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1.
Br J Clin Pharmacol ; 90(6): 1493-1502, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38500445

RESUMO

AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.


Assuntos
Interferon alfa-2 , Interferon-alfa , Janus Quinase 2 , Policitemia Vera , Polietilenoglicóis , Proteínas Recombinantes , Humanos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/administração & dosagem , Interferon alfa-2/administração & dosagem , Interferon alfa-2/efeitos adversos , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Masculino , Feminino , Pessoa de Meia-Idade , Janus Quinase 2/genética , Resultado do Tratamento , Relação Dose-Resposta a Droga , Idoso , Adulto
2.
Mar Drugs ; 22(1)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38248665

RESUMO

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier.


Assuntos
Quitosana , Neoplasias Pulmonares , Polietilenoglicóis , Polietilenoimina , Polifosfatos , Humanos , Animais , Camundongos , Nanogéis , Antioxidantes/farmacologia , Cloreto de Amônio , Benzimidazóis , Doxorrubicina/farmacologia , Compostos de Amônio Quaternário/farmacologia
3.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753480

RESUMO

Through dominant mutations, aminoacyl-tRNA synthetases constitute the largest protein family linked to Charcot-Marie-Tooth disease (CMT). An example is CMT subtype 2N (CMT2N), caused by individual mutations spread out in AlaRS, including three in the aminoacylation domain, thereby suggesting a role for a tRNA-charging defect. However, here we found that two are aminoacylation defective but that the most widely distributed R329H is normal as a purified protein in vitro and in unfractionated patient cell samples. Remarkably, in contrast to wild-type (WT) AlaRS, all three mutant proteins gained the ability to interact with neuropilin 1 (Nrp1), the receptor previously linked to CMT pathogenesis in GlyRS. The aberrant AlaRS-Nrp1 interaction is further confirmed in patient samples carrying the R329H mutation. However, CMT2N mutations outside the aminoacylation domain do not induce the Nrp1 interaction. Detailed biochemical and biophysical investigations, including X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange (HDX), switchSENSE hydrodynamic diameter determinations, and protease digestions reveal a mutation-induced structural loosening of the aminoacylation domain that correlates with the Nrp1 interaction. The b1b2 domains of Nrp1 are responsible for the interaction with R329H AlaRS. The results suggest Nrp1 is more broadly associated with CMT-associated members of the tRNA synthetase family. Moreover, we revealed a distinct structural loosening effect induced by a mutation in the editing domain and a lack of conformational impact with C-Ala domain mutations, indicating mutations in the same protein may cause neuropathy through different mechanisms. Our results show that, as with other CMT-associated tRNA synthetases, aminoacylation per se is not relevant to the pathology.


Assuntos
Alanina-tRNA Ligase/metabolismo , Doença de Charcot-Marie-Tooth/genética , Neuropilina-1/metabolismo , Alanina-tRNA Ligase/química , Alanina-tRNA Ligase/genética , Aminoacilação/genética , Células Cultivadas , Doença de Charcot-Marie-Tooth/sangue , Cristalografia por Raios X , Medição da Troca de Deutério , Humanos , Linfócitos , Mutação , Neuropilina-1/genética , Cultura Primária de Células , Ligação Proteica/genética , Domínios Proteicos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura , Espalhamento a Baixo Ângulo
4.
J Craniofac Surg ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847541

RESUMO

The paper presented the treatment procedure of a 2-year-old patient with unrepaired bilateral cleft lip and palate (BCLP). Complicated situation included severely protruded premaxilla and constricted upper dental arch, possibly related to delayed treatment of cleft lip and palate. Orthodontic expansion lasted for 8 months, including using fan-type expander for 3 months. After that, premaxillary osteotomy was performed to reset the premaxilla, and 4 months later, simultaneous repair of cleft lip and palate was taken. Follow-up evaluation in 5.5 years revealed acceptable language development and craniofacial profile, and maxillary growth was satisfactory. The treatment procedure of this patient provided an exploratory protocol for those patients with unrepaired BCLP who suffered from deteriorated preaxillary protrusion and constricted upper arch.

