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IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts

  • Jun Wang EMAIL logo , Qianyu Zhang , Yunjie Han , Jun Zhang and Nan Zheng
Published/Copyright: March 11, 2025
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Open Life Sciences
From the journal Open Life Sciences Volume 20 Issue 1

Abstract

This study aimed to investigate potential targets for the pathogenesis of atrial fibrillation to facilitate the development of effective treatments. Atrial fibroblasts were isolated and stimulated with 1 μM angiotensin-II (Ang-II) for 24 h. To increase interleukin 11 (IL-11) expression, overexpression plasmids were transfected into atrial fibroblasts. The role and the underlying mechanism of IL-11 in atrial fibrillation were examined by immunofluorescence, measurements of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), and western blotting assays. Results demonstrated that IL-11 was upregulated in Ang-II-elicited atrial fibroblasts. Ang-II treatment increases alpha-smooth muscle actin (α-SMA), ROS and MMP levels, and p62 expression but decreases microtubule-associated protein light chain 3 II/I (LC3 II/I) and Beclin-1 expressions in atrial fibroblasts. These effects were further amplified by IL-11 overexpression. Mechanistically, the mammalian target of rapamycin (mTOR) pathway expression was enhanced in Ang-II-induced atrial fibroblasts, which was further elevated by IL-11 upregulation. IL-11 facilitates Ang II-induced differentiation of atrial fibroblasts into myofibroblasts by promoting oxidative stress, mitochondrial dysfunction, and autophagy inhibition through the mTOR pathway.

Graphical Abstract

Keywords: Atrial fibrillation; atrial fibroblasts; Ang II; IL-11; oxidative stress; mitochondrial dysfunction; autophagy

1 Introduction

Atrial fibrillation is one of the most prevalent arrhythmia diseases observed in clinical practice, significantly increasing the risk of morbidity and mortality. Its complications, including strokes and heart failures, markedly diminish patients’ quality of life [1]. Atrial fibrillation affects over 33 million people worldwide, and the incidence of the condition increases with age, with a prevalence of about 8.5% among patients over 65 [1,2]. Age is thus recognized as a major risk factor, alongside others such as genetic predisposition, hypertension, obesity, diabetes, male gender, endurance, exercise, and obstructive sleep apnea [2]. The primary pathological characteristic of atrial fibrillation is atrial structural remodeling, characterized by cavity enlargement and wall tissue fibrosis [1]. A key initial step in this process is the differentiation of atrial fibroblasts into myofibroblasts, often induced by endocrine peptide hormones such as angiotensin-II (Ang-II) and transforming growth factor β (TGF-β). Fibrotic lesions gradually develop in the local tissue by excessive myofibroblast proliferation, mobility, and the synthesis/deposition of extracellular matrix (ECM) proteins [3]. These fibrotic lesions impede the conduction of electrical pacing signals in the heart, creating a substrate for re-entry circuits and thereby elevating the risk of atrial fibrillation [3]. While the atrial fibrillation mechanism is not fully understood, pathogenesis, such as oxidative stress, mitochondrial dysfunction, and autophagy, has been implicated in its progression [4,5]. To develop effective treatment strategies, it is essential to identify potential targets involved in the disease’s pathogenesis.

Interleukin 11 (IL-11) belongs to the IL-6 family and has multiple functions. In response to inflammatory microenvironments, it upregulates or downregulates inflammatory responses, contributing to the development and progression of several diseases [6–8]. Recent studies have focused on the role of IL-11 in cardiovascular disease, particularly in cardiac fibrosis [8,9]. Persistent activation of the IL-11 signaling pathway has been linked to heart failure [10,12,13]. Furthermore, the administration of recombinant human IL-11 has been shown to increase the incidence of atrial arrhythmias in elderly patients [11] and aged rats but not in adult rats [12]. Elevated IL-11 levels have been observed in atrial fibrillation and are correlated with serum markers of fibrosis, making IL-11 a potential therapeutic target for atrial fibrosis [11]. However, in atrial fibrillation, IL-11 mechanisms remain unclear.

This study aimed to explore the mechanism of IL-11 in Ang-II-induced atrial fibroblasts. The results showed that IL-11 facilitated the phenotypic changes in myofibroblasts under Ang II stimulation. At the molecular level, IL-11 promoted Ang II-induced oxidative stress, mitochondrial dysfunction, and autophagy in atrial fibroblasts. Mechanistically, the expression of the mammalian target of rapamycin (mTOR) pathway was reduced in Ang-II-induced atrial fibroblasts, which was further declined by the upregulation of IL-11. Overall, the results indicated that IL-11 enhanced Ang II-induced atrial fibroblasts to differentiate into myofibroblasts by exacerbating oxidative stress, mitochondrial dysfunction, and autophagy via the mTOR pathway. This study provides valuable insights and identifies a potential therapeutic target for the diagnosis and treatment of atrial fibrillation.

