HSCX treatment, and the total alkaloid recovery, decoloration and impurity removal ratios are determined to be 98.74%, 81.45% and 87.33%, respectively. This strategy can contribute to further alkaloid purification and pharmacological profiling of D. scandens extracts, as well as other plants with medicinal value.

Recent developments and controversies in therapeutic hypothermia after cardiopulmonary resuscitation.

Therapeutic hypothermia was recommended as the only neuroprotective treatment in comatose patients after return of spontaneous circulation (ROSC). With new evidence suggesting a similar neuroprotective effect of 36 °C and 33 °C, the term "therapeutic hypothermia" was substituted by "targeted temperature management" in 2011, which in turn was replaced by the term "temperature control" in 2022 because of new evidence of the similar effects of target normothermia and 33 °C. However, there is no clear consensus on the efficacy of therapeutic hypothermia. In this article, we provide an overview of the recent evidence from basic and clinical research related to therapeutic hypothermia and re-evaluate its application as a post-ROSC neuroprotective intervention in clinical settings.

A guide of column selection for two-dimensional liquid chromatography method development of natural alkaloids.

Natural products, especially alkaloids, are one of the most valuable, potential drug leads in drug discovery. As an efficient tool for complex samples, two-dimensional liquid chromatography (2D-LC) has become a powerful means of analysis and separation of natural alkaloids. Method development of 2D-LC is of great importance because it helps to enhance the selectivity, resolution and peak capacity of a separation system. However, due to the diversity of the nature and subclasses of natural alkaloids, peak tailing occurs frequently, making alkaloid separation complicated and time-consuming. To conquer such difficulties, we proposed a guide for column selection and combination in 2D-LC so as to improve the alkaloid separation. Based on a comprehensive evaluation of applicability and orthogonality of several columns, this guide would provide a simple but clear starting point for column selection of 2D-LC method development. The evaluation included seven columns to involve most separation mechanisms reported in alkaloid separation, and 49 natural alkaloid standards of various subclasses and natures. Detailed studies of peak shapes of every column were carried out as well, providing useful references to better understand the peak tailing issues of some analytes on specific columns. Subsequently, a 2D-LC method was developed using our guide to isolate an alkaloid sample from U. rhynchophylla, generating symmetrical peaks and a high orthogonality of 80.3%. Further, this evaluation process would help to have a quick understanding when a new stationary phase is designed.

Psychological contract breach and job performance of new generation of employees: Considering the mediating effect of job burnout and the moderating effect of past breach experience.

With the intensification of COVID-19 epidemic, it becomes prominent to discuss the issue about the influence of psychological contract breach on job performance of new generation of employees. Based on social exchange theory, fairness theory, and conservation of resource theory, this study constructed a relationship model between psychological contract breach and job performance of new generation of employees with considering the mediating effect of job burnout and the moderating effect of past breach experience. Our hypotheses were tested using data from 235 respondents working in Yunnan Province, China. The results were as follows: first, psychological contract breach had a significant negative effect on job performance of new generation of employees, whether in the whole sample or in two grouped samples; second, both in the overall sample and the grouped sample of state-owned enterprises, job burnout partially mediated the negative relationship between psychological contract breach and job performance of new generation of employees, and past experience of breach positively moderated the negative relationship between psychological contract breach and job performance of new generation of employees; third, in the grouped sample of non-state-owned enterprises, job burnout did not play a significant mediating role in the relationship between psychological contract breach and job performance of new generation of employees, and past breach experience did not play a significant moderating role in this relationship. These findings uncover the psychological mechanism underlying work performance of new generation of employees, and also provide useful theoretical reference for management practices of new generation of employees among different natures of enterprises.

microRNA-25-3p suppresses osteogenic differentiation of BMSCs in patients with osteoporosis by targeting ITGB3.

