Home Life Sciences SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
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SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling

  • Mangmang Chen , Luyou Ye and Shenglei Lin EMAIL logo
Published/Copyright: March 6, 2025

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease that affects 70–90% of individuals over the age of 75 and over 100 million people globally. Current treatments primarily offer symptomatic relief and do not effectively halt disease progression, highlighting the need for improved therapeutic strategies. Salt-inducible kinase 1 (SIK1) plays a role in regulating key physiological processes, including gluconeogenesis, glycolysis, and bone metabolism. Despite these insights, the specific role and underlying mechanisms of SIK1 in OA pathogenesis remain inadequately understood. This study aims to elucidate the function of SIK1 in OA cells. We observed that SIK1 was downregulated in a cell model of OA. The overexpression of SIK1 was found to inhibit IL-1β-induced chondrocyte apoptosis and inflammation. Additionally, SIK1 overexpression enhanced the activation of the CRTC2/CREB1 axis, suggesting a protective role for SIK1 in cartilage cells. In summary, SIK1 exerts a protective effect against IL-1β-induced cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling axis.

1 Introduction

Osteoarthritis (OA) is a chronic degenerative joint disease that significantly contributes to disability among the elderly [1]. The prevalence of OA is alarmingly high, affecting approximately 70–90% of individuals over the age of 75, with more than 100 million people globally suffering from this condition [2]. Clinically, OA is characterized by joint pain, swelling, deformity, and limited mobility [3]. The primary pathological features of OA include cartilage degradation, destruction, and the formation of osteophytes [3]. Despite its widespread impact, current pharmacological treatments, such as analgesics, primarily offer symptomatic relief and do not effectively prevent or slow disease progression [2,4]. The development of OA is closely associated with cartilage tissue lesions, and chondrocyte apoptosis is a key factor in cartilage damage. The disease presents a multifactorial etiology and complex pathogenesis [4], highlighting the urgent need for the development of more effective targeted therapies.

Research has established a strong positive correlation between chondrocyte apoptosis and the severity of OA. Reactive oxygen species (ROS) are crucial mediators of chondrocyte apoptosis [5]. It is known that excessive ROS accumulation can lead to mitochondrial dysfunction, which in turn promotes apoptosis in cartilage cells [6]. Recent studies have increasingly highlighted the central role of ROS in the pathogenesis of OA, particularly through the mechanisms of chondrocyte apoptosis and extracellular matrix degradation. This degradation involves both reduced matrix synthesis and increased matrix decomposition [6]. Additionally, inflammation-related osteoporosis, characterized by bone mass loss and damage to bone microstructure due to chronic infections or autoimmune diseases, further complicates the disease. Therefore, strategies aimed at inhibiting apoptosis and reducing ROS levels may provide new therapeutic avenues for the treatment of OA.

Salt-inducible kinase 1 (SIK1) is a serine/threonine kinase protein expressed across multiple tissues [7]. It belongs to the adenosine monophosphate-activated protein kinase family of serine/threonine kinases. It has been reported that inhibiting SIK1 could be a novel therapeutic approach for modulating pro-inflammatory and immunomodulatory pathways, with potential applications in treating inflammatory diseases [79]. SIK1 is essential for regulating various cellular processes, including electrolyte balance, carbohydrate and lipid metabolism, cell proliferation, and circadian rhythms [810]. For example, SIK1 regulates CRTC2-mediated gluconeogenesis under both physiological and high glucose conditions [11]. Targeting the SIK1-CRTC2 axis presents a potential strategy for managing diabetes [12]. Additionally, SIK1 activation by phanginin A has been shown to inhibit gluconeogenesis by enhancing PDE4 function and blocking the cAMP/PKA/CREB axis [13]. Furthermore, SIK1 and its isoform SIK3 influence aerobic glycolysis and breast cancer cell growth by targeting the p53 and mTOR pathways [14]. In the context of bone metabolism, SIK1 acts as a critical negative regulator of pre-osteoblast proliferation and osteoblast differentiation, with its inhibition being essential for BMP2 signaling during osteogenesis [10]. Recent studies suggest that SIK1 may also be a novel target for OA [15]. Despite these insights, the specific role and underlying mechanisms of SIK1 in OA remain poorly understood.

In this study, we aim to investigate the function of SIK1 in an in vitro model of OA, specifically focusing on its potential role in modulating chondrocyte apoptosis and inflammation. We hypothesize that SIK1 inhibits IL-1β-induced cartilage apoptosis and inflammation in vitro. Elucidating the role of SIK1 could lead to the development of novel therapeutic strategies for managing OA, potentially improving outcomes for patients affected by this debilitating condition.

