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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE · 2024 ·Vol. 53 ·期 4 ·1-16 · IF 5.7

Elimination of intracellular Ca2+ overload by BAPTA‑AM liposome nanoparticles: A promising treatment for acute pancreatitis

Zailin Fu,Dingsheng Wang,Caiyun Zheng,Minghua Xie,Yifang Chen,Yi Zhou,Yan Huang,Ying Song,Weiyong Hong

Calcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA‑AM), a cell‑permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models in vitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and in vivo, intra‑ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA‑AM‑loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5 to 75%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF‑α, IL‑6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca2+ overload in patients with AP.

研究领域: 药理学 · 医学 · 纳米技术 · 细胞生物学 · 炎症 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Inorganics · 2024 ·Vol. 12 ·期 6 ·152 · IF 3.1

Biodegradable Ca2+ Doped Mesoporous Silica Nanoparticles Promote Chemotherapy Synergism with Calcicoptosis and Activate Anti-Tumor Immunity

Chao Liu,Xiaohui Tang,Gaofei Huang

Mesoporous silica nanoparticles (MSNs), an excellent carrier material, have been widely used in tumor therapy as a vector for numerous therapeutic substances to boost therapeutical efficiency and specificity, such as loading them with chemotherapy drugs to improve the efficacy of chemotherapy. Nevertheless, they still face hurdles, such as lack of specificity and poor efficacy of monotherapy. The construction of multifunctional MSNs with excellent therapeutic effects by introducing metal ions has attracted the attention of many researchers. Herein, we demonstrated a calcium doped, chemotherapy drug doxorubicin (Dox) loaded, specific degradation nanoplatform, prepared using the sol–gel method by introducing calcium ions into an MSN framework, which enabled the doped nanoplatform to enhance chemotherapy and activate anti-tumor immune response. As a proof of concept, the doping of Ca2+endowed MSNs with excellent specific degradation and pH responsive drug release, and enabled the synergy of chemotherapy and calcicoptosis. Furthermore, this nanoplatform also effectively elicited immunogenic cell death (ICD) and promoted the maturation of dendritic cells (DCs), realizing the activation of the anti-tumor immune system. The Ca2+doped MSNs (CMSNs), that can activate immune response with specific degradation capability, demonstrate a practical strategy for the effective synergy between chemotherapy and calcicoptosis, providing a new paradigm for promoting chemotherapy-related treatment.

CAS / MDL: 25316-40-9 78-10-4
研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 药学 · 免疫学
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ANALYTICAL CHEMISTRY · 2014 · IF 5.825

Design of Ratiometric Emission Probe with Visible Light Excitation for Determination of Ca2+ in Living Cells

Qiaoling Liu,Huizhi Du,Xiaoze Ren,Wei Bian,Li Fan,Shaomin Shuang,Chuan Dong,Qin Hu,Martin M. F. Choi

An organic salt as a fluorescent probe based on intramolecular charge transfer for Ca2+ determination is developed. Ca2+ can be detected by ratiometric emission at 490 and 594 nm with an excitation wavelength of 405 nm. This probe is highly selective for Ca2+ over other divalent metal cations and displays a large Stokes shift of 189 nm that can avoid interference of the excitation light beam and autofluorescence of biological samples. The dissociation constant for Ca2+ is 2.25 ± 0.47 μM and pertinent to Ca2+ detection in cellular resting and dynamic states. The probe demonstrates its application in monitoring Ca2+ in living cells under confocal microscopic imaging.

