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1.
J Formos Med Assoc ; 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39242223

RÉSUMÉ

BACKGROUND/PURPOSE: Loneliness is prevalent among gay and bisexual men (GBM). This study evaluated the mediating effect of loneliness on the associations of perceived sexual stigma (PSS) and internalized sexual stigma (ISS) with suicide in 400 GBM. METHODS: A moderated mediation model was used to test the mediating effects of loneliness between the associations of PSS from family members and ISS with suicide and the moderating effects of sexual orientation, age, and education level on the mediating effects. RESULTS: The results indicated that both PSS and ISS were positively associated with suicide through the full mediation of loneliness. The association of ISS with loneliness was stronger in older GBM. CONCLUSIONS: Intervention programs promoting changes in attitudes toward GBM are warranted to prevent the development of PSS and ISS, loneliness, and suicide in this population.

2.
Mediators Inflamm ; 2024: 1484806, 2024.
Article de Anglais | MEDLINE | ID: mdl-39262415

RÉSUMÉ

Background: Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. Materials and Methods: To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. Results: This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. Conclusion: 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.


Sujet(s)
Colite , Sulfate dextran , Muqueuse intestinale , Souris de lignée C57BL , Tryptophane , Animaux , Sulfate dextran/toxicité , Colite/induit chimiquement , Colite/traitement médicamenteux , Souris , Muqueuse intestinale/effets des médicaments et des substances chimiques , Muqueuse intestinale/métabolisme , Tryptophane/analogues et dérivés , Tryptophane/pharmacologie , Inflammation/traitement médicamenteux , Mâle , Apoptose/effets des médicaments et des substances chimiques , Macrophages/effets des médicaments et des substances chimiques , Macrophages/métabolisme , Humains , Modèles animaux de maladie humaine , Jonctions serrées/effets des médicaments et des substances chimiques , Jonctions serrées/métabolisme
3.
Sci Rep ; 14(1): 20375, 2024 09 02.
Article de Anglais | MEDLINE | ID: mdl-39223300

RÉSUMÉ

During the COVID-19 pandemic, the online delivery model became the primary mode of education. With multiple pressures on society and families, mental health issues for parents have become particularly pronounced. Most of the current research has focused on the psychological state of education practitioners and children, with little attention to parents' mental health issues. Therefore, this study explored the attitudes and coping styles of parents who experienced the process of their children being taught online over a long period and the factors influencing their mental health. This cross-sectional study was conducted between November 2021 and January 2022, using an anonymous online questionnaire to survey 1500 parents with children aged 6-13 years. The Chinese versions of the Patient Health Questionnaire Depression Scale (PHQ-9), the Parenting Stress Scale (PSS), the General Mental Health Questionnaire (GHQ-12), and the Brief Coping Style Scale (SCSQ), and a related factors questionnaire were used to survey the subjects. The normal distribution of the data was examined using the Shapiro-Wilk method. A multivariate regression analysis was conducted to identify factors significantly associated with parental mental health during the COVID-19 pandemic. Only 30.24% of parents agreed with online classes during the pandemic, and 52.28% used positive coping methods during stressful situations. Multivariate regression models identified significant factors associated with parental mental health: parent's gender, child's grade level, perceived stress about online classes, whether the child has ADHD, positive or negative coping styles, and subjective attitudes of support for online classes or not. The results of the study suggest that as online classes become more socially acceptable, it is necessary to be concerned about the risk of mental illness for parents and develop policies and interventions, especially for parents who adopt negative coping styles and endorse online classes. The focus should be on the stress of online classes on parents, improving the acceptance of online classes and psychological well-being, regulating the way parents deal with their children, and targeting subgroups of children with ADHD symptoms during the COVID-19 pandemic.


