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Targeting unfolded protein response reverts ER stress and ER ca²⁺ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/c R321X

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JOURNAL OF TRANSLATIONAL MEDIcINE 2023年第1期21卷 340-340页

作者： Pietrafesa, Giusy De Zio, Roberta Scorza, Simona Ida Armentano, Maria Francesca Pepe, Martino Forleo, cinzia Procino, Giuseppe Gerbino, Andrea Svelto, Maria carmosino, Monica Univ Basilicata Dept Sci Potenza Italy Univ Bari Aldo Moro Dept Biosci Biotechnol & Environm Bari Italy Univ Bari Aldo Moro Dept Emergency & Organ Transplantat Cardiol Unit Bari Italy

BackgroundWe previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DcM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/c protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-cHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac ***-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targeting the UPR, salubrinal, guanabenz and empagliflozin to rescue ER stress and dysfunction. In these cells, the state of activation of both the UPR and the pro-apoptotic pathway were analyzed monitoring the expression levels of phospho-PERK, phospho-eIF2 alpha, ATF4, cHOP and PARP-cL. In addition, we measured ER-dependent intracellular ca2+ dynamics as indicator of proper ER *** found that salubrinal and guanabenz increased the expression levels of phospho-eIF2 alpha and downregulated the apoptosis markers cHOP and PARP-cL in LMNA R321X-cardiomyocytes, maintaining the so-called adaptive UPR. These drugs also restored ER ability to handle ca2+ in these cardiomyocytes. Interestingly, we found that empagliflozin downregulated the apoptosis markers cHOP and PARP-cL shutting down the UPR itself through the inhibition of PERK phosphorylation in LMNA R321X-cardiomyocytes. Furthermore, upon empagliflozin treatment, ER homeostasis, in terms of ER ability to store and release intracellular ca2+ was also restored in these *** provided evidence that the different drugs, although interfering with different steps of the UPR, were able to counteract pro-apoptotic processes

关键词： cardiomyocytes ER stress Lamin A c cardiomyopathy Guanabenz Empagliflozin

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Photo-and thermo-regulation by photonic crystals for extended longevity of c. elegans

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MEcHANISMS OF AGEING AND DEVELOPMENT 2023年第1期212卷 111819页

作者： Yu, Shuzhen Shao, Yating Qiu, Qineng cheng, Yu Qing, Renkun Wang, cai-Feng chen, Su Xu, chen Nanjing Univ Sch Life Sci State Key Lab Pharmaceut Biotechnol Nanjing 210023 Peoples R China Nanjing Tech Univ Coll Chem Engn State Key Lab Mat Oriented Chem Engn Nanjing 210009 Peoples R China

Methods allowing light energy to be modulated in a controllable fashion are potentially important for finding the correlation between light-related environmental factors and aging-related lifespan. Here, we report photo- and thermo-regulation based on photonic crystals (Pcs) for extended longevity of c. elegans. We show that Pcs can function as a regulator of visible spectrum to tune photonic energy received by ***. We provide direct evidence that lifespan depends on photonic energy, and the use of Pcs reflecting blue light (440-537 nm) gives 8.3 % increasement in lifespan. We demonstrate that the exposure to modulated light alleviates photo-oxidative stress and unfolded-protein response. We realize reflective passive cooling temperature using Pcs, and favorable low temperature could be created for worms to extend lifespan. This work offers a new path based on Pcs to resist negative effects light and temperature for longevity, provides an available platform for studying the role of light in aging.

