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The reduction in esters, nitriles, and imines requires harsh conditions (highly reactive reagents, high temperatures, and pressures) or complex metal-ligand catalytic systems. Catalysts comprising earth-abundant and less toxic elements are desirable from the perspective of green chemistry. In this study, we developed a green hydroboration protocol for the reduction in esters, nitriles, and imines at room temperature (25 °C) using pinacolborane as the reducing agent and a commercially available Grignard reagent as the catalyst. Screening of various alkyl magnesium halides revealed MeMgCl as the optimal catalyst for the reduction. The hydroboration and subsequent hydrolysis of various esters yielded corresponding alcohols over a short reaction time (~0.5 h). The hydroboration of nitriles and imines produced various primary and secondary amines in excellent yields. Chemoselective reduction and density functional theory calculations are also performed. The proposed green hydroboration protocol eliminates the requirements for complex ligand systems and elevated temperatures, providing an effective method for the reduction in esters, nitriles, and imines at room temperature.

Nandina domestica (Berberidaceae) has been used in traditional medicine for the treatment of cough. This plant is distributed in Korea, Japan, China, and India This study aimed to investigate the anti-inflammatory phytochemicals obtained from the N. domestica fruits. We isolated a biflavonoid-type phytochemical, robustaflavone (R), from N. domestica fruits through bioactivity-guided fractionation based on its capacity to inhibit inflammation. The anti-inflammatory mechanism of R isolated from N. domestica has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of R using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that R reduces the production of nitric oxide (NO), pro-inflammatory cytokine interleukin-1 beta (IL-1β), and IL-6. Western blot analysis showed that R suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and downregulates the expression of LPS-induced nuclear factor-kappa B (NF-κB) and the phosphorylation of extracellular-regulated kinases (pERK 1/2). Moreover, R inhibited IL-8 release in LPS-induced human colonic epithelial cells (HT-29). These results suggest that R could be a potential therapeutic candidate for inflammatory bowel disease (IBD).

The root of Smilax china L. is used in traditional Korean medicine. We found that the Smilax china L. root extract has strong antimicrobial activity against two Cutibacterium acnes strains (KCTC 3314 and KCTC 3320). The aim of this study was to identify the beneficial properties of Smilax china L. extracts for their potential use as active ingredients in cosmetics for the treatment of human skin acne. The high-performance liquid chromatography (HPLC) and liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC/QTOF/MS) methods were used to obtain the profile of secondary metabolites from the ethyl acetate-soluble fraction of the crude extract. Agar diffusion and resazurin-based broth microdilution assays were used to evaluate antimicrobial activity and minimum inhibitory concentrations (MIC), respectively. Among the 24 metabolites, quercetin, resveratrol, and oxyresveratrol were the most potent compounds against Cutibacterium acnes. Minimum inhibitory concentrations of quercetin, resveratrol, and oxyresveratrol were 31.25, 125, and 250 μg/mL, respectively.

Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.

Pladienolides, an emerging class of naturally occurring spliceosome modulators, exhibit interesting structural features, such as highly substituted 12-membered macrocycles and epoxide-containing diene side chains. The potential of pladienolides as anti-cancer agents is confirmed by H3B-8800, a synthetic analog of this natural product class, which is currently under Phase I clinical trials. Since its isolation in 2004 and the first total synthesis in 2007, a dozen total syntheses and synthetic approaches toward the pladienolide class have been reported to date. This review focuses on the eight completed total syntheses of naturally occurring pladienolides or their synthetic analogs, in addition to a synthetic approach to the main framework of the natural product.

Pancreatic cancer (PC) is one of the most aggressive malignancies in the world. Gemcitabine (Gem), a nucleoside pyrimidine analogue, is a first-line chemotherapeutic drug for PC, but the tumor response rate of Gem is very low and resistance to Gem has emerged as a major problem in the treatment of PC. Oat bran, used as animal and human food, has been found to be beneficial to health. In this study, effects of oat bran ethanol extract (OBE) on PC cells and Gem-resistant PC cells were investigated in vitro. OBE decreased cell survival and colony forming ability of PC cells, without any cytotoxicity on the normal pancreatic cells. Flow cytometry analysis and TUNEL assay showed that the OBE reduced G1/S phase transition and induced death in PC cells through AMPK activation and downregulation of JNK. Additionally, OBE could overcome Gem resistance through reduction in RRM1/2 expression and showed synergistic effect by combinatorial treatment with Gem on Gem-resistant PC cells. Additionally, LC-MS data showed that avenacoside A was a component of OBE. Thus, this study elucidated the anti-proliferative effect of OBE and synergistic effect of OBE with Gem on PC cells and Gem-resistant cells.