Sujet(s)
Adaptation psychologique , COVID-19 , Enseignement à distance , Santé mentale , Parents , Humains , COVID-19/psychologie , COVID-19/épidémiologie , Parents/psychologie , Mâle , Femelle , Enfant , Études transversales , Adolescent , Enseignement à distance/méthodes , Enquêtes et questionnaires , Adulte , Pandémies , Stress psychologique/épidémiologie , Stress psychologique/psychologie , SARS-CoV-2 , Pratiques éducatives parentales/psychologie , Attitude , Adulte d'âge moyen
4.
Cancer Innov ; 3(5): e139, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39257440

RÉSUMÉ

Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

7.
Ther Adv Hematol ; 15: 20406207241270806, 2024.
Article de Anglais | MEDLINE | ID: mdl-39149576

RÉSUMÉ

Background: Generics imatinib became an alternative treatment option for chronic myeloid leukemia (CML) patients in China. However, clinicians and patients alike harbor concerns regarding the long-term safety of generic imatinib. Objectives: Patients with chronic phase CML receiving frontline imatinib treatment. Design: A retrospective study was used to evaluate the blood concentration, effectiveness, and safety of generic in 170 CML patients. Methods: Imatinib plasma concentrations were detected by high-performance liquid chromatography-tandem mass spectrometry. Results: Among the 170 patients, 73 (42.9%) patients treated with branded imatinib as first-line therapy, while 22 (12.9%) switched to generic imatinib during treatment due to economic considerations. No significant differences in trough concentrations between branded and generic imatinib (1549.9 ± 648.8 ng/mL vs 1479.0 ± 507.0 ng/mL; p = 0.95). During the 2-year follow-up, there were no significant differences in molecular response rates (major molecular response (MMR): 33.3% vs 37.0%; deep molecular response: 56.9% vs 42.9%, p = 0.17) between the branded and generic imatinib. Both groups showed similar rates of switching to second-generation tyrosine kinase inhibitor (11.8% vs 15.1%, p = 0.56). Furthermore, there were no significant differences in event-free survival or failure-free survival between branded and generic imatinib. Twenty-two (12.9%) switched to generic imatinib during treatment, 68.2% maintained their level of response, 27.3% improved, and only one patient (4.5%) lost MMR. There were no significant differences in the incidence of various adverse events. Conclusion: Generic imatinib are equally effective and safe compared to branded molecules, both for newly diagnosed patients and those who switch from branded.

8.
Article de Anglais | MEDLINE | ID: mdl-39190880

RÉSUMÉ

Glioblastomas (GBM), the most common primary brain tumor, lack accurate prognostic markers and have a poor prognosis. Our study was designed to identify effective biomarkers for GBM prognosis analysis and development of precise treatments. Differentially expressed genes (DEGs) between GBM patients and controls were analyzed from the Xena database and GEPIA. Based on the screened DEGs, univariate COX and LASSO regression analysis were performed to identify the most relevant genes associated with GBM prognosis. Genes highly expressed in GBM patients were selected to construct receiver operating characteristic analysis and enrichment analysis was constructed on groups of high and low expression of adipocyte enhancer-binding protein 1 (AEBP1). CIBERSORT, ssGSEA and ESTIMATE were used to perform immune infiltration analysis. About 3297 DEGs were identified using data from Xena database; 8 prognostic genes were identified. AEBP1, which plays a role in neuronal differentiation and development, was positively correlated in GBMs with immune infiltration; its high expression in cancer patients is associated with short overall survival and advanced tumor staging. This study suggests that AEBP1 could serve as a prognostic marker for GBMs and that patients with high expression may have a better response to immunotherapy.

9.
Biomaterials ; 313: 122757, 2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-39178558

RÉSUMÉ

Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.

