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RNA 2022 May 26. Epub 2022 May 26.

University of Georgia;

CRISPR-Cas systems are functionally diverse prokaryotic anti-viral defense systems, which encompass six distinct types (I-VI) that each encode different effector Cas nucleases with distinct nucleic acid cleavage specificities. By harnessing the unique attributes of the various CRISPR-Cas systems, a range of innovative CRISPR-based DNA and RNA targeting tools and technologies have been developed. Here, we exploit the ability of type III-A CRISPR-Cas systems to carry out RNA-guided and sequence-specific target RNA cleavage for establishment of research tools for post-transcriptional control of gene expression. Read More

Genome Res 2022 May 26. Epub 2022 May 26.

Max Planck Institute for Biology

The birth of new genes is a major molecular innovation driving phenotypic diversity across all domains of life. Although repurposing of existing protein-coding material by duplication is considered the main process of new gene formation, recent studies have discovered thousands of transcriptionally active sequences as a rich source of new genes. However, differential loss rates have to be assumed to reconcile the high birth rates of these incipient de novo genes with the dominance of ancient gene families in individual genomes. Read More

Genome Res 2022 May 26. Epub 2022 May 26.

Hospital del Mar Medical Research Institute;

The unicellular yeast (fission yeast) retains many of the splicing features observed in humans and is thus an excellent model to study the basic mechanisms of splicing. Nearly half the genes contain introns, but the impact of alternative splicing in gene regulation and proteome diversification remains largely unexplored. Here we leverage Oxford Nanopore Technologies native RNA sequencing (dRNA), as well as ribosome profiling data, to uncover the full range of polyadenylated transcripts and translated open reading frames. Read More

Ren Fail 2022 Dec;44(1):923-932

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin.

Accumulating evidence has implicated that berberine (BBR) has a beneficial effect on diabetic kidney disease (DKD), but its mechanism is not clear. The aim of this study was to assess whether berberine could alleviate tubulointerstitial fibrosis and attenuate epithelial-to-mesenchymal transition (EMT) and its possible molecular mechanism. High-fat diet (HFD) followed by injection of STZ was used to induce diabetic rats . Read More

J Sch Psychol 2022 Jun 28;92:80-95. Epub 2022 Mar 28.

Department of Educational and Counselling Psychology, and Special Education, The University of British Columbia, Canada.

Although researchers have investigated technical adequacy and usability of written-expression curriculum-based measures (WE-CBM), the economic implications of different scoring approaches have largely been ignored. The absence of such knowledge can undermine the effective allocation of resources and lead to the adoption of suboptimal measures for the identification of students at risk for poor writing outcomes. Therefore, we used the Ingredients Method to compare implementation costs and cost-effectiveness of hand-calculated and automated scoring approaches. Read More

Genes Dev 2022 May 26. Epub 2022 May 26.

Division of Diabetes Endocrinology and Metabolism, Johns Hopkins University School of Medicine; Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida 33701, USA.

Accumulation of fat above the waist is an important risk factor in developing obesity-related comorbidities independently of BMI or total fat mass. Deciphering the gene regulatory programs of the adipose tissue precursor cells within upper body or abdominal (ABD) and lower body or gluteofemoral (GF) depots is important to understand their differential capacity for lipid accumulation, maturation, and disease risk. Previous studies identified the HOX transcript antisense intergenic RNA (HOTAIR) as a GF-specific lncRNA; however, its role in adipose tissue biology is still unclear. Read More

Genes Dev 2022 May 26. Epub 2022 May 26.

Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.

