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1.
Biomolecules ; 14(5)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38785973

RESUMEN

One of the hallmarks of cancer is metabolic reprogramming in tumor cells, and aerobic glycolysis is the primary mechanism by which glucose is quickly transformed into lactate. As one of the primary rate-limiting enzymes, pyruvate kinase (PK) M is engaged in the last phase of aerobic glycolysis. Alternative splicing is a crucial mechanism for protein diversity, and it promotes PKM precursor mRNA splicing to produce PKM2 dominance, resulting in low PKM1 expression. Specific splicing isoforms are produced in various tissues or illness situations, and the post-translational modifications are linked to numerous disorders, including cancers. hnRNPs are one of the main components of the splicing factor families. However, there have been no comprehensive studies on hnRNPs regulating PKM alternative splicing. Therefore, this review focuses on the regulatory network of hnRNPs on PKM pre-mRNA alternative splicing in tumors and clinical drug research. We elucidate the role of alternative splicing in tumor progression, prognosis, and the potential mechanism of abnormal RNA splicing. We also summarize the drug targets retarding tumorous splicing events, which may be critical to improving the specificity and effectiveness of current therapeutic interventions.


Asunto(s)
Empalme Alternativo , Ribonucleoproteínas Nucleares Heterogéneas , Neoplasias , Piruvato Quinasa , Humanos , Empalme Alternativo/genética , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Animales
2.
Adv Mater ; : e2313695, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38452281

RESUMEN

The osmotic energy, an abundant renewable energy source, can be directly converted to electricity by nanofluidic devices with ion-selective membranes. 2D nanochannels constructed by nanosheets possess abundant lateral interfacial ion-exchange sites and exhibit great superiority in nanofluidic devices. However, the most accessible orientation of the 2D nanochannels is parallel to the membrane surface, undoubtedly resulting in the conductivity loss. Herein, first vertically aligned 2D subnanochannel arrays self-assembled by a smectic liquid crystal (LC) network that exhibit high-performance osmotic energy conversion are demonstrated. The 2D subnanochannel arrays are fabricated by in situ photopolymerization of monomers in the LC phase. The as-prepared membrane exhibits excellent water-resistance and mechanical strength. The 2D subnanochannels with excellent cation selectivity and conductivity show high-performance osmotic energy conversion. The power density reaches up to about 22.5 W m-2 with NaCl solution under a 50-fold concentration gradient, which is among with ultrahigh power density. This membrane design concept provides promising applications in osmotic energy conversion.

3.
ACS Infect Dis ; 10(4): 1152-1161, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38442009

RESUMEN

Periodontitis, a chronic infectious disease in periodontal tissues, is characterized by an imbalance of alveolar bone resorption and remodeling, which eventually results in tooth loosening and even tooth loss. The etiology of periodontitis is polymicrobial synergy and dysbiosis, in which Porphyromonas gingivalis (P. gingivalis) is one of the primary pathogens responsible for periodontitis progression. The interplay of EphrinB2/EphB4 is crucial for osteoblast-osteoclast communication during bone remodeling and healing. This study investigates the mechanism of EphB4/EphrinB2 transduction modulating osteogenesis inhibition and bone resorption in periodontitis induced by P. gingivalis. An in vivo model of chronic periodontitis provoked by P. gingivalis was constructed, the inflammation and bone resorption were evaluated. The expression of EphB4 and EphrinB2 proteins in periodontal tissues was detected, which was also evaluated, respectively, in osteoblasts and osteoclasts infected with P. gingivalis in vitro. Then, a simulated coculture model of osteoblasts and osteoclasts was established to activate the forward and reverse pathways of EphB4/EphrinB2 with P. gingivalis infection. This study showed that P. gingivalis infection promoted alveolar bone resorption in rats and enhanced EphB4 and EphrinB2 expression in periodontal tissues. EphB4 and molecules associated with osteogenesis in osteoblasts infected with P. gingivalis were inhibited, while EphrinB2 and osteoclast differentiation-related markers in osteoclasts were activated. In conclusion, this study suggested that EphB4/EphrinB2 proteins were involved in alveolar bone remodeling in the process of periodontitis induced by P. gingivalis infection. Moreover, attenuated EphB4/EphrinB2 with P. gingivalis infection weakened osteoblast activity and enhanced osteoclast activity.


