Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

The aerial parts of Saururus chinensis (Lour.) Baill., known for its rich lignan content and diversepharmacological activities such as anti-inflammatory and anticancer effects, has not been extensively explored for its potential in preventing obesity. In this study, we investigated the inhibitory effect of methylene chloride fraction of S.chinensis (MCSC) on adipocyte differentiation using experimental models. Furthermore, we conducted a comprehensive chemical analysis employing HPLC and LC-ESI/MS to identify and characterize the main compounds responsible for these effects. MCSC significantly inhibited preadipocyte differentiation, accompanied by down-regulation of target genes involved in lipid synthesis and storage. This anti-adipogenic effect was mediated by the inhibition of CCAAT/ enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) expression. In a mouse model, oral administration of MCSC resulted in reduced body weight and adipose tissue weight, along with improvements in serum lipid profiles in high-fat diet-induced C57BL/6 obese mice. Active ingredients were identified as manassantin A and manassantin B through comparison of their spectrometric features with previously reported data.This evidence suggests that MCSC could be a potential candidate for the treatment and prevention of obesity-associateddiseases.

Many plant extracts have been recognized for their potential anti-cancer properties. Schoenoplectus triqueter (L.) Palla, commonly known as triangular rush (TAR) and part of the Cyperaceae family, predominantly thrives in the wetlands of the Huangpu Yangtze estuary. In this study, we explored the anti-cancer capabilities of TAR on lung cancer A549 cells. Our findings revealed that TAR was significantly more cytotoxic to A549 cells than to normal lung HEL 299 cells. TAR promoted apoptosis through enhanced caspase-3 activity and subsequent cleavage of poly ADP ribose polymerase (PARP). This apoptotic effect was associated with the downregulation of several STAT3-regulated genes, including Survivin, IAP-1, Cyclin D1, COX-2, and matrix metallopeptidase 9 (MMP-9). Moreover, TAR effectively reduced cell proliferation, invasion, and migration. The inhibition of STAT3 activation was achieved by blocking the upstream Janus activated kinases 1 and 2 (JAK1, JAK2), c-Src kinases, and the nuclear translocation of STAT3 in A549 cells. Additionally, TAR enhanced the effects of cisplatin through synergistic inhibition of STAT3 activation and increased apoptosis in A549 cells. Key compounds contributing to these biological activities were identified via LCHRMS analysis. Our results suggest that TAR blocks constitutive STAT3 activation, exhibiting anti-proliferative and pro-apoptotic effects in lung cancer A549 cells.

Inula helenium L. is rich source of eudesmane-type sesquiterpene lactones, mainly alantolactone and isoalantolactone, which have the various pharmacological functions. In this study, we examined the inhibitory effects of nitric oxide (NO) production of hexane, methylene chloride, ethyl acetate, butanol, and water fractions from I. helenium and investigated the anti-inflammatory effect of hexane fraction of I. helenium (HFIH) in LPS-induced RAW 264.7 cells. Quantification of alantolactone and isoalantolactone from HFIH was carried out for the standardization by multiple reaction monitoring using triple quadrupole mass spectrometer. HFIH significantly inhibited inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein as well as their downstream products NO and prostaglandin E₂ (PGE₂) in LPS-stimulated RAW 264.7 cells. Moreover, HFIH suppressed NF-κB transcriptional activity by decreasing the translocation of p65 to the nucleus. The in vivo study further confirmed that HFIH attenuated the paw edema induced by carrageenan in an acute inflammation model. These findings suggest that HFIH may be useful as a promising phytomedicine for inflammatory-associated diseases.
Carrageenan ; Cyclooxygenase 2 ; Edema ; Inflammation ; Inula ; Lactones ; Methylene Chloride ; Nitric Oxide ; Nitric Oxide Synthase ; RAW 264.7 Cells ; Staphylococcal Protein A ; Water

This study provides a statistical analysis of 1,226 cases of death occurring in Area 8, Seoul Metropolitan Police Agency (Gangseo, Yangcheon, and Guro Police Stations) from January 1 to December 31, 2017. There were 427 postmortem inspection cases in Gangseo, 393 in Yangcheon, 377 in Guro, and 29 in other areas. The number of autopsy cases was 69 in Gangseo, 70 in Yangcheon, 86 in Guro, and seven in other areas. According to the postmortem inspection reports, there were 593 cases of natural death and 336 cases of unnatural death, while in 297 cases the cause of death was unknown. Of the 297 unknown cases, autopsy rates from each police station were as follows: 54 of 99 cases (54.5%) in Gangseo, 60 of 101 cases (59.4%) in Yangcheon, 67 of 93 cases (72.0%) in Guro, and in all four cases (100%) from other areas. Unnatural deaths included 215 cases of suicide, nine cases of homicide, and 64 accidental death, while 48 cases were undetermined. Among the unnatural deaths, the cause of death included 138 cases of hanging, 72 cases of falls from a height, and 32 cases of poisoning. Since this statistical study is based on actual postmortem inspection data for 1,226 cases of death in the eight areas of Seoul (excluding deaths from traffic accidents), it raises issues relating to the current postmortem inspection system, and can be used as reference material for a comprehensive overview of causes of death.

