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1.
Cancer Med ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35521981

RESUMO

Tumor mutational burden (TMB) is an emerging predictive marker of response to immune checkpoint inhibitor therapies. We evaluated the correlation between clinical indicators and high-throughput sequencing results and TMB in lung adenocarcinoma patients, with the aim of finding simpler and more economical factors as surrogate markers for TMB. The medical records, next-generation sequencing data, and immunohistochemistry results of 340 lung adenocarcinoma patients who were admitted to the First Affiliated Hospital of Zhengzhou University between 2019 and 2020 were collected. The mutated genes were screened for, and the obtained mutated genes were subjected to functional enrichment analysis using R software. A protein-protein interaction (PPI) network was also constructed, and significant modules in the network were identified. Gene Ontology (GO) analyses were performed for the core genes. Univariate and multivariate correlation analyses were performed to judge the correlation between gene mutations and TMB. Genes with a junction mutation rate >1 were selected to construct PPI network and 13 high-connection core genes were screened. The results of GO enrichment analysis showed that the biological processes related to mutant core genes mainly included mitotic cell cycle and cell aging. Subsequently, ATM (p = 0.006) and PIK3CA (p = 0.008) mutation positivity were identified by univariate and multivariate correlation analysis, while TP53 (p = 0.003) and EGFR (p = 0.008) mutation negativity were significantly associated with elevated TMB. The results of this study demonstrate that ATM- and PIK3CA-positive and EGFR-negative mutation status are strongly associated with high levels of TMB and have the potential to be predictive biomarkers of response to immune checkpoint inhibitors in lung adenocarcinoma patients.

2.
Mol Ther Oncolytics ; 25: 98-120, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35506150

RESUMO

The tumor microenvironment (TME) is a well-recognized system that plays an essential role in tumor initiation, development, and progression. Intense intercellular communication between tumor cells and other cells (especially macrophages) occurs in the TME and is mediated by cell-to-cell contact and/or soluble messengers. Emerging evidence indicates that noncoding RNAs (ncRNAs) are critical regulators of the relationship between cells within the TME. In this review, we provide an update on the regulation of ncRNAs (primarily micro RNAs [miRNAs], long ncRNAs [lncRNAs], and circular RNAs [circRNAs]) in the crosstalk between macrophages and tumor cells in hepatocellular carcinoma (HCC). These ncRNAs are derived from macrophages or tumor cells and act as oncogenes or tumor suppressors, contributing to tumor progression not only by regulating the physiological and pathological processes of tumor cells but also by controlling macrophage infiltration, activation, polarization, and function. Herein, we also explore the options available for clinical therapeutic strategies targeting crosstalk-related ncRNAs to treat HCC. A better understanding of the relationship between macrophages and tumor cells mediated by ncRNAs will uncover new diagnostic biomarkers and pharmacological targets in cancer.

3.
Chemosphere ; : 134896, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561770

RESUMO

Ambient mass spectrometry thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) can rapidly identify chemicals without pretreatment of biological samples. This study used a rapid semi-quantitative TD-ESI/MS screening technique for the probe skin sampling of melamine workers occupationally exposed to different ambient melamine concentrations to create avatar-like body images, which were then used to study temporal and dynamic changes in nephrotoxic melamine exposure. We enrolled four voluntary melamine workers from one factory, each from one of four worksites. Melamine exposure was highest in manufacturing and molding, followed by grinding and polishing, packing, and administration, the lowest. Skin samples were collected Friday (end-of-shift) and Monday (pre-shift). Early morning one-spot urine samples were also collected right after skin sampling. 2198 probe skin samples were collected and subjected to semi-quantitative TD-ESI/MS analyses of melamine chemical within 40 h. After normalization, converted body image scores revealed exposure to be highest in the manufacturing worker on Friday and lowest in the administrative worker on Monday. The absolute differences (Friday minus Monday) of normalized body image scores were all significantly positive in each individual worker and across all four workers (permutation test, all p-values < 0.002). The slope estimates of the linear regression line between body image scores and urinary melamine levels were 0.81 (p-value = 0.008). We concluded that this fast and non-invasive technique can potentially be used to study temporal and dynamic changes in exposure to occupational hazards. A future study of developing an automatic and reproducible TD-ESI/MS sampling platform is needed.

