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1.
J Genet Genomics ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38849110

ABSTRACT

Plant height and heading date are important agronomic traits in wheat (Triticum aestivum L.) that affect final grain yield. In wheat, knowledge of pseudo-response regulator (PRR) genes on agronomic traits is limited. Here, we identify a wheat TaPRR95 gene by genome-wide association study to be associated with plant height. Triple allele mutant plants produced by CRISPR/Cas9 show increased plant height, particularly the peduncle, with an earlier heading date. The longer peduncle is mainly caused by the increased cell elongation at its upper section, whilst the early heading date is accompanied by elevated expression of flowering genes, such as TaFT and TaCO1. A peduncle-specific transcriptome analysis reveals up-regulated photosynthesis genes and down-regulated IAA/Aux genes for auxin signaling in prr95aabbdd plants that may act as a regulatory mechanism to promote robust plant growth. A haplotype analysis identifies a TaPRR95-B haplotype (Hap2) to be closely associated with reduced plant height and increased thousand-grain weight. Moreover, the Hap2 frequency is higher in cultivars than that in landraces, suggesting the artificial selection on the allele during wheat breeding. These findings suggest that TaPRR95 is a regulator for plant height and heading date, thereby providing an important target for wheat yield improvement.

2.
Int J Surg ; 110(6): 3633-3640, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38935829

ABSTRACT

Fascial plane blocks (FPBs) are gaining popularity in clinical settings owing to their improved analgesia when combined with either traditional regional anesthesia or general anesthesia during the perioperative phase. The scope of study on FPBs has substantially increased over the past 20 years, yet the exact mechanism, issues linked to the approaches, and direction of future research on FPBs are still up for debate. Given that it can be performed at all levels of the spine and provides analgesia to most areas of the body, the erector spinae plane block, one of the FPBs, has been extensively studied for chronic rational pain, visceral pain, abdominal surgical analgesia, imaging, and anatomical mechanisms. This has led to the contention that the erector spinae plane block is the ultimate Plan A block. Yet even though the future of FPBs is promising, the unstable effect, the probability of local anesthetic poisoning, and the lack of consensus on the definition and assessment of the FPB's success are still the major concerns. In order to precisely administer FPBs to patients who require analgesia in this condition, an algorithm that uses artificial intelligence is required. This algorithm will assist healthcare professionals in practicing precision medicine.


Subject(s)
Nerve Block , Humans , Nerve Block/methods , Pain Management/methods , Anesthetics, Local/administration & dosage , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy , Fascia/innervation
3.
Plants (Basel) ; 13(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732475

ABSTRACT

JASMONATE-ZIM DOMAIN (JAZ) repressor proteins work as co-receptors in the jasmonic acid (JA) signalling pathway and are essential for plant development and environmental adaptation. Despite wheat being one of the main staple food crops, until recently, comprehensive analysis of its JAZ gene family has been limited due to the lack of complete and high-quality reference genomes. Here, using the latest reference genome, we identified 17 JAZ genes in the wheat D-genome donor Aegilops tauschii. Then, 54 TaJAZs were identified in common wheat. A systematic examination of the gene structures, conserved protein domains, and phylogenetic relationships of this gene family was performed. Five new JAZ genes were identified as being derived from tandem duplication after wheat divergence from other species. We integrated RNA-seq data and yield QTL information and found that tandemly duplicated TaJAZ genes were prone to association with spike-related traits. Moreover, 12 TaJAZ genes were located within breeding selection sweeps, including 9 tandemly duplicated ones. Haplotype variation analysis of selected JAZ genes showed significant association of TaJAZ7A and TaJAZ13A with thousand-grain weight. Our work provides a clearer picture of wheat JAZ gene evolution and puts forward the possibility of using these genes for wheat yield improvement.

