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SH-U-454

✓ Approved

Bayer AG · 小分子 · 小分子

什么是 SH-U-454？

SH-U-454 是一种小分子，由Bayer AG研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

公司Bayer AG
药物类别小分子, 影像药物
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Bayer AG

治疗适应症

SH-U-454 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
Cardiac disordersArteriosclerosis coronary artery✓ Approved

相关研究文献

PubMedSkin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)2026-10-26

Clinical and Dermoscopic Features of Subungual Hemorrhage: A Retrospective Study of 420 Cases.

Wu Xiaoting X, Lin Zhaoping Z, Shen Xue X, Wang Jieyi J et al.

Subungual hemorrhage (SH) may be difficult to distinguish from nail unit melanoma, onychomycosis, and other nail disorders. Dermoscopy enables non-invasive visualization of subtle subungual structures and provides useful information for differential diagnosis. This study aimed to analyze the clinical and dermoscopic features of SH and explore their associations with lesion location, disease course, and nail involvement. Clinical and dermoscopic data of 420 patients diagnosed with SH between December 2018 and March 2024 were retrospectively collected from two tertiary hospitals in China. Patients aged 18-45 years accounted for 65.5% of the cohort, and 84.3% of lesions were located on the toenails. Most patients (69.5%) had a single lesion, and 73.8% and 79.3% showed no nail margin involvement or nail plate damage, respectively. Toenail involvement was more frequent in female (p = 0.003) and young adult (p = 0.002) patients. The predominant dermoscopic features were purplish-red/black pigmentation (72.9%), irregular morphology (71.0%), and linear or striated pseudopods surrounding the lesion (56.7%). Irregular morphology was significantly more frequent in toenail lesions, whereas linear morphology was more common in fingernail lesions (both p < 0.001). Irregular shapes were predominant (73.6%) in cases with a short-term course (< 3 months), whereas linear lesions accounted for 31.6% of lesions in patients with a long disease course (≥ 12 months). Lesion morphology was significantly associated with disease course (p < 0.001). Irregular morphology was also significantly associated with nail margin involvement (p < 0.001) and nail plate damage (p = 0.007), while linear or striated pseudopod lesions showed a significant association with nail margin involvement (p < 0.001). In this cohort, SH predominantly affected females and young adults and typically presented as a single toenail lesion. Dermoscopic features of SH varied according to lesion location and disease course, and irregular morphology was associated with nail margin involvement and nail plate damage. Recognition of characteristic dermoscopic features, together with clinical history and lesion evolution, may facilitate differentiation of SH from nail unit melanoma and other nail disorders, help avoid unnecessary biopsy in typical cases, and prompt further evaluation of suspicious lesions.

PMID 42928658
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PubMedJournal of animal science2026-10-26

Gestational heat stress alters the plasma metabolome of Bos indicus-influenced beef cows and modifies the calf metabolome at birth.

Izquierdo Vinicius S VS, Brauner Cassio C CC, Sousa Luciana M LM, Vendramini João M B JMB et al.

