BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Yang Ding,Shengyun Wan,Long Ma,Kaikai Wei,Kun Ye
Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 10 9 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis . PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O 2 ) for 24 h. The percentage of pro-inflammatory CD86 + macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.
研究领域:
心脏病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2023
·
IF 3.9
Yinzhong Chen,Wei Guo,Weizhao Lu,Xiucheng Guo,Weilu Gao,Zongsheng Yin
Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-β signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1β)-induced chondrocytes . The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1β-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1β-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα , and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.
研究领域:
风湿病学
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分子生物学
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炎症
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软骨生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Xun He,Jingsong Liu,Yugang Gong,Wei Lu,Xiaowei Sha,Chang Cao,Yanqun Li,Jiawei Wang
Background Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. Purpose Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. Study design The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). Methods The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4 + CD25 + FOXP3 + , CD4 + and CD8 + of skin tissue. And the levels of CD4 + and CD8 + , p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. Results Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4 + CD25 + FOXP3 + and CD4 + cells, while inhibited the number of CD8 + positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. Conclusion Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.
研究领域:
药理学
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免疫学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2019
·Vol. 10
·期 11
·7142-7151
·
IF 3.241
Wenwen Zhao,Xi Zeng,Fancheng Meng,Xiaolin Bi,Dahai Xu,Xiuping Chen,Qiu Li,Yantao Han
We report here an acidic polysaccharide, namely RSP-3, which ameliorates acute kidney injury and is obtained from Sanguisorba officinalis. We extracted and purified two polysaccharides from this herb based on the acidity and screened them for their effect in regulating the immunological activity of macrophages. Among them, RSP-3 exhibited significant anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated macrophages by decreasing TNF-α and IL-6 levels. Subsequently, we found that RSP-3 suppressed ER stress, reduced ROS production and blocked NF-κBp65 translocation. After fully characterizing RSP-3 with a series of analytical technologies, we tested its anti-acute kidney injury (AKI) effect in vivo. In a murine AKI model induced by LPS, treatment with RSP-3 effectively ameliorated renal function. Besides, it decreased the levels of TNF-α and IL-6 in serum and reduced macrophage infiltration in injured kidney tissue. In sum, RSP-3, with a significant protective effect against AKI by showing anti-inflammatory activity, may become a meaningful drug candidate for treatment of AKI.
研究领域:
药理学
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免疫学
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分子生物学
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肾病学
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DOI
PubMed
高影响因子
LIFE SCIENCES
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2018
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IF 3.234
Rongzong Qiu,Weifeng Yao,Haocong Ji,Dongdong Yuan,Xiaofeng Gao,Weiping Sha,Fei Wang,Pinjie Huang,Ziqing Hei
Background Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. Methods The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups. The survival of septic rats within 24 h was recorded. Tissue pathology, plasma IL-1β, IL-6, TNF-α, lipoxygenase-5 and lipoxin A4 were evaluated. Western blotting and immunostaining was used to determine expression of TLR4 , IκB , IKK , NF-κB p65 and pp65 in kidney tissue. Then qPCR was used to analyze the mRNA expression of renal α 2A -AR, α 2B -AR and α 2C -AR. Results Rat mortality and kidney inflammation were significantly increased in septic rats. Specifically, IL-1β, IL-6 and TNF-α plasma levels, NF-κB activity, and TLR4 expression in rat kidney tissues were increased after CLP. In the DEX treatment group, mortality was reduced, histology changes were minor, and lipoxygenase-5, and lipoxin A4 expression were increased. The expression of IL-1β, IL-6 and TNF-α, NF-κB activity and TLR4 expression in rat kidney tissues were also decreased. These results indicated that DEX treatment alleviates acute kidney injury induced by CLP. However, the effects of DEX were apparently suppressed by atipamezole in the DEX + AT group. Conclusion The current study demonstrated the protective effect of DEX on CLP-induced kidney injury, which may be effective by attenuating NF-κB pathway activation with lipoxin A4.
