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RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis

  • Lili Zhu and Le Qi EMAIL logo
Published/Copyright: October 8, 2025

Abstract

Gastric cancer is among the most common gastrointestinal malignancies with high morbidity and mortality rates, highlighting the need to further elucidate its pathogenesis and identify effective therapeutic targets. The regulatory factor X (RFX) gene family encodes transcription factors implicated in the development and progression of several cancers. Although RFX5 has been reported to influence tumor progression in various malignancies, its specific role in gastric adenocarcinoma remains unclear. In this study, we investigated the functional effects of RFX5 in gastric adenocarcinoma. Our findings revealed that RFX5 is highly expressed in gastric adenocarcinoma tissues. Silencing of RFX5 significantly inhibited cell proliferation and migration, while promoting apoptosis in gastric adenocarcinoma cells. Mechanistically, RFX5 knockdown activated the silent information regulator transcript 1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) signaling axis. These results suggest that RFX5 facilitates the growth and motility of gastric adenocarcinoma cells and suppresses apoptosis, at least in part, through modulation of the SIRT1/AMPK pathway.

1 Introduction

Gastric cancer remains one of the most prevalent gastrointestinal malignancies in China, with high morbidity and mortality rates [1]. Among its histological subtypes, gastric adenocarcinoma is the most common, accounting for approximately 90% of all gastric malignancies. This subtype originates from malignant epithelial cells exhibiting glandular differentiation of the gastric mucosa, with known risk factors including smoking and heavy alcohol consumption [2]. Although recent decades have seen improvements in early diagnosis and surgical techniques that have reduced overall mortality, the prognosis for many patients remains poor due to advanced-stage diagnosis with metastasis or recurrence at presentation [3]. Accordingly, elucidating the molecular mechanisms underlying disease progression and identifying effective therapeutic targets remain urgent clinical priorities.

The regulatory factor X gene family encodes transcription factors characterized by a highly conserved DNA-binding domain, and previous studies have demonstrated their involvement in cancer development and progression [4]. High expression of RFX4 has been associated with glioblastoma progression [5]. RFX5 has been shown to promote hepatocellular carcinoma (HCC) progression through transcriptional activation of KDM4A [6] and by inhibiting apoptosis [7]. In addition, RFX5 can transcriptionally activate LINC00504 in breast cancer cells, thereby promoting their growth in vitro [8]. Furthermore, miR-4319 inhibits lung cancer growth by suppressing YAP expression via regulation of LIN28-mediated stabilization of RFX5 [4]. However, the function of RFX5 in gastric adenocarcinoma remains unclear and requires further clarification. We selected RFX5 as a focus of investigation due to its established oncogenic roles in other malignancies, its overexpression in gastric adenocarcinoma tissues, and the unexplored potential of its mechanistic association with the silent information regulator transcript 1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) axis in this setting.

The SIRT1/AMPK axis plays a dual role in tumor development and progression. SIRT1 modulates several tumor-related proteins, such as p53 and NF-κB, through deacetylation, thereby influencing cellular apoptosis, inflammation, and metabolism [9,10]. Concurrently, AMPK functions as an energy sensor and can inhibit tumor growth by regulating key pathways such as mechanistic target of rapamycin (mTOR) and fatty acid biosynthesis [11,12].

This study aimed to clarify the role of RFX5 in gastric adenocarcinoma progression and to determine its regulatory interaction with the SIRT1/AMPK signaling pathway, thereby providing insights into its potential as a therapeutic target. We demonstrated that RFX5 promotes the growth and motility of gastric adenocarcinoma cells while suppressing apoptosis, effects that are mediated through the SIRT1/AMPK axis. These findings indicate that RFX5 may represent a novel oncogenic driver in gastric adenocarcinoma and offer a potential molecular target for therapeutic intervention in this disease.

2 Materials and methods

2.1 Cell Culture

The human gastric epithelial cell line GES-1 and the gastric adenocarcinoma cell lines MKN28, MGC803, and AGS were obtained from the American Type Culture Collection. All cell lines were cultured in Dulbecco’s Modified Eagle Medium supplemented with 10% fetal bovine serum and maintained at 37°C in a humidified incubator containing 5% CO2.

