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1.
Neural Regen Res ; 18(3): 618-625, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018186

RESUMO

Studies on ischemia/reperfusion (I/R) injury suggest that exogenous neural stem cells (NSCs) are ideal candidates for stem cell therapy reperfusion injury. However, NSCs are difficult to obtain owing to ethical limitations. In addition, the survival, differentiation, and proliferation rates of transplanted exogenous NSCs are low, which limit their clinical application. Our previous study showed that neuregulin1ß (NRG1ß) alleviated cerebral I/R injury in rats. In this study, we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1ß on PC12 cells injured by oxygen-glucose deprivation/reoxygenation (OGD/R). Our results found that 5 and 10 nM NRG1ß promoted the generation and proliferation of NSCs. Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1ß improved the level of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, nicotinamide adenine dinucleotide phosphate, and nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial damage in injured PC12 cells; these indexes are related to ferroptosis. Research has reported that p53 and solute carrier family 7 member 11 (SLC7A11) play vital roles in ferroptosis caused by cerebral I/R injury. Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4 (GPX4) was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells, but this change was alleviated after co-culturing NSCs with damaged PC12 cells. These findings suggest that NSCs pretreated with NRG1ß exhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

2.
J Family Med Prim Care ; 11(8): 4131-4134, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36352927

RESUMO

When the coronavirus disease (COVID-19) virus swept the world in December 2019, it brought widespread side-effects. While there is no specific treatment for COVID-19, individuals and collectives often respond rapidly to develop a routine, making the prevention and control of COVID-19 normalized and institutionalized and creating vaccines successfully in a short time. However, this situation also exposed a spectrum of problems triggered by lockdown, isolation, and vaccinations. Herein, we analyze the prevention management of COVID-19 from epidemic psychology in order to provide a new sight for overcoming the psychological problems of COVID-19.

3.
Sci Rep ; 12(1): 18949, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347913

RESUMO

The potential use of gelatin materials in the liquid composite molding manufacturing (LCM) process was investigated, with specific focus on the reinforcement deformation phenomenon. The adoptability of gelatin as a binder in a composite material with glass fiber for application in the LCM process was evaluated by analyzing the permeability and microscopic structure of the gelatin-coated glass fiber. To assess the tow deformation, the permeability of the non-crimped unidirectional glass fiber mat was evaluated at different flow rates that could be applied in the LCM process. Hysteresis of the permeability was observed as the flow rate increased and decreased, indicative of tow deformation. The permeability of the gelatin-treated glass fiber mat exhibited a relatively smaller variation than that of the untreated glass fiber at the same flow rate. Tow deformation in the untreated and gelatin-treated non-crimped glass fiber mats at different flow rates was evaluated by microscopic analysis and quantified using the tow thickness index. Relatively smaller variations in the permeability and minimal changes in the tow thickness of the gelatin-treated glass fiber mat were observed via microscopic analysis, indicating that gelatin effectively maintained the binding structure of the glass fiber mat.


Assuntos
Gelatina , Vidro , Gelatina/química , Vidro/química , Resinas Vegetais , Resinas Compostas/química , Teste de Materiais
4.
Nat Prod Res ; : 1-9, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36373778

RESUMO

Objectives: An ethanol extract of the whole plants of Saussurea medusa had been investigated to find novel anti-inflammatory sesquiterpenoids. Methods: Extensive spectroscopic data and chemical methods were applied to elucidate the structures of the compounds. Results: One new megastigmane sesquiterpenoid (1), along with 11 known analogues (2-12), were obtained from S. medusa. All isolates, except compounds 3 and 6, were mentioned from the studied plant for the first time. Compounds 1, 2, 4, 5, 7, 8 and 12 were firstly isolated from the genus Saussurea. Compounds 2, 9 and 10 were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC50 values ranging from 21.1 ± 1.7 to 46.7 ± 1.9 µM. Furthermore, iNOS expression experiment was performed to examine the interactions between the active compounds and the iNOS enzyme.