研究领域:
药理学
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肾病学
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免疫学
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重症医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2019
·
IF 3.361
Yuping Liu,Xiangliang Jiang,Yue Gu,Yan Chen
Cutaneous toxicities are the commonest side effects in patients with cancer treated using epidermal growth factor receptor inhibitors such as erlotinib . For patients with such toxicities, there is a lack of safe, effective pharmacological agents. Here we established a skin toxicity model and investigated the preventive and therapeutic effect of Diallyl Trisulfide (DATS) in vivo. The mouse skin toxicities model was established through continuous administration of erlotinib for 49 days. Meanwhile, the mice in the experimental group underwent DATS treatment for 49 days. Hematoxylin and eosin (HE) staining and oil red O staining of back and limb skin was performed to determine whether DATS aqueous extract can reverse the skin toxicities caused by erlotinib. Compared with the erlotinib group, the incidence of rash in the DATS group was lower. In addition, in the DATS group, the degree of skin redness and herpes was mild, the body weight was stable, and the activity was favorable. By comparing the HE and oil red O staining results for the mouse skin, the degree of keratin hyperplasia was determined to be lower in the experimental group than in the erlotinib group, and the number of purulent neutrophils decreased. The number of follicles was relatively less. The release of TNF-α, IL-6 and other inflammatory factors was reduced by DATS. Erlotinib hydrochloride can cause severe skin toxicities, and DATS prevents skin toxicities, its mechanism may be related to DATS reduced erlotinib-induced inflammatory injury .
研究领域:
肿瘤学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2022
·Vol. 46
·期 12
·e14460
·
IF 3.654
Jing Guo,Jian-Kai Tang,Bai-Fang Wang,Wen-Rui Yan,Ting Li,Xue-Jian Guo,Lei Zhang,Tao Wang,Qian-Yun Sun,Li-Wei Zhang
Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1β, NO, and PGE 2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. Practical applications Phillygenin is one of the major active ingredients in Forsythia suspensa . But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.
研究领域:
药理学
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炎症
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疼痛管理
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天然产物
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传统中药
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产品关联
DOI
PubMed
高影响因子
Journal of the Chinese Medical Association
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2023
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IF 3
Lian Shu,Li Wulin,Zhong Chunlian,Li Ye,Wu Changhui,Zhang Kun,Lin Jiangfei,Wang Weiyu,Katanaev Vladimir,Xie Xiaodong,Jia Lee
Background: Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. Methods: In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. Results: In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and IL-6 cytokine levels in mouse blood, while also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. Conclusion: In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.
研究领域:
肿瘤学
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免疫学
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药理学
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中医药
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产品关联
DOI
PubMed
高影响因子
Infection and Drug Resistance
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2023
·
IF 3.9
Lingna Xu,Ren-ai Xu,Dan Zhang,Shanshan Su,Hanyan Xu,Qing Wu,Yuping Li
Background: T helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown.Materials and methods: Six to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.Results: The proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01).Conclusion: The expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.
研究领域:
免疫学
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微生物学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Haocong Zhang,Liangbi Xiang,Hong Yuan,Hailong Yu
Spinal cord injury (SCI) is a severe central nervous system injury and microglia are major participants in neuroinflammation after injury. ADP-ribosylation factor-like GTPase 11 (ARL11) is a GTP-binding protein. Whether ARL11 is involved in the SCI progression is unknown. In the impactor-induced moderate SCI mouse model, ARL11 protein and mRNA expression were significantly increased in the injury site. LPS (100 ng/mL) and IFN-γ (20 ng/mL) were incubated with BV2 cells (immortalized mouse microglial cell line) to drive them into an M1-like phenotype. ARL11 up-regulation was also observed in activated microglia in SCI mice and LPS and IFN-γ treated BV2 cells. Basso Mouse Scale scores and inclined plate test revealed that ARL11 deletion promoted motor function recovery in SCI mice. Pathological examination showed ARL11 knockdown reduced spinal cord tissue damage, increased neuron numbers, and inhibited neuronal apoptosis in SCI mice. ARL11 knockdown notably inhibited IL-1β and IL-6 production in vivo and in vitro. Furthermore, ARL11 deletion significantly inhibited iNOS protein and mRNA expression in vivo and in vitro, and COX-2 expression in vivo . Mechanism studies revealed that ARL11 silencing decreased phosphorylated ERK1/2 protein expression. Additionally, ELF1 knockdown significantly inhibited ARL11 protein and mRNA expression in vitro . ELF1 acted as a transcription activator in regulating ARL11 expression by binding to the promoter. In conclusion, ARL11 knockdown protects neurons by inhibiting M1 microglia-induced neuroinflammation, thereby promoting motor functional recovery in SCI mice. This may occur in part under the regulation of ELF1. Our study provides a new molecular target for SCI treatment.
