BIOORGANIC & MEDICINAL CHEMISTRY
·
2023
·
IF 3.5
Wenbin Wang,Shiyang Zhou,Wenming Jiang,Guangying Chen
A series of 1-(2-oxocyclohexyl)butane-1, 3-dione derivatives were designed and synthesized as TLR4 inhibitors by modifying the core structure of the lead compound ((6, 8-dioxo-1, 2, 3, 4, 6, 7, 8, 8a-octahydronaphthalen-2-yl) carbamate)). In vitro , compound 3p significantly inhibited the proliferation of rat synovial cells, inhibited the proliferation of LPS-induced RAW264.7 cells, and inhibited TLR4 activity, with IC 50 values of 1.21 ± 0.09 μM, 0.73 ± 0.05 μM and 0.43 ± 0.03 μM, respectively, which was superior to the positive control methotrexate. In vivo anti-rheumatoid arthritis evaluation, compound 3p can significantly inhibit the inflammatory factors TNF-α, IL-1β and IL-6, so as to achieve the therapeutic purpose. In the preliminary mechanism study, compound 3p has obvious regulatory effects on the abnormal increase of TLR4, JAK2 and STAT3 protein and gene expression related to inflammatory signaling pathway in RAW264.7 cells. In summary, this study aims to develop more effective candidates for rheumatoid arthritis.
研究领域:
免疫学
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药理学
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医学
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DOI
PubMed
高影响因子
Research
·
2025
·
IF 10.7
Han Wang,Zhouyi Gan,Yueyue Wang,Dingmeng Hu,Lexiang Zhang,Fangfu Ye,Ping Duan
Endometriosis is marked by the ectopic growth, spread, and invasion of endometrial tissue beyond the uterus, resulting in recurrent bleeding, pain, reproductive challenges, and the formation of nodules or masses. Despite advancements in detection methods like ultrasound and laparoscopy, these techniques remain limited by low specificity and invasiveness, underscoring the need for a highly specific, noninvasive in vitro diagnostic method. This study investigates the potential of using menstrual blood as a noninvasive diagnostic sample for endometriosis by targeting genetic and inflammatory markers associated with endometriosis lesions. A novel digital droplet enzyme-linked immunosorbent assay (ddELISA) was developed, leveraging SiO 2 nanoparticles for the femtomolar-sensitive detection of inflammatory cytokines (OPN, IL-10, IL-6) in menstrual blood. Single-cell RNA sequencing revealed differentiation patterns across endometrial tissues and menstrual blood, affirming that menstrual blood replicates key inflammatory and immune properties of endometriosis. Furthermore, endometriosis menstrual blood endometrial cells derived from human menstrual blood displayed similar properties to endometrial stromal cells in endometriosis lesions, validating menstrual blood as a suitable in vitro diagnostic sample. In contrast to traditional ELISA, ddELISA supports multi-target detection with enhanced sensitivity and reduced processing time, allowing precise biomarker analysis from minimal sample volumes. Our ddELISA-based approach shows promise as a rapid, accessible, and accurate diagnostic tool for endometriosis, with potential for practical clinical application.