5.
Front Neurol ; 13: 952843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388233

RESUMO

Objectives: This study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients. Methods: All patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit method. Results: The SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, ß = 0.81), onset-to-needle time (≥3.5 = 1,<3.5=0, ß = 0.74), NIH Stroke Scale on admission (>10 = 2, ≤10 = 0, ß = 1.22), neutrophil percentage (≥80.0% = 1, <80% = 0, ß = 0.81), ASPECT score (≤11 = 2, >11 = 0, ß = 1.30), and age (>65 years = 1, ≤65 years = 0, ß = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675-2.34) and poor outcomes (OR 1.89; 95%CI 1.68-2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77-0.86). Similar results were obtained in the validation cohort. The Hosmer-Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close. Conclusion: The SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.

6.
Front Microbiol ; 13: 1040846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406423

RESUMO

Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage. Epidemiological data demonstrated that the high morbidity of T2DM occurs as a result of obesity and gradually develops into serious complications. To date, the mechanisms that underlie this observation are still ill-defined. In view of the effect of obesity on the gut microflora, Leprdb/db mice underwent antibiotic treatment and microbiota transplants to modify the gut microbiome to investigate whether microbes are involved in the development of diabetic nephropathy (DN) and/or diabetic retinopathy (DR). The mouse feces were collected for bacterial 16S ribosomal RNA gene sequencing. Cytokines including TNF-α, TGF-ß1, IFN-γ, IL-1ß, IL-6, IL-17A, IL-10, and VEGFA were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR and immunofluorescent assay. Eyes and kidney were collected for histopathological assay. Intestinal permeability was also detected using Evans Blue. The results showed that obesity influenced metabolic variables (including fast/fed glucose, insulin, and triglyceride), retinopathy and nephropathy, and the gut microbiota. Obesity mainly reduced the ratio of Bacteroidetes/Firmicutes and influenced relative abundance of Proteobacteria, Actinobacteria, and Spirochetes. Obesity also increased intestinal permeability, metabolic endotoxemia, cytokines, and VEGFA. Microbiota transplants confirm that obesity aggravates retinopathy and nephropathy through the gut microbiota. These findings suggest that obesity exacerbates retinopathy and nephropathy by inducing gut microbiota dysbiosis, which further enhanced intestinal permeability and chronic low-grade inflammation.

7.
Front Genet ; 13: 990301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276934

RESUMO

Background: Disorders of CD274 and PDCD1LG2 contribute to immune escape in human cancers, and treatment with anti-programmed death receptor 1 (PD-1) has been widely used in recurrent or metastatic tumors. However, integrated studies considering CD274 and PDCD1LG2 across cancers remain limited. Materials and Methods: Differences in expression levels of CD274 and PDCD1LG2 were analyzed in diverse cancer types using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The clinical information and matched expression profiles of TCGA patients were obtained to determine the prognostic value of CD274 and PDCD1LG2. Moreover, correlations between CD274 and PDCD1LG2 and the immune signature were analyzed by exploring the TIMER2 and TISIDB databases. We also investigated correlations between CD274 and PDCD1LG2 and immunotherapeutic biomarkers, including mismatch repair (MMR), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA methylation. Results: Expression levels of CD274 and PDCD1LG2 varied across multiple cancer types. CD274 and PDCD1LG2 not only impacted the prognosis of patients with cancer but were associated with clinical characteristics (lymph node metastasis, tumor stage, and sex) in kidney renal papillary cell carcinoma, thyroid carcinoma, and some other cancer types. Typically, CD274 and PDCD1LG2 could be strongly correlated with macrophages, dendritic cells, neutrophils, and CD8+ T-cells. Furthermore, CD274 and PDCD1LG2 expression were associated with various immunosuppressive biomarkers, such as CTLA4, TIGIT, and LAG3. In addition, CD274 and PDCD1LG2 were significantly associated with MMR, TMB, MSI, and DNA methylation. Finally, enrichment analysis confirmed that CD274 and PDCD1LG2 were associated with numerous biological pathways, such as: "Activation of Immune Reactions" and "Epithelial-Mesenchymal Transition," suggesting that CD274 and PDCD1LG2 play crucial roles in cancer immunity and tumor metastasis. Conclusion: CD274 and PDCD1LG2 play critical roles in cancer progression and immune response and could serve as effective biomarkers to predict the prognosis and immune signature of cancer.