4.
Nanomaterials (Basel) ; 12(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35564242

RESUMO

Foodborne pathogens have become the subject of intense interest because of their high incidence and mortality worldwide. In the past few decades, people have developed many methods to solve this challenge. At present, methods such as traditional microbial culture methods, nucleic acid or protein-based pathogen detection methods, and whole-genome analysis are widely used in the detection of pathogenic microorganisms in food. However, these methods are limited by time-consuming, cumbersome operations or high costs. The development of nanopore sequencing technology offers the possibility to address these shortcomings. Nanopore sequencing, a third-generation technology, has the advantages of simple operation, high sensitivity, real-time sequencing, and low turnaround time. It can be widely used in the rapid detection and serotyping of foodborne pathogens. This review article discusses foodborne diseases, the principle of nanopore sequencing technology, the application of nanopore sequencing technology in foodborne pathogens detection, as well as its development prospects.

5.
Molecules ; 27(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35565978

RESUMO

Oxygen/hydrogen-involved reactions are key reactions in many energy-related technologies, such as electrolytic water, electrocatalytic carbon dioxide reduction, electrochemical ammonia synthesis, rechargeable metal-air batteries, and renewable fuel cells [...].

7.
Front Neurosci ; 16: 854219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35527818

RESUMO

Background: Rehabilitation of post-stroke dysphagia is an urgent clinical problem, and repetitive transcranial magnetic stimulation (rTMS) has been widely used in the study of post-stroke function. However, there is no reliable evidence-based medicine to support the effect of rTMS on post-stroke dysphagia. This review aims to evaluate the effectiveness and safety of rTMS on post-stroke dysphagia. Methods: English-language literature published before December 20, 2021, were searched in six electronic databases. Identified articles were screened, data were extracted, and the methodological quality of included trials was assessed. Meta-analysis was performed using RevMan 5.3 software. The GRADE method was used to assess the quality of the evidence. Results: A total of 10 studies with 246 patients were included. Meta-analysis showed that rTMS significantly improved overall swallowing function (standardized mean difference [SMD]-0.76, 95% confidence interval (CI)-1.07 to-0.46, p < 0.0001, n = 206; moderate-quality evidence), Penetration Aspiration Scale (PAS) (mean difference [MD]-1.03, 95% CI-1.51 to-0.55, p < 0.0001, n = 161; low-quality evidence) and Barthel index scale (BI) (MD 23.86, 95% CI 12.73 to 34.99, p < 0.0001, n = 136; moderate-quality evidence). Subgroup analyses revealed that (1) rTMS targeting the affected hemisphere and targeting both hemispheres significantly enhanced overall swallowing function and reduced aspiration. (2) Low-frequency rTMS significantly enhanced overall swallowing function and reduced aspiration, and there was no significant difference between high-frequency rTMS and control group in reducing aspiration (p = 0.09). (3) There was no statistical difference in the dropout rate (low-quality evidence) and adverse effects (moderate-quality evidence) between the rTMS group and the control group. Conclusion: rTMS improved overall swallowing function and activity of daily living ability and reduced aspiration in post-stroke patients with good acceptability and mild adverse effects.

