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1.
Genome Biol ; 23(1): 197, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127735

RESUMO

BACKGROUND: It is challenging to determine the effect of DNA methylation on the epigenetic landscape and the function in higher organisms due to the lack of DNA methylation-free mutants. RESULTS: Here, the analysis of a recently generated Arabidopsis mutant completely devoid of DNA methylation reveals that DNA methylation underpins the genome-wide landscape of histone modifications. Complete loss of DNA methylation causes an upheaval of the histone modification landscape, including complete loss of H3K9me2 and widespread redistribution of active and H3K27me3 histone marks, mostly owing to the role of DNA methylation in initiating H3K9me2 deposition and excluding active marks and repressive mark H3K27me3; CG and non-CG methylation can act independently at some genomic regions while they act cooperatively at many other regions. The transcriptional reprogramming upon loss of all DNA methylation correlates with the extensive redistribution or switches of the examined histone modifications. Histone modifications retained or gained in the DNA methylation-free mutant serve as DNA methylation-independent transcriptional regulatory signals: active marks promote genome transcription, whereas the repressive mark H3K27me3 compensates for the lack of DNA hypermethylation/H3K9me2 at multiple transposon families. CONCLUSIONS: Our results show that an intact DNA methylome constitutes the scaffolding of the epigenomic landscape in Arabidopsis and is critical for controlled genome transcription and ultimately for proper growth and development.


Assuntos
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , DNA , Metilação de DNA , Epigênese Genética , Epigenômica , Histonas/metabolismo , Humanos
2.
Clin Nutr ; 41(10): 2284-2294, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36096062

RESUMO

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

3.
J Orthop Surg Res ; 17(1): 418, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104705

RESUMO

BACKGROUND AND OBJECTIVE: As an important mediator of intercellular interaction and formation of extracellular bone matrix, porous scaffolds are widely used for bone regeneration. Accumulating evidences demonstrate that microRNA are involved in the regulation of scaffolds-induced bone regeneration. Recently, we revealed that miR-210-3p was highly expressed during osteogenesis induced by HAG. In present study, we further explored the molecular mechanism underlying the effect of miR-210-3p on osteogenic differentiation. MATERIALS AND METHODS: In this study, miR-210-3p mimics and inhibitors were synthesized and transfected into MC3T3-E1 cells to explore their effects on osteogenic differentiation. The expression of osteogenic marker (Alp and Runx2) were detected by real-time quantitative PCR (qRT-PCR) and western blotting. After osteogenesis induction for 7 days, Alp staining were used to detected osteoblast differentiation of MC3T3-E1 cells. CCK8 and Transwell assays were performed to detected cell proliferation and migration. Then, top ranking list of target genes of miR-210-3p obtained from TargetScan and the expression of BDNF were detected by qRT-PCR and ELISA. The relationship between miR-210-3p and BDNF was verified by luciferase report assay. Furthermore, the effect of BDNF on osteoblast differentiation was verified by transfecting siRNA or adding BDNF to the culture medium. RESULTS: MiR-210-3p mimics markedly suppress osteogenic differentiation, cell migration and cell proliferation of MC3T3-E; nevertheless, silencing of miR-210-3p dramatically enhanced MC3T3-E1 osteogenesis, cell migration and proliferation. Furthermore, luciferase reporter assay verified that brain derived neurotrophic factor (BDNF) is a directly target of miR-210-3p. Moreover, BDNF siRNA significantly decreased the expression levels of ALP and cell migration. The addition of BDNF partially rescued the inhibition of osteogenesis by miR-210-3p. CONCLUSION: miR-210-3p inhibited the osteogenic differentiation via targeting BDNF. Our Results provide a promising target for regulating osteogenic differentiation.


