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1.
Comput Struct Biotechnol J ; 23: 1725-1739, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38689716

RESUMO

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.

2.
Diagn Pathol ; 19(1): 66, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730456

RESUMO

BACKGROUND: TFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics. CASE PRESENTATION: We report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient's molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-ß, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed. CONCLUSION: We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Carcinoma de Células Renais , Sequenciamento do Exoma , Neoplasias Renais , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Biomarcadores Tumorais/genética
3.
PeerJ ; 12: e17268, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708351

RESUMO

Objective: To study the efficacy of PADTM Plus-based photoactivated disinfection (PAD) for treating denture stomatitis (DS) in diabetic rats by establishing a diabetic rat DS model. Methods: The diabetic rat DS model was developed by randomly selecting 2-month-old male Sprague-Dawley rats and dividing them into four groups. The palate and denture surfaces of rats in the PAD groups were incubated with 1 mg/mL toluidine blue O for 1 min each, followed by a 1-min exposure to 750-mW light-emitting diode light. The PAD-1 group received one radiation treatment, and the PAD-2 group received three radiation treatments over 5 days with a 1-day interval. The nystatin (NYS) group received treatment for 5 days with a suspension of NYS of 100,000 IU. The infection group did not receive any treatment. In each group, assessments included an inflammation score of the palate, tests for fungal load, histological evaluation, and immunohistochemical detection of interleukin-17 (IL-17) and tumor necrosis factor (TNF-α) conducted 1 and 7 days following the conclusion of treatment. Results: One day after treatment, the fungal load on the palate and dentures, as well as the mean optical density values of IL-17 and TNF-α, were found to be greater in the infection group than in the other three treatment groups (P < 0.05). On the 7th day after treatment, these values were significantly higher in the infection group than in the PAD-2 and NYS groups (P < 0.05). Importantly, there were no differences between the infection and PAD-1 groups nor between the PAD-2 and NYS groups (P > 0.05). Conclusions: PAD effectively reduced the fungal load and the expressions of IL-17 and TNF-α in the palate and denture of diabetic DS rats. The efficacy of multiple-light treatments was superior to that of single-light treatments and similar to that of NYS.


Assuntos
Diabetes Mellitus Experimental , Desinfecção , Ratos Sprague-Dawley , Estomatite sob Prótese , Animais , Masculino , Ratos , Estomatite sob Prótese/microbiologia , Estomatite sob Prótese/radioterapia , Estomatite sob Prótese/tratamento farmacológico , Desinfecção/métodos , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-17/metabolismo , Modelos Animais de Doenças
4.
Virus Res ; 345: 199371, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38621598

RESUMO

BACKGROUND: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for three years. Coinfection with seasonal influenza may occur resulting in more severe diseases. The interaction between these two viruses for infection and the effect of antiviral treatment remains unclear. METHODS: A SARS-CoV-2 and influenza H1N1 coinfection model on Calu-3 cell line was established, upon which the simultaneous and sequential coinfection was evaluated by comparing the viral load. The efficacy of molnupiravir and baloxavir against individual virus and coinfection were also studied. RESULTS: The replication of SARS-CoV-2 was significantly interfered when the influenza virus was infected simultaneously or in advance (p < 0.05). On the contrary, the replication of the influenza virus was not affected by the SARS-CoV-2. Molnupiravir monotherapy had significant inhibitory effect on SARS-CoV-2 when the concentration reached to 6.25 µM but did not show any significant anti-influenza activity. Baloxavir was effective against influenza within the dosage range and showed significant effect of anti-SARS-CoV-2 at 16 µM. In the treatment of coinfection, molnupiravir had significant effect for SARS-CoV-2 from 6.25 µM to 100 µM and inhibited H1N1 at 100 µM (p < 0.05). The tested dosage range of baloxavir can inhibit H1N1 significantly (p < 0.05), while at the highest concentration of baloxavir did not further inhibit SARS-CoV-2, and the replication of SARS-CoV-2 significantly increased in lower concentrations. Combination treatment can effectively inhibit influenza H1N1 and SARS-CoV-2 replication during coinfection. Compared with molnupiravir or baloxavir monotherapy, combination therapy was more effective in less dosage to inhibit the replication of both viruses. CONCLUSIONS: In coinfection, the replication of SARS-CoV-2 would be interfered by influenza H1N1. Compared with molnupiravir or baloxavir monotherapy, treatment with a combination of molnupiravir and baloxavir should be considered for early treatment in patients with SARS-CoV-2 and influenza coinfection.


