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1.
Reprod Biol Endocrinol ; 19(1): 157, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627263

RESUMO

BACKGROUND: Infertility, an important source of stress, could affect sexual life. Extensive studies suggest that the incidence of sexual dysfunction is highly prevalent in infertile women. As the duration of infertility increases, the level of stress is also likely to increase even further, and this could aggravate psychological pain and cause sexual dysfunction. However, the effect of infertility duration on sexual health is unclear. METHODS: We conducted a case-control study in which 715 patients participated between September 1,2020 and December 25, 2020. We included patients diagnosed with infertility (aged between 20 to 45), who were divided into four groups according to their infertility durations: ≤ 2 years (Group I, n = 262), > 2 years but ≤ 5 years (Group II, n = 282), > 5 years but ≤ 8 years (Group III, n = 97), and > 8 years (Group IV, n = 74). A questionnaire survey on female sexual functions and psychological depression was administered to participants, and their female sexual functions and depression status were measured using the Female Sexual Function Index (FSFI) and Patient Health Questionnaire (PHQ-9), respectively. RESULTS: As the number of years of infertility increased, the PHQ-9 score as well as the incidence of psychological depression increased significantly (p < 0.05), but the total score of FSFI and those of its six domains/sub-scales were not significantly different among the four groups. An analysis of the relevant factors affecting sexual functions, using the multivariable logistic regression model, revealed that when the infertility duration was greater than 8 years, there was a significant increase in the incidence of sexual dysfunction [adjusted odds ratios (AOR) = 5.158, 95% confidence interval (CI): 1.935-13.746, P = 0.001], arousal disorder (AOR = 2.955, 95% CI: 1.194-7.314, P = 0.019), coital pain (AOR = 3.811, 95% CI: 1.045-13.897, P = 0.043), and lubrication disorder (AOR = 5.077, 95% CI: 1.340-19.244, P = 0.017). CONCLUSIONS: An increasing infertility duration is a risk factor for the occurrence of sexual dysfunction. Hence, as the infertility duration increases, the incidence of female sexual dysfunction and psychological distress could also increase, especially when the infertility duration is more than 8 years.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34617210

RESUMO

Insect feces are a new kind of biological organic fertilizer. Little is known about the influences of insect feces on rice growth and heavy metal migration from soil to rice plant. In this study, the effects of different amounts (CK (0%), T1 (2%), T2 (4%), T3 (6%), and T4 (8%)) of black soldier fly larvae (BSFL) feces on the rice growth and the migration/accumulation of heavy metals (Cd and Pb) were investigated by pot experiments within 2 years. The application of insect feces remarkably increased the contents of soil pH, organic matter, ammonium nitrogen, available phosphorus, and potassium. Meanwhile, the insect feces application reduced the weak acid-soluble contents of soil Cd and Pb by 8.3-56.8%, but increased those in the oxidizable (by 22.4-165.7%) and residual (by 1.8-225.6%) states. Except for the T4 treatment in the first year, all fertilization treatments increased the rice yield (up to 43.7% and 195.5% higher than those of CK within 2 years). Moreover, the insect feces application reduced the contents of Cd (8.3-66.7%) and Pb (6.4-61.8%) in different parts of rice. Under the same treatment, the metal contents in each part of rice in the second year were lower than those in the first year. The insect feces application decreased the absorption coefficients (24.4-57.5%) and secondary transport coefficients (3.6-44.1%) of Cd and Pb by rice plant. The findings implied that the insect feces might act as effective organic fertilizers for rice plants as well as reducing heavy metal accumulation in rice plants growing in polluted soil.

