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1.
Urol Oncol ; 41(1): 50.e1-50.e9, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36283930

RESUMO

PURPOSE: Urachal carcinoma (UC) is a rare genitourinary cancer with an insidious onset, high risk of recurrence, and a poor prognosis. Surgical resection alone has difficulty in controlling the tumor. We aim to explore treatment options and prognostic risk factors for UC based on a multicenter cohort and long-term follow-up database. MATERIALS AND METHODS: The clinical data, treatment and follow-up results of 163 patients with UC in 6 medical centers were analyzed retrospectively. Kaplan-Meier analysis and a Cox proportional hazards model were used to assess the treatment options and prognostic risk factors for UC. RESULTS: Kaplan-Meier analysis showed no difference in the 5-year recurrence-free survival rate (P =0.282) or overall survival rate (P =0.673) between extended partial cystectomy (EPC) and radical cystectomy (RC) for patients at stage III and below. Whether bilateral pelvic lymph nodes were dissected was also not significantly correlated with the patient's recurrence (P =0.921) or prognosis (P =0.741). Postoperative adjuvant chemotherapy significantly reduced the recurrence rate of patients with stage Ⅲb or below (P =0.005). Combined treatment of postoperative recurrence patients prolonged the survival time of patients compared with single chemotherapy or conservative treatment (34.022±5.031 vs. 12.837±2.349 or 6.192±0.875 months, P <0.001). Kaplan-Meier and univariate Cox regression analyses showed that age >55 years, Sheldon stage, carbohydrate antigen 19-9 (CA19-9) >9.935 U/mL, carbohydrate antigen 72-4 (CA724) >6.02 U/mL, and postoperative adjuvant chemotherapy were closely related to the overall survival and recurrence-free survival of patients (P <0.05). Multivariate Cox proportional hazard regression confirmed that the Sheldon stage and CA724 >6.02 U/mL were independent recurrence risk factors. CONCLUSIONS: EPC or RC provides similar oncologic results for UC, but bilateral pelvic lymph node dissection is not necessary in early-stage patients. Postoperative adjuvant chemotherapy can significantly reduce the recurrence rate, and combination therapy may provide better survival outcomes. CA724 can predict tumor recurrence or metastasis at an early stage.


Assuntos
Cistectomia , Excisão de Linfonodo , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Resultado do Tratamento , Cistectomia/métodos , Excisão de Linfonodo/métodos , Fatores de Risco , Quimioterapia Adjuvante
2.
Stem Cells Int ; 2022: 2361376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338026

RESUMO

Transforming growth factor-ß1 (TGF-ß1) is an important multifunctional cytokine with dual effects on stem cell differentiation. However, the role of TGF-ß1 on odontogenic differentiation of dental pulp stem cells (DPSCs) remains to be entirely elucidated. In the present study, we initially investigated the effect of TGF-ß1 at a range of concentrations (0.1-5 ng/mL) on the proliferation, cell cycle, and apoptosis of DPSCs. Subsequently, to determine the effect of TGF-ß1 on odontogenic differentiation, alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining assays at different concentrations and time points were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to determine the levels of odonto-/osteo-genic differentiation-related gene and protein expression, respectively. For in vivo studies, newly formed tissue was assessed by Masson's trichrome and von Kossa staining. Data indicated that TGF-ß1 inhibited DPSCs proliferation in a concentration-and time-dependent manner (p < 0.05) and induced cell cycle arrest but did not affect apoptosis. ALP activity was enhanced, while ARS reduced gradually with increasing TGF-ß1 concentrations, accompanied by increased expression of early marker genes of odonto-/osteo-genic differentiation and decreased expression of late-stage mineralization marker genes (p < 0.05). ALP expression was elevated in the TGF-ß1-treatment group until 14 days, and the intensity of ARS staining was attenuated at days 14 and 21 (p < 0.05). Compared with the control group, abundant collagen but no mineralized tissues were observed in the TGF-ß1-treatment group in vivo. Overall, these findings indicate that TGF-ß1 promotes odontogenic differentiation of DPSCs at early-stage while inhibiting later-stage mineralization processes.

