[Experimental study on promotion of peripheral nerve regeneration by selenium-methylselenocysteine].

Objective: To investigate the feasibility of selenium-methylselenocysteine (SMC) to promote peripheral nerve regeneration and its mechanism of action. Methods: Rat Schwann cells RSC96 cells were randomly divided into 5 groups, which were group A (without any treatment, control group), group B (adding 100 µmol/L H 2O 2), group C (adding 100 µmol/L H 2O 2+100 µmol/L SMC), group D (adding 100 µmol/L H 2O 2+200 µmol/L SMC), group E (adding 100 µmol/L H 2O 2+400 µmol/L SMC); the effect of SMC on cell proliferation was detected by MTT method, and the level of oxidative stress was detected by immunofluorescence for free radicals [reactive oxygen species (ROS)] after determining the appropriate dose group. Thirty-six 4-week-old male Sprague Dawley rats were randomly divided into 3 groups, namely, the sham operation group (Sham group), the sciatic nerve injury group (PNI group), and the SMC treatment group (SMC group), with 12 rats in each group; the rats in the PNI group were fed with food and water normally after modelling operation, and the rats in the SMC group were added 0.75 mg/kg SMC to the drinking water every day. At 4 weeks after operation, the sciatic nerves of rats in each group were sampled for neuroelectrophysiological detection of highest potential of compound muscle action potential (CMAP). The levels of inflammatory factors [interleukin 17 (IL-17), IL-6, IL-10 and oxidative stress factors catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)] were detected by ELISA assay. The luxol fast blue (LFB) staining was used to observe the myelin density, fluorescence intensity of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) was observed by immunofluorescence staining, and myelin morphology was observed by transmission electron microscopy with measurement of axon diameter. Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinases (p38MAPK), phosphorylated p38MAPK (p-p38MAPK), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Results: MTT assay showed that the addition of SMC significantly promoted the proliferation of RSC96 cells, and the low concentration could achieve an effective effect, so the treatment method of group C was selected for the subsequent experiments; ROS immunofluorescence test showed that group B showed a significant increase in the intensity of ROS fluorescence compared with that of group A, and group C showed a significant decrease in the intensity of ROS fluorescence compared with that of group B ( P<0.05). Neuroelectrophysiological tests showed that the highest potential of CMAP in SMC group was significantly higher than that in PNI and Sham groups ( P<0.05). ELISA assay showed that the levels of IL-6, IL-17, and MDA in PNI group were significantly higher than those in Sham group, and the levels of IL-10, SOD, and CAT were significantly lower; the levels of IL-6, IL-17, and MDA in SMC group were significantly lower than those in PNI group, and the levels of IL-10, SOD, and CAT were significantly higher ( P<0.05). LFB staining and transmission electron microscopy showed that the myelin density and the diameter of axons in the SMC group were significantly higher than those of the PNI group and the Sham group ( P<0.05). Immunofluorescence staining showed that the fluorescence intensity of GFAP and MBP in the SMC group were significantly stronger than those in the PNI group and Sham group ( P<0.05). Western blot showed that the relative expressions of Nrf2 and HO-1 proteins in the SMC group were significantly higher than those in the PNI group and Sham group, and the ratio of p-p38MAPK/p38MAPK proteins was significantly higher in the PNI group than that in the SMC group and Sham group ( P<0.05). Conclusion: SMC may inhibit oxidative stress and inflammation after nerve injury by up-regulating the Nrf2/HO-1 pathway, and then inhibit the phosphorylation of p38MAPK pathway to promote the proliferation of Schwann cells, which ultimately promotes the formation of myelin sheaths and accelerates the regeneration of peripheral nerves.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.

[Two new benzoyl-sesquiterpenes from Mesona chinensis].

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.

Anti-inflammatory naphthoquinone-monoterpene adducts and neolignans from Eugenia caryophyllata.

