Journal of Cleaner Production
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2026
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IF 10.7
Jiawen Zhang,Zhengtao Liu,Xusheng Wang,Shunhao Ai,Ji Li,Hongguang Cheng,Xiaonan Wang
Direct Cd exposure remains the dominant driver of mortality and enzyme exhaustion. • Soil microbiota loses diversity, whereas gut microbiota shows structural resilience. • SEM links soil and Cd to host toxicity via microbiomes as potential mediators. • We advocate a multi-tier risk assessment using micro-ecological indicators. Cadmium (Cd) contamination poses substantial risks to soil fauna, yet the combined roles of soil properties and microbial communities in mediating Cd toxicity remain poorly understood. Here, molecular, physiological, and microbiological endpoints were integrated to evaluate multilayered Cd effects on Eisenia fetida across three contrasting soils. Bioavailability assessments showed that soil properties strongly regulated Cd mobility and earthworm accumulation, outperforming total Cd as predictors of toxicity. Cd exposure induced oxidative stress, gene dysregulation, and growth inhibition, with marked soil-dependent variation. Bulk soil microbiota (BSM) and Earthworm gut microbiota (EGM) exhibited distinct but coordinated responses: BSM experienced community disruption, diversity loss, and an increased relative abundance of taxa associated with mobile genetic elements, whereas EGM exhibited structural resilience and an enrichment of putative stress-tolerance traits. Variance decomposition revealed that Cd exposure and soil properties accounted for an average of 53.8% and 46.2% of the explained variance in toxicity-related endpoints, respectively. Structural equation modeling suggested potential indirect pathways linking soil properties and Cd exposure to earthworm growth mediated by microbial communities (standardized effects: −0.68 and −0.17). Overall, Cd toxicity arises from coupled interactions among contamination levels, soil physicochemical traits, and microbial resilience, emphasizing the need to incorporate microbial processes into soil ecotoxicological risk assessments. Download: Download high-res image (294KB) Download: Download full-size image
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International Journal of Nanomedicine
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2026
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IF 8.7
Feifei Chen,Hui Jiang,Xueyi Song,Jianfeng Wang,Xu Ma,Quan Zhou,Abdullah Al Mamun,Lingna Li,Yunfang Zhou,Hongbin Xu,Shuanghu Wang
Introduction: Cerebral ischemic stroke has high mortality and disability rates with limited targeted therapeutic strategies. Biomimetic nanocarriers can optimize drug delivery efficiency and exert neuroprotection effects, providing a promising strategy for ischemia-reperfusion injury treatment.Methods: Hollow mesoporous silica nanoparticles (HMSNs) were synthesized via an improved Stoer method and loaded with imperatorin (IMP). Subsequently, neutrophil cell membranes (NCM) extracted from DMSO-induced HL-60 cells were coated onto the nanoparticles to construct NCM/IMP@HMSNs. Nanomaterial characterization was carried out. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models in SH-SY5Y cells and in vivo rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established to explore the underlying neuroprotective mechanisms.Results: The synthesized NCM/IMP@HMSNs nanoparticles possessed uniform particle size (~143 nm) and favorable stability, with an encapsulation efficiency of 31.84%. In vitro results revealed that IMP significantly increased the viability of OGD/R-injured SH-SY5Y cells compared with the model group. In vivo experiments showed that NCM/IMP@HMSNs efficiently accumulated in ischemic brain tissue, notably decreased mNSS scores, and reduced cerebral infarct volume by approximately 33.31% compared with the MCAO/R group. This nanosystem activated the Nrf2/ARE/Keap1 pathway, thereby upregulating HO-1 expression to strengthen antioxidant capacity, alleviate the accumulation of cerebral oxidative stress products, and regulate the activities of SOD, GSH, CAT and LDH.Conclusion: The biomimetic NCM/IMP@HMSNs nanoplatform enhances the neuroprotective efficacy against ischemia–reperfusion injury via activating the Nrf2/ARE/Keap1 pathway, offering a promising targeted therapeutic approach for ischemic stroke therapy.