8.
J Mater Chem B ; 10(42): 8664-8671, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36217743

RESUMO

Bacterial wound infection has brought a serious threat to human health and caused huge economic losses. Attempts to develop biomaterials with excellent antibacterial effects are meaningful to promote wound healing. Herein, we report a multifunctional nanoreactor with nutrient consumption and reactive oxygen species (ROS) generation capabilities for antibacterial and skin wound repair. The nanoreactor was constructed by the encapsulation of glucose oxidase (GOx) into a Cu2+-doped zeolite-based imidazole framework (ZIF-8) through a one-pot synthesis method. The nanoreactor not only consumes the nutrients of bacteria by the GOx-driven oxidation reaction, but also generates highly toxic hydroxyl radicals (˙OH) to kill bacteria via a Cu+-mediated Fenton-like reaction. Moreover, Zn2+ released from the nanoreactor is also capable of exhibiting synergistic antibacterial activity. In addition to mediating Fenton-like reactions, Cu2+ promotes angiogenesis to accelerate wound healing. Thus, the multifunctional nanoreactor has the ability to cut off the nutrient supply and starve the bacteria, produce ROS to kill bacteria, and promote angiogenesis to accelerate wound healing, enabling it to be promising for the treatment of wound infection.


Assuntos
Antibacterianos , Infecção dos Ferimentos , Humanos , Espécies Reativas de Oxigênio , Antibacterianos/farmacologia , Glucose Oxidase , Nutrientes , Nanotecnologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-36294070

RESUMO

Based on 447 samples collected from a shallow aquifer (depths from 0 to 150 m) in the Hetao Basin, Northern China, an integrated hydrogeochemical approach was used in this study to conceptualize the enrichment of high arsenic groundwater in the Hetao Basin. An unconventional method of distinguishing hydrogeochemical and physical processes from a dataset was tested by investigating the cumulative frequency distribution of ionic ratios expressed on a probability scale. By applying cumulative frequency distribution curves to characterize the distribution of ionic ratios throughout the Hetao Basin, hydrogeochemical indicators were obtained that distinguish the series of hydrogeochemical processes that govern groundwater composition. All hydrogeochemical processes can basically be classified as recharge intensity of groundwater, evaporation concentration intensity, and reductive degree controlling the spatial distribution of arsenic. By considering the three processes, we found that the concentration of arsenic was more than 10 µg/L when the (HCO3-+CO32-)/SO42- ratio was over 4.1 (strong reductive area). As the evaporation concentration intensity increased, the median value of arsenic increased from 10.74 to 382.7 µg/L in the median reductive area and rapidly increased from 89.11 to 461.45 µg/L in the strong reductive area. As the river recharge intensity increased (with the intensity index increasing from 0 to 5), the median value of arsenic dropped from 40.2 to 6.8 µg/L in the median reductive area and decreased more markedly from 219.85 to 23.73 µg/L in the strong reductive area. The results provide a new insight into the mechanism of As enrichment in groundwater.


Assuntos
Arsênio , Água Subterrânea , Poluentes Químicos da Água , Arsênio/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Água Subterrânea/química , Rios/química , China
10.
Appl Opt ; 61(25): 7349-7353, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256033

RESUMO

Frequency conversion imaging technology can provide an effective way for infrared detection against the limitations of conventional infrared detectors, such as expense and cooling requirements, but the converted luminescence intensity of frequency conversion materials limits the application of this technology. In this paper, a cascade material (CM) fusion method is proposed to improve the conversion luminous intensity and thus enhance the frequency conversion imaging effect at 1550 nm near infrared (NIR) excitation. First, we derived from the energy level transition mechanism of CM that the CM fusion method can achieve three excitations of substrate materials (SMs). It can improve the conversion luminescence intensity of SM in CM. Then, we experimentally prepared CM and SM films and simultaneously measured the frequency conversion imaging effect of the two films at 1550 nm NIR excitation. It was found that the weight ratio of doped material (DM) to SM affects the imaging enhancement of CM films. Therefore, we compared the imaging grayscale value intensity of CM films with different weight ratios under the same detection conditions. Finally, it was concluded that the best enhancement of frequency conversion imaging was achieved with a DM to SM weight ratio of 0.25 for this mechanism. The enhancement was about 3.11 times compared to SM films.