A phytochemical investigation on the buds of edible medicinal plant, Eugenia carvophyllata, led to the discovery of seven new compounds, caryophones A-G (1-7), along with two biogenetically-related known ones, 2-methoxy-7-methyl-1,4-naphthalenedione (8) and eugenol (9). Compounds 1-3 represent the first examples of C-5-C-1' connected naphthoquinone-monoterpene adducts with a new carbon skeleton. Compounds 4-7 are a class of novel neolignans with unusual linkage patterns, in which the C-9 position of one phenylpropene unit coupled with the aromatic core of another phenylpropene unit. The chemical structures of the new compounds were determined based on extensive spectroscopic analysis, X-ray diffraction crystallography, and quantum-chemical calculation. Among the isolates, compounds (-)-2, 3, 6, and 9 showed significant in vitro inhibitory activities against respiratory syncytial virus (RSV)-induced nitric oxide (NO) production in RAW264.7 cells.

Effect of enzymatic hydrolysis of arabinoxylan on the quality of frozen dough during the subfreezing process.

BACKGROUND: The objective of this investigation was to examine the impact of enzymatic hydrolysis of arabinoxylan (AX) on frozen dough quality under subfreezing conditions. The dough was subjected to freezing at -40 °C for 2 h and then stored at -9, -12, and -18 °C for 15 days. The water loss, freezable water content, water migration, and microstructure of the dough were measured. RESULTS: The dough containing 0.8% cellulase enzymatically hydrolyzed AX (CAX) required the shortest duration when traversing the maximum ice-crystal formation zone (6.5 min). The dough with xylanase enzymatically hydrolyzed AX (XAX) demonstrated a faster freezing rate than the dough with CAX. The inclusion of both XAX and CAX in the dough resulted in the lowest freezable water loss and reduced freezable water content and free-water content levels, whereas the inclusion of xylanase-cellulase combined with enzymatically hydrolyzed AX resulted in higher free-water content levels. The textural properties of the subfreezing temperature dough were not significantly different from the dough stored at -18 °C and sometimes even approached or surpassed the quality observed in the control group rather than the dough stored at -18 °C. In addition, the gluten network structure remains well preserved in XAX- and CAX-containing doughs with minimal starch damage. CONCLUSION: The enzymatic hydrolysis of AX from wheat bran can be used as a useful additive to improve the quality of frozen dough. © 2024 Society of Chemical Industry.

Tautomeric cinnamoylphloroglucinol-monoterpene adducts from Cleistocalyx operculatus and their antiviral activities.

Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1-3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1-3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4-C-1' linkage between 2,2,4-trimethyl-cinnamyl-ß-triketone and modified linear monoterpenoid motifs. Notably, compounds 1-3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV).

Bifidobacterium mitigates autoimmune hepatitis by regulating IL-33-induced Treg/Th17 imbalance via the TLR2/4 signaling pathway.

The present work aims to evaluate the efficacy of Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules (LCBLECs), a probiotic drug containing Bifidobacterium, in the treatment of autoimmune hepatitis (AIH). In this study, a mouse model of experimental autoimmune hepatitis (EAH) was established to investigate the effects of LCBLECs on AIH. The results showed that LCBLECs improved dysbiosis of gut microbiota, reduced liver injury, restored liver function, and maintained Treg/Th17 balance in EAH mice. In addition, LCBLECs restored Treg/Th17 balance in EAH mice by downregulating IL-33 production. Besides, LCBLECs also suppress IL-33 upregulation in EAH mice by inhibiting the TLR2/4 signaling pathway. Furthermore, LCBLECs also mitigated dysbiosis of gut microbiota and enhanced the efficacy of conventional treatment for AIH patients. To sum up, our findings revealed that LCBLECs exerted therapeutic effects on EAH mice by improving Treg/Th17 imbalance in an IL-33-dependent manner via the TLR2/4 signaling pathway and relieved the clinical symptoms of AIH patients, indicating Bifidobacterium supplementation with LCBLECs might be a potential adjuvant therapy for AIH treatment.

Six new coumarins from the roots of Toddalia asiatica and their anti-inflammatory activities.

We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC50) values of 3.22, 4.78, 8.90, and 4.31 µmol·L-1, respectively.

Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis.

Objective: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH. Methods: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT‒qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues. Results: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-ß cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner. Conclusion: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.

A multifunctional interlayer activated by lithiophilic electrospun Ag nanowires/polyvinylpyrrolidone nanofibers for efficient lithium storage.

