Effect of Ishige okamurae Extract on Osteoclastogenesis In Vitro and In Vivo.

We demonstrated the effect of Ishige okamurae extract (IOE) on the receptor activator of nuclear factor-κB ligand (RANKL)-promoted osteoclastogenesis in RAW 264.7 cells and confirmed that IOE inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation. IOE inhibited protein expression of TRAP, metallopeptidase-9 (MMP-9), the calcitonin receptor (CTR), and cathepsin K (CTK). IOE treatment suppressed the expression of activated T cell cytoplasmic 1 and activator protein-1, thus controlling the expression of osteoclast-related factors. Moreover, IOE significantly reduced RANKL-phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). It also reduced the RANKL-induced phosphorylation of NF-κB and nuclear translocation of p65. IOE inhibited Dex-induced bone loss and osteoclast-related gene expression in zebrafish larvae. HPLC analysis shows that IOE consists of 3.13% and 3.42% DPHC and IPA, respectively. Our results show that IOE has inhibitory effects on osteoclastogenesis in vitro and in vivo and is a potential therapeutic for osteoporosis.

Age-associated spinal stenosis in the turquoise killifish.

Aging triggers spinal degeneration, including common spinal stenosis, which causes back and leg pain in older individuals, significantly impacting their quality of life. Here, we explored aging traits in turquoise killifish spines, potentially offering a model for age-linked spinal stenosis in humans. Aged turquoise killifish exhibited body shape deformation and increased vertebral collapse, which was further accelerated by spawning. High-resolution CT scans revealed suppressed cortical bone thickness and hemal arch area in vertebrae due to spawning, and osteophyte formation was observed in both aged and breeding fish populations. Scale mineralization mirrored these changes, increasing with age but being suppressed by spawning. The expression of sp7, sox9b, axin1, and wnt4a/b genes can be utilized to monitor age- and reproduction-dependent spine deformation. This study demonstrates that turquoise killifish and humans share certain phenotypes of age-related vertebral abnormalities, suggesting that turquoise killifish could serve as a potential model for studying human spinal stenosis.

Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

Effect of Ishophloroglucin A Isolated from Ishige okamurae on In Vitro Osteoclastogenesis and Osteoblastogenesis.

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the bone remodeling process. This study aimed to investigate the effect of Ishophloroglucin A (IPA) isolated from Ishige okamurae on the function of osteoclasts and osteoblasts in vitro. First, we demonstrated the effect of IPA on osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW 264.7 cells. IPA inhibited the tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation in RANKL-induced RAW 264.7 cells. Moreover, it inhibited the RANKL-induced osteoclast-related factors, such as TRAP, matrix metalloproteinase-9 (MMP-9), and calcitonin receptor (CTR), and transcription factors, such as nuclear factor of activated T cells 1 (NFATc1) and c-Fos. IPA significantly suppressed RANKL-activated extracellular signal-regulated kinase (ERK), and NF-κB in RAW 264.7 cells. Our data indicated that the ERK and NF-κB pathways were associated with the osteoclastogenesis inhibitory activity of IPA. Next, we demonstrated the effect of IPA on osteoblastogenesis in MG-63 cells. IPA significantly promoted alkaline phosphatase (ALP) activity in MG-63 cells, along with the osteoblast differentiation-related markers bone morphogenetic protein 2 (BMP2), type 1 collage (COL1), p-Smad1/5/8, and Runx2, by activating the MAPK signaling pathways. Taken together, the study indicated that IPA could be effective in treating bone diseases, such as osteoporosis.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a high mortality. However, the treatment options for advanced HCC are limited to tyrosine kinase inhibitors, such as sorafenib and lenvatinib. Since previous regimens have an insufficient efficacy, the combination therapy of atezolizumab and bevacizumab (Ate/Bev) has been investigated, which showed an improvement in progression-free and overall survival. However, the adverse events of this combination therapy in advanced HCC have not been established. Herein, we report a novel case of an unresectable HCC and acute respiratory distress syndrome (ARDS) after a combination therapy of Ate/Bev. CASE SUMMARY: An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass. Liver magnetic resonance imaging and enhanced chest computed tomography (CT) were performed, which showed arterial hyperenhancement with washout in delayed phase suggesting HCC, and a well-defined metastatic solid nodule, respectively. F-18 fluorodeoxyglucose positron emission tomography (PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone, lumbar vertebrae, and femur. Because of the high burden of the intrahepatic tumor, transarterial radioembolization was initially performed; after 37 d, a combination therapy of Ate/Bev was administered. The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea. He was diagnosed with severe pneumonitis based on CT. Despite administering oxygen via a high-flow nasal cannula, the P/F ratio was only 74; therefore, the patient was diagnosed with ARDS based on the overall examination results. Low tidal volume with high positive end-expiratory pressure, sedative agents combined with a neuromuscular blocker, and a systemic steroid were promptly applied to manage the ARDS. However, the patient did not recover from the hypoxia and expired 31 h after being admitted. CONCLUSION: Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy, and patients should be closely monitored after therapy.

ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers.

Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.

Anti-inflammatory activity of Echinosophora koreensis nakai root extract in lipopolysaccharides-stimulated RAW 264.7 cells and carrageenan-induced mouse paw edema model.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinosophora koreensis Nakai is an endemic plant species distributed in a limited area within the Korean province of Gangwon, including the Yanggu-gun, Inje-gun, Cheorwon-gun, Chuncheon-si, and Hongcheon-gun counties. It is used in traditional medicine to treat various disorders, such as fever, skin diseases, diuresis, and neuralgia. MATERIALS AND METHODS: This study demonstrated the effects of E. koreensis Nakai root extract (EKRE) on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Cell viability was assessed through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nitric oxide (NO) production was measured using Griess reagent. Interleukin (IL)-6 and tumor necrosis factor (TNF) levels were assessed using enzyme-linked immunosorbent assays. Inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) expression were assessed using Western blot analysis. To examine the effects of EKRE in vivo, it was administered orally at doses of 50 or 200 mg/kg for 3 days in mice. Edema in the paws was induced through λ-carrageenan injection and measured hourly for up to 5 h using calipers. RESULTS: EKRE markedly suppressed LPS-generated NO, IL-6, and iNOS production in RAW 264.7 cells. Moreover, it suppressed the activation of the NF-κB and MAPK in LPS-stimulated cells. Furthermore, EKRE significantly inhibited carrageenan-induced edema in mouse paws. There were no significant differences in IL-6 and TNF production in paw tissue harvested from mice, but levels decreased at high EKRE concentrations (200 mg/kg). CONCLUSION: The results of this study provided validation for EKRE-induced inhibition of inflammatory responses in vitro and in vivo. This research suggested that EKRE is a promising treatment for inflammatory disorders.

Three new chromanes and one new flavone C-glycoside from Mallotus apelta.

Three new chromanes, malloapeltas J-L (1-3), and one new flavone C-glycoside, malloflavoside (4), together with four known compounds, apigenin 6-C-ß-D-xylopyranosyl-8-C-α-L-arabinopyranoside (5), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (6), apigenin 7-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (7), and acantrifoside E (8) were isolated from the methanol extract of the leaves of Mallotus apelta. Their chemical structures were determined using spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS methods. All the isolated compounds were evaluated their cytotoxic activity against human prostate cancer (PC-3) and human breast cancer (MCF-7) cells, but none of them showed cytotoxicities on both human cancer cell lines.

Natural Course of Asymptomatic Upper Gastrointestinal Subepithelial Lesion of 2 cm or Less in Size.

There is limited evidence of a natural course of an upper gastrointestinal (UGI)-subepithelial lesion (SEL) of 2 cm or less in size. This study aims to determine the natural course of UGI-SELs and find the risk factors of the endoscopic and endoscopic ultrasonography (EUS) findings associated with an increase in size. The medical records of 2539 patients with UGI-SELs between 2004 and 2016 were reviewed retrospectively. A total of 672 SELs of 2 cm or less in size were analyzed through EUS and followed up for at least 36 months. The mean follow-up duration was 68 months (range: 36-190 months), and 97 SELs (14.4%) showed an increase in size with a mean increase rate of 1.2 mm/year. Initial size (aOR 1.03, 95% confidence interval (CI) 1.01-1.06), an endoscopic finding of a hemorrhagic spot (aOR 3.13, 95% CI 1.14-8.60), and an EUS finding of a lesion in the fourth layer (aOR 1.87, 95% CI (1.21-2.88) were related to an increase in size. An endoscopic finding of translucidity (aOR 0.28, 95% CI (0.10-0.76) and an EUS finding of calcification (aOR 0.30, 95% CI 0.09-0.95) were inversely related to an increase in size. There was no death related to UGI-SELs during the follow-up. While most UGI-SELs of 2 cm or less in size showed no significant size change and favorable prognosis, an individualized follow-up strategy needs to be considered in case of the presence of hemorrhagic spots and lesions in the fourth layer.

