Cell Biochemistry and Biophysics最新文献

{"title":"Suppression of FcεRI-evoked Degranulation in RBL-2H3 Cells on Gelatin Methacryloyl Hydrogel.","authors":"Haruna Horisaka, Satoru Yokawa, Ruriko Suzuki, Rin Emoto, Rino Maeda, Tadahide Furuno","doi":"10.1007/s12013-024-01657-3","DOIUrl":"https://doi.org/10.1007/s12013-024-01657-3","url":null,"abstract":"<p><p>Cell-extracellular matrix (ECM) interactions play multiple roles in developmental, physiological, and pathological processes. ECM stiffness substantially affects cellular morphology, migration, and function. In this study, we investigated the effect of ECM comprising gelatin methacryloyl (GelMA) on the activation of rat basophilic leukemia (RBL-2H3) cells, a model mast cell line. Maintenance of intracellular Ca²⁺ concentration ([Ca²⁺]_i) elevation and subsequent degranulation, evoked by crosslinking the high-affinity IgE receptors (FcεRI), were significantly suppressed in RBL-2H3 cells on collagen-coated GelMA hydrogel than those on collagen-coated glass dishes and plastic wells. Thapsigargin and phorbol myristate acetate caused sustained [Ca²⁺]_i increase and degranulation to a similar extent in cells on both GelMA hydrogel and plastic wells/glass dishes. F-actin was clearly accumulated along the periphery of RBL-2H3 cells in plane attached to glass, but not GelMA hydrogel, suggesting that the loose actin cytoskeleton of RBL-2H3 cells on GelMA hydrogel caused suppressive degranulation through unstable FcεRI aggregation.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction Between Allopregnanolone and Amiloride Binding Sites on the GABA_A Receptor.","authors":"Julia V Bukanova, Rodion V Kondratenko, Elena I Solntseva","doi":"10.1007/s12013-024-01654-6","DOIUrl":"https://doi.org/10.1007/s12013-024-01654-6","url":null,"abstract":"<p><p>Allopregnanolone (Allo) is a positive allosteric modulator of the GABA_A receptor, and amiloride (Ami) is a competitive antagonist of the GABA_A receptor. The purpose of this work was to study the combined effect of Allo and Ami on functional activity of GABA_A receptor. The GABA-induced chloride current (I_GABA) was measured in isolated Purkinje cells of rat cerebellum using the patch-clamp technique and a system of fast application. Our results indicate that Allo suppresses the inhibitory effect of Ami on I_GABA, the IC₅₀ value of Ami concentration-response curve was increased from 164 to 547 µM (P < 0.001) in the presence of Allo. Next, GABA concentration-response curves (EC₅₀ = 5.8 µM) were constructed in the presence of Allo (EC₅₀ = 1.2 µM), Ami (EC₅₀ = 25.5 µM), and the combination of Allo+Ami (EC₅₀ = 3.2 µM). Changes in EC₅₀ values as a percentage relative to the control were calculated. The blocking effect of Ami is reduced in the presence of Allo (340% vs 150%, P < 0.01) and the potentiating effect of Allo does not change in the presence of Ami (78% vs 87%, P > 0.05). The results suggest that there is an allosteric relationship between the Allo and Ami binding sites on GABA_A receptor that operates in one direction, from Allo sites to Ami site, but not vice versa.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Elastin, F-Box and WD-40 Domain-Containing Protein 2, Fibrillin-1, and Alpha-Smooth Muscle Actin in Utilized Blood Vessels for explant culture-A New 3D in Vitro Vascular Model from Bovine Legs.","authors":"Mari Akiyama","doi":"10.1007/s12013-024-01647-5","DOIUrl":"https://doi.org/10.1007/s12013-024-01647-5","url":null,"abstract":"<p><p>Elastic fibers of the internal and external elastic laminae maintain blood vessel shapes. Impairment of smooth muscle cell function leads to vascular disease development. F-box and WD-40 domain-containing protein 2 (FBXW2) is associated with elastic fibers and osteocalcin expression for bone regeneration in the periosteum. Here, it is hypothesized that FBXW2 has different roles in periosteum and blood vessels. Furthermore, if FBXW2 would be a component of elastic fiber of