Assuntos
Antivirais , COVID-19 , Coinfecção , Dibenzotiepinas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , SARS-CoV-2 , Carga Viral , Replicação Viral , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , SARS-CoV-2/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Replicação Viral/efeitos dos fármacos , Dibenzotiepinas/uso terapêutico , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , COVID-19/virologia , Carga Viral/efeitos dos fármacos , Piridonas/farmacologia , Piridonas/uso terapêutico , Linhagem Celular , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Triazinas/farmacologia , Triazinas/uso terapêutico , Tratamento Farmacológico da COVID-19 , Hidroxilaminas/farmacologia , Hidroxilaminas/uso terapêutico , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Citidina/análogos & derivados
5.
Environ Toxicol Pharmacol ; 108: 104436, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599507

RESUMO

Plastics pose a hazard to the environment. Although plastics have toxicity, microplastics (MPs) and nanoplastics (NPs) are capable of interacting with the rest pollutants in the environment, so they serve as the carriers and interact with organic pollutants to modulate their toxicity, thus resulting in unpredictable ecological risks. PS-NPs and TDCIPP were used expose from 2 h post-fertilization (hpf) to 150 days post-fertilization (dpf) to determine the bioaccumulation of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and its potential effects on neurodevelopment in F1 zebrafish (Danio rerio) offspring under the action of polystyrene nano plastics (PS-NPs). The exposure groups were assigned to TDCIPP (0, 0.4, 2 or 10 µg/L) alone group and the PS-NPs (100 µg/L) and TDCIPP co-exposed group. F1 embryos were collected and grown in clean water to 5 dpf post-fertilization. PS-NPs facilitated the bioaccumulation of TDCIPP in the gut, gill, head,gonad and liver of zebrafish in a sex-dependent manner and promoted the transfer of TDCIPP to their offspring, thus contributing to PS-NPs aggravated the inhibition of offspring development and neurobehavior of TDCIPP-induced. In comparison with TDCIPP exposure alone, the combination could notably down-regulate the levels of the dopamine neurotransmitter, whereas the levels of serotonin or acetylcholine were not notably different. This result was achieved probably because PS-NPs interfered with the TDCIPP neurotoxic response of zebrafish F1 offspring not through the serotonin or acetylcholine neurotransmitter pathway. The increased transfer of TDCIPP to the offspring under the action of PS-NPs increased TDCIPP-induced transgenerational developmental neurotoxicity, which was proven by a further up-regulation/down-regulation the key gene and protein expression related to dopamine synthesis, transport, and metabolism in F1 larvae, in contrast to TDCIPP exposure alone. The above findings suggested that dopaminergic signaling involvement could be conducive to the transgenerational neurodevelopmental toxicity of F1 larval upon parental early co-exposure to PS-NPs and TDCIPP.


Assuntos
Dopamina , Microplásticos , Transdução de Sinais , Poluentes Químicos da Água , Peixe-Zebra , Animais , Dopamina/metabolismo , Poluentes Químicos da Água/toxicidade , Transdução de Sinais/efeitos dos fármacos , Microplásticos/toxicidade , Masculino , Feminino , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/anormalidades , Compostos Organofosforados/toxicidade , Nanopartículas/toxicidade , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/etiologia , Poliestirenos/toxicidade
6.
Vaccines (Basel) ; 12(4)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38675747

RESUMO

BACKGROUND: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac. METHODS: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors. RESULTS: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log10LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log10LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log10LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens, and S. salivarius was 0.03 (95% CI: 9.56 × 10-4-0.32), 0.03 (95% CI: 4.47 × 10-4-0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log10LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions. CONCLUSION: E. rectale,C. aerofaciens, and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

7.
Front Endocrinol (Lausanne) ; 15: 1365350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628586

RESUMO

Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.