10.
J Craniofac Surg ; 2024 Aug 28.
Article de Anglais | MEDLINE | ID: mdl-39194192

RÉSUMÉ

BACKGROUND: The authors retrospectively analyzed the perioperative data of 81 patients who underwent cranial tumor surgery to explore the factors influencing POCD in patients after the surgery. METHODS: The authors evaluated preoperative cognitive dysfunction using the Mini-Mental State Examination (MMSE) score measured. For patients whose cognitive function was normal, the authors retrieved the MMSE score on the seventh day after surgery and compared it to determine whether the patients had POCD. The authors used a univariate logistic regression analysis to analyze the perioperative factors in patients, namely, age, gender, history of underlying diseases, tumor size, peritumoral edema, duration of surgery, blood loss, intraoperative fluid infusion, and type of anesthetic drugs. The authors then performed a multivariate logistic regression analysis for the statistically significant factors. RESULTS: The authors found that 23 of 81 patients (28.4%) developed POCD. Univariate logistic analysis showed that a history of diabetes mellitus, peritumoral edema, intraoperative blood loss, and anesthetic drugs were the risk factors for patients developing POCD after cranial tumor surgery. Multivariate logistic regression analysis showed that a history of diabetes mellitus, peritumoral edema, and use of ciprofol as the anesthetic drug were independent risk factors for POCD after cranial tumor surgery. CONCLUSIONS: A history of diabetes mellitus, the degree of brain tumor edema, and the choice of anesthetic drugs significantly influence the occurrence of POCD in patients after cranial tumor surgery.

11.
Pediatr Neonatol ; 2024 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-39127594

RÉSUMÉ

BACKGROUND: The present research aimed to investigate the clinical value of plasma miR-190 in children with acute respiratory distress syndrome (ARDS) and the impact of miR-190 on LPS-induced ARDS cell models. METHODS: The plasma miR-190 levels were measured using real-time quantitative reverse transcription PCR (RT-qPCR). LPS-treated human pulmonary microvascular endothelial cells (HPMECs) were established and then transfected with miR-190 mimic, inhibitor, or miR-negative controls. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The effects of miR-190 on HPMEC proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry. The regulation of KLF15 by miR-190 was detected by luciferase report assay. RESULTS: The plasma miR-190 expression was increased in ARDS children and it was positively related to the severity and 28 day-survival. Plasma miR-190 could distinguish ARDS children from healthy children. Inhibition of miR-190 increased LPS-induced HPMEC cell proliferation and decreased cell apoptosis and inflammatory cytokines IL-6, IL-1ß, and TNF-α. KLF15 was a direct target of miR-190. CONCLUSION: Increased plasma miR-190 may be a clinical diagnostic and prognostic predictor for ARDS children. Inhibition of miR-190 may improve LPS-induced ARDS by increasing cell proliferation, inhibiting cell apoptosis and inflammatory response by targeting KLF15.

12.
J Hazard Mater ; 477: 135105, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-39047551

RÉSUMÉ

Incense-burning smoke is a deleterious air pollutant that initiates cytotoxic effects by inducing apoptosis in lung epithelial cells and also acts as a risk factor for lung cancers. Auramine, an ingredient of incense smoke, has been implicated in tumor progression and cellular sensitivity in non-small cell lung cancer (NSCLC) towards anti-cancer agents through unclear mechanisms. Tumor protein p53 (TP53)-activated long intergenic non-coding RNA-p21 (lincRNA-p21) undertakes a pivotal role in regulating cell apoptosis and chemosensitivity. TP53 mutations prevalent in 50% of NSCLC, contribute to diminished therapeutic efficacy. However, the influence of auramine on chemotherapy-induced lincRNA-p21 expression and apoptosis in NSCLC with different TP53 genetic statuses remains unexplored. This study disclosed that both wild-type p53 (wtp53) and mutant p53 (mutp53) mediate lincRNA-p21 expression, albeit through distinct promoter enhancers, p53-response element (p53RE) and non-B DNA structure G-quadruplex (GQ), respectively. Intriguingly, auramine functions as an effective stabilizer of the GQ structure, augmenting mutp53-mediated lincRNA-p21 expression and enhancing apoptosis and cellular sensitivity to chemotherapy in mutp53-expressing NSCLC cells. These findings suggest a mechanism by which mutp53, in the presence of auramine, is endowed with tumor-suppressing function akin to wtp53, thereby aiding in combating chemoresistance in NSCLC cells harboring TP53 mutations.


