北京若生智能科技有限公司
Drug Database
AL

alpha-1 proteinase (Trypsone / Trypsan)

✓ Approved

Grifols, S.A. · SERPINA1

什么是 alpha-1 proteinase？

alpha-1 proteinase 是一种治疗药物，由Grifols, S.A.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

商品名Trypsone, Trypsan
公司Grifols, S.A.
分子靶点SERPINA1
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Grifols, S.A.

作用机制

分子靶点

alpha-1 proteinase 作用于 1 个分子靶点：

SERPINA1serpin family A member 1 (PRO2275, nNIF)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

alpha-1 proteinase 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
Congenital, familial and genetic disordersCongenital emphysema✓ Approved

相关研究文献

PubMedTranslational cancer research2026-09-11

Comparative efficacy of liver resection vs. radiofrequency ablation for small hepatocellular carcinoma stratified by alpha-fetoprotein status: a retrospective cohort study using restricted mean survival time and number needed to treat analysis.

Chen Hong H, Zhou Junbin J

The choice between liver resection (LR) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) ≤3 cm remains controversial. This study evaluated whether alpha-fetoprotein (AFP) status modulates the comparative efficacy of these modalities using absolute benefit metrics. Patients with T1N0M0 HCC (≤3 cm) treated with LR or RFA were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. After 1:1 propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were analyzed. Restricted mean survival time (RMST) and number needed to treat (NNT) were utilized to quantify the absolute clinical gain of LR over RFA. Among 1,119 identified patients, 235 matched pairs were analyzed. LR demonstrated superior survival in the overall cohort (P<0.001). A significant interaction was observed between treatment modality and AFP status (Pinteraction<0.01). In AFP-negative patients, LR provided a profound survival advantage [CSS: hazard ratio (HR) =0.362; 95% confidence interval (CI): 0.220-0.594; P<0.001], translating into a substantial RMST extension of 8.1 months and a low NNT of 4. Conversely, in the AFP-positive subgroup, this surgical advantage was notably attenuated (CSS: HR =0.800; 95% CI: 0.555-1.152; P=0.23), with the RMST extension dropping to 3.5 months and the NNT increasing to 12. The superiority of LR over RFA in small HCC is significantly modulated by AFP-defined tumor biology. AFP-negative patients derive profound absolute survival gains from surgery, whereas benefits in AFP-positive cases are marginal, supporting RFA as a viable alternative for biologically aggressive tumors.

PMID 42724405
阅读全文 →
PubMedVirus genes2026-09-11

The interaction between HIV-1 central polypurine tract and host SAMHD1 dNTPase during HIV-1 vector transduction in human primary nondividing monocyte-derived macrophages.

Alvarez Natalie N NN, Burke Hannah S HS, Freeman Tzipporah T, Taki Sara S et al.

Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a dNTPase that depletes intracellular dNTP pools in nondividing cells such as human monocyte-derived macrophages (MDMs). These low dNTP levels suppress HIV-1 reverse transcription kinetics in MDMs. In contrast, viral protein X (Vpx), an accessory protein encoded by human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs), induces degradation of SAMHD1, thereby increasing cellular dNTP pools and promoting a more permissive infection in MDMs. Our previous study demonstrated that the central polypurine tract (cPPT) facilitates completion of HIV-1 reverse transcription, particularly when reverse transcription is kinetically delayed due to dNTP limitation in nondividing human lung fibroblasts. However, the role of cPPT during HIV-1 replication in macrophages where SAMHD1 establishes low dNTP pools and kinetically restricts viral reverse transcription remains untested. To address this question, we performed time-course analyses of transduction efficiency and fluorescence intensity in MDMs transduced with two distinct HIV-1 vector systems containing or lacking the cPPT sequence, in the presence or absence of Vpx. Our data show that while either cPPT insertion or Vpx treatment alone modestly increases HIV-1 vector transduction efficiency, the combined presence of cPPT and Vpx results in a pronounced enhancement of both transduction efficiency and fluorescence intensity in MDMs. Overall, these findings demonstrate that cPPT and Vpx act cooperatively to enhance HIV-1 vector transduction in nondividing MDMs, supporting an interplay between cPPT function and Vpx-mediated SAMHD1 degradation in macrophages.

