1.Therapeutic Potential of Hongjam in A Diethylnitrosamine and Thioacetamide-induced Hepatocellular Carcinoma Mouse Model
Young-Min HAN ; Hye-Rin AHN ; Da-Young LEE ; Moon-Young SONG ; Seung-Won LEE ; You-Kyung JANG ; Byeong Yeob JEON ; Eun-Hee KIM
Journal of Cancer Prevention 2024;29(4):165-174
		                        		
		                        			
		                        			 Hepatocellular carcinoma (HCC) is the most common and lethal type of primary liver cancer, frequently arising from chronic liver injury and inflammation. Despite treatment advancements, HCC prognosis remains poor, emphasizing the need for effective preventive and therapeutic strategies. This study investigates the hepatoprotective and anti-tumor effects of Hongjam, a steamed freeze-dried silkworm powder, in a diethylnitrosamine (DEN) and thioacetamide (TAA)-induced HCC mouse model. Mice were administered DEN intraperitoneally for 8 weeks, followed by TAA in drinking water for 9 weeks, with Hongjam supplementation (0.01, 0.1, and 1 g/kg) provided daily through food. Hongjam markedly reduced the tumor incidence, the size, and the histological lesions compared to the DEN/TAA group. Serum biochemical analysis revealed reduction in liver damage markers, including alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin, with a notable decrease in total bilirubin surpassing. Immunohistochemical and Western blot analyses demonstrated that Hongjam downregulated expression of proliferation markers, including Ki67, phosphorylation of protein kinase B, and proliferating cell nuclear antigen, while upregulating the pro-apoptotic protein Bcl-2-associated X protein, indicating its dual role in suppressing proliferation and promoting apoptosis. Furthermore, Hongjam inhibited angiogenesis by suppressing the expression of key markers, including interleukin 6, VEGF, hypoxia-inducible factor-1 subunit alpha, platelet-derived growth factor subunit beta, matrix metalloproteinase-2, and cluster of differentiation 31, thereby disrupting the tumor microenvironment. These findings suggest that Hongjam exerts multifaceted protective effects against HCC by targeting proliferation, apoptosis, and angiogenesis pathways, while also mitigating liver damage. This study highlights the potential of Hongjam as a functional food or a complementary therapeutic agent for HCC prevention and management. 
		                        		
		                        		
		                        		
		                        	
2.Multiple-wavelength radiation promotes hair growth by enhancing the early stages of hair follicle development in human dermal papilla cells and C57BL/6 mice
Soo Min KIM ; Tae-Rin KWON ; Dong Wook MOON ; Jungwook KIM ; Rae Hyun LIM ; Jungkwan LEE ; So Young LEE ; Ka Ram KIM ; Young Gue KOH ; Hye Sung HAN ; Sun Young CHOI ; Kwang Ho YOO
Medical Lasers 2024;13(1):35-46
		                        		
		                        			 Background:
		                        			We aimed to clarify the safety and efficacy of simultaneous skin exposure to blue, red, and infrared light. The purpose of this study was to confirm the mechanism by which multiple wavelengths increase hair development both in vivo and in vitro. 
		                        		
		                        			Methods:
		                        			Cultured human dermal papilla cells (hDPCs) were exposed to a 470/655/850 nm light-emitting diode (LED) array with a fixed energy density of 3.0 mW/cm 2 . We analyzed alkaline phosphatase (ALP) staining and activity. The relative expressions of ALP, VEGF, Shh, and OPN3 were examined using reverse transcriptasepolymerase chain reaction arrays 48 hours post-exposure and the protein levels related to extracellular signalregulated kinase (ERK)/protein kinase B (AKT)/glycogen synthase kinase 3 (GSK3)β signaling were assessed by western blotting. Next, we used H&E staining, hair growth scoring, skin thickness measurement, and the immunohistochemical analysis of the dorsal skin of C57BL/6 mice to investigate the effects of the mono- or combined-photobiomodulation (PBM) groups. 
		                        		
		                        			Results:
		                        			According to our findings, simultaneous irradiation with multi-wavelength LEDs at 470/655/850 nm increased the proliferation of hDPCs. Also, compared to the control group, the red wavelength and combined PBM groups had significantly improved skin thickness measurements. Overall, we concluded that the combined PBM therapy successfully induced the early onset of anagen and stimulated hair growth. 
		                        		