2.2 Reagents and antibodies

TRIzol reagent was purchased from Invitrogen (15596026). The PrimeScript RT Reagent Kit (RR047A) and SYBR Green PCR Kit (RR820A) were obtained from Takara. RIPA buffer (P0013B), BCA Protein Assay Kit (P0012S), enhanced chemiluminescence (ECL) detection kit (P0018S), CCK-8 kit (C0037), Annexin V-FITC/PI apoptosis detection kit (C1062), crystal violet staining solution (C0121), and Matrigel (BD Biosciences, 356234) for invasion assays were bought from Beyotime.

The following primary antibodies were purchased from Abcam and used at 1:1,000 dilution unless otherwise specified: RFX5 (Ab140621), SIRT1 (Ab110304), phospho-AMPK (Thr172) (Ab133448), total AMPK (Ab32047), BAX (Ab32503), BCL-2 (Ab182858), cleaved caspase-3 (Ab32042), caspase-3 (Ab32351), and GAPDH (Ab8245, 1:5,000).

2.3 Quantitative real-time PCR (qRT-PCR)

Total RNA was isolated using TRIzol reagent (Invitrogen, 15596026) following the manufacturer’s instructions. Reverse transcription was performed using the PrimeScript RT Reagent Kit (Takara, RR047A). qRT-PCR was conducted using the SYBR Green PCR Kit (Takara, RR820A). The following primers were used: RFX5: forward 5′-CCGGAAGGAGAGCCTACAGA-3′ and reverse 5′-GGAGTGTCGATGTCGTAGGG-3′; GAPDH: forward 5′-GGAGCGAGATCCCTCCAAAAT-3′ and reverse 5′-GGCTGTTGTCATACTTCTCATGG-3′

2.4 Western blot analysis

Protein samples (20–40 µg) were separated by sodium dodecyl sulfate - polyacrylamide gel electrophoresis (10–12%) and transferred onto polyvinylidene difluoride membranes (Millipore, IPVH00010). Membranes were blocked with 5% non-fat dry milk in tris-buffered saline with Tween-20 for 1 h at room temperature and incubated overnight at 4°C with primary antibodies. After washing, the membranes were incubated with appropriate HRP-conjugated secondary antibodies for 1 h at room temperature. Protein bands were visualized using the ECL detection kit (Beyotime, P0018S).

2.5 Cell growth assay

Cell viability was assessed using the CCK-8 assay (Beyotime, C0037). Cells were seeded into 96-well plates at a density of 5 × 103 cells per well. After incubation, 10 µL of CCK-8 reagent was added to each well, and absorbance at 450 nm was measured using a microplate reader.

2.6 Cell migration and invasion assays

Transwell assays were performed using 24-well Transwell chambers (Corning, 3422) with 8-μm pore size membranes. For migration assays, 5 × 104 cells were seeded into the upper chamber in serum-free medium. For invasion assays, Matrigel-coated Transwell chambers (BD Biosciences, 356234) were used. After 24 h, cells were fixed, stained with crystal violet, and counted under a phase-contrast microscope (Olympus IX73).

2.7 Flow cytometry for apoptosis analysis

Apoptosis was assessed using the Annexin V-FITC/PI Apoptosis Detection Kit (Beyotime, C1062) according to the manufacturer’s instructions. Samples were analyzed using a BD flow cytometer (338960).

2.8 Statistical analysis

Data are presented as mean ± SD. Statistical analysis was performed using GraphPad Prism 9.0 (GraphPad Software, USA). Student’s t-test was used for comparisons between two groups, and one-way ANOVA was applied for comparisons among multiple groups.

