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1.
J Hazard Mater ; 423(Pt A): 127104, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523482

RESUMO

Soils contamination with Cd result in detriment to the environmental quality. In-situ immobilization methods by applying clay minerals have been gaining prominence. The effects on sepiolite of thermal activation at different temperatures (300-750 °C), for removing Cd from aqueous solutions were evaluated, in order to consider their further application for soil remediation. The influence of activation temperature was investigated using XRD, SEM, and N2 adsorption-desorption measurements. The S-600 exhibited the maximum adsorption capacity (21.28 mg/g), despite its lower SSA, and Langmuir model described the adsorption isotherms better than the Freundlich equation. TCLP was used to quantify the remediation effects of thermal-activated sepiolite on simulated soils artificially polluted with Cd. The results indicated that the mobility of Cd in soil was effectively reduced after treating with thermal-activated sepiolite and the use of S-600 was the most efficient, reducing the TCLP-Cd by approximately 73% compared with the control test. The main remediation mechanism was considered as the cation exchange of Cd by Mg at the edges of octahedral sheet. This study showed that thermal-activated sepiolite could be promising amendments for remediation of Cd-contaminated soil.

2.
Adv Healthc Mater ; : e2101056, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34569175

RESUMO

Two-photon photodynamic therapy (2P-PDT) that employs photosensitizers (PSs) with 2P absorption is particularly intriguing in cancer treatment, in that 2P excitation enables precise spatial localization and deep tissue penetration. Here, a donor-π-acceptor PS (named TPBPy) with near infrared (NIR) aggregation-induced emission (AIE) is designed and synthesized for imaging-guided 2P-PDT. The maximal photoluminescence (PL) peak of TPBPy is as high as 720 nm when it is encapsulated in liposomes. Upon 2P irradiation by a laser in NIR-II window (λ = 1000 nm), TPBPy exhibits strong NIR-I PL in a multicellular tumor spheroids (MCTSs) model, showing an imaging depth of 210 µm that is significantly higher than upon one-photon irradiation. Moreover, TPBPy localizes specifically on mitochondrion, an important organelle in cell oxidative metabolism and apoptosis. When exposed to the NIR-II irradiation, TPBPy can efficiently generate singlet oxygen (1 O2 ) and trigger cell death. The efficacy of TPBPy-mediated 2P-PDT has also been validated using 4T1 tumor mouse model, the growth of which is significantly suppressed upon NIR-II laser irradiation. TPBPy herein serves as an excellent candidate to suppress deep tumor tissues through NIR-II 2P-PDT, and also renders a new paradigm to construct mitochondrion-anchored AIE luminogens for future cancer theranostic applications.

3.
J Sex Med ; 18(9): 1500-1510, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34348883

RESUMO

BACKGROUND: The correlation between long-term treatment outcomes with genotypes in congenital hypogonadotropic hypogonadism (CHH) males is rarely reported. AIM: To investigate the correlations among genotypes, phenotypes, and treatment outcomes for CHH male patients. METHODS: Whole exome sequencing was performed for 73 Chinese CHH males from one academic center. Patients self-selected one of the 4 treatments: pulsatile Gonadorelin pump (PGP), cyclical gonadotropins therapy (CGT), human menopausal gonadotropin monotherapy, or testosterone replacement treatment. Clinical assessments were performed every 3 months for 3 years. OUTCOMES: The pathogenicity of variants was determined. Baseline clinical features, spermatogenesis outcomes were analysed. RESULTS: 62 variants were identified in 51 patients (69.9%), 17 of which were novel. Among these mutations, variants on FGFR1, PROKR2, CHD7, ANOS1 and NSMF gene were 16.1%, 16.1%, 11.3%, 8.1% and 8.1% respectively. 11 patients followed the oligogenic pattern (21.6%). All CHD7 patients had hearing impairment or structural deformities of external/inner ear, and were diagnosed as CHARGE syndrome. 24.7% of CHH patients manifested with ear/hearing anomalies. KS patients had higher rates of cryptorchidism history and ear/hearing anomalies than normosmic CHH subjects. Male patients with PROKR2 mutations showed relatively better testicular development, less dental deformity when compared with FGFR1 mutations. About 30% normosmic patients defined by simple olfactory assessment showed olfactory nerve center (ONC) dysplasia under nasal sinus MRI examination. Among the CHH males treated with CGT or PGP, 70.2% reached spermatogenesis within 3 years of treatment. CLINICAL IMPLICATIONS: No direct correlation was observed between certain responsible genes and spermatogenic outcomes. When CHH patients were identified with CHD7 variants, ear/hearing evaluation should be carefully performed. The precise assessment of ONC development was advised for normosmic CHH subjects. STRENGTHS & LIMITATIONS: This study provided informative long-term treatment data of CHH male patients screened with whole exome sequencing. The limitations included small number of subgroups with multifaceted gene variants, clinical heterogeneity, and uncontrolled sperm-inducing treatment method. The seventeen novel mutations worth experimental validation in the future. CONCLUSION: The clinical severity is partially related with specific gene variants, and detailed individualized data and outcomes were provided. Ear/hearing anomalies were closely connected with CHD7 variants, and were common problems for CHH patients. Simple olfactory assessment underestimated the true olfactory deficit. L. Zhang, Y. Gao, Q. Du, et al. Genetic Profiles and Three-year Follow-up Study of Chinese Males With Congenital Hypogonadotropic Hypogonadism. J Sex Med 2021;18:1500-1510.


