Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about its anti-tumor mechanism in small cell lung ...cancer (SCLC). In this study, we found that curcumin can inhibit SCLC cell proliferation, cell cycle, migration, invasion and angiogenesis through suppression of the STAT3. SCLC cells were treated with curcumin (15 µmol/L) and the results showed that curcumin was effective in inhibiting STAT3 phosphorylation to downregulate of an array of STAT3 downstream targets ,which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion. Curcumin also suppressed the expression of proliferative proteins (Survivin, Bcl-X(L) and Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1). Knockdown of STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the increased cell proliferation ,cell survival, angiogenesis, invasion, migration and tumor growth. Our findings illustrate the biologic significance of IL-6/JAK/STAT3 signaling in SCLC progression and provide novel evidence that the pathway may be a new potential target for therapy of SCLC. It was concluded that curcumin is a potent agent in the inhibition of STAT3 with favorable pharmacological activity,and curcumin may have translational potential as an effective cancer therapeutic or preventive agent for SCLC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. ...This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy. We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the β-galactosidase positive staining rate (decreased 16%, p<0.01). Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression. MBNL1 prolonged the half-life of miR-130a-3p, and miR-130a-3p could negatively regulate STAT3 by binding to its mRNA 3′UTR. In db/db diabetic mice, we found an enhanced senescence level combined with low expression of MBNL1 and miR-130a-3p and high expression of STAT3 compared with db/m control mice during nephropathy development. Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice. Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Plant reproductive organs are vulnerable to heat, but regulation of heat-shock responses in inflorescence is largely uncharacterized. Here, we report that two of the SQUAMOSA PROMOTER BINDING ...PROTEIN- LIKE （SPL） transcriptional factors in Arabidopsis, SPL1 and SPL12, act redundantly in thermotolerance at the reproductive stage. The spll-1 sp112-1 inflorescences displayed hypersensitivity to heat stress, whereas overexpression of SPL 1 or SPL 12 enhanced the thermotolerance in both Arabidopsis and tobacco. RNA sequencing revealed 1939 upregulated and 1479 downregulated genes in wild-type inflorescence upon heat stress, among which one-quarter （1,040） was misregulated in spll-1 sp112-1, indicating that SPL1 and SPL12 contribute greatly to the heat-triggered transcriptional reprogramming in inflorescence. Notably, heat stress induced a large number of abscisic acid （ABA） responsive genes, of which -39% were disturbed in heat induction in spll-1 sp112-1 inflorescence. Preapplication of ABA and overex- pression of SPL1 restored the inflorescence thermotolerance in spll-1 sp112-1 and in the ABA biosynthesis mutant aba2-1, but not in the pyl sextuple mutant defective in ABA receptors PYR 1/PYL 1/PYL2/PYL4/PYL5/ PYL8. Thus, inflorescence thermotolerance conferred by SPL1 and SPL2 involves PYL-mediated ABA signaling. The molecular network consisting of SPL1 and SPL12 illustrated here shed new light on the mechanisms of plant thermotolerance at the reproductive stage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
(
) is a novel tumor suppressor gene generating long non-coding RNA (lncRNAs) in several types of human cancers. The expression and function of
in human brain glioma has yet to be elucidated. In this ...study,
was poorly expressed in tissues and cell lines of glioma, and the lower expression was correlated with glioma of the worse histological grade. Moreover, TUSC7 is a prognostic biomarker of glioma patients. Up-regulation of
suppressed cellular proliferation and invasion of glioma cells, and accelerated cellular apoptosis. Bioinformatics analysis showed that TUSC7 specifically binds to miR-23b. MiR-23b was up-regulated in glioma and negatively correlated with the expression of TUSC7. The miR-23b expression was inhibited remarkably by the upregulation of TUSC7 and the reciprocal inhibition was determined between TUSC7 and miR-23b.RNA pull-down and luciferase reporter assays were used to validate the sequence-specific correlation between miR-23b and TUSC7. TUSC7 inhibited the proliferation, migration and invasion of glioma cells and promoted cellular apoptosis largely bypassing miR-23b. We conclude that the lncRNA TUSC7 acted as a tumor suppressor gene negatively regulated by miR-23b, suggesting a novel therapeutic strategy against gliomas.
