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1.
Front Cell Dev Biol ; 12: 1466491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355120

RESUMO

As one of the key components of the immune system, mast cells are well known for their role in allergic reactions. However, they are also involved in inflammatory and fibrotic processes. Mast cells participate in all the stages of acute inflammatory responses, playing an immunomodulatory role in both innate and adaptive immunity. Mast cell-derived histamine, TNF-α, and IL-6 contribute to the inflammatory processes, while IL-10 mediates the suppression of inflammation. Crosstalk between mast cells and other immune cells is also involved in the development of inflammation. The cell-cell adhesion of mast cells and fibroblasts is crucial for fibrosis. Mast cell mediators, including cytokines and proteases, play contradictory roles in the fibrotic process. Here, we review the double-edged role of mast cells in inflammation and fibrosis.

2.
Biochem Pharmacol ; 230(Pt 1): 116551, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307317

RESUMO

With the abuse of antibiotics, multidrug resistant strains continue to emerge and spread rapidly. Therefore, there is an urgent need to develop new antimicrobial drugs. As a highly conserved cell division protein in bacteria, filamenting temperature-sensitive mutant Z (FtsZ) has been identified as a potential antimicrobial target. This paper reviews the structure, function, and action mechanism of FtsZ and a variety of natural and synthetic compounds targeting FtsZ, including 3-MBA derivatives, taxane derivatives, cinnamaldehyde, curcumin, quinoline and quinazoline derivatives, aromatic compounds, purpurin, and totarol. From these studies, FtsZ has a clear supporting role in the field of antimicrobial drug discovery. The urgent need and interest of antibacterial drugs will contribute to the discovery of new clinical drugs targeting FtsZ.

3.
Soc Cogn Affect Neurosci ; 19(1)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39096513

RESUMO

Recent studies using resting-state functional magnetic resonance imaging have shown that loneliness is associated with altered blood oxygenation in several brain regions. However, the relationship between loneliness and changes in neuronal rhythm activity in the brain remains unclear. To evaluate brain rhythm, we conducted an exploratory resting-state electroencephalogram (EEG) study of loneliness. We recorded resting-state EEG signals from 139 participants (94 women; mean age = 19.96 years) and analyzed power spectrum density (PSD) and functional connectivity (FC) in both the electrode and source spaces. The PSD analysis revealed significant correlations between loneliness scores and decreased beta-band powers, which may indicate negative emotion, attention, reward, and/or sensorimotor processing. The FC analysis revealed a trend of alpha-band FC associated with individuals' loneliness scores. These findings provide new insights into the neural basis of loneliness, which will facilitate the development of neurobiologically informed interventions for loneliness.


Assuntos
Encéfalo , Eletroencefalografia , Solidão , Descanso , Humanos , Feminino , Solidão/psicologia , Masculino , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Adulto Jovem , Eletroencefalografia/métodos , Descanso/fisiologia , Adulto , Adolescente , Ondas Encefálicas/fisiologia , Mapeamento Encefálico
4.
Adv Healthc Mater ; 13(23): e2400836, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38757738

RESUMO

Implantable neural electrodes are indispensable tools for recording neuron activity, playing a crucial role in neuroscience research. However, traditional neural electrodes suffer from limited electrochemical performance, compromised biocompatibility, and tentative stability, posing great challenges for reliable long-term studies in free-moving animals. In this study, a novel approach employing a hybrid film composed of poly(3,4-ethylenedioxythiophene)/functional gold nanoparticles (PEDOT/3-MPA-Au) to improve the electrode-neural interface is presented. The deposited PEDOT/3-MPA-Au demonstrates superior cathodal charge storage capacity, reduced electrochemical impedance, and remarkable electrochemical and mechanical stability. Upon implantation into the cortex of mice for a duration of 12 weeks, the modified electrodes exhibit notably decreased levels of glial fibrillary acidic protein and increased neuronal nuclei immunostaining compared to counterparts utilizing poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate). Additionally, the PEDOT/3-MPA-Au modified electrodes consistently capture high-quality, stable long-term electrophysiological signals in vivo, enabling continuous recording of target neurons for up to 16 weeks. This innovative modification strategy offers a promising solution for fabricating low-impedance, tissue-friendly, and long-term stable neural interfaces, thereby addressing the shortcomings of conventional neural electrodes. These findings mark a significant advancement toward the development of more reliable and efficacious neural interfaces, with broad implications for both research and clinical applications.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Ouro , Nanopartículas Metálicas , Polímeros , Ouro/química , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Polímeros/química , Nanopartículas Metálicas/química , Camundongos , Neurônios/metabolismo , Eletrodos Implantados , Masculino
5.
Chin Med ; 19(1): 62, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600597

