keyword
https://read.qxmd.com/read/38536617/whole-transcriptome-mapping-reveals-the-lncrna-regulatory-network-of-tfp5-treatment-in-diabetic-nephropathy
#1
JOURNAL ARTICLE
Hongyan Luo, Lirong Yang, Guoqing Zhang, Xi Bao, Danna Ma, Bo Li, Li Cao, Shilu Cao, Shunyao Liu, Li Bao, Jing E, Yali Zheng
BACKGROUND: TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear. OBJECTIVE: This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy. METHODS: We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6J control mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice...
March 27, 2024: Genes & Genomics
https://read.qxmd.com/read/38529190/targeting-hexokinase-2-for-oral-cancer-therapy-structure-based-design-and-validation-of-lead-compounds
#2
JOURNAL ARTICLE
Purbali Chakraborty, Syeda Lubna, Shouvik Bhuin, Deepika K, Manab Chakravarty, Trinath Jamma, Perumal Yogeeswari
The pursuit of small molecule inhibitors targeting hexokinase 2 (HK2) has significantly captivated the field of cancer drug discovery. Nevertheless, the creation of selective inhibitors aimed at specific isoforms of hexokinase (HK) remains a formidable challenge. Here, we present a multiple-pharmacophore modeling approach for designing ligands against HK2 with a marked anti-proliferative effect on FaDu and Cal27 oral cancer cell lines. Molecular dynamics (MD) simulations showed that the prototype ligand exhibited a higher affinity towards HK2...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38528310/danicopan-first-approval
#3
REVIEW
Connie Kang
Danicopan (Voydeya® ) is an oral complement factor D inhibitor that is being developed by Alexion AstraZeneca Rare Disease as add-on treatment to ravulizumab or eculizumab for patients with clinically significant extravascular haemolysis. Danicopan recently received approval in Japan for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH) when used in addition to a complement component 5 (C5) inhibitor. Subsequently, the European Medicines Agency adopted a positive opinion recommending the granting of marketing authorisation for danicopan for the treatment of patients with PNH who continue to have residual haemolytic anaemia despite treatment with a complement C5 inhibitor...
March 26, 2024: Drugs
https://read.qxmd.com/read/38526863/conn%C3%A2-s-syndrome-after-kidney-transplantation
#4
JOURNAL ARTICLE
Michaela Javorkova, Andrea Bystricanova, Martina Cirbusova, Marcela Cvoligova, Martin Chrastina, Juraj Maris, Janka Otavkova, Zuzana Zilinska
Conn's syndrome, defined as unilateral aldosterone-producing adenoma, accounts for 35-40% of cases of primary hyperaldosteronism. Primary hyperaldosteronism typically occurs in younger patients with poorly controlled arterial hypertension due to extracellular fluid retention, in whom at least a triple combination of antihypertensives, including a diuretic, is needed to maintain normotension. The clinical picture of arterial hypertension may be complemented by symptoms associated with hypokalaemia, such as weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria...
2024: Bratislavské Lekárske Listy
https://read.qxmd.com/read/38525109/b-cell-pathway-dual-inhibition-for-systemic-lupus-erythematosus-a-prospective-single-arm-cohort-study-of-telitacicept
#5
JOURNAL ARTICLE
Lanlan Ji, Yan Geng, Xiaohui Zhang, Xuerong Deng, Zhibo Song, Meng Tan, Ying Tan, Chenxue Qu, Zhuoli Zhang
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B-cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor-Fc fusion protein, which can neutralize both B-cell lymphocyte stimulator and a proliferation-inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty-seven participants were involved and followed for 6...
April 2024: MedComm
https://read.qxmd.com/read/38523508/promising-therapies-for-the-treatment-of-myasthenia-gravis
#6
REVIEW
Sanem Pinar Uysal, John A Morren
INTRODUCTION: Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with neuromuscular symptoms of varying severity and significant morbidity. The mainstay of treatment in MG is mitigation of the immune cascade with steroids and non-steroidal immunosuppressive therapies. The therapeutic strategies in MG are transitioning from broad and indiscriminate immunosuppression to novel agents targeting key steps in MG pathogenesis, including T cell activation, B cell proliferation, complement activation, maintenance of pathogenic antibody production, and proinflammatory cytokine production...
