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1.
Cancer Biol Ther ; 24(1): 2169040, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36729904

RESUMO

It has been recognized that depth of invasion (DOI) is closely associated with patient survival for most types of cancer. The purpose of this study was to determine the DOI optimal cutoff value and its prognostic value in laryngeal squamous carcinoma (LSCC). Most importantly, we evaluated the prognostic performance of five candidate modified T-classification models in patients with LSCC. LSCC patients from Harbin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital were divided into training group (n = 412) and validation group (n = 147). The primary outcomes were overall survival (OS) and relapse-free survival (RFS), and the effect of DOI on prognosis was analyzed using a multivariable regression model. We identified the optimal model based on its simplicity, goodness of fit and Harrell's consistency index. Further independent testing was performed on the external validation queue. The nomograms was constructed to predict an individual's OS rate at one, three, and five years. In multivariate analysis, we found significant associations between DOI and OS (Depth of Medium-risk invasion HR, 2.631; P < .001. Depth of high-risk invasion: HR, 5.287; P < .001) and RFS (Depth of high-risk invasion: HR, 1.937; P = .016). Model 4 outperformed the American Joint Committee on Cancer (AJCC) staging system based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves. Inclusion of DOI in the current AJCC staging system can improve the differentiation of T classification in LSCC patients.

2.
Bioorg Chem ; 133: 106389, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36731298

RESUMO

Garcinol is a polyisoprenylated benzophenone isolated from Garcinia. It has been reported to have a variety of intriguing biological effects, including anticancer, anti-inflammatory, and antioxidant capabilities. The purpose of this research is to thoroughly evaluate garcinol and a series of its analogues in terms of synthesis, structural diversity, biosynthesis, and potential for preventing carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone, which contain a unique cyclobutyl unit at C-5, were initially synthesized using the procedures utilized in the synthesis of garcinol. All the natural analogs of garcinol were produced at completion of the synthesis, and their structures and absolute configurations were clarified. Based on the synthesis, a possible biogenetic synthesis pathway towards cambogin, 13,14-didehydroxyisogarcinol via O-cyclization, and garcinopicrobenzophenone or eugeniaphenone via C-cyclization was proposed. The cytotoxicity of polyisoprenylated benzophenones produced in our group was tested, and the structure-activity relationship was summarized. The mechanism by which garcinol, cambogin, and 21' induce apoptosis was studied. Cambogin and 21' were shown to have a greater capacity to cause apoptosis in pancreatic cancer BXPC3 cells, and the suppression of BXPC3 cells by 21' might be attributed to the target of STAT3 signaling. Garcinol could cause pyroptosis and apoptosis in pancreatic cancer cells at the same time, which was the first time that garcinol was identified as a possible chemotherapeutic agent that could significantly promote pyroptosis in cancer cells.

3.
Food Chem ; 411: 135503, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36682165

RESUMO

The effects of cellulase hydrolysis separately combined with hydroxypropylation, carboxymethylation and phosphate crosslinking on the physicochemical properties and antioxidant activity of millet bran dietary fibre (MBDF) were investigated. Compared to cellulase hydrolysis alone, these dual modifications more effectively improved the soluble fibre content, water-swelling ability, viscosity, emulsifying capacity and cation-exchange capacity of MBDF but reduced the emulsion stability, brightness and polyphenol content of MBDF (P < 0.05). MBDF modified by cellulase hydrolysis combined with hydroxypropylation showed the highest emulsifying capacity (60.03 m2/g) and oil-adsorption capacity (3.32 g/g) but the lowest nitrite ion-adsorbing ability (NIAA). MBDF modified by cellulase hydrolysis with carboxymethylation showed the highest surface hydrophobicity, cation-exchange capacity (0.352 mmol/g) and NIAA (152.89 µg/g). MBDF modified by cellulase hydrolysis combined with phosphate crosslinking exhibited excellent copper ion-adsorbing ability (19.97 mg/g) and viscosity (19.33 cp). Moreover, these dual modifications all enhanced the Fe2+ chelating ability and reducing power of MBDF (P < 0.05).