研究领域: 生物化学 · 分子生物学 · 分析化学
✓ 已验证 DOI PubMed 高影响因子
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Applications in Energy and Combustion Science · 2021 · IF 0

Enhancing aromatic yield from catalytic pyrolysis of Ca2+-loaded lignin coupled with metal-modified HZSM-5

Huiyan Zhang,Bingbing Luo,Kai Wu,Han Wu,Jiajun Yu,Siyu Wang

Catalytic fast pyrolysis of lignin is easy to cause agglomeration and coking, resulting in low-yield aromatic hydrocarbons. Catalytic pyrolysis of modified lignin combined with metal-modified HZSM-5 was proposed to enhance the aromatic yield. The experiment results showed that chemical modification with Ca(OH) 2 not only inhibited the agglomeration behavior of lignin but also increased the yield of light phenolic compounds. Moreover, Ca 2+ -loaded lignin combined with metal-modified HZSM-5 was conducive to the formation of aromatics. The total yield of aromatics from the catalytic fast pyrolysis of Ca 2+ -loaded lignin over Zn/HZSM-5 was improved from 31.1 to 46.1 mg/g. The mechanism insight showed that Ca 2+ modification realized the chemical combination between Ca 2+ and the functional groups which are responsible for the agglomeration of lignin, and then the introduction of the Zn species suppressed the hydrogen transfer reaction and enhanced the dehydrogenation pathway, resulting in the increase of aromatic yield.

研究领域: 化学工程 · 能源科学 · 材料科学
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PHYTOMEDICINE · 2024 · IF 6.7

Melatonin protects RPE cells from necroptosis and NLRP3 activation via promoting SERCA2-related intracellular Ca2+ homeostasis.

Chengda Ren,Chengyu Hu,Ming Hu,Yan Wu,Yang Yang,Fang Lu

Background Melatonin is an antioxidant that also has anti-inflammatory effects. It has been reported to delay the progression of age-related macular degeneration (AMD), however, the mechanism has not been fully recognized. Purpose The aim of the present study was to investigate the effects of melatonin on sodium iodate (SI)-induced retinal degeneration and elucidate the specific mechanisms, then, provide novel targets in AMD treatment. Methods Retinal degeneration mouse model and in vitro retinal pigment epithelium (RPE) death model were established by SI treatment. Melatonin was administrated intraperitoneally at a concentration of 20, 40 or 80 mg/kg for in vivo study or treated at 48 h before SI treatment. To confirm the therapeutic effects of melatonin on mouse, the retinal structure and visual function were evaluated. The specific cell death rates were determined by CCK-8 assay, PI staining and protein level of RIPK3. The cytosolic or mitochondrial calcium levels were determined by Fluo-4AM or Rhod-2AM staining. Mitochondrial functions including mitochondrial dynamics, mitochondrial membrane potential, or mitochondrial permeability pore opening were evaluated. The proteins involved in endoplasmic reticulum (ER) stress were measured by western blot assay while the genes expression in calcium signaling pathway were measured by RT-qPCR. Results We show that melatonin protects RPE cells from necroptosis and NLRP3 inflammasome activation induced by SI. Mechanistically, melatonin suppresses ER stress and intracellular calcium overload triggered by SI through restoring the function of SERCA2. Silencing of SERCA2 or blocking of melatonin receptors inhibit the protective effects of melatonin. Melatonin reduces mitochondrial Ca 2+ levels and restores mitochondrial membrane potential. Constant mitochondrial Ca 2+ overload directly promote cell necroptosis through mitochondrial fission. Inhibition of mitochondrial fission by Mdivi-1 prevent necroptosis induced by SI without altering the level of mitochondrial Ca 2+ . Conclusions The results confirmed that melatonin protects RPE cells from SI-induced injury by regulates MT2/SERCA2/Ca 2+ axis. This study highlighted the potential of melatonin in the treatment of AMD and elucidated the mechanism and signaling pathway that mediate the protective effects.

