Profile of metacaspase gene expression in Plasmodium vivax field isolates from the Brazilian Amazon
CONCLUSION: The detection of metacaspases in P. vivax blood-stage parasites reported herein, allows the inclusion of these proteases as a potential candidate drug target for vivax malaria, while further investigations are still required to evaluate the activity, role and essentiality of metacaspases in P. vivax biology.PMID:38683374 | DOI:10.1007/s11033-024-09538-x (Source: Mol Biol Cell)
Source: Mol Biol Cell - April 29, 2024 Category: Molecular Biology Authors: Carolina Moreira Blanco Hugo Amorim Dos Santos de Souza Priscilla da Costa Martins Camila Fabbri Fernanda Souza de Souza Josu é da Costa Lima-Junior Stefanie Costa Pinto Lopes Lilian Rose Pratt-Riccio Cl áudio Tadeu Daniel-Ribeiro Paulo Renato Rivas Tot Source Type: research

Insights into metastatic roadmap of head and neck cancer squamous cell carcinoma based on clinical, histopathological and molecular profiles
Mol Biol Rep. 2024 Apr 29;51(1):597. doi: 10.1007/s11033-024-09476-8.ABSTRACTThe incidence of head and neck cancer (HNC), constituting approximately one in ten cancer cases worldwide, affects approximately 644,000 individuals annually. Managing this complex disease involves various treatment modalities such as systemic therapy, radiation, and surgery, particularly for patients with locally advanced disease. HNC treatment necessitates a multidisciplinary approach due to alterations in patients' genomes affecting their functionality. Predominantly, squamous cell carcinomas (SCCs), the majority of HNCs, arise from the upper a...
Source: Mol Biol Cell - April 29, 2024 Category: Molecular Biology Authors: Nicholas S Mastronikolis Alexander Delides Efthymios Kyrodimos Zoi Piperigkou Despoina Spyropoulou Evangelos Giotakis Evangelos Tsiambas Nikos K Karamanos Source Type: research

Scalable, Cost-Effective, and Decentralized DNA Barcoding with Oxford Nanopore Sequencing
Methods Mol Biol. 2024;2744:223-238. doi: 10.1007/978-1-0716-3581-0_14.ABSTRACTDNA barcodes are useful in biodiversity research, but sequencing barcodes with dye termination methods ("Sanger sequencing") has been so time-consuming and expensive that DNA barcodes are not as widely used as they should be. Fortunately, MinION sequencers from Oxford Nanopore Technologies have recently emerged as a cost-effective and efficient alternative for barcoding. MinION barcodes are now suitable for large-scale species discovery and enable specimen identification when the target species are represented in barcode databases. With a MinION...
Source: Mol Biol Cell - April 29, 2024 Category: Molecular Biology Authors: Amrita Srivathsan Rudolf Meier Source Type: research

Analyses of Nuclear Reads Obtained Using Genome Skimming
Methods Mol Biol. 2024;2744:247-265. doi: 10.1007/978-1-0716-3581-0_16.ABSTRACTIn this protocol paper, we review a set of methods developed in recent years for analyzing nuclear reads obtained from genome skimming. As the cost of sequencing drops, genome skimming (low-coverage shotgun sequencing of a sample) becomes increasingly a cost-effective method of measuring biodiversity at high resolution. While most practitioners only use assembled over-represented organelle reads from a genome skim, the vast majority of the reads are nuclear. Using assembly-free and alignment-free methods described in this protocol, we can compar...
Source: Mol Biol Cell - April 29, 2024 Category: Molecular Biology Authors: Siavash Mirarab Vineet Bafna Source Type: research

Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma
CONCLUSION: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.PMID:38683225 | DOI:10.1007/s11033-024-09517-2 (Source: Mol Biol Cell)
Source: Mol Biol Cell - April 29, 2024 Category: Molecular Biology Authors: Hyunsoo Kim Jiin Oh Min Kyoung Kim Kyung Hee Lee Daewon Jeong Source Type: research

Comparative evaluation of hesperetin-loaded graphene oxide nanosheets (Hsp-GO) as a drug delivery system for colon cancer: synthesis and anticancer efficiency assessment
CONCLUSIONS: These study highlight the potential of Hsp-GO as a promising anti-cancer nano-drug for colon cancer therapy.PMID:38683228 | DOI:10.1007/s11033-024-09504-7 (Source: Mol Biol Cell)
Source: Mol Biol Cell - April 29, 2024 Category: Molecular Biology Authors: Arezou Sabbagh Hadi Mehdi Haghi Abolfazl Barzegar Mohammad Ali Hosseinpour Feizi Source Type: research

Glutamine-mediated epigenetic regulation of cFLIP underlies resistance to TRAIL in pancreatic cancer
In this study, we demonstrated that glutamine (Gln) endows PDAC cells with resistance to TRAIL through KDM4C-mediated epigenetic regulation of cFLIP. Inhibition of glutaminolysis significantly reduced the cFLIP level, leading to TRAIL-mediated formation of death-inducing signaling complexes. Overexpression of cFLIP dramatically rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Alpha-Ketoglutarate (aKG) supplementation significantly reversed the decrease in the cFLIP level induced by glutaminolysis inhibition and rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Knockdown of glutamic-oxaloaceti...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Ji Hye Kim Jinyoung Lee Se Seul Im Boyun Kim Eun-Young Kim Hyo-Jin Min Jinbeom Heo Eun-Ju Chang Kyung-Chul Choi Dong-Myung Shin Jaekyoung Son Source Type: research

