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关键词： Melastoma dodecandrum   Isovitexin   TNF-alpha   Cell membrane chromatography   Key component  

摘要： Ethnopharmacological relevance: Melastoma dodecandrum (MD), a traditional ethnomedicine, has been widely used for the treatment of fractures, osteoarthritis, and osteoporosis due to its remarkable anti-inflammatory activity. However, the specific active components responsible for its therapeutic effects on orthopedic conditions remain unidentified. Aim of the study: This study aimed to screen and identify key active components in MD using a combination of cell membrane chromatography and mass spectrometry, followed by cellular validation. Materials and methods: A TNF-alpha-induced osteoblast injury model and an osteoblast membrane chromatography screening system were established to select and identify chemical components of MD that directly act on osteoblasts. The protective effects of MD on osteoblasts were assessed by evaluating cell viability, alkaline phosphatase (ALP) activity, cell mineralization and the expression of osteogenesis-related proteins OCN, RUNX2, and the TNF-alpha receptor protein TNFR1. Validation of the activity of individual components was also conducted. Results: MD significantly improved the viability of osteoblasts under TNF-alpha-induced injury, enhanced ALP activity, stimulated the expression of OCN and RUNX2 proteins, and decreased the expression of TNFR1. Cell membrane chromatography screening identified 32 chemical components, including 21 flavonoids, 6 organic acids, 2 phenylpropanoids, 2 terpenes, and 1 nucleotide. Molecular docking revealed that isovitexin could bind to the specific receptor TNFR1 on the cell membrane. Furthermore, cellular validation demonstrated that isovitexin significantly protected osteoblasts. Conclusions: MD and its pharmacologically active component, isovitexin, exhibit protective effects against TNF alpha-induced inflammatory injury in osteoblasts, laying a solid foundation for future drug development.

关键词： Corpus luteum   Fibroblast   Cytokine   Interleukin   Tumor necrosis factor   Prostaglandins   Microenvironment  

摘要： The corpus luteum is a temporary endocrine gland that is crucial for pregnancy, as it produces the progesterone needed to maintain optimal uterine conditions for implantation. In the absence of a conceptus, the corpus luteum becomes non-functional and undergoes rapid tissue remodeling to regress into a fibrotic corpus albicans. Early luteal regression is characterized by increased cytokine release. Because the role of fibroblasts in the bovine corpus luteum remains to be elucidated, the aim of this study was to elucidate the response of bovine luteal fibroblasts to inflammatory cytokines, tumor necrosis factor alpha (TNF alpha), and interleukin 1 beta (IL1 beta). Both cytokines induced canonical mitogen activated protein kinase (MAPK) signaling in luteal fibroblasts by phosphorylation of ERK1/2, p38 MAPK, and JNK. IL1 beta elevated expression and phosphorylation of cytosolic phospholipase A2 (cPLA2), an enzyme that mobilizes arachidonic acid for prostanoid synthesis. IL1 beta also elevated expression of prostaglandin-endoperoxide synthase 2 (PTGS2), another enzyme needed to synthesize prostanoids. IL1 beta increased PGF2 alpha and PGE2 levels in the culture medium over 20-fold. Inhibition of MAPKs with small-molecule inhibitors abrogated the stimulatory effects of IL1 beta. IL1 beta also induced prostaglandin production in steroidogenic cells;however, there was no elevation in cPLA2. Therefore, actions of IL1 beta differ based on ovarian cell type. All together, we have identified luteal fibroblasts as potential inflammatory mediators during luteal regression.

关键词： Hyperandrogenism   Infertility   Polymorphism   Polycystic ovary syndrome   rs1800587   rs1800795  

摘要： Background and Aim Infertility in women has various causes, one of which is ovulation disorders. Polycystic ovary syndrome (PCOS) affecting ovulation is a complex idiopathic disease in which genetic polymorphisms may be involved. This study aimed to investigate the relationship between IL-6 -174 G/C and IL-1A -889 G/A cytokine polymorphisms with polycystic ovary syndrome in a population of Iranian women. Materials and Methods In this case-control pilot study, 120 PCOS patients (60 infertile, LPI, and 60 women with recurrent pregnancy abortion, LPA) and 60 controls, CTRLs) participated. After genomic DNA extraction from peripheral blood, we investigated for the polymorphisms rs1800795 of the IL-6 -174 and rs1800587 of the IL-1A-889 using specific primers and PCR-RFLP followed by NlaIII enzyme digestion and PCR-ARMS techniques. Results There was a significant difference in the studied groups in terms of clinical characteristics (p-value < 0.05) except for the levels of HDL and LDL. Regarding demographic and clinical characteristics of patients, a significant correlation was observed between C/G and G/G genotypes of rs1800795 and FBS level (p value = 0.002). Also, rs1800587 showed a substantial relationship between CC and CT genotypes with the level of LH in LPI and the level of FBS in the LPAs (p value = 0.04). There was no significant difference between the frequencies of rs1800795 and frequencies of rs1800587 genotypes in the three studied groups (p value > 0.05).The studied variants were in Hardy-Weinberg equilibrium. Conclusion The present work showed that rs1800795 and rs1800587 were not directly associated with PCOS in Iranian patients while the SNPs showed an indirect relationship with some factors affecting the disease. However, using genome-wide association analysis is a proper suggestion to obtain more reliable information about the disease's genetic view. To our knowledge, this is the first report that implicates the role of the examined SNPs in an Iranian

