Article
Medicine, Research & Experimental
Sara H. Osum, Eunice I. Oribamise, Stanislas M. A. S. Corbiere, Mandy Taisto, Tyler Jubenville, Alex Coutts, Mark N. Kirstein, James Fisher, Christopher Moertel, Ming Du, David Bedwell, David A. Largaespada, Adrienne L. Watson
Summary: Neurofibromatosis type 1 (NF1) is caused by germline mutations in the tumor-suppressor gene NF1, leading to an increased risk of nervous system tumors. In this study, a minipig model of NF1 carrying a premature termination codon (PTC) was used to investigate the potential of nonsense suppression in restoring expression of the NF1-encoded protein neurofibromin. The results showed that nonsense suppression did not significantly increase neurofibromin in primary NF1-'- Schwann cells, but it reduced phosphorylated ERK.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Biochemistry & Molecular Biology
Ming-Han Wu, Rui-Yu Lu, Si-Jie Yu, Yi-Zhen Tsai, Ying-Chen Lin, Zhi-Yu Bai, Ruo-Yu Liao, Yi-Chiang Hsu, Chia-Chi Chen, Bi-He Cai
Summary: This study found that PTC124 can induce the expression of tumor suppressor genes NOTCH1 and FAT1 in head and neck squamous cell carcinoma, inhibiting cell proliferation and showing therapeutic potential.
Article
Biochemistry & Molecular Biology
Chia-Chi Chen, Ruo-Yu Liao, Fang-Yu Yeh, Yu-Rou Lin, Tze-You Wu, Alexa Escobar Pastor, Danny Danilo Zul, Yun-Chien Hsu, Kuan-Yo Wu, Ke-Fang Liu, Reiji Kannagi, Jang-Yi Chen, Bi-He Cai
Summary: In this study, a simple and affordable method was developed to create different clones of p53 with nonsense mutations for investigating the effects of PTC124. The results showed that PTC124 was more effective in rescuing C-terminal nonsense mutations of p53 than N-terminal ones.
Article
Biochemistry & Molecular Biology
Julie Carrard, Fiona Ratajczak, Josephine Elsens, Catherine Leroy, Rebekah Kong, Lucie Geoffroy, Arnaud Comte, Guy Fournet, Benoit Joseph, Xiubin Li, Sylvie Moebs-Sanchez, Fabrice Lejeune
Summary: The study has built a new screening system and identified two new molecules that can effectively inhibit nonsense-mediated mRNA decay (NMD). These molecules show no cellular toxicity at tested concentrations and have been validated in a lung cancer model with a nonsense mutation.
Article
Biology
Dylan B. Udy, Robert K. Bradley
Summary: NMD is an essential quality control pathway that detects and degrades mRNAs with premature termination codons. It not only suppresses mRNA levels, but also effectively limits the accumulation of proteins encoded by these mRNA molecules.
LIFE SCIENCE ALLIANCE
(2022)
Article
Medical Laboratory Technology
Mengya Zhang, Yanhong Lin, Xiao Zhang, Fenghua Lan, Jian Zeng
Summary: This study found that mutations c.683T > A and c.844C > T in the SMN1 gene can trigger spinal muscular atrophy (SMA) and activate the nonsense-mediated mRNA decay (NMD) pathway. Therefore, the role of NMD should be considered when studying the pathogenesis of these mutations.
CLINICA CHIMICA ACTA
(2022)
Article
Cell & Tissue Engineering
Amy Leung, Almudena Sacristan-Reviriego, Pedro R. L. Perdigao, Hali Sai, Michalis Georgiou, Angelos Kalitzeos, Amanda -Jayne F. Carr, Peter J. Coffey, Michel Michaelides, James Bainbridge, Michael E. Cheetham, Jacqueline van der Spuy
Summary: Leber congenital amaurosis type 4 (LCA4) is a severe sight impairment disease caused by AIPL1 mutations. Researchers used induced pluripotent stem cells (iPSCs) derived from renal epithelial cells to generate retinal organoids and found that the photoreceptor cells in these organoids exhibited the characteristics of LCA4. They also discovered a potential therapeutic drug, but its ability to restore the photoreceptor cells was limited.