4.
Int J Nanomedicine ; 18: 425-436, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36711003

RESUMO

Background: A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery. Methods: In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine-glycine-aspartic acid (RGD) ligands and endothelial cells. Results: The experimental results on the adhesion of ligand-coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C-43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs. Conclusion: The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.


Assuntos
Substitutos Sanguíneos , Nanopartículas , Temperatura , Ligantes , Células Endoteliais , Oligopeptídeos
5.
Int J Clin Pract ; 2023: 1907222, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36713951

RESUMO

Background: Prevention and timely treatment of gestational diabetes mellitus (GDM) are important to the prognosis of pregnant women and neonates. We aimed to conduct a meta-analysis to evaluate the effects and safety of vitamin D supplementation on GDM patients and neonates, to provide insights into clinical GDM treatment. Methods: Two authors searched the Medline, PubMed, Cochrane Library, Web of Science, Embase, CNKI, and Wanfang databases for randomized controlled trials (RCTs) on the effects and safety of vitamin D supplementation in GDM patients. The quality of the included RCTs was evaluated according to Cochrane handbook. RevMan 5.3 software was used for statistical analysis. Results: A total of 20 RCTs involving 1682 GDM patients were finally included, of whom 837 received vitamin D supplementation. Vitamin D supplementation in GDM patients increased the serum 25(OH)D level (SMD = 4.07, 95% CI: (2.73, 5.41)) and HDL level (SMD = 0.41, 95% CI: (0.23, 0.58)) and reduced serum LDL (SMD = -0.49, 95% CI: (-0.68, -0.29)), TG (SMD = -0.59, 95% CI: (-1.01, -0.17)), and TC (SMD = -0.67, 95% CI: (-1.19, -0.14)) levels in GDM patients (all P < 0.05). Besides, vitamin D supplementation reduced the risk of premature birth (OR = 0.37, 95% CI: (0.22, 0.62)), hyperbilirubinemia (OR = 0.38, 95% CI: (0.25, 0.58)), and neonatal hospitalization (OR = 0.38, 95% CI: (0.25, 0.58)) of neonates (all P < 0.05). No significant publication bias in synthesized results was found (all P > 0.05). Conclusions: Vitamin D supplementation improves the blood lipid level in GDM patients and reduces adverse neonatal outcomes. The dose and duration of vitamin D supplementation for safety need to be further investigated in future high-quality studies.


Assuntos
Diabetes Gestacional , Complicações na Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/prevenção & controle , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico
6.
Talanta ; 253: 123938, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150338

RESUMO

In this work, a chemiluminescence (CL) aptasensor for sensitive carcinoembryonic antigen (CEA) detection was constructed based on the CL system of luminol-H2O2-NaOH. Magnetic carbon nanotubes (MCNTs), as the base material, was modified with CEA-aptamer and DNA1, and was combined with the novel flower-shaped Ag@ZIF-67 of modified with DNA2 through the principle of base complementary pairing. CEA combined with aptamer when it existed in the solution. At the same time, MCNTs was adsorbed at the bottom of the container under the influence of external magnetic field, and Ag@ZIF-67 enhanced the CL signal. The CL aptasensor demonstrated high selectivity and sensitivity for CEA in human serum sample with (1-4): a detection limit of 4.53 × 10-3 ng/mL in case the detection range was 0.05-500 ng/mL. Furthermore, the proposed method had been shown great potential in cancer diagnosis.


