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1.
J Agric Food Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597928

RESUMO

Spinosad is a potent insecticide produced by Saccharopolyspora spinosa. However, it harbors certain limitations of a low growing rate and unfeasible genetic manipulation that can be overcome by adopting a superior platform, such as Streptomyces. Herein, we exploited the industrial tylosin-producing Streptomyces fradiae J1-021 for the heterologous production of spinosad. An engineered strain (HW01) with deletion of the tylosin biosynthetic gene cluster (BGC) was constructed and then transformed with the natural spinosad BGC. The distribution and expression levels of the tylosin BGC operons were assessed to construct a natural promoter library. The rate-limiting steps of spinosad biosynthesis were identified by analyzing the transcriptional expression of the spinosad biosynthetic genes. The stepwise engineering work involved the overexpression of the biosynthetic genes participating in rate-limiting pathways using strong promoters, affording an increase in spinosad production to 112.4 µg/L. These results demonstrate that strain HW01 has the potential to be used as a chassis for the heterologous production of polyketides.

2.
Mol Carcinog ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441297

RESUMO

Bladder cancer (BC) is a common and malignant tumor of the urinary tract, and its treatment options are limited. Tectoridin (TEC) has antitumor activity against prostate and colon cancer, but its effects on BC are poorly understood. BC cells were treated with increasing concentrations of TEC, and its effects on cell proliferation, migration, invasiveness, and apoptosis were assessed. Xenograft mouse model was used to evaluate the influences of TEC on BC tumor growth. Western blot analysis was conducted to explore the downstream pathways affected by TEC. TEC treatment decreased BC cell viability in a dose-dependent manner (IC50 ≈ 25 µM), and inhibited cell proliferation, migration, and invasiveness while promoting apoptosis. Clinical analysis revealed high expression of RAB27B in BC tumor tissues, particularly in advanced stages, correlating with an unfavorable prognosis. In vitro experiments demonstrated that TEC suppressed the PI3K/MAPK pathway by targeting RAB27B, and overexpression of RAB27B counteracted the antitumor effects of TEC. In xenograft models, TEC administration suppressed tumor growth, reduced tumor volume, inhibited cell proliferation, and suppressed the PI3K/MAPK pathway, highlighting its potential as an inhibitor of tumor growth. TEC suppresses BC tumor growth by targeting RAB27B and inactivating the PI3K/MAPK signaling and may provide a promising therapeutic target for BC treatment.

3.
AIDS Behav ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329557

RESUMO

Prior studies demonstrated that perceived social support is negatively associated with behavioral and mental health problems among people living with HIV (PLWH). However, longitudinal data regarding the associations between perceived social support, internalized HIV stigma, future orientation, and depressive symptoms are limited. The current study aimed to investigate the possible indirect relationship between these variables using four-wave follow-up data (6-month intervals) from a sample of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20, age range: 18-60 years; 63.9% men). All participants were asked to complete an adapted version of Perceived Social Support Scale, Internalized HIV Stigma Scale, Optimism About the Future Scale, and Center of Epidemiological Studies Depression Scale. Results indicated that perceived social support at baseline was negatively related to depressive symptoms at wave 4. Internalized HIV stigma at wave 2 and future orientation at wave 3 indirectly affected the linkage between perceived social support at baseline and depressive symptoms serially over time. This study highlights the essential role of perceived social support in alleviating depressive symptoms among PLWH, and underscores the complex interplay in which internalized HIV stigma and future orientation serially mediated the relationship between perceived social support and depressive symptoms. These findings suggest the need for integrated interventions to enhance social support, address HIV-related stigma, and promote positive future orientation, which could potentially alleviate depressive symptoms and promote mental well-being among PLWH.

