masoprocol (TT-100) / Insmed, University of California, TriAct Therap - LARVOL DELTA

Andean high-altitude dwellers with the NFKB1 haplotype (rs230511) are protected from acute mountain sickness (ASH 2025) - "The genotype frequencies were CC:50%, CT:50% and TT:0% in the AMS group and CC:0%, CT:0% and TT:100% in the control group (p<0.0001)...The CT genotype of NOS2 variant may also provide some protective effect. Larger cohorts and functional assays are needed to validate these associations and to further explore the molecular mechanisms by which the NFKB1 and NOS2 variants contribute to protection against AMS."

Anorexia • Cardiovascular • CNS Disorders • Gout • Inflammatory Arthritis • Insomnia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Sleep Disorder • NOS2

Optical genome mapping of a complex structural rearrangement family line on chromosome 18. (PubMed, Hereditas) - "OGM is of significant importance in the diagnosis and characterization of CCRs. OGM plays a critical role in diagnosing complex chromosomal rearrangements and has proven to be invaluable in clinical utility."

Journal • Developmental Disorders • Infertility • Mental Retardation • Sexual Disorders

GENESIS-IPF: PHASE 2A COHORT CHARACTERISTICS AND LUNG IMAGING INDICATE CORRELATES OF RESPONSE TO ISM001-055 (RENTOSERTIB) IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS (CHEST 2025) - P2 | " High-resolution computed tomography (HRCT) was obtained at baseline (week 0) for 69 of 71 participants in INS018-055-003 (NCT05938920), a randomized, double-blind, placebo-controlled Phase 2a study in patients with IPF conducted at 22 clinical sites in China. The enrollment profile and baseline severity of disease in GENESIS-IPF participants and individual treatment arms is typical of the UK IPF patient population. The timing and methods for evaluating lung function is appropriate, as evidenced by the strong correlation between FVC and lung volume, which aligns with the expected physiological relationship. Changes in FVC and ppFVC from baseline to week 12 suggest that the best outcomes may occur in patients with the lowest level of fibrosis and the highest rentosertib treatment dose."

Clinical • P2a data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • COL1A1 • CTNNB1 • IL10 • MMP10 • TGFB1

Protective effects of Tribulus Terrestris extract on cisplatin-induced ovarian damage: Antioxidants and anti-inflammatory insights. (PubMed, Hum Exp Toxicol) - "This study aims to evaluate the effects of TT extract on ovarian tissue damage induced by cisplatin.Material and MethodTwenty-five female BALB/c mice were divided into five groups (n = 5): Control, CIS (Cisplatin only), CIS + TT100 (100 mg/kg TT extract daily + CIS), CIS + TT300 (300 mg/kg TT + CIS), and CIS + TT500 (500 mg/kg TT daily + CIS). The expression of inflammatory markers TNF-α and IL-1β was higher in the CIS group and decreased in the TT-treated groups.ConclusionTribulus Terrestris extract effectively mitigates cisplatin-induced ovarian toxicity by enhancing follicular count, improving antioxidant activity, and reducing oxidative stress. TT treatment also elevated AMH and progesterone levels while decreasing inflammatory markers, underscoring its potential as a protective agent against cisplatin-induced ovarian damage."

Journal • Inflammation • Women's Health • IL1B • TNFA

DSF-YOLO for robust multiscale traffic sign detection under adverse weather conditions. (PubMed, Sci Rep) - "We demonstrate the effectiveness of our model on the TT-100 K dataset, the GTSDB dataset, and the BDD 100 K dataset, achieving improvements in mAP of 9%, 1.5%, and 2.6%, respectively. Compared to the baseline model, Cls and Loc metrics decreased by approximately 3 and 1.2.The experiments indicate that our model exhibits excellent generalization ability and robustness, successfully performing small target detection under complex weather conditions in the realm of traffic sign recognition."

Journal

Discovery and Functional Validation of EP3 Receptor Ligands with Therapeutic Potential in Cardiovascular Disease. (PubMed, Int J Mol Sci) - "TUCA, masoprocol, and pravastatin sodium have emerged as lead candidates and were validated in vitro using endothelial migration and platelet aggregation assays. TUCA exhibited the most consistent inhibitory effect on endothelial migration, whereas masoprocol and hydrocortisone significantly reduced platelet aggregation. These findings establish a multidimensional workflow for the rational identification of EP3 ligands and support their potential use in cardiovascular therapeutics."

Journal • Cardiovascular • Inflammation

Biomarker Analysis Reveals Antifibrotic and Anti-inflammatory Signatures in Idiopathic Pulmonary Fibrosis Patients Treated With INS018_055, an AI-discovered TNIK Inhibitor, in a 12-week Phase 2a Study (ATS 2025) - P2 | " Serum samples were collected from 43 of the 71 participants in INS018-055-003 (NCT05938920), a randomized, double-blind, placebo-controlled Phase IIa study in patients with IPF conducted at 22 clinical sites in China. We identified candidate biomarkers that assess and predict early therapeutic response in patients with IPF treated with INS018_055. These findings suggest dual antifibrotic and immunomodulatory mechanisms of action. Further validation of these biomarkers will be performed in our ongoing Phase 2 study conducted in the US (NCT05975983)."