Assuntos
Perfil Genético , Hipogonadismo , China , Seguimentos , Humanos , Hipogonadismo/genética , Masculino , Mutação
4.
Expert Opin Drug Discov ; : 1-15, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34455870

RESUMO

INTRODUCTION: Undruggable targets refer to clinically meaningful therapeutic targets that are 'difficult to drug' or 'yet to be drugged' via traditional approaches. Featuring characteristics of lacking defined ligand-binding pockets, non-catalytic protein-protein interaction functional modes and less-investigated 3D structures, these undruggable targets have been targeted with novel therapeutic entities developed with the progress of unconventional drug discovery approaches, such as targeted degradation molecules and display technologies. AREA COVERED: This review first presents the concept of 'undruggable' exemplified by RAS and other targets. Next, detailed strategies are illustrated in two aspects: innovation of therapeutic entities and development of unconventional drug discovery technologies. Finally, case studies covering typical undruggable targets (Bcl-2, p53, and RAS) are depicted to further demonstrate the feasibility of the strategies and entities above. EXPERT OPINION: Targeting the undruggable expands the scope of therapeutically reachable targets. Consequently, it represents the drug discovery frontier. Biomedical studies are capable of dissecting disease mechanisms, thus broadening the list of undruggable targets. Encouraged by the recent approval of the KRAS inhibitor Sotorasib, we believe that merging multiple discovery approaches and exploiting various novel therapeutic entities would pave the way for dealing with more 'undruggable' targets in the future.

5.
J Hazard Mater ; 421: 126707, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34315018

RESUMO

Triclosan (TCS) is an antimicrobial ingredient that has been widely incorporated in consumer products. TCS can cause hepatic damage by disturbing lipid metabolism, which is often accompanied with gut microbiota dysbiosis. However, the effects of gut microbiota on the TCS-induced liver injury are still unknown. Therefore, we constructed a mouse model based on five-week-old male C57BL/6 mice to investigate the effects of dietary TCS exposure (40 ppm) on liver injury. We found that TCS treatment for 4 weeks dramatically disturbed gut microbiota homeostasis, resulting in overproduction of lipopolysaccharides (LPS) and deficiency of secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA). In addition, TCS considerably increased intestinal permeability by reducing mucus excretion and expression of tight junction proteins (ZO-1, occludin and claudin 4), which facilitated translocation of LPS. The LPS accumulation in blood contributed to liver injury by triggering the inflammatory response via TLR4 pathway. In summary, this study provides novel insights into the underlying mechanisms of TCS-associated liver injury induced by gut microbiota via the gut-liver axis, and contributes to better interpretation of the health impact of the environmentally emerging contaminant TCS.

