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1.
J Environ Sci (China) ; 125: 499-512, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375933

RESUMO

Understanding the aerosol vertical characterization is of great importance to both climate and atmospheric environment. This study investigated the variations of aerosol profiles over eight regions of interest in China after clean air policy (2013-2019) and discussed the drivers of the vertical aerosol structure, using observations from active satellite measurements (CALIPSO). From the annual variation, the amplitude of extinction coefficient profiles showed a decreasing trend with fluctuations, and the maximum was 0.21 km-1 in Beijing-Tianjin-Hebei (JJJ). For regions suffered from air pollution, the variation was greatest below 0.45 km, while it was between 1-1.5 km for Sichuan Basin. The correlation coefficient between the relative humidity (RH) and the extinction coefficient indicated that the increase of RH inhibited the decrease of the extinction coefficient in the Yangtze River Delta. In most regions, the main aerosol subtypes were polluted dust and polluted continental, but they were coarser in JJJ and North West. The frequency of concurrency of dust and polluted dust aerosols decreased in JJJ, but polluted continental aerosols occurred more frequently. Further, the aerosol extinction coefficient profiles under different pollution conditions showed that it changed most during heavy pollution periods in JJJ, especially in 2017, with a significant aerosol loading between ∼700 and 1200 m. The atmospheric reanalysis data revealed that the weak convergence at low level and the divergence at high level supported the upward transport of aerosols in 2017. Overall, the differences in divergence allocation, RH, and wind filed were the main meteorological drivers.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Material Particulado/análise , Monitoramento Ambiental , Estações do Ano , Aerossóis/análise , Poluição do Ar/análise , Poeira/análise , China , Políticas
2.
Sci Total Environ ; 856(Pt 1): 158943, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36155042

RESUMO

The adverse health effects of phthalate esters (PAEs) and perfluoroalkyl substances (PFAS) in drinking water have attracted considerable attention. Our study investigated the effects of PAEs and PFAS on the bacterial community and the growth of potential human pathogenic bacteria in rural drinking water distribution systems. Our results showed that the total concentration of PAEs and PFAS ranged from 1.02 × 102 to 1.65 × 104 ng/L, from 4.40 to 1.84 × 102 ng/L in rural drinking water of China, respectively. PAEs concentration gradually increased and PFAS slowly decreased along the pipeline distribution, compared to concentrations in the effluents of rural drinking water treatment plants. The co-occurrence of higher concentrations of PAEs and PFAS changed the structure and function of the bacterial communities found within these environments. The bacterial community enhanced their ability to respond to fluctuating environmental conditions through up-regulation of functional genes related to extracellular signaling and interaction, as well as genes related to replication and repair. Under these conditions, co-occurrence of PAEs and PFAS promoted the growth of potential human pathogenic bacteria (HPB), therefore increasing the risk of the development of associated diseases among exposed persons. The main HPB observed in this study included Burkholderia mallei, Mycobacterium tuberculosis, Klebsiella pneumoniae, Acinetobacter calcoaceticus, Escherichia coli, and Pseudomonas aeruginosa. Contaminants including particles, microorganisms, PAEs and PFAS were found to be released from corrosion scales and deposits of pipes and taps, resulting in the increase of the cytotoxicity and microbial risk of rural tap water. These results are important to efforts to improve the safety of rural drinking water.


Assuntos
Água Potável , Fluorcarbonetos , Humanos , Ésteres/análise , Fluorcarbonetos/toxicidade , Dibutilftalato/análise , Bactérias
3.
J Ethnopharmacol ; 301: 115737, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36179952

