Editorial Material
Hematology
Monika Haemmerle
Summary: This study explores the role of Mnk1 in megakaryocytes and platelets, showing that it regulates protein synthesis and affects megakaryocyte ploidy and platelet production. These findings have clinical implications and contribute to our understanding of platelet function and thrombosis.
Article
Multidisciplinary Sciences
Muhammad Imran Khan, Eun Sun Jeong, Muhammad Zubair Khan, Jin Hyuk Shin, Jong Deog Kim
Summary: This study investigates the therapeutic potential of exosomes derived from neural stem cells in Alzheimer's disease. The results show that these exosomes can regulate the expression of key proteins involved in AD pathology and reduce neuroinflammation. Additionally, the exosomes enhance cell viability, suggesting their neuroprotective effects.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Joonhong Jun, Hyungwoo Moon, Songyi Yang, Junghun Lee, Jihyun Baek, Hyejin Kim, Hyunwook Cho, Kyungrim Hwang, Soyeon Ahn, Yuro Kim, Gibeom Kim, HyunTae Kim, Hoseok Kwon, Jung-Mi Hah
Summary: We have developed new inhibitors for c-Jun N-terminal kinase 3 (JNK3) as a potential treatment for Alzheimer's disease (AD). Through pharmacodynamic optimization studies, we identified benzimidazole compounds 2 and 3 as potential JNK3 inhibitors, but their unreliable pharmacokinetic properties led us to develop carbamate inhibitors 2h and 3h. In vitro studies validated carbamate inhibitors 2h and 3h as potent and highly selective JNK3 inhibitors with favorable pharmacokinetic profiles. Oral administration of 2h and 3h improved cognitive function in AD mouse models, indicating their potential as effective treatments for Alzheimer's disease. Carbamate JNK3 inhibitor 3h, in particular, restored cognitive function and reduced pTau levels in the hippocampal tissues of AD mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Neurosciences
Pol Andres-Benito, Margarita Carmona, Monica Jordan Pirla, Benjamin Torrejon-Escribano, JoseAntonio del Rio, Isidro Ferrer
Summary: The presence of various substances in the cytoplasmic granules of neurons in the hippocampus, including CK1-d, p38-P Thr180/Tyr182, and SAPK/JNK-P Thr183/Thr185, was confirmed in cases with positive neurofibrillary tangles (NFT) pathology, but not in middle-aged individuals. The early appearance of phosphorylated kinases and proteins in cytoplasmic granules suggests their role in the abnormal phosphorylation of tau protein at the early stages of granulovacuolar degeneration (GVD). Rating: 8/10
Article
Biochemistry & Molecular Biology
Seda Onder, Kevser Biberoglu, Melike Yuksel, Ozden Tacal
Summary: Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Recent studies focus on multi-targeted drug strategies. TBO, a potential candidate, shows promising effects on reducing amyloid levels and decreasing phosphorylated tau.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Cell Biology
Chen Wang, Jie Zeng, Li-Jie Li, Min Xue, Si-Li He
Summary: The study showed that Cdc25A regulates ferroptosis in cervical cancer cells by modulating the levels of PKM2 and ErbB2, affecting the response of cervical cancer cells to sorafenib treatment.
CELL DEATH & DISEASE
(2021)
Review
Pharmacology & Pharmacy
Yuran Qiu, Yuanhao Wang, Zongtao Chai, Duan Ni, Xinyi Li, Jun Pu, Jie Chen, Jian Zhang, Shaoyong Lu, Chuan Lv, Mingfei Ji
Summary: RAS is a key oncogenic protein, and mutations in it can lead to human cancer. Recent studies have identified several phosphorylation residues in RAS protein that can regulate its activity, providing a new direction for developing anti-RAS drugs. This review summarizes the research advances in RAS phosphorylation and provides insights into therapeutic strategies.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Clinical Neurology
Jean-Pierre Bellier, Yuqi Cai, Sarah M. Alam, Thorsten Wiederhold, Arica Aiello, Jonathan S. Vogelgsang, Sabina Berretta, Jasmeer P. Chhatwal, Dennis J. Selkoe, Lei Liu
Summary: A wide array of post-translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine-proline-proline (TPP). The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology.
