ABSTRACT
BACKGROUND: Savolitinib, a small molecule inhibitor, has gained approval as the inaugural medication in China that specifically targets MET kinase. Patients with advanced non-small cell lung cancer (NSCLC) who show MET exon 14 skipping now have a new and innovative treatment option available. CASE REPORT: In this case report, we describe a patient who experienced drug-induced liver injury (DILI) due to the administration of savolitinib. After being prescribed with savolitinib (400 mg per day, oral), a 73-year-old male diagnosed with stage IV NSCLC with MET exon 14 skipping mutation experienced an increase in liver enzymes and bilirubin levels according to his laboratory tests conducted one month later. Following a 14-day course of hepatoprotective medication, the liver function reverted back to its normal state. After receiving savolitinib (200 mg per day, oral) for one week, the patient was once again diagnosed with severe liver impairment. Then savolitinib was discontinued and received treatment with hepatoprotective drugs for one week. Following the restoration of normal liver function, another attempt was made to administer a small amount of savolitinib (100 mg per day, oral). Thus far, the patient has been followed up and there has been no recurrence of liver damage. Additionally, the lung CT scan revealed ongoing tumor shrinkage with no apparent indications of spreading or metastasis. The Roussel Uclaf Causality Assessment Method (RUCAM) determined that savolitinib was "highly probable" cause of DILI. Moderate-severe was determined to be the extent of DILI severity. CONCLUSION: To the best of our understanding, this is the initial instance of DILI resulting from the use of savolitinib as a standalone treatment in a real-world setting. During the administration of savolitinib, healthcare professionals should carefully consider the potential occurrence of DILI. Administering the patient with a small amount of savolitinib resulted in a remarkable response against the tumor, leading us to speculate that the effectiveness of savolitinib might be associated with its plasma concentration. Studying the pharmacokinetics and pharmacodynamics (PK/PD) of savolitinib is beneficial for tailoring and accurately prescribing the medication to each individual.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Chemical and Drug Induced Liver Injury , Lung Neoplasms , Humans , Male , Aged , Chemical and Drug Induced Liver Injury/etiology , Lung Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Acrylamides/adverse effects , Acrylamides/therapeutic use , Protein Kinase Inhibitors/adverse effectsABSTRACT
Dehalogenating bacteria are still deficient when targeted to deal with chlorinated hydrocarbons (CHCs) contamination: e.g., slow metabolic rates, limited substrate range, formation of toxic intermediates. To enhance its dechlorination capacity, biochar and its composites with appropriate surface activity and biocompatibility are selected for coupled dechlorination. Because of its special surface physical and chemical properties, it promotes biofilm formation by dehalogenating bacteria on its surface and improves the living environment for dehalogenating bacteria. Next, biochar and its composites provide active sites for the removal of CHCs through adsorption, activation and catalysis. These sites can be specific metal centers, functional groups or structural defects. Under microbial mediation, these sites can undergo activation and catalytic cycles, thereby increasing dechlorination efficiency. However, there is a lack of systematic understanding of the mechanisms of dechlorination in biogenic and abiogenic systems based on biochar. Therefore, this article comprehensively summarizes the recent research progress of biochar and its composites as a "Taiwan balm" for the degradation of CHCs in terms of adsorption, catalysis, improvement of microbial community structure and promotion of degradation and metabolism of CHCs. The removal efficiency, influencing factors and reaction mechanism of the degraded CHCs were also discussed. The following conclusions were drawn, in the pure biochar system, the CHCs are fixed to its surface by adsorption through chemical bonds on its surface; the biochar composite material relies on persistent free radicals and electron shuttle mechanisms to react with CHCs, disrupting their molecular structure and reducing them; biochar-coupled microorganisms reduce CHCs primarily by forming an "electron shuttle bridge" between biological and non-biological organisms. Finally, the experimental directions to be carried out in the future are suggested to explore the optimal solution to improve the treatment efficiency of CHCs in water.