研究领域:
妇科学
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分子生物学
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诊断学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
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IF 4.5
Huijia Mao,Yang Fan,Fang Tan,Xingyao Long
Objective: The present study aimed to investigate the uric acid-lowering effects of Bifidobacterium animalis QC08 and explore its underlying mechanisms.Methods: Hyperuricemia (HUA) model in mice was established using potassium oxonate (250 mg/kg) and yeast extract (15 g/kg). The serum levels of uric acid (UA), blood urea nitrogen (BUN), creatinine (Cr), and liver xanthine oxidase (XO) were measured in four groups, including normal group, control group, allopurinol group (5 mg/kg), and Bifidobacterium animalis QC08 group (1010 CFU/kg) using enzyme colorimetry. Additionally, serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assay (ELISA). Pathological changes in renal tissue were examined through hematoxylin–eosin (HE) staining.Results: In vivo experimental results indicated that compared with the normal group, the serum UA, Cr, and BUN levels, as well as the levels of inflammatory factors (TNF-α and IL-1β), and the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly elevated in the control group (p < 0.05). The expression levels of uric acid transport-related genes (UAT, ABCG2, and OAT1) in kidney tissue were significantly downregulated (p < 0.05), and evident kidney damage was found. In contrast, compared with the control group, the Bifidobacterium animalis QC08 group exhibited a significant decrease in serum UA, BUN, Cr, TNF-α, and IL-6 levels, along with reduced hepatic XOD and ADA activities (p < 0.05). Additionally, Bifidobacterium animalis QC08 was found to regulate the mRNA transcription of renal uric acid transporters, leading to significantly upregulation of the expression levels of UAT, ABCG2, and OAT1 genes (p < 0.05).Conclusion: Bifidobacterium animalis QC08 demonstrates certain uric acid-lowering, anti-inflammatory, and renal protective effects, which are associated with the inhibition of XOD activity and the modulation of the expression levels of uric acid transporter genes (UAT, ABCG2, and OAT1).
研究领域:
医学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
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IF 12.5
Bing Jiang,Chenglu Peng,Przemyslaw Zalewski,Jun He,Xiaoyang Li,Yiguo Zhao,Cuixia Sun,Yiping Cao,Wei Lu,Yapeng Fang
Resistant starch, recognized as a prebiotic, has demonstrated significant potential in alleviating various disease models but its intestinal safety study has been always overlooked. Banana starch (BS), a rich source of resistant starch, and its derived nanoparticles have been implicated in intestinal barrier dysfunction in our previous study. However, the short-term effects of BS consumption on gut health in healthy bodies remain unclear. Here, we show short-term consumption of BS and banana starch nanoparticles (BSNs) induces low-grade colitis in healthy mice. Specifically, BS significantly reduces the number of colon goblet cells, elevates the expression of TNF-α, IL-1β, and IL-6, and shortens colon length, collectively contributing to intestinal barrier damage and the onset of colitis. Mechanistic studies indicate that BS and BSNs disrupt gut microbiota homeostasis, downregulate the expression of proteins like ZO-1, Occludin, and Claudin-1, and impair the structural integrity of colonic tight junctions. Correlation analysis further underscores a strong association between gut microbiota composition and colitis-related markers. These findings indicate that prolonged consumption of BS and BS-derived nanoparticles may pose significant risks to intestinal health, warranting further attention.
研究领域:
营养学
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免疫学
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微生物学
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DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 11
·2400
·
IF 4.6
Ming Yuan,Huai Wang,Mingjun Yu,Sen Yao,Risheng Yao
Cisplatin (CIS) is a widely used chemotherapeutic agent that is highly effective against various cancers. However, its clinical application is frequently limited by its substantial nephrotoxic side effects. The gastrin-releasing peptide receptor (GRPR), a critical regulator in inflammatory diseases, has been identified as a promising therapeutic target. Our previous studies have demonstrated that the GRPR antagonists PD176252 and RH-1402 can mitigate CIS-induced nephrotoxicity through anti-inflammatory mechanisms. Based on these findings, we designed and synthesized a series of 2-arylpropanoic acid-L-tryptophan derivatives to enhance the therapeutic effects. Among these compounds,3mexhibited superior renal protection by significantly improving mouse renal tubular epithelial cell (mRTEC) viability from 50.2 ± 2.6% to 80.5 ± 3.9%, surpassing PD176252 (70.8 ± 1.4%) and RH-1402 (73.9 ± 3.7%). Moreover, compound3mmarkedly reduced the expression of kidney injury molecule-1 (KIM-1) and inflammatory cytokines [Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1)]. Finally, molecular docking results revealed that3mexhibited a high binding affinity for GRPR. Computational predictions using SwissADME further indicated that3mpossesses favorable drug-like properties, thereby supporting its potential as a promising candidate for mitigating CIS-induced nephrotoxicity.
