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1.
Cell ; 186(17): 3593-3605.e12, 2023 08 17.
Article in English | MEDLINE | ID: mdl-37516107

ABSTRACT

Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Animals , Arabidopsis/physiology , Fertilization , Pollen Tube , Seeds , Germ Cells, Plant
2.
Biochem Biophys Res Commun ; 695: 149451, 2024 02 05.
Article in English | MEDLINE | ID: mdl-38176173

ABSTRACT

BACKGROUND/OBJECTIVE: DT-13, the principal active component of Mysidium shortscapes from the Liliaceae family, has garnered substantial interest in cancer therapy owing to its potential anticancer properties. This study investigated the effects of DT-13 on the proliferation and apoptosis of human pancreatic cancer cell lines and aimed to elucidate the underlying mechanisms. METHODS: PANC1 and CFPAC1 cells were exposed to DT-13 and their proliferation was assessed using RTCA and clone formation assays. Apoptotic protein expression was analyzed by western blotting, and apoptotic cells were identified by flow cytometry. RNA was extracted from DT-13 treated and untreated PANC1 cells for RNA sequencing. Differentially expressed genes were identified and subjected to GO bioprocess, KEGG pathway analysis, and western blotting. Finally, to evaluate tumor growth, CFPAC1 cells were subcutaneously injected into BALB/c nude mice. RESULTS: DT-13 inhibited proliferation and induced apoptosis of PANC1 and CFPAC1 cells by activating the AMPK/mTOR pathway and suppressing p70 S6K. Moreover, DT-13 hindered the growth of CFPAC1 xenograft tumors in nude mice. CONCLUSIONS: DT-13 effectively inhibited the growth of human pancreatic cancer cells.


Subject(s)
AMP-Activated Protein Kinases , Pancreatic Neoplasms , Saponins , Animals , Humans , Mice , AMP-Activated Protein Kinases/drug effects , AMP-Activated Protein Kinases/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/metabolism , TOR Serine-Threonine Kinases/drug effects , TOR Serine-Threonine Kinases/metabolism , Xenograft Model Antitumor Assays , Saponins/pharmacology , Saponins/therapeutic use
3.
BMC Plant Biol ; 24(1): 23, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38166728

ABSTRACT

BACKGROUND: Spiraea L. is a genus comprising approximately 90 species that are distributed throughout the northern temperate regions. China is recognized as the center of species diversity for this genus, hosting more than 70 species, including 47 endemic species. While Spiraea is well-known for its ornamental value, its taxonomic and phylogenetic studies have been insufficient. RESULTS: In this study, we conducted sequencing and assembly of the plastid genomes (plastomes) of 34 Asiatic Spiraea accessions (representing 27 Asiatic Spiraea species) from China and neighboring regions. The Spiraea plastid genome exhibits typical quadripartite structures and encodes 113-114 genes, including 78-79 protein-coding genes (PCGs), 30 tRNA genes, and 4 rRNA genes. Linear regression analysis revealed a significant correlation between genome size and the length of the SC region. By the sliding windows method, we identified several hypervariable hotspots within the Spiraea plastome, all of which were localized in the SC regions. Our phylogenomic analysis successfully established a robust phylogenetic framework for Spiraea, but it did not support the current defined section boundaries. Additionally, we discovered that the genus underwent diversification after the Early Oligocene (~ 30 Ma), followed by a rapid speciation process during the Pliocene and Pleistocene periods. CONCLUSIONS: The plastomes of Spiraea provided us invaluable insights into its phylogenetic relationships and evolutionary history. In conjunction with plastome data, further investigations utilizing other genomes, such as the nuclear genome, are urgently needed to enhance our understanding of the evolutionary history of this genus.


Subject(s)
Genome, Chloroplast , Genome, Plastid , Rosaceae , Spiraea , Phylogeny , Evolution, Molecular , Genome, Chloroplast/genetics
4.
J Virol ; 97(11): e0106723, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37855618

ABSTRACT

IMPORTANCE: Many plant viruses are transmitted by insect vectors in a circulative manner. For efficient transmission, the entry of the virus from vector hemolymph into the primary salivary gland (PSG) is a step of paramount importance. Yet, vector components mediating virus entry into PSG remain barely characterized. Here, we demonstrate the role of clathrin-mediated endocytosis and early endosomes in begomovirus entry into whitefly PSG. Our findings unravel the key components involved in begomovirus transport within the whitefly body and transmission by their whitefly vectors and provide novel clues for blocking begomovirus transmission.


