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1.
Zhongguo Zhong Yao Za Zhi ; 45(5): 997-1003, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237438

RESUMO

To investigate the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling by observing the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the neurotransmitter, endocrine hormone and immune factor level in mice with deficiency-heat and deficiency-cold syndrome. KM male mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, and deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given with thyroid tablet solution(160 mg·kg~(-1)), and the mice in deficiency-cold group were given with hydrocortisone solution(25 mg·kg~(-1)) by intragastric administration every afternoon for 14 days. The mice in each administration group received corresponding drug. The neurotransmitter, endocrine hormone and immune factor levels in the mice were measured after the experiment. The Açaí alcohol extract, consistent with the Açaí powder, showed a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinna-momi Cortex, showing a regulatory effect on the deficiency-cold model mice. In this study, on the basis of proving that Açaí was was cool in property, it also revealed that alcohol extract of Açaí was cool while oil and water extract were warm in property based on the effect of Açaí on neuro-endocrine-immune network. The results suggested that the medicine property of Açaí was the result of the comprehensive action of the resolution components with different properties, and the alcohol extract of Açaí was proved as the material basis of Açaí cold medicine by using the methods of homogeneous comparison and heterogeneous disproval.

2.
PLoS One ; 15(4): e0230796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236130

RESUMO

BACKGROUND: Evidence from multiple studies suggests metabolic abnormalities play an important role in lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. The present study aimed to explore differences in the global metabolic response between male and female patients in LUAD and to identify the metabolic genes associated with lung cancer susceptibility. METHODS: Transcriptome and clinical LUAD data were acquired from The Cancer Genome Atlas (TCGA) database. Information on metabolic genes and metabolic subsystems were collected from the Recon3D human metabolic model. Two validation datasets (GSE68465 and GSE72094) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, gene set enrichment analysis and protein-protein interaction networks were used to identified key metabolic pathways and genes. Functional experiments were used to verify the effects of genes on proliferation, migration, and invasion in lung cancer cells in vitro. RESULTS: Samples of tumors and adjacent non-tumor tissue from both male and female patients exhibited distinct global patterns of gene expression. In addition, we found large differences in methionine and cysteine metabolism, pyruvate metabolism, cholesterol metabolism, nicotinamide adenine dinucleotide (NAD) metabolism, and nuclear transport between male and female LUAD patients. We identified 34 metabolic genes associated with lung cancer susceptibility in males and 15 in females. Most of the metabolic cancer-susceptibility genes had high prediction accuracy for lung cancer (AUC > 0.9). Furthermore, both bioinformatics analysis and experimental results showed that TAOK2 was down-regulated and ASAH1 was up-regulated in male tumor tissue and female tumor tissue in LUAD. Functional experiments showed that inhibiting ASAH1 suppressed the proliferation, migration, and invasion of lung cancer cells. CONCLUSIONS: Metabolic cancer-susceptibility genes may be used alone or in combination as diagnostic markers for LUAD. Further studies are required to elucidate the functions of these genes in LUAD.

3.
Phys Ther ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32157307

RESUMO

BACKGROUND: Virtual reality (VR) is a frequently used intervention for the rehabilitation of individuals with neurological disorders. PURPOSE: The aims of this review were to identify the short-term effect of VR on balance and to compare it with the effect of active interventions in individuals with Parkinson disease (PD). DATA SOURCES: Searches for relevant articles available in English were conducted using the MEDLINE (via PubMed), EMBASE, CENTRAL, CINAHL, PsycINFO, and Physiotherapy Evidence Database databases from inception until March 2019. STUDY SELECTION: All randomized controlled trials comparing the effect of training with VR and the effect of training without VR on balance in individuals with PD were included. DATA EXTRACTION: Two authors independently extracted data, assessed the methodological quality, and evaluated the evidence quality of the studies. DATA SYNTHESIS: Fourteen randomized controlled trials including 574 individuals were eligible for qualitative analyses, and 12 of the studies involving 481 individuals were identified as being eligible for meta-analyses. Compared with active interventions, the use of VR improved the Berg Balance Scale score mean difference = 1.23; 95% CI = 0.15 to 2.31; I2 = 56%). The Dynamic Gait Index and Functional Gait Assessment results were also significant after the sensitivity analyses (mean difference = 0.69; 95% CI = 0.12 to 1.26; I2 = 0%). Both provided moderate statistical evidence. (However, the Timed "Up & Go" Test and the Activities-Specific Balance Confidence Scale did not differ significantly. LIMITATIONS: Publication bias and diversity in the interventions were the main limitations. CONCLUSIONS: Existing moderate evidence of the effectiveness of VR with the Berg Balance Scale, Dynamic Gait Index, and Functional Gait Assessment for individuals with PD was promising. Although the differences did not reach the clinically important change threshold, VR was comparable to the active interventions and could be considered an adjuvant therapy for balance rehabilitation in individuals with PD.