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JOURNAL OF PHARMACEUTICAL SCIENCES
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2025
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IF 3.8
Xiaoxuan Fei,Junyi Pei,Simin Yan,Weihong Ge,Li Li,Jianjun Zou,Huimin Zhang,Lie Sun,Sifei Han,Luojuan Hu
Compared to classic intravenous (IV) administration, subcutaneous (SC) delivery of monoclonal antibodies (mAbs) offers new opportunities to improve patient compliance and healthcare efficiency. However, insufficient understanding of drug absorption process following SC administration, particularly the role of lymphatic transport, may hinder the development of SC formulations for mAbs. The current study aimed to examine the absorption route of widely used anti-PD-(L)1 mAbs following SC injection, and four marketed products (Pembrolizumab, Tislelizumab, Envafolimab, Sugemalimab) were selected as the model drugs. In the thoracic lymph duct cannulated rat model, all mAbs were found to be primarily absorbed via the lymphatics following SC injection, with 63.1–72.0% of the administered dose recovered in the thoracic lymph, contributing to >80% of SC bioavailability. This absorption pattern also resulted in elevated exposure of mAbs in draining lymph nodes (an order of magnitude higher drug concentrations compared to the systemic drug exposure). In addition, markedly different lymphatic absorption profiles were observed following SC administration at different sites, reflecting specific draining routes associated with certain anatomical regions in the rat. Our data suggested that the food pad is likely the optimal SC injection site for quantitative studies of lymphatic transport, whereas injection to the lower hind leg (a common SC injection site in previous studies) appeared to underestimate the absolute extent of lymphatic drug transport in the thoracic lymph-duct cannulated rat model, as these sites are drained by lymphatic networks that cannot be fully captured by the thoracic lymph-duct cannulation model.
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CNS & Neurological Disorders-Drug Targets
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2020
·Vol. 19
·期 1
·66-82
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IF 0
Xianbin Wang,Wei Ma,Tongtong Wang,Jinwei Yang,Zhen Wu,Kuangpin Liu,Yunfei Dai,Chenghao Zang,Wei Liu,Jie Liu,Yu Liang,Jianhui Guo,Liyan Li
Background: Brain-Derived Neurotrophic Factor (BDNF) plays critical roles during development of the central and peripheral nervous systems, as well as in neuronal survival after injury. Although proBDNF induces neuronal apoptosis after injury in vivo, whether it can also act as a death factor in vitro and in vivo under physiological conditions and after nerve injury, as well as its mechanism of inducing apoptosis, is still unclear. Objective: In this study, we investigated the mechanisms by which proBDNF causes apoptosis in sensory neurons and Satellite Glial Cells (SGCs) in Dorsal Root Ganglia (DRG) After Sciatic Nerve Transection (SNT). Methods: SGCs cultures were prepared and a scratch model was established to analyze the role of proBDNF in sensory neurons and SGCs in DRG following SNT. Following treatment with proBDNF antiserum, TUNEL and immunohistochemistry staining were used to detect the expression of Glial Fibrillary Acidic Protein (GFAP) and Calcitonin Gene-Related Peptide (CGRP) in DRG tissue; immunocytochemistry and Cell Counting Kit-8 (CCK8) assay were used to detect GFAP expression and cell viability of SGCs, respectively. RT-qPCR, western blot, and ELISA were used to measure mRNA and protein levels, respectively, of key factors in BDNF-TrkB, proBDNF-p75NTR/sortilin, and apoptosis signaling pathways. Results: proBDNF induced mitochondrial apoptosis of SGCs and neurons by modulating BDNF-TrkB and proBDNF-p75NTR/sortilin signaling pathways. In addition, neuroprotection was achieved by inhibiting the biological activity of endogenous proBDNF protein by injection of anti-proBDNF serum. Furthermore, the anti-proBDNF serum inhibited the activation of SGCs and promoted their proliferation. Conclusion: proBDNF induced apoptosis in SGCs and sensory neurons in DRG following SNT. The proBDNF signaling pathway is a potential novel therapeutic target for reducing sensory neuron and SGCs loss following peripheral nerve injury.
