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1.
J Cell Physiol ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595500

RESUMO

An in-depth understanding of circular RNAs (circRNAs) indicates that they are abundant in the eukaryotic transcriptome. Many circRNAs act as microRNA sponges; thus, they represent a new type of regulatory factor. However, the role of circRNA in colorectal cancer (CRC) remains largely unknown. Low circ_0021977 expression in patients with CRC is associated with higher tug-lymph node metastasis (TNM) stage and poorer prognosis compared with patients with high circ_0021977 expression. Moreover, miR-10b-5p was shown to be a target of circ_0021977, and p21 and p53 are suggested to be putative target genes of miR-10b-5p. The results showed that the circ_0021977/miR-10b-5p/p21&p53 regulatory axis suppresses proliferation, migration, and invasion by CRC cells. This evidence reveals new relationships and brings new highlights to the treatment of CRC.

2.
J Neurosurg Spine ; : 1-8, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653809

RESUMO

OBJECTIVE: Minimally invasive surgery (MIS) can be used as an alternative or adjunct to traditional open techniques for the treatment of patients with adult spinal deformity. Recent advances in MIS techniques, including advanced anterior approaches, have increased the range of candidates for MIS deformity surgery. The minimally invasive spinal deformity surgery (MISDEF2) algorithm was created to provide an updated framework for decision-making when considering MIS techniques in correction of adult spinal deformity. METHODS: A modified algorithm was developed that incorporates a patient's preoperative radiographic parameters and leads to one of 4 general plans ranging from basic to advanced MIS techniques to open deformity surgery with osteotomies. The authors surveyed 14 fellowship-trained spine surgeons experienced with spinal deformity surgery to validate the algorithm using a set of 24 cases to establish interobserver reliability. They then re-surveyed the same surgeons 2 months later with the same cases presented in a different sequence to establish intraobserver reliability. Responses were collected and analyzed. Correlation values were determined using SPSS software. RESULTS: Over a 3-month period, 14 fellowship-trained deformity surgeons completed the surveys. Responses for MISDEF2 algorithm case review demonstrated an interobserver kappa of 0.85 for the first round of surveys and an interobserver kappa of 0.82 for the second round of surveys, consistent with substantial agreement. In at least 7 cases, there was perfect agreement between the reviewing surgeons. The mean intraobserver kappa for the 2 surveys was 0.8. CONCLUSIONS: The MISDEF2 algorithm was found to have substantial inter- and intraobserver agreement. The MISDEF2 algorithm incorporates recent advances in MIS surgery. The use of the MISDEF2 algorithm provides reliable guidance for surgeons who are considering either an MIS or an open approach for the treatment of patients with adult spinal deformity.

3.
Neurosurgery ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625568

RESUMO

BACKGROUND: There is a paucity of investigation on the impact of spondylolisthesis surgery on back pain-related sexual inactivity. OBJECTIVE: To investigate predictors of improved sex life postoperatively by utilizing the prospective Quality Outcomes Database (QOD) registry. METHODS: A total of 218 patients who underwent surgery for grade 1 degenerative lumbar spondylolisthesis were included who were sexually active. Sex life was assessed by Oswestry Disability Index item 8 at baseline and 24-mo follow-up. RESULTS: Mean age was 58.0 ± 11.0 yr, and 108 (49.5%) patients were women. At baseline, 178 patients (81.7%) had sex life impairment. At 24 mo, 130 patients (73.0% of the 178 impaired) had an improved sex life. Those with improved sex lives noted higher satisfaction with surgery (84.5% vs 64.6% would undergo surgery again, P = .002). In multivariate analyses, lower body mass index (BMI) was associated with improved sex life (OR = 1.14; 95% CI [1.05-1.20]; P < .001). In the younger patients (age < 57 yr), lower BMI remained the sole significant predictor of improvement (OR = 1.12; 95% CI [1.03-1.23]; P = .01). In the older patients (age ≥ 57 yr)-in addition to lower BMI (OR = 1.12; 95% CI [1.02-1.27]; P = .02)-lower American Society of Anesthesiologists (ASA) grades (1 or 2) (OR = 3.7; 95% CI [1.2-12.0]; P = .02) and ≥4 yr of college education (OR = 3.9; 95% CI [1.2-15.1]; P = .03) were predictive of improvement. CONCLUSION: Over 80% of patients who present for surgery for degenerative lumbar spondylolisthesis report a negative effect of the disease on sex life. However, most patients (73%) report improvement postoperatively. Sex life improvement was associated with greater satisfaction with surgery. Lower BMI was predictive of improved sex life. In older patients-in addition to lower BMI-lower ASA grade and higher education were predictive of improvement.

