1.Kidney protective potential of lactoferrin: pharmacological insights and therapeutic advances
Md. Sarwar ZAHAN ; Kazi Ahsan AHMED ; Akhi MONI ; Alessandra SINOPOLI ; Hunjoo HA ; Md Jamal UDDIN
The Korean Journal of Physiology and Pharmacology 2022;26(1):1-13
Kidney disease is becoming a global public health issue. Acute kidney injury (AKI) and chronic kidney disease (CKD) have serious adverse health outcomes.However, there is no effective therapy to treat these diseases. Lactoferrin (LF), a multi-functional glycoprotein, is protective against various pathophysiological conditions in various disease models. LF shows protective effects against AKI and CKD.LF reduces markers related to inflammation, oxidative stress, apoptosis, and kidney fibrosis, and induces autophagy and mitochondrial biogenesis in the kidney. Although there are no clinical trials of LF to treat kidney disease, several clinical trials and studies on LF-based drug development are ongoing. In this review, we discussed the possible kidney protective mechanisms of LF, as well as the pharmacological and therapeutic advances. The evidence suggests that LF may become a potent pharmacological agent to treat kidney diseases.
2.Adenosine receptors as emerging therapeutic targets for diabetic kidney disease
Eun Seon PAK ; Jin Joo CHA ; Dae Ryong CHA ; Keizo KANASAKI ; Hunjoo HA
Kidney Research and Clinical Practice 2022;41(Suppl 2):S74-S88
Diabetic kidney disease (DKD) is now a pandemic worldwide, and novel therapeutic options are urgently required. Adenosine, an adenosine triphosphate metabolite, plays a role in kidney homeostasis through interacting with four types of adenosine receptors (ARs): A1AR, A2AAR, A2BAR, and A3AR. Increasing evidence highlights the role of adenosine and ARs in the development and progression of DKD: 1) increased adenosine in the plasma and urine of diabetics with kidney injury, 2) increased expression of each of the ARs in diabetic kidneys, 3) the protective effect of coffee, a commonly ingested nonselective AR antagonist, on DKD, and 4) the protective effect of AR modulators in experimental DKD models. We propose AR modulators as a new therapeutic option to treat DKD. Detailed mechanistic studies on the pharmacology of AR modulators will help us to develop effective first-in-class AR modulators against DKD.
3.Comparative Analysis of Health Patterns and Gaps due to Environmental Influences in South Korea and North Korea, 2000–2017
Yoorim BANG ; Jongmin OH ; Eun Mee KIM ; Ji Hyen LEE ; Minah KANG ; Miju KIM ; Seok Hyang KIM ; Jae Jin HAN ; Hae Soon KIM ; Oran KWON ; Hunjoo HA ; Harris Hyun-soo KIM ; Hye Won CHUNG ; Eunshil KIM ; Young Ju KIM ; Yuri KIM ; Younhee KANG ; Eunhee HA
The Ewha Medical Journal 2022;45(4):e14-
Objectives:
To conduct a comparative study of children’s health in South Korea versus North Korea focusing on air pollution.
Methods:
We used annual mortality rate, prevalence, and environmental indicators data from the World Bank and World Health Organizations (WHO). Trend analysis of the two Koreas was conducted to evaluate changes in health status over time. Spearman’s correlation analysis was used to find out the correlation between environmental indicators and children’s health status.
Results:
We found a distinct gap in children’s health status between the two Koreas. While North Korea reported a higher death rate of children than South Korea, both showed a decreasing trend with the gap narrowing from 2000 to 2017. The prevalence of overweight and obesity increased and that of thinness decreased in both Koreas. Except PM2.5 exposure, South Korea reported higher figures in most indicators of air pollutant emissions (South Korea, mean (SD)=28.3 (2.0); North Korea, mean (SD)=36.5 (2.8), P-value=0.002).
Conclusion
This study empirically discovered the gaps and patterns of children’s health between South Korea and North Korea. North Korean children experienced more severe health outcomes than children in South Korea. These findings imply that epigenetic modification caused by environmental stressors affect children’s health in the two Koreas despite similar genetic characteristics. Considering the gaps in children’s health between the two Koreas, more attention and resources need to be directed towards North Korea because the necessary commodities and services to improve children’s health are lacking in North Korea.
4.Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice
Songling JIANG ; Md Jamal UDDIN ; Xiaoying YU ; Lingjuan PIAO ; Debra DOROTEA ; Goo Taeg OH ; Hunjoo HA
Diabetes & Metabolism Journal 2022;46(6):829-842
Background:
Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist.
Methods:
Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD.
Results:
HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In Ppara deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury.
Conclusion
The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.
5.KF-1607, a Novel Pan Src Kinase Inhibitor, Attenuates Obstruction-Induced Tubulointerstitial Fibrosis in Mice
Debra DOROTEA ; Seungyeon LEE ; Sun Joo LEE ; Gayoung LEE ; Jung Beom SON ; Hwan Geun CHOI ; Sung-Min AHN ; Hunjoo HA
Biomolecules & Therapeutics 2021;29(1):41-51
Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson’s trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.
