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1.
Asian J Androl ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38727211

RESUMO

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

3.
Ultrasound Med Biol ; 50(4): 520-527, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38281886

RESUMO

OBJECTIVE: The aim of the work described here was to develop and validate a predictive model for cytokeratin 7 (CK7) expression in clear cell renal cell carcinoma (ccRCC) patients by combining multimodal ultrasound diagnostic techniques. METHODS: This retrospective study enrolled 157 surgically confirmed ccRCC patients. All patients underwent pre-operative multimodal ultrasound diagnostic examinations, including B-mode ultrasound (US), color Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The patients were randomly divided into a training group (103 cases) and a testing group (54 cases). Univariate and multivariate logistic regression analyses were performed in the training group to identify independent indicators associated with CK7 positivity. These indicators were included in the predictive model. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the model's discriminative ability and accuracy. Decision curve analysis (DCA) and nomogram visualization were used to assess the clinical utility of the predictive model. RESULTS: Univariate logistic regression analysis revealed that US and CDFI observations were not correlated with CK7 expression and could not predict it. Multivariate logistic regression analysis identified age (odds ratio [OR] = 0.953, 95% confidence interval [CI]: 0.909-0.999), wash-in pattern (OR = 0.180, 95% CI: 0.063-0.513) and enhancement homogeneity (OR = 11.610, 95% CI: 1.394-96.675) as independent factors related to CK7 positivity in ccRCC. Incorporating these variables into the predictive model resulted in areas under the receiver operating characteristic curve of 0.812 (95% CI: 0.711-0.913) for the training group and 0.792 (95% CI: 0.667-0.924) for the testing group. The calibration curve and DCA revealed that the model had good accuracy and clinical utility of the model. CONCLUSION: The combination of multimodal ultrasound diagnostic techniques in constructing a predictive model for CK7 expression in ccRCC patients has significant predictive value.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Estudos Retrospectivos , Queratina-7 , Ultrassonografia , Proteínas de Filamentos Intermediários , Neoplasias Renais/diagnóstico por imagem
4.
BMC Med Imaging ; 24(1): 26, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273224

RESUMO

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/patologia , Bexiga Urinária/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Ultrassonografia
5.
Front Pharmacol ; 14: 1217001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663256

RESUMO

Naringin is a kind of natural dihydro flavone, which mainly exists in citrus fruits of the Rutaceae family, as well as traditional Chinese medicines such as trifoliate orange, fingered citron, exocarpium citri grandis, and rhizoma dynamite. Modern pharmacological studies have shown that Naringin has excellent anti-tumor activity. Through reviewing the relevant literature at home and abroad in recent years, we summarized the pharmacological mechanism of Naringin to play an anti-cancer role in blocking tumor cell cycle, inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell invasion and metastasis, inducing tumor cell autophagy, reversing tumor cell drug resistance and enhancing chemotherapeutic drug sensitivity, as well as anti-inflammatory to prevent canceration, alleviate Adverse drug reaction of chemotherapy, activate and strengthen immunity, It provides theoretical basis and reference basis for further exploring the anticancer potential of Naringin and its further development and utilization.

6.
Cell Death Dis ; 14(8): 553, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620327

RESUMO

Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8+ cells (representing CD8+ T cells) and CD57+ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA+ cells and GSDMB+ cells were predominantly expressed in immune cells, especially in CD8 + T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA+ merged CD8+ T cells (0.11%) and GSDMB+ merged CD57+ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Linfócitos T CD8-Positivos , Piroptose/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Células Matadoras Naturais , Microambiente Tumoral
7.
BMC Med Imaging ; 23(1): 65, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217872

RESUMO

BACKGROUND: The usefulness of transvaginal two-dimensional shear wave elastography (2D SWE) for cervical lesions is still uncertain. This study was to explore the value of transvaginal 2D SWE in the evaluation of the stiffness of normal cervix and its change with different factors under strict quality control (QC). METHODS: Two hundred patients with normal cervix were included in this study and were examined using quantitative 2D SWE to evaluate cervical stiffness and its change with different factors under strict QC. RESULTS: Intra-observer concordance of transvaginal 2D SWE parameters in midsagittal planes were acceptable with intraclass correlation coefficients higher than 0.5. Transvaginal 2D SWE parameters were significantly higher than the corresponding transabdominal parameters. 2D SWE parameters of internal cervical os were significantly higher than the corresponding parameters of external cervical os in a transvaginal midsagittal plane. 2D SWE parameters of external cervical os increased significantly over 50 years old, while these parameters of internal cervical os didn't change significantly with increasing age. 2D SWE parameters of internal cervical os of horizontal position cervix were significantly higher than those of vertical position cervix. SWE parameters of normal cervix did not change according to different menstrual cycles, parities and human papilloma virus test results. CONCLUSIONS: Transvaginal 2D SWE under strict QC could provide quantitative, repeatable and reliable cervical stiffness information. Internal cervical os was stiffer than external cervical os. Menstrual cycles, parities and human papilloma virus test results wouldn't affect cervical stiffness. However, age and cervical positions should be taken into condition while interpreting 2D SWE results of cervical stiffness.


