Hyperuricemia is common during tuberculosis (TB) treatment, especially in association with pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events ...(MACEs) and hyperuricemia during TB treatment. We conducted a single-center retrospective cohort study. From January 2010 through June 2017, we assessed all consecutive TB patients at Chonnam National University Hospital in South Korea. Hyperuricemia was defined as serum uric acid levels exceeding 7.0 mg/dL (men) and 6.0 mg/dL (women). Of the 1,143 patients included, PZA was administered to 1,081 (94.6%), and hyperuricemia was detected in 941 (82.3%). Eight patients experienced MACEs. Multivariate analysis using logistic regression indicated that prior ischemic heart disease was associated with MACE development (OR,14.087; 95% CI,3.304-60.061; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184-12.299; P = 0.703). For patients without drug-resistant TB, the absence of hyperuricemia was associated with higher mortality (OR, 2.609; 95% CI, 1.066-6.389; P = 0.036), whereas hyperuricemia was associated with less worse outcomes (OR,0.316; 95% CI,0.173-0.576; P < 0.000). Although most patients treated with PZA developed hyperuricemia, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to consistent adherence to TB treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myostatin (MSTN), a negative regulator of skeletal muscle development, is the major gene of interest for improving animal breeding productivity, including for aquaculture. We introduced a CRISPR/Cas9 ...system to disrupt Paralichthys olivaceus MSTN (PoMSTN) using microinjection. Cas9 mRNA and sgRNAs targeting the first exon of the PoMSTN gene were co-injected into embryos of P. olivaceus. On-target mutations on the PoMSTN locus were generated in somatic tissues with 75.6% efficiency, and founders harboring germline mutations were produced in the F0 generation. In the F1 generation, restriction fragment length polymorphism analysis was applied to select biallelic mutants, and heterozygous biallelic mutants with PoMSTN disruption were obtained. PoMSTN-disrupted P. olivaceus exhibited greater body thickness and increased condition factor, indicating the enhancement of muscle mass with muscle hyperplasia. Expression of PoMSTN mRNA and protein was significantly reduced in the muscle of PoMSTN-disrupted P. olivaceus, and the mRNA expression of major myogenic regulatory factors (myogenin, MyoD, and Myf5) was differentially affected in PoMSTN-disrupted mutants. These results suggest that the establishment of a CRISPR/Cas9 system in P. olivaceus provides powerful tools for related genetic studies and breeding.
•A CRISPR/Cas9 system was introduced to disrupt Paralichthys olivaceus MSTN (PoMSTN).•PoMSTN−/− were obtained which exhibited greater body thickness and increased condition factor.•Expression of PoMSTN was reduced in the muscle of PoMSTN−/−.•The establishment of a CRISPR/Cas9 system in P. olivaceus provides powerful tools for genetic studies and breeding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are ...reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity.
Objectives
This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model.
Methods
The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 μg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 μg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days.
Results
The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 μg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC.
Conclusion
APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Continuous monitoring of the present genetic status is essential to preserve the genetic resource of wild populations. In this study, we sequenced regional Pacific abalone Haliotis discus samples ...from three different locations around the Korean peninsula to assess population structure, utilizing Genotyping-by-Sequencing (GBS) method. Using PstI enzyme for genome reduction, we demonstrated the resultant library represented the whole genome region with even spacing, and as a result 16,603 single nucleotide variants (SNVs) were produced. Genetic diversity and population structure were investigated using several methods, and a strong genetic heterogeneity was observed in the Korean abalone populations. Additionally, by comparison of the variant sets among population groups, we were able to discover 26 Korean abalone population-specific SNVs, potentially associated with phenotype differences. This is the first study demonstrating the feasibility of GBS for population genetic study on H. discus. Our results will provide valuable data for the genetic conservation and management of wild abalone populations in Korea and help future GBS studies on the marine mollusks.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Eukaryotic genome sequencing and de novo assembly, once the exclusive domain of well-funded international consortia, have become increasingly affordable, thus fitting the budgets of individual ...research groups. Third-generation long-read DNA sequencing technologies are increasingly used, providing extensive genomic toolkits that were once reserved for a few select model organisms. Generating high-quality genome assemblies and annotations for many aquatic species still presents significant challenges due to their large genome sizes, complexity, and high chromosome numbers. Indeed, selecting the most appropriate sequencing and software platforms and annotation pipelines for a new genome project can be daunting because tools often only work in limited contexts. In genomics, generating a high-quality genome assembly/annotation has become an indispensable tool for better understanding the biology of any species. Herein, we state 12 steps to help researchers get started in genome projects by presenting guidelines that are broadly applicable (to any species), sustainable over time, and cover all aspects of genome assembly and annotation projects from start to finish. We review some commonly used approaches, including practical methods to extract high-quality DNA and choices for the best sequencing platforms and library preparations. In addition, we discuss the range of potential bioinformatics pipelines, including structural and functional annotations (e.g., transposable elements and repetitive sequences). This paper also includes information on how to build a wide community for a genome project, the importance of data management, and how to make the data and results Findable, Accessible, Interoperable, and Reusable (FAIR) by submitting them to a public repository and sharing them with the research community.
