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The development of ulcerative colitis (UC) results from many factors such as intestinal microflora regulatory genes and immune environment. Studies in humans and research animals suggest mucosa health is associated with gut microbiota, but the detailed regulation mechanism is currently unknown. Baicalin, as a flavonoid, has been reported to play an anti-inflammatory role in several diseases, but its effect on UC and gut microbiota is still unclear. In this study, we characterized the protective effects of baicalin in a dextran sulfate sodium (DSS)-induced colitis mouse model and investigated the potential molecular mechanism. With a well-known DSS-induced UC model and consistent treatment with baicalin, we found that baicalin plays a critical role in treating DSS-induced colitis. Transcriptome analysis revealed that the IL17 and TNF pathway genes decreased in tissue after baicalin treatment. 16S DNA gene sequencing demonstrated that microbial diversity (observed species/Chao1/Shannon diversity) was increased in the baicalin treatment mice. Principal coordinate analysis using Bray-Curtis dissimilarity and UniFrac revealed microbial shifts in UC mice after baicalin treatment. All in all, our data showed that pretreatment with baicalin reduced intestinal inflammation and apoptosis status which was closely related to the altered gut microbiota to favor the genera Intestinimonas and Bacteroides.

In this review, compounds involving the derivative of planar π-conjugated groups are classified and summarized based on their crystal structures and accessible experimental and calculated data, and the prospects of the above materials are discussed.

A number of studies demonstrated that some tea extracts exert inhibitory effects on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). However, the effect of purple tea, a famous tea in China, on osteoclastogenesis remains unclear. In this study, a water-based purple tea extract (PTE) was found to suppress osteoclast formation, osteoclastic resorption pit area formation, and F-actin ring formation within RANKL-stimulated bone marrow macrophages (BMMs). Furthermore, our results demonstrated that PTE could inhibit expression of master transcription factors NFATc1 and c-Fos and their target genes

The first example of borate in the Lu–B–O–F system was demonstrated, possessing a short cut-off edge near 190 nm and the novel FBB [B9O22].

Type 2 diabetes mellitus (T2DM), a chronic low-grade inflammatory disease with high morbidity and mortality, is a serious threat to public health. Previously we demonstrated that a traditional Chinese medicine formulation, Jiedu Tongluo Tiaogan Formula (JDTL), exerted a favorable hypoglycemic effect due to unknown molecular mechanisms involving interactions among JDTL compounds and various cellular components. This study aimed to explore JDTL mechanisms for alleviating hyperglycemia using an integrated strategy incorporating system pharmacology, bioinformatics analysis, and experimental verification. This strategy entailed initial elucidation of JDTL chemical composition using fingerprint analysis via high performance liquid chromatography (HPLC). Next, functions of putative shared target genes and associated pathways were deduced using GO and KEGG pathway enrichment and molecular docking analyses. Ultimately, targets associated with JTDL anti-T2DM effects were found to be functionally associated with biological functions related to lipopolysaccharide and cytokine receptor binding. These results implicated PI3K-Akt signaling pathway involvement in JDTL anti-T2DM effects, as this pathway had been previously shown to play significant roles in glucose and lipid metabolism-related diseases. Furthermore, addition of JDTL to INS-1 and HepG2 cell cultures stimulated cellular mRNA-level and protein-level expression leading to enhanced production of IRS1, Akt, and PI3K. In summary, here JDTL bioactive ingredients, potential targets, and molecular mechanisms underlying JDTL anti-T2DM effects were identified using a multi-component, multi-target, and multi-channel analytical approach, thus providing an important scientific foundation to facilitate development of new drugs mechanistic strategies for preventing and treating T2DM.

The introduction of oxofluoride anion into anionic group assists to tune optical properties owing to the change of coordination, electronegativity, and according anionic framework. Here, we proposed a rational design of new compounds by fluorine-driven structure and optical property evolution. A new borophosphate Ba2BP3O11 with the monoclinic space group P21/c has been synthesized in the sealed system. Ba2BP3O11 exhibits a rare P–O–P bridge formation, which is the first example in alkaline-earth metal borophosphates. By further substituting [BO4]3− with [BO3F]4−, the first alkaline-earth metal/lead fluoroborophosphates M2BP2O8F (M = Ba and Pb) with the same space group were designed. Since the scissors effect of fluorine, in M2BP2O8F (M = Ba and Pb), a BO3F tetrahedron corner-sharing with three PO4 tetrahedra forms 1D chains along the b-axial direction, which are filled by MOn (M = Ba/Pb, n = 5, 6, 8) distorted polyhedra. The first principles calculation shows that the borophosphate Ba2BP3O11 has a birefringence about 0.013 @1,064 nm, while the fluoroborophosphates M2BP2O8F (M = Ba and Pb) have the values of 0.035 and 0.043 @1,064 nm, respectively. Such an apparent enhancement in birefringence is derived from synergies of the oxyfluoride and cation. The introduction of fluorine-containing heteroanionic groups provides a feasible strategy to design novel promising optical materials.

