更新于：2024-11-01

SMPD4

更新于：2024-11-01

基本信息

别名

FLJ20297、FLJ20756、KIAA1418

+ [10]

简介

Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:16517606, PubMed:25180167). It has a relevant role in the homeostasis of membrane sphingolipids, thereby influencing membrane integrity, and endoplasmic reticulum organization and function (PubMed:31495489). May sensitize cells to DNA damage-induced apoptosis (PubMed:18505924). In skeletal muscle, mediates TNF-stimulated oxidant production (By similarity).

关联

100 项与 SMPD4 相关的临床结果

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100 项与 SMPD4 相关的转化医学

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0 项与 SMPD4 相关的专利（医药）

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132

项与 SMPD4 相关的文献（医药）

2024-07-01·International Journal of Gynecology & Obstetrics

Prenatal diagnosis and outcomes in fetuses with duplex kidney

Article

作者: Huang, Ruibin ; Li, Fucheng ; Jing, Xiangyi ; Zhou, Hang ; Guo, Fei ; Fu, Fang ; Liao, Can ; Wang, You ; Yan, Shujuan ; Ma, Chunling ; Li, Dongzhi ; Chen, Huanyi ; Li, Ru ; Han, Jin ; Li, Lushan

AbstractObjectiveDuplex kidney is a relatively frequent form of urinary system abnormality. This study aimed to elucidate the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) for duplex kidney and the perinatal outcomes of duplex kidney fetuses.MethodsThis retrospective cohort study included 63 patients with duplex kidney diagnosed using antenatal ultrasound between August 2013 and January 2023. We reviewed the clinical characteristics, genetic test results, and pregnancy outcomes of the patients.ResultsAmong the 63 cases based on the inclusion criteria, the CMA detected seven (11.1%) clinically significant variants and nine variants of uncertain significance (VUS), and the pathogenic/likely pathogenic (P/LP) copy number variations (CNVs) in the recurrent region that were associated with prenatal duplex kidney included 17q12, 17p13.3, and 22q11.2. No significant disparity was observed in the CMA detection rate between the unilateral and bilateral groups, or between the isolated and non‐isolated groups. WES identified three (50%) P/LP single‐gene variants in six fetuses with duplex kidney. We detected the following pathogenic genes in the duplex kidney fetuses: KMT2D, SMPD4, and FANCI. Pregnancy termination in cases where clinically significant variants were detected by genetic testing was different in statistical significance from that in cases with negative results (9/10, 90.0% vs 8/48, 16.7%, P < 0.001).ConclusionThis study elucidated the value of CMA and WES for fetal duplex kidney, proving that CMA and WES may be useful tools in prenatal diagnosis and genetic counseling.

2024-04-01·International Journal of Pharmaceutics

Harnessing the potential of fatty Acid-Surfactant-Based micellar gel for enhanced topical delivery of Apremilast in psoriasis treatment

Article

作者: Sontakke, Arun ; Sharma, Reena ; Dighe, Sayali ; Jain, Sanyog ; Yadav, Vivek

Apremilast (APR) is a potent anti-psoriatic agent that inhibits the phosphodiesterase 4 enzyme. Due to the poor oral bioavailability and associated systemic side effects the clinical applicability of APR has been constrained. Nanotechnology-based carrier system presents a novel option to increase the efficacy of the topical treatment of APR. The current investigation deals with the development of fatty acid-surfactant conjugate-based hybrid mixed micellar gel (HMMG) for the topical delivery of APR. The developed micelles exhibited an average size of 83.59 ± 4.46 nm, PDI of 0.239 ± 0.047, % entrapment efficiency of ∼ 94.78 ± 3.98 %, with % practical drug loading of ∼11.37 ± 3.14 %. TEM analysis revealed the spherical shape of micelles. The hybrid micelles were further loaded in a carbopol®934P gel base for ease of application. Ex vivo permeation study revealed enhanced permeation and ∼ 38-fold higher retention in deeper layers of skin from a hybrid micellar gel. In vivo, assessment demonstrated augmented efficacy of APR-HMMG as compared to 0.1 % betamethasone valerate. Also, APR-HMMG showed no sign of irritation, suggesting superior safety as a topical application. Thus, the proposed formulation strategy represents a viable avenue for enhancing the therapeutic efficacy of various anti-psoriatic moieties.