Biomarker • Clinical • Late-breaking abstract • P2a data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • COL1A1 • CTNNB1 • CXCL12 • IL10 • IL7 • LTBP2 • LY9 • MMP10 • TGFB1

INS018-055, A Novel Traf2- and NCK-interacting Kinase (TNIK) Inhibitor, Improves Lung Function in Patients With Idiopathic Pulmonary Fibrosis: Results From a Randomized, Double-blind, Placebo-controlled Phase 2a Study (ATS 2025) - P2 | "Patients with % predicted FVC > 40%, FEV1/FVC ratio >0.7 and DLCO ≥ 25% and < 80% were randomized 1:1:1:1 at baseline to receive 30 mg INS018-055 QD (n=18), 30 mg INS018-055 BID (n=18), 60 mg INS018-055 QD (n=18) or placebo (n=17) orally for 12 weeks, with or without background anti-fibrotic therapy (pirfenidone or nintedanib). These results suggested that INS018-055 is well-tolerated in IPF patients and demonstrated a dose-dependent effect in lung function improvement within 12 weeks, supporting further development of INS018-055 in larger Phase 2b trials. Figure 1: Descriptive summary of FVC change from baseline at week 12, box plot, mean (SD)"

Clinical • P2a data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Tamarindus indica sub-products as potential tools for simultaneous management of diabetes and obesity. (PubMed, Food Funct) - "Chemical analyses revealed that all extracts present a great variety of phenolic compounds and that the seed extract possesses at least 5 unique compounds (ursodiol, masoprocol, lenticin, chenodeoxycolic acid and 13-keto-9Z,11E-octadecadienoic acid), which, according to docking studies, could be involved in the inhibition of both α-amylase and lipase. The overall conclusion is that the tamarind seed extract displays great potential for being used in the management of obesity and diabetes."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts. (PubMed, Sci Rep) - "Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30-90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts."

Journal • Preclinical • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Ventricular Tachycardia • NAV1

Anti-aging effect of glycerophosphocholine in Steinernema kraussei 0657L. (PubMed, Front Physiol) - "It can activate the IIS pathway by regulating the expression of daf-2, ins-18 and daf-16 genes, sek-1 and skn-1 genes of MAPK pathway, sod-3, ctl-1, gst-4 and other antioxidant genes...These results indicate that GPC is mainly involved in the lifespan regulation of S. kraussei 0657L and plays an important role in resistance to external stress by activating the insulin/IGF-1 signaling pathway and downstream PI3K/MAPK kinase, creating a new idea for improving the commercial efficacy of S. kraussei. It also laid a theoretical foundation for its further efficient development and utilization in the field of biological control."

Journal • CAT • IGF1 • SOD3

Uncovering hidden complex structural mechanisms: Conventional karyotype as a complement to chromosomal microarray (ACMG 2024) - "Chromosome analysis showed a complex rearrangement of chromosome 18, 46,XX,rec(18)dup(18p)inv(p11.21q2?1.33)dpat,inv(18)(q12.1q21.32)?ins(18)(q21.1p11.31p11.31)pat... We present cases ascertained during a three-month period in a single cytogenetics laboratory that demonstrate the utility of conventional chromosome analysis in providing a complete characterization of chromosomal abnormalities. These cases of seemingly straightforward copy number gains and losses represent mosaicism and complex chromosomal rearrangements that were not appreciated by CMA alone. The chromosomal findings have important diagnostic and recurrence implications for the patients being evaluated, thus emphasizing the necessity of complementary conventional chromosome analysis in clinical cytogenetic evaluation."

Autism Spectrum Disorder • Developmental Disorders • Genetic Disorders

Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity. (PubMed, Pharmacol Rep) - "The combined treatment with INS 18 U/kg + PIO 5 mg/kg was more effective in preventing advanced cachexia in TB rats than each treatment alone, emerging as the best approach, considering the lower dosage and higher efficacy. This combination completely preserved adipose mass and markedly reduced weight loss through a synergistic mechanism linked to improved insulin sensitivity. These findings provide new insights into the importance of drug combinations in effectively combating fat loss in advanced cachexia."

Combination therapy • Journal • Metastases • Preclinical • Cachexia • Oncology

Evaluation of Thiol Disulfide Homeostasis and Ischemia-Modified Albumin Levels as an Indicator of Oxidative Stress in Acne Vulgaris. (PubMed, Dermatol Pract Concept) - "Our study suggests that oxidative stress associated with AV disease pathogenesis may occur through mechanisms dependent on thiol and IMA levels. Therefore, in AV, oral supplementation or topical application of antioxidants may be a good way to increase drug efficacy or prevent potential harm."