关键词： Photo effect Thermal effect Photonic crystal Light energy Longevity c elegans

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Lack of antiviral activity of ivermectin against foot-and-mouth disease virus serotype O in BALB/c mice

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MIcROBIAL PATHOGENESIS 2023年第1期182卷 106245页

作者： Arshad, Sheeza Raza, Sohail Rafique, Rehan Altaf, Imran Sattar, Adeel Univ Vet & Anim Sci Inst Microbiol Lahore Pakistan Foot & Mouth Dis Res Ctr Lahore Pakistan Univ Vet & Anim Sci Dept Pharmacol & Toxicol Lahore Pakistan

Ivermectin is an FDA approved drug and showed in vitro antiviral activity against different serotypes of Footand-mouth disease virus (FMDV). We here assessed the effect of ivermectin in 12 day old female BALB/c mice infected with 50LD50 FMDV serotype O intraperitoneally. Initially FMDV was adopted on 3-day old BALB/c mice by blind passages. After successful adaptation of virus mice showed hind limb paralysis. Mice were divided in 6 different groups and each group has 6 mice. Ivermectin was given at clinically prescribed dose of 500 & mu;g/kg subcutaneously at different time interval. Ivermectin was given at 0 h post infection (hpi) and 12 hpi. Moreover we compared commercially available ivermectin with purified ivermectin preparation in sterilized DMSO. Viral load was evaluated through RT-qPcR and ELISA in different groups. Results showed that positive control and negative control has cT-value 26.28 and 38 respectively. Treated groups at 0hpi, 12hpi, purified ivermectin and pre-post treatment group has cT values 24.89, 29.44, 27.26 and 26.69 respectively that showed there was no significant reduction in virus load in treated groups as compare to positive control. In histopathology of lung tissue perialveolar capillaries were congested and alveoli were altelactic. Some emphysema was seen in alveoli and mild thickening in the alveolar wall was observed. In the alveolar epithelium mononuclear cells infiltration was seen. There was discoloration haemorrhages and enlargement of heart. Degeneration, fragmentation and loss of sarcoplasm were seen in the cardiac muscle fibers. Above results showed that ivermectin did not lessen lung and heart viral load. This study contributes that ivermectin does not have a significant antiviral effect when used in mice against FMDV serotype O, according to a growing body of research.

关键词： Foot-and-mouth disease virus Ivermectin BALB c Antiviral In vivo

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Effect of Pretreatment and c/N Ratio in Anaerobic Digestion on Biogas Production from coffee Grounds and Rice Husk Mixtures

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INTERNATIONAL JOURNAL OF RENEWABLE ENERGY DEVELOPMENT-IJRED 2023年第1期12卷 209-215页

作者： Budiyono, Budiyono Matin, Hashfi Hawali Abdul Yasmin, Ihzani Yulistra Priogo, Iwang Septo Univ Diponegoro Fac Engn Dept Chem Engn Semarang Indonesia Univ Sebelas Maret Fac Math & Nat Sci Study Program Environm Sci Surakarta Indonesia Univ Diponegoro Vocat Sch Semarang Indonesia

Indonesia has great potential in producing large quantities of renewable energy sources, such as biomass. Biogas is a renewable energy source produced from biomass. It is can be developed in agricultural countries producing rice and coffee, where a large amount of waste is produced in the form of rice husks and coffee grounds. This study examined the effect of physiochemical pretreatment and the c/N ratio on biogas production using coffee grounds and rice husk mixtures. Physical pretreatment was conducted by grinding the mixture up to 50 mesh size, followed by chemical pretreatment by soaking the mixture in 3% KOH;moreover, the variation in the c/N ratio was set at 25 and 30. Anaerobic bacteria were acquired from rumen fluid. The ratio of the coffee ground material, rice husks, and rumen fluid was 1:1:1. This research was conducted in duplicate under batch conditions at ambient temperature (25-35 oc) with a digester volume of 1.5 L. Biogas productivity was measured every 2 d for 60 d. The experimental results indicated that biogas production with a c/N ratio of 30 was 13.3-66.5% higher than that with a c/N ratio of 25. The inclusion of physical pretreatment at a c/N ratio of 30 increased biogas production by up to 31.3%. Moreover, the inclusion of a chemical pretreatment at a c/N ratio of 30 resulted in 30.3% higher biogas production. The kinetics model of biogas production showed that a c/N ratio of 30 with physical and alkaline pretreatment can produce maximum biogas yields of 6,619 mL and 6,570 mL, respectively. Overall, both pretreatments sequentially increased the production

