Skeletal muscle atrophy is a major complication associated with aging, chronic disease, and chemotherapy. Doxorubicin (Dox), a widely used anticancer agent, accelerates muscle wasting; however, the underlying cellular mechanisms remain poorly understood. In this study, we examined the effects of Dox on myogenic differentiation, senescence, and lipid metabolism using C2C12 myoblasts. Dox exposure impaired myotube formation without causing overt cytotoxicity. Mechanistically, Dox disrupted myogenic differentiation by inhibiting protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling, thereby de-repressing forkhead box O1/3 (FOXO1/3) and upregulating the muscle-specific ubiquitin ligases muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1), which promote proteolysis. Dox also decreased glycogen synthase kinase 3β (GSK3β) phosphorylation while paradoxically increasing total and phosphorylated β-catenin, indicating dysregulated Wnt/β-catenin signaling. These alterations were accompanied by a senescence-like phenotype, characterized by elevated senescence-associated β-galactosidase (SA-β-gal) activity, increased phosphorylated histone variant γH2AX, and activation of the p53–p21 axis. Notably, cellular senescence coincided with excessive lipid accumulation in myotubes. Dox reduced phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) while enhancing expression of key lipogenic regulators, thereby creating a metabolic environment favoring lipid storage. Collectively, these findings demonstrate that Dox not only suppresses myogenic differentiation but also induces premature senescence and metabolic reprogramming toward lipid accumulation. Targeting these pathways through AMPK activation, FOXO inhibition, or senolytic interventions may offer therapeutic strategies to preserve skeletal muscle integrity in patients undergoing chemotherapy.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 μg/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells.Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

Aortic dissection in pregnant patients results in an inpatient mortality rate of 8.6%. Owing to the pronounced mortality rate and speed at which aortic dissections progress, efficient early detection methods are crucial. Here, we highlight the importance of early chest computed tomography (CT) for differentiating aortic dissection from pulmonary embolism in pregnant patients with dyspnea. We present the unique case of a 38-year-old pregnant woman with elevated D-dimer and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, initially suspected of having a pulmonary embolism. Initial transthoracic echocardiography did not indicate aortic dissection. Surprisingly, after an emergency cesarean section, a chest CT scan revealed a DeBakey type I aortic dissection, indicating a diagnostic error. Our findings emphasize the need for early chest CT in pregnant patients with dyspnea and elevated D-dimer and NT-proBNP levels. This case report highlights the critical importance of considering both aortic dissection and pulmonary embolism in the differential diagnosis of such cases, which will inform future clinical practice.

Background: Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results: Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

Background: Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results: Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

When pericardial tamponade occurs to the left ventricular assist device (LVAD) implanted patients, typical hemodynamic signs of tamponade such as tachycardia and pulsus paradoxus may be masked by LVAD action. For those with normal heart, anesthetic management during pericardial tamponade operation before drainage is to restrict fluid administration and maintain perfusion pressure with vasopressor are recommended. But the things to concern are different in cases of patient with LVAD. Here, we describe a case of performing anesthesia with LVAD implanted patient for pericardial tamponade operation. A 58-year-old male with HeartWare™ (Medtronic, Framingham, MA, USA) LVAD implant was referred for cardiac tamponade surgery. After the induction of general anesthesia, his mean arterial pressure (MAP) decreased to 38 mmHg with device flow 1.8 L/min and device power 2.4 Watts at pump speed 2,400 RPM. Norepinephrine and Epinephrine infusion were initiated. MAP recovered to 70mmHg with device flow 3.7 L/min and power 3.0 Watts after the drainage of 1,200 cc of pericardial fluid. Cardiac tamponade with LVAD implanted patient present with decreased peak flow, mean flow and decreased pulsatility. LVAD flow depends on pump rotation, preload and afterload. In order to maintain flow in these patients, prevention of preload reduction is important. Since LVAD implantation becoming more popular as Bridge to transplantation and destination therapy, it is important for anesthesiologist to understand the LVAD parameters and factors that affect.
Anesthesia ; Anesthesia, General ; Arterial Pressure ; Cardiac Tamponade ; Drainage ; Epinephrine ; Heart ; Heart-Assist Devices ; Hemodynamics ; Humans ; Male ; Masks ; Middle Aged ; Norepinephrine ; Perfusion ; Pericardial Fluid ; Tachycardia

Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.
Acetaminophen ; Alanine Transaminase ; Animals ; Cell Death ; Cytochrome P-450 CYP2E1 ; Cytochromes ; Glutathione ; Humans ; Injections, Intraperitoneal ; Korea ; Lipid Peroxidation ; Liver ; Male ; Malondialdehyde ; Mice ; Mice, Inbred ICR ; Necrosis ; Oxidative Stress ; Rats