ALZHEIMERS & DEMENTIA
(2023)
Article
Multidisciplinary Sciences
Juan R. Perea, Esther Garcia, Laura Valles-Saiz, Raquel Cuadros, Felix Hernandez, Marta Bolos, Jesus Avila
Summary: Tauopathies are neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein. Inflammation, particularly the activation of microglia, is also involved in these diseases. The p38 MAPK pathway, primarily expressed in glia, has been associated with tau phosphorylation in neurodegenerative diseases like Alzheimer's Disease. Using a mouse model, researchers found increased p38 activation in microglia of the hippocampus during aging. Interestingly, these mice also displayed activated rod microglia, although p38 activation was decreased in this subpopulation. This suggests that rod microglia may have a neuroprotective phenotype in the context of tau pathology.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Reina Bassil, Kenneth Shields, Kevin Granger, Ivan Zein, Shirley Ng, Ben Chih
Summary: Researchers have developed an automated long-term culturing platform for human iPSC neurons, astrocytes, and microglia to model cellular aspects of Alzheimer's disease.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Isidro Ferrer, Pol Andres-Benito, Karina Ausin, Reinald Pamplona, Jose Antonio del Rio, Joaquin Fernandez-Irigoyen, Enrique Santamaria
Summary: The study found abnormal protein phosphorylation at the early stages of NFT pathology in the elderly and sporadic Alzheimer's disease (sAD), with protein phosphorylation abnormalities in the FC preceding the formation of NFTs and SPs. The most active period of dysregulated phosphorylation is at stages III-IV, when some individuals may be classified clinically as having mild cognitive impairment, which is a precursor stage in the progression to dementia.
Article
Virology
Chun-Chiao Yu, Pei-Chen Lin, Cho-Han Chiang, Shu-Tang Jen, Yen-Ling Lai, Shih-Chin Hsu, Lee-Chiang Lo, Jing-Jer Lin, Nei-Li Chan, Ming-Jiun Yu
Summary: In this study, we discovered for the first time that the ATP-binding domain of NS3 is involved in NS5A phosphorylation. In vitro assays showed that casein kinase I alpha is a very potent kinase responsible for NS5A phosphorylation at serines 225, 232, and 235. Our data suggest that ATP binding by NS3 probably results in conformational changes that recruit casein kinase I alpha to phosphorylate NS5A, initially at S225 and subsequently at S232 and S235. Our discovery reveals intricate requirements of the structural integrity of NS3 for NS5A hyperphosphorylation and HCV replication.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hilda Mirbaha, Dailu Chen, Vishruth Mullapudi, Sandi Jo Terpack, Charles L. White, Lukasz A. Joachimiak, Marc Diamond
Summary: The study reveals that the initiation of tauopathy is associated with the formation of seed-competent (M-s) tau monomers, which precedes the formation of insoluble fibrils. This research provides important insights into the origins of tauopathy and highlights the significance of M-s monomers in disease progression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hilda Mirbaha, Dailu Chen, Vishruth Mullapudi, Sandi Jo Terpack, Charles L. White, Lukasz A. Joachimiak, Marc Diamond
Summary: The research shows that in a mouse model of tauopathy, the disease begins with the formation of M-s monomers, whose conformational activity is independent of phosphorylation, and forms oligomers before further assembling into insoluble fibrils.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Di Xiao, Hani Jieun Kim, Ignatius Pang, Pengyi Yang
Summary: This study developed a statistical framework to identify stable phosphorylated sites in human phosphoproteomics datasets, which are evolutionarily conserved, functionally important, and enriched in core signaling and gene pathways. Particularly, SPSs in the RNA splicing pathway are frequent targets of cancer mutations, suggesting a potential link between dysregulated RNA splicing and cancer development through mutations on SPSs.
Review
Anesthesiology
R. L. H. Yim, K. M. M. Leung, C. C. M. Poon, M. G. Irwin
Summary: Parkinson's disease patients have a higher risk of peri-operative complications, necessitating multidisciplinary management and specialized care. Continuous dopaminergic treatment, peri-operative disease pathway development, and telemedicine are improving peri-operative care. Management for advanced Parkinson's disease is evolving with potential for integrated care and changes in anaesthetic management.
Review
Anesthesiology
C. C. Nestor, C. Ng, P. Sepulveda, M. G. Irwin
Summary: Mixing long- and short-acting local anaesthetics to hasten onset and extend duration may lead to ineffective solutions or potential harm due to pharmacokinetic principles; many local anaesthetic adjuncts are not approved for use, which can result in adverse events, and pharmaceutical compatibility needs to be confirmed before administration.
Review
Anesthesiology
C. K. E. Chung, C. C. M. Poon, M. G. Irwin
Summary: Surgery and anesthesia can cause stress to the brain, and monitoring with electroencephalography and cerebral oximetry can help assess anesthesia depth and cerebral metabolic activity. However, research results on the ability of these monitors to alleviate peri-operative neurocognitive complications have been contradictory. Understanding the changes in electroencephalography under anesthesia and those associated with aging is important for correctly interpreting anesthesia depth indices. Cerebral oximetry is useful for detecting cerebral desaturation and identifying higher-risk patients. An algorithm-based approach may be most effective in managing cerebral desaturation events.