Senescence is a stress-responsive tumor suppressor mechanism associated with expression of the senescence-associated secretory phenotype (SASP). Through the SASP, senescent cells trigger their own immune-mediated elimination, which if evaded leads to tumorigenesis. Senescent parenchymal cells are separated from circulating immunocytes by the endothelium, which is targeted by microenvironmental signaling. Read More

J Immunother Cancer 2022 May;10(5)

Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA

Background: Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( ombination daptive- nnate immunotherapy egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. Read More

J Immunother Cancer 2022 May;10(5)

Department of Medecine, Institut Bergonié, Bordeaux, France

Background: Tumor-associated macrophages (TAMs) having immunosuppressive properties are one of the most abundant immune cells in the tumor microenvironment (TME). Preclinical studies have highlighted the potential role of TAMs in resistance to immune checkpoint blockers (ICBs). Here, we investigated the predictive value of TAM infiltration in patients with non-small cell lung cancer (NSCLC) treated with ICBs and characterized their transcriptomic profiles. Read More

J Immunother Cancer 2022 May;10(5)

Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China

Background: Immunotherapy for hepatocellular carcinoma (HCC) exhibits limited clinical efficacy due to immunosuppressive tumor microenvironment (TME). Tumor-infiltrating macrophages (TIMs) account for the major component in the TME, and the dominance of M2 phenotype over M1 phenotype in the TIMs plays the pivotal role in sustaining the immunosuppressive character. We thus investigate the effect of bufalin on promoting TIMs polarization toward M1 phenotype to improve HCC immunotherapy. Read More

J Immunother Cancer 2022 May;10(5)

Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Cancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP. Read More

Eur Respir J 2022 May 26. Epub 2022 May 26.

Department of Immunology, Labor Berlin - Charité Vivantes GmbH, Berlin, Germany

Rapid and reliable diagnostic work-up of tuberculosis (TB) remains a major healthcare goal. In particular, discrimination of TB infection from TB disease with currently available diagnostic tools is challenging and time-consuming. This study aimed at establishing a standardised blood-based assay that rapidly and reliably discriminates TB infection from disease based on multiparameter analysis of TB antigen-reactive CD4 T cells acting as sensors for the TB stage-specific immune status. Read More

J Nutr Biochem 2022 May 23:109068. Epub 2022 May 23.

Academy of Scientific & Innovative Research, Dietetics & Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India-176061. Electronic address:

Cellular senescence is emerging as a major hallmark of aging, and its modulation presents an effective anti-aging strategy. This study attempted to understand the progression of cellular senescence in vivo, and whether it can be mitigated by chronic consumption of green tea catechin epigallocatechin gallate (EGCG). We profiled cellular senescence in various organs of mice at four different time-points of lifespan, and then explored the influence of EGCG consumption in impacting markers of cellular senescence, inflamm-aging, immunosenescence, and gut dysbiosis. Read More

Bone 2022 May 23:116448. Epub 2022 May 23.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research & Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Orthodontics, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, PR China. Electronic address:

Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease of the joint. The early manifestations of TMJ-OA are abnormal remodeling of condylar subchondral bone. In bone tissue, bone marrow mesenchymal stem cells (BMSCs) and osteoblasts play important roles in the differentiation and maturation of most hematopoietic cells. Read More

Gene 2022 May 23:146574. Epub 2022 May 23.

College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, Guangdong, 524088, P.R.China. Electronic address:

Glycerol-3-phosphate acyltransferase mitochondrial (GPAM) is an enzyme in animal lipid metabolism pathways that catalyzes the initial and most committed step of glycerolipid biosynthesis. The present study mainly focused on exploring the relationship between the GPAM gene and the lipid metabolism of mammary epithelial cells and the effect of GPAM on the related pathways of lipid metabolism. The GPAM gene was knocked out entirely in bovine mammary epithelial cells(BMECs) using CRISPR/Cas9 technology, and the mechanism by which the GPAM gene regulates lipid metabolism in BMECs was confirmed. Read More

Gene 2022 May 23:146612. Epub 2022 May 23.

Institute of Animal Husbandry & Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai, 201106, P.R. China. Electronic address:

Although graylag geese (A. anser) showed similar plumages of white, grey, and white with grey patches compared to those in swan geese (A. cygnoides), it was believed the substantial molecular mechanism for plumage variations were different. Read More

Gene 2022 May 23:146611. Epub 2022 May 23.

