Home Life Sciences Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
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Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells

  • Xiaoying Zheng , Shuning Zhang and Qiaobin Chen EMAIL logo
Published/Copyright: January 27, 2025

Abstract

Functional dyspepsia (FD) is a chronic disease that occurs in the gastroduodenal region and significantly impacts human health. Maslinic acid (MA), a pentacyclic triterpene acid, is the primary bioactive ingredient in Chinese medicinal herbs such as hawthorn, which exhibits beneficial impacts on the regulation of various disease progressions. However, the specific functions and associated pathways of MA in FD progression remain unclear and require further investigation. In this work, it was demonstrated that MA enhanced the cell viability of human gastric smooth muscle cells (HGSMCs). In addition, the mitochondrial dysfunctions induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) were rescued after MA treatment. Furthermore, autophagy was increased following CCCP treatment, but this phenomenon was counteracted after MA treatment. The oxidative stress, elevated after CCCP treatment, was alleviated following MA addition. Finally, the AMPK/SIRT1 pathway was suppressed after CCCP stimulation but was re-activated after MA treatment. In conclusion, it was uncovered that MA accelerated HGSMC viability and improved mitochondrial function, inhibited autophagy, alleviated oxidative stress, and stimulated the AMPK/SIRT1 pathway. This discovery may offer new insight into the therapeutic effects of MA in FD progression.

Graphical abstract

1 Introduction

Four types of diseases such as functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain (FAP), and abdominal migraine (AM) have been confirmed to be associated with adolescents’ functional gastrointestinal diseases [1,2]. FD refers to a chronic disease that occurs in the gastroduodenal region, which can cause early satiety during normal meals, postprandial satiety without any organic disease, and pain or a burning sensation in the upper abdomen [3,4]. Currently, no effective treatment has been identified for FD because of the complex etiology and pathophysiology of FD. As a result, the search for novel drugs remains a promising approach for the treatment of FD.

Maslinic acid (MA) is a pentacyclic triterpene acid and the primary bioactive component extracted from Chinese medicinal herbs (such as hawthorn, olive, and jujube) [5,6]. MA possesses antibacterial, antiviral, antioxidant, and anticancer activities and has attracted significant attention from the medical community. For instance, MA can inhibit cell apoptosis and necrosis, preserve the glomerulus, and thus exhibit a therapeutic effect on cisplatin-triggered nephrotoxicity in rats [7]. Additionally, MA attenuates inflammatory response, maintains the blood–milk barrier, and modulates intestinal flora, thereby relieving LPS-stimulated mastitis [8]. Furthermore, MA accelerates mitochondrial apoptosis and reduces HIF-1α expression in lung cancer [9]. Importantly, MA demonstrates gastroprotective activity through various mechanisms, which is beneficial for the mucus barrier [10]. Besides, an MA-enriched diet can affect transcriptomic and metabolomic reprogramming in Apc (Min/+) mice to alleviate intestinal tumorigenesis [11]. However, the detailed functions and associated pathways of MA in FD progression remain unclear.

In this work, it is purposed to explore the impacts of MA on mitochondrial function, autophagy, and oxidative stress. Our findings first revealed that MA enhanced human gastric smooth muscle cell (HGSMC) viability and improved mitochondrial function, inhibited autophagy, alleviated oxidative stress, and stimulated the AMPK/SIRT1 pathway. This study suggests that MA might be a promising drug for ameliorating FD progression.

2 Materials and methods

2.1 Cell lines, culture, and treatment

The HGSMCs were purchased from Shanghai Yaji Biotechnology Company (Shanghai, China). HGSMCs were incubated with the primary smooth muscle cell culture system (Icell, PriMed-iCell-004) containing 5% fetal bovine serum (FBS, Gibco Laboratories, USA) and penicillin/streptomycin antibiotic solution. HGSMCs were incubated at 37°C with 5% CO2 in Dulbecco’s modified Eagle’s medium (Gibco, New York, NY, USA) supplemented with 10% FBS. The culture media were changed every 48 h. HGSMCs from passages 4 to 6 were used in subsequent experiments.

Carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 10 μM, Absin, Shanghai, China) was used for treating HGSMCs for 4 h to mimic the FD cell model [12]. MA (Shanghai Huicheng Biotechnology Company, Shanghai, China) with different concentrations (0, 10, 20, 40, 80, and 160 μM) was utilized for treating HGSMCs for 24 h [13].