2 Materials and methods

2.1 Cell culture and treatment

The human chondrocyte cell line C28/I2 (HTX2308) was purchased from ATCC and cultured in DMEM/F-12 medium (Gibco, USA) supplemented with 10% FBS (Gibco, USA). The cells were maintained at 37°C in a 5% CO2 atmosphere. For the OA model, cells were treated with IL-1β (10 ng/mL, PeproTech, USA) for 24 h.

2.2 Viral infection

C28/I2 cells were infected with either ad-SIK1 or ad-NC, both purchased from GeneChem (Shanghai, China). Cell infection was conducted at a multiplicity of infection of 50 in the presence of 5 µg/mL polybrene (Beyotime, ST1382). After 24 h, the medium was replaced with fresh growth medium.

2.3 Western blot analysis

The proteins were separated by SDS-PAGE and transferred onto PVDF membranes (Millipore, USA). The membranes were blocked with 5% non-fat milk and incubated overnight at 4°C with primary antibodies. The primary antibodies used were SIK1 (1:1,000; ab62738, Abcam, UK), CRTC2 (1:1,000, ab236134; Abcam, UK), p-CRTC2 (1:1,000, ab76477; Abcam, UK), CREB1 (1:1,000, 9197; Cell Signaling Technology, USA), p-CREB1 (1:1,000, 9198; Cell Signaling Technology, USA), and β-actin (1:5,000, AF7018; Affinity Biosciences, USA). After washing, membranes were incubated with HRP-conjugated secondary antibodies (1:5,000; Beyotime, China) for 1 h, and the bands were visualized using an ECL detection kit (Beyotime, China) and quantified.

2.4 Cell Counting Kit-8 (CCK-8) assay

Cell viability was assessed using the CCK-8 (Beyotime, China). Absorbance was measured at 450 nm using a microplate reader (Bio-Rad, USA).

2.5 Flow cytometry for apoptosis

Apoptosis was assessed using the Annexin V-FITC/PI Apoptosis Detection Kit (Beyotime, China). Samples were analyzed with a flow cytometer (BD, USA), and the data were processed using the FlowJo software.

2.6 ROS assay

Intracellular ROS levels were measured with the ROS Assay Kit (Beyotime, China). Fluorescence was detected using a microscope (Olympus, Japan), the images were captured, and fluorescence intensity was quantified using ImageJ.

2.7 Enzyme-linked immunosorbent assay (ELISA)

The concentrations of TNF-α and IL-6 in the cell culture supernatants were determined using ELISA kits (Beyotime, China), and the corresponding absorbance was measured at 450 nm using a microplate reader (Bio-Rad, USA).

2.8 Statistical analysis

The data are expressed as mean ± SD. Statistical analyses were performed using GraphPad Prism 8 software. One-way ANOVA followed by Tukey’s post hoc test was used to determine differences, with a p-value of less than 0.05 considered statistically significant.

3 Results

3.1 SIK1 is downregulated in an in vitro model of OA

To investigate the expression of SIK1 in OA, we utilized an in vitro model of C28/I2 chondrocytes treated with IL-1β for 24 h. Immunoblot analysis revealed a significant downregulation of SIK1 in the IL-1β-treated group (Figure 1), which indicates that IL-1β treatment negatively affects SIK1 expression in chondrocytes.

Figure 1 
                  SIK1 is downregulated in an in vitro model of osteoarthritis. Immunoblot analysis was performed to assess the expression levels of SIK1 in C28/I2 cells treated with either control or IL-1β for 24 h. Data are presented as mean ± SD. **p < 0.01 versus control.
Figure 1

SIK1 is downregulated in an in vitro model of osteoarthritis. Immunoblot analysis was performed to assess the expression levels of SIK1 in C28/I2 cells treated with either control or IL-1β for 24 h. Data are presented as mean ± SD. **p < 0.01 versus control.

3.2 Overexpression of SIK1 inhibits IL-1β-stimulated chondrocyte apoptosis

Next, we assessed the impact of SIK1 overexpression on IL-1β-induced chondrocyte apoptosis. Immunoblot analysis showed that overexpression of SIK1 via ad-SIK1 infection increased SIK1 protein levels in C28/I2 cells under IL-1β treatment for 24 h (Figure 2a). The CCK-8 assay demonstrated enhanced cell viability in C28/I2 cells with SIK1 overexpression compared to the ad-NC group (Figure 2b). Moreover, flow cytometry analysis revealed a reduction in the apoptosis rate of C28/I2 cells overexpressing SIK1 under IL-1β treatment (Figure 2c). Additionally, the ROS assay showed that SIK1 overexpression decreased ROS levels in C28/I2 cells subjected to IL-1β treatment (Figure 2d). These findings collectively indicate that SIK1 overexpression mitigates IL-1β-induced apoptosis and oxidative stress in chondrocytes.