Sujet(s)
Antinéoplasiques , Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Mutation , ARN long non codant , Protéine p53 suppresseur de tumeur , Humains , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/anatomopathologie , Carcinome pulmonaire non à petites cellules/métabolisme , Protéine p53 suppresseur de tumeur/génétique , Protéine p53 suppresseur de tumeur/métabolisme , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , ARN long non codant/génétique , ARN long non codant/métabolisme , Mutation/effets des médicaments et des substances chimiques , Antinéoplasiques/pharmacologie , Apoptose/effets des médicaments et des substances chimiques , Fumée/effets indésirables , Lignée cellulaire tumorale , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques
13.
J Homosex ; : 1-21, 2024 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-39083042

RÉSUMÉ

This qualitative study was conducted to understand how gay and bisexual men (GBM) in Taiwan cope with childhood bullying because of their sexual orientation or gender nonconformity. We explored their journey from feeling disturbed to receiving social support, developing coping strategies, and achieving self-growth. Colaizzi's phenomenological approach was used to investigate subject experiences. Semi-structured interviews were conducted with 21 GBM who had experienced high-level sexual bullying in childhood. Relevant data were collected to assess their experiences of sexual bullying, their coping strategies, and subjective effects of corresponding adjustments in interpersonal interactions. Subject experiences concentrated on six themes related to sexual bullying and coping strategies: bullying at developmental stages, bullying everywhere, facing bullying alone, various impacts of bullying, overcoming challenges of interpersonal relationships, and building a strong and carefree self. Our findings can provide mental health professionals with key insights into the contexts of sexual bullying and the associated psychological distress in GBM. This study further clarifies the coping responses of these individuals and their psychological growth following such adverse experiences.

14.
Article de Anglais | MEDLINE | ID: mdl-38961535

RÉSUMÉ

Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.


Sujet(s)
Tumeurs du poumon , Protéomique , Carcinome pulmonaire à petites cellules , Humains , Carcinome pulmonaire à petites cellules/anatomopathologie , Carcinome pulmonaire à petites cellules/mortalité , Carcinome pulmonaire à petites cellules/thérapie , Carcinome pulmonaire à petites cellules/génétique , Carcinome pulmonaire à petites cellules/métabolisme , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/mortalité , Tumeurs du poumon/génétique , Tumeurs du poumon/métabolisme , Tumeurs du poumon/thérapie , Protéomique/méthodes , Pronostic , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Immunothérapie , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Protéome
15.
Article de Anglais | MEDLINE | ID: mdl-39002064

RÉSUMÉ

INTRODUCTION: Acute appendicitis is one of the most common acute abdominal issues requiring surgery and is usually treated by appendectomy. During the process of removing the appendix, the appendiceal artery is severed. In most individuals, the appendix is supplied by only one appendiceal artery. CASE PRESENTATION: A 50-year-old man underwent appendectomy. During the surgical procedure, the appendix artery and two accessory arteries of the appendix were severed, leading to massive hemorrhaging in the abdominal cavity, which ultimately resulted in the patient's unfortunate demise. CONCLUSION: Through this case, we hope that surgeons can learn more about the anatomy of the appendiceal artery and understand the possibility of accessory arteries to the appendix. During surgery, the blood vessels supplying the appendix should be carefully explored, and the "one-size-fits-all approach" should be avoided. Moreover, attention should be given to complications after appendectomy, and timely symptomatic treatment should be provided. Key points 1. Rare typing: The case of death due to improper handling of the accessory appendicular artery during appendectomy in patients with three appendiceal arteries is currently unreported. 2. Detailed anatomical knowledge: Surgeons performing an appendectomy need to make a detailed exploration of the blood vessel supply of the appendix to avoid ignoring anatomically different blood vessels. 3. Avoid a one-size-fits-all approach: In the surgical process, a "one-size-fits-all" approach should be avoided, that is, the same surgical approach should not be used in all cases, but should be adjusted according to the anatomical characteristics of the individual. 4. Observation of postoperative bleeding: In the perioperative period, peritoneal drainage should be closely observed. If a large amount of bloody fluid is found, timely surgical treatment should be carried out. 5. Attention to complications: Surgeons should pay.

