Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 134
Filter
1.
Food Sci Nutr ; 12(5): 3225-3236, 2024 May.
Article in English | MEDLINE | ID: mdl-38726419

ABSTRACT

Hepatic polypeptide nutrient solution (HP) is a mixture of hepatoprotective peptides derived from fresh porcine liver with various effects. However, the role and mechanisms of HP in nonalcoholic fatty liver disease (NAFLD) are still not well understood. We investigated the effects of HP NAFLD rats induced by high-cholesterol diet (HCD) and its underlying mechanisms. Rats were provided with HCD for 4 weeks and then received HP or metformin after 2 weeks of HCD feeding. The study found that HP reduced cholesterol and triglyceride levels in rats with NAFLD (all p < .05). Histopathological examination also showed that HP improved the liver lesions induced by the HCD diet. Furthermore, the oxidative stress and inflammatory responses of NAFLD rats treated with HP were also improved. In addition, it was discovered that HP triggered the activation of AMPK and decreased the expression of SREBP-1c and FAS while enhancing the expression of PPAR α and CPT-1 in liver. These findings indicated that HP might have therapeutic potential for NAFLD, possibly via activating AMPK signaling pathway.

2.
Food Chem ; 452: 139355, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38733679

ABSTRACT

Differently colored foxtail millet (Setaria italica) cultivars were compared regarding their amylose, B-complex vitamin, vitamin E, and phenolic compositions, as well as the bioaccessibility of their phenolics in simulated in vitro digestion. Dark-colored foxtail millets contained more thiamine, pyridoxine, and tocopherols, but less riboflavin, than light-colored ones. Phenolics were more abundant in dark-colored cultivars. Insoluble bound fractions accounted for 75%-83% of the total phenolics, with ferulic acid detected as the most plentiful compound. The major bioaccessible phenolic was free ferulic acid, with 100%-120% bioaccessibility, depending on cultivar, followed by p-coumaric acid and isoferulic acid (50%-80%). These relatively high bioaccessibilities were likely due to the release of soluble conjugated or insoluble bound phenolics during digestion. However, the contents of other free phenolics were largely decreased following in vitro digestion, resulting in low bioaccessibility, which also means that the release from the conjugated and bound fractions was poor.


Subject(s)
Digestion , Phenols , Setaria Plant , Phenols/metabolism , Phenols/chemistry , Phenols/analysis , Setaria Plant/chemistry , Setaria Plant/metabolism , Plant Extracts/chemistry , Plant Extracts/metabolism , Biological Availability , Models, Biological
3.
Front Cell Dev Biol ; 12: 1384450, 2024.
Article in English | MEDLINE | ID: mdl-38638528

ABSTRACT

Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients' tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.

5.
Sci Total Environ ; 923: 171456, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38442758

ABSTRACT

Although traditional organophosphate esters (OPEs) in soils have attracted widespread interest, there is little information on novel OPEs (NOPEs), especially in facility agriculture soils. In this work, we surveyed 11 traditional OPEs, four NOPEs, and four corresponding organophosphite antioxidant precursors (OPAs) for the NOPEs in soil samples collected from facility greenhouses and open fields. The median summed concentrations of traditional OPEs and NOPEs were 14.1 µg/kg (range: 5.38-115 µg/kg) and 702 µg/kg (range: 348-1952 µg/kg), respectively, in film-mulched soils from greenhouses. These concentrations were much higher than those in soils without mulch films, which suggests that OPEs in soils are associated with plastic mulch films. Tris(2,4-di-tert-butylphenyl) phosphate, which is a NOPE produced by oxidation of (2,4-di-tert-butylphenyl) phosphite, was the predominant congener in farmland soils, with concentrations several orders of magnitude greater than those of traditional OPEs. Comparisons of OPEs in different mulch films and the corresponding mulched soils revealed that degradable and black films caused more severe pollution than polyethylene and white films. Traditional OPEs, including tris(2-ethylhexyl) phosphate and tricresyl phosphate, exhibited moderate risks in farmland soils, especially in film-mulched soils. NOPEs, including trisnonylphenol phosphate, posed high ecological risks to the terrestrial ecosystem. Risk evaluations should be conducted for a broad range of NOPEs in the environment.


