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calcium polycarbophil (Polyful / Colonel)

✓ Approved

Astellas Pharma · 小分子 · 小分子

什么是 calcium polycarbophil？

calcium polycarbophil 是一种小分子，由Astellas Pharma研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Polyful, Colonel
公司Astellas Pharma
药物类别小分子
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Astellas Pharma

治疗适应症

calcium polycarbophil 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Gastrointestinal disordersIrritable bowel syndrome✓ Approved

相关研究文献

PubMedExperimental neurology2026-08-09

Calcified pituitary adenomas: First comprehensive characterization of a distinct clinical entity driven by GNAQ-mediated calcium-mitochondrial axis.

Rao Changjun C, Gong Lei L, Jia Jingyuan J, Cao Lei L et al.

Calcification in pituitary adenomas is a rare phenomenon, observed in only 0.2% to 8% of imaging studies and 5.4% to 25% of histopathological analyses, which complicates diagnosis and surgical intervention, yet its molecular underpinnings remain largely unknown. In this study, we retrospectively analyzed 115 patients with calcified pituitary adenomas, focusing on 36 cases with radiologically visible calcifications that we classified into four distinct subtypes, and performed molecular profiling via single-cell RNA sequencing and transcriptome sequencing. Our results identified a unique tumor cell subpopulation in calcified samples, which was enriched in pathways related to metal ion response and extracellular matrix reorganization but not osteogenic differentiation. We pinpointed GNAQ as a key gene, with its expression significantly elevated in calcified tissues. Functional experiments demonstrated that overexpressing GNAQ in GH3 pituitary adenoma cells induced calcium overload through the IP3R/CaMKII pathway, leading to mitochondrial dysfunction, increased reactive oxygen species, apoptosis, and ultimately extracellular calcium salt deposition, as confirmed by Alizarin Red staining. The calcium channel blocker verapamil was found to partially mitigate GNAQ-induced cytotoxicity. Furthermore, in mouse xenograft models, GNAQ overexpression promoted calcification and suppressed tumor proliferation. Collectively, our findings establish GNAQ as a critical driver of pituitary adenoma calcification, unveiling a unique "GNAQ-IP3/Ca2 + -mitochondrial apoptosis-calcification" axis that is distinct from the classical osteogenic pathway seen in tumors like craniopharyngioma, thereby providing new insights into the pathogenesis and potential therapeutic targeting of this condition.

PMID 42570836
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PubMediScience2026-08-09

Circadian pacemaker dynamics differ between diurnal and nocturnal mammals.

Muhl Vanessa V, Lopez-Lorenzo Daniela D, Pourmir Farina F, Sweck Samantha O SO et al.

Diurnal and nocturnal mammals are thought to share a functionally equivalent suprachiasmatic nucleus (SCN), the central circadian pacemaker, because standard measures look broadly similar across species. However, coarse readouts do not test when the SCN can be reset or how timing is coordinated across SCN space. We used long-duration ex vivo recordings, optogenetic perturbation, and single-cell calcium phase mapping to compare network dynamics in the nocturnal laboratory mouse (Mus musculus) and the diurnal four-striped grass mouse (Rhabdomys pumilio). Rhabdomys SCN molecular clock rhythms exhibited a longer intrinsic period than Mus and reached a different phase relationship to daily stimulation. Direct SCN stimulation at defined circadian times produced species-specific resetting responses, including a pronounced mid-subjective-day delay in Rhabdomys when Mus responses were minimal. Calcium phase mapping revealed a graded dorsomedial-to-ventrolateral progression in Rhabdomys and a sharper transition in Mus. Thus, coarse SCN similarity does not necessarily imply conserved pacemaker dynamics across species.

PMID 42571271
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PubMed3 Biotech2026-08-09

A β-TCP/PMMA composite bone cement promotes osteogenic differentiation of osteoporotic rBMSCs via Wnt/β-catenin pathway.

Chun Wang Rui R, Yang Yi Y, Chen Jia Hon JH, Geng Gui Min GM et al.

Osteoporosis-induced bone defects represent a severe clinical challenge that requires high-performance bone repair biomaterials. To address the limited osteoinductivity, excessive curing heat, and poor degradability of conventional PMMA bone cement, we developed a 1:1 β-tricalcium phosphate (β-TCP)/polymethyl methacrylate (PMMA) composite and an integrated computation-experimental framework. For the first time, we systematically clarified the osteoinductive mechanism of this composite in osteoporotic bone repair via a multidisciplinary strategy combining machine learning, multi-omics analysis, and cellular validation, instead of focusing solely on material composition optimization. Characterization showed that the composite had a uniform porous structure, suitable mechanical properties, low curing temperature, high degradation rate, and sustained calcium ion release. The high-accuracy random forest-convolutional neural network (RF-CNN) model predicted osteogenic potential and identified calcium ion release and pore structure as dominant osteogenic factors. Bioinformatics analysis screened 326 differentially expressed genes (DEGs), mainly enriched in the Wnt/β-catenin pathway, with Runx2, Bmp2, and Sp7 as key hub genes. Subsequent in vitro experiments validated that the composite significantly promoted proliferation, osteogenic differentiation, and mineralization of osteoporotic rat bone marrow mesenchymal stem cells (rBMSCs), reduced apoptosis, and upregulated core osteogenic genes by activating this pathway. This study provides a promising biomaterial for osteoporotic bone repair and a novel computation-assisted paradigm for bone regenerative material development.

PMID 42571078
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PubMedColloids and surfaces. B, Biointerfaces2026-08-09

Osteogenic and antibacterial coating containing strontium and calcium on zinc implants via redox-assisted co-deposition.

Zhang Guorui G, Wang Changping C, Ding Hongjie H, Guo Yingfan Y et al.