Subject(s)
Begomovirus , Endocytosis , Hemiptera , Animals , Begomovirus/physiology , Clathrin/metabolism , Endosomes , Hemiptera/metabolism , Hemiptera/virology , Plant Diseases , Salivary Glands/metabolism , Salivary Glands/virology
5.
Am J Pathol ; 193(9): 1208-1222, 2023 09.
Article in English | MEDLINE | ID: mdl-37328100

ABSTRACT

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.


Subject(s)
Oral Submucous Fibrosis , Humans , Rats , Animals , Oral Submucous Fibrosis/metabolism , Oral Submucous Fibrosis/pathology , Mouth Mucosa/metabolism , Mouth Mucosa/pathology , Epithelial-Mesenchymal Transition , Myofibroblasts/metabolism , Epithelial Cells/metabolism
6.
Drug Metab Dispos ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39214665

ABSTRACT

Compound probiotics have been widely used and commonly co-administered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (CYP450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin and chlorzoxazone. Male Wistar rats were administered with drinking water containing VSL#3 or not for 14 days and then intragastrically administered a CYP450s probe cocktail; This was done to investigate the host CYP450s metabolic phenotype. Stool, liver/jejunum and serum samples were collected for 16S rRNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both alpha and beta diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1,417 and 4,004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of CYP450s genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug-processing gene expression, and the intestinal structure in rats, which could be reasons for pharmacokinetic changes. Significance Statement This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of CYP450s probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the current study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, here combined with the bile acid profile and histopathological analysis.

7.
Cardiovasc Diabetol ; 23(1): 166, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730425

ABSTRACT

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.


Subject(s)
Antihypertensive Agents , Blood Glucose , Blood Pressure , Diabetes Mellitus, Type 2 , Genetic Predisposition to Disease , Glycemic Control , Guanine Nucleotide Exchange Factors , Polymorphism, Single Nucleotide , Aged , Female , Humans , Male , Middle Aged , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/adverse effects , Asian People/genetics , Biomarkers/blood , Blood Glucose/metabolism , Blood Glucose/drug effects , Blood Pressure/drug effects , Blood Pressure/genetics , China/epidemiology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Diabetic Angiopathies/genetics , Diabetic Angiopathies/diagnosis , DNA-Binding Proteins/genetics , East Asian People , Genetic Association Studies , Glycemic Control/adverse effects , Guanine Nucleotide Exchange Factors/genetics , Hypertension/genetics , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/diagnosis , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Phenotype , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
8.
J Biomed Sci ; 31(1): 47, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724973

ABSTRACT

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.


Subject(s)
Cell- and Tissue-Based Therapy , Induced Pluripotent Stem Cells , Precision Medicine , Humans , Precision Medicine/methods , Induced Pluripotent Stem Cells/cytology , Cell- and Tissue-Based Therapy/methods , Drug Evaluation, Preclinical/methods , Urine/cytology , Regenerative Medicine/methods
9.
Helicobacter ; 29(4): e13121, 2024.
Article in English | MEDLINE | ID: mdl-39097924

ABSTRACT

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.


Subject(s)
Anti-Bacterial Agents , Bismuth , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Tetracycline , Humans , Helicobacter Infections/drug therapy , Tetracycline/therapeutic use , Tetracycline/administration & dosage , Tetracycline/adverse effects , Male , Middle Aged , Female , Bismuth/therapeutic use , Bismuth/adverse effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Adult , Helicobacter pylori/drug effects , Treatment Outcome , China , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Drug Administration Schedule , Esomeprazole/therapeutic use , Esomeprazole/administration & dosage , Aged , Young Adult , Breath Tests , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects
10.
Dig Dis Sci ; 69(7): 2540-2547, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38700630

ABSTRACT

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Bismuth , Clarithromycin , Drug Administration Schedule , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Sulfonamides , Tetracycline , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/diagnosis , Helicobacter pylori/drug effects , Middle Aged , Male , Female , Tetracycline/administration & dosage , Tetracycline/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Bismuth/administration & dosage , Bismuth/therapeutic use , Bismuth/adverse effects , Adult , Clarithromycin/administration & dosage , Amoxicillin/administration & dosage , Sulfonamides/administration & dosage , Pyrroles/administration & dosage , Pyrroles/adverse effects , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Breath Tests , Treatment Outcome , Aged , China
11.
Mol Divers ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39212874

