Article
Pharmacology & Pharmacy
Helen Haixia Wu, Kerry-Leigh Ralph, Eliud Sepuldeva, Gale Hansen, Hua Li, Zhong-Fu Huang, Dongmei Liu, Michael Dziegelewski, Jennifer Ahlberg, Lee Frego, Steve Fogal, Susan van Tongeren, Christine Grimaldi, Tobias Litzenberger, David Presky, Sanjaya Singh, Scott Brodeur, Rachel Kroe-Barrett
Summary: The study presents a novel antibody BI 655064 targeting the CD40-CD40L pathway, which effectively neutralizes the pathogenesis of related diseases and has high therapeutic potential.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Biology
Younes Aftabi, Saleh Rafei, Habib Zarredar, Amir Amiri-Sadeghan, Mohsen Akbari-Shahpar, Zahra Khoshkam, Ensiyeh Seyedrezazadeh, Majid Khalili, Faramarz Mehrnejad, Sasan Fereidouni, B. Paige Lawrence
Summary: Various bioinformatic methods are used to predict the deleterious effects of SNPs, and the results may vary significantly. The ISNPranker web-tool was developed to integrate predictions from different predictors and rank SNPs based on this integrated analysis. Using this tool, the most deleterious cSNPs of the human AHR gene were identified, indicating potential sensitivity of AHR structure and function to specific variations in its coding sequences.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Cell Biology
Anton Klersy, Soeren Meyer, Florian Leuschner, Thorsten Kessler, Markus Hecker, Andreas H. Wagner
Summary: This study investigates the association between ADAM17-mediated CD40 shedding and inflammation in CC genotype human endothelial cells. Inhibition of ADAM17 prevented TNF-alpha-induced sCD40 and soluble vascular cell adhesion molecule-1 release, and reinforced CD40 surface abundance. Levels of sCD40 and the inflammatory biomarkers hs-CRP and IL-6 were positively correlated in the plasma of patients with CHD.
Article
Biochemistry & Molecular Biology
Sandra Wymann, Yun Dai, Anup G. Nair, Helen Cao, Glenn A. Powers, Anna Schnell, Genevieve Martin-Roussety, David Leong, Jason Simmonds, Kim G. Lieu, Mitchell J. de Souza, Marcel Mischnik, Shirley Taylor, Saw Yen Ow, Martin Spycher, Rebecca E. Butcher, Martin Pearse, Adrian W. Zuercher, Adriana Baz Morelli, Con Panousis, Michael J. Wilson, Tony Rowe, Matthew P. Hardy
Summary: This study identified a truncated soluble form of HuCR1, designated CSL040, as a more potent inhibitor of complement activation compared to other truncation variants. The pharmacokinetic studies in mice revealed that the level of sialylation is a major determinant of CSL040 clearance in vivo. In an experimental model of complement-mediated kidney damage, CSL040 showed significant attenuation of kidney damage, making it a potential therapeutic candidate for complement-mediated disorders.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Nina M. van Sorge, Daniel A. Bonsor, Liwen Deng, Erik Lindahl, Verena Schmitt, Mykola Lyndin, Alexej Schmidt, Olof R. Nilsson, Jaime Brizuela, Elena Boero, Eric J. Sundberg, Jos A. G. van Strijp, Kelly S. Doran, Bernhard B. Singer, Gunnar Lindahl, Alex J. McCarthy
Summary: Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a major cause of neonatal sepsis in humans. In a recent study, it was found that the surface-expressed beta protein of GBS binds to human CEACAM1 and CEACAM5 receptors, with the crystal structure revealing a novel IgI3 fold. This discovery suggests a potentially widely applicable mechanism for bacteria to target CEACAMs.