4.
AIDS Behav ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334862

RESUMO

Prescription opioid misuse (POM) among people living with HIV (PLWH) is a serious concern due to risks related to dependence and overdose, and PLWH may be at higher risk for POM due to psychosocial stressors including psychological distress. However, scant POM research has examined the role of HIV-related stigma (e.g., internalized stigma, enacted stigma) in POM among PLWH. Guided by minority stress theory, this study examined a hypothesized serial mediation among enacted stigma, internalized stigma, psychological distress, and POM within a sample of Chinese PLWH with pain symptoms enrolled in a wave (between November 2017 and February 2018) of a longitudinal cohort study in Guangxi (n = 116). Models were tested individually for six enacted stigma experiences, controlling for key demographic and health-related variables (e.g., CD4 + count). Results showed HIV-related workplace discrimination was the most common stigma experience (12%,) and 10.3% of PLWH reported POM. Indirect effect analyses showed that internalized stigma was indirectly associated with POM through psychological distress. Internalized stigma and psychological distress mediated the association between workplace discrimination and POM. Family discrimination, gossip, and healthcare discrimination were directly associated with POM. This study suggests that Chinese PLWH may engage in POM to cope with psychological distress that is rooted in HIV-related stigma and highlights the important context of workplace discrimination for PLWH. Implications for interventions to reduce POM among PLWH are discussed.

5.
AIDS Behav ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340222

RESUMO

Prior research has documented that anticipated HIV stigma may play an important predictive role in medication adherence among people living with HIV (PLWH). However, longitudinal data on the mechanisms underlying this linkage are scarce. The current study aimed to explore the longitudinal mediation association among anticipated HIV stigma, medication adherence support, HIV self-management, and medication adherence. A four-wave sample consisting of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20; 63.9% male) with a six-month interval was used in the current study. Participants were asked to complete self-report questionnaires. A path analysis model was analyzed. Results indicate that anticipated HIV stigma at baseline was positively related to medication adherence at Time 4 (T4). Medication adherence support at Time 2 (T2) and HIV self-management at Time 3 (T3) serially mediated the anticipated HIV stigma at Time 1 (T1) and medication adherence at T4. These findings provide critical insights into the mediating roles of medication adherence support and HIV self-management in the relationship between anticipated HIV stigma and medication adherence over time. Such an understanding has important implications for the development of tailored interventions and public health strategies aimed at improving medication adherence among PLWH in the context of HIV-related stigma.

6.
AIDS Care ; : 1-9, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289470

RESUMO

Parental HIV disclosure, where parents living with HIV (PLH) communicate their diagnosis to their children, is crucial for family communication. This study assessed intervention effects of a parental HIV disclosure intervention on psychosocial factors, focusing on child's age impact. Data from a randomized controlled trial involving 791 PLH in China were analyzed at baseline (W1), 6-month (W2), and 12-month follow-ups (W3). The study measured effects on psychosocial factors (HIV disclosure knowledge, outcome expectancy, action self-efficacy, and action planning) using the proportional latent change score method. Among PLH with children aged 6-9, the intervention yielded significant intervention effects on knowledge (ß = 0.190, p = .004), action self-efficacy (ß = 0.342, p = .001), and action planning (ß = 0.389, p < .001) from W1 to W2. For PLH with children aged 10-12, the intervention significantly enhanced action self-efficacy (ß = 0.162, p = .003) and action planning (ß = 0.367, p = .001) from W1 to W2, but there was a reduction in perceived benefits (ß = -0.175, p = 0.024) from W2 to W3. For PLH with children aged 13-15, significant intervention effects were observed on action planning, both from W1 to W2 (ß = 0.251, p = .045) and from W2 to W3 (ß = 0.321, p < .001). These findings highlight the importance of tailoring interventions to consider psychosocial factors and children's developmental stages to enhance HIV disclosure practices.