March 25, 2024: Expert Opinion on Pharmacotherapy
https://read.qxmd.com/read/38523060/immunomodulatory-drugs-in-sepsis-a-systematic-review-and-meta-analysis
#7
REVIEW
R C Robey, C Logue, C A Caird, J Hansel, T P Hellyer, J Simpson, P Dark, A G Mathioudakis, T Felton
Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors...
March 24, 2024: Anaesthesia
https://read.qxmd.com/read/38520965/the-myb-transcription-factor-smmyb113-directly-regulates-ethylene-dependent-flower-abscission-in-eggplant
#8
JOURNAL ARTICLE
Jing Chen, Senlin Jiang, Guobin Yang, Lujun Li, Jing Li, Fengjuan Yang
Flower abscission is an important developmental process that can significantly reduce the yield of horticultural plants. We previously reported that SmMYB113 is a key transcription factor promoting anthocyanin biosynthesis and improve fruit quality. However, the overexpression of SmMYB113 in eggplant increased flower drop rate and reduced fruit yield. Here, we elucidate the regulatory mechanisms of SmMYB113 on flower abscission in eggplant. RNA-seq analysis indicated that the regulation of flower abscission by SmMYB113 was associated with altered expression of genes related to ethylene biosynthesis and signal transduction, including ethylene biosynthetic genes SmACS1, SmACS8 and SmACO4...
March 19, 2024: Plant Physiology and Biochemistry: PPB
https://read.qxmd.com/read/38520170/a-comparison-of-sodium-glucose-co-transporter-2-inhibitor-kidney-outcome-trial-participants-with-a-real-world-chronic-kidney-disease-primary-care-population
#9
JOURNAL ARTICLE
Anna K Forbes, William Hinton, Michael D Feher, William Elson, José M Ordóñez-Mena, Mark Joy, Xuejuan Fan, Debasish Banerjee, Nicholas I Cole, Neil Munro, Martin Whyte, Rebecca J Suckling, Pauline A Swift, Simon de Lusignan
BACKGROUND/HYPOTHESIS: Observational studies suggest sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D), and the representativeness of the EMPA-KIDNEY trial has not been adequately explored. We hypothesised that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials...
March 22, 2024: Nephrology, Dialysis, Transplantation
https://read.qxmd.com/read/38519142/novel-chemotype-nlrp3-inhibitors-that-target-the-crid3-binding-pocket-with-high-potency
#10
JOURNAL ARTICLE
Lieselotte Vande Walle, Madhukar Said, Oonagh Paerewijck, Arinna Bertoni, Marco Gattorno, Bruno Linclau, Mohamed Lamkanfi
The NLRP3 inflammasome plays a central role in various human diseases. Despite significant interest, most clinical-grade NLRP3 inhibitors are derived from sulfonylurea inhibitor CRID3 (also called MCC950). Here, we describe a novel chemical class of NLRP3-inhibiting compounds (NIC) that exhibit potent and selective NLRP3 inflammasome inhibition in human monocytes and mouse macrophages. BRET assays demonstrate that they physically interact with NLRP3. Structural modeling further reveals they occupy the same binding site of CRID3 but in a critically different conformation...
June 2024: Life Science Alliance
https://read.qxmd.com/read/38518448/effect-of-dapagliflozin-on-collectins-and-complement-activation-in-plasma-from-patients-with-type-2-diabetes-and-albuminuria-data-from-the-dapkid-cohort
#11
JOURNAL ARTICLE
Mia Jensen, Mie K Eickhoff, Frederik Persson, Peter Rossing, Steffen Thiel, Søren W K Hansen, Yaseelan Palarasah, Per Svenningsen, Boye L Jensen
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT- 2) inhibitors exert cardiovascular and kidney-protective effects in people with diabetes. Attenuation of inflammation could be important for systemic protection. The lectin pathway of complement system activation is linked to diabetic nephropathy. We hypothesized that SGLT-2 inhibitors lower the circulating level of pattern-recognition molecules of the lectin cascade and attenuate systemic complement activation. METHODS: Analysis of paired plasma samples from the DapKid crossover intervention study where patients with type 2 diabetes mellitus (T2DM) and albuminuria were treated with dapagliflozin and placebo for 12 weeks (10 mg/day, n=36)...
