Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

OBJECTIVES: Salmonellosis outbreaks occurred at 2 restaurants 2 days apart, and an epidemiological investigation was conducted to determine whether the outbreaks were connected. METHODS: Case studies were conducted for both outbreaks. Stool samples were collected from individuals, and food samples were collected from the restaurants. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing analyses were performed on outbreak-related Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) isolates. Traceback investigations were also conducted for the ingredients from gimbap restaurants A and B. RESULTS: In total, 106 people from gimbap restaurant A and 5 from gimbap restaurant B met the case definition. Salmonella Enteritidis was detected in samples from 2 food handlers, 22 patients, and 1 food (iceberg lettuce) at gimbap restaurant A and from 1 patient at gimbap restaurant B. According to PFGE, all isolates were identified as SEGX01.089. The molecular typing of all isolates showed the same pattern, and the genetic distance was close according to phylogenetic analysis. Eggs were the only food ingredient that was supplied to both gimbap restaurants. CONCLUSIONS The outbreaks were caused by Salmonella Enteritidis, and the source of infections was suspected to be contaminated eggs. To prevent foodborne outbreaks of Salmonella, restaurants should heat eggs sufficiently, and egg farms need to establish management systems that prevent Salmonella infections.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.