Probiotics and Antimicrobial Proteins
·
2025
·
IF 4.4
Zhao Yi,Dai Zhengqun,Lang Yanmei,Li Rui,Zheng Hongyu,Mi Jiajia,He Xiu,Liu Jin,Xiang Rong,Mei Xueran,Liu Yang,Wang Yantang,Guo Huijie,Yang Qian,Ren Ke,Yang Tai
Chemotherapy-induced diarrhea (CID) is a frequent gastrointestinal side effect in cancer patients, particularly associated with the use of 5-fluorouracil (5-FU). This study aimed to isolate multiple Bacteroides strains from the feces of healthy individuals and identify Bacteroides eggerthii ( B. eggerthii ) S13-F8 as the optimal candidate for alleviating CID. Whole-genome sequencing of B. eggerthii S13-F8 was conducted to uncover its functional characteristics and explore the potential mechanisms underlying its protective effects against CID. The anti-CID efficacy of B. eggerthii S13-F8 was assessed using multiple parameters, including diarrhea severity, food intake, and body weight changes. Comprehensive analyses, including blood tests, intestinal histopathology, colon transcriptomics, and fecal metagenomics, were performed to elucidate its underlying mechanisms. In a 5-FU-induced mouse model, B. eggerthii S13-F8 significantly alleviated weight loss and diarrhea. Histological examination revealed that B. eggerthii S13-F8 preserved the villus height-to-crypt depth (V/C) ratio and protected goblet cells in colonic tissues. Gene expression analysis showed that B. eggerthii S13-F8 upregulated protective markers, such as Aqp8 , Slc26a3 , and mucin-related genes ( TFF3 , FCGBP , and Muc2 ), while downregulating pro-inflammatory mediators, including IL-1α , IL-22 , and Cxcl2 . Furthermore, B. eggerthii S13-F8 modulated gut microbiota composition by suppressing pathogenic bacteria ( Pseudomonas aeruginosa , Salmonella , γ-Proteobacteria, and Shigella ) and enriching beneficial taxa, such as Lactobacillus and Akkermansia muciniphila . In conclusion, B. eggerthii S13-F8 demonstrates significant potential in mitigating severe diarrhea caused by 5-FU chemotherapy, providing a strong foundation for its development as a live biotherapeutic for CID treatment.
研究领域:
医学
·
微生物学
·
基因组学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Chenchen Li,Juan Ge,Dan Song,Tao Liang,Zhen Li
Clinical chemotherapy drugs may induce severe hepatic damage and toxicity with prolonged use, which is a major concern among the various adverse effects associated with chemotherapy. Early diagnosis of chemotherapy-induced liver injury (CILI) is critical to prevent its progression into other liver diseases and potential liver failure. However, there is currently a lack of effective tools for early monitoring of CILI. To address this issue, it is developed a glutathione (GSH)-activated ratiometric second near-infrared (NIR-II) nano-probe, HCy-CL-RENPs, which utilizes rare earth ions-doped nanoparticles (RENPs) as the luminescence signal reporters and hemicyanine dye HCy-CL as the recognition unit to react with GSH, thereby modulating the NIR-IIb emission of RENPs. This probe exhibits high sensitivity and specificity for detecting GSH, along with excellent biocompatibility. Utilizing HCy-CL-RENPs, it is accurately evaluated the hepatotoxicity of different chemotherapy drugs and successfully detected CILI within 5 h after drug administration, significantly earlier than existing methods such as serum enzyme detection and biopsy. These findings indicate that the probe can facilitate early assessment of liver injury by monitoring changes in GSH levels, providing a robust tool for the early diagnosis of CILI and guiding personalized treatment strategies.
研究领域:
生物医学工程
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药理学
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肝脏病学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Mingyue Yin,Xinyi Xiao,Yang Xiao,Jingyan Zhou,Shuxian Liu,Xue Jiang,Xiaomin Han,Tao Zhuang,Yin Chen
Chemotherapy-induced peripheral neuropathy (CIPN) represents a common dose-limiting adverse effect of chemotherapeutic drugs, affecting 25-90% of cancer patients. However, currently available medications often show limited efficacy for CIPN, which necessitates the development of novel analgesics. An emerging perspective is that neuroinflammation represents one of the possible pathogeneses underlying CIPN. In our studies, isobolographic analysis revealed that co-administration of celecoxib with pregabalin or gabapentin produced antinociceptive effects for CIPN. Based on multimodal analgesia, two new co-drugs CEL-PRE and CEL-GBP were synthesized from celecoxib with pregabalin/gabapentin to achieve synergistic antinociceptive effects for CIPN. Both CEL-PRE and CEL-GBP showed more than 200 times higher water solubility than celecoxib. In vitro liver microsome assays showed that these co-drugs can be metabolized into two parent drugs within 30 min. CEL-PRE and CEL-GBP exhibited significant efficacy in paclitaxel-induced neuropathic pain models with ED 50 values of 4.27 mg/kg and 6.55 mg/kg, respectively. At equimolar doses, CEL-PRE and CEL-GBP demonstrated superior antinociceptive effects than single drugs for paclitaxel-induced neuropathy. Both of the two co-drugs can alleviate inflammation by inhibiting inflammatory mediators (IL-6, IL-1β, TNF-α, COX-2, and PGE 2 ) and suppress the expression of neuronal c-Fos, which were significantly elevated in CIPN. Additionally, CEL-PRE and CEL-GBP do not affect motor coordination in rotarod tests. Therefore, novel co-drugs CEL-PRE and CEL-GBP are promising candidates for treating CIPN.
