keyword
https://read.qxmd.com/read/38508975/targeting-antibody-mediated-complement-independent-mechanism-in-bullous-pemphigoid-with-diacerein
#1
JOURNAL ARTICLE
Yung-Tsu Cho, Chih-Hung Lee, Jing-Yi Lee, Chia-Yu Chu
BACKGROUND: Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments. OBJECTIVE: We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein...
March 6, 2024: Journal of Dermatological Science
https://read.qxmd.com/read/38455710/histological-sarcomatoid-transformation-in-a-lung-adenocarcinoma-patient-following-immune-checkpoint-blockade
#2
Xiuju Liang, Yaping Guan, Baocheng Wang, Xiaohong Liu, Jun Wang
Histological transformation is a phenomenon that is well described as one of the causes of tyrosine kinase inhibitor resistance in oncogene-driven non-small-cell lung cancer (NSCLC). The use of immune checkpoint inhibitors (ICIs) as a potential mechanism of acquired resistance to immunotherapy in NSCLC to small-cell lung cancer was also recently found. Here, we report the histological transformation of sarcomatoid carcinoma and metastasis in a lung adenocarcinoma patient without targetable genetic alterations who experienced long-term disease remission after nivolumab therapy...
2024: Therapeutic Advances in Medical Oncology
https://read.qxmd.com/read/38396775/the-african-swine-fever-virus-virulence-determinant-dp96r-suppresses-type-i-ifn-production-targeting-irf3
#3
JOURNAL ARTICLE
Niranjan Dodantenna, Ji-Won Cha, Kiramage Chathuranga, W A Gayan Chathuranga, Asela Weerawardhana, Lakmal Ranathunga, Yongkwan Kim, Weonhwa Jheong, Jong-Soo Lee
DP96R of African swine fever virus (ASFV), also known as uridine kinase ( UK ), encodes a virulence-associated protein. Previous studies have examined DP96R along with other genes in an effort to create live attenuated vaccines. While experiments in pigs have explored the impact of DP96R on the pathogenicity of ASFV, the precise molecular mechanism underlying this phenomenon remains unknown. Here, we describe a novel molecular mechanism by which DP96R suppresses interferon regulator factor-3 (IRF3)-mediated antiviral immune responses...
February 8, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38388899/saracatinib-prompts-hemin-induced-k562-erythroid-differentiation-but-suppresses-erythropoiesis-of-hematopoietic-stem-cells
#4
JOURNAL ARTICLE
Lina Ding, Diyu Chen, Yuanshuai Li, Yingjun Xie, Xiaofang Sun, Ding Wang
Human myeloid leukemia cells (such as K562) could be used for the study of erythropoiesis, and mature erythroid markers and globins could be induced during leukemia cell differentiation; however, the pathways involved are different compared with those of hematopoietic stem cells (HSCs).We identified the differentially expressed genes (DEGs) of K562 cells and HSCs associated with stem cells and erythroid differentiation. Furthermore, we showed that hemin-induced differentiation of K562 cells could be induced by serum starvation or treatment with the tyrosine kinase inhibitor saracatinib...
February 22, 2024: Human Cell
https://read.qxmd.com/read/38357791/clonal-hematopoiesis-of-indeterminate-potential-with-loss-of-tet2-enhances-risk-for-atrial-fibrillation-through-nlrp3-inflammasome-activation
#5
JOURNAL ARTICLE
Amy Erica Lin, Aneesh C Bapat, Ling Xiao, Abhishek Niroula, Jianchuan Ye, Waihay J Wong, Mridul Agrawal, Christopher J Farady, Andreas Boettcher, Christopher B Hergott, Marie McConkey, Patricio Flores-Bringas, Veronica Shkolnik, Alexander G Bick, David Milan, Pradeep Natarajan, Peter Libby, Patrick T Ellinor, Benjamin L Ebert
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored. METHODS: CHIP prevalence was determined in the UK Biobank, and incident AF analysis was stratified by CHIP status and clone size using Cox proportional hazard models...