2 Materials and methods

2.1 Atrial fibroblast isolation

Male wild-type C57BL/6J mice (6–8 weeks old) were obtained from Beijing Huafukang Biotechnology Co., Ltd (China). Mice were housed in a specific pathogen-free room for a week prior to the tests. Animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals and authorized by the Animal Research Ethics Committee of Cangzhou Central Hospital. Atrial fibroblasts were isolated according to the previous study [12]. A 70% alcohol spray was used to disinfect mice’s bodies, and their hearts were collected by inhalation of excessive isoflurane (#R510-22, RWD, Guangdong, China). The left atrial was dissected into approximately 1 mm3 tissue blocks and immersed in digestive solution (DMEM [11965, Solarbio], including 0.25% trypsin [T1350, Solarbio], 1,500 U/mL collagenase type-II [40508ES76, YEASEN, Shanghai, China] and 15 mg/L BSA [36100ES25, YEASEN]) after rinsing off blood in pre-cooled phosphate buffer saline (PBS, P1020, Solarbio, Beijing, China) 3–4 times. Digestion was carried out for 20 min at 37°C in a 75 revolutions per minute (rpm) shaker. After gently dissociating cells with an elbow pipette, the supernatant was gathered and combined with 10% FBS (S9020, Solarbio) neutralizing DMEM. To harvest pellets, cell suspensions were percolated through a 70 μm mesh and centrifuged for 5 min at 1,000 rpm. Pellets were then re-suspended in DMEM with 10% FBS and hatched for 60 min at 37°C. Differential attachment was used to obtain atrial fibroblasts. The cellular morphology of isolated atrial fibroblasts was captured under an inverted microscope (Olympus, Tokyo, Japan). Atrial fibroblasts were sustained in DMEM with 10% FBS and 1% penicillin/streptomycin (P1400, Solarbio), and atrial fibroblasts were employed for second passage investigations.

  1. Ethical approval: The research related to animal use has complied with all the relevant national regulations and institutional policies for the care and use of animals and has been approved by the Animal Research Ethics Committee of Cangzhou Central Hospital.

2.2 Cell treatment

Atrial fibroblasts were stimulated with 1 μM Ang-II for 24 h based on a previous report [12]. pcDNA vector plasmids carrying IL-11 sequences were also used to overexpress IL-11. Lipofectamine 3000 (L3000001, Invitrogen, Carlsbad, CA, USA) was then used to transfect them into atrial fibroblasts. Overexpression efficiency was evaluated using Western blots.

2.3 Immunofluorescence (IF) assay

IF experiments were conducted according to a previous study [13]. Atrial fibroblasts were seeded onto glass plates and cultured at 37°C with 5% CO2. After washing thrice with PBS, atrial fibroblasts were fixed with 4% paraformaldehyde (P1110, Solarbio) for 15 min at room temperature and rinsed with PBS thrice. Atrial fibroblasts were then incubated with BSA blocking buffer (SW3015, Solarbio), 0.2% Triton X-100 (T8200, Solarbio), and primary antibodies against vimentin (ab137321, Abcam, Cambridge, UK), von Willebrand factor (vWF, ab287962, Abcam), Desmin (ab15200, Abcam), and alpha-smooth muscle actin (α-SMA, ab7817, Abcam) overnight at 4°C. Subsequently, atrial fibroblasts were rinsed thrice with PBS and treated with donkey anti-Rabbit IgG H&L (Alexa Fluor® 647) (1:1,000, ab150075, Abcam) or goat anti-mouse IgG H&L (Alexa Fluor® 488) (1:1,000, ab150113, Abcam) for 1 h at room temperature. Atrial fibroblasts were stained with mounting medium, antifading (with DAPI) (S2110, Solarbio), and visualized using fluorescence microscopy (IX71, Olympus).

2.4 Reactive oxygen species (ROS) level examination

ROS levels were measured using dihydroethidium (DHE, S0063, Beyotime, Shanghai, China) based on the operating manual. Atrial fibroblasts were incubated with 5 μM DHE at 37°C and imaged under fluorescence microscopy.

2.5 Mitochondrial membrane potential (MMP) detection

MMP level was assessed using the Mitochondrial Membrane Potential Assay Kit with JC-1 (M8650, Solarbio) according to the operating manual. Atrial fibroblasts were mixed with 1 ml DMEM with JC-1 fluorescent dye and incubated for 20 min at 37°C. The cells were centrifuged for 5 min at 4°C at 600 × g. The supernatant was discarded, and atrial fibroblasts were resuspended in 1 × JC-1 buffer. Cell nuclei were stained with DAPI (C0065, Solarbio) and observed using a fluorescence microscope.