2024-02-01·Twin Research and Human Genetics

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

Article

作者: Ning, Feng ; Zhang, Dongfeng ; Yao, Jie ; Wang, Weijing

AbstractObesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (β = 1.86, p = .0004). The association between BMI and DNAm of 85 CpGs reached p < 1×10–4 level. Eleven BMI-related differentially methylated regions (DMRs) within LNCPRESS1, OGDHL, RNU1-44P, NPHS1, ECEL1P2, LLGL2, RNY4P15, MOGAT3, PHACTR3, and BAI2 were found. Of the 85 CpGs, 9 mapped to C10orf71-AS1, NDUFB5P1, KRT80, BAI2, ABCA2, PEX11G and FGF4 were significantly associated with SBP levels. Of the 9 CpGs, 2 within ABCA2 negatively mediated the association between BMI and SBP, with a mediating effect of −0.24 (95% CI [−0.65, −0.01]). BMI was also positively associated with DBP (β = 0.60, p = .0495). The association between BMI and DNAm of 193 CpGs reached p < 1×10−4 level. Twenty-five BMI-related DMRs within OGDHL, POU4F2, ECEL1P2, TTC6, SMPD4, EP400, TUBA1C and AGAP2 were found. Of the 193 CpGs, 33 mapped to ABCA2, ADORA2B, CTNNBIP1, KDM4B, NAA60, RSPH6A, SLC25A19 and STIL were significantly associated with DBP levels. Of the 33 CpGs, 12 within ABCA2, SLC25A19, KDM4B, PTPRN2, DNASE1, TFCP2L1, LMNB2 and C10orf71-AS1 negatively mediated the association between BMI and DBP, with a total mediation effect of −0.66 (95% CI [−1.07, −0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.

项与 SMPD4 相关的新闻（医药）

2024-06-27

·Pharmaceutical Technology

Verona scores FDA approval for Ohtuvayre as COPD maintenance therapy

Verona Pharma plans to launch Ohtuvayre in the US in the third quarter of this year. Image Credit: rafapress / Shutterstock. The US Food and Drug Administration (FDA) has approved Verona Pharma ’s Ohtuvayre (ensifentrine) as a maintenance treatment for chronic obstructive pulmonary disease (COPD) in adult patients. Ohtuvayre is an inhaled dual inhibitor of phosphodiesterase 3 and phosphodiesterase 4 enzymes and has bronchodilator and non-steroidal anti-inflammatory effects. Verona plans to launch the therapy in Q3 this year. “With substantial funding of up to $650m secured , Verona Pharma is well-positioned to distribute Ohtuvayre in the US, ensuring its availability even beyond 2026,” said Asiyah Nawab , Pharma Analyst at GlobalData. GlobalData is the parent company of Pharmaceutical Technology . The Ohtuvayre approval was based on the positive results from Phase III ENHANCE-1 and ENHANCE-2 trials (NCT04535986 and NCT04542057). The data from the pooled analysis of the studies showed significant improvements in the symptoms of COPD exacerbations, including dyspnea, breathlessness, cough, sputum, and chest symptoms, in patients with moderate to severe COPD. See Also: Verona scores FDA approval for Ohtuvayre as COPD maintenance therapy FDA go-ahead for Verona Ohtuvayre transforms US COPD exacerbator market Ohtuvayre is expected to generate global sales of $1.1bn by 2029, per a GlobalData analysis. The therapy’s major competitor is Sanofi and Regeneron Pharmaceutical’s blockbuster therapy Dupixent (dupilumab) . The US FDA is set to decide on the approval of monoclonal antibody, that targets both interleukin-4 (IL-4) and interleukin-13 (IL-13), in September. Dupixent has been approved for five other indications namely atopic dermatitis , asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis and prurigo nodularis. Such broad use is expected to increase Dupixent sales, with the therapy expected to generate $19.8bn in global sales in 2029, as per GlobalData analysis. Verona is also looking to expand the number of labelled indications for Ohtuvayre. The company plans to start a Phase II trial evaluating the therapy in patients with non-cystic fibrosis bronchiectasis, a respiratory condition where lung bronchi are damaged by repeated infections and inflammation. The company is expecting US FDA clearance to start the clinical trial, in the second half of this year. The company also plans to start a Phase II trial evaluating Ohtuvayre as a fixed-dose combination treatment with a long-acting muscarinic antagonist, glycopyrrolate, as a maintenance therapy for COPD. Verona intends to submit a related investigational new drug application (IND) to the FDA in the second half of this year.