研究领域:
神经生物学
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细胞生物学
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分子生物学
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Frontiers in Pharmacology
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2026
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IF 5.4
Yifan Guo,Fang Hu,Allan Zijian Zhao,Yingjuan Zeng,Haoying Chen,Ai Wang,Xiaoxi Li,Li Cong
Introduction Omega-3 polyunsaturated fatty acids (PUFAs) have been widely reported to exert beneficial effects in type 1 diabetes mellitus (T1DM). However, the mechanisms by which Omega-3 PUFAs influence pancreatic islet function through the gut-islet axis remain incompletely understood. This study aimed to investigate whether Omega-3 PUFAs-associated alterations in gut microbiota composition and their metabolites are involved in the modulation of the pancreatic islet microenvironment in T1DM, and to explore the potential immunological mechanisms underlying these effects. Methods Fecal microbiota transplantation (FMT) was performed to evaluate the effects of Omega-3 PUFAs-associated gut microbiota in non-obese diabetic (NOD) mice. Immune cell composition and inflammatory status within pancreatic islets were analyzed using transcriptomic profiling, flow cytometry, and immunohistochemistry. Metabolomics analysis was performed to investigate the association among Omega-3 PUFAs, gut microbiota, and microbiota-related metabolites. In vitro co-culture systems were further established to evaluate the effects of selected metabolites on macrophage polarization and insulin production and secretion in pancreatic β-cells. Results Omega-3 PUFAs treatment and FMT were associated with reduced islet inflammation and a marked enrichment of the Eubacterium coprostanoligenes group ( E. coprostanoligenes ). Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18β-glycyrrhetinic acid (18β-GA) showed a strong association with E. coprostanoligenes , and in vitro experiments suggested a potential involvement of E. coprostanoligenes in the metabolic conversion process related to 18β-GA. In co-culture systems, 18β-GA promoted macrophage polarization toward an M2-like phenotype, which was accompanied by increased insulin production and secretion in pancreatic β-cells. Conclusion These findings suggest that Omega-3 PUFAs-associated alterations in gut microbiota composition and 18β-GA-related metabolic changes may contribute to the modulation of the pancreatic immune microenvironment and β-cells function in T1DM. This study provides additional insights into lipid-microbiota-immune interactions relevant to T1DM and supports further investigation of microbiota-associated immune regulation.
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MOLECULAR MEDICINE
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2024
·Vol. 30
·期 1
·1-15
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IF 6
Zhang FengQi,Zhang YiYang,Zhou JiaWang,Cai Ying,Li ZhiYu,Sun Jing,Xie ZhiJun,Hao GuiFeng
Background Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions Quercetin’s action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status.
研究领域:
免疫学
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药理学
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风湿病学
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分子生物学
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Biomaterials Advances
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2022
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IF 0
Zhiwei Li,Jiaqi Bu,Xinyu Zhu,Hao Zhou,Kaiqun Ren,Paul K. Chu,Limin Li,Xiang Hu,Xiaofeng Ding
Programmed cell death receptor ligand 1 (PD-L1)/PD-1 signaling has been exploited to design inhibitors that deliver promising clinical outcome albeit with limited efficacy. Herein, we prepare graphene oxide (GO)-PEI-PEG with low cytotoxicity and long stability and GO-PEI-PEG delivers PD-L1 siRNAs to hepatocellular carcinoma (HCC) cells by the endocytosis-lysosome pathway. The functional GO-PEI-PEG/PD-L1 siRNAs decrease PD-L1 and PD-1 abundance, increase pro-inflammation cytokine IFN-γ and TNF-α release, and improve the proliferation activity of Jurkat T cells. Since GO-PEI-PEG targets the mouse liver effectively, the intrahepatic tumors in C57BL/6 mice are treated with GO-PEI-PEG/Pd-l1 siRNAs via the tail vein, resulting in shrinkage of the HCC tumors and boosting the anti-tumor efficacy in combination with oral sorafenib. A single treatment improves the total CD3 + and cytotoxic CD8 + T cell infiltration in the HCC tumor tissues and even spleen and upregulates the expression of Perforin, Gzmb, Ifng, Il-1b and Tnfa in the tumors after the combined treatment. Both the single and combined treatments enhance reactive oxygen species (ROS) accumulation, and improved HCC ferroptosis. The results suggest that GO-PEI-PEG delivered PD-L1 siRNAs combined with oral sorafenib can activate the adaptive immunity and tumor ferroptosis and reveal an effective therapy to treat advanced HCC patients.
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Frontiers in Microbiology
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2023
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IF 5.2
Huan-Huan Chen,Qi-Jun Wu,Tie-Ning Zhang,Yu-Hong Zhao
Background The association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown. Methods Fecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins. Results Non-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae , and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases. Conclusion We revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.
