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1.
Medicine (Baltimore) ; 103(23): e38466, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847710

RESUMO

RATIONALE: Sclerosing angiomatoid nodular transformation (SANT) of the spleen is an uncommon benign vascular lesion with an obscure etiology. It predominantly affects middle-aged women and presents with nonspecific clinical signs, making preoperative diagnosis challenging. The definitive diagnosis of SANT relies on pathological examination following splenectomy. This study aims to contribute to the understanding of SANT by presenting a case series and reviewing the literature to highlight the clinical presentation, diagnostic challenges, and treatment outcomes. PATIENT CONCERNS: In this retrospective study, we analyzed the clinical data of 3 patients with confirmed SANT admitted from November 2013 to October 2023. The cases include a 25-year-old male, a 15-year-old female, and a 39-year-old male, each with a splenic mass. DIAGNOSES AND INTERVENTIONS: All of the three cases were treated by laparoscopic splenectomy (LS). Pathological examination confirmed SANT in all cases. OUTCOMES: No recurrence or metastasis was observed during a 10-year follow-up for the first 2 cases, and the third case showed no abnormalities at 2 months postoperatively. Despite its rarity, SANT is a significant condition due to its potential for misdiagnosis and the importance of distinguishing it from malignant lesions. The study underscores the utility of LS as a safe and effective treatment option. LESSONS: SANT is a rare benign tumor of the spleen, and the preoperative diagnosis of whom is challenging. LS is a safe and effective treatment for SANT, with satisfactory surgical outcomes and favorable long-term prognosis on follow-up. The study contributes to the limited body of research on this rare condition and calls for larger studies to validate these findings and improve clinical management.


Assuntos
Esplenectomia , Neoplasias Esplênicas , Humanos , Masculino , Adulto , Feminino , Esplenectomia/métodos , Adolescente , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/cirurgia , Neoplasias Esplênicas/diagnóstico , Baço/patologia , Histiocitoma Fibroso Benigno/patologia , Histiocitoma Fibroso Benigno/cirurgia , Histiocitoma Fibroso Benigno/diagnóstico , Estudos Retrospectivos , Laparoscopia/métodos , Diagnóstico Diferencial , Esplenopatias/cirurgia , Esplenopatias/patologia , Esplenopatias/diagnóstico
2.
J Control Release ; 369: 722-733, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583575

RESUMO

The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.


Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas , Doxorrubicina , Sistemas de Liberação de Medicamentos , Chaperona BiP do Retículo Endoplasmático , Glioma , Camundongos Nus , Peptídeos , Animais , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/farmacocinética , Humanos , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Peptídeos/química , Peptídeos/administração & dosagem , Barreira Hematoencefálica/metabolismo , Proteínas de Choque Térmico/metabolismo , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Camundongos Endogâmicos BALB C , Receptores de Dopamina D2/metabolismo , Camundongos , Masculino
3.
Front Public Health ; 12: 1332095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633232

RESUMO

Introduction: Adolescent suicide is a prevalent issue globally, with various factors contributing to this phenomenon. This study aimed to investigate these factors and their interrelationships to better understand the causes of adolescent suicide and provide evidence for its prevention. Methods: This study conducted among middle school students in Liaoning Province, China, from April to May 2016, A cross-sectional survey was administered to 1,028 students aged 10-19, using instruments such as the Behavior Questionnaire-Revised (SBQ-R), Children's Perception of Interparental Conflict Scale (CPIC), and revised version of Inventory of Parent Attachment (IPPA-R). Result: Binary logistic regression analysis revealed that adolescents aged 15-19, adolescents with strong perceptions of parental conflict were at high risk of suicide intention. Adolescents living in rural areas, adolescents with high mother-child attachment, adolescents with high father-child attachment were at low risk of suicide intention. Furthermore, parent-child attachment played a mediating role between two dimensions of parental conflict perception (resolved situations and response effect) and suicide intention. Discussion: The study concludes that adolescents living in urban areas, older adolescents, adolescents with a high level of parental conflict intensity, and those with low levels of parent-child attachment are at high risk of suicide intention. parent-child attachment played a mediating role between two dimensions of parental conflict perception (resolved situations and response effect) and suicide intention. Interventions aimed at reducing family conflicts and improving parent-child relationships are recommended to decrease the incidence of adolescent suicide.