Assuntos
Peróxido de Hidrogênio , Nanotubos de Carbono , Humanos
7.
Nat Commun ; 13(1): 7455, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460692

RESUMO

Intracellular Ca2+ dysregulation is a key marker in septic cardiac dysfunction; however, regulation of the classic Ca2+ regulatory modules cannot successfully abolish this symptom. Here we show that the knockout of transient receptor potential canonical (TRPC) channel isoforms TRPC1 and TRPC6 can ameliorate LPS-challenged heart failure and prolong survival in mice. The LPS-triggered Ca2+ release from the endoplasmic reticulum both in cardiomyocytes and macrophages is significantly inhibited by Trpc1 or Trpc6 knockout. Meanwhile, TRPC's molecular partner - calmodulin - is uncoupled during Trpc1 or Trpc6 deficiency and binds to TLR4's Pococurante site and atypical isoleucine-glutamine-like motif to block the inflammation cascade. Blocking the C-terminal CaM/IP3R binding domain in TRPC with chemical inhibitor could obstruct the Ca2+ leak and TLR4-mediated inflammation burst, demonstrating a cardioprotective effect in endotoxemia and polymicrobial sepsis. Our findings provide insight into the pathogenesis of endotoxemic cardiac dysfunction and suggest a novel approach for its treatment.


Assuntos
Traumatismos Craniocerebrais , Endotoxemia , Insuficiência Cardíaca , Canais de Potencial de Receptor Transitório , Animais , Camundongos , Endotoxemia/complicações , Canal de Cátion TRPC6 , Lipopolissacarídeos/toxicidade , Receptor 4 Toll-Like , Inflamação
8.
Artigo em Inglês | MEDLINE | ID: mdl-36498118

RESUMO

Mining activities have led to serious environmental (soil erosion, degradation of vegetation, and groundwater contamination) and human health (musculoskeletal problems, diarrheal conditions, and chronic diseases) issues at desert mining areas in northwest China. Native plant species grown naturally in desert regions show a unique tolerance to arid and semiarid conditions and are potential candidates for soil phytoremediation. Here, an ex situ experiment involving pot planting of seedlings of three native plant species (Suaeda glauca, Artemisia desertorum, and Atriplex canescens) was designed to explore their phytoremediation potential and the underlying physiological mechanism. For Zn and Cu, the three plants were all with a biological accumulation coefficient (BAC) greater than 1. For Cd, Ni, and Pb, Atriplex canescens had the highest bioaccumulation concentrations (521.52, 862.23, and 1734.59 mg/kg), with BAC values (1.06, 1.30, 1.25) greater than 1, which indicates that Atriplex canescens could be a broad-spectrum metal extraction plant. Physiological analysis (antioxidation, extracellular secretions, photosynthesis, and hydraulics) showed that the three desert plants exploited their unique strategy to protect against the stress of complex metals in soils. Moreover, the second growing period was the main heavy metal accumulation and extraction stage concomitant with highest water use efficiency (iWUE). Taken together, the three desert plants exhibited the potent heavy metal extraction ability and physiological and ecological adaptability to a harsh polluted environment in arid desert areas, providing potential resources for the bioremediation of metal-contaminated soils in an arid and semiarid desert environment.


Assuntos
Artemisia , Atriplex , Chenopodiaceae , Metais Pesados , Poluentes do Solo , Humanos , Atriplex/metabolismo , Poluentes do Solo/análise , Biodegradação Ambiental , Metais Pesados/análise , Solo , Plantas/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-36497949

RESUMO

The physiological mechanisms and phytoremediation effects of three kinds of native quinoa in a desert mining area were studied. We used two different types of local soils (native soil and tailing soil) to analyze the changes in the heavy metal content, leaf physiology, photosynthetic parameters, stem hydraulics, and anatomical characteristics of potted quinoa. The results show that the chlorophyll content, photosynthetic rate, stomatal conductance, and transpiration rate of Kochia scoparia were decreased, but intercellular CO2 concentration (Ci) was increased under heavy metal stress, and the net photosynthetic rate (Pn) was decreased due to non-stomatal limitation. The gas exchange of Chenopodium glaucum and Atriplex centralasiatica showed a decrease in Pn, stomatal conductance (Gs), and transpiration rate (E) due to stomatal limitation. The three species showed a similar change in heavy metal content; they all showed elevated hydraulic parameters, decreased vessel density, and significantly thickened vessel walls under heavy metal stress. Physiological indicators such as proline content and activity of superoxide dismutase (SOD) and peroxidase (POD) increased, but the content of malondialdehyde (MDA) and glutathione (GSH), as well as catalase (CAT) activity, decreased in these three plants. Therefore, it can be concluded that these three species of quinoa, possibly the most dominant 30 desert plants in the region, showed a good adaptability and accumulation capacity under the pressure of heavy metal stress, and these plants can be good candidates for tailings remediation in the Jinchang desert mining area.