Assuntos
Aprendizado Profundo , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/diagnóstico por imagem , Qualidade de Vida , Órbita , Dor
8.
Microorganisms ; 12(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38674616

RESUMO

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

9.
Materials (Basel) ; 17(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612097

RESUMO

Nonmetallic ionic liquids (ILs) exhibit unique advantages in catalyzing poly (ethylene terephthalate) (PET) glycolysis, but usually require longer reaction times. We found that exposure to UV radiation can accelerate the glycolysis reaction and significantly reduce the reaction time. In this work, we synthesized five nonmetallic dibasic ILs, and their glycolysis catalytic activity was investigated. 1,8-diazabicyclo [5,4,0] undec-7-ene imidazole ([HDBU]Im) exhibited better catalytic performance. Meanwhile, UV radiation is used as a reinforcement method to improve the PET glycolysis efficiency. Under optimal conditions (5 g PET, 20 g ethylene glycol (EG), 0.25 g [HDBU]Im, 10,000 µW·cm-2 UV radiation reacted for 90 min at 185 °C), the PET conversion and BHET yield were 100% and 88.9%, respectively. Based on the UV-visible spectrum, it was found that UV radiation can activate the C=O in PET. Hence, the incorporation of UV radiation can considerably diminish the activation energy of the reaction, shortening the reaction time of PET degradation. Finally, a possible reaction mechanism of [HDBU]Im-catalyzed PET glycolysis under UV radiation was proposed.

10.
Microbiol Res ; 283: 127670, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479231

RESUMO

Tuberculosis (TB) is a highly lethal infectious disease that poses a global threat. Timely and accurate biomarker for TB diagnosis and treatment monitoring remains a pressing need. Ions, the crucial trace element for humans, may be potential targets for TB diagnosis and the forecasting of TB development. To explore the potential of ions as biomarkers, we measured and compared the levels of various ions in whole blood and plasma samples from healthy control (HC), pulmonary TB patients (TB), cured pulmonary TB patients (RxTB), and other non-TB pneumonia patients (PN) by using ultra-high performance liquid chromatography-tandem mass spectrometry. Our study demonstrated that Cu (AUC = 0.670), Pb (AUC = 0.660), and Zn (AUC = 0.701) in whole blood exhibited promising diagnostic performance for TB. Then we used a neural network (NNET) for TB prediction, the AUC values used to differentiate definite TB from HC or PN in plasma were 0.867 and 0.864, respectively. The AUC values used to differentiate definite TB from HC or PN in whole blood were 0.818 and 0.660, respectively. Our correlation analysis showed that Zn (r= 0.356, p=0.001) and Cu (r= 0.361, p=0.0004) in plasma are most closely related to disease severity. Additionally, six ions (Cu, Sb, V, Mn, Fe, Sr) in plasma and whole blood were altered following anti-TB therapy. These results showed that ions could be diagnostic biomarkers for TB. Furthermore, the level of particular ions can forecast the degree of lung damage and the success of the TB treatment. In conclusion, this study highlights the possibility of using ions from blood samples to enable rapid tuberculosis diagnosis.


Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Tuberculose/diagnóstico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Pulmão , Biomarcadores , Íons
11.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473829

RESUMO

CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8-61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log10LDA score = 4.39) and Bacteroides eggerthii (log10LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32-29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73-14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log10LDA score = 2.88) and II (log10LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species (B. eggerthii and B. uniformis) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.