		                        			Conclusion
		                        			These results suggest that PBM therapy regulates hair growth by activating the ERK/AKT/GSK3βsignaling pathway. Thus, multiple-wavelength radiation from devices combining radiation emitted by lowpower lasers and LEDs could be a new approach for promoting PBM-induced beneficial effects. 
		                        		
		                        		
		                        		
		                        	
3.Therapeutic Potential of Hongjam in A Diethylnitrosamine and Thioacetamide-induced Hepatocellular Carcinoma Mouse Model
Young-Min HAN ; Hye-Rin AHN ; Da-Young LEE ; Moon-Young SONG ; Seung-Won LEE ; You-Kyung JANG ; Byeong Yeob JEON ; Eun-Hee KIM
Journal of Cancer Prevention 2024;29(4):165-174
		                        		
		                        			
		                        			 Hepatocellular carcinoma (HCC) is the most common and lethal type of primary liver cancer, frequently arising from chronic liver injury and inflammation. Despite treatment advancements, HCC prognosis remains poor, emphasizing the need for effective preventive and therapeutic strategies. This study investigates the hepatoprotective and anti-tumor effects of Hongjam, a steamed freeze-dried silkworm powder, in a diethylnitrosamine (DEN) and thioacetamide (TAA)-induced HCC mouse model. Mice were administered DEN intraperitoneally for 8 weeks, followed by TAA in drinking water for 9 weeks, with Hongjam supplementation (0.01, 0.1, and 1 g/kg) provided daily through food. Hongjam markedly reduced the tumor incidence, the size, and the histological lesions compared to the DEN/TAA group. Serum biochemical analysis revealed reduction in liver damage markers, including alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin, with a notable decrease in total bilirubin surpassing. Immunohistochemical and Western blot analyses demonstrated that Hongjam downregulated expression of proliferation markers, including Ki67, phosphorylation of protein kinase B, and proliferating cell nuclear antigen, while upregulating the pro-apoptotic protein Bcl-2-associated X protein, indicating its dual role in suppressing proliferation and promoting apoptosis. Furthermore, Hongjam inhibited angiogenesis by suppressing the expression of key markers, including interleukin 6, VEGF, hypoxia-inducible factor-1 subunit alpha, platelet-derived growth factor subunit beta, matrix metalloproteinase-2, and cluster of differentiation 31, thereby disrupting the tumor microenvironment. These findings suggest that Hongjam exerts multifaceted protective effects against HCC by targeting proliferation, apoptosis, and angiogenesis pathways, while also mitigating liver damage. This study highlights the potential of Hongjam as a functional food or a complementary therapeutic agent for HCC prevention and management. 
		                        		
		                        		
		                        		
		                        	
4.Therapeutic Potential of Hongjam in A Diethylnitrosamine and Thioacetamide-induced Hepatocellular Carcinoma Mouse Model
Young-Min HAN ; Hye-Rin AHN ; Da-Young LEE ; Moon-Young SONG ; Seung-Won LEE ; You-Kyung JANG ; Byeong Yeob JEON ; Eun-Hee KIM
Journal of Cancer Prevention 2024;29(4):165-174
		                        		
		                        			
		                        			 Hepatocellular carcinoma (HCC) is the most common and lethal type of primary liver cancer, frequently arising from chronic liver injury and inflammation. Despite treatment advancements, HCC prognosis remains poor, emphasizing the need for effective preventive and therapeutic strategies. This study investigates the hepatoprotective and anti-tumor effects of Hongjam, a steamed freeze-dried silkworm powder, in a diethylnitrosamine (DEN) and thioacetamide (TAA)-induced HCC mouse model. Mice were administered DEN intraperitoneally for 8 weeks, followed by TAA in drinking water for 9 weeks, with Hongjam supplementation (0.01, 0.1, and 1 g/kg) provided daily through food. Hongjam markedly reduced the tumor incidence, the size, and the histological lesions compared to the DEN/TAA group. Serum biochemical analysis revealed reduction in liver damage markers, including alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin, with a notable decrease in total bilirubin surpassing. Immunohistochemical and Western blot analyses demonstrated that Hongjam downregulated expression of proliferation markers, including Ki67, phosphorylation of protein kinase B, and proliferating cell nuclear antigen, while upregulating the pro-apoptotic protein Bcl-2-associated X protein, indicating its dual role in suppressing proliferation and promoting apoptosis. Furthermore, Hongjam inhibited angiogenesis by suppressing the expression of key markers, including interleukin 6, VEGF, hypoxia-inducible factor-1 subunit alpha, platelet-derived growth factor subunit beta, matrix metalloproteinase-2, and cluster of differentiation 31, thereby disrupting the tumor microenvironment. These findings suggest that Hongjam exerts multifaceted protective effects against HCC by targeting proliferation, apoptosis, and angiogenesis pathways, while also mitigating liver damage. This study highlights the potential of Hongjam as a functional food or a complementary therapeutic agent for HCC prevention and management. 
		                        		
