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1.
Mol Divers ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878213

RESUMEN

Identifying tumor cells can be challenging due to cancer's complex and heterogeneous nature. Here, an efficacious phosphorescent probe that can precisely highlight tumor cells has been created. By combining the ruthenium(II) complex with oligonucleotides, we have developed a nanosized functional ruthenium(II) complex (Ru@DNA) with dimensions ranging from 300 to 500 nm. Our research demonstrates that Ru@DNA can readily traverse biomembranes via ATP-dependent endocytosis without carriers. Notably, the nanosized ruthenium(II) complex exhibits rapid and selective accumulation within tumor cells, possibly attributed to the nanoparticles' enhanced permeation and retention (EPR) effect. Ru@DNA can also effectively discern and label the transplanted cancer cells in the zebrafish model. Moreover, Ru@DNA is efficiently absorbed into the intestine and further distributed in the pancreas. Our findings underscore the potential of Ru@DNA as a DNA-based nanodevice derived from a functional ruthenium(II) complex. This innovative nanodevice holds promise as an efficient phosphorescent probe for both in vitro and in vivo imaging of living tumor cells.

3.
Int J Biol Macromol ; 268(Pt 2): 131642, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38641283

RESUMEN

To better treat bacteria-infected wounds and promote healing, new wound dressings must be developed. In this study, we obtained PA@Fe by chelating iron trivalent ions (Fe3+) with protocatechualdehyde (PA), which has a catechol structure. Subsequently, we reacted it with ethylene glycol chitosan (GC) via a Schiff base reaction and loaded vancomycin to obtain an antibacterial Gel@Van hydrogel with a photothermal response. The as-prepared Gel@Van hydrogel exhibited good injectability, self-healing, hemostasis, photothermal stability, biocompatibility, and antioxidant and antibacterial properties. Moreover, Gel@Van hydrogel achieved highly synergistic antibacterial efficacy through photothermal and antibiotic sterilization. In a mouse skin-damaged infection model, Gel@Van hydrogel had a strong ability to promote the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, indicating the great potential application value of Gel@Van hydrogel in the field of treating and promoting the healing of infected wounds.


Asunto(s)
Benzaldehídos , Catecoles , Hidrogeles , Hierro , Polisacáridos , Infección de Heridas , Antioxidantes/síntesis química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antibacterianos/síntesis química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Hidrogeles/síntesis química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Hierro/química , Polisacáridos/química , Catecoles/química , Benzaldehídos/química , Infección de Heridas/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Vancomicina/uso terapéutico , Terapia Fototérmica , Modelos Animales , Animales , Ratones , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico
4.
Cancer Sci ; 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613253

RESUMEN

Peripheral T-cell lymphoma (PTCL) is a highly aggressive type of non-Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. In vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL-18. Upregulated TLR4 activated its downstream NF-κB anti-apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF-κB anti-apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In-depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.

5.
Front Oncol ; 14: 1345190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571508

RESUMEN

Introduction: Tumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy. Methods: We have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS. Results: The median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0-32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710). Conclusion: The TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.

6.
Langmuir ; 40(17): 9082-9096, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38619979

RESUMEN

Great efforts have been devoted to the development of novel and multifunctional wound dressing materials to meet the different needs of wound healing. Herein, we covalently grafted quaternary ammonium groups (QAGs) containing 12-carbon straight-chain alkanes to the dextran polymer skeleton. We then oxidized the resulting product into oxidized quaternized dextran (OQD). The obtained OQD polymer is rich in antibacterial QAGs and aldehyde groups. It can react with glycol chitosan (GC) via the Schiff-base reaction to form a multifunctional GC@OQD hydrogel with good self-healing behavior, hemostasis, injectability, inherent superior antibacterial activity, biocompatibility, and excellent promotion of healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The biosafe and nontoxic GC@OQD hydrogel with a three-dimensional porous network structure possesses an excellent swelling rate and water retention capacity. It can be used for hemostasis and treating irregular wounds. The designed GC@OQD hydrogel with inherent antibacterial activity possesses good antibacterial efficacy on both S. aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria), as well as MRSA bacteria, with antibacterial activity greater than 99%. It can be used for the treatment of wounds infected by MRSA and significantly promotes the healing of wounds. Thus, the multifunctional antibacterial GC@OQD hydrogel has the potential to be applied in clinical practice as a wound dressing.


