RESUMEN
Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.
Asunto(s)
Indoles , Polímeros , Neoplasias de la Mama Triple Negativas , Xantonas , Xantonas/química , Xantonas/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Indoles/química , Indoles/farmacología , Polímeros/química , Humanos , Animales , Línea Celular Tumoral , Femenino , Porosidad , Ratones , Nanopartículas/químicaRESUMEN
Smart nanoparticles, which can respond to biological cues or be guided by them, are emerging as a promising drug delivery platform for precise cancer treatment. The field of oncology, nanotechnology, and biomedicine has witnessed rapid progress, leading to innovative developments in smart nanoparticles for safer and more effective cancer therapy. In this review, we will highlight recent advancements in smart nanoparticles, including polymeric nanoparticles, dendrimers, micelles, liposomes, protein nanoparticles, cell membrane nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, iron oxide nanoparticles, quantum dots, carbon nanotubes, black phosphorus, MOF nanoparticles, and others. We will focus on their classification, structures, synthesis, and intelligent features. These smart nanoparticles possess the ability to respond to various external and internal stimuli, such as enzymes, pH, temperature, optics, and magnetism, making them intelligent systems. Additionally, this review will explore the latest studies on tumor targeting by functionalizing the surfaces of smart nanoparticles with tumor-specific ligands like antibodies, peptides, transferrin, and folic acid. We will also summarize different types of drug delivery options, including small molecules, peptides, proteins, nucleic acids, and even living cells, for their potential use in cancer therapy. While the potential of smart nanoparticles is promising, we will also acknowledge the challenges and clinical prospects associated with their use. Finally, we will propose a blueprint that involves the use of artificial intelligence-powered nanoparticles in cancer treatment applications. By harnessing the potential of smart nanoparticles, this review aims to usher in a new era of precise and personalized cancer therapy, providing patients with individualized treatment options.
Asunto(s)
Nanopartículas del Metal , Nanotubos de Carbono , Neoplasias , Humanos , Oro/uso terapéutico , Inteligencia Artificial , Neoplasias/tratamiento farmacológico , Neoplasias/patología , PéptidosRESUMEN
BACKGROUND: The number of children in sexual minority parent families has increased. This systematic review aims to synthesise the evidence of disparities in family outcomes between sexual minority and heterosexual families and to identify specific social risk factors of poor family outcomes. METHODS: We systematically searched PubMed, the Web of Science, Embase, the Cochrane Library and APA PsycNet for original studies that compared family outcomes between sexual minority and heterosexual families. Two reviewers independently selected studies and assessed the risk of bias of included studies. Narrative synthesis and meta-analysis were conducted to synthesise evidence. RESULTS: Thirty-four articles were included. The narrative synthesis results revealed several significant findings for children's gender role behaviour and gender identity/sexual orientation outcomes. Overall, 16 of 34 studies were included in the meta-analyses. The quantitative synthesis results suggested that sexual minority families may perform better in children's psychological adjustment and parent-child relationship than heterosexual families (standardised mean difference (SMD) -0.13, 95% CI -0.20 to -0.05; SMD 0.13, 95% CI 0.06 to 0.20), but not couple relationship satisfaction (SMD 0.26, 95% CI -0.13 to 0.64), parental mental health (SMD 0.00, 95% CI -0.16 to 0.16), parenting stress (SMD 0.01, 95% CI -0.20 to 0.22) or family functioning (SMD 0.18, 95% CI -0.11 to 0.46). CONCLUSION: Most of the family outcomes are similar between sexual minority and heterosexual families, and sexual minority families have even better outcomes in some domains. Relevant social risk factors of poor family outcomes included stigma and discrimination, poor social support and marital status, etc. The next step is to integrate multiple aspects of support and multilevel interventions to reduce the adverse effects on family outcomes with a long-term goal of influencing policy and law making for better services to individuals, families, communities and schools.
Asunto(s)
Identidad de Género , Heterosexualidad , Masculino , Humanos , FemeninoRESUMEN
The relationship between baseline BMI and CD4+ T cells during follow-up in HIV patients in China requires further evaluation. We conducted a retrospective cohort study based on adult AIDS patients who underwent or received antiretroviral therapy from 2003 to 2019 in Guangxi, China. BMI was divided into categories and compared, and after adjusting for BMI being related to the change in CD4 lymphocyte count, with normal weight as the reference group, the BMI before treatment was positively correlated with the changes in CD4+ T cells at different time periods. Among them, obese patients had significant CD4+ cell gain. In patients with pretreatment CD4+ T lymphocyte counts <200 cells/µL, a higher BMI was associated with an increased likelihood of achieving immunologic reconstitution [≥350 cells/µL: AHR: 1.02(1.01, 1.04), P = 0.004; ≥500 cells/µL: AHR: 1.03 (1.01, 1.05), P = 0.004]. Underweight in HIV patients was a risk factor for poor viral suppression [AHR: 1.24 (1.04, 1.48), P = 0.016]. Our study demonstrated that HIV/AIDS patients receiving ART with higher baseline BMI had better immune reconstitution and that baseline BMI could be an important predictor of immune reconstitution in patients receiving ART. Baseline BMI was not associated with virological failure, but a lower baseline BMI indicated poor viral suppression during follow-up.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Adulto , Humanos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Índice de Masa Corporal , Estudios Retrospectivos , Terapia Antirretroviral Altamente Activa , China , Linfocitos T CD4-Positivos , Recuento de Linfocito CD4 , Antivirales/uso terapéutico , Carga ViralRESUMEN
INTRODUCTION: HIV self-testing (HIVST) provides a key measure for the early detection of HIV infection in men who have sex with men (MSM). However, dual HIV/syphilis self-testing in the MSM population has not been studied. We describe a randomised controlled trial to evaluate the effect of dual HIV/syphilis self-testing on the testing frequency among MSM in China. METHODS AND ANALYSIS: This randomised controlled trial will be implemented in Guangxi, China. 330 MSM, including 255 frequent testers and 75 less frequent testers, will be recruited and randomly assigned in a 1:1:1 ratio into one of three arms: a site-based testing arm, a single HIVST arm and a dual HIV/syphilis self-testing arm. Participants in the single HIVST arm and dual HIV/syphilis self-testing arm will receive two free finger-prick-based HIVST or HIV/syphilis self-testing kits at enrolment. The data will be collected at five separate times: baseline, 3 months, 6 months, 9 months and 12 months. The primary outcome is the mean frequency of HIV testing used by MSM after intervention comparing each group during the study period. The secondary outcome includes changes in sex behaviours (eg, number of male sex partners and the proportion of consistent condom use) and the mean number of HIV tests used by the social network members over the study period. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Medical Ethics Committee of Guangxi Medical University, China (20210173). The study results will be disseminated through conferences and academic journals. TRIAL REGISTRATION NUMBER: ChiCTR2100050898.
Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Sífilis , China/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH , Homosexualidad Masculina , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Autoevaluación , Encuestas y Cuestionarios , Sífilis/diagnósticoRESUMEN
BACKGROUND: HIV self-testing (HIVST) is a potential strategy to overcome challenges of HIV testing among men who have sex with men (MSM). However, for resource-limited settings, technology and diagnostic devices are lagging. Hence, we estimated the status and correlates of HIVST among MSM in resource-limited settings in China to inform the development of HIVST to reach United Nations Programme on HIV and AIDS (UNAIDS) targets to end HIV by 2030. METHODS: A cross-sectional study was conducted among MSM in Nanning, Guangxi, China, between August 2019 and January 2020. The HIVST status was collected and data on social network features, sociodemographic information, risk behaviours, etc. were compared between prior- and non-HIVST MSM. Logistic regression analyses were conducted to examine the correlates of HIVST. RESULTS: The prevalence of HIVST among 446 MSM was 40.4% (95% confidence interval [CI] 35.8-44.9%). The main component of sociocentric network contains more prior-HIVST MSM (38.3%) than non-HIVST MSM (28.6%, P =0.031). More MSM with individual features such as substance use during anal sex (22.8% vs 15.4%, P =0.049) and multiple sexual partners (76.1% vs 59.4%, P <0.001) were detected among prior-HIVST MSM. In multivariable analysis, prior HIVST was associated with the strong strength of ego-alter ties in the egocentric network (adjusted odds ratio [aOR] 1.72; 95% CI 1.09-2.71), HIV-infected partners (aOR, 7.17; 95% CI, 1.40-36.60), and vaginal intercourse (aOR, 0.38; 95% CI, 0.17-0.85). CONCLUSIONS: HIVST coverage among MSM in resource-limited settings is suboptimal. Integrating social networks into testing services may be viable to promote HIVST in MSM within resource-limited settings.
Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , China/epidemiología , Estudios Transversales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH , Homosexualidad Masculina , Humanos , Masculino , AutoevaluaciónRESUMEN
INTRODUCTION: This study aimed to investigate sexual orientation disclosure and mental health among young men who have sex with men (YMSMs). To this end, we constructed a chained multimediator model of sexual minority stigma, sexual minority identity, social support, and resilience, with the moderator of sexual orientation disclosure. METHODS: We conducted a cross-sectional survey of 345 YMSMs in Nanning, China. Bivariate analysis was used to evaluate factors associated with sexual orientation disclosure. Sexual minority stigma was used to predict identity, with social support as the step 1 mediator and resilience as the step 2 mediator. Sexual minority identity was analyzed using a chained moderated mediation model; sexual orientation disclosure was included as a moderator in all models to control its confounding effect. RESULTS: The average age of YMSMs was 20.0 ± 1.3 years. Bivariate analysis indicated that YMSMs who disclosed sexual orientation may have experienced less stigma (15.49 ± 3.02 vs 16.21 ± 2.74), obtained more social support (65.98 ± 11.18 vs 63.19 ± 11.13), had strong psychological resilience (37.40 ± 8.57 vs 35.39 ± 7.73), and had a more positive self-identity (104.12 ± 21.10 vs 95.35 ± 16.67); differences between subgroups were statistically significant (p < 0.05). Sexual minority stigma, perceived stigma, and enacted stigma were significantly associated with social support and resilience. The association between sexual minority stigma and sexual minority identity was significantly mediated by social support (indirect effect [95% CI] = - 3.307 [- 4.782, - 1.907]). Resilience significantly mediated the same association for identity (- 2.544 [- 4.052, - 1.114]). The chained relationship from sexual minority stigma to social support, resilience, and identity was also significant, with an indirect effect of - 0.404 [- 0.621, - 0.249]. CONCLUSION: Among YMSMs in China, sexual minority stigma affects sexual minority identity through social support and resilience. Given the psychological effects of stigma, social support and resilience must be considered to better promote positive self-identity and mental health among YMSMs.