February 15, 2024: Circulation
https://read.qxmd.com/read/38357697/adp-hep-induced-liquid-phase-condensation-of-tifa-traf6-activates-alpk1-tifa-dependent-innate-immune-responses
#6
JOURNAL ARTICLE
Liping Li, Jia Wang, Xincheng Zhong, Yaoyao Jiang, Gaofeng Pei, Xikang Yang, Kaixiang Zhang, Siqi Shen, Xue Jin, Gaoge Sun, Chaofei Su, Shuzhen Chen, Hang Yin
The ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with fork head-associated domain)-TRAF6 signaling pathway plays a pivotal role in regulating inflammatory processes, with TIFA and TRAF6 serving as key molecules in this cascade. Despite its significance, the functional mechanism of TIFA-TRAF6 remains incompletely understood. In this study, we unveil that TIFA undergoes liquid-liquid phase separation (LLPS) induced by ALPK1 in response to adenosine diphosphate (ADP)-β-D-manno-heptose (ADP-Hep) recognition...
2024: Research: a science partner journal
https://read.qxmd.com/read/38349966/gpcr-kinases-differentially-modulate-biased-signaling-downstream-of-cxcr3-depending-on-their-subcellular-localization
#7
JOURNAL ARTICLE
Julia Gardner, Dylan Scott Eiger, Chloe Hicks, Issac Choi, Uyen Pham, Anand Chundi, Ojas Namjoshi, Sudarshan Rajagopal
Some G protein-coupled receptors (GPCRs) demonstrate biased signaling such that ligands of the same receptor exclusively or preferentially activate certain downstream signaling pathways over others. This phenomenon may result from ligand-specific receptor phosphorylation by GPCR kinases (GRKs). GPCR signaling can also exhibit location bias because GPCRs traffic to and signal from subcellular compartments in addition to the plasma membrane. Here, we investigated whether GRKs contributed to location bias in GPCR signaling...
February 13, 2024: Science Signaling
https://read.qxmd.com/read/38331728/the-role-of-gpr81-camp-pka-pathway-in-endurance-training-induced-intramuscular-triglyceride-accumulation-and-mitochondrial-content-changes-in-rats
#8
JOURNAL ARTICLE
Lin Li, Xiangdeng Lai, Yihan Ni, Siyu Chen, Yaqian Qu, Zhiqiang Hu, Jingquan Sun
The athlete's paradox phenomenon involves the accumulation of intramuscular triglycerides (IMTG) in both insulin-resistant and insulin-sensitive endurance athletes. Nevertheless, a complete understanding of this phenomenon is yet to be achieved. Recent research indicates that lactate, a common byproduct of physical activity, may increase the accumulation of IMTG in skeletal muscle. This is achieved through the activation of G protein-coupled receptor 81 (GPR81) leads to the suppression of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway...
February 8, 2024: Journal of Physiological Sciences: JPS
https://read.qxmd.com/read/38241945/enhanced-macromolecular-substance-extravasation-through-the-blood-brain-barrier-via-acoustic-bubble-cell-interactions
#9
JOURNAL ARTICLE
Jifan Chen, Jean-Michel Escoffre, Oliver Romito, Tarik Iazourene, Antoine Presset, Marie Roy, Marie Potier Cartereau, Christophe Vandier, Yahua Wang, Guowei Wang, Pintong Huang, Ayache Bouakaz
The blood-brain barrier (BBB) maintains brain homeostasis, regulates influx and efflux transport, and provides protection to the brain tissue. Ultrasound (US) and microbubble (MB)-mediated blood-brain barrier opening is an effective and safe technique for drug delivery in-vitro and in-vivo. However, the exact mechanism underlying this technique is still not fully elucidated. The aim of the study is to explore the contribution of transcytosis in the BBB transient opening using an in-vitro model of BBB. Utilizing a diverse set of techniques, including Ca2+ imaging, electron microscopy, and electrophysiological recordings, our results showed that the combined use of US and MBs triggers membrane deformation within the endothelial cell membrane, a phenomenon primarily observed in the US + MBs group...
January 17, 2024: Ultrasonics Sonochemistry
https://read.qxmd.com/read/38217376/oxaloacetic-acid-induces-muscle-energy-substrate-depletion-and-fatigue-by-jnk-mediated-mitochondrial-uncoupling
#10
JOURNAL ARTICLE
Cong Yin, Rui Qin, Zewei Ma, Fan Li, Jiao Liu, Hong Liu, Gang Shu, Hairong Xiong, Qingyan Jiang
Fatigue is a common phenomenon closely related to physical discomfort and numerous diseases, which is severely threatening the life quality and health of people. However, the exact mechanisms underlying fatigue are not fully characterized. Herein, we demonstrate that oxaloacetic acid (OAA), a crucial tricarboxylic acid cycle intermediate, modulates the muscle fatigue. The results showed that serum OAA level was positively correlated with fatigue state of mice. OAA-treated induced muscle fatigue impaired the exercise performance of mice...