Assuntos
Metais Pesados , Metais Pesados/toxicidade , Fotossíntese , Superóxido Dismutase/metabolismo , Malondialdeído , Solo , Plantas/metabolismo , Antioxidantes/metabolismo , Glutationa/metabolismo
10.
Front Cell Infect Microbiol ; 12: 1045615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439212

RESUMO

Proteins containing Common in Fungal Extracellular Membrane (CFEM) domains uniquely exist in fungi and play significant roles in their whole life history. In this study, a total of 11 MbCFEM proteins were identified from Marssonina brunnea f. sp. multigermtubi (MULT), a hemibiotrophic pathogenic fungus on poplars that causes severe leaf diseases. Phylogenic analysis showed that the 11 proteins (MbCFEM1-11) were divided into three clades based on the trans-membrane domain and the CFEM domain. Sequence alignment and WebLogo analysis of CFEM domains verified the amino acids conservatism therein. All of them possess eight cysteines except MbCFEM4 and MbCFEM11, which lack two cysteines each. Six MbCFEM proteins with a signal peptide and without trans-membrane domain were considered as candidate effectors for further functional analysis. Three-dimensional (3D) models of their CFEM domains presented a helical-basket structure homologous to the crucial virulence factor Csa2 of Candida albicans. Afterward, four (MbCFEM1, 6, 8, and 9) out of six candidate effectors were successfully cloned and a yeast signal sequence trap (YSST) assay confirmed their secretion activity. Pathogen challenge assays demonstrated that the transient expression of four candidate MbCFEM effectors in Nicotiana benthamiana promoted Fusarium proliferatum infection, respectively. In an N. benthamiana heterogeneous expression system, MbCFEM1, MbCFEM6, and MbCFEM9 appeared to suppress both BAX/INF1-triggered PCD, whereas MbCFEM8 could only defeat BAX-triggered PCD. Additionally, subcellular localization analysis indicated that the four candidate MbCFEM effectors accumulate in the cell membrane, nucleus, chloroplast, and cytosolic bodies. These results demonstrate that MbCFEM1, MbCFEM6, MbCFEM8, and MbCFEM9 are effectors of M. brunnea and provide valuable targets for further dissection of the molecular mechanisms underlying the poplar-M. brunnea interaction.


Assuntos
Ascomicetos , Populus , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas de Membrana/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ascomicetos/metabolismo , Populus/metabolismo , Populus/microbiologia
11.
Biochem Biophys Res Commun ; 637: 276-285, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36410277

RESUMO

Myocardial Ischemic Injury is a serious threat to human health, and DJ-1 is involved in cardioprotection. The research intended to explore the effects and mechanism of DJ-1 to protect myocardium against ischemia injury. DJ-1 overexpression lentivirus vectors were transduced into the myocardium of SD rats and H9c2 cells, and an AMI model in vivo and a hypoxia model in vitro were established, respectively. Results showed that DJ-1 overexpression alleviated myocardial ischemia injury, as demonstrated by reduced the extent of myocardial infarction, improved cell survival, decreased LDH activity and CK-MB release. Furthermore, DJ-1 interacted with RACK1, activated AMPK/mTOR pathway, induced adaptive autophagy and protected the myocardium. However, RACK1 siRNA or compound C (an AMPK inhibitor) could weaken the above effect of DJ-1 on myocardium. In conclusion, DJ-1 could activate adaptive autophagy by the RACK1/AMPK/mTOR pathway and protect the myocardium against ischemia injury.