3 Results

3.1 RFX5 is highly expressed in gastric adenocarcinoma

To investigate the expression pattern of RFX5 in gastric adenocarcinoma, we first analyzed its mRNA levels using the GEPIA database. The results showed that RFX5 was significantly upregulated in gastric adenocarcinoma tissues (Figure 1a). To further validate this observation, we performed RT-qPCR analysis on clinical samples, including gastric adenocarcinoma tissues, precancerous lesions, and adjacent normal tissues. Consistent with the database findings, RFX5 mRNA levels were elevated in tumor tissues compared to both precancerous and normal tissues (Figure 1b). In addition, Western blot analysis revealed that RFX5 protein expression was increased in gastric adenocarcinoma cell lines relative to normal gastric epithelial cells (Figure 1c). These results suggest that RFX5 is overexpressed in gastric adenocarcinoma and may be involved in tumor progression.

Figure 1 
                  RFX5 is highly expressed in gastric adenocarcinoma. (a) RFX5 expression in stomach adenocarcinoma (STAD) tissues (T, n = 408) and normal tissues (N, n = 211) was analyzed using the GEPIA database. *P < 0.05. (b) Relative mRNA expression of RFX5 in tumor tissues, precancerous lesions, and adjacent normal tissues was measured by RT-qPCR. ***P < 0.001 vs tumor; $$$
                     P < 0.001 vs precancerous lesion. (c) Western blot analysis of RFX5 protein expression in normal gastric epithelial cells (GES-1) and gastric adenocarcinoma cell lines (MKN28, MGC803, AGS). The lower panel shows densitometric quantification of RFX5 normalized to GAPDH. *P < 0.05, ***P < 0.001 vs GES-1. Data are presented as mean ± SD.
Figure 1

RFX5 is highly expressed in gastric adenocarcinoma. (a) RFX5 expression in stomach adenocarcinoma (STAD) tissues (T, n = 408) and normal tissues (N, n = 211) was analyzed using the GEPIA database. *P < 0.05. (b) Relative mRNA expression of RFX5 in tumor tissues, precancerous lesions, and adjacent normal tissues was measured by RT-qPCR. ***P < 0.001 vs tumor; $$$ P < 0.001 vs precancerous lesion. (c) Western blot analysis of RFX5 protein expression in normal gastric epithelial cells (GES-1) and gastric adenocarcinoma cell lines (MKN28, MGC803, AGS). The lower panel shows densitometric quantification of RFX5 normalized to GAPDH. *P < 0.05, ***P < 0.001 vs GES-1. Data are presented as mean ± SD.

3.2 Knockdown of RFX5 inhibits the growth and migration of gastric adenocarcinoma cells

To explore the functional role of RFX5, we silenced its expression in AGS and MKN28 cells using shRNA (shRFX5). Western blot analysis confirmed effective knockdown of RFX5 protein (Figure 2a). CCK-8 assays demonstrated that RFX5 knockdown significantly reduced cell viability in both AGS and MKN28 cells (Figure 2b). Consistently, colony formation assays showed a marked decrease in the clonogenic capacity of gastric cancer cells following RFX5 knockdown (Figure 2c). To further assess the effect of RFX5 on cell motility, Transwell migration assays were performed. These results indicate that RFX5 silencing significantly reduced the migratory ability of AGS and MKN28 cells (Figure 2d).

Figure 2 
                  Knockdown of RFX5 inhibits the growth and migration of gastric adenocarcinoma cells. (a) Western blot analysis of RFX5 protein expression in AGS and MKN28 cells following transfection with RFX5-targeting shRNA (shRFX5). GAPDH was used as a loading control. Densitometric quantification of RFX5 expression relative to GAPDH is shown in the lower panel. (b) Cell viability of AGS and MKN28 cells after RFX5 knockdown was assessed using the CCK-8 assay. (c) Colony formation assay evaluating the proliferative capacity of AGS and MKN28 cells following RFX5 knockdown. Representative images are shown on the left; quantification of colony numbers is shown on the right. (d) Transwell migration (left) and invasion (right) assays of AGS and MKN28 cells following RFX5 knockdown. Representative images are shown; quantification of migrated and invaded cells is presented on the right. **P < 0.01, ***P < 0.001 vs shNC.
Figure 2