Assuntos
MicroRNAs , Osteogênese , Fator Neurotrófico Derivado do Encéfalo/genética , Diferenciação Celular/genética , MicroRNAs/metabolismo , Osteogênese/genética , RNA Interferente Pequeno
4.
Chin Herb Med ; 14(1): 104-110, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36120135

RESUMO

Objective: Fufang Biejia Ruangan Tablet (FBRT) is widely used for the treatment of liver fibrosis. However, Hominis Placenta (HP), as an important adjuvant of FBRT, has been restricted for medicinal using due to the limited availability, ethical controversy and safety issues. The present study aimed to investigate the therapeutic effects of novel FBRT (N-FBRT) with sheep placenta (SP) as substitute for HP on liver fibrosis and explore its possible mechanisms. Different dosages of SP in N-FBRT were also evaluated. Methods: Rats were subcutaneously injected with CCl4 to induce liver fibrosis and then treated with N-FBRT and FBRT. The anti-hepatic fibrosis effect was determined based on biomarkers analysis of liver function and hepatic fibrosis, and the liver pathology was visualized by H&E staining and Masson staining. The oxidative stress and inflammatory cytokines were also detected. Immunohistochemical staining of α-SMA, real time PCR and Western blotting were performed to evaluate hepatic stellate cells (HSCs) activation and TGF-ß1/Smad signaling pathway. Results: N-FBRT and FBRT could ameliorate CCl4-induced liver fibrosis and improve liver function, as evidenced by lowering serum biomarkers levels of liver function and hepatic fibrosis, and decreasing hepatic Hyp content and collagen deposition, and improving the hepatic morphology and architecture changes. Moreover, the anti-liver fibrosis effect was better when the dosage of SP used in N-FBRT was 1/2 of HP in FBRT. Administration of N-FBRT markedly alleviated oxidative stress and inflammatory cytokines, and inhibited α-SMA expression. Furthermore, the mRNA expression of Col I, Col III, α-SMA and TGF-ß1, and proteins expression of α-SMA, TGF-ß1, Smad2/3 and p-Smad2/3 were significantly down-regulated by N-FBRT treatment. Conclusion: SP can be used as substitute for HP to prepare N-FBRT for the treatment of liver fibrosis and the anti-liver fibrosis effect of N-FBRT is achieved by eliminating oxidative stress and inflammation, and inhibiting HSCs activation and ECM production by blocking TGF-ß1/Smad signaling pathway.

6.
Front Pharmacol ; 13: 977025, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059952

RESUMO

Background: The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with anticancer drug sensitivity, and provide new potential targets and treatment options for cancers. Methods: We investigated the differential expression of 15 efferocytosis-related molecules (Axl, Tyro3, MerTK, CX3CL1, Tim-4, BAI1, Stab2, Gas6, IDO1, Rac1, MFGE8, ICAM-1, CD47, CD31, and PD-L1) and other 12 common immune checkpoint-related molecules in tumor and normal tissues, the correlation between their expression and various clinicopathological features in 16 types of cancers using publicly available pancancer datasets in The Cancer Genome Atlas. We also analyzed the correlation of the expression of efferocytosis and immune checkpoint related molecules with 126 types of anticancer drugs sensitivity using drug-RNA-seq data. Results: There is a panel of circulating molecules among the 27 molecules. Based on the results of differential expression and correlation with various clinicopathological features of efferocytosis-related molecules in cancers, we identified new potential therapeutic targets for anticancer therapy, such as Axl for kidney renal clear cell carcinoma, Tyro3 for liver hepatocellular carcinoma, and IDO1 for renal papillary cell carcinoma. Except for BAI1, CD31, and MerTK, the enhanced expressions of Axl, Tyro3, Gas6, MFGE8, Stab2, Tim-4, CX3CL1, IDO1, Rac1, and PD-L1 were associated with decreased sensitivity of the cancer cells to many anti-cancer drugs; however, for other common immune checkpoint-related molecules, only enhanced expressions of PD-1, CD28, CTLA4, and HVEM were associated with decreased sensitivity of the cancer cells to a few drugs. Conclusion: The efferocytosis-related molecules were significantly associated with clinical outcomes in many types of cancers and played important roles in resistance to chemotherapy. Combination therapy targeting efferocytosis-related molecules and other immune checkpoint-related molecules is necessary to reduce resistance to chemotherapy.