Two new triterpenoid glycosides from Bacopa monnieri and their cytotoxic activity.

Using combined chromatographic methods, two new triterpenoid glycosides, bacopasaponin K (1) and bacopasaponin L (2), along with eight known compounds, bacopaside IV (3), bacopaside VII (4), bacopasaponin E (5), bacoside A3 (6), bacopasaponin F (7), bacopasaponin C (8), bacopaside I (9), and bacopaside II (10) were isolated from the methanol extract of the Bacopa monnieri. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS and comparing with the NMR data reported in the literature. All these compounds were evaluated for their cytotoxic activity using the cell counting kit-8 (CCK-8) assay. Compounds 4, 6, 8, and 10 exhibited potential cytotoxic effects against human lung cancer cells (PC9) and human colon cancer cells (SW620).

Effect of Pinoresinol and Vanillic Acid Isolated from Catalpa bignonioides on Mouse Myoblast Proliferation via the Akt/mTOR Signaling Pathway.

Growth and maintenance of skeletal muscle is essential for athletic performance and a healthy life. Stimulating the proliferation and differentiation of muscle cells may help prevent loss of muscle mass. To discover effective natural substances enabling to mitigate muscle loss without side effects, we evaluated muscle growth with several compounds extracted from Catalpa bignonioides Walt. Among these compounds, pinoresinol and vanillic acid increased C2C12, a mouse myoblast cell line, proliferation being the most without cytotoxicity. These substances activated the Akt/mammalian target of the rapamycin (mTOR) pathway, which positively regulates the proliferation of muscle cells. In addition, the results of in silico molecular docking study showed that they may bind to the active site of insulin-like growth factor 1 receptor (IGF-1R), which is an upstream of the Akt/mTOR pathway, indicating that both pinoresinol and vanillic acid stimulate myoblast proliferation through direct interaction with IGF-1R. These results suggest that pinoresinol and vanillic acid may be a natural supplement to improve the proliferation of skeletal muscle via IGF-1R/Akt/mTOR signaling and thus strengthen muscles.

Real-Time Longitudinal Evaluation of Tumor Blood Vessels Using a Compact Preclinical Fluorescence Imaging System.

Tumor angiogenesis is enhanced in all types of tumors to supply oxygen and nutrients for their growth and metastasis. With the development of anti-angiogenic drugs, the importance of technology that closely monitors tumor angiogenesis has also been emerging. However, to date, the technology for observing blood vessels requires specialized skills with expensive equipment, thereby limiting its applicability only to the laboratory setting. Here, we used a preclinical optical imaging system for small animals and, for the first time, observed, in real time, the entire process of blood vessel development in tumor-bearing mice injected with indocyanine green. Time-lapse sequential imaging revealed blood vessel volume and blood flow dynamics on a microscopic scale. Upon analyzing fluorescence dynamics at each stage of tumor progression, vessel volume and blood flow were found to increase as the tumor developed. Conversely, these vascular parameters decreased when the mice were treated with angiogenesis inhibitors, which suggests that the effects of drugs targeting angiogenesis can be rapidly and easily screened. The results of this study may help evaluate the efficacy of angiogenesis-targeting drugs by facilitating the observation of tumor blood vessels easily in a laboratory unit without large and complex equipment.

Anti-Inflammatory Activity of 4-((1R,2R)-3-Hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol Isolated from Juglans mandshurica Maxim. in LPS-Stimulated RAW 264.7 Macrophages and Zebrafish Larvae Model.

Juglans mandshurica Maxim., a traditional folk medicinal plant, is widely distributed in Korea and China. In our previous study, we isolated a new phenylpropanoid compound, 4-((1R,2R)-3-hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol (HHMP), from J. mandshurica. In the present study, we evaluated the anti-inflammatory activity of HHMP on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and zebrafish larvae. HHMP significantly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 production in a dose-dependent manner. Moreover, HHMP treatment considerably suppressed LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. We also demonstrated the mechanisms of HHMP inhibition of inflammatory responses in LPS-stimulated RAW 264.7 cells via Western blot analysis and immunofluorescence staining. Furthermore, HHMP significantly inhibited NO production in LPS-stimulated zebrafish larvae. Consequently, we established that HHMP significantly inhibited the LPS-induced activation of NF-κB and MAPK and the nuclear translocation of p65 in RAW 264.7 cells. Taken together, our findings demonstrate the effect of HHMP on LPS-induced inflammatory responses in vitro and in vivo, suggesting its potential to be used as a natural anti-inflammatory agent.

