Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 81
Filtrar
1.
Arch Virol ; 169(5): 115, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709425

RESUMO

Porcine circoviruses (PCVs) are a significant cause of concern for swine health, with four genotypes currently recognized. Two of these, PCV3 and PCV4, have been detected in pigs across all age groups, in both healthy and diseased animals. These viruses have been associated with various clinical manifestations, including porcine dermatitis and nephropathy syndrome (PDNS) and respiratory and enteric signs. In this study, we detected PCV3 and PCV4 in central China between January 2022 and February 2023. We tested fecal swabs and tissue samples from growing-finishing and suckling pigs with or without respiratory and systemic manifestations and found the prevalence of PCV3 to be 15.15% (15/99) and that of PCV3/PCV4 coinfection to be 4.04% (4/99). This relatively low prevalence might be attributed to the fact that most of the clinical samples were collected from pigs exhibiting respiratory signs, with only a few samples having been obtained from pigs with diarrhea. In some cases, PCV2 was also detected, and the coinfection rates of PCV2/3, PCV2/4, and PCV2/3/4 were 6.06% (6/99), 5.05% (5/99), and 3.03% (3/99), respectively. The complete genomic sequences of four PCV3 and two PCV4 isolates were determined. All four of the PCV3 isolates were of subtype PCV3b, and the two PCV4 isolates were of subtype PCV4b. Two mutations (A24V and R27K) were found in antibody recognition domains of PCV3, suggesting that they might be associated with immune escape. This study provides valuable insights into the molecular epidemiology and evolution of PCV3 and PCV4 that will be useful in future investigations of genotyping, immunogenicity, and immune evasion strategies.


Assuntos
Infecções por Circoviridae , Circovirus , Genótipo , Filogenia , Doenças dos Suínos , Circovirus/genética , Circovirus/isolamento & purificação , Circovirus/classificação , Animais , Suínos , China/epidemiologia , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Infecções por Circoviridae/veterinária , Infecções por Circoviridae/virologia , Infecções por Circoviridae/epidemiologia , Coinfecção/virologia , Coinfecção/veterinária , Coinfecção/epidemiologia , Genoma Viral/genética , Fezes/virologia
2.
Biomed Pharmacother ; 175: 116658, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38701562

RESUMO

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

3.
Adv Mater ; : e2401537, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768481

RESUMO

In the fabrication of inverted perovskite solar cells (PSCs), the wettability, adsorbability, and compactness of self-assembled monolayers (SAMs) on conductive substrates have critical impacts on the quality of the perovskite films and the defects at the buried perovskite-substrate interface, which control the efficiency and stability of the devices. Herein, three bisphosphonate-anchored indolocarbazole (IDCz)-derived SAMs, IDCz-1, IDCz-2, and IDCz-3, are designed and synthesized by modulating the position of the two nitrogen atoms of the IDCz unit to improve the molecular dipole moments and strengthen the π-π interactions. Regulating the work functions (WF) of FTO electrodes through molecular dipole moments and energy levels, the perovskite band bends upwards with a small offset for ITO/IDCz-3/perovskite, thereby promoting hole extraction and blocking electrons. As a result, the inverted PSC employing IDCz-3 as hole-collecting layer exhibits a champion PCE of 25.15%, which is a record efficiency for the multipodal SAMs-based PSCs. Moreover, the unencapsulated device with IDCz-3 can be stored for at least 1800 h with little degradation in performance.

