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1.
Toxicol Appl Pharmacol ; 490: 117020, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969211

ABSTRACT

This study explored the effects of 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) and bis (2-ethylhexyl) tetrabromophthalate (TBPH) on serum metabolites and lipids in male Sprague-Dawley (SD) rats. Rats were orally gavaged 250 mg/kg bw of BTBPE and 500 mg/kg bw of TBPH for 28 consecutive days. Serum samples were collected for metabolomics and lipidomics analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to explore changes in rat metabolic patterns. Least absolute shrinkage and selection operator (LASSO) regression models were established using serum levels of total thyroxine (TT4), free thyroxine (FT4), and rats' grouping information as variables to screen for robust differential substances. SuperPred was the database to obtain potential targets. The metabolomics and lipidomics results showed that BTBPE and TBPH had an impact on rat metabolic patterns, affecting pathways such as vitamin B6 synthesis. For BTBPE treatment, pyridoxal and ceramide (Cer) 24:0;4O were selected as differential substances related to thyroid hormones. For TBPH treatment, dehydroascorbic acid, acylcarnitine (CAR) 19:0, and diglyceride (DG) 38:4 were selected as differential substances related to thyroid hormones. Serotonin 2c receptor and cyclooxygenase-2 were chosen as potential targets of BTBPE and TBPH, respectively. In conclusion, this study found that BTBPE and TBPH impacted the metabolism of rats, and this effect may be related to changes in thyroid function.

2.
Front Vet Sci ; 11: 1404054, 2024.
Article in English | MEDLINE | ID: mdl-38895715

ABSTRACT

This study marks the first occasion that Streptococcus iniae has been isolated, identified, and characterized as the causative pathogen in spotted sea bass (Lateolabrax maculates). Infected fish exhibited a range of external symptoms, including scale loss, bleeding from the jaw, anus, and tail, among other signs, as well as internal manifestations such as congested liver, splenomegaly, branchial anemia, yellow fat syndrome, and intestinal edema. Notably, exophthalmia and meningoencephalitis-typical symptoms associated with previous S. iniae infections-were not observed. A predominant bacterial isolate (designated 10S01) was recovered from the pure culture of spleen of a diseased spotted sea bass in Zhuhai, China. The strain was then subjected to Gram staining, biochemical profiling, and molecular confirmation through 16S rRNA and gyrB gene, corroborating its identity as S. iniae. Pathogenicity was assessed by intraperitoneal injection challenge in spotted sea bass weighing approximately 13 g/fish, revealing a LD50 of 74 cfu/g-fish. The 10S01 strain demonstrated the ability to colonize various organs, including the spleen, liver, kidney, and brain, with a relatively higher affinity for the spleen. Furthermore, antimicrobial susceptibility testing indicated that the 10S01 strain was sensitive to 14 tested antibiotics, particularly chloramphenicol, ciprofloxacin, clarithromycin, florfenicol, ofloxacin, rifampicin, and trimethoprim/sulfamethoxazole, highlighting these as preferred treatments for S. iniae infections in spotted sea bass. These findings contribute significantly to our understanding of S. iniae pathogenesis and inform the prompt and appropriate antibiotic treatment of S. iniae infections.

3.
Fish Shellfish Immunol ; 150: 109648, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38777253

ABSTRACT

Laminin receptor (LR), which mediating cell adhesion to the extracellular matrix, plays a crucial role in cell signaling and regulatory functions. In the present study, a laminin receptor gene (SpLR) was cloned and characterized from the mud crab (Scylla paramamosain). The full length of SpLR contained an open reading frame (ORF) of 960 bp encoding 319 amino acids, a 5' untranslated region (UTR) of 66 bp and a 3' UTR of 49 bp. The predicted protein comprised two Ribosomal-S2 domains and a 40S-SA-C domain. The mRNA of SpLR was highly expressed in the gill, followed by the hepatopancreas. The expression of SpLR was up-regulated after mud crab dicistrovirus-1(MCDV-1) infection. Knocking down SpLR in vivo by RNA interference significantly down-regulated the expression of the immune genes SpJAK, SpSTAT, SpToll1, SpALF1 and SpALF5. This study shown that the expression level of SpToll1 and SpCAM in SpLR-interfered group significantly increased after MCDV-1 infection. Moreover, silencing of SpLR in vivo decreased the MCDV-1 replication and increased the survival rate of mud crabs after MCDV-1 infection. These findings collectively suggest a pivotal role for SpLR in the mud crab's response to MCDV-1 infection. By influencing the expression of critical innate immune factors and impacting viral replication dynamics, SpLR emerges as a key player in the intricate host-pathogen interaction, providing valuable insights into the molecular mechanisms underlying MCDV-1 pathogenesis in mud crabs.