关键词： Biogas coffee grounds rice husks physical pretreatment chemical pretreatment c N ratio

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Phytochemical content and antioxidant activity of different anatomical parts of corchorus olitorius and c. capsularis during different phenological stages

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HELIYON 2023年第6期9卷

作者： Biswas, Ashok Dey, Susmita Xiao, Aiping Huang, Siqi Birhanie, Ziggiju Mesenbet Deng, Yong Liu, Liangliang Li, Defang Chinese Acad Agr Sci Inst Bast Fiber Crops Annual Bast Fiber Breeding Lab Changsha 410205 Peoples R China Chinese Acad Agr Sci Inst Bast Fiber Crops Dept Chem Changsha 410205 Peoples R China Sylhet Agr Univ Dept Hort Sylhet 3100 Bangladesh Sylhet Agr Univ Dept Plant Pathol & Seed Sci Sylhet 3100 Bangladesh 348 Xianjiahu Rd Changsha 410205 Hunan Peoples R China

Different parts of corchorus olitorius and c. capsularis possess different antioxidant compounds. This study investigated the phytochemical components and antioxidant capacities of ultrasoundassisted extraction of different plant parts of both species using spectrophotometry at various phenological stages. Results also indicate that leaves, stems and roots of c. olitorius at various growth stages showed higher phytochemical components and antioxidant potential compared to c. capsularis. The phytochemical components from roots to leaves in c. olitorius including total polyphenol 0.97-11.11 mg GAE/g DW, total flavonoid 0.99-7.78 mg QE/g DW and total tannin 4.02-26.89 TA E/g DW, whereas c. capsularis total polyphenol 1.04-7.93 mg GAE/g DW, total flavonoid 0.77-5.5.92 mg QE/g DW and total tannin content 3.17-22.73 TA E/g DW. c. olitorius produced overall 22.23%, 13.61%, 12.24% higher total polyphenol, total flavonoid and total tannin, respectively compare to c. capsularis. Different parts extract also significantly affected antioxidant capacities including DPPH, ABTS, and FRAP activity with values of 22.03-79.46% inhibition, 10.84-104.10 & mu;mol TE/g DW, and 10.84-104.10 & mu;mol Fe2+/g DW respectively for c. olitorius, while c. capsularis demonstrated 14.03-70.97% of DPPH inhibition, 9.16-95.60 & mu;mol TE/g DW of ABTS and 5.31-71.82 & mu;mol Fe2+/g DW of FRAP activity. Moreover, leaves of the flowering stage, young stems and aged roots of both species displayed a higher content of phytochemical and antioxidant activities than other growth stages. A positive correlation between the phytochemical and antioxidant potential indicated that phenolic constituents solely affected antioxidant activity. Thus, this study established that the plant's parts and phenological growth stages significantly influence the concentration of phytoconstituents and antioxidant activities, and determine the harvesting stages of the different organs of c. olitorius and c. capsularis for consid

关键词： Growth stages Bioactive compounds Variation Antioxidant potential c olitorius capsularis

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Substantial rDNA copy number reductions alter timing of development and produce variable tissue-specific phenotypes in c. elegans

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GENETIcS 2023年第1期224卷 iyad039-iyad039页

作者： Morton, Elizabeth A. Hall, Ashley N. cuperus, Josh T. Queitsch, christine SUNY Coll Brockport Dept Biol Brockport NY 14420 USA Univ Wisconsin Madison Wisconsin Energy Inst Madison WI 53726 USA Univ Washington Mol & Cellular Biol Program Seattle WA 98195 USA Univ Washington Dept Genome Sci Seattle WA 98195 USA