RESUMO

BACKGROUND: Shenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating cerebral ischemia has not yet been fully elucidated. METHODS: An integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin-eosin (H&E) and Nissl's staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting. RESULTS: Integrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis. CONCLUSION: SMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical.

6.
Int Urol Nephrol ; 56(7): 2431-2440, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38466510

RESUMO

BACKGROUND: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. METHODS: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. RESULTS: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. CONCLUSIONS: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.


Assuntos
Taxa de Filtração Glomerular , Humanos , Masculino , Idoso , Feminino , China , Idoso de 80 Anos ou mais , Cistatina C/sangue , Creatinina/sangue , Estudos Retrospectivos , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico
7.
Magn Reson Imaging ; 108: 59-66, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38330724

RESUMO

Most brain metastases originate from lung cancer. The majority of cases of lung cancer can be categorized into squamous carcinoma and adenocarcinoma,necessitating distinct clinical treatments and yielding diverse prognoses.Therefore,accurate preoperative evaluation of pathological types through imaging techniques is essential. The objective of this study is to assess the capability of amide proton transfer-weighted(APTw) MRI in predicting the pathological types of brain metastases in lung cancer.Additionally,it seeks to evaluate whether APTw MRI can provide additional value to diffusion-weighted imaging(DWI) at MRI·In this study,a total of 32 participants(mean age,60 ± 9 years;14 men) underwent evaluation,comprising 9 with squamous carcinoma and 23 with adenocarcinoma.Interestingly,adenocarcinoma demonstrated elevated APTw values(2.70 ± 0.81% vs 1.82 ± 0.47%;P = 0.001) and a higher apparent diffusion coefficient(ADC) value(1.00 ± 0.40 × 10-3 mm2/s vs 0.77 ± 0.13 × 10-3 mm2/s;P<0.05) in comparison to squamous carcinoma. The area under the receiver operating characteristic curve(AUC) of APTw and ADC in distinguishing between squamous carcinoma and adenocarcinoma were found to be 0.84 and 0.63,respectively.Moreover,the combined area under the receiver operating characteristic curve of the two techniques is 0.84. Amide proton transfer-weighted has the potential to predict the pathological types of brain metastases in lung cancer.


Assuntos
Adenocarcinoma , Neoplasias Encefálicas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/diagnóstico por imagem , Prótons , Amidas , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem
8.
ACS Nano ; 18(2): 1702-1713, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38165231

RESUMO

Implantable neuroelectronic interfaces have gained significant importance in long-term brain-computer interfacing and neuroscience therapy. However, due to the mechanical and geometrical mismatches between the electrode-nerve interfaces, personalized and compatible neural interfaces remain serious issues for peripheral neuromodulation. This study introduces the stretchable and flexible electronics class as a self-rolled neural interface for neurological diagnosis and modulation. These stretchable electronics are made from liquid metal-polymer conductors with a high resolution of 30 µm using microfluidic printing technology. They exhibit high conformability and stretchability (over 600% strain) during body movements and have good biocompatibility during long-term implantation (over 8 weeks). These stretchable electronics offer real-time monitoring of epileptiform activities with excellent conformability to soft brain tissue. The study also develops self-rolled microfluidic electrodes that tightly wind the deforming nerves with minimal constraint (160 µm in diameter). The in vivo signal recording of the vagus and sciatic nerve demonstrates the potential of self-rolled cuff electrodes for sciatic and vagus neural modulation by recording action potential and reducing heart rate. The findings of this study suggest that the robust, easy-to-use self-rolled microfluidic electrodes may provide useful tools for compatible neuroelectronics and neural modulation.