Article
Immunology
Qi Huang, Wang-Dong Xu, Lin-Chong Su, Xiao-Yan Liu, An-Fang Huang
Summary: This study investigated CD40 gene polymorphisms in Chinese Han population with SLE and RA, finding associations between certain genotypes and alleles with susceptibility to the diseases. The findings suggest a potential role of CD40 gene polymorphisms in the pathogenesis of SLE and RA.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paula Aldaz, Amaya Fernandez-Celis, Natalia Lopez-Andres, Imanol Arozarena
Summary: Dexamethasone (DEXA) is commonly used in glioblastoma (GBM) patients to reduce brain inflammation, activating the glucocorticoid receptor (GR) which can influence the mineralocorticoid receptor (MR) signaling. MR signaling in GBM has been shown to have anti-proliferative effects and inhibit the self-renewal of GSCs, while spironolactone (SPI) may not have significant anti-neoplastic potential in GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Agata P. Perlinska, Wanda H. Niemyska, Bartosz A. Gren, Marek Bukowicki, Szymon Nowakowski, Pawel Rubach, Joanna I. Sulkowska
Summary: The fact that proteins can form knots in their chain has been known for almost 30 years. However, only a small fraction of these proteins are available in the Protein Data Bank due to their rarity. Recent advancements in machine learning methods have allowed us to analyze the entire proteome of a human organism, leading to the discovery of 51 credible knotted proteins (0.2% of human proteome). This research also unveiled a new type of knot, denoted as 6(3), which requires a more complex folding path than any previously reported knotted protein.
Article
Genetics & Heredity
Andrew R. Crowley, Simone Richardson, Marina Tuyishime, Madeleine Jennewein, Meredith J. Bailey, Jiwon Lee, Galit Alter, Guido Ferrari, Lynn Morris, Margaret E. Ackerman
Summary: Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have been statistically linked to various disease states. This study investigates the potential effects of IgG allotype on antibody function, specifically on Fc gamma R affinity and effector function. The results suggest that while there are differences in Fc gamma R affinity among allotypes, there is little evidence of significantly altered Fc gamma R-based effector function or antigen recognition activity associated with this genetic variability.
Article
Biochemistry & Molecular Biology
Jiaxuan Chen, Haitao Chen, Haoming Mai, Shuang Lou, Mengqi Luo, Haisheng Xie, Bin Zhou, Jinlin Hou, De-Ke Jiang
Summary: More than 250 million people worldwide are chronically infected with HBV, and our previous study found that a SNP, rs1883832, in the CD40 gene predisposes to chronic HBV infection. In this study, we confirmed that rs1883832 is the functional SNP of CD40 and identified ANXA2 as a negative regulatory protein that binds to the risk allele T of rs1883832 and reduces CD40 expression. CD40 was found to suppress HBV replication and transcription in hepatocytes through activating the JAK-STAT pathway and regulating the IFN-stimulated gene BST2. Inhibition of the JAK/STAT/BST2 axis attenuated CD40-induced antiviral effect.
HUMAN MOLECULAR GENETICS
(2023)
Article
Chemistry, Medicinal
Ivana Mejdrova, Jan Dusek, Krystof Skach, Alzbeta Stefela, Josef Skoda, Karel Chalupsky, Klara Dohnalova, Ivona Pavkova, Thales Kronenberger, Azam Rashidian, Lucie Smutna, Vojtech Duchoslav, Tomas Smutny, Petr Pavek, Radim Nencka
Summary: The nuclear constitutive androstane receptor (CAR, NR1I3) plays significant roles in hepatic functions and has been proposed as a target for metabolic or liver disease therapy. However, current CAR agonists have limited selectivity. We discovered derivatives that directly activate human CAR and are selective, non-toxic, and show in vivo activity, highlighting CAR as a therapeutic target.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Waldemar Schaefer, Tobias Staehler, Carolina Pinto Espinoza, Welbeck Danquah, Jan Hendrik Knop, Bjoern Rissiek, Friedrich Haag, Friedrich Koch-Nolte
Summary: P2X7, an ion channel gated by extracellular ATP, plays important roles in inflammation and apoptosis. Polymorphisms in the P2X7 gene are common, and their frequencies vary among different human populations. Considering P2X7 variants of participants is important in designing clinical trials targeting P2X7.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Nan-Rui Shi, Qi Wang, Jie Liu, Ji-Zhou Zhang, Bin-Lu Deng, Xiu-Min Hu, Jie Yang, Xin Wang, Xiang Chen, Yan-Qin Zuo, Ting-Ting Liu, Jia-Ling Zheng, Xin Yang, Peter Illes, Yong Tang
Summary: The study explored the relationship between genetic polymorphisms of A(2A)R and CD73 and epilepsy. The results showed that the TT genotype and T allele of rs4431401 in CD73 were genetic risk factors for epilepsy, while rs2267076, rs2298383, rs4822492, and rs4822489 polymorphisms of A(2A)R were mainly associated with female epilepsy patients.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Clinical Neurology
Annelie Shami, Andreas Edsfeldt, Eva Bengtsson, Jan Nilsson, Angela C. Shore, Andrea Natali, Faisel Khan, Esther Lutgens, Isabel Goncalves
Summary: This study found that elevated plasma levels of sCD40 and sCD40L are associated with cardiovascular disease, with sCD40 levels correlating with the severity of carotid atherosclerosis and predicting future cardiovascular events, while intra-plaque levels are associated with a vulnerable plaque phenotype.
