Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Objectives: . The supine sleep position and the rapid eye movement (REM) stage are widely recognized to exacerbate the severity of obstructive sleep apnea (OSA). Position-dependent OSA is generally characterized by an apnea-hypopnea index (AHI) that is at least twice as high in the supine position compared to other sleep positions. However, this condition can be misdiagnosed if a particular sleep stage—REM or non-REM (NREM)—predominates in a specific position. We explored the impact of the sleep stage on positional dependency in OSA. Methods: . Polysomnographic data were retrospectively analyzed from 111 patients with OSA aged 18 years or older, all of whom had an AHI exceeding five events per hour and slept in both supine and non-supine positions for at least 5% of the total sleep time. The overall ratio of non-supine AHI to supine AHI (NS/S-AHI ratio) was compared between total, REM, and NREM sleep. Additionally, a weighted NS/S-AHI ratio, reflecting the proportion of time spent in each sleep stage, was calculated and compared to the original ratio. Results: . The mean NS/S-AHI ratio was consistent between the entire sleep period and the specific sleep stages. However, the NS/S-AHI ratios for individual patients displayed poor agreement between total sleep and the specific stages. Additionally, the weighted NS/S-AHI ratio displayed poor agreement with the original NS/S-AHI ratio, primarily due to discrepancies in patients with mild to moderate OSA. Conclusion . The weighted NS/S-AHI ratio may help precisely assess positional dependency.

Background: Orbital complications arising from acute rhinosinusitis (ARS) are a major concern for clinicians and serve as important warning indicators of ARS. Prompt recognition and appropriate management are crucial for preventing potential vision-threatening sequelae. Orbital complications of rhinosinusitis are markedly more common in children than in adults. The aim of this study was to investigate the clinical characteristics and treatment outcomes of orbital complications of ARS in adult patients. Methods: This retrospective observational cohort study analyzed the medical records of 176 patients admitted for orbital cellulitis/abscess (ICD code: H050) who underwent orbit or paranasal computed tomography from January 2001 to February 2022 at a tertiary hospital. Results: Eighteen adults with a mean age of 53.2±18.9 years were diagnosed with orbital complications due to ARS: five (27.8%) had preseptal cellulitis, eight (44.4%) had orbital cellulitis, and five (27.8%) had subperiosteal orbital abscess. None of the patients had an orbital abscess or cavernous sinus thrombosis. All patients had unilateral orbital complications (7 right and 11 left) and were managed with intravenous antibiotics for an average of 10.3±6.6 days. Five patients with subperiosteal orbital abscesses underwent intranasal endoscopic drainage at an average of 1.4±1.9 days after admission, while two patients required additional external drainage. Complete recovery was observed in all patients. Conclusions Conservative antimicrobial therapy can be effective for treating orbital complications from ARS, and not all adult patients require immediate surgical intervention for subperiosteal abscesses. Nonetheless, careful monitoring is essential, and an ophthalmologist must check patients’ visual acuity to prevent irreversible blindness.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anticancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

Endoscopic medial maxillectomy (EMM) and its modifications are surgical techniques are used to treat recalcitrant maxillary sinusitis as well as maxillary sinus tumors. In this report, we propose a simple and efficient modification of EMM, called endoscopic trans-turbinal medial maxillectomy (ETTMM), by which the inferior turbinate (IT), nasolacrimal duct, and anatomical integrity of the nasal valve area are preserved. A total of 10 patients (five tumorous and five nontumorous maxillary diseases) underwent ETTMM. Briefly, a turbinate mucosal flap on the superior aspect of the IT was elevated after middle meatal antrostomy. Then a trans-turbinal window was developed to expose the inferior meatus, after which an extended maxillary antrostomy was generated. Finally, the turbinate mucosal flap was repositioned after complete removal of the antral lesions. All lesions were successfully treated using ETTMM. Our modification was easy to perform, and we achieved good endoscopic visualization and accessibility throughout the whole antrum by creating a trans-turbinal window and extended maxillary antrostomy. We could perform postoperative surveillance easily through the wide antrostomy using rigid endoscopes of various angles. ETTMM is a simple and useful modification of EMM that provides clear visualization and great accessibility to most aspects of the maxillary antrum while preserving the nasal functional units, including the IT and nasal valve area.

Metastasis to the sinonasal cavity is rare. Late recurrence, such as metastasis developing 10 years or more after nephrectomy, is even more rare. We present a rare case of late metastatic renal cell carcinoma (RCC) in the maxillary sinus after nephrectomy and discuss reported sinonasal metastatic RCC cases. A 64-year-old man presented with left nasal obstruction for the previous one year. He had undergone right nephrectomy to treat RCC 12 years prior. Paranasal sinus computed tomography and magnetic resolution imaging revealed a 4.6-cm-diameter mass exhibiting delayed contrast enhancement that filled the left maxillary sinus and the nasal cavity. Histologically, clear cell RCC was diagnosed. We resected the maxillary sinus tumor to resolve the nasal obstruction for palliative symptom relief. There has been no evidence of recurrence to date, 3 years postoperatively. When a patient with a history of RCC presents with a hypervascular paranasal sinus mass, metastatic RCC should be considered, despite history of nephrectomy. It is important to make an appropriate treatment plan depending on extent of metastases and location of the metastatic tumor.