This 3-year study evaluated the effects of heat stress mitigation during late gestation on the plasma metabolome of Bos indicus-influenced cow-calf pairs. On day 0 of each year (92 ± 19 days prepartum, n = 88/treatment/year), multiparous, pregnant Brangus crossbred cows were stratified by body condition score and body weight and allocated into 16 bahiagrass pastures (8 ha and 11 cows/pasture). Gestational treatments were randomly assigned to pastures and consisted of cows provided with (SH) or without (NSH) access to artificial shade (3.27 m2 per cow) from day 0 to 90. Blood samples were collected from cows on days 0, 30, and 60 (92 ± 19, 62 ± 19, and 32 ± 19 days prepartum, respectively), and from calves at birth, for plasma metabolome determination using liquid chromatography and flow injection analysis coupled with tandem mass spectrometry. Principal component and partial least squares-discriminant analyses were performed within each day to discriminate the treatments using SIMCA 18.0. Single metabolite concentrations were compared between groups using PROC MIXED in SAS, with Benjamini-Hochberg false discovery rate correction applied, and pathway analyses were performed using Ingenuity Pathway Analysis. A clear separation was observed on days 30 (R² = 0.76) and 60 (R² = 0.67) for the plasma metabolome of SH and NSH cows. Effects of treatment (P ≤ 0.05) were detected for 23 metabolites on day 30 and 17 metabolites on day 60. Twelve pathways related to putrescine, glycine, and arginine metabolism were downregulated (P ≤ 0.04), whereas tryptophan degradation X was upregulated (P = 0.02) in SH vs. NSH cows on day 30. On day 60, 23 pathways were upregulated (P ≤ 0.04) and serine biosynthesis and tyrosine degradation I tended to be upregulated (P = 0.05), whereas 4 pathways related to amino acid degradation were downregulated (P ≤ 0.01) in SH vs. NSH cows. At birth, a clear treatment separation was observed (R² = 0.73), with effects detected (P ≤ 0.03) for 10 metabolites and 50 metabolic pathways upregulated in SH vs. NSH calves, predominantly related to amino acid metabolism and antioxidant defense. In conclusion, gestational access to shade was associated with progressive alterations in the maternal lipid and amino acid metabolite profile and with differences in the neonatal metabolome at birth, consistent with a more favorable gestational nutritional environment.

PMID 42928605
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PubMedInorganic chemistry2026-10-26

Bioinspired Persulfidation of a Mononuclear Ni(II)-ONO Compound: Evidence for Sulfur/Nitrogen "Crosstalk".

Karmakar Soumik S, Halder Ritapravo R, Baral Lipika L, Pan Ritwika R et al.

Reactivity of a mononuclear Ni(II)-ONO compound, [Ni(6-COO--tpa)(ONO)] (2), with MeC(O)SH in a 1:2 ratio generated an unprecedented Ni(II)-persulfide compound, [Ni(6-COO--tpa)(SSC(O)Me)] (5), along with nitric oxide (NO) and nitrous oxide (N2O). The reaction proceeds by the generation of nitrous acid (HONO) and [Ni(6-COO--tpa)(SC(O)Me)] (4) followed by the reaction of free ONO- (from HONO) with either the coordinated MeC(O)S- in 4 or free MeC(O)S- to release thionitrite (SNO-) and MeC(O)O-. In the presence of protons, SNO- is converted to perthionitrite (SSNO-) and N2O (minor pathway). SSNO- decomposes to liberate elemental sulfur ([S]), which then reacts with the coordinated MeC(O)S- in 4 to generate 5. In contrast to this, SSNO-, generated in the reaction of 2 and MeC(O)S- in a 1:2 ratio, decomposes in the absence of protons to produce Sn2-, which, in turn, produces a rare example of a Ni(II)-SH compound, [Ni(6-COO--tpa)(SH)] (6). All the Ni(II) compounds and the intermediates have been characterized by a combination of structural and spectroscopic studies, and, based on these results, mechanisms for the reactions have been proposed. The present work thus demonstrates perthionitrite-mediated persulfidation involving mononuclear Ni(II) complexes 2 and 4, to generate the only example of a Ni(II)-persulfide compound, 5.

PMID 42929610
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PubMedChemistry & biodiversity2026-10-26

Integrated Metabolomics and Network Pharmacology Reveal Anti-Aging and Anti-MRSA Activities of Cucumis melo Var. flexuosus.

Khalil Mohammed N A MNA, Radwan Rasha A RA, Hassan Mariam M, Ahmed Noha A NA et al.

Cucumis melo var. flexuosus is traditionally used for the management of skin ailments; however, its phytochemical composition and bioactivities remain insufficiently characterized. Hereto, three fruit genotypes (LG, SH, and WH) and the leaves of the LG genotype (LGLV) were systematically investigated. More than 100 phytochemicals were tentatively identified in the investigated extracts utilizing LC-HRMS. Chemometric tools discerned samples in three distinct clusters. LGLV cluster characterized by richness in flavonoids, LG & SH cluster were enriched in glycerol- and lyso-phospholipids while WH was enriched in cerebroside. Network pharmacology revealed that flavonoids, phenolic acids and lysophospholipids were the key phytochemicals against skin aging and MRSA (Methicillin resistant Staphylococcus aureus). LGLV had the highest antioxidant activities in different in vitro assays. LGLV had the highest antibacterial, biofilm inhibition (IC50 = 0.322 mg/mL) and detachment activities against MRSA. Antibacterial efficacy was verified by in vivo MRSA skin infection model. Moreover, LGLV halted aging in H2O2-induced aging model in vitro human fibroblast cell culture as evidenced by flow cytometry and by the effective suppression of MMP-1 and IL-6, p53 and increment in TIMP-1 levels. These findings highlighted that leaves are a better sustainable source of bioactive compounds for the development of anti-MRSA and skin-protective products.