2.6 Western blotting

Atrial fibroblasts were lysed with RIPA lysis buffer (R0010, Solarbio) to isolate total proteins. Protein concentrations were measured with a BCA Protein Assay Kit (PC0020, Solarbio). Following electrophoresis using 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), protein samples (20 μg) were transferred to PVDF membranes (IPVH00010, EMD Millipore, Billerica, MA, USA). Membranes were treated with primary antibodies overnight at 4°C after blocking in 5% BSA blocking buffer (SW3015, Solarbio) for 1 h at room temperature. Membranes were then incubated for 1 h at room temperature with the secondary antibody goat anti-rabbit IgG H&L (HRP) (1:10,000, ab205718, Abcam). Bands were visualized using a BeyoECL Plus kit (P0018S, Beyotime), and the gray value was calculated using Image-ProPlus software (Media Cybernetics, Inc., Rockville, MD, USA). GAPDH acted as an internal reference. Primary antibodies included antibodies against IL-11 (1:5,000, PA5-95982, Invitrogen), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α, 1:1,000, ab191838, Abcam), mitochondrial transcription factor A (TFAM, 1:1,000, ab47517, Abcam), LC3 I/II (1:1,000, 4108, Cell Signaling Technology, Inc., Danvers, MA, USA), Beclin-1 (1:1,000, ab62557, Abcam), p62 (1:1,000, ab91526, Abcam), phosphorylated mTOR (1:5,000, p-mTOR, ab109268, Abcam), mTOR (1:5,000, ab245370, Abcam), and GAPDH (1:2,500, ab9485, Abcam).

2.7 Statistical analysis

Data analysis was performed using SPSS 20.0 (IBM, Armonk, New York, USA). Data are presented as mean ± standard deviation (SD). The normality distribution of data was analyzed using the Anderson–Darling test, D’Agostino–Pearson omnibus normality test, Shapiro–Wilk normality test, and Kolmogorov–Smirnov normality test with Dallal–Wilkinson–Lilliefor P value, and the results showed that the distribution of all data was normal. The one-way analysis of variance (ANOVA) followed by a Post Hoc Bonferroni test was used to determine statistical differences. P < 0.05 indicates statistically significant differences.

3 Results

3.1 IL-11 promotes phenotypic changes in Ang-II-induced atrial fibroblasts

To investigate IL-11’s role in atrial fibrillation, atrial fibroblasts were first isolated. The cellular morphology of isolated atrial fibroblasts is shown in Figure 1a. Additionally, the expression of vimentin, vWF, and desmin of isolated atrial fibroblasts was analyzed. The results showed that vimentin was positively expressed in the isolated atrial fibroblasts, while vWF and desmin were negatively expressed in the isolated atrial fibroblasts (Figure 1b). The isolated atrial fibroblasts were then stimulated with Ang II for 24 h. IL-11 protein expression was significantly increased in Ang II-treated atrial fibroblasts compared to control cells (P < 0.01, Figure 2a). Overexpression of IL-11 in atrial fibroblasts was achieved via transfection with an IL-11 overexpression plasmid (P < 0.01, Figure 2a). Ang-II treatment resulted in a marked increase in α-SMA in atrial fibroblasts, which was further enhanced by IL-11 overexpression (Figure 2b). These findings indicate that IL-11 promotes phenotypic changes in Ang-II-induced atrial fibroblasts.

Figure 1 Identification of the isolated atrial fibroblasts. (a) The cellular morphology of isolated atrial fibroblasts was captured under an inverted microscope. (b) The expression of vimentin, vWF, and Desmin of isolated atrial fibroblasts was analyzed by IF.
Figure 1

Identification of the isolated atrial fibroblasts. (a) The cellular morphology of isolated atrial fibroblasts was captured under an inverted microscope. (b) The expression of vimentin, vWF, and Desmin of isolated atrial fibroblasts was analyzed by IF.