Assuntos
Pais , Suicídio , Adolescente , Humanos , Estudos Transversais , Relações Pais-Filho , China/epidemiologia , Estudantes
4.
BMC Public Health ; 24(1): 787, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481184

RESUMO

BACKGROUND: Although previous studies have found that parenting style significantly predicts emotional and behavioral problems (EBPs) among Chinese adolescents, the mechanism between different parenting styles and EBPs requires in-depth investigation. In our study, we aimed to investigate the mediating effect of resilience, a positive psychological characteristic, between parenting style and EBPs among Chinese adolescents. METHODS: In this cross-sectional study, we used a multistage stratified cluster random sampling method to collect data in Shenyang, Liaoning Province from November to December 2019. Self-developed questionnaires were distributed to 1028 adolescents aged 10-18. Finally, the study consisted of 895 participants. The bootstrap method was used to investigate the role of resilience as a mediator in the relationship between different parenting styles and EBPs from a positive psychology perspective. RESULTS: The mean score of EBPs was 12.71 (SD = 5.77). After controlling for variables such as gender, age, left-behind children, family type and family income, resilience partially played a mediating role in the associations of paternal rejection (a × b = 0.051 BCa95%CI:0.023,0.080), maternal rejection (a × b = 0.055 BCa95%CI: 0.024, 0.086), paternal emotional warmth (a × b = -0.139 BCa95%CI: -0.182, -0.099) and maternal emotional warmth (a × b = -0.140 BCa95%CI: -0.182, -0.102), with EBPs. The effect sizes were11.28%, 11.51%, 40.76%, and 38.78%, respectively. CONCLUSIONS: Resilience could partially mediate the relationship between parenting style and EBPs, highlighting that parents should adopt a positive parenting style and that resilience improvement could be effective in reducing EBPs among Chinese adolescents.


Assuntos
Comportamento Problema , Resiliência Psicológica , Masculino , Criança , Humanos , Adolescente , Poder Familiar/psicologia , Estudos Transversais , China/epidemiologia
5.
Transl Oncol ; 44: 101929, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493517

RESUMO

BACKGROUND: The predictive value of the methylation of Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and H19 promoters in peripheral blood leukocytes as a non-invasive biomarker for the chemotherapy effect and prognosis gastric cancer (GC) is unclear. METHODS: The DNA methylation of H19 and MALAT1 between chemotherapy-sensitive and non-sensitive groups and between groups with better and worse survival of GC was compared using regression analyses. Several predictive nomograms were constructed. The genetic alteration of MALAT1 and H19 and the association between gene expression and immune status in GC were also investigated using bioinformatics analysis. RESULTS: Higher genetic methylations in peripheral blood were noticed in GC groups with poorer survival. The constructed nomograms presented strong predictive values for the chemotherapy effect and 3-year survival of disease-free survival, progression-free survival, and overall survival, with the area under the curve as 0.838, 0.838, 0.912, and 0.925, respectively. Significant correlations between MALAT1 or H19 expression and marker genes of immune checkpoints and immune pathways were noticed. The high infiltration of macrophages in H19-high and low infiltration of CD8+ T cells in MALAT1-high groups were associated with worse survival of GC. CONCLUSIONS: MALAT1 and H19 have the potential to predict the chemotherapy response and clinical outcomes of GC.

6.
J Surg Case Rep ; 2024(2): rjae027, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322356

RESUMO

Acute purulent enteritis is uncommon, which occasionally occurs in association with mechanical injuries from foreign bodies of helminth parasites and the contaminated food, leading to bacterial invasion. Herein we report a case of acute purulent enteritis after appendectomy. A 44-year-old male was diagnosed with right lower abdominal pain and vomiting. Acute appendicitis was diagnosed, and an open appendectomy was performed. Postoperatively, the patient developed symptoms of small intestine obstruction. A laparotomy revealed necrosis of the small intestine, and resection was performed. Pathological examination confirmed acute purulent enteritis. Acute purulent enteritis, which is a serious disease resulting in great disaster to patients, following appendectomy is uncommon. Prompt recognition and abdominal computerized tomography scanning are crucial for accurate diagnosis. Early intervention is necessary to prevent complications.