6.
J Am Chem Soc ; 143(27): 10054-10058, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34181390

RESUMO

The rapid development of digital society and artificial intelligence has triggered explosive demands for specialty plastics, especially conjugated polymers that are instrumental for flexible electronics and smart devices. The recycling and degradation of postconsumer conjugated polymers have become more important than ever to reduce the pressure to the environment. Here we report the discovery of an environmentally self-degradable conjugated polymer poly(deca-4,6-diynedioic acid), or PDDA. PDDA is stable in the dark or without oxygen when used as a functional material. However, when exposed to sunlight and air after the service life, PDDA disintegrates rapidly and fully decomposes through photooxidation in a week, yielding biocompatible, value-added succinic acid as a major degradation product. The complete degradation of PDDA into green upcycling products by sunlight in air, without leaving any microplastics, not only renders a pioneering paradigm of environmentally self-degradable conjugated polymers but also inspires developing effective strategies to completely degrade postconsumer conjugated polymers in a natural environment.

7.
Biomed Res Int ; 2021: 8814843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954199

RESUMO

Objective: This study is aimed at exploring the regulatory mechanism of 73HOXC-AS1 overexpression plasmid-activated Wntß-catenin classic signaling pathway and eukaryotic initiation factor 4A (eIF4AIII) expression increased by lentivirus-eIF4AIII-RNAi (44682-1) (LV-eIF4AIII-RNAi (44682-1)). Methods: Focusing on the occurrence and progression of gastric cancer, the human gastric cancer cell line BGC823 (University Experimental Center) was taken as the research object and was transfected after subculture. According to the different ways of transfection, the cells were divided into the P1 group (LV-eIF4AIII-RNAi (44682-1) overexpressed plasmid), the P2 group (pcDNA-HOXC-AS1 overexpressed plasmid), the P3 group (LV-eIF4AIII-RNAi (44682-1) + pcDNA-HOXC-AS1), and the P4 group (no transfection, control group). Cell proliferation was detected by CCK-8 (Cell Counting Kit-8) assay, Western blotting was adopted to detect Wnt3a and P-GSK3ß proteins, Transwell assay was adopted to detect the ability of cell migration and invasion, and cell cycle and apoptosis were detected by flow cytometry. Results: The results show that the protein expression levels of Wnt3a and P-GSK3ß (glycogen synthase kinase-3ß) in the P1 and P4 groups were lower than those in the P2 and P3 groups (P < 0.05). The cell activity and clone number of BGC823 in the P3 group were higher than those in the P1, P2, and P4 groups (P < 0.05). The apoptosis rate of BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups (P < 0.05). The proportion of BGC823 cells in the P3 group at the S phase was significantly higher than those in the P1, P2, and P4 groups, while the proportion in the G2 phase was significantly lower than those in the P1, P2, and P4 groups (P < 0.05). The number of migrating and invading BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups, while the number of migrating BGC823 cells in the P4 group was significantly lower than those in the P1 and P2 groups (P < 0.05). Conclusion: The 73HOXC-AS1 overexpression plasmid-activated Wntß-catenin classic signaling pathway and eIF4AIII expression increased by LV-eIF4AIII-RNAi (44682-1) could act together on BGC823 cells to improve cell proliferation activity, migration, and invasion; inhibit cell apoptosis; and prevent cells from entering the S phase.


Assuntos
Progressão da Doença , Fator de Iniciação 4A em Eucariotos/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Células Clonais , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Invasividade Neoplásica , Fosforilação , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética
8.
Molecules ; 26(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923350

RESUMO

In this paper, ultrasonic cellulase extraction (UCE) was applied to extract polyphenols from passion fruit. The extraction conditions for total phenol content (TPC) and antioxidant activity were optimized using response surface methodology (RSM) coupled with a Box-Behnken design (BBD). The results showed that the liquid-to-solid ratio (X2) was the most significant single factor and had a positive effect on all responses. The ANOVA analysis indicated quadratic models fitted well as TPC with R2 = 0.903, DPPH scavenging activity with R2 = 0.979, and ABTS scavenging activity with R2 = 0.981. The optimal extraction parameters of passion fruit were as follows: pH value of 5 at 30 °C for extraction temperature, 50:1 (w/v) liquid-to-solid ratio with extraction time for 47 min, the experimental values were found matched with those predicted. Infrared spectroscopy suggested that the extract contained the structure of polyphenols. Furthermore, three main polyphenols were identified and quantified by HPLC. The results showed the content of phenolic compounds and antioxidant activity of the optimized UCE were 1.5~2 times higher than that determined by the single extraction method and the Soxhlet extraction method, which indicates UCE is a competitive and effective extraction technique for natural passion fruit polyphenols.


