Sex differences in inflammation correlated with estrogen and estrogen receptor-ß levels in azoxymethane/dextran sodium sulfate-induced colitis-associated colorectal cancer mice.

Colorectal cancer (CRC) is a type of cancer that develops in the colon or rectum and is the second leading cause of cancer-related death worldwide. Several epidemiology studies have identified a significant sexual dimorphism in CRC, with women exhibiting a lower incidence rate and delayed onset compared to men. This study aims to investigate the sexual dimorphism in the inflammatory response in colitis-associated CRC and its relationship with estrogen and estrogen receptors. An azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model was used to induce colitis-associated CRC. Five-week-old male and female mice were randomly assigned into either the control group or the AOM/DSS CRC group, with 10 mice in each group. Colitis-associated CRC was induced by injecting AOM (10 mg/kg) and administering two-cycles of DSS treatment in the drinking water. The results revealed a significant decrease in colon length exclusively in the female group, indicating more severe colonic inflammation (P < 0.01). A significant interaction was identified between sex and AOM/DSS treatment in the female AOM/DSS group, with higher visceral fat weight compared to their male counterparts (P < 0.05). The female AOM/DSS group also exhibited elevated production of M1 macrophage-related pro-inflammatory cytokines, suggesting increased tumor-associated macrophage activity. Surprisingly, the male AOM/DSS group showed a marked increase in serum estradiol levels, while the female AOM/DSS group exhibited a decrease compared to the normal control group. Additionally, a notable upregulation of both estrogen receptor α and estrogen receptor ß expression was observed in the colon tissues of the AOM/DSS groups compared to the normal control groups, with estrogen receptor ß expression being particularly pronounced in females. Taken together, our findings suggest that a decline in endogenous estrogen and increased estrogen receptors potentially contribute to the pro-inflammatory response in early CRC by augmenting cytokine expressions associated with M1 macrophage polarization in females.

Reconstruction of Fibrocartilage with Fibrous Alignment of Type I Collagen in Scaffold-Free Manner.

For functional reconstruction of fibrocartilage, it is necessary to reproduce the essential mechanical property exhibited by natural fibrocartilage. The distinctive mechanical property of fibrocartilage is originated from the specific histological features of fibrocartilage composed of highly aligned type I collagen (Col I) and an abundant cartilaginous matrix. While the application of tensile stimulation induces highly aligned Col I, our study reveals that it also exerts an antichondrogenic effect on scaffold-free tissues constructed with meniscal chondrocytes (MCs) and induces downregulation of Sox-9 expression and attenuated glycosaminoglycan production. Modulation of mechanotransduction by blocking nuclear translocation of Yes-associated protein (YAP) ameliorated the antichondrogenic effect in the presence of tensile stimulation. Since MCs subjected to mechanical doses either by surface stiffness or tensile stimulation showed reversibility of YAP status even after a long-term exposure to mechanotransduction, fibrocartilage tissue was constructed by sequentially inducing tissue alignment by tensile stimulation followed by inducing cartilaginous matrix production in a tension-released state. The minimal tensile dose to constitute durable tissue alignment was screened by investigating the alignment of cytoskeleton and Col I after culturing the scaffold-free tissue constructs with various tensile doses (10% static tension for 1, 3, 7, and 10 days) followed by maintaining in a released state for 5 days. Fluorescence-conjugated phalloidin binding and immunofluorescence of Col I indicated that the duration of static tension for more than 7 days resulted in durable tissue alignment for at least 5 days in the tension-released state. The tissues subjected to tensile stimulation for 7 days followed by 14 days in a released state in chondrogenic media resulted in abundant cartilaginous matrix as well as uniaxial anisotropic alignment. Our results show that the optimized tensile dose can facilitate the successful reconstruction of fibrocartilage by modulating the characteristics of matrix production by MCs.

Attachment Insecurity and Stigma as Predictors of Depression and Anxiety in People Living With HIV.

