Frontiers in Pharmacology
·
2025
·
IF 4.8
Jinpeng Lv,Duo Meng,Huansha Zhang,Wenhui Xu,Xiaohong An,Chuanwei Yin,Kun Zou,Rongyin Gao
Introduction: Apigenin, a natural flavonoid with well-established antioxidant, anticancer, and anti-inflammatory activities, has recently attracted attention for its pigmentation-promoting effects. However, the underlying molecular mechanisms driving its melanogenic activity remain incompletely understood.Method: To investigate apigenin‘s effects on melanogenesis, human epidermal melanocytes (HEMCs), zebrafish embryos, and human skin explants were treated with apigenin. Melanin content, dendrite formation, and melanosome maturation were evaluated using spectrophotometry and transmission electron microscopy. Key signaling molecules and proteins involved in melanogenesis and melanosome transport were assessed by Western blotting and immunohistochemistry. The role of the c-KIT receptor was further explored through pharmacological inhibition and genetic knockdown approaches. Functional pigmentation was evaluated by assessing UVB-induced DNA damage markers.Results: Apigenin (10 μM) significantly increased melanin production by 1.8-fold in HEMCs, enhanced dendritic morphology, and promoted stage III–IV melanosome formation. Mechanistically, apigenin induced melanogenesis independently of the MC1R/cAMP/PKA pathway by directly binding to the c-KIT receptor, activating the Raf-1/ERK/RSK cascade, and upregulating MITF. This led to elevated expression of tyrosinase, TRP-1, TRP-2, and melanosome transport proteins Rab27a and Cdc42. Inhibition or knockdown of c-KIT abrogated these effects. In vivo, apigenin restored pigmentation in PTU-induced depigmented zebrafish and increased melanin content by 1.3-fold in human skin explants. Histological analysis confirmed effective melanin transfer to keratinocytes. Additionally, apigenin-treated skin showed reduced UVB-induced DNA damage, indicating enhanced photoprotection.Discussion: These findings demonstrate that apigenin stimulates melanogenesis through a novel c-KIT-dependent signaling pathway and promotes functional pigmentation with photoprotective benefits. Given its dietary origin, favorable safety profile, and multifaceted mechanisms, apigenin holds promise as a therapeutic agent for vitiligo and a natural pigmentation enhancer for dermatological use.
研究领域:
细胞生物学
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皮肤病学
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药理学
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DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Yunhe Yang,Yang Yang,Shuangshuang Wang,Huihui Li,David D.Y. Chen
The formation of G-quadruplex (G4) structures in oncogenic G-rich promoter regions are implicated in their biological functions, especially the inhibition of transcription. The binding of cations is thought to contribute to the stabilization of the G4 formation and competition against the duplex formation in the genomic sequence. Furthermore, it might affect the recognition of DNA-binding proteins. Therefore, measuring the interaction between G4 DNA and cations in a free solution environment is critical for evaluating G4 DNA biological functions. However, how binding to cations (K + and NH 4 + ) affects the folding equilibrium of the G4 structure remains unclear. In this work, a Taylor dispersion analysis (TDA) method using a capillary electrophoresis (CE) instrument was established for the quantitative characterization of the cation-dependent G4 formation in the human c-KIT oncogene promoter region, as well as diffusivities and hydrodynamic radii of DNA variations before and after folding. Our results showed that both K + and NH 4 + can induce the random-coiled c-KIT DNA to unfold and form a more unstretched intermediate state and then fold into tightly structured G4s with smaller size. The G4 size induced by NH 4 + was smaller than that induced by K + ions, though these two cations induced the c-KIT G4 DNA formation with similar binding constants (order of magnitude around 10 6 M −1 ). The TDA method can be widely used for rapid structural analyses of trace amounts of DNA mixtures, which effectively differentiate DNA variations or DNA-ligand complex conformations.
