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1.
Arch Virol ; 169(5): 96, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619633

RESUMO

In recent years, the pig industry in Xinjiang, China, has been severely impacted by outbreaks of porcine epidemic diarrhea (PED), despite vaccination efforts. In this study, we investigated the genetic characteristics of currently prevalent porcine epidemic diarrhea virus (PEDV) strains in the region. We collected 548 samples from animals with suspected PED on large-scale pig farms in Xinjiang. Of these, 258 tested positive for PEDV by RT-PCR, yielding an overall positivity rate of 47.08%. S1 gene sequencing and phylogenetic analysis were conducted on 23 randomly selected RT-PCR-positive samples. Three endemic strains of PEDV (PEDV/CH/XU/2020, PEDV/CH/XK/2020, and PEDV/CH/XA/2020) were isolated, and their complete genome sequences were analyzed for evidence of genetic recombination. Sequence comparison of the S gene indicated significant variations in the S1 gene of the Xinjiang strains compared to the vaccine strains CV777, AJ1102, and LWL, with 90.2%-98.5% nucleotide sequence identity. Notably, both the N-terminal and C-terminal domains of the S protein showed significant variation. Genetic evolutionary analysis identified the GIIa subtype as the dominant genotype among the epidemic strains in Xinjiang. Recombination analysis revealed inter-subtype recombination events in the PEDV/CH/XK/2020 and XJ1904-34 strains. These findings highlight the extensive genetic variation in the predominant GIIa genotype of PEDV in Xinjiang, which does not match the genotype of the currently used vaccine strains. These data may guide further efforts toward the development of effective vaccines for the control of PED.


Assuntos
Disenteria , Vírus da Diarreia Epidêmica Suína , Vacinas , Animais , Suínos , Filogenia , Vírus da Diarreia Epidêmica Suína/genética , Evolução Biológica , China/epidemiologia
2.
J Ethnopharmacol ; 329: 118146, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604512

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa Ledeb. (Rosaceae, A. pilosa) has been used in traditional medicine in China, Japan, Korea, and other Asian countries for treatment of acute and chronic enteritis and diarrhea. Secondary metabolites have been isolated and tested for biological activities. It remains unclear in terms of its potential components of anti-colorectal cancer properties. AIM OF THE STUDY: The study aimed to how extracts from A. pilosa and their components influenced tumor microenvironment and the colorectal tumor growth in vivo on AOM/DSS induced colorectal cancer mice, the metabolites of A. pilosa was also been studied. MATERIALS AND METHODS: Different methods have been used to extract different parts of A. pilosa. And the anti-proliferation effect of these extracts on colon cancer cells have been tested. The components of A. pilosa and its metabolites in vivo were analyzed by UPLC-QTOF-MS/MS. The anti-colorectal cancer (CRC) effects of A. pilosa and its components in vivo were studied on AOM/DSS induced CRC mice. The effects of constituents of A. pilosa on the composition of immune cells in tumor microenvironment (TME) were analyzed by flow cytometry. 16 S rDNA technology was used to analyze the effect of administration on the composition of intestinal microflora. Pathological section staining was used to compare the morphological changes and molecular expression of intestinal tissue in different groups. RESULTS: The constituent exists in root of A. pilosa showed the strongest anti-proliferation ability on colon cancer cells in vitro. The extract from the root of A. pilosa could attenuate the occurrence of colorectal tumors induced by AOM/DSS in a concentration-dependent manner. Administration of the extract from the root of A. pilosa could affect the proportion of γδT cells, tumor associated macrophages and myeloid derived suppressor cells in TME, increasing the proportion of anti-tumor immune cells and decrease the immunosuppressive cells in the TME to promote the anti-tumor immune response. The administration of the extract adjusted the composition of gut microbiota and its components Agrimoniin and Agrimonolide-6-o-glucoside showed the strongest anti-CRC effect in vivo with adjusting the gut microbiota differently. CONCLUSIONS: The extract from root of A. pilosa showed anti-colorectal cancer effects in vivo and in vitro, affecting the composition of gut microbiota and the anti-tumor immune response. Within all components of A. pilosa, Agrimoniin and Agrimonolide-6-o-glucoside showed remarkable anti-CRC efficiency in vivo and in vitro. Besides, the metabolites of extract from root of A. pilosa in gastrointestinal tract mainly composed of two parts: Agrimonolide-related metabolites and Urolithins. The extract from root of A. pilosa could contribute to potential drugs for assisting clinical anti-colon cancer therapy.

