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1.
Res Vet Sci ; 138: 62-68, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34111715

RESUMO

Haemophilus parasuis is the main agent of Glässer's disease, which causes substantial losses in pig production. However, the pathogenic mechanism and virulence factors of H. parasuis have not been fully determined. In this study, berberine is shown to have a good therapeutic effect in vivo against H. parasuis; the minimal inhibitory concentration (MIC) in vitro was 2 µg/mL. Berberine inhibited H. parasuis adhesion to and invasion of PK-15 pig kidney cells. Proteomics studies of H. parasuis after berberine treatment identified a total of 97 differentially-expressed proteins; 35 upregulated and 62 downregulated. Bioinformatics analysis showed that berberine may inhibit the growth of H. parasuis by affecting outer membrane proteins, transferrins, and energy metabolism. This study provides a basis for the development of new antibacterial agents.

2.
Life Sci ; 280: 119715, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34116113

RESUMO

AIMS: Resveratrol pretreatment can decrease ischemic cerebral injury and enhance proliferation of neural stem cells via mediation of Sonic Hedgehog signaling. However, it is relatively little known about whether neurorestorative effects of resveratrol are mediated by Shh signaling in ischemic cerebral injury. The present study tests whether the Shh signaling pathway mediates resveratrol to promote neurorestoration of ischemic cerebral injury. MATERIALS AND METHODS: Rats or neurons before middle cerebral artery occlusion/reperfusion (MCAO/R) or oxygen-glucose deprivation/reoxygenation (OGD/R) injury were pretreated with resveratrol. Immunohistochemistry is used to be determined BrdU+/DCX+, BrdU+/Nestin+ and BrdU+/NG2+ cell (markers of new proliferated neural stem/progenitor and oligodendrocyte precursor cell, respectively), BrdU+/MAP2+ and BrdU+/CNPase+ cell (markers of new mature neuron and oligodendrocyte, respectively), BrdU+/TUNEL+ cell (marker of apoptosis for new proliferated cell), SY, NF200, Iba-1 and GFAP (markers of synaptogenesis, axon, microglia and astrocyte, respectively). Shh and Gli-1 mRNAs were detected by RT-PCR assay. Iba-1, GFAP, Shh and Gli-1 proteins were detected by Western blot. KEY FINDINGS: Resveratrol pretreatment significantly reduced neurological deficit scores, promoted proliferation, differentiation, migration and survival of neural stem/progenitor and oligodendrocyte precursor cells, inhibited astrocyte and microglia activation, strengthened synaptophysin and NF200 expression, at the same time, promoted neurite outgrowth of neurons. Meanwhile, expression levels of Shh and Gli-1 proteins were significantly increased and Gli-1 translocated into the nucleus. However, cyclopamine, a Smo inhibitor, canceled the above effects of resveratrol. CONCLUSIONS: It may be mediated, at least partly, by the Shh signaling pathway that resveratrol pretreament promote neurorestoration of ischemic cerebral injury.

