Three undescribed dihydrostilbene glycosides from leaves of Camellia oleifera Abel. And their anti-inflammatory activity.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4-12) were also identified. The undescribed secondary metabolites 1-3 were elucidated as 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4'-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1-4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

Identification of potential key ferroptosis- and autophagy-related genes in myelomeningocele through bioinformatics analysis.

Myelomeningocele is a common congenital anomaly associated with polygenic disorders worldwide. However, the intricate molecular mechanisms underlying myelomeningocele remain elusive. To investigate whether ferroptosis and ferritinophagy contribute to the pathomechanism of myelomeningocele, differentially expressed genes (DEGs) were identified as novel biomarker and potential treatment agents. The GSE101141 dataset from Gene Expression Omnibus (GEO) was analyzed using GEO2R web tool to obtain DEGs based on |log2 fold change (FC)|≥1.5 and p < 0.05. Two datasets from the Ferroptosis Database (481 genes) and Autophagy Database (551 genes) were intersected with the DEGs from the GSE101141 dataset to identify ferroptosis- and autophagy-related DEGs using Venn diagrams. Functional and pathway enrichment, protein-protein interaction (PPI) network analyses were performed, and candidate genes were selected. Transcription factors (TFs), microRNAs (miRNAs), diseases and chemicals interacting with the candidate genes were identified. Receiver operating characteristic (ROC) curve analysis was performed to validate the diagnostic value of the candidate genes. Sixty ferroptosis-related and 74 autophagy-related DEGs were identified. These DEGs are involved in FoxO signaling pathway. Six candidate genes (EGFR, KRAS, IL1B, SIRT1, ATM, and MAPK8) were selected. miRNAs such as hsa-miR-27a-3p, hsa-miR-877-5p, and hsa-miR-892b, and TFs including P53, POU3F2, TATA are involved in regulation of candidate genes. Diseases such as schizophrenia, fibrosis, and neoplasms are the most relevant to the candidate genes. Chemicals, such as resveratrol, curcumin, and quercetin may have significant implications in the treatment of myelomeningocele. The candidate genes, especially MAPK8, also showed a high diagnostic value for myelomeningocele. These results help to shed light on the molecular mechanism of myelomeningocele and may provide new insights into diagnostic biomarker in the amniotic fluid and potential therapeutic agents of myelomeningocele.

Phytochemical constituents from rhizomes of Dryopteris crassirhizoma and their anti-inflammatory activity.

The phytochemical investigation on the rhizomes of Dryopteris crassirhizoma (Dryopteridaceae) resulted in the discovery of one novel compound, drycrassirhizomamide A (1), and one new natural product, drycrassirhizomamide B (2), as well as four known isolates, (S)-(-)-N-benzoylphenylalaninol (3), blumenol A (4), 8-C-glucosylnoreugenin (5), and dryopteroside (6). Their chemical structures were identified by NMR and mass spectroscopy. Compounds 1-2 were determined to be 1,19-diethyl 10-oxo-2,9,11,18-tetraazanonadecanedioate and C,C'-diethyl N,N'-1,6-hexanediylbis[carbamate]. The anti-inflammatory activities of these compounds were evaluated with LPS-stimulated RAW264.7 macrophage and BV2 microglia. The results showed that compounds 1-3 and 6 have inhibitory effects of NO production with IC50 values of 13.41, 30.36, 25.51, and 11.35 µM in LPS-stimulated RAW264.7 cells. Also, compounds 1 and 4-6 have abilities to inhibit NO production with the IC50 values of 40.11, 30.94, 15.76, and 16.79 µM in BV2 cells, which demonstrated that they may possess the potential anti-inflammatory activity.

Determination and analysis of whole genome sequence of recombinant GII.6[P7] norovirus in Ningxia, China.

