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Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577-1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216-1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion: A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI.
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Indice de masse corporelle , Prédisposition génétique à une maladie , Étude d'association pangénomique , Analyse de randomisation mendélienne , Humains , Femelle , Odds ratio , Polymorphisme de nucléotide simple , Tumeurs de l'appareil génital féminin/génétique , Tumeurs de l'appareil génital féminin/étiologie , Tumeurs de l'appareil génital féminin/épidémiologie , Facteurs de risque , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/génétiqueRÉSUMÉ
Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.
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The objective of this work was to investigate the sorption behavior of gases, namely CO2, CH4, and N2, by molecules of coal sampled from Linglu mine under different water inclusion rates. To this end, the adsorption, diffusion, adsorption heat, and potential energy distribution characteristics of the gases in the coal pores at different water inclusion rates were analyzed using molecular dynamics and grand canonical ensemble Monte Carlo methods. The results showed that the adsorption relationship of the coal molecules on CO2, CH4, and N2 exhibited a downtrend followed by an uptrend when the water content was increased from 0 to 3.6%. The adsorption amount of CO2 was approximately twice as much as those of CH4 and N2, indicating that the competitive adsorption advantage of CO2 compared with those of CH4 and N2 was unaffected by the water content. The trend in the average heat of adsorption was generally consistent with the trend in the density of coal molecules under different moisture contents. Under the same conditions, the diffusion coefficient within a coal molecule was negatively related to the water content in the system. The layer spacing of the water molecules (2.875 Å) was greater than the liquid-water layer spacing, indicating the formation of a water molecule layer at this point, which inhibited gas adsorption. This study lays a theoretical foundation for further investigating the microscopic mechanism of coal-water interaction.
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Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.
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Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.
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PURPOSE: To evaluate the associations between frailty and all-cause and cancer-related mortality. Additionally, the objective is to compare the magnitude of these associations between older adults and younger adults. METHODS: We gathered baseline data from NHANES (1999-2018) and developed a cumulative index consisting of 39 items to evaluate frailty. The National Death Index database was utilized to track the survival status of individuals. The Cox regression model was employed to estimate the associations between frailty status and all-cause and cancer-related mortality. RESULTS: Ultimately, 3398 cancer patients were included in the analysis, comprising 910 younger adults and 2488 older adults. Compared to non-frail patients, the elevated all-cause and cancer-related mortality among pre-frail patients was not statistically significant (HRs = 1.312, 95%CI: 0.956-1.800, P = 0.092; HRs = 1.462, 0.811-2.635, P = 0.207). However, a significant elevation of both all-cause and cancer-related mortality risk was observed among frail patients (HRs = 2.213, 1.617-3.030, P < 0.001; HRs = 2.463, 95%CI = 1.370-4.429, P = 0.003). Frailty individuals demonstrated a more pronounced association with the prediction of all-cause mortality in younger (HRs = 2.230, 1.073-4.634, P = 0.032) than in older adults (HRs = 2.090, 1.475-2.960, P < 0.001). Sensitivity analysis consistently revealed robust results. RCS plots suggested a progressively escalating dose-response correlation between frailty and both all-cause and cancer-related mortality risk. CONCLUSIONS: Pre-frailty did not result in an increase in mortality risks compared to non-frailty. However, frailty caused a higher all-cause and cancer-related mortality risk than non-frailty. Identifying those at risk and implementing targeted interventions may contribute to extending healthy life expectancy, regardless of age.
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Cause de décès , Fragilité , Tumeurs , Humains , Tumeurs/mortalité , Mâle , Femelle , Fragilité/mortalité , Études prospectives , Sujet âgé , Adulte d'âge moyen , Adulte , Sujet âgé de 80 ans ou plus , Études de cohortes , Évaluation gériatrique , Enquêtes nutritionnelles , Personne âgée fragile/statistiques et données numériques , Facteurs âges , Facteurs de risqueRÉSUMÉ
In order to study the effect of H2S on gas adsorption in a coal seam, the adsorption characteristics of single-component CO2, CH4, N2, and H2S and multicomponent H2S mixed with CO2, CH4, and N2 by anthracite were simulated by using the Grand Canonical Ensemble Monte Carlo (GCMC) method. The results show that the adsorption capacity of CO2, CH4, N2, and H2S in anthracite decreases with increasing temperature and increases with increasing pressure. The isothermal adsorption curves of CO2, CH4, N2, and H2S and different proportions of H2S/CH4, H2S/N2, and H2S/CO2 are highly consistent with the Langmuir equation, and the R 2 is above 0.99. Under different temperature and pressure conditions, the adsorption capacity of H2S and CO2 is stronger than that of coal for N2 and CH4, and the adsorption capacity difference is about 3 mmol/g. There is competitive adsorption among H2S, CO2, CH4, and N2, and H2S has a superior adsorption property. When H2S and other gases exist at the same time, the adsorption capacities of CH4, N2, and CO2 are reduced by 48-60%, 81-91%, and 51-66%, respectively.