7.
Front Oncol ; 12: 972357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091151

RESUMO

Objective: Using visual bibliometric analysis, the application and development of artificial intelligence in clinical esophageal cancer are summarized, and the research progress, hotspots, and emerging trends of artificial intelligence are elucidated. Methods: On April 7th, 2022, articles and reviews regarding the application of AI in esophageal cancer, published between 2000 and 2022 were chosen from the Web of Science Core Collection. To conduct co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references, and keywords in this field, VOSviewer (version 1.6.18), CiteSpace (version 5.8.R3), Microsoft Excel 2019, R 4.2, an online bibliometric platform (http://bibliometric.com/) and an online browser plugin (https://www.altmetric.com/) were used. Results: A total of 918 papers were included, with 23,490 citations. 5,979 authors, 39,962 co-cited authors, and 42,992 co-cited papers were identified in the study. Most publications were from China (317). In terms of the H-index (45) and citations (9925), the United States topped the list. The journal "New England Journal of Medicine" of Medicine, General & Internal (IF = 91.25) published the most studies on this topic. The University of Amsterdam had the largest number of publications among all institutions. The past 22 years of research can be broadly divided into two periods. The 2000 to 2016 research period focused on the classification, identification and comparison of esophageal cancer. Recently (2017-2022), the application of artificial intelligence lies in endoscopy, diagnosis, and precision therapy, which have become the frontiers of this field. It is expected that closely esophageal cancer clinical measures based on big data analysis and related to precision will become the research hotspot in the future. Conclusions: An increasing number of scholars are devoted to artificial intelligence-related esophageal cancer research. The research field of artificial intelligence in esophageal cancer has entered a new stage. In the future, there is a need to continue to strengthen cooperation between countries and institutions. Improving the diagnostic accuracy of esophageal imaging, big data-based treatment and prognosis prediction through deep learning technology will be the continuing focus of research. The application of AI in esophageal cancer still has many challenges to overcome before it can be utilized.

8.
Front Pharmacol ; 13: 963672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091756

RESUMO

Diabetic cardiomyopathy seriously affects quality of life and even threatens life safety of patients. The pathogenesis of diabetic cardiomyopathy is complex and multifactorial, and it is widely accepted that its mechanisms include oxidative stress, inflammation, insulin resistance, apoptosis, and autophagy. Some studies have shown that gut microbiota plays an important role in cardiovascular diseases. Gut microbiota and its metabolites can affect the development of diabetic cardiomyopathy by regulating oxidative stress, inflammation, insulin resistance, apoptosis, and autophagy. Here, the mechanisms of gut microbiota and its metabolites resulting in diabetic cardiomyopathy are reviewed. Gut microbiota may be a new therapeutic target for diabetic cardiomyopathy.

9.
Am J Clin Nutr ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36095136

RESUMO

BACKGROUND: Diagnosing cancer cachexia relies extensively on the patient-reported historic weight, and failure to accurately recall this information can lead to severe underestimation of cancer cachexia. OBJECTIVES: The present study aimed to develop inexpensive tools to facilitate the identification of cancer cachexia in patients without weight loss information. METHODS: This multicenter cohort study included 12774 patients with cancer. Cachexia was retrospectively diagnosed using Fearon's framework. Baseline clinical features, excluding weight loss, were modeled to mimic a situation where the patient is unable to recall their weight history. Multiple machine learning (ML) models were trained using 75% of the study cohort to predict cancer cachexia, with the remaining 25% of the cohort used to assess model performance. RESULTS: The study enrolled 6730 males and 6044 females (median age = 57.5 years). Cachexia was diagnosed in 5261 (41.2%) patients and most diagnoses were made based on the weight loss criterion. A 15-variable logistic regression (LR) model mainly comprising cancer types, gastrointestinal symptoms, tumor stage and serum biochemistry indices was selected among the various ML models. The LR model showed good performance for predicting cachexia in the validation data (area under the curve = 0.763, 95% confidence interval=[0.747, 0.780]). The calibration curve of the model demonstrated good agreement between predictions and actual observations (accuracy = 0.714, Kappa = 0.396, sensitivity = 0.580, specificity = 0.808, positive predictive value = 0.679, negative predictive value = 0.733). Subgroup analyses showed that the model was feasible in patients with different cancer types. The model was deployed as an online calculator and a nomogram, and was exported as predictive model markup language to permit flexible, individualized risk calculation. CONCLUSIONS: We developed a ML model that can facilitate the identification of cancer cachexia in patients without weight loss information, which might improve decision-making and lead to the development of novel management strategies in cancer care.

10.
Front Pharmacol ; 13: 950368, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081932

RESUMO

Background: Traumatic spinal cord injury (t-SCI) is a severe injury that has a devastating impact on neurological function. Blood spinal cord barrier (BSCB) destruction following SCI aggravates the primary injury, resulting in a secondary injury. A series of experimental treatments have been proven to alleviate BSCB destruction after t-SCI. Methods: From a screen of 1,189 papers, which were retrieved from Pubmed, Embase, and Web of science, we identified 28 papers which adhered to strict inclusion and exclusion criteria. Evans blue (EB) leakage on the first day post-SCI was selected as the primary result. Secondary outcomes included the expression of tight junction (TJ) proteins and adhesion junction (AJ) proteins in protein immunoblotting. In addition, we measured functional recovery using the Basso, Beattie, Besnahan (BBB) score and we analyzed the relevant mechanisms to explore the similarities between different studies. Result: The forest plot of Evans blue leakage (EB leakage) reduction rate: the pooled effect size of the 28 studies was 0.54, 95% CI: 0.47-0.61, p < 0.01. This indicates that measures to mitigate BSCB damage significantly improved in reducing overall EB leakage. In addition TJ proteins (Occludin, Claudin-5, and ZO-1), AJ proteins (P120 and ß-catenin) were significantly upregulated after treatment in all publications. Moreover, BBB scores were significantly improved. Comprehensive studies have shown that in t-SCI, inhibition of matrix metalloproteinases (MMPs) is the most commonly used mechanism to mitigate BSCB damage, followed by endoplasmic reticulum (ER) stress and the Akt pathway. In addition, we found that bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), which inhibit the TIMP2/MMP signaling pathway, may be the most effective way to alleviate BSCB injury. Conclusion: This study systematically analyzes the experimental treatments and their mechanisms for reducing BSCB injury in the early stage of t-SCI. BMSC-Exos, which inhibit MMP expression, are currently the most effective therapeutic modality for alleviating BSCB damage. In addition, the regulation of MMPs in particular as well as the Akt pathway and the ER stress pathway play important roles in alleviating BSCB injury. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324794.

11.
Mol Pharm ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36067352

RESUMO

Herein, an albumin-enriched nanocomplex was developed for the solubilization and intravascular administration of clopidogrel bisulfate (CLP). In particular, CLP nanoparticles (HS-CLP-NPs) were synthesized via an improved nab-technology method using Solutol HS-15, and bovine serum albumin (BSA) was further enriched on the nanoparticle surface forming a protein corona (BH-CLP-NPs). BH-CLP-NPs displayed an average size of 163.4 ± 10.5 nm, a zeta potential of 1.85 ± 0.03 mV, an encapsulation efficiency of 99.9%, and a drug loading capacity of 32.9%. The cumulative release of CLP from BH-CLP-NPs reached about 60% within 168 h. The pharmacokinetic study on the CLP metabolite indicated that the BSA-enriched nanoparticle showed greater in vivo exposure. Pharmacodynamic studies in the renal ischemia/reperfusion injury rat model further demonstrated the renal protective effect of systemically administered BH-CLP-NPs against acute kidney injury with significantly downregulated blood urea nitrogen and creatinine levels. Overall, the albumin-enriched nanocomplexes offer a neat and efficient strategy for the development of poorly water-soluble drugs to achieve intravascular administration.