Subject(s)
Amino Acid Sequence , Arthropod Proteins , Brachyura , Gene Expression Regulation , Immunity, Innate , Phylogeny , Receptors, Laminin , Sequence Alignment , Animals , Brachyura/genetics , Brachyura/immunology , Receptors, Laminin/genetics , Receptors, Laminin/immunology , Arthropod Proteins/genetics , Arthropod Proteins/immunology , Arthropod Proteins/chemistry , Immunity, Innate/genetics , Gene Expression Regulation/immunology , Sequence Alignment/veterinary , Gene Expression Profiling/veterinary , Base Sequence
4.
Article in English | MEDLINE | ID: mdl-38817199

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are an important group of organic toxic pollutants. Parent PAHs (pPAHs) are mainly metabolized into mono-hydroxylated PAHs (OH-PAHs) after entering the human body. Until now, it is still an urgent need to select appropriate exposure biomarkers for PAHs and analyze them at the trace level. Based on gas chromatography coupled with triple-quadrupole tandem mass spectrometry, we have developed a versatile analytical method for the systemic analysis of pPAHs and OH-PAHs in routinely collected biological samples. This method was further applied to analyze plasma, hair and urine samples from 24 rats exposed to 13 pPAH congeners at four levels. The detection rate for pPAHs in three types of samples was 100%, except for dibenz(a,h)anthracene (DahA) in plasma, while the detection rate for OH-PAHs ranged from 25% to 100%. A significant linear relationship was observed between pPAH exposure levels and their corresponding OH-PAH levels in three different types of samples. It was found that each unit increase in pPAH exposure level was associated with an increase in OH-PAHs ranging from 0.03% (0.01-0.05%) to 5.27% (1.74-8.81%). Furthermore, significant positive correlations were found between any two types of samples for most OH-PAHs, but not observed for most pPAHs. The correlation patterns of 1-hydroxypyrene (1-OH-PYR) across three types of samples differed from other congeners. Strong correlations were identified between five types of hydroxyphenanthrene (OH-PHE) and pPAH exposure levels. In conclusion, OH-PAHs were more sensitive exposure biomarkers than pPAHs, particularly in hair and urine samples.

5.
Ann Vasc Surg ; 105: 48-59, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38582200

ABSTRACT

BACKGROUND: Prognostic value of neutrophil/lymphocyte ratio (NLR) for pulmonary embolism (PE) has been reported in several retrospective studies. The purpose of this investigation was to perform a pooled analysis and external validation of predictive value of NLR. METHODS: PubMed, Embase, and Cochrane databases were searched from inception to November 5, 2022. A random effects model was used. Grade was used to evaluate the certainty of evidence. External validation was conducted in clinical cohorts before and after a propensity scoring matching (PSM). Covariates include basic clinical characteristics, such as age, gender, etc. The value of NLR in prediction model was also evaluated. RESULTS: A total of 15 studies comprising 5,874 patients were included. Pooled risk ratio of NLR was 2.33 (95% confidence interval [CI]: 1.97-2.75), with an area under the curve of 0.78 (95% CI: 0.74-0.81), a sensitivity of 0.75 (95% CI: 0.71-0.79), a specificity of 0.67 (95% CI: 0.61-0.73), and a median cut-off value of 5.7. Grade of Recommendations Assessment Development and Evaluation (GRADE) certainty analysis showed the quality of the evidence was moderate. Before (n = 336) and after (n = 152) propensity scoring matching, risk ratio of NLR was 2.69 (95% CI: 1.04-6.97) and 6.58 (95% CI: 1.99-17.75). A prediction model consisting of NLR, age, D-dimer, and simplified PE severity index had an area under the curve of 0.809 (95% CI: 0.738-0.88), a sensitivity of 0.638 (95% CI: 0.511-0.745), and a specificity of 0.851 (95% CI: 0.709-0.917). Net reclassification index (12%, P = 0.035) and integrated discrimination improvement (17%, P = 0.022) indicated an improvement caused by NLR. CONCLUSIONS: Prognostic value of NLR for PE was confirmed by meta-analysis and validated in an independent cohort, deserving further clinical application.


