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alpha-1 antitrypsin (Alfalastin / rhAAT, GTC)

✓ Approved

rEVO Biologics · SERPINA1 · 重组蛋白

什么是 alpha-1 antitrypsin？

alpha-1 antitrypsin 是一种重组蛋白，由rEVO Biologics研发。该药已获批，用于治疗相关适应症，给药途径：Unknown。

药物档案

商品名Alfalastin, rhAAT, GTC
公司rEVO Biologics
药物类别重组蛋白
分子靶点SERPINA1
给药途径Unknown
状态Approved
来源： ClinicalTrials.gov, rEVO Biologics

作用机制

分子靶点

alpha-1 antitrypsin 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 antitrypsin 针对 3 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Congenital, familial and genetic disordersCongenital emphysema✓ Approved
Skin and subcutaneous tissue disordersDermatitis allergicPreclinical
Skin and subcutaneous tissue disordersDermatitis atopicPreclinical

相关研究文献

PubMedJournal of biochemical and molecular toxicology2026-10-26

Theranekron Attenuates Inflammation, Oxidative Stress Index, and Apoptosis in Lipopolysaccharide-Induced Cardiovascular Toxicity: Association With Hypoxia-Inducible Factor-1 Alpha-Related Gene Expression.

Savran Mehtap M, Asci Halil H, Imeci Orhan O, Oguzlar Furkan Cagri FC et al.

This study aimed to evaluate the possible protective effects of Theranekron, an extract derived from Tarantula cubensis venom, on cardiovascular damage induced by lipopolysaccharide (LPS) in an experimental rat model. A total of 32 male Wistar Albino rats were randomly divided into 4 groups: Control, Lipopolysaccharide, Lipopolysaccharide plus Theranekron, and Theranekron alone. Lipopolysaccharide administration caused pronounced histopathological changes in the heart and aorta, including endothelial sloughing, hyperemia, hemorrhage, and infiltration of inflammatory cells. These pathological findings were accompanied by elevated oxidative stress markers, increased tumor necrosis factor-alpha and inducible nitric oxide synthase immunoreactivity, and increased caspase-3 immunoreactivity. Additionally, genes associated with the hypoxia-inducible factor-1 alpha (HIF-1α) pathway-such as interleukin 6, signal transducer and activator of transcription 3 (STAT3), and vascular endothelial growth factor-were significantly upregulated in the lipopolysaccharide group. Theranekron pretreatment was associated with partial attenuation of oxidative stress imbalance, of inflammatory and apoptotic immunoreactivity, and of the upregulation of HIF-1α-related transcripts. Overall, these findings suggest that Theranekron may offer partial protection against early LPS-induced cardiovascular injury.

PMID 42929009
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PubMedInternational journal of chronic obstructive pulmonary disease2026-10-26

Real-World Impact of Mepolizumab in COPD in a US Commercial and Medicare Claims Database.

Panettieri Reynold A RA, Paczkowski Rosirene R, Mei Hannah H, Burrows Emmeline E et al.

Mepolizumab reduces exacerbations in patients with chronic obstructive pulmonary disease (COPD) and was recently approved in the United States (US) for the add-on maintenance treatment of adult patients with inadequately controlled COPD and an eosinophilic phenotype. Given the limited real-world data on mepolizumab effectiveness in COPD, this study assessed its real-world impact in patients with COPD, prior to US regulatory approval of mepolizumab for COPD. Retrospective, longitudinal analysis from the US Komodo Research claims database (January 2016-June 2024). The first observed mepolizumab claim was defined as the index date. All patients were aged ≥40 years on index date, had ≥2 COPD diagnosis claims in the 12 months pre-index (baseline period) or on index date, and required ≥2 pharmacy/medical claims for mepolizumab from index date to end of observation. Patients with ≥2 asthma diagnosis claims or ≥1 diagnosis claim(s) for cystic fibrosis, lung cancer, interstitial lung disease, or α-1 antitrypsin deficiency during the baseline period or on index date were excluded. Outcomes assessed during the 12 months post- versus 12 months pre-mepolizumab initiation included annualized exacerbation rates, oral corticosteroid (OCS) use, and COPD-related healthcare resource utilization (HCRU). Descriptive analyses included 693 mepolizumab initiators (58% Medicare), while pre-post analyses included 470 patients with 12 months of pre- and post-initiation data. Annualized rate of moderate/severe exacerbations decreased by 41% (P<0.001) post- versus pre-mepolizumab. Relative reductions of 26% and 33% in rates of OCS dispensing and bursts were observed (P<0.001), and relative reductions of 22-37% in COPD-related HCRU including hospitalizations (P=0.038), emergency department visits (P<0.001), and outpatient visits (P<0.001). In this real-world retrospective study of US patients with COPD, initiation of mepolizumab was associated with significant reductions in COPD exacerbations, OCS use and COPD-related HCRU.