blood vessels, FBXW2 would be expressed where the well-known components elastin and fibrillin-1 are expressed. For this purpose, explant culture of blood vessels from bovine legs were performed for 5 weeks. It was found that elastin and FBXW2 were expressed within the elastic laminae, whereas fibrillin-1 was expressed around them. After explant culture, elastin and FBXW2 sustained the shape of the elastic fibers in the elastic lamina, whereas the fibrillin-1-rich layer became wide range and encompass toward intima and adventitia layers. Hematoxylin Eosin staining and immunohistochemistry of alpha-smooth muscle actin (α-SMA) revealed weakened media layer after 5 weeks culture. Although fibrillin-1 is a well-known component of elastic fibers and elastin, this study revealed that the location of fibrillin-1 is different from that of elastin, whereas FBXW2 is present in the same region as elastin from day 0 to week 5. In blood vessels, fibrillin-1 fibers around the elastic lamina may be oxytalan fibers. Thus, the proposed 3D in vitro model in this study is useful for identifying the mechanisms of vascular degradation.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Activation of the CCND1 Promoter by AP-1 and SOX Transcription Factors in PC3 Prostate Cancer Cells Can Be Prevented by Anacardic Acid Analogs.","authors":"Manon Brunie, Mika A Robichaud, Mohamed Touaibia, Luc J Martin","doi":"10.1007/s12013-024-01646-6","DOIUrl":"https://doi.org/10.1007/s12013-024-01646-6","url":null,"abstract":"<p><p>Targeting more than one in nine men before age 70, prostate cancer is the most common type of cancer in men. The increased levels of cyclins, leading to activation of cyclin-dependent kinases (CDKs), play a critical role in the increased proliferation of prostate cancer cells. In this study, the regulation of the cyclin D1 (CCND1) promoter activity by activator protein-1 (AP-1) and SRY-related HMG-box (SOX) transcription factors has been characterized in PC3 prostate cancer cells. The SOX and AP-1 transcription factors can cooperate to activate the CCND1 promoter in PC3 prostate cancer cells and such cooperation can be enhanced by protein kinase A (PKA) and/or mitogen-activated protein kinase kinase 1 (ERK kinase 1, MAP2K1) signaling pathways. Moreover, anacardic acid analogs have been assessed for their potential in reducing cell viability and CCND1 promoter activity. The anacardic acid analog 8b, obtained from γ-resorcylic acid, reduces the viability and proliferation of PC3 cells by decreasing CCND1 promoter activity. The effect of analog 8b, which perfectly mimics the structure of anacardic acid, can be attributed to the inhibition of the activities of the transcription factors SOX and AP-1, which are important regulators of CCND1 promoter activity in prostate cancer cells.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Synergistic Antioxidant, Anti-microbial and Adsorbent Potential of Andrographis Paniculata Extract and Gold Nanoparticles.","authors":"Hema Chandran, Gnana Sekaran Ramakrishnan, Janaki Ramaiah Mekala, Sai Ramesh Anjaneyulu","doi":"10.1007/s12013-024-01627-9","DOIUrl":"https://doi.org/10.1007/s12013-024-01627-9","url":null,"abstract":"<p><p>The present study introduces a minimalistic and cost-effective approach to synthesising Gold nanoparticles (AuNPs) using aqueous leaf extracts of Andrographis paniculata. In this synthesis, bioactive metabolites in the leaf extract act as reducing agents, converting Au³⁺ ions to metallic Au⁰, while proteins in the extract form a stabilising layer around the nanoparticles to prevent agglomeration and maintain particle size stability. The synthesised AuNPs were systematically characterised using a range of analytical techniques. UV-visible spectroscopy verified the presence of surface plasmon resonance, Fourier-transform infrared (FTIR) spectroscopy identified key functional groups, X-ray diffraction (XRD) revealed high crystallinity, and Transmission Electron