4.
BMC Genomics ; 20(1): 729, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606027

RESUMO

BACKGROUND: The tropical liver fluke, Fasciola gigantica causes fasciolosis, an important disease of humans and livestock. We characterized dynamic transcriptional changes associated with the development of the parasite in its two hosts, the snail intermediate host and the mammalian definitive host. RESULTS: Differential gene transcription analysis revealed 7445 unigenes transcribed by all F. gigantica lifecycle stages, while the majority (n = 50,977) exhibited stage-specific expression. Miracidia that hatch from eggs are highly transcriptionally active, expressing a myriad of genes involved in pheromone activity and metallopeptidase activity, consistent with snail host finding and invasion. Clonal expansion of rediae within the snail correlates with increased expression of genes associated with transcription, translation and repair. All intra-snail stages (miracidia, rediae and cercariae) require abundant cathepsin L peptidases for migration and feeding and, as indicated by their annotation, express genes putatively involved in the manipulation of snail innate immune responses. Cercariae emerge from the snail, settle on vegetation and become encysted metacercariae that are infectious to mammals; these remain metabolically active, transcribing genes involved in regulation of metabolism, synthesis of nucleotides, pH and endopeptidase activity to assure their longevity and survival on pasture. Dramatic growth and development following infection of the mammalian host are associated with high gene transcription of cell motility pathways, and transport and catabolism pathways. The intra-mammalian stages temporally regulate key families of genes including the cathepsin L and B proteases and their trans-activating peptidases, the legumains, during intense feeding and migration through the intestine, liver and bile ducts. While 70% of the F. gigantica transcripts share homology with genes expressed by the temperate liver fluke Fasciola hepatica, gene expression profiles of the most abundantly expressed transcripts within the comparable lifecycle stages implies significant species-specific gene regulation. CONCLUSIONS: Transcriptional profiling of the F. gigantica lifecycle identified key metabolic, growth and developmental processes the parasite undergoes as it encounters vastly different environments within two very different hosts. Comparative analysis with F. hepatica provides insight into the similarities and differences of these parasites that diverged > 20 million years ago, crucial for the future development of novel control strategies against both species.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31636070

RESUMO

Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of efforts, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika pathogenesis. Thus, in this study, we examined a series of novel anti-inflammatory compounds and found that treatment with compound 2d could dose-dependently reduce viral protein expression and viral progeny production in HEK-293 and Raw264.7 cells with four serotypes of DENV and ZIKV infection. As well, considering medication safety, compound 2d could not suppress cyclooxygenase-1 (COX-1) enzymatic activities and thus could prevent bleeding side effect. Moreover, compound 2d significantly inhibited COX-2 enzymatic activities and prostaglandin E2 levels, associated with viral replication, as compared with a selective COX-2 inhibitor, celecoxib. Furthermore, administering 5 mg/kg compound 2d to DENV-2-infected AG129 mice prolonged survival and reduced viremia and serum cytokine levels. Overall, compound 2d showed therapeutic safety and efficacy in vitro and in vivo and could be further developed as a potential therapeutic agent for flavivirus infection.