7.
AIDS Behav ; 28(2): 439-449, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38048016

RESUMO

Prior studies have demonstrated that HIV-related stigma (e.g., internalized HIV stigma) is detrimental to the physical and mental health (e.g., sleep impairment and depressive symptoms) of people living with HIV (PLWH). However, follow-up data are limited regarding the longitudinal relationships between internalized HIV stigma, future orientation, self-esteem, depressive symptoms, and sleep impairment. The present study attempted to examine a mediation model involving these variables among Chinese PLWH. A two-wave follow-up design (6 months intervals) was employed in a final sample of 1,140 Chinese PLWH (Mage = 41.63, SD = 9.29, age range: 21-67 years; 64.6% men). Participants completed Internalized HIV Stigma Scale, Optimism About the Future Scale, Rosenberg Self-Esteem Scale, Center of Epidemiological Studies Depression Scale, and an adapted version of Pittsburgh Sleep Quality Index. Results revealed that internalized HIV stigma at baseline had a significant direct relationship with sleep impairment over time, and a significant indirect relationship with increased sleep impairment over time via future orientation and depressive symptoms. Furthermore, the linkage between internalized HIV stigma and sleep impairment was serially mediated via self-esteem and depressive symptoms. This study highlights the deleterious effects of internalized HIV stigma on the physical and psychological health of PLWH. The findings suggest that interventions targeting internalized HIV stigma and related factors such as future orientation, self-esteem, and depressive symptoms may facilitate improvements in sleep quality and overall well-being among PLWH.


Assuntos
Depressão , Infecções por HIV , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Seguimentos , Depressão/epidemiologia , Depressão/psicologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Estigma Social , Sono , China/epidemiologia
8.
Asian J Surg ; 47(1): 134-139, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37225568

RESUMO

BACKGROUND: Although the laparoscopic treatment of pediatric inguinal hernia (PIH) has more benefits than traditional surgery, it is difficult to completely avoid the problem of recurrence. The aim of this study was to use a logistic regression model to investigate the causes of recurrence after laparoscopic percutaneous extraperitoneal repair (LPER) of PIH. PATIENTS AND METHODS: From June 2017 to December 2021, 486 cases of PIH were performed using LPER in our department. We utilized a two-port approach to implement LPER for PIH. All cases were followed up and the recurrent cases were recorded in detail. We used a logistic regression model to analyze the clinical data in order to find the reasons for recurrence. RESULTS: We completed 486 cases with an internal inguinal ostium high ligation using laparoscopic surgery without conversion. Patients were followed for 10-29 months with an average of 18.2 months and 8 cases had recurrent ipsilateral hernia, including 4 recurrent cases in 89 cases (4.49%) using absorbable suture, 1 in 7 cases (14.29%) with internal inguinal ostium larger than 25 mm, 2 in 26 cases (7.69%) with BMI greater than 21, 2 in 41 cases (4.88%) with postoperative chronic constipation. The total recurrence rate was 1.65%. A foreign body reaction occurred in 2 cases, there were no complications such as scrotal hematoma, trocar umbilical hernia and testicular atrophy, and no deaths in this study. Univariate logistic regression analysis showed that patient BMI, ligation suture, diameter of the internal inguinal ostium and postoperative chronic constipation were significant variables (P values 0.093, 0.027, 0.060 and 0.081). The multivariate logistic regression analysis showed that the ligation suture and the diameter of the internal inguinal ostium were the main risk factors for postoperative recurrence, the odds ratio (OR) value were 5.374 and 2.801, the P values 0.018 and 0.046, and the 95% CI were 2.513-11.642 and 1.134-9.125. The area under ROC curve (AUC) for the logistic regression model was 0.735 (the 95% CI 0.677-0.801, P < 0.01). CONCLUSION: An LPER for PIH is a safe and effective operation, but there still remains a small probability of recurrence. In order to reduce the recurrence rate of LPER, we should improve surgical skills, choose an appropriate ligature and avoid using LPER for a huge internal inguinal ostium (especially over 25 mm). It is appropriate to be converted to open surgery for the patients with a very wide internal inguinal ostium.