Three new tellurates, namely, K2BaPb0.62Ba0.38Te2O9 (1), Rb2BaPb0.7Ba0.3Te2O9 (2), and Ba2KLiTe2O9 (3), with hexagonal triple-perovskite structures have been designed via a cation substitution strategy. All three centrosymmetric compounds crystallize in the same hexagonal space group P63/mmc. In their structures, the [BTe2O9] (B = Pb/Ba for 1 and 2 and Li for 3) groups construct the final three-dimensional framework using face-sharing [Te2O9] dimmers and vertex-linked [BO6] linkages. Meanwhile, the theoretical calculations demonstrate the numerical differences of their birefringence. Thermal stability analysis and differential scanning calorimetry were performed, and UV-vis-NIR diffuse reflectance spectra and infrared spectra of the three title compounds were also characterized and analyzed.

Borates with tunable structure and property currently provide a new rich source for solid-state chemistry and materials science. Realization of property improvement via simple structural regulation is a rising hot spot of borate-based research. Herein, a new aluminoborate fluoride, Li

Androgen exposure may be an important factor in promoting the development of polycystic ovary syndrome (PCOS) and disease progression. Bushen Huoxue Formula (BHF), a traditional Chinese medicine, is prescribed in clinical settings as a PCOS remedy, albeit with unclear pharmacological effects on granulosa cells. The present research explores potentially advantageous BHF impacts and whereby BHF alleviates dehydroepiandrosterone (DHEA)-induced inflammation and endocrine disruption. Six chemical components in BHF were identified and fingerprint analysis showed good reproducibility. Using a human granulosa cell line (KGN), BHF effects on cell viability, secretion of steroidogenic and inflammatory factors were evaluated and TLR4/NF-κB pathway expression was examined. Our results demonstrate that BHF treatment of KGN cells in a DHEA-induced inflammatory state led to increased cell viability, decreased testosterone and estradiol production, and decreased CYP19A1 and HSD3B2 mRNA expression. Further experiments revealed that BHF inhibited the expression of pro-inflammatory cytokines and considerably hindered up-regulation in protein levels of TLR4, MyD88, and TRAF6, while inhibiting the activation of NF-κB and phosphorylation of IκBα. Collectively, BHF administration protected granulosa cells from DHEA-induced injuries through down-regulating pro-inflammatory cytokines and blocking the pathway of TLR4/NF-κB. Therefore, BHF hold promise as a therapeutic formulation for preventing androgen induced PCOS.

This paper reports the first carbonate-nitrate chloride, Na3Rb6(CO3)3(NO3)2Cl·(H2O)6, with two types of π-conjugated anionic groups, which has been characterized as a new UV birefringent crystal with large birefringence and a short UV cut-off edge.

Fluorine-containing compounds significantly enrich the diversity of inorganic chemical structures. Here, four alkaline-earth metal difluorophosphates with different space groups, namely NH4Mg(PO2F2)3 (Cmcm) (1), NH4Sr(PO2F2)3 (P1[combining macron]) (2), (NH4)2Ba(PO2F2)4 (P2/n) (3) and Ba(PO2F2)2 (I4[combining macron]2d) (4), were synthesized and their structures were determined for the first time. 4 is not only the first alkaline-earth-metal difluorophosphate, but also the first difluorophosphate reported to crystallize in the non-centrosymmetric space group I4[combining macron]2d of the tetragonal crystal system. All of the three-dimensional (3D) structures of the title compounds consist of isolated (PO2F2)-, AE-O and NH4+ units, while the differences of the cation radius result in various arrangements of the (PO2F2)- units, which leads to diverse crystal structures and the disparate optical anisotropy of the crystals. According to the deep-ultraviolet (DUV) transmittance spectrum, 3 exhibits a short DUV cut off edge (

