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1.
Biotechnol Prog ; : e3225, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775686

RESUMO

In utilizing glycerol to produce 1,3-propanediol by microbial fermentation, the problems of low utilization rate and poor production performance need to be addressed. Based on the analysis of a mathematical model for 1,3-propanediol production from glycerol by Klebsiella pneumoniae, this study theoretically investigated the effects of the dilution rate and the initial glycerol concentration in a two-stage fermentation process and the feasibility of applying the feedback control methods. First, the optimal operation conditions of initial glycerol concentration and dilution rate were obtained. Through the use of feedback control theory, a control strategy for dilution rate was designed and optimized to shorten the settling time (time required for fermentation to reach stability) from 60.92 to 36.68 h for the first reactor, and from 53.66 to 22.68 h for the second reactor. In addition, the yield of 1,3-propanediol in both two reactors reached up to 0.5 g·g-1 . The simulation results indicated that the feedback control strategy for dilution rate increased the product concentration, reduced the residual glycerol in the fermentation broth, and greatly improved the performance of the fermentation. A feeding strategy of automatic control for dilution rate has been established and will be applied as an effective guiding scheme in automatic continuous fermentations for production of 1,3-propanediol.

2.
Brain Behav Immun ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808295

RESUMO

Prolonged postsurgical pain, which is associated with multiple risk factors in the perioperative stage, is a common medical and social problem worldwide. Suitable animal models should be established to elucidate the mechanisms underlying the perioperative prolonged postsurgical pain. In this study, standard and modified social defeat stress mice models, including chronic social defeat stress (CSDS), chronic nondiscriminatory social defeat stress (CNSDS) and vicarious social defeat stress (VSDS), were applied to explore the effect of perioperative social defeat stress on postsurgical pain in male and female mice. Our results showed that exposure to preoperative CSDS could induce prolonged postsurgical pain in defeated mice regardless of susceptibility or resilience differentiated by the social interaction test. Similar prolongation of incision-induced mechanical hypersensitivity was also observed in both sexes upon exposing to CNSDS or VSDS in the preoperative period. Moreover, we found that using the modified CNSDS or VSDS models at different recovery stages after surgery could still promote abnormal pain without sex differences. Further studies revealed the key role of spinal microglial activation in the stress-induced transition from acute to prolonged postoperative pain in male but not female mice. Together, these data indicate that perioperative social defeat stress is a vital risk factor for developing prolonged postoperative pain in both sexes, but the promotion of stress-induced prolonged postoperative pain by spinal microglial activation is sexually dimorphic in mice.

3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 868-876, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622608

RESUMO

Objective: To define the gene expression characteristics in the peripheral blood of patients with lumbar disc extrusion (LDE) and the effect of nonoperative treatment on the gene expression. Methods: DNA microarray was used to identify semi-quantitatively the differentially expressed genes (DEGs) in the peripheral blood of patients with LDE and that of the healthy controls and the variation trend of these DEGs after nonoperative treatment. Enrichment analysis was done to reveal the functional characteristics of these DEGs, and network analysis was done to identify key genes that contribute to gene dysregulation. The levels of these key genes were measured by qRT-PCR to examine their expression in LDE patients and the controls, and the effect of nonoperative treatment on the expression level. Results: We identified 153 DEGs in the peripheral blood of LDE patients and healthy controls, including 131 upregulated genes and 22 downregulated genes. Enrichment analysis revealed that most of the DEGs were related to immunity and the inflammatory response. Network analysis revealed that toll-like receptor 4 ( TLR4 ), matrix metallopeptidase 9 ( MMP9) and myeloperoxidase ( MPO), cathelicidin antimicrobial peptide ( CAMP), resistin ( RETN), toll-like receptor 5 ( TLR5) were the key genes in the protein-protein interaction network. These key genes were all enriched into the terms releated to immunity and the inflammatory response. The patients experienced pain relief after nonoperative treatment. Among the 153 DEGs, TLR5 , interleukin 1 receptor antagonist ( IL1 RN) and solute carrier family 8 member A1 ( SLC8 A1) were downregulated after nonoperative treatment. qRT-PCR revealed that the levels of TLR4, MMP9 , MPO, CAMP, RETN, TLR5, IL1 RN and SLC8 A1 in the peripheral blood of the LDE patients were higher than those of the healthy control group ( P<0.05). In addition, TLR5 , IL1 RN and SLC8 A1 expression levels decreased after treatmentin in comparison with the levels before treatment ( P<0.05). Conclusion: Gene expression in the peripheral blood of LDE patients was characterized by the dysregulation of immune and inflammatory response-related genes, among which, TLR4, MMP9, MPO, CAMP, RETN and TLR5, the genes relevant to immune and inflammatory response, played a key role in the dysregulation of gene expression in the peripheral blood of LDE patients. The outcome of non-operative treatment may be related to the downregulation of the overexpressed TLR5, IL1 RN and SLC8 A1 in the peripheral blood of patients.


