Home Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
Article Open Access

Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features

  • Lihong Zhao , Li Liu , Yehua Liu , Hong Zheng and Ping Jiang EMAIL logo
Published/Copyright: February 8, 2024
Download Article (PDF)
Open Life Sciences
From the journal Open Life Sciences Volume 19 Issue 1

Abstract

Interstitial pneumonia with autoimmune features (IPAF) is a type of interstitial lung disease (ILD) with immune features that do not meet the diagnostic criteria for specific connective tissue diseases (CTDs). This retrospective case–control study investigated the role of serum B-cell-activating factor of the tumor necrosis factor family (BAFF) and interleukin (IL)-17 as biomarkers for IPAF. The differences in serum BAFF, IL-17, and IL-10 were compared among patients with idiopathic pulmonary fibrosis (IPF), IPAF, ILD associated with CTD (CTD-ILD), and healthy controls. The patients were treatment naïve. The correlations of BAFF with IL-10, IL-17, and pulmonary function were analyzed. The classifiable value of BAFF for IPAF was examined. The results showed that the serum levels of BAFF and IL-17 in the IPAF and CTD-ILD groups were higher than in the IPF group. High BAFF levels and high predicted diffusion capacity of the lungs for carbon monoxide (DLCO) were independent predictive factors for IPAF vs IPF. In the IPAF and CTD-ILD groups, serum BAFF levels were negatively correlated with predicted values of forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%) and positively correlated with serum IL-17 and IL-10 levels. The cutoff value of combined BAFF and IL-17 was 0.704, and the sensitivity and specificity for classifying IPAF were 78.9 and 95.7%, respectively. In conclusion, combining serum BAFF and IL-17 as a biomarker may have classifiable value in differentiating IPAF from other forms of ILD.

Keywords: interstitial lung disease; pneumonia autoimmune features; BAFF; interleukin-17; inflammatory mechanism

1 Introduction

Interstitial lung disease (ILD) is characterized by diffuse inflammation and/or fibrosis in the lung. Connective tissue diseases (CTDs) are inflammatory, immune-mediated disorders that can cause various pulmonary complications, especially different patterns of inflammation and fibrosis. Some ILDs associated with autoimmune features are not classifiable as CTDs. Some ILDs may be the only early manifestation of CTD. In 2015, the Connective Tissue Disease-Interstitial Lung Disease Working Group of the European Respiratory Society and the American Thoracic Society coined the term ‘interstitial pneumonia with autoimmune features’ (IPAF), established its classification criteria, and proposed the extrapulmonary clinical domains, serological domains, and morphological domains. IPAF can be classified by the presence of at least one feature from at least two of these domains [1]. Several studies have reported that the prognosis of ILD associated with CTD (CTD-ILD) is better than that of idiopathic pulmonary fibrosis (IPF) [2,3], and IPAF may be an early pulmonary manifestation of CTD. There are currently no management guidelines specific to IPAF.

IPAF often cannot be classified in time for many patients with ILD, especially those with nonspecific interstitial pneumonia (NSIP) with atypical extrapulmonary manifestations and negative or weakly positive serum autoantibody profiles, delaying treatment. Thus, an in-depth understanding of the inflammatory mechanism of IPAF and the identification of biomarkers to distinguish between IPAF and IPF is of great importance for the early diagnosis, treatment, and prognosis of the disease. Currently, there are limited studies on IPAF. Serum CXCL1, CXCL9, CXCL10, and CXCL11 are biomarkers of ILDs with immune features and can predict the therapeutic response of immunosuppressive agents [4,5]. Serum surfactant protein-A (SP-A), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) are inconsistent markers for evaluating alveolar epithelial cell injury and interstitial inflammation in the classification of IPAF. Some studies have reported that the above indicators have medium-high sensitivity and specificity for the classification of IPAF [6–8], but Kameda et al. found no difference in SP-A and SP-D levels among IPAF, IPF, and CTD-ILD [4].

B-cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is derived from monocytes, macrophages, dendritic cells, neutrophils, and activated T cells. BAFF is an important stimulating factor required for B-lymphocyte proliferation, differentiation, antibody secretion, and generation of effector T-cell-dependent immune response, which is closely related to various immune system diseases [9]. The BAFF levels in CTD-ILD are significantly higher than in chronic fibrotic ILD [10]. Given the immune features of IPAF, it is unclear whether the BAFF levels are as high as that of CTD and whether the immune-inflammatory mechanism of IPAF is similar to that of CTD.

In this study, the serum levels of BAFF, interleukin (IL)-10, and IL-17 were determined in patients with IPAF, CTD-ILD, and IPF, and the correlations among BAFF, IL-17, IL-10, lung function, and alveolar-arterial oxygen pressure difference (AaDO2) were analyzed. The significance of BAFF and IL-17 in the differential classification of IPAF and IPF was discussed.