Assuntos
Hérnia Inguinal , Laparoscopia , Criança , Humanos , Hérnia Inguinal/cirurgia , Hérnia Inguinal/etiologia , Resultado do Tratamento , Estudos Retrospectivos , Herniorrafia/efeitos adversos , Recidiva , Laparoscopia/efeitos adversos , Constipação Intestinal/cirurgia
9.
AIDS Behav ; 28(1): 105-114, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37812270

RESUMO

Appropriate parental HIV disclosures (i.e., parents living with HIV [PLH] tell their HIV diagnosis to their children) benefit parents, children, and family relations. Psychosocial factors could influence the decision-making process of parental HIV disclosure. Using the Health Action Process Approach to frame stages (pre-intention, intention, and action) in the decision-making process, this study aimed to investigate how psychosocial factors predict HIV disclosure stage transitions among PLH in China. Data were collected from a randomized clinical trial of a theory-based parental HIV disclosure intervention among 791 PLH. The predictive effects of psychosocial factors on disclosure stage transitions were examined using a Markov chain model matrix. Results showed that action self-efficacy and action planning were significant predictors of parental HIV disclosure stage transitions. Considering stage-specific psychosocial predictors may contribute to effective interventions to promote appropriate HIV disclosure among PLH in China.


Assuntos
Infecções por HIV , Pais , Revelação da Verdade , Humanos , China/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Pais/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Relações Pais-Filho
10.
AIDS Behav ; 28(2): 645-656, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38091128

RESUMO

Depression is one of the most common mental health problems among people living with HIV (PLWH). However, the longitudinal psychological mechanism underlying the link of internalized HIV stigma and depressive symptoms remains a research gap. This study attempted to articulate how and to what extent perceived social support and resilience mediate the longitudinal associations between internalized HIV stigma and depressive symptoms. A sample consisting of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20; 63.9% male) with a six-month interval and four waves of follow-up was used in the current study. Participants were asked to complete self-report questionnaires. The associations among main study variables were examined via a complete longitudinal mediation approach. Results indicated that the linkage between internalized HIV stigma at T1 and depressive symptoms at T4 was serially mediated by perceived social support at T2 and resilience at T3, and perceived social support at T2 and depressive symptoms at T3 serially mediated the relationship between resilience at T1 and internalized HIV stigma at T4. Depressive symptoms at a previous time point consistently predicted the levels of internalized HIV stigma at subsequent time points. The study highlights the complex interplay between internalized HIV stigma, mental health problems, and protective factors in a longitudinal context. The findings suggest the need to incorporate interventions aimed at enhancing social support and resilience in mental health programs for PLWH, as these factors may interrupt the pathway from internalized HIV stigma to depressive symptoms and potentially improve the overall psychological well-being of this population.


Assuntos
Infecções por HIV , Resiliência Psicológica , Humanos , Masculino , Adulto , Feminino , Depressão/epidemiologia , Depressão/psicologia , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Estigma Social , Apoio Social , China/epidemiologia
11.
Am J Cancer Res ; 13(11): 5684-5697, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058840

RESUMO

This study aimed to utilize circulating tumor cell-DNA (CTC-DNA) from liquid biopsies to monitor trastuzumab resistance in Gastric cancer (GC) and assess the limited response rate in HER2 metastatic gastric cancer. Given the heterogeneity of GC, we established a high-precision CTC detection system that effectively isolates tumor cells with high HER2 expression for downstream analysis. Targeted sequencing of 610 genes was conducted on 20 paired CTC and tissue samples to assess uniformity. A longitudinal analysis of CTC samples was then performed to monitor trastuzumab resistance throughout treatment. Targeted sequencing of the HER2 gene showed strong consistency with fluorescence in situ hybridization data. Detected HER2 Scna was superior in predicting tumor shrinkage and progression. Most patients with innate trastuzumab resistance exhibited elevated HER2 Scna levels during progression. PIK3CA mutations were significantly enriched, and ERBB2/4 gene mutations were predominant in patients with innate trastuzumab resistance. CTC-DNA sequencing provides new insights into gene alterations associated with trastuzumab resistance in HER2 mGC.

