keyword
https://read.qxmd.com/read/38543597/exploring-leptospira-interrogans-fdaargos_203-insights-into-amr-and-anti-phage-defense
#1
JOURNAL ARTICLE
Pavlo Petakh, Valentyn Oksenych, Oleksandr Kamyshnyi
Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, result in significant illness and, in some cases, significant death in human populations. This purpose of this study was to examine the genomic structure of Leptospira interrogans serovar Copenhageni strain FDAARGOS_203 to identify the specific genetic factors that contribute to antimicrobial resistance (AMR) and defense against phages. The genome, consisting of two contigs totaling 4,630,574 base pairs, underwent thorough examination for protein-coding sequences, transfer RNA genes, and ribosomal RNA genes...
March 8, 2024: Microorganisms
https://read.qxmd.com/read/38542474/anti-cancer-mechanisms-of-diarylpentanoid-ms17-1-5-bis-2-hydroxyphenyl-1-4-pentadiene-3-one-in-human-colon-cancer-cells-a-proteomics-approach
#2
JOURNAL ARTICLE
Kha Wai Hon, Syafiq Asnawi Zainal Abidin, Faridah Abas, Iekhsan Othman, Rakesh Naidu
Diarylpentanoids are synthesized to overcome curcumin's poor bioavailability and low stability to show enhanced anti-cancer effects. Little is known about the anti-cancer effects of diarylpentanoid MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in colon cancer cells. This study aimed to elucidate molecular mechanisms and pathways modulated by MS17 in colon cancer based on proteomic profiling of primary SW480 and metastatic SW620 colon cancer cells. Cytotoxicity and apoptotic effects of MS17 were investigated using MTT assay, morphological studies, and Simple Western analysis...
March 20, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38542224/mitochondrial-ribosomal-protein-mrps15-is-a-component-of-cytosolic-ribosomes-and-regulates-translation-in-stressed-cardiomyocytes
#3
JOURNAL ARTICLE
Florian David, Emilie Roussel, Carine Froment, Tangra Draia-Nicolau, Françoise Pujol, Odile Burlet-Schiltz, Anthony K Henras, Eric Lacazette, Florent Morfoisse, Florence Tatin, Jean-Jacques Diaz, Frédéric Catez, Barbara Garmy-Susini, Anne-Catherine Prats
Regulation of mRNA translation is a crucial step in controlling gene expression in stressed cells, impacting many pathologies, including heart ischemia. In recent years, ribosome heterogeneity has emerged as a key control mechanism driving the translation of subsets of mRNAs. In this study, we investigated variations in ribosome composition in human cardiomyocytes subjected to endoplasmic reticulum stress induced by tunicamycin treatment. Our findings demonstrate that this stress inhibits global translation in cardiomyocytes while activating internal ribosome entry site (IRES)-dependent translation...
March 13, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38539193/non-ribosomal-peptide-synthetase-nrps-encoding-products-and-their-biosynthetic-logics-in-fusarium
#4
REVIEW
Ziwei Huang, Wangjie Zhu, Yifan Bai, Xuelian Bai, Huawei Zhang
Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains...
March 27, 2024: Microbial Cell Factories
https://read.qxmd.com/read/38534705/scientific-rationale-and-clinical-basis-for-clindamycin-use-in-the-treatment-of-dermatologic-disease
#5
REVIEW
Maria K Armillei, Ivan B Lomakin, James Q Del Rosso, Ayman Grada, Christopher G Bunick
Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option...
March 17, 2024: Antibiotics
https://read.qxmd.com/read/38534656/antisense-and-functional-nucleic-acids-in-rational-drug-development
#6
REVIEW
Robert Penchovsky, Antoniya V Georgieva, Vanya Dyakova, Martina Traykovska, Nikolet Pavlova
This review is focused on antisense and functional nucleic acid used for completely rational drug design and drug target assessment, aiming to reduce the time and money spent and increase the successful rate of drug development. Nucleic acids have unique properties that play two essential roles in drug development as drug targets and as drugs. Drug targets can be messenger, ribosomal, non-coding RNAs, ribozymes, riboswitches, and other RNAs. Furthermore, various antisense and functional nucleic acids can be valuable tools in drug discovery...