2 Materials and methods

2.1 Study design and participants

It was a retrospective case–control study that included 19 patients with IPF, 23 patients with IPAF, and 23 patients with CTD-ILD, all hospitalized in the Department of Respiratory and Critical Care Medicine of Tianjin First Central Hospital between August 2019 and February 2021. The control group included 22 healthy subjects. All patients with IPF met the diagnostic criteria of the “Guidelines for the diagnosis and treatment of idiopathic pulmonary fibrosis” issued by the European Respiratory Society and the American Thoracic Society in 2011 [11]. Patients with IPAF met the classification criteria for IPAF [1] issued by the European Respiratory Society and the American Thoracic Society in 2015: extrapulmonary clinical domain, serological domain, and morphological domain classified by at least one feature from at least two of these domains. The diagnosis of CTD was in line with the diagnostic criteria for rheumatoid arthritis (2010) [12], the guidelines for diagnosis and treatment of idiopathic myositis (2017) [13], the guidelines for diagnosis and treatment of Sjogren’s syndrome (2016) [14], the Sharp criteria for mixed CTDs (1987) [15], and the guidelines for the diagnosis and treatment of systemic lupus erythematosus (2012) [16] issued by the American Rheumatism Society and European Rheumatism Society. All included patients were newly diagnosed and not yet treated by glucocorticoids, immunosuppressants, biological agents, or anti-fibrosis drugs. The included patients were older than 18 years and younger than 80 years. Patients with infection, malignant tumor, chronic heart, liver, or renal failure, ILD induced by drugs, dust, or radiation, sarcoidosis, allergic alveolitis, or those with missing lung function test data were excluded.

This study was reviewed and approved by the Ethics Committee of Tianjin First Central Hospital (Batch No. 2018N133KY). All subjects provided signed informed consent.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of Tianjin First Central Hospital (Batch No. 2018N133KY).

2.2 Collection of clinical information

The following patient data were recorded: sex, age, smoking history, arterial partial oxygen pressure (PaO2), alveolar-arterial oxygen pressure difference (AaDO2), and chest high-resolution computed tomography (HRCT). The HRCT manifestations were evaluated by two respiratory physicians and two radiologists with more than 10 years of experience and classified into NSIP, usual interstitial pneumonia (UIP), and others (except NSIP and UIP, such as organizing pneumonia, lymphocytic interstitial pneumonia, etc.).

2.3 Pulmonary function tests (PFTs)

PFTs were performed using the pulmonary function instrument (Jaeger, Germany) as per the ATS and ERS guidelines. The tests measured forced vital capacity (FVC) and the diffusion capacity of the lungs for carbon monoxide (DLCO).

2.4 Sample processing and measurement of serum markers

Fasting venous blood (4 ml) was drawn into an EDTA anticoagulant tube and centrifuged at 3,000 rpm for 10 min, with a radius of 6 cm. The supernatant was transferred to a clean EP tube and stored at −80°C. Serum BAFF, IL-10, and IL-17 levels were determined by enzyme-linked immunosorbent assay (ELISA). The absorbance was measured at 450 nm using an automatic microplate analyzer. The standard curve was drawn, and the sample concentration was calculated based on the absorbance value. The ELISA kits for IL-10, IL-17, and BAFF were purchased from Shanghai Fanke Biological Technology Co., Ltd.

2.5 Statistical analysis

Data were analyzed using SPSS 25.0 (SPSS, Inc., Chicago, IL, USA). Figures were drawn using Prism 9.0 (GraphPad Inc., La Jolla, CA, USA). The Kolmogorov–Smirnov test was used to verify the normal distribution. Categorical data were expressed as n (%), and continuous data were expressed as mean ± standard deviation. In the univariable analysis, categorical variables were compared using the chi-square test, which includes Pearson’s chi-square test and Fisher’s exact probability method, to assess inter-group differences. Continuous variables, on the other hand, were subjected to analysis of variance for inter-group comparisons, followed by post hoc analysis for pairwise comparisons. Pearson’s analysis was used for correlation. Univariable regression analyses were performed to examine the factors associated with IPF vs non-IPF. A multivariable regression analysis was performed to examine the association of variables with non-IPF after adjustment for age, sex, and smoking. Univariable and multiple (stepwise) logistic regression analyses were conducted to investigate the factors associated with IPAF vs IPF, IPAF vs CTD-ILD, and CTD-ILD vs IPF. The receiver operating characteristic (ROC) curve was drawn to calculate the optimal cutoff value, corresponding sensitivity and specificity based on Youden’s index, and the classifiable value of serum BAFF and IL-17 in identifying IPAF and IPF. P < 0.05 indicated a significant difference.

3 Results

3.1 Characteristics of the patients

This study included 23 patients in the IPAF group, 23 in the CTD-ILD group, 19 in the IPF group, and 22 healthy individuals. There were 4 males (17.4%) and 19 females (82.6%), aged 61.0 ± 10.6 years in the IPAF group, 5 males (21.7%) and 18 females (78.3%), aged 63.7 ± 12.5 years in the CTD-ILD group, 14 males (73.7%) and 5 females (26.3%), aged 67.6 ± 5.4 years in the IPF group, and 10 males (45.5%) and 12 females (54.5%), aged 61.7 ± 4.1 years in the control group. There were no significant differences in age among the four groups. Most patients in the IPAF and CTD-ILD groups were female (82.6 vs 78.3 vs 26.3%, p = 0.001). There were 3 (13.0%) smokers in the IPAF group, 6 (26.1%) in the CTD-ILD group, and 10 (52.6%) in the IPF group, with significantly more smokers in the IPF group (p = 0.022). The predicted DLCO%, AaDO2, serum BAFF, IL-17, and IL-10 levels were statistically different among the four groups (all p < 0.05), as shown in Table 1.

