disitertide (P144) / Digna Biotech - LARVOL DELTA

Clinical significance of SLIT2/ROBO1 expression in prostate cancer (PubMed, Zhonghua Bing Li Xue Za Zhi) - "The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis (P<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer (P<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of..."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology • ROBO1 • SLIT2 • TGFB1

Role of TGF-? in knee joint dysfunction following chemically-induced osteoarthritis in rats (IASP 2024) - "inhibitor [Disitertide (Tocris; UK... Transforming Growth Factor-? (TGF-?) inhibitor improves joint function with partial restoration of cartilage morphology in the MIA rat model of osteoarthritis. This promising finding needs further study in different rodent models of OA."

Preclinical • Anesthesia • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • GAPDH

Structures of Mature and Urea-Treated Empty Bacteriophage T5: Insights into Siphophage Infection and DNA Ejection. (PubMed, Int J Mol Sci) - "Atomic models of the head, connector complex, tail tube, and tail tip were built for mature T5, and atomic models of the connector complex, comprising the portal protein pb7, adaptor protein p144, and tail terminator protein p142, were built for urea-treated empty T5. Our findings revealed that the aforementioned proteins did not undergo global conformational changes before and after DNA ejection, indicating that these structural features were conserved among most myophages and siphophages. The present study elucidates the underlying mechanisms of siphophage infection and DNA ejection."

Journal • Infectious Disease

rAAV-Mediated PEX1 Retinal Gene Augmentation Results in Long-Term Improvements in Retinal Function and Structure in a Mouse Model of Mild Zellweger Spectrum Disorder (ASGCT 2024) - "Mol Ther 30(4S1): p 144...There, the gene can perform its required functions, restoring vision and retinal structure in the ZSD-mouse. Our results demonstrate the strong potential of gene therapy to preserve vision in ZSD, and support translating this therapy to those who need it."

Preclinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Metabolic Disorders • Ophthalmology • Retinal Disorders

TGF-β1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-β1/Smads signaling pathway inhibition. (PubMed, Arab J Gastroenterol) - "TGF-β1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-β1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting."

Journal • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Mood Disorders • IL1B • TGFB1 • TNFA

Omeprazole induces profibrotic gene expression in rat kidney: implication of TGF-β/Smad signaling pathway. (PubMed, Drug Chem Toxicol) - "However, simultaneous treatment of omeprazole and the TGF-β inhibitor, disitertide (P144) (1 mg/kg body weight i.p.) suppresses the TGF-β/Smad signaling pathway and subsequent production of CTGF and TIMP-1. Collectively, the current findings demonstrate that omeprazole has the ability to promote the expression of the profibrotic genes CTGF and TIMP-1 in a ROS and TGF-β dependent manner. The present study suggests the co-use of ROS scavenger to improve the therapeutic use of the PPI omeprazole."

Journal • Preclinical • Fibrosis • Immunology • CTGF • TGFB1 • TIMP1

PET imaging with [Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model. (PubMed, Front Oncol) - "[Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect. [Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies."

Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • TGFB1

AC.APS.P144. Measuring Outcomes in ACS: Our Lives Depend on It (AHA 2022) - No abstract available

Cardiovascular

Adherence to inhaled corticosteroids in pregnant asthmatics (BTS WM 2022) - "P144 Figure 1 Pick up rates of ICS treatmentConclusion Poor compliance to ICS treatment in asthma is not confined to pregnant asthmatics and may be a historical finding in these patients. However, an increase in ICS adherence following clinic review indicates that education and reinforcement of medication safety and importance of adherence to treatment is essential in this cohort and will undoubtedly improve clinical outcomes and reduce the risk of exacerbations.Patient concerns relating safety of inhaled therapies in pregnancy should be addressed early to improve patient outcomes in the high risk group.Trends to poor compliance in the absence of clinic review has led to the evolution of monthly appointments until review until delivery, rather than early discharge."

Asthma • Immunology • Obstetrics • Pulmonary Disease • Respiratory Diseases

Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity. (PubMed, Gut Microbes) - "Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation • HSPD1

TGF-β1 peptide-based inhibitor P144 ameliorates renal fibrosis after ischemia-reperfusion injury by modulating alternatively activated macrophages. (PubMed, Cell Prolif) - "Our study showed that the TGF-β1 peptide-based inhibitor P144 decreased renal fibrosis through the blockade of the TGF-β1-Smad3 signaling pathway and the modulation of macrophage polarization, suggesting its potential therapeutic use in IRI-induced renal fibrosis."