3.
RSC Adv ; 12(51): 33429-33439, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36425204

RESUMO

Five Mn-loaded catalysts were synthesized on γ-Al2O3, TiO2, ZrO2, nano γ-Al2O3 and nanoZrO2 supports. The catalytic ozonation of DCM (dichloromethane) was evaluated under industrial conditions (i.e., temperature, O3 input, H2O and SO2 content). According to results, >90% DCM conversion without O3 residue was achieved for all samples at 120 °C and an O3/DCM ratio of 6. At 20-120 °C, the highest Mn3+ content, abundant surface oxygen species and more weak acid sites led to the best performance of Mn/nanoAl2O3 (M/A-II). At 20 °C and 120 °C, 80% and 95% DCM can be degraded respectively on M/A-II at 20 °C with matched surface oxygen species and acidity. An O3/DCM ratio of 6 was optimal for performance and economy. For the effects of complex exhaust, both H2O and SO2 deactivated M/A-II. The H2O-induced deactivation was recoverable and also removed surface-deposited chlorine-containing species, enhancing the HCl selectivity. Finally, the Cl equilibrium of the reaction was comprehensively analyzed.

4.
Yi Chuan ; 44(10): 983-989, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384734

RESUMO

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the adenosine 5'-triphosphate binding cassette subfamily D member 1 (ABCD1) gene encoding a peroxisomal transmembrane protein, which has various clinical manifestations and a rapid progression from initial symptoms to fatal inflammatory demyelination. Therefore, identification of early clinical symptoms and further early diagnosis as well as treatment can effectively prevent disease development. In this study, we reported the laboratory and radiographic features in a rare case of X-ALD with 3-year skin hyperpigmentation as the only manifestation. And the ABCD1 gene was sequenced for the patient and his parents by a high-throughput sequencing method. The results of laboratory examination showed adrenocortical hypofunction and increased serum concentrations of very long-chain fatty acids. Brain MRI showed no obvious abnormal signal shadow. A hemizygous mutation of c.521A>C was detected in the ABCD1 gene of the patient, and his mother has the same site heterozygous mutation. Therefore, this patient was diagnosed as "X-linked adrenoleukodystrophy". During the follow-up, adrenocortical hypothyroidism did not improve, and brain MRI showed few high-FLAIR signals in the white matter of the right radial corona and left parietal lobe, suggesting possible brain injury. X-ALD patients with only skin manifestations but no neurological abnormalities are easily neglected, but early diagnosis and early intervention are important ways to delay the progression of this disease. Therefore, genetic testing for early X-ALD is recommended in all male children patients with skin pigmentation as the sole clinical presentation and subsequent diagnosis of adrenal hypofunction.


Assuntos
Adrenoleucodistrofia , Hiperpigmentação , Criança , Humanos , Masculino , Adrenoleucodistrofia/diagnóstico , Adrenoleucodistrofia/genética , Adrenoleucodistrofia/complicações , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP/genética , Testes Genéticos , Hiperpigmentação/etiologia , Hiperpigmentação/genética , Imageamento por Ressonância Magnética/efeitos adversos , Imageamento por Ressonância Magnética/métodos
5.
Environ Sci Technol ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36413583

RESUMO

The volatile organic compounds (VOCs) from cooking oil fumes are very complex and do harm to humans and the environment. Herein, we develop the high-efficiency and energy-saving synergistic photothermocatalytic oxidation approach to eliminate the mixture of heptane and hexanal, the representative VOCs with high concentrations in cooking oil fumes. The Pt/CeO2/TiO2 catalyst with nanosized Pt particles was prepared by the simple hydrothermal and impregnation methods, and the physicochemical properties of the catalyst were measured using numerous techniques. The Pt/CeO2/TiO2 catalyst eliminated the VOC mixture at low light intensity (100 mW cm-2) and low temperature (200 °C). In addition, it showed 25 h of catalytic stability and water resistance (water concentration up to 20 vol %) at 140 or 190 °C. It is concluded that O2 picked up the electrons from Pt to generate the •O2- species, which were transformed to the O22- and O- species after the rise in temperature. In the presence of water, the •OH species induced by light irradiation on the catalyst surface and the •OOH species formed via the thermal reaction were both supplementary oxygen species for VOC oxidation. The synergistic interaction of photo- and thermocatalysis was generated by the reactive oxygen species.