Assuntos
Técnicas de Imagem por Elasticidade , Feminino , Humanos , Pessoa de Meia-Idade , Técnicas de Imagem por Elasticidade/métodos , Colo do Útero/diagnóstico por imagem , Controle de Qualidade , Cirrose Hepática
8.
J Surg Res ; 287: 24-32, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36863270

RESUMO

INTRODUCTION: To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS). METHODS: Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded. RESULTS: After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05. CONCLUSIONS: The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock.


Assuntos
Choque Hemorrágico , Ratos , Masculino , Animais , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Hemorragia , Ressuscitação , Ácido Láctico
9.
Asian J Androl ; 25(3): 389-397, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35915541

RESUMO

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.


Assuntos
Exossomos , Infertilidade Masculina , MicroRNAs , Orquite , Escherichia coli Uropatogênica , Humanos , Masculino , Camundongos , Animais , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Exossomos/metabolismo , Macrófagos/metabolismo , Fenótipo , Infertilidade Masculina/metabolismo
10.
Inorg Chem ; 61(43): 16986-16991, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36264301

RESUMO

Herein, we represent a bimetallic approach to enhance the defect number, leading to eight defect sites per node in a metal-organic framework, showing both a higher SO2 adsorption capacity and higher SO2/CO2 selectivity. The results can be further strongly supported by density functional theory calculations.

11.
World J Gastroenterol ; 28(32): 4716-4725, 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36157921

RESUMO

BACKGROUND: The clinical management and prognosis differ between benign and malignant solid focal liver lesions (FLLs), as well as among different pathological types of malignant FLLs. Accurate diagnosis of the possible types of solid FLLs is important. Our previous study confirmed the value of shear wave elastography (SWE) using maximal elasticity (Emax) as the parameter in the differential diagnosis between benign and malignant FLLs. However, the value of SWE in the differential diagnosis among different pathological types of malignant FLLs has not been proved. AIM: To explore the value of two-dimensional SWE (2D-SWE) using Emax in the differential diagnosis of FLLs, especially among different pathological types of malignant FLLs. METHODS: All the patients enrolled in this study were diagnosed as benign, malignant or undetermined FLLs by conventional ultrasound. Emax of FLLs and the periphery of FLLs was measured using 2D-SWE and compared between benign and malignant FLLs or among different pathological types of malignant FLLs. RESULTS: The study included 32 benign FLLs in 31 patients and 100 malignant FLLs in 96 patients, including 16 cholangiocellular carcinomas (CCCs), 72 hepatocellular carcinomas (HCCs) and 12 liver metastases. Thirty-five FLLs were diagnosed as undetermined by conventional ultrasound. There were significant differences between Emax of malignant (2.21 ± 0.57 m/s) and benign (1.59 ± 0.37 m/s) FLLs (P = 0.000), and between Emax of the periphery of malignant (1.52 ± 0.39 m/s) and benign (1.36 ± 0.44 m/s) FLLs (P = 0.040). Emax of liver metastases (2.73 ± 0.99 m/s) was significantly higher than that of CCCs (2.14 ± 0.34 m/s) and HCCs (2.14 ± 0.46 m/s) (P = 0.002). The sensitivity, specificity and accuracy were 71.00%, 84.38% and 74.24% respectively, using Emax > 1.905 m/s (AUC 0.843) to diagnose as malignant and 23 of 35 (65.74%) FLLs with undetermined diagnosis by conventional ultrasound were diagnosed correctly. CONCLUSION: Malignant FLLs were stiffer than benign ones and liver metastases were stiffer than primary liver carcinomas. 2D-SWE with Emax was a useful complement to conventional ultrasound for the differential diagnosis of FLLs.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Técnicas de Imagem por Elasticidade , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/diagnóstico por imagem , Diagnóstico Diferencial , Técnicas de Imagem por Elasticidade/métodos , Humanos , Neoplasias Hepáticas/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Am J Transl Res ; 14(3): 2101-2108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422938