This study was conducted to investigate the impact of the microRNA (miR)-25-3p/ITGB3 axis on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from patients with osteoporosis (OP). BMSCs isolated from the bone marrow of healthy controls and OP patients were identified by flow cytometry, in which ITGB3 mRNA and miR-25-3p expression was detected by RT-qPCR and ITGB3, Runx2, OPN, ALP, and OSX protein expression by western blot. The binding between ITGB3 and miR-25-3p was assessed by dual-luciferase reporter gene and Ago2-RIP assays. BMSC osteogenic differentiation was observed by alizarin red staining and ALP activity. The differentiation of BMSCs to adipocytes and chondrocytes was measured by oil red O staining and alcian blue staining, respectively. BMSCs were successfully isolated from the bone marrow of healthy controls (normal-BMSCs) and OP patients (OP-BMSCs). ITGB3, Runx2, OPN, ALP, and OSX expression was poorer and miR-25-3p expression was higher in OP-BMSCs than in normal-BMSCs. Mechanistically, ITGB3 was negatively targeted by miR-25-3p. After osteogenic, adipogenic, and chondrogenic differentiation of BMSCs were successfully induced, adipogenic differentiation increased and osteogenic and chondrogenic differentiation decreased in OP-BMSCs compared with normal-BMSCs. Overexpression of ITGB3 facilitated mineralized nodule formation and elevated ALP activity and Runx2, OPN, and ALP expression in OP-BMSCs. miR-25-3p upregulation diminished mineralized nodule formation, ALP activity, and Runx2, OPN, and ALP expression in OP-BMSCs and normal-BMSCs, which was annulled by additional ITGB3 overexpression. miR-25-3p targets ITGB3, thereby suppressing osteogenic differentiation of BMSCs from OP patients.

SIRT5 promotes non-small cell lung cancer progression by reducing FABP4 acetylation level.

This study evaluates the role of SIRT5 in non-small cell lung cancer (NSCLC) progression and explores the underlying mechanism. The expression and correlation of SIRT5 and FABP4 in lung cancer were analyzed by the GEPIA database. The expression levels of SIRT5 and FABP4 in NSCLC cells were measured by qRT-PCR and western blot. The effect of SIRT5 and FABP4 on NSCLC cell development was determined. The interaction between SIRT5 and FABP4 was analyzed by co-immunoprecipitation (Co-IP). Tumor mass and volume were measured in nude mice to study the effect on the growth of NSCLC transplanted tumors. GEPIA database analysis showed that SIRT5 was highly expressed, while FABP4 was lowly expressed in lung cancer, which was consistent with the detection results of SIRT5 and FABP4 expressions in NSCLC cell lines. The expression of SIRT5 was negatively correlated with FABP4. Transfection of sh-SIRT5 in NSCLC cells led to a decrease in NSCLC cell malignancy, which was counteracted by sh-FABP4 transfection. Western blot and Co-IP showed that SIRT5 reduced FABP4 expression by inducting the deacetylation of FABP4. Nude mice in the sh-SIRT5 + sh-FABP4 group had significantly reduced tumor mass and volume compared with those in the sh-FABP4 group, while the tumor mass and volume in the sh-SIRT5 + sh-FABP4 group were increased in comparison to those in the sh-SIRT5 group. To conclude, collected evidence showed that SIRT5 promoted NSCLC cell development by reducing FABP4 acetylation level.

Psychological Distance Impacts Subgroup Reciprocity in Technological Innovation Networks: The Mediating Role of Divisive Faultlines.

As information flows at ever-increasing speeds across technological innovation networks, it is crucial to optimize reciprocity among partnering enterprises. However, the impact of psychological distance on subgroup reciprocity in such networks has not yet been investigated. To address this gap, the current study drew on theories of faultlines and cohesive subgroups to model the relationship between psychological distance and subgroup reciprocity within technological innovation networks. Our hypotheses were tested using data from 174 respondents working in Yunnan Province, China. The results were as follows: first, psychological distance had negative effects on subgroup reciprocity in technological innovation networks; second, relationship-divisive and innovation-divisive faultlines negatively impacted reciprocity within and between subgroups; third, the faultlines partially mediated the negative relationship between psychological distance and intra-subgroup reciprocity; and fourth, the negative relationship between psychological distance and subgroup reciprocity was not mediated by the faultlines. The findings uncover the psychological mechanism of subgroup reciprocity within technological innovation networks. They will inform the decision-making process of enterprises when selecting partners within their technological innovation networks and support the development of effective reciprocal relationships with other innovators.