Assuntos
Perfilação da Expressão Gênica , Regulação para Baixo , Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
4.
Front Genet ; 12: 713575, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539741

RESUMO

Fertility and reproductive performance are key drivers of dairy farm profitability. Hence, reproduction traits have been included in a large majority of worldwide dairy cattle selection indexes. The reproductive traits are lowly heritable but can be improved through direct genetic selection. However, most scientific studies and dairy cattle breeding programs have focused solely on the genetic effects of the dam (GED) on reproductive performance and, therefore, ignored the contribution of the service sire in the phenotypic outcomes. This study aimed to investigate the service sire effects on female reproductive traits in Holstein cattle from a genomic perspective. Genetic parameter estimation and genome-wide association studies (GWAS) were performed for the genetic effect of service sire (GESS) on conception rate (CR), 56-day non-return rate (NRR56), calving ease (CE), stillbirth (SB), and gestation length (GL). Our findings indicate that the additive genetic effects of both sire and dam contribute to the phenotypic variance of reproductive traits measured in females (0.0196 vs. 0.0109, 0.0237 vs. 0.0133, 0.0040 vs. 0.0289, 0.0782 vs. 0.0083, and 0.1024 vs. 0.1020 for GESS and GED heritability estimates for CR, NRR56, CE, SB, and GL, respectively), and these two genetic effects are positively correlated for SB (0.1394) and GL (0.7871). Interestingly, the breeding values for GESS on insemination success traits (CR and NRR56) are unfavorably and significantly correlated with some production, health, and type breeding values (ranging from -0.449 to 0.274), while the GESS values on calving traits (CE, SB, and GL) are usually favorably associated with those traits (ranging from -0.493 to 0.313). One hundred sixty-two significant single-nucleotide polymorphisms (SNPs) and their surrounding protein-coding genes were identified as significantly associated with GESS and GED, respectively. Six genes overlapped between GESS and GED for calving traits and 10 genes overlapped between GESS for success traits and calving traits. Our findings indicate the importance of considering the GESS when genetically evaluating the female reproductive traits in Holstein cattle.

5.
Ann Transl Med ; 9(16): 1321, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532458

RESUMO

Background: Epidermal growth factor receptor (EGFR) and BRAF are 2 driver genes in non-small cell lung cancer (NSCLC) which are normally mutually exclusive. It has been previously reported that the existence of BRAF V600E in EGFR-mutated NSCLC patients could cause resistance to EGFR tyrosine kinase inhibitors (TKIs), but the influence of other BRAF actionable mutations on resistance to EGFR-TKIs has not yet been investigated. Understanding the coexistence of EGFR and BRAF actionable mutations in Chinese NSCLC patients may be essential for further treatment and prognostic prediction. Methods: A total of 127 Chinese NSCLC patients harboring EGFR and BRAF co-mutations were enrolled in this study. We analyzed the mutation profiles of these patients through next-generation sequencing (NGS). We explored the associations between somatic mutations and patient characteristics, including tumor stage and age, among others. Results: The frequency of EGFR and BRAF co-mutation was 0.91% in Chinese NSCLC patients, compared with 0.97% in Western NSCLC patients (cBioPortal). Among the 127 patients with both EGFR and BRAF mutations, 93 of them harbored clinically significant mutations. The remaining 34 patients were found to have mutations of uncertain significance of either EGFR or BRAF. TP53 was the most frequently mutated gene in BRAF and EGFR co-mutation patients, accounting for around 58% (N=54/93). MET active mutations (amplification and exon 14 skipping) accounted for 12% (N=11/93). Approximately 18% of patients (N=17/93) with significant EGFR mutations were detected to have fusions/rearrangements of the BRAF gene. BRAF fusion was more likely detected in EGFR exon19del patients compared with non-exon19del patients (P value =0.015). In addition, EGFR T790M, the most TKI-resistant mutation, was not found in any patient with BRAF fusion/rearrangement. Conclusions: This study is the first to show different subtypes of EGFR and BRAF co-mutations in Chinese NSCLC patients. The prognosis of EGFR-TKI treatment may vary according to different BRAF actionable mutations. Aside from BRAF V600E, class II/III and BRAF fusions were found, which provides clues for investigating the resistance mechanisms of EGFR-TKIs in the future.

7.
Elife ; 102021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544549

RESUMO

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/imunologia , Vacinas Bacterianas/administração & dosagem , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Pneumonia Bacteriana/prevenção & controle , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/microbiologia , Administração Intranasal , Transferência Adotiva , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Imunidade Inata/efeitos dos fármacos , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/transplante , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Fatores de Tempo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Vacinação , Vacinas de Produtos Inativados/administração & dosagem
8.
Front Genet ; 12: 692479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413876

RESUMO

Objective: Alpha-dystroglycanopathy (α-DGP) is a subtype of muscular dystrophy caused by defects in the posttranslational glycosylation of α-dystroglycan (α-DG). Our study aimed to summarize the clinical and genetic features of POMT2-related α-DGP in a cohort of patients in China. Methods: Pedigrees, clinical data, and laboratory tests of patients diagnosed with POMT2-related α-DGP were analyzed retrospectively. The pathogenicity of variants in POMT2 were predicted by bioinformatics software. The variants with uncertain significance were verified by further analysis. Results: The 11 patients, comprising eight males and three females, were from nine non-consanguineous families. They exhibited different degrees of muscle weakness, ambulation, and intellectual impairment. Among them, three had a muscle-eye-brain disease (MEB)-like phenotype, five presented congenital muscular dystrophy with intellectual disability (CMD-ID), and three presented limb-girdle muscular dystrophy (LGMD). Overall, nine novel variants of POMT2, including two non-sense, one frameshift and six missense variants, were identified. The pathogenicity of two missense variants, c.1891G > C and c.874G > C, was uncertain based on bioinformatics software prediction. In vitro minigene analysis showed that c.1891G > C affects the splicing of POMT2. Immunofluorescence staining with the IIH6C4 antibody of muscle biopsy from the patient carrying the c.874G > C variant showed an apparent lack of expression. Conclusion: This study summarizes the clinical and genetic characteristics of a cohort of POMT2-related α-DGP patients in China for the first time, expanding the mutational spectrum of the disease. Further study of the pathogenicity of some missense variants based on enzyme activity detection is needed.

9.
Eur J Pharm Sci ; 166: 105981, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34428483

RESUMO

PURPOSE: Dexamethasone (Dex) is a widely used drug for the treatment of inflammatory and autoimmune conditions, however, long-term systemic use of Dex is associated with serious adverse effects. The objective of the present study was to develop an implantable device to avoid side effects and realize a controlled release of Dex at the implant site. METHODS: Hydrophobic Dex was incorporated into biodegradable polyesters derived from PCL and Pluronic® L64 (PCL-Pluronic L64-PCL, PCLC) by hot-melt extrusion (HME) method to prepare Dex/PCLC implantable devices. Drug loading and encapsulation efficiency, a series of physicochemical properties, and in vivo features of the implants were studied. RESULTS: The maximum value of the drug loading and encapsulation efficiency for the Dex/PCLC implants were up to 47% and 94%, respectively. Incorporation of Dex resulted in accelerated crystallization of PCLC, decreased the wettability, increased contact angles and viscosity, and accelerated Dex release rate and degradation rate from the implants in vivo. Moreover, Dex/PCLC implants showed excellent biocompatibility. Furthermore, the inflammatory response to the Dex/PCLC implants was less severe than that to the positive control group. CONCLUSION: All these results suggested that Dex/PCLC implants might be a safe and controlled local drug delivery system with excellent inflammatory response suppression effect.


Assuntos
Implantes Absorvíveis , Tecnologia de Extrusão por Fusão a Quente , Cristalização , Dexametasona , Sistemas de Liberação de Medicamentos , Implantes de Medicamento , Poliésteres
10.
J Appl Microbiol ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347910

