Acacetin inhibits inflammation by blocking MAPK/NF-κB pathways and NLRP3 inflammasome activation.

Objective: Our preliminary research indicates that acacetin modulates the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome, providing protection against Alzheimer's Disease (AD) and cerebral ischemic reperfusion injury. The mechanisms of acacetin to inhibit the activation of the NLRP3 inflammasome remain fully elucidated. This study aims to investigate the effects and potential mechanisms of acacetin on various agonists induced NLRP3 inflammasome activation. Methods: A model for the NLRP3 inflammasome activation was established in mouse bone marrow-derived macrophages (BMDMs) using Monosodium Urate (MSU), Nigericin, Adenosine Triphosphate (ATP), and Pam3CSK4, separately. Western blot analysis (WB) was employed to detect Pro-caspase-1, Pro-Interleukin-1ß (Pro-IL-1ß) in cell lysates, and caspase-1, IL-1ß in supernatants. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measured the release of IL-1ß, IL-18, and Tumor Necrosis Factor-alpha (TNF-α) in cell supernatants to assess the impact of acacetin on NLRP3 inflammasome activation. The lactate dehydrogenase (LDH) release was also assessed. The Nuclear Factor Kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways related proteins were evaluated by WB, and NF-κB nuclear translocation was observed via laser scanning confocal microscopy (LSCM). Disuccinimidyl Suberate (DSS) cross-linking was employed to detect oligomerization of Apoptosis-associated Speck-like protein containing a Caspase Recruitment Domain (ASC), and LSCM was also used to observe Reactive Oxygen Species (ROS) production. Inductively Coupled Plasma (ICP) and N-(6-methoxyquinolyl) acetoethyl ester (MQAE) assays were utilized to determined the effects of acacetin on the efflux of potassium (K+) and chloride (Cl-) ions. Results: Acacetin inhibited NLRP3 inflammasome activation induced by various agonists, reducing the release of TNF-α, IL-1ß, IL-18, and LDH. It suppressed the expression of Lipopolysaccharides (LPS)-activated Phosphorylated ERK (p-ERK), p-JNK, and p-p38, inhibited NF-κB p65 phosphorylation and nuclear translocation. Acacetin also reduced ROS production and inhibited ASC aggregation, thus suppressing NLRP3 inflammasome activation. Notably, acacetin did not affect K+ and Cl-ions efflux during the activation process. Conclusion: Acacetin shows inhibitory effects on both the priming and assembly processes of the NLRP3 inflammasome, positioning it as a promising new candidate for the treatment of NLRP3 inflammasome-related diseases.

Acacetin improves cognitive function of APP/PS1 Alzheimer's disease model mice via the NLRP3 inflammasome signaling pathway.

Background: Acacetin (5,7-dihydroxy-4'-methoxyflavone), one of the main extractions from Saussurea involucrata, has anti-inflammatory effects. Our previous study found that acacetin inhibited the Nod-like receptor pyrin domain containing 3 (NLRP3) signaling pathway after cerebral ischemia-reperfusion injury. NLRP3 inflammasome plays a role in Alzheimer's disease (AD) process. However, few studies have examined the effects of acacetin in AD. Methods: We randomly divided APP swe/PS1dE9 double transgenic mice into acacetin group (intraperitoneal injection of 25 mg/kg acacetin) and AD model group (intraperitoneal injection of same volume of saline). C57BL/6 mice were selected as control group (same treatment with AD model group). After treating for 30 days, a Morris water maze test was conducted to evaluate spatial learning and memory of the mice. Senile plaque (SP) formation was evaluated by immunohistochemistry. NLRP3 inflammasome-related inflammatory factors and amyloid-ß-42 were detected by Western blot or enzyme-linked immunosorbent assay. Results: Acacetin improved spatial learning and memory of AD mice and reduced APP/ß expression, thereby decreasing SP formation in the brain. Acacetin also reduced the expression of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), and interleukin-1ß (IL-1ß) and the release of inflammatory factors, tumor necrosis factor-α (TNF-α) and IL-1ß. Conclusions: Acacetin improved the learning and memory abilities of AD mice and exerted a protective effect on AD by inhibiting the NLRP3 signaling pathway and reducing SP formation.