3.
Medicine (Baltimore) ; 103(8): e37175, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394482

RESUMO

Recent epidemiological research suggests a possible negative correlation between Helicobacter pylori infection and inflammatory bowel disease (IBD). However, conflicting studies have provided unclear evidence regarding these causal relationships. Therefore, recommending specific prevention and treatment strategies for H. pylori infection and IBD is challenging. We used various antibodies (anti-H. pylori IgG, VacA, and GroEl) related to H. pylori infection as indicators. We acquired relevant genetic variants from public databases within the Genome-wide Association Studies (GWAS) dataset using IBDs tool variables from 2 different GWAS datasets. We thoroughly examined the data and screened for IVs that fulfilled these criteria. Subsequently, Bidirectional Mendelian randomization (MR) was conducted to predict the potential causality between the 2. To ensure the accuracy and robustness of our results, we conducted a series of sensitivity analyses. Based on our comprehensive MR analysis, no potential causal relationship was observed between H. pylori infection and IBD. Across various methodologies, including IVW, MR-Egger, and weighted median, our findings showed P values > .05. The only exception was observed in the reverse MR analysis using the MR-Egger method, which yielded a P value of < .05. However, because the IVW method is considered the most statistically significant method for MR, and its P value was > .05, we do not believe that a potential causal relationship exists between them. Our sensitivity analysis did not suggest significant horizontal pleiotropism. Although heterogeneity was detected in the analysis of IBD (IIBDGC source) versus H. pylori GroEL antibody levels (MR-Egger, Qp = 0.038; IVW, Qp = 0.043), the results remained reliable because we selected IVW as a random-effects model in our MR analysis method. Based on our MR research, no direct correlation was observed between H. pylori infection and IBD risk. This implies that eradicating H. pylori may not provide substantial benefits in preventing or treating regional IBD, and vice versa. Nevertheless, the use of H. pylori serological index substitution has limitations, and further research using histological diagnosis and additional MR studies is required to comprehensively assess the link between H. pylori infection and IBD.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Doenças Inflamatórias Intestinais , Humanos , Estudo de Associação Genômica Ampla , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/genética , Análise da Randomização Mendeliana , Anticorpos Antibacterianos , Doenças Inflamatórias Intestinais/genética
4.
Int Immunopharmacol ; 129: 111578, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38330795

RESUMO

BACKGROUND: Maintenance therapy (MT) for recurrent or metastatic cervical cancer remains non-standardized. This study assessed MT effectiveness using a comprehensive approach and identifies prognosis factors inpatients with recurrent or metastatic cervical cancer. METHODS: From January 2019 and December 2021, over 6000 patients from six Chinese institutions were retrospectively examined. Patients had recurrent/metastatic cervical cancer and underwent first-line chemotherapy with or without MT. We calculated overall and progression-free survival using Kaplan-Meier analysis, comparing via log-rank test, and conducted Cox regression for prognostic factors. RESULTS: Overall, 274 patients were stratified into an MT group (n = 77) and a non-MT group (n = 197). The 3-year OS rates were 52.5 % and 28.0 % for the MT and non-MT groups, respectively. The MT group had significantly enhanced median OS (37 vs. 21 months; HR, 0.43; 95 % CI, 0.30-0.61; P < 0.001) and PFS (21 vs. 14 months; HR, 0.65; 95 % CI, 0.47-0.90; P = 0.014) compared with the non-MT group. No significant differences in efficacy were observed among the various MT regimens, whether PD-1 monoclonal antibody, targeted therapeutic agents, or a combination of both. Extended PFS and OS were observed in patients receiving > 8 MT cycles. Multivariate analyses revealed that oligometastasis, MT, exclusive prior surgery (as opposed to combined surgery and radiotherapy), and extended interval before recurrence were independent OS predictors (P = 0.045, P < 0.001, P = 0.010, and P = 0.005, respectively); oligometastasis, concurrent radiotherapy, MT, and extended interval before recurrence were independent PFS predictors (P = 0.004, P = 0.007, P = 0.009, and P = 0.003). CONCLUSIONS: The MT integration markedly extended PFS and OS in patients diagnosed with recurrent or metastatic cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão
5.
J Minim Access Surg ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38214313