The genes that encode ribosomal RNAs are present in several hundred copies in most eukaryotes. These vast arrays of repetitive ribosomal DNA (rDNA) have been implicated not just in ribosome biogenesis, but also aging, cancer, genome stability, and global gene expression. rDNA copy number is highly variable among and within species;this variability is thought to associate with traits relevant to human health and disease. Here we investigate the phenotypic consequences of multicellular life at the lower bounds of rDNA copy number. We use the model caenorhabditis elegans, which has previously been found to complete embryogenesis using only maternally provided ribosomes. We find that individuals with rDNA copy number reduced to similar to 5% of wild type are capable of further development with variable penetrance. Such individuals are sterile and exhibit severe morphological defects, particularly in post-embryonically dividing tissues such as germline and vulva. Developmental completion and fertility are supported by an rDNA copy number similar to 10% of wild type, with substantially delayed development. Worms with rDNA copy number reduced to similar to 33% of wild type display a subtle developmental timing defect that was absent in worms with higher copy numbers. Our results support the hypothesis that rDNA requirements vary across tissues and indicate that the minimum rDNA copy number for fertile adulthood is substantially less than the lowest naturally observed total copy number. The phenotype of individuals with severely reduced rDNA copy number is highly variable in penetrance and presentation, highlighting the need for continued investigation into the biological consequences of rDNA copy number variation.

关键词： rDNA c elegans post-embryonic development

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Utility of Hematological Parameters in Early Diagnosis of Neonatal Sepsis in comparison to c-Reactive Protein

Journal of Health and Allied Sciences NU

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Journal of Health and Allied Sciences NU 2023年第2期14卷 174-177页

作者： Divya Joshi Shetty K. Padma Jayaprakash Shetty K. Shreya Goel Abena Hidangmayum Renal and Transplant Pathology Fellow at Institute of Kidney Disease and Research Centre Ahmedabad Gujarat India Department of Pathology KS Hegde Medical Academy Nitte (deemed to be) University Mangalore Karnataka India Fellow in Diagnostic Hematology Bharati Hospital Pune Maharashtra India Department of Pathology Babina Diagnostics Imphal Manipur India

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Sequencing-based network analysis provides a core set of genes for understanding hemolymph immune response mechanisms against Poly I:c stimulation in Amphioctopus fangsiao

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FISH & SHELLFISH IMMUNOLOGY 2023年第1期133卷 108544页

作者： chen, Xipan Liu, Xiumei cai, Dequan Wang, Weijun cui, cuiju Yang, Jianmin Xu, Xiaohui Li, Zan Ludong Univ Sch Agr Yantai 264025 Peoples R China Yantai Univ Coll Life Sci Yantai 264005 Peoples R China Weihai Marine Dev Res Inst Weihai 264200 Peoples R China Ludong Univ Sch Agr 186 Middle Hongqi Rd Yantai 264025 Peoples R China

Aquatic viruses can spread rapidly and widely in seawater for their high infective ability. Polyinosinic-polycytidylic acid (Poly I:c), a viral dsRNA analog, is an immunostimulant that has been proved to activate various immune responses of immune cells in invertebrate. Hemolymph is a critical site that host immune response in invertebrates, and its transcriptome information obtained from Amphioctopus fangsiao stimulated by Poly I:c is crucial for understanding the antiviral molecular mechanisms of this species. In this study, we analyzed gene expression data in A. fangsiao hemolymph tissue within 24 h under Poly I:c stimulation and found 1082 and 299 differentially expressed genes (DEGs) at 6 and 24 h, respectively. Union set (1,369) DEGs were selected for subsequent analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out for identifying DEGs related to immunity. Several significant immune-related terms and pathways, such as toll-like receptor signaling pathways term, inflammatory response term, TNF signaling pathway, and chemokine signaling pathway were identified. A protein-protein interaction (PPI) network was constructed for examining the relationships among immune-related genes. Finally, 12 hub genes, including EGFR, AcTG1, MAP2K1, and other nine hub genes, were identified based on the KEGG enrichment analysis and PPI network. The quantitative RT-PcR (qRT-PcR) was used to verify the expression profile of 12 hub genes. This research provides a reference for solving the problem of high mortality of A. fangsiao and other mollusks and provides a reference for the future production of some disease-resistant A. fangsiao.

