Neuroprotective properties of Madecassoside from Centella asiatica after hypoxic-ischemic injury.

Madecassoside is one of increasingly used constituent of Centella asiatica, a frequently prescribed crude drug in South eastern Asia and China for wound healing. In the present experiment, it exposes the neuroprotective nature of Madecassoside in GT1-7 cell lines, further, which the antioxidant activities are performed. The cellular toxicity was assessed using 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay with increased cell viability with IC50 2.5µg/ml. the regulation of antioxidant levels showed changes in madecassoside treated cell lysate viz., SOD assay. Also, the antioxidative assays confirmed the negligible cellular damage caused to the GT1-7 cell lines. Hence, the results advocate that the current antioxidant and antitumor activity be justified by the high concentration of phenolic constituents, primarily the triterpene present in the C. asiatica.

LncRNAs: new players in gliomas, with special emphasis on the interaction of lncRNAs With EZH2.

Gliomas are the most common primary malignancy in the brain, accounting for 50-60%. Despite all the efforts of cytoreductive surgery in combination with intense chemoradiotherapy, glioma remains an incurable disease. Recent studies have shown that long noncoding RNAs (lncRNAs) are involved in the pathology of gliomas. LncRNAs are involved in many cellular processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. In this review we focus on the dysregulation of lncRNAs in gliomas. We also address that epigenetic modification such as DNA methylation and microRNAs interact with lncRNAs in gliomas. In addition, the interaction of lncRNAs with signaling pathways in gliomas is discussed systematically, with particular emphasis on the interaction of lncRNAs with EZH2. Such approaches provide valuable insights into the potential future applications of lncRNAs in the treatment of gliomas.

TET family proteins: new players in gliomas.

DNA methylation at the 5-position of cytosine (5mC) in the mammalian genome has emerged as a pivotal epigenetic event that plays important roles in development, aging and disease. The three members of the TET protein family, which convert 5mC to 5-hydroxymethylcytosine, has provided a potential mechanism resulting in DNA demethylation and maintaining cellular identity. Recent studies have shown that epigenetic modifications play a key role in the regulation of the molecular pathogenesis of gliomas. In this review we focus on demonstrating the TET proteins in DNA demethylation and transcriptional regulation of different target genes. In addition, we address the role of TET proteins in gliomas. This review will provide valuable insights into the potential targets of gliomas, and may open the possibility of novel therapeutic approaches to this fatal disease.

Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension.

BACKGROUND: This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT). METHODS: According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin-eosin staining, and senescence-associated ß-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified. RESULTS: In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration. CONCLUSIONS: ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

[Mineral nitrogen accumulation and its spatial distribution in soils in dense planting dwarf rootstock apple orchard on the Weibei dry plateau, Northwest China]. / æ¸­åŒ—æ—±å¡¬çŸ®ç §å¯†æ¤è‹¹æžœå›­åœŸå£¤çŸ¿è´¨æ°®ç§¯ç´¯ä¸Žç©ºé—´åˆ†å¸ƒç‰¹å¾.

With the rapid development of dense apple tree plantings with the dwarf rootstock cultivation method, determining accumulation and distribution characteristics of soil mineral nitrogen in densely planted orchards with dwarf rootstock is important to enable scientific fertilization of apple orchards. We investigated densely planted apple orchards with dwarf rootstocks and different plant ages (6 a, 9 a, and 12 a). We collected soil samples under trees, between trees, between rows, and at the midpoints between the trees and rows, and examined the accumulation and distribution characteristics of nitrate, ammonium, and mineral nitrogen. The cumulative amount of nitrate in the 0-300 cm soil layer increased with plant age. The difference between orchards with different plant ages was significant and showed the trend 6 a<9 a<12 a. The cumulative amount of nitrate increased from 1729 kg·hm-2 to 3771 kg·hm-2 with increasing plant age. The ammonium content was low for orchards of all plant ages and had little effect on the accumulation and spatial distribution of mineral nitrogen. There were two accumulation peaks of nitrate nitrogen in the vertical direction. The depth of soil layer where the second accumulation peak was located decreased from 180 cm to 220 cm with increasing plant age. In the horizontal direction, soil nitrate nitrogen content between rows increased from 27 mg·kg-1 to 138 mg·kg-1 with increasing plant age, representing a more than 400% increase. The difference between orchards with different plant ages was significant. In summary, excessive usage of nitrogen fertilizer and serious leaching of nitrate were problematic in all orchards with different ages. Less nitrogen fertilizer should be applied, and anti-seepage measures should be used at the fertilization location to prevent the leaching of nitrate to deep layers.

