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1.
Int Immunopharmacol ; 94: 107503, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33647825

RESUMO

Our previous studies have implicated Caspase-1 signaling in driving the proinflammatory state of acute graft versus host disease (aGVHD). Therefore, we aimed to elucidate the mechanism of Caspase-1 in in murine models of aGVHD through specific inhibition of its activity with the decoy peptide Ac-YVAD-CMK. We transplanted bone marrow from donor C57BL/6 (H-2b) mice into recipient BALB/c (H-2Kd) mice and randomized the recipients into the following treatment cohorts: (1) allogeneic hematopoietic stem cell transplantation and splenic cell infusion control (PBS group); (2) low dose Ac-YVAD-CMK (AC low group); (3) and high dose Ac-YVAD-CMK (AC high group). Indeed, we observed that Caspase-1 inhibition by Ac-YVAD-CMK ameliorated pathological damage and inflammation in the liver, lungs, and colon elicited by aGVHD. This was associated with reduced mortality secondary to aGVHD. Mechanistically, we found that Caspase-1 inhibition modulated donor T cell expansion, restored the balance of Th1/Th17/Treg subsets, and markedly decreased serum levels and aGVHD target organ mRNA expression of IL-1ß, IL-18, and HMGB1. Thus, we demonstrate that inhibition of Caspase-1 by Ac-YVAD-CMK mitigates murine aGVHD by regulating Th1/Th17/Treg balance and attenuating its characteristic proinflammatory state.

2.
Signal Transduct Target Ther ; 6(1): 59, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33568623

RESUMO

It remains unknown for decades how some of the therapeutic fusion proteins positive in a small percentage of cancer cells account for patient outcome. Here, we report that osteosarcoma Rab22a-NeoF1 fusion protein, together with its binding partner PYK2, is sorted into exosomes by HSP90 via its KFERQ-like motif (RVLFLN142). The exosomal Rab22a-NeoF1 fusion protein facilitates the pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages. The exosomal PYK2 activates RhoA in its negative recipient osteosarcoma cells and induces signal transducer and activator of transcription 3 activation in its recipient macrophages to increase M2 phenotype. Consequently, lung metastases of its recipient osteosarcoma cells are promoted by this exosomal Rab22a-NeoF1 fusion protein, and this event can be targeted by disrupting its interaction with PYK2 using a designed internalizing RGD peptide.

3.
Eur J Cancer ; 147: 63-73, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33618200

RESUMO

OBJECTIVE: The mechanisms underlying the contribution of primary tumour to pre-metastatic niche formation remains largely unknown in hepatocellular carcinoma (HCC). We previously reported that the released LOXL2 from HCC cells under higher stiffness stimulation facilitated the formation of lung pre-metastatic niche. Here, we further clarified the pathological role of LOXL2 in promoting lung pre-metastatic niche formation and lung metastasis occurrence in HCC and its relevant molecular mechanism. METHODS: Using two different animal models and an in vitro system of mechanically tuneable gel mirroring lung tissue stiffness, we explored the underlying mechanism of LOXL2 in pre-metastatic niche formation. RESULTS: We applied tail vein injection of CM-LV-LOXL2-OEsimulating tumour-released soluble factors to induce lung pre-metastatic niche formation and found that the injected LOXL2 remarkably enhanced CD11b+/CD45+ bone marrow-derived cells (BMDCs) recruitment and fibronectin expression in lung. Subsequently, LOXL2-overexpressed xenograft HCC models validated that tumour-secreted LOXL2 significantly promoted the occurrence of pulmonary metastasis. In vitro, LOXL2 and LOXL2-caused matrix stiffening not only obviously upregulated the expressions of MMP9 and fibronectin in lung fibroblasts, but also evidently increased the number of adherent HCC cells and the expression of chemokine CXCL12. The activation of PI3K-AKT pathway mediated LOXL2-upregulated fibronectin. HCC patients in High-LOXL2 group had higher ratio of tumour recurrence than HCC patients in Low-LOXL2 group, supporting a significance of LOXL2 in HCC progression and unfavourable outcome. CONCLUSION: Primary tumour-released LOXL2 promotes lung pre-metastatic niche formation and lung metastasis occurrence. LOXL2-caused matrix stiffening synergistically regulates lung pre-metastatic niche formation. Targeting LOXL2-induced lung pre-metastatic niche may be a novel intervention approach against HCC metastasis.