3.
Front Biosci (Landmark Ed) ; 26(9): 485-495, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590461

RESUMO

Background: Dysregulated migration and invasion of endometrial stromal cells is implicated in the pathogenesis of endometriosis. Hypoxia functions as critical microenvironmental factor that results in promotion of endometrial stromal cells migration and invasion through up-regulation of autophagy. Paeonol functioned as a tumor suppressor in human ovarian cancer and promoted cytoprotective autophagy. However, the role of paeonol in hypoxia-induced autophagy in endometriosis remains unknown. Methods: Stromal cells were isolated from endometriotic patients by enzymatic digestion of ectopic endometrial tissues, and then characterized by immunohistochemical analysis of cytoskeleton 19 (CK19) and vimentin. Cellular morphology was evaluated under microscope. Cell viability, proliferation and apoptosis of stromal cells were assessed by Cell Counting Kit-8, EdU labeling and flow cytometry, respectively. Wound healing and transwell assays were performed to detect metastasis of the stromal cells. Hypoxia-induced autophagy was evaluated through immunohistochemistry and western blot. Results: Paeonol treatment dosage dependently decreased cell proliferation and metastasis of the ectopic endometrial stromal cells (ecESCs), while promoted the cell apoptosis. Hypoxia-induced autophagy in the ecESCs was repressed by paeonol through down-regulation of LC3-II/LC3-I and Beclin-1, while up-regulation of p62. Hypoxia-inducible factor-1α (HIF-1α) was reduced post paeonol treatment, and paeonol-induced increase of p62 and decrease of LC3-II/LC3-I and Beclin-1 were reversed by over-expression of HIF-1α. Over-expression of HIF-1α also attenuated the suppressive effect of paeonol on cell growth of ecESCs. Conclusions: Paeonol attenuated HIF-1α-induced promotion of ecESCs migration and invasion through reducing autophagy, and reduced HIF-1α-induced endometriotic lesion in rats, providing potential therapeutic strategy for the treatment of endometriosis.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 786-790, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511166

RESUMO

OBJECTIVES: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment. RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P˂0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions. CONCLUSIONS: In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.


Assuntos
Epilepsia , Animais , Camundongos , Estudos Prospectivos , Habilidades Sociais
5.
J Chromatogr A ; 1655: 462504, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34487881

RESUMO

Despite the extensive consumption of ginseng, precise quality control of different ginseng products is highly challenging due to the containing of ginsenosides in common for different Panax species or different parts (e.g. root, leaf, and flower) of a same species. Herein we performed a comparative investigation of diverse ginseng products by simultaneously assaying 15 saponins (notoginsenoside R1, ginsenosides Rg1, -Re, -Rf, -Ra2, -Rb1, -Rc, -Ro, -Rb2, -Rb3, -Rd, 20(R)-ginsenoside Rg3, 24(R)-pseudoginsenoside F11, chikusetsusaponins IV, and -IVa) using an ultra-high-performance liquid chromatography/charged aerosol detector (UHPLC-CAD) approach. Twelve Panax-derived ginseng products (involving P. ginseng root, P. quinquefolius root, P. notoginseng root, Red ginseng, P. ginseng leaf, P. quinquefolius leaf, P. notoginseng leaf, P. ginseng flower, P. quinquefolius flower, P. notoginseng flower, P. japonicus root, and P. japonicus var. major root) were considered. Benefiting from the condition optimization, the baseline resolution of 15 ginsenosides was achieved on a CORTECS UPLC Shield RP18 column. This method was validated as specific, precise (0.81-1.94% intra-day variation; 0.86-2.35% inter-day variation), and accurate (recovery: 90.73-107.5%), with good linearity (R2 > 0.999), high sensitivity (limit of detection: 0.02-0.21 µg; limit of quantitation: 0.04-0.42 µg) and sample stability (1.49-4.74%). Its application to 119 batches of ginseng samples unveiled vital information enabling the authentication of these different ginseng products. Detection of ginsenosides by CAD exhibited superiority over UV in sensitivity and the ability to monitor chromophore-free structures. Large-scale comparative studies by quantifying multiple markers provide methodological reference to the precise quality control of herbal medicine.