Assuntos
Vacinas contra COVID-19 , Microbioma Gastrointestinal , Vacinas de Produtos Inativados , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adenosina , Anticorpos Neutralizantes , Anticorpos Antivirais
12.
Huan Jing Ke Xue ; 45(3): 1457-1467, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471861

RESUMO

Urban rivers are the main receptors and transporters of microplastic pollution. Understanding the occurrence and environmental risk of microplastics in urban rivers can provide theoretical basis for further control of microplastic pollution. The Sishui River, a tributary of the Yellow River, was selected as the research object. A total of nine water samples were collected from sewage outlets of the Sishui River (Xingyang section). The microplastics in the collected samples were characterized by their sizes, shapes, and colors using a microscope. It was found that microplastics were mostly in the form of transparent fibers and fragments in the water body of sewage outlets, of which the size below 500 µm was relatively high. In addition, PET and PE polymers were identified as the main types using a laser infrared imager. The correlation analysis showed that there was a significant correlation between the PET and PE, indicating that they were similar in origin. The results of the environmental risk assessment showed that the type of microplastics was the main factor affecting the assessment results, whereas the risk values of six sewage samples containing PVC were high. However, the value of pollution load index revealed a low risk level of pollutants in the study area.

13.
Int J Radiat Biol ; 100(5): 791-801, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442139

RESUMO

PURPOSE: Radiotherapy with bladder preservation is highly acceptable among patients bearing bladder cancer (BCa), but the occurrence of secondary tolerance (ARR) during treatment is one of the important reasons for the failure of clinical radiotherapy. COX-2 has been frequently reported to be highly expressed and associated with radio-resistance in various cancers. In this study, the feasibility of Taraxasterol (Tara) as a radiosensitizer was investigated, and the target effect of Tara on COX-2 and its underlying mechanism were explored. METHODS AND MATERIALS: The toxicity of Tara toward BCa cells was detected with the MTT method and cells in response to IR or Tara + IR were compared by clone formation assay. Next, a small RNA interference system (siRNA) was employed to decrease endogenous COX-2 expression in BCa cells, and the stem cell-like features and motion abilities of BCa cells under different treatments were investigated using microsphere formation and transwell chamber assay, respectively. Meanwhile, the expression of a series of inflammation-related molecules and stem cell characteristic molecules was determined by qRT-PCR, western blot and ELISA method. In vivo studies, BCa cells were subcutaneously injected into the right flank of each male mouse. Those mice were then grouped and exposed to different treatment: Tara, IR, IR + Tara and untreated control. The volumes of each tumor were measured every two days and target proteins were detected with immunohistochemical (IHC) staining. RESULTS: The results show that COX-2 decline, due to COX-2 knocking-down or Tara treatment, could greatly enhance BCa cells' radiosensitivity and significantly decrease their migration, invasion and microsphere formation abilities, companied with the reduce of JAK2, phos-STAT3, MMP2 and MMP9 expression. However, Tara could not further reduce the expression of an above molecule of cells in COX-2-deficient BCa cells. Correspondingly, Tara treatment could not further enhance those siCOX-2 BCa cells response to IR. CONCLUSIONS: Our data support that Tara can improve the radiosensitivity of BCa cells by targeting COX-2/PGE2. The mechanism may involve regulating STAT3 phosphorylation, DNA damage response protein activation, and expression of MMP2/MMP9.


Assuntos
Ciclo-Oxigenase 2 , Janus Quinase 2 , Tolerância a Radiação , Fator de Transcrição STAT3 , Neoplasias da Bexiga Urinária , Janus Quinase 2/metabolismo , Humanos , Ciclo-Oxigenase 2/metabolismo , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Fator de Transcrição STAT3/metabolismo , Camundongos , Tolerância a Radiação/efeitos dos fármacos , Dinoprostona/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteróis/farmacologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Radiossensibilizantes/farmacologia , Masculino
15.
Environ Sci Technol ; 58(8): 3908-3918, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38329000