Subject(s)
Flame Retardants , Soil , Beijing , Ecosystem , Environmental Monitoring , Esters , Organophosphates , China , Phosphates , Agriculture , Flame Retardants/analysis
6.
Sci Total Environ ; 922: 171228, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38402974

ABSTRACT

UV-320 is classified as a Substance of Very High Concern (SVHC) by the European Chemicals Agency and has attracted significant attention due to its presence in the environment. Understanding the uptake, translocation and metabolic patterns of UV-320 in vegetables is essential for assessing their ability to bioaccumulate and potential risks to human health. In this study, we investigated the uptake and translocation of UV-320 in lettuce and radish by hydroponic experiments. The results showed that the root concentration factors (Croot/Csolution, RCF) of lettuce and radish were in the range of 47.9 to 464 mL/g and 194 to 787 mL/g, respectively. The transfer factors (Cshoot/Croot, TF) were observed to be 0.001-0.012 for lettuce and 0.02-0.05 for radish. Additionally, non-targeted screening identified twelve phase I and one phase II metabolites of UV-320 in vegetables, which were confirmed based on their molecular formulas and structures. The metabolic pathways involving oxidation, ketonylation and deamination were proposed in vegetables. Also, we have observed that UV-320 inhibits the growth of vegetables. Meanwhile, we evaluated the health risk of UV-320 in lettuce and radish and found that the consumption of lettuce is relatively safe, while the consumption of radish has a risk of HQ >1 for both adults and children, which should be seriously considered. This study provides valuable insights into the behavior and ecological risks of UV-320 in the environment.


Subject(s)
Raphanus , Vegetables , Adult , Child , Humans , Vegetables/chemistry , Plant Roots/metabolism , Biological Transport , Oxidation-Reduction , Lactuca
7.
Article in English | MEDLINE | ID: mdl-38040523

ABSTRACT

BACKGROUND: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. METHODS: Bile samples from 20 patients (10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by further bioinformatic analysis. RESULTS: Among the differentially-expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially-expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor (PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APOA-I and APOA-II, were confirmed using enzyme-linked immunosorbent assay. CONCLUSIONS: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

8.
Org Lett ; 25(51): 9136-9141, 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38100569

ABSTRACT

Herein, we found that treating N-substituted pyrrole-2-carboxaldehydes with arylalkenes in DMF in N2 at 120 °C could afford pyrrolidine scaffolds with an up to 85% yield. This approach has several remarkable features, such as atom and step economy, readily accessible raw materials, and easy-to-operate manner, providing a simple and efficient method for constructing complicated bicyclic pyrroles. Additionally, we have successfully synthesized 28 target compounds, which further demonstrates its practicality and wide applicability.

9.
Environ Sci Pollut Res Int ; 30(56): 118456-118467, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37910373

ABSTRACT

The open-air storage and disposal of livestock waste from family-operated livestock farms can be a potential health threat to rural residents. In this study, the occurrence and seasonal distribution of 8 potentially toxic elements, 24 antibiotics, and 4 estrogens were investigated in 44 waste samples from 11 rural farms in North China. The results showed that these micropollutants were ubiquitous in livestock waste, with concentration ranges of 238.9-4555 mg/kg for potentially toxic elements, not detected (ND) to 286,672 µg/kg for antibiotics and ND to 229.5 µg/kg for estrogens. The pollutants in animal wastes showed seasonal variation. Since these wastes are directly applicable to nearby farmland without treatment, the risks those wastes pose to farmland soils were also evaluated. Risk assessment results showed that Zn, Cd, Hg, FF and DC in swine manures were at high risk, while total estrogens in chicken and dairy cattle manures were at high risk. The results will provide important data for the regulation of animal wastes produced by small-scale livestock farms in rural areas of China.


