Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) has emerged as an innovative immunotherapy for hematological cancer treatment. However, the limited effect on solid tumors, complex processes, and excessive manufacturing costs remain as limitations of CAR-T therapy. Nanotechnology provides an alternative to the conventional CAR-T therapy. Owing to their unique physicochemical properties, nanoparticles can not only serve as a delivery platform for drugs but also target specific cells. Nanoparticle-based CAR therapy can be applied not only to T cells but also to CAR-natural killer and CAR-macrophage, compensating for some of their limitations. This review focuses on the introduction of nanoparticle-based advanced CAR immune cell therapy and future perspectives on immune cell reprogramming.

Background: This study assessed the relationship between non-participation in health checkups and all-cause mortality and morbidity, considering socioeconomic status. Methods: Healthy, middle-aged (35–54 years) working individuals who maintained either self-employed or employee status from 2006–2010 were recruited in this retrospective cohort study from the National Health Insurance Service in Korea. Health check-up participation was calculated as the sum of the number of health check-ups in 2007–2008 and 2009–2010.Adjusted hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality were estimated for each gender using multivariable Cox proportional hazard models, adjusting for age, income, residential area, and employment status. Interaction of non-participation in health check-ups and employment status on the risk of all-cause mortality was further analyzed. Results: Among 4,267,243 individuals with a median 12-year follow-up (median age, 44;men, 74.43%), 89,030 (2.09%) died. The proportion (number) of deaths of individuals with no, one-time, and two-time participation in health check-ups was 3.53% (n = 47,496), 1.66% (n = 13,835), and 1.33% (n = 27,699), respectively. The association between health checkup participation and all-cause mortality showed a reverse J-shaped curve with the highest adjusted HR (95% CI) of 1.575 (1.541–1.611) and 1.718 (1.628–1.813) for men and women who did not attend any health check-ups, respectively. According to the interaction analysis, both genders showed significant additive and multiplicative interaction, with more pronounced additive interaction among women who did not attend health check-ups (relative excess risk due to interaction, 1.014 [0.871−1.158]). Conclusion Our study highlights the significant reverse J-shaped association between health check-up participation and all-cause mortality. A pronounced association was found among self-employed individuals, regardless of gender.

OBJECTIVES: Lifestyles, including exercise behaviors, change continually over time. This study examined whether the clinical biomarkers (CBs) related to cardiometabolic diseases (CMDs) and their relationships differed with changes in exercise behavior. METHODS: The Ansan-Ansung cohort study (third to fifth phases; n=2,668) was used in the current study. Regular exercise behavior was investigated using a yeso questionnaire. Changes in exercise behavior were classified into 4 groups: Y-N, N-Y, Y-Y, and N-N, with “Y” indicating that a participant regularly engaged in exercise at a given time point and “N” indicating that he or she did not. Fourteen CBs related to CMDs were used, and the associations between changes in exercise behavior and relative changes in CBs were examined. CB networks were constructed and topological comparisons were conducted. RESULTS: Y-N was associated with increases in fasting blood sugar and insulin levels in men, and increased total cholesterol and low-density lipoprotein cholesterol levels in women. Meanwhile, N-Y was inversely associated with body fat percentage, visceral fat percentage, fasting insulin, and triglyceride level. Waist circumference played a central role in most networks. In men, more edges were found in the N-Y and Y-Y groups than in the N-N and Y-N groups, whereas women in the N-Y and Y-Y groups had more edges than those in the N-N and Y-N groups. CONCLUSIONS Consistent exercise or starting to engage in regular exercise had favorable effects on CBs related to CMDs, although their network patterns differed between the sexes.

Traditional epidemiological studies have identified a number of risk factors for various diseases using regression-based methods that examine the association between an exposure and an outcome (i.e., one-to-one correspondences). One of the major limitations of this approach is the “black-box” aspect of the analysis, in the sense that this approach cannot fully explain complex relationships such as biological pathways. With high-throughput data in current epidemiology, comprehensive analyses are needed. The network approach can help to integrate multi-omics data, visualize their interactions or relationships, and make inferences in the context of biological mechanisms. This review aims to introduce network analysis for systems epidemiology, its procedures, and how to interpret its findings.

Traditional epidemiological studies have identified a number of risk factors for various diseases using regression-based methods that examine the association between an exposure and an outcome (i.e., one-to-one correspondences). One of the major limitations of this approach is the “black-box” aspect of the analysis, in the sense that this approach cannot fully explain complex relationships such as biological pathways. With high-throughput data in current epidemiology, comprehensive analyses are needed. The network approach can help to integrate multi-omics data, visualize their interactions or relationships, and make inferences in the context of biological mechanisms. This review aims to introduce network analysis for systems epidemiology, its procedures, and how to interpret its findings.