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CARBOHYDRATE POLYMERS · 2015 · IF 4.074

Mechanistic insights into cellular immunity of chondroitin sulfate A and its zwitterionic N-deacetylated derivatives

Wuxia Zhang,Feifei Sun,Hong Niu,Qingjie Wang,Jinyou Duan

As a major component in extracellular matrix of the tissue, chondroitin sulfate A (CS-A) has been shown to exhibit either pro- or anti-inflammatory immune response which was largely dependent on its molecular size and cell types. In this study, we determined the signaling pathway involved in immune response of CS and its N -deacetylated derivative (dCS). Our data indicated that both CS and dCS could activate the NF-κB transcription factor in antigen presenting cells and induce TNF-α production through the TLR/MyD88 pathway. Further studies demonstrated that both CS and dCS had a potential in promoting the proliferation of spleen lymphocytes, and promoting the cytokines secretion by OVA-sensitized splenocytes. Thus, our finding provided a mechanistic insight into the understanding of cellular immunity of CS and dCS, which might be helpful to develop CS-based immune modulators against chronic inflammatory conditions, autoimmunity, infectious diseases, allergies and asthmatic conditions.

研究领域: 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC INFECTIOUS DISEASES · 2025 ·Vol. 25 ·期 1 ·1-16 · IF 3

Alleviating penicillin-resistant Streptococcus pneumoniae‑induced lung epithelial cell injury: mechanistic insights into effects of the optimized combination of main components from Yinhuapinggan granules

Lv Jiangbo,Wan Haofang,Yu Daojun,Zhou Huifen,Wang Wenba,Wan Haitong

ObjectivePenicillin-resistant Streptococcus pneumoniae (PRSP), for which novel treatment medicines are required, has expanded extensively due to the overuse of antibiotics. This study aimed to detect the optimal ratio of the combination of the main components based on Yinhuapinggan granules (YHPG) to generate novel treatment concepts for PRSP-induced lung injury.Methods Three representative main components: chlorogenic acid (C), amygdalin (A), and puerarin (P) were selected, and the optimal combination of these three components was determined by an orthogonal experiment. Investigations were conducted on the potential mechanisms underlying the protective effect of this optimized combination against PRSP-induced lung epithelial cell damage. Meanwhile, the bacteriostatic effect was further explored through the optimized combination of these natural products combined with penicillin G (PG).Results The optimized combination CAP (C: 16 µg/mL, A: 24 µg/mL, P: 24 µg/mL) screened by the orthogonal experimental design reduced cell damage in a model of human lung epithelial cells infected by PRSP, and the combination of CAP and PG had a synergistic effect. At the cellular level, CAP attenuated lung epithelial cell injury by modulating the TLRs/MyD88 inflammatory pathway. At the bacterial level, CAP modulated the virulence and drug resistance of PRSP, resulting in enhanced bacterial inhibition by the combination of CAP and PG.Conclusion Taken together, our results suggest that CAP can modulate or synergize with PG to modulate the TLRs/MyD88 pathway and attenuate PRSP-induced lung injury, and can be used as a potential drug for treating PRSP infection.

研究领域: 医学 · 药理学 · 感染性疾病 · 中药研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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GLYCOBIOLOGY · 2014 ·Vol. 24 ·期 12 ·1334-1342 · IF 3.747

Alteration in immune responses toward N-deacetylation of hyaluronic acid

Zhang Wuxia,Mu Haibo,Dong Dongqi,Wang Dongdong,Zhang Amin,Duan Jinyou

Hyaluronic acid (HA) is an ubiquitous nonsulfated glycosaminoglycan of the extracellular matrix in all mammalian connective tissues. Along with the age growth, HA will lose its N-acetyl groups in vivo; however, the significance of this physiological process remains largely unknown. Herein, three highly N-deacetylated HAs (dHAs), dHA-5 kDa (Mw: 5 kDa, DD: 100%), dHA-16 kDa (Mw: 16 kDa, DD: 94%) and dHA-110 kDa (Mw: 110 kDa, DD: 72%), were generated after hydrazinolysis. Their capability in the activation of antigen-presenting cells (APCs) was compared with that of their respective HAs. Our results demonstrated that both HAs and dHAs could activate the nuclear factor-kappa B (NF-κB) transcription factor in APCs and induced cytokine production through the Toll-like receptor (TLR)/MyD88 pathway. Notably, the capacity of dHAs in cytokine induction was much lower than that of HAs. In addition, the TLR-2 pathway was much involved following the appearance of zwitterionic motifs in dHAs. Thus, our findings highlight that N-deacetylation renders HA divergences in immune response, which might be implicated in age-induced functional change in endogenous glycosaminoglycans due to the structural modification in vivo.