12.
Curr Med Imaging ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37921155

RESUMO

BACKGROUND: Ovarian cancer is a common gynecological malignant tumor in women. Most patients have reached the advanced stage when they visit the hospital. In order to diagnose ovarian cancer at an early stage, treat it at an early stage, and improve the survival rate of patients, this study has used the imaging computed tomography (CT) method to diagnose stage IA ovarian cancer. PURPOSE: The purpose of this work was to study CT features of stage IA ovarian cancer, and compare the borderline tumor and stage IC ovarian cancer at the same time so as to improve the CT diagnosis of early ovarian cancer. METHODS: We retrospectively collected clinical and CT data of patients with stage I ovarian cancer and borderline ovarian tumor admitted to Nantong Tumor Hospital from 2013 to 2021. Altogether, 23 cases of patients (borderline ovarian tumor, 9 cases; stage IA ovarian cancer, 5 cases; stage IC ovarian cancer, 9 cases) were involved. CT characteristics of these patients were analyzed in terms of the tumor diameter, cystic solid structure, solid component, septation, enhancement, peritoneal thickening, ascites, and abdominal lymph nodes. RESULTS: CT features of stage IA ovarian cancer included large tumor size (average diameter: 15 cm), cystic solid structure (4/5; 80%), septation (4/5; 80%), and enhanced cystic wall, septum, or solid components of the tumor on contrast-enhanced CT (5/5; 100%) no peritoneal thickening (0/5; 0%), no ascites (0/5; 0%), and no abdominal lymph node enlargement (0/5; 0%). The tumor structure did not differ significantly between stage IA and IC ovarian cancers (p > 0.05), while intraperitoneal ascites did (χ2 = 0.031; p < 0.05). Stage IA and borderline ovarian tumors did not differ significantly in ovarian tumor structure (p > 0.05). CONCLUSION: CT features of stage IA ovarian cancer included large tumor size, cystic solid structure, septation, and enhanced cystic wall and solid parts in the tumors. No pelvic or abdominal metastasis was observed.

13.
Front Public Health ; 11: 1253834, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026404

RESUMO

Objective: College Students' sleep quality and daytime dysfunction have become worse since the COVID-19 outbreak, the purpose of this study was to explore the relationship between sleep quality and daytime dysfunction among college students during the COVID-19 (Corona Virus Disease 2019) period. Methods: This research adopts the form of cluster random sampling of online questionnaires. From April 5 to 16 in 2022, questionnaires are distributed to college students in various universities in Fujian Province, China and the general information questionnaire and PSQI scale are used for investigation. SPSS26.0 was used to conduct an independent sample t-test and variance analysis on the data, multi-factorial analysis was performed using logistic regression analysis. The main outcome variables are the score of subjective sleep quality and daytime dysfunction. Results: During the COVID-19 period, the average PSQI score of the tested college students was 6.17 ± 3.263, and the sleep disorder rate was 29.6%, the daytime dysfunction rate was 85%. Being female, study liberal art/science/ engineering, irritable (due to limited outdoor), prolong electronic entertainment time were associated with low sleep quality (p < 0.001), and the occurrence of daytime dysfunction was higher than other groups (p < 0.001). Logistics regression analysis showed that sleep quality and daytime dysfunction were associated with gender, profession, irritable (due to limited outdoor), and prolonged electronic entertainment time (p < 0.001). Conclusion: During the COVID-19 epidemic, the sleep quality of college students was affected, and different degrees of daytime dysfunction have appeared, both are in worse condition than before the COVID-19 outbreak. Sleep quality may was inversely associated with daytime dysfunction.