RESUMO

The heterogeneous photodegradation behavior of liquid crystal monomers (LCMs) in standard dust (standard reference material, SRM 2583) and environmental dust was investigated. The measured photodegradation ratios for 23 LCMs in SRM and environmental dust in 12 h were 11.1 ± 1.8 to 23.2 ± 1.1% and 8.7 ± 0.5 to 24.0 ± 2.8%, respectively. The degradation behavior of different LCM compounds varied depending on their structural properties. A quantitative structure-activity relationship model for predicting the degradation ratio of LCMs in SRM dust was established, which revealed that the molecular descriptors related to molecular polarizability, electronegativity, and molecular mass were closely associated with LCMs' photodegradation. The photodegradation products of the LCM compound 4'-propoxy-4-biphenylcarbonitrile (PBIPHCN) in dust, including •OH oxidation, C-O bond cleavage, and ring-opening products, were identified by nontarget analysis, and the corresponding degradation pathways were suggested. Some of the identified products, such as 4'-hydroxyethoxy-4-biphenylcarbonitrile, showed predicted toxicity (with an oral rat lethal dose of 50%) comparable to that of PBIPHCN. The half-lives of the studied LCMs in SRM dust were estimated at 32.2-82.5 h by fitting an exponential decay curve to the observed photodegradation data. The photodegradation mechanisms of LCMs in dust were revealed for the first time, enhancing the understanding of LCMs' environmental behavior and risks.


Assuntos
Poeira , Cristais Líquidos , Animais , Ratos , Relação Quantitativa Estrutura-Atividade , Fotólise
16.
J Phys Chem Lett ; 15(6): 1765-1773, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38329073

RESUMO

In Ni-rich layered oxide cathodes, one effective way to adjust the performance is by introducing dopants to change the degree of Li/Ni exchange. We calculated the formation energy of Li/Ni exchange defects in LiNi0.8Mn0.1X0.1O2 with different doping elements X, using first-principles calculations. We then proposed an interpretable machine learning method combining the Random Forest (RF) model and the Shapley Additive Explanation (SHAP) analysis to accelerate identification of the key factors influencing the formation energy among the complex variables introduced by doping. The valence state of the doping element effectively regulates Li/Ni exchange defects through changing the valence state of Ni and the strength of the superexchange interaction, and COOPSU-SD and MagO were proposed as two indicators to assess superexchange interaction. The volume change also affects the Li/Ni exchange defects, with a larger volume reduction corresponding to fewer Li/Ni exchange defects.

17.
Plant Dis ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389384

RESUMO

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a serious disease tothat threatens wheat production globally. It is imperative to explore novel resistance genes in order to control this disease throughby developing and planting resistant varieties. Here, we identified a wheat-Dasypyrum villosum 3V (3D) disomic substitution line, NAU3815 (2n=42), with a high level of powdery mildew resistance at both the seedling and adult-plant stages. Subsequently, NAU3815 was used to generate recombination between chromosomes 3V and 3D. Through genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH)GISH/FISH and 3VS, 3VL-specific markers analysis, four introgression lines were developed from the selfing progenies of 3V and 3D double monosomic line NAU3816, which was derived from the F1 hybrids of NAU3815/NAU0686. There were t3VS (3D) ditelosomic substitution line NAU3817, t3VL (3D) ditelosomic substitution line NAU3818, homozygous T3DL·3VS translocation line NAU3819, and homozygous T3DS·3VL translocation line NAU3820. Powdery mildew tests of these lines confirmed the presence of an all-stage and broad-spectrum powdery mildew resistance gene, Pm3VS, located on chromosome arm 3VS. When compared with the recurrent parent NAU0686 plants, the T3DL·3VS translocation line NAU3819 showed no obvious negative effect on yield-related traits. However, the introduction of the T3DL·3VS translocated chromosome had a strong effect on reducing the flag-leaf length. Consequently, the T3DL·3VS translocation line NAU3819 provides a new germplasm in breeding for both resistance and plant architecture.