6.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2856-2869, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472303

RESUMO

The environmental gas concentration affects the storage period and quality of fruits and vegetables. High concentration CO2 treating for a long time will cause damage to fruits, However, the specific molecular mechanism is unclear. To analyze the mechanism of CO2 injury in apple, high-throughput sequencing technology of Illumina Hiseq 4000 and non-targeted metabolism technology were used to analyze the transcriptome sequencing and metabolomics analysis of browning flesh tissue of damage fruit and normal pulp tissue of the control group. A total of 6 332 differentially expressed genes were obtained, including 4 187 up-regulated genes and 2 145 down regulated genes. Functional analysis of the differentially expressed genes confirmed that the occurrence of CO2 injury in apple was related to redox process, lipid metabolism, hormone signal transduction process and energy metabolism process. Twenty candidate browning genes were successfully screened, among which grxcr1 (md14g1137800) and gpx (md06g1081300) participated in the reactive oxygen species scavenging process, and pld1_ 2 (md15g1125000) and plcd (md07g1221900) participated in phospholipid acid synthesis and affected membrane metabolism. mdh1 (md05g1238800) participated in TCA cycle and affected energy metabolism. A total of 77 differential metabolites were obtained by metabolomic analysis, mainly organic acids, lipids, sugars and polyketones, including 35 metabolites related to browning. The metabolism of flavonoids was involved in the browning process of apple. Compared with the control tissue, the content of flavonoids such as catechin and quercetin decreased significantly in the damaged apple tissue, the antioxidant capacity of cells decreased, the redox state was unbalanced, and the cell structure was destroyed, resulting in browning. The results of this study further enrich the theoretical basis of CO2 damage, and provide reference for the practical application of high concentration CO2 preservation technology.


Assuntos
Malus , Dióxido de Carbono , Frutas , Regulação da Expressão Gênica de Plantas , Malus/genética , Metaboloma , Transcriptoma
7.
Chemosphere ; 286(Pt 3): 131831, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34411925

RESUMO

Microplastics (MPs) are pollutants that are widely distributed in the aquatic environment. Fish are directly exposed to water and are at risk of ingesting a large amount of MPs. In the present study, the grass carp were exposed to two concentrations of MPs (1000 and 100 µg/L) and fluorescence signals were detected in the liver digestion solution. Grass carp exposed to MPs for 21-days showed liver cytoplasmic vacuolation and inhibited growth. At the end of the exposure period, the fish treated with MPs exhibited inhibition of the antioxidant system and enhancement oxidative stress in comparison with the control group. The transcriptome analysis of grass carp was then performed to reveal the molecular mechanism of the response to MPs. In total, 1554 differentially expressed genes (DEGs) were identified. The results of GO and KEGG pathway analysis of the DEGs identified energy metabolism-related pathways and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Taken together, the present study not only highlighted oxidative stress and metabolism disorders related to MP ingestion, but also determined the risk of MP exposure to teleost.

8.
J Environ Sci (China) ; 107: 150-159, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412778

RESUMO

The black soldier fly larvae (BSFL) have been successfully applied to treat various organic wastes. However, the impacts of heavy metals on antibiotic resistance in the BSFL guts are poorly understood. Here, we investigated the effect of copper (exposure concentrations of 0, 100 and 800 mg/kg) on the antibiotic and metal resistance profiles in BSFL guts. A total of 83 antibiotic resistance genes (ARGs), 18 mobile genetic elements (MGEs) and 6 metal resistance genes (MRGs) were observed in larval gut samples. Exposure to Cu remarkably reduced the diversity of ARGs and MGEs, but significantly enhanced the abundances of gut-associated ARGs and MRGs. The levels of MRGs copA, czcA and pbrT were dramatically strengthened after Cu exposure as compared with CK (increased by 2.8-13.5 times). Genera Enterococcus acted as the most predominant potential host of multiple ARG, MGE and MRG subtypes. Meanwhile, high exposure to Cu aggravated the enrichment of potential pathogens in BSFL guts, especially for Escherichia, Enterococcus and Salmonella species. The mantel test and procrustes analysis revealed that the gut microbial communities could be a key determinant for antibiotic and metal resistance. However, no significant positive links were observed between MGEs and ARGs or MRGs, possibly suggesting that MGEs did not play a crucial role in shaping the ARGs or MRGs in BSFL guts under the stress of Cu. These findings extend our understanding on the impact of heavy metals on the gut-associated antibiotic and metal resistome of BSFL.