February 27, 2024: Antibiotics
https://read.qxmd.com/read/38527561/a-two-step-regulatory-circuit-involving-spo0a-abrb-activates-mersacidin-biosynthesis-in-bacillus-subtilis
#7
JOURNAL ARTICLE
Lars Lilge, Oscar P Kuipers
Due to intramolecular ring structures, the ribosomally produced and post-translationally modified peptide mersacidin shows antimicrobial properties comparable to those of vancomycin without exhibiting cross-resistance. Although the principles of mersacidin biosynthesis are known, there is no information on the molecular control processes for the initial stimulation of mersacidin bioproduction. By using Bacillus subtilis for heterologous biosynthesis, a considerable amount of mersacidin could be produced without the mersacidin-specific immune system and the mersacidin-activating secretory protease...
March 23, 2024: International Journal of Antimicrobial Agents
https://read.qxmd.com/read/38522235/empagliflozin-mitigates-cardiac-hypertrophy-through-cardiac-rsk-nhe-1-inhibition
#8
JOURNAL ARTICLE
Sha Chen, Kenneth Overberg, Zakiya Ghouse, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
BACKGROUND: SGLT2i reduce cardiac hypertrophy, but underlying mechanisms remain unknown. Here we explore a role for serine/threonine kinases (STK) and sodium hydrogen exchanger 1(NHE1) activities in SGLT2i effects on cardiac hypertrophy. METHODS: Isolated hearts from db/db mice were perfused with 1 µM EMPA, and STK phosphorylation sites were examined using unbiased multiplex analysis to detect the most affected STKs by EMPA. Subsequently, hypertrophy was induced in H9c2 cells with 50 µM phenylephrine (PE), and the role of the most affected STK (p90 ribosomal S6 kinase (RSK)) and NHE1 activity in hypertrophy and the protection by EMPA was evaluated...
March 23, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38464781/gut-microbiome-based-thiamine-metabolism-contributes-to-the-protective-effect-of-one-acidic-polysaccharide-from-selaginella-uncinata-desv-spring-against-inflammatory-bowel-disease
#9
JOURNAL ARTICLE
Haochen Hui, Zhuoya Wang, Xuerong Zhao, Lina Xu, Lianhong Yin, Feifei Wang, Liping Qu, Jinyong Peng
Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-β-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS)...
February 2024: Journal of Pharmaceutical Analysis
https://read.qxmd.com/read/38463791/a-comparative-transcriptomics-analysis-reveals-ethylene-glycol-derivatives-of-squalene-ameliorate-excessive-lipogenesis-and-inflammatory-response-in-3t3-l1-preadipocytes
#10
JOURNAL ARTICLE
Yu Cheng, Farhana Ferdousi, Bryan Angelo Foronda, Tran Ngoc Linh, Munkhzul Ganbold, Akira Yada, Takashi Arimura, Hiroko Isoda
Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38460182/anti-histone-and-anti-nucleosome-rather-than-anti-dsdna-antibodies-associate-with-ifn-induced-biomarkers-in-sudanese-and-swedish-systemic-lupus-erythematosus-patients
#11
JOURNAL ARTICLE
Sahwa Elbagir, NasrEldeen A Mohammed, Vilija Oke, Anders Larsson, Jan Nilsson, Amir Elshafie, Elnour M Elagib, Musa A M Nur, Iva Gunnarsson, Elisabet Svenungsson, Johan Rönnelid
OBJECTIVES: In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 interferon production, a hallmark of SLE. We measured antinuclear antibody (ANA) sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines. METHODS: We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N = 104 + 192)...
March 9, 2024: Rheumatology
https://read.qxmd.com/read/38458206/accuracy-of-the-tuberculosis-molecular-bacterial-load-assay-to-diagnose-and-monitor-response-to-anti-tuberculosis-therapy-a-longitudinal-comparative-study-with-standard-of-care-smear-microscopy-xpert-mtb-rif-ultra-and-culture-in-uganda
#12
JOURNAL ARTICLE
Emmanuel Musisi, Samuel Wamutu, Willy Ssengooba, Sharifah Kasiinga, Abdulwahab Sessolo, Ingvar Sanyu, Sylvia Kaswabuli, Josephine Zawedde, Patrick Byanyima, Praiscillia Kia, William Muwambi, Divine Tracy Toskin, Edgar Kigozi, Natasha Walbaum, Evelin Dombay, Mate Bonifac Legrady, Kizza David-Martin Ssemambo, Moses Joloba, Davis Kuchaka, William Worodria, Laurence Huang, Stephen H Gillespie, Wilber Sabiiti
BACKGROUND: In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. METHODS: For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda)...