4.
Ann Dyslexia ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33575979

RESUMO

This study examined the sources of reading comprehension difficulties in English language learners (ELLs). The characteristics of ELL poor comprehenders were compared to their English as a first language (EL1) peers. Participants included 124 ELLs who spoke Chinese as an L1 and 79 EL1 students. Using a regression technique based on age, non-verbal reasoning, word reading accuracy, and word reading fluency, three types of comprehenders (poor, average, and good) were identified within each language group. The groups were then compared on measures of oral language skills (vocabulary breadth, vocabulary depth, and listening comprehension), metalinguistic skills (morphological awareness and syntactic awareness), working memory, and higher-level processing skills (inference, conjunction use, and comprehension monitoring). ELL poor comprehenders had significantly lower scores than ELL average and good comprehenders on vocabulary breadth, listening comprehension, and morphological awareness, whereas there were no significant differences between the average and good comprehender groups on these skills. Additionally, both ELL poor and average comprehenders had lower scores than ELL good comprehenders on all three higher-level skills. Finally, results showed that ELL poor comprehenders scored lower than EL1 poor comprehenders on vocabulary breadth, listening comprehension, and morphological awareness, but the two groups did not differ on higher-level skills. Theoretical and educational implications for the identification and instruction of ELL poor comprehenders are discussed.

5.
Biochem Pharmacol ; : 114468, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33577889

RESUMO

Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool with many demonstrated applications in various phases of drug development and regulatory review. RNA interference (RNAi)-based therapeutics are a class of drugs that have unique pharmacokinetic properties and mechanisms of action. With an increasing number of RNAi therapeutics in the pipeline and reaching the market, there is a considerable amount of active research in this area requiring a multidisciplinary approach. The application of PBPK models for RNAi therapeutics is in its infancy and its utility to facilitate the development of this new class of drugs is yet to be fully evaluated. From this perspective, we briefly discuss some of the current computational modeling approaches used in support of efficient development and approval of RNAi therapeutics. Considerations for PBPK model development are highlighted both in a relative context between small molecules and large molecules such as monoclonal antibodies and as it applies to RNAi therapeutics. In addition, the prospects for drawing upon other recognized avenues of PBPK modeling and some of the foreseeable challenges in PBPK model development for these chemical modalities are briefly discussed. Finally, an exploration of the potential application of PBPK model development for RNAi therapeutics is provided. We hope these preliminary thoughts will help initiate a dialogue between scientists in the relevant sectors to examine the value of PBPK modeling for RNAi therapeutics. Such evaluations could help standardize the practice in the future and support appropriate guidance development for strengthening the RNAi therapeutics development program.

6.
J Cell Sci ; 134(4)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597156

RESUMO

The discovery of receptor clustering in the activation of adaptive immune cells has revolutionized our understanding of the physical basis of immune signal transduction. In contrast to the extensive studies of adaptive immune cells, particularly T cells, there is a lesser, but emerging, recognition that the formation of receptor clusters is also a key regulatory mechanism in host-pathogen interactions. Many kinds of innate immune receptors have been found to assemble into nano- or micro-sized domains on the surfaces of cells. The clusters formed between diverse categories of innate immune receptors function as a multi-component apparatus for pathogen detection and immune response regulation. Here, we highlight these pioneering efforts and the outstanding questions that remain to be answered regarding this largely under-explored research topic. We provide a critical analysis of the current literature on the clustering of innate immune receptors. Our emphasis is on studies that draw connections between the phenomenon of receptor clustering and its functional role in innate immune regulation.

7.
Proc Natl Acad Sci U S A ; 118(8)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33602822

RESUMO

Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail 1700102P08Rik, one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking Maps (Maps -/- ) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal Maps -/- spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult Maps -/- spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult Maps -/- pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in Maps -/- pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general.