Assuntos
Proteínas Quinases Ativadas por AMP , Traumatismos Cardíacos , Proteína Desglicase DJ-1 , Animais , Humanos , Ratos , Autofagia , Hipóxia , Isquemia , Miocárdio , Proteínas de Neoplasias , Ratos Sprague-Dawley , Receptores de Quinase C Ativada , Serina-Treonina Quinases TOR , Proteína Desglicase DJ-1/metabolismo
12.
J Morphol ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36373244

RESUMO

There are few detailed descriptions of the morphology of the male external genitalia, the urogenital papilla (UGP), of the Black Rockfish (Sebastes schlegelii Hilgendorf, 1880). The purpose of this study was to evaluate this organ histologically and to determine the time of development of the UGP in Black Rockfish. Twelve adult males, three adult females and around 500 juveniles were used in the experiment. The juveniles were divided into normal developmental and androgen groups. The androgen group was exposed to methyltestosterone (100 ug/L) for 2 h daily for 38 days. Samples (N=10 per sampling) were randomly selected for analysis every 5 days from 30-116 days after birth. Parameters assessed included the type of epithelium, composition of connective tissue, muscular tissue, and the timing of UGP development. Differences in these parameters between normal developmental and androgen groups were evaluated. The results indicated that the UGP of the adult fish contains the sperm duct and ureter, which have the function of transporting sperm and urine respectively. The androgen-treated juvenile fish developed the UGP earlier than the normal development group. This study provides a reference for understanding the external genitalia of other viviparous fishes by studying the UGP of the male Black Rockfish. This article is protected by copyright. All rights reserved.

13.
Nucleic Acids Res ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399488

RESUMO

Deciphering the cell-type composition in the tumor immune microenvironment (TIME) can significantly increase the efficacy of cancer treatment and improve the prognosis of cancer. Such a task has benefited from microarrays and RNA sequencing technologies, which have been widely adopted in cancer studies, resulting in extensive expression profiles with clinical phenotypes across multiple cancers. Current state-of-the-art tools can infer cell-type composition from bulk expression profiles, providing the possibility of investigating the inter-heterogeneity and intra-heterogeneity of TIME across cancer types. Much can be gained from these tools in conjunction with a well-curated database of TIME cell-type composition data, accompanied by the corresponding clinical information. However, currently available databases fall short in data volume, multi-platform dataset integration, and tool integration. In this work, we introduce TIMEDB (https://timedb.deepomics.org), an online database for human tumor immune microenvironment cell-type composition estimated from bulk expression profiles. TIMEDB stores manually curated expression profiles, cell-type composition profiles, and the corresponding clinical information of a total of 39,706 samples from 546 datasets across 43 cancer types. TIMEDB comes readily equipped with online tools for automatic analysis and interactive visualization, and aims to serve the community as a convenient tool for investigating the human tumor microenvironment.

14.
Biol Reprod ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36401879

RESUMO

Spermatogenesis is a dynamic cell developmental process that is essential for reproductive success. Vertebrates utilize a variety of reproductive strategies, including sperm diversity, and internal and external fertilization. Research on the cellular and molecular dynamic changes involved in viviparous teleost spermatogenesis, however, is currently lacking. Here, we combined cytohistology, 10 × genomic single-cell RNA-seq, and transcriptome technology to determine the dynamic development characteristics of the spermatogenesis of Sebastes schlegelii. The expressions of lhcgr (Luteinizing hormone/Choriogonadotropin receptor), fshr (follicle-stimulating hormone receptor), ar (androgen receptor), pgr (progesterone receptor), and cox (cyclo-oxygen-ase), as well as the prostaglandin E and F levels peaked during the maturation period, indicating that they were important for sperm maturation and mating. Fifteen clusters were identified based on the 10 × genomic single-cell results. The cell markers of the sub-cluster were identified by their upregulation; piwil, dazl, dmrt1 were upregulated and identified as spermatogonium markers, and sycp1/3 and spo11 were identified as spermatocyte markers. For Sebastes schlegelii, the sperm head nucleus was elongated (spherical to streamlined in shape), which is a typical characteristic for sperm involved in internal fertilization. We also identified a series of crucial genes associated with spermiogenesis, such as spata6, spag16, kif20a, trip10, and klf10, while kif2c, kifap3, fez2, and spaca6 were found to be involved in nucleus elongation. The results of this study will enrich our cellular and molecular knowledge of spermatogenesis and spermiogenesis in fish that undergo internal fertilization.