Two new alkaline-earth-metal fluoroiodate compounds, BaI2O5F2 and BaIO2F3, were successfully synthesized by replacing the O atoms in the iodates with F atoms via the hydrothermal method. They crystallize in centrosymmetric space groups P21/c and Cmca, respectively. Both compounds possess large birefringences (Δn) of 0.174 at 1064 nm for BaI2O5F2 and 0.133 at 1064 nm for BaIO2F3. Structurally, BaI2O5F2 has a large birefringence due to the highly polarizable [IO3F]2− with high anisotropic polarizability; for BaIO2F3, owing to the regulation of cationic polyhedra, the arrangement of [IO2F2]− anionic groups is well-ordered, and it exhibits large anisotropy. Also, both compounds exhibit a short UV cutoff edge, 230 and 234 nm, respectively. These results demonstrate that the two new alkaline-earth-metal fluoroiodate compounds will have potential applications as UV birefringent materials.

A new compound, namely (NH4)3PbCl5, has been synthesized via a low-temperature molten salt method in a closed system. It crystallizes in the orthorhombic Pnma (No. 62) space group. The crystal structure of (NH4)3PbCl5 features a distinct three-dimensional network constructed via hydrogen bonds that exist between ammonium and chloride anions. The UV-Vis-NIR diffuse reflectance spectrum displays a short UV cutoff edge at about 256 nm. Besides, the thermal behavior (TG and DSC) was also analyzed. To better understand the structure–property relationships of (NH4)3PbCl5, theoretical calculations based on density functional theory were also performed. The result shows that the birefringence is expected to be about 0.050 at 1064 nm, and the bandgap is about 4.45 eV, which is consistent with the experimental result.

A new compound Cs2AlB5O10 was synthesized by a high temperature solution method in open air. It features a DUV cutoff edge below 190 nm and a moderate SHG response (0.8 × KDP at 1064 nm), indicating that it may have certain application prospects in the UV nonlinear optical region.

The zero-order waveplates, the essential materials in altering the polarization state of optical waves, are significant in polarimetry and the laser industry. Restricted by birefringence and absorp...

Two new sodium aluminum borates, Na 3 AlB 8 O 15 and Na 3 Al 2 B 7 O 15 , have been successfully synthesized by the high-temperature solution method. They crystallize in the different space groups, P 2 1 / c and P 2/ c , respectively. The B-O configurations of β-Na 2 B 6 O 10 , Na 3 AlB 8 O 15 and Na 3 Al 2 B 7 O 15 are compared to feature complicated different dimensional open-framework structures caused by the substitution of [BO 4 ] by [AlO 4 ] covalent tetrahedra. Moreover, the experimental results indicate that Na 3 AlB 8 O 15 and Na 3 Al 2 B 7 O 15 have short ultraviolet (UV) cutoff edges (

Ultraviolet (UV) nonlinear optical (NLO) crystals which can produce short-wavelength lasers via a direct second harmonic generation (SHG) process are of great importance in modern laser technology. Currently, the exploration of UV NLO crystals in borosulfates is nearly stagnant since the non-phase matching (PM) property lies on the small birefringence induced by the intrinsically small optical anisotropy of the tetrahedral groups. Herein, for the first time, the planar [BO3 ] units were introduced into borosulfates leading to a boron-rich borosulfate (NH4 )2 B4 SO10 with unprecedented [B4 SO10 ]∞ layers and evidently enhanced birefringence. To the best of our knowledge, it achieves the shortest SHG PM wavelength of 252 nm in all reported borosulfates with deep UV cutoff edge (184 nm), large SHG response (1.1×KDP at 1064 nm and 0.15×β-BBO at 532 nm) and large birefringence (0.053 at 1064 nm) and is easy to grow single crystals via simple chemical vapor deposition method. These results confirm the feasibility of utilizing planar [BO3 ] units to optimize birefringence of borosulfates, and also open up broad prospects for UV NLO crystals in boron-rich borosulfates.