CBX3 antagonizes IFN γ/STAT1/PD-L1 axis to modulate colon inflammation and CRC chemosensitivity
EMBO Mol Med. 2024 Apr 29. doi: 10.1038/s44321-024-00066-6. Online ahead of print.ABSTRACTAs an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by u...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Yao Xiang Jorge Mata-Garrido Yuanji Fu Christophe Desterke Eric Batsch é Ahmed Hama ï Christine Sedlik Youssouf Sereme David Skurnik Abdelali Jalil Rachel Onifarasoaniaina Eric Frapy Jean-Christophe Beche Razack Alao Eliane Piaggio Laurence Arbibe Yunhu Source Type: research

Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression
EMBO Mol Med. 2024 Apr 29. doi: 10.1038/s44321-024-00071-9. Online ahead of print.ABSTRACTPolycystic kidney disease (PKD) is a genetic disorder characterized by bilateral cyst formation. We showed that PKD cells and kidneys display metabolic alterations, including the Warburg effect and glutaminolysis, sustained in vitro by the enzyme asparagine synthetase (ASNS). Here, we used antisense oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD murine models and show that treatment leads to a drastic reduction of total kidney volume (measured by MRI) and a prominent rescue of renal function in the mouse...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Sara Clerici Christine Podrini Davide Stefanoni Gianfranco Distefano Laura Cassina Maria Elena Steidl Laura Tronci Tamara Canu Marco Chiaravalli Daniel Spies Thomas A Bell Ana Sh Costa Antonio Esposito Angelo D'Alessandro Christian Frezza Angela Bachi Ale Source Type: research

GP64-pseudotyped lentiviral vectors target liver endothelial cells and correct hemophilia A mice
We report that VSV.G-LV transduced hepatocytes better than GP64-LV, however the latter showed improved transduction of liver sinusoidal endothelial cells (LSEC). Combining GP64-pseudotyping with the high surface content of the phagocytosis inhibitor CD47 further enhanced LSEC transduction. Coagulation factor VIII (FVIII), the gene mutated in hemophilia A, is naturally expressed by LSEC, thus we exploited GP64-LV to deliver a FVIII transgene under the control of the endogenous FVIII promoter and achieved therapeutic amounts of FVIII and correction of hemophilia A mice.PMID:38684862 | DOI:10.1038/s44321-024-00072-8 (Source: Molecular Medicine)
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Michela Milani Cesare Canepari Simone Assanelli Simone Merlin Ester Borroni Francesco Starinieri Mauro Biffi Fabio Russo Anna Fabiano Desir èe Zambroni Andrea Annoni Luigi Naldini Antonia Follenzi Alessio Cantore Source Type: research

Structural basis of closed groove scrambling by a TMEM16 protein
Nat Struct Mol Biol. 2024 Apr 29. doi: 10.1038/s41594-024-01284-9. Online ahead of print.ABSTRACTActivation of Ca2+-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown. Here we directly visualize how lipids associate at th...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Zhang Feng Omar E Alvarenga Alessio Accardi Source Type: research

Development and first-in-human study of PSMA-targeted PET tracers with improved pharmacokinetic properties
CONCLUSION: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects.TRIAL REGISTRATION: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chic...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Haodong Hou Yuan Pan Yanzhi Wang Yuze Ma Xiaobing Niu Suan Sun Guihua Hou Weijing Tao Feng Gao Source Type: research

CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML
J Cell Mol Med. 2024 May;28(9):e18308. doi: 10.1111/jcmm.18308.ABSTRACTDestruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient an...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Chunmei Guo Xinxin Lv Qiuling Zhang Lina Yi Yingying Ren Zhaopeng Li Jinsong Yan Shanliang Zheng Ming-Zhong Sun Shuqing Liu Source Type: research

Decreased intranuclear cardiac troponin I impairs cardiac autophagy through FOS/ATG5 in ageing hearts
J Cell Mol Med. 2024 May;28(9):e18357. doi: 10.1111/jcmm.18357.ABSTRACTIn our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Rui Min Liu Shan Huang Di Hu Lingjuan Liu Hui Chao Sun Jie Tian Bo Pan Source Type: research

YTHDF1 promotes gallbladder cancer progression via post-transcriptional regulation of the m6A/UHRF1 axis
J Cell Mol Med. 2024 May;28(9):e18328. doi: 10.1111/jcmm.18328.ABSTRACTGallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the prolifera...
Source: Molecular Medicine - April 29, 2024 Category: Molecular Biology Authors: Jiemin Chen Xuesong Bai Wenqin Zhang Zhiyu Yan Yongru Liu Shengnan Zhou Xi Wu Xiaodong He Aiming Yang Source Type: research