Assuntos
Antioxidantes/isolamento & purificação , Passiflora/química , Extratos Vegetais/química , Polifenóis/isolamento & purificação , Antioxidantes/química , Celulase/química , Cromatografia Líquida de Alta Pressão , Polifenóis/química , Ultrassom
9.
Cancer Biol Med ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33861527

RESUMO

Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest, and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy. Nanoparticles are ideal candidates as carriers for theranostic agents, which is attributed to their extraordinary physicochemical properties, including nanoscale sizes, functional properties, prolonged blood circulation, active or passive tumor targeting, specific cellular uptake, and in some cases, excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time. Overall, with the development of nanotechnology, theranostics has become a reality, and is now in the transition stage of "bench to bedside." In this review, we summarize recent progress on nanotechnology-based theranostics, i.e., nanotheranostics, that has greatly assisted traditional therapies, and has provided therapeutic strategies emerging in recent decades, as well as "cocktail" theranostics mixing various treatment modalities.

10.
Arthritis Res Ther ; 23(1): 97, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785060

RESUMO

BACKGROUND: To investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD). METHODS: Fifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. RESULTS: High 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. CONCLUSIONS: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.


Assuntos
Síndrome de Ativação Macrofágica , Doença de Still de Início Tardio , Adulto , Fluordesoxiglucose F18 , Humanos , Linfonodos/diagnóstico por imagem , Síndrome de Ativação Macrofágica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Doença de Still de Início Tardio/diagnóstico por imagem
11.
ACS Appl Mater Interfaces ; 13(13): 14911-14919, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33764749

RESUMO

Photosensitizers that can generate reactive oxygen species (ROS) upon irradiation have emerged as promising agents for photodynamic degradation of toxic amyloid aggregates that are linked to many amyloidogenic diseases. However, due to the ultrastable ß-sheet structure in amyloid aggregates and inefficient utilization of the generated ROS, it usually requires high stoichiometric concentration of the photosensitizer and/or intensive light irradiation to fully dissociate aggregates. In this work, we have developed a "bait-hook-devastate" strategy to boost the efficiency of the photodynamic degradation of amyloid aggregates. This strategy employs anionic polyacrylic acid as a bait to accumulate cationic human islet amyloid polypeptide (IAPP) aggregates and positively charged photosensitizer TPCI in a confined area through electronic interactions. Multiple characterization studies proved that the utilization rate of ROS generated by TPCI was remarkably improved via this strategy, which amplified the ability of TPCI to dissociate IAPP aggregates. Rapid and complete degradation of IAPP aggregates could be achieved by irradiating the system under very mild conditions for less than 30 min, and the IAPP-mediated cytotoxicity was also largely alleviated, providing a new paradigm to accelerate photodynamic degradation of amyloid aggregates for further practical applications.


Assuntos
Amiloide/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Proteólise/efeitos dos fármacos , Amiloide/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/ultraestrutura , Agregados Proteicos/efeitos dos fármacos , Agregados Proteicos/efeitos da radiação , Agregação Patológica de Proteínas/tratamento farmacológico , Agregação Patológica de Proteínas/metabolismo , Proteólise/efeitos da radiação , Ratos , Espécies Reativas de Oxigênio/metabolismo
12.
Chem Commun (Camb) ; 57(28): 3504-3507, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33690761

RESUMO

A metal-free 2-selenylation of tryptophan derivatives is reported, where the use of iodide as the catalyst and oxone as the oxidant is key to obtain high yields. Various functional groups within the di-seleny and the indole ring are tolerated, and no racemization is generally observed.