Two new sodium aluminum borates, Na

Under pathological conditions, human tau (htau) hyperphosphorylation promotes formation of proteotoxic intracellular amyloid aggregates that may underlie neurodegenerative diseases known as tauopathies, prompting researchers to develop treatments that inhibit htau aggregation as a promising therapeutic strategy. Ginsenosides, the main active constituents of Panax ginseng C. A. Meyer (ginseng), appear to inhibit tau aggregation and disassociation in tauopathy models, although their active components and molecular mechanisms are unknown. Here, we used a novel Caenorhabditis elegans (C. elegans) tauopathy model to identify ginsenoside monomers which may repress htau proteotoxicity. Our findings indicated that ginsenoside Rf prevented tau aggregation and reversed abnormal tau aggregation-induced phenotypes and alleviated neurodegeneration in worms. Notably, deep RNA-seq analysis of ginsenoside Rf-treated and untreated worms with tauopathy revealed that ginsenoside Rf altered expression levels of 24 up- and 36 down-regulated lncRNA transcripts, 32 up- and 22 down-regulated miRNAs and 65 up- and 30 down-regulated mRNA transcripts. Based on GO and KEGG pathway annotation analyses, identified mRNAs, miRNAs and lncRNAs-associated gene targets were functionally related to neuron-related terms (e.g., neuron development, axon and motor neuron axon guidance) and longevity regulating pathways. Importantly, RT-qRCR results suggested that 6 miRNAs (miR-786, miR-2208b, miR-34, miR-241, miR-247 and miR-4805), 8 lncRNAs (MSTRG.20812.2, MSTRG.22617.2, MSTRG.28210.13, MSTRG.5728.12, MSTRG.29708.1, MSTRG.3342.25, MSTRG.3342.31 and MSTRG.8841.8) and 7 mRNAs (nas-33, math-28, T14B4.19, col-17, rol-6, sqt-1 and irg-4) were potential targets of ginsenoside Rf inhibition of tauopathy. These results partially explain mechanisms underlying ginsenoside Rf-associated alleviation of htau proteotoxicity and will guide future strategies to discover potential therapeutic targets for preventing and alleviating tauopathies.

Ultraviolet (UV) nonlinear optical (NLO) crystals which can produce short-wavelength lasers via a direct second harmonic generation (SHG) process are of great importance in modern laser technology. Currently, the exploration of UV NLO crystals in borosulfates is nearly stagnant since the non-phase matching (PM) property lies on the small birefringence induced by the intrinsically small optical anisotropy of the tetrahedral groups. Herein, for the first time, the planar [BO

Mixed-anion compounds are among the most promising systems to design functional materials with enhanced properties. Among the phosphate–sulfate species, the [SO4]2− and [PO2F2]− tetrahedra are known and give rise to structural versatility. However, to date, the crystal structures of phosphate–sulfates with the coexistence of two distinct anion groups ([S2O7]2− and [PO2F2]−) in one compound are unknown. Here, a novel type of fluorooxophosphorsulfate, K4(PO2F2)2(S2O7) (KSPOF), is designed and synthesized via a high-temperature method in a closed system. The crystal structure is derived from single-crystal X-ray diffraction (C2/c, a = 13.000(10) A, b = 7.5430(10) A, c = 19.010(10) A, β = 130.070(10)°, and Z = 4). It is the first fluorooxophosphorsulfate with mixed-anion building units ([S2O7]2− and [PO2F2]−) and a unique drum-like cluster was found, which enriches the diversity of structures for fluorooxophosphorsulfate systems. Furthermore, the theoretical calculations indicate that KSPOF possesses moderate birefringence, which mainly originates from the distorted [PO2F2]− tetrahedron.

Chronically elevated free fatty acid levels can adversely affect pancreatic β-cells, leading to insulin resistance and eventually type 2 diabetes mellitus (T2DM). Polydatin (PD) from Polygonum cuspidatum has been shown to regulate blood lipid content and lower cholesterol levels. However, there have been no reports on the potential therapeutic effects and actions of PD on lipotoxicity in β-cells.This study aimed to investigate the protective effects of PD on palmitate (PA)-treated INS-1 insulinoma cells and diabetic mice.Cells were incubated with PA and varying concentrations of PD for 24 h. Viability assays, morphological observations, flow cytometric analysis, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to assess the effects of PD on PA-induced lipotoxicity. Western blotting was used to measure the endoplasmic reticulum stress (ERS) and the levels of autophagy-related factors after incubation with inducers and inhibitors of ERS and autophagy. Diabetic mice were treated with intragastric PD for 6 weeks followed by the measurement of their physiological and blood lipid indices and assessment of the results of histological and immunofluorescence analyses.Treatment with PD after PA exposure enhanced insulin secretion and the expression of diabetes-associated genes. PD promoted β-cell function by reducing the levels of proteins associated with ERS and autophagy while also attenuating ERS triggered by tunicamycin. PD also reduced tunicamycin-induced autophagy, indicating that it regulated ERS-mediated autophagy and reduced PA-induced cellular dysfunction. In addition, treatment of db/db mice with PD substantially reduced body weight gain, alleviated dyslipidemia, improved β-cell function, and reduced insulin resistance.These results suggest that PD protects β-cells from lipotoxicity-induced dysfunction and apoptosis by inhibiting ERS and preventing excessive autophagy. Our study provides a new basis for exploring the potential of PD against β-cell lipotoxicity and T2DM.

