ABSTRACT
Resting cells represent a survival strategy employed by diatoms to endure prolonged periods of unfavourable conditions. In the oceans, many diatoms sink at the end of their blooming season and therefore need to endure cold and dark conditions in the deeper layers of the water column. How they survive these conditions is largely unknown. We conducted an integrative analysis encompassing methods from histology, physiology, biochemistry, and genetics to reveal the biological mechanism of resting-cell formation in the model diatom Thalassiosira pseudonana. Resting-cell formation was triggered by a decrease in light and temperature with subsequent catabolism of storage compounds. Resting cells were characterised by an acidic and viscous cytoplasm and altered morphology of the chloroplast ultrastructure. The formation of resting cells in T. pseudonana is an energy demanding process required for a biophysical alteration of the cytosol and chloroplasts to endure the unfavourable conditions of the deeper ocean as photosynthetic organisms. However, most resting cells (> 90%) germinate upon return to favorable growth conditions.
Subject(s)
Chloroplasts , Diatoms , Light , Diatoms/ultrastructure , Diatoms/physiology , Diatoms/growth & development , Chloroplasts/metabolism , Chloroplasts/ultrastructure , Temperature , Aquatic Organisms , PhotosynthesisABSTRACT
Uremia (UR) is a terminal renal failure manifestation with a very high risk of death, high-flux hemodialysis (HFHD) is currently the most common treatment for UR in clinical practice. In this study, we analysed the therapeutic efficacy of HFHD plus Compound-α Ketoacid Tablets for UR under humanistic care. Firstly, we randomised 100 patients with UR into a research group (RG) for HFHD plus Compound-α Ketoacid Tablets therapy and a control group (CG) for HFHD treatment, with both therapies implemented under humanistic care. By way of comparison, we found that the study group had significantly better renal function after treatment and they had a lower inflammatory response. Also, the study group showed lower calcium and phosphorus metabolism and better immune function. Based on these results, we believe that HFHD + Compound-α Ketoacid Tablets under humanistic care have high clinical value.
Subject(s)
Calcium , Phosphorus , Renal Dialysis , Tablets , Uremia , Humans , Renal Dialysis/methods , Uremia/therapy , Uremia/metabolism , Female , Male , Calcium/metabolism , Middle Aged , Aged , AdultABSTRACT
Context: Chronic renal failure (CRF) is the outcome of the continuous progression of various chronic kidney diseases. Effective treatment of a wide range of diseases may require decreasing patients' negative emotions and enhancing their disease resilience. Narrative care focuses on patients' inner awareness, feelings, and experience of a disease, stimulating positive energy in the face of it. Objective: The study intended to investigate the effects of using narrative care during high flux hemodialysis (HFHD) on clinical outcomes and prognosis of quality of life (QoL) for patients with chronic renal failure (CRF), to provide a reliable theoretical reference for future clinical treatment. Design: The research team performed a randomized controlled trial. Setting: The study took place at the Blood Purification Center at the Affiliated Hospital of Medical School at Ningbo University in Ningbo, Zhejiang, China. Participants: Participants were 78 patients with CRF who received treat with HFHD at the hospital between January 2021 and August 2022. Intervention: The research team divided participants into two groups using the random number table method, with 39 participants in each group: (1) and intervention group who received narrative nursing care and (2) a control group who receive the usual care. Outcome Measures: The research team: (1) evaluated the clinical efficacy for both groups; (2) at baseline and postintervention, measured participants' blood creatinine (SCr) and blood urea nitrogen (BUN) using blood sampling; (3) counted adverse effects; (4) investigated participants' nursing satisfaction postintervention; (5) at baseline and postintervention, assessed psychology and QoL using the Self-Assessment Scale for Anxiety (SAS), the Self-Assessment Scale for Depression (SDS), and the General Quality of Life Inventory (GQOLI-74) scale. Results: No statistically significant differences existed between the groups in terms of efficacy or renal function postintervention (P > .05). The incidence of adverse reactions was significantly lower in the intervention group than in the control group postintervention (P = .033), and the group's nursing satisfaction was significantly higher (P = .042). In addition, participants' SAS and SDS scores decreased significantly in the intervention group postintervention (P < .05), while no change occurred for the control group (P > .05). Finally, the GQOLI-74 scores were all significantly higher in the intervention group than in the control group. Conclusions: Narrative care can effectively enhance the safety of HFHD treatment in CRF patients and reduce patients' negative emotions postintervention, which is important for improving their QoL.