		                        		
		                        		
		                        	
5.Association Between Individual Air Pollution (PM 10 , PM2.5) Exposure and Adverse Pregnancy Outcomes in Korea: A Multicenter Prospective Cohort, Air Pollution on Pregnancy Outcome (APPO) Study
Tae Gyu AHN ; Young Ju KIM ; Gain LEE ; Young-Ah YOU ; Soo Min KIM ; Rin CHAE ; Young Min HUR ; Mi Hye PARK ; Jin-Gon BAE ; Soo-Jeong LEE ; Young-Han KIM ; Sunghun NA
Journal of Korean Medical Science 2024;39(13):e131-
		                        		
		                        			 Background:
		                        			Prenatal exposure to ambient air pollution is linked to a higher risk of unfavorable pregnancy outcomes. However, the association between pregnancy complications and exposure to indoor air pollution remains unclear. The Air Pollution on Pregnancy Outcomes research is a hospital-based prospective cohort research created to look into the effects of aerodynamically exposed particulate matter (PM) 10 and PM 2.5 on pregnancy outcomes. 
		                        		
		                        			Methods:
		                        			This prospective multicenter observational cohort study was conducted from January 2021 to June 2023. A total of 662 women with singleton pregnancies enrolled in this study. An AirguardK ® air sensor was installed inside the homes of the participants to measure the individual PM 10 and PM 2.5 levels in the living environment. The time–activity patterns and PM 100 and PM 2.5 , determined as concentrations from the time-weighted average model, were applied to determine the anticipated exposure levels to air pollution of each pregnant woman. The relationship between air pollution exposure and pregnancy outcomes was assessed using logistic and linear regression analyses. 
		                        		
		                        			Results:
		                        			Exposure to elevated levels of PM 10 throughout the first, second, and third trimesters as well as throughout pregnancy was strongly correlated with the risk of pregnancy problems according to multiple logistic regression models adjusted for variables. Except for in the third trimester of pregnancy, women exposed to high levels of PM 2.5 had a high risk of pregnancy complications. During the second trimester and entire pregnancy, the risk of preterm birth (PTB) increased by 24% and 27%, respectively, for each 10 μg/m 3 increase in PM 10. Exposure to high PM 10 levels during the second trimester increased the risk of gestational diabetes mellitus (GDM) by 30%. The risk of GDM increased by 15% for each 5 μg/m 3 increase in PM2.5 during the second trimester and overall pregnancy, respectively. Exposure to high PM  10 and PM 2.5 during the first trimester of pregnancy increased the risk of delivering small for gestational age (SGA) infants by 96% and 26%, respectively. 
		                        		
		                        			Conclusion
		                        			Exposure to high concentrations of PM 10 and PM 2.5 is strongly correlated with the risk of adverse pregnancy outcomes. Exposure to high levels of PM10 and PM2.5 during the second trimester and entire pregnancy, respectively, significantly increased the risk of PTB and GDM. Exposure to high levels of PM 10 and PM2.5 during the first trimester of pregnancy considerably increased the risk of having SGA infants. Our findings highlight the need to measure individual particulate levels during pregnancy and the importance of managing air quality in residential environment. 
		                        		