关键词： Amphioctopus fangsiao Poly I c Immune response Protein -protein interaction networks Transcriptome

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Facile Directed Synthesis of (Z)-1-(Aryl(arylimino)methyl)piperidine-2,6-diones from c,N-Diarylformamidines

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ASIAN JOURNAL OF ORGANIc cHEMISTRY 2023年第8期12卷 e202300324-e202300324页

作者： Trukhanova, Yulia A. Spiridonova, Dar'ya V. Kuvaeva, Elena V. chernov, Nikita M. Alekseeva, Galina M. Sopova, Marina V. Fedorova, Elena V. Yakovlev, Igor P. St Petersburg State Univ Chem & Pharm Dept Organ Chem St Petersburg 197376 Russia St Petersburg State Univ Fac Geol Dept Crystallog Univ Emb 7-9 St Petersburg 199034 Russia St Petersburg State Univ Chem & Pharm Dept Analyt Chem St Petersburg 197376 Russia

A simple methodology has been developed for the synthesis of previously unstudied N-substituted glutarimide derivatives - (Z)-1-(aryl(arylimino)methyl)piperidine-2,6-diones 4 a-p obtained in one step from c,N-diarylformamidines 1 a-p and glutaric anhydride 6 with product yields from 46 up to 88 % and chromatographic purity from 94 to 99 %. The structures of the obtained compounds were proved using NMR spectroscopy H-1, c-13, X-ray diffraction analysis, mass spectroscopy, and elemental analysis. An in vivo study of the analgesic activity of a representative of series 4 a was carried out.

关键词： Amidines Analgesic activity c N-diarylformamidines Glutarimides X-ray

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A Twist-Box domain of the c. elegans Twist homolog, HLH-8, plays a complex role in transcriptional regulation

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GENETIcS 2023年第4期224卷 iyad066-iyad066页

作者： Gruss, Michael J. O'callaghan, colleen Donnellan, Molly corsi, Ann K. Catholic Univ Amer Dept Biol 620 Michigan Ave NE Washington DC 20064 USA

TWIST1 is a basic helix-loop-helix (bHLH) transcription factor in humans that functions in mesoderm differentiation. TWIST1 primarily regulates genes as a transcriptional repressor often through TWIST-Box domain-mediated protein-protein interactions. The TWIST-Box also can function as an activation domain requiring 3 conserved, equidistant amino acids (LXXXFXXXR). Autosomal dominant mutations in TWIST1, including 2 reported in these conserved amino acids (F187L and R191M), lead to craniofacial defects in Saethre-chotzen syndrome (ScS). caenorhabditis elegans has a single TWIST1 homolog, HLH-8, that functions in the differentiation of the muscles responsible for egg laying and defecation. Null alleles in hlh-8 lead to severely egg-laying defective and constipated animals due to defects in the corresponding muscles. TWIST1 and HLH-8 share sequence identity in their bHLH regions;however, the domain responsible for the transcriptional activity of HLH-8 is unknown. Sequence alignment suggests that HLH-8 has a TWIST-Box LXXXFXXXR motif;however, its function also is unknown. cRISPR/cas9 genome editing was utilized to generate a domain deletion and several missense mutations, including those analogous to ScS patients, in the 3 conserved HLH-8 amino acids to investigate their functional role. The TWIST-Box alleles did not phenocopy hlh-8 null mutants. The strongest phenotype detected was a retentive (Ret) phenotype with late-stage embryos in the hermaphrodite uterus. Further, GFP reporters of HLH-8 downstream target genes (arg-1::gfp and egl-15::gfp) revealed tissue-specific, target-specific, and allele-specific defects. Overall, the TWIST-Box in HLH-8 is partially required for the protein's transcriptional activity, and the conserved amino acids contribute unequally to the domain's function.

关键词： c elegans HLH-8 TWIST1 Saethre-chotzen syndrome Twist-Box domain tissue-specific transcriptional regulation

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