13.
Endocrine ; 72(3): 633-643, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33464540

RESUMO

PURPOSE: The distinction between congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) in patients with delayed puberty is difficult to distinguish, but important for timely treatment. The aim of this study is to perform a systematic review and meta-analysis to determine the diagnostic performance of serum inhibin B (INHB) levels for differentiating CHH and CDGP. METHODS: PubMed, EMBASE, and Cochrane Library databases were systematically searched from the date of database inception to November 10, 2019 for studies examining the use of serum INHB to discriminate between CHH and CDGP. Pooled odds ratios (OR), sensitivity, specificity, and 95% confidence intervals (CI) were calculated. The Quality Assessment of Diagnostic Studies-2 (QUADAS-2) was used to assess the quality of the included studies. Sub-analyses were performed including that based on testicular volume (TV) and study design. RESULTS: Seven studies, comprising of 349 patients (96 CHH and 253 CDGP), were included in the meta-analysis. For differentiating between CHH and CDGP, INHB level exhibited good diagnostic accuracy with a pooled sensitivity of 92% (95% confidence interval [CI]: 0.86-0.96, I2 = 0.4%, p = 0.4343), specificity of 92% (95% CI: 0.88-0.94, I2 = 68.1%, p = 0.0009), and pooled area under the receiver operating characteristic curve (AUC) of 0.9619. The cut-off values of INHB for boys were 56, 66, 80, 96, 94.7, 111, and 113 pg/ml (assay method standardized to Gen II ELISA). Sub-analyses showed that testicular volume and study design could be a source of statistically significant heterogeneity in specificity. In boys with a testicular volume of ≤3 ml, INHB performed well with a sensitivity of 92%, specificity of 98%, and AUC of 0.9956. CONCLUSION: INHB exhibits excellent diagnostic efficiency in distinguishing CHH from CDGP, especially in boys with severe puberty deficiency (TV ≤ 3 ml).


Assuntos
Hipogonadismo , Puberdade Tardia , Transtornos do Crescimento , Humanos , Hipogonadismo/diagnóstico , Inibinas , Masculino , Puberdade , Puberdade Tardia/diagnóstico
14.
Acta Neurol Belg ; 121(1): 95-106, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32960423

RESUMO

Ischemic stroke is a refractory disease generally caused by cerebral ischemic injury. Remote ischemic preconditioning (RIPC) caused by transient ischemia and reperfusion of the femoral artery exerts a protective effect on ischemic stroke-induced brain injury. This study was designed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection, namely, the biological effects of microRNA-144 on RIPC in mice with ischemic stroke and its effects on PTEN and Akt signaling pathways. Healthy adult C57BL6 mice were selected for the establishment of middle cerebral artery occlusion (MCAO). One hour before the start, remote ischemic preconditioning of limbs was performed in mice. Brain edema and infarct volume were measured. The expressions of microRNA-144, PTEN, and Akt were measured. The results showed that, compared with MCAO group, the RIPC group protected mice from cerebral ischemia-reperfusion injury, systemic accumulation of inflammatory cytokines, and accelerated apoptosis of parenchymal cells. In RIPC group, PTEN expression decreased, and mir-144 and Akt expression increased. The level of phosphorylated PTEN in the transfected microRNA-144 inhibitor group increased and the level of phosphorylated Akt reduced significantly. In conclusion, our results suggest that microRNA-144 may play a protective role in remote ischemic pretreatment by downregulating PTEN and upregulating Akt, suggesting that microRNA-144 via PTEN/Akt pathway may be of therapeutic significance in ischemic stroke.

15.
J Mater Chem B ; 9(2): 404-409, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33283827

RESUMO

Montmorillonite (MMT), as a naturally sourced and FDA-approved biomaterial, has attracted considerable attention due to its extensive application in biomedical areas, such as intestinal ailments, drug delivery, and additive manufacturing. In this work, two-dimensional montmorillonite (2D-MMT) ultrathin nanosheets were successfully prepared from sodium montmorillonite (Na-MMT) by utilizing a freeze-drying assisted method. Possessing a large specific surface area and increased number of exposed hydroxyl groups, 2D-MMT nanosheets exhibited better antibacterial ability than the original Na-MMT. More strikingly, we found that both 2D-MMT nanosheets and Na-MMT could generate reactive oxygen species (ROS) upon visible light illumination, which could promote their antibacterial efficiency. As a result, 2D-MMT nanosheets showed efficient antibacterial performance in the presence of light towards Escherichia coli with a simultaneous enhancement of surface adsorption and photodynamic ablation. What's more, a possible mechanism for ROS generation by MMT upon light illumination was first proposed in this work. The combination of the increased physical adsorption capacity and ROS generation ability of 2D-MMT nanosheets would help inspire the development of MMT as a promising antimicrobial candidate in the future.