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Numerous studies on poly γ‐d‐glutamicacid (γ‐PGA) production have investigated terrestrial renewable sources for reducing production costs, but there are no studies using waste marine resources so ...far. We aimed to develop a cost‐effective production method of γ‐d‐PGA by Bacillus sp. SJ‐10 using green macroalgae (Ulva sp.) as a major substrate without hydrolysis pretreatment. The SJ‐10 was shown to not only cause immediate tissue degradation of the Ulva membrane but also grew well as a sole substrate. The γ‐d‐PGA yield was 6.29 ± 0.34 g/L under optimized conditions via the response surface method, and the produced γ‐d‐PGA had a thermal decomposition temperature of 310°C and molecular weight of 250–1780 kDa. The calculated cost efficiency for the final yield was 32% when compared with complex media. Therefore, the present study provided a strategy for promoting an ecofriendly and cost‐effective means to produce γ‐d‐PGA via a marine renewable resource.
Numerous studies on poly γ‐d‐glutamic acid (γ‐PGA) production have investigated terrestrial renewable sources for reducing production costs, but there are no studies using waste marine resources so far. We aimed to develop a cost‐effective production method of γ‐PGA by Bacillus sp. SJ‐10 using green macroalgae (Ulva sp.) as a major substrate without hydrolysis pretreatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Osteoarthritis (OA) appears to be associated with various metabolic disorders, but the potential contribution of amino acid metabolism to OA pathogenesis has not been clearly elucidated. Here, we ...explored whether alterations in the amino acid metabolism of chondrocytes could regulate OA pathogenesis.
Expression profiles of amino acid metabolism-regulating genes in primary-culture passage 0 mouse chondrocytes were examined by microarray analysis, and selected genes were further characterised in mouse OA chondrocytes and OA cartilage of human and mouse models. Experimental OA in mice was induced by destabilisation of the medial meniscus (DMM) or intra-articular (IA) injection of adenoviruses expressing catabolic regulators. The functional consequences of arginase II (Arg-II) were examined in
mice and those subjected to IA injection of an adenovirus encoding Arg-II (Ad-Arg-II).
The gene encoding Arg-II, an arginine-metabolising enzyme, was specifically upregulated in chondrocytes under various pathological conditions and in OA cartilage from human patients with OA and various mouse models. Adenovirus-mediated overexpression of Arg-II in mouse joint tissues caused OA pathogenesis, whereas genetic ablation of
in mice (
) abolished all manifestations of DMM-induced OA. Mechanistically, Arg-II appears to cause OA cartilage destruction at least partly by upregulating the expression of matrix-degrading enzymes (matrix metalloproteinase 3 MMP3 and MMP13) in chondrocytes via the nuclear factor (NF)-κB pathway.
Our results indicate that Arg-II is a crucial regulator of OA pathogenesis in mice. Although chondrocytes of human and mouse do not identically, but similarly, respond to Arg-II, our results suggest that Arg-II could be a therapeutic target of OA pathogenesis.
The biological function of Acanthopanax sessiliflorus Harm (ASH) has been investigated on various diseases; however, the effects of ASH on arthritis have not been investigated so far. This study ...investigates the effects of ASH on rheumatoid arthritis (RA).