3.
Orthop Surg ; 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34109750

RESUMO

OBJECTIVE: To examine the incidence and risk factors of in-hospital prosthesis-related complications (PRCs) following total knee arthroplasty (TKA) using a large-scale national database. METHODS: A retrospective database analysis was performed based on Nationwide Inpatient Sample (NIS) from 2005-2014. Patients who underwent TKA were included. The recruited cases were divided into two groups according to the occurrence of PRCs. Patient demographics (age, sex, and race), hospital characteristics (type of admission and payer, and bedsize, teaching status, location, and region of hospital), length of stay (LOS), total charges during hospitalization, in-hospital mortality, comorbidities, and perioperative complications were analyzed. RESULTS: A total of 1,227,244 TKAs were captured from the NIS database. There were 8484 cases of in-hospital PRCs after TKA and the overall incidence was 0.69%, with a slight downward trend annually. Periprosthetic joint infection (PJI) was the main category among PRCs (0.20%), followed by mechanical loosening (0.04%), dislocation (0.02%), and periprosthetic fracture (PPF) (0.01%). Patients suffered from in-hospital PRCs were 3 years younger (64 years vs 67 years) and 6.51% more likely to be male (43.60% vs 37.09%) compared to the nonaffected population (P < 0.0001). Additionally, patients experiencing in-hospital PRCs after TKA were 2.11% less likely through elective admission (92.07% vs 94.18%) while 2.34% more likely in teaching hospital (45.53% vs 43.19%) than those without these complications (P < 0.0001). Furthermore, the occurrence of in-hospital PRCs was associated with longer LOS (4 days vs 3 days; P < 0.0001), more total charges ($53,418 vs $41,204, P < 0.0001), and higher in-hospital mortality (0.30% vs 0.07%; P < 0.0001). Multivariate logistic regression was performed to identify independent risk factors of in-hospital PRCs after TKA which included younger age, male, non-elective admission, teaching hospital, deficiency and chronic blood loss anemia, coagulopathy, congestive heart failure, depression, diabetes with chronic complications, fluid and electrolyte disorders, pulmonary circulation disorders, metastatic cancer, and weight loss. Besides, in-hospital PRCs after TKA were associated with secondary osteoarthritis, inflammatory arthritis, prior knee arthroscopy, acute renal failure, acute myocardial infarction, deep vein thrombosis, sepsis, transfusion, and wound dehiscence. CONCLUSION: It is beneficial to study the risk factors of in-hospital PRCs after TKA to ensure the appropriate management and optimize consequences although a relatively low incidence was identified.

4.
Plant Dis ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34156272

RESUMO

Camellia oleifera, an evergreen small tree or shrub with high medicinal and ecological values, is mainly distributed in subtropical regions of China. Camellia oil obtained from Camellia oleifera seeds is rich in unsaturated fatty acids and unique flavors, and has become a rising high-quality edible vegetable oil in south of China (Zhuang 2008). The tea-oil tree Camellia oleifera plays important economic and ecological roles in Hunan province. During collecting trips, seeds of C. oleifera with disease symptoms have been observed in almost all oil-tea forests. In lab, the seeds can be infected by wounds and directly, however, wound infection is more rapid. In oil-tea forests, the wound of seed is often caused by external factors such as mechanical and insects. Symptomatic seeds exhibited brown rot symptoms with irregular, black spots, brown necrosis of the kernels, and accounted for 65% of the surveyed seeds (Fig. 1). Rotted seeds were surface-sterilized for 1 min in 75% ethanol, 3 min in 1% sodium hypochlorite, then rinsed for 2 min in sterile water and blotted on dry sterile filter paper. Discolored seed tissues were cut into pieces of 3 mm × 3 mm using a sterile scalpel, placed on potato dextrose agar (PDA) medium, and then incubated for 7 days at 25°C with a 12-h photoperiod. After 7 days of incubation, circular fungal colonies with dense aerial mycelium, produced black, wet spore masses. Four-septate conidia were ellipsoidal to obovoid, measuring 24 (22 to 26) × 6.5 (6 to 7) µm (n = 30). Conidia had three median cells, which were dark brown, with a single basal hyaline appendage, 4 (3.5 to 4.5) µm long, and two to four (usually three) apical hyaline appendages, 32 (27 to 35) µm long, similar to these recorded by Crous et al. (2011). Two single-spore isolates cultured on PDA medium were selected for DNA extraction. The ITS region was amplified using primers ITS5 and ITS4 (White et al. 1990). The partial translation elongation factor 1-alpha (tef1-α) gene region was amplified using primers EF1-728F (O'Donnell et al. 1998) and EF-2 (Carbone & Kohn 1999). The partial ß-tubulin (tub2) was amplified using primers T1 and Bt2b (Glass & Donaldson 1995). The sequences of ITS (MW391815), tef1-α (MW398222), and tub2 (MW398223) were submitted to GenBank. BLAST analysis demonstrated that these sequences were 99%~100% similar to the sequences of ITS (MH553959), tef1-α (MH554377), and tub2 (MH554618) published for Neopestalotiopsis protearum. Phylogenetic analysis revealed that all the representative isolates recovered from symptomatic Camellia oleifera seeds showed 91% bootstrap support with Neopestalotiopsis protearum isolate in references (Fig. 2). Pathogenicity tests were conducted on 20 healthy seeds. We wounded the seeds by a sterilized needle on the middle position, and put the 5-mm-diameter agar plugs with actively grown mycelia (strain HNWC04) or pure PDA on the wound. We then covered the wounds with clean masking tape to prevent contamination and desiccation. After inoculation, the seeds were kept at 90 to 100% relative humidity at 25°C in a greenhouse for 3 weeks and monitored daily for lesion development. Twenty days after inoculation, all the seeds inoculated presented similar typical symptoms observed under natural conditions, whereas the control seeds showed no symptoms. Koch's postulates were fulfilled by reisolating the same fungus and verifying its colony and morphological characters as Neopestalotiopsis protearum. To our knowledge, this is the first report of Neopestalotiopsis protearum causing oil-tea seed rot in China.