Assuntos
Antibacterianos/metabolismo , Bentonita/química , Nanotecnologia/métodos , Fotoquimioterapia/métodos , Humanos , Espécies Reativas de Oxigênio
16.
Clin Psychol Psychother ; 28(4): 882-890, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33338313

RESUMO

Embitterment and in some cases also post-traumatic embitterment disorder (PTED) are relevant problem in the general population and even more so in psychiatric patients. PTED screening should be an essential component of routine mental health management, which can be done by the 21-item Post-traumatic Embitterment Disorder Self-Rating Scale (C-PTED-21), which measures the intensity of reactive stimulus bound embitterment. The PTED-21 German version was translated into Chinese, and 200 nonpsychiatric inpatients, reporting major negative life events, were recruited through convenience sampling to evaluate test performance. Ninety patients were selected for retest 2 weeks later to examine scale reliability. Factor analysis was used to assess construct validity and receiving operating characteristic curve analysis based on the "PTED standardized diagnostic interview" to assess diagnostic utility. Correlations with depression, somatic symptom, and anxiety scales were examined to assess aggregate validity. The C-PTED-21 demonstrated high internal consistency (Cronbach's α = 0.944) and good test-retest reliability (total score r = 0.783, individual item r value range, 0.635-0.889). Factor analysis revealed three common factors consistent with PTED core features. Total C-PTED-21 score was strongly correlated with the score on the nine-item Patient Health Questionnaire depression scale (PHQ-9, r = 0.735). Mean PTED-21 score ≥1.6 points distinguished clinical PTED as defined by diagnostic interview with 97.6% sensitivity and 90.5% specificity (AUC = 0.988, 95%CI: 0.976-0.999). The results show that the C-PTED-21 can assess the severity of PTED with good reliability and validity.

17.
Chin J Integr Med ; 26(12): 905-912, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33259023

RESUMO

OBJECTIVE: To investigate the effect of Chinese herbal formula Ermiao Powder (, EMP) on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis (RA). METHODS: Seventy-two rats were randomly divided into 6 groups according to body weight, including normal control group, collageninduced arthritis (CIA) group, three doses EMP groups, and methotrexate (MTX) group (n=12 per group). All of the rats except for those in the normal control group were given multipoint subcutaneous injection of bovine type II collagen to establish a CIA model. Three EMP groups received a high- (4.5 g/kg), medium- (3.0 g/kg), and low- (1.5 g/kg) doses of EMP by intragavage, respectively. MTX group was injected intraperitoneally MTX at 0.9 mg/kg once a week as the positive control. The administration was 3 consecutive weeks. Joint swelling, arthritis index, and body weight changes in different experimental groups of rats were tested. The joint damage was evaluated by masson staining. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry (IHC) were performed to evaluate the expression of CHRNA7, encoding α7 nicotinic acetylcholine receptor in the cholinergic anti-inflammatory pathway, in different tissues and their localization in the spleen and joints. RESULTS: CHRNA7 expression levels were significantly higher in the joints and spleens of CIA group than those in normal control group (both P<0.05). Moreover, the CHRNA7 mRNA and protein levels in the spleen and joints of MTX and three doses of EMP groups were significantly lower than CIA group (all P<0.05). Compared with the MTX group, treatment with low-dose EMP resulted in significant reduction of CHRNA7 mRNA and protein expression levels (P<0.05 or P<0.01). IHC showed positive signals of CHRNA7 in the white pulp and red pulp of the spleens of rats; CHRNA7 was expressed on fibroblast-like synoviocytes, macrophages, and endothelial cells in the joints of rats, and the expression in the joints of low-dose EMP group was significantly lower than that in the CIA group (P<0.01). CONCLUSIONS: Cholinergic anti-inflammatory pathway was involved in the generation of the inflammatory reaction in CIA rats, and EMP exerted therapeutic effect on RA through cholinergic anti-inflammatory pathway.