研究领域:
生物化学
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分子生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2025
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IF 5.1
Shuting Zou,Bin Xie,Zhentao An,Fang Li,Li Cui,Zhenhai Zhang,Weiquan Bu,Dandan He
Objective The aroma of the aromatic class of traditional Chinese medicines can promote gastrointestinal peristalsis. This study aimed to explore the mechanisms by which volatile oil from Citri Reticulatae Pericarpium Viride (VOCRPV) alleviates slow-transit constipation (STC).Methods The main active ingredients in VOCRPV were determined by High-Performance Liquid Chromatography (HPLC). Due to poor stability, an olive oil solution was prepared to enhance the volatile oil’s stability. A mouse model of STC was induced using loperamide hydrochloride. The mice’s body weight was monitored weekly. The number of fecal pellets, fecal water content, and small intestinal propulsion rate were detected. The colon tissues were analyzed using HE staining. The serum content of gastrointestinal hormones was measured using the corresponding ELISA kit. The protein expressions of stem cell factor (SCF) and c-Kit in colon tissues were detected by Western blot and immunohistochemistry methods. The 16S rRNA gene sequencing was used to detect the intestinal flora.Results The contents of p-isopropyl toluene, γ-Terpinene, and d-Limonene were determined by HPLC. VOCRPV and its olive oil solution significantly enhanced body weight, increased the number of fecal pellets, improved fecal water content, and boosted small intestinal propulsion rate in mice with loperamide-induced STC, while also repairing colon mucosa damage. They also increased gastrin (Gas) and motilin (MTL) levels in treated mice, upregulated the expression of SCF and c-Kit proteins, and restored intestinal flora balance in STC mice.Conclusion VOCRPV could effectively alleviate STC, and olive oil enhances its therapeutic effect. VOCRPV alleviates STC by elevating Gas and MTL levels, activating the SCF/c-Kit signaling pathway, and modulating intestinal flora.
研究领域:
中药学
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消化系统研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2023
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IF 2.8
Li Cui,Bin Zhang,Shuting Zou,Jing Liu,Pingrong Wang,Hui Li,Zhenhai Zhang
In this study we sought to elucidate the therapeutic effects of fenchone on constipation-predominant irritable bowel syndrome (IBS-C) and the underlying mechanisms. An IBS-C model was established in rats by administration of ice water by gavage for 14 days. Fenchone increased the reduced body weight, number of fecal pellets, fecal moisture, and intestinal transit rate, and decreased the enhanced visceral hypersensitivity in the rat model of IBS-C. In addition, fenchone increased the serum content of excitatory neurotransmitters and decreased the serum content of inhibitory neurotransmitters in the IBS-C rat model. Meanwhile, western blot and immunofluorescence experiments indicated that fenchone increased the expressions of SCF and c-Kit. Furthermore, compared with the IBS-C model group, fenchone increased the relative abundance of Lactobacillus , Blautia , Allobaculum , Subdoligranulum , and Ruminococcaceae_UCG-008 , and reduced the relative abundance of Bacteroides , Enterococcus , Alistipes , and Escherichia-Shigella on the genus level. Overall, fenchone ameliorates IBS-C via modulation of the SCF/c-Kit pathway and gut microbiota, and could therefore serve as a novel drug candidate against IBS-C.
研究领域:
药理学
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胃肠病学
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微生物学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2021
·Vol. 23
·期 5
·1-9
·
IF 2.952
Yang Yao,Ranyuan Luo,Shu Xiong,Chang Zhang,Yukun Zhang
Intestinal inflammation frequently occurs alongside dysmotility, which is characterized by altered myosin light chain phosphorylation levels. Curcumin, an active component from the ginger family, is reported to confer anti‑inflammatory effects. However, the effects of curcumin on both diarrhea and constipation associated inflammation remains to be elucidated. The present study was designed to investigate the effects of curcumin on diarrhea and constipation and to determine the related mechanisms. Sprague‑Dawley rats were used to establish diarrhea and constipation models via intracolonic acetic acid (4%) instillation or cold water gavage for 2 weeks, respectively. Blood samples were collected to measure the serum levels of the cytokines TNF‑α and IL‑1β using ELISA kits. Western blotting was performed to measure NF‑κB, RhoA, Rho‑related kinase 2, phosphorylated MLC20, phosphorylated myosin phosphorylated target subunit 1, 130k Da‑MLC kinase (MLCK), c‑kit tyrosine kinase protein expression, and reverse transcription‑quantitative PCR was conducted to measure MLCK expression levels. The results indicated that curcumin reversed the elevations in the pro‑inflammatory cytokines IL‑1β and TNF‑α by inhibiting the NF‑κB pathway in rats with diarrhea and constipation. The results also indicated that myosin light chain (MLC) phosphorylation in intestinal smooth muscle was positively and negatively associated with the motility of inflammation‑related diarrhea and constipation in rats, respectively. Curcumin significantly reversed the increased MLC phosphorylation in the jejunum of the rats with diarrhea, significantly enhanced the reductions in inflammatory mediators, including TNF‑α and IL‑1β, of rats with constipation and significantly ameliorated the related hyper‑motility and hypo‑motility in rats with both diarrhea and constipation. In conclusion, the potential roles of the MLC kinase, c‑kit tyrosine and Rho A/Rho‑associated kinase 2 pathways, which are involved in curcumin‑induced amelioration of inflammation‑related diarrhea and constipation, were explored in the present study. Results from the present study suggested that curcumin has potential therapeutic value for treating intestinal inflammation and inflammation‑related motility disorders.