5.
Sensors (Basel) ; 21(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073923

RESUMO

Aiming at addressing the problems of short battery life, low payload and unmeasured load ratio of logistics Unmanned Aerial Vehicles (UAVs), the Radial Basis Function (RBF) neural network was trained with the flight data of logistics UAV from the Internet of Things to predict the flight status of logistics UAVs. Under the condition that there are few available input samples and the convergence of RBF neural network is not accurate, a dynamic adjustment method of RBF neural network structure based on information entropy is proposed. This method calculates the information entropy of hidden layer neurons and output layer neurons, and quantifies the output information of hidden layer neurons and the interaction information between hidden layer neurons and output layer neurons. The structural design and optimization of RBF neural network were solved by increasing the hidden layer neurons or disconnecting unnecessary connections, according to the connection strength between neurons. The steepest descent learning algorithm was used to correct the parameters of the network structure to ensure the convergence accuracy of the RBF neural network. By predicting the regression values of the flight status of logistics UAVs, it is demonstrated that the information entropy-based RBF neural network proposed in this paper has good approximation ability for the prediction of nonlinear systems.

6.
Surg Today ; 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34120243

RESUMO

PURPOSE: The specific genes or pathways in fibroblasts responsible for the pathogenesis of postoperative abdominal adhesion (PAA) remain to be elucidated. We aim to provide a new insight into disease mechanisms at the transcriptome level. METHODS: Male Sprague-Dawley rats were used to establish a PAA model. Primary fibroblasts were separated from normal peritoneal tissue (NF) and postoperative adhesion tissue (PF). RNA sequencing was used to analyze the transcriptome in NF and PF. RESULTS: One thousand two hundred thirty-five upregulated and 625 downregulated DEGs were identified through RNA-Seq. A pathway enrichment analysis identified distinct enriched biological processes, among which the most prominent was related to immune and inflammatory response and fibrosis. HE staining and Masson's trichrome staining histologically validated the RNA-Seq results. Six hub genes, ITGAM, IL-1ß, TNF, IGF1, CSF1R and EGFR were further verified by RT-PCR. CONCLUSIONS: Our study revealed the roles of the immune and inflammatory responses and fibrosis in the process of PAA. We also found six hub genes that may be potential therapeutic targets for PPA.

