IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.

Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.

Health-related quality of life in female patients with reumatoid arthritis: a structural equation model.

PURPOSE: This study aimed to construct a structural equation model to explain and predict factors affecting the health-related quality of life (QoL) in female rheumatoid arthritis (RA) patients based on the health-related QoL model by Ferrans et al. (2005) and a literature review. METHODS: Patients (N=243) who were either registered members of an internet cafe composed of patients with RA or rheumatology outpatients at two tertiary general hospitals in Busan, Korea, were recruited via convenience sampling. Data were collected from July 2 to September 9, 2021, and the survey was conducted using a web-based questionnaire. The data were analyzed by SPSS and AMOS 26.0. RESULTS: The goodness-of-fit statistics of the final model exhibited good results (χ2/degree of freedom=2.68, Turker-Lewis index=.94, comparative fit index=.96, standardized root mean-squared residual=.04, root mean- square error of approximation=.08), and 11 out of 14 paths of the model were supported. The squared multiple correlation, which reflected the explanatory power of the environmental characteristics, symptoms, functional status, and perceived health status on health-related QoL, was 80%. In the hypothesis model, 10 paths had significant direct effects, 6 paths had significant indirect effects, and 12 paths had significant total (direct and indirect) effects. CONCLUSION: Considering that factors directly affecting the health-related QoL of female patients with RA were social support, symptoms (fatigue and depression), resilience, and perceived health status, and that resilience was the most influential factor, clinicians can encourage resilience. Hence, to improve the health-related QoL of female patients with RA, continuing management is necessary, using various intervention methods that focus on enhancing resilience from the early stage to the end of treatment for RA.

Melatonin Protects Bone Microarchitecture against Deterioration due to High-Fat Diet-Induced Obesity.

BACKGROUND: We evaluated the protective effects of melatonin against high-fat diet (HFD)-induced deterioration of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Four-week-old male C57BL/6 mice were divided into control (chow diet group), HFD, and HFD + melatonin-administered groups. Mice were sacrificed after 14 weeks, and the right femur was extracted. The microskeletal structure of the femur was analyzed using SkyScan1173 (version 1.6). A 3-dimensional image was reconstructed using the Nrecon (version 1.7.0.4) program. RESULTS: Bone volume (BV) was significantly increased in the HFD group compared with that in the normal diet group, and that of the melatonin group also increased significantly compared with BV of the normal diet group (p<0.05). Percent BV/total volume [TV] and bone surface/BV were significantly higher in both the HFD and melatonin groups than in the normal diet group (p<0.05), and the melatonin group had the highest BV/total volume (TV). BMD was lower in the HFD than in the normal diet group and was the highest in the melatonin group. CONCLUSIONS: This study shows that melatonin inhibited the deterioration of microarchitecture induced by a HFD. A better understanding of the protective effect of melatonin on bone microarchitecture and mechanisms could provide fracture prevention for people who are obese.

Protective Effects of Melatonin in High-Fat Diet-Induced Hepatic Steatosis via Decreased Intestinal Lipid Absorption and Hepatic Cholesterol Synthesis.

BACKGRUOUND: The preventative effect of melatonin on the development of obesity and the progression of fatty liver under a high-fat diet (HFD) has been well elucidated through previous studies. We investigated the mechanism behind this effect regarding cholesterol biosynthesis and regulation of cholesterol levels. METHODS: Mice were divided into three groups: normal chow diet (NCD); HFD; and HFD and melatonin administration group (HFD+M). We assessed the serum lipid profile, mRNA expression levels of proteins involved in cholesterol synthesis and reabsorption in the liver and nutrient transporters in the intestines, and cytokine levels. Additionally, an in vitro experiment using HepG2 cells was performed. RESULTS: Expression of hepatic sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) demonstrated that melatonin administration significantly reduces hepatic cholesterol synthesis in mice fed an HFD. Expression of intestinal sodium-glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), GLUT5, and Niemann-pick C1-like 1 (NPC1L1) demonstrated that melatonin administration significantly reduces intestinal carbohydrate and lipid absorption in mice fed an HFD. There were no differences in local and circulatory inflammatory cytokine levels among the NCD, HFD, and HFD+M group. HepG2 cells stimulated with palmitate showed reduced levels of SREBP, LDLR, and HMGCR indicating these results are due to the direct mechanistic effect of melatonin on hepatocytes. CONCLUSION: Collectively, these data indicate the mechanism behind the protective effects of melatonin from weight gain and liver steatosis under HFD is through a reduction in intestinal caloric absorption and hepatic cholesterol synthesis highlighting its potential in the treatment of obesity and fatty liver disease.