研究领域:
药理学
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肿瘤学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Yujie Chen,Hehua Lei,Zheng Cao,Cui Zhang,Lijun Liu,Xin Gao,Quanzhi Qin,Limin Zhang,Gang Chen
Sacha inchi (SI, Plukenetia volubilis L.) is a South American oleaginous crop with multiple health benefits and has been traditionally used to treat various ailments due to its bioactive ingredients such as polyphenols and flavonoids. In this study, a variety of compounds including three flavonoids (epigallocatechin, luteolin-3′,7-di-O-glucoside and cosmosiin), two polyphenols (gallic acid and 4-hydroxycoumarin) and three organic acids (malic acid, citric acid and 2-isopropylmalic acid) were firstly identified by UHPLC-QQQ-MS. Subsequently, in vitro results show that SI leaf aqueous extract (SILE) exhibit potential to lower uric acid (UA) by affecting mRNA levels of UA synthases (XO and HGPRT) with neglectable impacts on cell viability of liver cells (L02). In vivo experiments further suggest that SILE can effectively reduce the levels of serum UA and renal inflammatory cytokines ( Il-1β , Il-6 and Tnf-α ), and improve renal function indicators (serum Cr and BUN), thereby repairing kidney injury in both acute and chronic hyperuricemic (HUA) animal models. In addition, SILE also improve UA metabolism by inhibiting UA biosynthesis and reabsorption and promoting UA excretion. 1 H NMR-based metabolomics reveals that SILE effectively regulate the levels of glucose, amino acid, purine and pyrimidine that are involved in UA metabolic pathway in kidney of HUA mice. These findings demonstrate that SILE rich in polyphenols and flavonoids has a great potential for HUA treatment by inhibiting xanthine oxidase activity and improving UA metabolism.
研究领域:
药理学
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代谢生物学
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植物化学
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产品关联
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-18
·
IF 3.9
Liu Junhong,Li Ziwei,Zhang ZongYao,Shen Zhongyuan
Diabetic kidney disease (DKD) is a main complication of diabetes mellitus. experimental in vitro validation and Network pharmacology were used in this study to explore the potential mechanism of Huangkui capsules (HKC) in treating DKD. First, we used CCK8 to analyze the optimal drug concentration of HKC. Next, we used flow cytometry, ELISA, Scratch test, and immunofluorescence to examine the apoptosis, oxidative stress, inflammatory factors, and fibrotic factors (FN and α-SMA) expression in HK-2 cells. Thereafter, in order to determine the potential molecular mechanisms underlying the therapeutic effect of HKC in DKD. Compounds contained in HKC were explored by UPLC-Q-TOF-MS/MS. SwissTargetPrediction was utilized for predicting potential gene targets of these compounds. OMIM, DisGeNet and GeneCards databases were employed to identify DKD-related genes. Meanwhile, the association of compounds with DKD genes was examined by protein-protein interaction, GO and KEGG analysis. Finally, molecular docking and molecular dynamics simulation were adopted for further validation. The results showed that HKC had 40 active ingredients, 1051 possible gene targets, and 133 DKD-HKC intersection genes. IL6, TNF, GAPDH, AKT1, PPARG, and TP53 were candidate hub genes by which HKC exerted its anti-DKD function based on molecular docking, molecular dynamics simulation and experimental results. To conclude, this study sheds more lights on the possible pharmacological activities of HKC in DKD and a foundation for further clinical application.