7.
J Hazard Mater ; 413: 125441, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930963

RESUMO

The human gut microbiome is crucial in modulating host health mostly through bacterial metabolites. Chemical exposure is typical external stress which alters its composition and functionality. To date, very few studies have investigated the effect of feeding state on chemical-induced gut microbial metabolic dysregulations. Here, we set up an in vitro human gut microbiome and incorporated a metabolomics approach to investigate the effect of tetracycline (TET) at multiple doses (i.e., 10, 1, and 0.01 mg/L) on gut microbiome under the fed and fasted states. Overall, the metabolome was highly responsive at the fed state with 62 metabolites dysregulated while only 14 were altered at the fasted state under 10 mg/L (clinical TET dose). As expected, nutrient consumption was significantly inhibited under clinical TET dose at the fed state accumulating nutrients such as glutamate and leucine. Interestingly, at the fed state, TET could increase the synthesis of indole and phenyl derivatives including indole-3-aldehyde and hydrocinnamate, while inhibiting indoxyl, tryptamine, and vitamin B production, all of which have host health implications. Furthermore, metabolites like indoxyl and xanthurenic acid were still responsive at 0.01 mg/L (dietary TET dose). Collectively, results demonstrated that the feeding state greatly modulates the chemical-induced gut microbial metabolic alterations.


Assuntos
Microbioma Gastrointestinal , Antibacterianos/toxicidade , Humanos , Metaboloma , Tetraciclina/toxicidade , Xenobióticos/toxicidade
8.
Food Chem ; 358: 129863, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940298

RESUMO

Traditional high-salt fermented Suanyu is an ethnic fermented fish product in southwest China. Lactic acid bacteria (LAB) are the most appropriate strains because of their technological properties during ripening fermentation. The diversity of LAB in high-salt fermented Chinese Suanyu was examined through high-throughput sequencing (HTS), and the most suitable LAB strain was acquired through strain isolation and characterization, surimi simulation fermentation system, and principal component analysis (PCA). The processing adaptability of the strain was examined via Suanyu fermentation. Results showed that Lactobacillus, Tetragenococcus, and Weissella were the dominant bacteria in Suanyu, and their contributions were 53.99%, 35.60%, and 4.10%, respectively. The most suitable strain (Lactobacillus plantarum B7) rapidly produced acid, exhibited a strong antibacterial activity, showed salt tolerance, and had no amino acid decarboxylase activity. pH decreased to about 3.6. Eventually, the ability to tolerate 20% salt was observed, and the activity of amino acid decarboxylase was negative. Fermented Suanyu with B7 rapidly produced acid (11.7% d-1). The non-protein nitrogen (NPN) and total free amino acid (FAA) contents of fermented Suanyu were higher and its total volatile base nitrogen (TVB-N), thiobarbituric acid (TBARS), and biogenic amines (BAs) levels were lower than those of naturally fermented Suanyu. Therefore, B7 is a potential microbial starter for Suanyu industrial production.


Assuntos
Bactérias/metabolismo , Alimentos e Bebidas Fermentados/microbiologia , Produtos Pesqueiros/microbiologia , Aminoácidos/análise , Animais , Bactérias/genética , Aminas Biogênicas/análise , Fermentação , Microbiologia de Alimentos , Concentração de Íons de Hidrogênio , Lactobacillus plantarum/isolamento & purificação , Lactobacillus plantarum/metabolismo , RNA Ribossômico 16S , Weissella/isolamento & purificação
9.
J Cell Mol Med ; 25(12): 5586-5601, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33982835

RESUMO

Alternative polarization of macrophages regulates multiple biological processes. While M1-polarized macrophages generally mediate rapid immune responses, M2-polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)-derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E3 (PGE3 ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE3 played an anti-inflammatory role by inhibiting LPS and interferon-γ-induced M1 polarization and promoting interleukin-4-mediated M2 polarization (M2a). Further, we found that although PGE3 had no direct effect on the growth of prostate cancer cells in vitro, PGE3 could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE3 significantly inhibited prostate cancer cell growth in a cancer cell-macrophage co-culture system. Experimental results showed that PGE3 inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE3 regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE3 can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate cancer.