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine herb Celastrus orbiculatus Thunb. is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. Recent years, many studies have reported the significant effects of Celastrus orbiculatus Thunb. extract (COE) on gastric cancer. However, the specific mechanism by which COE regulates gastric cancer cytoskeleton remodeling and thus inhibits EMT has not yet been reported. AIM OF STUDY: To study the effect and mechanism of COE in inhibiting the epithelial-mesenchymal transition (EMT) and metastasis of gastric cancer cells, laying an experimental foundation for the clinical application and further development of COE. METHODS: The high-content cell dynamic tracking system was used to continuously track the trajectory of cell movement in real time. Through the high-content data, the average movement distance and movement speed of the cells are calculated. Additionally, the dynamic images of the cell movement in the high-content imaging system are derived to analyze the impact of COE on the movement of gastric cancer cells. Cytoskeleton staining experiment was performed to detect the effect of COE on the assembly of gastric cancer cell cytoskeleton proteins. Western blot was employed to detect the changes of EMT and metastasis-related proteins in the gastric cancer cells treated by COE. The effect of COE on the key regulatory protein Cofilin-1 (CFL1) of cell movement was examined by Western blot and protein degradation experiment. The effect of COE on EMT and metastasis of the gastric cancer cells lacking CFL1 was assessed by a transwell assay. The in vivo inhibitory effect of COE on EMT and metastasis of gastric cancer was determined by the animal living image system. IHC assays were used to detect the levels of EMT-related proteins in COE reversal in vivo. RESULT: The results showed that the movement distance and average movement speed of gastric cancer cells after COE treatment were significantly lower than those of the control group. Cytoskeleton staining experiments revealed that COE can significantly change the distribution of skeletal proteins in gastric cancer cells. Additionally, COE treatment significantly reduced the expression of Matrix metalloproteinases (MMP-2, MMP-9) and other proteins. Furthermore, COE can significantly accelerate the degradation of CFL1 protein, and both COE treatment and CFL1 deletion can significantly inhibit EMT and metastasis of gastric cancer cells. Lastly, the number of peritoneal metastases of gastric cancer cells was significantly reduced in animals after COE treatment. COE can reverse the levels of EMT-related proteins while reducing the expression levels of CFL1 protein in vivo. CONCLUSION: COE can significantly inhibit EMT and metastasis of gastric cancer cells in vivo and in vitro. This effect may be achieved by reducing the stability of CFL1 and inhibiting the assembly of actin in gastric cancer cells.


Assuntos
Celastrus , Neoplasias Gástricas , Animais , Transição Epitelial-Mesenquimal , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Cofilina 1/farmacologia , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Movimento Celular , Citoesqueleto de Actina
4.
Comput Math Methods Med ; 2022: 4224749, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341006

RESUMO

The aim of this research was to analyze the application of fuzzy C-means (FCM) algorithm-based ARM-Linux-embedded system in magnetic resonance imaging (MRI) images for prediction of brain tumors. The optimized FCM (OFCM) algorithm was proposed based on kernel function, and the ARM-Linux-embedded imaging system was designed under ARM9 chip and Linux recorder, which were applied in MRI images of brain tumor patients. It was found that the sensitivity, specificity, and accuracy of the OFCM algorithm (90.46%, 88.97%, and 97.46%) were greater obviously than those of the deterministic C-means clustering algorithm (80.38%, 77.98%, and 85.24%) and the traditional FCM algorithm (83.26%, 79.56%, and 86.45%), and the difference was statistically substantial (P < 0.05). The ME and running time of the OFCM algorithm decreased sharply in contrast to those of the deterministic C-means clustering algorithm and the traditional FCM algorithm (P < 0.05). There were great differences in fraction anisotropy (FA) and mean diffusion (MD) of tumor parenchymal area, surrounding edema area, and normal white matter area (P < 0.05). FA of stage III+IV was smaller than those of stage I and II (P < 0.05), while the apparent diffusion coefficient (ADC) of stage III+IV was greater than that of stage I and II (P < 0.05). In conclusion, the poor update data processing and low data clustering efficiency of FCM were solved by OFCM. Moreover, computational efficiency of ARM-Linux-embedded imaging system was improved, so as to better realize the prediction of brain tumor patients through ARM-Linux-embedded system based on adaptive FCM incremental clustering algorithm.


Assuntos
Neoplasias Encefálicas , Lógica Fuzzy , Algoritmos , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos
5.
J Nephrol ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472788