Figure 2 IL-11 enhances phenotypic changes in Ang-II-elicited atrial fibroblasts. Atrial fibroblasts were stimulated with 1 μM Ang-II for 24 h. IL-11 sequences were inserted into pcDNA vector plasmids and then transfected into atrial fibroblasts to overexpress IL-11. (A) IL-11 protein expression was detected by western blotting. Data were analyzed after normalization with GAPDH. **P < 0.01 vs. Control; ##P < 0.01 vs. Ang-II + Vector. N = 3. (B) α-SMA level was determined by immunofluorescence assays. Scale bar = 100 µm.
Figure 2

IL-11 enhances phenotypic changes in Ang-II-elicited atrial fibroblasts. Atrial fibroblasts were stimulated with 1 μM Ang-II for 24 h. IL-11 sequences were inserted into pcDNA vector plasmids and then transfected into atrial fibroblasts to overexpress IL-11. (A) IL-11 protein expression was detected by western blotting. Data were analyzed after normalization with GAPDH. **P < 0.01 vs. Control; ##P < 0.01 vs. Ang-II + Vector. N = 3. (B) α-SMA level was determined by immunofluorescence assays. Scale bar = 100 µm.

3.2 IL-11 enhances ROS production in Ang II-induced atrial fibroblasts

IL-11’s role in atrial fibrillation pathogenesis, such as oxidative stress, mitochondrial dysfunction, and autophagy, was explored in Ang-II-induced atrial fibroblasts. To determine IL-11’s role in oxidative stress, ROS levels were measured in Ang-II-induced atrial fibroblasts. The results showed a significant increase in ROS levels in Ang-II-treated atrial fibroblasts, which was further distinctly enhanced by IL-11 overexpression (Figure 3). These findings suggest that IL-11 enhances ROS production in Ang II-induced atrial fibroblasts.

Figure 3 IL-11 increases ROS production in Ang II-induced atrial fibroblasts. ROS levels were examined after atrial fibroblasts were incubated with DHE for 30 min at 37°C. Scale bar = 200 µm.
Figure 3

IL-11 increases ROS production in Ang II-induced atrial fibroblasts. ROS levels were examined after atrial fibroblasts were incubated with DHE for 30 min at 37°C. Scale bar = 200 µm.

3.3 IL-11 intensifies Ang II-induced mitochondrial dysfunction in atrial fibroblasts

IL-11’s role in mitochondrial dysfunction was probed in Ang-II-induced atrial fibroblasts. Ang II stimulation significantly increased the MMP level, which was further augmented by IL-11 overexpression (Figure 4a). Additionally, Ang-II treatment induced a significant decrease in the expression of PGC-1α and TFAM in atrial fibroblasts, which was further prominently reduced by IL-11 overexpression (Figure 4b and c). Altogether, mitochondrial dysfunction in Ang-II-stimulated atrial fibroblasts was aggravated by IL-11 overexpression.

Figure 4 IL-11 reinforces mitochondrial dysfunction in Ang II-induced atrial fibroblasts. (a) MMP levels were examined after atrial fibroblasts were stained with JC-1. Scale bar = 100 µm. (b and c) Relative protein expression of PGC-1α and TFAM was detected by western blotting. Data were analyzed after normalization with GAPDH. ***P < 0.001 vs control; #P < 0.05 and ###P < 0.001 vs Ang-II + vector. N = 3.
Figure 4

IL-11 reinforces mitochondrial dysfunction in Ang II-induced atrial fibroblasts. (a) MMP levels were examined after atrial fibroblasts were stained with JC-1. Scale bar = 100 µm. (b and c) Relative protein expression of PGC-1α and TFAM was detected by western blotting. Data were analyzed after normalization with GAPDH. ***P < 0.001 vs control; #P < 0.05 and ###P < 0.001 vs Ang-II + vector. N = 3.

3.4 IL-11 contributes to autophagy inhibition in Ang II-induced atrial fibroblasts

The role of IL-11 in autophagy was investigated in Ang-II-induced atrial fibroblasts. The expression levels of LC3 II/I and Beclin-1 were significantly reduced in Ang-II-induced atrial fibroblasts, and these reductions were further diminished by IL-11 overexpression (P < 0.001, Figure 5). Conversely, IL-11 overexpression further enhances p62 expression in Ang II-induced atrial fibroblasts (P < 0.001, Figure 5). Hence, IL-11 promotes autophagy inhibition in Ang II-induced atrial fibroblasts.

Figure 5 IL-11 facilitates autophagy inhibition in Ang II-elicited atrial fibroblasts. Relative protein expressions of LC3 I, LC3 II, LC3 II/I, p62, and Beclin-1 were determined by western blotting. Data were analyzed after normalization with GAPDH. **P < 0.01 and ***P < 0.001 vs control; ##P < 0.01 and ###P < 0.001 vs Ang-II + vector. N = 3.
Figure 5

IL-11 facilitates autophagy inhibition in Ang II-elicited atrial fibroblasts. Relative protein expressions of LC3 I, LC3 II, LC3 II/I, p62, and Beclin-1 were determined by western blotting. Data were analyzed after normalization with GAPDH. **P < 0.01 and ***P < 0.001 vs control; ##P < 0.01 and ###P < 0.001 vs Ang-II + vector. N = 3.

