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Background Treatment strategies targeting tumor-associated macrophages (TAMs) have been proposed in cancer areas. The functional alterations of macrophages in the microenvironment during the tumorigenesis of human epithelial cancer remain poorly understood. Here, we explored phenotypic alteration of macrophages during the development of oral squamous cell carcinoma (OSCC). Methods Conditioned media (CM) and exosome supernatants were harvested from normal oral epithelium, oral leukoplakia cells and OSCC cells. We measured phenotypic alteration of macrophages using flow cytometry, luminex assays, and quantitative real-time PCR assay. Intracellular signaling pathway analysis, mass spectrometry proteomics, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and bioinformatics analysis were performed to uncover the underlying mechanisms. Results THP-1-derived and PBMCs derived macrophages exhibited an M1-like phenotype but not M2-like phenotype, when treated with CM from OSCC cells but not with the CM from normal epithelium or leukoplakia cells. Further investigations revealed that macrophages were activated by taking up exosomes released from OSCC cells through p38, Akt, and SAPK/JNK signaling at the early phase. We further provided evidences that THBS1 derived from OSCC exosomes participated in the polarization of macrophages to an M1-like phenotype. Reciprocally, CM from exosomes induced M1-like TAMs and significantly promoted migration of OSCC cells. Conclusions We proposed a novel paracrine loop between cancer cells and macrophages based on exosomes from OSCC. Therefore, target management of M1-like TAMs polarized by exosomes shows great potential as a therapeutic target for the control of cancerous migration in OSCC.

To identify differences in human immunodeficiency virus (HIV) risky behavior and healthy practices between rural and urban men who have sex with men (MSM) in Southeast China, a cross-sectional study was conducted on MSM aged ≥ 18 years recruited from four community-based organizations (CBOs) in seven cities in Zhejiang Province between October 2022 and March 2023. An electronic survey questionnaire was completed by the study participants to collect HIV risky behavior and healthy practices. The chi-square test and multiple logistic regression were used for analysis. Among the 1,993 MSM participants, 21.1% (420) were rural MSM. Compared with urban MSM, rural MSM was more likely to have a low level of education (high school and below; 46.2% vs. 40.2%, p = 0.028) and a low annual income (≤ 90,000 RMB; 71.2% vs. 64.7%, p = 0.013). Multiple logistic regression showed that, compared with urban MSM in the past 6 months behaviors, rural MSM had lower odds of finding casual sex partners on the Internet (adjusted odds ratio [aOR]: 0.790, 95% confidence interval [CI]: 0.633–0.986), using stimulants with online casual sex partners (aOR: 0.688, 95% CI: 0.506–0.936), and high odds of ever having sex with a female (aOR: 1.460, 95% CI:1.036–2.058). Rural MSM reported lower odds of an HIV knowledge score of 2–3 (aOR: 0.586, 95% CI: 0.454–0.756), HIV testing more than twice (aOR: 0.583, 95% CI: 0.455–0.748), and obtaining four to five types of HIV information (aOR: 0.661, 95% CI: 0.529–0.826), as well as higher odds of high/very high awareness of HIV infection risk (aOR: 2.312, 95% CI: 1.638–3.263), compared to urban MSM. Rural MSM and urban MSM reported discrepancies in HIV risky behavior, HIV knowledge and HIV-related healthy practices. Paying more attention to HIV risky behavior and improving healthy practices in rural areas may help to prevent HIV transmission.

Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the proliferation of the Treg population in tumor‐infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO‐Y030, an antitumor chemical. GO‐Y030 inhibited the immune‐suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO‐Y030 inhibited the mTOR‐S6 axis in Tregs, which plays a pivotal role in their immune‐suppressive ability. GO‐Y030 also controlled the metabolism in cultured CD4+ T cells in the presence of TGF‐β + IL‐6; however, it did not prevent Th17 differentiation. Notably, GO‐Y030 significantly inhibited IL‐10 production from Th17 cells. In the tumor microenvironment, L‐lactate produced by tumors is known to support the suppressive ability of Tregs, and GO‐Y030 treatment inhibited L‐lactate production via metabolic changes. In addition, experiments in the B16‐F10 melanoma mouse model revealed that GO‐Y030 helped inhibit the anti‐PD‐1 immune checkpoint and reduce the Treg population in tumor‐infiltrating lymphocytes. Thus, GO‐Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti‐immune checkpoint inhibitors. Curcumin analog GO‐Y030 boosts cancer immunotherapy via metabolic changes.