RESUMO

ABSTRACT: Post-operative bile leakage (POBL) is a serious complication following hepatobiliary surgery, with potentially life-threatening consequences if left untreated. This article presents a successful case of POBL management without surgical intervention. A 31-year-old male, diagnosed with bile leakage before hospitalisation, underwent percutaneous biliary drainage (PTBD) to address bilomas. Follow-up after 3 months indicated biloma atrophy and POBL healing but revealed bile duct stenosis. The patient received a larger biliary drainage tube, and after 1 month, the biloma and tube were removed. A 1-year follow-up confirmed the patient's excellent health. This case underscores the safety and efficacy of PTBD for managing POBL, offering a non-invasive alternative for patients with this complication. PTBD presents a viable treatment option for POBL cases, minimising the need for surgical interventions and their associated risks.

6.
Cell Mol Life Sci ; 81(1): 69, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294557

RESUMO

Fibrosis is a typical aging-related pathological process involving almost all organs, including the heart, kidney, liver, lung, and skin. Fibrogenesis is a highly orchestrated process defined by sequences of cellular response and molecular signals mechanisms underlying the disease. In pathophysiologic conditions associated with organ fibrosis, a variety of injurious stimuli such as metabolic disorders, epigenetic changes, and aging may induce the progression of fibrosis. Sirtuins protein is a kind of deacetylase which can regulate cell metabolism and participate in a variety of cell physiological functions. In this review, we outline our current understanding of common principles of fibrogenic mechanisms and the functional role of SIRT3/6 in aging-related fibrosis. In addition, sequences of novel protective strategies have been identified directly or indirectly according to these mechanisms. Here, we highlight the role and biological function of SIRT3/6 focus on aging fibrosis, as well as their inhibitors and activators as novel preventative or therapeutic interventions for aging-related tissue fibrosis.


Assuntos
Sirtuína 3 , Sirtuínas , Humanos , Fígado , Fibrose
7.
Nat Neurosci ; 27(1): 116-128, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38012399

RESUMO

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.


Assuntos
Transtorno do Espectro Autista , Edição de Genes , Animais , Camundongos , Masculino , Transtorno do Espectro Autista/genética , Encéfalo , Mutação/genética , Fatores de Transcrição MEF2/genética
8.
J Biophotonics ; 17(1): e202300094, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37774123

RESUMO

The decreasing correlation of optical coherence tomography (OCT) images with depth is an unavoidable problem for the depth measurement of the digital volume correlation (DVC) based optical coherence elastography (OCE) method. We propose an OCE-DVC method to characterize biological tissue deformation in deeper regions. The method proposes a strategy based on reliability layer guided displacement tracking to achieve the OCE-DVC method for the deformation measurement in deep regions of OCT images. Parallel computing solves the computational burden associated with the OCE-DVC method. The layer-by-layer adaptive data reading methods are used to guarantee the parallel computing of high-resolution OCT images. The proposed method shown in this study nearly doubles the depth of quantitative characterization of displacement and strain. At this depth, the standard deviation of displacement and strain measurements is reduced by nearly 78%. Under nonuniform deformation field, OCE-DVC method tracked the displacement with large strain gradient in depth region.


