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1.
J Appl Biomater Funct Mater ; 21: 22808000221130168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36633288

RESUMO

BACKGROUND: To maintain and enhance the wound healing effects of mesenchymal stem cells (MSCs), a scaffold for hosting MSCs is needed, which ought to be completely biocompatible, durable, producible, and of human source. OBJECTIVE: To build a cell-extracellular matrix (ECM) complex assembled by human umbilical cord mesenchymal stem cells (HuMSCs) and to investigate its clinical potentials in promoting wound healing. METHOD: HuMSCs were isolated and expanded. When the cells of third passage reached confluency, ascorbic acid was added to stimulate the cells to deposit ECM where the cells grew in. Four weeks later, a cells-loaded ECM sheet was formed. The cell-ECM complex was observed under the scanning electron microscopy (SEM) and subjected to histological studies. The supernatants were collected and the cell-ECM complex was harvested at different time points and processed for enzyme-linked immune sorbent assay (ELISA) and mRNA analysis. The in vivo experiments were performed by means of implanting the cell-ECM complex on the mice back for up to 6 months and the specimens were collected for histological studies. RESULTS: After 4 weeks of cultivation with ascorbic stimulation, a sheet was formed which is mainly composed with HuMSCs, collagen and hyaluronic acid. The cell-ECM complex can sustain to certain tensile force. The mRNA and protein levels of vascular endothelial growth factor-α (VEGF-α), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and transforming growth factor-ß1 (TGF-ß1) were remarkably increased compared to monolayer-cultured cells. The implanted cell-ECM complex on mice was still noticeable with host cells infiltration and vascularization on 6 months. CONCLUSION: Our studies suggested that HuMSCs can be multi-cultivated through adding ascorbic stimulation and ECM containing collagen and hyaluronic acid were enriched around the cells which self-assembly formed a cell-ECM complex. Cell-ECM complex can improve growth factors secretion remarkably which means it may promote wound healing by paracrine.


Assuntos
Ácido Hialurônico , Fator A de Crescimento do Endotélio Vascular , Camundongos , Humanos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/fisiologia , Colágeno , Matriz Extracelular
2.
Exp Lung Res ; : 1-10, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36636918

RESUMO

Objective: Chronic pulmonary inflammation caused by long-term smoking is the core pathology of COPD. Alveolar macrophages (AMs) are involved in the pulmonary inflammation of COPD. The accumulation of damaged materials caused by impaired autophagy triggers inflammatory response in macrophages. As a key transcription regulator, transcription factor EB (TFEB) activates the transcription of target genes related autophagy and lysosome by binding to promoters, whereas it is unclarified for the relationship between inflammatory response induced by cigarette smoke extract (CSE) and TFEB-mediated autophagy. Thus, we investigated the role of TFEB-mediated autophagy in inflammatory response induced by CSE in NR8383 cells, and to explore its potential mechanism. Methods: Based on cell viability and autophagy, cells treated with 20% concentration of CSE for 24 h were selected for further studies. Cells were divided into control group, chloroquine (CQ, the autophagy inhibitor) group, CSE group, CSE + rapamycin (the autophagy inducer) group and CSE + fisetin (the TFEB inducer) group. The levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in supernatant were detected by ELISA kits. The protein expressions were tested by western blot. The intensity of fluorescence of Lysosome-associated membrane protein 1 (LAMP1) and TFEB was detected by immunofluorescence. Lyso-Tracker Red staining was applied to detect the lysosome environment. Results: CSE inhibited the cell viability, increased the contents of TNF-α, IL-1ß, IL-6, the ratio of LC3II/I, and the level of P62 protein. Besides, CSE decreased the fluorescence intensity of LAMP1 protein and Lyso-Tracker Red staining, as well as the ratio of nucleus/cytosol of TFEB protein. Activating autophagy with rapamycin alleviated CSE-induced inflammatory response. The activation of TFEB via fisetin alleviated CSE-induced autophagy impairment and lysosomal dysfunction, thus alleviated inflammatory response in NR8383 cells. Conclusion: CSE-induced inflammatory response in NR8383 cells, which may be related to the inhibition of TFEB-mediated autophagy.