4.
Metabolites ; 14(4)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38668352

RESUMO

Temperature is vital in plant growth and agricultural fruit production. Litchi chinensis Sonn, commonly known as litchi, is appreciated for its delicious fruit and fragrant blossoms and is susceptible to stress when exposed to low temperatures. This study investigates the effect of two cryoprotectants that counteract cold stress during litchi flowering, identifies the genes that generate the cold resistance induced by the treatments, and hypothesizes the roles of these genes in cold resistance. Whole plants were treated with Bihu and Liangli cryoprotectant solutions to protect inflorescences below 10 °C. The soluble protein, sugar, fructose, sucrose, glucose, and proline contents were measured during inflorescence. Sucrose synthetase, sucrose phosphate synthetase, antioxidant enzymes (SOD, POD, CAT), and MDA were also monitored throughout the flowering stage. Differentially expressed genes (DEGs), gene ontology, and associated KEGG pathways in the transcriptomics study were investigated. There were 1243 DEGs expressed after Bihu treatment and 1340 in the control samples. Signal transduction pathways were associated with 39 genes in the control group and 43 genes in the Bihu treatment group. The discovery of these genes may contribute to further research on cold resistance mechanisms in litchi. The Bihu treatment was related to 422 low-temperature-sensitive differentially accumulated metabolites (DAMs), as opposed to 408 DAMs in the control, mostly associated with lipid metabolism, organic oxidants, and alcohols. Among them, the most significant differentially accumulated metabolites were involved in pathways such as ß-alanine metabolism, polycyclic aromatic hydrocarbon biosynthesis, linoleic acid metabolism, and histidine metabolism. These results showed that Bihu treatment could potentially promote these favorable traits and increase fruit productivity compared to the Liangli and control treatments. More genomic research into cold stress is needed to support the findings of this study.

5.
Phytomedicine ; 128: 155385, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38569292

RESUMO

BACKGROUND: Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. PURPOSE: The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. METHODS: The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. RESULTS: The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of ß-catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1, and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. CONCLUSION: The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.


Assuntos
Azoximetano , Neoplasias Colorretais , Sulfato de Dextrana , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Camundongos , Masculino , Modelos Animais de Doenças , Metaboloma/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Colo/microbiologia
6.
Phytomedicine ; 129: 155615, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38615493

RESUMO

BACKGROUND: Metastasis driven by epithelial-mesenchymal transition (EMT) remains a significant contributor to the poor prognosis of colorectal cancer (CRC), and requires more effective interventions. GPR81 signaling has been linked to tumor metastasis, while lacks an efficient specific inhibitor. PURPOSE: Our study aimed to investigate the effect and mechanism of Gentisic acid on colorectal cancer (CRC) metastasis. STUDY DESIGN: A lung metastasis mouse model induced by tail vein injection and a subcutaneous graft tumor model were used. Gentisic acid (GA) was administered by an intraperitoneal injection. HCT116 was treated with lactate to establish an in vitro model. METHODS: MC38 cells with mCherry fluorescent protein were injected into tail vein to investigate lung metastasis ability in vivo. GA was administered by intraperitoneal injection for 3 weeks. The therapeutic effect was evaluated by survival rates, histochemical analysis, RT-qPCR and live imaging. The mechanism was explored using small interfering RNA (siRNA), Western blotting, RT-qPCR and immunofluorescence. RESULTS: GA had a therapeutic effect on CRC metastasis and improved survival rates and pathological changes in dose-dependent manner. GA emerged as an GPR81 inhibitor, effectively suppressed EMT and mTOR signaling in CRC induced by lactate both in vivo and in vitro. Mechanistically, GA halted lactate-induce degradation of DEPDC5 through impeding the activation of Chaperone-mediated autophagy (CMA). CONCLUSION: CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.


Assuntos
Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Humanos , Camundongos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/tratamento farmacológico , Células HCT116 , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Masculino , Serina-Treonina Quinases TOR/metabolismo
7.
Adv Sci (Weinh) ; : e2308438, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582099

RESUMO

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1-positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low-grade noninvasive and high-grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial-to-mesenchymal transition generated TPCS. TPCS has stem-cell-like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell-like epigenomic landscape, which might generate ITH without additional genetic diversification.