RESUMO

AIMS: The potential of gallnut tannin (GT) and Lactobacillus plantarum (LP) on fermentation characteristics, in vitro ruminal methane (CH4 ) production and microbiota of alfalfa silage was investigated. METHODS AND RESULTS: Alfalfa was ensiled with GT (20 and 50 g kg-1 dry matter [DM]) and LP (3 × 108  CFU per gram fresh matter) alone or in combination for 60 days. The GT and LP alone or in combination decreased DM losses, pH and non-protein nitrogen contents of alfalfa silage. All additive treatments decreased ruminal CH4 production, and increased propionic acid molar proportions and Fibrobacter succinogenes numbers. The LP treatment increased nutrient degradation, cellobiase, pectinase and protease activities, and Prevotella ruminicola abundance, whereas high-dose GT treatment inhibited these variables. Importantly, LP together with GT alleviated the adverse effects of high-dose GT supply alone by enhancing pectinase and protease activities as well as Rumincoccus flavefaciens and P. ruminicola growth. CONCLUSIONS: Combination of GT and LP can be used as an efficient additive to improve silage quality and utilization by ruminants. SIGNIFICANCE AND IMPACT OF THE STUDY: Using GT-LP combination has practical implications, particularly concerning effects of tannins on ruminal CH4 mitigation, which may alleviate inhibitory effects of tannins on feed digestion through modulating ruminal microbiota.

11.
J Phys Condens Matter ; 33(46)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34425563

RESUMO

The asymmetrical long-range hopping amplitudes have a rich influence on the topological properties. Here, a non-Hermitian model including the long-range hopping amplitudes is constructed to explore those properties. It can be found that an extra topological invariantW= 2 emerges as a consequence of the long-range hopping amplitudes. Furthermore, we find that the phaseW= 2 can be directly characterized by the generalized Brillouin zone (GBZ) itself through the concept of the argument principle. Meanwhile, a gapless phase dubbed as topological semimetal phase can be induced by the asymmetrical long-range hopping. Moreover, the physical origin of the topological semimetal phase can be explained by the solutions of eigen-equation. It is also shown that the skin modes exist as long as the GBZ and the Brillouin zone differ from each other. These interesting phases may be realized in an electrical-circuit simulator.

12.
Signal Transduct Target Ther ; 6(1): 309, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413288

RESUMO

Glioblastoma (GBM), one of the most common primary intracranial malignant tumours, is very difficult to be completely excised by surgery due to its irregular shape. Here, we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles (SPIONs) modified with indocyanine (Cy7) molecules and peptides (ANG or DANG) to locate malignant gliomas and guide accurate excision. Both peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro, and both could mediate precise aggregation of the nanoprobes at gliomas sites in in vivo magnetic resonance imaging (MRI) and ex vivo near-infrared (NIR) fluorescence imaging. However, compared with ANG/Cy7-SPIONs probes, DANG/Cy7-SPIONs probes exhibited better enhanced MR imaging effects. Combining all these features together, this MRI/NIR fluorescence imaging dual-modal nanoprobes modified with retro-enantio isomers of the peptide have the potential to accurately display GBMs preoperatively for precise imaging and intraoperatively for real-time imaging.

13.
Animals (Basel) ; 11(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209256

RESUMO

This study was conducted to evaluate the potential of hydrolysable tannin (chestnut tannin, CHT) without or with condensed tannin (quebracho tannin, QT) for modulating alfalfa silage fermentation characteristics and in vitro ruminal methane (CH4) production, fermentation profile, and microbiota. Alfalfa (235 g/kg fresh weight) was ensiled with no tannins (control), 2% CHT (CHT2), 5% CHT (CHT5), the combination of CHT and QT at 1% each (CHQ2), and CHT and QT at 2.5% each (CHQ5) of forage dry matter (DM). The CHQ2 treatment was more effective in reducing DM losses, pH, and ammonia-nitrogen to total nitrogen ratios of alfalfa silage than CHT2 and CHT5 treatments. All tannin treatments decreased ruminal CH4 production, and the magnitude of the decrease was greater for the combinations than the individual ones. Total volatile fatty acid (VFA) concentrations and DM degradation decreased by tannin treatments, but microbial protein (MCP) synthesis increased. The total VFA concentrations and DM degradation were lower with CHQ2 treatment than with CHT5 and CHQ5 treatments, but the MCP concentrations were comparable among these treatments. Tannin inclusion decreased the abundance of the anaerobic fungi Ruminococcus albus and Ruminococcus flavefaciens, but enhanced Fibrobacter succinogenes. The combination of CHT and QT alleviated the inhibition of CHT supply alone in Butyrivibrio fibrisolvens, Ruminobacer amylophilus, and Prevotella ruminicola as well as protease. The results revealed that a combination of HT from CHT and CT from QT at a low level can reduce proteolysis and CH4 production of alfalfa silage without impairing ruminal fermentation and microbiota.