3.
Chemosphere ; 317: 137854, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36649900

RESUMO

BACKGROUND: Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual blood metals on specific parameters of liver function in the general population. Hence, this study aimed to elucidate their associations. METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used in this cross-sectional study. Multivariate linear, and a quantile-based g-computation (qgcomp) were applied to explore the associations between blood metals [mercury (Hg), manganese (Mn), lead (Pb), cadmium (Cd), selenium (Se)], alone and in combination, and liver function parameters [alanine transaminase (ALT), aspartate transaminase (AST), ALT/AST, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and serum total bilirubin (TBIL)]. RESULTS: A total of 15,328 were included. Multivariate linear models indicated that liver function was significantly associated with blood heavy metals. The most significant relationship was found between Se and AST (ß 5.09, 95%CI (3.28,6.91), p<0.001), Mn and ALT (ß 1.24, 95%CI (0.57, 1.91), p<0.001). Furthermore, the qgcomp analysis showed that the combination of five blood metals was positively associated with AST, ALT, GGT, TBIL and HSI. Cd contributed the most to the correlation of AST (weight = 0.447), Se contributed the most to the association of ALT (weight = 0.438) and HSI (weight = 0.570), Pb contributed the most to the association of GGT (weight = 0.421) and Hg contributed the most to the correlation of TBIL (weight = 0.331). CONCLUSIONS: Blood heavy metal levels were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.

4.
World J Surg Oncol ; 21(1): 19, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691032

RESUMO

BACKGROUND: Nab-paclitaxel plus gemcitabine (AG) and modified FOLFIRINOX (FFX) are two systemic therapies that have been widely used as standard first-line chemotherapy regimens in metastatic pancreatic cancer. However, since there is no clinical trial to directly compare the efficacy and safety of the two regimens, it is not clear which regimen is more effective. In this study, we aim to examine and compare the efficacy and safety of AG and FFX as first-line chemotherapy regimens in Chinese patients with metastatic pancreatic cancer in a real-world setting. METHODS: We retrospectively evaluated the outcomes of 44 patients who were diagnosed with metastatic pancreatic cancer and were treated with either AG (n = 24) or FFX (n = 20) as first-line chemotherapy between March 2017 and February 2022 at Zhongnan Hospital of Wuhan University. Prognostic nutrition index (PNI) was calculated based on the serum albumin level and peripheral lymphocyte count. According to the optimal cutoff value of PNI, patients were divided into low PNI group (PNI < 43.70) and high PNI group (PNI ≥ 43.70). RESULTS: Of 44 patients in this study, 24 were treated with AG, and 20 were treated with FFX as first-line chemotherapy. No significant differences in baseline characteristics were found between the two groups. The objective response rate (ORR) was 16.7% in the AG group and 20.0% in the FFX group. The disease control rate (DCR) was 70.8% in the AG group and 60.0% in the FFX group. There was no significant difference in PFS or OS between the AG group and the FFX group. The median progression-free survival (PFS) was 4.67 months (95% confidence interval [CI], 2.91-6.42) in the AG group and 3.33 months (95% CI, 1.87-4.79, p = 0.106) in the FFX group. The median overall survival (OS) was 9.00 months (95% CI, 7.86-12.19) in the AG group and 10.00 months (95% CI, 7.70-12.27, p = 0.608) in the FFX group. The second-line treatment rate was 62.5% in the AG group and 55.0% in the FFX group. Immune checkpoint inhibitors (ICIs) based regimens are common second-line treatment options whether in AG or FFX group. Significantly more grade 3-4 peripheral neuropathy occurred in the AG than FFX groups (4 (20.8%) vs 0 (0.0%), p = 0.030*). The patients in the PNI (Prognostic nutrition index) ≥ 43.7 group had a significant longer median OS (PNI ≥ 43.7 vs PNI < 43.7: 10.33 vs 8.00 months, p = 0.019). CONCLUSION: AG and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer. Pancreatic cancer patients receiving first-line chemotherapy with good nutritional status are likely to have a better prognosis.


Assuntos
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Desoxicitidina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel/efeitos adversos , Albuminas , Fluoruracila , Leucovorina/uso terapêutico
5.
Opt Express ; 31(1): 745-754, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36607007

RESUMO

All-solid-state continuous-wave (CW) single-frequency tunable Ti:sapphire (Ti:S) laser is an important source in quantum optics and atomic physics. However, intracavity etalon (IE) locking is easily influenced by the intensity noise of the pump source in the low frequency band. In order to address this issue, a differential detector with dual-photodiodes (PDs) is designed and employed in the experiment. Both PDs are used to detect the lights of the pump source and the built Ti:S laser, respectively. As a result, the influence of the intensity noise of the pump source on the stability of the IE locking is successfully eliminated and the IE is stably locked to the oscillating longitudinal-mode of the laser. On this basis, a stable CW single-frequency tunable Ti:S laser is realized. The presented method is beneficial to attain a stable single-frequency tunable laser with immunity to the intensity noise of the pump source.