8.
BMC Med Imaging ; 24(1): 76, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561667

RESUMO

BACKGROUND: It is challenging to identify residual or recurrent fistulas from the surgical region, while MR imaging is feasible. The aim was to use dynamic contrast-enhanced MR imaging (DCE-MRI) technology to distinguish between active anal fistula and postoperative healing (granulation) tissue. METHODS: Thirty-six patients following idiopathic anal fistula underwent DCE-MRI. Subjects were divided into Group I (active fistula) and Group IV (postoperative healing tissue), with the latter divided into Group II (≤ 75 days) and Group III (> 75 days) according to the 75-day interval from surgery to postoperative MRI reexamination. MRI classification and quantitative analysis were performed. Correlation between postoperative time intervals and parameters was analyzed. The difference of parameters between the four groups was analyzed, and diagnostic efficiency was tested by receiver operating characteristic curve. RESULTS: Wash-in rate (WI) and peak enhancement intensity (PEI) were significantly higher in Group I than in Group II (p = 0.003, p = 0.040), while wash-out rate (WO), time to peak (TTP), and normalized signal intensity (NSI) were opposite (p = 0.031, p = 0.007, p = 0.010). Area under curves for discriminating active fistula from healing tissue within 75 days were 0.810 in WI, 0.708 in PEI, 0.719 in WO, 0.783 in TTP, 0.779 in NSI. All MRI parameters were significantly different between Group I and Group IV, but not between Group II and Group III, and not related to time intervals. CONCLUSION: In early postoperative period, DCE-MRI can be used to identify active anal fistula in the surgical area. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033072.


Assuntos
Meios de Contraste , Fístula Retal , Humanos , Imageamento por Ressonância Magnética/métodos , Curva ROC , Fístula Retal/diagnóstico por imagem , Fístula Retal/etiologia , Fístula Retal/cirurgia , Aumento da Imagem/métodos
9.
Pharmacol Res ; 202: 107128, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38438089

RESUMO

The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1. The activation of SREBP1 induced by VA then significantly facilitated the transcription of stearoyl-CoA desaturase 1 (SCD1) to exert an inhibitory effect on ferroptosis. By inhibiting the excessive death of intestinal epithelial cells caused by ferroptosis, VA effectively preserved the integrity of intestinal barrier and prevented the progression of unresolved inflammation. In conclusion, our study demonstrated that VA could alleviate colitis by restoring intestinal epithelium homeostasis through CA9/STIM1-mediated inhibition of ferroptosis, providing a promising therapeutic candidate for UC.


Assuntos
Colite , Ferroptose , Humanos , Animais , Camundongos , Ácido Vanílico , Molécula 1 de Interação Estromal , Colite/induzido quimicamente , Colite/tratamento farmacológico , Homeostase , Mucosa Intestinal , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Anidrase Carbônica IX , Antígenos de Neoplasias , Proteínas de Neoplasias
10.
ChemSusChem ; 17(6): e202301771, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385812

RESUMO

Optimized catalytic properties and reactant adsorption energy played a crucial role in promoting CO2 electrocatalysis. Herein, Cu7S4/Cu underwent in situ dynamic restructuring to generate S-Cu2O/Cu hybrid catalyst for effective electrochemical CO2 reduction to formate that outperformed Cu2O/Cu and Cu7S4. Thermodynamic and in situ Raman spectra revealed that the optimized adsorption of the HCOO* intermediate on S-Cu2O/Cu was regulated and the H2 pathway (surface H) was suppressed by S-doping. Meanwhile, Cu7S4/Cu nanoflowers created abundant boundaries for ECR and strengthened the CO2 adsorption by inducing Cu. These findings provide a new perspective on synthetic methods for various electrocatalytic reduction processes.

11.
Bioact Mater ; 33: 355-376, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38282639

RESUMO

Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis. They are frequently encountered in various creatures, including mammals, plants, and microbes. The aforementioned polymers are commonly derived from renewable sources, possess a notable level of compatibility with living organisms, and have a limited adverse effect on the environment. As a result, they hold considerable significance in the development of sustainable and environmentally friendly goods. In recent times, there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine, specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics. This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades. In this paper, we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers. Furthermore, we summarize the application of natural polymer materials in each stage of skin wound repair. Finally, we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.