4.
NEJM Evid ; 3(6): EVIDoa2400026, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38804790

ABSTRACT

BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , Humans , Male , Double-Blind Method , Female , Middle Aged , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/administration & dosage , Adult , COVID-19/virology , SARS-CoV-2 , Aged , Treatment Outcome , Organic Chemicals
5.
Sci Rep ; 14(1): 9223, 2024 04 22.
Article in English | MEDLINE | ID: mdl-38649732

ABSTRACT

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Gefitinib , Lung Neoplasms , Triazoles , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Gefitinib/pharmacology , Triazoles/pharmacology , Triazoles/chemistry , Triazoles/chemical synthesis , Apoptosis/drug effects , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Mice , Cell Line, Tumor , Cell Proliferation/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Xenograft Model Antitumor Assays , A549 Cells , Structure-Activity Relationship
6.
Polymers (Basel) ; 16(6)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38543333

ABSTRACT

In order to solve the problems of insufficient active functions (antibacterial and antioxidant activities) and the poor degradability of traditional plastic packaging materials, biodegradable chitosan (CS)/polyvinyl alcohol (PVA) nanocomposite active films reinforced with natural plant polyphenol-quercetin functionalized layered clay nanosheets (QUE-LDHs) were prepared by a solution casting method. In this study, QUE-LDHs realizes a combination of the active functions of QUE and the enhancement effect of LDHs nanosheets through the deposition and complexation of QUE and copper ions on the LDHs. Infrared and thermal analysis results revealed that there was a strong interface interaction between QUE-LDHs and CS/PVA matrix, resulting in the limited movement of PVA molecules and the increase in glass transition temperature and melting temperature. With the addition of QUE-LDHs, the active films showed excellent UV barrier, antibacterial, antioxidant properties and tensile strength, and still had certain transparency in the range of visible light. As QUE-LDHs content was 3 wt%, the active films exhibited a maximum tensile strength of 58.9 MPa, representing a significant increase of 40.9% compared with CS/PVA matrix. Notably, the UV barrier (280 nm), antibacterial (E. coli) and antioxidant activities (DPPH method) of the active films achieved 100.0%, 95.5% and 58.9%, respectively. Therefore, CS/PVA matrix reinforced with QUE-LDHs has good potential to act as an environmentally and friendly active packaging film or coating.

8.
Mol Plant ; 17(3): 438-459, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38310351

ABSTRACT

The spike architecture of wheat plays a crucial role in determining grain number, making it a key trait for optimization in wheat breeding programs. In this study, we used a multi-omic approach to analyze the transcriptome and epigenome profiles of the young spike at eight developmental stages, revealing coordinated changes in chromatin accessibility and H3K27me3 abundance during the flowering transition. We constructed a core transcriptional regulatory network (TRN) that drives wheat spike formation and experimentally validated a multi-layer regulatory module involving TaSPL15, TaAGLG1, and TaFUL2. By integrating the TRN with genome-wide association studies, we identified 227 transcription factors, including 42 with known functions and 185 with unknown functions. Further investigation of 61 novel transcription factors using multiple homozygous mutant lines revealed 36 transcription factors that regulate spike architecture or flowering time, such as TaMYC2-A1, TaMYB30-A1, and TaWRKY37-A1. Of particular interest, TaMYB30-A1, downstream of and repressed by WFZP, was found to regulate fertile spikelet number. Notably, the excellent haplotype of TaMYB30-A1, which contains a C allele at the WFZP binding site, was enriched during wheat breeding improvement in China, leading to improved agronomic traits. Finally, we constructed a free and open access Wheat Spike Multi-Omic Database (http://39.98.48.156:8800/#/). Our study identifies novel and high-confidence regulators and offers an effective strategy for dissecting the genetic basis of wheat spike development, with practical value for wheat breeding.


Subject(s)
Genome-Wide Association Study , Triticum , Triticum/genetics , Plant Breeding , Gene Regulatory Networks/genetics , Multiomics , Transcription Factors/genetics
9.
Med ; 5(1): 42-61.e23, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38181791

ABSTRACT

BACKGROUND: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. METHODS: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. FINDINGS: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. FUNDING: Funded by Sorrento Therapeutics.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Coronavirus Protease Inhibitors , SARS-CoV-2 , Animals , Humans , Mice , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cathepsin L/antagonists & inhibitors , COVID-19/prevention & control , Disease Models, Animal , Mice, Transgenic , Coronavirus Protease Inhibitors/chemistry , Coronavirus Protease Inhibitors/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , COVID-19 Drug Treatment/methods
10.
Curr Probl Cardiol ; 49(2): 102349, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38103818