March 15, 2024: Immunobiology
https://read.qxmd.com/read/38517653/iptacopan-first-approval
#12
REVIEW
Yahiya Y Syed
Iptacopan (FABHALTA® ) is an oral complement Factor B inhibitor developed by Novartis Pharmaceuticals for the treatment of complement-mediated diseases. Acting upstream of complement 5 in the alternative pathway, iptacopan inhibits both terminal complement-mediated intravascular haemolysis and complement 3-mediated extravascular haemolysis. On 5 December 2023, iptacopan received approval in the USA for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH). This article summarizes the milestones in the development of iptacopan leading to this first approval for PNH...
March 22, 2024: Drugs
https://read.qxmd.com/read/38517345/peptidoglycan-from-bacillus-anthracis-inhibits-human-macrophage-efferocytosis-in-part-by-reducing-cell-surface-expression-of-mertk-and-tim-3
#13
JOURNAL ARTICLE
Joshua S Mytych, Zijian Pan, Charmaine Lopez-Davis, Nancy Redinger, Christina Lawrence, Jadith Ziegler, Narcis I Popescu, Judith A James, A Darise Farris
Bacillus anthracis peptidoglycan (PGN) is a major component of the bacterial cell wall and a key pathogen-associated molecular pattern contributing to anthrax pathology, including organ dysfunction and coagulopathy. Increases in apoptotic leukocytes are a late-stage feature of anthrax and sepsis, suggesting there is a defect in apoptotic clearance. In this study, we tested the hypothesis that B. anthracis PGN inhibits the capacity of human monocyte-derived macrophages (MΦ) to efferocytose apoptotic cells...
March 1, 2024: ImmunoHorizons
https://read.qxmd.com/read/38517165/mutagenesis-and-functional-analysis-of-the-varicella-zoster-virus-portal-protein
#14
JOURNAL ARTICLE
Melissa A Visalli, Dakota J Nale Lovett, Ellyn M Kornfeind, Haley Herrington, Yi Tian Xiao, Daniel Lee, Patience Plair, S Garrett Wilder, Bret K Garza, Ashton Young, Robert J Visalli
Herpesviruses replicate by cleaving concatemeric dsDNA into single genomic units that are packaged through an oligomeric portal present in preformed procapsids. In contrast to what is known about phage portal proteins, details concerning herpesvirus portal structure and function are not as well understood. A panel of 65 Varicella-Zoster virus (VZV) recombinant portal proteins with five amino acid in-frame insertions were generated by random transposon mutagenesis of the VZV portal gene, ORF54. Subsequently, 65 VZVLUC recombinant viruses (TNs) were generated via recombineering...
March 22, 2024: Journal of Virology
https://read.qxmd.com/read/38516186/structural-insights-into-the-c-terminus-of-the-histone-lysine-n-methyltransferase-nsd3-by-small-angle-x-ray-scattering
#15
JOURNAL ARTICLE
Benny Danilo Belviso, Yunpeng Shen, Benedetta Carrozzini, Masayo Morishita, Eric di Luccio, Rocco Caliandro
NSD3 is a member of six H3K36-specific histone lysine methyltransferases in metazoans. Its overexpression or mutation is implicated in developmental defects and oncogenesis. Aside from the well-characterized catalytic SET domain, NSD3 has multiple clinically relevant potential chromatin-binding motifs, such as the proline-tryptophan-tryptophan-proline (PWWP), the plant homeodomain (PHD), and the adjacent Cys-His-rich domain located at the C-terminus. The crystal structure of the individual domains is available, and this structural knowledge has allowed the designing of potential inhibitors, but the intrinsic flexibility of larger constructs has hindered the characterization of mutual domain conformations...