6.
Exp Biol Med (Maywood) ; : 15353702221131888, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36408742

RESUMO

Prostate cancer (PCa) is one of the malignant tumors of urinary system with a high morbidity. Enhancer RNA is a subclass of long non-coding RNA transcribed from active enhancer regions, which plays a critical role in gene transcriptional regulation. However, the role of enhancer RNA (eRNA) in PCa remains extremely mysterious. This study is aimed at exploring key prognostic eRNAs in PCa. First, we downloaded gene expression data and clinical data of 33 cancer types from UCSC Xena platform. Second, we selected reported putative eRNA-target pairs and performed the Kaplan-Meier survival and correlation analysis to determine the crucial eRNAs most related to biochemical recurrence (BCR)-free survival. Third, we explored the clinical characteristics with the key eRNA GAS1 adjacent regulatory RNA (GAS1RR) and performed a computational difference algorithm and the Cox regression analysis. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the underlying mechanisms. Finally, we used the pan-cancer data from The Cancer Genome Atlas (TCGA) and performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of 18 pairs of specimens to prove the results we acquired. Among all 2695 putative eRNAs, 6 pairs of eRNA-target genes were prominently related to BCR-free survival. Growth arrest-specific protein 1 (GAS1) was a target gene of GAS1RR (r = 0.86, P < 0.001). Patients with low GAS1RR expression were likely to have unfavorable clinical characteristics. The result of computational Cox regression analysis demonstrated that GAS1RR may predict the prognosis of PCa independently. RT-qPCR results illuminated that GAS1RR and GAS1 were both downregulated in PCa tissues, and they show a strong positive correlation. GO and KEGG analyses revealed biological processes that GAS1RR was mainly associated with. Immune infiltration analysis indicated that GAS1RR expression is correlated with the infiltration level of six kinds of immune cells. Our results suggest that GAS1RR may be clinically useful in the prediction of PCa prognosis. Moreover, it may also be a prognostic predictor and theoretic target with great promise in PCa.

7.
ACS Omega ; 7(43): 39136-39146, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36340134

RESUMO

Accurate prediction of the phase inversion point (PIP) of crude oil emulsion (COE) will give important guiding significance to the mixed transportation technology during the crude oil mining process. The influence of water cut of a system on viscosity characteristics of the COE was studied by emulsification experiments with 16 kinds of crude oils having significant differences in physical properties. The results showed that under the condition of low water cut of a system, the crude oils can emulsify all the water to form stable W/O emulsions with apparent viscosities much higher than those of pure crude oils. When the water cut of a system exceeds a certain critical value, the crude oils have no ability to emulsify all water; instead, they are wrapped by a water phase and form unstable O/W emulsions, and their apparent viscosities decrease sharply compared with those of pure crude oils. The critical water cut of a system corresponding to the abrupt change of apparent viscosity of the COE is the PIP of the COE changing from the type of W/O to O/W. Furthermore, the apparent viscosities of stable W/O emulsions decrease with increasing shear rate and temperature and meanwhile increase dramatically with the increasing water cut of a system. The apparent viscosities of unstable O/W emulsions decrease with increasing shear rate, water cut of a system, and temperature and are far lower than those of pure crude oils. Four typical parameters were chose as the representation to describe the crude oil physical properties (COPPs), that is, the content of saturates, the content of aromatics, the content of surfactants, and the crude oil acid number. On the basis of the quantitative description of COPPs, a prediction model for the PIP of the COE was established. The results of model verification showed that the mean relative deviation of prediction results was 2.9%.