Allogeneic mesenchymal stem cells (MSCs) exhibit immunoregulatory function in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain incompletely understood. Here we show that the number of peripheral tolerogenic CD1c + dendritic cells (DCs) and the levels of serum FLT3L are significantly decreased in SLE patients especially with lupus nephritis, compared to healthy controls. Transplantation of allogeneic umbilical cord-derived MSCs (UC-MSCs) significantly up-regulates peripheral blood CD1c + DCs and serum FLT3L. Mechanistically, UC-MSCs express FLT3L that binds to FLT3 on CD1c + DCs to promote the proliferation and inhibit the apoptosis of tolerogenic CD1c + DCs. Conversely, reduction of FLT3L with small interfering RNA in MSCs abolishes the up-regulation of tolerogenic CD1c + DCs in lupus patients treated with MSCs. Interferon-γ induces FLT3L expression in UC-MSCs through JAK/STAT signaling pathway. Thus, allogeneic MSCs might suppress inflammation in lupus through up-regulating tolerogenic DCs. Promising pilot clinical trials of mesenchymal stem cells (MSCs) therapy of lupus await validation in larger, controlled trials. Here the authors show that MSCs expand CD1c + dendritic cells in cell culture by producing FLT3L, and that in lupus patients, circulating CD1c + dendritic cells and FLT3L are increased following MSCs therapy.

Cancer stem cells (CSCs) may be responsible for treatment resistance, tumor metastasis, and disease recurrence. Here we demonstrate that the Arf1-mediated lipid metabolism sustains cells enriched with CSCs and its ablation induces anti-tumor immune responses in mice. Notably, Arf1 ablation in cancer cells induces mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells (DCs) at tumor sites. The activated immune system finally elicits antitumor immune surveillance by stimulating T-cell infiltration and activation. Furthermore, TCGA data analysis shows an inverse correlation between Arf1 expression and T-cell infiltration and activation along with patient survival in various human cancers. Our results reveal that Arf1-pathway knockdown not only kills CSCs but also elicits a tumor-specific immune response that converts dying CSCs into a therapeutic vaccine, leading to durable benefits. Cancer stem cells (CSC) have been shown as the origin for therapeutic resistance and patient relapse. Here, the authors show that targeting Arf1-mediated lipid metabolism in CSC induces cell death but also an immunogenic anti-cancer response.

The massive increase in active TGF-β in the lungs, may be the result of at least three possible sources: 1), SARS-CoV-2 virus infection and consequent strong immune and inflammatory responses as well as dysregulation of the coagulation and fibrinolytic pathways induce massive activation of the latent (inactive) TGF-β in the lungs as well as latent TGF-β pool in the blood of patients. [...]a decrease in circulating levels of total (latent) TGF-β is expected in patients with all stages of pneumonia, especially from mild to severe stage of pneumonia; at the same time, more active TGF-β in the lungs may be observed; 2), SARS-CoV-2 virus infection induces massive increases of neutrophil infiltration into the lungs where, the neutrophils can release stored TGF-β that can be activated by elastase in neutrophils. TGF-β itself can be a potent chemokine-like molecule that recruits more neutrophils into lungs to form a positive feedback loop, which can contribute to local increases in total TGF-β release and TGF-β activation; 3), SARS-CoV-2 virus infection causes apoptosis of bronchial epithelial cells, pneumocytes, and T lymphocytes. [...]the sudden and uncontrolled increases in active TGF-β (possibly with the help of some proinflammatory cytokines such as TNFα, IL-6, and IL-1β) inevitably result in rapid and massive edema and fibrosis that remodels and ultimately blocks the airways.

Objective This study was conducted to explore the human immunodeficiency virus (HIV) status of and compare HIV knowledge, HIV testing, and other healthy behaviors between men who have sex with men and women (MSMW) and men who have sex with men only (MSMO), to provide a scientific basis for targeted HIV interventions for this population. Methods A cross-sectional survey was conducted to collect demographic and behavioral information using questionnaires for statistical analysis. Results Among 1,993 participants, 772 (38.7%) reported having sexual intercourse with women. The results of the multivariate logistic regression model analysis indicated that MSMW had a lower probability than MSMO of reporting HIV knowledge 1 (adjusted odds ratio [aOR]:0.556, 95% CI: 0.409–0.756), knowledge 2 (aOR:0.626; 95% CI, 0.515–0.761), knowledge 3 (aOR:0.569; 95% CI: 0.447–0.724), informing their HIV status to the last casual sex partners offline (aOR: 0.515, 95% CI: 0.358–0.743), HIV testing more than once in the past 6 months (aOR: 0.696, 95% CI: 0.521–0.931), and HIV testing in a hospital in the past 6 months (aOR: 0.696, 95% CI: 0.521–0.931). In contrast, MSMW had a higher probability of post-exposure prophylaxis (PEP) intake in the past 6 months (aOR: 2.252, 95% CI: 1.570–3.229), pre-exposure prophylaxis (PrEP) intake in the past 6 months (aOR: 1.630, 95% CI: 1.091–2.434), and cumulative HIV testing more than twice (aOR: 1.917, 95% CI: 1.434–2.563). Conclusion MSMW showed significant differences with MSMO in HIV knowledge and HIV related risky reduction behaviors. It is necessary to enhance awareness and skills on HIV self-testing, PEP, and PrEP among MSM. Encouraging HIV knowledge education and HIV testing service are important for MSMW. PEP and PrEP might be enhanced among MSMO for reducing the risk of HIV transmission.