12.
Int J Ophthalmol ; 15(8): 1273-1278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017042

RESUMO

AIM: To investigate the surgical outcomes of patients with chronic angle-closure glaucoma (CACG) treated with phacoemulsification (phaco)/endocyclophotocoagulation (ECP) with and without endoscopic goniosynechialysis (E-GSL). METHODS: A retrospective, nonrandomized, comparative case series was conducted. Patients with CACG who underwent phaco in combination with either ECP alone (ECP group) or GSL with ECP (E-GSL group) from 2018 to 2019 were followed for 12mo and reviewed. Clinical features and outcomes were identified and analyzed. The ECP and E-GSL groups were matched in age and baseline intraocular pressure (IOP). Changes in IOP, mean of visual acuity (VA), peripheral anterior synechiae (PAS) formation, and the number of glaucoma medications was examined. RESULTS: The ECP group included 32 eyes of 27 patients, and the E-GSL group included 32 eyes of 26 patients. The preoperative baseline IOP was 22.18±6.48 mm Hg in the ECP group and 22.95±6.71 mm Hg in the E-GSL group (P=0.644). The mean IOP reduction was 26.2% in the ECP group and 41.6% in the E-GSL group at 12mo. The mean postoperative VA (logMAR units) at 12mo was 0.47 in the ECP group and 0.36 in the E-GSL group. The reduction in PAS formation and the number of glaucoma medications was also higher in the ECP group than E-GSL group at 12mo. CONCLUSION: The phaco/ECP and phaco/E-GSL groups both achieve a significant reduction in IOP without complications associated with traditional glaucoma filtration surgeries.

13.
Entropy (Basel) ; 24(8)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36010818

RESUMO

Many similarity measure algorithms of nodes in weighted graph data have been proposed by employing the degree of nodes in recent years. Despite these algorithms obtaining great results, there may be still some limitations. For instance, the strength of nodes is ignored. Aiming at this issue, the relative entropy of the distance distribution based similarity measure of nodes is proposed in this paper. At first, the structural weights of nodes are given by integrating their degree and strength. Next, the distance between any two nodes is calculated with the help of their structural weights and the Euclidean distance formula to further obtain the distance distribution of each node. After that, the probability distribution of nodes is constructed by normalizing their distance distributions. Thus, the relative entropy can be applied to measure the difference between the probability distributions of the top d important nodes and all nodes in graph data. Finally, the similarity of two nodes can be measured in terms of this above-mentioned difference calculated by relative entropy. Experimental results demonstrate that the algorithm proposed by considering the strength of node in the relative entropy has great advantages in the most similar node mining and link prediction.

14.
Vaccines (Basel) ; 10(8)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36016098

RESUMO

Since the beginning of the COVID-19 pandemic, numerous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, including five variants of concern (VOC) strains listed by the WHO: Alpha, Beta, Gamma, Delta and Omicron. Extensive studies have shown that most of these VOC strains, especially the currently dominant variant Omicron, can escape the host immune response induced by existing COVID-19 vaccines to different extents, which poses considerable risk to the health of human beings around the world. In the present study, we developed a vaccine based on inactivated SARS-CoV-2 and an adjuvant consisting of aluminum hydroxide (alum) and CpG. The immunogenicity and safety of the vaccine were investigated in rats. The candidate vaccine elicited high titers of SARS-CoV-2-spike-specific IgG antibody and neutralizing antibody in immunized rats, which not only neutralize the original SARS-CoV-2, but also showed great cross-neutralization activity against the Beta, Delta and Omicron variants.