15.
Toxins (Basel) ; 14(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36356021

RESUMO

Curcin and Curcin C, both of the ribosome-inactivating proteins of Jatropha curcas, have apparent inhibitory effects on the proliferation of osteosarcoma cell line U20S. However, the inhibitory effect of the latter is 13-fold higher than that of Curcin. The mechanism responsible for the difference has not been studied. This work aimed to understand and verify whether there are differences in entry efficiency and pathway between them using specific endocytosis inhibitors, gene silencing, and labeling techniques such as fluorescein isothiocyanate (FITC) labeling. The study found that the internalization efficiency of Curcin C was twice that of Curcin for U2OS cells. More than one entering pathway was adopted by both of them. Curcin C can enter U2OS cells through clathrin-dependent endocytosis and macropinocytosis, but clathrin-dependent endocytosis was not an option for Curcin. The low-density lipoprotein receptor-related protein 1 (LRP1) was found to mediate clathrin-dependent endocytosis of Curcin C. After LRP1 silencing, there was no significant difference in the 50% inhibitory concentration (IC50) and endocytosis efficiency between Curcin and Curcin C on U2OS cells. These results indicate that LRP1-mediated endocytosis is specific to Curcin C, thus leading to higher U2OS endocytosis efficiency and cytotoxicity than Curcin.


Assuntos
Alcaloides , Jatropha , Osteossarcoma , Toxinas Biológicas , Humanos , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Jatropha/genética , Jatropha/metabolismo , Proteínas Inativadoras de Ribossomos/metabolismo , Toxinas Biológicas/metabolismo , Alcaloides/metabolismo , Clatrina/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo
16.
Antioxidants (Basel) ; 11(11)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36421410

RESUMO

Ferroptosis is associated with inflammatory diseases as a lethal iron-dependent lipid peroxidation; its role in the development of clinical mastitis (CM) in dairy cows is not well understood. The aim of this study was to identify differentially expressed proteins (DEPs) associated with iron homeostasis and apoptosis, and to investigate further their roles in dairy cows with CM. The results suggested that ferroptosis occurs in the mammary glands of Holstein cows with CM. Using data-independent acquisition proteomics, 302 DEPs included in 11 GO terms related to iron homeostasis and apoptosis were identified. In particular, heme oxygenase-1 (HMOX1) was identified and involved in nine pathways. In addition, ferritin heavy chain 1 (FTH1) was identified and involved in the ferroptosis pathway. HMOX1 and FTH1 were located primarily in mammary epithelial cells (MECs), and displayed significantly up-regulated expression patterns compared to the control group (healthy cows). The expression levels of HMOX1 and FTH1 were up-regulated in a dose-dependent manner in LPS induced MAC-T cells with increased iron accumulation. The expression levels of HMOX1 and FTH1 and iron accumulation levels in the MAC-T cells were significantly up-regulated by using LPS, but were lower than the levels seen with Erastin (ERA). Finally, we deduced the mechanism of ferroptosis in the MECs of Holstein cows with CM. These results provide new insights for the prevention and treatment of ferroptosis-mediated clinical mastitis in dairy animals.