研究领域:
神经科学
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炎症
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Xu Han,Xiaqing Wu,Fanglin Liu,Huan Chen,Hongwei Hou
Inflammation is the physiological response of the immune system to injury or infection, typically manifested by local tissue congestion, swelling, heat, and pain. Prolonged or excessive inflammation can lead to tissue damage and the development of many diseases. The anti-inflammatory effects of natural ingredients have been extensively researched and confirmed. This study investigated the effects of Chlorogenic acid (CGA) isomers —— 3-Caffeolyquninic acid (3-CQA), 4-Caffeolyquninic acid (4-CQA), and 5-Caffeolyquninic acid (5-CQA) —— on the inflammatory response and oxidative stress reaction induced by LPS in RAW264.7 cells. Overall, 3-CQA exhibited the most significant reduction in levels of TNF-α, IL-6, NO, and ROS. 4-CQA showed superior inhibition of TNF-α compared to 5-CQA (p < 0.05), while no significant difference in other parameters. We further used DARTS and CETSA to demonstrate that CGA isomers have stable affinity with AKR1B1. As a positive control, the AKR1B1 antagonist epalrestat exhibited similar effects to the CGA isomers. 3-CQA having the smallest half-inhibitory concentration (IC50) for AKR1B1, while 4-CQA and 5-CQA have similar values. AutoDock simulations of the docking conformations revealed minimal differences in the average binding energies of the CGA isomers. The main differences were that VAL47 formed a hydrogen bond with 3-CQA, whereas GLN49 formed hydrogen bonds with 4-CQA and 5-CQA. Additionally, the number of hydrophobic bonds involving PHE122 and LEU300 varies. Our conclusion is that differences in non-covalent interactions result in the varying inhibitory abilities of CGA isomers on AKR1B1, which further affect the anti-inflammatory and antioxidant effects of CGA isomers.
研究领域:
药理学
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免疫学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Yanke Lin,Shuai Wang,Zemin Yang,Lu Gao,Ziyue Zhou,Pei Yu,Baojian Wu
Bilirubin is an endogenous substance derived from heme catabolism. In this study, we aimed to assess the anti-inflammatory activity of bilirubin, and to determine the mechanism thereof. The anti-inflammatory activity of bilirubin was evaluated using lipopolysaccharide (LPS)-treated peritoneal macrophages (PMs) and Raw264.7 cells, and mice with alum-induced peritonitis. The mRNA and proteins of NOD-like receptor family pyrin domain containing 3 (Nlrp3) and inflammatory cytokines were determined using qPCR and Western blotting, respectively. Distribution of phosphorylated (p) p65 [a NF-κB (nuclear factor-κB) subunit] in the cytoplasm and nucleus were evaluated by immunofluorescence analysis and electrophoretic mobility shift assay. Bilirubin prior to LPS treatment decreased protein expressions of Nlrp3, pro-interleukin (IL)-1β and mature IL-1β in PMs, whereas bilirubin post LPS treatment showed no effects. Bilirubin prior to LPS treatment dose-dependently repressed expressions of Nlrp3 and IL-1β, and inhibited translocation of p-p65 to nucleus in Raw264.7 cells. Bilirubin treatment decreased myeloperoxidase activity and reduced the levels of inflammatory cytokines (i.e., IL-1β, TNFα and IL-6) in lavage fluid in mice with alum-induced peritonitis. This was accompanied by a lower mortality rate. In addition, the mRNAs of Nlr p3 and IL-1β in peritoneal exudates cells were decreased, and the levels of p-p65 and mature IL-1β proteins were reduced. In conclusion, bilirubin acted on inflammation and alleviated alum–induced peritonitis through inactivation of Nlrp3 inflammasome.
研究领域:
免疫学
·
炎症
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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