OBJECTIVE: The purpose of this study was to examine whether attachment insecurity, stigma, and certain demographic and medical factors predict depression and anxiety in people living with HIV (PLWH). METHODS: Participants were 147 PLWH who visited the outpatient infection clinic in Kyungpook National University Hospital (KNUH; Daegu, South Korea) between June 2020 and January 2021. We measured HIV-related stigma, attachment anxiety and avoidance, depressive symptoms, and anxiety symptoms. RESULTS: Logistic regression analysis showed that unemployment, longer time receiving antiretroviral therapy, higher attachment avoidance, and higher attachment anxiety were significant predictors of depression. Results also showed that longer time receiving antiretroviral therapy, higher attachment anxiety, and concern with public attitudes were significant predictors of anxiety. CONCLUSION: In addition to education to reduce public stigma, interventions to reduce PLWH's self-stigma should continue. We suggest attachment-based psychotherapy as an effective intervention to improve PLWH's mental health.

Psychiatry curriculum: How does it affect medical students' attitude toward psychiatry?

The purpose of this study was to identify the attitude of South Korean medical school students towards psychiatry and to analyze how lectures and clinical clerkship in psychiatry effect changes in students' attitudes. A total of 100 medical school students were recruited as subjects in the study, 86 of whom completed psychiatry lectures and underwent psychiatry clerkship from March 2015 to August 2018. The participating students completed a survey, which included demographic data, specialty choice, and attitude towards psychiatry. Subjects who completed lectures and clinical clerkship in psychiatry showed positive changes in attitude towards psychiatry in the following items: "Among mental health professionals, psychiatrists have the most authority and influence" (p = 0.002), "Psychiatrists frequently abuse their legal power to hospitalize patients against their will" (p < 0.001), and "Many people who could not obtain a residency position in other specialties eventually enter psychiatry" (p = 0.028). However, negative changes in attitude towards psychiatry were shown in the following item: "On average, psychiatrists make as much money as most other doctors" (p = 0.008). Also, specific medical school factors scored positively overall. Although it was not statistically significant, the questionnaire item "During my psychiatry rotation, psychiatry residents were good role models" was more positively observed by students after completion of psychiatry lectures and clerkship. After each curriculum, certain attitudes toward psychiatry were positively changed, but others either remained unchanged or were negatively changed. By using these study results to revise the current curriculum, medical school students' attitude towards psychiatry can be improved.

Serum-Derived Neuronal Exosomal microRNAs as Stress-Related Biomarkers in an Atopic Dermatitis Model.

Chronic allergic inflammatory skin disease-atopic dermatitis (AD)-is characterized by eczema, pruritus, xeroderma, and lichenification. Psychological stress is one cause of this disease; however, psychological stress will also result from the presence of AD symptoms. Previous studies have shown that psychological stress triggers neuroinflammation in the brain, where microRNAs (miRNAs) in the neuronal exosomes (nEVs) were analyzed to identify the composition of the miRNAs in the nEVs and how they were altered by AD. In this study, the AD model was induced by treatment with 2,4-dinitrochlorobenzene (DNCB). The expression patterns of neuroinflammation markers, such as brain-derived neurotrophic factor, cyclooxygenase-2, and glial fibrillary acidic protein, were subsequently evaluated over time. Among these groups, there was a significant difference in DNCB 14 days expression compared with the control; therefore, nEVs were isolated from serum and next-generation sequencing was performed. The results demonstrate that 9 miRNAs were upregulated and 16 were downregulated in the DNCB 14 days compared with the control. Previous studies have shown that some of these miRNAs are associated with stress and stress-induced depression, which suggests that the miRNAs in nEVs may also be stress-related biomarkers.

Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress.

Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers.

Biomaterials for Cell-Surface Engineering and Their Efficacy.

Literature in the field of stem cell therapy indicates that, when stem cells in a state of single-cell suspension are injected systemically, they show poor in vivo survival, while such cells show robust cell survival and regeneration activity when transplanted in the state of being attached on a biomaterial surface. Although an attachment-deprived state induces anoikis, when cell-surface engineering technology was adopted for stem cells in a single-cell suspension state, cell survival and regenerative activity dramatically improved. The biochemical signal coming from ECM (extracellular matrix) molecules activates the cell survival signal transduction pathway and prevents anoikis. According to the target disease, various therapeutic cells can be engineered to improve their survival and regenerative activity, and there are several types of biomaterials available for cell-surface engineering. In this review, biomaterial types and application strategies for cell-surface engineering are presented along with their expected efficacy.

