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1.
Biomaterials ; 312: 122709, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39094521

RESUMEN

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).


Asunto(s)
Bismuto , Neoplasias de la Mama , Oxígeno , Terapia por Ultrasonido , Bismuto/química , Femenino , Animales , Neoplasias de la Mama/terapia , Terapia por Ultrasonido/métodos , Oxígeno/química , Ratones , Ratones Endogámicos BALB C , Humanos , Línea Celular Tumoral , Rayos Infrarrojos , Nanoestructuras/química , Fototerapia/métodos
3.
Artículo en Inglés | MEDLINE | ID: mdl-39246141

RESUMEN

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patient. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.

4.
Asian J Surg ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39232960
5.
Chem Sci ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39246335

RESUMEN

Polyoxometalates (POMs) are a class of anionic metal-oxygen clusters with versatile biological activities. Over the past decade, an increasing number of POMs, especially Sb-rich POMs, have been proven to exert antitumor activity. However, the antitumor effects and mechanisms of POMs in the treatment of non-small cell lung cancer (NSCLC) remain largely unexplored. This study employed a Sb-rich {Sb21Tb7W56} POM (POM-1) for NSCLC therapy and investigated its mechanism of action. Our results demonstrated that POM-1 exhibited cytotoxicity against H1299 and A549 cells with IC50 values of 3.245 µM and 3.591 µM, respectively. The migration and invasion were also inhibited by 28.05% and 76.18% in H1299 cells, as well as 36.88% and 36.98% in A549 cells at a concentration of 5 µM. In a tumor xenograft mouse model, POM-1 suppressed tumor growth by 76.92% and 84.62% at doses of 25 and 50 mg kg-1, respectively. Transcriptomic analysis indicated the alteration of ferroptosis and apoptosis signaling pathways in POM-treated NSCLC cells. Subsequent experimentation confirmed the induction of ferroptosis, evidenced by 5.6-fold elevated lipid peroxide levels with treatment of 5 µM POM-1, alongside increased expression of ferroptosis-associated proteins. Additionally, the apoptosis induced by POM-1 was also validated by the 19.67% and 30.1% increase in apoptotic cells in H1299 and A549 cells treated with 5 µM POM-1, respectively, as well as the upregulated activation of caspase-3. In summary, this study reveals, for the first time, ferroptosis as the antitumor mechanism of Sb-rich POM, and that synergism with ferroptosis and apoptosis is a highly potent antitumor strategy for POM-based antitumor therapy.

6.
Aging (Albany NY) ; 162024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39227068

RESUMEN

Fibrinogen is an important plasma protein composed of three polypeptide chains, fibrinogen alpha (FGA), beta, and gamma. Apart from being an inflammation regulator, fibrinogen also plays a role in tumor progression. Liver cancer usually has a poor prognosis, with chronic hepatitis being the main cause of liver cirrhosis and hepatocellular carcinoma (HCC). FGA serves as a serological marker for chronic hepatitis, but its relationship with liver cancer remains unclear. Through bioinformatics analysis and agarose gel electrophoresis, we found that FGA was downregulated in HCC and correlated with tumor stage and grade. By constructing both FGA gene knockout and overexpression cell models, we demonstrated that overexpressing FGA inhibited migration and invasion of liver cancer cells through Transwell migration/invasion and wound healing assays. Western blotting experiments showed that FGA overexpression increased the expression of the epithelial-mesenchymal transition marker protein E-cadherin while decreasing N-cadherin and slug protein expression. In addition, FGA knockout activated the PI3K/AKT pathway. In a mouse model of metastatic tumors, overexpression of FGA restricted the spread of tumor cells. In conclusion, FGA exhibits an inhibitory effect on tumor metastasis, providing new insights for the treatment of advanced HCC metastatic tumors.