ABSTRACT

Four series of sulfonamide derivatives (13a-b, 14a-d, 15a-b, and 16a-d) were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) inhibitory activities. Of these, compounds 13b (IC50 = 0.130 µM) and 15a (IC50 = 0.130 µM) showed the highest inhibitory activities against ALK5 kinase, with activities similar to the positive control LY-2157299. Notably, we discovered that introduction of sulfonamide group at the 2-position of the central imidazole ring significantly increased ALK5 inhibitory activity. Compounds 13b and 15a did not show toxicity in A549 cells up to the maximum concentration of 50 µM, and effectively inhibited TGF-ß1-induced Smad-signaling and cell motility in A549 cells. The results indicate that compounds 13b and 15a are worth of further development as anticancer agents.

12.
Nucleic Acids Res ; 50(10): 5599-5616, 2022 06 10.
Article in English | MEDLINE | ID: mdl-35640597

ABSTRACT

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.


Subject(s)
Histones , Lysine , Animals , Chromatin/genetics , Gene Expression Regulation, Developmental , Histones/genetics , Histones/metabolism , Lysine/metabolism , Mice , Oocytes/metabolism , Oogenesis/genetics , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , Zygote
13.
Article in English | MEDLINE | ID: mdl-38551431

ABSTRACT

Objective: The objective of this study was to evaluate the effects of comfort care on perioperative outcomes and postoperative recovery of breast cancer patients. Evaluating comfort care is important in the context of breast cancer surgery because it can potentially alleviate pain, improve patient comfort, enhance postoperative recovery, and reduce complications, ultimately leading to better patient outcomes. Methods: Between March 2020 and December 2021, 78 patients undergoing breast cancer surgery at our hospital were randomly assigned to receive either routine nursing (routine group) or comfort care (experimental group). The comfort care intervention included various components such as health education, preoperative care, intraoperative care, postoperative care, pain care, and psychological care. The routine group received standard nursing care following medical advice. Results: The patient characteristics between the two groups were comparable. Comfort care resulted in significantly higher visual analog scale (VAS) scores, indicating reduced pain, and better improvement in functional recovery of the upper limb compared to routine nursing. Comfort care was also associated with better postoperative recovery, as evidenced by lower self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores. The experimental group had a significantly lower incidence of complications compared to the routine group. Additionally, the experimental group reported better 24-hour comfort and higher nursing satisfaction. Conclusion: In conclusion, comfort care effectively reduces postoperative pain, promotes postoperative recovery, improves patient emotions, lowers the incidence of complications, and enhances comfort and care satisfaction in breast cancer patients undergoing radical surgery. These findings highlight the importance of incorporating comfort care interventions in the perioperative management of breast cancer patients. Further research and implementation of comfort care strategies may have implications for improving clinical practice and patient outcomes in the future.

14.
Environ Toxicol ; 39(4): 2197-2207, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38124441

ABSTRACT

BACKGROUND: Diabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease-related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear. METHODS: CircTAOK1, microRNA (miR)-142-3p, and sex-determining region Y-box transcription factor 6 (SOX6) mRNA levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cleaved-caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR-142-3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay. RESULTS: CircTAOK1 and SOX6 expression levels were up-regulated, while miR-142-3p expression was down-regulated in DN serum and HG-treated HK-2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG-induced HK-2 cells. The inhibitory effect of circTAOK1 knockdown on HG-induced HK-2 cell injury was restored by miR-142-3p downregulation. CircTAOK1 acted as a sponge for miR-142-3p, and SOX6 was targeted by miR-142-3p. The overexpression of SOX6 could recover the effect of miR-142-3p overexpression on HG-induced HK-2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR-142-3p. CONCLUSION: CircTAOK1 knockdown inhibited HG-induced HK-2 cell damage in DN by the miR-142-3p/SOX6 axis.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , MicroRNAs , Humans , Diabetic Nephropathies/genetics , Apoptosis/genetics , Oxidative Stress/genetics , Inflammation/genetics , Collagen Type I , Glucose/pharmacology , Proto-Oncogene Proteins c-bcl-2 , MicroRNAs/genetics , SOXD Transcription Factors/genetics
15.
J Ment Health ; : 1-11, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654552