5.
Biomacromolecules ; 24(11): 4831-4842, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37677087

RESUMO

A diabetic foot ulcer is a common high-risk complication in diabetic patients, but there is still no universal dressing for clinical treatment. In this study, a novel dual-functional sulfated galactofucan polysaccharide/poly(vinyl alcohol) hydrogel (DPH20) is developed during freeze-thaw cycles. Experimental results indicated that DPH20 had a high specific surface area, a dense porous structure, and a good swelling property, which could effectively adsorb the exudates and keep the wound moist. Furthermore, DPH20 exhibited remarkably recruited macrophage capability and accelerated the inflammation stage by improving the expression of the mRNA of CCL2, CCR2, and CCL22 in macrophages. DPH20 could promote cell migration and growth factor release to accelerate tube formation under hyperglycemic conditions in cell models of L929s and HUEVCs, respectively. Significantly, DPH20 accelerates the reconstruction of the full-thickness skin wound by accelerating the recruitment of macrophages, promoting angiogenesis, and releasing the growth factor in the diabetic mouse model. Collectively, DPH20 is a promising multifunctional dressing to reshape the damaged tissue environment and accelerate wound healing. This study provides an efficient strategy to repair and regenerate diabetic skin ulcers.


Assuntos
Diabetes Mellitus , Hidrogéis , Camundongos , Animais , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Cicatrização , Álcool de Polivinil/farmacologia , Álcool de Polivinil/química , Macrófagos , Peptídeos e Proteínas de Sinalização Intercelular
6.
Anal Bioanal Chem ; 415(18): 4245-4254, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36102972

RESUMO

Chiral recognition is an emerging field of modern chemical analysis, and the development of health-related fields depends on the production of enantiomers. Cellulose is a kind of natural polymer material with certain chiral recognition ability. Limited by the chiral recognition ability of natural cellulose itself, more cellulose derivatives have been gradually developed for chiral recognition and separation. Based on the difference in action between cellulose derivatives and enantiomers, this work synthesized cellulose-tris(4-methylphenylcarbamate) (CMPC) chiral recognition mediators and a CMPC-functionalized extended-gate organic field effect transistor (EG-OFET) was constructed for the first time. Three chiral molecules were selected as model analytes to evaluate the enantiomeric recognition ability of the platform, including threonine (Thr), 2-chloromandelic acid (CA), and 1,2-diphenylethylenediamine (DPEA). The detection limit for 1,2-diphenylethylenediamine (DPEA) is down to 10-13 M. Through the amplification effect of the EG-OFET platform, the difference in the interaction between CMPC and three chiral molecules with different structures is converted into a current signal output. At the same time, the enantiomer discrimination mechanism of CMPC was further studied by means of spectroscopy and nuclear magnetic resonance.


Assuntos
Celulose , Etilenodiaminas , Celulose/química , Polímeros , Estereoisomerismo
7.
Retina ; 43(5): 860-863, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32604345

RESUMO

PURPOSE: To evaluate a novel surgical technique for transscleral fixation of the intraocular lens (IOL) with four hollow haptics using 8-0 polypropylene suture looping and overhand knot. METHODS: An 8-0 polypropylene suture was tied to a 10-0 polypropylene suture with an overhand knot. One set of 8-0 polypropylene suture was then passed through the IOL four haptics. The suture knot was buried by rotating into the sclera tunnel. Best-corrected visual acuity, intraocular pressure, and complications were determined. RESULTS: The IOLs were fixed with using an 8-0 polypropylene suture in 13 eyes of 11 patients with aphakia and dislocated crystalline lens. The mean preoperative corrected distance visual acuity was 0.71 ± 0.58 logarithm of the minimum angle of resolution (Snellen 20/103), and it improved to 0.24 ± 0.25 logarithm of the minimum angle of resolution (Snellen 20/35) at the final follow-up ( P < 0.05). No vitreous hemorrhage, hypotony, suture exposed, and pupillary capture of the IOL were observed in any of the patients. CONCLUSION: The authors have developed a new technique for transscleral IOL fixation with one set of an 8-0 polypropylene suture tied to a 10-0 polypropylene suture with an overhand knot. The overhand knot offers the opportunity to use an 8-0 polypropylene suture for the long-term safety and may not require the surgeon to learn any new technique.