6.
Epilepsia Open ; 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36588194

RESUMO

Epilepsy is one of the most common serious chronic neurological diseases affecting people of all ages globally. It is characterized by recurrent seizures. About 50 million people worldwide have epilepsy. Indubitably, people with epilepsy (PWE) may be without access to appropriate treatment. Many studies have examined the molecular mechanisms and clinical aspects of epilepsy; nonetheless, the treatment gap exists in some special areas. In the tropics, the specific geographical and ecological conditions and a lack of medical resources result in neglect or delay of diagnosis for PWE. Herein, we summarized the epidemiology of epilepsy in the tropics and discussed the disease burden and existing problems, aiming to offer a medical environment for patients in need and highlight the importance of reducing the epileptic disease burden in tropical countries.

7.
Int J Biol Macromol ; 229: 766-777, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36610562

RESUMO

Invertases are ubiquitous enzymes that catalyze the unalterable cleavage of sucrose into glucose and fructose, and are crucially involved in plant growth, development and stress response. In this study, a total of 17 putative invertase genes, including 3 cell wall invertases, 3 vacuolar invertases, and 11 neutral invertases were identified in apple genome. Subcellular localization of MdNINV7 and MdNINV11 indicated that both invertases were located in the cytoplasm. Comprehensive analyses of physicochemical properties, chromosomal localization, genomic characterization, and gene evolution of MdINV family were conducted. Gene duplication revealed that whole-genome or segmental duplication and random duplication might have been the major driving force for MdINVs expansion. Selection index values, ω, showed strong evidence of positive selection signatures among the INV clusters. Gene expression analysis indicated that MdNINV1/3/6/7 members are crucially involved in fruit development and sugar accumulation. Similarly, expression profiles of MdCWINV1, MdVINV1, and MdNINV1/2/7/11 suggested their potential roles in response to cold stress. Furthermore, overexpression of MdNINV11 in apple calli at least in part promoted the expression of MdCBF1-5 and H2O2 detoxification in response to cold. Overall, our results will be useful for understanding the functions of MdINVs in the regulation of apple fruit development and cold stress response.

8.
Inorg Chem ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690448

RESUMO

The low-lying excited-state properties of the water-solvated UO2Cl2 complexes, i.e., (H2O)nUO2Cl2 (n = 1-3), below 33,000 cm-1, are investigated based on the ab initio NEVPT2 and CCSD(T) with inclusion of scalar relativistic and spin-orbit coupling effects. The simulated luminescence spectral curves agree well with the experimental spectrum in aqueous solution at -120 °C. Water coordination is found to significantly affect the character of luminescent state, which is changed from the 3Φg state in UO2Cl2 to the 3Δg state in (H2O)2,3UO2Cl2. This is distinctly different from the observed unchanged nature of luminescent state in the cases of Ar coordination to UO2Cl2 and H2O coordination to UO2F2 in the previous work. Furthermore, by combining with the theoretical results for the solvated UO2F2 system, the reason why water coordination does not remarkably change the spectral shape of UO2Cl2, as opposed to UO2F2, was explained based on the analysis of two key spectral parameters, O-U-O symmetrical vibrational frequency and U-O bond length elongation. The roles of ligand field and spin-orbit coupling in the determination of luminescent state character and spectral shape in uranyl dihalide complexes are deeply discussed and summarized. These results deepen our understanding of the luminescent properties of uranyl complexes in aqueous solution.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36692413