11.
Virology ; 577: 43-50, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36279602

RESUMO

Acquired immunodeficiency syndrome (AIDS) caused by Human immunodeficiency virus type 1 (HIV-1) has a high tendency among illicit drug abusers. Recently, it is reported that abuse of fentanyl, a potent synthetic µ receptor-stimulating opioid, is an independent risk factor for HIV-1 infection. However, the mechanism of action in augmenting HIV-1 infection still remains elusive. In this study, we found that fentanyl enhanced infection of HIV-1 in MT2 cells, primary macrophages and Jurkat C11 cells. Fentanyl up-regulated CXCR4 and CCR5 receptor expression, which facilitated the entry of virion into host cells. In addition, it down-regulated interferon-ß (IFN-ß) and interferon-stimulated genes (APOBEC3F, APOBEC3G and MxB) expression in MT2 cells. Our findings identify an essential role of fentanyl in the positive regulation of HIV-1 infection via the upregulation of co-receptors (CXCR4/CCR5) and downregulation of IFN-ß and ISGs, and it may have an important role in HIV-1 immunopathogenesis.

12.
Opt Express ; 30(12): 21931-21942, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224903

RESUMO

Optical solitons, particle-like excitations ubiquitous in many fields, can bind to form soliton molecules with striking molecule-like interactions. However, the exotic soliton interactions in soliton molecules are still largely unexplored in dual-wavelength mode-locked fiber lasers. Here, we reveal the dynamics of dissipative soliton molecules with periodic solitons collision in a dual-wavelength ultrafast fiber laser. The soliton molecules with a central wavelength of 1532.8 nm and 1561 nm exhibit conspicuously different evolution characteristics attributed to the difference in gain spectral intensity and trapped potential. The long-wavelength soliton molecule swiftly recovers to the initial state after collision, while the short-wavelength soliton molecule has a remarkable variation in temporal separation and operation state. Moreover, the multiple intensive repulsion and attraction in soliton molecule with energy transfer between leading and trailing solitons, and the formation of triplet soliton molecule in short-wavelength with multiple switching have also been observed. The different oscillating solutions coexisting in dual-wavelength soliton molecules involving oscillating and sliding phase evolution confirm the multistability of the dissipative system. These findings shed new insights into the dynamics of soliton molecules and solitons collision in nonlinear systems.

13.
Opt Express ; 30(13): 23716-23724, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36225046

RESUMO

Nonlinear crystal frequency conversion imaging with direct detection by silicon-based detectors is an effective way to break through the limitations for existing near-infrared (NIR) detectors with expensive cost and high noise. In this paper, a broadband NIR detector imaging scheme based on the principle of nonlinear crystal frequency conversion (NCFCP) was proposed. A thin film of nonlinear crystal frequency conversion material (NCFCM) combined with a silicon-based detector was used to form a broadband NIR detector. The theoretically investigated energy transfer function was used as a guidance for experiment. Meanwhile, the relationship between the imaging effect and the energy transfer of the NCFCP-based compact broadband NIR detector in the NIR band was measured experimentally. The accuracy of the theoretical study had been verified by the measured transfer results.

14.
Nucleic Acids Res ; 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36243963

RESUMO

Antimicrobial toxins help prokaryotes win competitive advantages in intraspecific or interspecific conflicts and are also a critical factor affecting the pathogenicity of many pathogens that threaten human health. Although many studies have revealed that antagonism based on antimicrobial toxins plays a central role in prokaryotic life, a database on antimicrobial toxins remains lacking. Here, we present the prokaryotic antimicrobial toxin database (PAT, http://bioinfo.qd.sdu.edu.cn/PAT/), a comprehensive data resource collection on experimentally validated antimicrobial toxins. PAT has organized information, derived from the reported literature, on antimicrobial toxins, as well as the corresponding immunity proteins, delivery mechanisms, toxin activities, structural characteristics, sequences, etc. Moreover, we also predict potential antimicrobial toxins in prokaryotic reference genomes and show the taxonomic information and environmental distribution of typical antimicrobial toxins. These details have been fully incorporated into the PAT database, where users can browse, search, download, analyse and view informative statistics and detailed information. PAT resources have already been used in our prediction and identification of prokaryotic antimicrobial toxins and may contribute to promoting the efficient investigation of antimicrobial toxin functions, the discovery of novel antimicrobial toxins, and an improved understanding of the biological roles and significance of these toxins.