Figure 2 
                  Overexpression of SIK1 inhibits IL-1β-stimulated chondrocyte apoptosis. (a) Immunoblot analysis was performed to assess SIK1 expression levels in C28/I2 cells treated with either control or IL-1β, and infected with ad-NC or ad-SIK1 for 24 h. (b) CCK-8 assay was used to evaluate the impact of SIK1 overexpression on cell viability in C28/I2 cells, following treatment with control or IL-1β and infection with ad-NC or ad-SIK1 for 24 h. (c) Flow cytometry was employed to measure apoptosis rates in C28/I2 cells under the same conditions. (d) ROS assay was conducted to analyze ROS levels in C28/I2 cells, with ROS visualized in the green channel. Scale bar, 200 μm. Data are presented as mean ± SD. **p < 0.01, ***p < 0.001.
Figure 2

Overexpression of SIK1 inhibits IL-1β-stimulated chondrocyte apoptosis. (a) Immunoblot analysis was performed to assess SIK1 expression levels in C28/I2 cells treated with either control or IL-1β, and infected with ad-NC or ad-SIK1 for 24 h. (b) CCK-8 assay was used to evaluate the impact of SIK1 overexpression on cell viability in C28/I2 cells, following treatment with control or IL-1β and infection with ad-NC or ad-SIK1 for 24 h. (c) Flow cytometry was employed to measure apoptosis rates in C28/I2 cells under the same conditions. (d) ROS assay was conducted to analyze ROS levels in C28/I2 cells, with ROS visualized in the green channel. Scale bar, 200 μm. Data are presented as mean ± SD. **p < 0.01, ***p < 0.001.

3.3 Overexpression of SIK1 inhibits IL-1β-stimulated chondrocyte inflammation

We further evaluated the effect of SIK1 overexpression on the inflammatory response in IL-1β-stimulated chondrocytes. ELISA assays revealed that SIK1 overexpression reduced the secretion of TNF-α and IL-6 in C28/I2 cells treated with IL-1β, compared to control and ad-NC groups (Figure 3). These results suggest that SIK1 overexpression effectively suppresses the inflammatory response triggered by IL-1β in chondrocytes.

Figure 3 
                  Overexpression of SIK1 inhibits IL-1β-stimulated chondrocyte inflammation. ELISA assays were performed to measure the secretion of TNF-α (left) and IL-6 (right) from C28/I2 cells treated with control or IL-1β and infected with either ad-NC or ad-SIK1 for 24 h. Data are presented as mean ± SD. **p < 0.01, ***p < 0.001.
Figure 3

Overexpression of SIK1 inhibits IL-1β-stimulated chondrocyte inflammation. ELISA assays were performed to measure the secretion of TNF-α (left) and IL-6 (right) from C28/I2 cells treated with control or IL-1β and infected with either ad-NC or ad-SIK1 for 24 h. Data are presented as mean ± SD. **p < 0.01, ***p < 0.001.

3.4 Overexpression of SIK1 promotes the activation of the CRTC2/CREB1 signaling pathway

To elucidate the mechanisms underlying the effects of SIK1, we investigated the activation of the CRTC2/CREB1 signaling pathway in IL-1β-treated chondrocytes. Immunoblot analysis was performed to assess both the expression and phosphorylation levels of CRTC2 and CREB1 in C28/I2 cells subjected to IL-1β treatment. Our results indicated that overexpression of SIK1 led to increased phosphorylation of both CRTC2 and CREB1. This finding was corroborated by densitometric analysis, which confirmed elevated phosphorylation levels of CRTC2 and CREB1 (Figure 4). These observations collectively suggest that SIK1 overexpression activates the CRTC2/CREB1 signaling pathway in chondrocytes exposed to IL-1β.

Figure 4 
                  Overexpression of SIK1 promotes the activation of the CRTC2/CREB1 signaling pathway. Immunoblot analysis was conducted to evaluate the expression and phosphorylation levels of CRTC2 and CREB1 in C28/I2 cells treated with control or IL-1β for 24 h. Data are presented as mean ± SD. *p < 0.05, **p < 0.01.
Figure 4

Overexpression of SIK1 promotes the activation of the CRTC2/CREB1 signaling pathway. Immunoblot analysis was conducted to evaluate the expression and phosphorylation levels of CRTC2 and CREB1 in C28/I2 cells treated with control or IL-1β for 24 h. Data are presented as mean ± SD. *p < 0.05, **p < 0.01.