Zhejiang Mariculture Research Institute, Zhejiang Key Lab of Exploitation and Preservation of Coastal Bio-Resource, Wenzhou Key Laboratory of Marine Biological Genetics and Breeding, Wenzhou 325005, China. Electronic address:

Cadmium (Cd) pollution threatens the cultivation of the blood clam Tegillarca granosa (T. granosa) in coastal regions of the East China Sea. The molecular mechanisms regulating Cd stress response and detoxification in blood clams are largely unclear. Read More

J Proteomics 2022 May 23:104621. Epub 2022 May 23.

National Engineering Research Center of JUNCAO Technology, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address:

Aeromonas hydrophila is a widespread opportunistic pathogen of aquatic fishes in freshwater habitats. The current emergence of antimicrobial-resistant A. hydrophila has been reported in the world while the bacterial antibiotics adaptive mechanism remains poorly explored. Read More

Clin Immunol 2022 May 23:109045. Epub 2022 May 23.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China. Electronic address:

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Read More

Neurobiol Dis 2022 May 23:105775. Epub 2022 May 23.

Office of the Saskatchewan Multiple Sclerosis Clinical Research Chair, University of Saskatchewan, Saskatoon, SK S7K 0M7, Canada; Cameco MS Neuroscience Research Centre, College of Medicine, University of Saskatchewan, Saskatoon, SK S7K 0M7, Canada; Neurology Division, Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0X8, Canada; Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. Electronic address:

Neurodegeneration, the progressive loss or damage to neurons and axons, underlies permanent disability in multiple sclerosis (MS); yet its mechanisms are incompletely understood. Recent data indicates autoimmunity to several intraneuronal antigens, including the RNA binding protein (RBP) heterogenous nuclear ribonucleoprotein A1 (hnRNP A1), as contributors to neurodegeneration. We previously showed that addition of anti-hnRNP A1 antibodies, which target the same immunodominant domain of MS IgG, to mice with experimental autoimmune encephalomyelitis (EAE) worsened disease and resulted in an exacerbation of hnRNP A1 dysfunction including cytoplasmic mislocalization of hnRNP A1, stress granule (SG) formation and neurodegeneration in the chronic stages of disease. Read More

J Control Release 2022 May 23. Epub 2022 May 23.

The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address:

Currently, clinical intravesical instillation chemotherapy has been greatly compromised by the toxicological and physiological factors. New formulations that can specifically and efficiently kill bladder cancer cells are in urgent need to overcome the low residence efficiency and dose limiting toxicity of current ones. The combination of mucoadhesive nanocarriers and cancer cell selective prodrugs can to great extent address these limitations. Read More

Biochim Biophys Acta Mol Basis Dis 2022 May 23:166452. Epub 2022 May 23.

Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi 710072, China; Department of Immunology, Fourth Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, China. Electronic address:

CD226 is a costimulatory molecule that regulates immune cell functions in T cells, natural killer cells, and macrophages. Because macrophage-derived foam cell formation is a crucial factor contributing to the development of atherosclerosis, we aimed to evaluate the potential roles of CD226 in the pathogenesis of atherosclerosis. The effects of CD226 on atherosclerosis were investigated in CD226 and apolipoprotein E double-knockout (CD226 ApoE) mice fed with a high-cholesterol atherogenic diet. Read More

Insect Biochem Mol Biol 2022 May 23:103793. Epub 2022 May 23.

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, 70013, Greece; Pesticide Science Laboratory, Department of Crop Science, Agricultural University of Athens, 11855, Athens, Greece. Electronic address:

The olive fruit fly, Bactrocera oleae, the most serious pest of olives, requires the endosymbiotic bacterium Candidatus Erwinia dacicola in order to complete its development in unripe green olives. Hence, a better understanding of the symbiosis of Ca. E. Read More

Regul Toxicol Pharmacol 2022 May 23:105193. Epub 2022 May 23.