Table 1

Comparison of the clinical characteristics of the IPAF, CTD-ILD, and IPF groups with the healthy controls

Variable IPAF (n = 23) CTD-ILD (n = 23) IPF (n = 19) HC (n = 22) p
Age, years 61.0 ± 10.6 63.7 ± 12.5 67.6 ± 5.4 61.7 ± 4.1 0.093
Female, n (%) 19 (82.6) 18 (78.3) 5 (26.3) 12 (54.5) 0.001
Smoker, n (%) 3 (13.0) 6 (26.1) 10 (52.6) 8 (36.4) 0.022
HRCT type, n (%)
 NSIP 16 (69.6) 12 (52.2) 9 (47.4) 0.119
 UIP 4 (17.4) 8 (34.8) 10 (52.6) 0.089
 Other 3 (13.0) 3 (13.0) 0 (0) 0.123
Predicted FVC% 71.3 ± 17.7 73.1 ± 15.7 63.7 ± 15.3 0.158
Predicted DLCO% 46.7 ± 16.8 51.8 ± 15.8 30.1 ± 14.5 <0.001
AaDO2 (mmHg) 31.6 ± 11.5 24.9 ± 14.0 38.3 ± 12.7 0.005
BAFF (ng/ml) 1.9 ± 1.2 2.0 ± 1.4 1.0 ± 0.2 0.7 ± 0.2 <0.001
IL-17 (pg/ml) 8.5 ± 4.6 8.8 ± 6.4 5.4 ± 0.5 5.0 ± 1.7 0.002
IL-10 (pg/ml) 182.1 ± 92.7 177.4 ± 138.5 126.2 ± 11.5 99.1 ± 63.3 0.007

3.2 Comparison of serum BAFF, IL-17, and IL-10 among the IPAF, CTD-ILD, IPF, and healthy control groups

The serum levels of BAFF, IL-17, and IL-10 in the IPAF and CTD-ILD groups were significantly higher than in the healthy control group (p < 0.001, p = 0.005, p = 0.003; p < 0.001, p = 0.003, p = 0.005). The levels in the IPF group were not significantly different from the healthy control group. Compared with the IPF group, the serum BAFF and IL-17 levels in the IPAF and CTD-ILD groups were significantly higher (p = 0.002, p < 0.001; p = 0.016, p = 0.009). There were no significant differences between the CTD-ILD group and the IPAF group. There were no significant differences in IL-10 levels in the IPAF and CTD-ILD groups compared with the IPF group. There were no significant differences between the IPAF and CTD-ILD groups, as shown in Figure 1. After adjusting for age, sex, and smoking, BAFF levels were independently associated with non-IPF (adjusted odds ratio [aOR] = 0.001, 95% confidence interval [CI]: 0–0.076, p = 0.008), while IL-17 levels were not (aOR = 0.51, 95% CI: 0.15–1.35, p = 0.21) (Table 2). In the regression analysis for IPAF vs IPF, high predicted DLCO, BAFF, and IL-17 were risk factors for IPAF compared to IPF. Based on stepwise multiple logistic regression analysis, high BAFF levels and high predicted DLCO were independent predictive factors for IPAF vs IPF (aOR = 1.23, 95% CI: 1.11–1.38, p < 0.001; aOR = 1.01, 95% CI: 1.00–1.02, p < 0.001) (Table 3). There were no statistically significant differences in the characteristics between the IPAF and CTD-ILD groups. High BAFF levels and high predicted DLCO are independent predictive factors for CTD-ILD vs IPF (aOR = 0.87, 95% CI: 0.79–0.95, p < 0.001; aOR = 0.99, 95% CI: 0.98–0.99, p < 0.001).

Figure 1 Distribution of serum (a) BAFF, (b) IL-17, and (c) IL-10 in the IPAF (n = 23), CTD-ILD (n = 23), IPF (n = 19), and HC (n = 22) groups. A pairwise comparison of variables between the groups was performed using post hoc analysis. BAFF: B-cell-activating factor of the TNF family; IL-17: interleukin-17; IL-10: interleukin-10; IPAF: interstitial pneumonia with autoimmune features; CTD-ILD: interstitial lung disease associated with connective tissue disease; IPF: idiopathic pulmonary fibrosis; HC: healthy control.
Figure 1

Distribution of serum (a) BAFF, (b) IL-17, and (c) IL-10 in the IPAF (n = 23), CTD-ILD (n = 23), IPF (n = 19), and HC (n = 22) groups. A pairwise comparison of variables between the groups was performed using post hoc analysis. BAFF: B-cell-activating factor of the TNF family; IL-17: interleukin-17; IL-10: interleukin-10; IPAF: interstitial pneumonia with autoimmune features; CTD-ILD: interstitial lung disease associated with connective tissue disease; IPF: idiopathic pulmonary fibrosis; HC: healthy control.