Subject(s)
Kidney Failure, Chronic , Quality of Life , Humans , Prognosis , Kidney Failure, Chronic/therapy , Renal Dialysis , Treatment OutcomeABSTRACT
Approximately 85% of a single administered dose of 5-fluorouracil (5-FU) will be degraded by dihydropyrimidine dehydrogenase (DYPD). Studies have highlighted a link between the complete or partial loss of DYPD function and clinical responses to 5-FU; however, the underlying molecular basis of DPD deficiency remains poorly understood. Hence, the aim of the present study was to evaluate the prevailing hypothesis which suggests that overexpression of LINC00261 possesses the ability to modulate the methylation-dependent repression of DPYD, ultimately resulting in an elevation of the sensitivity of human esophageal cancer cells to 5-FU. LINC00261 levels were initially quantified, followed by analysis of DYPD methylation within the cancerous tissues collected from 75 patients diagnosed with esophageal cancer undergoing 5-FU-based adjuvant chemotherapy. In an attempt to determine the levels of LINC00261 related to the esophageal cancer cell resistance to 5-FU and to identify the interaction between the levels of LINC00261 and methylation of the DYPD promoter, esophageal cancer cells TE-1 and -5 were prepared, in which LINC00261 and the 5-FU-resistant TE-1 and -5 cells were overexpressed. The levels of LINC00261 were reduced among the cancerous tissues obtained from patients exhibiting resistance to 5-FU. Overexpression of LINC00261 was determined to dramatically inhibit proliferation and resistance to apoptosis among 5-FU-resistant TE-1 and -5 cells, whereas silencing of LINC00261 was determined to enhance proliferation and resistance to apoptosis among the TE-1 and -5 cells. DPYD, a confirmed target of LINC00261, displayed a greater incidence of DNA methylation among patient's sensitive to 5-FU. A key finding revealed that overexpressed LINC00261 could increase the methylation of the DPYD promoter through the recruitment of DNA methyltransferase (DNMT), which, in turn, acts to decrease DPYD activity in 5-FU-resistant TE-1 cells, whereas a reversible change was recorded once the demethylation reagent 5-aza-2'-deoxyctidine was employed to treat the 5-FU-resistant TE-1 cells. Taken together, the results of the study provided evidence emphasizing the distinct antitumor ability of LINC00261 in cases of esophageal cancer, which was manifested by overexpression of LINC00261 detected to increase the sensitivity of human esophageal cancer cells to 5-FU by mediating methylation-dependent repression of DPYD. Our study highlighted the potential of LINC00261 as a novel target capable of improving the chemotherapeutic response and survival of patients with esophageal cancer.-Lin, K., Jiang, H., Zhuang, S.-S., Qin, Y.-S., Qiu, G.-D., She, Y.-Q., Zheng, J.-T., Chen, C., Fang, L., Zhang, S.-Y. Long noncoding RNA LINC00261 induces chemosensitization to 5-fluorouracil by mediating methylation-dependent repression of DPYD in human esophageal cancer.
Subject(s)
DNA Methylation/drug effects , DNA, Neoplasm/metabolism , Dihydrouracil Dehydrogenase (NADP)/metabolism , Drug Resistance, Neoplasm/drug effects , Esophageal Neoplasms/metabolism , Fluorouracil/pharmacology , Neoplasm Proteins/metabolism , Promoter Regions, Genetic , RNA, Long Noncoding/metabolism , RNA, Neoplasm/metabolism , Animals , Cell Line, Tumor , DNA Methylation/genetics , DNA, Neoplasm/genetics , Dihydrouracil Dehydrogenase (NADP)/genetics , Drug Resistance, Neoplasm/genetics , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Proteins/genetics , RNA, Long Noncoding/genetics , RNA, Neoplasm/genetics , Xenograft Model Antitumor AssaysABSTRACT
Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species. In order to study the toxic effects, zebrafish embryos were exposed to metalaxyl at nominal concentrations of 5, 50 and 500â¯ng/L for 72â¯hr, and the cardiac development and functioning of larvae were observed. The results showed that metalaxyl exposure resulted in increased rates of pericardial edema, heart hemorrhage and cardiac malformation. The distance between the sinus venosus and bulbus arteriosus, stroke volume, cardiac output and heart rate were significantly increased in larvae exposed to 50 and 500â¯ng/L metalaxyl compared to solvent control larvae. Significant upregulation in the transcription of tbx5, gata4 and myh6 was observed in the 50 and 500â¯ng/L treatments, and that of nkx2.5 and myl7 was observed in the 5, 50 and 500â¯ng/L groups. These disturbances may be related to cardiac developmental and functional defects in the larvae. The activity of Na+/K+-ATPase and Ca2+-ATPase was significantly increased in zebrafish embryos exposed to 500â¯ng/L metalaxyl, and the mRNA levels of genes related to ATPase (atp2a11, atp1b2b, and atp1a3b) (in the 50 and 500â¯ng/L groups) and calcium channels (cacna1ab) (in the 500â¯ng/L group) were significantly downregulated; these changes might be associated with heart arrhythmia and functional failure.