8.
PLoS One ; 17(5): e0268262, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522690

RESUMO

Bovine mastitis is a common disease occurring in dairy farms and can be caused by more than 150 species of pathogenic bacteria. One of the most common causative organisms is Streptococcus agalactiae, which is also potentially harmful to humans and aquatic animals. At present, research on S. agalactiae in China is mostly concentrated in the northern region, with limited research in the southeastern and southwestern regions. In this study, a total of 313 clinical mastitis samples from large-scale dairy farms in five regions of Sichuan were collected for isolation of S. agalactiae. The epidemiological distribution of S. agalactiae was inferred by serotyping isolates with multiplex polymerase chain reaction. Susceptibility testing and drug resistance genes were detected to guide the clinical use of antibiotics. Virulence genes were also detected to deduce the pathogenicity of S. agalactiae in Sichuan Province. One hundred and five strains of S. agalactiae (33.6%) were isolated according to phenotypic features, biochemical characteristics, and 16S rRNA sequencing. Serotype multiplex polymerase chain reaction analysis showed that all isolates were of type Ia. The isolates were up to 100% sensitive to aminoglycosides (kanamycin, gentamicin, neomycin, and tobramycin), and the resistance rate to ß-lactams (penicillin, amoxicillin, ceftazidime, and piperacillin) was up to 98.1%. The TEM gene (ß-lactam-resistant) was detected in all isolates, which was in accordance with a drug-resistant phenotype. Analysis of virulence genes showed that all isolates harbored the cfb, cylE, fbsA, fbsB, hylB, and α-enolase genes and none harbored bac or lmb. These data could aid in the prevention and control of mastitis and improve our understanding of epidemiological trends in dairy cows infected with S. agalactiae in Sichuan Province.


Assuntos
Mastite Bovina , Infecções Estreptocócicas , Animais , Antibacterianos/farmacologia , Bovinos , Resistência Microbiana a Medicamentos , Feminino , Humanos , Mastite Bovina/epidemiologia , Mastite Bovina/microbiologia , Tipagem Molecular , Prevalência , RNA Ribossômico 16S , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae , Virulência/genética , Fatores de Virulência/genética
9.
Curr Org Synth ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35579128

RESUMO

BACKGROUND AND OBJECTIVE: As a key pharmacophore, cyano group widely exists in a variety of biologically active compounds. Besides, nitriles are also valuable intermediates for many common functional groups. in this current work, a new synthesis strategy was developed to obtain nitriles from aldehydes. METHODS: Using commercially available aldehydes as raw materias, hydroxylamine hydrochloride as nitrogen source, the corresponding nitrile compounds were successfully synthesized by one-pot method through the promotion of imidazole hydrochloride. And it was characterized by 1H NMR, 13C NMR and mass spectrometry. RESULTS: Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of nitriles. The highest yields (95%) was achieved using sulfolane as solvent, imidazole hydrochloride as promoter. CONCLUSION: In conclusion, we developed a new synthetic method for nitrile compounds from aldehydes. 27 examples of functionalized nitrile compounds have been synthesized in good to excellent yields. This methodology features that an environmentally benign imidazole hydrochloride replaces transition metal catalysts and oxidants required in conventional strategies to convert aldehydes to nitriles with good functional group tolerability. Further exploration of imidazole hydrochloride is ongoing in our laboratory.

10.
Front Immunol ; 13: 857490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422818

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, which has broken out worldwide for more than two years. However, due to limited treatment, new cases of infection are still rising. Therefore, there is an urgent need to understand the basic molecular biology of SARS-CoV-2 to control this virus. SARS-CoV-2 replication and spread depend on the recruitment of host ribosomes to translate viral messenger RNA (mRNA). To ensure the translation of their own mRNAs, the SARS-CoV-2 has developed multiple strategies to globally inhibit the translation of host mRNAs and block the cellular innate immune response. This review provides a comprehensive picture of recent advancements in our understanding of the molecular basis and complexity of SARS-CoV-2 protein translation. Specifically, we summarize how this viral infection inhibits host mRNA translation to better utilize translation elements for translation of its own mRNA. Finally, we discuss the potential of translational components as targets for therapeutic interventions.


Assuntos
COVID-19 , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Viral , Ribossomos/metabolismo , SARS-CoV-2
11.
Clin Neurophysiol ; 138: 163-172, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35453016