RESUMO

AIM: The study aimed to investigate the spectrum of biopsy-proven kidney disease in Chinese children. METHODS: Records of children 0-17 years old who underwent native kidney biopsy from June 1st, 2013 to December 31st, 2018 in the national inpatients' database of China were analyzed. Biopsy-proven kidney diseases of different sex, age groups, and diagnosis, and the changing patterns of kidney disease compared with the previous study were analyzed. RESULTS: A total of 21,311 patients from 232 hospitals with a median age of 11.34 years were included. Immunoglobulin A vasculitis with nephritis (IgAVN) was the most common pathological finding [29.17%, 95% confidence interval (confidence interval, CI) = 28.56-29.78], followed by IgA nephropathy (IgAN) (22.70%, 95% CI = 22.14-23.27). IgAN was the most common finding in patients with hematuria (60.75%, 95% CI = 58.83-62.65], proteinuria (33.43%, 95% CI = 30.54-36.42), and hematuria plus proteinuria (62.77%, 95% CI = 56.19-69.02). Minimal change disease was the most common finding (40.69%, 95% CI = 39.41-41.98) in nephrotic syndrome. The proportion of IgAVN in patients with biopsy-proven glomerular disease increased year by year during 2013-2018 (p for trend < 0.001) and was higher than that of 2004-2014 [29.41% (95% CI = 29.10-29.72) in 2013-2018 vs. 13.35% (95% CI = 12.97-13.73) 2004-2014, p < 0.001]. The proportion of hepatitis B virus associated nephritis during 2013-2018 was lower than that of  2004-2014 [0.44% (95% CI = 0.36-0.54) in 2013-2018 vs. 0.87% (95% CI = 0.67-1.10) in 2004-2014, p < 0.001]. CONCLUSIONS: IgAVN and IgAN were the most common types of pathological findings in children who underwent kidney biopsies from 2013 to 2018. The pathological spectrum of kidney biopsy changed over time.

6.
Front Immunol ; 13: 974265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439099

RESUMO

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8+ T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear. Materials and methods: The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8+ T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort. Results: Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman's r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19-0.75; p < 0.001). Conclusions: CFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Prognóstico , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Microambiente Tumoral
7.
Water Sci Technol ; 86(10): 2718-2731, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36450682

RESUMO

Nickle-copper ferrite (Ni0.5Cu0.5Fe2O4) supported on activated carbon (AC) (AC@Ni0.5Cu0.5Fe2O4) was synthesized and used as adsorbent, photocatalyst, and activator of peroxydisulfate (PDS) to realize the removal of ciprofloxacin (CIP). AC@Ni0.5Cu0.5Fe2O4 properties were characterized by scanning electron microscope equipped with energy-dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), N2 adsorption-desorption isotherm plot of Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH), vibrating sample magnetometer (VSM). A rapid removal rate (94.30%) of CIP was achieved on AC@Ni0.5Cu0.5Fe2O4/PDS/UV system with the condition of catalyst dosage 0.30 g/L, initial pH 7.3, PDS addition 0.20 mM, CIP concentration 10 mg/L (200 mL), UV 28 W, in 30 min. Free radical quenching experiments indicate that reactive species of superoxide (·O2-), holes (h+), sulfate radicals (SO4-·) and hydroxyl radicals (·OH) were produced and all worked. The reusability test demonstrated that AC@Ni0.5Cu0.5Fe2O4 could be recycled five times with minimal performance reduction for the removal of CIP. The XRD and SEM of the after used AC@Ni0.5Cu0.5Fe2O4 did not change significantly, which further showed its stability and recyclability. This work might provide new insight into the application of AC@Ni0.5Cu0.5Fe2O4 in photocatalysis coupled with adsorption in peroxydisulfate assisted system and has high potential in CIP removal.


Assuntos
Carvão Vegetal , Ciprofloxacina , Adsorção , Cobre , Radical Hidroxila
8.
Artigo em Inglês | MEDLINE | ID: mdl-36409304

RESUMO

The gel-based sensors have developed rapidly in recent years toward multifunctionality. However, there are still some challenges that need to be solved, such as poor mechanical properties and inaccessibility to wet or water environments. To address these issues, we have developed an ionogel with a semi-interpenetrating network structure by adopting poly(vinylidene fluoride-co-hexafluoropropylene) as the linear non-cross-linked network, a double-bonded ionic liquid and double-bonded capped polyurethane as the cross-linked network, and an ionic liquid as the conductive media. The obtained ionogel exhibits tunable mechanical properties (3.67-8.76 MPa) and excellent sensing properties (IG-20, GF = 8.2). The superb environmental stability and self-healing properties of the ionogel were also demonstrated. Meanwhile, adhesion, self-healing, and sensing performance were guaranteed for underwater due to the presence of a large number of C-F bonds. We strongly believe that this ionogel with excellent mechanical properties and underwater communication is expected for monitoring the health of the human body and information transmission in the future.