This study provides a statistical analysis of 1,226 cases of death occurring in Area 8, Seoul Metropolitan Police Agency (Gangseo, Yangcheon, and Guro Police Stations) from January 1 to December 31, 2017. There were 427 postmortem inspection cases in Gangseo, 393 in Yangcheon, 377 in Guro, and 29 in other areas. The number of autopsy cases was 69 in Gangseo, 70 in Yangcheon, 86 in Guro, and seven in other areas. According to the postmortem inspection reports, there were 593 cases of natural death and 336 cases of unnatural death, while in 297 cases the cause of death was unknown. Of the 297 unknown cases, autopsy rates from each police station were as follows: 54 of 99 cases (54.5%) in Gangseo, 60 of 101 cases (59.4%) in Yangcheon, 67 of 93 cases (72.0%) in Guro, and in all four cases (100%) from other areas. Unnatural deaths included 215 cases of suicide, nine cases of homicide, and 64 accidental death, while 48 cases were undetermined. Among the unnatural deaths, the cause of death included 138 cases of hanging, 72 cases of falls from a height, and 32 cases of poisoning. Since this statistical study is based on actual postmortem inspection data for 1,226 cases of death in the eight areas of Seoul (excluding deaths from traffic accidents), it raises issues relating to the current postmortem inspection system, and can be used as reference material for a comprehensive overview of causes of death.
Accidental Falls ; Autopsy ; Cause of Death ; Homicide ; Humans ; Poisoning ; Police ; Seoul ; Statistics as Topic ; Suicide

We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson’s disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.

From January 1, 2016 to December 31, 2016, a total of 1147 postmortem inspection cases in Area 8, Seoul Metropolitan Police Agency (Gangseo, Yangcheon, and Guro police stations) were statistically analyzed. Autopsies were performed in 205 cases (17.9%), and the autopsy rates were 17.6% (75/426 cases) in the Gangseo police station, 9.5% (34/357 cases) in the Yangcheon police station, and 24.3% (82/337 cases) in the Guro police station. For 288 cases with an unknown cause of death, the autopsy rates were 70.0% (60/87 cases) in the Gangseo police station, 28.6% (26/91 cases) in the Yangcheon police station, and 63.1% (65/103 cases) in the Guro police station. For 65 cases due to fall from height, the autopsy rate was 7.7% (n=5). Of the 187 cases due to hanging, 155 cases were classified as suicide at the scene with a 4.5% (n=7) autopsy rate and 32 cases were classified as an undetermined manner of death at the scene with a 15.6% (n=5) autopsy rate. The distribution of the “manner of death” was natural death, 45% (n=516); unnatural death, 29.9% (n=343); and other and undetermined, 25.1% (n=288). Proportions of dispatch times were 50.9% (584 cases) during work hours (09:00–18:00), 13.8% (n=158) during evening hours (18:00–21:00), 13.4% (n=154) at night (21:00–00:00), 11% (n=126) at dawn (00:00–06:00), and 10.9% (n=125) during morning hours (06:00–09:00). The male-to-female ratio was 1.86:1 (746:401). These statistics are valuable for the evaluation of postmortem inspections by experts.
Autopsy ; Cause of Death ; Humans ; Police ; Seoul* ; Suicide

BACKGROUND: Because conventional echocardiographic parameters have several limitations, strain echocardiography has often been introduced in clinical practice. However, there are also obstacles in using it in clinical practice. Therefore, we wanted to find the current status of awareness on using strain echocardiography in Korea. METHODS: We conducted a nationwide survey to evaluate current use and awareness of strain echocardiography from the members of the Korean Society of Echocardiography. RESULTS: We gathered total 321 questionnaires from 25 cardiology centers in Korea. All participants were able to perform or interpret echocardiographic examinations. All participating institutions performed strain echocardiography. Most of our study participants (97%) were aware of speckle tracking echocardiography and 185 (58%) performed it for clinical and research purposes. Two-dimensional strain echocardiography was the most commonly used modality and left ventricle (LV) was the most commonly used cardiac chamber (99%) for clinical purposes. Most of the participants (89%) did not think LV strain can replace LV ejection fraction (LVEF) in their clinical practice. The common reasons for not performing routine use of strain echocardiography was diversity of strain measurements and lack of normal reference value. Many participants had a favorable view of the future of strain echocardiography. CONCLUSION: Most of our study participants were aware of strain echocardiography, and all institutions performed strain echocardiography for clinical and research purposes. However, they did not think the LV strain values could replace LVEF. The diversity of strain measurements and lack of normal reference values were common reasons for not using strain echocardiography in clinical practice.
Cardiology ; Echocardiography* ; Heart Ventricles ; Korea* ; Reference Values

This study describes the anti-inflammatory, anti-oxidant, and melanogenesis inhibition activities of methanol extract and various organic solvent fractions of Arecae Pericarpium. We examined the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells, 1,1-diphenyl-2-picrylhydrazine (DPPH) scavenging activity, mushroom tyrosinase inhibition activity and melanin contents. The study showed that, among all tested fractions, methylene chloride fraction showed the strongest inhibition of LPS-induced NO production in RAW 264.7 cells (IC₅₀ value 8.89 µg/mL) and DPPH radical scavenging activity (EC₅₀ value 21.39 µg/mL). Methylene chloride and ethyl acetate fractions similarly inhibited mushroom tyrosinase activity. Methanol extract exhibited strongest reduction of melanin content in B16F10 melanoma cells. Based on the bioactivity assay results, methylene chloride and ethyl acetate fractions were further separated. Eight phenolic compounds were isolated, which are dimeric syringol (1), catechol (2), 4-hydroxybenzaldehyde (3), vanillin (4), 4-hydroxyacetophenone (5), apocynin (6), protocatechuic acid (7) and 4-hydroxybenzoic acid (8). Among the isolated compounds tested, catechol showed the strongest inhibition of LPS-induced NO production in RAW 264.7 cells. Catechol also showed the concentration-dependent NF-κB inhibition activity. Arecae Pericarpium might have potentials to be developed as anti-inflammatory agent or dermatological product for skin-whitening agent.
Agaricales ; Areca* ; Melanins ; Melanoma ; Methanol ; Methylene Chloride ; Monophenol Monooxygenase ; Nitric Oxide ; Phenol ; RAW 264.7 Cells