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Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.
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Lung cancer is a leading cause of death globally, with lung adenocarcinoma being the most common subtype. Despite advancements in targeted therapy, drug resistance remains a major challenge. This study investigated the impact of Bacillus coagulans on drug resistance in lung adenocarcinoma cells. The cells were pretreated with B. coagulans culture filtrate (BCCF), and functional assays were performed, including cell proliferation, cell cycle, apoptosis, and immunofluorescence staining. Results showed that BCCF induced cell cycle arrest at the S phase, reducing cell proliferation and suppressing drug resistance marker P-glycoprotein expression in BCCF-treated resistant cells rather than BCCF-treated control cells. Moreover, drug-resistant cells exhibited the ability for epithelial-mesenchymal transition, which could contribute to their necrosis through the iron-mediated cell death pathway upon BCCF treatment. Proteomic analysis identified downregulation of DNA mismatch repair protein PMS2 after BCCF treatment. These findings suggest that B. coagulans may modulate the DNA repair pathway, influencing drug resistance in lung adenocarcinoma cells. In conclusion, this study highlights the potential impact of B. coagulans on drug-resistant lung adenocarcinoma cells. Further investigation and understanding of the regulatory mechanisms by which B. coagulans modulates drug resistance in lung adenocarcinoma can aid in the development of more effective treatment strategies to improve the prognosis of lung cancer patients.
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Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.
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OBJECTIVE: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. METHODS: In 2022, a total of 4684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes was determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. RESULTS: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5, 47) = 18.233, p < 0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5, 47) = 2.037, p = 0.091). CONCLUSION: This study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.
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COVID-19 , Génome viral , Phylogenèse , Quarantaine , SARS-CoV-2 , Humains , COVID-19/épidémiologie , COVID-19/transmission , COVID-19/virologie , COVID-19/prévention et contrôle , Hong Kong/épidémiologie , SARS-CoV-2/génétique , SARS-CoV-2/classification , Distanciation physique , Mâle , Femelle , Adulte , Adulte d'âge moyen , Adolescent , Enfant , Sujet âgé , Jeune adulteRÉSUMÉ
This study aimed to improve the traceability of rice-producing areas to address the increasing demand for accurate methods to confirm food quality and safety. Compound-specific δ13C of fatty acids, δ13C of starch and bulk of rice were measured. PCA, PLS-DA and VIP value analysis of the obtained data were performed to track the source of rice from the six regions. The PLS-DA model established with bulk δ13C, starch δ13C, and fatty acid δ13C, which clearly separated the rice from six regions. The VIP graph showed the value of starch, C18:0 and C18:2 δ13C values (VIP > 1) were important to distinguish the origin of rice. Also, according to loading plots the contribution of starch δ13C was the largest. The findings indicate that the introduction of starch δ13C improves the precision of rice traceability and provides an effective method for identifying rice origin.