Assuntos
Dípteros , Metais Pesados , Animais , Cobre/toxicidade , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Incidência , Larva , Metais Pesados/toxicidade
9.
BMC Genomics ; 22(1): 620, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399686

RESUMO

BACKGROUND: Grass carp (Ctenopharyngodon idella) is one of the most widely cultivated fishes in China. High stocking density can reportedly affect fish growth and immunity. Herein we performed PacBio long-read single-molecule real-time (SMRT) sequencing and Illumina RNA sequencing to evaluate the effects of high stocking density on grass carp transcriptome. RESULTS: SMRT sequencing led to the identification of 33,773 genes (14,946 known and 18,827 new genes). From the structure analysis, 8,009 genes were detected with alternative splicing events, 10,219 genes showed alternative polyadenylation sites and 15,521 long noncoding RNAs. Further, 1,235, 962, and 213 differentially expressed genes (DEGs) were identified in the intestine, muscle, and brain tissues, respectively. We performed functional enrichment analyses of DEGs, and they were identified to be significantly enriched in nutrient metabolism and immune function. The expression levels of several genes encoding apolipoproteins and activities of enzymes involved in carbohydrate enzymolysis were found to be upregulated in the high stocking density group, indicating that lipid metabolism and carbohydrate decomposition were accelerated. Besides, four isoforms of grass carp major histocompatibility complex class II antigen alpha and beta chains in the aforementioned three tissue was showed at least a 4-fold decrease. CONCLUSIONS: The results suggesting that fish farmed at high stocking densities face issues associated with the metabolism and immune system. To conclude, our results emphasize the importance of maintaining reasonable density in grass carp aquaculture.


Assuntos
Carpas , Doenças dos Peixes , Processamento Alternativo , Animais , Carpas/genética , Carpas/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Transcriptoma
10.
J Med Virol ; 93(11): 6163-6171, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34260072

RESUMO

Borna disease virus (BoDV-1) can infect the hippocampus and limbic lobes of newborn rodents, causing cognitive deficits and abnormal behavior. Studies have found that neuroinflammation caused by viral infection in early life can affect brain development and impair learning and memory function, revealing the important role of neuroinflammation in cognitive impairment caused by viral infection. However, there is no research to explore the pathogenic mechanism of BoDV-1 in cognition from the direction of neuroinflammation. We established a BoDV-1 infection model in rats, and tested the learning and memory impairment by Morris water maze (MWM) experiment. RNAseq was introduced to detect changes in the gene expression profile of BoDV-1 infection, focusing on inflammation factors and related signaling pathways. BoDV-1 infection impairs the learning and memory of Sprague-Dawley rats in the MWM test and increases the expression of inflammatory cytokines in the hippocampus. RNAseq analysis found 986 differentially expressed genes (DEGs), of which 845 genes were upregulated and 141 genes were downregulated, and 28 genes were found to be enriched in the toll-like receptor (TLR) pathway. The expression of TLR4, MyD88, and IRF5 in the hippocampus was significantly changed in the BoDV-1 group. Our results indicate that BoDV-1 infection stimulates TLR4/MyD88/IRF5 pathway activation, causing the release of downstream inflammatory factors, which leads to neuroinflammation in rats. Neuroinflammation may play a significant role in learning and memory impairment caused by BoDV-1 infection.

11.
Protein Cell ; 12(10): 769-787, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34291435

RESUMO

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/ß signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/ß-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aß plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/ß-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

12.
Front Immunol ; 12: 633324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262558

RESUMO

In the process of microbial invasion, the inflammation reaction is induced to eliminate the pathogen. However, un-controlled or un-resolved inflammation can lead to tissue damage and death of the host. MicroRNAs (miRNAs) are the signaling regulators that prevent the uncontrolled progress of an inflammatory response. Our previous work strongly indicated that miR-142a-3p is related to the immune regulation in grass carp. In the present study, we found that the expression of miR-142a-3p was down-regulated after infection by Aeromonas hydrophila. tnfaip2 and glut3 were confirmed as be the target genes of miR-142a-3p, which were confirmed by expression correlation analysis, gene overexpression, and dual luciferase reporter assay. The miR-142a-3p can reduce cell viability and stimulate cell apoptosis by targeting tnfaip2 and glut3. In addition, miR-142a-3p also regulates macrophage polarization induced by A. hydrophila. Our results suggest that miR-142a-3p has multiple functions in host antibacterial immune response. Our research provides further understanding of the molecular mechanisms between miRNAs and their target genes, and provides a new insights for the development of pro-resolution strategies for the treatment of complex inflammatory diseases in fish.