CAS / MDL: 7646-79-9 73-31-4
研究领域: 眼科学 · 药理学 · 细胞生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science Advances · 2024 ·Vol. 10 ·期 16 · IF 11.7

Photocatalytic manipulation of Ca2+ signaling for regulating cellular and animal behaviors via MOF-enabled H2O2 generation

Zherui Zhang,Yuhao Luo,Yuanhong Ma,Yaofeng Zhou,Dingcheng Zhu,Wanhua Shen,Junqiu Liu

The in situ generation of H2O2 in cells in response to external stimulation has exceptional advantages in modulating intracellular Ca2+ dynamics, including high controllability and biological safety, but has been rarely explored. Here, we develop photocatalyst-based metal-organic frameworks (DCSA-MOFs) to modulate Ca2+ responses in cells, multicellular spheroids, and organs. By virtue of the efficient photocatalytic oxygen reduction to H2O2 without sacrificial agents, photoexcited DCSA-MOFs can rapidly trigger Ca2+ outflow from the endoplasmic reticulum with single-cell precision in a repeatable and controllable manner, enabling the propagation of intercellular Ca2+ waves (ICW) over long distances in two-dimensional and three-dimensional cell cultures. After photoexcitation, ICWs induced by DCSA-MOFs can activate neural activities in the optical tectum of tadpoles and thighs of spinal frogs, eliciting the corresponding motor behaviors. Our study offers a versatile optical nongenetic modulation technique that enables remote, repeatable, and controlled manipulation of cellular and animal behaviors.

CAS / MDL: 7789-78-8 57-66-9
研究领域: 细胞生物学 · 生物医学工程 · 神经科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LUMINESCENCE · 2024 ·Vol. 39 ·期 10 ·e4914 · IF 3.2

Sensitive Detection and Cell Imaging of Ca2+ Based on a “Turn-On” Schiff Base Fluorescent Probe

Lingjie Hou,Linlin Wang,Chenhua Deng,Pengyue Jin,Chaochao Wen,Wenjia Zhang,Wenting Liang

Ca 2+ ion as a second messenger in signaling pathway plays many vital roles in many biological phenomena. Thus, it is of significance for developing effective probes to detect Ca 2+ ion specifically. Herein, a new Schiff base fluorescent probe FPH , fluorescein monoaldehyde (2-aminomethylpyridine) hydrazone, was designed and synthesized to identify Ca 2+ in DMSO aqueous solution. The probe FPH revealed significant responses to Ca 2+ with a fluorescence enhancement at 540 nm, exhibiting an evident fluorescence change from ultraweak luminescence to bright green. Otherwise, the FPH displayed a good linear range of 0.67 × 10 −6 to 3.33 × 10 −6 mol/L with a lower detection limit at 7.02 × 10 −8 mol/L. The probe FPH were further successfully utilized to detect Ca 2+ in living cells by an increased bright green fluorescence.

CAS / MDL: 2321-07-5 3731-51-9
研究领域: 生物化学 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2026 · IF 4.2

The role of Ca2+-calcineurin signaling pathway on the antifungal activity of Murrayone against Botrytis cinerea

Yao Yu,Wanyun Zhu,Huiying Han,Xinru Li,Yiping Hou,Yuxin Zhou,Min Wei,Yiyun Qian,Min Yin,Yanqin Jiang,Pingping Song

BACKGROUND Botrytis cinerea causes serious gray mold disease in a wide range of crops, resulting in significant economic losses annually. Our preliminary studies demonstrated that Murrayone exhibited antifungal activity against various plant pathogens, including B. cinerea . However, its antifungal mechanism against B. cinerea remains unclear. This study aimed to investigate the role of the Ca 2+ -calcineurin signaling pathway in the antifungal activity of Murrayone against B. cinerea . RESULTS Murrayone exhibited efficacy against B. cinerea in both in vitro and in vivo assays. It markedly reduced intracellular Ca 2+ concentrations in the mycelia. The antifungal activity of Murrayone was influenced by CaCl 2 , the calcium channel blocker verapamil, and the calcineurin inhibitor cyclosporin A. Murrayone treatment significantly downregulated the expression of key genes ( Bccch1, Bcmid1, BccnA, Bcpmc1 , and Bcpmr1 ) in the Ca 2+ -calcineurin signaling pathway. Patch-clamp analysis suggested that Murrayone acted as a potential Ca 2+ channel blocker. CONCLUSION Murrayone significantly decreases the cytosolic Ca 2+ concentration and disrupts Ca 2+ homeostasis in B. cinerea . Its antifungal mechanism is linked to the Ca 2+ -calcineurin signaling pathway, potentially through acting as a calcium channel blocker. This work provides a theoretical foundation for developing Murrayone as a promising antifungal candidate and promotes its further application. © 2026 Society of Chemical Industry.