Asunto(s)
Resorción Ósea , Periodontitis , Receptor EphB2 , Receptor EphB4 , Animales , Ratas , Resorción Ósea/genética , Resorción Ósea/metabolismo , Resorción Ósea/microbiología , Osteoclastos/metabolismo , Periodontitis/microbiología , Porphyromonas gingivalis/metabolismo , Receptor EphB4/genética , Receptor EphB4/metabolismo , Transducción de Señal , Receptor EphB2/metabolismo , Infecciones por Bacteroidaceae/metabolismo , Infecciones por Bacteroidaceae/microbiología
4.
Dalton Trans ; 53(1): 215-222, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38032350

RESUMEN

Solar energy can be harvested using biological light-driven ion pumps for the sustainability of life. It remains a significant challenge to develop high-performance artificial light-driven ion pumps for solar energy harvesting in all solid-state materials. Here, we exploit the benefits of short channel lengths and efficient light absorption to demonstrate efficient photo-driven ion transport in slightly reduced vertical graphene oxide membranes (GOMs). Remarkably, this photo-driven ion pump exhibits excellent ability, countering a 10-fold electrolyte concentration gradient. We propose a plausible mechanism where light illumination enhances the electric potential of ion channels on GOMs triggered by the separation of photoexcited charge carriers between the sp2 and sp3 carbon clusters. This results in the establishment of an electric potential difference across the effective ion channels composed of sp3 carbon clusters, thus driving the directional transport of cations from the illuminated side to the non-illuminated side. The promising results of this study provide new possibilities for the application of vertical 2D nanofluidic membranes in areas such as artificial photosynthesis, light harvesting, and water treatment.

5.
Shock ; 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37878471

RESUMEN

BACKGROUND: Recent studies have shown that ferroptosis is involved in the evolution of acute lung injury (ALI), a serious respiratory pathological process leading to death. However, the regulatory mechanisms underlying ferroptosis in ALI remain largely unknown. The current study analyzed and identified a ferroptosis-related gene signature for ALI. METHODS: Key genes associated with ferroptosis in ALI were identified by bioinformatics analysis. GSE104214, GSE18341, and GSE17355 datasets were downloaded from the Gene Expression Omnibus database. The signature genes were screened by least absolute shrinkage and selection operator (LASSO) regression, and the key genes of ALI were screened by weighted correlation network analysis (WGCNA), followed by immune infiltration analysis and functional enrichment analysis. In addition, mRNA expression of key genes in the lungs of mice with hemorrhagic shock and sepsis was verified. RESULTS: A total of 2132 differential genes were identified by various analyses, and nine characteristic genes were detected using Lasso regression. We intersected nine signature genes with WGCNA module genes and finally determined four key genes (PROK2, IL6, TNF, SLC7A11). All four key genes were closely correlated with immune cells and regulatory genes of ALI, and the expression of the four genes was significantly different in the lung tissues of hemorrhagic shock and sepsis models. Besides, the ferroptosis related molecules GPX4 and ACSL4 showed remarkable difference in these models. CONCLUSION: These results indicate that PROK2, IL6, TNF, SLC7A11 may be key regulatory targets of ferroptosis during ALI. This study proved that ferroptosis is a common pathophysiological process in three ALI models.