Groups were divided into control (no treatment), CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group.

2.2 CCK-8 assay

The HGSMCs (1,000 cells/well) were seeded into the 96-well plate for 24 h. In each well, CCK-8 solution (10 μL, Dojindo Laboratories, Kumamoto, Japan) was added and incubated for 2 h. Finally, using the spectrophotometer (Thermo Fisher Scientific, MA, USA), cell viability was measured.

2.3 Detection of adenosine triphosphate (ATP)

The ATP level was determined by the ATP commercial kit (No. A095, Jiancheng Bioengineering Institute, Nanjing, China). Briefly, HGSMCs were re-suspended in ddH2O (500 μL). After homogenization, the mixture was centrifuged to collect the supernatant. The optical density value (636 nm) was confirmed by a spectrophotometer (Thermo Fisher Scientific, MA, USA).

2.4 JC-1 staining

Mitochondrial membrane potential (MMP) level was evaluated through JC-1 staining. The HGSMCs in different groups were treated with JC-1 solution (0.5 mL, Yeasen, Shanghai, China) for 15 min. Next, HGSMCs were centrifuged and then resuspended in a buffer solution. After washing, images were captured using a fluorescent microscope (Olympus, Tokyo, Japan).

2.5 Western blot

Proteins (extracted from HGSMCs) were separated under sodium dodecyl sulfate-polyacrylamide gel electrophoresis (10%). Next, proteins were transferred to polyvinylidene difluoride (PVDF, Beyotime, Shanghai, China) membranes. After blocking, the membranes were incubated with primary antibodies for 12 h and followed by secondary antibodies (1:2,000; ab7090; goat anti-rabbit IgG H&L [HRP]) for 2 h. Finally, using the chemiluminescence detection kit (Thermo Fisher Scientific, Inc.), the protein expressions were measured.

The primary antibodies used were as follows: LC3B (autophagy marker, 1:2,000; ab192890; Rabbit; Abcam, Shanghai, China), P62 (1:10,000; ab109012; Rabbit), p-SIRT1 (1:1,000; ab76039; Rabbit), SIRT1 (0.5 µg/mL; ab110304; Mouse), p-AMPK (1:1,000; ab92701; Rabbit), AMPK (1:1,000; ab32047; Rabbit), and GAPDH (1:500; ab8245; Mouse).

2.6 Immunofluorescence (IF) assay (for autophagy evaluation)

The LC3B fluorescence intensity was measured for autophagy evaluation. HGSMCs were seeded in the 24-well plates for 24 h. Next, cells were fixed with 4% paraformaldehyde for 20 min and permeabilized with 0.25% Triton X-100 for 10 min. After blocking, the coverslips were incubated with a primary antibody against LC3B (1 µg/mL; ab192890; Rabbit; Abcam, Shanghai, China), then followed by the fluorescent secondary antibody. For nuclear staining, 4′,6-diamidino-2-phenylindole dihydrochloride was used. Images were captured under one fluorescent microscope (Olympus, Tokyo, Japan).

2.7 Detection of ROS

The reactive oxygen species (ROS, E004-1-1, Nanjing Jiancheng Technology Co., Ltd., Nanjing, China) was used to evaluate the ROS fluorescence intensity. HGSMCs were incubated with dichloro-dihydro-fluorescein diacetate for 20 min. After washing with phosphate-buffered saline, the ROS fluorescence intensity was evaluated under the fluorescence microscope (Olympus, Tokyo, Japan).

2.8 Detection of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) (oxidative stress)

MDA (ab118970, Abcam, Shanghai, China), SOD (ab65354), and GSH-Px (ab65322) commercial kits were adopted to evaluate the levels of MDA, GSH, and SOD in the supernatant.

2.9 Statistical analysis

All results were expressed as mean ± standard deviation (SD) with three times repetitions. Statistical analysis was performed using GraphPad Prism Software 9 (GraphPad Software, USA). The comparisons between the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM groups were conducted using the one-way ANOVA with Tukey’s post hoc test. The p-value of <0.05 was considered statistically significant.

