Hereditas最新文献

Objective: To systematically review the latest evidence on risk factors and surgical treatment for gallbladder cancer (GBC), with a focus on current controversies and consensus in international guidelines, analyze the application prospects of minimally invasive surgery in advanced GBC, and provide direction for clinical practice and future research.

Methods: Literature on GBC risk factors, molecular mechanisms, and treatment strategies published from 2018 to 2024 was retrieved from databases including PubMed, Web of Science, and CNKI. The retrieved literature was summarized, compared, and critically analyzed.

Results: The pathogenesis of GBC involves a combination of genetic, environmental, and metabolic factors. Beyond gallstones and polyps, mutations in TP53 and ERBB2/ERBB3 genes, metabolic syndrome (obesity, hyperglycemia, hyperlipidemia), and chronic infections (Salmonella, Helicobacter) are significant risk factors. Surgical resection remains the primary curative approach, yet the optimal extent of surgery is debated: Is hepatic resection always necessary for T1b stage? What is the oncological safety of laparoscopic surgery for T2 stage? What is the value of extended resection for T4 stage? Recently, targeted therapies (e.g., against ERBB2, NTRK) and mmune checkpoint inhibitors (anti-PD-1/PD-L1)have shown promise in advanced GBC.

Conclusion: Combating GBC requires a comprehensive strategy encompassing health education, screening of high-risk populations, precise staging, and individualized multimodal treatment. Future research should focus on building molecular subtype-based prognostic models, conducting high-level clinical studies to resolve surgical controversies, and exploring the integration of novel adjuvant therapies with traditional surgery.

Background: N6-methyladenosine (m6A) methylation modification plays an essential role in the molecular pathogenesis of preeclampsia (PE). This study aimed to explore m6A modification in in vitro PE model, involving RNA binding motif protein 15 (RBM15) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB).

Methods: PE was induced by lipopolysaccharide (LPS) in HTR8/SVneo cells. Real-time quantification PCR was used for mRNA detection and Western blotting was used for protein detection. Cell cytokines were examined using enzyme-linked immunosorbent assay. Cell functions were evaluated using EdU assay, flow cytometry, and transwell assay. RNA immunoprecipitation assay and dual-luciferase reporter assay were utilized for validating molecular interaction.

Results: FOSB was highly expressed in placenta tissues from PE patients. Functionally, LPS-induced inflammation, proliferation inhibition, cell apoptosis and migration suppression were significantly abolished following FOSB knockdown. RBM15 upregulated FOSB expression via inducing m6A modification of FOSB mRNA. YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) acted as an m6A reader protein, and RBM15 enhanced the binding between YTHDF1 and FOSB. RBM15 knockdown relieved LPS-caused trophoblast cell injury by inhibiting FOSB.

Conclusion: These results collectively suggested that RBM15 accelerated trophoblast cell dysfunction via mediating m6A modification of FOSB mRNA through the identification by YTHDF1.

Parkinson's disease (PD) is closely linked to mitochondrial dysfunction and mitophagy, a key mechanism in PD pathogenesis. However, no dedicated bibliometric analysis of mitophagy in PD exists. This study used data from the Web of Science Core Collection to map the global research landscape of mitophagy in PD. The analysis of 1,578 publications (2007-2024) identifies the United States as the most productive country. McGill University ranks as the top institution, and Nobutaka Hattori is the most prolific author. The journal Autophagy is the journal with the highest number of publications in this field. Core research themes included PINK1/Parkin, mitochondrial quality control, α-synuclein, neuroinflammation, and ferroptosis. The study provides insights into the current status of global collaboration and translational progress in this field. Future efforts should aim to further explore new pathways, enhance clinical translation, and promote collaborative partnerships to advance research and address challenges in the field.

Background: The incidence of pediatric ulcerative colitis (UC) is increasing yearly, and it is urgent to explore precise diagnostic biomarkers and molecular mechanisms. This study aims to investigate the diagnostic value of miR-340-5p in pediatric UC and its molecular mechanism mediated through targeting MAP3K2.

Methods: Eighty-five pediatric UC patients and 50 healthy controls were enrolled. The expression levels of miR-340-5p and MAP3K2 were detected by qRT-PCR, and Pearson's correlation analysis was conducted. An in vitro model was established by inducing HT-29 cells with dextran sulfate sodium. The target was verified by dual-luciferase assay. Flow cytometry, ELISA, and oxidative stress detection were used to verify the cellular functions regulated by the miR-340-5p/MAP3K2 axis.

Results: In pediatric patients with UC, miR-340-5p was significantly downregulated and negatively correlated with PUCAI, CRP, and ESR (P < 0.0001). Additionally, the diagnostic area of miR-340-5p under the ROC curve was 0.908. Mechanistically, miR-340-5p directly interacts with MAP3K2, leading to suppressed expression of its mRNA and protein. Functional experiments revealed that miR-340-5p overexpression reversed DSS-induced exacerbated cell apoptosis, reduced levels of TNF-α, IL-6, IL-17, IL-1β, and MDA, and increased GSH. Conversely, the beneficial effects of miR-340-5p were attenuated by oe-MAP3K2 overexpression.