Subject(s)
Estrogens , Livestock , Cattle , Swine , Animals , Estrogens/analysis , Farms , Anti-Bacterial Agents/analysis , Chickens , China , Environmental Monitoring/methods , Risk Assessment , Soil
10.
Drug Des Devel Ther ; 17: 3047-3060, 2023.
Article in English | MEDLINE | ID: mdl-37808345

ABSTRACT

Background: Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood. Purpose: The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways. Methods: The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot. Results: SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition. Conclusion: SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.


Subject(s)
Hypercholesterolemia , Non-alcoholic Fatty Liver Disease , Rats , Animals , AMP-Activated Protein Kinases/metabolism , Sirtuin 1/metabolism , PPAR alpha/metabolism , PPAR alpha/pharmacology , PPAR alpha/therapeutic use , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/pharmacology , Liver , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Lipid Metabolism , Palmitic Acid/pharmacology
11.
Iran J Public Health ; 52(4): 756-765, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37551179

ABSTRACT

Background: Local anesthetic lidocaine is one of the most common pain therapies, but high concentration of lidocaine induced neurotoxicity and its mechanism is unclear. Exosomal microRNAs (miRNAs) is implicated in neuronal diseases, but its role in lidocaine induced neurotoxicity remains to be elucidated. Methods: All the experiments were performed at Huzhou Key Laboratory of Molecular Medicine, Huzhou City, Jiangsu Province, China in 2022. Lidocaine was used to induce apoptosis of SH-SY5Y cells. Exosomes isolated from bone marrow mesenchymal stem cells (BMSC-exos) were used to co-treat SH-SY5Y cells with lidocaine. Cell apoptosis was measured using a flow cytometer. PKH-67 Dye was used for exosome uptake assay. miR-21-5p mimics/inhibitors, or negative controls were transfected with Lipo2000 to study its effect on lid-induced injury. Interactions between miR-21-5p and PDCD4 was analyzed by luciferase reporter assay. Results: Administration of BMSC-exo protected SH-SY5Y cells against lidocaine induced apoptosis. Suppressing miR-21-5p dramatically enhanced PDCD4, but miR-21-5p overexpression sharply down-regulated PDCD4. Mechanism study showed that miR-21-5p bound to 3'-UTR of PDCD4 to inhibit it. Suppressing miR-21-5p reversed the effect of BMSC-exo on Lid-induced injury. Results also indicate that miR-21-5p regulated lidocaine-induced injury through targeting PDCD4. Conclusion: BMSC-exos protected SH-SY5Y cells against lidocaine induced apoptosis through miR-21-5p by targeting PDCD4, which may develop new strategy in the management of lidocaine-induced neurotoxicity.

12.
Chem Biol Interact ; 382: 110631, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37451664

ABSTRACT

Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.


Subject(s)
Neoplasms , Telomerase , Humans , Telomerase/genetics , Telomerase/metabolism , Aging , Neoplasms/drug therapy , Neoplasms/genetics , Telomere/metabolism , Stem Cells/metabolism , Cellular Senescence
13.
Se Pu ; 41(6): 527-534, 2023 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-37259878