8.
Cancer Cell Int ; 22(1): 346, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369040

RESUMO

BACKGROUND: Prostate cancer (PCa) is currently the major malignancy in men. It is becoming increasingly clear that competitive endogenous RNA (ceRNA) regulation networks are important in a wide variety of cancers. Nevertheless, there is still much to learn about the biological functions of the ceRNA network in prostate cancer. METHODS: The ceRNA network was constructed using the "GDCRNATools" package. Based on survival analysis, we obtained AC005154.6/hsa-miR-29c-3p/CCNL2 for further analysis. The prognostic model based on this ceRNA network was constructed by univariate and multivariate Cox regression methods. Furthermore, functional enrichment analysis, mutation landscape analysis, immune infiltration analysis, drug sensitivity analysis, methylation analysis, pan-cancer analysis, and molecular experiments of CCNL2 were carried out to investigate the role of CCNL2 in tumorigenesis. RESULTS: We identified the AC005154.6/CCNL2 axis as a risk factor that can promote the progression of prostate cancer by bioinformatics analysis and molecular experiments. Immune infiltration analysis suggested that CCNL2 may act as a novel biomarker for treatment decisions. The methylation level of CCNL2 was significantly decreased in tumor samples, possibly contributing to the upregulation of CCNL2 in prostate cancer. Moreover, CCNL2 is differentially expressed in multiple cancers and is tightly correlated with immune infiltration. CONCLUSION: The current study constructed a ceRNA network, AC005154.6/hsa-miR-29c-3p/CCNL2. Potentially, this biomarker can be used for early diagnosis and decision-making about prostate cancer treatment.

9.
Front Oncol ; 12: 870676, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212426

RESUMO

Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3]) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequent mutations in sporadic SPTCL, suggesting the individuals harboring HAVCR2(TIM-3) germline mutations are highly susceptible to familial or sporadic SPTCL. Here, we identify a novel germline compound heterozygous mutation of TIM-3 gene,c.245A>G (p.Tyr82Cys) and c.265C>T(p.Arg89Cys) variations in a single familial case with EBV-positive peripheral T-cell lymphoma(NOS),accompanied HLH;we also detected Tyr82Cys germline mutation in TIM-3 gene in one sporadic patient with cutaneous T cell lymphoma. We screened the distributive frequencies for TIM-3 mutations in healthy controls(n=87), B-(n=79) or T-cell lymphoma(n=25) not SPTCL, and the results showed that the mutation was found in two out of 25 patients with T-cell lymphoma but was not detected in 79 patients with B-cell lymphoma nor in a group of 87 controls. The mRNA expression of TIM-3 on primary cells and transfected HEK293 cells reduced significantly, indicating Tyr82Cys and Arg89Cys mutations is a loss-of function mutations on TIM-3,resulting in a weakened TIM-3 signaling. Our results suggest Tyr82Cys TIM-3 germline mutations are not only limited in SPTCL, and also occurred in other types of T-cell lymphoma, especially complicated HLH. TIM-3 mutations may be an predisposing factor for T-cell lymphoma and molecular marker for auxiliary diagnosis in T cell lymphoma,especially complicated with HLH.

10.
Int J Mol Sci ; 23(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36233144

RESUMO

(1) The phytohormones gibberellins (GAs) play a crucial role in plant growth and development, such as seed germination, flowering, fruiting, and stem elongation. Although many biological roles of GAs have been studied intensively, the molecular mechanisms of GAs in woody plants are still unclear. (2) In this study, we investigated the effects of exogenous application of GAs on Neolamarckia cadamba. (3) The height and biomass of N. cadamba increased after 7 days of GA treatment, especially on the second internode. Transcriptome analysis showed that although the majority of genes involved in the GA signaling pathway were up-regulated, the expression of GA20 oxidase (GA20ox) and GA3 oxidase (GA3ox) was down-regulated in the 3 days GA-treated group compared to the CK group. The expression of the cell elongation-related basic helix-loop-helix genes bHLH74 and bHLH49 was up-regulated in the GA-treated group compared with the CK group. Transcriptional expression levels of transcription factors involved in hormone signaling were changed, mainly including bHLH, ethylene response factor (ERF), and WRKY families. In addition, the transcriptional expression level of the key enzymes engaged in the phenylalanine pathway was downregulated after GA treatment. (4) In brief, our findings reveal the physiological and molecular mechanisms of exogenous GA treatment stimulation in N. cadamba.