ABSTRACT
In China, saline-alkali lands constitute 5.01% of the total land area, having a significant impact on both domestic and international food production. Rapeseed (Brassica napus L.), as one of the most important oilseed crops in China, has garnered considerable attention due to its potential adaptability to saline conditions. Breeding and improving salt-tolerant varieties is a key strategy for the effective utilization of saline lands. Hence, it is important to conduct comprehensive research into the adaptability and salt tolerance mechanisms of Brassica napus in saline environments as well as to breed novel salt-tolerant varieties. This review summarizes the molecular mechanism of salt tolerance, physiological and phenotypic indexes, research strategies for the screening of salt-tolerant germplasm resources, and genetic engineering tools for salt stress in Brassica napus. It also introduces various agronomic strategies for applying exogenous substances to alleviate salt stress and provide technological tools and research directions for future research on salt tolerance in Brassica napus.
ABSTRACT
Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This α-coronavirus causes significant economic losses in the global swine industry. The study focused on the papain-like protease (PLpro), which plays a crucial role in coronavirus immune evasion by mediating deubiquitination. Targeting PLpro could potentially disrupt viral replication and enhance antiviral responses. The results demonstrated that myricetin effectively inhibited TGEV-induced cytopathic effects in a dose-dependent manner, with an EC50 value of 31.19 µM. Myricetin significantly reduced TGEV viral load within 48 h after an 8-h co-incubation period. Further investigations revealed that myricetin at a concentration of 100 µM directly inactivated TGEV and suppressed its intracellular replication stage. Moreover, pretreatment with 100 µM myricetin conferred a protective effect on PK-15 cells against TGEV infection. Myricetin competitively inhibited PLpro with an IC50 value of 6.563 µM. Molecular docking experiments show that myricetin binds to the Cys102 residue of PLpro through conventional hydrogen bonds, Pi-sulfur, and Pi-alkyl interactions. This binding was confirmed through site-directed mutagenesis experiments, indicating myricetin as a potential candidate for preventing and treating TGEV infection.
ABSTRACT
Background: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety. Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis. Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035-12.727; P = 0.044), Cmin greater than 2.3 µg/mL (OR: 7.37; 95% CI: 1.571-34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732-51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139-152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 µg/mL and AUC = 82.0 mg h/L. Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 µg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.
ABSTRACT
The stink bug, Riptortus pedestris (Fabricius) (Hemiptera: Alydidae), is a highly destructive pest that significantly damages legume crops in East and South Asia. Neonicotinoid insecticides containing thiamethoxam are widely used to control R. pedestris in soybean fields. However, the current knowledge on the impact of different thiamethoxam concentrations on R. pedestris growth and reproduction is lacking and insufficient. The present study investigated the effects of thiamethoxam on the biological traits of R. pedestris after treatment with LC10 (19.8 mg/L), LC20 (31.6 mg/L), LC30 (44.2 mg/L), LC40 (58.9 mg/L), and LC50 (77.0 mg/L) concentrations. These five thiamethoxam concentrations (LC10~LC50) reduced adult longevity and fecundity in the F1 generation females. Thiamethoxam treatment also significantly decreased the population trend index, intrinsic rate of increase, net reproductive rate, gross reproductive rate, and finite rate of increase and increased the mean generation time. These results show that thiamethoxam hinders and suppresses the development and growth of the F1 population of R. pedestris. Thiamethoxam is recommended for spray control during peak adult emergence, as it not only has a controlling effect on the parental generation but also a negative impact on the F1 generations.
ABSTRACT
BACKGROUND: The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored. METHODS: Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation. RESULTS: Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients. CONCLUSIONS: Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Disease Progression , Eukaryotic Initiation Factor-4A , Lung Neoplasms , RNA, Circular , YAP-Signaling Proteins , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , RNA, Circular/genetics , RNA, Circular/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Animals , YAP-Signaling Proteins/metabolism , Mice , Eukaryotic Initiation Factor-4A/metabolism , Eukaryotic Initiation Factor-4A/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Female , Cell Line, Tumor , Cell Proliferation , RNA Precursors/metabolism , RNA Precursors/genetics , Male , RNA Splicing , Apoptosis , MicroRNAs/genetics , MicroRNAs/metabolism , Mice, Nude , Gene Expression Regulation, Neoplastic , DEAD-box RNA HelicasesABSTRACT
Purpose: Polymyxin B-immobilized hemoperfusion (PMX-HP) is a therapeutic strategy for removing circulating endotoxins from patients with sepsis or septic shock. However, the survival advantage of PMX-HP treatment remains controversial for patients with sepsis/septic shock. Therefore, this study collected all the clinical trials to assess the effect and the safety of PMX-HP treatment. Methods: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for eligible trials fromtheir inception through June 30, 2023. All clinical trials that investigated the effect of polymyxin B hemoperfusion in patients who died with sepsis or septic shock within 28-day mortality were eligible. The Cochrane Risk of Bias Assessment instrument and the ROBINS-I tool were used to assess the risk of bias. Results: A total of 30 trials, including 25680 adult patients, were included. PMX-HP decreased 28-day mortality (OR 0.75, 95 % CI 0.65-0.88; pï¼0.00001). Subgroup analysis revealed that 28-day mortality was significantly reduced after PMX-HP treatment in the mixed infection site group and in the age under 70 years old group. PMX-HP might also lower endotoxin levels (MD -1.22, 95 % CI -1.62 - 0.81, p < 0.00001) and improve SOFA scores (MD -2.11, 95 % CI -3.80- 0.43, p = 0.01). PMX-HP was not linked to the development of significant adverse events (p = 0. 05). Conclusion: Our findings suggest that PMX-HP therapy can reduce 28-day mortality in individuals with sepsis or septic shock. The therapeutic effect may be due to the ability of PMX-HP to lower endotoxin levels and enhance hemodynamics. However, further assessment of the clinical effects of PMX-HP on sepsis or septic shock is required.