Momordica charantia (bitter melon) efficacy and safety on glucose metabolism in Korean prediabetes participants: a 12-week, randomized clinical study.

This study was performed to investigate the effects of bitter melon extract (BME) on glucose metabolism, insulin resistance, and various metabolic parameters of participants with prediabetes. A 12-week randomized placebo-controlled clinical study was conducted with prediabetic patients. A total of 76 participants were randomly assigned to initiate the study. In the final analysis, 33 and 32 subjects were included in the BME and placebo groups, respectively. Results showed that 75 g oral glucose tolerance test (OGTT) blood glucose level decreased in BME group after 12 weeks. The glucose level after 30 min of glucose ingestion decreased significantly. The glucagon level in the BME group after 12 weeks significantly decreased 120 min after 75 g OGTT. These results suggested that bitter melon exhibits glucose-lowering effects through suppression of glucagon levels in people with prediabetes.

Effectiveness of Non-Contact Dietary Coaching in Adults with Diabetes or Prediabetes Using a Continuous Glucose Monitoring Device: A Randomized Controlled Trial.

We aimed to evaluate the effectiveness of dietary coaching and continuous glucose monitoring (CGM) in patients with diabetes or prediabetes to improve their behavioral skills and health outcomes. A randomized controlled study with pre- and post-testing was conducted. Data were collected between November 2020 and April 2021. Forty-five patients with diabetes or prediabetes who used a CGM device were enrolled and analyzed. Dietary education, individual coaching and group coaching were provided to participants in the experimental group for 4 weeks. After the intervention, the thigh circumference in men significantly differed between the two groups (z = -2.02, p = 0.044). For women, participants in the experimental group showed greater improvement in eating self-efficacy compared with those in the control group (z = -2.66, p = 0.008). Insomnia was negatively related to the change in eating self-efficacy (r = -0.35, p = 0.018) and increase in thigh circumference (r = -0.35, p = 0.017). Even if used within a short intervention period, non-contact dietary coaching programs can help enhance behavioral skills, such as eating self-efficacy and health outcomes, such as thigh circumference. Moreover, the changed variables can indirectly improve other health outcomes in patients with diabetes or prediabetes.

Impact of Anxiety, Social Support, and Taegyo Practice on Maternal-Fetal Attachment in Pregnant Women Having an Abortion.

PURPOSE: The purpose of the study was to identify effects of anxiety, social support, and Taegyo practice toward maternal-fetal attachment in pregnant women having an abortion. METHOD: Participants included 99 pregnant women having an abortion, who participated in this study. Collected data were analyzed using descriptive statistics, t-test, ANOVA, Pearson's correlation, and multiple regression with the SPSS WIN 23.0 program. RESULTS: Maternal-fetal attachment was significantly negatively correlated with anxiety, and significantly positively correlated with social support and Taegyo practice. Spousal support and Taegyo practice, explained 43.8% of participants' maternal-fetal attachment. CONCLUSION: Results indicate that less anxiety and more social support, and Taegyo practice in pregnant women having an abortion, were associated with stronger maternal-fetal attachment. To strengthen the maternal-fetal attachment of pregnant women having an abortion experience, it would be necessary to develop and implement the Taegyo program, focusing on practicing Taegyo-related encouragement. Additionally, it is recommended that nursing intervention is provided, to encourage families to participate in the Taegyo practice together throughout the gestational period, and to maintain a positive relationship among partners.

Clinical significance of trabecular bone score for prediction of pathologic fracture risk in patients with multiple myeloma.