研究领域:
药理学
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肿瘤学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Science Translational Medicine
·
2022
·Vol. 14
·期 673
·
IF 19.319
Sisi Xie,Chenyu Jiang,Meng Wu,Ying Ye,Biying Wu,Xiaoting Sun,Xue Lv,Ruibo Chen,Wen Yu,Qi Sun,Yuting Wu,Rongliang Que,Huilan Li,Ling Yang,Wen Liu,Ji Zuo,Lasse D. Jensen,Guichun Huang,Yihai Cao,Yunlong Yang
Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet–induced circulating β-hydroxybutyrate (β-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-β-hydroxybutyrate dehydrogenase (BDH)–mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked β-OHB–induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body–MCT1–BDH–histone acetylation–platelet biogenesis axis in megakaryocytes and propose a nontoxic, low-cost dietary intervention for combating CIT.
研究领域:
医学
·
分子生物学
·
营养学
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DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Wenjie Dai,Bo Xu,Liyang Ding,Zhen Zhang,Hong Yang,Tiantian He,Ling Liu,Xiuying Pei,Xufeng Fu
Primary ovarian insufficiency (POI) in younger women (under 40) manifests as irregular periods, high follicle-stimulating hormone (FSH), and low estradiol (E2), often triggered by chemotherapy. Though mesenchymal stem cell (MSC) therapy shows promise in treating POI, its exact mechanism remains unclear. This study reveals that human umbilical cord-derived MSCs (hUC-MSCs) can protect ovarian granulosa cells (GCs) from cyclophosphamide (CTX)-induced ferroptosis, a form of cell death driven by iron accumulation. CTX, commonly used to induce POI animal model, triggered ferroptosis in GCs, while hUC-MSCs treatment mitigated this effect, both in vivo and in vitro . Further investigations using ferroptosis and autophagy inhibitors suggest that hUC-MSCs act by suppressing ferroptosis in GCs. Interestingly, hUC-MSCs activate a protective antioxidant pathway in GCs via NRF2, a stress-response regulator. Overall, our findings suggest that hUC-MSCs improve ovarian function in CTX-induced POI by reducing ferroptosis in GCs. This study not only clarifies the mechanism behind the benefits of hUC-MSCs but also strengthens the case for their clinical use in treating POI. Additionally, it opens up a new avenue for protecting ovaries from chemotherapy-induced damage by regulating ferroptosis.
研究领域:
干细胞生物学
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生殖医学
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肿瘤学
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细胞死亡机制
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药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Jing Xu,Zhenwei Yang,Xuemin Cao,Jibin Liu,Yubo Yang,Jing Qi,Zhaozheng Ren,Siyuan Yin,Yuhan Liu,Yujuan Zhu,Lin Chen,Feng Wang
Chemotherapy-induced peripheral neuropathy (CIPN), a severe neurological complication caused by chemotherapeutic agents, posed a significant challenge in pain management due to its complex pathogenesis involving oxidative stress, neuroinflammation, and metabolic dysregulation. Herein, the study develops novel microenvironment-responsive piezoelectric nanofibers (PPK) with piezoelectric nanoparticles by electrospinning, which can be applied to alleviate CIPN with ultrasound. The thioether bond in PPK nanofibers underwent phase transformations in ROS environments, which endowed the nanofiber with ROS sensitivity. Furthermore, ultrasound induced piezoelectric PPK nanofibers with enhanced electrokinetic effect. Cellular experiments validate the robust ROS scavenging ability of the PPK nanofibers alongside high biocompatibility. Moreover, PPK nanofibers exhibit marked downregulation of inflammatory factors in nerve cells. Notably, after the implantation in CIPN rats, the PPK nanofibers are found to sustain accumulation at the dorsal root ganglion (DRG) area and significantly alleviate thermal hyperalgesia and mechanical allodynia. Moreover, the treatment using PPK nanofibers demonstrates attenuation of neuroinflammation and satellite glial cells activation in DRGs of CIPN rats. To investigate the underlying mechanism, transcriptomic profiling further unveils PPK-mediated activation of glycolytic pathways and metabolic reprogramming, which potentially provide new clues for neural recovery. Collectively, this work establishes a promising therapeutic platform for mitigating CIPN and other neurological complications.