CAS / MDL: 152-11-4
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Pharmaceuticals · 2026 · IF 5.7

Naringin Attenuates Diabetic Neuropathic Pain and Modulates TRPV1-Related Ca2+ Dysregulation and MAPK/NF-ΚB Signaling

Xiaoyi Qiu,Lisha Chen,Ting Han,Hongji Wang,Juping Xing,Jiayi Zheng,Changshui Xu

Background/Objectives:Diabetic neuropathic pain (DNP) is a common complication of diabetes characterized by sensory abnormalities, including mechanical allodynia and thermal hyperalgesia. This study aimed to investigate the effects of naringin on experimental DNP and evaluate its association with dorsal root ganglion (DRG) neuronal injury, TRPV1-related calcium imbalance, and inflammatory signaling.Methods:Primary rat DRG neurons were exposed to high-glucose/high-free-fatty-acid (HGHF) conditions (50 mM glucose and 0.60 mM free fatty acids) and treated with naringin (40 or 80 μM). Cell viability, apoptosis, intracellular Ca2+levels, gene/protein expression, and signaling changes were assessed using CCK-8 assay, Annexin V-FITC/PI flow cytometry, Fluo-4 AM imaging, qRT-PCR, and Western blotting. Male Sprague–Dawley rats were fed a high-fat/high-sucrose diet for 4 weeks, injected with streptozotocin (35 mg kg−1), and treated with naringin (50 mg kg−1day−1) by gavage for 2 weeks.Results:HGHF exposure increased neuronal injury, TRPV1 expression, intracellular Ca2+accumulation, and p38 MAPK/NF-κB signaling activation. Naringin attenuated these changes in vitro, with stronger effects observed at 80 μM. In DNP rats, naringin improved pain-related behaviors, partially alleviated metabolic abnormalities, reduced TRPV1 expression and serum IL-1β/TNF-α levels, and decreased phosphorylation of p38 MAPK, NF-κB p65, and ERK in DRGs.Conclusions:Naringin alleviated experimental DNP-associated behavioral and molecular abnormalities, suggesting potential protective effects involving neuronal injury, calcium regulation, and inflammatory responses.

✓ 已验证 DOI 高影响因子
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MATERIALS CHEMISTRY AND PHYSICS · 2026 · IF 5.2

Ca2+ doping tuned structure, oxygen content and electrical transport in Sr0.725Y0.275CoO3-δ for NTCR thermosensitive materials

Hao Yang,Yule Li,Yuchen Xie,Changchun Yu,Zifeng Li,Xuting Sun,Songlin Tan,Qingming Chen,Hui Zhang

A series of (Sr 1- x Ca x ) 0.725 Y 0.275 CoO 3-δ ceramic materials were synthesized via the sol-gel method. X-ray diffraction (XRD) measurements revealed that all the samples crystallized into a tetragonal phase with the I4 / mmm space group, and an excessive doping concentration of Ca 2+ ( x  > 0.42) would induce the formation of the Ca 3 Co 2 O 6 secondary phase. X-ray photoelectron spectroscopy (XPS) results demonstrated an increase in the Co 4+ concentration, and iodometric titration further confirmed that appropriate doping with Ca 2+ can reduce oxygen vacancies (δ) (with oxygen content increasing from 2.60 to 2.64). This led to a significant decrease in electrical resistivity owing to the elevated carrier concentration and reduced hole scattering. All the samples exhibited a negative temperature coefficient of resistance (NTCR), a typical semiconducting characteristic. For the sample with x  = 0.14, the absolute value of the NTCR reached the maximum, and its value remained less than −4%·K −1 over the operating temperature range of 230 K to 330 K, coupled with a low electrical resistivity. This sample thus holds broad application prospects as a high-stability and high-responsivity thermosensitive material for uncooled infrared detection.