Microscopy (TEM) indicated particle sizes ranging from approximately 4-15 nm. Additionally, Energy Dispersive X-ray (EDX) analysis confirmed the elemental composition of the nanoparticles. The biological efficacy of the synthesised AuNPs was rigorously evaluated. Antioxidant activity, assessed via DPPH and ABTS assays, showed notable results, with inhibition rates of 87.35% and 75% at a sample concentration of 100 µg/mL, respectively. In vitro cytotoxicity studies on Vero cells demonstrated a significant reduction in cell viability, reaching a minimum of 18.22% at the highest tested concentration of 100 µg/mL. Antimicrobial assays indicated strong activity against Salmonella typhii and Escherichia coli, with comparatively lower efficacy against Pseudomonas aeruginosa and Bacillus cereus. Furthermore, adsorption studies showed the AuNPs' high efficiency in removing 99% of crystal violet dye (500 mg/L) within 30 min under optimised conditions (pH 4.5, temperature 33 °C, and an AuNP dosage of 200 mg/L). This comprehensive analysis indicates that the synthesised AuNPs from A. paniculata exhibit promising properties for applications in biomedicine and wastewater treatment.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apatinib Mesylate Inhibits Cell Proliferation and the Metastasis of Esophageal Squamous Cell Carcinoma Through ERK/ELK-1/Snail Pathway.","authors":"Xiang Feng, Di Xu, Zhuqin Xing, Qian Zhang","doi":"10.1007/s12013-024-01631-z","DOIUrl":"https://doi.org/10.1007/s12013-024-01631-z","url":null,"abstract":"<p><p>This study aimed to evaluate the impact of apatinib (APT) mesylate on the growth, migration ability, and underlying mechanisms in esophageal squamous cell carcinoma (ESCC) cell lines Kyse30 and Kyse150. Additionally, the anti-metastatic effects of APT mesylate were further validated in a nude mouse xenograft metastasis model. In vitro, APT mesylate treatment significantly reduced cell viability and migration ability in both cell lines in a dose- and time-dependent manner. Western blot analysis showed that APT mesylate inhibited the expression of proteins involved in the ERK/ELK-1/Snail signaling pathway, including ERK1/2, Snail, N-cadherin, and Vimentin, while upregulating E-cadherin expression. In vivo, APT mesylate administration notably decreased the number of pulmonary metastatic nodules in nude mice, with higher doses showing more pronounced effects. The 200 mg/kg high-dose group exhibited a significantly lower number of metastatic nodules compared to the cisplatin (CIS) group. The results suggest that APT mesylate inhibits ESCC cell proliferation and migration primarily by suppressing the ERK/ELK-1/Snail signaling pathway, which mediates epithelial-mesenchymal transition (EMT) and reduces metastasis and invasiveness. This study provides experimental evidence for the potential clinical application of APT mesylate in targeted therapy for ESCC, indicating its promising clinical value.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine and Cyperus rotundus extract nanoformulations protect the rats against Staphylococcus-induced mastitis via antioxidant and anti-inflammatory activities: role of MAPK signaling.","authors":"Hanan A Edres, Ingi H Elmassry, Mohamed A Lebda, Sarah I Othman, Dina R S Gad El-Karim, Hassan A Rudayni, Sawsan Kh M Ebied, Ahmed A Allam, Aml E Hashem","doi":"10.1007/s12013-024-01628-8","DOIUrl":"https://doi.org/10.1007/s12013-024-01628-8","url":null,"abstract":"<p><p>Berberine (BER) and Cyperus rotundus rhizomes extract (CRE) are phytochemicals characterized by broad-spectrum pharmacological activity that could tackle the side effects of conventional mastitis therapies, however, they undergo a modest bioavailability. In the current study, nanoformulations of BER and CRE chitosan hydrogel (BER/CH-NPs, CRE/CH-NPs) were investigated for their antibacterial, antioxidant, anti-inflammatory and anti-apoptotic effects against S. aureus-induced mastitis in a rat