8.
Fam Pract ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615372

RESUMO

OBJECTIVES: To examine the validity and reliability of the Mandarin version of the Treatment Burden Questionnaire (TBQ) among stroke patients. BACKGROUND: Stroke patients need long-term management of symptoms and life situation, and treatment burden has recently emerged as a new concept that can influence the health outcomes during the rehabilitation process. METHODS: The convenience sampling method was used to recruit 187 cases of stroke patients in a tertiary grade hospital in Tianjin for a formal investigation. Item analysis, reliability and validity tests were carried out. The reliability test included internal consistency and test-retest reliability. And as well as content, structure and convergent validity were performed for the validity test. RESULTS: Of the 187 completed questionnaires, only 180 (96.3%) were suitable for analysis. According to the experts' evaluation, the I-CVI of each item was from 0.833 to 1.000, and the S-CVI was 0.967. The exploratory factor analysis yielded three-factor components with a cumulative variation of 53.054%. Convergent validity was demonstrated using measures of Morisky's Medication Adherence Scale 8 (r = -0.450, P < 0.01). All correlations between items and global scores ranged from 0.403 to 0.638. Internal consistency reliability and test-retest reliability were found to be acceptable, as indicated by a Cronbach's α of 0.824 and an intraclass correlation coefficient of 0.846, respectively. CONCLUSIONS: The Mandarin TBQ had acceptable validity and reliability. The use of TBQ in the assessment of treatment burden of stroke survivor may benefit health resources allocation and provide tailor therapeutic interventions to construct minimally disruptive care.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33537836

RESUMO

PURPOSE: We dual-labeled an intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (mAb) and evaluated its effectiveness for lesion detection and surgical navigation in pancreatic ductal adenocarcinoma (PDAC) via multiple noninvasive imaging approaches, including positron emission tomography (PET), near-infrared fluorescence (NIRF), and Cerenkov luminescence imaging (CLI). METHODS: ICAM-1 expression in PDAC cell lines (BxPC-3 and AsPC-1) was assessed via flow cytometry and immunofluorescent staining. An ICAM-1 mAb labeled by IRDye 800CW and radionuclide zirconium-89 (denoted as [89Zr]Zr-DFO-ICAM-1-IR800) was synthesized. Its performance was validated via in vivo comparative PET/NIRF/CLI and biodistribution (Bio-D) studies in nude mice bearing subcutaneous BxPC-3/AsPC-1 tumors or orthotopic BxPC-3 tumor models using nonspecific IgG as an isotype control tracer. RESULTS: ICAM-1 expression was strong in the BxPC-3 and minimal in the AsPC-1 cell line. Both multimodality imaging and Bio-D data exhibited more prominent uptake of [89Zr]Zr-DFO-ICAM-1-IR800 in BxPC-3 tumors than in AsPC-1 tumors. The uptake of [89Zr]Zr-DFO-IgG-IR800 in BxPC-3 tumors was similar to that of [89Zr]Zr-DFO-ICAM-1-IR800 in AsPC-1 tumors. These results demonstrate the desirable affinity and specificity of [89Zr]Zr-DFO-ICAM-1-IR800 compared to [89Zr]Zr-DFO-IgG-IR800. Orthotopic BxPC-3 tumor foci could also be clearly delineated by [89Zr]Zr-DFO-ICAM-1-IR800. An intermodal match was achieved in the ICAM-1-targeted immunoPET/NIRF/CLI. The positive expression levels of ICAM-1 in BxPC-3 tumor tissue were further confirmed by immunohistopathology. CONCLUSION: We successfully developed a dual-labeled ICAM-1-targeted tracer for PET/NIRF/CLI of PDAC that can facilitate better diagnosis and intervention of PDAC upon clinical translation.

10.
Pediatr Surg Int ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538868

RESUMO

PURPOSE: Postoperative adhesive bowel obstruction (ABO) is a common complication especially in complicated appendicitis. This study aimed to analyze the risk factors for ABO following appendectomy in children with complicated appendicitis, and establish a scoring model for predicting postoperative ABO and treatment option to relieve the obstruction. METHODS: From December 2014 to January 2020, all files of consecutive patients with complicated appendicitis underwent appendectomy were reviewed. Univariate and multivariate analyses were used to screen out the risk factors of postoperative ABO, and establish a scoring model for predicting postoperative ABO and surgical relief to relieve the obstruction. RESULTS: Of the 780 patients, 87 (11.2%) had ABO following appendectomy, including 27 who underwent surgical relief. Age ≤ 6 years, overweight and obesity, duration of symptoms ≥ 36 h, C-reactive protein ≥ 99 mg/L, duration of operation ≥ 60 min, intraoperative peritoneal lavage, and postoperative flatus time ≥ 20 h were independent risk factors for postoperative ABO. The final scoring model for postoperative ABO included factors above, and exhibited a high degree of discrimination (area under the curve [AUC]: 0.937; 95% confidence interval [CI] 0.913-0.960) corresponding to an optimal cut-off value of 6: 82.8% sensitivity, 92.6% specificity. Furthermore, the scoring model showed a sensitivity of 74.1% and a specificity of 91.7% for patients wo underwent surgical relief to relieve obstruction with the optimal cut-off value of 9. CONCLUSION: Risk factors for postoperative ABO should be taken seriously in children with complicated appendicitis. The scoring model is a novel but promising method to predict postoperative ABO and provide reference for clinical decision-making to relieve the obstruction.