Subject(s)
Lymphocytes , Neutrophils , Predictive Value of Tests , Pulmonary Embolism , Humans , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Pulmonary Embolism/mortality , Lymphocyte Count , Prognosis , Risk Factors , Female , Reproducibility of Results , Male , Middle Aged , Aged , Risk Assessment , Adult
6.
Plant Cell Physiol ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619133

ABSTRACT

Brassinosteroids (BRs) perform crucial functions controlling plant growth and developmental processes, encompassing many agronomic traits in crops. Studies of BR-related genes involved in agronomic traits have suggested that BRs could serve as a potential target for crop breeding. Given the pleiotropic effect of BRs, a systematic understanding of their functions and molecular mechanisms is conducive for application in crop improvement. Here, we summarize the functions and underlying mechanisms by which BRs regulate the several major crop agronomic traits, including plant architecture, grain size, as well as the specific trait of symbiotic nitrogen fixation in legume crops. For plant architecture, we discuss the roles of BRs in plant height, branching number, and leaf erectness and propose how progress in these fields may contribute to designing crops with optimal agronomic traits and improved grain yield by accurately modifying BR levels and signaling pathways.

7.
J Agric Food Chem ; 72(15): 8859-8870, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38564481

ABSTRACT

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.


Subject(s)
Fatty Acids, Monounsaturated , Fish Oils , Water , Triglycerides/chemistry , Fish Oils/chemistry , Digestion
8.
Aging (Albany NY) ; 16(4): 3420-3530, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38349886

ABSTRACT

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide. Early detection is critical for the risk stratification and early intervention of progressive DKD. Serum creatinine (sCr) and urine output are used to assess kidney function, but these markers are limited by their delayed changes following kidney pathology, and lacking of both sensitivity and accuracy. Hence, it is essential to illustrate potential diagnostic indicators to enhance the precise prediction of early DKD. A total of 194 Chinese individuals include 30 healthy participants (Stage 0) and 164 incidents with type 2 diabetes (T2D) spanning from DKD's Stage 1a to 4 were recruited and their serums were subjected for untargeted metabolomic analysis. Random forest (RF), a machine learning approach, together with univariate linear regression (ULR) and multivariate linear regression (MvLR) analysis were applied to characterize the features of untargeted metabolites of DKD patients and to identify candidate DKD biomarkers. Our results indicate that 2-(α-D-mannopyranosyl)-L-tryptophan (ADT), succinyladenosine (SAdo), pseudouridine and N,N,N-trimethyl-L-alanyl-L-proline betaine (L-L-TMAP) were associated with the development of DKD, in particular, the latter three that were significantly elevated in Stage 2-4 T2D incidents. Each of the four metabolites in combination with sCr achieves better performance than sCr alone with area under the receiver operating characteristic curve (AUC) of 0.81-0.91 in predicting DKD stages. An average of 3.9 years follow-up study of another cohort including 106 Stage 2-3 patients suggested that "urinary albumin-to-creatinine ratio (UACR) + ADT + SAdo" can be utilized for better prognosis evaluation of early DKD (average AUC = 0.9502) than UACR without sexual difference.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Humans , Diabetic Nephropathies/metabolism , Diabetes Mellitus, Type 2/complications , Follow-Up Studies , Random Forest , Glomerular Filtration Rate , Biomarkers , China
9.
Molecules ; 29(4)2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38398579