Protective Effect of Brassica napus L. Hydrosols against Inflammation Response in RAW 264.7 Cells.

OBJECTIVE: To demonstrate the anti-inflammatory activity of Brassica napus L. hydrosols (BNH) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. METHODS: Composition analysis of BNH was conducted via gas chromatography-mass spectrometry after BNH were extracted. The nitric oxide (NO) production was measured using the Griess assay. Prostaglandin E2 (PGE2) production was evaluated with enzyme-linked immunosorbent assay. The effects of BNH on LPS-induced pro-inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated using Western blot analysis. Furthermore, phosphorylation of nuclear factor-kappa B (NF-κB) and nuclear translocation of NF-κB p65 were evaluated with Western blot analysis and immunofluorescence staining, respectively. RESULTS: Compared with LPS-stimulated cells, BNH markedly decreased the generation of NO and PGE2 in LPS-stimulated RAW 264.7 cells (P<0.01 or P<0.05). Moreover, BNH inhibited protein levels of iNOS and COX-2 (P<0.01). Phosphorylation of NF-κB and nuclear translocation of NF-κB p65 was significantly inhibited by BNH (P<0.01 or P<0.05). CONCLUSION: The anti-inflammatory activities of BNH were mediated via blockage of the NF-κB signaling pathways in LPS-stimulated RAW 264.7 cells.

Metabolite Profiling of Methanolic Extract of Gardenia jaminoides by LC-MS/MS and GC-MS and Its Anti-Diabetic, and Anti-Oxidant Activities.

In this study, the methanolic extract from seeds of Gardenia jasminoides exhibited strong antioxidant and enzyme inhibition activities with less toxicity to NIH3T3 and HepG2 cells at the concentration of 100 µg/mL. The antioxidant activities (DPPH and ABTS), α-amylase, and α-glucosidase inhibition activities were found higher in methanolic extract (MeOH-E) than H2O extract. Besides, 9.82 ± 0.62 µg and 6.42 ± 0.26 µg of MeOH-E were equivalent to 1 µg ascorbic acid for ABTS and DPPH scavenging, respectively while 9.02 ± 0.25 µg and 6.52 ± 0.15 µg of MeOH-E were equivalent to 1 µg of acarbose for inhibition of α-amylase and α-glucosidase respectively. Moreover, the cell assay revealed that the addition of MeOH-E (12.5 µg/mL) increased about 37% of glucose uptake in insulin resistant (IR) HepG2 as compared to untreated IR HepG2 cells. The LC- MS/MS and GC-MS analysis of MeOH-E revealed a total of 54 compounds including terpenoids, glycosides, fatty acid, phenolic acid derivatives. Among the identified compounds, chlorogenic acid and jasminoside A were found promising for anti-diabetic activity revealed by molecular docking study and these molecules are deserving further purification and molecular analysis.

1-Cinnamoyltrichilinin from Melia azedarach Causes Apoptosis through the p38 MAPK Pathway in HL-60 Human Leukemia Cells.

Acute myeloid leukemia (AML) is an aggressive type of human leukemia with a low survival rate, and its complete remission remains challenging. Although chemotherapy is the first-line treatment of AML, it exerts toxicity in noncancerous cells when used in high doses, thus necessitating the development of novel compounds with a high therapeutic window. This study aimed to investigate the anticancer effects of several compounds derived from the fruits of Melia azedarach (a tree with medicinal properties). Among them, 1-cinnamoyltrichilinin (CT) was found to strongly suppress the viability of HL-60 human leukemia cells. CT treatment induced apoptosis and increased nuclear fragmentation and fractional DNA content in HL-60 cells in a dose-dependent manner. CT induced phosphorylation of p38 mitogen-activated protein kinases (p38), though not of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), and activated Bcl-2 family proteins towards the proapoptosis and cleavage of caspase-3 and poly (ADP-ribose) polymerase. Both CT-mediated apoptosis and apoptotic protein expression were reversed by treatment with the p38 inhibitor, thereby indicating the p38 pathway to be critical in CT-stimulated apoptosis. The results collectively indicated CT to suppress HL-60 survival by activating the p38 pathway and inducing apoptosis, hence being a novel potential therapeutic agent for AML.

Eckol from Ecklonia cava ameliorates TNF-α/IFN-γ-induced inflammatory responses via regulating MAPKs and NF-κB signaling pathway in HaCaT cells.