3.5 IL-11 facilitates mTOR pathway activation in Ang-II-induced atrial fibroblasts

To investigate the potential mechanisms of IL-11 in atrial fibrillation, the activation of the mTOR pathway was examined in Ang II-induced atrial fibroblasts. The results demonstrated that p-mTOR/mTOR protein expression was enhanced in Ang-II-induced atrial fibroblasts, which was further elevated by IL-11 overexpression (P < 0.001, Figure 6). Collectively, IL-11 facilitates mTOR pathway activation in Ang-II-induced atrial fibroblasts.

Figure 6 IL-11 enhances mTOR pathway activation in Ang-II-evoked atrial fibroblasts. Relative protein expressions of mTOR, p-mTOR, and p-mTOR/mTOR were quantified by western blotting. Data were analyzed after normalization with GAPDH. *P < 0.05 vs control; ###P < 0.01 and ###P < 0.001 vs Ang-II + vector. N = 3.
Figure 6

IL-11 enhances mTOR pathway activation in Ang-II-evoked atrial fibroblasts. Relative protein expressions of mTOR, p-mTOR, and p-mTOR/mTOR were quantified by western blotting. Data were analyzed after normalization with GAPDH. *P < 0.05 vs control; ###P < 0.01 and ###P < 0.001 vs Ang-II + vector. N = 3.

4 Discussion

Atrial fibrillation is the most prevalent arrhythmia worldwide, contributing significantly to morbidity, mortality, and socioeconomic burden [4]. Current treatment approaches, such as catheter ablation techniques and antiarrhythmic medicines, have limited efficacy and side effects [14]. Developing gene-based therapies for atrial fibrillation presents an innovative and promising approach to treat atrial fibrillation [15]. In this study, we observed that IL-11 was upregulated in Ang-II-induced atrial fibroblasts, consistent with results from persistent atrial fibrillation patients and Ang II-treated fibrosis mouse models [11]. Ang-II treatment increases α-SMA, ROS, and MMP levels and p62 expression but decreases LC3 II/I and Beclin-1 expression in atrial fibroblasts. Atrial fibroblasts overexpressing IL-11 further confirmed the role of Ang-II in these indicators. Mechanistically, mTOR pathway expression was enhanced in Ang-II-induced atrial fibroblasts, which was further elevated by IL-11 upregulation. Overall, IL-11 promoted Ang II-induced atrial fibroblasts to differentiate into myofibroblasts by enhancing oxidative stress, mitochondrial dysfunction, and autophagy inhibition, involving in the mTOR pathway.

As a crucial mediator for atrial fibrosis, Ang-II abnormally stimulates atrial fibroblasts, driving their proliferation and transformation into a secretory phenotype known as myofibroblasts [3]. Myofibroblast phenotypes are characterized by α-SMA production. When myofibroblasts are produced, an overabundance of ECM is synthesized and deposited, eventually leading to fibrotic lesions in surrounding tissues [16]. These fibrotic lesions pose an increased risk of atrial fibrillation by obstructing the conduction of the heart’s electrical pacing signals [17]. Here, we found the increase of α-SMA in Ang-II-induced atrial fibroblasts was further enhanced by IL-11 overexpression, indicating that IL-11 promotes phenotypic changes in Ang-II-induced atrial fibroblasts. Similar results were also reported by Cong and colleagues, in which Ang II treatment fostered IL-11 expression and α-SMA intensity, while treatment with IL-11 antagonist reduced α-SMA-positive myofibroblasts in atrial tissue from the fibrosis mouse model [11]. Besides, IL-11 has been proven to transform fibroblasts into α-SMA-positive myofibroblasts in TGFβ1-stimulated human tracheal epithelial cells and primary rat tracheal fibroblasts [18]. Thus, IL-11 facilitates phenotypic changes in myofibroblasts in Ang-II-induced atrial fibroblasts.