Comparative Evaluation of Synovial Multipotent Stem Cells and Meniscal Chondrocytes for Capability of Fibrocartilage Reconstruction.

OBJECTIVE: Meniscus tissue is composed of highly aligned type I collagen embedded with cartilaginous matrix. This histological feature endows mechanical properties, such as tensile strength along the direction of the collagen alignment and endurance to compressive load induced by weight bearing. The main objective of this study was to compare the fibrocartilage construction capability of different cell sources in the presence of mechanical stimuli. DESIGN: Synovial multipotent stem cells (SvMSCs) and meniscal chondrocytes (MCs) from immature and mature rabbits were maintained under similar conditions for comparative evaluation of growth characteristics and senescence tendency. The differentiation potential of cell sources, including fibrocartilage generation, were comparatively evaluated. To determine the capability of fibrocartilage generation, cultured cell sheets were rolled up to produce cable-form tissue and subjected to chondrogenic induction in the presence or absence of static tension. RESULTS: Although SvMSCs showed superior cell growth characteristics during in vitro cell expansion, senescence-associated ß-galactosidase expression was consistently higher, compared with MCs. MCs showed glycosaminoglycan (GAG)-rich matrix formation during default in vitro chondrogenesis. While application of static tension significantly reduced GAG production, MCs continued to show robust tissue growth. SvMSCs showed inferior chondrogenic differentiation and diminished tissue growth in the presence of static tension. CONCLUSIONS: While SvMSCs produced fibrous tissue during default in vitro chondrogenesis, their fibrocartilage generation potential in the presence of static tension was significantly lower, compared with MCs. Our results support evaluation of cellular response to tensile stimulus as a decisive factor in determining the ideal cell source for fibrocartilage reconstruction.

Personality Types as Predictors of Breast Cancer Screening Compliance in Korean Patients: A Mixed-Method Approach.

OBJECTIVE: The purpose of this study is to identify personality types that can influence breast cancer screening (BCS) compliance among Korean women with breast cancer using a mixed-method approach. METHODS: The participants consisted of 93 women who underwent surgery for breast cancer between July 2010 and March 2012. The demographic and medical characteristics of the participants were evaluated through structured interviews. To identify personality types, in-depth interviews were performed and the transcribed interviews were evaluated using interpretive phenomenological analysis. The participants were categorized into two groups (compliance and non-compliance) based on compliance with the Korean Breast Cancer Society recommendations for BCS. RESULTS: Five personality types were identified through phenomenological analysis. There were significant differences in the chi-square test results for the BCS compliance and non-compliance groups according to age (p=0.048), cancer stage (p<0.001), and personality types (p=0.018). Logistic regression showed that the odds ratio for compliance with BCS was 9.35 (p=0.01) for individuals with a cautious-organized personality type, 9.38 (p=0.02) for those with a cautious-dependent personality, and 10.58 (p=0.04) for those with a sensitive-downcast personality compared to those with a cautious personality type. CONCLUSION: Participants with cautious-organized, cautious-dependent, and sensitive-downcast personality types were less likely to follow the BCS recommendations than those with a cautious personality type. This study provides a basis for the future development of an effective questionnaire to investigate the personality types of individuals with breast cancer in order to predict compliance with BCS.

CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment.