11.
Histochem Cell Biol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398435

RESUMO

Exploring the three-dimensional (3D) morphology of neurons is essential to understanding spinal cord function and associated diseases comprehensively. However, 3D imaging of the neuronal network in the broad region of the spinal cord at cellular resolution remains a challenge in the field of neuroscience. In this study, to obtain high-resolution 3D imaging of a detailed neuronal network in the mass of the spinal cord, the combination of synchrotron radiation micro-computed tomography (SRµCT) and the Golgi-cox staining were used. We optimized the Golgi-Cox method (GCM) and developed a modified GCM (M-GCM), which improved background staining, reduced the number of artefacts, and diminished the impact of incomplete vasculature compared to the current GCM. Moreover, we achieved high-resolution 3D imaging of the detailed neuronal network in the spinal cord through the combination of SRµCT and M-GCM. Our results showed that the M-GCM increased the contrast between the neuronal structure and its surrounding extracellular matrix. Compared to the GCM, the M-GCM also diminished the impact of the artefacts and incomplete vasculature on the 3D image. Additionally, the 3D neuronal architecture was successfully quantified using a combination of SRµCT and M-GCM. The SRµCT was shown to be a valuable non-destructive tool for 3D visualization of the neuronal network in the broad 3D region of the spinal cord. Such a combinatorial method will, therefore, transform the presentation of Golgi staining from 2 to 3D, providing significant improvements in the 3D rendering of the neuronal network.

12.
Small ; : e2005073, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33460246

RESUMO

Due to the tunable skeletons, variable pore environments, and predesignable structures, covalent organic frameworks (COFs) can be served as a versatile platform to tailor redox activities for efficient energy storage. Redox-active COFs with specific functional groups can not only promote high-speed mass transport in the permanently open channels, but also provide dense active sites for reversible redox reactions so as to efficiently adsorb the electrolyte ions, thus becoming emerging and promising electroactive materials. This review summarizes the design principles and synthetic methods of redox-active COFs, with a focus on surveying the representative advances in supercapacitors. The key progress, major challenges, and future directions in this promising field are highlighted as well.

13.
Phytomedicine ; 82: 153441, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387968

RESUMO

BACKGROUND: Oxidative stress induces mitochondrial dysfunction, causing memory loss. Long noncoding RNAs influence mitochondrial function and suppress oxidative stress by regulating target protein expression and gene transcription. Celastrol, a natural antioxidant extracted from Tripterygium wilfordii Hook F. ("Thunder of God Vine"), effectively alleviates oxidative stress-mediated tissue injury. In the present study, we examined the effects of celastrol on memory dysfunction induced by ischemia/reperfusion (I/R) and elucidated the mechanisms underlying these effects. METHODS: C57BL/6 mice were used to mimic I/R using the bilateral common carotid clip reperfusion method, and a hippocampal cell line (HT-22) cells were used to establish a model of oxygen-glucose deprivation/reoxygenation (OGD/R). We observed changes in behavior and mitochondrial structure. Cell activity, cell respiration, and antioxidant capacity were measured. MAP3K12, p-JNK, p-c-Jun, p-Akt/Akt, PI3K, Bcl-2, and Bax expression were evaluated. RESULTS: I/R or OGD/R significantly increased AK005401 and MAP3K12 expression, further attenuating PI3K/Akt activation, promoting reactive oxygen species generation and causing mitochondrial dysfunction and cell apoptosis, thereby resulting in memory dysfunction. Celastrol increased antioxidant capacity, inhibited cell apoptosis, and improved mitochondrial function, effectively improving learning and memory by downregulating AK005401 and MAP3K12 and activating PI3K/Akt. CONCLUSIONS: The AK005401/MAP3K12 signaling pathway has an important role in I/R-mediated hippocampal injury, and celastrol can potentially reduce or possibly prevent I/R-induced neuronal injury by downregulating AK005401/MAP3K12 signaling.