RESUMO

OBJECTIVE: Recent neuroimaging studies have demonstrated that burnout is linked to specific anatomical and functional abnormalities in the brain. However, topological alterations of brain networks are not yet characterized in burnout. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 32 female participants with burnout and 30 matched healthy controls. Subsequently, we employed graph theoretical and network-based statistic (NBS) methods to analyze the functional connectivity. We further explored the causal influences between brain regions using the Granger Causal Analysis. Finally, partial correlation analyses were conducted between clinical scores and the altered network properties as well as connectivity metrics. RESULTS: Both the participants with burnout and healthy controls displayed a small-world organization. However, participants with burnout showed increased characteristic path length and decreased global efficiency. Corresponding local changes were mainly distributed in the visual network (2/3,66.67%). With the network-based statistic (NBS) approach, significantly decreased effective connectivities were observed mainly between the visual network and the right hippocampus. In addition, characteristic path length and nodal local efficiency of the left fusiform gyrus showed a significant negative correlation with depression severity. CONCLUSIONS: The present psychopathological findings reflect the disrupted global integration of the functional network related to the traits of participants with burnout. SIGNIFICANCE: These findings deliver novel insights from a full network perspective into the brain mechanisms of burnout.

13.
Arch Pharm Res ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35478401

RESUMO

One new clerodane-type furanoditerpenoid tinosinoid A (1) and nine new nor-clerodane analogs tinosinoids B-J (2-10) have been isolated from the stems of Tinospora sinensis. The structures of the new compounds with absolute configurations have been elucidated by spectroscopic means, including MS, NMR and ECD techniques, as well as chemical correlation. Compound 1 is a rare sulfur-containing clerodane diterpenoid incorporating a 2-mercaptoethanol unit via a thioether bond, while compounds 4/5 and 9 represent two pairs of unusual equilibrium regioisomers through an interesting intramolecular transesterification. Our bioassays established that 1 and 8 displayed moderate antiproliferative effects against two human tumor cell lines, and 9 and 10 showed significant α-glucosidase inhibitory activities. A kinetics study revealed that compound 10 was a noncompetitive α-glucosidase inhibitor, and its possible binding mode to the enzyme was further probed by molecular docking experiments.

14.
Ann Med ; 54(1): 1233-1243, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35486415

RESUMO

OBJECTIVE: Ischemia-reperfusion injury affects postoperative transplanted kidney function in kidney transplant recipients. Dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation, but its propensity to cause bradycardia and hypotension may adversely affect microcirculation. This study investigated the effect of dexmedetomidine on postoperative renal function and sublingual microcirculation in kidney recipients. METHODS: The enrolled kidney transplant recipients were randomly allocated to the control group or dexmedetomidine group. After anaesthesia induction, patients in the dexmedetomidine group received dexmedetomidine infusion until 2 h after surgery. Sublingual microcirculation was recorded using an incident dark-field video microscope and analysed. The primary outcomes were the creatinine level on a postoperative day 2 and total vessel density at 2 h after surgery. RESULTS: A total of 60 kidney recipients were analysed, and the creatinine levels on postoperative day 2 were significantly lower in the dexmedetomidine group than in the control group (1.5 (1.1-2.4) vs. 2.2 (1.7-3.0) mg/dL, median difference -0.6 (95% CI, -0.7 to -0.5) mg/dL, p = .018). On a postoperative day 7, the creatinine levels did not differ significantly between the two groups. Total vessel density at 2 h after surgery did not differ significantly between the two groups. CONCLUSION: We found that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine infusion, but total vessel density was not significantly different between the intervention and control groups. Key messagesIschemia-reperfusion injury affects postoperative transplanted kidney function, and dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation in other clinical conditions.This study showed that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine.Dexmedetomidine's side effect of bradycardia and hypotension may affect microcirculation, our results revealed that the perioperative sublingual microcirculation did not differ significantly in kidney transplant recipients receiving dexmedetomidine.


Assuntos
Dexmedetomidina , Hipotensão , Transplante de Rim , Traumatismo por Reperfusão , Bradicardia , Creatinina , Dexmedetomidina/efeitos adversos , Humanos , Rim , Transplante de Rim/efeitos adversos , Microcirculação , Traumatismo por Reperfusão/prevenção & controle
15.
Biomed Pharmacother ; 150: 112998, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489281