ABSTRACT

BACKGROUND: Positive psychological interventions (PPIs) are known to be effective in alleviating depression. However, the effect of PPIs on positive and negative emotions in depressed participants is not unclear. AIMS: To systematically investigate the effects of PPIs on positive and negative emotions in depressed individuals. METHODS: 6 databases were searched for randomized controlled trials of PPIs in individuals with depressive disorders or depressive symptoms. Hedges' g value was computed using a random-effects model to determine effect sizes. RESULTS: 14 trials from 13 studies were included. Our meta-analysis showed that PPIs had significant but small effects on improving positive affect (g = 0.33, p = .02), life satisfaction (g = 0.26, p = .03), happiness (g = 0.62, p = .03) and depression (g = -0.32, p = .001), and negligible effects on improving well-being (g = 0.13, p = .24) and negative affect (g = -0.15, p = .31). Subgroup analyses of depression showed that PPIs have experienced benefits in improving depression in most subgroups. In addition, none of the subgroup analyses performed for outcomes other than depression found PPIs to be more effective than controls. CONCLUSION: PPIs can improve positive affect, life satisfaction, happiness and depression in depressed individuals, but further studies are needed to validate their effects on well-being, and negative affect.

16.
Int Wound J ; 21(4): e14562, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38130102

ABSTRACT

Burn injuries result in localised tissue damage and precipitate systemic responses; routine clinical treatments, which typically include metabolic nutritional support and anti-infection therapies, do not yield optimal outcomes. Therefore, we aimed to systematically evaluate the effects of ulinastatin on wound infection and healing in patients with burns to provide reliable evidence-based recommendations for burn treatment. An electronic search of the Web of Science, PubMed, Cochrane Library, Embase, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, supplemented by manual searches, was conducted from database inception to October 2023 to collect randomised controlled trials (RCTs) assessing the efficacy of ulinastatin for the treatment of burns. Two researchers screened all retrieved articles according to the inclusion and exclusion criteria; the included studies were evaluated for quality, and the relevant data were extracted. Stata 17.0 software was employed for data analysis. Overall, 8 RCTs with 803 patients were included, with 404 and 399 in the ulinastatin and conventional treatment groups, respectively. The analysis revealed that wound infections (odds ratio [OR] = 0.08, 95% CI: 0.02-0.35, p = 0.001) and complications (OR = 0.21, 95% CI: 0.10-0.42, p < 0.001) were significantly lower, and wound healing time (standardised mean differences [SMD] = -1.31, 95% CI: -2.05 to -0.57, p = 0.001) was significantly shorter, in the ulinastatin groups than in the control group. This meta-analysis revealed that ulinastatin can effectively reduce the incidence of wound infections and complications and significantly shorten the duration of wound healing in patients with burns, thereby promoting early recovery in these patients.


Subject(s)
Burns , Glycoproteins , Wound Healing , Wound Infection , Humans , Burns/drug therapy , Burns/complications , Wound Healing/drug effects , Wound Infection/drug therapy , Wound Infection/prevention & control , Glycoproteins/therapeutic use , Glycoproteins/pharmacology , Randomized Controlled Trials as Topic , Male , Female , Adult , Middle Aged , Trypsin Inhibitors/therapeutic use
17.
Mycoscience ; 64(6): 150-155, 2024.
Article in English | MEDLINE | ID: mdl-39229282

ABSTRACT

A powdery mildew was found on Leontopodium leontopodioides (Asteraceae) in China. Phylogenetic analyses using a combination of internal transcribed spacer and 28S rDNA sequences showed that this species, which clusters as sister to Neoerysiphe joerstadii, is allied to N. galii, N. geranii, and N. nevoi. This species differs from the closely allied N. joerstadii in the number and size of asci (3-10 asci, 55-75 × 20-40 µm versus 16-32 asci, 40-60 × 20-30 µm). This species is morphologically very similar to N. gnaphalii, but clearly differs from this species in having larger chasmothecia and colorless appendages. Therefore, the powdery mildew on L. leontopodioides is described as N. leontopodii sp. nov.