PMID 42928917
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PubMedAutophagy2026-10-26

AKT1-phosphorylated TERT assembles a FOXO3-MYC transcriptional complex that drives ERphagy and proteostasis in post-mitotic RPE.

Babu Vishnu Suresh VS, Ghosh Sayan S, Bammidi Sridhar S, Jiwon Ryu R et al.

The retinal pigment epithelium (RPE) sustains lifelong proteostasis under chronic stress, yet how post-mitotic cells activate macroautophagy/autophagy when canonical kinase pathways suppress it remains unresolved. Here we demonstrate that AKT1 (protein kinase B alpha), drives autophagy through a non-canonical transcriptional mechanism triggered by isoform imbalance. In RPE and age-related macular degeneration (AMD) models, AKT2 (protein kinase B beta) hyperactivation destabilizes MTORC2 (mechanistic target of rapamycin complex 2) and engages RPS6KB/S6K (ribosomal protein S6 kinase beta) -mediated IRS-1 (insulin Receptor Substrate 1) inhibition, creating a feedforward autophagic arrest. Compensatory AKT1 activation via MTORC2 phosphorylates TERT (telomerase reverse transcriptase) at serine 824, driving nuclear translocation that is independent of telomere maintenance. In the nucleus, TERT assembles with FOXO3 (forkhead Box O3) and MYC (MYC proto-oncogene, bHLH transcription factor) into a tripartite transcriptional complex that occupies the EIF2AK3/PERK promoter (eukaryotic translation initiation factor 2-alpha kinase 3/ protein kinase R-like endoplasmic reticulum kinase), enabling EIF2AK3 transcriptional activation. This activity converts the unfolded protein response from pro-apoptotic to cytoprotective: EIF2AK3-ATF4 (activating transcription factor 4) signaling promotes core autophagy machinery biogenesis and selective ERphagy through the receptors TEX264 (testis expressed 264) and CCPG1(cell cycle progression 1), which prevents pathological EIF2AK3 clustering and preserves tubular ER architecture in diseased RPE. Using C. elegans phosphorylation-deficient mutants, mouse models and AMD patient iPSC-RPE, we establish that AKT1-mediated TERT phosphorylation is an evolutionarily conserved prerequisite for FOXO/DAF-16 nuclear function and lysosomal homeostasis in post-mitotic cells, offering therapeutic potential through targeted pharmacologic inhibition of AKT2.Abbreviations: ACTB: actin, beta; AKT1: AKT serine/threonine kinase 1; AKT2: AKT serine/threonine kinase 2; ALP: autophagy-lysosomal pathway; AMD: age-related macular degeneration, ATF4: activating transcription factor 4; ATG3: autophagy related 3; ATG4B: autophagy related 4B cysteine peptidase; ATG7: autophagy related 7; CCPG1: cell cycle progression 1; CFH: complement factor H; C57BL/6J: C57 black 6J; DMSO: dimethyl sulfoxide; MYC: MYC proto-oncogene, bHLH transcription factor; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE-1α: endoplasmic reticulum to nucleus signaling 1; ERphagy: endoplasmic reticulum-selective autophagy; FOXO1: forkhead box O1; FOXO3: forkhead box O3; iPSC-RPE: induced pluripotent stem cell-derived retinal pigment epithelium; ITGB1/integrin β1: integrin subunit beta 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPKAP1/SIN1: MAPK associated protein 1; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR complex 2; PBS: phosphate-buffered saline; PI3K: phosphoinositide 3-kinase; RICTOR: RPTOR independent companion of MTOR complex 2; RPE: retinal pigment epithelium; RPTOR: regulatory associated protein of MTOR complex 1; SQSTM1/p62: sequestosome 1; TERT: telomerase reverse transcriptase; TEX264: testis expressed 264, ER-phagy receptor; UPR: unfolded protein response; VCL: vinculin; WT: wild type.

PMID 42929416
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PubMedEcology2026-10-26

Community history modifies how plant diversity shapes beta multifunctionality.