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Isotopes du carbone , Acides gras , Oryza , Amidon , Oryza/composition chimique , Oryza/classification , Isotopes du carbone/analyse , Amidon/analyse , Amidon/composition chimique , Acides gras/analyse , Acides gras/composition chimiqueRÉSUMÉ
PURPOSE: Women with gestational diabetes mellitus (GDM) or obesity are vulnerable to impaired gestational cardiovascular health (CVH) and cardiovascular disease (CVD) in the future. It is unclear if prenatal vitamin D supplementation improves gestational CVH, especially in women at high risk for developing CVD. Our goal was to find out if vitamin D supplementation could protect against gestational CVH, including the women with GDM or obesity. DESIGN: We randomly assigned women with a serum 25(OH)D concentration < 75 nmol/L to receive 1600 IU/d (intervention group) or 400 IU/d (control group) of vitamin D3 for two months at 24-28 weeks' gestation. The primary outcome was gestational CVH marks (lipids, inflammatory cytokines, endothelial function). RESULTS: There were 1537 participants divided into the intervention (N = 766) and control groups (N = 771). No baseline differences existed among study groups in CVH markers. At the two-month visit, the intervention group's HDL-C levels (2.01 ± 0.39 VS 1.96 ± 0.39 mmol/L) were significantly higher than those of the control group, while the hs-CRP levels were significantly lower (3.28 ± 2.02 VS 3.64 ± 2.42 mg/L). Subgroup analysis found that HDL-C, TC, hs-CRP, E-Selectin, and SBP were improved in the intervention group among women with GDM or overweight/obesity, and the improvement was not found in women without GDM or overweight/obesity. Vitamin D supplementation significantly decreased the mean triglyceride-glucose index at the two-month visit in women with GDM. CONCLUSIONS: Vitamin D supplementation at mid-gestation might optimize the gestational CVH status for pregnant women, particularly the women with GDM or obesity, which is advantageous for later-life primary prevention of CVD. CLINICAL TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100051914, 10/9/2021, Prospective registered, https://www.chictr.org.cn/showproj.aspx?proj=134700 ).
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This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.
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BACKGROUND: Autoimmune skin diseases (ASDs) such as psoriasis and vitiligo, in addition to causing visible skin symptoms, are closely associated with psychological health issues. However, a comprehensive understanding of the prevalence of these psychological comorbidities in affected individuals is lacking. This study aims to identify the prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with ASDs. METHOD: PubMed, MEDLINE, Web of Science, and Cochrane Library searches were conducted from 1993 to May 2024. Observational studies reporting prevalence data for anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation among people with ASDs were included in the analysis. The Newcastle-Ottawa scale was used to evaluate the quality of studies. RESULTS: The study included 114 studies from 37 countries including 823,975 participants. The estimated pooled prevalence of anxiety in patients with ASDs was 33.3% (95% CI: 27.3-29.3%). The estimated pooled prevalence of depression was 33.7% (95% CI: 29.2-38.1%). The estimated pooled prevalence of sleeping problems was 45.0% (95% CI:31.6-58.4%). The estimated pooled prevalence of cognitive impairment and suicidal ideation was 30.8% (95% CI:15.0-46.7%) and 21.6% (95% CI:13.4-29.8%), respectively. The most common mental disorder in patients with systemic lupus erythematosus and psoriasis was sleeping problems at 55.9% (95% CI: 35.6-76.1%, I2 = 97%) and 39.0% (95% CI: 21.1-56.9%, I2 = 99%). CONCLUSION: Among patients with ASDs, anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation were common. The most prevalent mental disorder among patients with systemic lupus erythematosus and psoriasis was sleeping problems. Those with ASDs may experience considerable psychological burdens, and integrated mental health support is necessary for their treatment.
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Anxiété , Maladies auto-immunes , Dysfonctionnement cognitif , Dépression , Maladies de la peau , Troubles de la veille et du sommeil , Idéation suicidaire , Humains , Troubles de la veille et du sommeil/épidémiologie , Prévalence , Maladies auto-immunes/épidémiologie , Dysfonctionnement cognitif/épidémiologie , Dysfonctionnement cognitif/étiologie , Dépression/épidémiologie , Maladies de la peau/épidémiologie , Anxiété/épidémiologie , Comorbidité , Psoriasis/épidémiologie , Psoriasis/psychologieRÉSUMÉ
Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.
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Électroacupuncture , Glycolyse , Lactoyl glutathione lyase , Néovascularisation pathologique , Tumeurs du sein triple-négatives , Animaux , Femelle , Humains , Souris , Lignée cellulaire tumorale , Prolifération cellulaire , Électroacupuncture/méthodes , Cellules endothéliales/métabolisme , Cellules endothéliales de la veine ombilicale humaine , Lactoyl glutathione lyase/métabolisme , Lactoyl glutathione lyase/génétique , Souris de lignée BALB C , Néovascularisation pathologique/métabolisme , Paclitaxel/pharmacologie , Méthylglyoxal/métabolisme , Tumeurs du sein triple-négatives/génétique , Tumeurs du sein triple-négatives/métabolisme , Tumeurs du sein triple-négatives/anatomopathologie , Tumeurs du sein triple-négatives/thérapie , Tests d'activité antitumorale sur modèle de xénogreffe , Danio zébréRÉSUMÉ
Background: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients' emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown. Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores. Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials. Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.