RESUMO

INTRODUCTION: Alternatives such as remotely delivered therapy in the home environment or telehealth represent an opportunity to increase overall cardiac rehabilitation (CR) utilization. Implementing alternatives into regular practice is the next step in development; however, the cost aspect is essential for policymakers. Limited economic budgets lead to cost-effectiveness analyses before implementation. They are appropriate in cases where there is evidence that the compared intervention provides a similar health benefit to usual care. This systematic review aimed to compare the cost-effectiveness of exercise-based telehealth CR interventions compared to standard exercise-based CR. EVIDENCE ACQUISITION: PubMed and Web of Science databases were systematically searched up to August 2022 to identify randomized controlled trials assessing patients undergoing telehealth CR. The intervention was compared to standard CR protocols. The primary intent was to identify the cost-effectiveness. Interventions that met the criteria were home-based telehealth CR interventions delivered by information and communications technology (telephone, computer, internet, or videoconferencing) and included the results of an economic evaluation, comparing interventions in terms of cost-effectiveness, utility, costs and benefits, or cost-minimization analysis. The systematic review protocol was registered in the PROSPERO Registry (CRD42022322531). EVIDENCE SYNTHESIS: Out of 1525 identified studies, 67 articles were assessed for eligibility, and, at the end of the screening process, 12 studies were included in the present systematic review. Most studies (92%) included in this systematic review found strong evidence that exercise-based telehealth CR is cost-effective. Compared to CBCR, there were no major differences, except for three studies evaluating a significant difference in average cost per patient and intervention costs in favor of telehealth CR. CONCLUSIONS: Telehealth CR based on exercise is as cost-effective as CBCR interventions. Funding telehealth CR by third-party payers may promote patient participation to increase overall CR utilization. High-quality research is needed to identify the most cost-effective design.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36695341

RESUMO

AIM: Despite the well-documented short to medium-term effectiveness of eHealth (electronic health) secondary prevention interventions on patients with cardiovascular disease (CVD), there is limited empirical evidence regarding long-term effectiveness. This review aims to evaluate the long-term effects of eHealth secondary prevention interventions on the health outcomes of patients with CVD. METHODS AND RESULTS: This systematic review and meta-analysis followed Cochrane Handbook for Systematic Reviews of Interventions. EMBASE, Medline, Web of Science, and Scopus were searched from 1990 to May 2022. Randomized controlled trials investigating the effects of eHealth secondary prevention on health outcomes of CVD patients that collected end-point data at ≥ 12 months were included. RevMan 5.3 was used for risk of bias assessment and meta-analysis. Ten trials with 1,559 participants were included. Data pooling suggested that eHealth programs have significantly reduced low-density lipoprotein cholesterol (LDL-C) [n = 6; SMD = -0.26, 95%CI (-0.38, -0.14), I2 = 17%, p < .001]; systolic blood pressure [n = 5; SMD = -0.46, 95% CI, (-0.84, -0.08), I2 = 90%, p = 0.02]; and, re-hospitalization, reoccurrence, and mortality [RR = 0.36, 95% CI [0.17, 0.77], I2 = 0%, p = .009]. Effects on behavioral modification, physiological outcomes of body weight and blood glucose, and quality of life were inconclusive. CONCLUSION: eHealth secondary prevention is effective in improving long-term management of risk factors and reducing the reoccurrence of cardiac events in patients with CVD. Results are inconclusive for behavior modification and quality of life. Exploring, implementing and strengthening strategies in eHealth secondary prevention programs that focus on maintaining behavior changes and enhancing psychosocial elements should be undertaken. REGISTRATION: PROSPERO CRD42022300551.

11.
Brief Bioinform ; 24(1)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36545790

RESUMO

Cell-cell communications are vital for biological signalling and play important roles in complex diseases. Recent advances in single-cell spatial transcriptomics (SCST) technologies allow examining the spatial cell communication landscapes and hold the promise for disentangling the complex ligand-receptor (L-R) interactions across cells. However, due to frequent dropout events and noisy signals in SCST data, it is challenging and lack of effective and tailored methods to accurately infer cellular communications. Herein, to decipher the cell-to-cell communications from SCST profiles, we propose a novel adaptive graph model with attention mechanisms named spaCI. spaCI incorporates both spatial locations and gene expression profiles of cells to identify the active L-R signalling axis across neighbouring cells. Through benchmarking with currently available methods, spaCI shows superior performance on both simulation data and real SCST datasets. Furthermore, spaCI is able to identify the upstream transcriptional factors mediating the active L-R interactions. For biological insights, we have applied spaCI to the seqFISH+ data of mouse cortex and the NanoString CosMx Spatial Molecular Imager (SMI) data of non-small cell lung cancer samples. spaCI reveals the hidden L-R interactions from the sparse seqFISH+ data, meanwhile identifies the inconspicuous L-R interactions including THBS1-ITGB1 between fibroblast and tumours in NanoString CosMx SMI data. spaCI further reveals that SMAD3 plays an important role in regulating the crosstalk between fibroblasts and tumours, which contributes to the prognosis of lung cancer patients. Collectively, spaCI addresses the challenges in interrogating SCST data for gaining insights into the underlying cellular communications, thus facilitates the discoveries of disease mechanisms, effective biomarkers and therapeutic targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Perfilação da Expressão Gênica , Transcriptoma , Comunicação Celular
12.
Plant Physiol ; 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36461944

