• Title/Summary/Keyword: CA therapy

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Canonical Transient Receptor Potential Channels and Their Link with Cardio/Cerebro-Vascular Diseases

  • Xiao, Xiong;Liu, Hui-Xia;Shen, Kuo;Cao, Wei;Li, Xiao-Qiang
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.471-481
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    • 2017
  • The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of $Ca^{2+}$ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebro-vascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury. Collectively, TRPCs could become a group of drug targets with important physiological functions for the therapy of human cardio/cerebro-vascular diseases.

cAMP Response Element-Binding Protein- and Phosphorylation-Dependent Regulation of Tyrosine Hydroxylase by PAK4: Implications for Dopamine Replacement Therapy

  • Won, So-Yoon;You, Soon-Tae;Choi, Seung-Won;McLean, Catriona;Shin, Eun-Young;Kim, Eung-Gook
    • Molecules and Cells
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    • v.44 no.7
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    • pp.493-499
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    • 2021
  • Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S40, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4S474, which represents PAK4 activity, and phosphorylated THS40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.

Effects of Cognitive Training Using Tablet PC Applications on Cognitive Function, Daily Living and Satisfaction in Subacute Stroke Patients (테블릿 pc 어플리케이션을 사용한 인지훈련이 아급성 뇌졸중 환자의 인지기능, 일상생활 및 만족감에 미치는 영향)

  • Moon, Jong-Hoon;Won, Young-Sik
    • The Journal of the Korea institute of electronic communication sciences
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    • v.12 no.1
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    • pp.219-228
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    • 2017
  • The aim of this study was investigated the effect of cognitive training using tablet pc applications on cognitive function, daily living, and satisfaction in subacute stroke patients. This study participated in fourteen subacute stroke inpatients, in I general hospital, at located in Incheon. All subjects assigned that randomized each seven patients in experimental and control group. Two groups received to traditional cognitive therapy during half hour/day, 5 times per week, for 4 weeks. Experimental group performed additionally that cognitive training using tablet pc applications for 30 min/day. The outcome measures were the K-MMSE(: Korea-Mini Mental State Examination), MoCA-K(: Montreal Cognitive Assessments-Korea), MBI(: Modified Barthel Index), VAS(: Visual Analog Scale) for cognitive function, daily living, satisfaction. In results, Both group showed significant improvements after intervention in MoCA-K, MBI(p<.05). In comparison of change between two groups, experimental group showed significant improvements than control group in MoCA-K(p<.05). In comparison of satisfaction of two groups, both group was not significant difference(p>.05). we suggested that Cognitive training using tablet pc applications expected to positive effects the improvements of cognitive function in subacute stroke patients.

A Study of Cognitive Function and Driving Status of Elderly Owner Driver (노인운전자들의 인지기능과 운전실태에 대한 연구)

  • Kim, Hun-Ju;Kam, Kyung-Yoon;Shin, Joong-Il
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.5
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    • pp.2946-2952
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    • 2014
  • The purpose of this study is to provide some basic information for elderly driving safety, by analyzing the current state. This study analyzed 128 survey questionnaires given to senior welfare center user in P city and evaluated Montreal Cognitive Assessment Korean Version(MoCA-K) and Neurobehavioral Cognitive Status Examination(NCSE) for checked 41 owner drivers by questionnaires. 32% of total elderly persons was owner driver, and 56.1% of elderly drivers was driving everyday. 56.1% of elderly persons was driving for 1-2hours per day. 46.3% of elderly persons was using a car for leisure activity and 31.7% of elderly drivers was experienced a car accident. As cognitive function evaluation, some elderly drivers showed scores lower than average in subcategories of cognitive functions for driving a car. So, methodical evaluation system for accurate evaluation of deficit ability and driving re-education system will be required for safety driving of elderly person. In future, a legal approach of government as driver licence management and renewal system will be required for safety driving of elderly person.

Quantitative Assessment of the Relative Antineoplastic Potential of the n-butanolic Leaf Extract of Annona Muricata Linn. in Normal and immortalized Human Cell Lines

  • George, V. Cijo;Kumar, D.R. Naveen;Rajkumar, V.;Suresh, P.K.;Kumar, R. Ashok
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.699-704
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    • 2012
  • Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of $Annona$ $muricata$ L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and $DPPH^*$radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (P<0.05) positive correlation of phenolic compounds with free radical scavenging potential. The results revealed that the extract was moderately cytotoxic to normal cells with a mean IC50 value of 52.4 ${\mu}g$ when compared with those obtained for cancerous cells (IC50 values of 29.2 ${\mu}g$ for MDA-MB-435S and 30.1 ${\mu}g$ for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of $Annona$ $muricata$. Isolation of the active metabolites from the extract is in prospect.

