Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.
Adenosine Triphosphate ; Cardiovascular Diseases ; Cause of Death ; Heart Failure ; Heart ; Homeostasis ; Mitochondria ; Mitochondrial Degradation ; Organelles ; Quality Control ; Spermidine ; Unfolded Protein Response

No abstract available.
Antiemetics* ; Drug Therapy, Combination* ; Humans ; Ondansetron*

PURPOSE: This study primarily aimed to investigate the short- and long-term remission rates of type 2 diabetes (T2D) in patients who underwent surgical treatment for gastric cancer, especially patients who were non-obese, and secondarily to determine the potential factors associated with remission. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients with T2D who underwent radical gastrectomy for gastric cancer, from January 2008 to December 2012. RESULTS: T2D improved in 39 out of 70 (55.7%) patients at the postoperative 2-year follow-up and 21 of 42 (50.0%) at the 5-year follow-up. In the 2-year data analysis, preoperative body mass index (BMI) (P=0.043), glycated hemoglobin (A1C) level (P=0.039), number of anti-diabetic medications at baseline (P=0.040), reconstruction method (statistical difference was noted between Roux-en-Y reconstruction and Billroth I; P=0.035) were significantly related to the improvement in glycemic control. Unlike the results at 2 years, the 5-year data analysis revealed that only preoperative BMI (P=0.043) and A1C level (P=0.039) were statistically significant for the improvement in glycemic control; however, the reconstruction method was not. CONCLUSIONS: All types of gastric cancer surgery can be effective in short- and long-term T2D control in non-obese patients. In addition, unless long-limb bypass is considered in gastric cancer surgery, the long-term glycemic control is not expected to be different between the reconstruction methods.
Body Mass Index ; Diabetes Mellitus, Type 2* ; Follow-Up Studies* ; Gastrectomy* ; Gastroenterostomy ; Glycemic Index ; Hemoglobin A, Glycosylated ; Humans ; Illegitimacy* ; Methods ; Retrospective Studies ; Statistics as Topic ; Stomach Neoplasms*

In Korea, proximal gastrectomy has recently attracted attention as a better choice of function-preserving surgery for proximal early gastric cancer than total gastrectomy. Of the various strategies to overcome reflux symptoms from remnant stomach, double tract reconstruction not only reduces the incidence of anastomosis-related complications, but is also sufficiently reproducible as a laparoscopic procedure. Catching up with the recent rise of single-port laparoscopic surgeries, we performed a pure single-port laparoscopic proximal gastrectomy with DTR. This procedure was designed by merging the function-preserving concept of proximal gastrectomy with single-port laparoscopic total gastrectomy.
Gastrectomy* ; Gastric Stump ; Incidence ; Korea ; Laparoscopy ; Stomach Neoplasms*

PURPOSE: The aim of this study was to compare two methods of tumor localization during totally laparoscopic distal gastrectomy (TLDG) in patients with gastric cancer. METHODS: From March 2014 to November 2014, patients in whom TLDG had been engaged for middle third gastric cancer enrolled in this study. The patients were allocated to either the radiography or endoscopy group based on the type of tumor localization technique. Clinicopathologic outcomes were compared between the 2 groups. RESULTS: The accrual was suspended in November 2014 when 39 patients had been enrolled because a failed localization happened in the radiography group. The radiography and endoscopy groups included 17 (43.6 %) and 22 patients (56.4 %), respectively. Mean length of the proximal resection margin did not differ between the radiography and endoscopy groups (4.0 ± 2.6 and 2.8 ± 1.2 cm, respectively; P = 0.077). Mean localization time was longer in the radiography group than in the endoscopy group (22.7 ± 11.4 and 6.9 ± 1.8 minutes, respectively, P < 0.001). There were no statistically significant differences in the incidence of severe complications between the 2 groups (5.9% and 4.5%, respectively, P = 0.851). CONCLUSION: As an intraoperative tumor localization for TLDG, radiologic method was unsafe even though other comparable parameters were not different from that of endoscopy group. Moreover, intraoperative endoscopic localization may be advantageous because it is highly accurate and contributes to reducing operation time.
Endoscopy ; Gastrectomy* ; Humans ; Incidence ; Laparoscopy ; Methods* ; Radiography ; Stomach Neoplasms*

PURPOSE: The aim of this study was to compare two methods of tumor localization during totally laparoscopic distal gastrectomy (TLDG) in patients with gastric cancer. METHODS: From March 2014 to November 2014, patients in whom TLDG had been engaged for middle third gastric cancer enrolled in this study. The patients were allocated to either the radiography or endoscopy group based on the type of tumor localization technique. Clinicopathologic outcomes were compared between the 2 groups. RESULTS: The accrual was suspended in November 2014 when 39 patients had been enrolled because a failed localization happened in the radiography group. The radiography and endoscopy groups included 17 (43.6 %) and 22 patients (56.4 %), respectively. Mean length of the proximal resection margin did not differ between the radiography and endoscopy groups (4.0 ± 2.6 and 2.8 ± 1.2 cm, respectively; P = 0.077). Mean localization time was longer in the radiography group than in the endoscopy group (22.7 ± 11.4 and 6.9 ± 1.8 minutes, respectively, P < 0.001). There were no statistically significant differences in the incidence of severe complications between the 2 groups (5.9% and 4.5%, respectively, P = 0.851). CONCLUSION: As an intraoperative tumor localization for TLDG, radiologic method was unsafe even though other comparable parameters were not different from that of endoscopy group. Moreover, intraoperative endoscopic localization may be advantageous because it is highly accurate and contributes to reducing operation time.
Endoscopy ; Gastrectomy* ; Humans ; Incidence ; Laparoscopy ; Methods* ; Radiography ; Stomach Neoplasms*