14.
Oncol Rep ; 45(3): 1295-1305, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33469680

RESUMO

Non­small cell lung cancer (NSCLC) is the leading cause of cancer­related deaths worldwide. Cisplatin­based chemotherapy currently represents the main treatment option for patients with NSCLC. The aim of the present study was to evaluate effect of single nucleotide polymorphisms (SNPs) within the excision repair cross­complementing group 5 (ERCC5) gene on susceptibility to NSCLC, as well as the responsiveness to and toxicity of cisplatin chemotherapy. A total of 506 patients with NSCLC and 510 healthy controls were recruited for the present study. All DNA samples were genotyped by the Agena MassARRAY platform. Logistic regression analysis was carried out to assess the relationship between ERCC5 polymorphisms with NSCLC susceptibility and responsiveness to chemotherapy. The rs4771436 TG­GG genotype was associated with increased NSCLC risk. When the data were stratified according to age, sex, tobacco smoking, body mass index and histological type, ERCC5 polymorphisms (rs2016073, rs4771436, rs11069498 and rs4150330) were associated with NSCLC risk. Furthermore, the A allele and GA­AA genotype of rs11069498 were related to the response to chemotherapy. ERCC5 (rs11069498 and rs4150330) polymorphisms were associated with the increased risk of toxicity. However, rs4771436 in ERCC5 gene was significantly correlated with the reduced risk of toxicity. These results suggested a potential relationship between ERCC5 polymorphisms, the risk of NSCLC and the sensitivity to cisplatin­based chemotherapy among Chinese populations.

15.
Chem Asian J ; 16(5): 503-506, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33470007

RESUMO

Amide synthesis is one of the most important transformations in organic chemistry due to their ubiquitous presence in our daily life. In this communication, a palladium catalyzed cascade azidation/carbonylation of aryl halides for the synthesis of amides was developed. Both iodo- and bromobenzene derivatives were transformed to the corresponding amides using PdCl2 /xantphos as the catalyst system and sodium azide as the nitrogen-source. The reaction proceeds via a cascade azidation/carbonylation process. A range of alkyl and halogen substituted amides were prepared in moderate to good yields.

16.
Drug Deliv ; 28(1): 218-228, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33501868

RESUMO

Retinal degeneration (RD) refers to a group of blinding retinopathies leading to the progressive photoreceptor demise and vision loss. Treatments against this debilitating disease are urgently needed. Intraocular delivery of exosomes represents an innovative therapeutic strategy against RD. In this study, we aimed to determine whether the subretinal delivery of RPE-derived exosomes (RPE-Exos) can prevent the photoreceptor death in RD. RD was induced in C57BL6 mice by MNU administration. These MNU administered mice received a single subretinal injection of RPE-Exos. Two weeks later, the RPE-Exos induced effects were evaluated via functional, morphological, and behavior examinations. Subretinal delivery of RPE-Exos efficiently ameliorates the visual function impairments, and alleviated the structural damages in the retina of MNU administered mice. Moreover, RPE-Exos exert beneficial effects on the electrical response of the inner retinal circuits. Treatment with RPE-Exos suppressed the expression levels of inflammatory factors, and mitigated the oxidative damage, indicating that subretinal delivery of RPE-Exos constructed a cytoprotective microenvironment in the retina of MNU administered mice. Our data suggest that RPE-Exos have therapeutic effects against the visual impairments and photoreceptor death. These findings will enrich our knowledge of RPE-Exos, and highlight the discovery of a promising medication for RD.

17.
Chemosphere ; 262: 127606, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805650

RESUMO

PerFluoroOctane Sulfonate (PFOS), is a toxic anthropogenic chemical that has been produced and gradually released into the environment for the past seven decades. An accurate audit of global PFOS contamination and contaminated sites are yet to be published. The available technologies to remediate PFOS contaminated soil are limited and often basic strategies such as temporary soil containment are adopted as immediate measures to manage the contaminated sites. In this study, the in situ soil flushing technique is assessed for its capacity to remediate soil contaminated with PFOS. A complete treatment process with several operation units was proposed such as solvent flushing, ground water pumping, solvent recovery and water treatment for PFOS. Potential solvents were identified and it was observed that more than 98% PFOS removal could be attained by flushing with five bed volumes of 50% ethanol. In addition, the study investigated thirteen commercially available filter materials and identified PFA694E, K6362, MP 62, Amberlite IRA 67 and Dowexoptopore V493 as suitable to eliminate PFOS with competitive PFOS adsorption characteristics. The proposed method can be recommended to remediate PFOS in recognised contaminated soils, such as those at defence sites. Furthermore, a contaminated site with favourable characteristics to implement the suggested method was identified in Australia and described in this paper.