10.
Mol Phylogenet Evol ; 162: 107202, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33992786

RESUMO

The tribe Senecioneae is one of the largest tribes in Asteraceae, with a nearly cosmopolitan distribution. Despite great efforts devoted to elucidate the evolution of Senecioneae, many questions still remain concerning the systematics of this group, from the tribal circumscription and position to species relationships in many genera. The hybridization-based target enrichment method of next-generation sequencing has been accepted as a promising approach to resolve phylogenetic problems. We herein develop a set of single-/low-copy genes for Senecioneae, and test their phylogenetic utilities. Our results demonstrate that these genes work highly efficiently for Senecioneae, with a high average gene recovery of 98.8% across the tribe and recovering robust phylogenetic hypotheses at different levels. In particular, the delimitation of the Senecioneae has been confirmed to include Abrotanella and exclude Doronicum, with the former sister to core Senecioneae and the latter shown to be more closely related to Calenduleae. Moreover, Doronicum and Calenduleae are inferred to be the closest relatives of Senecioneae, which is a new hypothesis well supported by statistical topology tests, morphological evidence, and the profile of pyrrolizidine alkaloids, a special kind of chemical characters generally used to define Senecioneae. Furthermore, this study suggests a complex reticulation history in the diversification of Senecioneae, accounting for the prevalence of polyploid groups in the tribe. With subtribe Tussilagininae s.str. as a case study showing a more evident pattern of gene duplication, we further explored reconstructing the phylogeny in the groups with high ploidy levels. Our results also demonstrate that tree topologies based on sorted paralogous copies are stable across different methods of phylogenetic inference, and more congruent with the morphological evidence and the results of previous phylogenetic studies.

11.
Cancer Lett ; 513: 36-49, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33991616

RESUMO

Endometrial cancer (EC) is becoming one of the most common gynecologic malignancies. Lipid metabolism is a hallmark feature of cancers. The molecular mechanisms underlying lipid metabolism in EC remain unclear. In this study, we revealed that many lipid metabolism-related genes were aberrantly expressed in endometrial cancer tissues, especially ACLY. Upregulated ACLY promoted EC cell proliferation and colony formation, and attenuated apoptosis. Mechanistically, cotreatment with obesity-related factors (estradiol, insulin and leptin) promoted nuclear translocation of ACLY through Akt-mediated phosphorylation of ACLY at Ser455. Nuclear-localized ACLY increased histone acetylation levels, thus resulting in upregulation of pyrimidine metabolism genes, such as DHODH. Moreover, STAT3 altered the ACLY expression at the transcriptional level via directly binding to its promoter region. In conclusion, our findings clarify the roles and mechanisms of ACLY in endometrial cancer and ACLY could link obesity risk factors to the regulation of histone acetylation. We believe that novel therapeutic strategies for EC can be designed by targeting the ACLY axis.

12.
Biol Chem ; 402(6): 703-715, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33951764

RESUMO

Liver fibrosis is a common consequence of chronic liver diseases involved with the activation of hepatic stellate cells (HSCs) and endoplasmic reticulum (ER) stress. Irisin is a small polypeptide hormone that shows beneficial effects on metabolic disorders. The current study aimed to investigate the biological function of irisin on hepatic fibrosis. A mouse model of carbon tetrachloride (CCl4)-induced hepatic fibrosis was established. CCl4-treated mice showed elevated serum levels of AST and ALT, increased collagen accumulation, induced ER stress, and upregulated expressions of pro-fibrotic proteins in the liver compared to the controls. The administration of irisin, however, ameliorated CCl4-induced hepatic fibrosis in both cultured HSCs and mice. PKR-like ER kinase (PERK) is a key component of the ER stress-associated signaling pathway. We found that irisin treatment improved the stability of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) via regulating the phosphorylation of PERK in mouse livers and isolated HSCs. Also, the knockdown of HNRNPA1 eliminated the hepatoprotective effects of irisin on hepatic fibrosis and ER stress. In summary, this study showed that irisin alleviated ER stress and hepatic fibrosis by inhibiting PERK-mediated HNRNPA1 destabilization, suggesting that irisin may represent a promising therapeutic strategy for patients with liver fibrosis.