RESUMO

OBJECTIVE: To investigate the effects of low molecular weight heparin (LMWH) combined with hyperbaric oxygen (HBO) on the neurologic function and coagulation factors of patients with intracranial venous thrombosis (ICVT). METHODS: The clinical data of 80 patients with ICVT admitted to the No. 2 Hospital of Baoding from February 2020 to January 2021 were retrospectively analyzed. Patients were assigned to a control group (n=32) and a research group (n=48) according to different treatment methods. The neurological function score, and the levels of D-dimer (D-D), fibrinogen (FIB), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were compared between the two groups. The two groups were also compared regarding the curative effect, toxic and side effects, as well as quality of life (QoL). RESULTS: After treatment, the National Institutes of Health Stroke Scale (NIHSS) score was significantly lower in the research group compared to the control group. At 1, 2 and 3 weeks after treatment, the levels of D-D and FIB, as well as inflammatory factors TNF-α and CRP were lower in the research group compared to the control group. The overall response rate was significantly higher in the research group compared to the control group, while there was no significant difference in the total incidence of toxic and adverse effects between the two groups. After treatment, the QoL of patients assessed by the Generic Quality of Life Inventory-74 (GQOLI-74) from the domains of physical, social, and psychological function as well as material life status was significantly better in the research group. CONCLUSIONS: LMWH combined with HBO can effectively improve the clinical efficacy and neurologic function of patients with ICVT and reduce the levels of coagulation factors and inflammatory factors.

13.
Zhonghua Nan Ke Xue ; 28(10): 873-880, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37838952

RESUMO

OBJECTIVE: To explore the relationship of the exposure to phthalate esters (PAE) and polycyclic aromatic hydrocarbons (PAH) with clinical premature delivery during early pregnancy. METHODS: We conducted a baseline questionnaire survey among 821 pregnant women undergoing prenatal examination in Hubei Provincial Maternal and Child Health Care Hospital, collected their morning urine samples and followed them up to the outcomes of pregnancy. We quantitatively analyzed 10 PAE and 10 PAH metabolites in the urine samples, followed by Mann-Whitney U test, chi-square test, and logistic regression analysis. RESULTS: The detection rate of the 5 factors exposed to was >80% while that of phthalic acid monobenzyl ester (MBzP) was <50% in PAEs; that of the 5 factors exposed to was >80%, that of 3-hydroxyphene (3-OHPHE) was 86.91% while that of 4-hydroxyphene (4-OHPHE) was <50% in PAHs. Logistic regression analysis showed that the risk of premature delivery was higher in the high MBzP- than in the low MBzP-exposure group (aOR = 2.26, 95% CI: 1.17-4.39). CONCLUSION: High MBzP-exposure may be a risk factor for premature delivery.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Criança , Humanos , Feminino , Gravidez , Estudos de Coortes , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Fatores de Risco , Família , Ésteres
14.
Zhonghua Nan Ke Xue ; 28(9): 806-811, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37839006

RESUMO

OBJECTIVE: To explore the association of the 25-hydroxy vitamin D (25(OH)D) level in the serum with the early pregnancy outcome of frozen-thawed embryo transfer (FET). METHODS: We selected 119 infertile women that underwent FET and detection of serum 25(OH)D in the Department of Reproductive Medicine of the General Hospital of Central Theater Command from April 2020 to December 2021. According the level of serum 25(OH)D, we divided the patients into three groups: 25(OH)D <45.0 nmol/L (n = 59), 25(OH)D 45.0-75.0 nmol/L (n= 47), and 25(OH)D ≥75.0 nmol/L but <375.0 nmol/L) (n = 13), compared the basic information and the rates of clinical pregnancy, embryo implantation and adverse pregnancy among the three groups, and investigated the factors affecting the early pregnancy outcome using binary logistic regression analysis. RESULTS: No statistically significant differences were observed among the three groups in the age (≤42 yr), body mass index (BMI), endometrial thickness at the transplantation day (≥7 mm), numbers of embryos transferred and high-quality embryos transferred, or rates of clinical pregnancy, embryo implantation and adverse pregnancy (P > 0.05). Binary logistic regression analysis showed that the rate of early clinical pregnancy was significantly correlated with the level of serum 25(OH)D (OR: 1 064, P = 0.040) and the number of high-quality embryos transferred (OR: 0.495, P = 0.004), but not with the age (≤42 yr), BMI, endometrial thickness at the transplantation day (≥ 7 mm), number of embryos transferred, or the levels of E2 and progesterone at the transplantation day (P > 0.05). CONCLUSION: The level of serum 25(OH)D is positively correlated with the early pregnancy outcome of FET. A high serum 25 (OH) D level can improve the outcome and can be used as a good indicator to predict the success rate of FET.