Assuntos
Técnicas de Imagem por Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Reprodutibilidade dos Testes , Tomografia de Coerência Óptica/métodos
9.
Int J Mol Sci ; 24(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38139310

RESUMO

The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal regenerative microenvironment and capable of accommodating intricate root canal systems. This study utilized porcine dental pulp to derive the decellularized extracellular matrix (dECM) via appropriate decellularization protocols. The resultant dECM was dissolved in an acid pepsin solution to form dECM hydrogels. The analysis encompassed evaluating the microstructure and rheological properties of dECM hydrogels and evaluated their biological properties, including in vitro cell viability, proliferation, migration, tube formation, odontogenic, and neurogenic differentiation. Gelatin methacrylate (GelMA) hydrogel served as the control. Subsequently, hydrogels were injected into treated dentin matrix tubes and transplanted subcutaneously into nude mice to regenerate dental pulp tissue in vivo. The results showed that dECM hydrogels exhibited exceptional injectability and responsiveness to physiological temperature. It supported the survival, odontogenic, and neurogenic differentiation of dental pulp stem cells in a 3D culture setting. Moreover, it exhibited a superior ability to promote cell migration and angiogenesis compared to GelMA hydrogel in vitro. Additionally, the dECM hydrogel demonstrated the capability to regenerate pulp-like tissue with abundant blood vessels and a fully formed odontoblast-like cell layer in vivo. These findings highlight the potential of porcine dental pulp dECM hydrogel as a specialized scaffold material for dental pulp regeneration.


Assuntos
Matriz Extracelular Descelularizada , Hidrogéis , Camundongos , Animais , Suínos , Hidrogéis/farmacologia , Hidrogéis/química , Polpa Dentária , Camundongos Nus , Regeneração , Tecidos Suporte/química , Engenharia Tecidual/métodos , Matriz Extracelular
10.
Sheng Wu Gong Cheng Xue Bao ; 39(12): 4915-4926, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38147991

RESUMO

A simple, fast, and visual method for detecting antibodies against peste des petits ruminants virus (PPRV) using colloidal gold strips was developed. In this study, the pET-32a-N was transformed into Escherichia coli Rosetta (DE3) for expression. Hybridoma cell lines were generated by fusing SP2/0 myeloma cells with splenocytes from immunized mice with the expressed and purified N protein of PPRV. The PPRV N protein was labeled with colloidal gold particles as the gold-labeled antigen. The N protein served as the gold standard antigen and as the test (T) line-coated antigen, while the monoclonal antibody served as the quality control (C) line-coated antibody to assemble the colloidal gold immunochromatographic test strips for detecting antibodies against the N protein of PPRV. Hybridoma cell line designated as 1F1 was able to stably secrete the monoclonal antibody against the N protein of PPRV. The titer of 1F1 monoclonal antibody in ascites was 1:128 000 determined by indirect enzyme-linked immunosorbent assays (ELISA), and the immunoglobulin subtype of the monoclonal antibody was IgG1, with kappa chain. The obtained monoclonal antibody was able to specifically recognize the N protein of PPRV, as shown by Western blotting and indirect immunofluorescent assay (IFA). The developed colloidal gold test strip method was able to detect PPRV antibodies specifically, and there was no difference between different batches of the test strips. Testing of a total of 122 clinical sera showed that the compliance rate of the test strip with ELISA test was 97.6%.The test strip assay developed in this study has good specificity, reproducibility, and sensitivity, and it can be used for the rapid detection of PPRV antibodies.