Assuntos
Microfluídica , Nervo Isquiático , Eletrodos , Eletrônica , Encéfalo
9.
Exp Cell Res ; 435(2): 113931, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38253280

RESUMO

The mortality rate linked with nephrotic syndrome (NS) is quite high. The renal tubular injury influences the response of NS patients to steroid treatment. KN motif and ankyrin repeat domains 2 (KANK2) regulates actin polymerization, which is required for renal tubular cells to maintain their function. In this study, we found that the levels of KANK2 in patients with NS were considerably lower than those in healthy controls, especially in NS patients with acute kidney injury (AKI). To get a deeper understanding of the KANK2 transcriptional control mechanism, the core promoter region of the KANK2 gene was identified. KANK2 was further found to be positively regulated by E2F Transcription Factor 1 (E2F1), Transcription Factor AP-2 Gamma (TFAP2C), and Nuclear Respiratory Factor 1 (NRF1), both at mRNA and protein levels. Knocking down E2F1, TFAP2C, or NRF1 deformed the cytoskeleton of renal tubular cells and reduced F-actin content. EMSA and ChIP assays confirmed that all three transcription factors could bind to the upstream promoter transcription site of KANK2 to transactivate KANK2 in renal tubular epithelial cells. Our study suggests that E2F1, TFAP2C, and NRF1 play essential roles in regulating the KANK2 transcription, therefore shedding fresh light on the development of putative therapeutic options for the treatment of NS patients.


Assuntos
Síndrome Nefrótica , Fator 1 Nuclear Respiratório , Humanos , Fator 1 Nuclear Respiratório/metabolismo , Síndrome Nefrótica/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica , Regiões Promotoras Genéticas/genética , Fator de Transcrição E2F1/genética , Fator de Transcrição AP-2/genética
10.
Immun Inflamm Dis ; 11(9): e997, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37773712

RESUMO

BACKGROUND: Influenza virus (IV) is a leading cause of respiratory tract infections, eliciting responses from key innate immune cells such as Macrophages (MQs), Neutrophils, and Dendritic Cells (DCs). These cells employ diverse mechanisms to combat IV, with Inflammasomes playing a pivotal role in viral infection control. Cellular death mechanisms, including Pyroptosis, Apoptosis, and Necroptosis (collectively called PANoptosis), significantly contribute to the innate immune response. METHODS: In this updated review, we delve into the intricate relationship between PANoptosis and Inflammasomes within innate immune cells (MQs, Neutrophils, and DCs) during IV infections. We explore the strategies employed by IV to evade these immune defenses and the consequences of unchecked PANoptosis and inflammasome activation, including the potential development of severe complications such as cytokine storms and tissue damage. RESULTS: Our analysis underscores the interplay between PANoptosis and Inflammasomes as a critical aspect of the innate immune response against IV. We provide insights into IV's various mechanisms to subvert these immune pathways and highlight the importance of understanding these interactions to develop effective antiviral medications. CONCLUSION: A comprehensive understanding of the dynamic interactions between PANoptosis, Inflammasomes, and IV is essential for advancing our knowledge of innate immune responses to viral infections. This knowledge will be invaluable in developing targeted antiviral therapies to combat IV and mitigate potential complications, including cytokine storms and tissue damage.


Assuntos
Infecções por Orthomyxoviridae , Orthomyxoviridae , Humanos , Inflamassomos/metabolismo , Síndrome da Liberação de Citocina , Imunidade Inata , Orthomyxoviridae/metabolismo , Antivirais
11.
Cell Rep ; 41(5): 111570, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36323263

RESUMO

An appropriate balance between explorative and defensive behavior is essential for the survival and reproduction of prey animals in risky environments. However, the neural circuit and mechanism that allow for such a balance remains poorly understood. Here, we use a semi-naturalistic predator threat test (PTT) to observe and quantify the defense-exploration balance, especially risk exploration behavior in mice. During the PTT, the activity of the putative dorsal CA3 glutamatergic neurons (dCA3Glu) is suppressed by predatory threat and risk exploration, whereas the neurons are activated during contextual exploration. Moreover, optogenetic excitation of these neurons induces a significant increase in risk exploration. A circuit, comprising the dorsal CA3, dorsal lateral septal, and dorsomedial hypothalamic (dCA3Glu-dLSGABA-DMH) areas, may be involved. Moreover, activation of the dCA3Glu-dLSGABA-DMH circuit promotes the switch from defense to risk exploration and suppresses threat-induced increase in arousal.