ABSTRACT

While nanoporous graphene oxide (GO) is recognized as one of the most promising reverse osmosis desalination membranes, limited attention has been paid to controlling desalination performance through the large GO pores, primarily due to significant ion leakage resulting in the suboptimal performance of these pores. In this study, we employed a molecular dynamics simulation approach to demonstrate that Mg2+ ions, adhered to carboxylated GO nanopores, can function as gates, regulating the transport of ions (Na+ and Cl-) through the porous GO membrane. Specifically, the presence of divalent cations near a nanopore reduces the concentration of salt ions in the vicinity of the pore and prolongs their permeation time across the pore. This subsequently leads to a notable enhancement in salt rejection rates. Additionally, the ion rejection rate increases with more adsorbed Mg2+ ions. However, the presence of the adsorbed Mg2+ ions compromises water transport. Here, we also elucidate the impact of graphene oxidation degree on desalination. Furthermore, we design an optimal combination of adsorbed Mg2+ ion quantity and oxidation degree to achieve high water flux and salt rejection rates. This work provides valuable insights for developing new nanoporous graphene oxide membranes for controlled water desalination.

10.
Front Cardiovasc Med ; 11: 1253554, 2024.
Article in English | MEDLINE | ID: mdl-38374993

ABSTRACT

Purpose: This study aimed to investigate the effect of Marshall ethanol infusion (VOM-Et) in the vein on mitral isthmus (MI) ablation. Methods: Patients with persistent atrial fibrillation (AF) were grouped into vein of VOM-Et combined with radiofrequency (RF) ablation (VOM-Et-RF) and RF groups. The primary outcome was MI block immediate block rate after surgery. Stratified analysis was also performed for factors affecting the outcome measures. Results: A total of 118 consecutive patients underwent AF ablation at Taizhou Hospital of Zhejiang Province from January 2018 to December 2021. Successful bidirectional perimitral block was achieved in 96% of patients in VOM-Et-RF (69 of 72) and in 76% of patients in the RF group (35 of 46) (P < 0.01). In the subgroup analysis, male sex, elder than 60 years, Left atrial diameter <55 mm, and AF duration <3 years were associated with the benefits of VOM-Et in AF Patients. Conclusion: The vein of Marshall ethanol infusion for catheter ablation can improve the MI block rate. Male sex, elder age, smaller Left atrial diameter and shorter AF duration may have significant benefits for VOM-Et.

11.
Medicine (Baltimore) ; 103(3): e36978, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38241570

ABSTRACT

RATIONALE: Papillary thyroid carcinoma (PTC), the predominant subtypes accounting for approximately 85% of thyroid carcinomas, has a rapidly increasing global incidence rate. Statistically, approximately 74.6% PTC patients had the genomic variants of BRAF, especially BRAFV600E mutation, which has been reported to stratify patients and guide clinic-therapies. However, some PTC patients may carry other nonclassical mutation patterns of BRAF, due to the complex of genomic instability. And the spectrum of BRAF mutation was not fully characterized. We reported a novel BRAF mutation pattern of PTC. PATIENT CONCERNS: A 59-year-old woman was admitted to our hospital because of the slight enlargement of bilateral cervical lymph nodes in July 2023. DIAGNOSIS: Ultrasonography revealed that the bilateral thyroid nodules of the patients both presented 1 hypoechoic nodule, which was graded as 3 of the elastic score, and the small calcification in the right lobe (Chinese-Thyroid Imaging Reporting and Data System 4c). Pathological diagnosis showed the interstitial collagen change and focal follicular epithelial papillary hyperplasia with atypical hyperplasia of the bilateral thyroid. Further puncture pathology showed that the patient had a malignant thyroid lesion with the phenotypes of papillary carcinoma and diagnosed with malignancy subsequently. Additionally, the patient harbored a novel insert on BRAF exon 15, a 6-base fragment AGACAG inserting between c.1798 and c.1799. INTERVENTIONS: The patient was undergone on microwave ablation of thyroid carcinoma on July 28, 2023. After the surgery, the patient was treated on anti-infection, cold saline external application of bilateral thyroid swelling supportive treatment. OUTCOMES: No postoperative complications or recurrence and metastasis were found. LESSONS: This is the first case of the novel nonclassical genomic variant of BRAF. Our study extends the spectrum of BRAF mutations. The patient had a favorable response to microwave ablation, indicating that in spite of the association between this mutation and high-grade malignant phenotype, this genomic variant of BRAF did not have a detrimental effect on the response of clinical treatment.