Background: Endoplasmic reticulum stress (ERS) and excessive autophagy are increasingly recognized as risk factors associated with development and progression of β-cell dysfunction. Jiedu Tongluo Tiaogan Formula (JTTF) has known anti-glucotoxicity activities, but its pharmacological effects on pancreatic cell are not clearly understood. This study was designed to investigate JTTF effects/mechanisms on in vitro glucotoxicity (HG)-induced ERS and excessive autophagic damage of pancreatic cells in vitro and on in vivo pancreatic injury in db/db mice. Methods: The chemical composition of a JTTF preparation were analyzed using high-performance liquid chromatographic fingerprinting. Meanwhile, cell viability, glucose-stimulated insulin secretion, insulin biosynthesis dysfunction, Ca2+ overload, ERS and excessive autophagy were assessed in JTTF-pretreated pancreatic β-cells with HG-induced injury. Hematoxylin and eosin staining and immunohistochemical analyses of pancreatic tissues revealed effects of in vivo JTTF pretreatment on development of HG-induced pancreatic injury in db/db mice. Results: Five JTTF chemical components were identified. Our results revealed that JTTF treatment protected β-cells from HG injury by increasing insulin biosynthesis and glucose-stimulated insulin secretion (GSIS), while also decreasing Ca2+ overload, ERS and excessive autophagy. Furthermore, protective effects of JTTF treatment against HG-induced β-cell ERS and excessive autophagy were linked to regulation of CaMKKβ/AMPK pathway functions, while JTTF administration as confirmed to reverse pancreatic injury in db/db mice. Conclusions: Collectively, the results presented here indicate that JTTF may prevent islet cell dysfunction in T2DM mice by inhibiting CaMKKβ/AMPK pathway-mediated ERS and excessive autophagy. These findings enhance our understanding of mechanisms underlying beneficial JTTF-induced amelioration of T2DM.

Fluorine-containing compounds significantly enrich the diversity of inorganic chemical structures. Here, four alkaline-earth metal difluorophosphates with different space groups, namely NH4Mg(PO2F2)3 (Cmcm) (1), NH4Sr(PO2F2)3 (P1[combining macron]) (2), (NH4)2Ba(PO2F2)4 (P2/n) (3) and Ba(PO2F2)2 (I4[combining macron]2d) (4), were synthesized and their structures were determined for the first time. 4 is not only the first alkaline-earth-metal difluorophosphate, but also the first difluorophosphate reported to crystallize in the non-centrosymmetric space group I4[combining macron]2d of the tetragonal crystal system. All of the three-dimensional (3D) structures of the title compounds consist of isolated (PO2F2)-, AE-O and NH4+ units, while the differences of the cation radius result in various arrangements of the (PO2F2)- units, which leads to diverse crystal structures and the disparate optical anisotropy of the crystals. According to the deep-ultraviolet (DUV) transmittance spectrum, 3 exhibits a short DUV cut off edge (180 nm). Solid state 19F and 31P magic-angle spinning NMR spectroscopy was used to verify the presence of covalent P-F bonds in 3. The different size effects, as well as the coordination environments of the Mg2+, Sr2+, and Ba2+ cations, on the structures as a whole have been discussed in detail. In addition, the calculated birefringence values were observed to differ from 0.011 to 0.033 for the four compounds.