ABSTRACT

Halogenated polycyclic aromatic hydrocarbons (H-PAHs), including chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) and brominated polycyclic aromatic hydrocarbons (Br-PAHs), are compounds in which one or more hydrogen atoms replaced by chlorine or bromine atoms. These compounds are not only difficult to degrade but also highly fat soluble and toxic. They are a new type of high-risk organic pollutants with structures similar to those of dioxins, and their toxicity is even higher than that of the parent polycyclic aromatic hydrocarbons (PAHs). The bioaccumulation of H-PAHs can be predicted by their octanol-water partition coefficient (Kow); in general, higher bioaccumulation capacity and Kow values indicate greater fat solubility. Therefore, animal-derived foods with higher fat contents, such as animal meat, milk, aquatic products, and their processed forms, are more likely to be contaminated with higher contents of H-PAHs than those with lower fat contents. In this work, a gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) method coupled with stable isotope dilution was established to determine 15 H-PAHs in aquatic products. The instrument and pretreatment methods were systematically optimized. The GC-MS/MS used in this method can effectively eliminate matrix interferences and features high sensitivity and low analytical cost; thus, it has good application prospects. The samples were added with an isotope internal standard before extraction to calibrate the loss of the tested substance during the pretreatment process, extracted by accelerated solvent extraction, purified using gel permeation chromatography and PRiME HLB columns, and then analyzed by GC-MS/MS. The use of two DB-5MS chromatographic columns (30 m×0.25 mm×0.25 µm) and microplate fluidics technology to connect chromatographic columns 1 and 2 in series led to better separation effects, good peak shapes, and high target compound responses. The 15 H-PAHs demonstrated good linearities in the range of 1-50 µg/L, with correlation coefficients (r) greater than or equal to 0.993. The relative standard deviation (RSD) values of the relative response factor (RRF) of the H-PAHs were less than 9%, the method detection limit (MDL) was 0.009-0.072 µg/kg, and the method quantification limit (MQL) was 0.031-0.240 µg/kg. Three spiked levels of 0.25, 1.0, 2.5 µg/kg were added to the blank samples to determine the recovery and precision. The recoveries for these spiked levels were 74.6%-116.8%, 77.8%-123.2%, and 71.9%-124.8%, respectively, and the corresponding RSDs were 0.6%-8.2%, 0.6%-9.0%, and 0.4%-10.6%, respectively. The total actual content of H-PAHs in aquatic product samples was 0.60-3.54 µg/kg. Among the H-PAHs investigated, 9-chlorophenanthrene (9-ClPhe) showed the greatest detection rate (100%) and highest content (1.15 µg/kg), indicating that H-PAHs widely exist in aquatic products. Thus, further assessment of the dietary exposure risk of these compounds is necessary. The developed method simplifies the pretreatment step, and has the advantages of simplicity, rapid analysis, high recoveries, and good stability. It is suitable for the qualitative and quantitative analysis of H-PAHs in actual aquatic product samples and provides reliable technical support for the residue status and risk assessment of H-PAHs in aquatic products.


Subject(s)
Environmental Pollutants , Polycyclic Aromatic Hydrocarbons , Animals , Gas Chromatography-Mass Spectrometry/methods , Tandem Mass Spectrometry/methods , Polycyclic Aromatic Hydrocarbons/analysis , Environmental Pollutants/analysis , Isotopes
14.
Plant Phenomics ; 5: 0040, 2023.
Article in English | MEDLINE | ID: mdl-37022332

ABSTRACT

Accurate and high-throughput plant phenotyping is important for accelerating crop breeding. Spectral imaging that can acquire both spectral and spatial information of plants related to structural, biochemical, and physiological traits becomes one of the popular phenotyping techniques. However, close-range spectral imaging of plants could be highly affected by the complex plant structure and illumination conditions, which becomes one of the main challenges for close-range plant phenotyping. In this study, we proposed a new method for generating high-quality plant 3-dimensional multispectral point clouds. Speeded-Up Robust Features and Demons was used for fusing depth and snapshot spectral images acquired at close range. A reflectance correction method for plant spectral images based on hemisphere references combined with artificial neural network was developed for eliminating the illumination effects. The proposed Speeded-Up Robust Features and Demons achieved an average structural similarity index measure of 0.931, outperforming the classic approaches with an average structural similarity index measure of 0.889 in RGB and snapshot spectral image registration. The distribution of digital number values of the references at different positions and orientations was simulated using artificial neural network with the determination coefficient (R 2) of 0.962 and root mean squared error of 0.036. Compared with the ground truth measured by ASD spectrometer, the average root mean squared error of the reflectance spectra before and after reflectance correction at different leaf positions decreased by 78.0%. For the same leaf position, the average Euclidean distances between the multiview reflectance spectra decreased by 60.7%. Our results indicate that the proposed method achieves a good performance in generating plant 3-dimensional multispectral point clouds, which is promising for close-range plant phenotyping.