Assuntos
Ácidos Alcanossulfônicos/análise , Recuperação e Remediação Ambiental/métodos , Fluorcarbonetos/análise , Poluentes do Solo/análise , Adsorção , Austrália , Poluição Ambiental , Água Subterrânea , Solo , Purificação da Água
18.
Artigo em Inglês | MEDLINE | ID: mdl-33257560

RESUMO

Seasonal cycles govern life on earth, from setting the time for the mating season to influencing migrations and governing physiological conditions like hibernation. The effect of such changing conditions on behavior is well-appreciated, but their impact on the brain remains virtually unknown. We investigate long-term seasonal changes in the mammalian brain, known as Dehnel's effect, where animals exhibit plasticity in body and brain sizes to counter metabolic demands in winter. We find large seasonal variation in cellular architecture and neuronal activity in the smallest terrestrial mammal, the Etruscan shrew, Suncus etruscus Their brain, and specifically their neocortex, shrinks in winter. Shrews are tactile hunters, and information from whiskers first reaches the somatosensory cortex layer 4, which exhibits a reduced width (-28%) in winter. Layer 4 width (+29%) and neuron number (+42%) increase the following summer. Activity patterns in the somatosensory cortex show a prominent reduction of touch-suppressed neurons in layer 4 (-55%), the most metabolically active layer. Loss of inhibitory gating occurs with a reduction in parvalbumin-positive interneurons, one of the most active neuronal subtypes and the main regulators of inhibition in layer 4. Thus, a reduction in neurons in layer 4 and particularly parvalbumin-positive interneurons may incur direct metabolic benefits. However, changes in cortical balance can also affect the threshold for detecting sensory stimuli and impact prey choice, as observed in wild shrews. Thus, seasonal neural adaptation can offer synergistic metabolic and behavioral benefits to the organism and offer insights on how neural systems show adaptive plasticity in response to ecological demands.

19.
J Vet Pharmacol Ther ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289178

RESUMO

Physiologically based pharmacokinetic (PBPK) models are growing in popularity due to human food safety concerns and for estimating drug residue distribution and estimating withdrawal intervals for veterinary products originating from livestock species. This paper focuses on the physiological and anatomical data, including cardiac output, organ weight, and blood flow values, needed for PBPK modeling applications for avian species commonly consumed in the poultry market. Experimental and field studies from 1940 to 2019 for broiler chickens (1-70 days old, 40 g - 3.2 kg), laying hens (4-15 months old, 1.1-2.0 kg), and turkeys (1 day-14 months old, 60 g -12.7 kg) were searched systematically using PubMed, Google Scholar, ProQuest, and ScienceDirect for data collection in 2019 and 2020. Relevant data were extracted from the literature with mean and standard deviation (SD) being calculated and compiled in tables of relative organ weights (% of body weight) and relative blood flows (% of cardiac output). Trends of organ or tissue weight growth during different life stages were calculated when sufficient data were available. These compiled data sets facilitate future PBPK model development and applications, especially in estimating chemical residue concentrations in edible tissues to calculate food safety withdrawal intervals for poultry.

20.
Cell Biol Int ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289183

RESUMO

Ischemia-reperfusion (I/R) injury is a major cause of cardiomyocyte apoptosis after vascular recanalization, which was mimicked by a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes in vitro. In this study, we explored an optimal H/R duration procedure using the AnaeroPack System. To study H/R procedure, cardiomyocytes were exposed to AnaeroPack System with sugar and serum-free medium, followed by reoxygenation under normal condition. Cell injury was detected through lactate dehydrogenase (LDH) and cardiac troponin (c-Tn) release, morphological changes, cell apoptosis and expression of apoptosis-related proteins. The results showed that the damage to H9c2 cells increased with prolonged hypoxia time, as demonstrated by increased apoptosis rate, LDH and c-Tn release, HIF-1α expression, as well as decreased expression of Bcl-2. Furthermore, hypoxia for 10 h and reoxygenation for 6 h exhibited the highest apoptosis rate and damage cytokine release; in addition, cells were deformed, small and visibly round. After 12 h of hypoxia, majority of the cells were dead. Taken together, this study showed that subjecting H9c2 cells to the AnaeroPack System for 10 h and reoxygenation for 6 h can achieve a practicable and repeatable H/R injury model. This article is protected by copyright. All rights reserved.

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