Subject(s)
Alanine/analogs & derivatives , Heart/growth & development , Water Pollutants, Chemical/toxicity , Alanine/toxicity , Animals , Embryo, Nonmammalian , Heart/drug effects , Zebrafish/embryologyABSTRACT
BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer. Little is known about the genetic changes that occur in esophageal cells during the development of ESCC. We performed next-generation sequence analyses of esophageal nontumor, intraepithelial neoplasia (IEN), and ESCC tissues from the same patients to track genetic changes during tumor development. METHODS: We performed whole-genome, whole-exome, or targeted sequence analyses of 227 esophageal tissue samples from 70 patients with ESCC undergoing resection at Shantou University Medical College in China from 2012 through 2015 (no patients had received chemotherapy or radiation therapy); we analyzed normal tissues, tissues with simple hyperplasia, dysplastic tissues (IEN), and ESCC tissues collected from different regions of the esophagus at the same time. We also obtained 1191 nontumor esophageal biopsy specimens from the Chaoshan region (a high-risk region for ESCC) of China (a high-risk region for ESCC) and performed immunohistochemical and histologic analyses to detect inflammation. RESULTS: IEN and ESCC tissues had similar mutations and copy number alterations, at similar frequencies; these differed from mutations detected in tissues with simple hyperplasia. IEN tissues had mutations associated with apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like-mediated mutagenesis (a DNA damage mutational signature). Genetic analyses indicated that most ESCCs were formed from early stage IEN clones. Trunk mutations (mutations shared by >10% of paired IEN and ESCC tissues) were in genes that regulate DNA repair and cell apoptosis, proliferation and adhesion. Mutations in TP53 and CDKN2A and copy number alterations in 11q (contains CCND1), 3q (contains SOX2), 2q (contains NFE2L2), and 9p (contains CDKN2A) were considered to be trunk variants; these were dominant mutations detected at high frequencies in clones of paired IEN and ESCC samples. In the esophageal biopsy samples from high-risk individuals (residing in the Chaoshan region), 68.9% had an evidence of chronic inflammation; the level of inflammation was correlated with atypical cell structures and markers of DNA damage. CONCLUSIONS: We analyzed mutations and gene copy number changes in nontumor, IEN, and ESCC samples, collected from 70 patients. IEN and ESCCs each had similar mutations and markers of genomic instability, including apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like. Genomic changes observed in precancerous lesions might be used to identify patients at risk for ESCC.
Subject(s)
Carcinoma in Situ/genetics , Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , Esophagitis/metabolism , Esophagus/pathology , APOBEC Deaminases/genetics , Apoptosis/genetics , Cell Adhesion/genetics , Cell Proliferation/genetics , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 3/genetics , Chromosomes, Human, Pair 9/genetics , Cyclin-Dependent Kinase Inhibitor p16 , Cyclin-Dependent Kinase Inhibitor p18/genetics , DNA Copy Number Variations , DNA Mutational Analysis , DNA Repair/genetics , Esophagitis/pathology , Esophagus/metabolism , High-Throughput Nucleotide Sequencing , Humans , Hyperplasia/genetics , NF-E2-Related Factor 2/genetics , Phylogeny , SOXB1 Transcription Factors/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
Previously, we found that ASP-ASP-ASP-TYR (DDDY) from Dendrobium aphyllum has a minimum inhibitory concentration of 36.15 mg/mL against Pseudomonas aeruginosa. Here, we explored the antibacterial mechanism of DDDY and its potential preservation applications. Metabolomic and transcriptomic analyses revealed that DDDY mainly affects genes involved in P. aeruginosa membrane transport and amino acid metabolism pathways. Molecular dynamics simulation revealed that DDDY had a stronger effect on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine phospholipid membranes than on 1-palmitoyl-2-oleoyl-lecithin or 1-palmitoyl-2-oleoyl phosphatidylglycerol membranes, with high DDDY concentrations displaying stronger efficacy on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine. Mechanistically, the N-terminal of DDDY first bound to the phospholipid head group, while its C-terminal amino acid residue bound the hydrophobic tail, thereby creating a gap in the membrane when the phospholipids were clustered by hydrogen bonding. Finally, DDDY inhibited the growth of food microorganisms inoculated onto chestnut kernels, suggesting that DDDY is a promising antibacterial agent against multidrug-resistant gram-negative bacteria.