Oxidative stress refers to an imbalance between ROS production and antioxidants [19]. ROS overproduction increases oxidative stress [20]. Increased ROS levels have been associated with atrial fibrillation [21]. Antioxidants, such as vitamin C, decrease the risk of postoperative atrial fibrillation [21,22]. This study discovered that increased ROS levels in Ang-II-stimulated atrial fibroblasts were further enhanced by IL-11 overexpression. However, IL-11 reduces ROS release in H2O2-induced PC12 cells [23]. Further research is needed to fully elucidate the role IL-11 plays in different diseases through its diverse molecular mechanisms. Notably, IL-11 promotes oxidative stress in Ang-II-induced atrial fibroblasts, but its broader impact on disease progression remains to be fully understood. Energy-producing organelles, mitochondria, play a crucial role in energy metabolism and the maintenance of myocardium redox balance [24,25]. Both experimental and clinical studies have demonstrated a reduction in ATP levels, loss of MMP, and fragmentation of the mitochondrial network, which causes contractile dysfunction and atrial fibrillation [26,27]. Therefore, several studies investigated mitochondrial dysfunction’s role in atrial fibrillation development [28,29]. Herein, Ang II stimulation resulted in an increase in MMP level, which was further enhanced by IL-11 overexpression. Assessing MMP is crucial in evaluating mitochondrial function. Besides, overexpression of IL-11 further aggravated the reduction in the expression of PGC-1α and TFAM in Ang-II-induced atrial fibroblasts. PGC-1α is a crucial transcriptional regulator of mitochondrial biogenesis, in which NRF1 acts as a principal target of PGC-1α. NRF1 activation raises TFAM expression, which primarily aids in mitochondrial DNA replication and maintenance [30]. Widjaja and colleagues [31] also reveal that IL-11 induces mitochondrial dysfunction in acetaminophen-evoked liver injury. Overall, IL-11 accelerates Ang II-induced mitochondrial dysfunction in atrial fibroblasts.

An autophagosome is formed when phagophores enclose proteins, RNA, and glycogen to initiate the breakdown process known as autophagy. Lysosome hydrolases then break down the inclusion. Autophagy is a physiological process by which cells maintain their homeostasis and regenerate their organelles. However, some cell stressors can also cause autophagy dysregulation. Cardiac autophagy is impaired in patients with postoperative atrial fibrillation after coronary artery bypass surgery [32]. Autophagy also promotes the profibrotic role of osteopontin in atrial fibrosis [33]. Additionally, a small-molecule-integrated stress response inhibitor is also reported to inhibit autophagy to assist its ameliorative role in atrial fibrillation [34]. Besides, autophagy-related genes have been identified as potential biomarkers and therapeutic targets in atrial fibrillation [35]. In this study, LC3 II/I and Beclin-1 downregulation and p62 upregulation were observed in Ang-II-induced atrial fibroblasts, which were intensified by IL-11 overexpression. Beclin-1 is crucial for autophagy’s initial step when it forms trimers with P13K and Atg14 and persistently attracts autophagy-related proteins [36]. By processing the LC3 precursor, Atg4 creates soluble LC3-I. LC3-II-PE is linked to phosphatidylethanolamine (PE) by Atg7 and Atg3, leading to lipid-soluble LC3-II-PE, which enhances autophagolysosome membranes until autophagolysosome formation [36]. Upon binding to the ubiquitinated protein, p62 joins forces with LC3-II, which is found in the cytoplasm, to form a complex that is ultimately broken down by lysosomes. Throughout the autophagic process, p62 will be continually eaten [36]. Sharma et al. [37] reported that mice treated with a long-acting IL-11 analog exhibit a decreased expression of Sqstm1, a marker of autophagy. Thus, IL-11 boosts autophagy inhibition in Ang II-elicited atrial fibroblasts, suggesting a possible treatment for atrial fibrosis by suppression of IL-mediated autophagy.

The conserved protein kinase, mTOR, connects the metabolic pathways in a wide range of species and is essential for cell metabolism, a fundamental biological process involved in cell growth, survival, and development [38]. The mTOR pathway also regulates other critical physiological functions such as autophagy, lipid synthesis, mitochondrial biogenesis, and cell survival [39]. mTOR deficiency and inhibition affect the heart differently, depending on the pathological and physiological state. In the embryonic and neonatal stages, the systemic or cardiac-specific mTOR knockout mice die in embryonic and neonatal stages mainly due to left ventricular dilatation and malfunction. This inhibits cell development, protein synthesis, mitochondrial activity, and sarcomere structure maintenance [39]. In unstressed settings, mTOR signaling is essential for the development of the cardiovascular system in the embryo and for maintaining cardiovascular integrity and function in the postnatal period [39]. Further, total genetic disruption of either mTORC1 or mTORC2 impairs the heart’s ability to adapt to mechanical and ischemia injury. This hinders compensatory cardiac hypertrophy in response to stress [40,41]. Inversely, partial and selective suppression of mTORC1 has been shown to provide cardioprotection to various cardiac pathological conditions, including pathological hypertrophy, cardiac aging, and genetic and metabolic cardiomyopathies [41]. This suggests the prospective therapeutic intervention of pharmacological suppression of mTORC1 for the management of cardiovascular ailments. This study found that p-mTOR/mTOR protein expression was enhanced in Ang-II-induced atrial fibroblasts, which was further elevated by IL-11overexpression. IL-11 is demonstrated to be secreted from damaged mammalian cells to signal through LKB1/mTOR in autocrine and paracrine [42]. Besides, Widjaja et al. [43] reported that activation of ERK/mTOR/P70S6K is essential for protein translation in TGFβ1-stimulated human cardiac fibroblasts, which is mediated by IL-11. The results from the same team show that IL-11 activates mTOR signaling and identify that the IL-11/mTOR axis acts as a signaling commonality in stromal, epithelial, and cancer cells [44]. Together, IL-11 facilitates mTOR pathway activation in Ang-II-induced atrial fibroblasts.