Assuntos
Lentes Intraoculares , Esclera , Humanos , Esclera/cirurgia , Polipropilenos , Implante de Lente Intraocular/métodos , Suturas , Técnicas de Sutura , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
8.
Retina ; 43(12): 2059-2063, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35982505

RESUMO

PURPOSE: To report the results of a novel surgical four-point transscleral suture fixation of intraocular lens (IOL) with four hollow haptics using the double-suture technique. METHODS: We retrospectively reviewed the medical records of 15 eyes of 15 patients who underwent 4-point transscleral suture fixation of a foldable IOL using the double-suture technique. Preoperative data and follow-up data for at least 4 months were collected for all patients. RESULTS: The IOLs were fixed and centered well. The mean preoperative corrected distance visual acuity was 0.70 ± 0.54 logarithm of the minimum angle of resolution (Snellen 20/102), and it improved to 0.29 ± 0.26 logarithm of the minimum angle of resolution (Snellen 20/39) at the final follow-up ( P = 0.001). No vitreous hemorrhage, hypotony, suture breakage, retinal detachment, IOL dislocation, and iris capture was detected during the follow-up period in any of the patients. CONCLUSION: We have developed a novel technique for 4-point transscleral suture fixation of IOL using the double-suture technique with 9-0 polypropylene suture. This technique seemed to be safe and it may not require the surgeon to learn any new technique.


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/métodos , Polipropilenos , Estudos Retrospectivos , Esclera/cirurgia , Técnicas de Sutura , Suturas
9.
Retina ; 43(11): 2003-2009, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490780

RESUMO

PURPOSE: To explore clinical efficacy of vitrectomy combined with intravitreal antibiotics in treating severe endophthalmitis after open-globe trauma in patients. METHODS: The records of all patients who received vitrectomy combined with intravitreal for the severe post-traumatic endophthalmitis with light perception or worse between 2010 and 2022 were retrospectively reviewed. Patients received vitrectomy combined with intravitreal antibiotics, repeated intravitreal antibiotics with or without vitreous aspiration, and retinal repair after the infection was controlled. Efficacy of severe post-traumatic endophthalmitis was analyzed. RESULTS: One hundred and twenty-one patients (121 eyes) were included in this study. The mean BCVA improved from 4.03 ± 0.18 logarithm of the minimum angle of resolution to 1.75 ± 1.41 logarithm of the minimum angle of resolution ( P < 0.001) at the end of the follow-up period, which increased in 106 eyes (87.60%). Infection was successfully controlled in all eyes, 88 eyes within two operations. Pathogens including streptococci (odds ratio [OR] = 6.68, P < 0.001), fungi (OR = 15.23, P < 0.001), and mixed infection (OR = 6.67, P < 0.05) were related to the number of operations. Finally, 60 eyes (49.59%) received silicone oil filling, 25 received gas tamponade, and the remaining 36 received no tamponade; complete vitrectomy was performed in all eyes with intraocular tamponade. All eyes for gas tamponade and no tamponade had been remained stable without retinal detachment and proliferative vitreoretinopathy after 6-month follow-up. The rate of recurrent retinal detachment after silicone oil tamponade was 4.96% (six eyes), including 1.65% (two eyes) of proliferative vitreoretinopathy; these eyes underwent reoperation of retinal detachment repair. CONCLUSION: Vitrectomy combined with intravitreal antibiotics may be an effective treatment option for severe post-traumatic endophthalmitis.