15.
Plant Phenomics ; 5: 0027, 2023.
Article in English | MEDLINE | ID: mdl-36939450

ABSTRACT

Silique morphology is an important trait that determines the yield output of oilseed rape (Brassica napus L.). Segmenting siliques and quantifying traits are challenging because of the complicated structure of an oilseed rape plant at the reproductive stage. This study aims to develop an accurate method in which a skeletonization algorithm was combined with the hierarchical segmentation (SHS) algorithm to separate siliques from the whole plant using 3-dimensional (3D) point clouds. We combined the L1-median skeleton with the random sample consensus for iteratively extracting skeleton points and optimized the skeleton based on information such as distance, angle, and direction from neighborhood points. Density-based spatial clustering of applications with noise and weighted unidirectional graph were used to achieve hierarchical segmentation of siliques. Using the SHS, we quantified the silique number (SN), silique length (SL), and silique volume (SV) automatically based on the geometric rules. The proposed method was tested with the oilseed rape plants at the mature stage grown in a greenhouse and field. We found that our method showed good performance in silique segmentation and phenotypic extraction with R 2 values of 0.922 and 0.934 for SN and total SL, respectively. Additionally, SN, total SL, and total SV had the statistical significance of correlations with the yield of a plant, with R values of 0.935, 0.916, and 0.897, respectively. Overall, the SHS algorithm is accurate, efficient, and robust for the segmentation of siliques and extraction of silique morphological parameters, which is promising for high-throughput silique phenotyping in oilseed rape breeding.

16.
Environ Pollut ; 318: 120935, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36566917

ABSTRACT

Ultraviolet absorbers (UVAs) are emerging pollutants of concern owing to their environmental persistence and endocrine-disrupting effects. UVAs are added to agricultural films to prevent UV-induced degradation, potentially leading to the release of UVAs into the soil. In this study, the occurrence of four frequently used UVAs (UV-324, UV-326, UV-328, and UV-531) in film-mulched agricultural soils (using conventional polyethylene films and biodegradable films) was investigated. Results showed that the UVA concentrations were several orders of magnitude higher in film-mulched soil (mean 91.4 µg/kg) than in unmulched soil (mean 0.08 µg/kg), indicating that mulch films are important sources of UVAs released into agricultural soil. Notably, the mean UVA concentration was up to 10 times higher in biodegradable-film-mulched soils than in polyethylene (PE) film-mulched soils; this result is consistent with our finding that the mean UVA concentration was 448 times higher in commercial biodegradable films than in PE films. In simulated migration experiments, UVAs migrated more readily into the soil from the biodegradable film than from the PE film. To our knowledge, this is the first report demonstrating that the use of mulch films may cause the accumulation of UVAs in agricultural soils as non-point sources. In particular, biodegradable plastic mulches can release more UVAs into soils.


Subject(s)
Biodegradable Plastics , Environmental Pollutants , Soil , Agriculture/methods , Polyethylene , Plastics
17.
J Org Chem ; 88(1): 143-153, 2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36563294

ABSTRACT

An efficient method of Rh(III)-catalyzed coupling reaction between 2-arylquinazolinones and gem-difluorostyrenes has been developed. In this work, two diverse structures of monofluoroalkenes and isoindolo[1,2-b]quinazolin-10(12H)-one derivatives were respectively synthesized by controlling the amount of additives (Ca(OH)2 and AgNTf2) to achieve controlled stepwise breaking of the C-F bonds of gem-difluorostyrenes. This reaction has the characteristics of a wide range of substrates and good functional group tolerance. Meanwhile, several control experiments were conducted and a plausible mechanism was proposed.

18.
Int J Clin Exp Pathol ; 16(12): 368-377, 2023.
Article in English | MEDLINE | ID: mdl-38188349

ABSTRACT

It has been demonstrated that interfering with the expression of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) results in impaired programmed death 1 ligand 1 (PD-L1) protein expression in human tumor cells. PD-L1 relies on CMTM6 to inhibit T cell responses and promote tumor cell proliferation. The aim of the present study was to investigate the expression of CMTM6 and PD-L1 in cervical cancer and their clinical significance. Immunohistochemistry was used to detect the expression of CMTM6 and PD-L1 in 50 normal cervical tissues and 102 cervical cancer tissue samples. The results showed that CMTM6 and PD-L1 expression was associated with clinical staging, lymph node metastasis, distant metastasis, and tumor differentiation. In addition, there was a positive association between the expression of CMTM6 and that of PD-L1 in cervical cancer tissue. Survival analysis results showed that high expression of CMTM6 and PD-L1 was positively correlated with poor prognosis in patients. Univariate analysis showed that lymph node metastasis was associated with the prognosis of cervical cancer patients. Cox analysis indicated that PD-L1 is a risk factor affecting the survival time of cervical cancer patients. In conclusion, the expression of CMTM6 and PD-L1 is elevated in cervical cancer tissue and closely related to poor prognosis. Therefore, CMTM6 and PD-L1 may be new molecular targets for the treatment of cervical cancer.

19.
Viruses ; 14(12)2022 12 02.
Article in English | MEDLINE | ID: mdl-36560709

ABSTRACT

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In addition to the common genogroup J IHNV, genogroup U has been newly discovered in China. However, there is no effective DNA vaccine to fight against this emerging genogroup U IHNV in China. In this study, DNA vaccines encoding the IHNV viral glycoprotein (G) gene of the GS2014 (genogroup J) and BjLL (genogroup U) strains isolated from northern China were successfully developed, which were identified by restriction analysis and IFA. The expression of the Mx-1 gene and G gene in the spleens and muscles of the injection site as well as the titers of the serum antibodies were measured to evaluate the vaccine efficacy by RT-qPCR and ELISA. We found that DNA vaccine immunization could activate Mx1 gene expression and upregulate G gene expression, and the mRNA levels of the Mx1 gene in the muscles were significantly higher than those in the spleens. Notably, DNA vaccine immunization might not promote the serum antibody in fish at the early stage of immunization. Furthermore, the efficacy of the constructed vaccines was tested in intra- and cross-genogroup challenges by a viral challenge in vivo. It seemed that the DNA vaccines were able to provide great immune protection against IHNV infection. In addition, the genogroup J IHNV-G DNA vaccine showed better immune efficacy than the genogroup U IHNV-G or divalent vaccine, which could provide cross-immune protection against the genogroup U IHNV challenge. Therefore, this is the first study to construct an IHNV DNA vaccine using the G gene from an emerging genogroup U IHNV strain in China. The results provide great insight into the advances of new prophylactic strategies to fight both the genogroup J and U IHNV in China.


Subject(s)
Fish Diseases , Infectious hematopoietic necrosis virus , Oncorhynchus mykiss , Rhabdoviridae Infections , Vaccines, DNA , Viral Vaccines , Animals , Vaccines, DNA/genetics , Infectious hematopoietic necrosis virus/genetics , Genotype , China/epidemiology , Rhabdoviridae Infections/prevention & control , Rhabdoviridae Infections/veterinary , Viral Vaccines/genetics
20.
J Org Chem ; 87(21): 14738-14752, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36269195

ABSTRACT

A novel route for a SnCl2-promoted tandem reduction, ammonolysis, condensation, and deamination reaction which uses nitrile and 2-nitro-N-phenylbenzenesulfonamide/N-(2-nitrophenyl)benzenesulfonamide to synthesize derivatives of benzothiadiazine/1-(phenylsulfonyl)-1H-benzimidazole has been developed. The method features convenient operation and good functional group tolerance. In addition, it employs unsensitive and inexpensive SnCl2/i-PrOH as the reaction reagent and provides a direct approach for the synthesis of pharmaceutically important targets.


Subject(s)
Benzimidazoles , Benzothiadiazines , Deamination
SELECTION OF CITATIONS
SEARCH DETAIL
...