17.
Animals (Basel) ; 12(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36230328

RESUMO

Maternal deprivation (MD) in early life induces dysbiosis in the host gut microbiota, which is a key determinant of abnormal behavior in stress model individuals. Compared with the early parenting environment of the wild, captive giant pandas face frequent and premature maternal separation. Will this lead to imbalance in intestinal flora and stress in captive giant pandas? The purpose of this research is to evaluate the possible adverse effects of the traditional parenting mode on the gut microbiota of captive giant pandas. The results showed that the frequent and premature maternal separation at early stages of the young did not change α and ß diversity indices of the gut microbes, but it increased the relative abundance of s_Clostridium_tetani and s_Clostridium_sp_MSJ_8 (significantly positively correlated with the metabolism of propionic acid) and also the concentrations of fecal metabolites that are related to stress (N-acetyl-l-aspartic acid and corticosterone) in the intestinal tract of giant pandas in adulthood. Thereby, the function of protein digestion and absorption in the intestines of captive giant pandas was decreased, and the metabolism of short-chain fatty acids was disturbed. In conclusion, the parenting experience of early maternal separation could adversely affect the stress caused by the unfavorable parenting environment in the early life of captive giant pandas related to the gut microbiota of the captive giant pandas in adulthood.

18.
Sci China Life Sci ; 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36271983

RESUMO

The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.

19.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36232661

RESUMO

The adsorption separation and extraction of low-concentration boron from salt-lake brine have great significance. Magnetic separation avoids the problem of adsorbent granulation and improves the usage efficiency. The silicon-based adsorbents have attracted interest due to their superior acid and alkali resistance, in which polyhydroxy graphene enhances the adsorption of boron ions. Herein different boron adsorbents, derived by magnetic separation, were developed and characterized by SEM, TEM, XPS, VSM, FT-IR, and XRD analysis. The adsorption-desorption performance of boron adsorbents with different compositions was evaluated. The isotherms and kinetics parameters of the boron extraction were evaluated based on adsorption-desorption tests. The graphene-based magnetic adsorbent (Go-Fe3O4@SiO2@mSiO2-Glu) registered a high boron adsorption capacity of 23.90 mg/g at pH = 9 in the boron solution and 24.84 mg/g for East Taigener salt-lake brine. The Na+, Mg2+, Ca2+, and Cl- ions have little interference with the boron adsorption. The adsorbents exhibit magnetic separation performance and good cycle life. The results showed that acid-alkali desorption solution has little effect on the adsorbents, and the composite of graphene enhances the adsorption of boron ions. The adsorbents developed in this study are promising to recover boron from low-concentration boron-containing salt-lake brines.


Assuntos
Grafite , Poluentes Químicos da Água , Adsorção , Álcalis , Boro , Glucose , Grafite/química , Cetoácidos , Lagos , Fenômenos Magnéticos , Sais , Silício , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Clin Chim Acta ; 537: 146-153, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36279941

RESUMO

BACKGROUND AND AIMS: To establish reference intervals (RIs) for PTX-3 and to validate the performance of these RIs in a population including healthy volunteers and Takayasu's arteritis (TAK) patients. MATERIALS AND METHODS: Plasma PTX-3 levels were determined in 166 healthy volunteers and 63 TAK patients. RIs were established in healthy volunteers according to guidelines from the Clinical and Laboratory Standards Institute (CLSI, C28-A3). Global assessment was used to quantitatively diagnose active/non-active TAK patients. Screening and monitoring performances were validated by identifying active TAK patients from the whole population or diagnosed TAK patients. RESULTS: The PTX-3 RI was calculated to be 0.87-2.78 ng/mL. For screening purposes, 1.55 ng/mL had a high sensitivity of 90.32 % and the RI upper limit (2.78 ng/mL) had a high specificity of 97.94 %. For monitoring purposes, the sensitivity/specificity of the cut-off value (1.55 ng/mL) and RI median were 90.32 %/90.63 % and 80.85 %/90.63 %, respectively. These screening and monitoring performances of PTX-3 were superior to those of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). CONCLUSION: The distribution of serum PTX-3 levels was stable and uniform across the population. The screening and monitoring performances of the cut-off value and RI-derived values of PTX-3 were higher than CRP and ESR.


Assuntos
Arterite de Takayasu , Humanos , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/metabolismo , Proteína C-Reativa/metabolismo , Voluntários Saudáveis , Sedimentação Sanguínea , Valores de Referência
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