研究领域:
药理学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Hongyan Wang,Lin Shi,Zhongxu Zhang,Long Chen,Xinli Xu,Weiwei Ding,Chuntao Chen,Dongping Sun
Managing uncontrolled and noncompressible bleeding presents a major challenge in emergency trauma care. Methods to halt bleeding quickly and efficiently, without applying direct pressure on the wound, have become a key focus of research. Herein, a novel fructose-modified chitosan/gelatin composite sponge has been developed, exhibiting high elasticity, low rebound pressure, and excellent cell compatibility. This material can rapidly return to its original form in around 1.5 s after being compressed by 80% upon contact with water. Additionally, experimental results from a rat liver wound model demonstrated that it exhibited a clear hemostatic effect. The hemostatic time was shortened from 204 ± 15.35 s to 53.3 ± 6.54 s, and the blood loss was reduced from 867 ± 153.15 mg to 187 ± 61.06 mg. Moreover, it can promote tissue healing by inhibiting the production of inflammatory factors including TNF-α, MCP-1, and IL-6. This material offers an effective solution for noncompressible tissue injuries.
研究领域:
生物材料学
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创伤医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Xiaogan Zhao,Tao Lin,Wenkai Jiang,Yihan Lin,Luyao Xiao,Yufang Tian,Kai Ma,Changliang Zhang,Feng Ji,Ghahvechi Chaeipeima Mahsa,Xin Rui,Wei Li
Lactobacillus helveticus LZ-R-5 (R-5), a strain with high epithelial adhesion and bioactive exopolysaccharide production, was isolated from Tibetan kefir grains. This study investigated its potential to alleviate intestinal inflammation using a DSS-induced colitis model in BALB/c mice. We integrated microbial diversity and serological analyses to assess changes in gut flora and cytokines following the R-5 treatment. Pathological assessments showed that R-5 reduced crypt distortion in the proximal colon and mitigated hepatic immune challenges by enhancing gut barrier function. The increased relative expression of TGF-β1 and the downregulation of NLRP3-related inflammatory factors were conducive to preventing organ damage in the thymus and spleen of mice with colitis. Additionally, R-5 stimulated GPR43 expression and improved epithelial nutrition, promoting mucin production to prevent enterotoxin leakage. It also modulated the gut microbiota by suppressing Bacteroides and Erysipelatoclostridium, leading to a microbiota composition more akin to that of normal flora.
研究领域:
微生物学
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免疫学
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消化系统疾病
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产品关联
DOI
PubMed
高影响因子
Diabetes Metabolic Syndrome and Obesity-Targets and Therapy
·
2021
·
IF 3.168
Hongfang Zeng,Xiaoli Li,Duanfang Zhou,Ning Wang,Xiaoping Yu,Liangyuan Long,Hao Cheng,Shuyu Zhou,Zhengze Shen,Weiying Zhou
Purpose To examine the pharmacological effects of Qihu on type 2 diabetes mellitus using db/db mice. Materials and Methods Thirty-seven db/db mice were randomly divided into the following 5 groups: diabetes model control group (DM group; n = 7), administered with the adjuvant 0.3% carboxymethyl cellulose-Na; positive control group (Met group; n = 8), administered with metformin (0.13 g/kg bodyweight); Qihu-L group (n = 7), administered with a low dose of Qihu (0.75 g/kg bodyweight), Qihu-M group (n = 7), administered with a medium dose of Qihu (1.5 g/kg bodyweight); Qihu-H group (n = 8), administered with a high dose of Qihu (3.0 g/kg bodyweight). BKS mice (n = 8) were used as the negative control group. The db/db mice were administered with drugs through oral gavage for 28 days. The random blood glucose levels, glucose tolerance test, bodyweight, food intake, and blood lipid levels of the mice were measured during the experimental period. The liver and pancreas tissues were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses. Results Compared with the DM group, the Qihu groups exhibited decreased bodyweight gain. The blood glucose levels in the Qihu-L, Qihu-M, and Qihu-H were 31.46%, 43.73%, and 51.83%, respectively, lower than those in the DM group. The triglyceride levels were significantly downregulated and the swelling and steatosis of the hepatocytes were significantly lower in the Qihu-M and Qihu-H groups than in the DM group. Qihu downregulated the expression of IL-1β, IL-6, and TXNIP and upregulated the AMP-activated protein kinase (AMPK) signaling pathway in the pancreas and liver tissues of db/db mice. Conclusion The anti-diabetic effects of Qihu are mediated through the activation of the AMPK/Txnip signaling and the downregulation of the secretion of inflammatory factors in db/db mice.