He Yan Y, Yang Rui R, Mao Lingfeng L

Research on ecosystem multifunctionality (EMF) has mainly quantified the magnitude of multiple functions within local communities (alpha multifunctionality [alpha-EMF]), whereas less is known about variation in function profiles among communities (beta multifunctionality [beta-EMF]). We asked how plant diversity affects variation in ecosystem function profiles among communities and whether this relationship depends on community history. We analyzed 5-year means of six ecosystem functions from 240 subplots in the DELTa-BEF, short for DEterminants of Long-Term Biodiversity Effects on Ecosystem Functioning Experiment, comparing new communities without experimental plant or soil history, resown communities retaining soil history, and old communities with continuous plant and soil histories. We adapted a variance-based beta diversity framework to quantify beta-EMF and partition it into local contributions to beta multifunctionality (LCBM) and function contributions to beta multifunctionality (FCBM). Plant diversity increased alpha-EMF in all treatments, with stronger increases in resown and old than in new communities. Richness was not detectably related to LCBM in new communities but was associated with lower LCBM in resown communities and higher LCBM in old communities, with the clearest contrast between the resown and old treatments. Leaf area index contributed more to beta-EMF than expected under equal contributions (20.2%), whereas basal respiration contributed less (13.2%); the other four functions did not differ from the equal-contribution expectation. Thus, similar gains in local multifunctionality can be accompanied by contrasting patterns of spatial functional heterogeneity, depending on community history. Partitioning beta-EMF into local and function contributions provides a practical way to identify which communities and functions contribute to spatial heterogeneity.

PMID 42928695
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PubMedApplied immunohistochemistry & molecular morphology : AIMM2026-10-26

The Utility and Potential Pitfalls of Fibroblast Activation Protein-Alpha (FAP) Immunohistochemistry in Diagnosing Invasive Colorectal Adenocarcinoma in Biopsies.

Cui Min M, Xue Yue Y, Willis Joseph J

Diagnosing invasive colorectal adenocarcinoma (CRC) in limited biopsy samples can be challenging. This study evaluates fibroblast activation protein-α (FAP)'s role in diagnosing CRC and identifies potential pitfalls. To evaluate the expression pattern of FAP in CRC, we analyzed 168 cases of CRC with established diagnosis, including 30 whole slides and 138 cases from a tissue microarray (TMA). The study group includes 33 colorectal lesion biopsies with diagnostic challenges, identified retrospectively over 9 years in 1 institution. These biopsies were initially not diagnosed as CRC and confirmed to be so upon subsequent resection. Six additional cases of adenoma and 4 cases of solitary rectal ulcers were also evaluated. FAP was expressed in the cancer stroma of 161/168 (96%) of CRC cases, including 29/30 whole slides and 132/138 TMA. The diagnosis of 33 challenging cases by H&E included adenoma (n=4), high-grade dysplasia (HGD, n=16), and concerning for CRC (n=13). Among these cases, all 20 cases of adenoma or HGD were FAP-negative. Out of 13 "concerning for CRC" cases, 9 (69%) showed FAP positivity in the stroma. Five of 6 additional adenomas were FAP-negative, while 1 adenoma showed FAP staining in scar tissue from the prior biopsy site. Of the 4 cases of solitary rectal ulcers, 1 exhibited weak FAP expression in the granulation tissue. In conclusion, FAP immunohistochemistry may assist in diagnosing CRC in challenging cases. Due to FAP positivity in benign conditions, such as scar tissue and benign ulcers, awareness of the pitfalls is important when applying FAP immunostaining in practice.

PMID 42929204
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PubMedEpidemiologia (Basel, Switzerland)2026-10-26

Psychometric Evaluation of the Serbian MacNew Heart Disease Health-Related Quality of Life Questionnaire Before and After Elective Coronary Artery Bypass Grafting.

Nesic Ivan I, Oyewole Olufemi O OO, Vukovic Petar P, Kaitovic Marko M et al.

Background/Objectives: To evaluate the psychometric properties of the MacNew Heart Disease Health-Related Quality of Life Questionnaire (MacNew HRQL) in patients who underwent elective coronary artery bypass grafting (CABG) in Serbia. Methods: Recruitment of participants was organized at the Institute for Cardiovascular Diseases "Dedinje". The MacNew HRQL was administered prior to having CABG, and 1, 6 and 12 months after CABG. The scale was compared to the Short Form-36 (SF-36) and Depression, Anxiety and Stress Scale-21 (DASS-21). Clinical data were obtained from medical records. Results: A total of 192 patients had complete follow-up data (80.2% male, 64.1 ± 7.6 years old). The Cronbach's alpha and McDonald's omega coefficients were ≥0.80. The original three-factor structure was supported by indices on the confirmatory factor analysis using the Unweighted Least Squares estimator (ULS) at 6 and 12 months post-CABG, but not at baseline and 1 month after CABG. Longitudinal measurement invariance suggested that models were not supported. The MacNew HRQL global score correlated with clinical parameters at all four time points. All MacNew HRQL domains correlated with mental and physical scores of the SF-36 and with depression, anxiety and stress scores. Conclusions: The MacNew HRQL in Serbian had good internal consistency and construct validity. The three-factor structure was most favorable under the ULS at 6 and 12 months post-CABG. As the measurement invariance was not supported, changes in scores over time cannot be interpreted unequivocally as changes in the same underlying constructs. The scores right before and after CABG should be interpreted with caution.

PMID 42930332
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