International Journal of Molecular Sciences最新文献

{"title":"Prometastatic Potential of Non-Functionalized Multiwalled Carbon Nanotubes in the MDA-MB-436 Breast Cancer Cell Line Model.","authors":"Magdalena Matysiak-Kucharek, Krzysztof Sawicki, Marcin Kruszewski, Jacek Kurzepa, Lucyna Kapka-Skrzypczak","doi":"10.3390/ijms26062777","DOIUrl":"10.3390/ijms26062777","url":null,"abstract":"<p><p>Multiwalled carbon nanotubes (MWCNTs) are used in many areas of industry and medicine. However, there is evidence suggesting profibrogenic action of MWCNTs, probably via the epithelial-mesenchymal transition mechanism (EMT). The aim of this study was to evaluate the prometastatic activity of 5-20 nm and 50-80 nm MWCNTs against cells of the MDA-MB-436 line. We used MTT and NR assays to determine MWCNTs' cytotoxicity and the level of malonylodialdehyde and thiol compounds as indicators of oxidative stress. qRT-PCR was used to examine the expression of EMT markers. The QCM Chemotaxis Cell Migration Assay was used to assess cell migration, while the Cytokine Array Kit and Apoptosis Array Kit were used to determine cytokine expression and induction of apoptosis. The interleukin 6, C-X-C motif chemokine ligand 8, and tumor growth factor beta 1 (TGFB1) secretion was determined by ELISA. MWCNTs were toxic to MDA-MB-436 cells and induced cell death via the apoptosis pathway. MWCNTs induced a low level of oxidative stress and were associated with increased secretion of pro-inflammatory cytokines and chemokines, including proteins important in breast cancer metastasis. Cells incubated with MWCNTs showed increased expression of mesenchymal EMT markers. However, in contrast to these results, the migration of MWCNT-treated cells increased only modestly relative to untreated cells. Also, the secretion of TGFB1, a key inducer and regulator of EMT, increased only slightly. In summary, the multifaceted effect of MWCNTs on cancer cells encourages further work on the safety of nanomaterials.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Myeloid Cells in Mild Cases of COVID-19 Upregulate the Intracellular Fc Receptor <i>TRIM21</i> and Transcribe Proteasome-Associated Molecules.","authors":"Andrea Henriques-Pons, Maria Clicia S Castro, Vanessa S Silva, Maiana O C Costa, Helena S I L Silva, Maria Emilia M T Walter, Anna Cristina C Carvalho, Alba C M A Melo, Kary Ocaña, Marcelo T Dos Santos, Marisa F Nicolas, Fabrício A B Silva","doi":"10.3390/ijms26062769","DOIUrl":"10.3390/ijms26062769","url":null,"abstract":"<p><p>Much remains to be understood about COVID-19, but the protective role of antibodies (Igs) is widely accepted in SARS-CoV-2 infection. Igs' functions are mainly carried out by receptors that bind to their Fc portion (FcR), and less attention has been dedicated to the cytoplasmic members of this family. In this work, we used single-cell RNA sequencing (scRNA-seq) data to discern cell populations in bronchoalveolar lavage fluid obtained from healthy individuals and patients with mild or severe COVID-19. Then, we evaluated the transcription of neonatal FcR (FcRn, <i>FCGRT</i> gene) and tripartite motif-containing protein 21 (<i>TRIM21</i>) and its downstream signaling components. The TRIM21 pathway is vital for virus infections as it has a dual function, leading opsonized viruses to degradation by proteasomes and the activation of innate inflammatory anti-virus response. The transcriptional level of <i>FCGRT</i> showed no statistical differences in any cell population comparing the three groups of patients. On the other hand, <i>TRIM21</i> transcription was significantly higher in myeloid cells collected from patients with mild COVID-19. When comparing mild with severe cases, there was no statistical difference in <i>TRIM21</i> transcription in lung adaptive lymphoid cells and innate lymphoid cells (ILC). Yet, we analyzed the transcription of all downstream signaling molecules in myeloid and, as most cells expressed the receptor, in adaptive lymphoid cells. Moreover, ILCs from mild cases and all cell populations from severe cases were missing most downstream components of