Asunto(s)
Antibacterianos , Quitosano , Escherichia coli , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Animales , Quitosano/química , Quitosano/farmacología , Dextranos/química , Dextranos/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Ratones , Polisacáridos/química , Polisacáridos/farmacología
7.
Environ Sci Pollut Res Int ; 31(9): 13100-13121, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38240976

RESUMEN

To study the extent of green finance development in China, this article constructs a green finance index system and employs the entropy value method to measure China's green finance by using a yearly provincial panel data from 2001 to 2020. The Thiel and Moran indices are then used to systematically analyze the temporal and spatial distribution of China's regional green finance. The findings are summarized as follows. Firstly, the overall green finance index in China experiences an upward trend. The development of green finance in the eastern region is superior to that in other regions in terms of absolute value and growth rate. Moreover, the differences in China's green finance index have shown an increasing trend over the last two decades, which is mostly contributed by the intra-regional differences. Finally, the inter-regional distribution of green finance index demonstrates that green finance development has a spatial spillover effect.


Asunto(s)
Desarrollo Económico , China , Entropía
8.
Lab Invest ; 104(3): 100326, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38237739

RESUMEN

To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in ß-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.


Asunto(s)
Disección Aórtica , Espectrometría de Masas en Tándem , Ratones , Humanos , Animales , Cromatografía Liquida , Disección Aórtica/genética , Miocitos del Músculo Liso/metabolismo , Ratones Noqueados , Modelos Animales de Enfermedad , Proteínas del Choque Térmico HSP20/metabolismo
9.
J Transl Med ; 22(1): 54, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38218880

RESUMEN

BACKGROUND: Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation. METHODS: The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin. RESULTS: The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3' untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin. CONCLUSIONS: MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.


Asunto(s)
Histonas , MicroARNs , Humanos , Ratas , Animales , Histonas/metabolismo , Células Madre , Diferenciación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Dentina , Células Cultivadas , Histona Demetilasas con Dominio de Jumonji/genética
10.
Exp Neurol ; 369: 114543, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37743001

RESUMEN

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal and regenerative ability as they mature, their loss after injury or disease is irreversible and often leads to functional impairments. Unfortunately, therapeutic options for CNS diseases are still limited, and effective treatments for these notorious diseases are warranted to be explored. At present, stem cell therapy has emerged as a potential therapeutic strategy for improving the prognosis of CNS diseases. Accumulating preclinical and clinical evidences have demonstrated that multiple molecular mechanisms, such as cell replacement, immunoregulation and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases. However, several issues have yet to be addressed to support its clinical application. Thus, this review article aims to summarize the role and underlying mechanisms of stem cell therapy in treating CNS diseases. And it is worthy of further evaluation for the potential therapeutic applications of stem cell treatment in CNS disease.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Humanos , Enfermedades del Sistema Nervioso Central/terapia , Trasplante de Células Madre , Neuronas
11.
J Cardiovasc Dev Dis ; 10(9)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37754798

RESUMEN

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

12.
J Clin Med ; 12(4)2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36836067

RESUMEN

BACKGROUND: Minimally invasive stereotactic catheter aspiration becoming a promising surgical alternative for intracerebral hemorrhage (ICH) patients. Our goal is to determine the risk factors that lead to poor functional outcomes in patients undergoing this procedure. METHODS: Clinical data of 101 patients with stereotactic catheter ICH aspiration were retrospectively reviewed. Univariate and multiple logistic analyses were used to identify risk factors for poor outcomes 3 months and 1 year after discharge. Univariate analysis was used to compare the functional outcome between early (<48 h after ICH onset) and late hematoma evacuation (≥48 h after ICH onset) groups, as well as for the odd ratios assessment in terms of rebleeding. RESULTS: Independent factors for poor 3-month outcome included lobar ICH, ICH score > 2, rebleeding, and delayed hematoma evacuation. Factors for poor 1-year outcome included age > 60, GCS < 13, lobar ICH, and rebleeding. Early hematoma evacuation was linked to a lower likelihood of poor outcome both 3 months and 1 year post-discharge, but with higher risk of postoperative rebleeding. CONCLUSIONS: Lobar ICH and rebleeding independently predicted both poor short- and long-term outcomes in patients with stereotactic catheter ICH evacuation. Early hematoma evacuation with preoperative rebleeding risk evaluation may benefit patients with stereotactic catheter ICH evacuation.

