Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes.

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 µg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco's phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.

Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus.

To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.

BACKGROUND: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. OBJECTIVE: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. METHODS: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. RESULTS: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. CONCLUSION: CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

Prevalence, clinical correlations, comorbidities, and suicidal tendencies in pathological Korean gamblers: results from the Korean Epidemiologic Catchment Area Study.

OBJECTIVE: Based on the National Epidemiological Survey of Psychiatric Disorders in South Korea conducted in 2006, we examined the prevalence, clinical correlations, comorbidities, and suicidal tendencies of pathological gamblers in the community. METHOD: Of the 6,510 participants who completed the Korean version of the Composite International Diagnostic Interview (K-CIDI) administered by trained lay interviewers, 5,333 subjects fully completed the Diagnostic Interview Schedule (DIS) exploring pathological gambling. The DIS has 13 items mapping to 10 criteria. Endorsement of five DSM-IV criteria was considered to reflect pathological gambling, and we considered endorsement of one to four criteria to indicate problem gambling. The frequencies of psychiatric disorders and suicidal tendency were analyzed among pathological/problem gamblers in comparison with controls; both odds ratios and significance levels were calculated. RESULTS: The lifetime prevalence rates of pathological gambling and problem gambling were 0.8% and 3.0%, respectively. Of pathological gamblers, 79.1% had at least one psychiatric illness in comparison to the control level of 28.1%, and 62.0% of problem gamblers also had psychiatric conditions. Associations between pathological/problem gambling and alcohol use disorder, nicotine dependence, mood disorder, anxiety disorder, and suicidality were overwhelmingly positive and significant (p < 0.05), even after controlling for age and gender. Male gender, divorced/separated/widowed marital status, and urban living were all associated with increased risks of pathological and problem gambling (p < 0.05). CONCLUSION: Pathological/problem gambling is highly associated with substance abuse, mood and anxiety disorders, and suicidality, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in gamblers.

Partial versus full PTSD in the Korean community: prevalence, duration, correlates, comorbidity, and dysfunctions.

A few studies have been conducted on the prevalence of partial posttraumatic stress disorder (PTSD), but points of agreement and disagreement between full and partial PTSD have not been fully investigated. We interviewed a representative sample of 6,258 subjects, ages 18-64 years, in household visits using the Korean version of the Composite International Diagnostic Interview (K-CIDI 2.1). "Partial PTSD" was defined as >/=1 symptom in each of the three symptom groups (Criteria B, C, and D) and duration of >/=1 month (Criterion E). Estimated lifetime prevalence of partial PTSD was 2.7%, and that of full PTSD was 1.7%. A "female gender" risk factor was significantly associated with both partial and full PTSD. The mean duration of partial PTSD was 6.5 years, which was not significantly different from the 5.7 year duration of full PTSD. Traumas associated with the development of partial rather than full PTSD were "natural disaster with fire" and "military combat" in men, and "witnessing a traumatic situation" and "learning about traumas to others" in women, whereas "threatened by others" was more associated with the development of full PTSD. The rates of multiple comorbid disorders and of comorbid major depressive disorder and dysfunctions in work during the 1-month period prior to interview did not differ significantly between the partial and full PTSD groups. In conclusion, partial PTSD did not differ significantly from full PTSD in terms of duration, comorbidity, and dysfunction, but they differed markedly in terms of associated trauma types.