9.
Animals (Basel) ; 12(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36428402

RESUMO

This experiment was conducted to investigate the effects of methionine analogues 2-hydroxy-4-methylthio butanoic acid isopropyl ester (HBMi) on growth performance, nutrient apparent digestibility, serum metabolite, serum free amino acids, and rumen fermentation parameters of yaks. Twenty-four male Maiwa yaks (252.79 ± 15.95 kg) were randomly allocated to four dietary treatments: basic diet (CON), or three HBMi (MetaSmart (MS); Adisseo Inc., Antony, France) supplementation treatments: MS1 (5 g), MS2 (10 g), and MS3 (15 g). The results showed that the increase in the supplemented MS levels linearly increased the average daily gain (p < 0.05), while the serum alkaline phosphatase activity and malondialdehyde content were increased when yaks were fed with 15 g/d MS (p < 0.05). The diet supplemented with MS linearly increased the percentages of glutamic acid and proline, and linearly or quadratically decreased the percentages of isoleucine, phenylalanine, and valine (p < 0.05). Furthermore, supplementation of 10 g/d and 15 g/d MS increased ruminal microbial crude protein (p < 0.05). The ratio of acetate to propionate in the MS2 group was lower than those in CON and MS1 groups (p < 0.05). In summary, a diet supplemented with 10 g/d MS could be an effective way to improve the growth performance of fattening yaks without negative effects.

10.
ACS Omega ; 7(45): 40963-40972, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36406503

RESUMO

An efficient [4 + 1] annulation reaction between in situ generated azoalkene intermediates and α-bromocarbonyls has been established. A series of skeletally diverse aza-heterocycles with a functionalized quaternary center were obtained in up to 89% yield under mild conditions.

11.
Nat Struct Mol Biol ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411341

RESUMO

The preinitiation complex (PIC) assembles on promoters of protein-coding genes to position RNA polymerase II (Pol II) for transcription initiation. Previous structural studies revealed the PIC on different promoters, but did not address how the PIC assembles within chromatin. In the yeast Saccharomyces cerevisiae, PIC assembly occurs adjacent to the +1 nucleosome that is located downstream of the core promoter. Here we present cryo-EM structures of the yeast PIC bound to promoter DNA and the +1 nucleosome located at three different positions. The general transcription factor TFIIH engages with the incoming downstream nucleosome and its translocase subunit Ssl2 (XPB in human TFIIH) drives the rotation of the +1 nucleosome leading to partial detachment of nucleosomal DNA and intimate interactions between TFIIH and the nucleosome. The structures provide insights into how transcription initiation can be influenced by the +1 nucleosome and may explain why the transcription start site is often located roughly 60 base pairs upstream of the dyad of the +1 nucleosome in yeast.

12.
Int J Biol Macromol ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36356876

RESUMO

Polymer based protein engineering provides an attractive strategy to endow novel properties to protein and overcome the inherent limitations of both counterparts. The exquisite control of site and density of attached polymers on the proteins is crucial for the bioactivities and properties of the protein-polymer bioconjugates, but is still a challenge. Collagen is the major structural protein in extracellular matrix of animals. Based on the advancements of polymer-based protein engineering, collagen bioconjugates has been widely fabricated and applied as biomaterials. However, the site-specific synthesis of well-defined collagen-polymer bioconjugates is still not achieved. Herein, a versatile strategy for the specific modification of N-terminal α-amino groups in collagen was developed. Firstly, all reactive amino groups of tropocollagen (collagen with telopeptides) were protected by succinic anhydride. Then, the telopeptides were digested to give the active N-terminal α-amino groups, which were subsequently attached with poly(N-isopropylacrylamide) (PNIPAAm) via "grafting from" method based on the atom transfer radical polymerization (ATRP). The site-specific N-terminal PNIPAAm modified succinylated collagen was prepared and its structure, thermal responsive behaviour, and properties was explored.