13.
Biochem Biophys Rep ; 33: 101368, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36685613

RESUMEN

The insect larvae of Apriona germari, Apriona swainsoni and other closely related species are related to the insects that bore through the stems of the Caesalpinia decapetala. Because of therich nutritional as well as medicinal value of edible A. germari, it is often used to nourish the body, enhance immunity, and to treat ailments such as diarrhea. The soluble protein content of A. germari was determined using Kjeldahl and Soxhlet extraction methods. The crude fat content and the content of various fatty acids was determined by the normalization method, normalization method refers to that after the fat in the sample is extracted by hydrolysis ether solution, it is saponified and methylated under alkaline conditions to generate fatty acids and methyl esters, which are analyzed by capillary column gas chromatography and quantitatively measured by area normalization method. Amino acid content determined using an amino acid analyzer after acid hydrolysis showed 17 kinds of amino acids. A diarrhea mouse model was established by injecting a suspension of Escherichia coli into the abdominal cavity of mice. The mice were then fed with A. germari fodders at dose concentrations of 12%, 8%, 4% and 0%. The number of E. coli was determined from the intestinal tracts of mice; the activities of antioxidant enzymes and digestive enzymes in the serum were determined. Eleven kinds of fatty acids were detected in A. germari; unsaturated fatty acids accounted for 71.87% of the total fatty acids. A. germari is an edible resource insect with high nutritional value. Mice fed with A. germari showed an increase in the activity of antioxidant enzymes and digestive enzymes in the serum, which helped in the effective inhibition and reduction in the total number of intestinal bacteria and E. coli. The results indicate that A. germari has high nutritional value; A. germari also has a certain therapeutic effect on diarrhea caused by E. coli in mice.

14.
Aging Dis ; 13(6): 1823-1844, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36465183

RESUMEN

Stroke is a devastating disease associated with high mortality and disability worldwide, and is generally classified as ischemic or hemorrhagic, which share certain similar pathophysiological processes. Oxidative stress is a critical factor involved in stroke-induced injury, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, brain edema, and neuronal death. To alleviate these serious secondary brain injuries, neuroprotective agents targeting oxidative stress inhibition may serve as a promising treatment strategy. Melatonin is a hormone secreted by the pineal gland, and has various properties, such as antioxidation, anti-inflammation, circadian rhythm modulation, and promotion of tissue regeneration. Numerous animal experiments studying stroke have confirmed that melatonin exerts considerable neuroprotective effects, partially via anti-oxidative stress. In this review, we introduce the possible role of melatonin as an antioxidant in the treatment of stroke based on the latest published studies of animal experiments and clinical research.

15.
Neurosci Lett ; 781: 136648, 2022 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-35469820

RESUMEN

Intracerebral hemorrhage is a type of acute cerebrovascular disease that remains one of the main causes of death and disability. After the onset of ICH, different types of severe pathophysiological changes can cause great damage to brain tissue, including neuroinflammation. Our study demonstrated the effect of PEA on modulating microglia phenotype and neuroinflammation, as well as the possible underlying mechanisms after ICH for the first time. The phenotypic transformation of microglia and simulation of neuroinflammation after ICH in vitro was induced by hemoglobin on BV2 cells. Additionally, the experiment in vivo model was induced by collagenase injection in mice. The role of PEA on hematoma clearance was also discussed. Western blot, ELISA and immunofluorescence staining were used to determine the phenotypic polarization of microglia and neuroinflammation. In order to evaluate the role of PPAR-α in the anti-inflammatory effect of PEA after ICH, the PPAR-α antagonist GW6471 was utilized. Behavior tests examined the effect of PEA on improving neuronal function. Our results showed that PEA can ameliorate neuroinflammation by inhibiting upregulation of NF-κB, IL-1ß and TNF-α, both in vivo and in vitro. Additionally, PEA can improve motor function in ICH mice and promotes hematoma clearance. At the same time, PEA can increase the levels of PPAR-α in the nucleus. Hence, PPAR-α antagonists can reverse the protective effects of PEA on neuroinflammation. These results suggest that PEA is involved in microglia polarization, attenuating the activation of neuroinflammation, as well as improving motor function after ICH. This, at least in part, may contribute to the involvement of PPAR-α modulation of NF-κB.