Assuntos
Apoptose/genética , Carpas/genética , Citocinas/genética , Transportador de Glucose Tipo 3/genética , Infecções por Bactérias Gram-Negativas/veterinária , Macrófagos/fisiologia , MicroRNAs/genética , Aeromonas hydrophila/imunologia , Aeromonas hydrophila/patogenicidade , Animais , Carpas/imunologia , Carpas/microbiologia , Células Cultivadas , Citocinas/classificação , Infecções por Bactérias Gram-Negativas/imunologia , Inflamação/imunologia , Rim/citologia , Rim/microbiologia , Macrófagos do Fígado/microbiologia , Ativação de Macrófagos , MicroRNAs/classificação , Transdução de Sinais
13.
J Immunother Cancer ; 9(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34272308

RESUMO

BACKGROUND: Mesenteric lymph nodes (MLNs) are critical draining lymph nodes of the immune system that accommodate more than half of the body's lymphocytes, suggesting their potential value as a cancer immunotherapy target. Therefore, efficient delivery of immunomodulators to the MLNs holds great potential for activating immune responses and enhancing the efficacy of antitumor immunotherapy. Self-microemulsifying drug delivery systems (SMEDDS) have attracted increasing attention to improving oral bioavailability by taking advantage of the intestinal lymphatic transport pathway. Relatively little focus has been given to the lymphatic transport advantage of SMEDDS for efficient immunomodulators delivery to the MLNs. In the present study, we aimed to change the intestinal lymphatic transport paradigm from increasing bioavailability to delivering high concentrations of immunomodulators to the MLNs. METHODS: Chlorogenic acid (CHA)-encapsulated SMEDDS (CHA-SME) were developed for targeted delivery of CHA to the MLNs. The intestinal lymphatic transport, immunoregulatory effects on immune cells, and overall antitumor immune efficacy of CHA-SME were investigated through in vitro and in vivo experiments. RESULTS: CHA-SME enhanced drug permeation through intestinal epithelial cells and promoted drug accumulation within the MLNs via the lymphatic transport pathway. Furthermore, CHA-SME inhibited tumor growth in subcutaneous and orthotopic glioma models by promoting dendritic cell maturation, priming the naive T cells into effector T cells, and inhibiting the immunosuppressive component. Notably, CHA-SME induced a long-term immune memory effect for immunotherapy. CONCLUSIONS: These findings indicate that CHA-SME have great potential to enhance the immunotherapeutic efficacy of CHA by activating antitumor immune responses.

14.
Sci Total Environ ; 794: 148645, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34198083

RESUMO

The extensively accumulation of nitrate in different water resources is currently regarded as one of the most predominant threats facing aquatic organisms on worldwide scale. In recent years, a growing body of evidences have been attempting to uncover the influences of nitrate on fish growth and health, thereby evaluating its environment security. However, the systematic assessment and intrinsic mechanism of such influences are apparently devoid. Hence, this investigation employed systematic analysis, meta-analysis and bioinformatic analysis to evaluate the nitrate biotoxicity. We first speculated two levels of nitrate concentration according to forty-four published bibliographies. Systematic analysis indicated that the broad variations of fish sensitivity to chronic and acute nitrate exposures were found in juvenile and larval stage, respectively, comparing to egg. Meta-analysis further revealed that survival rate, CF and SGR were significantly improved in low nitrate concentration during chronic exposure. Such improvements were reflected by Total mean differences (TMD) and 95% CIs (Confidence Intervals): Survival rate (-4.06 [-7.67, -0.45]), Fulton's condition factor (CF) (-0.03 [-0.03, -0.02]) and Specific growth rate (SGR) (-0.10 [-0.16, -0.04]). To trace the impact, the alternations of molecular expression and histology in brain, gill, liver, intestine, and blood suggested that the chronic and acute nitrate exposures could result in abnormal tissue structures and molecular dynamics. Moreover, omics analysis via integrating intestinal microbiome (microbial composition; %) and liver transcriptome (Gene Ontology: biological processes) revealed that the low concentration exposure induced a weakly immune response in fish liver and it matched to the intestinal immune response. Overall, current study has filled the gaps in the field of nitrate toxicity. It could also provide a novel insight for the evaluation of pollutant toxicity on aquatic species.