15.
Front Microbiol ; 13: 942932, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966695

RESUMO

Smoked horsemeat sausage is a famous fermented traditional food in Xinjiang, China. However, the microbial diversity and its potential contributions to the flavor components of smoked horsemeat sausage are unclear. In this study, the microbial community and flavor components of smoked horsemeat sausage from six regions of Xinjiang were measured by using amplicon sequencing and headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology, respectively. Relations among microbial communities, flavor components and environmental factors were subsequently predicted based on redundancy analysis (RDA) and Monte Carlo permutation tests. Although smoked horsemeat sausage samples from different regions possessed distinct microbial communities, lactic acid bacteria (LAB) were identified as the dominant consortium in smoked horsemeat sausage. Lactobacillus, Vagococcus, Lactococcus, and Carnobacterium were detected at high abundance in different sausages. The moisture content, nitrite content, and pH of the sausage might be important factors influencing the dominant bacterial community, according to the RDA. Among the dominant consortia, the eight core bacterial genera showed considerable correlations with the formation of sixteen volatile compounds in smoked horsemeat sausage based on multivariate statistical analysis. For example, the levels of Leuconostoc and Lactobacillus were positively correlated with those of 1-hexadecanol, hexyl acetate, 2-methyl-phenol, 1-pentanol, d-limonene, and 2-heptanone, and the levels of Leuconostoc, Lactobacillus, and Weissella were negatively correlated with those of 1-octanol, acetic acid, octanal, heptanal, and 1-hexanol. This study will provide a theoretical basis for understanding the microbial metabolic modes of Xinjiang smoked horsemeat sausages.

16.
Front Microbiol ; 13: 901762, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966708

RESUMO

It has been generally hypothesized that mobile elements can induce genomic rearrangements and influence the distribution and functionality of toxic/bioactive peptide synthesis pathways in microbes. In this study, we performed in depth genomic analysis by completing the genomes of 13 phylogenetically diverse strains of the bloom-forming freshwater cyanobacteria Planktothrix spp. to investigate the role of insertion sequence (IS) elements in seven pathways. Chromosome size varied from 4.7-4.8 Mbp (phylogenetic Lineage 1 of P. agardhii/P. rubescens thriving in shallow waterbodies) to 5.4-5.6 Mbp (Lineage 2 of P. agardhii/P. rubescens thriving in deeper physically stratified lakes and reservoirs) and 6.3-6.6 Mbp (Lineage 3, P. pseudagardhii/P. tepida including planktic and benthic ecotypes). Although the variation in chromosome size was positively related to the proportion of IS elements (1.1-3.7% on chromosome), quantitatively, IS elements and other paralogs only had a minor share in chromosome size variation. Thus, the major part of genomic variation must have resulted from gene loss processes (ancestor of Lineages 1 and 2) and horizontal gene transfer (HGT). Six of seven peptide synthesis gene clusters were found located on the chromosome and occurred already in the ancestor of P. agardhii/P. rubescens, and became partly lost during evolution of Lineage 1. In general, no increased IS element frequency in the vicinity of peptide synthesis gene clusters was observed. We found a higher proportion of IS elements in ten breaking regions related to chromosomal rearrangements and a tendency for colocalization of toxic/bioactive peptide synthesis gene clusters on the chromosome.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35958905

RESUMO

Objective: Osteoarthritis (OA) is the most common degenerative joint disorder and a leading cause of disability. A previous randomized controlled trial has shown that Gubitong (GBT) recipe can improve OA-related symptoms and articular function without noticeable side effects. However, the underlying mechanisms remain unclear. This study aims to explore the therapeutic mechanisms of the GBT recipe for OA through in vivo and in vitro experiments. Methods: Rats of the OA model were established by Hulth surgery and intervened with the GBT recipe and then were subjected to pathological assessment of the cartilage. Matrix metalloproteinase 13 (MMP-13) expression in cartilage tissues was assessed by immunohistochemical staining. Chondrocytes were isolated from sucking rats and stimulated with LPS to establish an in vitro model. After intervened by water extraction of the GBT recipe, the fluorescent signal of Mtphagy Dye and mitochondrial membrane potential (Δψm) were detected to determine the states of mitophagy and mitochondrial dynamics of chondrocytes in vitro, respectively. Western blot test was used to detect levels of proteins related to catabolism of the cartilage matrix, mitophagy, and PI3K/AKT pathway. Results: In in vivo experiments, the GBT recipe can effectively inhibit the cartilage degeneration of chondrocytes in OA rats, as well as markedly suppress the expression of MMP-13. In vitro experiments on LPS-induced chondrocytes exhibited increase in mitochondrial depolarization and excessive mitophagy, and the GBT recipe can alleviate these changes. LPS-stimulated chondrocytes showed increases in MMP-13, PINK1, and Parkin in cell lysates and LC3II/LC3I ratio in the mitochondrial fraction, and the GBT recipe can inhibit these increases in a dose-dependent manner. Moreover, the GBT recipe can attenuate the abnormal activation of PI3K/AKT pathway induced by LPS. Conclusion: The GBT recipe exhibits chondroprotective effects through inhibiting excessive mitophagy of chondrocytes, which may be associated with its inhibitory effect on the abnormal activation of PI3K/AKT pathway.