6.
Int Immunopharmacol ; 115: 109715, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37724955

RESUMEN

Diabetic nephropathy (DN) is a common leading cause of end-stage renal disease (ESRD). Podocyte injury is a major pathogenesis of DN. Pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) is insufficient to fully prevent the development of ESRD. The present investigation aims to evaluate the protective function of valsartan, an angiotensin receptor blocker, alone and in combination with angiopoietin-like protein 3 (Angptl3) knockout against renal damage and podocyte injury in streptozotocin (STZ)-induced diabetic mice. The mice were divided into four groups: normal control group, STZ-induced DN group, valsartan + DN group (val, 100 mg/kg, po), and Angptl3-/- + valsartan + DN group. Tests on kidney function, renal pathology, podocyte ultrastructure, podocyte apoptosis, reactive oxygen species (ROS) production, and autophagy were performed. The combined Angptl3 knockout/valsartan treatment significantly attenuated diabetes-induced renal pathological damage and improved podocyte ultrastructure compared with valsartan alone. The combined administration ameliorated glomerular injury by increasing nephrin, podocin, and CD2-associated protein (CD2AP) expression levels and inhibiting podocyte loss by apoptosis. Compared with valsartan alone, Angptl3-/- and valsartan combination therapy significantly improved the renal function, as demonstrated by decreasing levels of serum urea nitrogen, creatinine, and urinary albumin. Additionally, the combination treatment significantly activated autophagy and reduced the ROS production than valsartan alone. These findings highlight the role of valsartan to Angptl3 knockout could have much better outcome that opens the future for drugs that could inhibit Angptl3.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Fallo Renal Crónico , Podocitos , Animales , Ratones , Nefropatías Diabéticas/tratamiento farmacológico , Valsartán/uso terapéutico , Estreptozocina , Proteína 3 Similar a la Angiopoyetina , Diabetes Mellitus Experimental/tratamiento farmacológico , Especies Reactivas de Oxígeno
7.
Cell Death Dis ; 14(9): 601, 2023 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-37689694

RESUMEN

Minimal change disease (MCD) is the common type of nephrotic syndrome (NS) in children. Currently, there is an urgent need to explore new treatments because of the significant side effects of long-term use of glucocorticoids and immunosuppressive drugs and the failure to reduce proteinuria in some patients. Angiopoietin-like protein 3 (Angptl3) is an essential target of NS, and anti-ANGPTL3-FLD monoclonal antibody (mAb) significantly reduces proteinuria in mice with adriamycin nephropathy (AN). However, some proteinuria is persistent. Minnelide, a water-soluble prodrug of triptolide, has been used for the treatment of glomerular disease. Therefore, the present study aimed to investigate whether minnelide combined with mAb could further protect mice with AN and the underlying mechanisms. 8-week-old C57BL/6 female mice were injected with 25 mg/kg of Adriamycin (ADR) by tail vein to establish the AN model. A dose of 200 µg/kg of minnelide or 20 mg/kg of mAb was administered intraperitoneally for the treatment. In vitro, the podocytes were treated with 0.4 µg/mL of ADR for 24 h to induce podocyte injury, and pretreatment with 10 ng/mL of triptolide for 30 min or 100 ng/mL of mAb for 1 h before ADR exposure was used to treat. The results showed that minnelide combined with mAb almost completely ameliorates proteinuria and restores the ultrastructure of the podocytes in mice with AN. In addition, minnelide combined with mAb restores the distribution of Nephrin, Podocin, and CD2AP and reduces the level of inflammatory factors in mice with AN. Mechanistically, minnelide combined with mAb could further alleviate apoptosis and promote autophagy in mice with AN by inhibiting the mTOR signaling pathway. In vitro, triptolide combined with mAb increases the expression of Nephrin, Podocin, and CD2AP, alleviates apoptosis, and promotes autophagy. Overall, minnelide combined with mAb completely protects the mice with AN by promoting autophagy and inhibiting apoptosis.


Asunto(s)
Anticuerpos Monoclonales , Enfermedades Renales , Femenino , Animales , Ratones , Ratones Endogámicos C57BL , Anticuerpos Monoclonales/farmacología , Proteinuria/tratamiento farmacológico , Apoptosis , Autofagia , Doxorrubicina/farmacología
8.
Molecules ; 28(15)2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37570850

RESUMEN

Azobenzene mesogens have garnered considerable research attention in the realm of photo-responsive materials due to their reversible trans-cis isomerization. In this paper, we demonstrate an azobenzene inverse opal film synthesized via photo-polymerization from a SiO2 opal template. The proposed design exhibits intriguing optical properties, including dynamic fluorescent features, distinct fluorescent enhancement, and an anti-fake micropattern with a switchable structure color. This work holds significant importance for advancing the development of novel optical devices.