13.
Oncogene ; 40(23): 3959-3973, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33986509

RESUMO

Metastasis is a major cause of cancer-related deaths. Tumor-intrinsic properties can determine whether tumor metastasis occurs or not. Here, by comparing the gene expression patterns in primary colorectal cancer (CRC) patients with or without metastasis, we found that Collagen Triple Helix Repeat Containing 1 (CTHRC1) in primary CRC served as a metastasis-associated gene. Animal experiments verified that CTHRC1 secreted by CRC cells promoted hepatic metastasis, which was closely correlated with macrophage infiltration. Depletion of macrophages by liposomal clodronate largely abolished the promoting effect of CTHRC1 on CRC liver metastasis. Furthermore, we demonstrated that CTHRC1 modulated macrophage polarization to M2 phenotypes through TGF-ß signaling. A mechanistic study revealed that CTHRC1 bound directly to TGF-ß receptor II and TGF-ß receptor III, stabilized the TGF-ß receptor complex, and activated TGF-ß signaling. The combination treatment of CTHRC1 monoclonal antibody and anti-PD-1 blocking antibody effectively suppressed CRC hepatic metastasis. Taken together, our data demonstrated that CTHRC1 is an intrinsic marker of CRC metastasis and further revealed that CTHRC1 promoted CRC liver metastasis by reshaping infiltrated macrophages through TGF-ß signaling, suggesting that CTHRC1 could be a potential biomarker for the early prediction of and a therapeutic target of CRC hepatic metastasis.

14.
Cancer Lett ; 514: 90-102, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34023418

RESUMO

Effective treatment regimens for triple-negative breast cancer (TNBC) are relatively scarce due to a lack of specific therapeutic targets. Epidermal growth factor receptor (EGFR) signaling is highly active in TNBC and is associated with poor prognosis. Most EGFR antagonists, which significantly improve outcome in lung and colon cancer, have shown limited clinical effects in breast cancer. However, limiting EGFR expression in TNBC is a potential strategy for improving the clinical efficacy of EGFR antagonists. Here, we found that the gamma-aminobutyric acid type A receptor π subunit (GABRP), as a membrane protein enriched in TNBC stem cells, interacted with EGFR and significantly sustained its expression, resulting in stemness maintenance and chemotherapy resistance. Silencing GABRP induced down-regulation of EGFR signaling, which hindered cell stemness and enhanced sensitivity to chemotherapies, including paclitaxel, doxorubicin, and cisplatin. We also identified that retigabine, an FDA-approved drug for adjunctive treatment of seizures, increased the sensitivity of EGFR to gefitinib in gefitinib-resistant cells. Our findings show that GABRP can sustain the stemness of TNBC via modulating EGFR expression, suggesting that GABRP may be a potential therapeutic target that can address EGFR inhibitor resistance in TNBC.

15.
J Colloid Interface Sci ; 600: 278-287, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34022724

RESUMO

Lithium-sulfur batteries (LSBs) have attracted much attention due to their high theoretical specific capacity, energy density and low cost. However, the commercial application of LSBs is hindered due to the lithium polysulfide (LiPS) shuttle as well as the sluggish reaction kinetics. Herein, cobalt selenide (Co0.85Se) nanowire arrays have been constructed on a carbon-modified separator by an in-situ electrodeposition technique without any other post-treatments such as coating with other ancillary materials. The introduced three-dimensional (3D) conductive carbon layer comprising of carbon nanotube (CNT) and acetylene black (AB) not only serves as the effective support for Co0.85Se (CS) but also builds a hierarchical structure to promote the e- transfer. The as-obtained CS-CNT/AB presents a strong anchoring effect on LiPSs and high electrocatalytic activity for sulfur reaction kinetics. As a result, the LSBs inserted with electrodeposition-enabled CS modified separator exhibit an outstanding rate capability (1560.4 mAh g-1 at 0.1 C) and relatively low capacity decay of only 0.068% per cycle over 500 cycles at 2.0 C. This study provides a promising strategy to realize the rational construction of high-efficiency and long-life LSBs.