4.
G3 (Bethesda) ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161086

RESUMO

Drought stress is an important crop yield limiting factor worldwide. Plant physiological responses to drought stress are driven by changes in gene expression. While drought-responsive genes (DRGs) have been identified in maize, regulation patterns of gene expression during progressive water deficits remain to be elucidated. In this study, we generated time-series transcriptomic data from the maize inbred line B73 under well-watered and drought conditions. Comparisons between the two conditions identified 8,626 DRGs and which the stages (early, middle, and late drought) at which DRGs occurred. Different functional groups of genes were regulated at the three stages. Specifically, early and middle DRGs display higher copy number variation among diverse Zea mays lines, and they exhibited stronger associations with drought tolerance as compared to late DRGs. In addition, correlation of expression between small RNAs (sRNAs) and DRGs from the same samples identified 201 negatively sRNA/DRG correlated pairs, including genes showing high levels of association with drought tolerance, such as two glutamine synthetase genes, gln2 and gln6 The characterization of dynamic gene responses to progressive drought stresses indicates important adaptive roles of early and middle DRGs, as well as roles played by sRNAs in gene expression regulation upon drought stress.

5.
Ann Rheum Dis ; 79(4): 518-524, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32114510

RESUMO

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. METHODS: We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. RESULTS: We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. CONCLUSION: Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.

6.
EBioMedicine ; 53: 102674, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32113159

RESUMO

BACKGROUND: Autoantibodies against tumor associated antigens are highly related to cancer progression. Autoantibodies could serve as indicators of tumor burden, and have the potential to monitor the response of treatment and tumor recurrence. However, how the autoantibody repertoire changes in response to cancer treatment are largely unknown. METHODS: Sera of five lung adenocarcinoma patients before and after surgery, were collected longitudinally. These sera were analyzed on a human proteome microarray of 20,240 recombinant proteins to acquire dynamic autoantibody repertoire in response to surgery, as well as to identify the antigens with decreased antibody response after tumor excision or surgery, named as surgery-associated antigens. The identified candidate antigens were then used to construct focused microarray and validated by longitudinal sera collected from a variety of time points of the same patient and a larger cohort of 45 sera from lung adenocarcinoma patients. FINDINGS: The autoantibody profiles are highly variable among patients. Meanwhile, the autoantibody profiles of the sera from the same patient were surprisingly stable for at least 3 months after surgery. Six surgery-associated antigens were identified and validated. All the five patients have at least one surgery-associated antigen, demonstrating this type of biomarkers is prevalent, while specific antigens are poorly shared among individuals. The prevalence of each antigen is 2%-14% according to the test with a larger cohort. INTERPRETATION: To our knowledge, this is the first study of dynamically profiling of autoantibody repertoires before/after surgery of cancer patients. The high prevalence of surgery-associated antigens implies the possible broad application for monitoring of tumor recurrence in population, while the low prevalence of specific antigens allows personalized medicine. After the accumulation and analysis of more longitudinal samples, the surgery-associated serum biomarkers, combined as a panel, may be applied to alarm the recurrence of tumor in a personalized manner. FUNDING: Research supported by grants from National Key Research and Development Program of China Grant (No. 2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813), Open Foundation of Key Laboratory of Systems Biomedicine (No. KLSB2017QN-01), Science and Technology Commission of Shanghai Municipality Medical Guidance Science &Technology Support Project (16411966100), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20172005), Shanghai Municipal Commission of Health and Family Planning Outstanding Academic Leaders Training Program (2017BR055) and National Natural Science Foundation of China (81871882).

7.
Int J Mol Sci ; 21(6)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32183481

RESUMO

The polymorphic membrane protein D (PmpD) is a highly conserved outer membrane protein which plays an important role in pathogenesis during Chlamydia psittaci infection. In this study, we evaluated the ability of the N-terminus of PmpD (PmpD-N) to modulate the functions of chicken macrophages and the signaling pathway(s) involved in PmpD-N-induced Toll-like receptors (TLRs), as well as interleukin (IL)-6 and IL-10 cytokine secretions. Thus, HD11 macrophages were treated with exogenous and intracellular PmpD-N of C. psittaci. The chlamydial growth was evaluated by enumeration of chlamydial loads in the infected macrophages. The phagocytic function of macrophages following PmpD-N treatment was detected by fluorescein-labeled Escherichia coli (E. coli). The concentration of nitric oxide (NO) secreted by HD11 macrophages was measured by the amount of NO2- in the culture supernatant using the Griess method. The cytokine secretions were assessed using multiplex cytokine ELISA kits. Expression levels of TLRs, myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) were analyzed by a Western blotting assay, as well as a luciferase assay, while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The nuclear translocation of the transcription factor NF-κB was confirmed by evaluating its ability to combine with the corresponding promoter using the electrophoretic mobility shift assay (EMSA). After treatment with exogenous or endogenous PmpD-N, chlamydial loads and phagocytic functions were reduced significantly compared with those of the plasmid vector group, while NO secretions were reduced significantly compared with those of the lipopolysaccharide (LPS) treatment. Stimulation of HD11 cells with PmpD-N provoked the secretion of the Th2 cytokines, IL-6, and IL-10 and upregulated the expression of TLR2, TLR4, MyD88, and NF-κB. Furthermore, inhibition of TLR2, MyD88, and NF-κB in HD11 cells significantly decreased IL-6 and IL-10 cytokine levels, while NO production and phagocytosis increased significantly, strongly suggesting their involvement in PmpD-N-induced Th2 cytokine secretion and macrophage dysfunction. Our data indicate that C. psittaci PmpD-N inhibited macrophage functions by activating the Th2 immune response and the TLR2/MyD88/NF-κB signaling pathway.