We investigated the protective effect of the bioactive compound eckol on inflammatory-related skin lesions in vitro. HaCaT cells were stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mixture, and treated with various concentration of eckol (25, 50, and 100 µg/ml). The expression of pro-inflammatory cytokines and chemokines were analyzed by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), respectively. Mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways regulate immune and inflammation responses. Phosphorylation of MAPKs and NF-κB, indicating activation of respective signaling pathways, was examined by western blot analysis. Treatment of TNF-α and IFN-γ promoted the mRNA expression and production of pro-inflammatory cytokines and chemokines in HaCaT cells. However, eckol significantly suppressed the these mediators. Furthermore, activation of TNF-α/IFN-γ-induced MAPKs and NF-κB signaling pathway was inhibited by eckol treatment. Eckol also hampered the TNF-α/IFN-γ-mediated nuclear translocation of NF-κB p65 in HaCaT cells. Taken together, our findings demonstrate that eckol shows effective protective activity against TNF-α/IFN-γ-induced skin inflammation.

Central Diabetes Insipidus Associated with Orbital Apex Syndrome.

Orbital apex syndrome (OAS) manifests as multiple cranial nerve palsies caused by an abnormal nerve response to inflammation or other processes. Central diabetes insipidus (CDI) is characterized by deficient synthesis or secretion of antidiuretic hormone. A 62-year-old woman underwent myringotomy for otitis media with effusion. Two months after the procedure, symptoms of hearing loss had not improved, and she underwent left tympanoplasty and mastoidectomy. After surgery, she presented with left ocular pain and visual loss. Neurologic examination revealed ptosis, total ophthalmoplegia, and a relative afferent pupillary defect on the left eye. Magnetic resonance imaging showed an asymmetric contrast-enhancing lesion in the left orbital apex and left cavernous sinus, with adjacent dural thickening and enhancement. OAS was diagnosed, and steroid treatment was started. During the regular follow-up period, she reported polyuria, and CDI was diagnosed. Treatment with intranasal desmopressin 10 µg twice daily was started, and symptoms greatly improved. The mechanism underlying the association of CDI with OAS is unclear, and further research is needed. The present case suggests that polyuria in OAS should alert neurologists and ophthalmologists to possible CDI.

Protective Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde from Polysiphonia morrowii Harvey against Hydrogen Peroxide-Induced Oxidative Stress In Vitro and In Vivo.

We investigated the protective effects of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) from Polysiphonia morrowii Harvey against hydrogen peroxide (H2O2)-induced apoptosis in Vero cells. BDB exhibited scavenging activity for DPPH, hydroxyl, and alkyl radicals. BDB also inhibited H2O2-induced lipid peroxidation, cell death, and apoptosis in Vero cells by inhibiting the production of ROS. To evaluate the molecular mechanisms of apoptosis inhibition, the expression of Bax/Bcl-xL and NF-κB was assessed by western blot assay. BDB significantly suppressed the cleavage of caspase-9 and PARP and reduced Bax levels in H2O2-induced Vero cells. Besides, BDB suppressed the phosphorylation of NF-κB and the translocation of p65 in H2O2-induced cells. Furthermore, we evaluated the effect of BDB on ROS production, cell death, and lipid peroxidation in an H2O2-stimulated zebrafish embryo model. Taken together, these results indicated that ROS generation and cell death were significantly inhibited by BDB in zebrafish embryos, thereby proving that BDB exerts excellent antioxidant activity in vitro and in vivo.

3­Bromo­5­(ethoxymethyl)­1,2­benzenediol inhibits LPS-induced pro-inflammatory responses by preventing ROS production and downregulating NF-κB in vitro and in a zebrafish model.

The anti-inflammatory effects of 3­bromo­5­(ethoxymethyl)­1,2­benzenediol (BEMB) from Polysiphonia morrowii were evaluated in lipopolysaccharide (LPS)-induced RAW264.7 cells and zebrafish embryo. BEMB showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS), and the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in the LPS-activated RAW264.7 cells and zebrafish embryo without cytotoxicity. Moreover, BEMB suppressed the protein and mRNA expression levels of nuclear factor (NF)-κB (p65 and inhibitor of NF-κB [IκB]-A) in RAW264.7 cells and zebrafish embryo, respectively. Collectively, the results of this study indicate that BEMB suppressed the production of pro-inflammatory mediators such as NO, iNOS, and COX-2 as well as their regulation in LPS-induced RAW264.7 cells and zebrafish embryos by inhibiting ROS production and NF-κB expression. Therefore, this study suggests that BEMB could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.