✓ 已验证 DOI 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2026 · IF 6.8

Elephantopus scaber suppresses ConA-induced T cell activation by inhibiting NF-κB and Ca2+/NFAT signaling

Min Cai,Congyu Wu,Muqing Wang,Qian Chen,Yilin Guo,Yu Liu,Xin Huang,Yuan Gao,Yun Qi

Ethnopharmacological relevance Elephantopus scaber L. ( E. scaber ) is a heat-clearing and detoxifying traditional Chinese medicine. Clinically, it is used for treating some immuno-inflammatory diseases associated with excessive T cell activation. However, its action and mechanism on T cells are still ambiguous. Aim of the study This study aims to investigate the molecular mechanism of the ethanol extract of E.scaber (ESE) in ConA-induced T cell activation models. Materials and methods IL-2 transcription and translation levels were determined by RT- q PCR and ELISA. CD4 + naïve T cells were sorted using the flow cytometer. Western blot assay was used for determining intracellular protein levels. Cytoplasmic and mitochondrial Ca 2+ concentrations were measured by fluorometric assays. Results ESE not only dampened the proliferation of splenic lymphocytes, but also decreased IL-2 production in ConA-activated T cells without affecting its mRNA stability. It could inhibit the activation of NFAT and NF-κB pathways, showed as impeding the nuclear translocation of NFAT and p65. Regarding the upstream signaling, ESE significantly decreased cytoplasmic Ca 2+ (Ca 2+ [c] ) level in a model-independent manner. Although it failed to affect plasma membrane Ca 2+ -ATPase, Na + /Ca 2+ exchanger, and mitochondrial Ca 2+ uptake, it affected sarco/endoplasmic Ca 2+ -ATPase (SERCA) pathway. It also hindered IκBα phosphorylation and subsequent degradation. In vivo , ESE reduced IL-2 levels in local and systemic T cell activation models. Conclusion Through inhibiting the activation of SERCA/Ca 2+ [c] /NFAT and NF-κB pathways, ESE markedly decreased ConA-induced IL-2 production in vitro and in vivo . This study provides not only a modern explanation for the traditional uses of E. scaber , but also a scientific guidance for clinical practice.

✓ 已验证 DOI PubMed 高影响因子
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RSC Advances · 2017 ·Vol. 7 ·期 76 ·48238-48244 · IF 3.108

Morphology control and enhancement of 1.5 μm emission in Ca2+/Ce3+ codoped NaGdF4:Yb3+, Er3+ submicrorods

Jiangyun Dai,Chao Yang,Hong Zhang,Hua Zhang,Guoying Feng,Shouhuan Zhou

The successful synthesis of rare earth doped nano/microcrystals with the desired morphology, uniform monodispersity, and intense infrared emission is of fundamental significance, and would facilitate their application in infrared emission-related miniaturization and integration in optoelectronics. However, simultaneously controlling the morphology and enhancing the infrared emission through simple and effective methods has not been well explored. In this study, via Ca2+ doping with an optimized concentration of 25 mol% in the hydrothermal solution, irregular NaGdF4:Yb/Er submicrocrystals converted into highly uniform submicrorods. Meanwhile, an obvious enhancement of visible upconversion (UC) and near-infrared (NIR) downconversion (DC) emission were obtained, probably due to the improved morphology and lowering the local crystal field symmetry around the rare earth ions induced by Ca2+ doping. Furthermore, Ce3+ ions with an optimized concentration of 2 mol% were codoped to intentionally tailor the branching ratio through efficient energy transfer from Er3+ to Ce3+. As a result, the ∼1530 nm emission intensity of the NaGdF4: 25Ca/2Ce/20Yb/2Er submicrorods increased by about 6.4 times in comparison with the NaGdF4:20Yb/2Er counterpart.

研究领域: 材料科学 · 光学工程 · 纳米技术 · 稀土化学 · 光电子学
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