13.
Front Neurol ; 13: 970610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425799

RESUMO

Background: Migraine plays an important role in some subgroups of children with recurrent vertigo. Moreover, the migraine component varies from definite to possibly absent as defined in this spectrum of three disorders-vestibular migraine of childhood (VMC), probable VMC (pVMC), and recurrent vertigo of childhood (RVC). However, studies on the sensory organization of balance control in these three disorders are rare. Objective: To explore the balance control of children with RVC, VMC, and pVMC, when the three sensory systems are challenged. Method: A retrospective analysis was performed on 125 children with VMC (18 female and 15 male; aged 11.64 ± 2.74), pVMC (10 female and eight male; aged 11.78 ± 2.51), and RVC (32 female and 42 male; aged 11.10 ± 2.60). All children in each subtype were divided into groups of children aged ≤ 12 years old and 13-17 years old. Vestibular examination screening and assessment for postural control using the six conditions of the sensory organization test (SOT) were performed. The three primary outcome measures were: equilibrium score (ES), strategy score (SS), and sensory analysis score of the SOT. Results: Equilibrium score under six different conditions and composite score increased with age (all P-values < 0.05). The somatosensory and visual scores also improved with growing (P-values < 0.05). However, vestibular scores did not increase significantly with age as the other senses did (P > 0.05). In the children ≤ 12 year-old group, children with VMC had a significantly higher visual preference score than those with pVMC and RVC (P < 0.05). There was an effect of age on the horizontal HIT. Ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), and unilateral weakness (UW) values showed no significant difference among three diseases. Conclusion: Compared with patients at the age of 13-17 years old and with RVC and pVMC (both ≤ 12 years old), children with VMC had a higher degree of reliance on visual signals to maintain their balance and a poorer central integration of peripheral information before reaching 12 years of age. In addition, vision may predominate by weakening vestibular function based on visuo-vestibular interactions. It must be noted that peripheral vestibular examinations could not distinguish the three disease subtypes.

14.
Molecules ; 27(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36432106

RESUMO

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.


Assuntos
Produtos Biológicos , Celastrus , Neoplasias Gástricas , Humanos , Celastrus/química , Produtos Biológicos/farmacologia , Transição Epitelial-Mesenquimal , Linhagem Celular Tumoral , Extratos Vegetais/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Processos Neoplásicos
15.
Molecules ; 27(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364307

RESUMO

Natural products have multifarious bioactivities against bacteria, fungi, viruses, cancers and other diseases due to their diverse structures. Nearly 65% of anticancer drugs are natural products or their derivatives. Thus, natural products play significant roles in clinical cancer therapy. With the development of biosynthetic technologies, an increasing number of natural products have been discovered and developed as candidates for clinical cancer therapy. Here, we aim to summarize the anticancer natural products approved from 1950 to 2021 and discuss their molecular mechanisms. We also describe the available synthetic biology tools and highlight their applications in the development of natural products.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , Humanos , Biologia Sintética , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fungos , Neoplasias/tratamento farmacológico
16.
J Mater Chem B ; 10(44): 9249-9257, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36321642

RESUMO

Incomplete tumor ablation and subsequent tumor metastasis usually occur during photothermal anti-tumor processes. The combination of photothermal and immunotherapy has proven to be a promising method to conquer technical challenges. Inhibiting the programmed death ligand-1 (PD-L1)/programmed cell death protein 1 (PD-1) immune pathway represents one of the most successful immunotherapy strategies. Whereas, the PD-L1 expression level significantly differs, leading to a relatively low response rate to the immune checkpoint blockade (ICB) approaches. Therefore, improving the expression level of PD-L1 becomes one potential method to enhance the response rate. Herein, NIH 3T3 cells were educated to steadily express PD-1 protein. Furthermore, the synthesized molybdenum nitride was then coated with PD-1 protein-modified cytomembrane, which endows it with immune checkpoint blocking capability. Moreover, under the irradiation of near-infrared light, the local mild heat released from the molybdenum nitride causes the apoptosis of tumor cells. More importantly, the elevated temperature simultaneously helps elevate the expression level of PD-L1, further enhancing the response rate of ICB. Finally, the PD-1 cytomembrane coatings interact with the upregulated PD-L1, leading to the activation of the immune system. In summary, we confirmed that the PD-1 protein-coated molybdenum nitride could synergistically ablate tumors and avoid metastasis.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Camundongos , Animais , Humanos , Feminino , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias da Mama/terapia , Molibdênio/farmacologia , Imunoterapia , Fatores Imunológicos
17.
Neurosci Lett ; : 136964, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36375627

RESUMO

Glioma is one of the most common intracranial malignant tumors worldwide, accounting for 30%-40% of primary brain tumors. Long non-coding RNAs (lncRNAs) have been implicated in cancer malignant progression. Glioma is classified into multiple subtypes, but lncRNA expression pattern in different subtypes are not fully described. Here, we reported that lncRNA-LINC00941 was highly expressed in all glioma subtypes. Overexpression of lncRNA-LINC00941 in U87 cells promoted cellular proliferation and invasiveness, and suppressed apoptosis. Our findings suggest that lncRNA-LINC00941 may function as an oncogenic factor in glioma, and targeting lncRNA-LINC00941 could be developed into a strategy for glioma management.