ABSTRACT
The fruit shape of cucumber is an important agronomic trait, and mining regulatory genes, especially dominant ones, is vital for cucumber breeding. In this study, we identified a short and fat fruit mutant, named sff, from an EMS mutagenized population. Compared to the CCMC (WT), sff (MT) exhibited reduced fruit length and increased dimeter. Segregation analysis revealed that the sff phenotype is controlled by a semi-dominant single gene with dosage effects. Through map-based cloning, the SFF locus was narrowed down to a 52.6â¯kb interval with two SNPs (G651A and C1072T) in the second and third exons of CsaV3_1G039870, which encodes an IQD family protein, CsSUN. The G651A within the IQ domain of CsSUN was identified as the unique SNP among 114 cucumber accessions, and it was the primary cause of the functional alteration in CsSUN. By generating CsSUN knockout lines in cucumber, we confirmed that CsSUN was responsible for sff mutant phenotype. The CsSUN is localized to the plasma membrane. CsSUN exhibited the highest expression in the fruit with lower expression in sff compared to WT. Histological observations suggest that the sff mutant phenotype is due to increased transverse cell division and inhibited longitudinal cell division. Transcriptome analysis revealed that CsSUN significantly affected the expression of genes related to cell division, expansion, and auxin signal transduction. This study unveils CsSUN's crucial role in shaping cucumber fruit and offers novel insights for cucumber breeding.
Subject(s)
Cucumis sativus , Fruit , Mutation , Plant Proteins , Cucumis sativus/genetics , Cucumis sativus/metabolism , Cucumis sativus/growth & development , Fruit/genetics , Fruit/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Phenotype , Polymorphism, Single Nucleotide , Gene Expression Regulation, PlantABSTRACT
BACKGROUND: Chronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear. METHODS: A total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety. RESULTS: With a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day. CONCLUSIONS: Twenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day.
Subject(s)
Chronic Pain , Mental Disorders , Humans , Chronic Pain/epidemiology , Male , Female , Middle Aged , Mental Disorders/epidemiology , Incidence , United Kingdom/epidemiology , Adult , Cohort Studies , Aged , Sedentary Behavior , Exercise/physiology , Anxiety/epidemiology , Depression/epidemiologyABSTRACT
BACKGROUND: Fried food has increased in popularity worldwide. However, deep frying can increase the production of peroxidative toxins in food, which might be harmful to fetal development. The antioxidative effect of vitamin D3 (VD3) has been reported previously. OBJECTIVES: This study aimed to explore how maternal VD3 supplementation in an oxidized-oil diet during gestation affects fetal antioxidative ability and development. METHODS: Pregnant mice were randomly assigned into 3 groups: Control group (diet with fresh soybean oil), OSO group [diet with oxidized soybean oil (OSO)], and OSOV group (diet with OSO and 10,000 IU/Kg VD3). Mice were fed with the corresponding diet during gestation. On day 16.5 of gestation, the placenta and fetus were harvested to analyze antioxidative status. RESULTS: Maternal oxidized-oil diet during gestation significantly reduced placental vessel abundance, labyrinth zone area, and fetal body weight. However, dietary VD3 supplementation prevented these negative effects of oxidized-oil diet. Maternal intake of oxidized-oil diet increased serum concentrations of malondialdehyde, total-nitric oxide synthase, and inducible nitric oxide synthase, whereas VD3 supplementation showed a protection effect on it. Additionally, maternal VD3 supplementation increased the levels of antioxidative enzymes and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby protecting placenta and fetus from apoptosis and oxidative stress caused by an oxidized-oil diet. The gene expression and protein levels of a fatty acid transporter solute carrier family 27 member 1 in the fetal liver were increased by maternal VD3 supplementation under oxidized-oil diet. Notably, NRF2 could be co-immunoprecipitated with the VD receptor in the placenta. CONCLUSIONS: Maternal VD3 supplementation could protect fetus from oxidized-oil diet induced developmental impairment by alleviating oxidative stress in the placenta and fetus through the VD receptor/NRF2 pathway, at least partially. Thus, ensuring adequate levels of VD3 through supplementation is often critical during pregnancy.