Phylogeography and evolutionary dynamics analysis of porcine delta-coronavirus with host expansion to humans.

From 2003 onwards, three pandemics have been caused by coronaviruses: severe acute respiratory syndrome coronavirus (SARS-CoV); middle east respiratory syndrome coronavirus (MERS-CoV); and, most recently, SARS-CoV-2. Notably, all three were transmitted from animals to humans. This would suggest that animals are potential sources of epidemics for humans. The emerging porcine delta-coronavirus was reported to infect children. This is a red flag that marks the ability of PDCoV to break barriers of cross-species transmission to humans. Therefore, we conducted molecular genetic analysis of global clade PDCoV to characterize spatiotemporal patterns of viral diffusion and genetic diversity. PDCoV was classified into three major lineages, according to distribution and phylogenetic analysis of PDCoV. It can be inferred based on the analysis results of the currently known PDCoV strains that PDCoV might originate in Asia. We also selected six special spike amino acid sequences to align and analyze to find seven significant mutation sites. The accumulation of these mutations may enhance dynamic movements, accelerating spike protein membrane fusion events and transmission. Altogether, our study offers a novel insight into the diversification, evolution, and interspecies transmission and origin of PDCoV and emphasizes the need to study the zoonotic potential of the PDCoV and comprehensive surveillance and enhanced biosecurity precautions for PDCoV.

Synthesis, X-ray crystal structures and optical properties of novel substituted pyrazoly 1,3,4-oxadiazole derivatives.

Novel pyrazoly 1,3,4-oxadiazole derivatives were synthesized and characterized by (1)H NMR, IR, HRMS and X-ray diffraction analysis. UV-vis absorption and fluorescence properties of these compounds in different solutions showed that the maximum absorption wavelength was not significantly changed in different solvents; however, maximal emission wavelength was red-shifted with the increase of solvent polarity. Absorption λ(max) and emission λ(max) was less correlated with substituent groups on aryl rings.

The synthesis, X-ray crystal structure and optical properties of novel 5-aryl-3-ferrocenyl-1-pyridazinyl-pyrazoline derivatives.

A series of novel 5-aryl-3-ferrocenyl-1-pyridazinyl pyrazoline derivatives was synthesized by the reaction of ferrocenyl chalcone and 3-chloro-6-hydrazinylpyridazine in 10-65% yields. The compounds were characterized using IR, (1)H NMR, HRMS spectroscopic techniques and representative compounds 3c and 4c were assigned based on the X-ray crystallographic structure. The absorption and fluorescence characteristics of the compounds were investigated in chloroform, tetrahydrofuran and acetonitrile, respectively. The results showed that the absorption maxima of the compounds varied from 323 to 327 nm depending on the groups bonded to benzene and pyridazine ring. The maximum emission spectra of compounds in CHCl(3) were dependent on groups in pyridazine ring in which a strong donating-electron group such as propoxyl group on pyridazine ring in N-1 position of pyrazoline made the emission wavelength of 4a-4e small red shifte than that of compounds 3a-3e with chlorine group. The intensity of absorption and fluorescence was also correlated with substituent on aryl ring in C-5 position of pyrazoline. In addition, the absorption spectra of these compounds changed very little, but the fluorescence spectra had much change with increasing solvent polarity.

