1.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
2.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
3.A ruptured aneurysmal subarachnoid hemorrhage and vasospasm initially manifesting as acute ischemic stroke: a case report
Joongwon PARK ; Wonseok JEON ; Junho CHOI ; Chulho KIM
Journal of Neurocritical Care 2024;17(2):75-78
Background:
Most aneurysmal subarachnoid hemorrhages (SAHs) are accompanied by focal neurological deficits caused by a thunderclap headache. The neurological symptoms of aneurysmal SAH rarely present as vasospasm-induced cerebral ischemia.Case Report: A 51-year-old male presented to the emergency department with weakness in the left upper and lower limbs combined with dysarthria, which developed on the day of admission. An initial brain computed tomography scan revealed no clear signs of hemorrhage. However, the patient’s age (51 years) and history of thunderclap headache prompted further evaluation. Finally, the patient was diagnosed with vasospasm-induced ischemic stroke, caused by a ruptured cerebral aneurysm.
Conclusion
For patients with abrupt focal neurological deficits and severe thunderclap headaches, further consideration of aneurysmal rupture and the resulting vasospasm-induced cerebral ischemia may prevent the worst complications of stroke due to misdiagnosis.
4.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
5.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
6.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
7.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
8.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
9.A ruptured aneurysmal subarachnoid hemorrhage and vasospasm initially manifesting as acute ischemic stroke: a case report
Joongwon PARK ; Wonseok JEON ; Junho CHOI ; Chulho KIM
Journal of Neurocritical Care 2024;17(2):75-78
Background:
Most aneurysmal subarachnoid hemorrhages (SAHs) are accompanied by focal neurological deficits caused by a thunderclap headache. The neurological symptoms of aneurysmal SAH rarely present as vasospasm-induced cerebral ischemia.Case Report: A 51-year-old male presented to the emergency department with weakness in the left upper and lower limbs combined with dysarthria, which developed on the day of admission. An initial brain computed tomography scan revealed no clear signs of hemorrhage. However, the patient’s age (51 years) and history of thunderclap headache prompted further evaluation. Finally, the patient was diagnosed with vasospasm-induced ischemic stroke, caused by a ruptured cerebral aneurysm.
Conclusion
For patients with abrupt focal neurological deficits and severe thunderclap headaches, further consideration of aneurysmal rupture and the resulting vasospasm-induced cerebral ischemia may prevent the worst complications of stroke due to misdiagnosis.
10.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

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