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ENVIRONMENTAL MICROBIOLOGY
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2021
·Vol. 23
·期 9
·5147-5163
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IF 5.491
Can Zhang,Meng Cai,Shanshan Chen,Fan Zhang,Tongshan Cui,Zhaolin Xue,Weizhen Wang,Borui Zhang,Xili Liu
Summary Asparagine (Asn, N )-linked glycosylation within N glyco -X-S/T; X ≠ P motif is a ubiquitously distributed post-translational modification that participates in diverse cellular processes. In this work, N -glycosylation inhibitor was shown to prevent Phytophthora sojae growth, suggesting that N -glycosylation is necessary for oomycete development. We conducted a glycoproteomic analysis of P. sojae to identify and map N -glycosylated proteins and to quantify differentially expressed glycoproteins associated with mycelia, asexual cyst, and sexual oospore developmental stages. A total of 355 N -glycosylated proteins was found, containing 496 glycosites, potentially involved in glycan degradation, carbon metabolism, glycolysis, or other metabolic pathways. Through PNGase F deglycosylation assays and site-directed mutagenesis of a GPI transamidase protein (GPI16) upregulated in cysts and a heat shock protein 70 (HSP70) upregulated in oospores, we demonstrated that both proteins were N -glycosylated and that the N glyco -N motif is a target site for asparagine – oligosaccharide linkage. Glycosite mutations of Asn 94 N glyco -X-S/T in the GPI16 led to impaired cyst germination and pathogenicity, while mutation of the previously unknown Asn 270 N glyco -N motif in HSP70 led to decreased oospore production. In addition to providing a map of the oomycete N -glycoproteome, this work confirms that P. sojae has evolved multiple N -glycosylation motifs essential for growth.
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Food & Function
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2020
·Vol. 11
·期 11
·9535-9546
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IF 4.171
Na Deng,Ruixue Guo,Bisheng Zheng,Tong Li,Rui Hai Liu
The effects of whole grain highland barley (WGH) with rich phenolics on glucose metabolism, the insulin pathway, and microRNA (miRNA) expression in db/db mice were explored in the present study. Supplementation with WGH decreased the levels of blood glucose, glycosylated serum protein (GSP), insulin, and inflammatory cytokines in db/db mice. Furthermore, WGH administration triggered a remarkable amelioration of glucose intolerance and insulin resistance. The hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) activities and the G6PC, PEPCK, and forkhead transcription factor 1 (FOXO1) mRNA levels in the WGH-treated group were also reduced. Moreover, WGH promoted the glycogen storage in the liver via up-regulating the activities of hexokinase (HK) and glycogen synthase (GS) and the phosphorylation of glycogen synthase kinase 3β (GSK3β) protein, while down-regulating the GSK3β mRNA level. The protein expression of phosphatidylinositol 3-kinase (PI3K), the phosphorylation of protein kinase B (Akt), and the mRNA levels of insulin receptor substrate-1 (IRS-1), PI3K and Akt were also up-regulated by WGH treatment. Moreover, WGH significantly augmented the expression of miRNA-26a and miRNA-451, but reduced those of miRNA-126a and miRNA-29a. These results demonstrated that WGH exhibits a hypoglycemic effect through regulating the IRS-1/PI3K/Akt pathway and related miRNAs, further modulating the expression of G6PC, PEPCK, and FOXO1 mRNAs and p-GSK3β protein, thus inhibiting hepatic gluconeogenesis, improving glycogen synthesis and alleviating insulin resistance. Therefore, this study suggested WGH as an effective candidate to ameliorate the hyperglycemia of type 2 diabetes mellitus.
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ENVIRONMENTAL POLLUTION
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2020
·
IF 6.793
Jing Zhan,Xiaoran Ma,Donghui Liu,Yiran Liang,Peize Li,Jingna Cui,Zhiqiang Zhou,Peng Wang
Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host’s physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.
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Journal of Cancer
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2020
·
IF 3.565
Ying Song,Chen Li,Yahan Fu,Qiu Xie,Jun Guo,Guangming Li,Huiwen Wu
The integrin receptor protein talin plays vital roles in intracellular chemical and mechanical activities, and it is implicated in the high invasion and poor prognosis of non-small cell lung cancer (NSCLC). To better understand the mechanism underlying the function of talin in NSCLC invasion and metastasis, a few newly designed tension probe based on Förster resonance energy transfer was used for real-time observation of tension changes in A549 cells. High NSCLC cell aggressiveness was found to be accompanied with inward talin and outward glial fibrillary acidic protein (GFAP) tensions, which are closely associated with microfilament (MF) force and intracellular osmotic potential. The increased osmotic pressure resulted from the production of intracellular protein nanoparticles and the related ion influx. Furthermore, integrin activation was found to adjust the talin and GFAP tensions. Disruption of the interaction between talin and MFs blocked the mechanical source of talin, reducing both talin tension and osmotic pressure and thus inhibiting NSCLC cell invasion and migration. Consequently, our study demonstrates that talin is involved in NSCLC invasion and migration via its inward tension and that the integrin pathway is correlated closely with protein-nanoparticle-induced outward osmotic pressure.
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