Asunto(s)
Etanolaminas , FN-kappa B , PPAR alfa , Ácidos Palmíticos , Amidas/farmacología , Animales , Hemorragia Cerebral/tratamiento farmacológico , Etanolaminas/farmacología , Hematoma/tratamiento farmacológico , Hematoma/metabolismo , Ratones , Microglía/efectos de los fármacos , Microglía/patología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , PPAR alfa/metabolismo , Ácidos Palmíticos/farmacología
16.
Oxid Med Cell Longev ; 2022: 4295208, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35186185

RESUMEN

BACKGROUND: Ferroptosis is a newly identified form of programmed cell death caused by iron-dependent lipid peroxidation. Our study was designed to determine the expression patterns and role of 15-lipoxygenase-1 (ALOX15) in subarachnoid hemorrhage (SAH) and to investigate whether cepharanthine (CEP) can inhibit ferroptosis by inhibiting ALOX15 in specific cell types. METHODS: A mouse model of SAH was developed by the endovascular perforation method. bEend.3 endothelial cells and BV2 microglial cells as well as RSL3 and hemin were used to simulate SAH in vitro. Mice and cell lines were treated with CEP and a group of specific oxygenase inhibitors to explore the protection effect from ferroptosis. Lipid peroxidation staining with BODIPY 581/591 C11 and transmission electron microscopy were used to identify ferroptosis in vitro and in vivo. RESULTS: In the present study, the accumulation of lipid peroxide, a defect in the glutathione peroxidase 4 (GPx4)/glutathione (GSH) antioxidant system, highly expressed ALOX15 in microglia and endothelium, and ferroptotic changes in microglial mitochondria confirmed the occurrence of ferroptosis after SAH in vivo. Further, CEP was shown to inhibit ferroptosis and improve neurological function by downregulating the expression of ALOX15. During in vitro experiments, we investigated the important role ALOX15 in RSL3-induced endothelial ferroptosis. In addition, we found that M2-type microglia are more sensitive to RSL3-induced ferroptosis than M1-type microglia and that hemin probably induced ferroptosis in M2-type microglia by increasing ALOX15 levels and decreasing GPx4 levels. The effect of CEP treatment was also demonstrated in vitro. CONCLUSIONS: In summary, to the best of our knowledge, this is the first study demonstrating that ferroptosis occurred in the microglia and endothelium after SAH, and this process was facilitated by increased ALOX15 levels. More importantly, treatment with CEP could inhibit ferroptosis through downregulating the expression of ALOX15.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Araquidonato 15-Lipooxigenasa/metabolismo , Bencilisoquinolinas/uso terapéutico , Lesiones Encefálicas/tratamiento farmacológico , Células Endoteliales/metabolismo , Ferroptosis/efectos de los fármacos , Microglía/efectos de los fármacos , Hemorragia Subaracnoidea/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/farmacología , Bencilisoquinolinas/farmacología , Modelos Animales de Enfermedad , Humanos , Ratones
17.
Front Mol Biosci ; 9: 807418, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35187083

RESUMEN

HCC is one of the most common types of malignancies worldwide and the fourth-leading cause of cancer deaths. Thus, there is an urgent need to search for novel targeted therapies in HCC. 186 m6a-related lncRNAs were screened for subsequent analysis. Two distinct m6A modification clusters were identified to be associated with the overall prognosis in TCGA-LIHC based on the m6A-related lncRNAs profiling, followed by univariate Cox regression analysis. In addition, four m6A-related lncRNAs prognostic signatures were developed and validated that could predict the OS of HCC patients, followed by univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. Moreover, four m6A-related lncRNAs were identified to be related to HCC prognosis. ESTIMATE was used to evaluate the stromal score, immune score, ESTIMATE score, and tumor purity of each HCC sample. ssGSEA was performed to identify the enrichment levels of 29 immune signatures in each sample. Finally, quantitative real-time polymerase chain reaction shown that KDM4A-AS1, BACE1-AS, and NRAV expressions were upregulated in HCC patients. We proved that our m6A-related lncRNAs signature had powerful and robust ability for predicting OS of different HCC subgroups.

18.
J Neurochem ; 160(1): 113-127, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34482541

RESUMEN

Stroke is the primary reason for death and disability worldwide, with few treatment strategies to date. Neurosteroids, which are natural molecules in the brain, have aroused great interest in the field of stroke. Neurosteroids are a kind of steroid that acts on the nervous system, and are synthesized in the mitochondria of neurons or glial cells using cholesterol or other steroidal precursors. Neurosteroids mainly include estrogen, progesterone (PROG), allopregnanolone, dehydroepiandrosterone (DHEA), and vitamin D (VD). Most of the preclinical studies have confirmed that neurosteroids can decrease the risk of stroke, and improve stroke outcomes. In the meantime, neurosteroids have been shown to have a positive therapeutic significance in some post-stroke complications, such as epilepsy, depression, anxiety, cardiac complications, movement disorders, and post-stroke pain. In this review, we report the historical background, modulatory mechanisms of neurosteroids in stroke and post-stroke complications, and emphasize on the application prospect of neurosteroids in stroke therapy.


Asunto(s)
Fármacos Neuroprotectores/farmacología , Neuroesteroides/farmacología , Accidente Cerebrovascular , Animales , Humanos
19.
Transplant Proc ; 53(10): 3080-3086, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34749996

RESUMEN

BACKGROUND: Renal transplantation is an effective treatment for end-stage renal disease, which involves pathophysiologic processes such as ischemia-reperfusion injury and immune rejection. The degree of ischemia-reperfusion injury is closely related to the functional state of the transplanted kidney. At present, the allogeneic kidney transplantation model has been widely used in related research. The traditional kidney transplantation model has the disadvantages of complicated vascular anastomosis, difficulty in ureteral reconstruction. The aim of this study was to establish a rat autologous orthotopic kidney transplantation model based on non-anastomotic technique. METHODS: Inbred Wistar rats weighing 260 to 280 g were selected. The rats were anesthetized by intraperitoneal injections of 40 mg/kg body weight pentobarbital sodium. We exposed and freed the left kidney after laparotomy and separated the left renal artery and left renal vein, abdominal aorta, and posterior vena cava. A purse-string suture with a diameter of 1 to 2 mm was made through the tunica media of the abdominal aorta. A puncture was made through the center of the purse-string suture. The in-dwelling needle was placed in the renal artery along the blood flow direction, and was infused with constant flow of 4°C heparinized lactated ringer's solution until the kidney became pale yellow. The renal vein was ligated and the renal artery was clamped. The in-dwelling needle was removed, purse-string suture was ligated, and the kidney was stored in a self-made autologous kidney transplant cold storage bag for 4 hours. We then opened the vein and artery, removed the cold storage bag, and rewarmed with 37°C normal saline. The abdomen was then closed layer by layer. RESULTS: Fifty-two orthotopic renal transplantations were performed, which included pre-experimental (40 operations) and experimental stages (12 operations). The success rates of the 2 stages were 75% and 91.7%, respectively. The main causes of failure were intraoperative hemorrhagic shock and postoperative infection. The operation time of orthotopic renal transplantation was 360 ± 30 minutes, including 30 ± 10 minutes for dissociation and management of kidney and blood vessels, 1 ± 0.5 minutes for warm ischemia and 240 ± 10 minutes for cold storage. Rats were sacrificed at 1 day and 7 day respectively. The rats were in good condition after operation. They could eat and drink freely. At 24 hours and 1 week after transplantation, the kidney's blood supply was good, the intestine was light or showed no adhesions, and the abdominal cavity had no ascites or peculiar smell. Hematoxylin & eosin (H&E) staining showed that there were no obvious pathologic changes in the sham group. The orthotopic kidney transplantation 1-day group showed pathologic changes of ischemia-reperfusion, such as swelling, necrosis, shedding, and cast formation of renal tubular cells. The orthotopic kidney transplantation 7-day group recovered well, with mild dilation of the renal capsule and mild dilatation of the renal tubules. CONCLUSION: The new model of autologous kidney transplantation is simple to use, does not require vascular anastomosis and ureteral reconstruction, and has a high success rate.


Asunto(s)
Trasplante de Riñón , Anastomosis Quirúrgica , Animales , Riñón/cirugía , Ratas , Ratas Wistar , Venas Renales/cirugía
20.
Nat Cell Biol ; 23(9): 1013-1022, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34489574

RESUMEN

Piwi-interacting RNAs (piRNAs) are predominantly expressed in germ cells and function in gametogenesis in various species. However, Piwi-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear to be widely representative of mammals. Thus, the function of piRNAs in mammalian oogenesis remains largely unclear. Here, we generated Piwil1- and Mov10l1-deficient golden hamsters and found that all female and male mutants were sterile, with severe defects in embryogenesis and spermatogenesis, respectively. In Piwil1-deficient female hamsters, the oocytes and embryos displayed aberrant transposon accumulation and extensive transcriptomic dysregulation, and the embryos were arrested at the two-cell stage with impaired zygotic genome activation. Moreover, PIWIL1-piRNAs exert a non-redundant function in silencing endogenous retroviruses in the oocytes and embryos. Together, our findings demonstrate that piRNAs are indispensable for generating functional germ cells in golden hamsters and show the value of this model species for piRNA studies in gametogenesis, especially those related to female infertility.


Asunto(s)
Desarrollo Embrionario/fisiología , Células Germinativas/metabolismo , Oocitos/metabolismo , ARN Interferente Pequeño/genética , Animales , Proteínas Argonautas/genética , Cricetinae , Fertilidad/fisiología , Masculino , Mesocricetus/genética , Espermatogénesis/genética , Testículo/metabolismo
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