9.
Front Pediatr ; 11: 1113484, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37266537

RESUMEN

Background: Angiopoietin-like 3 (ANGPTL3) is a secretory glycoprotein. It has been demonstrated that ANGPTL3 level was upregulated in minimal change nephrotic syndrome (MCNS) kidney tissues. Subsequently, our group found that ANGPTL3 level was closely correlated with nephropathy in vivo and in vitro. Hence, whether ANGPTL3 level could be correlated with the proteinuria level, and assessment of disease severity of nephrotic syndrome (NS) remained to be investigated. This study aimed to analyzed the correlation between the levels of ANGPTL3 in serum and urine of patients with nephrotic syndrome and proteinuria, and assessed the severity of the patients' disease. In future clinical translation, the level of ANGPTL3 in serum, urine will be used as a biomarker to better predict the development of nephrotic syndrome. Methods: A total of 200 NS patients and 80 healthy controls (age, 1-18 years) were admitted to our institution between 2021 and 2022. The etiology of NS included primary nephrotic syndrome (PNS, n = 144) and NS with other causes (n = 56). A total of 280 serum samples and 244 urinary samples were collected to determine ANGPTL3 level using enzyme-linked immunosorbent assay (ELISA). Results: Serum ANGPTL3 and urinary ANGPTL3/Cre were remarkably elevated in NS patients compared with those in healthy controls. Furthermore, serum ANGPTL3 and urinary ANGPTL3/Cre were significantly correlated with proteinuria level. Additionally, multivariate linear regression analysis demonstrated that serum ALB was independently correlated with serum ANGPTL3 and PRO/CR was independently correlated with urinary ANGPTL3/Cre in NS patients. Conclusion: Serum ANGPTL3 and urinary ANGPTL3/Cre showed a promising performance in the diagnosis of NS, and served as novel potential noninvasive biomarkers to assess disease severity of NS. Further exploration of the role of ANGPTL3 level may shed a new light on the treatment of NS.

10.
Adv Mater ; 35(33): e2302436, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37202898

RESUMEN

Ferroelectricity has been separately found in numerous solid and liquid crystal materials since its first discovery in 1920. However, a single material with biferroelectricity existing in both solid and liquid crystal phases is very rare, and the regulation of biferroelectricity has never been studied. Here, solid-liquid crystal biphasic ferroelectrics, cholestanyl 4-X-benzoate (4X-CB, X = Cl, Br, and I), which exhibits biferroelectricity in both the solid and liquid crystal phases, is presented. It is noted that the ferroelectric liquid crystal phase of 4X-CB is a cholesteric one, distinct from the ordinary chiral smectic ferroelectric liquid crystal phase. Moreover, 4X-CB shows solid-solid and solid-liquid crystal phase transitions, of which the transition temperatures gradually increase from Cl to Br to I substitution. The spontaneous polarization (Ps ) of 4X-CB in both solid and liquid crystal phases can also be regulated by different halogen substitutions, where the 4Br-CB has the optimal Ps because of the larger molecular dipole moment. To the authors' knowledge, 4X-CB is the first ferroelectric with tunable biferroelectricity, which offers a feasible case for the performance optimization of solid-liquid crystal biphasic ferroelectrics.

11.
JACS Au ; 3(4): 1196-1204, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37124294

RESUMEN

Ferroelectric materials are a special type of polar substances, including solids or liquid crystals. However, obtaining a material to be ferroelectric in both its solid crystal (SC) and liquid crystal (LC) phases is a great challenge. Moreover, although cholesteric LCs inherently possess the advantage of high fluidity, their ferroelectricity remains unknown. Here, through the reasonable H/F substitution on the fourth position of the phenyl group of the parent nonferroelectric dihydrocholesteryl benzoate, we designed ferroelectric dihydrocholesteryl 4-fluorobenzoate (4-F-BDC), which shows ferroelectricity in both SC and cholesteric LC phases. The fluorination induces a lower symmetric polar P1 space group and a new solid-to-solid phase transition in 4-F-BDC. Beneficial from fluorination, the SC and cholesteric LC phases of 4-F-BDC show clear ferroelectricity, as confirmed by well-shaped polarization-voltage hysteresis loops. The dual ferroelectricity in both SC and cholesteric LC phases of a single material was rarely found. This work offers a viable case for the exploration of the interplay between ferroelectric SC and LC phases and provides an efficient approach for designing ferroelectrics with dual ferroelectricity and cholesteric ferroelectric liquid crystals.