8.
Inorg Chem ; 59(5): 2636-2640, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32058709

RESUMO

Encapsulation of flavin mononucleotide (FMN) in a porphyrinatomanganese(III)-based cubic cage allowed the fast reduction of manganese(III) porphyrin in the presence of nicotinamide adenine dinucleotide (NADH). This supramolecular system was capable of efficiently activating dioxygen and catalyzing the oxidation of benzyl alcohol. Control experiments suggested that the close proximity between FMN and manganese(III) porphyrins forced by the host-guest interaction might benefit the electron-transfer process from the FMN cofactor to the metal centers.

9.
Spinal Cord ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034295

RESUMO

STUDY DESIGN: A pre-post observational study. OBJECTIVES: To evaluate the safety and feasibility of a new rehabilitation robotic device for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI). SETTING: Three hospitals in Sichuan Province, China. METHODS: Individuals aged 15-75 years with an SCI between vertebrae six (T6) and lumbar 1 (L1) and complete motor paralysis participated in an exoskeletal-assisted walking (EAW) programme (2 weeks, 5 days/week, 30 min/day). Data were collected pre-, mid- (week 1) and post-intervention (week 2). RESULTS: Twenty-eight individuals (mean age = 41.3, 71% males) participated in the EAW programme. The distance walked during the 6-min walking test (6MWT) increased relative to that at baseline, during week 1 (13.0 ± 5.3 m) and week 2 (16.2 ± 5.3 m) when wearing the exoskeleton. The walking speed during the 10-m walking test (10MWT) increased from 0.039 ± 0.016 to 0.045 ± 0.016 m/s. The Hoffer walking ability grade, the Spinal Cord Independence Measure (SCIM), and the Walking Index for SCI II (WISCI II) changed after 2 weeks of EAW. No improvement in lower extremity motor score (LEMS) was observed. The rates of adverse events and serious adverse events were 21% and 4%, respectively. CONCLUSIONS: The EAW programme with the new robotic exoskeleton provided potential meaningful improvements in mobility for individuals with SCI and had few adverse events.

10.
Microb Pathog ; 142: 104095, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32097745

RESUMO

Mycotoxins are secondary metabolites produced mainly by fungi belonging to the genera Aspergillus, Fusarium, Penicillium, Claviceps, and Alternaria that contaminate basic food products throughout the world, whether developing countries becoming predominantly affected. Currently, more than 500 mycotoxins are reported in which the most important concern to public health and agriculture include AFB1, OTA, TCTs (especially DON, T-2, HT-2), FB1, ZEN, PAT, CT, and EAs. The presence of mycotoxin in significant quantities poses health risks varying from allergic reactions to death on both humans and animals. This review brings attention to the present status of mycotoxin contamination of food products and recommended control strategies for mycotoxin mitigation. Humans are exposed to mycotoxins directly through the consumption of contaminated foods while, indirectly through carryover of toxins and their metabolites into animal tissues, milk, meat and eggs after ingestion of contaminated feeds. Pre-harvest (field) control of mycotoxin production and post-harvest (storage) mitigation of contamination represent the most effective approach to limit mycotoxins in food and feed. Compared with chemical and physical approaches, biological detoxification methods regarding biotransformation of mycotoxins into less toxic metabolites, are generally more unique, productive and eco-friendly. Along with the biological detoxification method, genetic improvement and application of nanotechnology show tremendous potential in reducing mycotoxin production thereby improving food safety and food quality for extended shelf life. This review will primarily describe the latest developments in the formation and detoxification of the most important mycotoxins by biological degradation and other alternative approaches, thereby reducing the potential adverse effects of mycotoxins.