12.
Sci Total Environ ; 914: 169844, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190915

RESUMO

The synergistic strategy for fine particulate matter (PM2.5) and O3 pollution prevention and control has emerged as a pivotal approach in combating air pollution. Volatile organic compounds (VOCs) serve as crucial precursors to both O3 and secondary organic aerosols (SOAs), with motor vehicles representing one of their significant sources. In this study, a standard for establishing a database of VOC species emission factors for motor vehicles was developed, and a database containing 134 VOC species was constructed through field tests and literature surveys. The VOC emissions of light-duty gasoline passenger vehicles (LDGPVs) comprised primarily alkanes and aromatics. The VOC emissions of light-duty diesel trucks (LDDTs) comprised mostly alkanes. Regarding low-speed trucks, 3-wheel vehicles, medium-duty diesel trucks (MDDTs) and heavy-duty diesel trucks (HDDTs), their VOC emissions comprised mainly oxygenated volatile organic compounds (OVOCs). The update of emission standards resulted in a reduction in VOC species emission factors while altering the composition of VOCs. Attention should be directed toward isopentane, benzene and dichloromethane emitted by LDGPVs, dodecane, undecane, ethene and propene emitted by LDDTs, and acetaldehyde emitted by HDDTs. VOC species originating from LDGPVs were more dispersed than those originating from LDDTs and HDDTs. In addition, variations in VOC species were observed among motor vehicles with different fuel types. Toluene, ethene, benzene, m,p-xylene, isopentane, hexanal, ethyne and 1,2,4-trimethylbenzene were the predominant VOC species emitted by gasoline vehicles. Diesel vehicles emitted mainly dodecane, formaldehyde, propene, undecane, acetaldehyde, ethene, decane and benzene. The results could enhance our comprehension of the emission characteristics of VOC species originating from motor vehicles and provide data support and a scientific foundation for achieving synergistic PM2.5 and O3 pollution prevention and control.

13.
Curr Neuropharmacol ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38037913

RESUMO

Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.

14.
Front Microbiol ; 14: 1296038, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029146

RESUMO

Introduction: Due to the existence of grass carp reovirus (GCRV), grass carp hemorrhagic disease occurs frequently, and its high pathogenicity and infectivity are great challenges to the aquaculture industry. As a highly pathogenic pathogen, the outbreak of hemorrhagic disease often causes tremendous economic losses. Therefore, it is important to rapidly and accurately detect GCRV on site to control timely. Methods: In this study, recombinant enzyme amplification (RPA) combined with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system was employed to establish a method to detect the vp7 gene of grass carp reovirus type 1. This method can be adopted for judging the results by collecting fluorescence signal, ultraviolet excitation visual fluorescence and test strip. Results: Combined with the RPA amplification experiment, the detection limit of the RPA-CRISPR method can reach 7.2 × 101 copies/µL of vp7 gene per reaction, and the detection process can be completed within 1 h. In addition, this method had no cross-reaction with the other 11 common aquatic pathogens. Then, the performance of the RPA-CRISPR/Cas13a detection method was evaluated by comparing it with the real-time fluorescence quantitative PCR detection method of clinical samples. The results of RPA-CRISPR/Cas13a detection were shown to be in consistence with the results obtained from the real-time fluorescence quantitative PCR detection. The coincidence rate of this method with 26 GCRV clinical samples was 92.31%. Discussion: In summary, this method has high sensitivity, specificity and on-site practicability for detecting GCRV type 1, and has great application potential in on-site GCRV monitoring.