Assuntos
Infertilidade Feminina , Resultado da Gravidez , Feminino , Gravidez , Humanos , Infertilidade Feminina/terapia , Criopreservação , Transferência Embrionária , Vitamina D , Taxa de Gravidez , Estudos Retrospectivos
15.
J Ethnopharmacol ; 285: 114845, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34800645

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-ji Hua-yu (SJHY) formula is a Chinese herbal prescription for diabetic ulcers (DUs) treatment, which can accelerate wound reconstruction and shorten the healing time. However, its mechanism role maintains unclear. AIM OF THE STUDY: To elucidate the molecular mechanisms of SJHY application on DUs. MATERIALS AND METHODS: To begin with, transcriptome sequencing was adopted to identified differentially expression mRNAs among normal ulcers, DUs, and DUs + SJHY treatment in vivo. Liquid chromatography-tandem mass spectrometry was applied for the quality control of SJHY formula. GO and KEGG enrichment analysis were used to identify the mechanisms underlying the therapeutic effect of SJHY formula, and then gene set enrichment analysis and ingenuity pathway analysis were conducted for functional analysis. Further, qPCR detection was performed in vivo for validation. RESULTS: SJHY administration could regulate the glucose metabolic process, AMPK and HIF-1 pathway to accelerate healing processes of DUs. Besides, CRHR1, SHH, and GAL were identified as the critical targets, and SLC6A3, GRP, FGF23, and CYP27B1 were considered as the upstream genes of SJHY treatment. Combined with animal experiments, the prediction results were validated in DUs mice model. CONCLUSIONS: This study used modular pharmacology analysis to identify the biomarkers of SJHY formula and provide the potential therapeutic targets for DUs treatment as well.


Assuntos
Medicamentos de Ervas Chinesas , Úlcera Cutânea , Animais , Humanos , Camundongos , Complicações do Diabetes , Diabetes Mellitus Experimental , Medicamentos de Ervas Chinesas/uso terapêutico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Cicatrização/efeitos dos fármacos
16.
Front Pharmacol ; 12: 726158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867329

RESUMO

Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand-receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.

17.
Front Immunol ; 12: 743354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764959

RESUMO

Macrophages are functionally plastic and can thus play different roles in various microenvironments. Testis is an immune privileged organ, and testicular macrophages (TMs) show special immunosuppressive phenotype and low response to various inflammatory stimuli. However, the underlying mechanism to maintain the immunosuppressive function of TMs remains unclear. S100A9, a small molecular Ca2+ binding protein, is associated with the immunosuppressive function of macrophages. However, no related research is available about S100A9 in mouse testis. In the present study, we explored the role of S100A9 in TMs. We found that S100A9 was expressed in TMs from postnatal to adulthood and contributed to maintaining the immunosuppressive phenotype of TMs, which is associated with the activation of PI3K/Akt pathway. S100A9 treatment promotes the polarization of bone marrow-derived macrophages from M0 to M2 in vitro. S100A9 was significantly increased in TMs following UPEC-infection and elevated S100A9 contributed to maintain the M2 polarization of TMs. Treatment with S100A9 and PI3K inhibitor decreased the proportion of M2-type TMs in control and UPEC-infected mouse. Our findings reveal a crucial role of S100A9 in maintaining the immunosuppressive function of TMs through the activation of PI3K/Akt pathway, and provide a reference for further understanding the mechanism of immunosuppressive function of TMs.