While the GII.4 norovirus was the predominant genotype, non-GII.4 genotype was increasingly focused since the non-GII.4 genotype caused regional epidemics. In this study, the detection rate was16.51% (183/1108) in Ningxia from January to December 2020. Among identified genotypes, GII.4[P31] and GII.4[P16] were the dominant genotypes (n = 20 and 18, respectively) while GII.6[P7] was the main type (n = 6) in non-GII.4 strains which was mainly detected in from May to July. The whole genome sequences of the norovirus diarrhea samples identified as GII.6 [P7] with Ct ≤ 30 collected in 2020 were determined. In this study, the complete genome sequences of norovirus strains PL20-044 and QTX20-071 were identified and analyzed phylogenetically. Phylogenetic analysis of the ORF1and ORF2 regions showed that these strains evolved from the GII·P7-GII.6 strains detected in recent years from different country. The results showed that PL20-044 had intra-type recombination with GII·P7-GII.6c and GII·P7-GII.6a, while QTX20-071 had intre-type recombination within GII·P7-GII.6a. The evolutionary rates of the RdRp gene region of the GII·P7 genotype and the VP1 gene region of the GII.6 genotype were 2.91 × 10-3 (95%HPDs2.32-3.51 × 10-3) and 2.61 × 10-3 (95%HPDs2.14-3.11 × 10-3) substitutions/site/year, respectively. Comparative analysis of the amino acid mutation sites in VP1 with the GII·P7-GII.6a strains before 1997, the later detected strains have changed in aa131 and aa354. Moreover, PL20-044 strains showed special mutations at aa316 and aa395. These results help to understand the norovirus genotype circulating in the human population in Ningxia, and discover the evolutionary characteristics of the GII·P7-GII.6 strain.

Research progress on aging mechanism and drugs and the role of stem cells in anti-aging process.

There have been many discussions on longevity from ancient times to the present day. In the Laozi, it is said, "Heaven and earth are long and enduring because they do not arise from themselves, so they can live forever." In Zhuangzi - Zai You, it is also said, "Keep your mental peace, and your body will be healthy. Don't strain your body and don't consume your spirit to live a long life." It is clear that people attach importance to anti-aging and the desire for longevity. Throughout human history, we have treated aging as an inevitable process, but with the development of medical science, we have become more aware of the various molecular changes in the human body. In an aging society, more people are suffering from age-related diseases such as osteoporosis, Alzheimer's disease, and cardiovascular disease, which has led to a search for anti-aging. However, by 'living longer' we mean not only living but also living longer in good health. The mechanisms of aging are still unclear and there is a great deal of interest and curiosity in how to combat aging effectively. Some potential criteria exist for the determination of anti-aging drugs: the first criterion is the ability to exert life-extending effects in model organisms, preferably in mammals; the second criterion is the ability to prevent or delay several age-related diseases in mammals; and the third criterion is the ability to inhibit the transition of cells from a quiescent to a senescent state. Based on these criteria, the current anti-aging drugs often involved are rapamycin, metformin, curcumin and other polyphenols, polysaccharides, resveratrol, etc. The most studied and relatively well-understood pathways and factors of aging are currently known to include seven enzymes, six biological factors, and one chemical, which mainly involve more than ten pathways such as Nrf2/SKN-1; NFκB; AMPK; P13K/AKT; IGF; and NAD.

Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation.

The traditional herb Eleutherococcus henryi Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of E. henryi. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways.

Facile immobilization of his-tagged Microbacterial esterase on Ni-SBA-15 with enhanced stability for efficient synthesis of key chiral intermediate of d-biotin.

A series of nickel-incorporated SBA-15 mesoporous molecular sieves (Ni-SBA-15) were prepared as support for the immobilization of his-tagged recombinant Microbacterium esterase. The Ni-SBA-15 could strongly and specific absorb the his-tagged esterase from cell disrupted supernatant. It was found that the nickel amount in Ni-SBA-15 has dramatic influence on the activity and thermo-stability of immobilized enzyme, while the kinds of nickel precursor had little effect on enzyme stability. The morphology, chemical composition and structure of the best support NiCl2-SBA-15 (Ni-SBA-15 prepared from NiCl2 precursor) were characterized by various spectroscopy techniques. The immobilized esterase retained full activity of free esterase and showed high immobilized yield (> 90%) with higher thermo-stability, pH stability and organic solvent resistance compared with free enzyme. The optimum reaction temperature increased from 35 to 40 °C and the optimal reaction pH moved from 10.0 to 8.0 after enzyme immobilization. The immobilized esterase exhibited excellent storage stability and keeping 92% of the initial activity after 30 days' storage at 25 °C. In addition, the immobilized esterase had excellent reusability for the synthesis of key chiral intermediate of d-biotin and the substrate conversion could still keep 100% after 13 cycles continuously. Finally, optical pure (4S, 5R)-hemiester was obtained in 80.8% isolated yield and 99% purity in the gram preparative scale.