Nynas AB, P.O. Box 10 700, SE-121 29, Stockholm, Sweden; CONCAWE, Boulevard Du Souverain 165, Mineral Hydrocarbons Task Force, B-1160, Brussels, Belgium.

The carcinogenicity and developmental toxicity of unrefined mineral oil is related to its 3-7 ring polycyclic aromatic compounds (PAC) content. Therefore, refining operations focus on the targeted removal PAC from mineral oil that may contain aromatics of low toxicological concern. There are thus, two types of aromatic substances in mineral oil: hazardous and non-hazardous. Read More

Fish Shellfish Immunol 2022 May 23. Epub 2022 May 23.

Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, China. Electronic address:

With the further study of long noncoding RNAs (lncRNAs), an increasing number of biological studies have demonstrated that lncRNAs are involved in various physiological processes, including cell proliferation, apoptosis, invasion, development and disease states. However, unlike mammals, little is known about the role of lncRNAs in the innate immunity of teleost fish. Here, we identify a lncRNA, named LTCONS5539, as critical role in the antiviral and antibacterial response of miiuy croaker and the results showed that lncRNA LTCONS5539 plays a critical regulatory role on TRAF6. Read More

Fish Shellfish Immunol 2022 May 23. Epub 2022 May 23.

School of Ocean, Yantai University, Yantai, China.

Mammalian toll-like receptor 5 (TLR5) is crucial for recognizing bacterial flagellin and initiating the inflammatory signaling cascades via myeloid differentiation factor 88 (MyD88) signaling pathway, which plays vital role in innate immune against pathogenic bacteria. Herein, we reported the signaling pathway and antibacterial property of tongue sole (Cynoglossus semilaevis) membrane forms of TLR5 (i.e. Read More

Biochimie 2022 May 23. Epub 2022 May 23.

Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Golestan University of Medical Sciences, Babol, Iran. Electronic address:

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Read More

Prostaglandins Other Lipid Mediat 2022 May 23:106650. Epub 2022 May 23.

Department of Oral Biology & Diagnostic Sciences, Augusta University, Augusta, GA. 30912; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt. Electronic address:

Numerous studies have demonstrated a sexual dimorphism in blood pressure (BP) control in spontaneously hypertensive rats (SHR), however the mechanisms remain to be further elucidated. Based on the established role of arachidonic acid metabolites and heme oxygenase (HO) in BP control, we hypothesize that higher BP in male SHR is associated with differential expression in renal HO and arachidonic acid metabolizing enzymes vs. female SHR. Read More

Brain Res Bull 2022 May 23. Epub 2022 May 23.

Research Service, VA Boston Healthcare System, West Roxbury, MA, 02132 USA.

Post-traumatic stress disorder (PTSD) is a trauma-related condition that produces distressing fear memory intrusions, avoidance behaviors, hyperarousal/startle, stress responses and insomnia. This review focuses on the importance of the orexin neural system as a novel mechanism related to the pathophysiology of PTSD. Orexinergic neurons originate in the lateral hypothalamus and project widely to key neurotransmitter system neurons, autonomic neurons, the hypothalamic-pituitaryadrenal (HPA) axis, and fear-related neural circuits. Read More

Fitoterapia 2022 May 23:105222. Epub 2022 May 23.

College of Materials & Chemical Engineering, Chuzhou University, 1 West Huifeng Road, Chuzhou 239000, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address:

A series of novel nitrogenous heterocycle substituted 23-Hydroxybetulinic acid (23-HBA) derivatives with amide linkages at the C-3 position were designed, synthesized and evaluated for their antitumor activities. The biological screening results showed that most of the derivatives exhibited more potent antiproliferative activities than 23-HBA. In particular compound II-9 exhibited the most potent activities with IC values ranging from 1. Read More