研究领域:
药理学
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胃肠病学
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炎症
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Tianyuan Bian,Shitao Gao,Xinyu Sun,Songtao Zhou,Yufeng Pei,Jie Song
G-quadruplexes (G4s) are noncanonical DNA structures that regulate gene expression by serving as mechanical barriers. Telomeric DNA and oncogenic promoter regions (e.g., c-KIT and h-RAS) often contain multiple G-quadruplex structures, which may regulate the transcription of adjacent genes through their interactions. These G4 clusters hold significant therapeutic potential as drug targets for cancer treatment. Thus, understanding the interactions within G4 clusters is of considerable importance. However, current bulk measurements struggle to elucidate the dynamic interactions among multiple intrastranded G4s due to the presence of potential interstrand interactions. Herein, we establish a single-molecule platform to investigate the intrastrand interactions between G4s in the c-KIT promoter region. Our results reveal that these G4 units interact to form higher-order structures, with kit* acting as a key regulator that couples and influences the formation and stability of adjacent G4 units. This single-molecule platform can also detect interactions between small-molecule ligands and consecutive G4 clusters. Compared to CX-5461, PDS is a more effective inhibitor of c-KIT. This single-molecule detection method provides robust support for investigating the intrastrand interactions between consecutive G4 structures.
研究领域:
分子生物学
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生物物理学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
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2015
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IF 1.206
Chuan Li,Shao-Ping Nie,Ke-Xue Zhu,Tao Xiong,Chang Li,Joshua Gong,Ming-Yong Xie
Lactobacillus plantarum, as a probiotic, has many functional properties in human intestinal tract. This study examined the effects of L. plantarum NCU116 on loperamide-induced constipation in a mouse model. Loperamide (5 mg kg−1) was injected subcutaneously to induce constipation. Animals were divided to five groups: normal group, constipation group, constipation plus three doses of L. plantarum NCU116 groups (NCU116-L, 107 CFU/mL; NCU116-M, 108 CFU/mL; NCU116-H, 109 CFU/mL; respectively). Mice were treated with the probiotic for 15 d to assess the anti-constipation effects. Fecal parameters, intestinal transit ratio and the production of fecal short chain fatty acids, histological of colon and immunohistochemical in colonic interstitial cells of Cajal (ICC) by c-kit were all improved in L. plantarum NCU116-treated mice as compared to the constipation group. These results demonstrate that L. plantarum NCU116 enhanced gastrointestinal transit and alleviated in mice with loperamide-induced constipation.
研究领域:
胃肠病学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Yao Li,Zi-Yu Liang,Hai-Lin Wang
Summary Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2′-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1. Mechanistic studies suggested that 6mdA enhances and prolongs the activation of erythropoiesis-associated master gene c-Kit and its downstream signaling, leading to expansion and accumulation of EPCs. Collectively, we demonstrate that 6mdA can efficiently stimulate the EPC hyperproliferation and provide a new regenerative medicine recipe to improve ex vivo generation of red blood cells.