4-(p-Tolyl-amino)-benzaldehyde.

In the title compound, C(14)H(13)NO, the dihedral angle between the aromatic rings is 66.08 (9)°. Chains are formed along the b axis through inter-molecular N-H⋯O hydrogen bonds. The crystal structure is further stabilized by C-H⋯π inter-actions.

2-[5-(1,3-Benzodioxol-5-yl)-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thia-zole.

In the title compound, [Fe(C(5)H(5))(C(24)H(18)N(3)O(2)S)], the pyrazoline ring adopts a twist conformation. The thia-zole ring forms dihedral angles of 83.7 (2) and 34.4 (2)° with the benzene ring of the benzodioxole ring and the fused phenyl ring, respectively. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯π inter-action. The crystal packing features inter-molecular C-H⋯N, C-H⋯O hydrogen bonds and weak C-H⋯π inter-actions.

4-(o-Tolyl-amino)-benzaldehyde.

In the title compound, C(14)H(13)NO, the dihedral angle between the aromatic rings is 49.64 (18)°. The crystal structure is stabilized by N-H⋯O, C-H⋯O and C-H⋯π hydrogen bonds.

(E)-2,4-Dichloro-6-{1-[(2-chloro-eth-yl)imino]-eth-yl}phenol.

The title Schiff base compound, C(10)H(10)Cl(3)NO, was prepared by the condensation of 1-(3,5-dichloro-2-hy-droxy-phen-yl)ethanone with chloro-ethyl-amine. The imine adopts an E configuration with respect to the C=N bond. The H atom of the phenolic OH group is disordered over two positions with site occupation factors of 0.52 (7) and 0.48 (7), respectively, and the major occupancy component is involved in an intramolecular N-H⋯O hydrogen bond. The compound therefore exists in an iminium-phenolate as well as in the imino-phenol form. In the crystal, mol-ecules are connected by C-H⋯O and C-H⋯Cl hydrogen bonds and Cl⋯Cl inter-actions [3.7864 (9) Å] into a three-dimensional network. In addition, inter-molecular π-π stacking inter-actions [centroid-centroid distance = 4.4312 (9) Å] are observed.

Berberine mitigates high glucose-induced podocyte apoptosis by modulating autophagy via the mTOR/P70S6K/4EBP1 pathway.

AIMS: This study aimed to investigate the characteristics and mechanism of autophagy on podocyte apoptosis under high glucose (HG) conditions and further explore the effect of berberine on podocyte autophagy, apoptosis and the potential mechanism. MATERIALS AND METHODS: The levels of LC3II/I in podocytes stimulated with HG were detected at 0, 2, 4, 8, 12, 24, 36 and 48 h by western blotting. CCK-8 was used to detect the viability of podocytes. The level of autophagy was detected by western blotting, transmission electron microscopy and immunofluorescence. Podocyte apoptosis was analysed by using Hoechst staining, western blotting, annexin V/propidium iodide dual staining, and confocal microscopy. Then, podocytes were transfected with siRNA to silence mTOR, and the expression levels of proteins and mRNA involved in the mTOR/P70S6K/4EBP1 pathway were further investigated by western blotting and qRT-PCR. KEY FINDINGS: In this study, we found significantly reduced LC3II/LC3I and increased p62 in podocytes stimulated with HG for 24 h, and the level of autophagy reached a minimum at 24 h. Berberine restored podocyte viability and significantly attenuated HG-mediated inhibition of autophagy, as evidenced by the increased expression of LC3II/LC3I, the number of autophagosomes and the inhibition of p62. Moreover, berberine counteracted HG-induced podocyte apoptosis and injury, which was negatively correlated with the autophagy effect. Notably, silencing mTOR with siRNA augmented the inhibition of P70S6k and 4EBP1 phosphorylation, which was similar to the effect of berberine. SIGNIFICANCE: Berberine activates podocyte autophagy by inhibiting the mTOR/P70S6K/4EBP1 signaling pathway, thereby alleviating podocyte apoptosis.