In summary, IL-11 was upregulated in Ang-II-induced atrial fibroblasts. IL-11 promotes the differentiation of Ang II-induced atrial fibroblasts into myofibroblasts by enhancing oxidative stress, mitochondrial dysfunction, and autophagy inhibition, processes that are involved in the mTOR pathway. However, several limitations should be addressed in future research. To further support the current study’s results, further studies should investigate the relevant indicators in more detail. This could include additional examinations of α-SMA expression using western blotting and immunohistochemistry, measurements of MDA, GSH, and SOD concentrations, and assessment of autophagy flux. Furthermore, the direct role of the mTOR pathway by using pharmacological blockers or gene interference can be explored in subsequent studies. In addition, the role of IL-11 in atrial fibrillation should be verified in vivo. Animal models, such as mice treated with Ang-II to induce atrial fibrillation, could be used to investigate the role of IL-11 in oxidative stress, mitochondrial dysfunction, and autophagy. Moreover, animal experiments could also confirm the involvement of the mTOR pathway using pharmacological blockers, thus solidifying the conclusions of this study. Overall, this study provides a better understanding and potential target for atrial fibrillation detection and treatment.

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Acknowledgements

The authors are grateful for the reviewer’s valuable comments that improved the manuscript.

  1. Funding information: This work was supported by the Hebei Province Natural Science Foundation (Grant No. H2023110015).

  2. Author contributions: JW and QZ designed the study, completed the experiment, and supervised the data collection. YH analyzed the data and interpreted the data. JZ and NZ prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have accepted responsibility for the entire content of this manuscript and consented to its submission to the journal, reviewed all the results, and approved the final version of the manuscript.

  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.

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Received: 2024-08-27
Revised: 2024-12-25
Accepted: 2025-01-18
Published Online: 2025-03-11