When pericardial tamponade occurs to the left ventricular assist device (LVAD) implanted patients, typical hemodynamic signs of tamponade such as tachycardia and pulsus paradoxus may be masked by LVAD action. For those with normal heart, anesthetic management during pericardial tamponade operation before drainage is to restrict fluid administration and maintain perfusion pressure with vasopressor are recommended. But the things to concern are different in cases of patient with LVAD. Here, we describe a case of performing anesthesia with LVAD implanted patient for pericardial tamponade operation. A 58-year-old male with HeartWareâ„¢ (Medtronic, Framingham, MA, USA) LVAD implant was referred for cardiac tamponade surgery. After the induction of general anesthesia, his mean arterial pressure (MAP) decreased to 38 mmHg with device flow 1.8 L/min and device power 2.4 Watts at pump speed 2,400 RPM. Norepinephrine and Epinephrine infusion were initiated. MAP recovered to 70mmHg with device flow 3.7 L/min and power 3.0 Watts after the drainage of 1,200 cc of pericardial fluid. Cardiac tamponade with LVAD implanted patient present with decreased peak flow, mean flow and decreased pulsatility. LVAD flow depends on pump rotation, preload and afterload. In order to maintain flow in these patients, prevention of preload reduction is important. Since LVAD implantation becoming more popular as Bridge to transplantation and destination therapy, it is important for anesthesiologist to understand the LVAD parameters and factors that affect.

When pericardial tamponade occurs to the left ventricular assist device (LVAD) implanted patients, typical hemodynamic signs of tamponade such as tachycardia and pulsus paradoxus may be masked by LVAD action. For those with normal heart, anesthetic management during pericardial tamponade operation before drainage is to restrict fluid administration and maintain perfusion pressure with vasopressor are recommended. But the things to concern are different in cases of patient with LVAD. Here, we describe a case of performing anesthesia with LVAD implanted patient for pericardial tamponade operation. A 58-year-old male with HeartWareâ„¢ (Medtronic, Framingham, MA, USA) LVAD implant was referred for cardiac tamponade surgery. After the induction of general anesthesia, his mean arterial pressure (MAP) decreased to 38 mmHg with device flow 1.8 L/min and device power 2.4 Watts at pump speed 2,400 RPM. Norepinephrine and Epinephrine infusion were initiated. MAP recovered to 70mmHg with device flow 3.7 L/min and power 3.0 Watts after the drainage of 1,200 cc of pericardial fluid. Cardiac tamponade with LVAD implanted patient present with decreased peak flow, mean flow and decreased pulsatility. LVAD flow depends on pump rotation, preload and afterload. In order to maintain flow in these patients, prevention of preload reduction is important. Since LVAD implantation becoming more popular as Bridge to transplantation and destination therapy, it is important for anesthesiologist to understand the LVAD parameters and factors that affect.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It is characterized by the accumulation of lipids without alcohol intake and often progresses to non-alcoholic steatohepatitis (NASH), liver fibrosis, and end-stage liver diseases such as cirrhosis or cancer. Although animal models have greatly contributed to the understanding of NAFLD, studies on the disease progression in humans are still limited. In this study, we used the recently reported high-fat L-methionine-defined and choline-deficient (HFMCD) diet to rapidly induce NASH and compared the responses to HFMCD in ICR mice from three different countries: Korea (supplied by the National Institute of Food and Drug Safety Evaluation), USA, and Japan during 6 weeks. Feeding HFMCD did not cause significant differences in weight gain in comparison with mice fed control diet. Relative weight of the liver increased gradually, while the relative weight of the kidneys remained unchanged. The parameters of liver injury (serum activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) increased rapidly from 1 week and remained elevated for as long as 6 weeks. Histopathological analysis showed that the accumulation of hepatic lipids induced by HFMCD was prominent at 1 week after diet supplementation and increased further at 6 weeks. Inflammatory markers were significantly increased in a time-dependent manner by HFMCD. The mRNA levels of TNF-α and IL-6 were elevated approximately 15-fold relative to control diet and that of IL-1β was increased more than 20-folds at 6 week after the onset of HFMCD intake. In addition, mRNA expression of fibrosis markers such as α-SMA, TGFβ1, and Col1a1 were also significantly increased at 6 week. In summary, the responses of Korl:ICR mice by intake of HFMCD diet were similar to those of ICR mice from other sources, which suggests that Korl:ICR mice is also a useful resource to study the pathogenesis of diet-induced NAFLD.