RESUMO

Fructokinase (FRK) activates fructose through phosphorylation, which sends the activated fructose into primary metabolism and regulates fructose signaling capabilities in plants. The apple (Malus × domestica) FRK gene MdFRK2 shows especially high affinity to fructose, and its overexpression decreases fructose levels in the leaves of young plants. However, in the current study of mature plants, fruits of transgenic apple trees overexpressing MdFRK2 accumulated a higher level of fructose than wild-type (WT) fruits (at both young and mature stages). Transgenic apple trees with high mRNA MdFRK2 expression showed no significant differences in MdFRK2 protein abundance or FRK enzyme activity compared to WT in mature leaves, young fruits, and mature fruits. Immunoprecipitation-mass spectrometry analysis identified an skp1, cullin, F-box (SCF) E3 ubiquitin ligase, calcyclin-binding protein (CacyBP), that interacted with MdFRK2. RNA-sequencing analysis provided evidence for ubiquitin-mediated post-transcriptional regulation of MdFRK2 protein for the maintenance of fructose homeostasis in mature leaves and fruits. Further analyses suggested an MdCacyBP-MdFRK2 regulatory module in which MdCacyBP interacts with and ubiquitinates MdFRK2 to facilitate its degradation by the 26S proteasome, thus decreasing the FRK enzyme activity to elevate fructose concentration in transgenic apple trees. This result uncovered an important mechanism underlying plant fructose homeostasis in different organs through regulating MdFRK2 protein level via ubiquitination and degradation. Our study provides usable data for the future improvement of apple flavor and expands our understanding of the molecular mechanisms underlying plant fructose content and signaling regulation.

13.
J Med Chem ; 65(24): 16234-16251, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36475645

RESUMO

With the emergence and rapid spreading of NDM-1 and existence of clinically relevant VIM-1 and IMP-1, discovery of pan inhibitors targeting metallo-beta-lactamases (MBLs) became critical in our battle against bacterial infection. Concurrent with our fragment and high-throughput screenings, we performed a knowledge-based search of known metallo-beta-lactamase inhibitors (MBLIs) to identify starting points for early engagement of medicinal chemistry. A class of compounds exemplified by 11, discovered earlier as B. fragilis metallo-beta-lactamase inhibitors, was selected for in silico virtual screening. From these efforts, compound 12 was identified with activity against NDM-1 only. Initial exploration on metal binding design followed by structure-guided optimization led to the discovery of a series of compounds represented by 23 with a pan MBL inhibition profile. In in vivo studies, compound 23 in combination with imipenem (IPM) robustly lowered the bacterial burden in a murine infection model and became the lead for the invention of MBLI clinical candidates.


Assuntos
Infecções Bacterianas , Inibidores de beta-Lactamases , Animais , Camundongos , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , Inibidores de beta-Lactamases/química , Imipenem/farmacologia , Imipenem/uso terapêutico , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Testes de Sensibilidade Microbiana
14.
J Med Chem ; 65(24): 16801-16817, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36475697

RESUMO

Inhibition of leucine-rich repeat kinase 2 (LRRK2) kinase activity represents a genetically supported, chemically tractable, and potentially disease-modifying mechanism to treat Parkinson's disease. Herein, we describe the optimization of a novel series of potent, selective, central nervous system (CNS)-penetrant 1-heteroaryl-1H-indazole type I (ATP competitive) LRRK2 inhibitors. Type I ATP-competitive kinase physicochemical properties were integrated with CNS drug-like properties through a combination of structure-based drug design and parallel medicinal chemistry enabled by sp3-sp2 cross-coupling technologies. This resulted in the discovery of a unique sp3-rich spirocarbonitrile motif that imparted extraordinary potency, pharmacokinetics, and favorable CNS drug-like properties. The lead compound, 25, demonstrated exceptional on-target potency in human peripheral blood mononuclear cells, excellent off-target kinase selectivity, and good brain exposure in rat, culminating in a low projected human dose and a pre-clinical safety profile that warranted advancement toward pre-clinical candidate enabling studies.