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ) has previously been found to have effective anti-oxidant and anti-lipid-peroxidative activity. We aimed to elucidate whether HTHQ can prevent dopaminergic neuronal cell death by investigating the effect on l-DOPA-induced cytotoxicity in PC12 cells. HTHQ protected from both l-DOPA-induced cell death and superoxide dismutase activity reduction. When assessing the effect of HTHQ on oxidative stress-related signaling pathways, HTHQ inhibited l-DOPA-induced phosphorylation of sustained extracellular signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1/2). HTHQ also normalized l-DOPA-reduced Bcl-2-associated death protein (Bad) phosphorylation and Bcl-2-associated X protein (Bax) expression, promoting cell survival. Taken together, HTHQ exhibits protective effects against l-DOPA-induced cell death through modulation of the ERK1/2-p38MAPK-JNK1/2-Bad-Bax signaling pathway in PC12 cells. These results suggest that HTHQ may show ameliorative effects against oxidative stress-induced dopaminergic neuronal cell death, although further studies in animal models of Parkinson’s disease are required to confirm this.

A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (2⁻7). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,2„S)- and (2R,2„S)-4′-hydroxy-5-methoxy-7,8-(2,2-dimethyl-3-hydroxy-2,3-dihydro-4H-pyrano)-flavanones (2 and 3), (2S)- and (2R)-7,4′-dihydroxy-5-methoxy-8-(2,3-dihydroxy-3-methylbutyl)-flavanones (4 and 5) which were new oxygenated derivatives, along with (2R)- and (2S)-4′-hydroxy-5-methoxy-2„-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanones (6 and 7) on the basis of spectroscopic data. These results could contribute to understanding the metabolic fates of the major beer prenylflavanone isoxanthohumol that occur in mammalian system.

Fibrosis is a common pathological feature in most kinds of chronic kidney disease. Transforming growth factor β1 (TGF-β1) signaling is the master pathway regulating kidney fibrosis pathogenesis, in which mothers against decapentaplegic homolog 3 (SMAD3) with signal transducer and activator of transcription 3 (STAT3) act as the integrator of various pro-fibrosis signals. We examine the effects of pomolic acid (PA) on mice with unilateral ureteral obstruction (UUO) and TGF-β1 stimulated kidney fibroblast cells. UUO mice were observed severe tubular atrophy, and tubulointerstitial fibrosis and extracellular matrix (ECM) deposition at seven days postoperatively. However, PA-treated UUO mice demonstrated only moderate injury, minimal fibrosis, and larger reductions in the expression of ECM protein and epithelial-mesenchymal transition (EMT) progress. PA inhibited the SMAD-STAT phosphorylation in UUO mice. PA effects were also confirmed in TGF-β1 stimulated kidney fibroblast cells. In this study, we first demonstrated that PA ameliorates fibroblast activation and renal interstitial fibrosis. Our results indicate that PA may be useful as a potential candidate in the prevention of chronic kidney disease.

The aim of this study was to investigate the anti-angiogenic effects of the hexane fraction of Adenophora triphylla var. japonica root extract (HAT) and its influence on the development of erlotinib resistance in human lung cancer cells. HAT significantly reduced the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). The phosphorylation levels of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream molecules were decreased via HAT, indicating its anti-angiogenic potential in endothelial cells (ECs). A docking analysis demonstrated that β-sitosterol and lupeol, representative components of HAT, exhibit a high affinity for binding to VEGFR2. In addition, conditioned media from HAT-pretreated H1299 human lung cancer cells attenuated cancer-cell-induced chemotaxis of HUVECs, which was attributed to the decreased expression of angiogenic and chemotactic factors in H1299 cells. Interestingly, co-culture of erlotinib-sensitive PC9 human lung cancer cells with HUVECs induced erlotinib resistance in PC9 cells. However, co-culture with HAT-pretreated HUVECs partially restored the sensitivity of PC9 cells to erlotinib. HAT inhibited the development of erlotinib resistance by attenuating hepatocyte growth factor (HGF) production by ECs. Taken together, our results demonstrate that HAT exerts its anticancer effects by regulating the crosstalk between ECs and lung cancer cells.

Predicting photolithography performance in silico for a given materials combination is essential for developing better patterning processes. However, it is still an extremely daunting task because of the entangled chemistry with multiple reactions among many material components. Herein, we investigated the EUV-induced photochemical reaction mechanism of a model photoacid generator (PAG), triphenylsulfonium cation, using atomiC–Scale materials modeling to elucidate that the acid generation yield strongly depends on two main factors: the lowest unoccupied molecular orbital (LUMO) of PAG cation associated with the electron-trap efficiency ‘before C–S bond dissociation’ and the overall oxidation energy change of rearranged PAG associated with the proton-generation efficiency ‘after C–S bond dissociation’. Furthermore, by considering stepwise reactions accordingly, we developed a two-parameter-based prediction model predicting the exposure dose of the resist, which outperformed the traditional LUMO-based prediction model. Our model suggests that one should not focus only on the LUMO energies but also on the energy change during the rearrangement process of the activated triphenylsulfonium (TPS) species. We also believe that the model is well suited for computational materials screening and/or inverse design of novel PAG materials with high lithographic performances.

Chronic stress has been reported to stimulate the release of catecholamines, including norepinephrine (NE) and epinephrine (E), which promote cancer progression by activating the adrenergic receptor (AR). Although previous studies showed that β2-AR mediated chronic stress-induced tumor growth and metastasis, the underlying mechanism has not been fully explored. In this study, we aimed to investigate the molecular mechanism by which β2-AR exerts a pro-metastatic function in hepatocarcinoma (HCC) cells and breast cancer (BC) cells. Our results showed that Hep3B human HCC cells and MDA-MB-231 human BC cells exhibited the highest ADRB2 expression among diverse HCC and BC cell lines. NE, E, and isoprenaline (ISO), adrenergic agonists commonly increased the migration and invasion of Hep3B cells and MDA-MB-231 cells. The phosphorylation level of Src was significantly increased by E/NE. Dasatinib, a Src kinase inhibitor, blocked E/NE-induced migration and invasion, indicating that AR agonists enhanced the mobility of cancer cells by activating Src. ADRB2 knockdown attenuated E/NE-induced Src phosphorylation, as well as the metastatic ability of cancer cells, suggesting the essential role of β2-AR. Taken together, our results demonstrate that chronic stress-released catecholamines promoted the migration and invasion of HCC cells and BC cells via β2-AR-mediated Src activation.

Heat stress can be caused by various environmental factors. When exposed to heat stress, oxidative stress and inflammatory reaction occur due to an increase of reactive oxygen species (ROS) in the body. In particular, inflammatory responses induced by heat stress are common in muscle cells, which are the most exposed to heat stress and directly affected. Gintonin-Enriched Fraction (GEF) is a non-saponin component of ginseng, a glycolipoprotein. It is known that it has excellent neuroprotective effects, therefore, we aimed to confirm the protective effect against heat stress by using GEF. C2C12 cells were exposed to high temperature stress for 1, 12 and 15 h, and the expression of signals was analyzed over time. Changes in the expression of the factors that were observed under heat stress were confirmed at the protein level. Exposure to heat stress increases phosphorylation of p38 and extracellular signal-regulated kinase (ERK) and increases expression of inflammatory factors such as NLRP3 inflammasome through lysophosphatidic acid (LPA) receptor. Activated inflammatory signals also increase the secretion of inflammatory cytokines such as interleukin 6 (IL-6) and interleukin 18 (IL-18). Also, expression of glutathione reductase (GR) and catalase related to oxidative stress is increased. However, it was confirmed that the changes due to the heat stress were suppressed by the GEF treatment. Therefore, we suggest that GEF helps to protect heat stress in muscle cell and prevent tissue damage by oxidative stress and inflammation.

The Sleeping Beauty (SB) transposon system is non-viral and uses insertional mutagenesis, resulting in the permanent expression of transferred genes. Although the SB transposon is a useful method for establishing a mouse tumor model, there has been difficulty in using this method to generate tumors in the prostate. In the present study, electroporation was used to enhance the transfection efficiency of the SB transposon. To generate tumors, three constructs (a c-Myc expression cassette, a HRAS (HRas proto-oncogene, GTPase) expression cassette and a shRNA against p53) contained within the SB transposon plasmids were directly injected into the prostate. Electroporation was conducted on the injection site after the injection of the DNA plasmid. Following the tumorigenesis, the tumors were monitored by animal PET imaging and identified by gross observation. After this, the tumors were characterized by using histological and immunohistochemical techniques. The expression of the targeted genes was analyzed by Real-Time qRT-PCR. All mice subjected to the injection were found to have prostate tumors, which was supported by PSA immunohistochemistry. To our knowledge, this is the first demonstration of tumor induction in the mouse prostate using the electroporation-enhanced SB transposon system in combination with c-Myc, HRAS and p53. This model serves as a valuable resource for the future development of SB-induced mouse models of cancer.