Assuntos
Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Animais , Camundongos , Peste dos Pequenos Ruminantes/diagnóstico , Peste dos Pequenos Ruminantes/prevenção & controle , Anticorpos Monoclonais , Reprodutibilidade dos Testes , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Cabras
11.
PLoS One ; 18(10): e0293284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37871103

RESUMO

This paper empirically investigates the impact mechanism of short-term debt for long-term use and the default risk of supply chain firms with the data of Chinese A-share listed firms from 2007 to 2021. The study shows that there is a significant U-curve relationship between short-term debt for long-term use and supply chain firms' default risk, and too high or too low a level of short-term loans and long-term investments will worsen firms' default risk. In addition, firm performance plays an mediating effect in the process of short-term debt for long-term investment affecting the default risk of supply chain firms. Finally, customer effect and firm heterogeneity play a moderating role in the impact of short-term loans and long-term investments on the default risk of supply chain firms, and the U-shaped relationship will be strengthened under the high-intensity customer effect. This study has important theoretical and practical significance for analyzing the impact of default risk contagion in supply chain enterprises.


Assuntos
Comércio , Indústrias , Investimentos em Saúde , China , Investimentos em Saúde/economia , Comércio/economia , Indústrias/economia
12.
Nucleic Acids Res ; 51(20): e105, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37843111

RESUMO

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells. We then perform deaminase engineering for two deaminases lamprey LjCDA1 and human APOBEC3A, and generate divergent CBE variants with eliminated DSB-associated DNA damage risks, in addition to minimized DNA/RNA off-target edits. Furthermore, the editing scopes and sequence preferences of APOBEC3A-derived CBEs could be further diversified by internal fusion strategy. Taken together, this study provides updated evaluation platform for DSB-associated DNA damage risks of CBEs and further generates a series of safer toolkits with diversified editing signatures to expand their applications.


Assuntos
Citosina , Edição de Genes , Humanos , RNA/genética , Dano ao DNA , DNA/genética , Sistemas CRISPR-Cas
13.
J Virol Methods ; 321: 114809, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37683936

RESUMO

Peste des petits ruminants virus (PPRV) causes a very devastating disease in sheep and goats. Rapid diagnosis and immunisation have been identified as key strategies for successful prevention of the disease. Therefore, a sensitive fluorescent microsphere immunochromatography test strips (FM-ICTS) was developed for rapid detection of special antibodies of PPRV in goats and sheep serum. The FM-ICTS were successfully prepared by fluorescent microspheres (FM) as tracer, which were covalently coupled to PPRV nucleocapsid protein (NP). The NP and monoclonal antibody of NP were separately dispensed onto a nitrocellulose membrane as test and quality control lines, respectively. The critical threshold for determining negative or positive through the ratio of the fluorescent signal of the test line and the control line (T/C) is 0.050. The repeatability of the FM-ICTS was excellent, with an overall average CV of 3.17 %. The detection limit of this assay was 1:5120. Additionally, the FM-ICTS no cross reaction with the sera of other related diseases was observed, only reacting with anti-PPRV serum. 70 serum samples were tested by FM-ICTS and commercial ELISA kit, and the results showed good agreement. Overall, a promising pen-side diagnostic tool was developed for the rapid qualitatively/semi-quantitatively detection of PPRV antibodies within 15 min.


Assuntos
Elementos da Série dos Lantanídeos , Ruminantes , Ovinos , Animais , Microesferas , Anticorpos Antivirais , Cabras , Corantes , Cromatografia de Afinidade , Proteínas do Nucleocapsídeo
14.
Fitoterapia ; 171: 105687, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37769998

RESUMO

Two new and six known ent-pimaranes were isolated from Flickingeria fimbriata. One of them possesses a rare carbon skeleton. It is the first time such a compound with this specific carbon skeleton has been isolated from a natural source. The structure and absolute configuration were determined by NMR, MS, and X-ray diffraction analysis. The biosynthetic pathway of the rare skeleton was proposed and suggested a new pathway for these nor-ent-pimarane analogues. All isolated compounds were screened for inhibitory activity against acetylcholinesterase (AChE). The compound 4 exhibits potent inhibitory effect on AChE with the 50% inhibitory concentration (IC50) being 5.8 µM, which is close to that of the positive control (Huperzine A). This is the first report about inhibitory activity on AChE of ent-pimaranes.