15.
ACS Nano ; 17(20): 19993-20001, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37787582

RESUMO

Inflammatory bowel disease (IBD) is a common inflammatory bowel disease with a high incidence rate and serious consequences. Attempts in this area are focusing on developing efficient delivery systems for relieving IBD. Herein, we present a kind of near-infrared-II (NIR-II)-activated pollen-derived micromotor (PDMM) as an efficient delivery system for treating IBD. These PDMMs are pollen grains with half of them covered by a gold (Au) layer, which can result in an asymmetric thermal gradient around the PDMMs under NIR-II irradiation, thereby forming a thermophoretic force to drive PDMMs to move spontaneously. Besides, the inherent spiny and hollow architectures of pollen grains endowed the PDMMs with outstanding capacity of adherence and drug delivery, respectively. Based on these features, we have demonstrated that the PDMMs could move actively in vivo with the irradiation of NIR-II light and adhere to the surrounding tissues for drug delivery. Thus, the PDMMs loaded with dexamethasone show desirable curative effects on treating IBD. These results indicated that the proposed PDMM-based delivery system has great potential in clinic gastrointestinal administration.


Assuntos
Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos
16.
J Appl Genet ; 64(3): 493-505, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37542613

RESUMO

A-to-I RNA editing is a prevalent type of RNA modification in animals. The dysregulation of RNA editing has led to multiple human cancers. However, the role of RNA editing has never been studied in osteosarcoma, a complex bone cancer with unknown molecular basis. We retrieved the RNA-sequencing data from 24 primary osteosarcoma patients and 3 healthy controls. We systematically profiled the RNA editomes in these samples and quantitatively identified reliable differential editing sites (DES) between osteosarcoma and normal samples. RNA editing efficiency is dramatically increased in osteosarcoma, presumably due to the significant up-regulation of editing enzymes ADAR1 and ADAR2. Up-regulated DES in osteosarcoma are enriched in 3'UTRs. Strikingly, such 3'UTR sites are further enriched in microRNA binding regions of gene EMP2 and other oncogenes, abolishing the microRNA suppression on target genes. Accordingly, the expression of these tumor-promoting genes is elevated in osteosarcoma. There might be an RNA editing-dependent pathway leading to osteosarcoma. We expanded our knowledge on the potential roles of RNA editing in oncogenesis. Based on these molecular features, our work is valuable for future prognosis and diagnosis of osteosarcoma.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Animais , Humanos , MicroRNAs/genética , Edição de RNA/genética , Regulação para Cima/genética , Osteossarcoma/genética , Neoplasias Ósseas/genética , Regiões 3' não Traduzidas/genética , Glicoproteínas de Membrana/genética
17.
Sci Adv ; 9(35): eadh5016, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37647408

RESUMO

Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma cholesterol is a typical feature of Crohn's disease (CD); however, its impact on mucosal healing remains unclear. Here, we identified an essential role of sorting nexin 10 (SNX10) in maintaining the stemness of ISCs. SNX10 expression in intestinal tissues positively correlates with the severity of human CD and mouse colitis. Conditional SNX10 knockout in intestinal epithelial cells or ISCs promotes intestinal mucosal repair by maintaining the ISC population associated with increased intracellular cholesterol synthesis. Disassociation of ERLIN2 with SCAP by SNX10 deletion enhances the activation of SREBP2, resulting in increased cholesterol biosynthesis. DC-SX029, a small-molecule inhibitor of SNX10, was used to verify the druggable potential of SNX10 for the treatment of patients with CD. Our study provides a strategy for mucosal healing through SREBP2-mediated stemness restoration of ISCs.


Assuntos
Doenças Inflamatórias Intestinais , Nexinas de Classificação , Animais , Humanos , Camundongos , Mucosa Intestinal , Intestinos , Nexinas de Classificação/genética , Células-Tronco
18.
Environ Sci Technol ; 57(28): 10308-10318, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37419883