Assuntos
Doença de Parkinson , Ratos , Humanos , Animais , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson/tratamento farmacológico , Indazóis/farmacologia , Indazóis/uso terapêutico , Leucócitos Mononucleares/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Encéfalo/metabolismo , Trifosfato de Adenosina
15.
Front Psychol ; 13: 1061327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36533049

RESUMO

Objective: There is limited research exploring the experiences of people living with advanced cancer in the Gaza Strip (GS), Palestine. Thus, this study aimed to determine the level of psychological distress, anxiety, and depression among advanced cancer patients in the GS and identify factors associated with a high level of distress. Materials and methods: A secondary analysis was performed using primary data from a larger study focusing on supportive care needs in advanced cancer patients in GS. Three hundred sixty-one patients agreed to participate and filled out the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression was conducted to identify factors associated with high distress levels. Results: Over two-thirds of advanced cancer patients (70.6%) reported a high level of distress. They also reported a significantly higher distress level than patients with early cancer (96.5 vs. 3.5%; p = 0.001). About 92.8% of participants reported depression and anxiety symptoms. Physical, emotional, and practical problems were the primary sources of distress. Breast cancer patients were more likely to have psychological distress than colon and stomach cancer patients. Newly diagnosed patients had a higher level of anxiety, depression, and distress than those who had a cancer diagnosis for an extended period. Conclusion: Patients with advanced cancer in the GS exhibited a significantly higher level of psychological distress, depression and anxiety than patients with advanced cancer elsewhere. Efforts should be made to identify psychological distress as a routine part of oncology practice. Future research should further explore the causes of psychological distress in cancer patients in conflict zones and feasible mitigation strategies.

16.
Biosensors (Basel) ; 12(12)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36551037

RESUMO

Diagnostic blood cell counting is of limited use in monitoring a minimal number of leukaemia cells, warranting further research to develop more sensitive and reliable techniques to identify leukaemia cells in circulation. In this work, a hemin-graphene nanocomposite-based aptasensor was developed for ultrasensitive colorimetric detection of leukaemia cells (CEM) using magnetic enrichment. Hemin-conjugated graphene oxide nanocomposites (HGNs) were prepared by hydrazine reduction using graphene oxide nanosheets and hemins. Hence, the prepared HGNs become able to absorb single-stranded DNA and acquire peroxidase-like activity. The aptamer sgc8c, which recognizes a specific target on leukaemia cells, was absorbed onto HGNs to capture the target CEM cancer cells. The captured target cells that associated with the HGNs were then concentrated and separated by magnetic beads (MBs) coated with sgc8c aptamers, forming a HGN-cell-MB sandwich structure. These sandwich structures can be quantified via an oxidation reaction catalysed by HGNs. By utilizing dual signal amplification effects generated by magnetic enrichment and the improved peroxidase activity of HGNs, the biosensor allowed for highly sensitive detection of 10 to 105 CEM cells with an ultra-low limit of detection (LOD) of 10 cells under optimal conditions. It is expected that the proposed aptasensor can be further employed in monitoring the minimal residual disease during the treatment of leukaemia.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Grafite , Leucemia , Nanocompostos , Humanos , Grafite/química , Hemina/química , Colorimetria/métodos , Aptâmeros de Nucleotídeos/química , Nanocompostos/química , Leucemia/diagnóstico , Técnicas Biossensoriais/métodos , Peroxidases , Fenômenos Magnéticos , Limite de Detecção , Técnicas Eletroquímicas/métodos
17.
Cell Death Dis ; 13(12): 1073, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572672

RESUMO

The failing heart is characterized by an increase in glucose uptake and glycolytic rates that is not accompanied by a concomitant increase in glucose oxidation. Lower coupling of glucose oxidation to glycolysis possibly owes to unchanged or reduced pyruvate oxidation in mitochondria. Therefore, increasing pyruvate oxidation may lead to new therapies for heart disease. Dihydrolipoamide dehydrogenase (DLD) is a component of the pyruvate dehydrogenase complex (PDH). DLD mutations or defects are closely associated with metabolic diseases. However, few studies explore the effects of DLD mutants or acylation status on PDH activity and pyruvate metabolism. P300 is protein 2-hydroxyisobutyryltransferases in cells, and P300-dependent lysine 2-hydroxyisobutyrylation of glycolytic enzymes affects glucose metabolism. However, there are no relevant reports on the effect of 2-hydroxyisobutyrylation on the energy metabolism of heart failure, and it is worth further in-depth study. In this study, we showed that 2-hydroxyisobutyrylation is an essential protein translational modification (PTM) that regulates the activity of pyruvate dehydrogenase complex (PDHc). In a mouse model of transverse aortic constriction (TAC)-induced cardiac hypertrophy, the 2-hydroxyisobutylation of DLD was significantly increased, related to the decrease in PDH activity. In addition, our data provide clear evidence that DLD is a direct substrate of P300. As one of the main active ingredients of ginseng, ginsenoside Rg3 (Rg3) can reduce the 2-hydroxyisobutylation levels of DLD and restore the PDH activity by inhibiting the acyltransferase activity of P300, thereby producing beneficial effects whenever the heart is injured. Therefore, this study suggests a novel strategy for reversing myocardial hypertrophy.