Knockdown of RFX5 inhibits the growth and migration of gastric adenocarcinoma cells. (a) Western blot analysis of RFX5 protein expression in AGS and MKN28 cells following transfection with RFX5-targeting shRNA (shRFX5). GAPDH was used as a loading control. Densitometric quantification of RFX5 expression relative to GAPDH is shown in the lower panel. (b) Cell viability of AGS and MKN28 cells after RFX5 knockdown was assessed using the CCK-8 assay. (c) Colony formation assay evaluating the proliferative capacity of AGS and MKN28 cells following RFX5 knockdown. Representative images are shown on the left; quantification of colony numbers is shown on the right. (d) Transwell migration (left) and invasion (right) assays of AGS and MKN28 cells following RFX5 knockdown. Representative images are shown; quantification of migrated and invaded cells is presented on the right. **P < 0.01, ***P < 0.001 vs shNC.

3.3 Knockdown of RFX5 promotes apoptosis in gastric adenocarcinoma cells

To determine whether RFX5 influences apoptosis, flow cytometry was performed following RFX5 knockdown. The apoptotic cell population was markedly increased in AGS and MKN28 cells after RFX5 silencing (Figure 3a). Western blot analysis of apoptosis-related proteins further supported this finding. Specifically, RFX5 knockdown led to increased expression of BAX and cleaved caspase-3, accompanied by a decrease in BCL-2 expression (Figure 3b). These results suggest that RFX5 knockdown induces apoptosis in gastric adenocarcinoma cells by modulating key regulators of the apoptotic pathway.

Figure 3 
                  Knockdown of RFX5 promotes apoptosis in gastric adenocarcinoma cells. (a) Flow cytometry analysis of apoptosis in AGS and MKN28 cells following RFX5 knockdown. Representative scatter plots display apoptotic cell distribution in the Control, shNC, and shRFX5 groups. Quantification of apoptotic rates is presented in the bar graphs on the right. (b) Western blot analysis of apoptosis-related proteins, including BAX, BCL-2, cleaved caspase-3, and total caspase-3, in AGS and MKN28 cells after RFX5 knockdown. GAPDH served as a loading control. Quantification of protein expression levels is shown as BAX/GAPDH, BCL-2/GAPDH, and cleaved caspase-3/caspase-3 ratios in the bar graphs. ***P < 0.001 vs shNC.
Figure 3

Knockdown of RFX5 promotes apoptosis in gastric adenocarcinoma cells. (a) Flow cytometry analysis of apoptosis in AGS and MKN28 cells following RFX5 knockdown. Representative scatter plots display apoptotic cell distribution in the Control, shNC, and shRFX5 groups. Quantification of apoptotic rates is presented in the bar graphs on the right. (b) Western blot analysis of apoptosis-related proteins, including BAX, BCL-2, cleaved caspase-3, and total caspase-3, in AGS and MKN28 cells after RFX5 knockdown. GAPDH served as a loading control. Quantification of protein expression levels is shown as BAX/GAPDH, BCL-2/GAPDH, and cleaved caspase-3/caspase-3 ratios in the bar graphs. ***P < 0.001 vs shNC.

3.4 Knockdown of RFX5 activates the SIRT1/AMPK axis

To investigate the molecular mechanism underlying RFX5-mediated tumor progression, we examined its effect on the SIRT1/AMPK signaling axis. Western blot analysis revealed that RFX5 knockdown resulted in increased expression of SIRT1 and elevated levels of phosphorylated AMPK (p-AMPK), while total AMPK levels remained unchanged (Figure 4a). Further analysis showed that the increase in SIRT1 expression following RFX5 depletion could be reversed by co-silencing SIRT1 (Figure 4b). Notably, SIRT1 knockdown also reversed the reduction in cell proliferation and the increase in apoptosis induced by RFX5 knockdown in AGS and MKN28 cells, as demonstrated by CCK-8, colony formation, and flow cytometry assays (Figure 4c–e). These findings suggest that RFX5 negatively regulates the SIRT1/AMPK axis, and its depletion activates this tumor-suppressive pathway in gastric adenocarcinoma cells.