关键词： Diabetic nephropathy   Strobilanthes sarcorrhiza   Phenolic extract   NF-kappa B/IL-1 beta   Glycerophospholipid metabolism  

摘要： Strobilanthes sarcorrhiza, a folk medicine from China, is known to treat kidney deficiency and lumbago. However, its protective effects and mechanisms against diabetic nephropathy (DN) remain unclear. This study aimed to investigate the effects and mechanisms of Strobilanthes sarcorrhiza root phenolic extract (CTS) on streptozotocin (STZ)-induced DN in mice. Firstly, the constituents in CTS were characterized by UPLC-QTOF-MS. Thirty-three constituents were identified, including 12 phenylethanoid glycosides and their derivatives, 14 phenylpropanoid glycosides derivatives, 6 polyphenols derivatives, and 1 other constituent. Then, utilizing the identified constituents of CTS, network pharmacology was used to anticipate potential pathways against DN. Thirty-two out of thirty-three constituents showed anti-DN activity;their mechanism of action was significantly linked to tumor-, glycosylation-, metabolism-related pathways, etc. Furthermore, the effectiveness of CTS against DN and its in vivo mechanism was assessed by combining immunohistochemistry, untargeted metabolomics, biochemical evaluation, and histopathological examination. The findings showed that CTS improved blood glucose and lipid levels in diabetic mice, reduced serum levels of ALT, CREA, UREA, IL-1 beta, and IL-17, decreased pathological damage and fibrosis in kidney tissue, and lowered the protein expression of VEGF, Laminin, TNF-alpha, and NF-kappa B in kidney tissue. Metabolomics results indicated that CTS alleviated DN mainly by regulating glycerophospholipid metabolism. To the best of our knowledge, this study is the first to report that Strobilanthes sarcorrhiza attenuates DN, potentially through the inhibition of the NF-kappa B pathway, leading to a reduction in the inflammatory response and fibrosis of renal tissue. These findings suggest that Strobilanthes sarcorrhiza could be a promising therapeutic agent for DN.

关键词： TiO2   Ionic liquid   Carbon quantum dots   Inverse opal   Slow photon effect  

摘要： Photocatalytic reduction of CO2 exhibits unsatisfactory photocatalytic performance owing to the inefficient separation of photogenerated electron-hole pairs, low CO2 capture efficiency and limited visible light absorption on most photo-catalysts. Herein, Ti-F bridged IL-CuCQDs-F/TiO2 inverse opal composite (IO-CFTi) was constructed for boosting CO2 visible-photo reduction via slow photo effect. In this work, ethylenediaminetetraacetic acid (EDTA(Cu)) and imidazole ionic liquid 1-(2-Hydroxyethyl)-3-methylimidazolium tetrafluoroborate ([HOEtMIM][BF4]) were employed to confine grow of IL-CuCQDs-F within TiO2 inverse opal supporter via Ti-F bonds connection. Unique IL-CuCQDs-F efficiently expended light absorption towards visible region, and the confined growth of IL-CuCQDs-F within the TiO2 inverse opal cavity achieved the photoelectric conversion and efficient CO2 capture. Moreover, their Ti-F bonding interface of IO-CFTi assisted photogenerated electron transportation from TiO2 to CO2 for its reduction in this system. Consequently, IO-CFTi achieved a substantially increased CO production rate of 78.1 mu mol & sdot;h(- 1)& sdot;g(- 1) with 98 % selectivity. This improved performance in CO2 photoreduction positions the nanocomposite as a promising material for preservation of the environment and conversion of energy.