14.
Adv Healthc Mater ; : e2100706, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296536

RESUMO

Antibacterial photodynamic therapy (PDT) is one of the emerging methods for curbing multidrug-resistant bacterial infections. Effective fluorescent photosensitizers with dual functions of bacteria imaging and PDT applications are highly desirable. In this study, three cationic and heteroleptic cyclometalated Ir(III) complexes with the formula of [Ir(CˆN)2 (NˆN)][PF6 ] are prepared and characterized. These Ir(III) complexes named Ir(ppy)2 bP, Ir(1-pq)2 bP, and Ir(2-pq)2 bP are comprised of three CˆN ligands (i.e., 2-phenylpyridine (ppy), 1-phenylisoquinoline (1-pq), and 2-phenylquinoline (2-pq)) and one NˆN bidentate co-ligand (bP). The photophysical characterizations demonstrate that these Ir(III) complexes are red-emitting, aggregation-induced emission active luminogens. The substitution of phenylpyridine with phenylquinoline isomers in the molecules greatly enhances their UV and visible-light absorbance as well as the photoinduced reactive oxygen species (ROS) generation ability. All three Ir(III) complexes can stain both Gram-positive and Gram-negative bacteria efficiently. Interestingly, even though Ir(1-pq)2 bP and Ir(2-pq)2 bP are constitutional isomers with very similar structures and similar ROS generation ability in buffer, the former eradicates bacteria much more effectively than the other through white light-irradiated photodynamic inactivation. This work will provide valuable information on the rational design of Ir(III) complexes for fluorescence imaging and efficient photodynamic inactivation of bacteria.

15.
J Neurosci ; 41(34): 7278-7299, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34272314

RESUMO

Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2(3Y), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats. These data provide a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlight that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.SIGNIFICANCE STATEMENT Several studies have demonstrated the high comorbidity of negative affective disorders in patients with chronic pain. Understanding the affective aspects related to chronic pain may facilitate the development of novel therapies for more effective management. Here, we unravel that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain, and LTD at the amygdaloid LA/BLA-CeA synapse mediated by GluA2-containing AMPAR endocytosis underlies the comorbid aversive and depressive symptoms in neuropathic pain. This study provides a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlights that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.

16.
Mol Pain ; 17: 17448069211023230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34102915

RESUMO

Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassium channel on both CGRP+ and IB4+ nerve fibers in the hindpaw skin, on CGRP+ nerve fibers in the tibial periosteum which lacks IB4+ fibers innervation, and on CGRP+ and IB4+ dorsal root ganglion (DRG) neurons in rats. Moreover, we found a decreased expression of TRESK in the corresponding nerve fibers within the hindpaw skin, the tibial periosteum and the DRG neurons in bone cancer rats. Overexpression of TRESK in DRG neurons attenuated both cancer-induced spontaneous pain (partly reflect skeletal pain) and evoked pain (reflect cutaneous pain) in tumor-bearing rats, in which the relief of evoked pain is time delayed than spontaneous pain. In contrast, knockdown of TRESK in DRG neurons produced both spontaneous pain and evoked pain in naïve rats. These results suggested that the differential distribution and decreased expression of TRESK in the periosteum and skin, which is attributed to the lack of IB4+ fibers innervation within the periosteum of the tibia, probably contribute to the behavioral divergence of cancer-induced spontaneous pain and evoked pain in bone cancer rats. Thus, the assessment of spontaneous pain and evoked pain should be accomplished simultaneously when evaluating the effect of some novel analgesics in animal models. Also, this study provides solid evidence for the role of peripheral TRESK in both cancer-induced spontaneous pain and evoked cutaneous pain.

18.
Br J Nutr ; : 1-7, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155966

RESUMO

To investigate the influences of cobalt (Co) and folic acid (FA) on growth performance and rumen fermentation, Holstein male calves (n 40) were randomly assigned to four groups according to their body weights. Cobalt sulphate at 0 or 0·11 mg Co/kg DM and FA at 0 or 7·2 mg/kg DM were used in a 2 × 2 factorial design. Average daily gain was elevated with FA or Co supplementation, but the elevation was greater for supplementing Co in diets without FA than with FA. Supplementing FA or Co increased DM intake and total-tract nutrient digestibility. Rumen pH was unaltered with FA but reduced with Co supplementation. Concentration of rumen total volatile fatty acids was elevated with FA or Co inclusion. Acetate percentage and acetate to propionate ratio were elevated with FA inclusion. Supplementing Co decreased acetate percentage and increased propionate percentage. Activities of xylanase and α-amylase and populations of total bacteria, fungi, protozoa, Ruminococcus albus, Fibrobacter succinogenes and Prevotella ruminicola increased with FA or Co inclusion. Activities of carboxymethyl-cellulase and pectinase increased with FA inclusion and population of methanogens decreased with Co addition. Blood folates increased and homocysteine decreased with FA inclusion. Blood glucose and vitamin B12 increased with Co addition. The data suggested that supplementing 0·11 mg Co/kg DM in diets containing 0·09 mg Co/kg DM increased growth performance and nutrient digestibility but had no improvement on the effects of FA addition in calves.

