Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.

Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.

Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.

This study aimed to identify the clinical characteristics of molar root-incisor malformation (MRIM) and provide clinical considerations for treatments. Panoramic radiographs and electronic medical records of 64 patients with MRIM were retrospectively reviewed. Age, gender, follow-up period, medical history, complications, distribution of MRIM teeth, treatment, and prognosis were analyzed. Females were affected 1.56 times more than males, and the average age was 8.2 years. Dental complications, including periapical lesions, abscesses, and alveolar bone loss, were observed in 71.9%, and eruption disturbance of adjacent teeth was noticed in 37.5%. Most patients had medical histories in the first year of life. The most prevalent history was prematurity or low birthweight, followed by neurological conditions, surgeries, medications, and infections. All patients had MRIM on permanent first molars. The primary second molars were the second most frequently involved, followed by maxillary permanent central incisors and primary first molars. The prevalence was low on permanent lateral incisors and canines. Extraction was the most prevalent treatment done on MRIM-affected teeth, and most extraction sockets were managed by the eruption of permanent second molars. Few cases received endodontic treatment but with low success rates. Early detection of MRIM and prompt, appropriate treatment are important to avoid unnecessary discomfort from complications.

This study aimed to identify the clinical characteristics of molar root-incisor malformation (MRIM) and provide clinical considerations for treatments. Panoramic radiographs and electronic medical records of 64 patients with MRIM were retrospectively reviewed. Age, gender, follow-up period, medical history, complications, distribution of MRIM teeth, treatment, and prognosis were analyzed. Females were affected 1.56 times more than males, and the average age was 8.2 years. Dental complications, including periapical lesions, abscesses, and alveolar bone loss, were observed in 71.9%, and eruption disturbance of adjacent teeth was noticed in 37.5%. Most patients had medical histories in the first year of life. The most prevalent history was prematurity or low birthweight, followed by neurological conditions, surgeries, medications, and infections. All patients had MRIM on permanent first molars. The primary second molars were the second most frequently involved, followed by maxillary permanent central incisors and primary first molars. The prevalence was low on permanent lateral incisors and canines. Extraction was the most prevalent treatment done on MRIM-affected teeth, and most extraction sockets were managed by the eruption of permanent second molars. Few cases received endodontic treatment but with low success rates. Early detection of MRIM and prompt, appropriate treatment are important to avoid unnecessary discomfort from complications.

This study aimed to identify the clinical characteristics of molar root-incisor malformation (MRIM) and provide clinical considerations for treatments. Panoramic radiographs and electronic medical records of 64 patients with MRIM were retrospectively reviewed. Age, gender, follow-up period, medical history, complications, distribution of MRIM teeth, treatment, and prognosis were analyzed. Females were affected 1.56 times more than males, and the average age was 8.2 years. Dental complications, including periapical lesions, abscesses, and alveolar bone loss, were observed in 71.9%, and eruption disturbance of adjacent teeth was noticed in 37.5%. Most patients had medical histories in the first year of life. The most prevalent history was prematurity or low birthweight, followed by neurological conditions, surgeries, medications, and infections. All patients had MRIM on permanent first molars. The primary second molars were the second most frequently involved, followed by maxillary permanent central incisors and primary first molars. The prevalence was low on permanent lateral incisors and canines. Extraction was the most prevalent treatment done on MRIM-affected teeth, and most extraction sockets were managed by the eruption of permanent second molars. Few cases received endodontic treatment but with low success rates. Early detection of MRIM and prompt, appropriate treatment are important to avoid unnecessary discomfort from complications.

Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA.However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Background: This study investigated the outcomes of biventricular repair using right ventricle to pulmonary artery (RV-PA) conduit placement in patients aged <1 year. Methods: Patients aged <1 year who underwent biventricular repair using an RV-PA conduit between 2011 and 2020 were included in this study. The outcomes of interest were death from any cause, conduit reintervention, and conduit dysfunction (peak velocity of ≥3.5 m/sec or moderate or severe regurgitation). Results: In total, 141 patients were enrolled. The median age at initial conduit implantation was 6 months. The median conduit diameter z-score was 1.3. The overall 5-year survival rate was 89.6%. In the multivariable analysis, younger age (p=0.006) and longer cardiopulmonary bypass time (p=0.001) were risk factors for overall mortality. During follow-up, 61 patients required conduit reintervention, and conduit dysfunction occurred in 68 patients. The 5-year freedom from conduit reintervention and dysfunction rates were 52.9% and 45.9%, respectively. In the multivariable analysis, a smaller conduit z-score (p<0.001) was a shared risk factor for both conduit reintervention and dysfunction. Analysis of variance demonstrated a nonlinear relationship between the conduit z-score and conduit reintervention or dysfunction. The hazard ratio was lowest in patients with a conduit z-score of 1.3 for reintervention and a conduit z-score of 1.4 for dysfunction. Conclusion RV-PA conduit placement can be safely performed in infants. A significant number of patients required conduit reintervention and had conduit dysfunction. A slightly oversized conduit with a z-score of 1.3 may reduce the risk of conduit reintervention or dysfunction.