Assuntos
Giberelinas , Reguladores de Crescimento de Plantas , Rubiaceae , Etilenos , Regulação da Expressão Gênica de Plantas , Giberelinas/metabolismo , Giberelinas/farmacologia , Hormônios , Oxirredutases/metabolismo , Fenilalanina/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Rubiaceae/genética , Rubiaceae/crescimento & desenvolvimento , Fatores de Transcrição/metabolismo , Transcriptoma
11.
Org Lett ; 24(44): 8197-8201, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36305630

RESUMO

Fused polycyclic furans are privileged structural scaffolds in materials chemistry, including organic semiconductors. Specifically, indeno[1,2-c]furans are an interesting type of polycyclic furans featuring a fused furan and indenone framework. Unfortunately, limited studies on their photophysical properties have been performed, probably owing to the lack of efficient and straightforward approaches to those compounds. Herein, we have developed a cobalt-catalyzed radical-polar crossover cyclization of the readily available o-alkynylaryl ß-carbonyls to afford diverse indeno[1,2-c]furans. Photophysical and DFT calculations were also carried out, suggesting that the obtained indeno[1,2-c]furans exhibit promising electronic and optical properties.

12.
Bioorg Chem ; 129: 106217, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36283176

RESUMO

BACKGROUND: Multiple myeloma (MM) is a hematological malignancy of plasma cells characterized by the production of monoclonal immunoglobulin protein. Despite significant advances in the treatment of MM, it remains an incurable disorder owing to its resistance to chemotherapy and refractory nature. Inhibitors of histone deacetylases (HDACIs) have been identified as promising therapeutic drugs for cancer treatment. At present, numerous HDACIs are under study for the treatment of MM in monotherapy or in conjunction with other agents. OBJECTIVES: In the present study, we investigated the anti-MM effect of CC1007, which was designed to indirectly inhibit class IIa HDACs by binding to myocyte enhancer factor-2 (MEF2) and blocking the targets regulated by the HDAC-MEF2 complex. DESIGN: The effect of CC1007 on human MM cell lines, namely U266 and MM1.S, and CD138+ cells collected from the bone marrow of patients with MM was evaluated. METHODS: The cells were subjected to growth-inhibition assay, apoptosis assay, cell cycle analysis, real-time PCR, western blotting, immunofluorescence, co-immunoprecipitation, ChIP assay, and siRNA transfection. Statistical differences were compared using two-tailed t tests or one-way analysis of variance followed by the Bonferroni post hoc test. RESULTS: CC1007 inhibited the proliferation of MM cell lines and primary MM cells and induced their apoptosis and cell cycle arrest. Furthermore, CC1007 decreased the expression of MEF2C and HDAC7, thereby disturbing their interaction and promoting the overexpression of Nur77, a target of MEF2C. The overexpression of Nur77 and its translocation from the nucleus to the cytoplasm resulted in its binding to B-cell lymphoma 2 on the mitochondrial surface, thereby inducing the release of cytochrome C and activating the mitochondrial apoptotic pathway. CONCLUSIONS: Since CC1007 demonstrates remarkable anti-MM effect on MM cells, it may be a promising drug for the treatment of MM.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Regulação para Cima , Linhagem Celular Tumoral , Histona Desacetilases/metabolismo , Apoptose , Inibidores de Histona Desacetilases/farmacologia
13.
Front Immunol ; 13: 981502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189238