12.
Molecules ; 28(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37110759

RESUMEN

Two-dimensional van der Waals (vdW) heterostructures are potential candidates for clean energy conversion materials to address the global energy crisis and environmental issues. In this work, we have comprehensively studied the geometrical, electronic, and optical properties of M2CO2/MoX2 (M = Hf, Zr; X = S, Se, Te) vdW heterostructures, as well as their applications in the fields of photocatalytic and photovoltaic using density functional theory calculations. The lattice dynamic and thermal stabilities of designed M2CO2/MoX2 heterostructures are confirmed. Interestingly, all the M2CO2/MoX2 heterostructures exhibit intrinsic type-II band structure features, which effectively inhibit the electron-hole pair recombination and enhance the photocatalytic performance. Furthermore, the internal built-in electric field and high anisotropic carrier mobility can separate the photo-generated carriers efficiently. It is noted that M2CO2/MoX2 heterostructures exhibit suitable band gaps in comparison to the M2CO2 and MoX2 monolayers, which enhance the optical-harvesting abilities in the visible and ultraviolet light zones. Zr2CO2/MoSe2 and Hf2CO2/MoSe2 heterostructures possess suitable band edge positions to provide the competent driving force for water splitting as photocatalysts. In addition, Hf2CO2/MoS2 and Zr2CO2/MoS2 heterostructures deliver a power conversion efficiency of 19.75% and 17.13% for solar cell applications, respectively. These results pave the way for exploring efficient MXenes/TMDCs vdW heterostructures as photocatalytic and photovoltaic materials.

13.
Front Public Health ; 11: 1077564, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36866102

RESUMEN

Background: The mpox (monkeypox) outbreak has been declared to be a public health emergency of international concern by the Director-General of World Health Organization in July 2022. However, evidence regarding the awareness, knowledge, and worry about mpox in the general population remains scant. Methods: A community-based survey targeting community residents was preliminarily conducted in Shenzhen, China in August 2022 by using a convenience sampling method. Information on mpox-related awareness, knowledge, and worry was collected from each participant. Binary logistic regression analyses with the stepwise procedure were applied to explore the factors associated with awareness, knowledge, and worry about mpox. Results: A total of 1028 community residents were included in the analysis (mean age: 34.70 years). Among these participants, 77.9% had ever heard of mpox, and 65.3% were aware of the global outbreak of mpox. However, only about half of them had a high level of knowledge regarding mpox (56.5%) and related symptoms (49.7%). More than one-third of them (37.1%) expressed a high level of worry about mpox. Having high knowledge levels of mpox and related symptoms were positively associated with a high level of worry (OR: 1.79, 95%CI: 1.22~2.63 for a single high knowledge level; OR: 1.98, 95%CI: 1.47~2.66 for both high knowledge levels). Conclusions: This study identified the gaps in public awareness and specific knowledge of mpox in Chinese people, providing scientific evidence for the prevention and control network of mpox at the community level. Targeted health education programs are of urgent need, which should be implemented along with psychological interventions to release public worry if necessary.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Mpox , Adulto , Humanos , Pueblo Asiatico , China , Brotes de Enfermedades , Educación en Salud
14.
Appl Biochem Biotechnol ; 195(12): 7379-7396, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37000351

RESUMEN

Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children. The current major therapy is hormones for most steroid-sensitive patients. However, many patients have recurrent relapses of the disease and require long-term immunosuppression, leading to significant morbidity due to the side effects of the drugs. Therefore, better drugs need to be urgently explored to treat nephrotic syndrome while avoiding the side effects of drugs. Minnelide, a water-soluble prodrug of triptolide, has been proved to be effective in treating cancers in many clinical trials. This study aimed to investigate the therapeutic effect of minnelide in mice with adriamycin (ADR) nephropathy, its underlying protection mechanisms, and its reproductive toxicity. Minnelide was administered intraperitoneally to 6-8-week female mice with adriamycin nephropathy for 2 weeks, and the urine, blood, and kidney tissues were taken to analyze the therapeutic effect. In addition, we evaluated reproductive toxicity by measuring the levels of gonadal hormones and observing the histological changes in ovaries and testes. Primary mouse podocytes were exposed to puromycin (PAN) to damage the cytoskeleton and induce apoptosis, and then, triptolide was used to evaluate the therapeutic effect and underlying protection mechanisms in vitro. It was observed that minnelide dramatically alleviated proteinuria and apoptosis in mice with adriamycin nephropathy. In vitro, triptolide ameliorated puromycin-induced cytoskeletal rearrangement and apoptosis via reactive oxygen species-mediated mitochondrial pathway. In addition, minnelide caused no reproductive toxicity to male and female mice. The results suggested that minnelide might be a promising drug for nephrotic syndrome.


