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INTRODUCTION: Recent investigations have highlighted the intratumoral administration of Toll-like receptor (TLR) ligands as a promising approach to initiate localized immune responses and enhance antitumor immunity. However, the clinical application of these ligands is limited by their rapid dissemination from the tumor microenvironment, raising concerns about reduced effectiveness and systemic toxicity. METHODS: To address these challenges, our study focused on the intratumoral delivery of mRNA encoding UNE-C1, a TLR2/6 ligand known for its efficacy and low toxicity profile. We explored the potential of UNE-C1 to induce immunogenic cell death (ICD) through autocrine mechanisms, facilitated by the release of damage-associated molecular patterns (DAMPs) triggered by TLR2 activation. RESULTS: Our findings indicate that sensitivity to UNE-C1-induced cell death is dependent on the expression levels of TLR2 and the Fas-associated death domain (FADD) in cancer cells. Furthermore, we investigated the paracrine activation of dendritic cells (DCs) by UNE-C1 via TLR2 signaling, which primes a CD8+ T cell response essential for tumor regression. DISCUSSION: Our results advocate for the intratumoral delivery of UNE-C1 via mRNA therapy as a promising strategy for innovative antitumor treatments.

Background: Suicide is a significant yet preventable public health issue. Body mass index (BMI) is a readily measurable indicator associated with various health outcomes. However, the relationship between BMI and suicidal death risk is complex and warrants further investigation, particularly within contemporary, non-Western contexts with consideration of potential confounders. The purpose of this study was to investigate the relationship between BMI and the risk of suicidal death. Methods: This study was nationwide, retrospective, observational study based on Korean National Health Insurance Service database. We analyzed 4,045,081 participants who were aged > 19 years and underwent national health surveillance in 2009. The participants were categorized according to their BMI (underweight: < 18.5 kg/m², normal weight: 18.5–23 kg/m², overweight: 23–25 kg/m², class I obesity: 25–30 kg/m², and class II obesity: > 30 kg/m²). The primary outcome was the death events caused by suicide which was defined by International Classification of Disorders (ICD-10) codes (X60–X84) and death records documented by the Korea National Statistical Office. Multivariate Cox proportional hazard regression analysis was performed to estimate the risk of suicidal death with respect to BMI categories after adjusting for potential confounders (age, sex, income, diabetes, hypertension, dyslipidemia, smoking, drinking, exercise, self-abuse, waist circumference, schizophrenia, bipolar disorder, eating disorder, cancer, anxiety, and substance use disorder). Results: Underweight individuals had an increased risk (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.31–1.57) while overweight (HR 0.79, 95% CI 0.76–0.83), class I (HR 0.76, 95% CI 0.71–0.80) and class II obesity (HR 0.71, 95% CI 0.63–0.81) were associated with decreased risks of suicidal deaths compared to those of the normal weight individuals (BMI 18.5–23). This trend was consistent regardless of the presence of major depressive disorder (MDD) or the type of living arrangements of the participants. Conclusions: Suicidal death risk was inversely correlated with BMI categories, independent of MDD or living arrangements. Our data suggests the importance of physiological factors associated with body mass in understanding suicidal death risk. Furthermore, these data provide valuable insights to where the public health resources should be invested to reduce suicidal death rates. [ABSTRACT FROM AUTHOR]

Background: This national population-based study aimed to assess the cumulative burden of non-alcoholic fatty liver disease (NAFLD) measured via the fatty liver index (FLI) and its association with kidney cancer risk in young men aged 20–39. Methods: Using the Korean National Health Insurance Service database, we examined a cohort of 1,007,906 men (age 20–39) who underwent four consecutive annual check-ups from 2009 to 2012. The FLI, calculated from body mass index values, waist circumference, triglyceride levels, and gamma-glutamyl transferase levels, was used to quantify the cumulative burden of NAFLD (FLI ≥ 60). The study population was followed until a kidney cancer diagnosis was made, death occurred, or the advent of 2020. Results: Over a mean follow-up of 7.74 years, 649 subjects developed kidney cancer. An increasing mean FLI was associated with an elevated hazard ratio (HR) for kidney cancer. The cumulative frequency of NAFLD (0–4) showed a corresponding increase in the HR for kidney cancer. This association persisted after adjusting for lifestyle factors including smoking, alcohol consumption, and physical activity. Subjects with improved NAFLD had a decreased risk of kidney cancer compared to those with persistent or aggravated NAFLD. Conclusions: This study revealed a significant association between NAFLD and kidney cancer in young men. Addressing NAFLD may offer a valuable opportunity to mitigate premature morbidity and mortality associated with young-onset kidney cancer in subsequent generations. [ABSTRACT FROM AUTHOR]

We have developed a 3D single-particle-tracking (SPT) system based around the two-photon laser-scanning fluorescence microscope that can track particles in all three dimensions and at a high frequency response. We have implemented two different techniques to achieve this goal. The techniques employ feedback control in order to track the particle but differ in the approach they use to ascertain the particle's 3D position. The first technique scans a small volume around a particle to build up a volumetric image that is then used to determine the particle position. The second technique scans only a single plane but utilizes optical aberrations which have been introduced into the optical system that break the axial symmetry of the point spread function and serves as an indicator of the particle's axial position. The current system has a frequency response at the video rate and an axial range of 100 μm. We tested the system by tracking well-defined test trajectories, and by tracking particles in model systems. We identified several different modes of motion in sucrose solutions and agarose gels, including the transient trapping of particles in the microdomains of agarose gels.