Conclusions: miR-340-5p may serve as a diagnostic biomarker for pediatric UC and exerts its effects by targeting MAP3K2 to regulate cell apoptosis, inflammatory responses, and oxidative stress.

Objective: To investigate the effects of "Shengjiang Powder", a representative formula for "simultaneous treatment of liver and heart," on liver tissue inflammation and fibrosis in mice with atherosclerosis(AS) concurrent with non-alcoholic fatty liver disease (NAFLD).

Methods: Ten wild-type male C57/B6J mice were assigned to the control group, and 40 ApoE -/- mouse were randomly divided into the model group, atorvastatin group, and traditional Chinese medicine (TCM) treatment groups. The model group, atorvastatin group, and TCM treatment groups were fed a high-fat Western diet for 12 weeks. Atorvastatin and TCM groups were administered via gavage, while the control group and model group received sterile purified water via gavage for 12 weeks. Serum levels of ALT, AST, TRIG, TC, LDL, as well as liver tissue levels of SOD, MDA, and GSH were measured. HE staining was used to evaluate liver tissue morphology and inflammatory infiltration. Western blot was used to detect the effect of Shengjiang Powder on the activation of AMPK/mTOR signaling pathway. Network pharmacology analysis was performed beforehand to identify potential targets of Shengjiang Powder in regulating fatty liver and atherosclerosis, with AMPK identified as a key target.

Results: Compared with the model group, the Shengjiang Powder treatment reduced serum levels of TRIG, TC, and LDL (P < 0.05), increased liver SOD and GSH activity (P < 0.01), decreased MDA (P < 0.01), alleviated liver steatosis, reduces the area of aortic sinus plaques, improved hepatic steatosis and inflammation, inhibited the expression of inflammatory factors and activated the AMPK/mTOR signaling pathway, consistent with the network pharmacology prediction that AMPK is a critical regulatory target.

Conclusion: Treatment with "Shengjiang Powder," a representative formula for "simultaneous treatment of liver and heart," can slow the progression of atherosclerosis and concurrent NAFLD. The dosage shows a positive correlation with efficacy, and this effect is related to the regulation of liver oxidative stress and inflammation-induced fibrosis pathways.

Aim: This study explored the diagnostic value and molecular mechanism of lncRNA MEG8 in deep vein thrombosis (DVT).

Methods: This study included 120 patients with DVT and 100 healthy individuals as research subjects. Expression of lncRNA MEG8 and miR-296-5p in subjects' serum were detected by RT-qPCR. Diagnostic ability of MEG8 for DVT occurrence analyzed by ROC curve. Logistic analysis was used to identify risk factors for DVT. Associations between MEG8 and other parameters were explored by Pearson correlation analysis. Migration, viability and apoptosis of transfected HUVECs were detected by Transwell method, CCK-8 assay and flow cytometry, respectively. In addition, inflammatory cytokines were detected using ELISA kits. The luciferase reporter assay established the interaction between MEG8 and miR-296-5p.

Results: In patients with DVT, lncRNA MEG8 levels were significantly upregulated, and ROC curves showed high diagnostic ability. In addition, MEG8 was positively associated with TAT and D-dimer. In vitro experiments showed that overexpression of MEG8 inhibited HUVECs migration and viability, promoted apoptosis, and upregulated inflammatory factors such as IL-6, IL-1β, and TNF-α, while silencing of MEG8 showed the opposite effect. In addition, MEG8 regulated miR-296-5p expression by sponging it, and the dual luciferase reporter assay verified a direct interaction between them. Clinical samples revealed that serum miR-296-5p levels were diminished in DVT patients as well as negatively correlated with MEG8. Furthermore, miR-296-5p inhibitor reversed the role of MEG8 silencing on regulation of HUVECs migration, viability and inflammatory cytokines.

Conclusion: This study revealed that MEG8 acts critically in DVT development through sponging miR-296-5p for the first time, providing a new molecular target for early diagnosis and targeted therapy of DVT.

Artificial propagation is an important conservation technique to mitigate the loss of native freshwater mussel diversity. In vitro propagation is an alternative method of metamorphosing freshwater mussel larvae (glochidia) to juveniles without a host fish, but the methodology is still evolving in its rates of metamorphosis. This study provides the first comparison of gene expression in freshwater mussel glochidia metamorphosed in different culture media: M199, L-15, and M199 supplemented with lipids. Compared to the commonly used M199, 1.2% of the transcriptome of glochidia reared in the other culture media showed significantly altered expression levels. Of these differentially expressed transcripts, 86% were the same regardless of whether glochidia were metamorphosed in the different basal culture medium L-15 or in M199 supplemented with lipids. We discuss the Gene Ontology categories with the highest number of differentially expressed transcripts, as well as those categories that were over-represented in the different culture media compared to the whole transcriptome. Our results suggest that the external environment can have a significant impact on the physiology of metamorphosing glochidia and may potentially impact the health and survival of juveniles.