6.
Pestic Biochem Physiol ; 160: 30-39, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519255

RESUMO

An exploration of novel control strategies for Leptinotarsa decemlineata is becoming more pressing given rapid evolution of insecticide resistance and rise of production loss of potato. Dietary delivery of bacterially expressed double-stranded RNA (dsRNA) is a promising alternative for management. An important first step is to uncover possible RNA-interference (RNAi)-target genes effective against both young and old larvae. Taiman (Tai) is a basic-helix-loop-helix/Per-Arnt-Sim transcription factor that is involved in the mediation of both juvenile hormone (JH) and 20-hydroxyecdysone (20E) signaling. In the present paper, we found that continuous ingestion of dsTai for three days by third (penultimate)-instar larvae caused approximately 20% larval mortality and 80% pupation failure. The larval lethality resulted from failed cuticle and tracheae shedding, which subsequently reduced foliage consumption and nutrient absorption, and depleted lipid stores. In contrast, pupation failure derived from disturbed JH and 20E signals, and disordered nutrient homeostasis including, among others, inhibition of trehalose metabolism and reduction of chitin content. Knockdown of LdTai caused similar larval lethality and pupation impairment in second and fourth (final) larval instars. Therefore, LdTai is among the most attractive candidate genes for RNAi to control L. decemlineata larvae.

7.
Epigenetics ; : 1-11, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31509087

RESUMO

DNA methylation and histone modifications are two major epigenetic marks in mammalian cells. Previous studies have revealed that these two mechanisms interact although a quantitative model of these is still lacking in mammalian cells. Here we sought to develop such a model by systematically evaluating the quantitative relationship between DNA methylation and the core histone modification marks in human epigenomes. This model reflects the interactions of ADD and PWWP domains of DNA methyltransferase (DNMTs) with histone 3 lysine tails. Our analysis integrated 35 whole genome bisulphite sequencing data sets (about 800 million CpG sites), 35 chromatin states and 175 ChIP-Seq histone modification profiles across 35 human cell types. The logistic regression model we built shows that more than half of the variance across DNA methylomes can be explained by the five-core histone modification across varied types of human cell and tissue samples. Importantly, we find that H3K4me3 has a dramatic effect in DNA methylation patterning, highlighting the essential interaction between ADD domain of DNMTs and histone 3 lysine 4 in human. Moreover, our model suggests DNA methylation is generally inhibited by the presence of H3K4me3, H3K4me1 and H3K27me3, while increased levels are found in regions that are marked by H3K9me3 and H3K36me3. In summary, our results provide a comprehensive evaluation of the crosstalk between DNA methylation and histone modification in a variety of human cell types, and shows that DNA methylation patterns can be largely explained by interactions between histone 3 lysine tails and specific domains of DNA methyltransferases.

8.
J Oral Rehabil ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549419

RESUMO

BACKGROUND: The Fonseca anamnestic index (FAI) offers a simple, low-cost, patient-reported method for screening temporomandibular disorders (TMDs). OBJECTIVES: This study described the development of the Chinese version of the FAI (FAI-C) and examined its reliability and validity when compared to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). METHODS: The FAI-C was created by translation and cross-cultural adaptation of the English instrument following international guidelines. Psychometric evaluation of the FAI-C was carried out on a sample of 613 patients with TMDs and 57 controls. Reliability of the FAI-C was determined by means of internal consistency and test-retest methods while validity was ascertained by criterion-related validity. Criterion validity was examined via Cohen's kappa, sensitivity and specificity when compared with DC/TMD Axis I diagnoses. RESULTS: Cronbach's alpha value (internal consistency) for total FAI-C score was 0.669, and intra-class correlation coefficient (ICC) value (test-retest reliability) was 0.823. For criterion validity, kappa coefficient value was 0.633 while sensitivity and specificity was 95.9% and 71.9%, respectively. CONCLUSION: The Chinese version of the FAI demonstrated acceptable reliability and good validity. The FAI-C could thus be used as an instrument for screening TMDs in Chinese literate populations.