OBJECTIVE: New nonsteroidal anti-inflammatory drugs (NSAIDs) with highly selective cyclooxygenase-2 (COX-2) inhibition afford protection against gastropathy, but their acute and long-term effects on the central nervous system are unclear. Our aim was to investigate the influence of COX-2 specific inhibitor (celecoxib) on cognitive function. METHODS: Within the context of a randomized controlled parallel trial of NSAIDs for osteoarthitis (OA), we performed a battery of neuropsychological tests in consecutive 10 osteoarthritis patients with celecoxib (200 mg/day) and 13 osteoarthritis patients with diclofenac (100 mg/day) before and after 4 weeks by clinical psychologists who were not involoved in the study and unaware of study protocols and treatment allocation. The tests were performed randomly in sequence in order to minimize learning effect. The examed cognitive domains included memory, reasoning/problem solving, simple and complex attention, visual-spatial processing, and psychomotor speed. RESULTS: Demographic characteristcs (age, sex, disease duration, functional status measured by patient's and physician's global assessment and KWOMAC, CES depression score, education level) were not significantly different between both treatment groups. In all cognitive domains, we did not find out significant cognitive decline before and after treatments either with celecoxib or diclofenac. There was no difference in the change of cognitive function between both treatment groups. CONCLUSION: The short-term use of COX-2 specific inhibitor as well as conventional NSAID may not impair cognitive function. The long-term follow up study using large number of patients is in progress.
Anti-Inflammatory Agents, Non-Steroidal ; Central Nervous System ; Cognition ; Cyclooxygenase 2 ; Depression ; Diclofenac ; Education ; Follow-Up Studies ; Humans ; Learning ; Memory ; Neuropsychological Tests ; Osteoarthritis ; Pilot Projects* ; Psychology ; Celecoxib

BACKGROUND AND OBJECTIVES: Recent studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF)-associated hospitalization and mortality in patients with diabetes. However, it is not clear whether SGLT2 inhibitors have a cardiovascular benefit in patients without diabetes. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role in HF without diabetes. METHODS: Cardiomyopathy was induced in C57BL/6J mice using intraperitoneal injection of doxorubicin (Dox). Mice with HF were fed a normal chow diet (NCD) or an NCD containing 0.03% EMPA. Then we analyzed their phenotypes and performed in vitro experiments to reveal underlying mechanisms of the EMPA's effects. RESULTS: Mice fed NCD with EMPA showed improved heart function and reduced fibrosis. In vitro studies showed similar results. Phloridzin, a non-specific SGLT inhibitor, did not show any protective effect against Dox toxicity in H9C2 cells. SGLT2 inhibitor can cause increase in blood ketone levels. Beta hydroxybutyrate (βOHB), which is well known ketone body associated with SGLT2 inhibitor, showed a protective effect against Dox in H9C2 cells and in Dox-treated mice. These results suggest elevating βOHB might be a convincing mechanism for the protective effects of SGLT2 inhibitor. CONCLUSIONS SGLT2 inhibitors have a protective effect in Dox-induced HF in mice. This implied that SGLT2 inhibitor therapy could be a good treatment strategy even in HF patients without diabetes.

BACKGROUND AND OBJECTIVES: Recent studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF)-associated hospitalization and mortality in patients with diabetes. However, it is not clear whether SGLT2 inhibitors have a cardiovascular benefit in patients without diabetes. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role in HF without diabetes. METHODS: Cardiomyopathy was induced in C57BL/6J mice using intraperitoneal injection of doxorubicin (Dox). Mice with HF were fed a normal chow diet (NCD) or an NCD containing 0.03% EMPA. Then we analyzed their phenotypes and performed in vitro experiments to reveal underlying mechanisms of the EMPA's effects. RESULTS: Mice fed NCD with EMPA showed improved heart function and reduced fibrosis. In vitro studies showed similar results. Phloridzin, a non-specific SGLT inhibitor, did not show any protective effect against Dox toxicity in H9C2 cells. SGLT2 inhibitor can cause increase in blood ketone levels. Beta hydroxybutyrate (βOHB), which is well known ketone body associated with SGLT2 inhibitor, showed a protective effect against Dox in H9C2 cells and in Dox-treated mice. These results suggest elevating βOHB might be a convincing mechanism for the protective effects of SGLT2 inhibitor. CONCLUSIONS: SGLT2 inhibitors have a protective effect in Dox-induced HF in mice. This implied that SGLT2 inhibitor therapy could be a good treatment strategy even in HF patients without diabetes.
3-Hydroxybutyric Acid ; Animals ; Cardiomyopathies ; Diet ; Doxorubicin ; Doxycycline ; Fibrosis ; Heart Failure ; Heart ; Hospitalization ; Humans ; In Vitro Techniques ; Injections, Intraperitoneal ; Mice ; Mortality ; Phenotype ; Phlorhizin