Coadministration of fluconazole to boost subtherapeutic sirolimus concentrations: A case report
Pharmacol Res Perspect. 2024 Jun;12(3):e1198. doi: 10.1002/prp2.1198.ABSTRACTIndividual sirolimus whole blood concentrations are highly variable, critically influenced by the concomitant use of cytochrome P450 (CYP) 3A inducers or inhibitors, and also modulated by food. Therapeutic drug monitoring is therefore recommended, especially at treatment start or in circumstances that can influence sirolimus exposure. In this case report, we highlight the challenge of achieving therapeutic sirolimus concentrations and present pragmatic solutions with regimen adaptions, pharmacokinetic enhancement (use of a drug-drug interaction), ...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Camilo Scherkl Andreas D Meid Sven E Cuntz Laura Classen Johanna Weiss David Czock Walter E Haefeli Source Type: research
Hemisynthesis and cytotoxic evaluation of manoyl oxide analogs from sclareol: effect of two tertiary hydroxyls & amp; Heck coupling on cytotoxicity
Nat Prod Res. 2024 Apr 18:1-10. doi: 10.1080/14786419.2024.2342558. Online ahead of print.ABSTRACTSclareol, a bioactive diterpene alcohol isolated from Salvia sclarea, was subjected to structural modification and cytotoxic evaluation. Boron-Heck-coupled analogs of manoyl oxide were prepared from sclareol in a two-step reaction scheme. In the first step manoyl oxide was prepared from sclareol using cerium (IV) ammonium nitrate. Further the structural modification of manoyl oxide via Palladium (II) catalysed Boron-Heck coupling reaction produced a new series of compounds. All the synthesised compounds were screened for in vi...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Ifshana Gani Zahidul Islam Sofi Gursimar Kaur Anindya Goswami Khursheed Ahmad Bhat Source Type: research
Saikosaponin a promotes neutrophil extracellular trap formation and bactericidal activity
This study aimed to investigate the effects of SSa, one of the major triterpenoid saponins extracted from Radix bupleuri, on neutrophil extracellular trap (NET) formation and the mechanism associated with this process. Using Sytox green and immunofluorescence assays, we found SSa rapidly induced NET formation, which depended on NADPH oxidase (NOX)-independent ROS production and autophagy. Pharmacologic inhibitor studies indicated that ERK and PI3K/AKT signalling were also required for SSa-induced NET formation, whereas protein arginine deiminase 4 (PAD4) was not required. Furthermore, we found that SSa promoted neutrophil ...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Lanqiu Zhang Zhengwei Hu Lei Yang Tianyu Liu Jing Xun Qi Zhang Ximo Wang Hejun Gao Zhongkui Jin Source Type: research
Deuterium metabolic imaging differentiates glioblastoma metabolic subtypes and detects early response to chemoradiotherapy
Cancer Res. 2024 Apr 18. doi: 10.1158/0008-5472.CAN-23-2552. Online ahead of print.ABSTRACTMetabolic subtypes of glioblastoma have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. Here, we used 2H magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) measurements of [6,6'-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived glioblastoma xenografts in vivo. The metabolism of patient-derived cells was fi...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Jacob Chen Ming Low Jianbo Cao Friederike Hesse Alan J Wright Anastasia Tsyben Islam Alshamleh Richard Mair Kevin M Brindle Source Type: research
Omental preadipocytes stimulate matrix remodeling and IGF signaling to support ovarian cancer metastasis
Cancer Res. 2024 Apr 18. doi: 10.1158/0008-5472.CAN-23-2613. Online ahead of print.ABSTRACTOvarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed that omental preadipocytes enhance the tumor initiation capacity of ovarian cancer cells. Secreted factors from preadipocytes supported ca...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Jennifer A Waters Mikella Robinson Omar Lujano-Olazaba Cassidy Lucht Samuel F Gilbert Carrie D House Source Type: research
Fc-silent anti-TIGIT antibodies potentiate anti-tumor immunity without depleting regulatory T cells
Cancer Res. 2024 Apr 18. doi: 10.1158/0008-5472.CAN-23-2455. Online ahead of print.ABSTRACTTIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding. Here, we show...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Dana Piovesan Amber E de Groot Soonweng Cho Amy E Anderson Rebecca D Ray Amita Patnaik Paul G Foster Casey G Mitchell Alejandra Y Lopez Espinoza Wandi S Zhu Carlo E Stagnaro Hema Singh Xiaoning Zhao Lisa Seitz Nigel P Walker Matthew J Walters Kelsey E Siv Source Type: research
CD106 in tumor-specific exhausted CD8+ T cells mediates immunosuppression by inhibiting TCR signaling
Cancer Res. 2024 Apr 18. doi: 10.1158/0008-5472.CAN-23-0453. Online ahead of print.ABSTRACTT cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T cell exhaustion, such as PD-1, can reinvigorate tumor-specific T cells and activate anti-tumor immunity in various types of cancer. Here, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA-sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells sup...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Yuto Naoi Takao Morinaga Joji Nagasaki Ryo Ariyasu Youki Ueda Kazuo Yamashita Wenhao Zhou Shusuke Kawashima Katsushige Kawase Akiko Honobe-Tabuchi Takehiro Ohnuma Tatsuyoshi Kawamura Yoshiyasu Umeda Yu Kawahara Yasuhiro Nakamura Yukiko Kiniwa Osamu Yamasa Source Type: research
CD58 alterations govern antitumor immune responses by inducing PD-L1 and IDO in diffuse large B-cell lymphoma