February 2024: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/38203544/beta-blockade-prevents-cardiac-morphological-and-molecular-remodelling-in-experimental-uremia
#11
JOURNAL ARTICLE
Shanmugakumar Chinnappa, Azhar Maqbool, Hema Viswambharan, Andrew Mooney, Laura Denby, Mark Drinkhill
Heart failure and chronic kidney disease (CKD) share several mediators of cardiac pathological remodelling. Akin to heart failure, this remodelling sets in motion a vicious cycle of progressive pathological hypertrophy and myocardial dysfunction in CKD. Several decades of heart failure research have shown that beta blockade is a powerful tool in preventing cardiac remodelling and breaking this vicious cycle. This phenomenon remains hitherto untested in CKD. Therefore, we set out to test the hypothesis that beta blockade prevents cardiac pathological remodelling in experimental uremia...
December 27, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38183839/bovine-parainfluenza-type-3-virus-induces-incomplete-autophagy-to-promote-viral-replication-by-activated-beclin1-in-vitro
#12
JOURNAL ARTICLE
Yu Han, Chongyang Wang, Kejia Lu, Xiaoyu Dong, Zhengwu Chang, Riteng Zhang, Qili Hou, Xinglong Wang, Sa Xiao, Haijin Liu, Zengqi Yang
Bovine Parainfluenza virus Type 3 (BPIV3) is one of the most important pathogens in cattle, capable of causing severe respiratory symptoms. Numerous studies have shown that autophagy plays a diverse role in the infection process of various pathogens. The influence of autophagy machinery on BPIV3 infection has not yet been confirmed. In the present study, we initially demonstrated that the expression of LC3 was significantly increased and exhibited a notable increase in double or single-membrane vesicles under a transmission electron microscope during BPIV3 infection...
January 3, 2024: Veterinary Microbiology
https://read.qxmd.com/read/38182566/mammalian-target-of-rapamycin-inhibition-protects-glioma-cells-from-temozolomide-induced-cell-death
#13
JOURNAL ARTICLE
Benedikt Sauer, Nadja I Lorenz, Iris Divé, Kevin Klann, Anna-Luisa Luger, Hans Urban, Jan-Hendrik Schröder, Joachim P Steinbach, Christian Münch, Michael W Ronellenfitsch
Glioblastoma is an incurable brain tumor with a median survival below two years. Trials investigating targeted therapy with inhibitors of the kinase mTOR have produced ambiguous results. Especially combination of mTOR inhibition with standard temozolomide radiochemotherapy has resulted in reduced survival in a phase II clinical trial. To date, this phenomenon is only poorly understood. To recreate the therapeutic setting in vitro, we exposed glioblastoma cell lines to co-treatment with rapamycin and temozolomide and assessed cell viability, DNA damage and reactive oxygen species...
January 5, 2024: Cell Death Discovery
https://read.qxmd.com/read/38134935/age-dependent-loss-of-cohesion-protection-in-human-oocytes
#14
JOURNAL ARTICLE
Bettina P Mihalas, Gerard H Pieper, Mansour Aboelenain, Lucy Munro, Vlastimil Srsen, Cerys E Currie, David A Kelly, Geraldine M Hartshorne, Evelyn E Telfer, Andrew D McAinsh, Richard A Anderson, Adele L Marston
Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis as a common cause. We found that loss of a specific pool of the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon. Our data indicate that SGO2 preserves sister chromatid cohesion in meiosis by protecting a "cohesin bridge" between sister chromatids. In human oocytes, SGO2 localizes to both sub-centromere cups and the pericentromeric bridge, which spans the sister chromatid junction...
December 14, 2023: Current Biology: CB
https://read.qxmd.com/read/38091837/the-significance-of-caloric-restriction-mimetics-as-anti-aging-drugs
#15
REVIEW
Khloud Nassar, Doaa El-Mekawey, Ahmed E Elmasry, Mohamed S Refaey, Mai El-Sayed Ghoneim, Yaseen A M M Elshaier
Aging is an intricate process characterized by the gradual deterioration of the physiological integrity of a living organism. This unfortunate phenomenon inevitably leads to a decline in functionality and a heightened susceptibility to the ultimate fate of mortality. Therefore, it is of utmost importance to implement interventions that possess the capability to reverse or preempt age-related pathology. Caloric restriction mimetics (CRMs) refer to a class of molecules that have been observed to elicit advantageous outcomes on both health and longevity in various model organisms and human subjects...