18.
Angew Chem Int Ed Engl ; : e202407596, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39363761

ABSTRACT

Host-guest chemistry of chiral metal-organic frameworks (MOFs) has endowed them with circularly polarized luminescence (CPL), it is still limited for MOFs to systematically tune full-color CPL emissions and sizes. This work directionally assembles the chiral ligands, metal sites and organic dyes to prepare a series of crystalline enantiomeric D/L-Cd/Zn-n MOFs (n = 1 ~ 5, representing the adding amount of dyes), where D/L-Cd/Zn with the formula of Cd2(D/L-Cam)2(TPyPE) and Zn2(D/L-Cam)2(TPyPE) (D/L-Cam = D/L-camphoric acid, TPyPE = 4,4',4'',4'''-(1,2-henediidenetetra-4,1-phenylene)tetrakis[pyridine]) were used as the chiral platforms.  The framework-dye-enabled emission and through-space chirality transfer facilitate D/L-Cd/Zn-n bright full-color CPL activity. The ideal yellow CPL of D-Cd-5 and D-Zn-4, with |glum| as 4.9 × 10-3 and 1.3 × 10-3 and relatively high photoluminescence quantum yield of 40.79% and 45.40%, are further assembled into a white CPL light-emitting diode. The crystal sizes of D/L-Cd/Zn-n were found to be strongly correlated to the types and additional amounts of organic dyes, that the positive organic dyes allow for the preparation of > 7 mm bulks and negative dyes account for sub-20 µm particles. This work opens a new avenue to fabricate full-color emissive CPL composites and provides a potentially universal method for controlling the size of optical platforms.

19.
Mol Med ; 29(1): 113, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37605109

ABSTRACT

OBJECTIVE: To elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease. METHODS AND RESULTS: The effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression. Our molecular assessment revealed that AGEs activate the RAGE-NF-κB signaling, which then recruits the NF-κB subunit p65 to the RAGE promoter and consequently enhances RAGE transcription, thereby forming a positive feedback loop between the NF-κB signaling and RAGE expression. Increased NF-κB signaling ultimately upregulated Caveolin-1, promoting LDL transcytosis, and inhibition of RAGE suppressed AGE-induced LDL transcytosis. In ApoE-/- mice on a high-fat diet, atherosclerotic plaque formation was accelerated by AGEs but suppressed by EC-specific knockdown of RAGE. CONCLUSION: AGEs accelerate the development of diabetes-related AS by increasing the LDL transcytosis in ECs through the activation of the RAGE/NF-κB/Caveolin-1 axis, which may be targeted to prevent or treat diabetic macrovascular complications.


Subject(s)
Atherosclerosis , NF-kappa B , Animals , Mice , Receptor for Advanced Glycation End Products/genetics , Caveolin 1/genetics , Endothelial Cells , Transcytosis , Glycation End Products, Advanced
20.
Environ Microbiol ; 25(7): 1238-1249, 2023 07.
Article in English | MEDLINE | ID: mdl-36808192

ABSTRACT

Dimethylsulfoniopropionate (DMSP) is a marine organosulfur compound with important roles in stress protection, marine biogeochemical cycling, chemical signalling and atmospheric chemistry. Diverse marine microorganisms catabolize DMSP via DMSP lyases to generate the climate-cooling gas and info-chemical dimethyl sulphide. Abundant marine heterotrophs of the Roseobacter group (MRG) are well known for their ability to catabolize DMSP via diverse DMSP lyases. Here, a new DMSP lyase DddU within the MRG strain Amylibacter cionae H-12 and other related bacteria was identified. DddU is a cupin superfamily DMSP lyase like DddL, DddQ, DddW, DddK and DddY, but shares <15% amino acid sequence identity with these enzymes. Moreover, DddU proteins forms a distinct clade from these other cupin-containing DMSP lyases. Structural prediction and mutational analyses suggested that a conserved tyrosine residue is the key catalytic amino acid residue in DddU. Bioinformatic analysis indicated that the dddU gene, mainly from Alphaproteobacteria, is widely distributed in the Atlantic, Pacific, Indian and polar oceans. For reference, dddU is less abundant than dddP, dddQ and dddK, but much more frequent than dddW, dddY and dddL in marine environments. This study broadens our knowledge on the diversity of DMSP lyases, and enhances our understanding of marine DMSP biotransformation.


Subject(s)
Carbon-Sulfur Lyases , Sulfonium Compounds , Amino Acid Sequence , Carbon-Sulfur Lyases/genetics , Carbon-Sulfur Lyases/metabolism , Oceans and Seas , Sulfonium Compounds/metabolism , Sulfides/metabolism
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