Figure 4 
                  Knockdown of RFX5 activates the SIRT1/AMPK pathway. (a) Western blot analysis of p-AMPK, total AMPK, and SIRT1 protein levels in AGS and MKN28 cells following RFX5 knockdown (shRFX5). GAPDH was used as a loading control. Quantification of p-AMPK/AMPK and SIRT1/GAPDH ratios is shown in the lower panels. (b) Western blot analysis of SIRT1 expression in AGS and MKN28 cells after the indicated transfections. (c) CCK-8 assay assessing cell viability in AGS and MKN28 cells after RFX5 or SIRT1 knockdown. (d) Colony formation assay evaluating the proliferative capacity of AGS and MKN28 cells following knockdown of RFX5 or SIRT1. (e) Flow cytometry analysis of apoptosis in AGS and MKN28 cells following the indicated transfections. ***P < 0.001 vs shNC.
Figure 4

Knockdown of RFX5 activates the SIRT1/AMPK pathway. (a) Western blot analysis of p-AMPK, total AMPK, and SIRT1 protein levels in AGS and MKN28 cells following RFX5 knockdown (shRFX5). GAPDH was used as a loading control. Quantification of p-AMPK/AMPK and SIRT1/GAPDH ratios is shown in the lower panels. (b) Western blot analysis of SIRT1 expression in AGS and MKN28 cells after the indicated transfections. (c) CCK-8 assay assessing cell viability in AGS and MKN28 cells after RFX5 or SIRT1 knockdown. (d) Colony formation assay evaluating the proliferative capacity of AGS and MKN28 cells following knockdown of RFX5 or SIRT1. (e) Flow cytometry analysis of apoptosis in AGS and MKN28 cells following the indicated transfections. ***P < 0.001 vs shNC.

4 Discussion

This study demonstrated that RFX5 is highly expressed in gastric adenocarcinoma and that its knockdown significantly inhibits cell proliferation and migration while promoting apoptosis. Moreover, RFX5 depletion led to activation of the SIRT1/AMPK axis, suggesting that RFX5 contributes to tumor progression by negatively regulating this signaling pathway. Collectively, these findings indicate that RFX5 may represent a potential therapeutic target in gastric adenocarcinoma.

The oncogenic role of RFX5 has been reported in several malignancies, including HCC, glioblastoma, and breast cancer [7]. For instance, in HCC, RFX5 has been shown to promote tumor progression through transcriptional activation of KDM4A [13] and to facilitate cell growth in breast cancer cells [14]. However, prior to this study, the role of RFX5 in gastric adenocarcinoma had not been clearly defined. Our results provide new evidence that RFX5 promotes the malignant phenotype of gastric cancer cells and exerts these effects via modulation of the SIRT1/AMPK axis. This finding expands the known oncogenic functions of RFX5 and highlights its potential tissue-specific regulatory mechanisms in cancer.

The SIRT1/AMPK axis is recognized for its context-dependent role in tumor biology, functioning either as a tumor suppressor or promoter depending on the cellular environment [15,16]. SIRT1 regulates several tumor-associated proteins, including p53 and NF-κB, thereby modulating apoptosis, inflammation, and metabolic processes [17]. AMPK, as a key energy sensor, governs cell proliferation, autophagy, and metabolic stability by modulating downstream pathways such as mTOR and lipid biosynthesis [18,19]. Previous studies have indicated that activation of the SIRT1/AMPK axis can suppress tumor growth through induction of apoptosis and cell cycle arrest [20,21]. Our findings support this interpretation, as RFX5 knockdown resulted in increased SIRT1 expression and AMPK phosphorylation, indicating that RFX5 suppresses this tumor-inhibitory pathway to facilitate gastric cancer progression. These results suggest that targeting RFX5 may represent a promising therapeutic approach to reactivate SIRT1/AMPK signaling and suppress tumor growth in gastric adenocarcinoma.