Assuntos
Endoftalmite , Descolamento Retiniano , Vitreorretinopatia Proliferativa , Humanos , Vitrectomia , Descolamento Retiniano/cirurgia , Vitreorretinopatia Proliferativa/cirurgia , Óleos de Silicone , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Acuidade Visual , Endoftalmite/diagnóstico , Endoftalmite/etiologia , Endoftalmite/cirurgia , Resultado do Tratamento
10.
Ecotoxicol Environ Saf ; 253: 114674, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36827899

RESUMO

Excessive fluoride exposure can cause liver injury, but the specific mechanisms need further investigation. We aimed to explore the role of impaired lysosomal biogenesis and defective autophagy in fluoride-induced hepatotoxicity and its potential mechanisms, focusing on the role of transcription factor E3 (TFE3) in regulating hepatocyte lysosomal biogenesis. To this end, we established a Sprague-Dawley (SD) rat model exposed to sodium fluoride (NaF) and a rat liver cell line (BRL3A) model exposed to NaF. The results showed that NaF exposure diminished liver function and led to apoptosis as well as autophagosome accumulation and impaired autophagic degradation. In addition, NaF exposure caused compromised lysosome biogenesis and decreased lysosomal degradation, and inhibited TFE3 nuclear translocation. Notably, the mTOR inhibitors rapamycin (RAPA) and Ad-TFE3 promoted lysosomal biogenesis and enhanced lysosomal degradation function. Furthermore, RAPA and Ad-TFE3 reduced NaF-induced apoptosis by alleviating impaired autophagic degradation. In conclusion, NaF impairs lysosomal biogenesis by inhibiting TFE3 nuclear translocation, decreasing lysosomal degradation function, resulting in impaired autophagic degradation, and ultimately inducing apoptosis. Therefore, TFE3 may be a promising therapeutic target for fluoride-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fluoretos , Ratos , Animais , Fluoretos/toxicidade , Fluoretos/metabolismo , Ratos Sprague-Dawley , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Autofagia , Fluoreto de Sódio/toxicidade , Lisossomos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
11.
Ecotoxicol Environ Saf ; 250: 114490, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36628887

RESUMO

Fluoride can induce hepatotoxicity, but the mechanisms responsible are yet to be investigated. This study sought to investigate the role and mechanism of mitochondrial reactive oxygen species (mtROS), autophagy, and ferroptosis in fluoride-induced hepatic injury with a focus on the role of mtROS-mediated cross-talk between autophagy and ferroptosis. To this end, an in vivo Sprague-Dawley rat model and in vitro BRL3A cells were exposed to sodium fluoride (NaF). The results revealed that NaF exposure diminished the mitochondrial membrane potential, increased mtROS production and TOMM20 expression, and induced autophagic flux blockage and ferroptosis in vivo and in vitro. Furthermore, the autophagy activator (RAPA) enhanced GPX4 expression while inhibiting ACSL4 expression, reduced the accumulation of ferrous ions in BRL3A cells, and restored lipid peroxidation levels, thus inhibiting ferroptosis. Fer-1, a ferritinase inhibitor, downregulated the expression of LC3-II and p62, increased the number of autolysosomes while decreasing the number of autophagosomes, and alleviated the blockage of autophagic flux by improving autophagic degradation. These results suggest the occurrence of a cross-talk between autophagy and ferroptosis. The mtROS inhibitor (Mito-TEMPO) could alleviate autophagic flux blockage and inhibit ferroptosis in NaF-induced liver injury. In addition, the cross-talk between NaF-induced autophagy and ferroptosis was dependent on the mtROS pathway.


Assuntos
Ferroptose , Ratos , Animais , Fluoretos/toxicidade , Ratos Sprague-Dawley , Autofagia , Fluoreto de Sódio , Fígado
12.
Ecotoxicol Environ Saf ; 250: 114511, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608573