19.
Orphanet J Rare Dis ; 16(1): 277, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127034

RESUMO

BACKGROUND: To evaluate the efficacy, safety and health economics of sequential everolimus in treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC). METHODS: In this prospective cohort study, patients met the inclusion criteria received standard or sequential treatment according to their willingness. All patients received an initial dose of everolimus (10 mg oral, once a day) for 3 months. The standard treatment group maintained 10 mg QD for 12 months, while the sequential treatment group reduced the dose to 5 mg QD from the 4th month. The efficacy, serum everolimus concentration and safety were evaluated at 1, 3, 6, 9 and 12 months after treatment. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in the total volume of target AML relative to baseline. RESULTS: Between June 1, 2016 and June 1, 2017, a total of 53 patients were included. Twenty-three patients received standard treatment, 30 patients received sequential treatment. At 1, 3, 6, 9 and 12 months after treatment, the proportion of patients whose total target tumor volume decreased by ≥ 50% from baseline was 39.1% versus 36.7%, 43.5% versus 56.7%, 47.8% versus 50%, 47.8% versus 60% and 47.8% versus 23.3% respectively (P > 0.05 for all). The overall response rate of skin lesions in the two groups was 40.4%, and the response rates of skin lesions at different times were similar for two groups (P > 0.05 for all). Major adverse effects (AEs) included mouth ulceration, hypertriglyceridemia, hypercholesterolemia, menstrual disorders. There was no significant difference between the two groups in the incidence of AEs at 3 months after treatment. The incidence of overall and grade 3/4 AEs at 12 months after treatment were significantly lower in the sequential treatment group. The average direct cost of the two groups in 12 months was $15,466 and $11,120, respectively. CONCLUSIONS: Compared to standard treatment, sequential treatment was equally effective, with a lower incidence of adverse events and a lower direct cost, suggesting that it may be an alternative treatment for AML associated with TSC.


Assuntos
Angiomiolipoma , Antineoplásicos , Neoplasias Renais , Esclerose Tuberosa , Angiomiolipoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Humanos , Neoplasias Renais/tratamento farmacológico , Estudos Prospectivos , Esclerose Tuberosa/tratamento farmacológico
20.
Sci Rep ; 11(1): 11513, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075198

RESUMO

Brucellosis is one of the major public health problems in China, and human brucellosis represents a serious public health concern in Xinjiang and requires a prediction analysis to help making early planning and putting forward science preventive and control countermeasures. According to the characteristics of the time series of monthly reported cases of human brucellosis in Xinjiang from January 2008 to June 2020, we used seasonal autoregressive integrated moving average (SARIMA) method and nonlinear autoregressive regression neural network (NARNN) method, which are widely prevalent and have high prediction accuracy, to construct prediction models and make prediction analysis. Finally, we established the SARIMA((1,4,5,7),0,0)(0,1,2)12 model and the NARNN model with a time lag of 5 and a hidden layer neuron of 10. Both models have high fitting performance. After comparing the accuracies of two established models, we found that the SARIMA((1,4,5,7),0,0)(0,1,2)12 model was better than the NARNN model. We used the SARIMA((1,4,5,7),0,0)(0,1,2)12 model to predict the number of monthly reported cases of human brucellosis in Xinjiang from July 2020 to December 2021, and the results showed that the fluctuation of the time series from July 2020 to December 2021 was similar to that of the last year and a half while maintaining the current prevention and control ability. The methodology applied here and its prediction values of this study could be useful to give a scientific reference for prevention and control human brucellosis.


Assuntos
Brucelose/epidemiologia , Modelos Biológicos , Redes Neurais de Computação , Estações do Ano , China , Feminino , Previsões , Humanos , Incidência , Masculino , Estudos Retrospectivos
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