PMID 42928631
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PubMedPharmacology research & perspectives2026-10-26

CCR1 Antagonism by BX471 Attenuates Neuroinflammation and Apoptosis: Preliminary Findings From an In Vitro Model of Neuronal Injury.

Hasan Ahmed A, Mannino Deborah D, Scuderi Sarah Adriana SA, Buccarello Lucia L et al.

Neuronal injury as traumatic brain injury (TBI) triggers a complex pathophysiological cascade involving inflammatory and apoptosis processes. BX471 is a selective C-C chemokine receptor type 1 (CCR1) antagonist that showed a promising effect in modulating neuroinflammation in central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effect of BX471 on the inflammatory pathway and apoptotic process in an in vitro model of induced-neuronal injury using SH-SY5Y neuroblastoma cells. Firstly, cytotoxicity was assessed by MTT assay to determine the optimal effective concentrations and the best temporal window for BX471 activity. Then, SH-SY5Y cells were subjected to a scratch injury to mimic a neuronal injury and were treated with different concentrations of BX471. ELISA and qRT-PCR were used to analyze the expression level of the CCR1/chemokines axis (CCR1, RANTES, MIP-1α), inflammatory markers (TNF-α, IL-1β, IL-6, NF-κB, IκBα, and PPAR𝛾), and the apoptotic pathway (Bcl2, BAX, P53, and cleaved caspase 3). The results showed that BX471 significantly improved the cell viability and inhibited the CCR1/chemokine axis and pro-inflammatory cytokines as well as modulating the apoptotic course. Overall, these results suggest that BX471 may reduce neuronal injury by inhibiting neuroinflammation and apoptosis, and that its neuroprotective effect, mediated through the CCR1 signaling pathway, deserves further investigation in in vivo models.

PMID 42928994
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PubMedDalton transactions (Cambridge, England : 2003)2026-10-26

Tailoring phase modifiers for selective uranium extraction: conventional and phosphate ores.

Gautier M M, Lin J J, Guerinoni E E, Daronnat L L et al.

Selective uranium extraction from sulfate and phosphate-based leachates remains challenging due to co-extraction of impurities such as Mo, Zr, and Fe, which limits process efficiency and economic viability. This study investigates how the nature and concentration of phase modifiers influence uranium selectivity across three mining systems: two conventional uranium ores and one phosphate-associated ore. U, Mo and Zr were quantified by ICP-OES, while Fe was analyzed by gamma-ray spectrometry. Results show that phase modifier effects on selectivity are highly system dependent. In AMEX-based sulfate systems, increasing EXXAL 10 enhances selectivity through systematic improvements in extraction performance: in Mine A, U/Zr increases from 50 to 221 at 50 vol% (vs. 5 vol% industrial conditions), while in Mine B, U/Mo increases from 377 to 1459 at 22 vol%, with optimal U/Zr selectivity between 10-50 vol%. In contrast, the phosphate-based Mine C exhibits a weakly structured organic phase, with dimer-dominated extractant species and limited sensitivity to phase modifier addition; optimal selectivity is achieved at low modifier content, where 2 vol% EXXAL 13 increases the U/Fe ratio from 61 to 214. These results highlight the importance of system-specific phase modifier optimization for maximizing uranium selectivity. SAXS analysis further reveals that extractant molecules self-assemble into reverse aggregates whose structure and inter-aggregate interactions are strongly influenced by phase modifier concentration. Crucially, these structural modifications directly correlate with selectivity variations, demonstrating that phase modifier effects are fundamentally mediated through changes in extractant aggregation in the organic phase.

PMID 42929761
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