Subject(s)
Proto-Oncogene Proteins B-raf , Thyroid Neoplasms , Female , Humans , Middle Aged , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Hyperplasia , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/pathology , Mutation , Genomics
13.
Child Care Health Dev ; 50(1): e13160, 2024 01.
Article in English | MEDLINE | ID: mdl-37594198

ABSTRACT

BACKGROUND: Rural left-behind adolescents are more vulnerable to Internet addiction and depressive and anxious symptoms due to the lack of family support and parental supervision. This study was the first to investigate the longitudinal relationships between Internet addiction and depressive and anxious symptoms and to examine the mediating roles of resilience and friendship quality in rural left-behind adolescents. METHODS: Included in this study, which was from a longitudinal study conducted five times over 2 years, were 1001 rural left-behind adolescents. The internationally used scales for depressive and anxious symptoms, Internet addiction, resilience and friendship quality were administered. A structural equation model was used for analysis. RESULTS: The prevalence of Internet addiction, depressive and anxious symptoms among rural left-behind adolescents were 17.7%, 35.8% and 27.6%, respectively. Internet addiction predicted the later depressive and anxious symptoms (ß = 0.200, 95% confidence interval [CI]: 0.116-0.274 and ß = 0.263, 95% CI: 0.188-0.330). Resilience acted as an independent mediator in the relationships between Internet addiction and depressive and anxious symptoms (ß = 0.037 and 0.034, P < 0.01). Resilience and friendship quality played a chain-mediating role on the longitudinal relationships between Internet addiction and depressive and anxious symptoms (ß = 0.011 and 0.010, P < 0.001). The mediating effects accounted for 24.0% and 16.7% of the total effects, respectively. CONCLUSION: Resilience and friendship quality play an independent or chain-mediating role in longitudinal relationships between Internet addiction and depressive and anxious symptoms. The findings inform targeted intervention strategies to improve the mental health of left-behind adolescents.


Subject(s)
Friends , Resilience, Psychological , Humans , Adolescent , Internet Addiction Disorder , Longitudinal Studies , China/epidemiology , Internet
14.
Clin Cardiol ; 47(1): e24178, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37933170

ABSTRACT

BACKGROUND: Catheter ablation (CA) is currently used to treat persistent atrial fibrillation (PeAF). However, its effectiveness is limited. This study aimed to estimate the effectiveness of the vein of Marshall absolute ethanol injection (VOM-EI) for PeAF ablation. HYPOTHESIS: Adjunctive vein of Marshall ethanol injection (VOM-EI) strategies are more effective than conventional catheter ablation (CA) and have similar safety outcomes. METHODS: We extensively searched the literature for studies evaluating the effectiveness and safety of VOM-EI + CA compared with CA alone. The primary endpoint was the rate of acute bidirectional block of the isthmus of the mitral annulus (MIBB). The secondary endpoints were atrial fibrillation (AF) or atrial tachycardia (AT) recurrence over 30 seconds after a 3-month blanking period. Weighted pooled risk ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated using a random effects model. RESULTS: Based on the selection criteria, nine studies were included in this systematic review, including patients with AF (n = 2508), persistent AF (n = 1829), perimitral flutter (n = 103), and perimitral AT (n = 165). There were 1028 patients in the VOM-EI + CA group and 1605 in the CA alone group. The VOM-EI + CA group showed a lower rate of AF/AT relapse (RR = 0.70; 95% CI = 0.53-0.91; p = .008) and a higher rate of acute MIBB (RR = 1.29; 95% CI = 1.11-1.50; p = .0007) than the CA alone group. CONCLUSION: Our meta-analysis revealed that adjunctive VOM-EI strategies are more effective than conventional CA and have similar safety outcomes.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Ethanol/adverse effects , Feasibility Studies , Infusions, Intravenous , Coronary Vessels , Catheter Ablation/adverse effects , Treatment Outcome
15.
Toxicology ; 501: 153713, 2024 01.
Article in English | MEDLINE | ID: mdl-38135142

ABSTRACT

Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3-1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3-1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid.