7.
Adv Healthc Mater ; 13(6): e2303261, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37961920

RESUMO

Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA (pSP), named G5-BGG/pSP complex, is developed to activate NALT and to promote both systemic and mucosal immune defense. G5-BGG/pSP could traverse mucosal barriers and deliver DNA to the target cells because of its superior nasal retention and permeability characteristics. The intranasal G5-BGG/pSP complex elicits robust antigen-specific immune responses, such as the notable production of IgG antibody against several virus variants. More importantly, it induces elevated levels of antigen-specific IgA antibody and a significant expansion of the lung-resident T lymphocyte population. Notably, the intranasal G5-BGG/pSP complex results in antigen expression and maturation of dendritic cells in nasal mucosae. These findings exhibit the potential of G5-BGG, a novel cationic material, as an effective gene carrier for intranasal vaccines to obtain robust systemic and mucosal immunity.


Assuntos
COVID-19 , Vacinas , Humanos , Imunidade nas Mucosas , SARS-CoV-2 , COVID-19/prevenção & controle , DNA , Células Dendríticas
8.
Gene ; 898: 148109, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38142898

RESUMO

OBJECTIVE: The objective of this study is to comprehensively investigate the potential value of BNIP3 and DAPK1 methylation in peripheral blood leukocytes as a non-invasive biomarker for the detection of gastric cancer (GC), prediction of chemotherapy efficacy, and prognosis assessment. PATIENTS AND METHODS: Initially, multiple bioinformatic analyses were employed to explore the genetic landscape and biological effects of BNIP3 and DAPK1 in GC tissues. Subsequently, case-control and prospective follow-up studies were conducted to compare the differences in BNIP3 and DAPK1 methylation levels in peripheral blood leukocytes among GC patients and healthy controls, as well as between patients exhibiting sensitivity and resistance to platinum plus fluorouracil treatment, and between patients with varying survival outcomes of GC. Additionally, several predictive nomograms were constructed based on the identified CpG sites and relevant clinical parameters to forecast the occurrence of GC, chemotherapy efficacy, and prognosis. RESULTS: The upregulation of BNIP3 and DAPK1 was found to be associated with the development and poorer survival outcomes of GC. Furthermore, the expression of BNIP3/DAPK1 exhibited an inverse relationship with their DNA methylation levels and demonstrated a positive correlation with immune cell infiltration, as well as the IC50 values of 5-Fluorouracil and Cisplatin in GC tissues. Increased infiltration of macrophages in the high-expression groups was observed to be linked to unfavorable GC survival. In the case-control and follow-up studies, lower methylation levels of BNIP3 and DAPK1 were identified in the peripheral leukocytes of GC patients compared to healthy controls. Hypomethylation was also associated with more aggressive subtypes, diminished chemotherapy efficacy, and poorer survival outcomes in GC. CONCLUSION: The DNA methylation of BNIP3 and DAPK1 in peripheral blood leukocytes holds promise as a novel non-invasive biomarker for predicting the occurrence of GC, chemotherapy efficacy, and prognosis assessment.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Estudos Prospectivos , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/metabolismo , Metilação de DNA , Leucócitos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo
9.
Discov Med ; 35(179): 975-981, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38058062