The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system,focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.

The purpose of this study was to explore the situations and factors influencing casual sexual behavior among male college students, in order to provide scientific evidences and measures of the prevention and control for HIV/AIDS. Using the stratified cluster sampling method, male college students who self-reported sexual behavior were selected as survey subjects in 13 colleges and universities in 11 cities of Zhejiang Province from October to November 2018. We used a custom online questionnaire to collect information on the demographic characteristics, sexual attitudes, sexual behaviors, and HIV interventions of the respondents. The χ2 test was performed on the composition ratios between different groups. With the occurrence of casual sexual behavior as the dependent variable, logistic regression was used to analyze the factors influencing casual male sexual behavior. A total of 2734 male college students were surveyed, aged 20.20±1.41 years, of which 595 had casual sex, accounting for 21.7%. The rate of HIV prevention awareness among the participants was 85.1%. Multivariate analysis showed that receiving a self-assessment of HIV risk conducted by the school (Ajusted OR = 1.45, 95% CI = 1.14-1.84), knowing that HIV self-test kits were available at school (Ajusted OR = 2.02, 95% CI = 1.56-2.62), accepting one-night stands (Ajusted OR = 2.82, 95% CI = 2.18-3.66), accepting commercial sex (Ajusted OR = 1.95, 95% CI = 1.53-2.48), being a man who has sex with men (Ajusted OR = 1.81, 95% CI = 1.37-2.39), being a senior (Ajusted OR = 0.46, 95% CI = 0.30-0.71), having knowledge of HIV/AIDS prevention and treatment (Ajusted OR = 0.66, 95% CI = 0.51-0.86), and knowing that the CDC provides HIV testing services (Ajusted OR = 0.56, 95% CI = 0.41-0.77) were factors influencing male college students' casual sexual behavior. Male college students who have causal sexual behaviors have a high degree of openness in sexual attitudes, insufficient knowledge of AIDS prevention, and knowledge of HIV testing-related information but low testing rates. For male college students' HIV prevention education intervention, it is necessary to emphasize the establishment of correct sexual attitudes and concepts and promote safe sexual behaviors to prevent the spread of HIV.

Consistent condom use with casual partners is critical for preventing the transmission of human immunodeficiency virus (HIV) among male university students. This study aimed to determine the level of consistent condom use and explore the correlates of condom use consistency in male university students in eastern China. A descriptive cross-sectional survey was conducted in 13 universities in Zhejiang Province, which involved the recruitment of 31,674 students by stratified random sampling. Among them, 545 male students who engaged in casual sex in the year prior to this study were included. Adjusted and unadjusted logistic regression models were used to examine the correlates associated with consistent condom use. Among the 545 male university students, only 205 (37.6%) consistently used condoms in the previous year. The following correlates were associated with higher rates of consistent condom use: 1) Knowledge, specifically, the number of correct answers to “HIV infection can be determined by appearance” (AOR: 2.06, 95% CI: 1.21–3.49); 2) never finding casual partners on the internet during the past over the prior year (AOR: 0.63; 95% CI: 0.40–0.99); 3) never drinking alcohol before casual sex during the last over the prior year (AOR: 0.30; 95% CI: 0.20–0.46); 4) never engaging in commercial sex (AOR: 0.57; 95% CI: 0.34–0.96); and 5) high condom self-efficacy score (AOR: 2.55; 95% CI: 1.44–4.49). The study found a low level of consistent condom use among male university students. Promoting condom self-efficacy, reducing web-based casual sex, drinking before sex, and commercial sex are essential to improving the level of consistent condom use among male university students to reduce the transmission of HIV.