研究领域:
药理学
·
内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 5
·2416
·
IF 4.6
Junchen Liu,Yuehang Wu,Wenrui Ma,Hongyan Zhang,Xianyao Meng,Huirong Zhang,Miaomiao Guo,Xiao Ling,Li Li
Panax notoginseng(Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However,Panax notoginsengflower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX–2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL–37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography–tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX–2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.Keywords:Panax notoginsengflower;UVB;inflammatory factor;antibacterial peptide LL-37;total saponin;LC/MS/MS
研究领域:
药理学
·
生物化学
·
药物化学
·
化妆品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmacognosy Magazine
·
2025
·
IF 0.9
Yezhou Li,Chengjian Tang
Background and PurposeAlginate and gelatin have biocompatibility and biodegradability for drug formulations or carriers, but the roles and mechanisms in cartilage injury (CI) repair remain unclear. This research investigated the application of alginate-collagen hydrogel (ACH) in rat CI repair and its related mechanisms through in vitro and in vivo experiments.Materials and MethodsAlginate and modified collagen solutions were mixed to prepare the ACH. The obtained samples were characterized, and their sustained release properties were determined. L929 mouse fibroblasts were assigned into a blank control group (BC group, untreated), a positive control group (PC group, treated with 6.4% phenol), a negative control group (NC group, treated with tissue culture polystyrene), and an ACH group (treated with ACH). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay assessed cell viability. Meanwhile, the cytotoxicity of the ACH and its impact on cell proliferation and cell attachment capabilities were analyzed. Thirty 4-week-old specific pathogen-free Sprague-Dawley rats were randomly grouped into a chondrocyte group (chondrocytes collected and cultured), a cPAGE group (chondrocytes treated with ACH), a model group (CI model), and an mPAGE group (CI model treated with ACH). The influence of ACH on chondrocyte proliferation and type II collagen (COL-II) expression were assessed via cell counting kit 8 (CCK-8) assay and immunofluorescence staining. Furthermore, the impacts of ACH on chondrocyte tissue and COL-II expression were analyzed using Safranin O-Fast Green staining, the International Cartilage Repair Society (ICRS) score, and COL-II tissue staining. Immunoblotting was utilized to detect tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB), matrix metalloproteinase 13 (MMP-13), and COL-II proteins in cartilage tissue.ResultsThe release rate of the constructed ACH reached over 85% within 72 h and achieved degradation equilibrium within 5 days with a weight loss rate of over 60%. L929 fibroblast culture results showed that the ACH posed no significant cytotoxicity, and cell attachment results were not obviously different from those on tissue culture plates (p < .05). MTT assay results demonstrated that the ACH exerted no adverse effects on L929 cell proliferation and growth, indicating good biocompatibility. CCK-8 and COL-II results indicated that chondrocyte proliferation in the cPAGE group was markedly higher versus that in the chondrocyte group (p < .05). Besides, animal experiments unveiled that, relative to the CI group, the mPAGE group had more chondrocytes, upregulated COL-II, and higher ICRS scores (p < .05). MMP-13, NF-κB, and TNF-α were downregulated, and COL-II was upshifted in the mPAGE group, with remarkable differences (p < .05).ConclusionACH exhibited excellent biocompatibility and low cytotoxicity, promoted cell proliferation and growth, and facilitated chondrocyte proliferation in rat CI repair, offering a valuable research foundation for CI treatment.
研究领域:
生物材料学
·
组织工程学
·
医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）