7.
Int J Clin Health Psychol ; 24(3): 100489, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220119

RESUMEN

Background: Poor mental health literacy (MHL) in the global population significantly contributes to the treatment gap associated with mental disorders. In the digital age, leveraging Internet-based MHL interventions offers scalability and broader accessibility. This meta-analysis aimed to evaluate the effects of Internet-based interventions in improving MHL and mental health. Method: Up to Feb 2024, seven databases were searched for Internet-based interventions on MHL (knowledge, stigma, help-seeking attitudes and intentions) and mental disorders (general distress, anxiety, and depressive symptoms). The random-effects meta-analyses at post-intervention and long-term follow-up assessments were performed. Results: Twenty-nine eligible studies involving 11,582 participants were included. Significant positive effects were observed across various domains: knowledge increase (immediate: g = 0.459, 95 %CI: 0.285 to 0.634; follow-up: g = 0.487, 95 %CI: 0.348 to 0.626), immediate stigma reduction (g = -0.332, 95 %CI: -0.479 to -0.186), immediate enhancement of help-seeking attitudes (g = 0.168, 95 %CI: 0.046 to 0.3291) and help-seeking intentions (g = 0.135, 95 %CI: 0.072 to 0.198), as well as immediate mental health improvements (g = -0.074, 95 %CI: -0.115 to -0.033). Conclusion: Overall, these findings underscore the promising effects of internet-based interventions in improving MHL and mental health, while maintaining these effects over time remains challenging, particularly in reducing stigma and promoting long-term help-seeking behaviors. Addressing methodological limitations, adopting a more interactive approach, and implementing targeted interventions are crucial to maximizing the effectiveness and advancing mental health care worldwide.

8.
Ther Adv Neurol Disord ; 17: 17562864241273079, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282636

RESUMEN

Background: Hereditary transthyretin amyloidosis (ATTRv; v for variant) with polyneuropathy is a rare, progressive, and fatal autosomal dominant disorder. Therapies such as liver transplantation and TTR stabilizations have limitations. Patisiran is a small interfering RNA (siRNA), offering potential as a genetic-level therapy for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). However, evidence on patisiran's efficacy and safety for ATTRv-PN remains limited. Objectives: This study aimed to further clarify patisiran's efficacy and safety for ATTRv-PN by meta-analysis. Design: Systematic review and meta-analysis. Methods: After literature searches in PubMed, Ovid MEDLINE, Embase, JBI EBP, Cochrane, and ClinicalTrials.gov databases on 7 June 2024, 11 studies with 503 patients were included and clinical data were extracted. Results: Results showed an 88% (95% confidence interval (CI): 81%-94%) pooled responsiveness rate. The standardized mean difference of modified Neuropathy Impairment Score plus 7 nerve tests (mNIS + 7) scores was -0.18 (95% CI: -0.32 to -0.03, p-value 0.018) and Norfolk Quality of Life-Diabetic Neuropathy was -0.21 (95% CI: -0.35 to -0.08, p-value 0.002). In total, 413 adverse events (AEs) (84.8%), 158 serious AEs (32.4%), and 37 deaths (7.6%) were recorded. Most of AEs were mild to moderate. No deaths were attributed to patisiran. However, there is no statistically significant improvement in Neuropathy Impairment Scores. Conclusion: In conclusion, patisiran was effective and safe for patients with ATTRv-PN. More large-scale clinical trials and long-term studies are necessary to further validate patisiran's efficacy and safety. Trial registration: PROSPERO registration ID: CRD42023428838.

9.
Front Microbiol ; 15: 1422574, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234537

RESUMEN

Introduction: Both the incidence and mortality rates associated with methicillin-resistant Staphylococcus aureus (MRSA) have progressively increased worldwide. A nucleic acid testing system was developed in response, enabling swift and precise detection of Staphylococcus aureus (S. aureus) and its MRSA infection status. This facilitates improved prevention and control of MRSA infections. Methods: In this work, we introduce a novel assay platform developed by integrating Pyrococcus furiosus Argonaute (PfAgo) with recombinase polymerase amplification (RPA), which was designed for the simultaneous detection of the nuc and mecA genes in MRSA. Results: This innovative approach enables visual MRSA detection within 55 mins, boasting a detection limit of 102 copies/µL. Characterized by its high specificity, the platform accurately identifies MRSA infections without cross-reactivity to other clinical pathogens, highlighting its unique capability for S. aureus infection diagnostics amidst bacterial diversity. Validation of this method was performed on 40 clinical isolates, demonstrating a 95.0% accuracy rate in comparison to the established Vitek2-COMPACT system. Discussion: The RPA-PfAgo platform has emerged as a superior diagnostic tool, offering enhanced sensitivity, specificity, and identification efficacy for MRSA detection. Our findings underscore the potential of this platform to significantly improve the diagnosis and management of MRSA infection.