December 4, 2023: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38089466/nonallosteric-activation-of-posttranslational-modification-enzymes-by-active-site-directed-inhibitors
#16
JOURNAL ARTICLE
Alessandro Pesaresi
Activation-by-inhibition is a biochemical paradox seldom observed in exosite enzymes, wherein active site-bound inhibitors unexpectedly lead to enzyme activation. This intriguing phenomenon occurs at low, undersaturating substrate concentrations, posing a significant challenge in drug discovery, especially when targeting enzymes such as protein kinases, proteases, and other posttranslational modification enzymes. These enzymes often rely on accessory recognition sites known as exosites, which contribute to complex substrate binding mechanisms and unique kinetic behaviors...
December 2024: Computational and Structural Biotechnology Journal
https://read.qxmd.com/read/38068928/the-effect-of-adipocyte-secreted-factors-in-activating-focal-adhesion-kinase-mediated-cell-signaling-pathway-towards-metastasis-in-breast-cancer-cells
#17
JOURNAL ARTICLE
Noshin Mubtasim, Lauren Gollahon
Obesity-associated perturbations in the normal secretion of adipocytokines from white adipocytes can drive the metastatic progression of cancer. However, the association between obesity-induced changes in secretory factors of white adipocytes and subsequent transactivation of the downstream effector proteins impacting metastasis in breast cancer cells remains unclear. Focal adhesion kinase, a cytoplasmic signal transducer, regulates the biological phenomenon of metastasis by activating downstream targets such as beta-catenin and MMP9...
November 22, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37980751/transcriptome-analysis-of-ovarian-tissues-highlights-genes-controlling-energy-homeostasis-and-oxidative-stress-as-potential-drivers-of-heterosis-for-egg-number-and-clutch-size-in-crossbred-laying-hens
#18
JOURNAL ARTICLE
Adamu Mani Isa, Yanyan Sun, Yuanmei Wang, Yunlei Li, Jingwei Yuan, Aixin Ni, Hui Ma, Lei Shi, Hailai Hagos Tesfay, Yunhe Zong, Panlin Wang, Pingzhuang Ge, Jilan Chen
Heterosis is the major benefit of crossbreeding and has been exploited in laying hens breeding for a long time. This genetic phenomenon has been linked to various modes of nonadditive gene action. However, the molecular mechanism of heterosis for egg production in laying hens has not been fully elucidated. To fill this research gap, we sequenced mRNAs and lncRNAs of the ovary stroma containing prehierarchical follicles in White Leghorn, Rhode Island Red chickens as well as their reciprocal crossbreds that demonstrated heterosis for egg number and clutch size...
October 4, 2023: Poultry Science
https://read.qxmd.com/read/37980488/transcription-factor-lhx9-lim-homeobox-9-enhances-pyruvate-kinase-pkm2-activity-to-induce-glycolytic-metabolic-reprogramming-in-cancer-stem-cells-promoting-gastric-cancer-progression
#19
JOURNAL ARTICLE
Hongying Zhao, Rongke Jiang, Zhijing Feng, Xue Wang, Chunmei Zhang
BACKGROUND: Glycolytic metabolic reprogramming is a phenomenon in which cells undergo altered metabolic patterns during malignant transformation, mainly involving various aspects of glycolysis, electron transport chain, oxidative phosphorylation, and pentose phosphate pathway. This reprogramming phenomenon can be used as one of the markers of tumorigenesis and development. Pyruvate kinase is the third rate-limiting enzyme in the sugar metabolism process by specifically catalyzing the irreversible conversion of PEP to pyruvate...
November 18, 2023: Journal of Translational Medicine
https://read.qxmd.com/read/37961097/ligand-dependent-mechanisms-of-c-c-chemokine-receptor-5-ccr5-trafficking-revealed-by-apex2-proximity-labeling-proteomics
#20
Siyi Gu, Svetlana Maurya, Alexis Lona, Leire Borrega-Roman, Catherina Salanga, David J Gonzalez, Irina Kufareva, Tracy M Handel
UNLABELLED: CC chemokine receptor 5 (CCR5) contributes to inflammatory responses by driving cell migration and scavenging chemokine to shape directional chemokine gradients. A drug against CCR5 has been approved for blocking HIV entry into cells. However, targeting CCR5 for the treatment of inflammatory diseases and cancer has had limited success because of the complex biology and pharmacology of this receptor. CCR5 is activated by many natural and engineered chemokines that elicit distinct receptor signaling and trafficking responses, including some that sequester the receptor inside the cell...
November 3, 2023: bioRxiv
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