Assuntos
Nitratos , Poluentes Químicos da Água , Animais , Organismos Aquáticos , Biologia Computacional , Peixes , Brânquias , Nitratos/toxicidade , Poluentes Químicos da Água/toxicidade
15.
J Nanobiotechnology ; 19(1): 199, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225762

RESUMO

BACKGROUND: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. RESULTS: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. CONCLUSIONS: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy.

16.
J Alzheimers Dis ; 82(4): 1635-1649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219730

RESUMO

BACKGROUND: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer's disease (AD); however, the exact effect and mechanism remain unknown. OBJECTIVE: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. METHODS: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. RESULTS: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-ß42 (Aß42) and Aß40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3ß (GSK3ß) inactivation via upregulating GSK3ß (pSer9). CONCLUSION: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aß production and tau phosphorylation, which is related to GSK3ß inactivation.

17.
Neurochem Res ; 46(9): 2427-2438, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34165668

RESUMO

Nucleoprotein (P40) is one of the most important proteins of Borna disease virus 1 (BoDV-1), but which proteins it would bind to in the pathogenesis of BoDV-1-infected hosts is unknown. We used lentivirus LV5-P40 overexpressing P40 to infect primary hippocampal neurons and characterized the interactome of P40 with co-immunoprecipitation (Co-IP) followed by mass spectrometry (MS) analysis. These interacting protein partners revealed the pathogenesis of BoDV-1-infected hosts. We also show for the first time that P40 interacts with 5HT2CR in rat neurons, which may be the molecular basis leading to neuropsychiatric diseases such as anxiety disorders and behavioral abnormalities after BoDV-1 infection of hosts.

18.
Zhongguo Fei Ai Za Zhi ; 24(5): 372-376, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34034462

RESUMO

The echinoderm microtubule associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) were fractured and fused to become EML4-ALK. Most of these EML4-ALK-positive non-small cell lung cancer patients respond well to the ALK inhibitor. Many patients can benefit from drug target therapy for a long time, and some patients can achieve long-term survival of more than 7 years under the optimized treatment mode. This patient has lung adenocarcinoma positive for EML4-ALK fusion gene, but the treatment outcome is obviously different from that of other patients with lung cancer positive for EML4-ALK fusion gene. After the first to third generations of ALK inhibitor targeted therapy and chemotherapy, the disease progresses rapidly, the drug resistance time is short, the survival time is short, and the benefit is limited. The patient received targeted therapy of Crizotinib, Ceritinib and Lorlatinib successively from July 15, 2019, followed by two chemotherapy courses of Bevacizumab combined with Pemetrexed and Carboplatin. The patient died on September 10, 2020, with a survival of 15 months. At the same time, the treatment showed common adverse reactions of ALK inhibitors. This paper analyzed the therapeutic effect and treatment dilemma of this patient, and provided an exploration direction for the treatment of patients with EML4-ALK fusion gene positive lung cancer.
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19.
Sci Rep ; 11(1): 8434, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875708

RESUMO

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

20.
J Phys Chem Lett ; : 4187-4194, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900088

RESUMO

The strong metal-support interaction (SMSI) is one of the most important concepts in heterogeneous catalysis, which has been widely investigated between metals and active oxides triggered by reductive atmospheres. Here, we report the oxidative strong metal-support interaction (O-SMSI) effect between Pt nanoparticles (NPs) and inert hexagonal boron nitride (h-BN) sheets, in which Pt NPs are encapsulated by oxidized boron (BOx) overlayers derived from the h-BN support under oxidative conditions. De-encapsulation of Pt NPs has been achieved by washing in water, and the residual ultrathin BOx overlayers work synergistically with surface Pt sites for enhancing CO oxidation reaction. The O-SMSI effect is also present in other h-BN-supported metal catalysts such as Au, Rh, Ru, and Ir within different oxidative atmospheres including O2 and CO2, which is determined by metal-boron interaction and O affinity of metals.

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