Assuntos
COVID-19 , Qualidade do Sono , Humanos , Feminino , Masculino , Estudos Transversais , COVID-19/epidemiologia , Estudantes , China/epidemiologia
14.
Medicine (Baltimore) ; 102(34): e34647, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653737

RESUMO

The "real world" treatment mode and clinical efficacy of locally advanced esophageal squamous cell carcinoma (LAESCC) are unclear. Meanwhile, the role of immunotherapy in the clinical practice is also puzzling. We conducted the research to investigate the statue of "real world" LAESCC. The clinical data of patients with locally advanced esophageal squamous cell carcinoma which met the criteria from January 2010 to December 2019 have been retrospectively analyzed, and the distribution of clinical treatment patterns has been analyzed. They cover such aspects as dfferences in survival time and further analysis of the differences in overall survival (OS) and progression-free survival (PFS) between patients who received immunotherapy and those who did not receive immunotherapy. What is more, Cox risk regression model has also been used to evaluate the risk factors affecting the prognosis of LAESCC. The cases of a total of 5328 newly diagnosed patients with esophageal cancer were collected, and a total of 363 patients were included in the study, with a median age of (46.2 ± 7.8) years old; 84 (23.1%) and 279 (76.9%) patients received 1L and ≥ 2L, respectively; Concurrent chemoradiotherapy (74.1%) and paclitaxel combined with platinum-based chemotherapy (14.3%) were the main first-line treatment options; fluorouracil combined with cisplatin regimen-based chemotherapy (63.8%) was the main treatment option for ≥ 2L, of which 69 patients (25.3%) received immunization treatment; OS of patients with 1 line of therapy and ≥ 2L were (22.4 ± 7.2) months and (38.7 ± 8.5) months, respectively, and the comparison between groups was statistically significant (P < .05); among 69 patients with ≥ 2L who received immunotherapy, PFS and The OS was (14.6 ± 6.9) and (45.3 ± 9.7) respectively, and the comparison between the groups was statistically significant (all P < .05). Cox multivariate analysis has shown that clinical stage, immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are the main factors affecting OS. and immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are independent factors affecting PFS. Concurrent chemoradiotherapy is currently one of the standard treatments for LAESCC, and most patients are still willing to receive second-line or above treatments. Adding immunotherapy to standard treatment modalities may further optimize clinical treatment modalities and improve patient outcomes.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Adulto , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/terapia , Neoplasias Esofágicas/terapia , Estudos Retrospectivos , Imunoterapia , Quimiorradioterapia
15.
AIDS Behav ; 27(12): 4052-4061, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37392272

RESUMO

Previous research has documented that HIV-related stigma (e.g., internalized and anticipated stigma) is detrimental to the mental health of people living with HIV (PLWH). However, longitudinal data on the bidirectional relationship between HIV-related stigma and depression symptoms are limited. The purpose of this study was to examine the bidirectional association among internalized and anticipated HIV stigma and depression symptoms among Chinese PLWH. A four-wave longitudinal design (6 months intervals) was employed among 1,111 Chinese PLWH (Mage = 38.58, SD = 9.16, age range: 18-60 years; 64.1% men). The bidirectional model was examined using a random-intercept cross-lagged panel model (RI-CLPM), which evaluated the within- and between-person effects of study variables. At the within-person level, results indicated that depression symptoms at T2 mediated the linkage between internalized HIV stigma at T1 and anticipated HIV stigma at T3, and that anticipated HIV stigma at both T2 and T3 mediated the relationship between depression symptoms at the previous time point and internalized HIV stigma at the subsequent time point. Furthermore, a bidirectional association was found between anticipated HIV stigma and depression symptoms across four waves. At the between-person level, internalized and anticipated HIV stigma were significantly associated with depression symptoms. This study highlights the complex interplay between different forms of HIV-related stigma and mental health problems among PLWH and underscores the importance of considering the bidirectional relationship between the development of psychopathology and stigmatization process in clinical practice.