Given the high invasiveness and recurrence rates associated with gastric adenocarcinoma, the identification of novel therapeutic targets remains critically important. The observed upregulation of RFX5 in gastric cancer tissues, along with its regulatory influence on the SIRT1/AMPK signaling axis, suggests that RFX5 may function not only as a diagnostic biomarker but also as a potential therapeutic target. Pharmacological inhibition of RFX5 could offer a promising treatment strategy, particularly for patients exhibiting elevated RFX5 expression. Furthermore, therapeutic approaches aimed at activating the SIRT1/AMPK pathway may be employed in combination with standard therapies to improve clinical outcomes. As RFX5 knockdown leads to SIRT1/AMPK pathway activation, which is associated with suppressed cell proliferation and enhanced apoptosis, the development of RFX5-targeted agents, including small-molecule inhibitors or RNA-based therapeutics, warrants further investigation for potential clinical application.

There are several limitations that should be acknowledged. First, most of our experiments were conducted in vitro, and further in vivo validation using appropriate animal models is necessary to confirm our findings. Second, although we demonstrated that RFX5 modulates the SIRT1/AMPK signaling axis, it remains unclear whether additional pathways contribute to its tumor-promoting effects. Further investigations are warranted to elucidate potential downstream effectors or cooperative signaling mechanisms involved in gastric cancer progression. Third, our analysis was based on a relatively small cohort of clinical samples, which may limit the generalizability of the results. Therefore, larger-scale clinical studies are needed to determine whether RFX5 expression is significantly associated with patient prognosis and disease severity.

Future research should aim to further elucidate the mechanisms through which RFX5 contributes to tumor progression in gastric adenocarcinoma. Specifically, it will be important to investigate whether RFX5 regulates additional cancer hallmarks, such as angiogenesis, metabolic reprogramming, and immune evasion [22,23]. Additionally, studies assessing the correlation between RFX5 expression and patient survival outcomes may offer valuable prognostic insights. The development of preclinical models to evaluate the therapeutic efficacy of RFX5-targeted interventions will be essential for advancing translational applications. Moreover, considering that RFX5 interacts with multiple signaling pathways, combination strategies targeting both RFX5 and the SIRT1/AMPK axis should be explored to assess potential synergistic effects in tumor suppression. Finally, in vivo validation using animal models will be necessary to confirm these findings and investigate the therapeutic potential of targeting RFX5 with SIRT1/AMPK modulators for gastric adenocarcinoma treatment.

In conclusion, this study provides the first evidence that RFX5 promotes the proliferation and migration of gastric adenocarcinoma cells while suppressing apoptosis, primarily through inhibition of the SIRT1/AMPK signaling axis. These findings offer new insights into the molecular mechanisms underlying gastric adenocarcinoma progression and highlight RFX5 as a potential therapeutic target for future clinical intervention.


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  1. Funding information: This work was supported by the Research and Development Fund of the Institute (Grant No. 2024YKJ06).

  2. Author contributions: Lili Zhu, Le Qi – designed the study and carried them out; Lili Zhu – supervised the data collection, Le Qi – analyzed the data, Lili Zhu, Le Qi – interpreted the data, Lili Zhu, Le Qi – 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 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: 2025-03-25
Revised: 2025-06-25
Accepted: 2025-08-05
Published Online: 2025-10-08

© 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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  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. Ecology and Environmental Science
  130. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  131. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  132. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  133. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  134. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  135. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  136. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  137. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  138. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  139. Agriculture
  140. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  141. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  142. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  143. Animal Science
  144. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  145. Plant Sciences
  146. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  147. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  148. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  149. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  150. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  151. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  152. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  153. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  154. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  155. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  156. Food Science
  157. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  158. Review on role of honey in disease prevention and treatment through modulation of biological activities
  159. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  160. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  161. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  162. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  163. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  164. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  165. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  166. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  167. The dilemma of food genetics and improvement
  168. Bioengineering and Biotechnology
  169. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  170. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  171. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  172. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  173. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  174. Corrigendum
  175. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  176. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
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