RESUMO

BACKGROUND: Idiopathic epiretinal membrane (iERM) is a common disorder of the vitreomacular interface characterized by decreased visual acuity and metamorphopsia. This study aimed to analyze the association between the anatomical change of the retina and functional outcomes in iERM patients so as to derive the prognostic factors of visual acuity (VA) and metamorphopsia. METHODS: Forty-five patients (one eye per patient; 45 eyes in total) who underwent pars plana vitrectomy and membrane peeling for iERM by a single surgeon were enrolled in this retrospective study. The results on best-corrected visual acuity (BCVA) and metamorphopsia as well as retinal images were obtained before the surgery and 1, 3, 6 months after the surgery. The BCVA and retinal microstructure, including central retinal thickness (CRT), ganglion cell layer (GCL) thickness, inner nuclear layer (INL) and outer nuclear layer + outer plexiform layer (ONL+OPL), and continuity of photoreceptor inner/outer segment (IS/OS) junction before and after iERM surgery were compared using paired samples t-test (continuous variables) or Chi-square test (categorical variables). Multiple regression analysis was carried out to explore the association among BCVA, M-score, and the parameters derived from optical coherence tomography. RESULTS: Compared with preoperative data, a significant improvement in BCVA was observed 1, 3, and 6 months postoperatively (t = 5.37, p < 0.0001; t = 7.29, p < 0.0001; t = 6.44, p < 0.0001 for 1, 3, and 6 months postoperatively, respectively), whereas the M-score only decreased significantly 3 and 6 months after the surgery (t = 2.36, p = 0.02; t = 5.00, p < 0.0001, respectively). In comparison with the baseline, the CRT, INL, and ONL+OPL thickness showed a significant decrease at each postoperative follow-up time, and GCL thickness (t = 3.86, p = 0.0002) and IS/OS disruption ratio (χ2 = 4.86, p = 0.027) were markedly reduced only 6 months postoperatively. Six-month postoperative BCVA was considerably associated with preoperative CRT and ONL+OPL thickness, as well as postoperative CRT, ONL+OPL thickness, and severity of IS/OS disruption. Moreover, the M-score after surgery was markedly correlated with both the preoperative and postoperative INL and CRT thickness. CONCLUSIONS: Both VA and M-score in iERM patients were significantly improved after vitrectomy. Pre- and post-operative CRT was significantly associated with both postoperative BCVA and M-score. Besides, pre- and post-operative INL thickness was correlated to postoperative metamorphopsia, and postoperative BCVA was associated with postoperative ONL+OPL thickness and IS/OS integrity.


Assuntos
Membrana Epirretiniana , Humanos , Membrana Epirretiniana/cirurgia , Vitrectomia/efeitos adversos , Estudos Retrospectivos , Retina/diagnóstico por imagem , Retina/cirurgia , Transtornos da Visão/etiologia , Transtornos da Visão/cirurgia , Tomografia de Coerência Óptica/métodos
10.
Front Public Health ; 11: 1202980, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693711

RESUMO

Background: The global burden of digestive diseases has been rising in the last 30 years. The rates and trends of incidence, deaths, and disability-adjusted life-years (DALYs) for digestive diseases need to be investigated. Methods: We extracted the data on overall digestive diseases and by cause between 1990-2019 from the Global Burden of Diseases 2019 website, including the absolute number and the corresponding age-standardized rates of incidence (ASIR), deaths (ASDR), and DALYs (ASDALYs). Results: Globally, the incident cases, deaths, and DALYs of digestive diseases in 2019 increased by 74.44, 37.85, and 23.46%, respectively, compared with that in 1990, with an increasing ASIR of 0.09%, as well as decreasing ASDR and ASDALYs of 1.38 and 1.32% annually. The sociodemographic index (SDI) of overall digestive diseases showed a slight increase in ASIR from low to middle-low regions. The downtrend in ASDR and ASDALYs was found in all SDI regions. The burden of incidence was higher in females, while the burden of deaths and DALYs was higher in males for the overall digestive diseases and most causes. The estimated annual percentage changes were significantly associated with the baseline ASIR, ASDR, and ASDALYs for the overall digestive diseases, and the negative correlations between ASDR, ASDALYs, and human development index both in 1990 (R = -0.68, R = -0.69) and 2019 (R = -0.71, R = -0.73) were noticed. Conclusion: The findings indicate that digestive diseases remain a significant public health burden, with substantial variation across countries, sexes, and age groups. Therefore, implementing age, gender, and country-specific policies for early screening and targeted interventions could significantly reduce the global burden of digestive diseases.