Subject(s)
Thyroglobulin , Thyroid Gland , Male , Humans , Rats , Animals , Thyroglobulin/genetics , Thyroglobulin/metabolism , Thyroglobulin/pharmacology , Interleukin-10/genetics , Thyroxine , Interleukin-6/metabolism , Rats, Sprague-Dawley , Iodide Peroxidase/genetics , Iodide Peroxidase/metabolism , RNA, Messenger/metabolism
16.
Dev Comp Immunol ; 153: 105127, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38160871

ABSTRACT

Hypoxia-inducible factors -1 (HIF-1) is a crucial transcription factor that regulates the expression of glycolytic genes. Our previous study proved that the Mud crab dicistrovirus-1 (MCDV-1) can induce aerobic glycolysis that favors viral replication in mud crab Scylla paramamosain. However, the role of HIF-1 on key glycolytic genes during the MCDV-1 infection has not been examined. In this study, the intricate interplay between HIF-1 and the key glycolysis enzyme, lactate dehydrogenase (LDH), was investigated after MCDV-1 infection. The expression of LDH was significant increased after MCDV-1 infection. Additionally, the expression of HIF-1α was upregulated following MCDV-1 infection, potentially attributed to the downregulation of prolyl hydroxylase domains 2 expression. Subsequent examination of the SpLDH promoter identified the presence of hypoxia response elements (HREs), serving as binding sites for HIF-1α. Intriguingly, experimental evidence demonstrated that SpHIF-1α actively promotes SpLDH transcription through these HREs. To further elucidate the functional significance of SpHIF-1α, targeted silencing was employed, resulting in a substantial reduction in SpLDH expression, activity, and lactate concentrations in MCDV-1-infected mud crabs. Notably, SpHIF-1α-silenced mud crabs exhibited higher survival rates and lower viral loads in hepatopancreas tissues following MCDV-1 infection. These results highlight the critical role of SpHIF-1α in MCDV-1 pathogenesis by regulating LDH gene dynamics, providing valuable insights into the molecular mechanisms underlying the virus-host interaction.


Subject(s)
Brachyura , Dicistroviridae , Animals , Brachyura/metabolism , Lactic Acid/metabolism , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Hypoxia-Inducible Factor 1/genetics , Hypoxia-Inducible Factor 1/metabolism , Hypoxia
17.
Fish Shellfish Immunol ; 143: 109235, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37989447

ABSTRACT

Activating transcription factor 6 (ATF6) is critical for regulation of unfolded protein response (UPR), which is involved in the endoplasmic reticulum (ER) proteostasis maintenance and cellular redox regulation. In the present study, a ATF6 gene from the mud crab (designated as Sp-ATF6) has been cloned and identified. The open reading frame of Sp-ATF6 was 1917 bp, encoding a protein of 638 amino acids. The deduced amino acid sequences of Sp-ATF6 contained a typical basic leucine zipper (BZIP domain). Sp-ATF6 was widely expressed in all tested tissues, with the highest expression levels in the hemocytes and the lowest in the muscle. Subcellular localization showed that Sp-ATF6 was expressed in both nucleus and cytoplasm of S2 cells. The expression level of Sp-ATF6 was induced by hydrogen peroxide and V. parahaemolyticus challenge, indicating that the ATF6 pathway was activated in response to ER stress. In order to know more about the regulation mechanism of the Sp-ATF6, RNA interference experiment was investigated. Knocking down Sp-ATF6 in vivo can decrease the expression of antioxidant-related genes (CAT and SOD) and heat shock proteins (HSP90 and HSP70) after V. parahaemolyticus infection. All these results suggested that Sp-ATF6 played a crucial role in the defense against environmental stress and pathogen infection in crustaceans.


Subject(s)
Brachyura , Animals , Brachyura/microbiology , Hydrogen Peroxide , Activating Transcription Factor 6/genetics , Activating Transcription Factor 6/metabolism , Phylogeny , Amino Acid Sequence , Bacteria/metabolism , Arthropod Proteins/chemistry , Immunity, Innate/genetics
18.
Aging (Albany NY) ; 15(17): 8630-8663, 2023 09 13.
Article in English | MEDLINE | ID: mdl-37708239