ABSTRACT

In routine clinical practice, the diagnosis and treatment of cardiovascular disease (CVD) rely on data in a variety of formats. These formats comprise invasive angiography, laboratory data, non-invasive imaging diagnostics, and patient history. Artificial intelligence (AI) is a field of computer science that aims to mimic human thought processes, learning capacity, and knowledge storage. In cardiovascular medicine, artificial intelligence (AI) algorithms have been used to discover novel genotypes and phenotypes in established diseases enhance patient care, enable cost effectiveness, and lower readmission and mortality rates. AI will lead to a paradigm change toward precision cardiovascular medicine in the near future. The promise application of AI in cardiovascular medicine is immense; however, failure to recognize and ignorance of the challenges may overshadow its potential clinical impact. AI can facilitate every stage in cardiology in the imaging process, from acquisition and reconstruction, to segmentation, measurement, interpretation, and subsequent clinical pathways. Along with new possibilities, new threats arise, acknowledging and understanding them is as important as understanding the machine learning (ML) methodology itself. Therefore, attention is also paid to the current opinions and guidelines regarding the validation and safety of AI. This paper provides a outline for clinicians on relevant aspects of AI and machine learning, selection of applications and methods in cardiology to date, and identifies how cardiovascular medicine could incorporate AI in the future. With progress continuing in this emerging technology, the impact for cardiovascular medicine is highlighted to provide insight for the practicing clinician and to identify potential patient benefits.


Subject(s)
Artificial Intelligence , Cardiovascular Diseases , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/therapy , Feasibility Studies , Algorithms , Machine Learning
11.
Curr Probl Cardiol ; 49(1 Pt C): 102205, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37967803

ABSTRACT

Cardiovascular disease (CVD) and cancer are the two leading causes of morbidity and mortality in the world. The emerging field of cardio-oncology has revealed that these seemingly disparate disease processes are intertwined, owing to the cardiovascular sequelae of anticancer therapies, shared risk factors that predispose individuals to both cardiovascular disease and cancer, as well the possible potentiation of cancer growth by cardiac dysfunction. As a result, interest has increased in understanding the fundamental biological mechanisms that are central to the relationship between CVD and cancer. CVD and cancer frequently coincide in the same patient and often complicate each other. To date, much of the focus in cardio-oncology has been on the cardiovascular complications developed during cancer progression and as a result of cancer treatment. However, the reverse can also be true, and patients with CVD have been shown to be at increased risk of developing cancer (reverse cardio-oncology), as reviewed previously. Recently, the American Heart Association (AHA) updated the Life's Essential 8 (LE8) score, which captures modifiable risk factors, including smoking, body mass index, physical activity, sleep, dietary habits, blood pressure, fasting glucose, and total cholesterol levels, to assess CVH. Many studies have demonstrated a robust association between LE8 and CVD and all-cause mortality in the general population. Beyond assessment and monitoring, using metrics such as LE8 has the unique advantage to identify modifiable risk factors and refers cancer survivors for targeted interventions to manage their CVD risk. Future research in larger study samples is needed to investigate whether the optimal CVD defined by LE8 may differ in population subgroups and implement and evaluate CVD promotion interventions in the high-risk cancer survivor population.


Subject(s)
Cancer Survivors , Cardiovascular Diseases , Neoplasms , United States , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Risk Factors , Smoking/epidemiology , Blood Pressure , Neoplasms/epidemiology
12.
Medicine (Baltimore) ; 102(48): e36230, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38050305