Assuntos
Carga Global da Doença , Políticas , Feminino , Humanos , Masculino , Saúde Pública
11.
Clin Chim Acta ; 541: 117252, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36781041

RESUMO

BACKGROUND: Lack of comprehending key factors of schizophrenia relapse has impeded its effective treatment, indicating that the mechanism clarification and available intervention of schizophrenia relapse required further amelioration. METHOD: Based on the integration of LC-MS and 1H NMR metabolomics, a weighted correlation network was established to screen pivotal factors of accelerating schizophrenia relapse. Then, the cluster most correlated with schizophrenia relapse was explored, and the biological function of cluster was investigated. Next, the key biomarker related to schizophrenia relapse was obtained through multiple algorithms. Moreover, the Lilikoi algorithm and correlation analysis were implemented to reveal the association between key biomarker and schizophrenia relapse. RESULT: Results showed that 458 different forms of metabolites were identified for structuring the weighted correlation network. The module-trait correlation indicated that the turquoise module was the most highly correlated with schizophrenia relapse. Further, network analysis revealed that, in turquoise module, cluster 1 composed of 139 metabolites (involved in lipid metabolism and energy metabolism) was the most important subnetwork relevant to schizophrenia relapse. Finally, phenylalanylphenylalanine was recommended as the key biomarker related to schizophrenia relapse. Moreover, the correlation analysis indicated that phenylalanylphenylalanine might affect the progression of schizophrenia by intervening in energy metabolism. CONCLUSION: In summary, critical factors of schizophrenia relapse have been revealed in our research, expounding the schizophrenia progression more systemically, which could shed some light on improving the intervention of schizophrenia relapse.


Assuntos
Esquizofrenia , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Metabolômica/métodos , Biomarcadores
12.
J Control Release ; 354: 538-553, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36641120

RESUMO

Evidence is mounting that there is a significant gap between the antitumor efficacy of nanodrugs in preclinical mouse tumor models and in clinical human tumors, and that differences in tumor models are likely to be responsible for this gap. Herein, we investigated the enhanced permeability and retention (EPR) effect in mouse lung cancer models with different tumor growth rates, volumes and locations, and analyzed the nanodrug tumor targeting behaviors limited by tumor vascular pathophysiological characteristics in various tumor models. The results showed that the fast-growing tumors were characterized by lower vascular tight junctions, leading to higher vascular paracellular transport activity and nanodrug tumor accumulation. The paracellular transport activity increased with the growth of tumor, but the vascular density and transcellular transport activity decreased, and as a result, the average tumor accumulation of passive targeting nanodrugs decreased. Orthotopic tumors were rich in blood vessels, but had low vascular transcellular and paracellular transport activities, making it difficult for nanodrug accumulation in orthotopic tumors via passive targeting strategies. The antitumor efficacy of passive targeting nanodrugs in various lung cancer-bearing mice validated the aforementioned nanodrug accumulation behavior, and nanodrugs based on the angiogenesis-tumor sequential targeting strategy achieved obviously improved efficacy in orthotopic lung cancer-bearing mice. These results suggest that the EPR effect varies in different tumor models and should not be used as a universal targeting strategy for antitumor nanodrugs. Besides, attention should be paid to the animal tumor models in the evaluation of nanodrugs so as to avoid exaggerating the antitumor efficacy.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Humanos , Camundongos , Animais , Nanopartículas/uso terapêutico
13.
Front Oncol ; 12: 916907, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35785154