研究领域:
神经病学
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生物材料学
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疼痛医学
·
转化医学
·
纳米医学
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分子神经生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yi Han,Yanchao Liu,Xiaoyi Ma,Aijun Shen,Yiqiong Liu,Nopphon Weeranoppanant,Haiqing Dong,Yan Li,Tianbin Ren,Le Kuai,Bin Li,Maomao An,Yongyong Li
Chemotherapy-induced neutropenia, a symptom of neutrophil depletion, makes cancer patients highly susceptible to invasive fungal infection with substantial morbidity and mortality. To address the cryptococcal brain infection in this condition, this study attempts to arm neutrophils (NEs) with antibiotics to potentiate the antifungal capability of NEs. To allow effective integration, amphotericin B, a potent antibiotic, is assembled with albumin nanoparticles through hydrophobic and hydrogen-bond interactions to form [email protected] nanoparticles (A-NPs). The nutrient composition (albumin) and virus-like size (~40 nm) facilitate efficient uptake of A-NPs by NEs to construct the antibiotics-armed NEs. It is demonstrated that the armed NEs can maintain the intrinsic biological functions of NEs, such as cell viability and capacity of migration to an inflammatory site. In a neutropenic mouse model of brain fungal infection, the treatment with the armed NEs allows for preventing fungal invasion more effectively than that with the native NEs, without the apparent systemic toxicity. Such a synergistic anti-infection system maximizes the antifungal effects by taking advantage of NEs and antibiotics. It provides a potential NEs-mediated therapeutic approach for treating fungal infection caused by chemotherapy-induced neutropenia.
研究领域:
肿瘤学
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药理学
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纳米技术
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传染病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2024
·
IF 5.2
Chao Sun,Qiushuang Ma,Liya Feng,Jianbo Ji,Dandan Du,Pengfei Shang,Xiuli Guo
Aims This study aims to investigate the role of SOD3 in gastric cancer (GC) progression and its impact on chemotherapy efficacy and toxicity. It further seeks to evaluate the therapeutic potential of MCP in enhancing SOD3 activity to improve treatment outcomes and reduce chemotherapy-induced peripheral neurotoxicity (CIPN). Materials and methods We used overexpression plasmids and small interfering RNAs (siRNAs) to modulate the expression of SOD3 and Desmocollin2 (DSC2) in gastric cancer cells. Molecular biology experiments were performed to analyze pathway-related protein expression and molecular interactions. In vitro and in vivo experiments were conducted to evaluate the effects of modified citrus pectin (MCP) and oxaliplatin (OXA), individually and in combination, on gastric cancer progression and CIPN. Key findings SOD3 inhibited the proliferation, migration, and invasion of GC cells via SOD3/EGFR/PKP3/DSC2 axis. MCP selectively increased SOD3 levels and enhanced its anti-tumor effects. Combined treatment with MCP and OXA synergistically inhibited GC progression in vitro and in vivo, while MCP alleviated CIPN, enabling OXA dose reduction without compromising efficacy. Significance The findings revealed that SOD3 played a critical tumor-suppressive role in gastric cancer by modulating the SOD3/EGFR/PKP3/DSC2 axis. MCP, a natural compound that selectively boosted SOD3 levels, enhanced chemotherapy efficacy while reducing peripheral neurotoxicity, providing a promising strategy to improve gastric cancer treatment and mitigate chemotherapy-related side effects.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·Vol. 26
·期 4
·106414-106414
·
IF 5.8
Hu Liu,Xin Qing,Lijun Peng,Ding Zhang,Wei Dai,Zhilai Yang,Jiqian Zhang,Xuesheng Liu
Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a progressive and disturbing peripheral neuropathy with currently no effective treatment. Aberrant production of reactive oxygen species (ROS) in macrophages near peripheral nerves plays a dominant role in CIPNP; however, traditional ROS scavengers have difficulty maintaining viability to target macrophages in vivo . Mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized to treat CIPNP. The anti-ROS and anti-inflammatory effects of mSPIONs were assessed in J774A.1 cells and sciatic nerves in a nociception mouse model induced with vincristine (VCR). We found that the mSPIONs significantly reduced ROS levels in vitro and in vivo . Furthermore, mSPIONs administration specifically reduced IL-6 and TNF-α levels in macrophages near the sciatic nerve and relieved VCR-induced peripheral neuropathic pain. Inhibition of the VCR-upregulated HIF1α/NF-κB signaling pathway may be involved in the alleviation of inflammation. These results provide a new approach for relieving CIPNP using a nanozyme.