Table 2

Comparison of the clinical characteristics between the IPF and non-IPF groups using univariable and multivariable logistic regression analyses

Non-IPF (n = 46) IPF (n = 19) OR 95% CI p aOR 95% CI p
Variable
Age, years 62.3 (11.5) 67.6 (5.40) 1.07 [0.99;1.14] 0.07 1.05 [0.96, 1.21] 0.352
Sex, %
 Male 9 (19.6%) 14 (73.7%) Ref. Ref. Ref. Ref.
 Female 37 (80.4%) 5 (26.3%) 0.09 [0.02;0.31] <0.001 0.1 [0.01, 0.69] 0.028
Smoking, %
 No 37 (80.4%) 9 (47.4%) Ref. Ref. Ref. Ref.
 Yes 9 (19.6%) 10 (52.6%) 4.42 [1.39;14.8] 0.012 1.22 [0.12, 11.95] 0.861
HRCT type, %
 NSIP 28 (60.9%) 9 (47.4%) Ref. Ref.
 UIP 12 (26.1%) 10 (52.6%) — —
 Other 6 (13.0%) 0 (0.00%) — —
Predicted FVC% 72.2 (16.5) 63.7 (15.3) 0.97 [0.94;1.00] 0.064
Predicted DLCO% 49.2 (16.3) 30.1 (14.5) 0.91 [0.87;0.96] <0.001
AaDO2 (mmHg) 28.2 (13.1) 38.3 (12.7) 1.07 [1.02;1.13] 0.011
BAFF (ng/ml) 1.98 (1.26) 0.98 (0.23) 0.00 [0.00;0.06] 0.001 0.001 (0, 0.076) 0.008
IL-17 (pg/ml) 8.64 (5.51) 5.35 (0.50) 0.37 [0.18;0.74] 0.005 0.51 (0.15, 1.35) 0.21
IL-10 (pg/ml) 180 (117) 126 (11.5) 0.98 [0.96;1.00] 0.090

IPF: idiopathic pulmonary fibrosis; OR: odds ratio; CI: confidence interval; aOR: adjusted odds ratio; HRCT: high-resolution computed tomography; NSIP: nonspecific interstitial pneumonia; UIP: usual interstitial pneumonia; FVC: forced vital capacity; DLCO: diffusion capacity of the lungs for carbon monoxide; AaDO2: alveolar-arterial oxygen pressure difference; BAFF: B-cell-activating factor of the TNF family; IL: interleukin.

Table 3

Comparison of the clinical characteristics between the IPAF and IPF groups using univariable and stepwise multivariable logistic regression analyses

Non-IPF (n = 46) IPF (n = 19) OR 95% CI p aOR 95% CI p
Variable
Age, years 61.0 (10.6) 67.6 (5.4) 0.9 [0.82; 0.99] 0.03 0.99 [0.98, 1.00] 0.19
Sex, %
 Male 4 (17.4%) 14 (73.7%) Ref. Ref. Ref. Ref.
 Female 19 (82.6%) 5 (26.3%) 13.3 [3.01; 58.72] <0.001
Smoking, %
 No 20 (87.0%) 9 (47.4%) Ref. Ref. Ref. Ref.
 Yes 3 (13.0%) 10 (52.6%) 0.14 [0.03; 0.65] 0.01 0.74 [0.58, 0.94] 0.01
HRCT type, %
 NSIP 16 (69.6%) 9 (47.4%) Ref. Ref. Ref. Ref.
 UIP 4 (17.4%) 10 (52.6%) 0.22 [0.05; 0.93] 0.04 0.94 [0.73; 1.23] 0.66
 Other 3 (13.0%) 0 (0.00%) — —
Predicted FVC% 71.3 (17.7) 63.7 (15.3) 1.03 [0.99; 1.07] 0.15
Predicted DLCO% 46.7 (16.8) 30.1 (14.5) 1.07 [1.02; 1.13] 0.01 1.01[1.00; 1.02] <0.001
AaDO2 (mmHg) 31.6 (11.5) 38.3 (12.7) 0.95 [0.9; 1.01] 0.09
BAFF (ng/ml) 1.90 (1.20) 0.98 (0.23) 386.16 [6.71; 22234.28] <0.001 1.23 (1.11, 1.38) <0.001
IL-17 (pg/ml) 8.50 (4.60) 5.35 (0.50) 5.09 [1.54; 16.78] 0.01
IL-10 (pg/ml) 182.1(92.7) 126.2 (11.5) 1.02 [1;1.05] 0.06

IPAF: interstitial pneumonia with autoimmune features; IPF: idiopathic pulmonary fibrosis; OR: odds ratio; CI: confidence interval; aOR: adjusted odds ratio; HRCT: high-resolution computed tomography; NSIP: nonspecific interstitial pneumonia; UIP: usual interstitial pneumonia; FVC: forced vital capacity; DLCO: diffusion capacity of the lungs for carbon monoxide; AaDO2: alveolar-arterial oxygen pressure difference; BAFF: B-cell-activating factor of the TNF family; IL: interleukin.