Background: T2DM is considered to be a chronic low-grade inflammatory disease, because of its high morbidity and mortality, diabetes poses a tremendous potential threat to public health. Our previous studies have shown that a traditional Chinese medicine formula, Jiedu Tongluo Tiaogan Formula (JDTL) exerts favorable hypoglycemic effect, however, its molecular mechanism and the interaction among various components need to be further elucidated. This study aimed to explore the mechanism of JDTL in the treatment of T2DM using an integrated strategy of system pharmacology, bioinformatics analysis, and experimental verification. Materials and Methods: First, the compounds of JDTL were searched from public databases, and the "compound-target " network was constructed to predict the potential active components and targets. Subsequently, bioinformatics analysis was used to identify potential targets and signaling pathways, including PPI, GO pathways and KEGG pathways. Finally, the pharmacological effects and mechanisms of JDTL were verified by molecular docking and cell experiments. Results: Analysis by GO and KEGG pathway enrichment revealed that these targets were associated with lipopolysaccharide, membrane microdomain, cytokine receptor binding, and JDTL could regulate the PI3K/Akt signaling pathway. Furthermore, we have proved that JDTL could improve the mRNA expression and protein expression of IRS1, AKT, and PI3K in the INS-1 cell and HepG2 cells. Conclusion: The present study elucidated the active ingredients, potential targets, and molecular mechanism of JDTL in the treatment of T2DM, and revealed the characteristics of JDTL in multi-component, multi-target and multi-channel. It also provided an important scientific basis for new drug development and mechanism research of T2DM.

Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents ofIn this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated.GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NADThis study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

Three new tellurates, namely, K

A new compound Cs

Mixed-anion compounds are among the most promising systems to design functional materials with enhanced properties. Among the phosphate-sulfate species, the [SO4]2- and [PO2F2]- tetrahedra are known and give rise to structural versatility. However, to date, the crystal structures of phosphate-sulfates with the coexistence of two distinct anion groups ([S2O7]2- and [PO2F2]-) in one compound are unknown. Here, a novel type of fluorooxophosphorsulfate, K4(PO2F2)2(S2O7) (KSPOF), is designed and synthesized via a high-temperature method in a closed system. The crystal structure is derived from single-crystal X-ray diffraction (C2/c, a = 13.000(10) Å, b = 7.5430(10) Å, c = 19.010(10) Å, β = 130.070(10)°, and Z = 4). It is the first fluorooxophosphorsulfate with mixed-anion building units ([S2O7]2- and [PO2F2]-) and a unique drum-like cluster was found, which enriches the diversity of structures for fluorooxophosphorsulfate systems. Furthermore, the theoretical calculations indicate that KSPOF possesses moderate birefringence, which mainly originates from the distorted [PO2F2]- tetrahedron.

The zero-order waveplates, the essential materials in altering the polarization state of optical waves, are significant in polarimetry and the laser industry. Restricted by birefringence and absorption edge, few materials can have moderately small birefringence (Δ

Spectroscopic analysis of HPLC-purified 7.3-kD Acorus tatarinowii Schott root polysaccharide ASP2-1 (FT-IR, NMR) revealed respective monosaccharide proportions of glucose: galactose: arabinose: xylose: galacturonic acid: mannose: rhamnose: glucuronic acid:fucose of 49.1:16.0:11.6:10.2:5.3:2.9:2.2:1.7:0.8. In vitro, ASP2-1 inhibited osteoclastogenesis-associated bone resorption, RANKL-induced osteoclastogenesis and F-actin ring formation and suppressed osteoclastogenesis-associated gene expression (e.g., TRAP, OSCAR, Atp6v0d2, αV, β3, MMP9 and CtsK) as shown via RT-PCR. ASP2-1-treated RANKL-stimulated bone marrow-derived macrophages exhibited decreased levels of NFATc1 and c-Fos mRNAs and corresponding transcription factor proteins, elevated expression of negative NFATc1 regulators (Mafb, IRF8, Bcl6) and reduced their upstream negative regulator (Blimp1) expression. ASP2-1 inhibition of NFATc1 expression involved PLCγ2-Ca2+ oscillation-calcineurin axis suppression, reflecting suppression of RANKL-induced PLCγ2 activation (and associated Ca2+ oscillation) and calcineurin catalytic subunit PP2BAα expression without inhibiting NF-κB and MAPKs activation or phosphorylation. Staining (H&E, TRAP) and micro-CT assays revealed ASP2-1 attenuated bone destruction and osteoclast over-activation and improved tibia micro-architecture in a murine LPS-induced bone loss model. Thus, ASP2-1 may alleviate inflammatory bone loss-associated diseases.