RESUMO

Behçet's syndrome (BS) is a chronic form of relapsing multisystem vasculitis, characterized by recurrent oral and genital ulcers. Intestinal BS is a special type of BS. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BS, and punched-out ulcers can be observed in the intestine or esophagus. At present, there is no recognized radical treatment for intestinal BS. Glucocorticoids and immunosuppressants are currently the main drugs used to improve the condition. Although it has been reported that monoclonal anti-TNF antibodies may be effective for some refractory intestinal BS, further randomized, prospective trials are necessary to confirm these findings. Some patients are restricted from using biological agents because of serious allergic reactions of drugs, inconvenient drug injections or the impact of the novel coronavirus epidemic. If endoscopic remission (endoscopic healing) is not achieved for a prolonged period of time, serious complications, such as perforation, fistula formation, and gastrointestinal bleeding can be induced. Therefore, it is necessary to develop new treatment methods for controlling disease progression. We reviewed the relevant literature, combined with the analysis of the correlation between the pathogenesis of BS and the mechanism of Janus kinase (JAK) inhibition, and considered that tofacitinib (TOF) may be effective for managing refractory intestinal BS. We report for the first time that four patients with severe refractory intestinal BS were successfully treated with TOF. We hope to provide valuable information on JAK inhibitors as potential therapeutic targets for the treatment of severe refractory intestinal BS.


Assuntos
Síndrome de Behçet , Inibidores de Janus Quinases , Piperidinas , Pirimidinas , Anticorpos Monoclonais/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Fatores Biológicos/uso terapêutico , COVID-19/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Intestinos/patologia , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases , Piperidinas/uso terapêutico , Estudos Prospectivos , Pirimidinas/uso terapêutico , Inibidores do Fator de Necrose Tumoral , Úlcera/tratamento farmacológico
14.
Front Immunol ; 13: 970938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304458

RESUMO

We recently identified a high-affinity C1q-ApoE complex in human artery atherosclerotic intima lesions and in human amyloid plaques of Alzheimer's Disease brains defining a common pathogenetic pathway of two diverse diseases, i.e. atherosclerosis and dementia. C1q is the initiating and controlling protein of the classical complement cascade (CCC), which occupies a key role in multiple acute and chronic inflammatory tissue responses. C1q is largely produced by myeloid cells including Kupffer cells (KCs) and subsequently secreted into the circulation as an inactive preprotein. Its binding partner, Apolipoprotein E (ApoE), is produced by KCs and hepatocytes and it is also secreted into the circulation, where it regulates essential steps of lipid transport. In addition to its major source, ApoE can be produced by non-liver cells including immune cells and multiple other cells depending on local tissue contexts. To initiate the CCC cascade, C1q must be activated by molecules as varied as oxidized lipids, amyloid fibrils, and immune complexes. However, ApoE is mute towards inactive C1q but binds at high-affinity to its activated form. Specifically, our studies revealed that ApoE is a CCC-specific checkpoint inhibitor via the formation of the C1q-ApoE complex. We proposed that it may arise in multiple if not all CCC-associated diseases and that its presence indicates ongoing CCC activity. Here, we turned to the liver to examine C1q-ApoE complexes in human B- and C-viral hepatitis and nonalcoholic fatty liver disease (NAFLD). In addition, we used multidrug-resistance-2 gene-knockout (Mdr2-KO) mice as a model for inflammatory liver disease and hepatocellular carcinoma (HCC) pathogenesis. In normal murine and human livers, KCs were the major C1q-producing cell type while hepatocytes were the primary ApoE-forming cell type though the C1q-ApoE complex was rare or nonexistent. However, significant numbers of C1q-ApoE complexes formed in both Mdr2-KO, human viral hepatitis, and NAFLD around portal triads where immune cells had infiltrated the liver. Additionally, high numbers of C1q-ApoE complexes emerged in human livers in areas of extracellular lipid droplets across the entire liver parenchyma in NAFLD-affected patients. Thus, the C1q-ApoE complex is a new pathological hallmark of viral hepatitis B and C and NAFLD.