the pathway. We observed that members of the ubiquitin-proteasome system (UPS) and other components associated with TRIM21 proteasomal degradation were transcribed in mild cases. Despite the transcription of the danger sensors <i>DDX58</i> and <i>IFIH1</i>, the transcriptional level of inflammatory <i>IL1B</i> and <i>IL18</i> was generally very low, along with the <i>NLRP3</i> danger sensor, members of the NF-κB pathway, and <i>TNF</i>. Therefore, our data suggest that TRIM21 may contribute to SARS-CoV-2 protection by reducing the viral load, while the inflammatory branch of the pathway would be silenced, leading to no pathogenic cytokine production.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the Human Leukocyte Antigen Complex on Idiopathic Pulmonary Fibrosis Development and Progression in the Sardinian Population.","authors":"Marina Serra, Stefano Mocci, Silvia Deidda, Maurizio Melis, Luchino Chessa, Sara Lai, Erika Giuressi, Caterina Mereu, Celeste Sanna, Michela Lorrai, Michela Murgia, Federica Cannas, Alessia Mascia, Andrea Perra, Roberto Littera, Sabrina Giglio","doi":"10.3390/ijms26062760","DOIUrl":"10.3390/ijms26062760","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by the disruption of the alveolar and interstitial architecture due to extracellular matrix deposition. Emerging evidence suggests that genetic susceptibility plays a crucial role in IPF development. This study explores the role of human leukocyte antigen (<i>HLA</i>) alleles and haplotypes in IPF susceptibility and progression within the genetically distinct Sardinian population. Genotypic data were analyzed for associations with disease onset and progression, focusing on allele and haplotype frequencies in patients exhibiting slow (S) or rapid (R) progression. While no significant differences in <i>HLA</i> allele frequencies were observed between IPF patients and controls, the <i>HLA-DRB1*04:05</i> allele and the extended haplotype (<i>HLA-A*30:02</i>, <i>B*18:01</i>, <i>C*05:01</i>, <i>DQA1*05:01</i>, <i>DQB1*02:01</i>, <i>DRB1*03:01</i>) were associated with a slower disease progression and improved survival (log-rank = 0.032 and 0.01, respectively). At 36 months, carriers of these variants demonstrated significantly better pulmonary function, measured with single-breath carbon monoxide diffusing capacity (DLCO%p) (<i>p</i> = 0.005 and 0.02, respectively). Multivariate analysis confirmed these findings as being independent of confounding factors. These results highlight the impact of <i>HLA</i> alleles and haplotypes on IPF outcomes and underscore the potential of the Sardinian genetic landscape to illuminate immunological mechanisms, paving the way for predictive biomarkers and personalized therapies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation in Penile Squamous Cell Carcinoma: A Comprehensive Review.","authors":"Mateusz Czajkowski, Piotr M Wierzbicki, Maciej Dolny, Marcin Matuszewski, Oliver W Hakenberg","doi":"10.3390/ijms26062785","DOIUrl":"10.3390/ijms26062785","url":null,"abstract":"<p><p>Inflammation appears to play a crucial role in the development and progression of penile cancer (PeCa). Two molecular pathways of PeCa are currently described: HPV-dependent and HPV-independent. The tumor immune microenvironment (TIME) of PeCa is characterized by the presence of tumor-associated macrophages, cancer-associated fibroblasts, and tumor-infiltrating lymphocytes. The components of the TIME produce pro-inflammatory cytokines and chemokines, which have been found to be overexpressed in PeCa tissues and are associated with tumor progression and unfavorable prognoses. Additionally, the nuclear factor kappa B (NF-κB) pathway and secreted phosphoprotein 1 (SPP1) have been implicated in PeCa pathogenesis. Elevated C-reactive protein (CRP) levels and the neutrophil-to-lymphocyte ratio (NLR) have been identified as potential prognostic biomarkers in PeCa. This overview presents the complex contribution of the inflammatory process and collates projects aimed at modulating TIME in PeCa.