16.
Pediatr Res ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050269

RESUMO

BACKGROUND: Perinatal inflammation combined with hypoxia-ischemia (HI) exacerbates injury in the developing brain. Therapeutic hypothermia (HT) is standard care for neonatal encephalopathy; however, its benefit in inflammation-sensitized HI (IS-HI) is unknown. METHODS: Twelve newborn piglets received a 2 µg/kg bolus and 1 µg/kg/h infusion over 52 h of Escherichia coli lipopolysaccharide (LPS). HI was induced 4 h after LPS bolus. After HI, piglets were randomized to HT (33.5 °C 1-25 h after HI, n = 6) or normothermia (NT, n = 6). Amplitude-integrated electroencephalogram (aEEG) was recorded and magnetic resonance spectroscopy (MRS) was acquired at 24 and 48 h. At 48 h, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive brain cell death, microglial activation/proliferation, astrogliosis, and cleaved caspase-3 (CC3) were quantified. Hematology and plasma cytokines were serially measured. RESULTS: Two HT piglets died. aEEG recovery, thalamic and white matter MRS lactate/N-acetylaspartate, and TUNEL-positive cell death were similar between groups. HT increased microglial activation in the caudate, but had no other effect on glial activation/proliferation. HT reduced CC3 overall. HT suppressed platelet count and attenuated leukocytosis. Cytokine profile was unchanged by HT. CONCLUSIONS: We did not observe protection with HT in this piglet IS-HI model based on aEEG, MRS, and immunohistochemistry. Immunosuppressive effects of HT and countering neuroinflammation by LPS may contribute to the observed lack of HT efficacy. Other immunomodulatory strategies may be more effective in IS-HI. IMPACT: Acute infection/inflammation is known to exacerbate perinatal brain injury and can worsen the outcomes in neonatal encephalopathy. Therapeutic HT is the current standard of care for all infants with NE, but the benefit in infants with coinfection/inflammation is unknown. In a piglet model of inflammation (LPS)-sensitized HI, we observed no evidence of neuroprotection with cooling for 24 h, based on our primary outcome measures: aEEG, MRS Lac/NAA, and histological brain cell death. Additional neuroprotective agents, with beneficial immunomodulatory effects, require exploration in IS-HI models.

17.
Curr Neuropharmacol ; 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030620

RESUMO

Alzheimer's disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Over the past decade, a string of disappointing clinical trial results has forced us to shift our focus to the preclinical stage of AD, which represents the most promising therapeutic window. However, the accurate diagnosis of preclinical AD requires the presence of brain ß-amyloid deposition determined by cerebrospinal fluid or amyloid-positron emission tomography, significantly limiting routine screening and diagnosis in non-tertiary hospital settings. Thus, an easily accessible marker or tool with high sensitivity and specificity is highly needed. Recently, it has been discovered that individuals in the late stage of preclinical AD may not be truly "asymptomatic" in that they may have already developed subtle or subjective cognitive decline. In addition, advances in blood-derived biomarker studies have also allowed detection of pathologic changes in preclinical AD. Exosomes, as cell-to-cell communication messengers, can reflect the functional changes of their source cell. Methodological advances have made it possible to extract brain-derived exosomes from peripheral blood, making exosomes an emerging biomarker carrier and liquid biopsy tool for preclinical AD. The eye and its associated structures have rich sensory-motor innervation. In this regard, studies have indicated that they may also provide reliable markers. Here, our report covers the current state of knowledge of neuropsychological and eye tests as screening tools for preclinical AD and assesses the value of blood and brain-derived exosomes as carriers of biomarkers in conjunction with the current diagnostic paradigm.