Assuntos
Comportamento Exploratório , Hipotálamo , Animais , Camundongos , Ácido gama-Aminobutírico , Neurônios
12.
Front Pharmacol ; 13: 907980, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052125

RESUMO

Purpose: The incidence of uric acid (UA)-induced kidney injury is increasing owing to the high incidence of hyperuricemia in recent years. The flower of Abelmoschus manihot (Linneus) Medik is a traditional Chinese medicinal herb widely used in the treatment of some kidney diseases. In our previous study, we reported that the total extract of A. manihot L. flower (TEA) attenuated adriamycin-induced renal tubular cell injury. In this study, we aimed to evaluate the role of TEA in UA-induced tubular cell injury. Methods: Normal rat proximal epithelial NRK-52E cells were incubated with UA to mimic hyperuricemia conditions. The role of TEA in the renal tubular cells was also assessed. The cellular morphology was observed using phase-contrast microscopy, and cell viability was analyzed using the Cell Counting kit-8. Living and dead cells were stained using a Calcein-AM/PI double stain kit. The release of lactate dehydrogenase (LDH) was analyzed by LDH cytotoxicity Assay Kit. The expression of target proteins was analyzed using western blot analysis. Results: UA triggered NRK-52E cell injury, as evidenced by morphological changes, detachment of cells from the bottom, cell swelling, large bubbles blowing from cell membrane and loss of cell viability. UA increased release of LDH. UA induced the expression of p-ERK1/2 and the subsequent activation of caspase-8, caspase-3, and NLRP3 inflammasomes. Pyroptosis was elicited by UA after gasdermin E N-terminal (GSDME-NT) was cleaved from gasdermin E (GSDME). Z-DEVD-FMK, a caspase-3 inhibitor, suppressed the expression of both NLRP3 and GSDME-NT, but not that of caspase-8. INF39, an NLRP3 inhibitor, altered the expression of GSDME-NT expression, but not that caspase-3 and caspase-8. TEA alleviated UA-induced cell injury by suppressing ERK1/2/caspase-8/caspase-3/NLRP3/GSDME signaling. Conclusion: GSDME-mediated pyroptosis was involved in UA-induced renal tubular cell injury. This is the first study to report that TEA protects renal tubular epithelial cells against UA by inhibiting the ERK/1/2/caspase-8/caspase-3/NLRP3/GSDME pathway.

13.
Front Pharmacol ; 13: 819826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645824

RESUMO

Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

14.
Chemosphere ; 302: 134884, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35551937

RESUMO

Volatile organic compounds (VOCs) are the main precursor for ozone formation and hazardous to human health. Light alkane as one of the typical VOCs is difficult to degrade to CO2 and H2O by catalytic degradation method due to its strong C-H bond. Herein, a series of ultrafine Ru nanoclusters (<0.95 nm) enveloped in silicalite-1 (S-1) zeolite catalysts were designed and prepared by a simple one-pot method and applied for catalytic degradation of propane. The results demonstrate that the enveloped Ru1@S-1 catalyst has excellent propane degradation performance. Its T95 is as low as 294 °C with moisture, and the turnover frequency (TOF) value is up to 5.07 × 10-3 s-1, evidently higher than that of the comparison supported catalyst (Ru1/S-1). Importantly, Ru1@S-1 exhibits superior thermal stability, water resistance and recyclability, which should be attributed to the confinement and shielding effect of the S-1 shell. The in-situ DRIFTS result reveals that the propane degradation over Ru1@S-1 follows the Mars-van-Krevelen (MvK) mechanism, where the hydroxy from the framework of zeolite can provide the active oxygen species. Our work provides a new candidate and guideline for an efficient and stable catalyst for the low-temperature degradation of the light alkane VOCs.