The first enantioselective total synthesis of (−)‐aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly ...enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3‐disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C−H activation conditions.
The enantioselective total synthesis of (−)‐aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. cod=1,5‐cyclooctadiene, Tf=trifluoromethanesulfonyl.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial ...structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high‐glucose and high‐fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high‐glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin ‐induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase SOD, malondialdehyde MDA, gp91phox, Cyt‐Cyto C), enhanced cell apoptosis (Bax/Bcl‐2, Cleaved caspase‐3, TUNEL‐positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1‐Foxo1 and PI3K‐Akt pathways.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The miR156-targeted squamosa promoter binding protein like (SPL) transcription factors function as an endogenous age cue in regulating plant phase transition and phase-dependent morphogenesis, but ...the control of SPL output remains poorly understood. In Arabidopsis thaliana the spatial pattern of trichome is a hallmark of phase transition and governed by SPLs. Here, by dissecting the regulatory network controlling trichome formation on stem, we show that the miR171-targeted lost meristems 1 (LOM1), LOM2 and LOM3, encoding GRAS family members previously known to maintain meristem cell polarity, are involved in regulating the SPL activity. Reduced LOM abundance by overexpression of miR171 led to decreased trichome density on stems and floral organs, and conversely, constitutive expression of the miR171-resistant LOM (rLOM) genes promoted trichome production, indicating that LOMs enhance trichome initiation at reproductive stage. Genetic analysis demonstrated LOMs shaping trichome distribution is dependent on SPLs, which positively regulate trichome repressor genes TRICHOMELESS 1 (TCL1) and TRIPTYCHON (TRY). Physical interaction between the N-terminus of LOMs and SPLs underpins the repression of SPL activity. Importantly, other growth and developmental events, such as flowering, are also modulated by LOM-SPL interaction, indicating a broad effect of the LOM-SPL interplay. Furthermore, we provide evidence that MIR171 gene expression is regulated by its targeted LOMs, forming a homeostatic feedback loop. Our data uncover an antagonistic interplay between the two timing miRNAs in controlling plant growth, phase transition and morphogenesis through direct interaction of their targets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anaerobic digestion, an economic and energy-efficient biological process, is extensively applied in the treatment of a variety of wastewater streams and organic wastes. However, the ineffective ...mineralization of degradation-resistant organic wastes is considered a limiting factor for this promising technology, and has prevented it from being widely adopted for the anaerobic treatment of chemical-industrial organic wastewater. In this work, the advantages and benefits of anaerobic digestion and those conventional physical/chemical/biological methods are compared. This review also suggests the current challenges and barriers to the application of anaerobic digestion to the treatment of chemical-industrial organic wastewater by considering some typical degradation-resistant organic wastes as examples. Design improvements are required to enhance the degradation from refractory organics to fermentable organics. The applications of the up-flow anaerobic sludge blanket, anaerobic membrane bioreactor and their derivatives are highly recommended in the anaerobic treatment of chemical-industrial organic wastewater. While some state-of-the-art physical/chemical technologies have been widely reported and are currently applied in anaerobic treatment of chemical-industrial organic wastewater, high energy consumption and low efficiency of these processes is an obstacle to their smooth operation and presents clear difficulties. Therefore, this work provides some perspectives for future applications and practical advice for improving and enhancing the hydrolysis step of those degradation-resistant organic wastes. Synergistic processes, such as the co-culturing method, co-digestion and nitrate-reducing anaerobic digestion are suggested as a means to achieve the effective anaerobic treatment of chemical-industrial organic wastewater and sustainable regeneration of cleaner production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The first catalytic asymmetric total synthesis of the heptacyclic alkaloid (−)-communesin F is described. A key step features an iridium-catalyzed asymmetric intermolecular cascade cyclization, ...constructing the lower N,N-aminal-containing CDEF tetracyclic core in one step. Another notable element is the closure of final ring system (A ring) via a facile reduction of a twisted amide and concomitant cyclization activated by mesylation of N,O-hemiaminal intermediate.
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IJS, KILJ, NUK, PNG, UL, UM
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