Assuntos
Abietanos , Dendrobium , Abietanos/farmacologia , Acetilcolinesterase , Estrutura Molecular , Carbono , Inibidores da Colinesterase/farmacologia
15.
Cancer Med ; 12(19): 19744-19757, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37766594

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR-B1), a multi-ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR-B1 in CRC development has not been reported. AIMS: This study aimed to clarify the importance of SR-B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. MATERIALS & METHODS: In this study, we used SR-B1 gene knockdown mice to study the effect of SR-B1 on colitis-induced or APCmin/+ -induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin-eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high-throughput sequencing. RESULTS: The results showed that SR-B1 knockdown reduced the tumor load of colitis-induced or APCmin/+ -induced CRC. SR-B1 knockdown improved the immune microenvironment by affecting the level of tumor-associated macrophage (TAM), mononuclear myeloid-derived suppressor cells (M-MDSCs), granulocytic myeloid-derived suppressor cells (G-MDSCs), programmed cell death-ligand 1 (PD-L1), and human leukocyte antigen class I-B (HLA-B), and also reduced the level of low-density lipoprotein receptor (LDL-R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR-B1 knockdown can also trigger the anti-CRC effect of anti-PD 1 in colitis-induced CRC. DISCUSSION: SR-B1 deficiency significantly improved the immunity in tumor microenvironment of colitis-induced or APCmin/+ -induced CRC. In addition, the microbiota changes caused by SR-B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti-PD1 therapy. The mechanism of action of SR-B1 deficiency on the development of CRC still needs further in-depth research. CONCLUSION: This study provides a new treatment strategy for treating CRC by affecting the expression of SR-B1 in intestine.


Assuntos
Colite , Neoplasias Colorretais , Receptores Depuradores Classe B , Animais , Humanos , Camundongos , Colesterol/metabolismo , Colite/complicações , Colite/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ligantes , RNA Ribossômico 16S , Carga Tumoral , Microambiente Tumoral , Receptores Depuradores Classe B/genética
16.
Clin Transl Med ; 13(8): e1339, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37496319

RESUMO

BACKGROUND: The incidence of renal cell carcinoma (RCC) has increased in recent years. Metastatic RCC is common and remains a major cause of mortality. A regulatory role for circular RNAs (circRNAs) in the occurrence and progression of RCC has been identified, but their function, molecular mechanisms, and potential clinical applications remain poorly understood. METHODS: High-throughput RNA sequencing was used to explore the differential expression of circRNAs and their related pathways in RCC patients. Transwell and CCK-8 assays were used to assess the function of hsa_circ_0057105 in RCC cells. The clinical relevance of hsa_circ_0057105 was evaluated in a cohort of RCC patients. The hsa_circ_0057105 regulatory axis was defined using RNA pull-down, luciferase reporter assays, and fluorescence in situ hybridization assays, and the in vivo effect of hsa_circ_0057105 was validated using animal experiments. RESULTS: Single-sample gene set enrichment analysis and correlation analysis of RNA-seq data showed that hsa_circ_0057105 was potentially oncogenic and may serve to regulate epithelial-mesenchymal transition (EMT) activation in RCC. Hsa_circ_0057105 expression was associated with advanced TNM stages and was an independent prognostic factor for poor RCC patient survival. Phenotypic studies show that hsa_circ_0057105 can enhance the migration and invasion abilities of RCC cells. Further, hsa_circ_0057105 was shown to inhibit the expression of miR-577, a miRNA that regulated the expression of both COL1A1, which induced EMT activation, and VDAC2, which modulated ferroptosis sensitivity. The dual regulatory roles of hsa_circ_0057105 on EMT and ferroptosis sensitivity were verified using rescue experiments. Animal studies confirmed that hsa_circ_0057105 increased the metastatic ability and ferroptosis sensitivity of RCC cells in vivo. CONCLUSIONS: In RCC, hsa_circ_0057105 regulates COL1A1 and VDAC2 expression through its sponge effect on miR-577, acting like a 'double-edged sword'. These findings provide new insight into the relationship between EMT and ferroptosis in RCC and provide potential biomarkers for RCC surveillance and treatment.