10.
Int Immunopharmacol ; 142(Pt A): 113139, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278061

RESUMEN

INTRODUCTION: Hepcidin, a central regulatory molecule of iron metabolism, is upregulated through the IL-6/STAT3 signaling pathway in inflammatory and infectious states, contributing to the pathogenesis of various diseases. In chronic apical periodontitis (CAP), Porphyromonas gingivalis (P. gingivalis) and its lipopolysaccharides (LPS) activate various immune responses in vivo, contributing to disease progression. This study evaluated the role and mechanism of hepcidin in P. gingivalis-induced bone tissue damage in CAP, focusing on its promotion of macrophage M1 polarization via the IL-6/STAT3 signaling pathway. METHODS: We analyzed a GSE77459 dataset from the GEO database, containing data from inflammatory and normal dental pulp tissues. RT-qPCR and immunofluorescence staining were used to detect the expression of hepcidin in human CAP tissues and its relationship with macrophages. Mouse bone marrow derived macrophages (BMDMs) were cultured in vitro and stimulated with P. gingivalis LPS. The effects of Stattic on macrophage hepcidin expression, IL-6 expression, STAT3 phosphorylation, and macrophage polarization were detected by ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. RESULTS: Hepcidin expression in human inflammatory dental pulp tissues was upregulated via the IL-6/STAT3 pathway and correlated with macrophage polarization. Hepcidin-encoding genes were found to be highly expressed and primarily associated with M1 macrophages in CAP tissues. In vitro experiments revealed that P. gingivalis LPS stimulation induced macrophages to express hepcidin through the IL-6/STAT3 pathway and polarize to M1. Additionally, the IL-6/STAT3 pathway inhibitor Stattic suppressed these changes. CONCLUSIONS: Our study demonstrates that in CAP, macrophages highly express hepcidin, which subsequently alters macrophage metabolism, regulates M1 polarization, and leads to bone tissue destruction.

11.
Int J Mol Sci ; 25(17)2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39273650

RESUMEN

Breast cancer (BC) has become the most life-threatening cancer to women worldwide, with multiple subtypes, poor prognosis, and rising mortality. The molecular heterogeneity of BC limits the efficacy and represents challenges for existing therapies, mainly due to the unpredictable clinical response, the reason for which probably lies in the interactions and alterations of diverse cell death pathways. However, most studies and drugs have focused on a single type of cell death, while the therapeutic opportunities related to other cell death pathways are often neglected. Therefore, it is critical to identify the predominant type of cell death, the transition to different cell death patterns during treatment, and the underlying regulatory mechanisms in BC. In this review, we summarize the characteristics of various forms of cell death, including PANoptosis (pyroptosis, apoptosis, necroptosis), autophagy, ferroptosis, and cuproptosis, and discuss their triggers and signaling cascades in BC, which may provide a reference for future pathogenesis research and allow for the development of novel targeted therapeutics in BC.


Asunto(s)
Autofagia , Neoplasias de la Mama , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Femenino , Autofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Muerte Celular , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Terapia Molecular Dirigida , Apoptosis/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Animales , Necroptosis/efectos de los fármacos
12.
Asian J Surg ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271343