3 Results

3.1 MA accelerated cell viability of HGSMCs

The chemical structure of MA is displayed in Figure 1a. Next, it was demonstrated that cell viability was gradually increased after MA treatment (20, 40, 80, and 160 μM), and 20, 40, and 80 μM MA treatments were chosen for further experiments (Figure 1b). In summary, MA accelerated the cell viability of HGSMCs.

Figure 1 
                  MA accelerated cell viability of HGSMCs. (a) The chemical structure of MA. (b) The cell viability of MA treatment (0, 10, 20, 40, 80, and 160 μM) was confirmed through the CCK-8 assay. ***p < 0.001 vs MA (0 μM).
Figure 1

MA accelerated cell viability of HGSMCs. (a) The chemical structure of MA. (b) The cell viability of MA treatment (0, 10, 20, 40, 80, and 160 μM) was confirmed through the CCK-8 assay. ***p < 0.001 vs MA (0 μM).

3.2 MA ameliorated mitochondrial function in HGSMCs

The ATP level was decreased after CCCP induction, but this reduction was mitigated after MA treatment (20, 40, and 80 μM) (Figure 2a). Additionally, the MMP levels decreased after CCCP addition, but this effect was reversed after MA treatment (Figure 2b). Taken together, MA ameliorated mitochondrial function in HGSMCs.

Figure 2 
                  MA ameliorated mitochondrial function in HGSMCs. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. (a) The ATP level was confirmed through the ATP commercial kit. (b) The MMP level was evaluated through JC-1 staining. ***p < 0.001 vs the control group; ^p < 0.05, ^^^p < 0.001 vs the CCCP group.
Figure 2

MA ameliorated mitochondrial function in HGSMCs. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. (a) The ATP level was confirmed through the ATP commercial kit. (b) The MMP level was evaluated through JC-1 staining. ***p < 0.001 vs the control group; ^p < 0.05, ^^^p < 0.001 vs the CCCP group.

3.3 MA restrained autophagy in HGSMCs

The protein expression of LC3II/LC3I was increased and that of P62 was attenuated after CCCP stimulation, but these impacts were counteracted after MA addition (Figure 3a). Moreover, the LC3B fluorescence intensity was heightened after CCCP induction, but this increase was neutralized after MA treatment (Figure 3a and b). Overall, MA restrained autophagy in HGSMCs.

Figure 3 
                  MA restrained autophagy in HGSMCs. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. (a) The protein expressions of LC3-I, LC3-II, and P62 were tested through western blot. (b) The LC3B fluorescence intensity was verified through the IF assay. ***p < 0.001 vs the control group; ^^p < 0.01, ^^^p < 0.001 vs the CCCP group.
Figure 3

MA restrained autophagy in HGSMCs. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. (a) The protein expressions of LC3-I, LC3-II, and P62 were tested through western blot. (b) The LC3B fluorescence intensity was verified through the IF assay. ***p < 0.001 vs the control group; ^^p < 0.01, ^^^p < 0.001 vs the CCCP group.

3.4 MA alleviated oxidative stress in HGSMCs

The ROS fluorescence intensity increased after CCCP treatment, but this effect was reduced after MA addition (Figure 4a). Besides, the levels of malondialdehyde increased, while SOD and GSH-Px levels decreased after CCCP addition, but these effects were rescued after MA treatment (Figure 4b). In summary, MA alleviated oxidative stress in HGSMCs.

Figure 4 
                  MA alleviated oxidative stress in HGSMCs. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. (a) The ROS fluorescence intensity was measured through the ROS commercial kit. (b) The levels of MDA, SOD, and GSH-Px were examined through the commercial kits. ***p < 0.001 vs the control group; ^p < 0.05, ^^p < 0.01, ^^^p < 0.001 vs the CCCP group.
Figure 4

MA alleviated oxidative stress in HGSMCs. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. (a) The ROS fluorescence intensity was measured through the ROS commercial kit. (b) The levels of MDA, SOD, and GSH-Px were examined through the commercial kits. ***p < 0.001 vs the control group; ^p < 0.05, ^^p < 0.01, ^^^p < 0.001 vs the CCCP group.

3.5 MA triggered the AMPK/SIRT1 pathway

The protein expressions of p-SIRT1/SIRT1 and p-AMPK/AMPK decreased after CCCP stimulation, but these changes were offset after MA addition (Figure 5), indicating that MA activated the AMPK/SIRT1 pathway.