RESUMO

Diabetic nephropathy (DN), which is characterized by renal fibrosis, is a major complication of diabetes, a disease that afflicted more than 460 million people worldwide in 2019. Pyroptosis is an essential signaling pathway in DN-related injuries, such as renal fibrosis. Pyrroloquinoline quinone (PQQ) is a naturally occurring bioactive compound that protects human kidney 2 (HK-2) cells from oxidative stress-induced damage caused by high glucose concentrations. However, the nature and underlying mechanism of the effect of PQQ on DN-related renal fibrosis remains unclear. In this study, we evaluated whether PQQ has potential protective effects against renal fibrosis due to DN by establishing type 1 diabetes in mice via streptozotocin treatment and then inhibiting their pyroptosis signaling pathway. We found that compared to control mice, the area of renal fibrosis and injury were significantly increased in diabetic mice, and this was accompanied by increased levels of expression of collagen Ⅰ and transforming growth factor-ß1; increased concentrations of the inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α; and activation of the pyroptosis pathway components nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, IL-1ß, and IL-18. All of these changes were reversed by PQQ treatment. Analogously, we treated cultured HK-2 cells with a high concentration of glucose (35 mmol/L), which caused these cells to exhibit significantly increased concentrations of reactive oxygen species (ROS), phosphorylated (p)-nuclear factor kappa B (NF-κB), p-IkappaB, NLRP3, caspase-1, IL-1ß, and IL-18, and the loss of mitochondrial transmembrane potential. However, PQQ treatment significantly blunted these effects. In conclusion, in this study we demonstrated that PQQ attenuates renal fibrosis by alleviating mitochondrial dysfunction, reducing ROS production, and inhibiting the activation of the NF-κB/pyroptosis pathway under conditions of DN and hyperglycemia.

16.
Ecotoxicol Environ Saf ; 237: 113510, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35468440

RESUMO

Nitrite in the aquatic environment potentially disturbs thyroid hormone (TH) homeostasis in peripheral tissues, but little is known about TH metabolism in the intestine. This study investigated the serum concentrations of THs and thyroid-stimulating hormone (TSH) as well as the activity of intestinal iodothyronine deiodinases (IDs) of grass carp (Ctenopharyngodon idellus) exposed to various concentrations of nitrite (0, 8, 25, or 50 mg/L) for 96 h. Acute nitrite exposure significantly altered the triiodothyronine (T3) levels and the morphology of thyroid follicles at 96 h. Thyroxine (T4), free T4 levels and intestinal IDs activities showed an increase trend under nitrite stress. After 96 h exposure, nitrite down-regulated the expressions levels of intestinal Akt1 protein, sugar transporter genes, and thyroid hormone receptor (TR) signaling pathway genes except for tr É‘1 and tr É‘2. Moreover, the expressions levels of pparγ, cpt1α, cd36, fabp2 and fatp4 were down-regulated, whereas fabp6 and lpl were up-regulated in the 50 mg/L exposure group at 96 h. The results indicate that acute nitrite exposure has the potential to disturb the homeostasis of intestinal TH metabolism, which in turn alters TRs genes transcription, down-regulates sugar transporter activities, and promotes the energy expenditure in gut of grass carp.


Assuntos
Carpas , Hormônios Gastrointestinais , Animais , Carpas/metabolismo , Hormônios Gastrointestinais/metabolismo , Homeostase , Iodeto Peroxidase/genética , Nitritos , Açúcares/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Tiroxina , Tri-Iodotironina/metabolismo
17.
Int J Mol Sci ; 23(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35409050

RESUMO

(1) Background: In recent years, the porcine reproductive and respiratory syndrome virus (PRRSV) has become a virulent pathogen that has caused devastating diseases and economic losses worldwide in the swine industry. IRPS has attracted extensive attention in the field of virology. However, it is not clear that IRPS has an antiviral effect on PRRSV at gene and protein levels. (2) Methods: We used transcriptomic and proteomic analysis to investigate the antiviral effect of IRPS against PRRSV. Additionally, a microbiome was used to explore the effects of IRPS on gut microbes. (3) Results: IRPS significantly extenuated the pulmonary pathological lesions and inflammatory response. We used transcriptomic and proteomic analysis to investigate the antiviral effect of IRPS against PRRSV. In the porcine model, 1669 differentially expressed genes (DEGs) and 370 differentially expressed proteins (DEPs) were identified. Analysis of the DEG/DEP-related pathways indicated immune-system and infectious-disease (viral) pathways, such as the NOD-like receptor (NLR) signaling pathway, toll-like receptor (TLR) signaling pathway, and Influenza A-associated signaling pathways. It is noteworthy that IRPS can inhibit NLR-dependent gene expression, then reduce the inflammatory damage. IRPS could exert beneficial effects on the host by regulating the structure of intestinal flora. (4) Conclusions: The antiviral effect of IRPS on PRRSV can be directly achieved by omics techniques. Specifically, the antiviral mechanism of IPRS can be better elucidated by screening target genes and proteins using transcriptome and proteome sequencing, and then performing enrichment and classification according to DEGs and DEPs.