RESUMEN

BACKGROUND: The increasing comprehension of spleen function has led to the gradual endorsement of laparoscopic partial splenectomy (LPS) as a treatment option for benign spleen lesions. However, it is important to note that the LPS technique remains challenging. This study explores the standardized process and surgical techniques in LPS, aiming to promote the application of this technique. METHODS: The clinical data of 20 patients with benign cystic or solid spleen lesions who underwent LPS at Shunde Hospital, Southern Medical University were retrospectively collected. Data include age, gender, imaging data, surgical process, and postoperative complications. Additionally, the surgical techniques and standardization process were recorded in detail. RESULTS: All 20 cases completed LPS without conversion to laparotomy or splenectomy. The surgical time was 162.25 ± 37.96 min, the intraoperative blood loss was 93.00 ± 58.40 mL, no blood products were transfused during the operations, and the removed volume of the spleen was about 34.75 ± 12.19 %. There were no postoperative complications such as intra-abdominal bleeding, intra-abdominal infection, pancreatic fistula, and residual splenic infarction. Postoperative pleural effusion occurred in four cases, and symptoms improved after symptomatic treatment. The postoperative hospital stay was 7.0 ± 1.4 days. There were no perioperative deaths. The residual splenic vessels were normal during the follow-up period, and no vascular embolism occurred. CONCLUSIONS: LPS is a safe, feasible, and effective surgical method for patients with benign cystic or solid spleen lesions. Subsequently, mastering related surgical techniques and standardized surgical procedures can control the surgical risks in suitable cases, making LPS the standard procedure for treating benign spleen diseases.

13.
BMC Surg ; 24(1): 254, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256669

RESUMEN

BACKGROUND: Non-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines. METHODS: A retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods. RESULTS: The study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062-7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate-risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001). CONCLUSION: This investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes.


Asunto(s)
Neoplasias Endometriales , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Femenino , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Guías de Práctica Clínica como Asunto , Resultado del Tratamiento , Medición de Riesgo/métodos , Factores de Riesgo , Supervivencia sin Enfermedad
14.
Front Public Health ; 12: 1421211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257951

RESUMEN

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.


Asunto(s)
COVID-19 , Miastenia Gravis , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Adulto , Factores de Riesgo , Anciano , Índice de Severidad de la Enfermedad , Comorbilidad
15.
J Autoimmun ; 149: 103305, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265193

RESUMEN

Immune-mediated neuropathy (IMN) is a group of heterogenous neuropathies caused by intricate autoimmune responses. For now, known mechanisms of different IMN subtypes involve the production of autoantibodies, complement activation, enhanced inflammation and subsequent axonal/demyelinating nerve damages. Recent therapeutic studies mainly focus on specific antibodies and small molecule inhibitors previously approved in rheumatoid diseases. Initial strategies based on the pathophysiologic features of IMN should be explored. Adoptive cell therapy (ACT) refers to the emerging immunotherapies in which circulating immunocytes are collected from peripheral blood and modified with killing and immunomodulatory capacities. It consists of chimeric antigen receptor-T cell therapy, T cell receptor-engineered T cell, CAR-Natural killer cell therapy, and others. In the last decade, ACT has demonstrated extraordinary potentials in treating cancers, infectious diseases and autoimmune diseases. Versatile combinations of targets, chimeric domains and effector cells greatly empower ACT to treat complicated immune disorders. In this review, we summarized the advances of ACT and envisioned suitable strategies for different IMN subtypes.

16.
Mater Horiz ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264270

RESUMEN

Efficient enrichment and accurate diagnosis of cancer cells from biological samples can guide effective treatment strategies. However, the accessibility and accuracy of rapid identification of tumor cells have been hampered due to the overlap of white blood cells (WBCs) and cancer cells in size. Therefore, a diagnosis system for the identification of tumor cells using reliable surface-enhanced Raman spectroscopy (SERS) bioprobes assisted with high-efficiency microfluidic chips for rapid enrichment of cancer cells was developed. According to this, a homogeneous flower-like Cu2O@Ag composite with high SERS performance was constructed. It showed a favorable spectral stability of 5.81% and can detect trace alizarin red (10-9 mol L-1). Finite-difference time-domain (FDTD) simulation of Cu2O, Ag and Cu2O@Ag, decreased the fluorescence lifetime of methylene blue after adsorption on Cu2O@Ag, and surface defects of Cu2O observed using a spherical aberration-corrected transmission electron microscope (AC-TEM) demonstrated that the combined effects of electromagnetic enhancement and promoted charge transfer endowed the Cu2O@Ag with good SERS activity. In addition, the modulation of the absorption properties of flower-like Cu2O@Ag composites significantly improved electromagnetic enhancement and charge transfer effects at 532 nm, providing a reliable basis for the label-free SERS detection. After the cancer cells in blood were separated by a spiral inertial microfluidic chip (purity >80%), machine learning-assisted linear discriminant analysis (LDA) successfully distinguished three types of cancer cells and WBCs with high accuracy (>90%). In conclusion, this study provides a profound reference for the rational design of SERS probes and the efficient diagnosis of malignant tumors.