RESUMO

Fluoride is capable of inducing developmental neurotoxicity; regrettably, the mechanism is obscure. We aimed to probe the role of lysosomal biogenesis disorder in developmental fluoride neurotoxicity-specifically, the regulating effect of the transient receptor potential mucolipin 1 (TRPML1)/transcription factor EB (TFEB) signaling pathway on lysosomal biogenesis. Sprague-Dawley rats were given fluoridated water freely, during pregnancy to the parental rats to 2 months after delivery to the offspring. In addition, neuroblastoma SH-SY5Y cells were treated with sodium fluoride (NaF), with or without mucolipin synthetic agonist 1 (ML-SA1) or adenovirus TFEB (Ad-TFEB) intervention. Our findings revealed that NaF impaired learning and memory as well as memory retention capacities in rat offspring, induced lysosomal biogenesis disorder, and decreased lysosomal degradation capacity, autophagosome accumulation, autophagic flux blockade, apoptosis, and pyroptosis. These changes were evidenced by the decreased expression of TRPML1, nuclear TFEB, LAMP2, CTSB, and CTSD, as well as increased expression of LC3-II, p62, cleaved PARP, NLRP3, Caspase1, and IL-1ß. Furthermore, TRPML1 activation and TFEB overexpression both restored TFEB nuclear protein expression and promoted lysosomal biogenesis while enhancing lysosomal degradation capacity, recovering autophagic flux, and attenuating NaF-induced apoptosis and pyroptosis. Taken together, these results show that NaF promotes the progression of developmental fluoride neurotoxicity by inhibiting TRPML1/TFEB expression and impeding lysosomal biogenesis. Notably, the activation of TRPML1/TFEB alleviated NaF-induced developmental neurotoxicity. Therefore, TRPML1/TFEB may be promising markers of developmental fluoride neurotoxicity.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Fluoretos , Neuroblastoma , Síndromes Neurotóxicas , Canais de Potencial de Receptor Transitório , Animais , Humanos , Ratos , Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fluoretos/toxicidade , Lisossomos , Neuroblastoma/metabolismo , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Ratos Sprague-Dawley , Fluoreto de Sódio/toxicidade , Canais de Potencial de Receptor Transitório/metabolismo
13.
Ecotoxicol Environ Saf ; 255: 114772, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36924562

RESUMO

Chronic fluoride exposure can cause developmental neurotoxicity, however the precise mechanisms remain unclear. To explore the mechanism of mitophagy in fluoride-induced developmental neurotoxicity, specifically focusing on PRKAA1 in regulating the PINK1/Parkin pathway, we established a Sprage Dawley rat model with continuous sodium fluoride (NaF) exposure and an NaF-treated SH-SY5Y cell model. We found that NaF exposure increased the levels of LC3-Ⅱ and p62, impaired autophagic degradation, and subsequently blocked autophagic flux. Additionally, NaF exposure increased the expression of PINK1, Parkin, TOMM-20, and Cyt C and cleaved PARP in vivo and in vitro, indicating NaF promotes mitophagy and neuronal apoptosis. Meanwhile, phosphoproteomics and western blot analysis showed that NaF treatment enhanced PRKAA1 phosphorylation. Remarkably, the application of both 3-methyladenosine (3-MA; autophagy inhibitor) and dorsomorphin (DM; AMPK inhibitor) suppressed NaF-induced neuronal apoptosis by restoring aberrant mitophagy. In addition, 3-MA attenuated an increase in p62 protein levels and NaF-induced autophagic degradation. Collectively, our findings indicated that NaF causes aberrant mitophagy via PRKAA1 in a PINK1/Parkin-dependent manner, which triggers neuronal apoptosis. Thus, regulating PRKAA1-activated PINK1/Parkin-dependent mitophagy may be a potential treatment for NaF-induced developmental neurotoxicity.


Assuntos
Neuroblastoma , Síndromes Neurotóxicas , Ratos , Humanos , Animais , Mitofagia/fisiologia , Fluoretos/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Mitocôndrias/metabolismo , Neuroblastoma/metabolismo , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Fluoreto de Sódio/toxicidade , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo
14.
Molecules ; 28(9)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37175356

RESUMO

Oral health is crucial to daily life, yet many people worldwide suffer from oral diseases. With the development of oral tissue engineering, there is a growing demand for dental biomaterials. Addressing oral diseases often requires a two-fold approach: fighting bacterial infections and promoting tissue growth. Hydrogels are promising tissue engineering biomaterials that show great potential for oral tissue regeneration and drug delivery. In this review, we present a classification of hydrogels commonly used in dental research, including natural and synthetic hydrogels. Furthermore, recent applications of these hydrogels in endodontic restorations, periodontal tissues, mandibular and oral soft tissue restorations, and related clinical studies are also discussed, including various antimicrobial and tissue growth promotion strategies used in the dental applications of hydrogels. While hydrogels have been increasingly studied in oral tissue engineering, there are still some challenges that need to be addressed for satisfactory clinical outcomes. This paper summarizes the current issues in the abovementioned application areas and discusses possible future developments.