Figure 5 
                  MA triggered the AMPK/SIRT1 pathway. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. The protein expressions of p-SIRT1, SIRT1, p-AMPK, and AMPK were determined through western blot. ***p < 0.001 vs the control group; ^^p < 0.01, ^^^p < 0.001 vs the CCCP group.
Figure 5

MA triggered the AMPK/SIRT1 pathway. Groups were separated into the control, CCCP, CCCP+MA 20 μM, CCCP+MA 40 μM, and CCCP+MA 80 μM group. The protein expressions of p-SIRT1, SIRT1, p-AMPK, and AMPK were determined through western blot. ***p < 0.001 vs the control group; ^^p < 0.01, ^^^p < 0.001 vs the CCCP group.

4 Discussion

Abundant extracts from Chinese herbs have focused curing FD. For example, magnoloside A can influence brain-gut peptides and gut microbiota to alleviate FD symptoms [14]. In addition, paeoniflorin triggers the release of acetylcholine to ameliorate abnormalities in FD rats [15]. Moreover, hesperidin modulates mitophagy to facilitate gastric motility in FD rats [16]. MA is one pentacyclic triterpene acid and exhibits beneficial effects on the progression of various diseases [711]. Nevertheless, the detailed functions and associated pathways of MA in FD progression remain unclear. Similarly, this study demonstrated that MA can accelerate the cell viability of HGSMCs.

Mitochondria are organelles that are highly dynamic, and they can produce ATP and participate in the modulation of oxidative stress and cell apoptosis [17]. Moreover, autophagy plays a pivotal role in maintaining mitochondrial homeostasis [18]. Therefore, maintenance of normal autophagy-mediated mitochondrial functions and oxidative stress is vital for cellular functions [19]. Many researchers have investigated autophagy, mitochondrial functions and oxidative stress in FD progression. For instance, quercetin modulates the PI3K/AKT pathway in FD to improve mitochondrial function and reduce inflammation, thereby relieving H2O2-triggered oxidative stress damage [20]. Moreover, Chaihu Shugan San affects mitophagy to enhance gastric motility in FD rats [21]. ZhiShiXiaoPi tang retards the mTOR pathway to restrain autophagy-evoked corticosterone to improve FD [22]. In addition, Shen-Ling-Bai-Zhu-San can stimulate the energy metabolism pathways and weaken oxidative stress in FD [23]. Similar to these previous studies, in this project, it was discovered that the strengthened mitochondrial functions stimulated by CCCP induction were restored after MA treatment. Furthermore, autophagy was exacerbated after CCCP addition, but this phenomenon was reversed after MA treatment. The oxidative stress was increased after CCCP treatment, but this effect was alleviated after MA addition.

The AMPK/SIRT1 pathway is a key pathway that is closely associated with autophagy and oxidative stress and has been reported in multiple diseases. For example, pterostilbene influences the AMPK/SIRT1 pathway to restrain oxidative stress and airway inflammation to ameliorate asthma [24]. Additionally, in diabetic kidney disease, metformin affects the AMPK/SIRT1 pathway to relieve oxidative stress and enhance autophagy [25]. Moreover, in dry eye disease, salidroside modulates the AMPK/SIRT1 pathway to stimulate autophagy and mitigate oxidative stress [26]. Importantly, it has been discovered that MA can trigger the AMPK/SIRT1 pathway to improve diabetic nephropathy [27]. However, the regulatory effects of MA on the AMPK/SIRT1 pathway in FD progression remain unclear. In this work, the AMPK/SIRT1 pathway was retarded after CCCP stimulation, but this change was offset after MA addition.

In conclusion, it was uncovered that MA accelerated HGSMCs viability and improved mitochondrial function, inhibited autophagy, alleviated oxidative stress, and stimulated the AMPK/SIRT1 pathway. However, this work also has some limitations, such as a shortage of clinical investigations, human samples, animal experiments, and deep experiments on other phenotypic indicators (autophagy, oxidative stress, mitochondrial function). Therefore, in the future, more experiments will be made.


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  1. Funding information: Authors state no funding involved.

  2. Author contributions: Xiaoying Zheng designed the study, completed the experiment, and supervised the data collection; Shuning Zhang analyzed the data and interpreted the data; and Qiaobin Chen 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: 2024-08-07
Revised: 2024-11-28
Accepted: 2024-12-10
Published Online: 2025-01-27

© 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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  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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