18.
Colloids Surf B Biointerfaces ; 220: 112914, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36252533

RESUMO

The skin can be easily injured and attacked by external pathogens, leading to wound infection and wound healing delay. Traditional dressings adhere to wounds only and can cause secondary damage to the new epithelium and bleeding. Herein, a highly adhesive zwitterionic composite hydrogel wound dressing (PDA/PSBMA/NFC/Zn2+ [PSNZn]) with outstanding antibacterial properties, good biocompatibility and excellent rheological properties was prepared by introducing zinc ion-loaded polydopamine (PDA)-coated nanofibrillated cellulose into a covalently-crosslinked sulfobetaine methacrylate (SBMA) network. In vitro and in vivo experiments showed the broad-spectrum and lasting antibacterial activity of the PSNZn composite hydrogel against Escherichia coli and Staphylococcus aureus. In summary, the PSNZn composite hydrogel is an excellent wound dressing candidate with efficient antibacterial properties, high adhesion, excellent biocompatibility and good rheological properties.


Assuntos
Antioxidantes , Hidrogéis , Hidrogéis/farmacologia , Adesivos/farmacologia , Cicatrização , Antibacterianos/farmacologia
19.
Cell Biol Int ; 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36200534

RESUMO

DDX46, a member of DEAD-box (DDX) proteins, is associated with various cancers, while its involvement in the pathogenesis of breast cancer hasn't been reported so far. The study demonstrated the overexpression of DDX46 in human breast cancer cells and tissue samples, and correlated with high histological grade and lymph node metastasis. Downregulation of DDX46 in the breast cancer cell lines inhibited their proliferation and invasiveness in vitro. Furthermore, the growth of MDA-MB-231 xenografts was suppressed in nude mice by DDX46 knockingdown. Taken together, our findings suggest that DDX46 is an oncogenic factor in human breast cancer, and a potential therapeutic target.

20.
Front Genet ; 13: 1000652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186455

RESUMO

Background: Owing to the heterogeneity displayed by hepatocellular carcinoma (HCC) and the complexity of tumor microenvironment (TME), it is noted that the long-term effectiveness of the cancer therapy poses a severe clinical challenge. Hence, it is essential to categorize and alter the treatment intervention decisions for these tumors. Materials and methods: "ConsensusClusterPlus" tool was used for developing a secure molecular classification system that was based on the cuproptosis-linked gene expression. Furthermore, all clinical properties, pathway characteristics, genomic changes, and immune characteristics of different cell types involved in the immune pathways were also assessed. Univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) analyses were used for designing the prognostic risk model associated with cuproptosis. Results: Three cuproptosis-linked subtypes (clust1, clust2, and clust3) were detected. Out of these, Clust3 showed the worst prognosis, followed by clust2, while Clust1 showed the best prognosis. Three subtypes had significantly different enrichment in pathways related to Tricarboxylic Acid (TCA) cycle, cell cycle, and cell senescence (p < 0.01). The clust3 subtype with poor prognosis had a low "ImmuneScore" and low immune cell infiltration, and the three subtypes had significant differences in the antigen processing and presentation pathway of the macrophages. Clust1 had a low TIDE score and was sensitive to immunotherapy. Then, according to the prognosis-related genes of cuproptosis, a prognosis risk model related to cuproptosis was constructed, containing seven genes (KIF2C, PTTG1, CENPM, CDC20, CYP2C9, SFN, and CFHR3). "High" group had a higher TIDE score compared to the TIDE score value shown by the "Low" group, which benefited less from immunotherapy, whereas the "High" group patients were more sensitive to the conventional drugs. Finally, the prognosis risk model related to cuproptosis was combined with clinical pathological characteristics to further improve the prognostic model and survival prediction. Conclusion: Three new molecular subgroups based on cuproptosis-linked genes were revealed, and a cuproptosis-related prognostic risk model comprising seven genes was established in this study, which could assist in predicting the prognosis and identifying the patients benefit from immunotherapy.

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