Assuntos
Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , MicroRNAs , Animais , Carcinoma de Células Renais/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Ferroptose/genética , Transição Epitelial-Mesenquimal/genética , Hibridização in Situ Fluorescente , MicroRNAs/genética , Neoplasias Renais/metabolismo
17.
Orthop J Sports Med ; 11(6): 23259671231168894, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37332534

RESUMO

Background: Mechanoreceptors in the posterior cruciate ligament (PCL) can produce proprioception, which is an important reason why patients choose cruciate-retaining total knee arthroplasty (TKA). The number of mechanoreceptors in the PCL of patients with knee osteoarthritis (OA) is unknown. Purpose: To provide a theoretical basis for estimating the number of mechanoreceptors in the PCL by evaluating the relationship between this number and patient age or OA severity. Study Design: Cross-sectional study; Level of evidence, 3. Methods: An overall 28 PCLs from patients with knee OA were collected at the time of TKA and grouped according to patient age (group A, 60-69 years [n = 8]; group B, 70-79 years [n = 12]; group C, ≥80 years [n = 8]) and OA based on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (group I, ≤80 [n = 8]; group II, 81-120 [n = 10]; group III, >120 [n = 10]). Hematoxylin and eosin and S-100 immunohistochemical staining were performed on the slices near the tibial attachment of the PCL, and the number of mechanoreceptors in each slice was counted. Multifactor analysis of variance was used to evaluate the relationship between the number of mechanoreceptors and patient age or WOMAC score. Results: The number of mechanoreceptors (mean ± SD) in groups A, B, and C was 24.00 ± 15.19, 30.92 ± 11.41, and 23.38 ± 11.39, respectively, with no significant between-group differences. The number of mechanoreceptors in groups I, II, and III was 43.50 ± 4.99, 25.00 ± 5.27, and 15.20 ± 5.61, with significant differences between groups I and II, groups I and III, and groups II and III (P < .001 for all). Conclusion: In patients with knee OA, age had no significant effect on mechanoreceptor count, but the number of mechanoreceptors in the PCL decreased significantly with higher (worse) WOMAC score. These findings suggest that in patients of any age with high WOMAC scores, there may be little value as it relates to knee proprioception in performing a PCL-retaining TKA.

18.
Sci Total Environ ; 895: 165071, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37356767

RESUMO

Global climate change is expected to further intensify the global water cycle, leading to more rapid evaporation and more intense precipitation. At the same time, the growth and expansion of natural vegetation caused by climate change and human activities create potential conflicts between ecosystems and humans over available water resources. Clarifying how terrestrial ecosystem evapotranspiration responds to global precipitation and vegetation facilitates a better understanding of and prediction for the responses of global ecosystem energy, water, and carbon budgets under climate change. Relying on the spatial and temporal distribution of evapotranspiration, precipitation, and solar-induced chlorophyll fluorescence (SIF) from remote sensing platforms, we decouple the interaction mechanism of evapotranspiration, precipitation, and vegetation in linear and nonlinear scenarios using correlation and partial correlation analysis, multiple linear regression analysis, and binning. Major conclusions are as follows: (1) As a natural catalyst of the global water cycle, vegetation plays a crucial role in regulating the relationship between climate change and the water­carbon-energy cycle. (2) Vegetation, a key parameter affecting the water cycle, participates in the entire water cycle process. (3) The increase in vegetation productivity and photosynthesis plays a dominant role in promoting evapotranspiration in vegetated areas, while the increase in precipitation dominates the promotion of evapotranspiration in non-vegetated areas.

19.
Eur Thyroid J ; 12(3)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36944106

RESUMO

Background: Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors. Methods: A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed. Results: All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561-4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232-0.879). Conclusion: GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.