18.
Biochemistry (Mosc) ; 86(5): 568-576, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33993864

RESUMO

Recent studies have predominantly focused on the role of B cells in metabolic diseases, yet the function of B cells in adipose homeostasis remains unclear. Pax transactivation domain-interacting protein (PTIP), a licensing factor for humoral immunity, is necessary for B cell development and activation. Here, using mice that lack PTIP in B cells (PTIP-/- mice), we explored the role of B cells in adipose homeostasis under physiological conditions. Fat deposition in 8-week-old mice was measured by micro-CT, and PTIP-/- mice presented a marked decrease in the deposition of subcutaneous adipose tissue (SAT). Untargeted lipidomics revealed that the triglyceride composition in SAT was altered in PTIP-/- mice. In addition, there was no difference in the number of adipocyte progenitor cells in the SAT of wild-type (WT) and PTIP-/- mice as measured by flow cytometry. To study the effects of steady-state IgM and IgG antibody levels on fat deposition, PTIP-/- mice were injected intraperitoneally with serum from WT mice once every 3-4 days for 4 weeks. The iSAT mass of the recipient mice showed no significant increase in comparison to the controls after 4 weeks of injections. Our findings reveal that PTIP plays an essential role in regulating subcutaneous adipocyte size, triglyceride composition, and fat deposition under physiological conditions by controlling B cells. The decreased subcutaneous fat deposition in PTIP-/- mice does not appear to be related to the number of adipocyte progenitor cells. The steady-state levels of IgM and IgG antibodies in vivo are not associated with the subcutaneous fat deposition.

19.
Appl Microbiol Biotechnol ; 105(10): 4269-4284, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33990856

RESUMO

Enterococcus faecium WEFA23 was previously found effectively against adherence and colonization of Listeria monocytogenes CMCC54007, which might be closely related to its surface layer protein (SLP). In this study, the protective of SLP of E. faecium WEFA23 against infection of L. monocytogenes CMCC54007 was systemically investigated. In vitro assay showed that SLP actively inhibited L. monocytogenes internalization into Caco-2 cell line, with decreasing mRNA level of pro-inflammation cytokines and virulence factors and restoring destroyed intestinal barrier. In vivo assay through excluding SLP of E. faecium WEFA23 by 5 M LiCl represented that SLP increased body weight, reduced mortality and cell counts of L. monocytogenes CMCC54007 in tissues of mice. Further researches showed that SLP protected against L. monocytogenes CMCC54007 infection by modulation of intestinal permeability and immunity, namely, it decreased fluorescein isothiocyanate (FITC)-Dextran in serum, ameliorated destroyed colon structure, and increased number of goblet cells and protein level of TJ protein (Claudin-1, Occludin, and ZO-1) in colon. For immunity, SLP decreased number of CD4+ and CD8+ T cells in liver, mRNA level, and content of pro-inflammatory factors IL-6, IL-1ß, IFN-γ ,TNF-α, and NO, and restored the structure of liver and spleen. Key Points•SLP of E. faecium inhibited L. monocytogenes internalization and colonization•SLP of E. faecium ameliorated host intestinal barrier dysfunction•SLP of E. faecium decreased pro-inflammatory cytokines and cells.


Assuntos
Enterococcus faecium , Listeria monocytogenes , Listeriose , Animais , Linfócitos T CD8-Positivos , Células CACO-2 , Humanos , Listeriose/prevenção & controle , Proteínas de Membrana , Camundongos , Permeabilidade
20.
Artigo em Inglês | MEDLINE | ID: mdl-33909498

RESUMO

Abnormal airway remodeling is a common pathologic change seen in chronic respiratory diseases. Altered proliferation and differentiation of airway smooth muscle cells (ASMCs) are the major component of airway remodeling, and the resultant structural abnormalities are difficult to restore. Understanding of airway smooth muscle regulation is urgently needed in order to identify potential intervention targets. MYOCD (or Myocardin) and Myocardin related transcription factors (MRTFs) are key co-transcription factors in muscle growth, which have not been extensively investigated in airway smooth muscle cells. In addition, the RhoA/ROCK signaling pathway is known to play an important role in airway remodeling partly through regulating the proliferation and differentiation of ASMCs, which may be connected with MYOCD/MRTF co-transcription factors. This minireview focuses on this newly recognized and potentially important RhoA/ROCK-MYOCD/MRTFs pathway in controlling airway smooth muscle growth and remodeling.

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