9.
Org Lett ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31441309

RESUMO

The concise, divergent total syntheses of four illudalane sesquiterpenes using an indanone as the key intermediate are reported. The key elements in these total syntheses, which involve only four to six operational steps, consist of a Suzuki cross-coupling and a one-pot Diels-Alder/oxidative aromatization reaction.

10.
Cancer Med ; 8(13): 6106-6113, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436046

RESUMO

Although targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of nonmelanoma skin cancer (NMSC), the most common type of skin cancer, remains obscure. Here, we report that Src-associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2-transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2-transgenic mice. Moreover, Sam68 plays a critical role in DNA damage-induced DNA repair and nuclear factor kappa B (NF-κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together, our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC.

11.
Front Immunol ; 10: 1531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333663

RESUMO

We characterized the porcine tissue transcriptional landscapes that follow Toxoplasma gondii infection. RNAs were isolated from liver, spleen, cerebral cortex, lung, and mesenteric lymph nodes (MLNs) of T. gondii-infected and uninfected (control) pigs at days 6 and 18 postinfection, and were analyzed using next-generation sequencing (RNA-seq). T. gondii altered the expression of 178, 476, 199, 201, and 362 transcripts at 6 dpi and 217, 223, 347, 119, and 161 at 18 dpi in the infected brain, liver, lung, MLNs and spleen, respectively. The differentially expressed transcripts (DETs) were grouped into five expression patterns and 10 sub-clusters. Gene Ontology enrichment and pathway analysis revealed that immune-related genes dominated the overall transcriptomic signature and that metabolic processes, such as steroid biosynthesis, and metabolism of lipid and carboxylic acid, were downregulated in infected tissues. Co-expression network analysis identified transcriptional modules associated with host immune response to infection. These findings not only show how T. gondii infection alters porcine transcriptome in a tissue-specific manner, but also offer a gateway for testing new hypotheses regarding human response to T. gondii infection.

12.
Parasit Vectors ; 12(1): 373, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358041

RESUMO

BACKGROUND: The protozoan parasite Toxoplasma gondii infects and alters the neurotransmission in cerebral cortex and other brain regions, leading to neurobehavioral and neuropathologic changes in humans and animals. However, the molecules that contribute to these changes remain largely unknown. METHODS: We have investigated the impact of T. gondii infection on the overall metabolism of mouse cerebral cortex. Mass-spectrometry-based metabolomics and multivariate statistical analysis were employed to discover metabolomic signatures that discriminate between cerebral cortex of T. gondii-infected and uninfected control mice. RESULTS: Our results identified 73, 67 and 276 differentially abundant metabolites, which were involved in 25, 37 and 64 pathways at 7, 14 and 21 days post-infection (dpi), respectively. Metabolites in the unsaturated fatty acid biosynthesis pathway were upregulated as the infection progressed, indicating that T. gondii induces the biosynthesis of unsaturated fatty acids to promote its own growth and survival. Some of the downregulated metabolites were related to pathways, such as steroid hormone biosynthesis and arachidonic acid metabolism. Nine metabolites were identified as T. gondii responsive metabolites, namely galactosylsphingosine, arachidonic acid, LysoSM(d18:1), L-palmitoylcarnitine, calcitetrol, 27-Deoxy-5b-cyprinol, L-homophenylalanine, oleic acid and ceramide (d18:1/16:0). CONCLUSIONS: Our data provide novel insight into the dysregulation of the metabolism of the mouse cerebral cortex during T. gondii infection and have important implications for studies of T. gondii pathogenesis.