HPV vaccination acceptability among men who have sex with men in Urumqi, China.

BACKGROUND: Human papillomavirus (HPV) infection is common among men who have sex with men (MSM), especially among Human Immunodeficiency Virus (HIV)-infected MSM. The prevalence of HPV among MSM, accounts for the higher incidence of HPV-related cancer observed in this population. It is well known that targeted HPV vaccination is an effective way to prevent HPV infection; an intervention which could be beneficial for a high-risk group such as MSM. The current study aimed to assess the attitudes towards and acceptability of the HPV vaccine among MSM in in Urumqi, China. METHODS: A total of 253 HIV-uninfected and 205 HIV-infected MSM (in Urumqi, China participated in the current cross-sectional study. Information on HPV-related knowledge, willingness to be vaccinated as well as demographic data were collected through a self-administered survey. A logistic regression model was applied to determine the predictors of HPV vaccine acceptability among the population. RESULTS: The survey results indicated that only 218 (47.6%) of MSM questioned were aware of the term HPV, nevertheless, once awareness was established the prevalence of acceptability of free HPV vaccine was recorded at 96.7% of the total MSM sample. However, HIV-uninfected and HIV-infected MSM demonstrated significantly different attitudes in regard to their acceptability of free HPV vaccination (94.9% vs. 99.0%, p < 0.001) as well as their willingness to pay for the HPV vaccination (64.8% vs. 80.5%, p < 0.001), with the HIV-infected group being significantly more receptive towards HPV immunization. A multivariate logistic regression analysis indicated that local residency, employment status, hepatitis B vaccination status, previous awareness of HPV and HIV status were independent predictors of the participants' willingness to pay for HPV vaccination. CONCLUSIONS: Participants in the current study demonstrated poor knowledge of HPV but the majority of MSM were willing to accept HPV vaccine after consultation; with HIV-infected MSM displaying higher acceptability towards a potential HPV vaccination than HIV-uninfected MSM. MSM who were previously aware of HPV were more likely to be willing to pay for HPV vaccine.

Prevalence and risk factors of anal human papillomavirus infection among HIV-negative men who have sex with men in Urumqi city of Xinjiang Uyghur Autonomous Region, China.

BACKGROUND: Infection with human papillomavirus (HPV) is the most common sexually transmitted infection among men who have sex with men (MSM). Study on prevalence and risk factors of anal HPV infection among HIV-negative MSM in Northwestern China was rare. METHODS: We performed a cross-sectional study of HPV prevalence using anal swab specimens among HIV-negative MSM in Urumqi city of Xinjiang Uyghur Autonomous Region, China between April 1st and October 30th in 2016. Prevalence of any anal HPV infection, high-risk and low-risk HPV infection was estimated. Risk factors associated with any anal HPV infection was analyzed using univariate and multivariate logistic regression models. RESULTS: Among 538 potential participants, 500(92.9%) were recruited in this study. The genotyping results of anal HPV infection were available for all. Of them, 259 (51.8%), 190 (38.0%) and 141(28.2%) were positive for at least one of the targeted 37 HPV genotypes, high-risk HPV genotypes, and any low-risk HPV genotypes. The most prevalent anal HPV genotype was HPV 6(11.8%), followed by HPV 16(11.2%), HPV 11(10.8%), HPV 51(7.0%) and HPV 18(5.4%).Among those infected with at least one of the targeted 37 anal HPV genotypes, 75(29.0%), 155(59.8%) and 191(73.7%) were infected with 2-valent, quadrivalent and 9-valent HPV vaccine-covered genotypes. Receptive anal intercourse in the past year was the only predictor of any anal HPV infection in multivariate logistic regression model. CONCLUSION: Prevalence of any anal HPV infection and high-risk HPV infection among HIV-negative MSM in Urumqi city of Xinjiang is high. The majority of genotypes detected in our study were covered by quadrivalent and 9-valent HPV vaccines. Regular anal exams and early HPV vaccination among MSM may be considered in future HPV prevention programs in Xinjiang, China.