4 Discussion

OA is a prevalent degenerative joint disease that significantly impairs mobility, especially in the elderly [3]. Current treatment modalities primarily offer symptomatic relief, failing to effectively arrest disease progression [16,17]. Thus, elucidating the underlying mechanisms of OA and identifying novel therapeutic targets is essential for the development of more effective treatments. Recent research has highlighted the potential role of various molecular pathways in OA, among which SIK1 has emerged as a promising candidate. In this present study, we investigated the role of SIK1 in OA, focusing on its impact on chondrocyte apoptosis and inflammation.

Apoptosis and inflammation are critical processes in OA pathogenesis [18,19]. Chondrocyte apoptosis contributes to cartilage degradation, a defining feature of OA, while inflammation exacerbates joint damage and pain. This study found that SIK1 is downregulated in an in vitro model of OA. Notably, the overexpression of SIK1 significantly inhibited IL-1β-stimulated chondrocyte apoptosis and inflammation. These findings indicate that SIK1 plays a protective role in maintaining cartilage integrity and suggest its potential as a therapeutic target for OA.

SIK1, a serine/threonine kinase, is known for its regulatory roles in various physiological processes, including metabolism and circadian rhythms [9]. In the context of OA, our results demonstrate that SIK1 overexpression can mitigate IL-1β-induced apoptotic and inflammatory responses in chondrocytes, which implies that SIK1 may help preserve cartilage by preventing cell death and reducing inflammatory mediators. The protective effects of SIK1 on chondrocytes underscore its potential utility in developing new treatments aimed at preserving joint function in OA patients.

Furthermore, SIK1’s role extends beyond OA to several other diseases. It has been shown to regulate gluconeogenesis in diabetes, modulate cell growth in breast cancer through the p53 and mTOR pathways, and influence bone metabolism [14,20]. These diverse functions of SIK1 illustrate its context-dependent actions, which vary based on the specific cellular environment. In OA, our findings suggest that SIK1’s ability to inhibit apoptosis and inflammation could be harnessed to create targeted therapies addressing the complex nature of the disease.

CRTC2 and CREB1 are pivotal proteins involved in regulating metabolism and stress responses [21]. The CRTC2/CREB1 signaling axis is essential for mediating inflammatory and apoptotic responses. Specifically, CRTC2, a co-activator of the cyclic AMP-response element binding protein (CREB), plays a significant role in maintaining glucose homeostasis in the liver and in several inflammatory diseases [21]. This study found that SIK1 overexpression enhances the activation of the CRTC2/CREB1 pathway in chondrocytes. This activation likely represents a key mechanism through which SIK1 exerts its protective effects against IL-1β-induced apoptosis and inflammation. By promoting the CRTC2/CREB1 signaling, SIK1 may counteract the harmful effects of inflammatory cytokines in OA.

The involvement of the CRTC2/CREB1 pathway in OA is gaining recognition. This pathway influences the expression of genes associated with cell survival and inflammation, thereby playing a crucial role in how chondrocytes respond to inflammatory stimuli. Our findings further support the significance of this pathway in OA, demonstrating that its activation by SIK1 can mitigate IL-1β-induced damage in chondrocytes. These results support the potential of targeting the CRTC2/CREB1 pathway as a therapeutic strategy for OA.

Despite the promising results, this study has some limitations that should be highlighted. The in vitro model used does not fully replicate the complex in vivo environment of OA-affected joints. To validate our findings, further studies utilizing animal models and clinical samples are necessary. Additionally, the specific molecular interactions between SIK1 and the CRTC2/CREB1 pathway require further investigation. Future research should also address potential side effects and optimize delivery methods for SIK1-based therapies.

In conclusion, this study provides novel insights into the role of SIK1 in OA, illustrating its capacity to inhibit apoptosis and inflammation in chondrocytes through the CRTC2/CREB1 axis. These findings suggest that SIK1 could be a valuable target for developing new OA treatments. Thus, the continued exploration of SIK1’s mechanisms and its interactions with other molecular pathways will be essential for advancing OA therapy and enhancing patient outcomes.


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  1. Funding information: Authors state no funding involved.

  2. Author contributions: Mangmang Chen, Shenglei Lin – designed the study and carried them out; Mangmang Chen, Luyou Ye, Shenglei Lin – supervised the data collection, Mangmang Chen, Luyou Ye, Shenglei Lin – analyzed the data, interpreted the data, Mangmang Chen, Shenglei Lin – prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

  3. Conflict of interest: Authors state no conflicts 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: 2024-07-16
Revised: 2024-09-14
Accepted: 2024-11-14
Published Online: 2025-03-06

© 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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  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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