Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.