Journal • Cardiovascular • Fibrosis • Immunology • Reperfusion Injury • SMAD3 • TGFB1

Cis- and Trans-eQTM Analysis Reveals Novel Epigenetic Markers of Atopy in Nasal Airway Epithelium (ATS 2022) - "Of interest, more associations were identified in subjects with atopy (p=144,069) than in control subjects (p=191)... Our trans-eQTM study of atopy in nasal epithelium reveals novel associations between DNA methylation and gene expression that would not have been captured through cis-eQTM analysis. While most findings were specific to nasal epithelium, some overlapped between nasal epithelium and white blood cells."

Allergy • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • HLA-DQB1

Ginsenoside Rh4 Suppresses Metastasis of Gastric Cancer via SIX1-Dependent TGF-β/Smad2/3 Signaling Pathway. (PubMed, Nutrients) - "Further validation by proteomic screening, co-treatment with disitertide, and SIX1 signal silencing revealed that SIX1, a target of Rh4, induced EMT by activating the TGF-β/Smad2/3 signaling pathway. In summary, our discoveries demonstrated the essential basis of the anti-GC metastatic effects of Rh4 via suppressing the SIX1-TGF-β/Smad2/3 signaling axis, which delivers a new idea for the clinical treatment of GC."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TGFB1

P144 a Transforming Growth Factor Beta Inhibitor Peptide, Generates Antifibrogenic Effects in a Radiotherapy Induced Fibrosis Model. (PubMed, Curr Oncol) - "P144 administration clearly reduces RIF and opens a new potential co-treatment approach to reduce complications in soft tissue sarcoma (STS) radiotherapy. Further studies are required to establish whether the dosage and timing optimization of P144 administration, in different RIF phases, might entirely avoid fibrosis associated with STS brachytherapy."

Journal • Fibrosis • Immunology • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TGFB1

Platelet-derived factors induce placental plasminogen activator inhibitor-1 (GTH 2022) - "Additionally, BeWo cells were treated with forskolin and the peptide P144, which encompasses amino acids 730–743 from the membrane-proximal ligand-binding domain of TGFBR3... In conclusion, our results suggest that platelet-derived factors induce placental PAI-1 expression via TGFBR3 receptor signalling. Increased activation of maternal platelets may contribute to significantly upregulated placental PAI-1 in preeclampsia."

Gynecology • PAI1

"Our poster P144 Well being gap: one size MS service does not fit all @ectrimscongress #ECTRIMS2021 come and see us @GavinGiovannoni @DrWBRO @TheNeuroAcademy @AgneStraukiene @ruthstross @OvercomingMS @MSTrust @mssocietyuk" (@Sue_NHiS)

Anti-TGFβ (Transforming Growth Factor β) Therapy With Betaglycan-Derived P144 Peptide Gene Delivery Prevents the Formation of Aortic Aneurysm in a Mouse Model of Marfan Syndrome. (PubMed, Arterioscler Thromb Vasc Biol) - "P144 prevents the onset of aortic aneurysm but not its progression. Results indicate the importance of reducing the excess of active TGFβ signaling during the early stages of aortic disease progression."

Journal • Preclinical • Cardiovascular • Gene Therapies • Genetic Disorders • Palliative care • APOA1 • PCR • TGFB1 • TGFB2

Discovery of Selective Transforming Growth Factor β Type II Receptor Inhibitors as Antifibrosis Agents. (PubMed, ACS Med Chem Lett) - "Recently, fresolimumab and disitertide, two peptidic TGF-β blockers, demonstrated significant therapeutic effects toward human skin fibrosis. In this report, we disclose selective TGF-β type II receptor (TGF-βRII) inhibitors that exhibited high functional selectivity in cell-based assays. The representative compound 29 attenuated collagen type I alpha 1 chain (COL1A1) expression in a mouse fibrosis model, which suggests that selective inhibition of TGF-βRII-dependent signaling could be a new treatment for fibrotic disorders."