Asunto(s)
Enfermedades Renales , Síndrome Nefrótico , Podocitos , Humanos , Niño , Ratones , Masculino , Femenino , Animales , Doxorrubicina/toxicidad , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/metabolismo , Podocitos/metabolismo , Podocitos/patología , Enfermedades Renales/inducido químicamente , Proteinuria/tratamiento farmacológico , Proteinuria/metabolismo , Proteinuria/patología , Puromicina/metabolismo , Puromicina/farmacología , Puromicina/uso terapéutico
16.
Shock ; 59(5): 754-762, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36840514

RESUMEN

ABSTRACT: Background: Hemorrhagic shock-induced acute lung injury (ALI) is commonly associated with the posthemorrhagic shock mesenteric lymph (PHSML) return. Whether excessive autophagy is involved in PHSML-mediated ALI remains unclear. The relationship between estrogen treatment and PHSML or autophagy needs to verify. The current study will clarify the role of estrogen in reducing PHSML-mediated ALI through inhibition of autophagy. Methods: First, a hemorrhagic shock model in conscious rats was used to observe the effects of 17ß-estradiol (E2) on intestinal blood flow, pulmonary function, intestinal and pulmonary morphology, and expression of autophagy marker proteins. Meanwhile, the effect of PHSML and autophagy agonist during E2 treatment was also investigated. Secondly, rat primary pulmonary microvascular endothelial cells were used to observe the effect of PHSML, PHSML plus E2, and E2-PHSML (PHSML obtained from rats treated by E2) on the cell viability. Results: Hemorrhagic shock induced intestinal and pulmonary tissue damage and increased wet/dry ratio, reduced intestinal blood flow, along with pulmonary dysfunction characterized by increased functional residual capacity and lung resistance and decreased inspiratory capacity and peak expiratory flow. Hemorrhagic shock also enhanced the autophagy levels in intestinal and pulmonary tissue, which was characterized by increased expressions of LC3 II/I and Beclin-1 and decreased expression of p62. E2 treatment significantly attenuated these adverse changes after hemorrhagic shock, which was reversed by PHSML or rapamycin administration. Importantly, PHSML incubation decreased the viability of pulmonary microvascular endothelial cells, while E2 coincubation or E2-treated lymph counteracted the adverse roles of PHSML. Conclusions: The role of estrogen reducing PHSML-mediated ALI is associated with the inhibition of autophagy.


Asunto(s)
Lesión Pulmonar Aguda , Choque Hemorrágico , Ratas , Animales , Ratas Sprague-Dawley , Choque Hemorrágico/complicaciones , Choque Hemorrágico/tratamiento farmacológico , Choque Hemorrágico/metabolismo , Células Endoteliales/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , Estrógenos/farmacología , Estrógenos/uso terapéutico , Autofagia
17.
J Control Release ; 354: 615-625, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36641123