ABSTRACT

Aging is responsible for the main intrinsic triggers of cancers; however, the studies of aging risk factors in cancer animal models and cancer patients are rare and insufficient to be represented in cancer clinical trials. For a better understanding of the complex regulatory networks of aging and cancers, 8 candidate aging related long noncoding RNAs (CarLncs) identified from the healthy aging models, centenarians and their offsprings, were selected and their association with kidney renal clear cell carcinoma (KIRC) was explored by series of cutting edge analyses such as support vector machine (SVM) and random forest (RF) algorithms. Using data downloaded from TCGA and GTEx databases, a regulatory network of CarLncs-miRNA-mRNA was constructed and five genes within the network were screened out as aging related feature genes for developing KIRC prognostic models. After a strict filtering pipeline for modeling, a formula using the transcript per million (TPM) values of feature genes "LncAging_score = 0.008* MMP11 + 0.066* THBS1-IT1 + (-0.014)* DYNLL2 + (-0.030)* RMND5A+ 0.008* PEG10" was developed. ROC analysis and nomogram suggest our model achieves a great performance in KIRC prognosis. Among the 8 CarLncs, we found that THBS1-IT1 was significantly dysregulated in 12 cancer types. A comprehensive pan-cancer analysis demonstrated that THBS1-IT1 is a potential prognostic biomarker in not only KIRC but also multiple cancers, such as LUSC, BLCA, GBM, LGG, MESO, PAAD, STAD and THCA, it was correlated with tumor microenvironment (TME) and tumor immune cell infiltration (TICI) and its high expression was related with poor survival.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , RNA, Long Noncoding , Animals , Aged, 80 and over , Humans , RNA, Long Noncoding/genetics , Prognosis , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Biomarkers , Kidney , Tumor Microenvironment
19.
Food Chem Toxicol ; 180: 114027, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37696466

ABSTRACT

As an alternative to octabromodiphenyl ether (octa-BDE), 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) has been widely used in a variety of combustible materials, such as plastics, textiles and furniture. Previous studies have demonstrated the thyroid toxicity of traditional brominated flame retardants for example octa-BDE clearly. Nevertheless, little is known about the thyroid toxicity of alternative novel brominated flame retardants BTBPE. In this study, it was demonstrated that BTBPE in vivo exposure induced FT4 reduction in 2.5, 25 and 250 mg/kg bw treated group and TT4 reduction in 25 mg/kg bw treated group. TG, TPO and NIS are key proteins of thyroid hormone synthesis. The results of Western blot and RT-PCR from thyroid tissue showed decreased protein levels and gene expression levels of TG, TPO and NIS as well as regulatory proteins PAX8 and TTF2. To investigate whether the effect also occurred in humans, anthropogenic Nthy-ori 3-1 cells were selected. Similar results were seen in vitro condition. 2.5 mg/L BTBPE reduced the protein levels of PAX8, TTF1 and TTF2, which in turn inhibited the protein levels of TG and NIS. The results in vitro experiment were consistent with that in vivo, suggesting possible thyrotoxic effects of BTBPE on humans. It was indicated that BTBPE had the potential interference of T4 generation and the study provided more evidence of the effects on endocrine disorders.

20.
Fish Shellfish Immunol ; 141: 109078, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37716494

ABSTRACT

Heat shock proteins play an important role in host defense, and modulate immune responses against pathogen infection. In this study, a novel HSC70 from the mud crab (designated as SpHSC70) was cloned and characterized. The full length of SpHSC70 contained a 58 bp 5'untranslated region (UTR), an open reading frame (ORF) of 2,046 bp and a 3'UTR of 341 bp. The SpHSC70 protein included the conserved DnaK motif. The mRNA of SpHSC70 was highly expressed in the hemocytes, heart and hepatopancreas, and lowly expressed in the intestine. The subcellular localization results indicated that SpHSC70 was localized in both the cytoplasm and the nucleus. Moreover, SpHSC70 was significantly responsive to bacterial challenge. RNA interference experiment was designed to investigate the roles of SpHSC70 in response to bacterial challenge. V. parahaemolyticus infection induced the expression levels of SpPO, SpHSP70, SpSOD and SpCAT. Knocking down SpHSC70 in vivo can decrease the expression of these genes after V. parahaemolyticus infection. These results suggested that SpHSC70 could play a vital role in defense against V. parahaemolyticus infection via activating the immune response and antioxidant defense signaling pathways in the mud crab.


Subject(s)
Brachyura , Vibrio Infections , Vibrio parahaemolyticus , Animals , Vibrio parahaemolyticus/physiology , Vibrio Infections/microbiology , RNA Interference , Bacteria/metabolism , Arthropod Proteins , Phylogeny
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