Journal • Dermatology • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • COL1A1 • TGFB1

Bombyx mori can synthesize ascorbic acid through the l-gulose pathway to varying degrees depending on developmental stage. (PubMed, Arch Insect Biochem Physiol) - "The AsA content increased significantly during E144 h-E168 h in the late embryonic stage and P48 h-P144 h in the middle-late pupal stage, in which exogenous VC was not ingested...The GULO activity in the pupal fat body dramatically decreased when the screened BmGulo-like gene (BGIBMGA005735) was knocked down with small interfering RNA; in addition, the survival rate and hatching rate of eggs significantly decreased 21% and 44%, respectively, and embryonic development was delayed. Thus, Bombyx mori can synthesize AsA through the l-gulose pathway, albeit with low activity, and this synthesis ability varies with developmental stages."

Journal

Ginsenoside Rb3 Alleviates the Toxic Effect of Cisplatin on the Kidney during Its Treatment to Oral Cancer via TGF-β-Mediated Mitochondrial Apoptosis. (PubMed, Evid Based Complement Alternat Med) - "The research aimed to confirm the role of the transforming growth factor-β (TGF-β) in cisplatin- (CPT-) evoked kidney toxicity and elucidate the mechanism that ginsenoside Rb3 (Rb3) could alleviate the kidney toxicity by CPT during its treatment to oral cancer via TGF-β-mediated mitochondrial apoptosis. Additionally, after treating with the TGF inhibitor of disitertide, Rb3 exhibited no alleviation effects on CPT-evoked cellular apoptosis ratio, inhibition of Bax expression, and induction of Bcl-2 expression in GP-293 cells. Rb3 could alleviate CPT-evoked toxic effects on kidney cells during its treatment to oral cancer via TGF-β-mediated mitochondrial apoptosis."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Renal Cell Carcinoma • Solid Tumor • BCL2 • CASP3 • CASP8 • CASP9

Osseointegration around dental implants biofunctionalized with TGFβ-1 inhibitor peptides: an in vivo study in beagle dogs. (PubMed, J Mater Sci Mater Med) - "Accordingly, better results in the experimental groups were proven both by the quantitative and the qualitative analysis. Surface biofunctionalization with TGF-β1 inhibitor peptides, P17 and P144, resulted in better quantitative and qualitative parameters relative to implant osseointegration."

Journal • Preclinical

Mesenchymal Stem Cell-Derived Exosomal microRNA-3940-5p Inhibits Colorectal Cancer Metastasis by Targeting Integrin α6. (PubMed, Dig Dis Sci) - "MSC-exosomal miR-3940-5p inhibits invasion and EMT of CRC cells as well as growth and metastasis of tumors through targeting ITGA6 and the following TGF-β1 inactivation. This study may provide novel insights into exosome-based treatment for CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ITGA6

Sports Behavior in Middle-Aged Individuals With Uncorrected Anomalous Coronary Artery From the Opposite Sinus of Valsalva (AHA 2016) - "Although a majority of patients with ACAOS were informed about their diagnosis, only a minority of patients were counseled about sports restriction. Most of the counseled patients were patients with ACAOS and IAC but counseling had no significant effect on sports behavior at follow-up."

Clinical • Biosimilar

Early reduction of large layer V corticospinal motor neurons precedes the inflammatory response and upregulation of phosphorylated-tau following repetitive mild TBI (Neuroscience 2017) - "...Sham and TBI rats were euthanized at acute (p90), short (p144) or long (p235) time points... Following repeat mild TBI, rats that display severe motor deficits and progressive CTE-like brain pathology exhibit a significant reduction in large layer V corticospinal motor neurons that precedes the microglia response and upregulation of P-tau. This suggests that early targeting of neuronal cell damage could be beneficial to altering the progression of CTE caused by repetitive head injury. By continuing to elucidate the underlying mechanisms of this disease, appropriate treatment strategies can be developed and applied."

CNS Disorders

P144, a TGF-β1 antagonist peptide, synergizes with sildenafil and enhances erectile response via amelioration of cavernosal fibrosis in diabetic rats (J Sex Med) - PMID: 24134744; "Diabetic rats exhibited a decreased erectile response, severe corporal veno-occlusive dysfunction (CVOD), and structural alterations including cavernosal fibrosis and decreased smooth muscle content....Treatment with P144 synergized sildenafil and significantly increased erectile response by the potential antifibrotic activity."

Preclinical • Fibrosis