RESUMO

Growing evidence has shown the oncogenic function of matrix metallopeptidase 7 (MMP7) in various tumors. However, no systemic pan-cancer analysis on the association between MMP7 and different cancers based on big clinical data is available. TIMER2, GEPIA2, UALCAN, cBioPortal, String, Metascape, and other web databases were searched in the present study. Generally, MMP7 expression is significantly upregulated in most The Cancer Genome Atlas (TCGA) cancer types compared to the paired normal controls, yet is downregulated in tumor tissues of invasive breast carcinoma (BRCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), and skin cutaneous melanoma (SKCM). MMP7 protein expression is notably higher in the primary tumor tissues of colon cancer, lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC) than in normal tissues and is significantly lower in the primary tumor tissues of breast cancer, clear cell renal carcinoma, and ovarian cancer. Furthermore, MMP7 expression is strongly associated with pathological stages, clinical outcomes, tumor mutational burden (TMB), and microsatellite instability (TSI). Gene amplification was detected in most TCGA cancer types. In addition, the missense mutation is the primary type of MMP7 genetic alteration in tumors. Significant positive correlations between MMP7 expression and cancer-associated fibroblasts (CAFs) have been demonstrated in most TCGA cancers. MMP7 expression was also found to be positively correlated with infiltration of dendritic cells and macrophages in some specific tumor types. Functional enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) methods revealed that RNA processing and DNA damage checkpoints might reveal the pathogenetic mechanisms of MMP7. This pan-cancer analysis provides a clear panorama for the tumorigenic roles of MMP7 across different cancer types. Moreover, MMP7 could be a potential drug therapeutic target in such cancers.

14.
Acta Pharm Sin B ; 12(4): 2000-2013, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35847517

RESUMO

Thrombolytic agents have thus far yielded limited therapeutic benefits in the treatment of thrombotic disease due to their short half-life, low targeting ability, and association with serious adverse reactions, such as bleeding complications. Inspired by the natural roles of platelets during thrombus formation, we fabricated a platelet-based delivery system (NO@uPA/PLTs) comprising urokinase (uPA) and arginine (Arg) for targeted thrombolysis and inhibition of re-embolism. The anchoring of uPA to the platelet surface by lipid insertion increased the thrombotic targeting and in vivo circulation duration of uPA without disturbing platelet functions. Nitric oxide (NO) generated by the loaded Arg inhibited platelet aggregation and activation at the damaged blood vessel, thereby inhibiting re-embolism. NO@uPA/PLTs effectively accumulated at the thrombi in pulmonary embolism and carotid artery thrombosis model mice and exerted superior thrombolytic efficacy. In addition, the platelet delivery system showed excellent thrombus recurrence prevention ability in a mouse model of secondary carotid artery injury. The coagulation indicators in vivo showed that the platelet-based uPA and NO co-delivery system possessed a low hemorrhagic risk, providing a promising tool for rapid thrombolysis and efficient inhibition of posttreatment re-embolism.

15.
Cell Cycle ; 21(22): 2444-2454, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35848940

RESUMO

Failure of the normal process of cell death pathways contributes to the defection of immune systems and the occurrence of cancers. The key genes, the multimolecular mechanisms, and the immune functions of these genes in pan-cancers remain unclear. Using online databases of The Cancer Genome Atlas, GEPIA2, TISIDB, HPA, Kaplan-Meier Plotter, PrognoScan, cBioPortal, GSCALite, TIMER, and Sangerbox, we identified the key genes from the six primary cell death-related pathways and performed a comprehensive analysis to investigate the multimolecular characteristics and immunological functions of the hub genes in 33 human cancers. We identified five hub genes in the six primary cell death-related pathways (JUN, NFKB1, CASP3, PARP1, and TP53). We found that CASP3, PARP1, and TP53 were overexpressed in 28, 23, and 27 cancers. The expression of the five genes was associated with the development and prognosis of many cancers. Particularly, JUN, NFKB1, CASP3, and TP53 have prognostic values in Brain Lower Grade Glioma (LGG), while PARP1 and CASP3 could predict the survival outcomes in Adrenocortical carcinoma (ACC). In addition, an extensive association between five genes' expression, DNA methylation, and tumor-immune system interactions was noticed. The five cell death-related hub genes could function as potential biomarkers for various cancers, particularly LGG and ACC. The immunological function analysis of the five genes also proposes new targets for developing immunosuppressants and improving the immunotherapy efficacy of cancers. However, further extensive clinical and experimental research are required to validate their clinical values.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias , Humanos , Caspase 3/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Neoplasias/genética , Morte Celular
16.
J Control Release ; 346: 32-42, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35378211