RESUMEN

Immunomodulatory therapy has become a promising method for the clinical treatment of many diseases. Recently, pilot studies revealed that immunomodulatory therapy exhibited good effects on the treatment of cardiovascular diseases, but many problems remain to be solved, such as useful platforms for drug co-delivery and combination therapies. In this study, we designed and constructed the multifunctional nanoparticle Rapa@UiO-66-NH-FAM-IL-1Ra (RUFI) for the treatment of atherosclerotic cardiovascular disease. This nanoplatform combined the advantages of metal-organic frameworks (MOFs) for drug co-delivery, rapamycin and IL-1Ra for immunomodulation, IL-1Ra for cellular targeting, and 5-FAM for fluorescence imaging. RUFI exhibited good drug release of rapamycin and IL-1Ra and specific cytotoxicity for inflammatory macrophages in vitro. In an atherosclerotic model of diet-fed ApoE-/- mice, RUFI significantly targeted and reduced atherosclerosis plaques in coronary arteries, carotid arteries, and aortas. Mechanistic studies indicated that RUFI modulated macrophage phenotype, cytokine expression, and autophagy. This study demonstrated that combination therapy with rapamycin and IL-1Ra via MOF carriers enhanced the immunoregulatory effects against atherosclerosis. This drug co-delivery system suggests that MOF carriers loaded with immunomodulators are promising treatments for atherosclerosis or other inflammatory diseases.


Asunto(s)
Aterosclerosis , Estructuras Metalorgánicas , Placa Aterosclerótica , Ratones , Animales , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Sirolimus
18.
Int Immunopharmacol ; 115: 109656, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36608441

RESUMEN

Minimal change disease (MCD) is the common type of nephrotic syndrome in children. There is an urgent need to explore new treatment methods as current treatments have many drawbacks and cause significant side effects. Our group found that Angiopoietin-like protein 3 (Angptl3) is closely related to renal disease and Angptl3 knockout significantly alleviated proteinuria in mice with adriamycin nephropathy (AN), however, some proteinuria was still present. Minnelide is a water-soluble prodrug of triptolide which has been used for the treatment of glomerular diseases. Therefore, this study aimed to investigate whether minnelide, combined with Angptl3 knockout, could completely protect mice with AN and its mechanism. AN was induced in B6;129S5 female mice by tail vein injection of 25 mg/kg of Adriamycin (ADR), and treatment with 200 ug/kg/d of minnelide. The results showed that minnelide combined with Angptl3 knockout completely reduced proteinuria and restored the foot processes in mice with AN. Moreover, in Angptl3 knockout mice with AN, minnelide restored the distribution of nephrin, podocin and cd2ap and reduced inflammatory factors (Tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-1ß (IL-1ß)). Through RNA sequencing and related experiments, we found minnelide could ameliorate fibrosis and apoptosis by inhibiting TGF-ß1-Smad2 and p53 pathways in Angptl3 knockout mice with AN, respectively. In Angptl3 knockout primary podocytes, triptolide alleviates ADR-induced decreases in nephrin, podocin and cd2ap, upregulation of Bax and downregulation of Bcl-2. Overall, our study shows that minnelide combined with Angptl3 knockout completely protects mice with AN by inhibiting the TGF-ß1-smad2 and p53 pathways.


Asunto(s)
Enfermedades Renales , Podocitos , Animales , Femenino , Ratones , Proteína 3 Similar a la Angiopoyetina , Doxorrubicina , Enfermedades Renales/patología , Ratones Noqueados , Proteinuria/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
19.
Molecules ; 27(23)2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36500227

RESUMEN

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4 nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4 NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4 NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4 NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.


Asunto(s)
Arteritis , Hipertermia Inducida , Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Terapia Fototérmica , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Arteritis/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Neoplasias/tratamiento farmacológico
20.
Nat Commun ; 13(1): 7095, 2022 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-36402778

RESUMEN

3D photonic crystals (PCs) have attracted extensive attention due to their unique optical properties. However, fabricating 3D PCs structure by 3D printing colloidal particles is limited by control of assembly under a fast-printing speed. Here, we employ continuous digital light processing (DLP) 3D printing strategy with hydrogen bonds assisted colloidal inks for fabricating well-assembled 3D PCs structures. Stable dispersion of colloidal particles inside UV-curable system induced by hydrogen bonding and suction force induced by continuous curing manner cooperatively realize the simultaneous macroscopic printing and microscopic particle assembly, which endows volumetric color property. Structural color can be well regulated by controlling the particle diameter and printing speed, through which various complex 3D structures with desired structural color distribution and optical light-guide properties are acquired. This 3D color construction approach shows great potential in customized jewelry accessories, decoration and optical device preparation, and will innovate the development of structural color.

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