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAR₂ Serves an Indispensable Role in Controlling PAR₄ Oncogenicity: The β-Catenin-p53 Axis.","authors":"Priyanga Appasamy, Jeetendra Kumar Nag, Hodaya Malka, Rachel Bar-Shavit","doi":"10.3390/ijms26062780","DOIUrl":"10.3390/ijms26062780","url":null,"abstract":"<p><p>Although the role of G-protein-coupled receptors (GPCRs) in cancer is acknowledged, GPCR-based cancer therapy is rare. Mammalian protease-activated receptors (PARs), a sub-group of GPCRs, comprise four family members, termed PAR_1-4. Here, we demonstrate that PAR₂ is dominant over PAR₄ oncogene in cancer. We performed a knockdown of <i>Par2</i>/<i>f2rl1</i> and expressed C-terminally truncated PAR₂ (TrPAR₂), incapable of inducing signaling, to assess the impact of PAR₂ on PAR₄ oncogenic function by β-catenin stabilization assessment, immunoprecipitation, and xenograft tumor generation in <i>Nude</i>/<i>Nude</i> mice. PAR₂ and PAR₄ act together to promote tumor generation. Knockdown <i>Par2</i> and TrPAR₂ inhibited the PAR₂ and PAR₄-induced β-catenin levels, nuclear dishevelled 1(DVL1), and TOP<i>flash</i> reporter activity. Likewise, PAR₂ and PAR₄-induced invasion and migration were inhibited when <i>Par2</i> was knocked down or in the presence of TrPAR₂. PAR cyclic (4-4) [P<i>c</i>(4-4)], a PAR-based compound directed toward the PAR pleckstrin homology (PH)-binding site, effectively inhibited PAR₂ oncogenic activity. P<i>c</i>(4-4) inhibition is mediated via the increase in p53 level and the up-regulation of p21 as caspase-3 as well. Overall, we showed that in the absence of PAR₂ signaling, the PAR₄ pro-tumor functions are significantly inhibited. P<i>c</i>(4-4) inhibits PAR₂ acting via the modification of <i>wt</i> p53, thus offering a powerful drug measure for fighting cancer.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interaction Between the <i>asb5a</i> and <i>asb5b</i> Subtypes Jointly Regulates the L-R Asymmetrical Development of the Heart in <i>Zebrafish</i>.","authors":"Wanbang Zhou, Wanwan Cai, Yongqing Li, Luoqing Gao, Xin Liu, Siyuan Liu, Junrong Lei, Jisheng Zhang, Yuequn Wang, Zhigang Jiang, Xiushan Wu, Xiongwei Fan, Fang Li, Lan Zheng, Wuzhou Yuan","doi":"10.3390/ijms26062765","DOIUrl":"10.3390/ijms26062765","url":null,"abstract":"<p><p>The <i>asb5</i> gene, a member of the Asb protein subfamily characterized by six ankyrin repeat domains, is highly conserved and comprises two subtypes, <i>asb5a</i> and <i>asb5b</i>, in <i>zebrafish</i>. Our previous research has demonstrated that a deficiency of the <i>asb5</i> gene significantly impairs early cardiac contractile function, highlighting its close relationship with heart development. <i>Zebrafish asb5</i> expression was disrupted by both morpholino (MO) antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. A high-throughput RNA-Seq analysis was used to analyze the possible molecular regulatory mechanism of <i>asb5</i> gene deletion leading to left-right (L-R) asymmetry defects in the heart. Whole-mount in situ hybridization (WISH) was conducted to evaluate gene expression patterns of Nodal signaling components and the positions of heart organs. Heart looping was defective in <i>zebrafish asb5</i> morphants. Rescue experiments in the <i>asb5</i>-deficiency group (inactivating both <i>asb5a</i> and <i>asb5b</i>) demonstrated that the injection of either <i>asb5a</i>-mRNA or <i>asb5b</i>-mRNA alone was insufficient to rectify the abnormal L-R asymmetry of the heart. In contrast, the simultaneous injection of both <i>asb5a</i>-mRNA and <i>asb5b</i>-mRNA successfully rescued the morphological phenotype. A high-throughput RNA-Seq analysis of embryos at 48 h post fertilization (hpf) revealed that numerous genes associated with L-R asymmetry exhibited expression imbalances in the <i>asb5</i>-deficiency group. WISH further confirmed that the expression of genes such as <i>fli1a</i>, <i>acta1b</i>, <i>hand2</i>, <i>has2</i>, <i>prrx1a</i>, <i>notch1b</i>, and <i>foxa3</i> were upregulated, while the expression of <i>mei2a</i> and <i>tal1</i> was downregulated. These results indicated that loss of the <i>asb5</i> gene in <i>zebrafish</i> led