关键词： F. aubertii   Inflammation   Acute lung injury   Transcriptomics   Proteomics   IL-17A/NF-kappa B  

摘要： Ethnopharmacological relevance: Fallopia aubertii (L. Henry) Holub (F. aubertii), a traditional Tibetan medicine, is used in China for treating respiratory inflammatory diseases, including acute lung injury (ALI). However, the chemical constituents of F. aubertii and its anti-inflammatory mechanisms in the lungs remain poorly understood. Aim of the study: This study aimed to identify the chemical constituents of the F. aubertii extract (FAE), evaluate its effectiveness in reducing ALI in mice, and elucidate the underlying mechanisms of its action. Materials and methods: The chemical composition of FAE was determined using UPLC-LTQ Velos Pro-Orbitrap Elite. Network pharmacology was employed to predict the mechanisms by which FAE might mitigate ALI. Mice were administered FAE orally for seven days, followed by intratracheal instillation of lipopolysaccharide (LPS) to induce ALI. On the final day, the mice were euthanized, and their lungs were collected for transcriptome analysis, proteomics, pharmacodynamic evaluation, and mechanistic studies. Hematoxylin and eosin (H&E) staining assessed lung pathology. Transcriptome and proteomic analyses, along with real-time quantitative PCR (RT-qPCR) and western blotting, were used to investigate FAE's effects on lung inflammation and related signaling pathways. In vitro experiments further explored the anti-ALI mechanisms of FAE. Immunofluorescence assays in RAW264.7 cells examined the nuclear translocation of NF-kappa B. Results: Fifty-one compounds were identified in FAE, predominantly flavonoid glycosides. Network pharmacology suggested that FAE may inhibit ALI by modulating the NF-kappa B pathway and Th17 differentiation. RNA-seq analysis indicated that FAE might suppress inflammation through the IL-17 signaling pathway, with these findings corroborated by mRNA level measurements in vivo and in vitro. FAE alleviated LPS-induced ALI by modulating the IL-17A signaling pathway, which was confirmed through proteomic analysis. We

关键词： Group 2 innate lymphoid cells (ILC2s)   Myeloid-derived suppressor cells (MDSCs)   Interleukin-33(IL-33)   Interleukin-13(IL-13)   Cervical cancer (CC)  

摘要： The interleukin-33(IL-33) - group 2 innate lymphoid cells (ILC2s) - interleukin-13(IL-13) - monocytic myeloid- derived suppressor cells (M-MDSCs) axis plays a critical role in promoting immune evasion in tumors;however, its specific function in cervical cancer remains poorly understood. In this study, we observed that the proportion of IL-33-ILC2s-IL-13-M-MDSCs were significantly elevated in both cervical cancer patients and the subcutaneous U14 cervical cancer mouse model, compared to normal controls. Our results suggest that IL-33 stimulates ILC2s to secrete IL-13, which, in turn, regulates M-MDSCs to enhance their immune evasion capabilities. Notably, in vitro blockade of IL-33 and IL-13 partially restored the levels and functions of both ILC2s and M-MDSCs. In conclusion, these findings imply that the overactivation of the IL-33-ILC2s-IL-13-M-MDSCs axis may contribute to cervical cancer progression. However, further in vivo blockade studies are required to fully elucidate the precise mechanisms underlying this interaction and to assess its potential therapeutic implications for cervical cancer.

关键词： SLE   IL-37   Cytokine targeted therapy   Cytokine   Immunotherapy  

摘要： Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated immune responses and inflammation. Interleukin-37 (IL-37) is a recently discovered immunomodulatory cytokine with potential anti-inflammatory properties. This systematic review explores the relationship between IL and 37 and SLE disease activity, and evaluates its potential as a therapeutic agent. Methods: Electronic databases were searched for studies investigating IL-37 and SLE. Data on IL-37 levels, SLE Disease Activity Index (SLEDAI) score, genetic polymorphisms, and its therapeutic effects from pre-clinical studies were extracted. Results: Previous studies presented conflicting findings on IL-37 levels in SLE patients. Some reported positive correlations with disease activity, while others observed associations between lower IL-37 and increased activity. Genetic variations in the IL-37 gene linked to SLE susceptibility have been reported. Pre-clinical studies using engineered mesenchymal stem cells or direct IL-37 treatment showed promise in reducing disease severity in mouse models and cell cultures of SLE. The analysis of multiple studies reveals that IL-37 expression varies significantly across different SLE subtypes. Conclusions: While a potential link exists between IL and 37 and disease activity, genetic predisposition, and therapeutic benefit, further research is needed. Future studies with standardized designs, larger and more diverse populations, and mechanistic investigations are crucial to determine the therapeutic potential of IL-37 for SLE. This review highlights the need for well-designed clinical trials to evaluate the safety and efficacy of IL-37 therapy in patients with SLE.