3.3 Correlation of BAFF with lung function, AaDO2, IL-10, and IL-17

This study analyzed the correlations of serum BAFF with predicted values of FVC% and DLCO%, AaDO2, IL-10, and IL-17 in the IPAF and CTD-ILD groups. The serum BAFF levels were negatively correlated with the predicted DLCO% and FVC% (r = −0.349, p = 0.017; r = −0.315, p = 0.033), and positively correlated with serum IL-17 and IL-10 levels (r = 0.681, p < 0.001; r = 0.546, p < 0.001), as shown in Figure 2. There were no significant correlations between serum BAFF levels and AaDO2.

Figure 2 Correlation analysis of serum BAFF with (a and b) PFT parameters, (c) IL-17, and (d) IL-10 in the IPAF and CTD-ILD groups. BAFF: B-cell-activating factor of the TNF family; IL-17: interleukin-17; IL-10: interleukin-10; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; IPAF: interstitial pneumonia with autoimmune features; CTD-ILD: interstitial lung disease associated with connective tissue disease.
Figure 2

Correlation analysis of serum BAFF with (a and b) PFT parameters, (c) IL-17, and (d) IL-10 in the IPAF and CTD-ILD groups. BAFF: B-cell-activating factor of the TNF family; IL-17: interleukin-17; IL-10: interleukin-10; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; IPAF: interstitial pneumonia with autoimmune features; CTD-ILD: interstitial lung disease associated with connective tissue disease.

3.4 Classifiable value of serum BAFF and IL-17 levels for IPAF

We used an ROC curve analysis to evaluate the sensitivity and specificity of serum BAFF and IL-17 levels as biomarkers for the differential classification of IPAF from IPF. Based on the area under the ROC curve (AUC), when the cutoff value for BAFF was 1.150 ng/ml, the sensitivity and specificity were 78.3 and 84.2%, respectively (Youden’s index: 0.625, AUC = 0.871, 95% CI = 0.765–0.976). When the cutoff value for IL-17 was 6.565 pg/ml, the sensitivity and specificity were 60.9 and 100%, respectively (Youden’s index: 0.609, AUC = 0.868, 95% CI = 0.759–0.978). When the cutoff value of BAFF and IL-17 combination was 0.704, the sensitivity and specificity were 78.9 and 95.7%, respectively (Youden’s index: 0.746, AUC = 0.931, 95% CI = 0.86–1.00) (Figure 3a and b). When differentiating CTD-ILD from IPF, using a cutoff value of 0.596, BAFF and IL-17 combination achieved 84.2% sensitivity and 78.3% specificity (Youden’s index: 0.625, AUC = 0.883, 95% CI = 0.786–0.981), while BAFF alone achieved 69.6% sensitivity and 100% specificity using a cutoff of 1.427 (Youden’s index: 0.696, AUC = 0.926, 95% CI = 0.852–1.000) and IL-17 alone achieved 60.9% sensitivity and 100% specificity using a cutoff of 6.37 (Youden’s index: 0.609, AUC = 0.743, 95% CI = 0.584–0.901) (Figure 3c and d).

Figure 3 (a and b) ROC curve analysis of different serum BAFF and IL-17 levels between patients with IPAF and IPF. (c and d) ROC curve analysis of different serum BAFF and IL-17 levels between patients with CTD-ILD and IPF. BAFF: B-cell-activating factor of the TNF family; IL-17: interleukin-17.
Figure 3

(a and b) ROC curve analysis of different serum BAFF and IL-17 levels between patients with IPAF and IPF. (c and d) ROC curve analysis of different serum BAFF and IL-17 levels between patients with CTD-ILD and IPF. BAFF: B-cell-activating factor of the TNF family; IL-17: interleukin-17.

4 Discussion

The serum levels of BAFF, IL-17, and IL-10 in the ILD groups and the control group were determined in this study. The results showed that the serum BAFF and IL-17 in the IPAF and CTD-ILD groups were significantly higher than in the IPF and control groups. High serum BAFF levels and high predicted DLCO were independent predictive factors for IPAF vs IPF. There were no significant differences in BAFF and IL-17 between CTD-ILD and IPAF groups. The serum BAFF levels were negatively correlated with the predicted FVC% and DLCO%. The sensitivity and specificity of the serum BAFF and IL-17 combination as a biomarker for the differential classification of IPAF from other types of ILD were high. Despite the absence of guidelines for IPAF management, identifying biomarkers of IPAF is of great importance for determining the autoimmune cause of ILD. Both BAFF and IL-17 are inflammatory markers, indicating that CTD-ILD and IPAF might share the same or a similar inflammatory response. Therefore, when BAFF and IL-17 were elevated in ILD, it suggested some autoimmune factors, as previously suggested [17,18].