Journal • Acne Vulgaris • Cardiovascular • Dermatology

Characteristics of patients with asthma using single inhaler triple therapy (SITT) in the USA (ERS 2023) - "All-cause and asthma-specific resource use was similar across both groups before TT initiation (Figure 1). Conclusions Differences in baseline clinical characteristics were noted between TT100/200 groups, with older and more severe patients initiating high dose FF/UMEC/VI."

Clinical • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Masoprocol: a promising candidate for targeting insulin resistance by inhibiting resistin with optimal druglikeness Potentials: an in silico approach. (PubMed, J Biomol Struct Dyn) - "However, ioversol did not prove satisfying drug-likeness properties, while masoprocol showed the most favourable pharmacokinetic and drug-likeness properties. This study has demonstrated that masoprocol offers a novel inhibitory effect on resistin with the highest ligand affinity, making it a promising drug for combating insulin resistance.Communicated by Ramaswamy H. Sarma."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • RETN

"Statin ⏬#YAP/TEAD ⏬TGFβ ⏫KLF signaling in hiPSC-#EndothelialCell New statin target🤠 GGTase-RhoA-YAP axis-> Hyperglycemic #EndMT Diabetic endothelial dysfunction Dr. Joseph Wu lab @NatureCVR 2023 @chun_liu_86 @twinsmc18 @Nazish_Sayed @Joseph_C_Wu https://t.co/iiFIUMOwBn" (@HaoYin20)

Diabetes • RHOA • TGFB1

A novel peptide derived from Haematococcus pluvialis residue exhibits anti-aging activity in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway. (PubMed, Food Funct) - "Further studies illustrated that HPp up-graded the mRNA transcription of the genes associated with the insulin/insulin-like growth factor signaling (IIS) pathway and some co-factors, including daf-16, daf-2, ins-18, and sir-2.1...Taken together, HPp could promote longevity with improved stress resistance and antioxidant properties in vivo through the IIS pathway. These data suggested that HPp might serve as a good source of anti-aging actives, and in particular, laid a foundation for the high value-added application of marine microalgae."

Journal • IGF1 • SOD3

"@DrJessTaylor @AvertixMedical @TTGimaging @digiradcorp @NatalieStaplin @ManuelGorostidi @pnatarajanmd @JJheart_doc @AllanaLeBlanc @DrJPChaput @Joseph_C_Wu @chun_liu_86 @twinsmc18 @stanleyqilab @Nazish_Sayed @firstage5 @StanfordCVI @GreenstoneBio @kottmaier_md @arnoldgehrke" (@Cardiac_Wire)

"Congrats @twinsmc18!" (@JustinChen_1)

"Detailed protocol for hPSC-/hiPSC-derived cardiac #Pericytes PDGFRβ+ NG2+ ACTA2+ TE-7- SMMHC- GATA4+ TBX20+ "keep early cardiac pericytes at a very high confluency"⏫complete EMT+differentiation via paracrine @twinsmc18 @Joseph_C_Wu @STARProtocols 2023 https://t.co/FkIEfh4Jft" (@HaoYin20)

ACTA2 • PDGFRB

Genetic analysis of a Chinese pedigree with 18q21.2-q22.3 duplication and deletion in two offspring respectively resulting from a maternal intrachromosomal insertion (PubMed, Zhonghua Yi Xue Yi Chuan Xue Za Zhi) - "The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree."

Journal • Developmental Disorders

CRISPR/Cas9-Targeted Disruption of Two Highly Homologous Arabidopsis thaliana DSS1 Genes with Roles in Development and the Oxidative Stress Response. (PubMed, Int J Mol Sci) - "The homozygous mutant lines with large indels (dss1(I)del25 and dss1(V)ins18) were phenotypically characterized during plant development and their sensitivity to oxidative stress was analyzed...In this work, the dss1 double mutant was not obtained due to embryonic lethality. These results suggest that the DSS1(V) protein could be an important molecular component in plant abiotic stress response."

Journal

"Please check out our new protocol for differentiating human #iPSC derived #cardiacpericytes published @CircAHA. These cells are integral for coronary microvasculature. Congrats @twinsmc18 @chun_liu_86 @ShaneRZhao1 and @StanfordCVI @Illumina scientists https://t.co/c7xD4nTDFD" (@Joseph_C_Wu)

"Our recent work vascularizing hPSC-derived cardiac & hepatic organoids, aiming to overcome a major bottleneck in the stem cell & regenerative medicine fields; @firstage5 @LeiTian20 @KitchenerWilson @evlyall @twinsmc18 @DetlefObal @Joseph_C_Wu & other @StanfordCVI authors" (@oscarabilez)