ABSTRACT
Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice-Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.
ABSTRACT
BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. METHODS: 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. RESULTS: MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg-1·h-1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), µg·kg-1·min-1, P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant. CONCLUSIONS: Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection. TRIAL REGISTRATION: The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323).
Subject(s)
Colorectal Neoplasms , Laparoscopy , Neuromuscular Blockade , Postoperative Complications , Humans , Male , Female , Aged , Laparoscopy/methods , Laparoscopy/adverse effects , Colorectal Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Neuromuscular Blockade/methods , Neuromuscular Blockade/adverse effects , Incidence , Aged, 80 and over , Heart Injuries/epidemiology , Heart Injuries/etiologyABSTRACT
Pullorum disease (PD) is a bacterial infection caused by Salmonella pullorum (S. pullorum) that affects poultry. It is highly infectious and often fatal. Antibiotics are currently the mainstay of prophylactic and therapeutic treatments for PD, but their use can lead to the development of resistance in pathogenic bacteria and disruption of the host's intestinal flora. We added neomycin sulfate and different doses of tannic acid (TA) to the drinking water of chicks at 3 days of age and infected them with PD by intraperitoneal injection of S. pullorum at 9 days of age. We analyzed intestinal histopathological changes and the expression of immune-related genes and proteins by using the plate smear method, histological staining, real-time fluorescence quantitative PCR, ELISA kits, and 16S rRNA Analysis of intestinal flora. The results demonstrate that S. pullorum induces alterations in the immune status and impairs the functionality of the liver and intestinal barrier. We found that tannic acid significantly ameliorated S. pullorum-induced liver and intestinal damage, protected the intestinal physical and chemical barriers, restored the intestinal immune barrier function, and regulated the intestinal flora. Our results showed that TA has good anti-diarrhoeal, growth-promoting, immune-regulating, intestinal barrier-protecting and intestinal flora-balancing effects, and the best effect was achieved at an additive dose of 0.2%.
ABSTRACT
Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.
ABSTRACT
BACKGROUND: Glehnia littoralis is a medicinal and edible plant species having commercial value and has several hundred years of cultivation history. Polyploid breeding is one of the most important and fastest ways to generate novel varieties. To obtain tetraploids of G. littoralis in vitro, colchicine treatment was given to the seeds and then were screened based on morphology, flow cytometry, and root tip pressing assays. Furthermore, transcriptome analysis was performed to identity the differentially expressed genes associated with phenotypic changes in tetraploid G. littoralis. RESULTS: The results showed that 0.05% (w/v) colchicine treatment for 48 h was effective in inducing tetraploids in G. littoralis. The tetraploid G. littoralis (2n = 4x = 44) was superior in leaf area, leaf thickness, petiole diameter, SPAD value (Chl SPAD), stomatal size, epidermal tissues thickness, palisade tissues thickness, and spongy tissues thickness to the diploid ones, while the stomatal density of tetraploids was significantly lower. Transcriptome sequencing revealed, a total of 1336 differentially expressed genes (DEGs) between tetraploids and diploids. Chromosome doubling may lead to DNA content change and gene dosage effect, which directly affects changes in quantitative traits, with changes such as increased chlorophyll content, larger stomata and thicker tissue of leaves. Several up-regulated DEGs were found related to growth and development in tetraploid G. littoralis such as CKI, PPDK, hisD and MDP1. KEGG pathway enrichment analyses showed that most of DEGs were enriched in metabolic pathways. CONCLUSIONS: This is the first report of the successful induction of tetraploids in G. littoralis. The information presented in this study facilitate breeding programs and molecular breeding of G. littoralis varieties.