研究领域:
纳米技术
·
药理学
·
神经科学
·
肿瘤学
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DOI
PubMed
高影响因子
Reproductive Sciences
·
2020
·Vol. 27
·期 7
·1502-1512
·
IF 2.616
Feng Xiushan,Ling Li,Zhang Wenqian,Liu Xiaohan,Wang Yaping,Luo Yanjing,Xiong Zhengai
Human amnion–derived mesenchymal stem cell (hAD-MSC) transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced primary ovarian insufficiency (POI). However, ensuring that stem cells home to the ovary to improve their effects on ovarian injury is challenging. This research aimed to directly inject ovarian tissue with hAD-MSCs and improve the homing of stem cells to the ovary. The animals were divided into POI, hAD-MSC (tail vein) treatment, hAD-MSC (in situ) treatment, and control groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). The hAD-MSCs isolated from the amnion were injected into the tail vein or ovary of POI rats. The estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, and proteome of the ovaries were evaluated. hAD-MSCs were successfully isolated and cultured from the amnion. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantation increased body weight, improved the AMH levels and follicle numbers, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs (in situ) upregulated 24 proteins and downregulated 4 proteins. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantations can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. The paracrine proteome of hAD-MSCs in the ovarian microenvironment can protect against chemotherapy-induced damage by reducing apoptosis and promoting angiogenesis, cell proliferation, and gene expression.
研究领域:
干细胞生物学
·
生殖医学
·
肿瘤学
·
蛋白质组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PAIN
·
2023
·
IF 4
Yuehong Zhang,Xuelin Huang,Wen-Jun Xin,Shilang He,Jie Deng,Xiangcai Ruan
Projections from the periaqueductal gray (PAG) to the rostral ventromedial medulla (RVM) are known to engage in descending pain modulation, but how the neural substrates of the PAG-RVM projections contribute to neuropathic pain remains largely unknown. In this study, we showed somatostatin-expressing glutamatergic neurons in the lateral/ventrolateral PAG that facilitate mechanical and thermal hypersensitivity in a mouse model of chemotherapy-induced neuropathic pain. We found that these neurons form direct excitatory connections with neurons in the RVM region. Inhibition of this PAG-RVM projection alleviates mechanical and thermal hypersensitivity associated with neuropathy, whereas its activation enhances hypersensitivity in the mice. Thus, our findings revealed that somatostatin neurons within the PAG-RVM axial are crucial for descending pain facilitation and can potentially be exploited as a useful therapeutic target for neuropathic pain. Perspective We report the profound contribution of somatostatin neurons within the PAG-RVM projections to descending pain facilitation underlying neuropathic pain. These results may help to develop central therapeutic strategies for neuropathic pain.
研究领域:
神经科学
·
疼痛研究
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2021
·
IF 3.5
Meiting Wang,Jiaxian Wang,Alex Y.P. Tsui,Zhaomin Li,Yizhe Zhang,Qi Zhao,Hongyan Xing,Xijie Wang
The awareness of the long-term toxicities of cancer survivors after chemotherapy treatment has been gradually strengthened as the population of cancer survivors grows. Generally, chemotherapy-induced peripheral neurotoxicity (CIPN) is studied by animal models which are not only expensive and time-consuming, but also species-specific differences. The generation of human induced pluripotent stem cells (hiPSCs) and differentiation of peripheral neurons have provided an in vitro model to elucidate the risk of CIPN. Here, we developed a drug-induced peripheral neurotoxicity model using hiPSC-derived peripheral neurons (hiPSC-PNs) to study the mechanisms of different chemotherapeutic agents on neuronal viability using LDH assay, a cell apoptosis assay determined by caspase 3/7 activation, neurite outgrowth, ion channel expression and neurotransmitter release following treatment of cisplatin, bortezomib, ixabepilone, or pomalidomide. Our data showed that the multiple endpoints of the hiPSC-PNs model had different sensitivity to various chemotherapeutic agents. Furthermore, the chemotherapeutics separated cell viability from the decrease in neurite lengthand changed levels of ion channels and neurotransmitters to a certain extent. Thus, we study the mechanisms of peripheral neurotoxicity induced by chemotherapeutic agents through changes in these indicators.
研究领域:
肿瘤学
·
神经科学
·
干细胞生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
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