March 5, 2024: The Lancet. Microbe
https://read.qxmd.com/read/38454480/inhibition-of-ogfod1-by-fg4592-confers-neuroprotection-by-activating-unfolded-protein-response-and-autophagy-after-ischemic-stroke
#13
JOURNAL ARTICLE
Jian Xie, Yuan Zhang, Bin Li, Wen Xi, Yu Wang, Lu Li, Chenchen Liu, Ling Shen, Bing Han, Yan Kong, HongHong Yao, Zhijun Zhang
BACKGROUND: Acute ischemic stroke is a common neurological disease with a significant financial burden but lacks effective drugs. Hypoxia-inducible factor (HIF) and prolyl hydroxylases (PHDs) participate in the pathophysiological process of ischemia. However, whether FG4592, the first clinically approved PHDs inhibitor, can alleviate ischemic brain injury remains unclear. METHODS: The infarct volumes and behaviour tests were first analyzed in mice after ischemic stroke with systemic administration of FG4592...
March 7, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38453942/genomic-insights-and-anti-phytopathogenic-potential-of-siderophore-metabolome-of-endolithic-nocardia-mangyaensis-nh1
#14
JOURNAL ARTICLE
Irina V Khilyas, Maria I Markelova, Liia R Valeeva, Tatiana M Ivoilova, Elena Shagimardanova, Alexander V Laikov, Anna A Elistratova, Ekaterina S Berkutova, Guenter Lochnit, Margarita R Sharipova
Actinobacteria are one of the predominant groups that successfully colonize and survive in various aquatic, terrestrial and rhizhospheric ecosystems. Among actinobacteria, Nocardia is one of the most important agricultural and industrial bacteria. Screening and isolation of Nocardia related bacteria from extreme habitats such as endolithic environments are beneficial for practical applications in agricultural and environmental biotechnology. In this work, bioinformatics analysis revealed that a novel strain Nocardia mangyaensis NH1 has the capacity to produce structurally varied bioactive compounds, which encoded by non-ribosomal peptide synthases (NRPS), polyketide synthase (PKS), and post-translationally modified peptides (RiPPs)...
March 7, 2024: Scientific Reports
https://read.qxmd.com/read/38451091/ribosome-profiling-reveals-downregulation-of-ump-biosynthesis-as-the-major-early-response-to-phage-infection
#15
JOURNAL ARTICLE
Patrick B F O'Connor, Jennifer Mahony, Eoghan Casey, Pavel V Baranov, Douwe van Sinderen, Martina M Yordanova
UNLABELLED: Bacteria have evolved diverse defense mechanisms to counter bacteriophage attacks. Genetic programs activated upon infection characterize phage-host molecular interactions and ultimately determine the outcome of the infection. In this study, we applied ribosome profiling to monitor protein synthesis during the early stages of sk1 bacteriophage infection in Lactococcus cremoris . Our analysis revealed major changes in gene expression within 5 minutes of sk1 infection. Notably, we observed a specific and severe downregulation of several pyr operons which encode enzymes required for uridine monophosphate biosynthesis...
March 7, 2024: Microbiology Spectrum
https://read.qxmd.com/read/38448411/the-rna-m-6-a-reader-igf2bp3-regulates-nfat1-irf1-axis-mediated-anti-tumor-activity-in-gastric-cancer
#16
JOURNAL ARTICLE
Lichen Ge, Yalan Rui, Cheng Wang, Yingmin Wu, Hongsheng Wang, Junjun Wang
N6 -methyladenosine (m6 A) and its associated reader protein insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) are involved in tumor initiation and progression via regulating RNA metabolism. This study aims to investigate the biological function and clinical significance of IGF2BP3 in gastric cancer (GC). The clinical significance of IGF2BP3 was evaluated using tumor related databases and clinical tissues. The biological role and molecular mechanism of IGF2BP3 in GC progression were investigated by multi-omics analysis including Ribosome sequence (Ribo-seq), RNA sequence (RNA-seq) and m6 A sequence (m6 A-seq) combined with gain- and loss- of function experiments...