Article
Biochemistry & Molecular Biology
Atze J. Bergsma, Stijn L. M. In't Groen, Fabio Catalano, Manjiro Yamanaka, Satoru Takahashi, Toshika Okumiya, Ans T. van der Ploeg, W. W. M. Pim Pijnappel
Summary: A study presented a generic assay for identifying variants affecting mRNA expression and splicing in Pompe disease. The assay was able to detect aberrant splicing caused by mRNA degradation, aiding in functional analysis and targeted treatment development for the disease.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Chemistry, Medicinal
Nesrine Benslimane, Federica Miressi, Camille Loret, Laurence Richard, Angelique Nizou, Ioanna Pyromali, Pierre-Antoine Faye, Frederic Favreau, Fabrice Lejeune, Anne-Sophie Lia
Summary: Nonsense mutations play a role in peripheral neuropathies by causing premature termination codons at the mRNA level. Readthrough molecules or NMD inhibitors, such as amlexanox, could be potential therapies for hereditary neuropathies. In the study, treatment with amlexanox on patient-derived neuronal cells carrying a specific mutation resulted in stabilization of GDAP1 mRNAs and restoration of mitochondrial morphology, highlighting the potential of readthrough molecules and NMD inhibitors for the treatment of genetic alterations in peripheral neuropathies.
Article
Surgery
Rahil H. H. Shah, Shyam Vedantam, Shria Kumar, Sunil Amin, Michelle Pearlman, Sean Bhalla
Summary: By analyzing 17 studies involving 1198 patients, it was found that intragastric balloon (IGB) therapy for 6 months can significantly reduce fasting blood glucose, systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein, and triglyceride levels. This suggests that IGB therapy can not only promote weight loss but also improve insulin resistance, blood pressure, and dyslipidemia.
Article
Nutrition & Dietetics
Laurent Maimoun, Safa Aouinti, Marion Puech, Patrick Lefebvre, Melanie Deloze, Pascal de Santa Barbara, Eric Renard, Jean-Paul Christol, Justine Myzia, Marie-Christine Picot, Denis Mariano-Goulart, David Nocca
Summary: This longitudinal study aimed to analyze the changes in body composition (BC) following sleeve gastrectomy (SG) and its effects on glucose, lipids, inflammation, and resting energy expenditure (REE). The study found that after 1 month, losses of lean tissue mass (LTM) and fat mass (FM) were comparable, but at 12 months, the loss of FM exceeded that of LTM. VAT also decreased significantly over this period, and biological parameters normalized while REE was reduced. Beyond 12 months, there were no substantial variations in most BC, biological, and metabolic parameters.
Article
Genetics & Heredity
Hamza Bakhtiar, Kyle T. Helzer, Yeonhee Park, Yi Chen, Nicholas R. Rydzewski, Matthew L. Bootsma, Yue Shi, Paul M. Harari, Marina Sharifi, Martin Sjostrom, Joshua M. Lang, Menggang Yu, Shuang G. Zhao
Summary: By using RNA phenocopy signatures of key cancer driver gene mutations, this study demonstrates an improved ability to predict response to targeted therapies. The phenocopy signatures were found to increase the accuracy of drug response predictions and identify additional cancer cell lines that respond well to targeted treatments. The results suggest the importance of routine RNA sequencing in addition to standard DNA sequencing for selecting patients for targeted therapies.
NPJ GENOMIC MEDICINE
(2022)
Article
Medicine, General & Internal
Orlando Martins, Philipp Sahrmann, Joao Ramos, Francisco Caramelo, Sergio Matos, Isabel Poiares Baptista
Summary: Peri-implantitis treatment options are varied, and this study suggests that resective surgery and implantoplasty may be effective in certain cases. Prior to implantoplasty, non-surgical treatments are necessary. Results show significant improvements in clinical parameters over a 24-month follow-up period.
MEDICINA-LITHUANIA
(2022)
Article
Gastroenterology & Hepatology
Niels Teich, Harald Gruemmer, Eric Joergensen, Thomas Liceni, Frank Holtkamp-Endemann, Tim Fischer, Susanne Hohenberger
Summary: The study aimed to evaluate the changes in work productivity, capacity for daily activities, and HRQoL in UC patients treated with golimumab in Germany. The results showed that golimumab led to significant improvements in work productivity, daily activity, HRQoL, and disease-related hospitalization rates in moderate to severe UC patients.
BMC GASTROENTEROLOGY
(2021)
Article
Orthopedics
Cliff Lange, Henning Madry, Jagadeesh K. Venkatesan, Gertrud Schmitt, Susanne Speicher-Mentges, David Zurakowski, Michael D. Menger, Matthias W. Laschke, Magali Cucchiarini
Summary: In adult sheep, rAAV-mediated sox9 gene transfer enhanced osteochondral repair after 6 months and reduced changes of perifocal osteoarthritis.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2021)