17.
Allergol Immunopathol (Madr) ; 52(5): 73-79, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39278854

RESUMEN

This study examines the therapeutic effects of Shengmai Powder (SMP) on both in vitro and in vivo models of chronic obstructive pulmonary disease (COPD) and the underlying mechanisms. Cigarette smoke and cigarette extracts were used to create in vitro and in vivo models of COPD. ELISA was used to measure the levels of pro-inflammatory factors (IL-6, TNF-α, and IL-1ß) in mouse lung tissue and alveolar macrophages. Flow cytometry assessed the phagocytic capacity of alveolar macrophage. Western blotting was used to analyze the expression of RhoA, PPARγ, IκBα, p-IκBα, P65, and p-P65 in alveolar. The results show that SMP reversed the increased levels of pro-inflammatory factors (IL-6, TNF-α, and IL-1ß) in mouse lung tissue and alveolar macrophages induced by cigarette smoke and cigarette extract. SMP also restored the decreased fluorescence intensity and RhoA levels in alveolar macrophages caused by cigarette extract. Additionally, SMP increased PPARγ expression and decreased IκBα and P65 phosphorylation in alveolar macrophages exposed to cigarette extract. Also, the effects of SMP were reversed by PPARγ inhibitors. The study concluded that SMP regulates alveolar macrophage phagocytic function through the PPAR-γ/NF-κB pathway, thereby improving the chronic inflammatory state of COPD.


Asunto(s)
Combinación de Medicamentos , Medicamentos Herbarios Chinos , Macrófagos Alveolares , PPAR gamma , Enfermedad Pulmonar Obstructiva Crónica , Animales , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/inmunología , PPAR gamma/metabolismo , Medicamentos Herbarios Chinos/farmacología , Ratones , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/inmunología , Modelos Animales de Enfermedad , Fagocitosis/efectos de los fármacos , Humanos , Masculino , Citocinas/metabolismo , Polvos , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo
18.
Artículo en Inglés | MEDLINE | ID: mdl-39229762

RESUMEN

Purpose: The early detection of breast cancer in women under the age of 40 has posed significant challenges. This can be attributed in part to the limited research conducted on the breast cancer in this age group, particularly with regards to large sample sizes. We aimed to address this gap by analyzing and comparing the ultrasound imaging and pathological characteristics of breast cancer in women aged under 40 and those aged 40 and above. Methods: A retrospective assessment was conducted to examine the ultrasound imaging and clinicopathologic characteristics of 555 women with surgically confirmed breast cancers. The patient cohort consisted of 160 individuals below the age of 40 and 395 individuals aged 40 years and above. Results: Our study identified the breast cancer in patients under 40 years was more likely to show regular shape (p = 0.043) compared with tumors in patients who were 40 years and over. Furthermore, in young female patients (<40 years), irregular shape was correlated with the HER2-enriched type (p = 0.02), circumscribed margin (p = 0.001), and a lack of calcifications (p = 0.02) were associated with the triple-negative type. In another group (≥40 years), only a lack of calcifications (p = 0.003) were associated with the triple-negative type. Conclusion: Breast cancer in women under the age of 40 exhibits distinct ultrasonographic characteristics patterns that vary across different immunophenotypes, which may provide certain predictive information for physicians.