Assuntos
Di-Hidrolipoamida Desidrogenase , Ácido Pirúvico , Camundongos , Animais , Di-Hidrolipoamida Desidrogenase/genética , Complexo Piruvato Desidrogenase/metabolismo , Cardiomegalia/genética , Glucose/metabolismo
18.
Front Plant Sci ; 13: 1052464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388499

RESUMO

Arbuscular mycorrhizal fungi (AMF) and plants form a symbiotic relationship that promotes plant growth and development. However, the regulatory mechanisms through which AMF promote plant growth and development are largely unexplored. In this study, the apple rootstock M26 was assessed physiologically, transcriptionally and metabolically when grown with and without AMF inoculation. AMF significantly promoted the number of lateral root (LR) increase and shoot elongation. Root transcriptomic and metabolic data showed that AMF promoted lateral root development mainly by affecting glucose metabolism, fatty acid metabolism, and hormone metabolism. Shoot transcriptomic and metabolic data showed that AMF promoted shoot elongation mainly by affecting hormone metabolism and the expression of genes associated with cell morphogenesis. To investigate whether shoot elongation is caused by root development, we analyzed the root/shoot dry weight ratio. There was a correlation between shoot growth and root development, but analysis of root and shoot metabolites showed that the regulation of AMF on plant shoot metabolites is independent of root growth. Our study bridged the gap in the field of growth and development related to AMF.

19.
Ther Adv Med Oncol ; 14: 17588359221138383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425871

RESUMO

Immunotherapy has been used in the clinical treatment of colorectal cancer (CRC); however, most patients fail to achieve satisfactory survival benefits. Biomarkers with high specificity and sensitivity are being increasingly developed to predict the efficacy of CRC immunotherapy. In addition to DNA alteration markers, such as microsatellite instability/mismatch repair and tumor mutational burden, immune cell infiltration and immune checkpoints (ICs), epigenetic changes and no-coding RNA, and gut microbiomes all show potential predictive ability. Recently, the hypoxic tumor microenvironment (TME) has been identified as a key factor mediating CRC immune evasion and resistance to treatment. Hypoxia-inducible factor-1α is the central transcription factor in the hypoxia response that drives the expression of a vast number of survival genes by binding to the hypoxia response element in cancer and immune cells in the TME. Hypoxia regulates angiogenesis, immune cell infiltration and activation, expression of ICs, and secretion of various immune molecules in the TME and is closely associated with the immunotherapeutic efficacy of CRC. Currently, various agents targeting hypoxia have been found to improve the TME and enhance the efficacy of immunotherapy. We reviewed current markers commonly used in CRC to predict therapeutic efficacy and the mechanisms underlying hypoxia-induced angiogenesis and tumor immune evasion. Exploring the mechanisms by which hypoxia affects the TME will assist the discovery of new immunotherapeutic predictive biomarkers and development of more effective combinations of agents targeting hypoxia and immunotherapy.

20.
J Antibiot (Tokyo) ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434277

RESUMO

On the basis of the one strain-many compounds (OSMAC) strategy, two new cyclic thiopeptides, geninthiocins E and F, together with four known geninthiocin derivatives, geninthiocins A, B, C, and val-geninthiocin were isolated from Streptomyces sp. CPCC 200267. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and Marfey's method. Geninthiocin E (1), val-geninthiocin (3), geninthiocin A (4), and geninthiocin B (5) exhibited significant anti-influenza A virus activities with the IC50 values of 28.7, 15.3, 7.3, and 18.3 µM, respectively. Compounds 3 and 4 showed moderate antibacterial activities against Staphylococcus aureus.

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