16.
Gut ; 72(12): 2307-2320, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37507218

RESUMO

OBJECTIVE: Checkpoint immunotherapy unleashes T-cell control of tumours but is suppressed by immunosuppressive myeloid cells. The transmembrane protein MS4A4A is selectively highly expressed in tumour-associated macrophages (TAMs). Here, we aimed to reveal the role of MS4A4A+ TAMs in regulating the immune escape of tumour cells and to develop novel therapeutic strategies targeting TAMs to enhance the efficacy of immune checkpoint inhibitor (ICI) in colorectal cancer. DESIGN: The inhibitory effect of MS4A4A blockade alone or combined with ICI treatment on tumour growth was assessed using murine subcutaneous tumour or orthotopic transplanted models. The effect of MS4A4A blockade on the tumour immune microenvironment was assessed by flow cytometry and mass cytometry. RNA sequencing and western blot analysis were used to further explore the molecular mechanism by which MS4A4A promoted macrophages M2 polarisation. RESULTS: MS4A4A is selectively expressed by TAMs in different types of tumours, and was associated with adverse clinical outcome in patients with cancer. In vivo inhibition of MS4A4A and anti-MS4A4A monoclonal antibody treatment both curb tumour growth and improve the effect of ICI therapy. MS4A4A blockade treatment reshaped the tumour immune microenvironment, resulting in reducing the infiltration of M2-TAMs and exhausted T cells, and increasing the infiltration of effector CD8+ T cells. Anti-MS4A4A plus anti-programmed cell death protein 1 (PD-1) therapy remained effective in large, treatment-resistant tumours and could induce complete regression when further combined with radiotherapy. Mechanistically, MS4A4A promoted M2 polarisation of macrophages by activating PI3K/AKT pathway and JAK/STAT6 pathway. CONCLUSION: Targeting MS4A4A could enhance the ICI efficacy and represent a new anticancer immunotherapy.


Assuntos
Neoplasias , Macrófagos Associados a Tumor , Humanos , Animais , Camundongos , Linfócitos T CD8-Positivos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Macrófagos , Microambiente Tumoral , Proteínas de Membrana/metabolismo
17.
Front Cell Infect Microbiol ; 13: 1150042, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351180

RESUMO

African swine fever (ASF) is a disease that causes severe economic losses to the global porcine industry. As no vaccine or drug has been discovered for the prevention and control of ASF virus (ASFV), accurate diagnosis and timely eradication of infected animals are the primary measures, which necessitate accurate and effective detection methods. In this study, the truncated ASFV I329L (amino acids 70-237), was induced using IPTG and expressed in Escherichia coli cells. The highly antigenic viral protein I329L was used to develop an indirect enzyme-linked immunosorbent assay (iELISA), named I329L-ELISA, which cut-off value was 0.384. I329L-ELISA was used to detect 186 clinical pig serum samples, and the coincidence rate between the indirect ELISA developed here and the commercial kit was 96.77%. No cross-reactivity was observed with CSFV, PRRSV, PCV2, or PRV antibody-positive pig sera, indicating good specificity. Both intra- assay and inter-assay coefficients were below 10%, and the detection sensitivity of the iELISA reached 1:3200. In this study, an iELISA for ASFV antibody detection was developed based on the truncated ASFV I329L protein. Overall, the I329L-ELISA is a user-friendly detection tool that is suitable for ASFV antibody detection and epidemiological surveillance.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Febre Suína Africana/diagnóstico , Anticorpos Antivirais , Proteínas Virais , Ensaio de Imunoadsorção Enzimática/métodos
18.
Microbiome ; 11(1): 124, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264459