Assuntos
Compostos Orgânicos Voláteis , Zeolitas , Alcanos , Catálise , Humanos , Propano , Temperatura , Compostos Orgânicos Voláteis/química , Zeolitas/química
15.
Bioengineered ; 13(5): 12927-12940, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35611792

RESUMO

Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with AKI were significantly higher than those in normal controls. Furthermore, elevated levels of NLRP3 and cell pyroptosis were found in renal tubular epithelial cells after LPS treatment. Transcription factor ETS Proto-Oncogene 1 (ETS1) could bind to the upstream promoter transcription site of NLRP3 to transactivate NLRP3 in renal tubular epithelial cells. The cell pyroptosis level also decreased by knocking down ETS1. It is concluded that knocking down of ETS1 may reduce the renal tubular epithelial pyroptosis by regulating the transcription of NLRP3, thus relieving AKI. ETS1 is expected to be a molecular target for the treatment of AKI.


Assuntos
Injúria Renal Aguda , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína Proto-Oncogênica c-ets-1 , Piroptose , Injúria Renal Aguda/etiologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proto-Oncogenes , Piroptose/genética
16.
J Oncol ; 2022: 6100187, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35178091

RESUMO

Kidney renal clear cell carcinoma (KIRC) has a poor prognosis and a high death rate globally. Cancer prognosis is strongly linked to immune-related genes (IRGs), according to numerous research. We utilized KIRC RNA-seq data from the TCGA database to build a prognostic model incorporating seven immune-related (IR) lncRNAs, and we constructed the model using LASSO regression. Additionally, we calculated a risk score for each patient using a prognostic model that divided patients into high-risk and low-risk groups. The ESTIMATE and CIBERSORT methodologies were then used to analyze the differences in the tumor microenvironment of the two groups of patients. Finally, we predicted three small molecule drugs that may have potential therapeutic effects for high-risk patients. We combined the acute kidney injury dataset to obtain differential genes that may serve standard biological functions with two risk groups. Our study shows that the model we constructed for IR-lncRNAs has reliable predictive efficacy for patients with KIRC.

17.
Cancer Cell Int ; 21(1): 424, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376212

RESUMO

BACKGROUND: Glioma is a common primary central nervous system tumour, and therapeutic drugs that can effectively improve the survival rate of patients in the clinic are lacking. Bufalin is effective in treating various tumours, but the mechanism by which it promotes the apoptosis of glioma cells is unclear. The aim of this study was to investigate the drug targets of bufalin in glioma cells and to clarify the apoptotic mechanism. METHODS: Cell viability and proliferation were evaluated by CCK-8 and colony formation assays. Then, the cell cycle and apoptosis, intracellular ion homeostasis, oxidative stress levels and mitochondrial damage were assessed after bufalin treatment. DARTS-PAGE technology was employed and LC-MS/MS was performed to explore the drug targets of bufalin in U251 cells. Molecular docking and western blotting were performed to identify potential targets. siRNA targeting Annexin A2 and the DRP1 protein inhibitor Mdivi-1 were used to confirm the targets of bufalin. RESULTS: Bufalin upregulated the expression of cytochrome C, cleaved caspase 3, p-Chk1 and p-p53 proteins to induce U251 cell apoptosis and cycle arrest in the S phase. Bufalin also induced oxidative stress in U251 cells, destroyed intracellular ion homeostasis, and caused mitochondrial damage. The expression of mitochondrial division-/fusion-related proteins in U251 cells was abnormal, the Annexin A2 and DRP1 proteins were translocated from the cytoplasm to mitochondria, and the MFN2 protein was released from mitochondria into the cytoplasm after bufalin treatment, disrupting the mitochondrial division/fusion balance in U251 cells. CONCLUSIONS: Our research indicated that bufalin can cause Annexin A2 and DRP1 oligomerization on the surface of mitochondria and disrupt the mitochondrial division/fusion balance to induce U251 cell apoptosis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34266375