ABSTRACT

INTRODUCTION: Acute mitral regurgitation (MR) due to papillary muscle rupture (PMR) is a rare but lethal mechanical complication of acute myocardial infarction (MI). The treatment of patients with post-MI PMR, especially those with cardiogenic shock, presents great challenges due to the high surgical risk. PATIENT CONCERNS: We report an 80-year-old woman with a history of hypertension and diabetes mellitus, presented with chest pain. Despite an early percutaneous coronary intervention and transfer to the intensive care unit, her general condition and hemodynamic parameters continued to deteriorate rapidly. DIAGNOSIS: Evidenced by electrocardiogram, echocardiogram and coronary angiography, the patient was diagnosed with acute lateral and posterior ST-segment elevation MI, cardiogenic shock, PMR, severe MR, and pulmonary edema. INTERVENTIONS: The patient received percutaneous mitral valve repair with MitraClip (Abbott Vascular, Santa Clara, CA, USA) supported by extracorporeal membranous oxygenation and intra-aortic balloon pump. OUTCOMES: The patient was discharged with relief of heart failure symptoms, reduced MR, and recovery of cardiac function, remaining in a stable condition in New York Heart Association class I after 15-month outpatient follow up. CONCLUSION: Transcatheter edge-to-edge repair with MitraClip can serve as a viable alternative to surgery in reducing MR in post-MI PMR patients at high surgical risk.


Subject(s)
Cardiac Surgical Procedures , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Myocardial Infarction , Humans , Female , Aged, 80 and over , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/surgery , Shock, Cardiogenic/etiology , Myocardial Infarction/complications , Myocardial Infarction/surgery , Myocardial Infarction/diagnosis , Cardiac Surgical Procedures/adverse effects , Echocardiography , Treatment Outcome , Heart Valve Prosthesis Implantation/adverse effects
13.
Int J Biol Macromol ; 253(Pt 1): 126653, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37659483

ABSTRACT

The applications of alginate derived from seaweed polysaccharide in food packaging are restricted due to their inherent deficient antibacterial, antioxidant and UV barrier properties. In this study, nitrogen-functionalized carbon dots (NCDs) with active functions (0.5-3 %) and layered clay (1 %) with barrier property were introduced to construct alginate based active films via solution casting method. The results showed that the synthesized spherical NCDs had a particle size of 2-3 nm, and the internal structure of NCDs was similar to graphene, with a large number of active groups (-NH2, -OH, etc.) on the surface. Infrared analysis revealed that NCDs could form strong hydrogen bonds with alginate matrix, which slowed down the deterioration of mechanical properties and reduced the surface wettability. With the addition of NCDs, active functions and surface hydrophobicity of the active films were enhanced significantly (P < 0.05). When the amount of NCDs reached 3 %, UV barrier, antioxidant and antibacterial properties of the active films were increased by 50.0 %, 61.1 % and 70.1 %, respectively. The addition of NCDs could enhance the anti-browning ability of alginate based coatings and extend the shelf life of banana significantly. Therefore, a suitable amount of NCDs (1-2 %) and layered clay (1 %) can synergistically improve comprehensive performance of alginate based films and promote their food packaging application used as active films/inner coatings.


Subject(s)
Alginates , Carbon , Clay , Antioxidants/pharmacology , Food Packaging , Anti-Bacterial Agents/pharmacology , Nitrogen
14.
Front Pharmacol ; 14: 1238587, 2023.
Article in English | MEDLINE | ID: mdl-37608893

ABSTRACT

Based on the modification of the structure of dolutegravir, we introduced 1,2,3-triazole moieties with different substituted groups and obtained a lot of novel dolutegravir derivatives. The activity of A549 cells treated with the derivatives was examined, and most compounds showed good inhibitory effects. Among them, compounds 4b and 4g were the most effective, and inhibited the growth of A549 cells with IC50 values of 8.72 ± 0.11 µM and 12.97 ± 0.32 µM, respectively. In addition, compound 4g induced apoptosis and clonal suppression in A549 tumor cells. Compound 4g also activated the LC3 signaling pathway to induce autophagy in tumor cells, and activated the γ-H2AX signaling pathway to induce DNA damage in tumor cells.