to the disordered development of L-R asymmetry in the heart, resulting in an imbalance in the expression of genes associated with the regulation of L-R asymmetry. Subsequently, we examined the expression patterns of classical Nodal signaling pathway-related genes using WISH. The results showed that the midline barrier factor gene <i>lefty1</i> was downregulated at early stages in the <i>asb5</i>-deficiency group, and the expression of <i>spaw</i> and <i>lefty2</i>, which are specific to the left lateral plate mesoderm (LPM), was disrupted. This study reveals that the two subtypes of the <i>asb5</i> gene in <i>zebrafish</i>, <i>asb5a</i> and <i>asb5b</i>, interact and jointly regulate the establishment of early cardiac L-R asymmetry through the Nodal-<i>spaw</i>-<i>lefty</i> signaling pathway.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Multifaceted Impact of Karrikin Signaling in Plants.","authors":"Qilin Deng, Hongyang Wang, Yanhong Qiu, Dexin Wang, Yang Xia, Yumeng Zhang, Manying Pei, Yinling Zhao, Xiulan Xu, Haijun Zhang","doi":"10.3390/ijms26062775","DOIUrl":"10.3390/ijms26062775","url":null,"abstract":"<p><p>Karrikins (KARs), produced during wildfires, are bioactive compounds that stimulate seed germination in fire-prone ecosystems and influence broader plant-environment interactions. These compounds act through the α/β hydrolase receptor KARRIKIN INSENSITIVE2 (KAI2), which perceives KARs as analogs of the hypothesized phytohormone KAI2 ligand (KL). KAR signaling shares molecular parallels with strigolactones (SLs), another class of butenolide plant hormones, and regulates diverse processes such as seedling development, root architecture, photomorphogenesis, and stress responses. Despite its multifaceted roles, the mechanistic basis of KAR-mediated regulation remains poorly understood. This review synthesizes insights into KAR signaling mechanisms, emphasizing recent advances in signal transduction pathways and functional studies. It also addresses key unresolved questions, including the identity of endogenous KL and the crosstalk between KARs and other hormonal networks. By elucidating these mechanisms, KAR-based strategies hold promises for enhancing crop resilience and sustainability, offering novel avenues for agricultural innovation in changing environments.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seco-Duocarmycin SA in Aggressive Glioblastoma Cell Lines.","authors":"Ann Morcos, Yeonkyu Jung, Ryan N Fuller, Antonella Bertucci, Amy Nguyen, Quanqing Zhang, Tobias Emge, Kristopher E Boyle, Nathan R Wall, Marcelo Vazquez","doi":"10.3390/ijms26062766","DOIUrl":"10.3390/ijms26062766","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is among the most lethal primary brain tumors and is characterized by significant cellular heterogeneity and resistance to conventional therapies. This study investigates the efficacy of seco-duocarmycin SA (seco-DSA), a novel DNA alkylating agent. Initial investigations using a colony formation assay revealed that seco-DSA exhibits remarkable potential with IC₅₀ values lower than its natural DSA counterpart. Cell viability assay indicated that LN18 cells showed a markedly greater sensitivity to DSA than T98G cells. Furthermore, seco-DSA achieved its full cytotoxic effect within 8 h of drug incubation in GBM cell lines. Although seco-DSA induced a concentration-dependent increase in apoptotic cell death, the extent of apoptosis did not fully account for the observed decrease in cell viability. Instead, seco-DSA treatment resulted in significant cell cycle arrest in S and G2/M phases. These findings suggest that seco-DSA's cytotoxicity in GBM cells is primarily due to its ability to disrupt cell cycle progression, though the precise mechanisms of action remain to be fully established, and further research is needed. Proteomic analysis of treated cells also indicates dysregulation of proteins involved in senescence, apoptosis, and DNA repair, alluding to seco-DSA-induced arrest as a major mechanism of GBM disruption. Data are available via ProteomeXchange with the dataset identifier \"PXD061023\". Our reports promote the future exploration of seco-DSA's therapeutic potential, representing a critical step toward developing a more targeted and effective treatment for GBM.