15.
Carbohydr Polym ; 298: 120102, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36241325

RESUMO

Pharmaceuticals and personal care products (PPCPs) are gaining attention due to their persistence in the environment. Therefore, the development of novel adsorbents to remove them is strongly anticipated. In this study, an improved dual ice-template assembly method had been used for the preparation of ZIF-67/QGO/SB-CS aerogel through ZIF-67, benzoquinone-modified graphene oxide (QGO), and sulfobetaine-modified chitosan (SB-CS) for the adsorption and removal of PPCPs in water. We reported for the first time that the chitosan composite aerogel has antifouling, bacterial filtration and oil-water separation abilities with excellent PPCPs adsorption performance and reusable, which would be a viable option for long-lasting adsorbents for PPCPs in water.


Assuntos
Quitosana , Cosméticos , Poluentes Químicos da Água , Adsorção , Benzoquinonas , Gelo , Preparações Farmacêuticas , Água , Poluentes Químicos da Água/análise
16.
Bioorg Med Chem ; 72: 116968, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36054994

RESUMO

Oxetanocin A (Oxt-A), a novel oxetanosyl N-glycoside nucleoside, was isolated from Bacillus megaterium in 1986. It carries an oxetane ring on the sugar moiety of the nucleoside scaffold, which contributes to differences in its structure from those of common tetrahydrofuranyl-based nucleosides. In view of the unique 3D-spatial framework, the complete synthesis of Oxt-A has been achieved by multiple research groups. The pharmacological properties of this natural product have also been broadly investigated by pharmacists and chemists since its discovery. Notably, the potential antiviral effect of Oxt-A has captured attention of researchers in the field of antiviral agent development. Furthermore, epidemic outbreaks caused by viruses have been stimulating the preparation and modification of various Oxt-A analogs over the past few decades. However, none of the studies have overviewed the antiviral efficacies of this naturally occurring scaffold yet. Thus, the present review summarizes the synthesis, structural modification, and antiviral activities of Oxt-A and its derivatives. We believe that these comprehensive descriptions will provide a novel perspective for the discovery of antivirus drugs with well-improved performance and pave newer paths for combating sudden public health issues triggered by viruses in the future.


Assuntos
Antivirais , Produtos Biológicos , Adenina/análogos & derivados , Antivirais/química , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Nucleosídeos/farmacologia , Açúcares
17.
Front Immunol ; 13: 964118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059470

RESUMO

Background: Necroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear. Methods: We extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed. Results: A total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942. Conclusion: Our research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.


Assuntos
Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/genética , Variações do Número de Cópias de DNA , Humanos , Necroptose/genética , Proteínas do Tecido Nervoso/genética , Prognóstico , Receptores Acoplados a Proteínas G/genética , Receptores de Neurotransmissores , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/genética
18.
Cancer Sci ; 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36156330

RESUMO

Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti-angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic-related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient-derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET-1), an important regulator of angiogenesis and the hypoxia-related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET-1-induced hypoxia-inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.

20.
Front Surg ; 9: 907086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132196

RESUMO

Objective: The objective of the study is to analyze the influencing factors on the results of thyroid fine-needle aspiration biopsy (FNAB). Method: A total of 339 patients who underwent FNAB in our hospital from December 2018 to July 2021 were retrospectively selected. The patients were chosen according to the gender ratio, age, and thyroid ultrasound characteristics and were divided into three groups: (1) a 22G needle vacuum aspiration group (Group 1, n = 85), (2) a 22G biopsy needle non-vacuum aspiration group (Group 2, n = 50), and (3) a 25G biopsy needle non-vacuum aspiration group (Group 3, n = 204). Patients in these groups were evaluated for determining the FNAB dissatisfaction rate of pathological samples. A bivariate regression analysis of independent risk factors related to the unsatisfactory pathological diagnosis of samples was performed. Results: The specimen dissatisfaction rates of the three groups were 22/85 (25.9%), 15/50 (30%), and 18/186 (9.7%), respectively. The overall sample dissatisfaction rate was 55/339 (16.2%), and the sample satisfaction rate of Group 3 was higher than that of Groups 1 and 2 (P < 0.05). Logistic bivariate regression analysis showed that the age of the patients and the capillary sampling needles and aspiration methods were two independent risk factors for determining the dissatisfaction rate of FNAB pathological samples. Conclusion: A 25G capillary sampling aspiration biopsy needle was selected to perform FNAB in thyroid nodules without vacuum aspiration, which could effectively improve the accuracy of FNAB results with a high specimen satisfaction rate.

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