A new non-centrosymmetric borate fluoride, Pb3Ba7B7O20F exhibiting a large powder second harmonic generation (SHG) response (5 × KH2PO4) at 1064 nm was obtained in the open system. To the best of our acknowledge, it displays the strongest SHG response among the reported lead-barium borates. More interestingly, its three-dimensional (3D) framework contains the 1D Pb-B-O chain and isolated PbB3O8 groups, which is the first compound with two different dimensional Pb-B-O frameworks in the inorganic lead-containing borate system. The first-principles theoretical calculations are carried out to understand the origin of its linear and nonlinear optical properties.

The clustered regularly interspaced short palindromic repeat (CRISPR) - CRISPR-associated protein 9 (CRISPR-Cas9) system has emerged as a versatile molecular tool for genome editing in various organisms in recent years (Tsai and Joung, 2016). In this system, the endonuclease of Cas9 is directed to DNA targets by a synthetic guide RNA (sgRNA). The ribonucleoprotein complex of Cas9 and sgRNA recognizes the DNA sequence that is complementary to the 5′-end guide sequence (also referred to as the spacer) of the sgRNA and the presence of a protospacer adjacent motif (PAM) preceding the targeting site.

Objective Pig brain polypeptides (PBP), active polypeptides hydrolysate extracted from fresh porcine brain tissue, has been shown to have neuroprotective effects in both in vitro and in vivo studies. The present study aimed to explore the molecular mechanisms underlying the neuroprotective effects of PBP in corticosterone (CORT)-induced rat adrenal pheochromocytoma PC12 cells. Methods Cell viability and lactate dehydrogenase (LDH) release were measured in PC12 cells induced with 200 μM CORT in the presence or absence of various concentrations of PBP for 48 h. Intracellular reactive oxygen species (ROS) generation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and glutathione (GSH) content were examined to analyze the effect of PBP on CORT-induced oxidative stress. The levels of pro-inflammatory factors, the percentage of apoptotic cells, and apoptosis-related protein expression in PC12 cells were determined. Results PBP is mainly composed of protein subunits with molecular weights ranging from 1000 to 10,000 Da. PBP treatment increased cell viability and decreased the release of LDH in CORT-stimulated PC12 cells. Moreover, PBP reduced the level of CORT-induced oxidative stress by decreasing ROS levels and increasing SOD, GSH-Px activities and GSH content. PBP had an inhibitory effect on the CORT-induced inflammatory response through inhibition of the NF-κB signaling pathway. PBP also inhibited CORT-induced apoptosis by downregulating the mitochondrial apoptotic signaling pathway. Conclusion These results suggest that PBP exerts a neuroprotective effect against CORT-induced cell injury by inhibiting oxidative stress, inflammation, and apoptosis. PBP could act as a neuroprotective agent against nerve injury induced by CORT.

Background Higher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. It has been reported that ginseng saponin extract (GSE) has an inhibitory effect on the hyperactivity of the HPA axis induced by stresses and increased corticosterone level induced by intraperitoneal injection of adrenocorticotrophic hormone (ACTH) in mice. However, the molecular mechanisms by which GSE and its active ginsenosides inhibit corticosterone secretion remain elusive. Main methods Y1 mouse adrenocortical cells were treated with ACTH for up to 60 min to establish a cell model of corticosterone secretion. After treatment with different concentrations of GSE or ginsenoside monomers for 24 h prior to the addition of ACTH, analyses of cAMP content, PKA activity, and the levels of steroidogenesis regulators, melanocortin-2 receptor (MC2R), and melanocortin-2 receptor accessory protein (MRAP) in ACTH-induced Y1 cells were performed. Results We demonstrated that GSE inhibits ACTH-stimulated corticosterone production in Y1 cells by inhibiting factors critical for steroid synthesis. Ginsenoside Rd, an active ingredient of GSE, inhibits corticosterone secretion in the cells and impedes ACTH-induced corticosterone biosynthesis through down-regulation of proteins in the cAMP/PKA/CREB signaling pathway. In addition, Western blot and qPCR analyses showed that ginsenoside Rd attenuated the induction of MC2R and MRAP by ACTH. Conclusion Our findings indicate that ginsenoside Rd inhibits ACTH-induced corticosterone production through blockading the MC2R-cAMP/PKA/CREB pathway in adrenocortical cells. Overall, this mechanism may represent an important therapeutic option for the treatment of stress-related disorders, further supporting the pharmacological benefits of ginseng.