Preparative chromatography behavior of palmitoleic acid on octadecyl stationary phases with different densities.

The availability of various high-purity unsaturated fatty acids has a wide range of needs due to their different activities. The nonlinear preparative chromatography behavior and principle for purification of palmitoleic acid with octadecyl bonded stationary phases were studied. The peak broadening and the concentration distribution of the target compounds were used to compare different C18 stationary phases. In preparative liquid chromatography, the C18 stationary phases with low, medium, and high bonding density showed different peak broadening and concentration distribution results. Medium bonding density C18 was suitable for the purification of ethyl palmitoleic acid. The forward broadening was much greater than the backward broadening on medium bonding density C18 column. And the highest concentration distribution of impurities and the main peak was not crossed in this column. Due to the low content of crude ethyl palmitoleic acid sample, a two-step purified method yields an oily product with purity of 96.57% in the GC method. This method would be universal and extensible for constructing purification method for other unsaturated fatty acids.

Chemical profiling of Qingfei Paidu Decoction by triplex off-line two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Qingfei Paidu Decoction is a Chinese medicine formula that has been proved effective in the treatment of coronavirus disease 2019. However, the comprehensive separation and characterization of Qingfei Paidu Decoction are of a great challenge due to the diversity of chemical components in a wide range of polarity. In this study, a triplex off-line two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is developed for the analysis of Qingfei Paidu Decoction. One reversed-phase liquid chromatography×hydrophilic interaction liquid chromatography system and two reversed-phase liquid chromatography×reversed phase liquid chromatography systems were constructed to separate polar components and weak-polar components in Qingfei Paidu Decoction, respectively. Benefiting from the good orthogonality of two-dimensional liquid chromatography and high sensitivity of quadrupole time-of-flight MS, chemical components with different polarities and content were discovered. A total of 749 peaks were detected in positive and negative ionization mode and presented as a four-dimensional data plot. Meanwhile, 498 compounds belonging to 14 categories were tentatively identified. These results provide good supplementary to elucidate the material basis of Qingfei Paidu Decoction. The triplex off-line two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry strategy can be a powerful and efficient tool for the separation and characterization of chemical substances in traditional Chinese medicine formulas.

An 8-ferroptosis-related genes signature from Bronchoalveolar Lavage Fluid for prognosis in patients with idiopathic pulmonary fibrosis.

BACKGROUND: With the rapid advances of genetic and genomic technologies, the pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) were gradually becoming clear, however, the prognosis of IPF was still poor. This study aimed to systematically explore the ferroptosis-related genes model associated with prognosis in IPF patients. METHODS: Datasets were collected from the Gene Expression Omnibus (GEO). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to create a multi-gene predicted model from patients with IPF in the Freiburg cohort of the GSE70866 dataset. The Siena cohort and the Leuven cohort were used for validation. RESULTS: Nineteen differentially expressed genes (DEGs) between the patients with IPF and control were associated with poor prognosis based on the univariate Cox regression analysis (all P < 0.05). According to the median value of the risk score derived from an 8-ferroptosis-related genes signature, the three cohorts' patients were stratified into two risk groups. Prognosis of high-risk group (high risk score) was significantly poorer compared with low-risk group in the three cohorts. According to multivariate Cox regression analyses, the risk score was an independently predictor for poor prognosis in the three cohorts. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) confirmed the signature's predictive value in the three cohorts. According to functional analysis, inflammation- and immune-related pathways and biological process could participate in the progression of IPF. CONCLUSIONS: These results imply that the 8-ferroptosis-related genes signature in the bronchoalveolar lavage samples might be an effective model to predict the poor prognosis of IPF.