2-(4-Chloro-phen-yl)-5-(3,4-dimethoxy-pheneth-yl)-6,7-dihydro-pyrazolo[1,5-a]pyrazin-4(5H)-one.

In the title compound, C(22)H(22)ClN(3)O(3), the dihedral angles between the planes of the benzene rings and the pyrazole ring are 16.05 (10) and 84.84 (10)°. The conformation of the six-membered heterocyclic ring is close to a screw-boat. The crystal packing is stabilized by weak inter-molecular C-H⋯O inter-actions and is also consolidated by C-H⋯π inter-actions.

1-(4-tert-Butyl-benz-yl)-3-phenyl-1H-pyrazole-5-carboxylic acid.

In the title compound, C(21)H(22)N(2)O(2), the mean plane of the pyrazole ring makes dihedral angles of 18.80 (12) and 77.13 (5)°, respectively, with the mean planes of the phenyl and tert-butyl-benzyl rings. The carboxylate group is inclined at 8.51 (14)° with respect to the pyrazole ring. The crystal structure displays inter-molecular O-H⋯O hydrogen bonding, generating centrosymmetric dimers.

9-O-Butyl-berberrubinium bromide.

In the title compound, C(23)H(24)NO(4) (+)·Br(-), the butyl chain is disordered between two conformations; the occupancies refined to 0.735 (7) and 0.265 (7). The dihedral angle between the naphthalene ring system and the phenyl ring is 11.6 (2)°. In the crystal structure, the cations are packed via π-π inter-actions into stacks propagating in the [010] direction. Weak inter-molecular C-H⋯O and C-H⋯Br hydrogen bonds contribute further to the crystal packing stability.

4-Benzyl-7-chloro-2H-1,4-benz-oxazin-3(4H)-one.

In the title compound, C(15)H(12)ClNO(2), the two benzene rings are nearly perpendicular to each other [dihedral angle = 89.99 (13)°]. The O atom of the six-membered heterocyclic ring is disordered over two sites in a ratio of 0.46 (4):0.54 (4) and is displaced from the mean plane formed by other five atoms, resulting an envelope conformation of the six-membered hetercycle ring.

[Simultaneous determination of PAHs in food by low-temperature constant-energy synchronous fluorescence spectrometry].

The authors developed a rapid analytical method that could determine the PAHs in food samples simultaneously by the coupled approach of Shpol' skii spectroscopy and constant-energy synchronous fluorescence scanning technique. Low-fat food samples, which were just extracted with octane and high-fat food samples pre-processed with saponification and extracting, could be analyzed immediately. The recoveries ranged from 80.2% to 98.9% and the correlation coefficients of the linearity were higher than 0.993 8. This method was selective, simple, rapid and inexpensive.

Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells.

A series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were synthesized by the reaction of ethyl 3-aryl-1-(2-bromoethyl)-1H-pyrazole-5-carboxylate and amine in the general heating condition and microwave-assisted condition. The structures of the compounds were determined by IR, (1)H NMR and mass spectroscopy, in addition, representative single-crystal structures were characterized by using X-ray diffraction analysis. Preliminary biological evaluation showed that the compounds could inhibit the growth of A549 cells in dosage- and time-dependent manners. The study on structure-activity relationships showed that compounds with 4-chlorophenyl group at pyrazole moiety, such as 5-benzyl-2-(4-chlorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (3o) had much more inhibitory effects. Compound 3o was the most effective small molecule in inhibiting A549 cell growth and might perform its action through modulating autophagy.

5-Alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives inhibit growth of lung cancer A549 cell by inducing apoptosis.

we found that 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives 8d, 8e and 8f could effectively induce apoptosis in A549 lung cancer cells and elevate the levels of integrin beta4 and ROS. The data suggested that these compounds might be promising agents for the cancer therapy, and these compounds would be useful tools for further investigate the functions of integrin beta4 in regulation of the cancer cell apoptosis.