Assuntos
Aterosclerose , Carcinoma Hepatocelular , Hepatite Viral Humana , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Carcinoma Hepatocelular/patologia , Complemento C1q , Neoplasias Hepáticas/patologia , Apolipoproteínas E , Camundongos Knockout , Aterosclerose/complicações
15.
Dis Markers ; 2022: 8058160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246559

RESUMO

Prostate cancer is one of the most common malignancies in men. Calcium signaling is implicated in the progression of prostate cancer and plays a critical role in immune cell function. However, whether specific calcium channel-related genes play a crucial role in the immune cell infiltration levels of prostate cancer requires further research. In this study, we performed an integrated analysis of transcriptional, clinical, and somatic mutation data from The Cancer Genome Atlas database and identified the hub calcium channel-related gene P2RX2 to be associated with the prognosis and immune infiltration of prostate cancer. P2RX2 expression was positively correlated with immune cell infiltration levels and the expression of immune checkpoint genes, and downregulation of P2RX2 led to poor survival in patients with prostate cancer. Furthermore, we validated the molecular and clinical characteristics of P2RX2 by using multiple databases and conducting in-vitro experiments. Additionally, drug sensitivity analysis revealed that patients with low P2RX2 expression were sensitive to docetaxel and Bicalutamide. In conclusion, we revealed an association between calcium channel-related genes and prostate cancer, and identified P2RX2 as a biomarker for early diagnosis, prognosis prediction, and aiding treatment decisions for patients with prostate cancer.


Assuntos
Canais de Cálcio , Neoplasias da Próstata , Canais de Cálcio/genética , Docetaxel , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Purinérgicos P2X2
16.
Front Cell Neurosci ; 16: 1016682, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313616

RESUMO

Background: Intracranial aneurysm (IA) causes more than 80% of nontraumatic subarachnoid hemorrhages (SAHs). The mechanism of ferroptosis involved in IA formation remains unclear. The roles played by competitive endogenous RNA (ceRNA) regulation networks in many diseases are becoming clearer. The goal of this study was to understand more fully the ferroptosis-related ceRNA regulation network in IA. Materials and methods: To identify differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially expressed lncRNAs (DELs) across IA and control samples, the GEO datasets GSE122897 and GSE66239 were downloaded and analyzed with the aid of R. Ferroptosis DEGs were discovered by exploring the DEGs of ferroptosis-related genes of the ferroptosis database. Potentially interacting miRNAs and lncRNAs were predicted using miRWalk and StarBase. Enrichment analysis was also performed. We utilized the STRING database and Cytoscape software to identify protein-protein interactions and networks. DAB-enhanced Prussian blue staining was used to detect iron in IA tissues. Results: Iron deposition was evident in IA tissue. In all, 30 ferroptosis DEGs, 5 key DEMs, and 17 key DELs were screened out for constructing a triple regulatory network. According to expression regulation of DELs, DEMs, and DEGs, a hub triple regulatory network was built. As the functions of lncRNAs are determined by their cellular location, PVT1-hsa-miR-4644-SLC39A14 ceRNA and DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA networks were constructed. Conclusion: CeRNA (PVT1-hsa-miR-4644-SLC39A14 and DUXAP8-hsa-miR-378e/378f-SLC2A3) overexpression networks associated with ferroptosis in IA were established.

17.
World Neurosurg ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36058489

RESUMO

BACKGROUND: Ferroptosis is involved in traumatic spinal cord injury (SCI), and its inhibition may improve functional recovery after traumatic SCI. This study investigated whether metformin (Met) can have a neuroprotective effect in SCI repair by inhibiting ferroptosis. METHODS: We assessed functional change to determine the long-term effects after intraperitoneal injection of Met in SCI rats with the Basso-Beattie-Bresnahan locomotor rating scale. Malondialdehyde level and relative expression of key proteins, inflammatory cytokines, and nuclear factor E2-related factor 2 signalling molecules were determined in SCI rats and PC12 cells exposed to FeCl3 solution. RESULTS: Met treatment decreased the contents of malondialdehyde, regulated the levels of inflammatory factors, activated the nuclear factor E2-related factor 2 signalling pathway, and improved long-term outcomes by ameliorating SCI-induced locomotor deficits. In vitro studies further confirmed the beneficial and antiferroptotic actions of Met partly through activation of nuclear factor E2-related factor 2 signalling. CONCLUSION: Met can have a neuroprotective effect on SCI repair partly through antiferroptotic effects.