March 6, 2024: Cell Death & Disease
https://read.qxmd.com/read/38443577/phage-proteins-target-and-co-opt-host-ribosomes-immediately-upon-infection
#17
JOURNAL ARTICLE
Milan Gerovac, Kotaro Chihara, Laura Wicke, Bettina Böttcher, Rob Lavigne, Jörg Vogel
Bacteriophages must seize control of the host gene expression machinery to replicate. To bypass bacterial anti-phage defence systems, this host takeover occurs immediately upon infection. A general understanding of phage mechanisms for immediate targeting of host transcription and translation processes is lacking. Here we introduce an integrative high-throughput approach to uncover phage-encoded proteins that target the gene expression machinery of Pseudomonas aeruginosa immediately upon infection with the jumbo phage ΦKZ...
March 2024: Nature Microbiology
https://read.qxmd.com/read/38433011/unraveling-the-complex-pathophysiology-of-white-matter-hemorrhage-in-intracerebral-stroke-a-single-cell-rna-sequencing-approach
#18
JOURNAL ARTICLE
Lisha Ye, Xiaoyan Tang, Jun Zhong, Wenfeng Li, Ting Xu, Chao Xiang, Jianjun Gu, Hua Feng, Qianqian Luo, Guohua Wang
AIM: This study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral hemorrhage (ICH). METHODS: Using varying doses of collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification was achieved through behavioral assays, hematoma volume, and histological evaluations. Single-cell suspensions from the hemorrhaged region of the ipsilateral striatum on day three post-ICH were profiled using single-cell RNA sequencing (scRNA-seq)...
March 2024: CNS Neuroscience & Therapeutics
https://read.qxmd.com/read/38432538/snakehead-vesiculovirus-shvv-leader-rna-interacts-with-host-antiviral-factors-rps8-and-l13a-and-promotes-virus-replication
#19
JOURNAL ARTICLE
Yan Ji, Rui Cheng, Xuan Zhou, Jiaqi Zhang, Xiaodan Liu, Suhong Sheng, Chi Zhang
To evade host antiviral response, viruses have evolved to take advantage of their noncoding RNAs (ncRNAs). Snakehead vesiculovirus (SHVV), a newly isolated fish rhabdovirus from diseased hybrid snakehead, has caused high mortality to the cultured snakehead fish during the past years in China. However, little is known about the mechanisms of its pathogenicity. Our study revealed that overexpression of the 30-nt leader RNA promoted SHVV replication. RNA-protein binding investigation revealed that SHVV leader RNA could interact with host 40S ribosomal protein S8 (RPS8) and 60S ribosomal protein L13a (L13a)...
March 1, 2024: Fish & Shellfish Immunology
https://read.qxmd.com/read/38424218/dual-inhibition-of-nampt-and-pak4-induces-anti-tumor-effects-in-3d-spheroids-model-of-platinum-resistant-ovarian-cancer
#20
JOURNAL ARTICLE
Kei Kudo, Yoshimi Endo Greer, Teruhiko Yoshida, Brittney S Harrington, Soumya Korrapati, Yusuke Shibuya, Leah Henegar, Jeffrey B Kopp, Takeo Fujii, Stanley Lipkowitz, Christina M Annunziata
Ovarian cancer follows a characteristic progression pattern, forming multiple tumor masses enriched with cancer stem cells (CSCs) within the abdomen. Most patients develop resistance to standard platinum-based drugs, necessitating better treatment approaches. Targeting CSCs by inhibiting NAD+ synthesis has been previously explored. Nicotinamide phosphoribosyltransferase (NAMPT), which is the rate limiting enzyme in the salvage pathway for NAD+ synthesis is an attractive drug target in this pathway. KPT-9274 is an innovative drug targeting both NAMPT and p21 activated kinase 4 (PAK4)...
February 29, 2024: Cancer Gene Therapy
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