© 2025 the author(s), published by De Gruyter

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

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https://doi.org/10.1515/biol-2025-1063
Keywords for this article
Atrial fibrillation; atrial fibroblasts; Ang II; IL-11; oxidative stress; mitochondrial dysfunction; autophagy
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  3. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  4. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  5. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  6. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  7. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  8. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  9. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
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  11. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  12. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  13. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  14. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  15. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  16. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  17. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  18. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  19. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  20. Changes in blood glucose and metabolism in hyperuricemia mice
  21. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  22. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  23. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  24. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  27. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  29. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  30. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  31. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  32. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  33. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  34. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
  38. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  40. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  41. A case of bloodstream infection caused by Neisseria gonorrhoeae
  42. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  43. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  44. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  45. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  46. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  47. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  48. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  49. Sodium butyrate aids brain injury repair in neonatal rats
  50. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  51. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  52. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  53. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  54. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  55. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  56. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  57. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  58. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  59. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  60. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  61. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  62. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  63. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  64. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  65. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  66. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  67. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  68. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  69. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  70. Oncolytic bacteria: A revolutionary approach to cancer therapy
  71. A de novo meningioma with rapid growth: A possible malignancy imposter?
  72. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  73. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  74. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  75. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  76. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  77. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  78. Evaluation and application analysis of animal models of PIPNP based on data mining
  79. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  80. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  81. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  82. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  83. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  84. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  85. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  86. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  87. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  88. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  89. RNF144A and RNF144B: Important molecules for health
  90. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  91. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  92. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  93. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  94. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  95. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  96. Understanding risk factors and prognosis in diabetic foot ulcers
  97. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  98. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  99. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  100. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  101. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  102. Pulmonary cryptococcosis with headache as the first presentation: A case report
  103. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  104. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  105. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  106. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  107. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  108. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  109. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  110. Wound healing and signaling pathways
  111. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  112. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  113. Research progress on the impact of curcumin on immune responses in breast cancer
  114. Biogenic Cu/Ni nanotherapeutics from Descurainia sophia (L.) Webb ex Prantl seeds for the treatment of lung cancer
  115. Dapagliflozin attenuates atrial fibrosis via the HMGB1/RAGE pathway in atrial fibrillation rats
  116. Glycitein alleviates inflammation and apoptosis in keratinocytes via ROS-associated PI3K–Akt signalling pathway
  117. ADH5 inhibits proliferation but promotes EMT in non-small cell lung cancer cell through activating Smad2/Smad3
  118. Apoptotic efficacies of AgNPs formulated by Syzygium aromaticum leaf extract on 32D-FLT3-ITD human leukemia cell line with PI3K/AKT/mTOR signaling pathway
  119. Novel cuproptosis-related genes C1QBP and PFKP identified as prognostic and therapeutic targets in lung adenocarcinoma
  120. Bee venom promotes exosome secretion and alters miRNA cargo in T cells
  121. Treatment of pure red cell aplasia in a chronic kidney disease patient with roxadustat: A case report
  122. Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status
  123. Kynurenine facilitates renal cell carcinoma progression by suppressing M2 macrophage pyroptosis through inhibition of CASP1 cleavage
  124. RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis
  125. ALKBH5 exacerbates early cardiac damage after radiotherapy for breast cancer via m6A demethylation of TLR4
  126. Phytochemicals of Roman chamomile: Antioxidant, anti-aging, and whitening activities of distillation residues
  127. Circadian gene Cry1 inhibits the tumorigenicity of hepatocellular carcinoma by the BAX/BCL2-mediated apoptosis pathway
  128. The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells
  129. Longitudinal monitoring of autoantibody dynamics in patients with early-stage non-small-cell lung cancer undergoing surgery
  130. The potential role of rutin, a flavonoid, in the management of cancer through modulation of cell signaling pathways
  131. Construction of pectinase gene engineering microbe and its application in tobacco sheets
  132. Construction of a microbial abundance prognostic scoring model based on intratumoral microbial data for predicting the prognosis of lung squamous cell carcinoma
  133. Sepsis complicated by haemophagocytic lymphohistiocytosis triggered by methicillin-resistant Staphylococcus aureus and human herpesvirus 8 in an immunocompromised elderly patient: A case report
  134. Sarcopenia in liver transplantation: A comprehensive bibliometric study of current research trends and future directions
  135. Advances in cancer immunotherapy and future directions in personalized medicine
  136. Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis
  137. Heat stroke associated with novel leukaemia inhibitory factor receptor gene variant in a Chinese infant
  138. PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation
  139. Hyperosmolar hyperglycemic state with severe hypernatremia coexisting with central diabetes insipidus: A case report and literature review
  140. Efficacy and mechanism of escin in improving the tissue microenvironment of blood vessel walls via anti-inflammatory and anticoagulant effects: Implications for clinical practice
  141. Merkel cell carcinoma: Clinicopathological analysis of three patients and literature review
  142. Genetic variants in VWF exon 26 and their implications for type 1 Von Willebrand disease in a Saudi Arabian population
  143. Lipoxin A4 improves myocardial ischemia/reperfusion injury through the Notch1-Nrf2 signaling pathway
  144. High levels of EPHB2 expression predict a poor prognosis and promote tumor progression in endometrial cancer
  145. Knockdown of SHP-2 delays renal tubular epithelial cell injury in diabetic nephropathy by inhibiting NLRP3 inflammasome-mediated pyroptosis
  146. Exploring the toxicity mechanisms and detoxification methods of Rhizoma Paridis
  147. Concomitant gastric carcinoma and primary hepatic angiosarcoma in a patient: A case report
  148. Ecology and Environmental Science
  149. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  150. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  151. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  152. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  153. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  154. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  155. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  156. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  157. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  158. Temperature-dependent development, predation, and life table of Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) feeding on Myzus persicae (Sulzer) (Homoptera: Aphididae)
  159. Eleonora’s falcon trophic interactions with insects within its breeding range: A systematic review
  160. Agriculture
  161. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  162. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  163. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  164. Molecular mechanism of follicular development in laying hens based on the regulation of water metabolism
  165. Animal Science
  166. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  167. Plant Sciences
  168. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  169. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  170. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  171. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  172. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  173. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  174. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  175. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  176. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  177. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  178. Using plant electrical signals of water hyacinth (Eichhornia crassipes) for water pollution monitoring
  179. Food Science
  180. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  181. Review on role of honey in disease prevention and treatment through modulation of biological activities
  182. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  183. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  184. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  185. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  186. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  187. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  188. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  189. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  190. The dilemma of food genetics and improvement
  191. Bioengineering and Biotechnology
  192. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  193. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  194. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  195. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  196. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  197. Corrigendum
  198. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  199. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
  200. Retraction
  201. Retraction of “Down-regulation of miR-539 indicates poor prognosis in patients with pancreatic cancer”
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