15.
Plant Biotechnol J ; 21(10): 1990-2001, 2023 10.
Article in English | MEDLINE | ID: mdl-37589238

ABSTRACT

Plant breeding is constrained by trade-offs among different agronomic traits by the pleiotropic nature of many genes. Genes that contribute to two or more favourable traits with no penalty on yield are rarely reported, especially in wheat. Here, we describe the editing of a wheat auxin response factor TaARF12 by using CRISPR/Cas9 that rendered shorter plant height with larger spikes. Changes in plant architecture enhanced grain number per spike up to 14.7% with significantly higher thousand-grain weight and up to 11.1% of yield increase under field trials. Weighted Gene Co-Expression Network Analysis (WGCNA) of spatial-temporal transcriptome profiles revealed two hub genes: RhtL1, a DELLA domain-free Rht-1 paralog, which was up-regulated in peduncle, and TaNGR5, an organ size regulator that was up-regulated in rachis, in taarf12 plants. The up-regulation of RhtL1 in peduncle suggested the repression of GA signalling, whereas up-regulation of TaNGR5 in spike may promote GA response, a working model supported by differential expression patterns of GA biogenesis genes in the two tissues. Thus, TaARF12 complemented plant height reduction with larger spikes that gave higher grain yield. Manipulation of TaARF12 may represent a new strategy in trait pyramiding for yield improvement in wheat.


Subject(s)
Gene Editing , Triticum , Triticum/genetics , Gibberellins , Plant Breeding , Agriculture , Edible Grain/genetics
16.
Front Chem ; 11: 1222825, 2023.
Article in English | MEDLINE | ID: mdl-37408559

ABSTRACT

Indoleamine 2,3-dioxygenase 1 (IDO1) has attracted much attention in the field of cancer immunotherapy as an immunomodulatory enzyme. To identify potential IDO1 inhibitors, a novel series of compounds with N,N-diphenylurea and triazole structures were synthesized. The designed compounds underwent organic synthesis, and subsequent enzymatic activity experiments targeting IDO1 confirmed their activity at the molecular level. These experiments provided validation for the efficacy of the designed compounds in inhibiting IDO1, compound 3g exhibited an IC50 value of 1.73 ± 0.97 µM. Further molecular docking study further explained the binding mode and reaction potential of compound 3g with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases.

17.
Nutrients ; 15(10)2023 May 18.
Article in English | MEDLINE | ID: mdl-37242256

ABSTRACT

The relationship between the structure of peptides LR5 (LHKFR) and YR6 (YGLYPR) and their antioxidant and anti-inflammatory activity remains unclear. Herein, leucine, tyrosine, proline, and phenylalanine at different positions in the peptides were replaced by Alanine (Ala), and two new pentapeptides (AR5 and LAR5) and four hexapeptides (AGR6, YAR6, YLR6, and YGR6) were obtained. The effect of Ala replacement on the hydrophobicity, cytotoxicity, NO inhibition rate, and active oxygen radical scavenging ability of these peptides and their antioxidant and anti-inflammatory abilities were investigated. The results indicated that the hydrophobicity of the peptides was associated with their amino acid composition and their specific sequence. However, hydrophobicity had no significant effect on cytotoxicity. Ala replacement was shown to enhance hydrophobicity and consequently increased the antioxidant and anti-inflammatory activity of the peptides. The molecular docking studies indicated that the amino acid interactions of the peptide with the Keap1 protein influenced the hydrophobicity and thus affected the antioxidant activity of the peptide.


Subject(s)
Alanine , Oryza , Alanine/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Amino Acid Sequence , Molecular Docking Simulation , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , Peptides/pharmacology , Peptides/chemistry , Amino Acids , Anti-Inflammatory Agents/pharmacology
18.
Int J Biol Macromol ; 236: 123630, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36773867

ABSTRACT

As a traditionally used packaging material, natural cellulose-based paper has poor barrier properties to water and oxygen, which severely limits its wide application in food packaging. In this study, we report a new sustainable approach to producing hydrophobic, high-barrier, and antibacterial packaging materials from cellulose paper. In this process, commercially available microcrystalline cellulose was first modified by long-chain stearic acid to form hydrophobic microcrystalline cellulose ester and then mixed with stearic acid as filler in the subsequent surface coating of bagasse fibre paper. The microcrystalline cellulose ester/stearic acid-coated paper (MSP) exhibited good water repellency and oxygen barrier activity due to a continuous hydrophobic film that formed, which completely covered the pores of the original bagasse fibre paper. The coated MSP sample also showed excellent dimensional stability in water and a good wet tensile strength of 16 MPa. In addition, poly(hexamethylene guanidine) (PHMG) was chemically grafted onto the free carboxyl groups of the MSP surface layer, and the resulting MSP-g-PHMG samples exhibited excellent antibacterial activity against Escherichia coli and Listeria monocytogenes. The biodegradable cellulose-based MSP-g-PHMG sample significantly delayed the decay of raspberry during storage, indicating its potential application in food packaging.