Subject(s)
Gene Expression Profiling , Phenotype , Tetraploidy , Transcriptome , Colchicine/pharmacology , Caryophyllales/genetics , Gene Expression Regulation, Plant , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/anatomy & histologyABSTRACT
BACKGROUND: This systematic review and meta-analysis aimed to report the evaluation of the prevalence and risk of nonalcoholic fatty liver disease (NAFLD) among adult psoriatic patients in a systematic review and meta-analysis. METHODS: A comprehensive search was conducted across 4 databases of PubMed, Scopus, Cochrane Library, and Web of Science to collect relevant studies until November 30, 2023, without any restrictions for finding observational studies. The comprehensive meta-analysis version 3.0 software was used to calculate effect sizes, showing the event rate (ER), odds ratio (OR), and a 95% confidence interval (CI) to evaluate NAFLD risk or prevalence in psoriatic patients and controls or psoriatic patients alone. The quality scoring was performed by 1 author based on the Newcastle-Ottawa Scale tool. Publication bias, meta-regression analysis, and sensitivity analyses were performed. Additionally, Trial Sequential Analysis (TSA) was performed using TSA software. RESULTS: A total of 581 records were identified among the databases and electronic sources. At last, 41 studies involving 607,781 individuals were included in the meta-analysis. The pooled ER of NAFLD among psoriatic patients was 29.5% (95%CI: 19.6%-41.7%) and I2â =â 99.79%. The pooled OR of NAFLD in psoriatic patients compared to controls was 1.685 (95%CI: 1.382-2.055; P < .001) and I2â =â 87.96%. CONCLUSIONS: The study found a significant link between psoriasis and NAFLD, with psoriatic patients having a higher chance of developing NAFLD compared to the controls. The study calls for regular NAFLD screening in psoriatic patients to prevent liver complications.
Subject(s)
Non-alcoholic Fatty Liver Disease , Psoriasis , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Psoriasis/epidemiology , Psoriasis/complications , Prevalence , Adult , Risk FactorsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-â in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-â (35.34 kDa), and the structural characterization indicated that CVP-AP-â was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-â attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.
Subject(s)
Anti-Inflammatory Agents , Antioxidants , Plant Leaves , Plant Stems , Polysaccharides , Plant Leaves/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Polysaccharides/chemistry , Animals , Plant Stems/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Mice , Swine , Plant Extracts/pharmacology , Plant Extracts/chemistry , Intestines/drug effects , RAW 264.7 CellsABSTRACT
The isochorismate synthase (ICS) proteins are essential regulators of salicylic acid (SA) synthesis, which has been reported to regulate resistance to biotic and abiotic stresses in plants. Clubroot caused by Plasmodiophora brassicae is a common disease that threatens the yield and quality of Oilseed rape (Brassica napus L.). Exogenous application of salicylic acid reduced the incidence of clubroot in oilseed rape. However, the potential importance of the ICS genes family in B. napus and its diploid progenitors has been unclear. Here, we identified 16, 9, and 10 ICS genes in the allotetraploid B. napus, diploid ancestor Brassica rapa and Brassica oleracea, respectively. These ICS genes were classified into three subfamilies (I-III), and member of the same subfamilies showed relatively conserved gene structures, motifs, and protein domains. Furthermore, many hormone-response and stress-related promoter cis-acting elements were observed in the BnaICS genes. Exogenous application of SA delayed the growth of clubroot galls, and the expression of BnaICS genes was significantly different compared to the control groups. Protein-protein interaction analysis identified 58 proteins involved in the regulation of ICS in response to P. brassicae in B. napus. These results provide new clues for understanding the resistance mechanism to P. brassicae.
Subject(s)
Brassica napus , Disease Resistance , Gene Expression Regulation, Plant , Plant Diseases , Plasmodiophorida , Brassica napus/parasitology , Brassica napus/genetics , Disease Resistance/genetics , Gene Expression Regulation, Plant/drug effects , Plant Diseases/parasitology , Plant Diseases/genetics , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Multigene Family , Salicylic Acid/pharmacology , Salicylic Acid/metabolism , Genome, Plant , Intramolecular TransferasesABSTRACT
Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.