研究领域:
血液学
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分子生物学
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再生医学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qi Wenbo,Xu Lijian,Zhao Shuangdan,Zheng Jiahua,Tian Yanpeng,Qi Xuejun,Huang Xianghua,Zhang Jingkun
Herein we report a facile approach for chitosan-heparin hydrogels with controlled release manner and their applications for intrauterine adhesion. The sol precursor was converted to gel at physiological temperature in 15 min. FTIR, SEM and swelling test were performed to characterize their compositions, morphologies and stability. In vitro releasing profiles was investigated in PBS solutions. Intrauterine injured rat model was established and treated with different methods. The results of H&E staining, Masson trichrome staining, western blots assay, immunohistochemical staining and immunofluorescence staining revealed that endogenous c-kit positive stem cells (HSCs) were recruited to the injury site and promoted the wound recovery. After 7 days' treatment, uterus treated with SDF-1α releasing hydrogel showed no difference with control group on endometrial thickness, glands number and fibrosis level. This work provides a possible method for intrauterine adhesion healing.
研究领域:
组织工程
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再生医学
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生物材料
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
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2016
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IF 3.146
Yang Liu,Yachen Xu,Zhenhua Wang,Dezhong Wen,Wentian Zhang,Sebastian Schmull,Haiyan Li,Yao Chen,Song Xue
Electrospun nanofibrous sheets get increasing attention in myocardial infarction (MI) treatment due to their good cytocompatibility to deliver transplanted stem cells to infarcted areas and due to mechanical characteristics to support damaged tissue. Cardiac extracellular matrix is essential for implanted cells since it provides the cardiac microenvironment. In this study, we hypothesized high concentrations of cardiac nature protein (NP), namely elastin and collagen, in hybrid polycaprolactone (PCL) electrospun nanofibrous sheets could be effective as cardiac-mimicking patch. Optimal ratio of elastin and collagen with PCL in electrospun sheets (80% NP/PCL) was selected based on cytocompatibility and mechanical characteristics. Bone-marrow (BM) c-kit + cells anchoring onto NP/PCL sheets exhibited increased proliferative capacity compared with those seeded on PCL in vitro. Moreover, we examined the improvement of cardiac function in MI mice by cell-seeded cardiac patch. Green Fluorescent Protein (GFP)-labeled BM c-kit + cells were loaded on 80% NP/PCL sheets which was transplanted into MI mice. Both 80% NP/PCL and c-kit + -seeded 80% NP/PCL effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. C-kit + -seeded 80% NP/PCL was even superior to the 80% NP/PCL alone and both superior to PCL. GFP + cells were identified both in the sheets and local infarcted area where transplanted cells underwent cardiac differentiation after 4 weeks. To the best of our knowledge, this is the first report that sheets with high concentrations of nature proteins loaded with BM c-kit + cells might be a novel promising candidate for tissue-engineered cardiac patch to improve cardiac repair after MI.
研究领域:
生物医学工程
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心脏病学
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组织工程
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产品关联
DOI
PubMed
高影响因子
World Journal of Gastrointestinal Surgery
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2023
·
IF 2
Fan Ding,Run Guo,Fang Chen,Li-Ping Liu,Zheng-Yu Cui,Yi-Xing Wang,Gang Zhao,Hai Hu
BACKGROUND Impaired interstitial cells of Cajal (ICCs) are central to the pathophysiology of acute cholecystitis (AC). Common bile duct ligation is a common model of AC, producing acute inflammatory changes and decrease in gallbladder contractility. AIM To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC. METHODS Methylene blue (MB) with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control (NC), AC12h, AC24h, and AC48h groups of guinea pigs. Hematoxylin and eosin and Masson-stained gallbladder tissues were scored for inflammatory changes. ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot. RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility. The frequency of SW and gallbladder contractility were significantly lower in the AC12h group. Compared with the NC group, the density and ultrastructure of ICCs were remarkably impaired in the AC groups, especially in the AC12h group. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group. CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility. The density and ultrastructure of ICCs were clearly impaired in the early stage of AC, while CCKAR and CX43 were significantly reduced at end stage.
研究领域:
胃肠病学
·
生理学
·
病理生理学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Long Fang,Ruofei Zhang,Lin Shi,Jiaying Xie,Long Ma,Yili Yang,Xiyun Yan,Kelong Fan
The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of C-KIT protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）