BAFF is an important stimulator of B-lymphocyte proliferation, differentiation, antibody secretion, and generation of effector T-cell-dependent immune response. Autoantibodies are produced by BAFF-activated B lymphocytes and released into the blood circulation. The expression of BAFF is significantly increased in systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome, systemic sclerosis, and dermatomyositis and is closely related to disease activity, autoantibody production, and titer [19–23]. Serum BAFF levels are significantly increased in the early stages of polymyositis and rheumatoid arthritis, suggesting that BAFF is involved in the early onset of the disease [19,22]. Blocking BAFF activity decreases the severity of autoimmune diseases such as chronic colitis [24]. Belimumab is an anti-BAFF therapy under exploration for managing CTD-ILD [25]. Autoantibody reduction therapy has been shown to improve the lung function of patients with IPF [26]. A previous study showed that BAFF levels combined with ultrasound B lines could effectively differentiate among different types of IPFs, including IPAF [18]. This study showed that the serum BAFF levels of the patients in the IPAF and CTD-ILD groups were higher than in the IPF group, and the BAFF levels in the CTD-ILD group were higher than in the IPAF group. It indicates that IPAF is different from IPF and may be consistent with the inflammatory nature of CTD-ILD. BAFF was also independently associated with IPAF after adjustment for age, sex, and smoking. IPAF can occur in the early stage of CTD but without the inflammation intensity typical of CTD. Hence, biomarkers for the early classification of IPAF could be useful.

BAFF levels in dermatomyositis and mixed CTD patients with interstitial pneumonia were significantly higher than in patients without [22,27]. In addition, serum BAFF levels in the CTD-ILD group were significantly higher than in patients with chronic fibrous interstitial pneumonia and healthy controls and were negatively correlated with the predicted FVC% in the CTD-ILD group. Immunohistochemical analysis of lung specimens of CTD-ILD patients revealed that BAFF was strongly positive in the alveolar wall, peripheral airway, and lymphatic follicles [10]. In addition, BAFF is higher in UIP induced by autoimmune diseases than in IPF and negatively correlated with lung function [28]. As supported by the above studies, the present study showed that the BAFF levels were negatively correlated with predicted FVC% and DLCO%. Thus, the BAFF levels might be used to assess the extent of autoimmune inflammation in IPAF.

In addition to the involvement of BAFF in the differentiation of CTDs as an effector inflammatory cytokine secreted by T lymphocytes, ILs also play important roles in this process. IL-17, an effector cytokine secreted by Th17 cells, is a landmark pro-inflammatory factor that can induce a cascade amplification effect of other pro-inflammatory factors and chemokines and further trigger inflammatory responses, playing an important role in the pathogenesis of various CTDs. BAFF upregulates the expression of CD28/B7 and CD40/CD154 by binding to BAFF receptors and promotes the interaction between T and B lymphocytes, resulting in the generation of IL-17 and autoantibodies [29]. Patients with positive anti-tRNA synthase antibodies and ILD develop lung disease progression and show continuously elevated cytokines secreted by Th17 [30]. In this study, the levels of serum IL-17 in the IPAF and CTD-ILD groups were higher than in the IPF group, supporting the similarity between IPAF and CTD-ILD inflammation. Still, IL-17 levels were not independently associated with non-IPF after adjustment for age, sex, and smoking.

Recently, clinicians have been looking for effective biomarkers to distinguish between IPAF and IPF. KL-6, SP-D, SP-A, CXCL1, CXCL9, CXCL10, and CXCL11 have been reported, but the results are not consistent, and the proposed biomarkers cannot effectively distinguish between IPF, IPAF, and CTD-ILD [4–8,31]. As a superior regulator of serum autoantibodies, BAFF reflects the changes in autoimmune inflammation earlier and is more sensitive than autoantibodies. IL-17, as a signature pro-inflammatory factor of autoimmune inflammation, can be used as an effective biomarker to distinguish IPAF from IPF. Better sensitivity and specificity can be achieved by combining BAFF and IL-17. NSIP is the most common tissue type of IPAF and CTD-ILD, and about 10–52% of patients with idiopathic NSIP are eventually diagnosed with a specific type of CTD during follow-up [32,33]. Thus, for patients with ILD, especially patients with NSIP (accounting for 69.6% of the IPAF group in this study), the combination of BAFF and IL-17 can help to distinguish IPAF from other types of ILDs. Whether treatment with glucocorticoids and immunosuppressors could also avoid or delay the damage to other organs remains to be examined.

This study had some limitations. It was a single-center retrospective study with a small sample size, and there may be some selection bias. The cross-sectional nature of the study and the lack of longitudinal assessments prevented the determination of cause-to-effect relationships and the predictive value of BAFF and IL-17 for IPAF. It is necessary to conduct multicenter prospective studies and increase the sample size in the future. Besides, histopathological verification was not conducted in this study, which needs further confirmation.

In conclusion, the combination of BAFF and IL-17 is a sensitive biomarker for differentiating IPAF and IPF, which has great clinical significance. IPAF and CTD-ILD differ from IPF, and both have similar inflammatory characteristics. IPAF may be the early stage of CTD, and the treatment should focus on CTD. Early intervention could avoid multiple organ injuries, affecting patients’ quality of life and prognosis.

tel: +86-13752145615

  1. Funding information: This study was supported by the Science and Technology Foundation of Tianjin First Central Hospital (CF201827).