18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1045-1048, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086612

RESUMO

Cardiovascular diseases (CVDs) have been ranked as the leading cause for deaths. The early diagnosis of CVDs is a crucial task in the medical practice. A plethora of efforts were given to the automated auscultation of heart sound, which leverages the power of computer audition to develop a cheap, non-invasive method that can be used at any time and anywhere for measuring the status of the heart. Nevertheless, previous works ignore an important factor, namely, the privacy of the user data. On the one hand, learnt models are always hungry for bigger data. On the other hand, it can be difficult to protect personal private information when collecting such large amount of data. In this dilemma, we propose a federated learning (FL) framework for the heart sound classification task. To the best of our knowledge, this is the first time to introduce FL to this field. We conducted multiple experiments, analysed the impact of data distribution across collaborative institutions on model quality and learning patterns, and verified the feasibility and effectiveness of FL based on real data. Non- independent identically distributed (Non-IID) data and model quality can be effectively improved by adding a strategy of globally sharing data.


Assuntos
Ruídos Cardíacos , Auscultação , Privacidade
19.
Mikrochim Acta ; 189(10): 376, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36074274

RESUMO

A novel near-infrared (NIR) light-triggered smart nanoplatform has been developed for cancer targeting and imaging-guided combined photothermal-chemo treatment. Notably, Ag2S has a dual function of photothermal therapy and fluorescence imaging, which greatly simplifies the structure of the system. It can emit fluorescence at 820 nm under an excitation wavelength of 560 nm. The phase-change molecule of 1-tetradecanol (TD) is introduced as a temperature-sensitive gatekeeper to provide the nanocarrier with controlled release capability of doxorubicin (DOX). The nanocarrier (HAg2S@mSiO2-TD/DOX) shows a high drug loading capacity of 26.3% and exhibits an apparent NIR-responsive DOX release property. Under NIR irradiation, the photothermal effect of HAg2S nanocores facilitated the release of DOX through the melting of TD. The cytotoxicity test shows that the nanocarriers have good biocompatibility. As the same time, the synergistic combination leads to a better cancer inhibition effect than individual therapy alone in vitro. Cell uptake tests indicate that the carriers have excellent fluorescence imaging ability and high cellular uptake for HepG2 cells. This work provides a new strategy for the fabrication of smart nanocarriers with simple structures for fluorescence-mediated combination cancer therapy. Fabrication of a smart drug delivery system based on hollow Ag2S@mSiO2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy.


Assuntos
Nanopartículas , Neoplasias , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Fluorescência , Humanos , Nanopartículas/química , Neoplasias/tratamento farmacológico
20.
ChemSusChem ; : e202201670, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151588

RESUMO

Inhibiting the shuttle effect caused by soluble lithium polysulfides (LiPSs) is of importance for lithium-sulfur (Li-S) batteries. Here, a strategy was developed to construct protective layers by self-assembly networks to regulate the LiPSs. 2,5-Dichloropyridine (25DCP) holds two kinds of functional groups. Among them, the two C-Cl bonds were nucleophilic substituted by S in LiPSs to form long chains. The pyridine N interacted with Li in other LiPSs via Li bonds to form a short chain. As a result, the long chains were cross-linked by the short chain to form an insoluble network. The as-prepared network covered the sulfur electrode interface to suppress the shuttle effect of the subsequently generated LiPSs. Furthermore, 25DCP improved the redox dynamics by changing the energy level and electronic structure of the sulfur species. Therefore, the Li-S batteries with 25DCP exhibited good electrochemical performance. This work provides a feasible strategy for regulating the LiPSs.

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