PMID 42722809
阅读全文 →
PubMedTranslational cancer research2026-09-11

Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.

Wang Gennian G, Cheng Hua H, Zhang Yaping Y, Guo Xiaohu X et al.

Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, have garnered significant attention from the global scientific community due to their potential threats to human health, particularly their association with the occurrence and development of cancer. The goal of our study is to create a predictive marker for pancreatic ductal adenocarcinoma (PAAD) based on MNPs-related genes, with the purposes of predicting survival outcomes and assessing the tumor immune microenvironment. Using multi-cohort data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC), we assessed the association between MNPs and PAAD prognosis through the Xiantao Academic (https://www.xiantao.love/). The development of a prognostic signature was followed by an assessment of its significance through the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and decision curve analysis (DCA). The validity of the risk model was confirmed through the ICGC and GSE71729 cohorts. The model was then assessed for levels of tumor immune infiltration. To explore MNPs-related genes expression characteristics within immune cells in PAAD, we performed single-cell RNA sequencing and spatial transcriptomics analysis through the Sparkle Platform (https://grswsci.top/). Finally, in vitro experiments were conducted to investigate the biological function of interleukin 1 alpha (IL1A). A four-gene signature comprising XDH, IL1A, KIF20A, and ASPM, based on MNPs, was developed to stratify PAAD patients into two distinct risk groups. The high-risk group showed a significantly poorer prognosis. A similar trend was verified in the external cohorts ICGC and GSE71729. The signature risk score affected immune cell infiltration in the PAAD microenvironment. The infiltration of B cells, CD8+ T cells, cytotoxic cells, immature dendritic cells (iDCs), mast cells, plasmacytoid dendritic cell (pDC), T cells, Tem cells, T follicular helper (TFH) cells, and T helper 17 (Th17) cells had a positive correlation with the low-risk group. In contrast, high-risk patients tended to have increased number of T helper (Th2) cells and higher expression of SIGLEC15, CD274, IGSF8. Knockdown of IL1A in PAAD cells inhibited their tumor proliferation ability in vitro. Using MNPs-related genes, we built a prognostic model for PAAD, revealing that patients with high-risk scores are likely to have a worse prognosis. This model is designed to develop personalized treatment strategies tailored to the specific needs of each patient, thereby improving clinical outcomes for PAAD patients. Furthermore, IL1A could be a promising therapeutic candidate for PAAD.

PMID 42724844
阅读全文 →
PubMedBrain communications2026-09-11

A meta-analysis of periodic and aperiodic electrophysiological features in Parkinson's disease.

Norouzi Hamzeh H, Ietswaart Magdalena M, Adair Jason J, Learmonth Gemma G

Parkinson's disease is characterized by a range of motor and non-motor changes that can negatively impact quality of life. Many studies have identified potential clinical electrophysiological correlates of Parkinson's disease with an aim of developing new methods of identifying at-risk patients and forming the basis of therapeutic interventions. However, these studies do not present consistent results, and a formal meta-analysis is warranted to identify reliable EEG or magnetoencephalography (M/EEG) characteristics across datasets. In this meta-analysis of open-access M/EEG datasets (n = 6; 4 EEG and 2 MEG), we compared periodic and aperiodic characteristics of resting-state recordings in 368 patients with Parkinson's disease and 570 age-matched healthy controls. Specifically, we compared the power and peak frequency of unadjusted and aperiodic-adjusted alpha- and beta-band oscillations, and the exponent and offset, across the two groups. Parkinson's patients had a consistently elevated aperiodic exponent and offset. Patients also had higher unadjusted beta-band power, but this was no longer present when the aperiodic features were removed, suggesting that previous findings of elevated beta activity in Parkinson's disease could be confounded by aperiodic activity rather than reflecting true oscillatory differences. Patients also had higher adjusted and unadjusted alpha-band power and a slower alpha peak frequency compared with controls, whereas no group difference in beta peak frequency was identified. In conclusion, this large cohort meta-analysis points to a broadly consistent pattern of both periodic and aperiodic changes in Parkinson's patients in M/EEG signals that may be used to develop diagnostics and targeted interventions in the future.