ABSTRACT
AVLP-2, a novel acidic polysaccharide, was isolated and purified from Amomum villosum Lour. The structural characteristics of the polysaccharides were characterized using monosaccharide composition, methylation, FT-IR, and NMR techniques. Results showed that AVLP-2 comprises galactose and glucose monomers, has a molecular weight of 10.488 kDa, and has backbone structures â4)-α-d-GalAp-(1â3,4)-α-d-GalAp-(1â, â4)-α-d-GalAp-(1â6)-α-d-Galp-(1â, and nâ6)-α-d-Galp-(1â4)-ß-d-Glcp-(1â, with α-d-Galp-(1â branches. Furthermore, AVLP-2 had a significant protective effect against oxidative stress in alcohol-induced injury and LPS inflammation models GES-1 cells by regulating the levels of ROS and inflammatory factors. In the animal experiments, AVLP-2 improved the oxidative stress status of the gastric mucosa by increasing SOD activity and GSH levels and inhibiting the excessive generation of malondialdehyde in tissues. The levels of MPO, IL-1ß, IL-10, and NF-κB p65 were downregulated, while that of TNF-α was upregulated by AVLP-2 treatment, thereby reducing the alcohol-induced inflammation.
Subject(s)
Amomum , Amomum/chemistry , Animals , Ethanol , Gastric Mucosa , Inflammation , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Spectroscopy, Fourier Transform InfraredABSTRACT
Procymidone (PCM), a dicarboximide fungicide, is widely used in agriculture to control plant diseases. In the present study, zebrafish embryos were exposed to PCM at 0, 10, 100 and 1000 ng/L for 72 h, the development and cardiac functioning of larvae were observed and determined. The results showed that hatching rate was significantly decreased in the 1000 ng/L treatment, and pericardial edema rate and spine curvature rate were significantly increased in the 100 and 1000 ng/L groups. The PCM-treated larvae exhibited an increased heart rate as well as arrhythmia, and shortened low jaw. The transcription levels of cardiac development-related genes tbx5, nkx2.5, tnnt2, gata4, myh6, myl7, cdh2, ryr2 were altered, which might be responsible for the cardiac developmental and functioning defects in the larvae. The deformation in bone development might be related with the impaired transcription levels of ihh, shh, bmp2b, bmp4, gh, igf1, sox9, gli2. The activities of Na+/K+-ATPase and Ca2+-ATPase were significantly inhibited by 100 ng/L and 1000 ng/L PCM exposure, which might be a cause for the occurrence of pericardial edema and skeletal deformation. The results of this study will be helpful in evaluating the potential threat of PCM to fish population in the aquatic environment.
Subject(s)
Bridged Bicyclo Compounds/chemistry , Zebrafish/embryology , AnimalsABSTRACT
This study was conducted to investigate the biomarkers that appear to be correlated with cancer-related fatigue (CRF) and the adverse reactions (ADRs) to chemotherapy. A total of 100 lung cancer patients were selected and CRF prior to and following chemotherapy was evaluated. The plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 and the level of 17-hydroxycorticosteroid (17-OHCS) in the urine were analyzed and correlated with CRF and the ADRs associated with chemotherapy. The incidence of CRF was found to be 88.0% and ADRs following chemotherapy occurred in 15.0% of the patients. An increase in the TNF-α and IL-1 levels was detected in patients with CRF. The level of 17-OHCS in the urine was found to be elevated in cases that experienced ADRs following chemotherapy. In conclusion, CRF is closely correlated with increased plasma levels of TNF-α and IL-1. Furthermore, an abnormally elevated 17-OHCS level in the urine may be an important indicator predicting ADR development following chemotherapy.