A three-dimensional lithiophilic electrospun nanofiber framework with a Ag nanowires/polyvinylpyrrolidone (AgNWs/PVP) hybrid as a multifunctional interlayer has been designed to protect lithium metal anodes. The full cells with a LiFePO4 cathode and AgNWs/PVP interlayer have also realized excellent stable cyclability over 1000 cycles and high-rate capability.

Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from Cleistocalyx operculatus: A Synthetic Strategy Based on Biogenetic Building Blocks.

A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).

Secoiridoid glycosides from the fruits of Ligustrum lucidum and their in vitro anti-inflammatory activity.

Seven new secoiridoid glycosides (1-7), together with a known analogue (8), were isolated from the fruits of Ligustrum lucidum. Their structures with absolute configurations were determined by HR-ESI-MS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectroscopic analysis, as well as biogenetic consideration. Compounds 1 and 2 are the first examples of secoiridoid glycoside dimers featuring a rare rearranged oleoside-type secoiridoid moiety, and compounds 3-7 represent a new class of oleoside-type secoiridoid glycosides with unusual stereochemistry at C-1 position. A plausible biosynthetic pathway for this group of unusual secoiridoid glycosides was also proposed herein. In addition, the isolates were evaluated for their in vitro anti-inflammatory activity, and all tested compounds exhibited modest inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Discovery of Hexahydrofuro[3,2-b]furans as New Kinase-Selective and Orally Bioavailable JAK3 Inhibitors for the Treatment of Leukemia Harboring a JAK3 Activating Mutant.

Janus kinase 3 (JAK3) is a potential target for the treatment of hematological malignancies. Herein, we report the discovery of a series of new orally bioavailable irreversible JAK3 kinase inhibitors. The representative compound 12n potently inhibited JAK3 kinase activity with an IC50 value of 1.2 nM and was more than 900-fold selective over JAK1, JAK2, and Tyk2. Cell-based assays revealed that 12n significantly suppressed phosphorylation of JAK3 and the downstream effectors STAT3/5 and also robustly restrained proliferation of BaF3 cells transfected with JAK3M511I activating mutation and human leukemia U937 cells harboring JAK3M511I with IC50 values of 22.9 and 20.2 nM, respectively. More importantly, 12n showed reasonable pharmacokinetic (PK) properties, and oral administration of 12n at a dose of 50 mg/kg twice daily led to tumor regression in a U937 cell inoculated xenograft mouse model. Thus, 12n represents a promising lead compound for further optimization to discover new therapeutic agents for hematological malignancies.

Efficient and selective removal of Pb2+ from aqueous solution by using an O- functionalized metal-organic framework.

Lead (Pb) is one of the most widespread and highly toxic heavy metals in the environment. The design and synthesis of adsorbent materials for the selective and efficient removal of Pb2+ from aqueous solution has received much attention. Herein, the ligand 4,4'-azoxydibenzoic acid with the O- group was elaborately selected to construct a novel Pr-based MOF for Pb2+ removal. The as-prepared MOF adsorbents with high stability exhibited ultra-high selectivity for Pb2+, even in the presence of various highly concentrated competitive ions (with the ratios from 1 : 5 to 1 : 50). Also, a high uptake capacity (560.26 mg g-1) can be achieved for the MOF material, due to the availability of sufficient adsorption sites. The strong electrostatic attraction and coordination interaction between the numerous active O- sites on MOF adsorbents and Pb2+ can account for the good adsorption performance for Pb2+, which was systematically verified by zeta potential, FT-IR and XPS studies.

Discovery and Biomimetic Synthesis of a Polycyclic Polymethylated Phloroglucinol Collection from Rhodomyrtus tomentosa.

Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues (5 and 6) and two known biogenetically related dimers (10 and 11), were isolated from Rhodomyrtus tomentosa. Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.

Luminescent Two-Dimensional Metal-Organic Framework Nanosheets with Large π-Conjugated System: Design, Synthesis, and Detection of Anti-Inflammatory Drugs and Pesticides.