16.
Pediatr Int ; 66(1): e15764, 2024.
Article de Anglais | MEDLINE | ID: mdl-38995187

RÉSUMÉ

BACKGROUND: The objective of this study was to develop the Parenting Difficulties in Infectious Disease Pandemic Inventory (PDIDPI) for the assessment of parenting difficulties during the coronavirus disease 2019 (COVID-19) pandemic and to examine its psychometric properties. METHODS: The 31-item PDIDPI was developed on the basis of the results of focus group interviews. An exploratory factor analysis using principal axis factoring was conducted to examine the PDIDPI factor structure. The internal consistency was assessed using Cronbach α values. The test-retest reliability was assessed using the intraclass correlation coefficient (ICC). The concurrent validity was established by examining the correlations of the PDIDPI with Fear of COVID-19 Scale and Center for Epidemiologic Studies Depression Scale (CESD) scores. RESULTS: We determined that the PDIDPI has seven factors: infection, school and learning, life change, care burden, daily living, health care, and emotion and behavior. The PDIDPI also had good internal consistency (α = 0.685-0.929) and acceptable test-retest reliability (ICC = 0.404-0.794). Regarding concurrent validity, the overall PDIDPI and its seven factors were all significantly associated with depression, determined by the CESD (r = 0.223-0.370), but not all factors were significantly associated with fear of COVID-19 (r = 0.082-0.203). CONCLUSIONS: Our findings support the psychometric properties of the PDIDPI, confirming its utility for evaluating the multifaceted challenges parents face in child management during the COVID-19 pandemic.


Sujet(s)
COVID-19 , Pratiques éducatives parentales , Psychométrie , Humains , COVID-19/psychologie , COVID-19/épidémiologie , Psychométrie/méthodes , Pratiques éducatives parentales/psychologie , Femelle , Mâle , Reproductibilité des résultats , Adulte , Enquêtes et questionnaires , Enfant , SARS-CoV-2 , Groupes de discussion , Japon/épidémiologie , Dépression/épidémiologie , Dépression/psychologie , Dépression/diagnostic , Pandémies , Analyse statistique factorielle , Parents/psychologie , Enfant d'âge préscolaire
17.
Int J Biol Sci ; 20(9): 3257-3268, 2024.
Article de Anglais | MEDLINE | ID: mdl-38993553

RÉSUMÉ

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo. Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke.


Sujet(s)
Tumeurs osseuses , Mouvement cellulaire , Interleukine-6 , Tumeurs du poumon , Interleukine-6/métabolisme , Tumeurs du poumon/métabolisme , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/secondaire , Humains , Tumeurs osseuses/secondaire , Tumeurs osseuses/métabolisme , Animaux , Souris , Transduction du signal , Lignée cellulaire tumorale , Ostéolyse/métabolisme , Fumée/effets indésirables , Fumer/effets indésirables
18.
Viruses ; 16(7)2024 Jul 17.
Article de Anglais | MEDLINE | ID: mdl-39066313

RÉSUMÉ

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but it also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for an HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. A mechanistic study using Biacore and docking analysis revealed that YZH-106 bound directly to the PreS2 domain of L- and M-HBsAg, thereby blocking their entry into the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provides the basis for the design of a novel compound therapy to target HBsAg against HBV infection.


Sujet(s)
Antigènes de surface du virus de l'hépatite B , Virus de l'hépatite B , Lysosomes , Réplication virale , Humains , Virus de l'hépatite B/effets des médicaments et des substances chimiques , Virus de l'hépatite B/génétique , Antigènes de surface du virus de l'hépatite B/métabolisme , Lysosomes/métabolisme , Réplication virale/effets des médicaments et des substances chimiques , Hépatite B/virologie , Hépatite B/traitement médicamenteux , Antiviraux/pharmacologie , Protéolyse , Cellules HepG2 , Hépatocytes/virologie , Hépatocytes/métabolisme , Simulation de docking moléculaire , Liaison aux protéines , Précurseurs de protéines
19.
J Neuroimmune Pharmacol ; 19(1): 38, 2024 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-39066908