Assuntos
Isatis , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Antivirais , Polissacarídeos , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Síndrome Respiratória e Reprodutiva Suína/genética , Proteoma , Proteômica , Suínos , Transcriptoma
18.
Front Microbiol ; 13: 854908, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387089

RESUMO

With the improper use of antibiotics, an increasing number of multidrug-resistant bacteria have been reported worldwide, posing challenges for disease treatment. Klebsiella pneumoniae is an important zoonotic pathogen that colonises the respiratory tract. Endolysin therapy has emerged with the development of phages. In this study, a lytic phage vB_KpnS_MK54 was isolated from the drinking water of a forest musk deer (FMD) farm in Sichuan Province. It was the first reported phage obtained from FMD. The primary biological characteristics were determined, and whole-genome sequencing analysis was performed. The phage which belongs to the family Siphoviridae is highly specific for lytic host bacteria and is moderately adaptable to different environments. Whole-genome sequencing results showed that the phage genome size was 46,218 bp. There were 80 coding DNA sequences (CDSs) in total, 32 of which had known functions. The last CDS is the phage endolysin LysG24. A new peptide-modified endolysin (LysCA) was constituted by connecting the cecropin A peptide residues with LysG24 to investigate the antibacterial activities of both LysG24 and LysCA. The results showed that the lytic profile of LysG24 and LysCA was wider than that of phage MK54. For in vitro tests, both endolysins destroyed 99% of the host bacteria within 6 h. The lysing ability and environmental adaptability of LysCA were significantly stronger than those of LysG24. For in vivo tests, LysG24 and LysCA exhibited therapeutic effects in a mouse model of pneumonia wherewith the mice were infected with K. pneumoniae (LPKP), wherein both LysG24 and LysCA can effectively reduce the pulmonary inflammatory response. The LPKP bacterial load in the treatment group was significantly lower than that in the bacterial group, among which LysCA displayed a more obvious therapeutic effect. Furthermore, the safety test showed that the endolysins had no toxic effects on mice. In general, both LysG24 and LysCA showed excellent antibacterial activity in vivo and in vitro, with high safety and strong adaptability to the environment, manifesting their latent potential as new antimicrobial agents.

19.
Nano Lett ; 22(9): 3707-3712, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35467349

RESUMO

Amyloid peptide (AP) self-assembly is a hierarchical process. However, the mechanistic rule of guiding peptides to organize well-ordered nanostructure in a clear and precise manner remains poorly understood. Herein we explored the molecular insight of AP motif aggregates underlying hierarchical process with helical fibrillar structure by atomic force microscope, cryo-electron microscopy (cryo-EM), and molecular dynamics simulation. AP assembly encompasses well-ordered twisted fibrils with uniform morphology, size, and periodicity. More importantly, a heterozipper ß-sheet was identified in a protofilament of AP assembly determined by cryo-EM with a high resolution of 3.5 Å. Each peptide heterozipper was further composed of two antiparallel ß strands and arranged by an alternative manner in a protofilament. The hydrophobic core and hydrophilic area in each zipper played the significant role for peptide assembling. This work proposed and verified the rule facilitating the basic building unit to form twisted fibrils and gave the explanation of peptide hierarchical assembling.

20.
Front Chem ; 10: 867318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433636

RESUMO

Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis, Sophora alopecuroides, Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.

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