α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

  • Kim, Myoungjae;Chin, Young-Won;Lee, Eun Joo
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.609-617
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    • 2017
  • Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

Effects of the Herbal-Acupuncture with Corni Fructus Extract at Eumgok(KI10) on Osteoporosis in Ovariectomized Mice (음곡(陰谷)(KI10) 산수유 약침이 난소적출 생쥐의 골다공증에 미치는 영향)

  • Kim, Kwang-Sung;Lee, Byung-Ryul;Yang, Gi-Young;An, Taek-Won;Yim, Yun-Kyoung
    • Korean Journal of Acupuncture
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    • v.27 no.1
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    • pp.63-85
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    • 2010
  • Objective & Method: The purpose of this study is to investigate the effects of herbal-acupuncture with Corni Fructus extract (CF-HA) at Eumgok(KI10) on osteoporosis in ovariectomized (OVX) ddy mice. I carried out several experimental items to analyze the changes in body weight, uterine weight, uterus index, tibial length, the ash bone weight, tibial BMD, the levels of serum ALP, osteocalcin, Ca, P and the levels of tibial Ca, P, Ca/P ratio, and we performed histological and histomorphological analysis as well. Result: 1. CF-HA at Eumgok(KI10) significantly did not increase the level of bone mineral density in overiectomized mice. 2. CF-HA at Eumgok(KI10) significantly decreased the level of serum phosphorus in ovariectomized mice and sinificantly increased the level of serum calcium in ovariectomized mice. 3. CF-HA at Eumgok(KI10) significantly increased the levels of tibial calcium and phosphorus in ovariectomized mice. 4. CF-HA at Eumgok(KI10) significantly decreased the number of tibial osteoclast like cell in ovariectomized mice. 5. In the histomorphometric analysis of tibia, GPL(growth plate length) was significantly decreased by CF-HA at Eumgok(KI10) in ovariectomized mice. Conclusions: These results suggest that CF-HA at Eumgok(KI10) may have useful therapy effects on osteoporosis in ovariectomized mice.

Correlation of Cognitive Function and Dual-task Performance in Elderly (노인의 인지기능, 손의 기민성 및 인지과제를 결합한 이중과제 수행과의 상관성 연구)

  • Kwak, Ho-Soung
    • Journal of The Korean Society of Integrative Medicine
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    • v.10 no.4
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    • pp.83-91
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    • 2022
  • Purpose: The goal of this study was to investigate changes in dual-task performance according to age and difficulty of cognitive tasks for the in community-dwelling elderly populations, as well as to examine their changes in hand dexterity according to age and cognitive function. Methods: A total of 135 people aged 65 years old and over participated in the study. To evaluate each participant's dual-task performance, each participant completed a dual task. To assess their cognitive function, the Korean Mini-Mental State Examination (MMSE-K) and the Korean version of Montreal Cognitive Assessment (MoCA-K) were the tools used. Participants were divided into three groups based on their age: 65-69 years, 70-79 years, and 80-89 years. Results: The findings showed that age groups and the difficulty of the cognitive task significantly affected the amount of time required for dual-task performance (p<.001). Additionally, the dual-task correct response rate (CRR) decreased significantly with age groups and the difficulty of the cognitive task (p<.001). The amount of time required for finger dexterity performance increased significantly with age groups (mean score±standard deviation [SD]; 19.46±2.26 in subjects aged 65-69 years; 21.92±2.61 in subjects aged 70-79 years; and 23.82±2.92 in subjects aged 80-89 years; p<.001). Moreover, as a result of the correlation between hand dexterity and cognitive function, MoCA-K was -0.563 and MMSE-K was -.412, showing a statistically significant correlation (p<.001). Conclusions: Age and the difficulty of the cognitive task affect the community-dwelling elderly populations in terms of dual-task performance and dual-task CRR. In addition, aging and general cognition have an impact on hand dexterity. Based on the results of this study, it is anticipated that the results will serve as a reference for domestic clinical trials that confirm cognitive decline in the elderly using dual task and hand dexterity evaluation.

Laparoscopic radical distal pancreatosplenectomy with celiac axis excision following neoadjuvant chemotherapy for locally advanced pancreatic cancer

  • Yeon Su Kim;Ji Su Kim;Sung Hyun Kim;Ho Kyoung Hwang;Woo Jung Lee;Chang Moo Kang
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.26 no.1
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    • pp.118-123
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    • 2022
  • A recent successful prospective randomized control study comparing open distal pancreatectomy with laparoscopic distal pancreatectomy (LDP) has shown that LDP is a safe and effective surgical modality in treating left-sided pancreatic pathological conditions requiring surgical extirpation. With the accumulating surgical experiences and improved surgical techniques, we recently reported several cases of successful LDP in advanced pancreatic cancer following neoadjuvant chemotherapy. Herein, we report a case of LDP with celiac axis resection (LDP-CAR) in locally advanced pancreatic cancer (LAPC) following neoadjuvant chemotherapy. A 58-yearold female with LAPC was referred to our institution. Computed tomography (CT) findings revealed a 24-mm mass in the pancreatic body that showed celiac artery (CA), common hepatic artery abutment. There was no abutment with superior mesenteric artery, superior mesenteric vein, and portal vein. From these findings, Neoadjuvant chemotherapy (FORFIRINOX) was performed biweekly. After 8 cycles of chemotherapy, the tumor size was slightly decreased (24 mm to 16 mm), but still abutting to CA. After 14 cycles of chemotherapy, CT revealed the same tumor size (16 mm) still abutting to CA. LDP-CAR was performed. Intraoperative ultrasonography gastric perfusion and hepatic perfusion were confirmed using indocyanine green. The patient recovered without complications and was discharged from the hospital nine days after the surgery.

Ginsenoside Rg1 treatment protects against cognitive dysfunction via inhibiting PLC-CN-NFAT1 signaling in T2DM mice

  • Xianan Dong ;Liangliang Kong ;Lei Huang ;Yong Su ;Xuewang Li;Liu Yang;Pengmin Ji ;Weiping Li ;Weizu Li
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.458-468
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    • 2023
  • Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca2+) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca2+ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.