13.
Parasit Vectors ; 12(1): 281, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159882

RESUMO

BACKGROUND: The liver fluke Fasciola gigantica modulates several signaling pathways in infected buffaloes to facilitate its survival and establishment of persistent infection. In response to the parasite invasion, buffaloes activate innate and adaptive immune responses to counter the parasite infection. To detect new proteins that might be involved in the interaction between F. gigantica and the buffaloes, and that also might serve as biomarkers for fasciolosis, we used proteomic techniques to study the serum proteome of buffaloes during F. gigantica infection. Here, we used an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach to identify serum proteins that are differentially expressed in infected buffaloes compared to uninfected control buffaloes. Additionally, we applied a parallel reaction monitoring (PRM) assay to validate specific proteins identified by the iTRAQ method. RESULTS: A total of 313, 459 and 399 proteins were identified at 3, 42 and 70 days post-infection, respectively; of these 92, 93 and 138 were differentially abundant proteins. Some of the identified differentially abundant proteins, including complement factor H related 5, complement component C6, complement component C7, amine oxidase, plasma serine protease inhibitor and lysozyme, are known to be involved in complement system activation, blood coagulation, platelet activation, lymphocyte's adhesion and lysozyme hydrolysis. Analysis of data for all three time points after infection identified six significantly upregulated proteins in infected serum that separated infected and uninfected buffaloes into distinct clusters. Further PRM analysis confirmed the expression of five proteins, namely MHC class I antigen, Beta-2-microglobulin, NID2 protein, Fetuin-B and Fibrinogen gamma-B chain. CONCLUSIONS: These findings provide novel insights into the serum proteomics signature of buffaloes during F. gigantica infection.


Assuntos
Búfalos/parasitologia , Fasciolíase/sangue , Fasciolíase/veterinária , Proteoma , Animais , Búfalos/imunologia , Fasciola , Fasciolíase/imunologia
15.
Leukemia ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171817

RESUMO

MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy, and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B-cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (-)-SDS-1-021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.

16.
Cancer Cell ; 35(6): 901-915.e4, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185213

RESUMO

Increasing evidence demonstrates that interleukin-10 (IL-10), known as an immunosuppressive cytokine, induces antitumor effects depending on CD8+ T cells. However, it remains elusive how immunosuppressive effects of IL-10 contribute to CD8+ T cell-mediated antitumor immunity. We generated Cetuximab-based IL-10 fusion protein (CmAb-(IL10)2) to prolong its half-life and allow tumor-targeted delivery of IL-10. Our results demonstrated potent antitumor effects of CmAb-(IL10)2 with reduced toxicity. Moreover, we revealed a mechanism of CmAb-(IL10)2 preventing dendritic cell (DC)-mediated CD8+ tumor-infiltrating lymphocyte apoptosis through regulating IFN-γ production. When combined with immune checkpoint blockade, CmAb-(IL10)2 significantly improves antitumor effects in mice with advanced tumors. Our findings reveal a DC-regulating role of IL-10 to potentiate CD8+ T cell-mediated antitumor immunity and provide a potential strategy to improve cancer immunotherapy.

17.
Opt Express ; 27(12): 17262-17273, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252939

RESUMO

In this work, we study the crystalline defect induced optical scattering loss inside photonic waveguide. Volume current method is implemented with a close form of dyadic Green's function derived. More specifically, threading dislocation induced scattering loss inside AlN waveguides in UV-visible spectrum wavelengths are studied since this material is intrinsically accompanied with high densities of dislocations (typically on order of 108-1010cm-2). The results from this study reveal that threading dislocations contribute significant amount of scattering loss when material is not MOCVD grown. Additionally, the scattering loss is strongly dependent on polarization and waveguide geometries: TM modes exhibit higher scattering loss compared with TE modes, and the multimode large core waveguides are more susceptible to threading dislocations compared with single mode waveguides and high-aspect-ratio waveguides. Conclusions from this work can be supported by several recently published investigations on III-N based photonic devices. The model derived from this work can also be easily altered to fit other material systems with other types of crystalline defects.