RESUMO

Chemotherapy is still the mainstay treatment for metastatic triple-negative breast cancers (TNBC) currently in clinical practice. The unmet needs of chemotherapy for metastatic TNBC are mainly from the insufficient drug delivery and unavailable targeting strategy that thwart the whole progression of metastatic TNBC. The in vivo ligands-mediated active targeting efficiency is usually affected by protein corona. While, the protein corona-bridged natural targeting, in turn, provides a new way for specific drug delivery. Herein, we develop a novel metastatic progression-oriented in vivo self-assembled Cabazitaxel nanocrystals (CNC) delivery system (PC/CNC) through the CNC automatically absorbing functional plasma proteins (transferrin, apolipoprotein A-IV and apolipoprotein E) in vivo, aiming to achieve the simultaneously targeted delivery to primary tumors, circulating tumor cells and metastatic lesions. With the unique advantages of superhigh drug-loading and protein corona empowered active targeting properties to tumor cells, HUVECs, active-platelets and blood-brain barrier/blood-tumor barrier, the PC/CNC exhibits a significantly improved therapeutic effect in metastatic TNBC therapy compared with free drug and CNC-loaded liposomes.


Assuntos
Nanopartículas , Coroa de Proteína , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Humanos , Lipossomos , Nanopartículas/química , Neoplasias de Mama Triplo Negativas/patologia
17.
J Infect Dev Ctries ; 16(2): 283-290, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35298423

RESUMO

INTRODUCTION: The high development of tourism is considered a factor that facilitates the global spread of infectious diseases. The association between tourism and the epidemic of coronavirus diseases 2019 (COVID-19) remains unclear. METHODOLOGY: We retrieved the data of COVID-19 in 178 countries/territories from the Center for Systems Science and Engineering at Johns Hopkins University. Data on tourism indicators were collected from the World Tourism Organization. We used Spearman's correlation analysis to explore the association between tourism and the epidemic of COVID-19. RESULTS: We find that international tourism expenditure, international tourism receipts, international tourist arrivals, and international tourism exports were significantly correlated with the total number of cases (rs=0.86, rs=0.79, rs=0.80, rs=0.81, respectively), the daily growth of cases of COVID-19 (rs=0.84, rs=0.76, rs=0.78, rs=0.78, respectively), and the number of cases (per million persons) (rs=0.52, rs=0.53, rs=0.36, rs=0.53, respectively) (p < 0.0001 for all), especially in places with high-income. Tourism as percentage of exports was slightly associated with the total number of cases and the daily growth of cases (rs=-0.33, rs=-0.33) (p < 0.0001 for both). CONCLUSIONS: The clinical and public health care providers must realize the potential for the transmission of infections across regions and put more effort to prevent and respond to future infections.


Assuntos
COVID-19 , Doenças Transmissíveis , COVID-19/epidemiologia , Humanos , Turismo , Viagem
18.
Clin Chim Acta ; 524: 84-95, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863699

RESUMO

BACKGROUND: Lack of clinically specific biomarkers has impeded the precise diagnosis of schizophrenia, meanwhile, limited comprehending of pathogenesis for schizophrenia has restricted the effective treatment. METHOD: An integrated multi-omic approach, combining metabolomic platform (LC-MS and 1H NMR) and transcriptomic platform, was established to differentiate healthy subjects from schizophrenia patients. Based on filtered metabolites and genes, characteristic spectrums were further built. Then, representative metabolites and genes were screened out through Boruta algorithm. Moreover, characteristic diagnostic formulas were established via LASSO regression analysis. RESULT: As a result, 86 differential metabolites (in line with amino acid metabolism, etc.) and 189 differential expression genes (involving in amino acid metabolic process, etc.) were obtained as potential biomarkers for schizophrenia. The latent interaction between metabolites with genes, such as HMGCLL1 with energy metabolism, etc., was further studied through the analysis of pathway-based integration. Moreover, fine predictive ability was attributed to characteristic metabolomic/transcriptomic diagnostic spectrums/formulas. CONCLUSION: The functional relationships of filtered metabolites and genes were studied, which could elaborate the pathological process of schizophrenia more systemically, supplying more precise information on mechanism description and diagnostic evidence of schizophrenia.