		                        		
		                        		
		                        	
6.Risk Factors for the Mortality of Patients With Coronavirus Disease 2019Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study
Tae Wan KIM ; Won-Young KIM ; Sunghoon PARK ; Su Hwan LEE ; Onyu PARK ; Taehwa KIM ; Hye Ju YEO ; Jin Ho JANG ; Woo Hyun CHO ; Jin-Won HUH ; Sang-Min LEE ; Chi Ryang CHUNG ; Jongmin LEE ; Jung Soo KIM ; Sung Yoon LIM ; Ae-Rin BAEK ; Jung-Wan YOO ; Ho Cheol KIM ; Eun Young CHOI ; Chul PARK ; Tae-Ok KIM ; Do Sik MOON ; Song-I LEE ; Jae Young MOON ; Sun Jung KWON ; Gil Myeong SEONG ; Won Jai JUNG ; Moon Seong BAEK ;
Journal of Korean Medical Science 2024;39(8):e75-
		                        		
		                        			 Background:
		                        			Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. 
		                        		
		                        			Methods:
		                        			We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan–Meier (KM) method. 
		                        		
		                        			Results:
		                        			Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010–1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312–7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). 
		                        		
		                        			Conclusion
		                        			Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO. 
		                        		
		                        		
		                        		
		                        	
7.Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study
Tae Young HAN ; Dong Hyun SHIM ; Yu Jin LEE ; Young Bok LEE ; Ha Yeh Rin KOO ; Min Kyung SHIN ; Tae Eun KIM ; Yong Hyun JANG ; Jin Seon BANG ; Hyung Don KOOK ; Jiyoung AHN ; Hye Jung JUNG ; Chan Ho NA
Annals of Dermatology 2023;35(1):38-45
		                        		
		                        			 Background:
		                        			Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. 
		                        		
		                        			Objective:
		                        			This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. 
		                        		
		                        			Methods:
		                        			We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agentstreated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator’s global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and postvaccination. Adverse reactions to the COVID-19 vaccination were observed. 
		                        		
		                        			Results:
		                        			The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001).However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. 
		                        		
		                        			Conclusion
		                        			No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient. 
		                        		
		                        		
		                        		
		                        	
8.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2023;38(3):450-450
		                        		
		                        		
		                        		
		                        	
9.Monitoring α-synuclein Aggregation Induced by Preformed α-synuclein Fibrils in an In Vitro Model System
Beom Jin KIM ; Hye Rin NOH ; Hyongjun JEON ; Sang Myun PARK
Experimental Neurobiology 2023;32(3):147-156
		                        		
		                        			
		                        			 Parkinson’s disease (PD) is characterized by the presence of α-synuclein (α-syn) inclusions in the brain and the degeneration of dopamine-producing neurons. There is evidence to suggest that the progression of PD may be due to the prion-like spread of α-syn aggregates, so understanding and limiting α-syn propagation is a key area of research for developing PD treatments. Several cellular and animal model systems have been established to monitor α-syn aggregation and propagation. In this study, we developed an in vitro model using A53T α-syn-EGFP overexpressing SH-SY5Y cells and validated its usefulness for high-throughput screening of potential therapeutic targets. Treatment with preformed recombinant α-syn fibrils induced the formation of aggregation puncta of A53T α-syn-EGFP in these cells, which were analyzed using four indices: number of dots per cell, size of dots, intensity of dots, and percentage of cells containing aggregation puncta. Four indices are reliable indicators of the effectiveness of interventions against α-syn propagation in a one-day treatment model to minimize the screening time. This simple and efficient in vitro model system can be used for high-throughput screening to discover new targets for inhibiting α-syn propagation. 
		                        		
		                        		
		                        		
		                        	
10.Empiric Anti-Pseudomonal β-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching
Moon Seong BAEK ; Ae-Rin BAEK ; Sang-Bum HONG ; Soohyun BAE ; Hye Kyeong PARK ; Changhwan KIM ; Hyun-Kyung LEE ; Woo Hyun CHO ; Jin Hyoung KIM ; Youjin CHANG ; Heung Bum LEE ; Hyun-Il GIL ; Beomsu SHIN ; Kwang Ha YOO ; Jae Young MOON ; Jee Youn OH ; Kyung Hoon MIN ; Kyeongman JEON ;
Journal of Korean Medical Science 2023;38(41):e353-
		                        		
		                        			 Background:
		                        			There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric antipseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP. 
		                        		
		                        			Methods:
		                        			This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019.Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem β-lactam monotherapy and fluoroquinolone combination therapy groups.Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias. 
		                        		
		                        			Results:
		                        			In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286).There was no significant difference in 30-day mortality between the two groups (16.8% vs.18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782–3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups. 
		                        		
		                        			Conclusion
		                        			Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to β-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR. 
		                        		
		                        		
		                        		
		                        	
            
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