  2. Author contributions: P.J.: conceptualization; L.H.Z.: methodology; L.Li: software; H.Z.: validation; L.L.: formal analysis; L.H.Z.: investigation; H.Z.: resources; Y.H.L.: data curation; L.H.Z.: writing – original draft; P.J.: writing – review and editing; L.H.Z.: writing – visualization; P.J.: writing – supervision; L.H.Z.: writing – project administration; L.H.Z.: writing – funding acquisition.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

[1] Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: Interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46(4):976–87.10.1183/13993003.00150-2015Search in Google Scholar PubMed

[2] Navaratnam V, Ali N, Smith CJ, McKeever T, Fogarty A, Hubbard RB. Does the presence of connective tissue disease modify survival in patients with pulmonary fibrosis? Respir Med. 2011;105(12):1925–30.10.1016/j.rmed.2011.08.015Search in Google Scholar PubMed

[3] Nayfeh AS, Chippa V, Moore DR Nonspecific interstitial pneumonitis. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Venu Chippa declares no relevant financial relationships with ineligible companies. Disclosure: Douglas Moore declares no relevant financial relationships with ineligible companies; 2023.Search in Google Scholar

[4] Kameda M, Otsuka M, Chiba H, Kuronuma K, Hasegawa T, Takahashi H, et al. CXCL9, CXCL10, and CXCL11; biomarkers of pulmonary inflammation associated with autoimmunity in patients with collagen vascular diseases-associated interstitial lung disease and interstitial pneumonia with autoimmune features. PLoS one. 2020;15(11):e0241719.10.1371/journal.pone.0241719Search in Google Scholar PubMed PubMed Central

[5] Liang M, Jiang Z, Huang Q, Liu L, Xue Y, Zhu X, et al. Clinical association of chemokine (C-X-C motif) ligand 1 (CXCL1) with interstitial pneumonia with autoimmune features (IPAF). Sci Rep. 2016;6:38949.10.1038/srep38949Search in Google Scholar PubMed PubMed Central

[6] Xue M, Cai C, Zeng Y, Xu Y, Chen H, Hu H, et al. Krebs von den Lungen-6 and surfactant protein-A in interstitial pneumonia with autoimmune features. Medicine. 2021;100(4):e24260.10.1097/MD.0000000000024260Search in Google Scholar PubMed PubMed Central

[7] Wang J, Zheng P, Huang Z, Huang H, Xue M, Liao C, et al. Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features. BMC Pulm Med. 2020;20(1):315.10.1186/s12890-020-01336-ySearch in Google Scholar PubMed PubMed Central

[8] Yamakawa H, Hagiwara E, Ikeda S, Iwasawa T, Otoshi R, Tabata E, et al. Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia. Respir Invest. 2019;57(5):422–9.10.1016/j.resinv.2019.03.006Search in Google Scholar PubMed

[9] Smulski CR, Eibel H. BAFF and BAFF-receptor in B cell selection and survival. Front Immunol. 2018;9:2285.10.3389/fimmu.2018.02285Search in Google Scholar PubMed PubMed Central

[10] Hamada T, Samukawa T, Kumamoto T, Hatanaka K, Tsukuya G, Yamamoto M, et al. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease. BMC Pulm Med. 2015;15:110.10.1186/s12890-015-0105-0Search in Google Scholar PubMed PubMed Central

[11] Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.10.1164/rccm.2009-040GLSearch in Google Scholar PubMed PubMed Central

[12] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81.10.1002/art.27584Search in Google Scholar PubMed

[13] Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76(12):1955–64.10.1136/annrheumdis-2017-212786Search in Google Scholar PubMed

[14] Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017;76(1):9–16.10.1136/annrheumdis-2016-210571Search in Google Scholar PubMed

[15] Tanaka Y, Kuwana M, Fujii T, Kameda H, Muro Y, Fujio K, et al. 2019 Diagnostic criteria for mixed connective tissue disease (MCTD): From the Japan research committee of the ministry of health, labor, and welfare for systemic autoimmune diseases. Mod Rheumatol. 2021;31(1):29–33.10.1080/14397595.2019.1709944Search in Google Scholar PubMed

[16] Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86.10.1002/art.34473Search in Google Scholar PubMed PubMed Central

[17] Gurczynski SJ, Moore BB. IL-17 in the lung: The good, the bad, and the ugly. Am J Physiol Lung Cell Mol Physiol. 2018;314(1):L6–16.10.1152/ajplung.00344.2017Search in Google Scholar PubMed PubMed Central

[18] Wang Y, Xie X, Zheng S, Du G, Chen S, Zhang W, et al. Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease. Front Med (Lausanne). 2022;9:1066111.10.3389/fmed.2022.1066111Search in Google Scholar PubMed PubMed Central

[19] Hernandez-Breijo B, Parodis I, Novella-Navarro M, Martinez-Feito A, Navarro-Compan V, Diaz-Almiron M, et al. Low serum BAFF concentration is associated with response to TNF inhibitors in seropositive patients with rheumatoid arthritis. J Clin Med. 2022;11(17):5207.10.3390/jcm11175207Search in Google Scholar PubMed PubMed Central