Assuntos
Antitireóideos , Doença de Graves , Humanos , Criança , Antitireóideos/uso terapêutico , Estudos Retrospectivos , População do Leste Asiático , Doença de Graves/diagnóstico , Recidiva
20.
Plant Dis ; 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36916847

RESUMO

Red clover (Trifolium pratense) is becoming increasingly important in grassland systems (sheep and beef) due to its high productivity, protein content and nitrogen-fixing ability which allows lower N fertilizer use (Murray et al. 2007). In June 2021, an unidentified foliar disease occurred seriously in experimental fields of red clover (25.61°N, 102.48°E) in Kunming city, Yunnan Province, China. Disease incidence was approximately 55% with an average disease severity of 41.1% in the fields (about 1.5 ha). Initially, the symptoms consisted of cicular to oval leaf spots with dark brown edges. In severely diseased plots, the diseased spots continued to expand and fuse along the leaf veins, forming long and narrow leaf spots, and the middle of the leaves were decayed and hollow. To isolate the pathogen, small pieces (3×3 mm) from the margin of infected lesions were surface-sterilized in 75% ethanol solution for 30 s, 1% NaClO solution for 90 s, rinsed three times with sterilized distilled water, air dried, and plated onto potato dextrose agar (PDA). The same fungus was isolated in 90% of the samples and purified by transferring the hyphal tip from the edge of colonies to fresh PDA plates. The colonies produced relatively dense light-grayish aerial mycelium in the early stage, which turned grayish upon mature, and then dark brown on the back of the colonies with dense small black patches. Conidiophores were unbranched, straight or flexuous, accompanied by slight or obvious swelling of its apical cells. Conidia were olive brown, irregularly round, 1 to 3 transverse septa, 0 to 2 longitudinal or oblique septa, and measured 16.0 - (24.8)- 30.1 × 13.9 - (21.4) - 28.6 µm (n = 50). Morphological characteristics were consistent with those described for Stemphylium vesicarium (Simmons, 1967). For molecular identification, total genomic DNA was isolated from mycelia collected from 6 day-old colonies of three representative isolates LZQF-1-LZQF-3 using the Omega D3195 fungal genomic DNA extraction kit. Fragments of three genes, including those encoding the ITS region of rDNA, calmodulin gene (cmdA), and glyceraldehyde-3-phosphate dehydrogenase (gpd) regions of isolates LZQF-1-LZQF-3 were amplified by the primers described previously (Woudenberg et al. 2017) and sequenced. Resulting sequences of representative strain LZQF-1 were deposited in GenBank with accession numbers of OL615093 (ITS), OL624541 (cmdA) and OL624538 (gpd), respectively. A nucleotide BLAST search revealed ITS, cmdA and gpd sequences to be 100%, 100% and 99.0% similar to the corresponding sequences (accessions numbers KU850563.1, KU850853.1 and KU850710.1) of ex-type strain CBS 370.51 of S. vesicarium. The three locus datasets were combined by SequenceMatrix 1.8 (Vaidya et al. 2011), and the strain LZQF-1-LZQF-3 and S. vesicarium (CBS 192.86, CBS 370.51 and CBS 205.82) formed a subclade with 99% bootstrap support. Pathogenicity tests were performed on LZQF-1 in a greenhouse at 18 °C-26 °C with 75% relative humidity. Three pots each containing three 50-day-old red clover were sprayed with the conidial suspension (3 × 105 conidia/ml) while another three pots were sprayed with sterile water as a control. Two weeks later, the inoculated leaves showed oval leaf spots with dark brown edges, distinctive symptoms of S. vesicarium infection. S. vesicarium was reisolated and confirmed by morphological and molecular features. There were no symptoms on the control leaves. S. vesicarium as a pathogen causing leaf spot disease has been reported on red clover in Canada (Jasalavich et al. 1995) and in Russia (Babuschkina et al. 1995). To our knowledge, this is the first report of leaf spot of red clover caused by S. vesicarium in China. The identification of Stemphylium leaf spot lays the groundwork for future investigations into epidemiology and management of S. vesicarium on red clover.

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