Cancer Res. 2024 Apr 18. doi: 10.1158/0008-5472.CAN-23-2874. Online ahead of print.ABSTRACTRecurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Xiyue Xu Yidan Zhang Yaxiao Lu Xiaoyan Zhang Cuicui Zhao Jiesong Wang Qingpei Guan Yingfang Feng Meng Gao Jingwei Yu Zheng Song Xia Liu Zahra Golchehre Lanfang Li Weicheng Ren Qiang Pan-Hammarstr öm Huilai Zhang Xianhuo Wang Source Type: research
The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF- β signaling
CONCLUSION: FURIN is a novel, frequent genetic predisposition for abdominal-, thoracic-, and multiple aortic or middle sized artery aneurysms in older patients, by affecting intracellular TGF-β signaling, depending on individual genetic backgrounds.PMID:38636100 | DOI:10.1093/cvr/cvae078 (Source: Cell Research)
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Zongsheng He Arne S IJpma Dianne Vreeken Daphne Heijsman Karen Rosier Hence J M Verhagen Jorg de Bruin Hennie T Br üggenwirth Jolien W Roos-Hesselink Jos A Bekkers Danny Huylebroeck Heleen van Beusekom John W M Creemers Danielle Majoor-Krakauer Source Type: research
Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss
Hear Res. 2024 Apr 12;447:109008. doi: 10.1016/j.heares.2024.109008. Online ahead of print.ABSTRACTThe auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofug...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: V Fuentes-Santamar ía Z Ben ítez-Maicán J C Alvarado I S Fern ández Del Campo M C Gabald ón-Ull M A Merch án J M Juiz Source Type: research
Modulators targeting protein-protein interactions in Mycobacterium tuberculosis
Microbiol Res. 2024 Mar 7;284:127675. doi: 10.1016/j.micres.2024.127675. Online ahead of print.ABSTRACTTuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), mainly transmitted through droplets to infect the lungs, and seriously affecting patients' health and quality of life. Clinically, anti-TB drugs often entail side effects and lack efficacy against resistant strains. Thus, the exploration and development of novel targeted anti-TB medications are imperative. Currently, protein-protein interactions (PPIs) offer novel avenues for anti-TB drug development, and the study of...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Guofeng Luo Tianqi Ming Luchuan Yang Lei He Tao Tao Yanmei Wang Source Type: research
KSCBi005-A-10(hiPSC-HIF1alphaKO), a HIF1alpha knockout human induced pluripotent stem cell line, for demonstrating the role of cellular response to hypoxia
Stem Cell Res. 2024 Apr 6;77:103415. doi: 10.1016/j.scr.2024.103415. Online ahead of print.ABSTRACTUnder hypoxia, hypoxia-inducible factor (HIF)-1 regulates hypoxia-inducible genes, such as vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2. It is an oxygen-dependent transcriptional activator that plays a crucial role in tumor angiogenesis and mammalian embryo development. It is a heterodimeric protein comprising a constitutively expressed HIF-1β subunit and the highly regulated HIF-1α subunits. Using CRISPR-Cas9 genome editing, we generated biallelic HIF-1α mutants in human induced pluripoten...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Hyeong-Jun Han Jung-Hyun Kim Source Type: research
Efficient generation of induced pluripotent stem cell lines from healthy donors' peripheral blood mononuclear cells of different genders
Stem Cell Res. 2024 Apr 15;77:103421. doi: 10.1016/j.scr.2024.103421. Online ahead of print.ABSTRACTPeripheral blood mononuclear cell (PBMC) are recognized as a conveniently collected reprogramming resource. Several methods are available in academia to reprogram PBMC into induced pluripotent stem cells (iPSC). In this research, we reprogrammed PBMC of different genders by using non-integrative non-viral liposome electrotransfer containing the reprogramming factors OCT4, SOX2, KLF4, and c-MYC. The three obtained iPSC cell lines were karyotypically normal and showed significant tritiated differentiation potential in vitro an...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Yunfeng Gao Yanhong Cheng Bao Lin Dan Xiao Junjie Wen Jingyu Xu Ran Zheng Mengna Zhang Cheguo Cai Junyuan Hu Source Type: research
Effect of 2-aminoethoxydiphenyl borate on the functions of mouse skeletal muscle mitochondria
Biochem Biophys Res Commun. 2024 Apr 16;712-713:149944. doi: 10.1016/j.bbrc.2024.149944. Online ahead of print.ABSTRACTThis work examined the effect of 2-aminoethoxydiphenyl borate (2-APB) on the functioning of isolated mouse skeletal muscle mitochondria and modeled its putative interaction with mitochondrial proteins. We have shown that 2-APB is able to dose-dependently suppress mitochondrial respiration in state 3 and 3UDNP driven by substrates of complex I and II. This effect of 2-APB was accompanied by a slight dose-dependent decrease in mitochondrial membrane potential and appears to be due to inhibition of complex I ...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Mikhail V Dubinin Alexander V Chulkov Anastasia D Igoshkina Alena A Cherepanova Natalia V Mikina Source Type: research
Extracorporeal membrane oxygenation (ECMO) during aplasia: A bridge towards myopericarditis recovery after autologous hematopoietic stem cell transplant for systemic sclerosis and recent Coronarovirus disease (COVID-19) vaccination
This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infecti...
Source: Cell Research - April 18, 2024 Category: Cytology Authors: Carlotta Cacciatore Mathilde Baudet Estelle Jean Simona Presente Marylou Para Romain Sonneville Dimitri Arangalage Nassim Ait Abdallah Flore Sicre de Fontbrune Pedro Henrique Prata Benjamin Crichi Baptiste Hervier Nathalie Parquet Gilles Soulat Elie Mouss Source Type: research