18.
Biochem Biophys Res Commun ; 532(4): 576-583, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32900488

RESUMO

Spinal cord injury (SCI) leads to severe and long-lasting neurological disability. Presently, the lack of effective therapies for SCI is largely attributable to an incomplete understanding of its pathogenesis. F-box and WD repeat domain-containing protein 7 (FBW7, also known as FBXW7) is a type of E3 ubiquitin ligase complex, and plays essential roles in regulating different pathological and physiological processes. In this study, we attempted to explore the effects of FBW7 on SCI progression by the in vivo and in vitro experiments. SCI mice showed significantly reduced expression of FBW7 in spinal cord tissues. Promoting FBW7 expression via intrathecal injection of AAV9/FBW7 effectively improved locomotor function in SCI mice. Neuronal death in spinal cords of SCI mice was obviously ameliorated by FBW7 over-expression, along with greatly decreased expression of cleaved Caspase-3. In addition, microglial activation in spinal cord specimens was detected in SCI mice through increasing Iba-1 expression levels, which was, however, attenuated in SCI mice injected with AAV9/FBW7. Additionally, FBW7 over-expression dramatically restrained inflammatory response in spinal cord tissues of SCI mice, as evidenced by the down-regulated expression of tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) through blocking the activation of nuclear factor-κB (NF-κB) signaling. These anti-inflammatory effects of FBW7 were confirmed in LPS-stimulated mouse microglial BV2 cells. Finally, our in vitro studies showed that conditional medium (CM) collected from LPS-incubated BV2 cells markedly induced apoptosis in the isolated primary spinal neurons; However, this effect was overtly ameliorated by CM from LPS-exposed BV2 cells over-expressing FBW7. Thus, FBW7-regulated inflammation in microglial cells was involved in the amelioration of neuronal apoptosis during SCI development. Collectively, these findings illustrated that FBW7 expression was down-regulated in spinal cords of SCI mice, and promoting its expression could effectively mitigate SCI progression by repressing microglial inflammation and neuronal death.


Assuntos
Apoptose , Proteína 7 com Repetições F-Box-WD/metabolismo , Neurônios/citologia , Traumatismos da Medula Espinal/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Mielite/metabolismo , Ratos Sprague-Dawley
19.
Curr Top Med Chem ; 20(27): 2506-2517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32703134

RESUMO

BACKGROUND: Metal nanomaterials are widely used in various fields, including targeted therapy and diagnosis. They are extensively used in targeted drug delivery and local treatments. However, the toxicity associated with these materials could lead to severe adverse health effects. METHODS: In this study, we investigated the relationships between the toxicity and structures of metal nanoparticles by using theoretical calculations and quantitative structure-activity relationships. Twenty four physicochemical descriptors and toxicity data of 23 types of metal nanoparticles were selected as samples, and a multiple linear regression model was established to obtain a toxicity prediction equation with 5 descriptors with an R2 of 0.910. Structures of copper nanoparticles were designed based on the model, and the structure with low toxicity was searched. The multiple nonlinear regression model was used to further improve the prediction accuracy. RESULTS: The R2 values were 0.995 in the training set and 0.988 in the test set, which indicated that the prediction accuracy improved. Based on the result of multiple linear regression, we designed copper nanoparticles with low toxicity. CONCLUSION: The study confirmed that the quantitative structure-activity relationship was a reasonable method for predicting the toxicity and designing the structures with low toxicity of metal nanoparticles.

20.
Chem Commun (Camb) ; 56(56): 7785-7788, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32542273

RESUMO

We report the synthesis and comprehensive characterization of a new platinum-AIEgen coordination complex. Possessing a high 1O2 quantum yield of 0.75 in water, the complex efficiently kills cisplatin-resistant cancer cells under mild white light irradiation. Its strong fluorescence upon binding with proteins also enables direct visualization of its intracellular distribution.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Complexos de Coordenação/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imagem Molecular/métodos , Platina/química , Linhagem Celular Tumoral , Humanos
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