OBJECTIVES: Osteolytic bone lesions are common complications in multiple myeloma (MM), and can have an impact on quality of life due to the risk of fractures. Trabecular bone score (TBS) is a novel texture index derived from dual energy x-ray absorptiometry (DXA) of lumbar spine (LS) images that provides information about bone microarchitecture. The aim of this study was to evaluate whether TBS is useful in predicting bone fractures in MM patients. METHODS: TBS was calculated retrospectively from existing DXA images of the LS, in 20 patients with newly diagnosed MM. We analyzed the development of fractures in these patients. RESULTS: The median age of the patients was 66 years (range, 49-77 years). Osteolytic bone lesions were observed in 18 patients (90%) at the time of diagnosis. The median duration of follow-up was 40.0 months (95% confidence interval [CI], 33.2-46.2), 6 fracture events (long-bone fractures in 5 events, vertebral fracture in 1) occurred in 5 patients (25%). There were no significant differences between patients who experienced new onset fractures and patients who did not for all TBSs and T-scores, although the fracture group had lower levels than the no fracture group. However, among TBSs of individual LSs, only L2 showed significantly lower scores in patients who developed fractures (1.135 ±â€¯0.085 [95% CI, 1.030-1.241] vs. 1.243 ±â€¯0.169 [95% CI, 1.149-1.336], P = 0.032). CONCLUSIONS: TBS of the LS in MM patients may be helpful in predicting development of fractures; however, further investigation is needed.

Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1α-VEGF signaling axis.

A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Previously, we have shown that GV1001 interacts with heat shock proteins (HSPs) and penetrates cell membranes to be localized in the cytoplasm. In this study, we have found that GV1001 lowered the level of intracellular and surface HSPs of various cancer cells. In hypoxic conditions, GV1001 treatment of cancer cells resulted in decreases of HSP90, HSP70, and HIF-1α. Subsequently, proliferation of cancer cells and synthesis of VEGF were significantly reduced by treatment using GV1001 in hypoxic conditions. In an experiment using a nude mouse xenograft model, GV1001 exerted a similar tumor suppressive effect, further confirming its anti-tumor efficacy. Higher apoptotic cell death, reduced proliferation of cells, and fewer blood vessels were observed in GV1001-treated tumors compared to control. In addition, significant reduction of Tie2+ CD11b+ monocytes, which were recruited by VEGF from tumor cells and play a critical role in angiogenesis, was observed in GV1001-treated tumors. Collectively, the results suggest that GV1001 possesses potential therapeutic efficacy in addition to its ability to induce anti-cancer immune responses by suppressing both HSP70 and HSP90.

Heat shock protein-mediated cell penetration and cytosolic delivery of macromolecules by a telomerase-derived peptide vaccine.

A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Here, we report an unexpected function of GV1001 as a cell-penetrating peptide (CPP). GV1001 was delivered into a variety of cells including various cancer cell lines and primary blood cells. Moreover, the delivered GV1001 was predominantly located in the cytoplasm of the cells, while a significantly higher proportion of TAT peptide was localized in the nucleus. Macromolecules such as proteins, DNA and siRNA, which were linked to GV1001 by direct covalent conjugation or non-covalent complexation through poly-lysine, were successfully delivered into cells, indicating that GV1001 can be used as a carrier for macromolecules. Expression of the delivered DNA, and lowered expression of the target gene by the delivered siRNA, suggest the potential therapeutic use of GV1001. Pull-down analysis identified Heat Shock Protein 90 (HSP90) and 70 (HSP70) as GV1001 interacting proteins. Treatment of Anti-HSP90 and HSP70 antibodies lowered the internalization of GV1001, indicating that the interaction is critical for the efficient internalization of GV1001. Collectively, the results of this study suggest the pharmaceutical potential of GV1001, already proven safe in clinical trials, as a carrier for the delivery of macromolecular therapeutics into cells, in addition to its own anti-cancer activity.

Correlation of right atrial appendage velocity with left atrial appendage velocity and brain natriuretic Peptide.