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Hydroxycoumarin Exhibits Antinociceptive and Anti-Inflammatory Effects Through Cytokine Modulation: An Integrated In Silico and In Vivo Study.","authors":"Diogo Vilar da Fonsêca, Juliana Sousa Rocha, Pablo R da Silva, Hugo Natan de Sá Novaes Pereira, Lucas Vinicius Novaes Dos Santos, Melquisedec Abiaré Dantas de Santana, Alan F Alves, Adiel H O Pontes, Joás de Souza Gomes, Cícero F Bezerra Felipe, Damião Pergentino de Sousa, Marcus T Scotti, Luciana Scotti","doi":"10.3390/ijms26062788","DOIUrl":"10.3390/ijms26062788","url":null,"abstract":"<p><p>Chronic pain significantly impacts quality of life and is often accompanied by inflammation, a natural bodily response that can become harmful when excessive. The orofacial region is commonly affected, making effective treatment crucial. However, current drugs often cause undesirable side effects, highlighting the need for new pharmacological alternatives. 4-hydroxycoumarin (4-HC), a natural compound, has shown promising antinociceptive and anti-inflammatory effects, but studies confirming its specific properties are limited. In silico analyses suggest that 4-HC exhibits favorable pharmacokinetic characteristics, not interacting with P-glycoprotein and successfully crossing the blood-brain barrier. Molecular docking studies indicate that its effects may be mediated through NMDA_R or by inhibiting iNOS. Our study assessed the antinociceptive and anti-inflammatory effects of 4-HC in animal models at doses of 25, 50, and 75 mg/kg. 4-HC significantly reduced abdominal contortions induced by acetic acid and decreased nociceptive rubbing in orofacial pain models induced by formalin, glutamate, and capsaicin. Interactions with opioid receptors were not observed, suggesting that 4-HC's antinociceptive effect does not involve this pathway. Additionally, 4-HC reduced paw edema induced by carrageenan and significantly decreased leukocyte migration and TNF-α levels. These findings highlight the therapeutic potential of 4-HC and warrant further investigation into its mechanisms.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse Subsets of γδT Cells and Their Specific Functions Across Liver Diseases.","authors":"Chenjie Zhan, Chunxiu Peng, Huaxiu Wei, Ke Wei, Yangzhi Ou, Zhiyong Zhang","doi":"10.3390/ijms26062778","DOIUrl":"10.3390/ijms26062778","url":null,"abstract":"<p><p>γδT cells, a distinct group of T lymphocytes, serve as a link between innate and adaptive immune responses. They are pivotal in the pathogenesis of various liver disorders, such as viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), liver fibrosis, autoimmune liver diseases, and hepatocellular carcinoma (HCC). Despite their importance, the functional diversity and regulatory mechanisms of γδT cells remain incompletely understood. Recent advances in high-throughput single-cell sequencing and spatial transcriptomics have revealed significant heterogeneity among γδT cell subsets, particularly Vδ1⁺ and Vδ2⁺, which exhibit distinct immunological roles. Vδ1⁺ T cells are mainly tissue-resident and contribute to tumor immunity and chronic inflammation, while Vδ2⁺ T cells, predominantly found in peripheral blood, play roles in systemic immune surveillance but may undergo dysfunction in chronic liver diseases. Additionally, γδT17 cells exacerbate inflammation in NAFLD and ALD, whereas IFN-γ-secreting γδT cells contribute to antiviral and antifibrotic responses. These discoveries have laid the foundation for the creation of innovative solutions. γδT cell-based immunotherapeutic approaches, such as adoptive cell transfer, immune checkpoint inhibition, and strategies targeting metabolic pathways. Future research should focus on harnessing γδT cells' therapeutic potential through targeted interventions, offering promising prospects for precision immunotherapy in liver diseases.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}