18.
PLoS Pathog ; 15(6): e1007898, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31251784

RESUMO

Attaching/Effacing (A/E) bacteria include human pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and their murine equivalent Citrobacter rodentium (CR), of which EPEC and EHEC are important causative agents of foodborne diseases worldwide. While A/E pathogen infections cause mild symptoms in the immunocompetent hosts, an increasing number of studies show that they produce more severe morbidity and mortality in immunocompromised and/or immunodeficient hosts. However, the pathogenic mechanisms and crucial host-pathogen interactions during A/E pathogen infections under immunocompromised conditions remain elusive. We performed a functional screening by infecting interleukin-22 (IL-22) knockout (Il22-/-) mice with a library of randomly mutated CR strains. Our screen reveals that interruption of the espF gene, which encodes the Type III Secretion System effector EspF (E. coli secreted protein F) conserved among A/E pathogens, completely abolishes the high mortality rates in CR-infected Il22-/- mice. Chromosomal deletion of espF in CR recapitulates the avirulent phenotype without impacting colonization and proliferation of CR, and EspF complement in ΔespF strain fully restores the virulence in mice. Moreover, the expression levels of the espF gene are elevated during CR infection and CR induces disruption of the tight junction (TJ) strands in colonic epithelium in an EspF-dependent manner. Distinct from EspF, chromosomal deletion of other known TJ-damaging effector genes espG and map failed to impede CR virulence in Il22-/- mice. Hence our findings unveil a critical pathophysiological function for EspF during CR infection in the immunocompromised host and provide new insights into the complex pathogenic mechanisms of A/E pathogens.

19.
Angew Chem Int Ed Engl ; 58(34): 11846-11851, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31237402

RESUMO

A highly enantioselective formal conjugate allyl addition of allylboronic acids to ß,γ-unsaturated α-ketoesters has been realized by employing a chiral NiII /N,N'-dioxide complex as the catalyst. This transformation proceeds by an allylboration/oxy-Cope rearrangement sequence, providing a facile and rapid route to γ-allyl-α-ketoesters with moderate to good yields (65-92 %) and excellent ee values (90-99 % ee). The isolation of 1,2-allylboration products provided insight into the mechanism of the subsequent oxy-Cope rearrangement reaction: substrate-induced chiral transfer and a chiral Lewis acid accelerated process. Based on the experimental investigations and DFT calculations, a rare boatlike transition-state model is proposed as the origin of high chirality transfer during the oxy-Cope rearrangement.

20.
Brain Behav Immun ; 80: 777-792, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108168

RESUMO

The progressive increase in the prevalence of obesity in the population can result in increased healthcare costs and demands. Recent studies have revealed a positive correlation between pain and obesity, although the underlying mechanisms still remain unknown. Here, we aimed to clarify the role of microglia in altered pain behaviors induced by high-fat diet (HFD) in male mice. We found that C57BL/6CR mice on HFD exhibited enhanced spinal microglial reaction (increased cell number and up-regulated expression of p-p38 and CD16/32), increased tumor necrosis factor-α (TNF-α) mRNA and brain-derived neurotrophic factor (BDNF) protein expression as well as a polarization of spinal microglial toward a pro-inflammatory phenotype. Moreover, we found that using PLX3397 (a selective colony-stimulating factor-1 receptor (CSF1R) kinase inhibitor) to eliminate microglia in HFD-induced obesity mice, inflammation in the spinal cord was rescued, as was abnormal pain hypersensitivity. Intrathecal injection of Mac-1-saporin (a saporin-conjugated anti-mac1 antibody) resulted in a decreased number of microglia and attenuated both mechanical allodynia and thermal hyperalgesia in HFD-fed mice. These results indicate that the pro-inflammatory functions of spinal microglia have a special relevance to abnormal pain hypersensitivity in HFD-induced obesity mice. In conclusion, our data suggest that HFD induces a classical reaction of microglia, characterized by an enhanced phosphorylation of p-38 and increased CD16/32 expression, which may in part contribute to increased nociceptive responses in HFD-induced obesity mice.

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