Assuntos
Hidrogéis , Engenharia Tecidual , Humanos , Materiais Biocompatíveis/farmacologia , Hidrogéis/farmacologia , Periodonto
15.
BMC Oral Health ; 23(1): 607, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644424

RESUMO

BACKGROUND: Temporomandibular joint disorders (TMD) is the most common non-dental pain complaint in the maxillofacial region, which presents a variety of symptoms and signs, including temporomandibular joints (TMJ) and masticatory muscle pain, joint noise, tinnitus, headaches, irregular or restricted mandibular function, masticatory difficulty, and restricted mouth opening. When comes to the relationship between obesity and TMD, it has remained controversial and inconsistent, therefore, we first conducted this meta-analysis to estimate the unclear relationship between obesity and TMD. METHODS: Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Subjects were divided into five groups according to BMI level in this study, including the normal weight group: 18.5 ≤ BMI < 25, overweight group: 25 ≤ BMI < 30, obesity group: BMI ≥ 30, control group: BMI < 25, and overweight and obesity group: BMI ≥ 25. Statistics analyses were conducted using Stata (15.0). The number of PROSPERO was CRD42022368315. RESULTS: Eight studies were included in this study, and six articles with a total of 74,056 participants were synthesized for meta-analysis. Compared to normal weight individuals, overweight and obesity together decreased the risk of TMD (OR = 0.66, 95% CI = 0.46-0.95), and it was significantly decreased by obesity alone (OR = 0.58). Moreover, it was lower in obesity compared with control subjects (OR = 0.83, 95% CI = 0.73-0.94). Furthermore, in overweight and obese individuals, it was much lower in obesity than in overweight (OR = 0.82, 95% CI = 0.71-0.94). CONCLUSIONS: Obesity is not a risk factor for TMD, and maybe a protective factor for TMD, of which patients with larger BMI are less likely to suffer from TMD pain. Therefore, the value of BMI should be taken into consideration in the assessment of TMD.


Assuntos
Sobrepeso , Transtornos da Articulação Temporomandibular , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/epidemiologia , Fatores de Risco , Dor
16.
J Biol Inorg Chem ; 27(6): 595-603, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35976437

RESUMO

For ratiometrically imaging peroxynitrite (ONOO-) in living cells, we devised and fabricated a novel fluorescent nanoprobe, NC-NP530/460, in this study. To achieve ratiometric fluorescence response towards ONOO-, NC-NP530/460 used 3-(2-benzothiazolyl) coumarin (Cou-Bz) as the internal reference and 1,8-naphthimide derivative (Naph-PN) as a fluorescent ONOO- probe. These compounds were incorporated into an amphiphilic block polymer called Pluronic F-127. In addition to an ultrafast response to ONOO-, NC-NP530/460 also showed great selectivity and sensitive detection (detection limit was 4.51 µM). It was important to note that NC-NP530/460 demonstrated solid performance for ONOO- fluorescence ratio imaging in living cells, highlighting its potential for ONOO--related chemical biology research.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Corantes Fluorescentes/química , Imagem Óptica/métodos , Ácido Peroxinitroso/química , Polímeros
17.
Ecotoxicol Environ Saf ; 236: 113500, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35421827