2024: Frontiers in Molecular Biosciences
https://read.qxmd.com/read/38513233/paroxysmal-nocturnal-hemoglobinuria-related-thrombosis-in-the-era-of-novel-therapies-a-2043-patient-years-analysis
#16
JOURNAL ARTICLE
Carmelo Gurnari, Hussein Awada, Simona Pagliuca, Danai Dima, Fauzia Ullah, Naomi Kawashima, Yasuo Kubota, Ceylan Colak, Valeria Visconte, Bhumika J Patel, Vikram Dhillon, Naimisha Marneni, Suresh Kumar Balasubramanian, Ashwin Kishtagari, Taha Bat, Jaroslaw P Maciejewski
Thrombophilia is one of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anti-complement treatment has revolutionized the natural history of PNH with control of the hemolytic process and abolition of thrombotic events (TE). However, no guidelines exist for the management of thromboembolic complications in this setting, with type and duration of anti-coagulation depending on individual practices. Besides, a scarcity of data is present on the efficacy of direct oral anti-coagulants (DOACs)...
March 21, 2024: Blood
https://read.qxmd.com/read/38510242/antibody-dependent-cellular-cytotoxicity-inducing-anti-egfr-antibodies-as-effective-therapeutic-option-for-cutaneous-melanoma-resistant-to-braf-inhibitors
#17
JOURNAL ARTICLE
Elena Muraro, Barbara Montico, Benedict Lum, Francesca Colizzi, Giorgio Giurato, Annamaria Salvati, Roberto Guerrieri, Aurora Rizzo, Elisa Comaro, Vincenzo Canzonieri, Andrea Anichini, Michele Del Vecchio, Roberta Mortarini, Massimo Milione, Alessandro Weisz, Maria Antonietta Pizzichetta, Fiona Simpson, Riccardo Dolcetti, Elisabetta Fratta, Luca Sigalotti
INTRODUCTION: About 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR)...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38503264/water-quality-monitoring-with-the-multiplexed-assay-mitooxtox-for-mitochondrial-toxicity-oxidative-stress-response-and-cytotoxicity-in-arec32-cells
#18
JOURNAL ARTICLE
Jungeun Lee, Maria König, Georg Braun, Beate I Escher
Mitochondria play a key role in the energy production of cells, but their function can be disturbed by environmental toxicants. We developed a cell-based mitochondrial toxicity assay for environmental chemicals and their mixtures extracted from water samples. The reporter gene cell line AREc32, which is frequently used to quantify the cytotoxicity and oxidative stress response of water samples, was multiplexed with an endpoint of mitochondrial toxicity. The disruption of the mitochondrial membrane potential (MMP) was quantified by high-content imaging and compared to measured cytotoxicity, predicted baseline toxicity, and activation of the oxidative stress response...
March 19, 2024: Environmental Science & Technology
https://read.qxmd.com/read/38498159/role-of-the-complement-system-in-kidney-cell-death-induced-by-loxosceles-venom-sphingomyelinases-d
#19
JOURNAL ARTICLE
Cinthya Kimori Okamoto, Carmen W van den Berg, Paula C Pohl, Denise V Tambourgi
Envenomation by Loxosceles spiders can result in local and systemic pathologies. Systemic loxoscelism, which can lead to death, is characterized by intravascular hemolysis, platelet aggregation, and acute kidney injury. Sphingomyelinase D (SMase D) in Loxosceles spider venom is responsible for both local and systemic pathologies, and has been shown to induce metalloprotease activity. As the complement system is involved in many renal pathologies and is involved in hemolysis in systemic loxoscelism, the aim of this study was to investigate its role and the role of complement regulators and metalloproteases in an in vitro model of Loxosceles venom induced renal pathology...
March 18, 2024: Archives of Toxicology
https://read.qxmd.com/read/38495135/foxm1-promotes-the-progression-of-non-small-cell-lung-cancer-by-inhibiting-mir-509-5p-expression-via-binding-to-the-mir-509-5p-promoter-region
#20
JOURNAL ARTICLE
Mengcha Tian, Jiaming Li, Huihui Wu, Yuying Wu
BACKGROUND: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. OBJECTIVE: The mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated...
March 15, 2024: Heliyon
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