model. The experiment was conducted on 80 early lactating female albino rats allocated into 6 groups; control, mastitis, BER/CH-NPs (1 and 0.5 mg), CRE/CH-NPs (0.5 and 0.25 mg), BER/CH-NPs + CRE/CH-NPs (0.5 + 0.25 and 0.25 + 0.125 mg). The nanoparticles were given by oral gavage once every other day from day 2 to day 12 after parturition. On the 13^th day, intra-mammary inoculation with 100 µl of S. aureus suspension containing 2.1 × 10⁸ CFU/ml in all groups except the control group. The results expressed the effect of BER/CH-NPs and CRE/CH-NPs on mammary gland tissue including significantly diminished viable bacterial load as well as attenuated the levels of MPO, MDA, caspase-3 with elevating Nrf2 level, and modulating glutathione redox. Also, the nanoformulations resulted in attenuation of the mRNA expression of TLR2, NOD2, Keap-1 and MAPK signaling pathway additional to the immune reactivity of NF-κB P65 and p-ERK as well as the preservation of the regular alveolar architecture. The supplementation of the berberine and Cyperus rotundus extract nanoformulations could be a prospective protective approach against Staphylococcal mastitis via their antibacterial, antioxidant, antiapoptotic, anti-inflammatory and modulation of MAPK signaling pathway.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeic Acid Phenethyl Ester Enhances Bone Repair-related Factors in MC3T3-E1 Cells.","authors":"Hitomi Kuramoto, Tadashi Nakanishi, Hiromichi Yumoto, Daisuke Takegawa, Katsuhiro Mieda, Keiichi Hosaka","doi":"10.1007/s12013-024-01644-8","DOIUrl":"https://doi.org/10.1007/s12013-024-01644-8","url":null,"abstract":"<p><p>Apical periodontitis is an inflammatory disease caused by bacterial infection in the root canal that spreads to the apical periodontal tissues, resulting in bone resorption around the root apex as the disease progresses. Vascular endothelial growth factor (VEGF), a growth factor involved in angiogenesis, plays an important role in bone remodeling. We reported that caffeic acid phenethyl ester (CAPE), a bioactive substance of propolis, induces VEGF in odontoblast-like cells and dental pulp cells. However, the effects of CAPE on bone tissues remain unclear. This study was aimed to investigate the effects of CAPE on MC3T3-E1 cells, mice preosteoblast line. As a result, CAPE up-regulated the production of VEGF and induced the phosphorylation of extracellular signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK), and stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) in MC3T3-E1 cells. Furthermore, CAPE increased the expression of factors involved in osteoblast differentiation, runt-related transcription factor 2 (Runx2), Osterix, and Wnt5a/b in MC3T3-E1 cells. In this study, we show that CAPE could induce bone repair-related factors in MC3T3-E1 cells.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress Monitoring Platform: A Longitudinal In vitro Multinuclear (¹H/¹⁹F) MR Spectroscopic Study.","authors":"Pravat K Mandal, Yashika Arora, Avantika Samkaria, Joseph C Maroon, Vincenzo Fodale, Yatin Mehta, Yue-Fang Chang","doi":"10.1007/s12013-024-01640-y","DOIUrl":"https://doi.org/10.1007/s12013-024-01640-y","url":null,"abstract":"<p><p>Glutathione (GSH) is a master antioxidant that counters oxidative stress. Clinical studies have confirmed significant depletion of GSH in the hippocampus and the substantia nigra as an early diagnostic biomarker for Alzheimer's disease (AD) and Parkinson disease (PD), respectively. External agents like anesthetics (inhaled and intravenous) have a different impact on GSH. There is significant depletion of the serum GSH peroxidase level after surgery with isoflurane anesthesia that is not found in patients administered intravenous propofol. The objective of this study is to evaluate the GSH level associated with isoflurane in vitro phantom model using non-invasive magnetic resonance (MR) spectroscopy and to detect residual isoflurane in a solution. MRS data was generated