[20] Veenbergen S, Kozmar A, van Daele PLA, Schreurs MWJ. Autoantibodies in Sjogren’s syndrome and its classification criteria. J Transl Autoimmun. 2022;5:100138.10.1016/j.jtauto.2021.100138Search in Google Scholar PubMed PubMed Central

[21] Mameli G, Cocco E, Frau J, Arru G, Caggiu E, Marrosu MG, et al. Serum BAFF levels, methypredsinolone therapy, Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis infection in multiple sclerosis patients. Sci Rep. 2016;6:29268.10.1038/srep29268Search in Google Scholar PubMed PubMed Central

[22] Kryštůfková O, Hulejová H, Mann HF, Pecha O, Půtová I, Ekholm L, et al. Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis. Arthritis Res Ther. 2018;20(1):158.10.1186/s13075-018-1650-8Search in Google Scholar PubMed PubMed Central

[23] Salazar-Camarena DC, Ortíz-Lazareno P, Marín-Rosales M, Cruz A, Muñoz-Valle F, Tapia-Llanos R, et al. BAFF-R and TACI expression on CD3 + T cells: Interplay among BAFF, APRIL and T helper cytokines profile in systemic lupus erythematosus. Cytokine. 2019;114:115–27.10.1016/j.cyto.2018.11.008Search in Google Scholar PubMed

[24] Zhang Y, Tao M, Chen C, Zhao X, Feng Q, Chen G, et al. BAFF blockade attenuates DSS-induced chronic colitis via inhibiting NLRP3 inflammasome and NF-kappaB activation. Front Immunol. 2022;13:783254.10.3389/fimmu.2022.783254Search in Google Scholar PubMed PubMed Central

[25] Ahmed S, Handa R. Management of connective tissue disease-related interstitial lung disease. Curr Pulmonol Rep. 2022;11(3):86–98.10.1007/s13665-022-00290-wSearch in Google Scholar PubMed PubMed Central

[26] Kulkarni T, Valentine VG, Fei F, Tran-Nguyen TK, Quesada-Arias LD, Mkorombindo T, et al. Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations. PLoS one. 2021;16(11):e0260345.10.1371/journal.pone.0260345Search in Google Scholar PubMed PubMed Central

[27] Kaneko T, Amano H, Kawano S, Minowa K, Ando S, Watanabe T, et al. Increased serum concentration of BAFF/APRIL and IgA2 subclass in patients with mixed connective tissue disease complicated by interstitial lung disease. Mod Rheumatol. 2014;24(2):310–5.10.3109/14397595.2013.843748Search in Google Scholar PubMed

[28] Zhao YY, Lian HJ, Li S, Fang CL, Huang H, Xu ZJ. The role of B cell activating factor in the differential diagnosis of usual interstitial pneumonia. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chin J Tuberc Respir Dis. 2018;41(7):544–50.Search in Google Scholar

[29] Zhang F, Song SS, Shu JL, Li Y, Wu YJ, Wang QT, et al. BAFF upregulates CD28/B7 and CD40/CD154 expression and promotes mouse T and B cell interaction in vitro via BAFF receptor. Acta Pharmacol Sin. 2016;37(8):1101–9.10.1038/aps.2016.15Search in Google Scholar PubMed PubMed Central

[30] Ramos-Martinez E, Falfán-Valencia R, Pérez-Rubio G, Mejia M, Buendía-Roldán I, González-Pérez MI, et al. Anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies associated with interstitial lung disease: Pulmonary disease progression has a persistent elevation of the Th17 cytokine profile. J Clin Med. 2020;9(5):1356.10.3390/jcm9051356Search in Google Scholar PubMed PubMed Central

[31] Miądlikowska E, Rzepka-Wrona P, Miłkowska-Dymanowska J, Białas AJ, Piotrowski WJ. Review: Serum biomarkers of lung fibrosis in interstitial pneumonia with autoimmune features-what do we already know? J Clin Med. 2021;11(1):79.10.3390/jcm11010079Search in Google Scholar PubMed PubMed Central

[32] Romagnoli M, Nannini C, Piciucchi S, Girelli F, Gurioli C, Casoni G, et al. Idiopathic nonspecific interstitial pneumonia: An interstitial lung disease associated with autoimmune disorders? Eur Respir J. 2011;38(2):384–91.10.1183/09031936.00094910Search in Google Scholar PubMed

[33] Lee SH, Park MS, Kim SY, Kim DS, Kim YW, Chung MP, et al. Factors affecting treatment outcome in patients with idiopathic nonspecific interstitial pneumonia: a nationwide cohort study. Respir Res. 2017;18(1):204.10.1186/s12931-017-0686-7Search in Google Scholar PubMed PubMed Central

Received: 2023-03-10
Revised: 2023-11-15
Accepted: 2023-11-17
Published Online: 2024-02-08

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
https://doi.org/10.1515/biol-2022-0814
Keywords for this article
interstitial lung disease; pneumonia autoimmune features; BAFF; interleukin-17; inflammatory mechanism
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 22.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0814/html
Scroll to top button