Two-dimensional (2D) metal-organic framework (MOF) nanosheets, with largely exposed surface area and highly accessible active sites, have emerged as a novel kind of sensing material. Here, a luminescent 2D MOF nanosheet was designed and synthesized by a facile top-down strategy based on a three-dimensional (3D) layered MOF {[Zn(H2L)(H2O)2]·H2O}n (Zn-MOF; H4L = 3,5-bis(3',5'-dicarboxyphenyl)-1H-1,2,4-triazole). With a large π-conjugated system and rigid planar structure, ligand H4L was elaborately selected to construct the bulk Zn-MOF, which can be readily exfoliated into 2D nanosheets, owing to the weak interlayer interactions and easy-to-release H2O molecules in the interspaces of 2D layers. Given the great threat posed to the ecological environment by anti-inflammatory drugs and pesticides, the developed luminescent Zn-MOF nanosheets were utilized to determine these organic pollutants, achieving highly selective and sensitive detection of diclofenac sodium (DCF) and tetramethylthiuram disulfide (TMTD). Compared to the detection limits of 3D Zn-MOF (7.72 ppm for DCF, 6.01 ppm for TMTD), the obviously lower detection limits for 2D Zn-MOF nanosheets toward DCF (0.20 ppm) and TMTD (0.18 ppm) further revealed that the largely exposed surface area with rigid planar structure and ultralarge π-conjugated system greatly accelerated electron transfer, which brought about a vast improvement in response sensitivity. The remarkable quenching performance for DCF and TMTD stems from a combined effect of photoinduced electron transfer and competitive energy absorption. The possible sensing mechanism was systematically investigated by the studies of powder X-ray diffraction, UV-vis, luminescence lifetime, and density functional theory calculations.

Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities.

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.

Phloroglucinol-derived lipids from the leaves of Syzygium cumini and their neuroprotective activities.

Based on the typical HPLC-UV-MS profiles and characteristic 1H NMR signals, twelve new phloroglucinol-derived lipids (1-12), featuring a long linear aliphatic side chain, together with three known ones (13-15) were isolated from the ethanol extract of the leaves of Syzygium cumini. Their structures were elucidated on the basis of extensive NMR spectroscopic analyses and mass spectrometric data. Compounds 1-5 characterize an enolizable ß,ß'-tricarbonyl motif with a cyclohexa-3,5-dien-1-one core that is hitherto undescribed in phloroglucinol-derived lipids. Compounds 4 and 10-12 are novel phloroglucinol-derived lipids containing an uncommon methylene interrupted trans double bond in their polyunsaturated aliphatic side chains. A polyketide biogenetic pathway for those phloroglucinol-derived lipids was also proposed. In addition, the isolates were evaluated for their neuroprotective activities against oxygen-glucose deprivation and re­oxygenation (OGD/R)-induced Neuro-2a cell injury. Notably, compounds 1, 5, and 10-12 significantly improved viability of Neuro-2a cells after OGD/R damage.

Caffeic acid oligomers from Mesona chinensis and their In Vitro antiviral activities.

The phytochemical study of the aerial part of Mesona chinensis led to the isolation of five new caffeic acid oligomers (1-5), as well as four known analogues (6-9). The structures of the new compounds including their absolute configurations were elucidated by comprehensive spectroscopic analysis, chemical method, and quantum-chemical electronic circular dichroism (ECD) calculation. Among the isolates, compound 7 showed significant in vitro antiviral activity on respiratory syncytial virus (RSV).

The role of Mg value and moisture content of decomposed products during the decomposition process of carnallite in aqueous solution: a novel monitoring method.

The amount of water is the crucial factor for the decomposition of carnallite in aqueous solution. A novel method for monitoring the decomposition process of carnallite in aqueous solution based on the Mg value and moisture content of the decomposed products was investigated in this study. Based on the principle of mass conservation of MgCl2 during the decomposition of carnallite in aqueous solution, a functional model of Mg value in decomposed products was established. The functional model of moisture content in decomposed products was obtained by the water equilibrium condition of the reaction system. The experiments were performed by dissolving carnallite in aqueous solution under different water conditions, and the Mg value and moisture content were determined for the decomposed products. The results showed that: (1) the Mg value and moisture content of the decomposed products have a nonlinear variation when the amount of water used to dissolve carnallite is not suitable, and (2) an excess amount of water used to dissolve carnallite would lead to a linear change in the Mg value and moisture content of the decomposed products. It was found that the intersection of these two changes is the appropriate location for the decomposition of carnallite in aqueous solution. The Mg value and moisture content of the decomposed products are thus presented as a novel monitoring method for these applications within the potash processing industry.