RÉSUMÉ

Repetitive exposure of innate immune cells to a subthreshold dosage of endotoxin components may modulate inflammatory responses. However, the regulatory mechanisms in the interactions between the central nervous system (CNS) and the immune system remain unclear. This study aimed to investigate the effects of lipopolysaccharide (LPS) preconditioning in repeated social defeat stress (RSDS)-induced abnormal immune responses and behavioral impairments. This study aimed to elucidate the mechanisms that underlie the protective effects of repeated administration of a subthreshold dose LPS on behavioral impairments using the RSDS paradigm. LPS preconditioning improved abnormal behaviors in RSDS-defeated mice, accompanied by decreased monoamine oxidases and increased glucocorticoid receptor expression in the hippocampus. In addition, pre-treated with LPS significantly decreased the recruited peripheral myeloid cells (CD11b+CD45hi), mainly circulating inflammatory monocytes (CD11b+CD45hiLy6ChiCCR2+) into the brain in response to RSDS challenge. Importantly, we found that LPS preconditioning exerts its protective properties by regulating lipocalin-2 (LCN2) expression in microglia, which subsequently induces expressions of chemokine CCL2 and pro-inflammatory cytokine. Subsequently, LPS-preconditioning lessened the resident microglia population (CD11b+CD45intCCL2+) in the brains of the RSDS-defeated mice. Moreover, RSDS-associated expressions of leukocytes (CD11b+CD45+CCR2+) and neutrophils (CD11b+CD45+Ly6G+) in the bone marrow, spleen, and blood were also attenuated by LPS-preconditioning. In particular, LPS preconditioning also promoted the expression of endogenous antioxidants and anti-inflammatory proteins in the hippocampus. Our results demonstrate that LPS preconditioning ameliorates lipocalin 2-associated microglial activation and aberrant immune response and promotes the expression of endogenous antioxidants and anti-inflammatory protein, thereby maintaining the homeostasis of pro-inflammation/anti-inflammation in both the brain and immune system, ultimately protecting the mice from RSDS-induced aberrant immune response and behavioral changes.


Sujet(s)
Lipopolysaccharides , Souris de lignée C57BL , Défaite sociale , Stress psychologique , Animaux , Lipopolysaccharides/toxicité , Souris , Mâle , Stress psychologique/immunologie , Microglie/effets des médicaments et des substances chimiques , Microglie/métabolisme , Microglie/immunologie , Comportement animal/effets des médicaments et des substances chimiques , Hippocampe/effets des médicaments et des substances chimiques , Hippocampe/métabolisme , Hippocampe/immunologie , Lipocaline-2/métabolisme
20.
Neurochem Int ; 179: 105811, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39053771

RÉSUMÉ

Psychological stress induces neuroinflammatory responses, which are associated with the pathogenesis of various psychiatric disorders, such as posttraumatic stress disorder and anxiety. Osthole-a natural coumarin isolated from the seeds of the Chinese herb Cnidium monnieri-exerts anti-inflammatory and antioxidative effects on the central nervous system. However, the therapeutic benefits of osthole against psychiatric disorders remain largely unknown. We previously demonstrated that mice subjected to repeated social defeat stress (RSDS) in the presence of aggressor mice exhibited symptoms of posttraumatic stress disorder, such as social avoidance and anxiety-like behaviors. In this study, we investigated the therapeutic effects of osthole and the underlying molecular mechanisms. Osthole exerted therapeutic effects on cognitive behaviors, mitigating anxiety-like behaviors and social avoidance in a mouse model of RSDS. The anti-inflammatory response induced by the oral administration of osthole was strengthened through the upregulation of heme oxygenase-1 expression. The expression of PPARα was inhibited in mice subjected to RSDS. Nonetheless, osthole treatment reversed the inhibition of PPARα expression. We identified a positive correlation between heme oxygenase-1 expression and PPARα expression in osthole-treated mice. In conclusion, osthole has potential as a Chinese herbal medicine for anxiety disorders. When designing novel drugs for psychiatric disorders, researchers should consider targeting the activation of PPARα.


Sujet(s)
Coumarines , Récepteur PPAR alpha , Défaite sociale , Stress psychologique , Animaux , Mâle , Souris , Administration par voie orale , Anxiété/traitement médicamenteux , Anxiété/métabolisme , Comportement animal/effets des médicaments et des substances chimiques , Coumarines/pharmacologie , Coumarines/administration et posologie , Souris de lignée C57BL , Récepteur PPAR alpha/métabolisme , Stress psychologique/traitement médicamenteux , Stress psychologique/métabolisme
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