RESUMO

BACKGROUND: The effects of air pollutants, particularly polycyclic aromatic hydrocarbons (PAHs), on the skin microbiome remain poorly understood. Thus, to better understand the interplay between air pollutants, microbiomes, and skin conditions, we applied metagenomics and metabolomics to analyze the effects of PAHs in air pollution on the skin microbiomes of over 120 subjects residing in two cities in China with different levels of air pollution. RESULTS: The skin microbiomes differentiated into two cutotypes (termed 1 and 2) with distinct taxonomic, functional, resistome, and metabolite compositions as well as skin phenotypes that transcended geography and host factors. High PAH exposure was linked to dry skin and cutotype 2, which was enriched with species with potential biodegradation functions and had reduced correlation network structure integrity. The positive correlations identified between dominant taxa, key functional genes, and metabolites in the arginine biosynthesis pathway in cutotype 1 suggest that arginine from bacteria contributes to the synthesis of filaggrin-derived natural moisturizing factors (NMFs), which provide hydration for the skin, and could explain the normal skin phenotype observed. In contrast, no correlation with the arginine biosynthesis pathway was observed in cutotype 2, which indicates the limited hydration functions of NMFs and explains the observed dry skin phenotype. In addition to dryness, skin associated with cutotype 2 appeared prone to other adverse conditions such as inflammation. CONCLUSIONS: This study revealed the roles of PAHs in driving skin microbiome differentiation into cutotypes that vary extensively in taxonomy and metabolic functions and may subsequently lead to variations in skin-microbe interactions that affect host skin health. An improved understanding of the roles of microbiomes on skin exposed to air pollutants can aid the development of strategies that harness microbes to prevent undesirable skin conditions. Video Abstract.


Assuntos
Poluentes Atmosféricos , Microbiota , Hidrocarbonetos Policíclicos Aromáticos , Pele/química , Poluentes Atmosféricos/análise , Biodegradação Ambiental , Microbiota/genética , Monitoramento Ambiental
19.
AIDS Behav ; 27(10): 3508-3514, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37074629

RESUMO

Prescription opioid misuse (POM) is a concern in people living with HIV (PLWH). Pain interference is a robust factor, and its influences would occur through anxiety and resilience. Limited POM studies attend to Chinese PLWH. This study examined POM and its underlying psychological mechanism using data of PLWH with pain (n = 116) from a cohort study in Guangxi. The PROCESS macro was employed to examine a hypothesized moderated mediation model among pain interference, resilience, anxiety, and POM. Results showed 10.3% PLWH engaged in past-three-month POM. After controlling for demographics, HIV-related clinical outcomes, and pain severity, anxiety mediated the association between pain interference and POM (ß = 0.46, 95% CI = 0.01 to 10.49), and the mediation was moderated by resilience (moderated mediation index = - 0.02, 95% CI = - 0.784 to - 0.001). Chinese PLWH seem to misuse opioids to cope with pain-related anxiety. Resilience appears to offer protection.


Assuntos
Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Humanos , Estudos de Coortes , População do Leste Asiático , China/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Ansiedade/epidemiologia , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor
20.
PLoS One ; 18(3): e0283031, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37000807

RESUMO

BACKGROUND: In Guangxi province of China, there is a high prevalence of HIV in the general population and in men who have sex with men (MSM). However, there is still a low proportion of MSM among people living with HIV. This apparent contradiction could be due to the high proportion of potential non-disclosed MSM (pnMSM) among reported heterosexual men. We analyzed the genetic linkage of HIV specimens to address this problem aiming to (1) identify the optimal genetic distance threshold, which gave the highest number of genetic clusters, (2) document the proportion of potential non-disclosed MSM (pnMSM) among self-reported heterosexual men, and (3) determine predictors for pnMSM. METHODS: Pairwise genetic distances were computed among all samples. The genetic distance threshold giving the highest number of genetic clusters was identified. Self-reported heterosexual men were identified as belonging to the pnMSM group if they could be linked to any MSM in their cluster. Multinomial logistic regression was used to determine associated factors of being pnMSM. RESULTS: The optimal genetic distance threshold was 0.75% substitutions/site. Among 896 self-reported heterosexual men, the frequency (percentage and 95% confidence interval) was 62 (6.9%, 5.2-8.6%) for pnMSM, 779 (86.9%, 84.7-89.1%) for indeterminate men and 55 (6.1%, 4.5-7.7%) for potential heterosexual men, respectively. Self-reported heterosexual men who were younger, single and more educated were more likely to be pnMSM. CONCLUSION: Based on these findings, there is a need to pay more attention to sexually active, young and educated self-reported heterosexual men and provide them with voluntary counselling and testing and specific HIV prevention services.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Heterossexualidade , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Autorrelato , Redes Reguladoras de Genes , China/epidemiologia
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