18.
Inflamm Res ; 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962796

RESUMO

AIMS: Systemic inflammation plays an important role in cancer cachexia. However, among the systemic inflammatory biomarkers, it is unclear which has optimal prognostic value for cancer cachexia. METHODS: The Kaplan-Meier method was used and the log-rank analysis was performed to estimate survival differences between groups. Cox proportional hazard regression analyses were conducted to assess independent risk factors for all-cause mortality. RESULTS: The C-reactive protein-to-albumin ratio (CAR) was the optimal prognostic assessment tool for patients with cancer cachexia, with 1-, 3-, and 5-year predictive powers of 0.650, 0.658, and 0.605, respectively. Patients with a high CAR had significantly lower survival rates than those with a low CAR. Moreover, CAR can differentiate the prognoses of patients with the same pathological stage. Cox proportional risk regression analyses showed that a high CAR was an independent risk factor for cancer cachexia. For every standard deviation increase in CAR, the risk of poor prognosis for patients with cancer cachexia was increased by 20% (hazard ratio = 1.200, 95% confidence interval = 1.132-1.273, P < 0.001). CONCLUSIONS: CAR is an effective representative of systemic inflammation and a powerful factor for predicting the life function and clinical outcome of patients with cancer cachexia.

19.
Metabolomics ; 18(9): 71, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36036299

RESUMO

INTRODUCTION: Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates. OBJECTIVE: We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics. METHODS: In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GC‒MS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LC‒MS) were used to analyze the samples for untargeted metabolomics and lipidomics. RESULTS AND CONCLUSION: GC‒MS-based metabolomics revealed 1336 metabolic features, while LC‒MS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Diagnóstico Diferencial , Humanos , Lipidômica , Metabolômica
20.
Nanoscale ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36039653

RESUMO

The epidemic of multidrug-resistant Gram-negative bacteria is an ever-growing global concern. Polymyxin B (PMB), a kind of "old fashioned" antibiotic, has been revived in clinical practice and mainly used as last-line antibiotics for otherwise untreatable serious infections because the incidence of the resistance to PMB is currently relatively low in comparison with other antibiotics in vivo owing to the unique bactericidal mechanism of PMB. However, serious adverse side effects, including nephrotoxicity and neurotoxicity, hamper its clinical application. Herein, we describe the development of a nanoparticle that can target sites of inflammation and forcedly release PMB specifically in the area of Gram-negative bacteria. This particle was constructed through the electrostatic self-assembly of hyaluronic acid (HA) and PMB molecules in order to realize the safe and effective treatment of pneumonia. After systemic administration, PMB-HA nanoparticles were found to actively accumulate in the lungs, precisely target the CD44 receptors over-expressed on the membrane of activated endothelial cells in inflammatory sites, and then come into contact with the bacteria resident in the damaged alveolar-capillary membrane. Due to the electrostatic and hydrophobic interactions between PMB and the lipopolysaccharide (LPS) in the outer membranes of bacteria, the PMB molecules in the PMB-HA nanoparticles are expected to escape from the nanoparticles to insert into the bacteria via competitive binding with LPS. Through shielding the cationic nature of PMB, PMB-HA nanoparticles also possess outstanding biosafety performance in comparison to free PMB. It is thus believed that this smart delivery system may pave a new way for the resurrection of PMB in the future clinical treatment of bacterial inflammatory diseases.

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