CAS / MDL: 9067-32-7
研究领域: 免疫学 · 生物化学 · 分子生物学 · 老年医学
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NUTRITION · 2023 · IF 4.4

The effects of enteral nutrition supplemented with octanoic acid on LPS-induced intestinal injury: role of PPARγ/STAT-1/MyD88 pathway

Jiabao Tang,Xiaohua Li,Wei Li,Chun Cao

Objective Enteral nutrition (EN) is the key therapy in septic patients. Different formulas of EN have various effects on gastrointestinal sepsis. Therefore, we investigated the effects of EN supplemented with octanoic acid (OA) on lipopolysaccharide (LPS) induced intestinal injury and explored the potential mechanism. Methods First, to investigate the effects of EN supplemented with OA on LPS-induced intestinal injury, rats were randomly divided into four groups: the sham, LPS, LPS + EN, and LPS + EN + OA groups. Then, to explore whether EN supplemented with OA can prevent LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway, rats were randomly divided into five groups: the sham, LPS, LPS + EN + OA, LPS + EN + OA +SR202, and LPS + pioglitazone groups. All rats received nutritional support for three days. We examined the serum levels of inflammatory factors, pathological changes, goblet cell density, intestinal tight junction protein expression, and the PPARγ/STAT-1/MyD88 pathway in the ileum and colon. In addition, the effect of OA on intestinal epithelium injury was also explored in vitro. Results EN supplemented with OA significantly decreased the serum levels of inflammatory factors and prevented intestinal barrier dysfunction compared with EN alone (P < 0.05). Inhibiting the PPARγ/STAT-1/MyD88 pathway exacerbated effects of EN supplemented with OA on intestinal injury (P < 0.05). Activation of the PPARγ/STAT-1/MyD88 pathway prevented intestinal injury (P < 0.05). OA also exerted a similar effect on intestinal epithelium injury in vitro. Conclusion EN supplemented with OA prevents LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway.

研究领域: 营养学 · 胃肠病学 · 免疫学 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

The role of phlorizin liposome-embedded oxidized sodium alginate/carboxymethyl chitosan in diabetic wound healing

Xiaoyu Wu,Chuanbo Ding,Xinglong Liu,Qiteng Ding,Shuai Zhang,Yue Wang,Chenran Xin,Hewei Wei,Rui Mao,Guiping Zhang,Ting Zhao,Wencong Liu

Wound healing in diabetic patients is often complicated by issues like inflammation, infection, bleeding, and fluid retention. To tackle these challenges, it is essential to create hydrogel dressings with anti-inflammatory, antibacterial, and antioxidative properties. This study aimed to synthesize Phlorizin-Liposomes (PL) through the thin-film dispersion method and integrate them into an oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) hydrogel scaffold, resulting in an OSA/CMCS/PL (PLOCS) composite hydrogel via a Schiff base reaction. Characterization of the composite was performed using FTIR, TEM, and SEM techniques. The research assessed the swelling behavior, antibacterial effectiveness, and biocompatibility of the PLOCS composite hydrogel, while also investigating how PLOCS facilitates diabetic wound healing. The results demonstrated that PLOCS effectively controls drug release, possesses favorable swelling and degradation characteristics, and shows significant antioxidative properties along with in vitro biocompatibility. Histological analysis confirmed that PLOCS supports the proliferation of healthy epithelial tissue and collagen production. Western blotting indicated that PLOCS diminishes inflammation by inhibiting the TLR4/NF-κB/MyD88 pathway and activates Nrf2 to boost wound healing, increasing the levels of antioxidative enzymes such as HO-1, NQO1, and GCLC. In summary, PLOCS presents a promising new option for advanced wound dressings aimed at treating diabetic ulcers.

CAS / MDL: 298-93-1
研究领域: 材料科学 · 生物医学工程 · 药剂学 · 伤口愈合 · 糖尿病
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