Subject(s)
Cellulose , Food Packaging , Food Packaging/methods , Cellulose/pharmacology , Cellulose/chemistry , Anti-Bacterial Agents/pharmacology , Carbohydrates , Water , Esters/chemistry , Oxygen
19.
Anal Methods ; 15(3): 343-352, 2023 01 19.
Article in English | MEDLINE | ID: mdl-36594622

ABSTRACT

For environmental safety, it is important to establish a simple, rapid, and sensitive method for emerging pollutants. Here, a dispersive solid-phase extraction (d-SPE) method based on an iron-based metal-organic framework (Fe-MIL-88-NH2) combined with high-performance liquid chromatography (HPLC) was developed for tetrabromobisphenol A (TBBPA) in water samples. Fe-MIL-88-NH2 was synthesized using a solvothermal method and completely characterized. Fe-MIL-88-NH2 had good water stability and gave a maximum adsorption capacity of 40.97 mg g-1 for TBBPA. The adsorption of TBBPA on Fe-MIL-88-NH2 followed Langmuir adsorption models and a pseudo-second-order kinetic model. The bromine ion and the hydroxyl group of TBBPA could form strong hydrogen bond interactions with the amino protons around the cavity of Fe-MIL-88-NH2, which was in accord with the molecular simulation calculations. Furthermore, several important d-SPE parameters were optimized, such as the amount of materials, extraction time, pH, ionic strength, elution solvent type, and volume. The established method showed good linearity in the concentration range of 0.005-100 µg g-1 (r2 ≥ 0.9996). This method's limits of detection (LOD) and quantification (LOQ) were 0.001 µg g-1 and 0.005 µg g-1, respectively. The recoveries in spiked water samples ranged from 87.5% to 104.9%. The proposed method was applied successfully to detect TBBPA in environmental water samples.


Subject(s)
Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Adsorption , Iron/chemistry , Solid Phase Extraction/methods , Water
20.
Cancer Biother Radiopharm ; 38(2): 132-139, 2023 Mar.
Article in English | MEDLINE | ID: mdl-32822226

ABSTRACT

Background: The procancer effect of TEA domain transcription factor 4 (TEAD4) has been gradually discovered. However, its expression in esophageal cancer (EC) cells and its effect on proliferation and apoptosis have not been reported. In this study, we investigated the possible role of TEAD4 in EC cells. Materials and Methods: TEAD4 messenger RNA and protein expression were assessed in EC cell lines by real-time quantitative-PCR and Western blot. Gene silencing approach was employed to investigate the potential role of TEAD4 in cellular growth, proliferation, migration, and invasion in EC cells. The interaction between TEAD4 and transcription factor 7 (TCF7) was verified by co-immunoprecipitation reaction. The cell apoptosis rates of KYSE-30 cells were detected by flow cytometry. Meanwhile, the expression of apoptosis-related proteins in KYSE-30 cells was detected by Western blot analysis. Results: TEAD4 was significantly increased in EC cell lines, interference of TEAD4 inhibited EC cell viability, invasion, and migration, and promotes apoptosis. TCF7 was found when using STRING website to interact with TEAD4 proteins and TCF7 was significantly increased in EC and knockdown expression of TEAD4 hindered biological function of KYSE-30 cells and this effect was reversed by overexpression of TCF7. Conclusions: The findings concluded that TEAD4 is highly expressed in EC cells and gene silencing of TEAD4 inhibits proliferation and promotes apoptosis of EC cells by regulating TCF7. These findings suggested that TEAD4 might be a novel therapeutic target for the prevention of EC.


Subject(s)
Esophageal Neoplasms , Transcription Factors , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , T Cell Transcription Factor 1/genetics , T Cell Transcription Factor 1/metabolism , Cell Line, Tumor , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Cell Proliferation/genetics , Gene Silencing , Apoptosis/genetics , TEA Domain Transcription Factors
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