Background and objectives: As the etiology of intracranial aneurysm (IA) remains uncertain and unruptured IA management continues to be debated, investigating biomarkers of the disease remains critical. This study thus evaluated the involvement of miR-188-5p in IA diagnosis, prognosis, and development to advance understanding of IA pathophysiology and treatment strategies.

Materials and methods: A case-control study involving 73 IA patients and 79 healthy controls was conducted to assess the diagnostic and prognostic value of miR-188-5p in IA. A PDGF-BB-induced VSMC dedifferentiation model was constructed to explore the mechanisms. The qRT-PCR was employed to test the expression of biomolecules, while dual luciferase reporter assays were performed to ensure biomolecule interaction.

Results: The serum expression of miR-188-5p was relatively higher in IA patients than in healthy controls. High serum expression of miR-188-5p exhibited both diagnostic utility for IA detection and predictive capacity for assessing rupture risk. MiR-188-5p inhibited α-SMA and SM22α expression, promoted MMP-2 and MMP-9 expression, and facilitated oxidative stress and proinflammatory cytokine expression in phenotypically switched VSMCs. MiR-188-5p negatively regulated IL6ST expression in phenotypically switched VSMCs. IL6ST mediated the modification of miR-188-5p in phenotypically switched VSMCs.

Conclusion: MiR-188-5p was a biomarker for IA and its rupture. MiR-188-5p might assist IA progression by inducing VSMC phenotypic switching and cell damage. MiR-188-5p affected VSMCs by downregulating IL6ST. MiR-188-5p might be the potential target for predicting and controlling the development of IA.

Background: Carboplatin resistance represents a critical therapeutic challenge in non-small cell lung cancer (NSCLC) treatment. Although KHSRP has been implicated in lung cancer progression, its molecular mechanisms and impacts on chemotherapy sensitivity remain elusive. Notably, KHSRP has the capacity to activate the transcription of HMGB1, an oncogene known to influence chemotherapy sensitivity. However, it remains to be determined whether KHSRP affects chemotherapy response in NSCLC via HMGB1.

Methods: KHSRP expression in NSCLC cells was analyzed using qRT-PCR. Cell proliferation, apoptosis, and migration were evaluated using colony formation, flow cytometry and wound healing assays. A luciferase reporter assay was conducted to assess whether KHSRP transcriptionally regulates HMGB1. Additionally, A549 cell xenografts were established in nude mice to investigate the tumor growth-promoting effects of KHSRP in vivo.

Results: KHSRP expression was notably elevated in NSCLC cells. Overexpression of KHSRP remarkably promoted A549 cell proliferation, migration, and epithelial-mesenchymal transition (EMT); while KHSRP knockdown exhibited the opposite effects. Mechanically, KHSRP notably promoted the transcription of HMGB1 and upregulated its expression in A549 cells. Importantly, deficiency of KHSRP remarkably enhanced the suppressive effects of carboplatin on A549 cell proliferation, migration, EMT and HMGB1 expression. Meanwhile, in vivo experiments demonstrated that downregulation of KHSRP potentiated the inhibitory effect of carboplatin on tumor growth in tumor-bearing nude mice.

Conclusion: These findings demonstrate that silencing of KHSRP enhances the drug sensitivity of carboplatin in NSCLC, potentially mediated through the inhibition of HMGB1. Targeting KHSRP may represent a promising therapeutic strategy to improve chemotherapy efficacy in NSCLC.

Objective: Cisplatin (DDP) is the major chemotherapeutic drug used to treat gastric cancer (GC). However, DDP-associated side effects and resistance chemoresistance have limited its clinical application. Psoralidin (PSO) is the main extract of Psoralea corylifolia and has antitumor effects. The present study is designed to investigate the antitumor functions and mechanisms of PSO and DDP in GC.

Methods: GC cells (HGC-27 and MKN-45 cells) were treated with PSO (2.5 to 120 µM) and/or DDP. A CCK-8 assay, colony formation assay, and EdU staining were used to test cell proliferation. Cell migration and invasion were tested via a transwell assay. An in vivo assay in nude mice was carried out to analyze the influence of PSO and DDP on tumor growth. H&E staining was conducted to test the histopathological changes of organs and tumor tissues. Ferroptosis-associated indicators, including GSH, MDA, Fe²⁺ levels, were examined. Western blotting was conducted to determine the profiles of ACSL4, GPX4, AIFM2, and SLC7A11.

Results: PSO impeded GC cell proliferation, migration, invasion, and growth in vivo. PSO exhibited no significant toxic effects on organs and mitigated DDP-mediated liver and kidney injuries. The combination of PSO and DDP exhibited enhanced inhibitory functions. PSO and DDP can significantly promote GC cell ferroptosis. Moreover, PSO promoted ACSL4 expression and suppressed GPX4, AIFM2, and SLC7A11.

Conclusion: The combination of PSO and DDP has synergistic antitumor effects on GC cells by inducing ACSL4-mediated ferroptosis. PSO may serve as a nontoxic adjuvant to enhance DDP's efficacy and reduce side effects in GC.