Supercritical carbon dioxide (CO
) was used for ASH extract preparation, and its primary components, pimaric and kaurenoic acids, were identified using gas chromatography-mass spectrometer (GC-MS). Collagenase-induced arthritis (CIA) was used as the RA model, and primary cultures of articular chondrocytes were used to examine the inhibitory effects of ASH extract on arthritis in three synovial joints: ankle, sole, and knee.
Pimaric and kaurenoic acids attenuated pro-inflammatory cytokine-mediated increase in the catabolic factors and retrieved pro-inflammatory cytokine-mediated decrease in related anabolic factors in vitro; however, they did not affect pro-inflammatory cytokine (IL-1β, TNF-α, and IL-6)-mediated cytotoxicity. ASH effectively inhibited cartilage degradation in the knee, ankle, and toe in the CIA model and decreased pannus development in the knee. Immunohistochemistry demonstrated that ASH mostly inhibited the IL-6-mediated matrix metalloproteinase. Gene Ontology and pathway studies bridge major gaps in the literature and provide insights into the pathophysiology and in-depth mechanisms of RA-like joint degeneration.
To the best of our knowledge, this is the first study to conduct extensive research on the efficacy of ASH extract in inhibiting the pathogenesis of RA. However, additional animal models and clinical studies are required to validate this hypothesis.
MAF1 is a global suppressor of RNA polymerase III-dependent transcription, and is conserved from yeast to human. Growing evidence supports the involvement of MAF1 in the immune response of mammals, ...but its biological functions in fish are unknown. We isolated and characterized
from the olive flounder
(
). The coding region of
comprised 738 bp encoding a 245-amino-acid protein. The deduced PoMAF1 amino acid sequence shared features with those of MAF1 orthologues from vertebrates.
mRNA was detected in all tissues examined, and the levels were highest in eye and muscle tissue. The
mRNA level increased during early development. In addition, the
transcript level decreased during viral hemorrhagic septicemia virus (VHSV) infection of flounder hirame natural embryo (HINAE) cells. To investigate the role of
in VHSV infection, single-cell-derived
knockout HINAE cells were generated using the clustered regularly interspaced short palindromic repeats/CRISPR-associated-9 (CRISPR/Cas9) system, and cell clones with complete disruption of
were selected.
disruption increased the VHSV glycoprotein (G) mRNA levels during VHSV infection of HINAE cells, implicating PoMAF1 in the immune response to VSHV infection. To our knowledge, this is the first study to characterize fish
, which may play a role in the response to viral infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Scope
High dietary sugar and sweeteners are suspected to cause the development of rheumatoid arthritis (RA) symptoms through the induction of proinflammatory cytokine release. However, the mechanisms ...by which increased dietary sugar affects RA etiology are not yet fully understood. The study uses a mouse model of collagen‐induced RA (CIA) to investigate the relationship between excessive sugar consumption and RA risk.
Methods and results
RA‐associated pathological features are assessed in the nonimmunized (NI) control group, the CIA‐positive control group, and the CIA + high‐sucrose diet (CIA+HS, 63% calories from sucrose) group. Compared with the CIA group, the CIA+HS group shows a greater increase in paw thickness and clinical scores, as well as, a higher degree of pannus formation and inflammation in the knee, ankle, and sole tissues. Moreover, the infiltration of immune cells is increased in the CIA+HS group. Although the expression of hepatic lipogenic genes, is not altered, that of toll‐like receptor (TLR4) and IL‐1β is considerably elevated in the CIA+HS group.
Conclusions
These findings suggest that excessive sucrose consumption causes hepatic fibrosis and inflammation, contributing to the pathophysiology of RA.
High‐sucrose diet enhances TLR4, IL‐1β, and TGF‐β expression in the liver, also increases TGF‐β expression in immune cells, activates mast cells, neutrophils, and osteoclasts in joint tissue, and increases synovitis, pannus, and cartilage degeneration in joint tissue. Therefore, excessive sugar consumption is a risk factor for RA pathogenesis which is mediated by metabolic perturbations and chronic inflammation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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