PMID 42724388
阅读全文 →
PubMedNature communications2026-09-11

AAT/SERPINA1 Pi*Z variant linked to gestational length and preterm birth prevention via AAT in mice.

Koivulehto E E, Pasanen A A, Haapalainen A M AM, Tiensuu H H et al.

About 10% of pregnancies end prematurely before 37 weeks, without effective prevention therapies. Previously, we identified rare damaging variants in SERPINA1 encoding alpha-1-antitrypsin (AAT) in families with recurrent spontaneous preterm births and detected decreased protein and transcript levels of AAT/SERPINA1 from placentas in spontaneous preterm births. Here, we investigate genetic associations between SERPINA1 variants and gestational duration and evaluate AAT supplementation as a therapeutic intervention in a mouse model of preterm birth. SERPINA1 Pi*Z variant (rs28929474-T) is associated with gestational duration (P < 5×10-8) in European-ancestry mothers with spontaneous preterm and term deliveries. We detect a nine-day decrease in gestational duration and a fourfold odds for preterm birth vs. term birth in Pi*Z homozygotes (Pi*ZZ), compared to other genotypes. In transgenic mice without endogenous AAT, exogenous Prolastin® treatment inhibits lipopolysaccharide induced preterm births (P < 0.05). Supplemented AAT is preferentially deposited in the placenta. Our findings support AAT's protective role in spontaneous preterm births and highlight its therapeutic potential, particularly in SERPINA1 Pi*ZZ genotype carriers.

PMID 42722639
阅读全文 →
PubMedTranslational cancer research2026-09-11

Midkine restrains T-cell mediated anti-tumor immunity by suppressing macrophage M1 polarization in lung adenocarcinoma.

Qian Ting T, Sun Zijian Z, Wang Xin X, Sun Yan Y

Lung adenocarcinoma (LUAD) is characterized by a highly immunosuppressive tumor microenvironment (TME), which limits the efficacy of current anti programmed cell death protein 1 (anti-PD-1) immunotherapy. Midkine (MDK), a heparin-binding growth factor, is frequently overexpressed in various malignancies; however, its specific role in regulating anti-tumor immunity in LUAD remains unclear. This study aimed to investigate the immunomodulatory role of MDK in LUAD, and to evaluate the therapeutic potential of MDK neutralization. In this study, we analyzed single-cell sequencing datasets and validated MDK expression across multiple non-small cell lung cancer (NSCLC) cell lines. To explore the immunomodulatory functions of MDK, we established ex vivo co-culture models using human peripheral blood mononuclear cells (PBMCs) and LUAD cells. We assessed the impact of recombinant MDK and an MDK-neutralizing antibody (α-MDK) on T cell proliferation, differentiation, and cytotoxicity, as well as macrophage polarization, using flow cytometry, lactate dehydrogenase (LDH) release assays, and multiplex cytokine measurement. We confirmed that MDK is significantly upregulated in malignant LUAD cells compared to normal lung epithelial cells. Functional analysis revealed that MDK signaling suppresses T cell-mediated anti-tumor immunity by inhibiting the expansion of cytotoxic CD8+ T cells and restricting T helper type 1 cell (TH1) polarization. Furthermore, MDK impaired the polarization of macrophages towards the pro-inflammatory M1 phenotype, and dampened antigen-presenting cell function. Notably, blocking MDK signaling with a neutralizing antibody effectively reversed these immunosuppressive effects, restoring T cell cytotoxicity and enhancing the secretion of pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Our findings demonstrate that MDK acts as a key regulator in the LUAD TME by simultaneously restraining T cell activation and M1 macrophage polarization. These data suggest that targeting MDK offers a promising therapeutic strategy to overcome immune suppression and improve clinical outcomes in LUAD.

PMID 42724375
阅读全文 →

注册免费账户还可查看另外 9996 篇文献

免费注册查看全部文献 →

了解更多alpha-1 proteinase