RESUMO

Nonroad agricultural machinery (NRAM) emissions constitute a significant source of air pollution in China. Full-volatility organics originating from 19 machines under 6 agricultural activities were measured synchronously. The diesel-based emission factors (EFs) for full-volatility organics were 4.71 ± 2.78 g/kg fuel (average ± standard deviation), including 91.58 ± 8.42% volatile organic compounds (VOCs), 7.94 ± 8.16% intermediate-volatility organic compounds (IVOCs), 0.28 ± 0.20% semivolatile organic compounds (SVOCs), and 0.20 ± 0.16% low-volatility organic compounds (LVOCs). Full-volatility organic EFs were significantly reduced by stricter emission standards and were the highest under pesticide spraying activity. Our results also demonstrated that combustion efficiency was a potential factor influencing full-volatility organic emissions. Gas-particle partitioning in full-volatility organics could be affected by multiple factors. Furthermore, the estimated secondary organic aerosol formation potential based on measured full-volatility organics was 143.79 ± 216.80 mg/kg fuel and could be primarily attributed to higher-volatility-interval IVOCs (bin12-bin16 contributed 52.81 ± 11.58%). Finally, the estimated emissions of full-volatility organics from NRAM in China (2021) were 94.23 Gg. This study provides first-hand data on full-volatility organic EFs originating from NRAM to facilitate the improvement of emission inventories and atmospheric chemistry models.


Assuntos
Poluentes Atmosféricos , Praguicidas , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Aerossóis/análise
19.
Mater Horiz ; 10(9): 3237-3256, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37278612

RESUMO

The skin serves as the primary barrier between the human body and external environment, and is therefore susceptible to damage from various factors. In response to this challenge, animal tissue-derived biomaterials have emerged as promising candidates for wound healing due to their abundant sources, low side-effect profiles, exceptional bioactivity, biocompatibility, and unique extracellular matrix (ECM) mimicry. The evolution of modern engineering technology and therapies has allowed these animal tissue-derived biomaterials to be transformed into various forms and modified to possess the necessary properties for wound repair. This review provides an overview of the wound healing process and the factors that influence it. We then describe the extraction methods, important properties, and recent practical applications of various animal tissue-derived biomaterials. Our focus then shifts to the critical properties of these biomaterials in skin wound healing and their latest research developments. Finally, we critically examine the limitations and future prospects of biomaterials generated from animal tissues in this field.


Assuntos
Materiais Biocompatíveis , Alicerces Teciduais , Animais , Humanos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Engenharia Tecidual/métodos , Cicatrização/fisiologia , Pele
20.
Sci Total Environ ; 894: 164993, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37343865

RESUMO

Volatile organic compound (VOC) emissions originating from nonroad mobile sources constitute an important but uncertain source of secondary organic aerosols (SOAs) and ozone (O3). In this study, we investigated the emission factors (EFs) of 120 individual VOC species for 40 machines via gas chromatography-mass spectrometry/flame ionization detection and high-performance liquid chromatography. The results showed that the diesel-based VOC EF for the tested machines was 4.18 ± 2.55 (average ± standard deviation) g/kg fuel, dominated by alkanes (38.20 % ± 18.08 %) and oxygenated VOCs (OVOCs; 30.94 % ± 15.71 %). The machine type, rated power, emission standards, and operating conditions affected the emissions of VOCs and their components, and this effect maybe mostly depends on the fuel combustion efficiency. The VOC species were primarily distributed in the C1-C2 and C4-C6 (based on the carbon number) and B4-B6 (based on the saturated vapor concentration) intervals. Furthermore, the estimated formation potential (FP) values of SOAs and O3 from VOCs were 21.02 ± 15.57 mg/kg fuel and 15.96 ± 11.87 g/kg fuel, respectively. VOC control based on the SOA formation potential (SOAFP) and ozone formation potential (OFP) could be more effective in the mitigation of fine particulate matter (PM2.5) and O3 pollution because the top 5 species ranked by percentage contribution accounted for 83.09 % ± 9.59 % and 51.78 % ± 14.38 % of the estimated SOAFP and OFP, respectively. Finally, the emission estimates showed that the VOC emissions originating from construction and agricultural machinery in China (2020) reached 64.05 and 95.24 Gg, respectively. We provide species-specific VOC EFs and detailed emission characteristics to facilitate a comprehensive understanding of gas emissions originating from nonroad mobile sources and an update of emission inventories and atmospheric chemistry models.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA