Review
Biochemistry & Molecular Biology
Akash Gupta, Jeremias G. Galletti, Zhiyuan Yu, Kevin Burgess, Cintia S. de Paiva
Summary: Neurotrophins, including NGF, BDNF, NT-3, and NT-4, play important roles in promoting neuron differentiation, development, and survival. NGF has been approved for the treatment of neurotrophic keratitis, while the other neurotrophins are less studied in ocular surface diseases. Neurotrophin analogs with panTrk activity and TrkC selectivity show promise as novel drugs for treating dry eye disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Terri Kagan, Gloria Stoyanova, Richard A. Lockshin, Zahra Zakeri
Summary: This study investigates the different functions of ceramide in cellular differentiation and dedifferentiation. The results suggest that the function of ceramide heavily depends on its intracellular location, and further understanding of its function requires resolving its location during cellular status changes.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Neurosciences
Yi-jun Liu, Xiao-feng Chen, Li-ping Zhou, Feng Rao, Dian-ying Zhang, Yan-hua Wang
Summary: This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect. Results showed that Wnt5a could promote Schwann cell proliferation and the expression of various neurotrophic factors, and the Wnt5a/Fn group outperformed the control groups in terms of nerve regeneration and functional recovery 12 weeks after the operation. The Wnt5a/Fn nerve conduit may promote peripheral nerve defect regeneration by facilitating multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Ophthalmology
Jae Yong Kim, Jin Hyoung Park, Soon-Suk Kang, Sae-Byeok Hwang, Hungwon Tchah
Summary: The study demonstrated that topical application of NGF delays the progression of diabetic cataracts by attenuating polyol pathway activation and increasing Na+/K+-ATPase protein levels.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Chemistry, Medicinal
Marian N. Aziz, Linh Nguyen, Yan Chang, Delphine Gout, Zui Pan, Carl J. Lovely
Summary: The discovery of a new class of extracellular-signal-regulated kinase (ERK) inhibitors was achieved through the development of novel 2-imino-5-arylidene-thiazolidine analogues. These targeted thiazolidines were synthesized using a solid support-mediated reaction and showed good chemical and physical stability. The best compound among the synthesized library, (Z)-5-((Z)-4-bromobenzylidene)-N-(4-methoxy-2-nitrophenyl)-4,4-dimethylthiazolidin-2-imine (6g), demonstrated high selectivity in cell viability assays and selective inhibition of phosphorylation in the ERK pathway. Molecular modeling techniques confirmed the observed activity and suggested potential for the development of bioactive 2-imino-5-arylidene-thiazolidines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nian Liu, Xin Wang, Qinglin Fu, Qiaohua Qin, Tianxiao Wu, Ruicheng Lv, Dongmei Zhao, Maosheng Cheng
Summary: In this study, 38 pyrazolo[3,4-b]pyridine derivatives were synthesized based on scaffold hopping and computer-aided drug design. The activities of these derivatives in inhibiting TRKA were evaluated, and compound C03 showed promising activity with good selectivity and plasma stability, making it a potential candidate for further exploration.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Shen-Sui Li, Chen-Zhou Wu, Bo-Wen Zhang, Ling Qiu, Wen Chen, Yi-Hang Yuan, Xing-Chen Liu, Chun-Jie Li, Long-Jiang Li
Summary: The study demonstrated that NGF expression is upregulated after radiotherapy and plays a protective role in salivary glands by reducing radiation-induced cell apoptosis and protecting against damage. NGF protects salivary glands from radiation-induced apoptosis by de-phosphorylating JNK kinase rather than promoting AKT phosphorylation.
Article
Chemistry, Medicinal
Debora Bublitz Anton, Julia Galvez Bulhoes Pedreira, Maria Luiza Zvirtes, Stefan A. Laufer, Rodrigo Gay Ducati, Marcia Goettert, Luis Fernando Saraiva Macedo Timmers
Summary: The SARS-CoV-2 virus has caused a global pandemic, infecting over 688 million people and resulting in around 6.8 million deaths. The virus induces lung inflammation and the release of pro-inflammatory cytokines, making anti-inflammatory therapies important in addition to antiviral drugs. The main protease (MPro) of SARS-CoV-2 is a potential drug target as it is essential for viral replication. In this study, six kinase inhibitors were evaluated for their inhibitory activity against SARS-CoV-2 MPro, and BIRB-796 and Baricitinib were identified as potential inhibitors with dual antiviral and anti-inflammatory activity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Polymer Science
Qiuxia Li, Litao Sun, Xiaobei Huang, Shuai Liu, Haiyang Yong, Chenfei Wang, Jianzhong Li, Dezhong Zhou
Summary: Biodegradable and lipid-like highly branched poly(beta-amino ester)s (HPAESA) were developed to enhance the biological functions of adipose-derived stem cells by gene transfection. HPAESA showed significantly higher efficiency and cell viability, as well as the ability to promote neurite outgrowth.
Article
Biochemistry & Molecular Biology
Renfei Wu, Koukou Li, Mingheng Yuan, Kathy Qian Luo
Summary: NGFR was identified as a novel driver for transforming TNBC into higher grade metastatic tumors, with its high expression associated with tumor malignancy and negative correlation with TNBC patient survival. The study provides the basis for developing NGFR as a diagnostic, prognostic marker, and therapeutic target for TNBC patients in the future.
Review
Oncology
Patrycja Klos, Dariusz Chlubek
Summary: In this review, the researchers discuss the effectiveness of plant-derived terpenoids in treating melanoma. They present the results of studies on the anti-melanoma properties of terpenoids and the synergistic effects of combining them with other treatments. The review also includes examples of drug delivery systems that improve the uptake of terpenoids by melanoma tissue.
Review
Behavioral Sciences
Ying Xue, Hongyan Liang, Rui Yang, Kunhong Deng, Mimi Tang, Mengqi Zhang
Summary: Neurotrophic factors play a crucial role in providing nutritional support to neurons and influencing their proliferation and survival. Recent studies have shown that these factors have opposing effects through different receptors. Understanding the complex relationship between neurotrophic factors and depression may lead to new insights into treatment approaches.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zijun Wang, Brian K. Kennedy, Lik-Wei Wong, Sreedharan Sajikumar
Summary: Age-induced impairments in learning and memory are caused by changes in hippocampal synaptic plasticity. The p75 neurotrophin receptor (p75(NTR)) and mechanistic target of rapamycin (mTOR) are involved in synaptic plasticity processes. The interaction between p75(NTR) and mTOR mediates age-induced impairment of hippocampal synaptic plasticity. However, the specific effects of this interaction and the role of mTOR in age-induced cognitive decline are still unclear.
Article
Biochemistry & Molecular Biology
Zijun Wang, Brian K. Kennedy, Lik-Wei Wong, Sreedharan Sajikumar
Summary: Age-induced impairments in learning and memory are caused by changes to hippocampal synaptic plasticity. The p75 neurotrophin receptor (p75(NTR)) and mechanistic target of rapamycin (mTOR) play a role in this process. The interaction between p75(NTR) and mTOR affects hippocampal synaptic plasticity and cognitive decline in aged mice.