BACKGROUND: Left atrial appendage (LAA) anatomy and function have been well characterized both in healthy and diseased people, whereas relatively little attention has been focused on the right atrial appendage (RAA). We sought to evaluate RAA flow velocity and to compare these parameters with LAA indices and with a study of biomarkers, such as brain natriuretic peptide, among patients with sinus rhythm (SR) and atrial fibrillation (AF). METHODS: In a series of 79 consecutive patients referred for transesophageal echocardiography, 43 patients (23 with AF and 20 controls) were evaluated. RESULTS: AF was associated with a decrease in flow velocity for both LAA and RAA [LAA velocity-SR vs. AF: 61 ± 22 vs. 29 ± 18 m/sec (p < 0.01), RAA velocity-SR vs. AF: 46 ± 20 vs. 19 ± 8 m/sec (p < 0.01)]. Based on simple linear regression analysis, LAA velocity and RAA velocity were positively correlated, and RAA velocity was inversely correlated with brain natriuretic peptide (BNP). CONCLUSION: AF was associated with decreased RAA and LAA flow velocities. RAA velocity was found to be positively correlated with LAA velocity and negatively correlated with BNP. The plasma BNP concentration may serve as a determinant of LAA and RAA functions.

Effects of Helicobacter pylori eradication in patients with immune thrombocytopenic purpura.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and chronic idiopathic thrombocytopenic purpura (ITP) has been confirmed; however, no clear evidence for the effectiveness of H. pylori eradication on ITP exists thus far. The purpose of this study was to investigate platelet recovery in chronic ITP after H. pylori eradication. METHODS: A total of 25 patients (18 male, 7 female; the median age of 55 years) diagnosed with ITP, whose platelet counts were less than 100×10(3)/µL, were enrolled. They were tested for H. pylori infection by the rapid urea test or urea breath test. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. RESULTS: Of the 25 patients, 23 (92%) were diagnosed with H. pylori infection. Of all the ITP patients, 11 (44%) exhibited a complete response (CR) to H. pylori eradication therapy; 6 (24%), a partial response (PR); and 8 (32%) were nonresponsive (NR). Predictive factors of response after H. pylori eradication therapy were platelet counts at the initial response (27.3% responders among patients with platelet counts <100×10(3)/µL vs 100% responders among patients with platelet counts ≥100×10(3)/µL, P<0.001) and H. pylori infectivity (73.9% responders among the H. pylori positive patients vs 0% responders among the H. pylori negative patients, P=0.032). CONCLUSION: This study confirmed the efficacy of H. pylori eradication in increasing the platelet count in ITP patients. Further studies with a larger number of patients are necessary to identify the crucial predictive factors responsible for platelet recovery in chronic ITP patients with the H. pylori infection.

Prevalence of human papillomavirus and Chlamydia trachomatis infection among women attending cervical cancer screening in the Republic of Korea.

Cervical cancer screening with the conventional Papanicolaou test is recommended for the women aged 30 years and more in Korea. Cervical infection with human papillomavirus (HPV) is the most important cause of cervical cancer and Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection and may also be associated with risk of cervical cancer. A cross-sectional study of women attending the National Cervical Cancer Screening Program in Busan and Suwon was carried out. Exfoliated cervical cells were collected, and questionnaires were administered to 4595 women. High-risk HPV types and CT were tested by Hybrid Capture 2 (HC2). HPV genotyping of 355 high-risk HPV-positive women at HC2 was performed using linear array. Age-standardized prevalence of high-risk HPV types and CT was 10.4% (95% confidence interval: 9.5-11.3) and 4.3% (95% confidence interval: 3.7-4.8). That 68.5% of women were high-risk HPV-positive at HC2 was confirmed by Linear Array whereas 17.5% seemed to be infected with only low-risk HPV types, not normally detected by HC2. Korean women showed a relatively high prevalence of high-risk HPV and a rather low prevalence of CT. As in cancer-free women in other Asian populations, HPV 52, 58, and 39 were detected more frequently than HPV 16. Cross-reaction of HC2 with low-risk HPV types is of some concern, were the test to be used in primary screening.