Assuntos
Calgranulina B/imunologia , Privilégio Imunológico/imunologia , Macrófagos/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Testículo/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/imunologia
18.
Urol Oncol ; 39(12): 837.e19-837.e28, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34654644

RESUMO

AIM: This study aimed to evaluate the value of real-time contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CECT) in the differential diagnosis of clear cell renal cell carcinoma (CCRCC), papillary renal cell carcinoma (PRCC), and chromophobe renal cell carcinoma (CRCC). MATERIALS AND METHODS: In the present study, 82 patients with CCRCC, 24 patients with PRCC, and 19 patients with CRCC were confirmed by pathology of the resected tumor. All patients were evaluated by CEUS and CECT before the operation. In addition, the contrast enhancement mode of CEUS and CECT and the contrast parameters of the region of interest (ROI) time-intensity curve between the lesions and the surrounding normal renal parenchyma by CEUS were compared and analyzed. RESULTS: Compared with the pathological results, the diagnostic accuracy of ultrasound in the 3 groups was 87.8% (72/82), 83.3% (20/24) and 73.7% (14/19). There was no significant difference between CEUS and CECT in the diagnostic accuracy of all groups (P>0.05). Meanwhile, compared with the surrounding renal parenchyma by CEUS, 82.5% (66/80) of CCRCC lesions showed "fast-forward and fast/slow-retrograde," while 83.3% (20/24) of PRCC, and 84.2% (16/19) showed "slow-forward and fast/slow-retrograde." Significant differences in the enhancement modes of CEUS were found among the CCRCC, PRCC, and CRCC lesions (P < 0.05). And the enhancement modes could be quantitatively analyzed by the ROI time-intensity curve of the lesion. Moreover, lesions enhanced by CECT and 74.4% (61/82) of CCRCC lesions showed "fast-forward and fast/slow-retrograde," while 66.7% (16/24) of PRCC and 84.2% (16/19) of CRCC showed "slow-forward and fast/slow-retrograde." The contrast modes and enhancement uniformity of CEUS and CECT showed no significant differences among the CCRCC, PRCC, and CRCC lesions (P > 0.05). CONCLUSION: CEUS and quantitative analysis of ROI time-intensity curve can be used for differential diagnosis of the 3 RCC subtypes. The combination of CEUS and CECT can help us differentiate RCC subtypes and is of great significance for clinical treatment strategies and prognostication.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Meios de Contraste/uso terapêutico , Neoplasias Renais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Diferenciação Celular , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Front Oncol ; 11: 604882, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712601

RESUMO

OBJECTIVE: A proportional hazard model was applied to develop a large-scale prognostic model and nomogram incorporating clinicopathological characteristics, histological type, tumor differentiation grade, and tumor deposit count to provide clinicians and patients diagnosed with colon cancer liver metastases (CLM) a more comprehensive and practical outcome measure. METHODS: Using the Transparent Reporting of multivariable prediction models for individual Prognosis or Diagnosis (TRIPOD) guidelines, this study identified 14,697 patients diagnosed with CLM from 1975 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) 21 registry database. Patients were divided into a modeling group (n=9800), an internal validation group (n=4897) using computerized randomization. An independent external validation cohort (n=60) was obtained. Univariable and multivariate Cox analyses were performed to identify prognostic predictors for overall survival (OS). Subsequently, the nomogram was constructed, and the verification was undertaken by receiver operating curves (AUC) and calibration curves. RESULTS: Histological type, tumor differentiation grade, and tumor deposit count were independent prognostic predictors for CLM. The nomogram consisted of age, sex, primary site, T category, N category, metastasis of bone, brain or lung, surgery, and chemotherapy. The model achieved excellent prediction power on both internal (mean AUC=0.811) and external validation (mean AUC=0.727), respectively, which were significantly higher than the American Joint Committee on Cancer (AJCC) TNM system. CONCLUSION: This study proposes a prognostic nomogram for predicting 1- and 2-year survival based on histopathological and population-based data of CLM patients developed using TRIPOD guidelines. Compared with the TNM stage, our nomogram has better consistency and calibration for predicting the OS of CLM patients.

20.
Inorg Chem ; 60(11): 8211-8217, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34018393

RESUMO

Encapsulating a certain guest molecule in an assigned molecular compartment and then endowing the corresponding potential remains a huge challenge for metal-organic frameworks. To this end, we demonstrate a good example, for the first time, based on an actinide-based MOF. The used MOF (namely, ECUT-300) shows a unique uranyl-TPE anionic skeleton with three distinct cages, viz., mesopore A (2.8 nm), mesopore B (2.0 nm), and micropore C (0.9 nm). Through solid-liquid reaction, a RhB+ molecule can be encapsulated into ECUT-300 with the exact location in mesopore B, whereas the encapsulation of a metal-organic cation of [Fe(tpy)2]3+ was observed with the location in micropore C, suggesting unprecedented classified encapsulation. Impressively, the potential of the resulting guest@MOF composites is also highly dependent on the type of encapsulated guest molecules, for example, white-light emission for RhB+ and selective adsorption of C2H2 over CO2 for [Fe(tpy)2]3+.

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