Biodegradable zinc (Zn)-based implants are emerging as one of the leading candidate materials for orthopedic applications owing to their favorable degradation behavior and mechanical properties; however, their clinical translation is delayed by insufficient surface bioactivity. In this study, a multifunctional composite coating incorporating strontium (Sr) and calcium (Ca) was fabricated on Zn implants via a redox-assisted co-deposition strategy. This method harnesses the strong oxidizing power of permanganate to controllably dissolve the Zn substrate, facilitating the gradient incorporation of Ca2⁺ and Sr2⁺ through hydroxyl-mediated cross-linking and resulting in a composite structure with a concentration gradient. The process is completed within 30 min under mild temperature and atmospheric pressure without the need for specialized equipment. The coating operates through a dual mechanism: it regulates the degradation behavior of the Zn substrate and modulates Zn2⁺ release kinetics to mitigate cytotoxicity from excessive local ion concentrations, while simultaneously leveraging the synergistic effects of Ca2⁺ and Sr2⁺ to enhance hemocompatibility and long-term cytocompatibility. Moreover, the coating promotes osteogenic activity by activating osteogenesis-related signaling pathways and stimulating cell adhesion, spreading, migration, and differentiation, alongside conferring antibacterial properties, thus achieving a balanced osteogenic-antimicrobial functionality. This surface modification strategy offers a novel and scalable approach for engineering biodegradable Zn-based implants, demonstrating strong potential for clinical translation in orthopedics.

PMID 42570436
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PubMedCellular signalling2026-08-09

CaMKIIγ inhibition attenuates osteoclastogenesis via the NF-κB-NFATc1 axis and protects against ovariectomy-induced osteoporosis.

Qiu Yisen Y, Fang Ningnan N, An Bang B, Teng Ganghong G et al.

Osteoporosis features excessive osteoclast-mediated bone resorption, and long-term safety concerns with current antiresorptives and rebound after discontinuation underscore the need for new therapeutic targets. Calcium/calmodulin-dependent kinases (CaMKs) have been linked to osteoclastogenesis, yet which CaMKII isoform is functionally essential and therapeutically actionable remains incompletely defined. Here, we investigated the role of calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ) in the osteoclast lineage, examined its downstream signaling mechanisms, and evaluated whether its pharmacological inhibition protects against ovariectomy-induced bone loss. CaMKIIγ expression increased during osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL), and shRNA-mediated Camk2g knockdown in RAW 264.7 cells markedly reduced multinucleated osteoclast formation. Functionally, Camk2g knockdown disrupted F-actin ring organization and reduced osteoclast resorptive pit formation. Berbamine (BBM), a reported CaMKIIγ inhibitor, phenocopied these inhibitory effects at non-cytotoxic concentrations during osteoclast differentiation, with maximal inhibition when applied during early differentiation. RNA sequencing and quantitative PCR revealed coordinated repression of osteoclastogenic gene programs upon CaMKIIγ inhibition. Pathway enrichment analyses implicated NF-κB signaling, and western blotting confirmed that Camk2g knockdown and BBM preferentially attenuated early RANKL-induced p65 phosphorylation, accompanied by reduced downstream nuclear factor of activated T cells 1 (NFATc1) induction. In ovariectomized mice, BBM administration at 25 or 50 mg/kg per day by intraperitoneal injection partially preserved trabecular microarchitecture and reduced osteoclast presence, as shown by micro-CT and histological staining. These findings identify CaMKIIγ as a regulator of osteoclastogenesis and support CaMKIIγ inhibition as a potential strategy to prevent postmenopausal bone loss.

PMID 42570747
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PubMedTheriogenology2026-08-09

Bulls carrying the myostatin genotype show impaired sperm cryotolerance.

Tamargo Carolina C, Muiño Rodrigo R, Matínez Elena N EN, Yeste Marc M et al.

While the myostatin (MSTN) gene is responsible for the double-muscled phenotype in cattle and has been associated with alterations in metabolism and energy homeostasis. its potential effects on sperm function and fertility remain poorly understood. This study evaluated whether the MSTN genotype affects post-thaw sperm cryotolerance and its relationship with field fertility in Asturiana de los Valles bulls. Frozen-thawed semen from 15 homozygous MSTN-mutated (mh/mh) and 15 wild-type (+/+) bulls were assessed after 30 and 240 min of incubation at 37 °C. Sperm motility and kinematic parameters were analyzed by computer-assisted sperm analysis (CASA), whereas sperm functionality variables were evaluated by flow cytometry. Fertility was assessed using 90-day non-return rates (NRR) from 10,416 artificial inseminations. Post-thaw incubation significantly reduced sperm motility and altered all CASA kinematic parameters. Although total motility declined more markedly over time in MSTN carriers, most kinematic descriptors did not differ between genotypes. In contrast, flow cytometry revealed clear genotype-dependent differences. Sperm from MSTN carrier bulls showed lower acrosome integrity, increased membrane lipid disorder, reduced intracellular calcium levels, and altered oxidative status, together with significant Genotype × Time interactions for reactive oxygen species, superoxide production, and calcium dynamics. These findings indicate reduced functional stability and lower cryotolerance in sperm from MSTN carriers. Fertility analyses further showed that post-thaw sperm viability after prolonged incubation was positively associated with fertility at first service in MSTN carriers, whereas CASA-derived kinematic traits exhibited weaker and non-genotype-specific associations. In conclusion, the MSTN genotype negatively affects post-thaw sperm cryotolerance and functional stability. Reduced fertility in double-muscled bulls appears to be more closely related to impaired resilience to cryopreservation-induced stress than to alterations in conventional sperm kinematic parameters.

PMID 42570472
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