Near the bone remodeling compartments (BRC), extracellular calcium concentration (Ca2+o) is locally elevated and bone marrow stromal cells (BMSCs) close to the BRC can be exposed to high calcium concentration. The calcium-sensing receptor (CaSR) is known to play a key role in maintaining extracellular calcium homeostasis by sensing fluctuations in the levels of extracellular calcium (Ca2+o). When human BMSCs (hBMSCs) were exposed to various calcium concentrations (1.8, 3, 5, 10, 30 mM), moderate-high extracellular calcium concentrations (3-5 mM) stimulated proliferation, while a high calcium concentration (30 mM) inhibited the proliferation. Exposure to various calcium concentrations did not induce significant differences in the apoptotic cell fraction. Evaluation of multi-lineage differentiation potential showed no significant difference among various calcium concentration groups, except for the high calcium concentration (30 mM) treated group, which resulted in increased calcification after in vitro osteogenic differentiation. Treatment of NPS2143, a CaSR inhibitor, abolished the stimulatory effect on hBMSCs proliferation and migration indicating that CaSR is involved. These results suggest that the calcium concentration gradient near the BRC may play an important role in bone remodeling by acting as an osteoblast-osteoclast coupling mechanism through CaSR.

Microfluidic-Printed Microcarrier for In Vitro Expansion of Adherent Stem Cells in 3D Culture Platform.

Microcarrier-based stem cell expansion cultures can increase the dimensions of in vitro stem cell cultures from 2D to 3D. The culture handling process then becomes more efficient compared with conventional 2D cultures. However, the use of spherical plastic microcarriers complicates the monitoring of cell culture. To facilitate monitoring, transparent disc-shaped microcarriers are manufactured using a light-initiated microfluidic printing system and the obtained microcarriers are named as 2.5D microcarrier. The 2.5D microcarriers (diameter/height ≈ 5) enable us to use conventional monitoring tools in 2D-based platform during the in vitro expansion on a 3D culture platform. Surface modification via a 1 h-long poly-dopamine (PDA) reaction can maintain the transparent nature of the microcarriers while optimizing the cell attachment. The surface marker expression and differentiation potential of the 2.5D microcarrier-expanded stem cells reveal that the characteristics and functionalities preserved during expansion. The 2.5D microcarrier is readily integrated into an on-bead assay to conserve reagents and permit a high number (n = 9) of repeated measurements with reliable results. These results demonstrate that the 2.5D microcarrier-based scale-up culture provides a valuable tool for the in vitro expansion of adherent stem cells, especially if repetitive monitoring is required.

A Pathophysiological Validation of Collagenase II-Induced Biochemical Osteoarthritis Animal Model in Rabbit.

BACKGROUND: Current dilemma working with surgically-induced OA (osteoarthritis) model include inconsistent pathological state due to various influence from surrounding tissues. On the contrary, biochemical induction of OA using collagenase II has several advantageous points in a sense that it does not involve surgery to induce model and the extent of induced cartilage degeneration is almost uniform. However, concerns still exists because biochemical OA model induce abrupt destruction of cartilage tissues through enzymatic digestion in a short period of time, and this might accompany systemic inflammatory response, which is rather a trait of RA (rheumatoid arthritis) than being a trait of OA. METHODS: To clear the concern about the systemic inflammatory response that might be caused by abrupt destruction of cartilage tissue, OA was induced to only one leg of an animal and the other leg was examined to confirm the presence of systemic degenerative effect. RESULTS: Although the cartilage tissues were rapidly degenerated during short period of time upon biochemical induction of OA, they did not accompanied with RA-like process based on the histology data showing degeneration of articular cartilage occurred only in the collagenase-injected knee joint. Scoring evaluation data indicated that the cartilage tissues in non-induced joint remained intact. Neutrophil count transiently increase between day 8 and day 16, and there were no significant change in other complete blood count profile showing a characteristics of OA disease. CONCLUSION: These study shows that biochemically induced cartilage degeneration truly represented uniform and reliable OA state.

Five Month-Persistent Extrapyramidal Symptoms following a Single Injection of Paliperidone Palmitate: A Case Report.

Long-acting injectable (LAI) antipsychotics are useful in the treatments for schizophrenic patients with poor adherence due to their maintaining feature of therapeutic plasma level without daily administrations. However, their long-lasting property can cause complicated problems such as a long-lasting side effect. We report a patient who experienced LAI-induced extrapyramidal symptoms (EPSs) for 5 months after a single injection. During that period, every trial to ameliorate this condition turned out to be a failure. The 3-month formulation of paliperidone palmitate is now close at hand. We have to be aware of possible long-lasting adverse events and confirm the tolerability to LAI before use.