6.Development of Gender-Sensitive Comprehensive Health Matrix: A Comparative Study on the Cases of Sustainable Development Goals Countries and North Korea Based on Gender-Sensitive Indicators
Yoorim BANG ; Youngrin KWAG ; Eun Mee KIM ; Eunhee HA ; Oran KWON ; Hae Soon KIM ; Hyesook KIM ; Seok Hyang KIM ; Miju KIM ; Eunshil KIM ; Jae Jin HAN ; Kooyoung JUNG ; Hunjoo HA
Journal of the Korean Society of Maternal and Child Health 2020;24(1):40-51
Purpose:
South Korea ranked 18th out of the 162 participating countries in the 2019 report on sustainable development goals (SDGs). Among the 17 specified goals, it has the most difficulty in achieving gender equality (SDG 5). This shortcoming is manifested in the lack of studies on gender-sensitive indicators. The study aims to establish the significance of the development of a comprehensive health matrix to concretize the concept of gender-sensitivity which is often considered as abstract.
Methods:
An integrated analysis of health determinants was conducted through a convergence study involving medical, social and natural sciences. This analysis was based on both literature reviews and focusgroup discussions. The 6 following focal points were chosen based on the SDGs: gender equality, medicine, education, economy, nutrition, and environment. Objective quantitative indicators were then designated to each of the 6 areas and comparatively analyzed for South Korea, North Korea, and the other SDGs countries. Four areas on sexual and reproductive health were also selected.
Results:
The results indicated that South Korea scored much lower than North Korea and the other SDGs countries in terms of gender equality. It was also behind North Korea in education, although North Korea had a comparatively lower ranking in the rest of the areas. On the other hand, it fared better than the aforementioned countries with respect to environment, nutrition, medicine, and economy.
Conclusion
A comprehensive gender-sensitive health matrix was developed to refine the abstract concept of gender-sensitivity through objective quantitative indicators that assess the health status of a country by means of a scoring system. Gender equality was also confirmed as a common and significant component in the disciplines of sexual and reproductive health and comprehensive health.
7.Development of Gender-Sensitive Comprehensive Health Matrix: A Comparative Study on the Cases of Sustainable Development Goals Countries and North Korea Based on Gender-Sensitive Indicators
Yoorim BANG ; Youngrin KWAG ; Eun Mee KIM ; Eunhee HA ; Oran KWON ; Hae Soon KIM ; Hyesook KIM ; Seok Hyang KIM ; Miju KIM ; Eunshil KIM ; Jae Jin HAN ; Kooyoung JUNG ; Hunjoo HA
Journal of the Korean Society of Maternal and Child Health 2020;24(1):40-51
Purpose:
South Korea ranked 18th out of the 162 participating countries in the 2019 report on sustainable development goals (SDGs). Among the 17 specified goals, it has the most difficulty in achieving gender equality (SDG 5). This shortcoming is manifested in the lack of studies on gender-sensitive indicators. The study aims to establish the significance of the development of a comprehensive health matrix to concretize the concept of gender-sensitivity which is often considered as abstract.
Methods:
An integrated analysis of health determinants was conducted through a convergence study involving medical, social and natural sciences. This analysis was based on both literature reviews and focusgroup discussions. The 6 following focal points were chosen based on the SDGs: gender equality, medicine, education, economy, nutrition, and environment. Objective quantitative indicators were then designated to each of the 6 areas and comparatively analyzed for South Korea, North Korea, and the other SDGs countries. Four areas on sexual and reproductive health were also selected.
Results:
The results indicated that South Korea scored much lower than North Korea and the other SDGs countries in terms of gender equality. It was also behind North Korea in education, although North Korea had a comparatively lower ranking in the rest of the areas. On the other hand, it fared better than the aforementioned countries with respect to environment, nutrition, medicine, and economy.
Conclusion
A comprehensive gender-sensitive health matrix was developed to refine the abstract concept of gender-sensitivity through objective quantitative indicators that assess the health status of a country by means of a scoring system. Gender equality was also confirmed as a common and significant component in the disciplines of sexual and reproductive health and comprehensive health.
8.Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury
Md Jamal UDDIN ; Debra DOROTEA ; Eun Seon PAK ; Hunjoo HA
Biomolecules & Therapeutics 2020;28(3):213-221
Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a nonreceptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.
9.Enrichment of Short-Chain Ceramides and Free Fatty Acids in the Skin Epidermis, Liver, and Kidneys of db/db Mice, a Type 2 Diabetes Mellitus Model
Minjeong KIM ; Haengdueng JEONG ; Buhyun LEE ; Yejin CHO ; Won Kee YOON ; Ahreum CHO ; Guideock KWON ; Ki Taek NAM ; Hunjoo HA ; Kyung Min LIM
Biomolecules & Therapeutics 2019;27(5):457-465
Patients with diabetes mellitus (DM) often suffer from diverse skin disorders, which might be attributable to skin barrier dysfunction. To explore the role of lipid alterations in the epidermis in DM skin disorders, we quantitated 49 lipids (34 ceramides, 14 free fatty acids (FFAs), and cholesterol) in the skin epidermis, liver, and kidneys of db/db mice, a Type 2 DM model, using UPLC-MS/MS. The expression of genes involved in lipid synthesis was also evaluated. With the full establishment of hyperglycemia at the age of 20 weeks, remarkable lipid enrichment was noted in the skin of the db/db mice, especially at the epidermis and subcutaneous fat bed. Prominent increases in the ceramides and FFAs (>3 fold) with short or medium chains (
10.Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice
Jinhyuk NA ; Soo An CHOI ; Adnan KHAN ; Joo Young HUH ; Lingjuan PIAO ; Inah HWANG ; Hunjoo HA ; Youngja H PARK
Biomolecules & Therapeutics 2019;27(2):134-144
The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and 3β, 7α-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and α/γ-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

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