RESUMO

Fluoride is capable of inducing developmental neurotoxicity, yet its mechanisms remain elusive. We aimed to explore the possible role and mechanism of autophagic flux blockage caused by abnormal lysosomal pH in fluoride-induced developmental neurotoxicity, focusing on the role of V-ATPase in regulating the neuronal lysosomal pH. Using Sprague-Dawley rats exposed to sodium fluoride (NaF) from gestation through delivery until the neonatal offspring reached six months of age as an in vivo model. The results showed that NaF impaired the cognitive abilities of the offspring rats. In addition, NaF reduced V-ATPase expression, diminished lysosomal degradation capacity and blocked autophagic flux, and increased apoptosis in the hippocampus of offspring. Consistently, these results were validated in SH-SY5Y cells incubated with NaF. Moreover, NaF increased the SH-SY5Y lysosomal pH. Mechanistically, V-ATPase B2 overexpression and ATP effectively restored V-ATPase expression, reducing NaF-induced lysosomal alkalinization while increasing lysosomal degradation capacity. Notably, those above pharmacological and molecular interventions diminished NaF-induced apoptosis by restoring autophagic flux. Collectively, the present findings suggested that NaF impairs the lysosomal pH raised by V-ATPase. This leads to reduced lysosomal degradation capacity and triggers autophagic flux blockage and apoptosis, thus contributing to neuronal death. Therefore, V-ATPase might be a promising indicator of developmental fluoride neurotoxicity.


Assuntos
Fluoretos , Síndromes Neurotóxicas , Adenosina Trifosfatases/metabolismo , Animais , Autofagia , Fluoretos/metabolismo , Concentração de Íons de Hidrogênio , Lisossomos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Ratos , Ratos Sprague-Dawley , Fluoreto de Sódio/toxicidade
18.
Molecules ; 27(14)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35889287

RESUMO

As the most advanced aerogel material, silica aerogel has had transformative industrial impacts. However, the use of silica aerogel is currently limited to the field of thermal insulation materials, so it is urgent to expand its application into other fields. In this work, silica aerogel/resin composites were successfully prepared by combining silica aerogel with a resin matrix for dental restoration. The applications of this material in the field of dental restoration, as well as its performance, are discussed in depth. It was demonstrated that, when the ratio of the resin matrix Bis-GMA to TEGDMA was 1:1, and the content of silica aerogel with 50 µm particle size was 12.5%, the composite achieved excellent mechanical properties. The flexural strength of the silica aerogel/resin composite reached 62.9546 MPa, which was more than five times that of the pure resin. Due to the presence of the silica aerogel, the composite also demonstrated outstanding antibacterial capabilities, meeting the demand for antimicrobial properties in dental materials. This work successfully investigated the prospect of using commercially available silica aerogels in dental restorative materials; we provide an easy method for using silica aerogels as dental restorative materials, as well as a reference for their application in the field of biomedical materials.


Assuntos
Resinas Compostas , Dióxido de Silício , Bis-Fenol A-Glicidil Metacrilato , Teste de Materiais , Tamanho da Partícula
19.
Molecules ; 27(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36235046

RESUMO

In this study, a green, highly efficient and low energy consumption preparation method of cellulose nanofiber (CNF) was developed by using agricultural and forestry waste durian rinds as raw materials. The power of ultrasonic treatment was successfully reduced to only 360 W with low molecular weight liquid DMSO. The obtained durian rind-based CNF had a diameter of 8-20 nm and a length of several micrometers. It had good dispersion and stability in water, and could spontaneously cross-link to form hydrogel at room temperature when the concentration was more than 0.5%. The microscopic morphology and compressive properties of CNF aerogels and composite cellulose aerogels prepared from durian rind-based CNF were evaluated. It was found that CNF could effectively prevent the volume shrinkage of aerogel, and the concentration of CNF had a significant effect on the microstructure and mechanical properties of aerogel. The CNF aerogel with 1% CNF exhibited a sheet structure braced by fibers, which had the strongest compression performance. The porosity of CNF aerogels was high to 99%. The compressive strength of the composite cellulose aerogel with durian rind-based CNF was effectively enhanced.


Assuntos
Bombacaceae , Nanofibras , Celulose/química , Dimetil Sulfóxido , Hidrogéis , Nanofibras/química , Água
20.
J Nanobiotechnology ; 19(1): 142, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001148

RESUMO

BACKGROUND: Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. RESULTS: HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. CONCLUSION: Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.


Assuntos
Vacinas Anticâncer/uso terapêutico , Tratamento Farmacológico/métodos , Imunidade/efeitos dos fármacos , Imunidade/efeitos da radiação , Terapia Fototérmica/métodos , Doxorrubicina/administração & dosagem , Ácido Hialurônico , Hidrogéis , Indóis/química , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Polímeros/administração & dosagem , Polímeros/química
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