18.
Acta Biomater ; 176: 77-98, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38176673

RESUMO

Prussian blue (PB) nanoparticles (NPs) and Prussian blue analogs (PBAs) can form metal-organic frameworks through the programmable coordination of ferrous ions with cyanide. PB and PBAs represent a burgeoning class of hybrid functional nano-systems with a wide-ranging application spectrum encompassing biomedicine, cancer diagnosis, and therapy. A comprehensive overview of recent advancements is crucial for gaining insights for future research. In this context, we reviewed the synthesis techniques and surface modification strategies employed to tailor the dimensions, morphology, and attributes of PB NPs. Subsequently, we explored advanced biomedical utilities of PB NPs, encompassing photoacoustic imaging, magnetic resonance imaging, ultrasound (US) imaging, and multimodal imaging. In particular, the application of PB NPs-mediated photothermal therapy, photodynamic therapy, and chemodynamic therapy to cancer treatment was reviewed. Based on the literature, we envision an evolving trajectory wherein the future of Prussian blue-driven biological applications converge into an integrated theranostic platform, seamlessly amalgamating bioimaging and cancer therapy. STATEMENT OF SIGNIFICANCE: Prussian blue, an FDA-approved coordinative pigment with a centuries-long legacy, has paved the way for Prussian blue nanoparticles (PB NPs), renowned for their remarkable biocompatibility and biosafety. These PB NPs have found their niche in biomedicine, playing crucial roles in both diagnostics and therapeutic applications. The comprehensive review goes beyond PB NP-based cancer therapy. Alongside in-depth coverage of PB NP synthesis and surface modifications, the review delves into their cutting-edge applications in the realm of biomedical imaging, encompassing techniques such as photoacoustic imaging, magnetic resonance imaging, ultrasound imaging, and multimodal imaging.


Assuntos
Ferrocianetos , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Medicina de Precisão , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imageamento por Ressonância Magnética/métodos
19.
Sci Rep ; 14(1): 37, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167455

RESUMO

Diagnosing low-grade and high-grade endometrial stromal sarcoma (LG-ESS and HG-ESS) is a challenge. This study aimed to identify biomarkers. 22 ESS cases were analyzed using Illumina microarrays. Differentially expressed genes (DEGs) were identified via Limma. DEGs were analyzed with String and Cytoscape. Core genes were enriched with GO and KEGG, their pan-cancer implications and immune aspects were studied. 413 DEGs were found by exome sequencing, 2174 by GSE85383 microarray. 36 common genes were identified by Venn analysis, and 10 core genes including RBFOX1, PCDH7, FAT1 were selected. Core gene GO enrichment included cell adhesion, T cell proliferation, and KEGG focused on related pathways. Expression was evaluated across 34 cancers, identifying immune DEGs IGF1 and AVPR1A. Identifying the DEGs not only helps improve our understanding of LG-ESS, HG-ESS but also promises to be potential biomarkers for differential diagnosis between LG-ESS and HG-ESS and new therapeutic targets.


Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Feminino , Humanos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Biologia Computacional
20.
Nat Commun ; 15(1): 503, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218848

RESUMO

Powdery mildew poses a significant threat to wheat crops worldwide, emphasizing the need for durable disease control strategies. The wheat-Dasypyrum villosum T5AL·5 V#4 S and T5DL·5 V#4 S translocation lines carrying powdery mildew resistant gene Pm55 shows developmental-stage and tissue-specific resistance, whereas T5DL·5 V#5 S line carrying Pm5V confers resistance at all stages. Here, we clone Pm55 and Pm5V, and reveal that they are allelic and renamed as Pm55a and Pm55b, respectively. The two Pm55 alleles encode coiled-coil, nucleotide-binding site-leucine-rich repeat (CNL) proteins, conferring broad-spectrum resistance to powdery mildew. However, they interact differently with a linked inhibitor gene, SuPm55 to cause different resistance to wheat powdery mildew. Notably, Pm55 and SuPm55 encode unrelated CNL proteins, and the inactivation of SuPm55 significantly reduces plant fitness. Combining SuPm55/Pm55a and Pm55b in wheat does not result in allele suppression or yield penalty. Our results provide not only insights into the suppression of resistance in wheat, but also a strategy for breeding durable resistance.


Assuntos
Ascomicetos , Triticum , Triticum/genética , Alelos , Ascomicetos/genética , Melhoramento Vegetal , Poaceae/genética , Resistência à Doença/genética , Doenças das Plantas/genética
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