RESUMO

Honey is a traditional food additive that can be used to preserve food, increase the flavour of food, and enhance the effect of some functional foods. Mulberry leaf is a popular tea, and it is also an anti-diabetic medicinal material. In the traditional processing of mulberry leaf tea, honey is a commonly used additive. This study used ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to measure the changes in the contents of 11 components of mulberry leaves before and after processing using honey as an additive. We analysed the absorption and elimination characteristics of mulberry leaves before and after processing in diabetes in vivo models, and then compared the effect of mulberry leaves before and after processing in resisting hyperglycaemia and hyperlipidaemia damage in in vitro models. The results showed that honey, as an additive, not only improves the dissolution of mulberry leaves, but in diabetes models also increases the utilisation of some components. In an in vitro model, honey mulberry leaves could significantly reduce the apoptosis of vascular endothelial cells. This demonstrated that the traditional processing method using honey as an additive could promote the anti-diabetic effect of mulberry tea. So far, this is the first research report on the quality and role of honey as an additive in mulberry leaf processing.Abbreviations: ML: mulberry leaves; HML: honey mulberry leaves; QC: quality control; HQC: high quality control sample; LLOQ: lower limit of quantification; LQC: low-quality control sample; MQC: medium-quality control sample; MRM: multiple reaction monitoring; STZ: streptozotocin.


Assuntos
Bebidas/análise , Diabetes Mellitus/induzido quimicamente , Mel/análise , Morus/química , Folhas de Planta/química , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Área Sob a Curva , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Dieta Hiperlipídica , Açúcares da Dieta/administração & dosagem , Açúcares da Dieta/efeitos adversos , Células Endoteliais/efeitos dos fármacos , Manipulação de Alimentos , Meia-Vida , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
19.
Sensors (Basel) ; 21(2)2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33435373

RESUMO

For the law enforcement agencies, lawful interception is still one of the main means to intercept a suspect or address most illegal actions. Due to its centralized management, however, it is easy to implement in traditional networks, but the cost is high. In view of this restriction, this paper aims to exploit software-defined network (SDN) technology to contribute to the next generation of intelligent lawful interception technology, i.e., to optimize the deployment of intercept access points (IAPs) in hybrid software-defined networks where both SDN nodes and non-SDN nodes exist simultaneously. In order to deploy IAPs, this paper puts forward an improved equal-cost multi-path shortest path algorithm and accordingly proposes three SDN interception models: T interception model, ECMP-T interception model and Fermat-point interception model. Considering the location relevance of all intercepted targets and the operation and maintenance cost of operators from the global perspective, by the way, we further propose a restrictive minimum vertex cover algorithm (RMVCA) in hybrid SDN. Implementing different SDN interception algorithms based RMVCA in real-world topologies, we can reasonably deploy the best intercept access point and intercept the whole hybrid SDN with the least SDN nodes, as well as significantly optimize the deployment efficiency of IAPs and improve the intercept link coverage in hybrid SDN, contributing to the implementation of lawful interception.

20.
Sensors (Basel) ; 20(16)2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32784420

RESUMO

The weighted K-nearest neighbor (WKNN) algorithm is a commonly used fingerprint positioning, the difficulty of which lies in how to optimize the value of K to obtain the minimum positioning error. In this paper, we propose an adaptive residual weighted K-nearest neighbor (ARWKNN) fingerprint positioning algorithm based on visible light communication. Firstly, the target matches the fingerprints according to the received signal strength indication (RSSI) vector. Secondly, K is a dynamic value according to the matched RSSI residual. Simulation results show the ARWKNN algorithm presents a reduced average positioning error when compared with random forest (81.82%), extreme learning machine (83.93%), artificial neural network (86.06%), grid-independent least square (60.15%), self-adaptive WKNN (43.84%), WKNN (47.81%), and KNN (73.36%). These results were obtained when the signal-to-noise ratio was set to 20 dB, and Manhattan distance was used in a two-dimensional (2-D) space. The ARWKNN algorithm based on Clark distance and minimum maximum distance metrics produces the minimum average positioning error in 2-D and 3-D, respectively. Compared with self-adaptive WKNN (SAWKNN), WKNN and KNN algorithms, the ARWKNN algorithm achieves a significant reduction in the average positioning error while maintaining similar algorithm complexity.

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