Review
Chemistry, Medicinal
Hala B. El-Nassan, Mustafa A. Al-Qadhi
Summary: The tropomyosin receptor tyrosine kinases (TRKs), encoded by NTRK genes, regulate cell proliferation in the nervous system and have been found to be fused or mutated in various cancers. Small molecule TRK inhibitors have been developed and some have entered clinical trials, with two (larotrectinib and entrectinib) approved by FDA for treating TRK-fusion positive solid tumors. However, resistance to these drugs due to TRK enzyme mutations has been observed. Therefore, next generation TRK inhibitors have been discovered to overcome acquired resistance, and selective TRK subtype inhibitors with minimal CNS side effects have also been reported. This review summarizes the efforts made in the past three years in the design and discovery of novel TRK inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Neurosciences
Simone S. E. Nielsen, Mikkel R. Holst, Kristine Langthaler, Elisabeth Helena Bruun, Birger Brodin, Morten S. Nielsen
Summary: The mechanisms of transferrin receptor trafficking across brain capillary endothelial cells are not well understood but are important for maintaining brain iron homeostasis and developing drug delivery strategies. This study used expansion microscopy and immunofluorescence-based transport studies to investigate the distribution and sorting of transferrin receptor in these cells. The findings reveal different sorting mechanisms for transferrin receptor depending on the direction of trafficking, with the highest transcytosis capacity observed in the brain-to-blood direction. These results have implications for understanding brain iron homeostasis and optimizing drug delivery to the brain.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Biochemistry & Molecular Biology
Sabrina Nicolo, Alberto Antonelli, Michele Tanturli, Ilaria Baccani, Chiara Bonaiuto, Giuseppe Castronovo, Gian Maria Rossolini, G. Mattiuz, M. G. Torcia
Summary: Vaginal dysbiosis, characterized by decreased Lactobacillus abundance, facilitates the infection of sexually transmitted pathogens, including high-risk human papilloma viruses (HPVs) associated with cervical cancer development. In this study, SiHa cells, an HPV-16-transformed epithelial cell line, were exposed to representative vaginal microbial communities to investigate their impact on the expression of HPV oncogenes. The results showed that Lactobacillus crispatus and Lactobacillus gasseri modulated the expression of HPV oncogenes, while other dysbiotic bacteria had contrasting effects. These findings highlight the protective role of L. crispatus against neoplastic progression of HR-HPV infected cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pierluigi Reveglia, Carmela Paolillo, Antonella Angiolillo, Gabriella Ferretti, Ruggero Angelico, Rossana Sirabella, Gaetano Corso, Carmela Matrone, Alfonso Di Costanzo
Summary: Alzheimer's disease is the most common cause of dementia in the elderly population. It not only affects the brain, but also disturbs the overall metabolism of the body. Analysis of blood samples from patients with AD revealed significant dysregulation of metabolites, including upregulation of glycerophospholipids and ceramide, and downregulation of glutamic acid, other phospholipids, and sphingolipids. Pathway analysis showed that at least five metabolic pathways related to polar compounds were dysregulated in AD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
S. Decherchi, G. Ciccotti, A. Cavalli
Summary: We address the problem of estimating free energy from the perspectives of regularization and Bayes estimation theory. By utilizing prior knowledge of the free energy, we reformulate the Bennett acceptance ratio method and present a numerical algorithm to solve it. Additionally, we provide a closed formula to estimate confidence in the prior. Finally, the derived estimators are tested on a toy model.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Riccardo Aguti, Mattia Bernetti, Stefano Bosio, Sergio Decherchi, Andrea Cavalli
Summary: Allostery is a crucial feature of biomolecular systems, impacting their functioning through intricate interplays between residues and protein structures. Computational approaches for correlation estimation provide insights into these complexes but can lead to different conclusions and outcomes. This article compares three computational methods on pharmaceutical targets, revealing consensus in some aspects but also highlighting the importance of different notions in identifying specific pockets and communications.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Organic
Dina Scarpi, Nunzia Favale, Ernesto G. Occhiato
Summary: A highly efficient method for the one-pot synthesis of ring-fused 5-hydrazino-2-cyclopentenone derivatives is achieved through the catalysis of gold(I). Suitable enynyl acetates are mixed with a dialkylazodicarboxylate in the presence of a gold(I) catalyst to undergo cycloisomerization, hetero-Diels-Alder, and ring-opening reactions, resulting in the target compounds.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
S. Decherchi, A. Cavalli
Summary: Optimal transport theory is a growing field of mathematics with numerous applications. In this work, we utilize optimal transport for computational free energy estimation and demonstrate its effectiveness in optimizing barriers of alchemical transformations through analytical and simulation-based approaches.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Nutrition & Dietetics
Angela Silvano, Niccolo Meriggi, Sonia Renzi, Viola Seravalli, Maria Gabriella Torcia, Duccio Cavalieri, Mariarosaria Di Tommaso
Summary: Cervical shortening is a known risk factor for preterm birth. The vaginal microbiome plays a crucial role in pregnancy and maternal and fetal outcomes. This study investigated the vaginal microbiome in women with a short cervix compared to those with a normal cervical length. The results showed that there were differences in the abundance of certain bacterial taxa between the two groups, with Staphylococcus and Pseudomonas being more common in women with a short cervix.