Letter
Anesthesiology
C. C. Nestor, P. Sepulveda, M. G. Irwin
Letter
Anesthesiology
C. C. Nestor, P. Sepulveda, M. G. Irwin
Article
Cell Biology
Yanjing He, Yin Cai, Tianhao Sun, Liangqing Zhang, Michael G. Irwin, Aimin Xu, Zhengyuan Xia
Summary: Acute myocardial infarction is a leading cause of death worldwide. Restoration of blood flow may lead to ischemia/reperfusion injury. This study found that miR-503 exacerbated I/R injury via inactivation of PI3K/Akt and STAT3 pathways.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Anesthesiology
S. Agarwal, K. El-Boghdadly
Summary: This position statement highlights the importance of prioritising equity, diversity and inclusion in anaesthesia and medicine. The Anaesthesia Editors outline their policies and practices to achieve these goals, including transparent recruitment practices and removing barriers to leadership roles. They commit to regularly reviewing and improving their policies and embracing equity, diversity and inclusion.
Letter
Emergency Medicine
Wei Deng, Steven Wang, Rex Pui Kin Lam, Timothy Hudson Rainer, Michael Garnet Irwin
ANNALS OF EMERGENCY MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Qiu Qiu, Joshua C. J. Chew, Michael G. Irwin
Summary: Opioids are still important in postoperative analgesia, but the focus is on using them as part of multimodal regimens to avoid their complete use. The development of new drugs with more favorable adverse effect profiles may increase safety while maintaining efficacy.
EXPERT OPINION ON PHARMACOTHERAPY
(2022)
Review
Anesthesiology
L. M. Hughes, M. G. Irwin, C. C. Nestor
Summary: Propfol-remifentanil-based total intravenous anaesthesia is commonly used in clinical practice due to its favorable pharmacokinetic profile. However, interruption in remifentanil supply presents an opportunity to explore alternative opioids and consider adjuncts to propofol-based anaesthesia. This article provides an overview of different opioids and their administration methods, as well as the role of non-opioid adjuncts in total intravenous anaesthesia.
Article
Anesthesiology
L. Q. Yang, L. Zhu, X. Shi, C. H. Miao, H. B. Yuan, Z. Q. Liu, W. D. Gu, F. Liu, X. X. Hu, D. P. Shi, H. W. Duan, C. Y. Wang, H. Weng, Z. L. Huang, L. Z. Li, Z. Z. He, J. Li, Y. P. Hu, L. Lin, S. T. Pan, S. H. Xu, D. Tang, D. I. Sessler, J. Liu, M. G. Irwin, W. F. Yu, POLMA-EP Investigators
Summary: In a clinical study, it was found that using a supraglottic airway device rather than a tracheal tube can reduce postoperative pulmonary complications in older patients undergoing non-cardiothoracic surgery under general anesthesia.
Review
Nursing
Jiayin Ruan, Shucheng Chen, Jiagui Liang, Fiona Yan Yee Ho, Teris Cheung, Janice Yuen Shan Ho, Wai Chi Chan, Haiyong Chen, Dennis Cheuk Wing Au, Rebecca Wing Yan Lee, Yim Wah Mak, Wing Fai Yeung
Summary: This study conducted a systematic review and meta-analysis and found that TCM-based integrated health interventions were effective in relieving depression. However, due to the low quality of the included studies, future rigorous randomized controlled trials are needed to provide more robust evidence.
JOURNAL OF CLINICAL NURSING
(2023)
Article
Anesthesiology
W. Deng, C. C. Nestor, K. M. M. Leung, J. Chew, H. Wang, S. Wang, M. G. Irwin
Summary: The amount of aerosol generation from positive pressure ventilation via supraglottic airway devices in low-risk patients was quantified and compared to aerosol levels during conversation and coughing. The study found that the aerosol concentration generated by supraglottic airway insertion and removal was significantly lower than that produced during talking and coughing. The proportion of easily inhaled and small particles was also much lower during insertion and removal compared to talking and coughing.
Review
Medicine, General & Internal
Abigail Silva, Barbara Costa, Irene Castro, Joana Mourao, Nuno Vale
Summary: This review aims to discuss the current information on drug interactions in the perioperative period. Drug interactions during this period can affect the efficacy and safety of treatment. There are three types of drug interactions. It is important to recognize that drug interactions may increase toxicity and reduce efficacy, increasing the risk of complications. Thoroughly reviewing a patient's medication list and vigilant monitoring are essential in minimizing risks.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Cell Biology
Ran You, Yuen-Shan Ho, Raymond Chuen-Chung Chang
Summary: The increasing amount of particulate matter (PM) in the ambient air is associated with a higher risk of neurodegenerative diseases. Studies have shown that PM-induced neurotoxicity, neuroinflammation, oxidative stress, and damage in blood-brain barrier and neurovascular units contribute to the development of neurodegenerative diseases.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
