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

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)

Prediction of New Risk Genes and Potential Drugs for Rheumatoid Arthritis from Multiomics Data. (PubMed, Comput Math Methods Med) - "Furthermore, drug repositioning prediction of the HRGs revealed three potential targets (ERBB2, IL6ST, and MAPK1) and nine possible drugs for RA treatment, of which two IL-6 receptor antagonists (tocilizumab and sarilumab) have been approved for RA treatment and four drugs (trastuzumab, lapatinib, masoprocol, and arsenic trioxide) have been reported to have a high potential to ameliorate RA. In summary, we believe that this study provides new clues for understanding the pathogenesis of RA and is important for research regarding the mechanisms underlying RA and the development of therapeutics for this condition."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • GP130 • HER-2 • IL6 • IL6ST • MAPK1

A Cooling Vest Improves Surgeons' Thermal Comfort Without Improving Cognitive Performance (ASA 2021) - "Continuous core body temperature was measured with wireless technology throughout surgery using iThermonitor WT701 (Raiing Medical, Boston, MA) and mean-skin temperatures from four sites were measured with TEMP TRAQ TT-100 (Blue Spark Technologies, Westlake, OH)...Presumably consequently, surgeons' thermal comfort was significantly improved during prolonged and strenuous orthopedic operations. Cognitive performance was well preserved, but not improved by cooling."

Fatigue • Orthopedics

[VIRTUAL] A Cooling Vest Improves Surgeons' Thermal Comfort Without Improving Cognitive Performance (ASA 2021) - "Continuous core body temperature was measured with wireless technology throughout surgery using iThermonitor WT701 (Raiing Medical, Boston, MA) and mean-skin temperatures from four sites were measured with TEMP TRAQ TT-100 (Blue Spark Technologies, Westlake, OH)...Presumably consequently, surgeons' thermal comfort was significantly improved during prolonged and strenuous orthopedic operations. Cognitive performance was well preserved, but not improved by cooling."

Fatigue • Orthopedics

Targeting multiple conformations of SARS-CoV2 Papain-Like Protease for drug repositioning: An in-silico study. (PubMed, Comput Biol Med) - "Further MD simulations for these drugs complexed with PLpro suggested the superior stability and binding of dobutamine and masoprocol inside the binding site compared to Benserazide. Generally, this approach can facilitate identifying drugs for repositioning via targeting multiple conformations of a crucial target for the rapidly emerging COVID-19 pandemic."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Hydrogen extends Caenorhabditis elegans longevity by reducing reactive oxygen species. (PubMed, PLoS One) - "At the transcript level, the expression of age-1 and let-363 was obviously decreased, while the expression of ins-18 was increased at the same time point (14 d)...Taken together, our data showed that hydrogen is a valuable antioxidant that can significantly reduce the body's ROS levels and extend the lifespan of C. elegans. This study also laid a foundation for the subsequent application of hydrogen in antiaging studies."

Journal

FDA lifts hold on trials of Insmed lung drug, shares up (Reuters) - Insmed stopped pursuing the development of its cancer products rhIGFBP-3 & INSM-18

Drug discontinuation • Oncology

Pharmacokinetic and efficacy study of nordihydroguaiaretic acid (NDGA) in non metastatic recurrent prostate cancer (clinicaltrials.gov) - P2, N=12; N=28 -> 12; Active, not recruiting -> Completed; Completion date: May 2010 -> Jun 2011

Completion date • Enrollment • Trial completion • Oncology

Differential regulation of the lipoxygenase pathway in shrimp hepatopancreases and ovaries during ovarian development in the black tiger shrimp Penaeus monodon. (PubMed) - "...Treatment with nordihydroguaiaretic acid resulted in the reduction of 8-HEPE, suggesting the enzyme-dependent catalysis of 8-HEPE in hepatopancreases...Furthermore, PmLOX expression increased steadily as shrimp ovary maturation progressed, while PmLOX expression and the amount of 8-HEPE decreased in shrimp hepatopancreases. These findings not only suggest differential requirements for hydroxy fatty acid biosynthesis in shrimp ovaries and hepatopancreases during the P. monodon ovarian development, but also provide insights into the LOX pathway in marine crustaceans."

Journal • Biosimilar

Antiviral activity of nordihydroguaiaretic acid and its derivative tetra-O-methyl nordihydroguaiaretic acid against West Nile virus and Zika virus. (PubMed) - Antimicrob Agents Chemother - "Flaviviruses are positive strand RNA viruses distributed all over the world that infect millions of people every year, and for which no specific antiviral agents have been approved. Moreover, treatment with NDGA, M4N, PF-429242, and Fatostatin also inhibited the multiplication of the mosquito-borne flavivirus Zika virus (ZIKV), which has been recently associated with birth defects (microcephaly) and neurological disorders. Our results point to SREBP inhibitors such as NDGA and M4N as potential candidates for further antiviral development against medically relevant flaviviruses."

Journal • Biosimilar • Hepatitis C Virus • Immunology • Infectious Disease