Review
Biochemistry & Molecular Biology
Ruifeng Chen, Xuan Wang, Zilin Li, Yumei Dai, Wenya Du, Lixian Wu
Summary: Toll-like receptor 2 (TLR2) is important in tuberculosis development. However, the association between TLR2 polymorphisms and tuberculosis susceptibility has not been explored. This study systematically searched relevant databases and included 37 studies, involving 6 polymorphisms and a total of 9,474 cases and 10,295 controls. The results showed that only the TLR2 rs5743708 polymorphism was significantly associated with a higher tuberculosis risk, while other TLR2 polymorphisms were not associated with tuberculosis susceptibility.
Article
Cell Biology
Kai J. Rogers, Olena Shtanko, Laura L. Stunz, Laura N. Mallinger, Tina Arkee, Megan E. Schmidt, Dana Bohan, Bethany Brunton, Judith M. White, Steve M. Varga, Noah S. Butler, Gail A. Bishop, Wendy Maury
Summary: CD40 expression in peritoneal M phi s restricts early infection of a broad range of RNA viruses. CD154/CD40 interactions stimulate IL-12 production, leading to IFN-gamma production and proinflammatory polarization of M phi s, protecting the cells from infection. These CD40-dependent events protect mice against virus challenge.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Nutrition & Dietetics
Cynthia M. Kroeger, Keisuke Ejima, Bridget A. Hannon, Tanya M. Halliday, Bryan McComb, Margarita Teran-Garcia, John A. Dawson, David B. King, Andrew W. Brown, David B. Allison
Summary: The use of classic nonparametric tests in the presence of unequal variance can lead to increased false positive rates and decreased statistical power. This study found that the Type I error rates for Fisher's ANOVA and Kruskal-Wallis deviated from expected levels as heterogeneity increased, especially with imbalanced sample sizes. Authors, editors, and reviewers are provided with guidance for selecting appropriate statistical tests when assumptions are violated.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2021)
Article
Biochemistry & Molecular Biology
Amy L. Whillock, Tiffany K. Ybarra, Gail A. Bishop
Summary: TRAF3 has diverse signaling functions, inhibiting homeostatic survival in B lymphocytes, while enhancing T-cell effector functions. It plays a role in inhibiting noncanonical NF-kappa B activation, CD40 and BAFF-R signaling in B cells, and its absence promotes abnormal survival of malignant B cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Kyp L. Oxley, Brett M. Hanson, Ashley N. Zani, Gail A. Bishop
Summary: Utilizing patient B lymphocytes to create a cancer vaccine showed improved survival rates, reduced tumor size, and delayed time of tumor appearance, indicating a promising alternative strategy for clinical translation.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Chet R. Villa, Angela Lorts, Jennifer Kasten, Clifford Chin, Tarek Alsaied, Greg Tiao, Jaimie D. Nathan, Anna L. Peters, Andrew M. Misfeldt, Mark Vranicar, David L. Morales
CIRCULATION-HEART FAILURE
(2021)
Editorial Material
Endocrinology & Metabolism
Yasaman Jamshidi-Naeini, Andrew W. Brown, Tapan Mehta, Deborah H. Glueck, Lilian Golzarri-Arroyo, Keith E. Muller, Carmen D. Tekwe, David B. Allison
Editorial Material
Biochemistry & Molecular Biology
Colby J. Vorland, Xiwei Chen, Daniella E. Chusyd, Luis M. Mestre, Stephanie L. Dickinson, David B. Allison, Andrew W. Brown
Article
Biochemistry & Molecular Biology
Emma L. Hornick, Alicia M. Wallis, Gail A. Bishop
Summary: Type I interferons (IFNs) are powerful tools used by host cells to fight against intracellular pathogens. This study reveals the role of tumor necrosis factor receptor-associated factor 3 (TRAF3) and phosphatase PTPN22 in regulating CD4(+) T cell activation by type I IFNs. The balance between signals from IFNAR and other cytokine receptors influences CD4(+) T cell differentiation and function during infections.