Article
Microbiology
Leonardo Sorrentino, Walter Toscanelli, Matteo Fracella, Marta De Angelis, Federica Frasca, Carolina Scagnolari, Laura Petrarca, Raffaella Nenna, Fabio Midulla, Anna Teresa Palamara, Lucia Nencioni, Alessandra Pierangeli
Summary: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are common causes of hospitalization in children, with RSV being more severe. The study investigated the interplay between interferon (IFN) responses and nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant activity in RSV and HRV infections. The findings suggest that reduced NRF2 activation in RSV-infected infants may contribute to the severity of bronchiolitis.
Article
Medicine, Research & Experimental
Gabriella Ferretti, Sara Serafini, Antonella Angiolillo, Paola Monterosso, Alfonso Di Costanzo, Carmela Matrone
Summary: Recently, measurable peripheral biomarkers in the plasma of patients with Alzheimer's disease have gained clinical interest. This study analyzes the changes in plasma levels of Aβ42, TNFα, and metabolites in AD patients and compares them with healthy elderly subjects. The study highlights the potential of combining different plasma signatures for patient stratification and personalized approaches in AD.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Sarmistha Majumdar, Francesco Di Palma, Francesca Spyrakis, Sergio Decherchi, Andrea Cavalli
Summary: Tyrosine kinases play critical roles in cellular machinery, and dysregulation of their active or inactive forms is associated with diseases like cancer. This study aimed to comprehensively understand the flexibility-activity relationships of tyrosine kinases, focusing on pockets and fluctuations. By conducting molecular dynamics simulations, pocket and residue fluctuation analysis, and using a complementary machine learning approach, we studied 43 different tyrosine kinases. We found that the inactive forms often exhibit increased flexibility, particularly at the DFG motif level. Notably, using long simulations and a decision tree, we identified a semi-quantitative fluctuation threshold of the DGF+3 residue, beyond which the kinase is more likely to be in the inactive form.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Pedro J. Buigues, Sascha Gehrke, Magd Badaoui, Balint Dudas, Gaurav Mandana, Tianyun Qi, Giovanni Bottegoni, Edina Rosta
Summary: For the human muscarinic receptor 3 (hMR3), the unbinding paths of tiotropium and its analogues were investigated, revealing a consistent qualitative mechanism and identifying the structural bottleneck. The machine learning-based analysis highlighted the important role of the ECL2/TM5 junction in the transition state. Additionally, relevant changes at the intracellular end of the TM6 helix leading to the ICL3 kinase domain were identified, emphasizing the significance of residue L482 in signal transduction.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Behavioral Sciences
Carmela Matrone, Gabriella Ferretti
Summary: Autism spectrum disorder (ASD) is a pervasive disorder characterized by difficulties in social communication and repetitive behaviors. The causes of ASD are still not fully understood despite numerous hypotheses and research efforts. This review highlights the role of SEMA3A in neurodevelopment and its potential as a target for identifying unique patterns of ASD and predicting the prognosis of affected individuals.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Correction
Neurosciences
Filomena Iannuzzi, Vincenza Frisardi, Lucio Annunziato, Carmela Matrone