19.
Front Immunol ; 15: 1371662, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39221249

RESUMEN

Background: The relationship between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is widely known; however, causal evidence of this link is lacking. Here, we aimed to determine the causal effect of peripheral immune cells, specifically total white blood cells, lymphocytes, monocytes, basophils, eosinophils, and neutrophils, as well as lymphocyte subset traits, on the IgAN risk using a Mendelian randomization (MR) analysis. Methods: The inverse-variance weighted (IVW) method was used for the primary analysis. We applied three complementary methods, including the weighted median, MR-Egger regression, and MR-PRESSO, to detect and correct for the effect of horizontal pleiotropy. Additionally, we performed a multivariable MR (MVMR) analysis, adjusting for the effects of C-reactive protein (CRP) levels. The roles of specific lymphocyte subtypes and their significance have garnered interest. Bidirectional two-sample MR analysis was performed to test the potential causal relationships between immune traits, including median fluorescence intensities (MFIs) and the relative cell count (AC), and IgAN. Results: The IVW-MR analysis suggested a potential causal relationship between lymphocyte counts and IgAN in Europe (OR per 1-SD increase: 1.43, 95% CI: 1.08-1.88, P = 0.0123). The risk effect of lymphocytes remained even after adjusting for CRP levels using the MVMR method (OR per 1-SD increase: 1.44, 95% CI: 1.05-1.96, P = 0.0210). The other sensitivity analyses showed a consistent trend. The largest GWAS published to date was used for peripheral blood immunophenotyping to explore the potential causal relationship between peripheral immune cell subsets and IgAN. Six AC-IgAN and 14 MFI-IgAN pairs that reached statistical significance (P < 0.05) were detected. Notably, CD3, expressed in eight subsets of T cells, consistently showed a positive correlation with IgAN. The bidirectional MR analysis did not reveal any evidence of reverse causality. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. Conclusions: Genetically determined high lymphocyte counts were associated with IgAN, supporting that high lymphocyte counts is causal risk factor for IgAN.


Asunto(s)
Glomerulonefritis por IGA , Análisis de la Aleatorización Mendeliana , Humanos , Glomerulonefritis por IGA/genética , Glomerulonefritis por IGA/inmunología , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple
20.
Clin Interv Aging ; 19: 1471-1478, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206053

RESUMEN

Background: Management strategies for stable angina include pharmacotherapy, revascularization, and exercise-based cardiac rehabilitation (CR). The optimal treatment for stable angina patients with severe coronary artery stenosis remains unclear. This study aimed to compare interventional therapy with exercise rehabilitation in this population. Methods: Fifty stable angina patients with severe coronary stenosis who underwent stent implantation were included in the optimal medical therapy (OMT) plus percutaneous coronary intervention (PCI) group, and 50 patients who did not undergo interventional treatment were included in OMT plus CR group receiving exercise rehabilitation guidance for one year. Cardiovascular composite endpoint events, cardiopulmonary fitness, and quality of life scale scores were assessed after one year. Results: No significant difference in incidence of cardiovascular composite endpoint events was observed between OMT plus PCI group with OMT plus CR group (20.0% vs 14.6%) after one year. Cardiopulmonary fitness represented as peak VO2 (19.2±3.5 vs 17.6±3.2 mL/kg/min), peak load (120±19 vs 108±20 W), and AT (13.5±1.5 vs 12.1±1.3 mL/kg/min) were significantly higher in the rehabilitation group than the intervention group after one year. Both groups showed improvement in their quality of life, but the rehabilitation group improved in more scales. Conclusion: Interventional therapy did not reduce cardiovascular events compared to exercise-based rehabilitation in stable angina patients with severe coronary artery stenosis, but the rehabilitation can improve cardiovascular fitness and quality of life more.


Asunto(s)
Angina Estable , Rehabilitación Cardiaca , Estenosis Coronaria , Terapia por Ejercicio , Intervención Coronaria Percutánea , Calidad de Vida , Humanos , Masculino , Femenino , Anciano , Terapia por Ejercicio/métodos , Persona de Mediana Edad , Estenosis Coronaria/terapia , Estenosis Coronaria/rehabilitación , Angina Estable/rehabilitación , Angina Estable/terapia , Rehabilitación Cardiaca/métodos , Resultado del Tratamiento , Stents , Capacidad Cardiovascular , Fármacos Cardiovasculares/uso terapéutico
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