utilizing a 3T MR scanner (Prisma, Siemens) equipped with a 64-channel ¹H head coil and dual tune (¹⁹F/¹H) head coil. The GSH data acquisition was performed using the MEGA-PRESS pulse sequence using experimental parameters: ON = 4.40 ppm, OFF = 5.00 ppm, TE = 120 ms, TR = 2500 ms, voxel size = 25 × 25 × 25 mm and average = 32. Isoflurane was detected using ¹⁹F MRS studies using ¹⁹F/¹H head coil. GSH data was processed using KALPANA package and ¹⁹F data was processed using Siemens package. The GSH peak area (without isoflurane) in a phosphate-buffered solution (PBS) solution (control) showed a slow decline over time due to natural oxidation of GSH to dimeric glutathione (GSSG). On the contrary, the GSH peak area in similar model is reduced significantly (p = 0.016) due to isoflurane induced oxidation of GSH to GSSG compared to control. We also report a concise general method for data generation and processing of ¹H MRS data for GSH as well as ¹⁹F monitoring platform using ¹⁹F MR spectroscopy. This is the first report wherein both ¹H and ¹⁹F spectroscopy are applied to generate MRS data along with a unique data processing method. This method is highly sensitive and specifically detects GSH without ambiguity as well as isoflurane due to the unique chemical shift patterns of CF₃ and CHF₂ moieties. This non-invasive MRS approach is developed to monitor GSH-isoflurane interaction leading to oxidative stress and this approach can be extended for other inhaled anesthetics. This methodology using non-invasive ¹⁹F MR spectroscopy needs further development for future clinical studies.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indoleamine 2, 3-dioxygenase Regulates the Differentiation of T Lymphocytes to Promote the Growth of Gastric Cancer Cells through the PI3K/Akt/mTOR Pathway.","authors":"Xiulian Xu, Huayan Yuan, Qijun Lv, Zhenjiang Wu, Wenhai Fan, Jianjun Liu","doi":"10.1007/s12013-024-01641-x","DOIUrl":"https://doi.org/10.1007/s12013-024-01641-x","url":null,"abstract":"<p><p>To investigate the regulatory mechanism of indoleamine 2, 3-dioxygenase (IDO) in T lymphocyte differentiation and its role in promoting the growth of gastric cancer (GC) cells through the PI3K/Akt/mTOR pathway. GC cell lines (MFC and NCI-N87) and PBMC cells were co-cultured and IDO inhibitor 1-methyl-tryptophan (1-MT) was added. The proliferation was detected by CCK-8, the apoptosis was detected by flow cytometry, and the contents of TNF-α, IL-1β, IL-6, IL-8, and INF-γ were detected by ELISA. The expression levels of PI3K, p-PI3K, Akt, p-Akt, mTOR, and p-mTOR were tested using Western blot, and the proportion of CD4⁺/CD8⁺, CD4⁺CD25⁺Foxp3⁺Treg cells was detected by flow cytometry. C57BL/6 mice were used to establish the MFC GC mouse model and treated with 1-MT. The changes in body weight and tumor diameter were measured. Ki-67, CD4⁺, CD8⁺, and CD25⁺ expressions were detected by immunohistochemistry. IDO promoted the proliferation of MFC and NCI-N87 cells, inhibited apoptosis, and decreased the levels of TNF-α, IL-1β, IL-6, IL-8, and INF-γ in the supernatant after co-culture with BPMC. The expressions of p-AKT, p-mTOR, and p-PI3K increased after 1-MT treatment. The proportion of CD4⁺/CD8⁺ cells was increased and the proportion of Treg cells was decreased in PBMC cells after the addition of 1-MT. Overexpression of IDO suppressed T cells differentiation by inhibiting the PI3K/Akt/mTOR pathway. In vivo, 1-MT treatment reduced the tumor size and weight, increased CD4⁺ and CD8⁺ positive area proportion, and decreased Ki-67 and CD25⁺ positive area proportion. Co-culture of GC cells and immune cells promotes the proliferation of GC cells and inhibits apoptosis, which can be reversed by 1-MT. IDO may suppress the proliferation of T lymphocyte through inhibiting the PI3K/Akt/mTOR signaling pathway. This provides new evidence for the potential of exploiting IDO inhibitors for GC treatment.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}