Assuntos
Esquizofrenia , Cromatografia Líquida , Humanos , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Espectrometria de Massas em Tandem , Transcriptoma
19.
Medicine (Baltimore) ; 100(49): e28137, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889276

RESUMO

RATIONALE: Agenesis of the dorsal pancreas (ADP) is a rare congenital anomaly of the pancreas. ADP is associated with some other medical problems such as diabetes mellitus, abdominal pain/bloating, pancreatitis, pancreatic neuroendocrine tumor and so on. In this study, we present a case of ADP with chronic suppurative pancreatitis, summarize the clinical characteristics of the reported cases in China and review the correlative literature. PATIENT CONCERNS: A 51-year-old Chinese man, with a history of impaired fasting glucose, presented with jaundice, pruritus and dark urine. Laboratory analysis showed abnormal liver function and elevated carbohydrate antigen 19-9. DIAGNOSES: Contrast-enhanced computed tomography demonstrated a mass located at the head of pancreas and complete absence of the body and tail of pancreas. Endoscopic retrograde cholangiopancreatography demonstrated an eccentric malignant stricture about 1.6cm of distal common bile duct. INTERVENTIONS: The patient underwent pancreaticoduodenectomy because of the suspicion of pancreatic tumor. The postoperative pathological result was chronic suppurative pancreatitis, with moderate hyperplasia in focal ductal epithelium. OUTCOMES: A long-term follow-up shows that the patient is asymptomatic with well-controlled diabetes mellitus and pancreatic exocrine insufficiency. LESSONS: ADP is a quite rare congenital malformation of the pancreas with poorly-understood pathogenesis. The diagnosis of ADP depends on the imaging examination. The therapeutic strategy varies from person to person due to the different accompanying conditions.


Assuntos
Anormalidades Congênitas , Pâncreas/anormalidades , Pâncreas/diagnóstico por imagem , Pancreatite Crônica/complicações , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreaticoduodenectomia , Pancreatite Crônica/diagnóstico , Tomografia Computadorizada por Raios X
20.
Cancer Control ; 28: 10732748211043667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34615385

RESUMO

INTRODUCTION: The early diagnosis and detection could greatly improve the clinical outcome of gastric cancer (GC) patients. However, the non-invasive biomarkers for GC detection remain to be identified. METHOD: We used online databases (GEPIA, UALCAN, Kaplan-Meier plotter, TIMER, and MEXPRESS) to explore the association between H19 or metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in tissues and the occurrence, development, prognosis, the levels of immune cell infiltration, and methylation of GC; the correlation between mRNA expression and DNA methylation levels of genes were also examined. Methylation levels of H19 or MALAT1 in peripheral blood were compared between 150 GC patients and 100 healthy controls (HCs). Predictive nomograms were constructed among female and male groups for GC diagnosis. The calibration curves, Hosmer-Lemeshow test, and decision curve analysis were also used to examine the nomograms' predictive ability and clinical values. RESULTS: Using multiple online databases, we found that the mRNA expressions of H19 and MALAT1 in tissues were related to the occurrence of GC, and such expressions were associated with immune cell infiltration of GC and negatively correlated with DNA methylation levels of H19 and MALAT1. H19 gene, H19C island, and MALAT1B island, as well as 20 CpG sites were hypermethylated in peripheral blood of GC patients compared with HCs; similar results were also found in female and male groups (P < .05 for all). The combination of H19c3, H19c4, MALAT1b12, and age, as well as the combination of H19b7, H19c1, H19c5, and age in the nomograms could distinguish GC patients from HCs in the female group and male group, respectively. CONCLUSION: We found statistically significant hypermethylation of H19 and MALAT1 promoters in GC patients, and meaningful sensitivity and specificity of MALAT1 and H19 methylation in discriminating GC and HCs were observed in both female and male groups, which indicates that the peripheral blood-based DNA methylation of H19 and MALAT1 could act as potential non-invasive biomarkers for the diagnosis of GC.


Assuntos
RNA Longo não Codificante/biossíntese , Neoplasias Gástricas/patologia , Biomarcadores Tumorais , Índice de Massa Corporal , China , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Sensibilidade e Especificidade , Fatores Sexuais , Neoplasias Gástricas/sangue
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