Editorial Material
Endocrinology & Metabolism
David B. Allison, Dennis M. Bier, Julie L. Locher
INTERNATIONAL JOURNAL OF OBESITY
(2023)
Article
Pediatrics
Sindhu Pandurangi, Seung Kim, Akihiro Asai, Alexander Bondoc, William Balistreri, Kathleen Campbell, Alexander Miethke, Anna Peters, Michael Rogers, Amy Taylor, Suzanna Labib Attia, Troy Gibbons, Bhargava Mullapudi, Rachel Sheridan, Greg Tiao, Jorge A. Bezerra
Summary: This study aimed to evaluate the efficacy of personalized use of antibiotics and corticosteroids in patients with biliary atresia after surgery. The results showed that the personalized medication group had a significantly higher success rate of bile drainage compared to the conventional treatment group, and also maintained more native livers at 2 years. Therefore, personalized medication may help improve postoperative bile drainage.
JOURNAL OF PEDIATRIC SURGERY
(2023)
Article
Pediatrics
Anna L. Peters, Michael Rogers, Gousia Begum, Qin Sun, Lin Fei, Daniel Leino, David Hildeman, Ervin Steve Woodle
Summary: This study retrospectively analyzed cases of late liver cellular rejection in children and found that higher levels of serum gamma-glutamyl transpeptidase, presence of autoantibodies, and increased CD8(+) T-cell infiltration are associated with delayed response to treatment for late cellular rejection.
PEDIATRIC TRANSPLANTATION
(2023)
Editorial Material
Surgery
Milad Rezvani, Kathleen M. Campbell, Carlos E. Prada, Anna L. Peters
Summary: Liver transplantation can transfer genetic defects in metabolic pathways, and this case highlights the occurrence of metabolic crisis and early allograft dysfunction due to an acquired argininosuccinate lyase deficiency. The recipient's genetic testing revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme. Postoperative ischemia/reperfusion injury increased metabolic demand beyond the enzymatic capacity of the allograft. This case emphasizes the importance of considering occult metabolic variants in the allograft during early allograft dysfunction.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Pediatrics
Anna L. Peters, Seung Kim, Reena Mourya, Akihiro Asai, Amy Taylor, Michael Rogers, Kathleen Campbell, Lin Fei, Alexander Miethke, William F. Balistreri, Jorge A. Bezerra
Summary: This study evaluated the increase in the number of cases and the association with adenovirus in children with non-A-E severe acute hepatitis from late 2021 to early 2022. Despite a significant proportion of children with acute liver failure, the overall survival rate remains high.
JOURNAL OF PEDIATRICS
(2023)
Letter
Education & Educational Research
Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Colby J. Vorland, Abu Bakkar Siddique, Deborah H. Glueck, David B. Allison
JOURNAL OF SCHOOL HEALTH
(2023)
Article
Nutrition & Dietetics
Muna J. Tahir, Keisuke Ejima, Peng Li, Ellen W. Demerath, David B. Allison, David A. Fields
Summary: The study found that at 6 months of age, breastfed infants had lower fat-free mass but higher trunk fat mass and body fat percent compared to formula-fed infants. Adjusted analysis showed significantly lower total fat-free mass and significantly higher body fat percent in breastfed infants. No other significant associations were observed.
MATERNAL AND CHILD NUTRITION
(2021)