11.
Medicine (Baltimore) ; 99(7): e19200, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049858

RESUMO

Elderly individuals with non-dipper hypertension are at high risk of cardiovascular disease because of increased stiffness of peripheral arteries. Since, vitamin D deficiency is prevalent in elderly Chinese. We examined whether reduced plasma levels of 25-hydroxyvitamin D [25(OH)D] may help promote this stiffness.Hypertensive patients at least 60 years old without history of peripheral arterial disease at our hospital were retrospectively divided into dipper and non-dipper groups according to the results of 24-hour ambulatory blood pressure monitoring. Plasma levels of 25(OH)D were measured by enzyme immunoassay. Peripheral arterial stiffness was measured based on the cardio-ankle vascular index (CAVI).Of the 155 patients enrolled, 95 (61.3%) were diagnosed with non-dipper hypertension and these patients had significantly lower plasma levels of 25(OH)D than the 60 patients with dipper hypertension (19.58 ±â€Š5.97 vs 24.36 ±â€Š6.95 nmol/L, P < .01) as well as significantly higher CAVI (8.46 ±â€Š1.65 vs 7.56 ±â€Š1.08 m/s, P < .01). Vitamin D deficiency was significantly more common among non-dipper patients (57.9% vs 31.7%, P < .01). Multivariate regression showed that age and 25(OH)D were independently related to CAVI, with each 1-ng/ml decrease in 25(OH)D associated with a CAVI increase of +0.04 m/s.Non-dipper hypertension is associated with vitamin D deficiency and reduced plasma levels of 25(OH)D. The latter may contribute to stiffening of peripheral arteries, increasing the risk of cardiovascular disease.


Assuntos
Hipertensão/sangue , Rigidez Vascular , Vitamina D/análogos & derivados , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vitamina D/sangue
12.
Foodborne Pathog Dis ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31934792

RESUMO

This study investigated occurrence and antimicrobial resistance profiles of Campylobacter spp. isolates in beef cattle on five cow-calf operations in South Africa. A total of 537 fecal samples from adult beef cattle (n = 435) and rectal swabs from calves (n = 102) were screened for Campylobacter jejuni, Campylobacter coli, and Campylobacter upsaliensis by culture and polymerase chain reaction. Furthermore, 86 Campylobacter spp. isolates including 46 C. jejuni, 24 C. coli, and 16 C. upsaliensis were tested for antimicrobial resistance against a panel of 9 antimicrobials. Overall, Campylobacter spp. was detected in 29.7% of cattle. Among the 158 Campylobacter spp.-positive cattle, 61.8% carried C. jejuni, 25% carried C. coli, and 10% carried C. upsaliensis. Five animals (3.1%) had mixed infections: three cows carried C. jejuni and C. coli concurrently, one cow had both C. jejuni and C. upsaliensis, and one cow harbored C. coli and C. upsaliensis. Antimicrobial resistance profiling among 86 Campylobacter spp. isolates revealed that 52.3% of the isolates were resistant to one or more antimicrobials. Antimicrobial resistance was observed in 46.7% of C. jejuni isolates, 35.6% of C. coli, and 17.8% of C. upsaliensis. Thirty-six percent of isolates were resistant to clindamycin, 19.7% to nalidixic acid, 18.6% to tetracycline, and 17.4% to erythromycin. Lower resistance rates were recorded for azithromycin (8.1%), florfenicol (3.4%), gentamicin (4.8%), and telithromycin and ciprofloxacin (5.8%). Multidrug resistance (MDR) was observed in 32.5% of isolates. Significantly higher levels of MDR were detected among C. jejuni (36.9%) and C. coli (33.3%) isolates in comparison to C. upsaliensis (18.7%). Two main multiresistance patterns were detected: nalidixic acid/clindamycin (17.8%) and tetracycline/clindamycin (14.2%). To the best of our knowledge, this is the first study which has shown that beef cattle on cow-calf operations in South Africa constitute an important reservoir and a potential source of clinically relevant and antimicrobial resistant Campylobacter spp. strains.

13.
BMC Genomics ; 21(1): 19, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906861

RESUMO

BACKGROUND: Growth hormone inducible transmembrane protein (GHITM) is a highly conserved transmembrane protein. This study was conducted to investigate the role of GHITM gene in the apoptosis and growth of the golden apple snail Pomacea canaliculate. RESULTS: The complete cDNA of this gene was cloned using the rapid amplification of cDNA ends (RACE) method and subjected to bioinformatics analysis. The full-length cDNA was 2242 bp, including an open reading frame of 1021 bp that encoded a protein of 342 amino acid residues. The mRNA expression profiles of GHITM gene in different tissues (liver, kidney, gonad and foot) and different growth phases (6-months old and 2-years old) showed that it was expressed in various tissues and different growth phases. Silencing of the GHITM gene by RNAi (RNA interference) experiments revealed that the GHITM gene possibly plays a role in inhibiting apoptosis through detecting the Caspase (Cysteine-requiring Aspartate Protease)-3 activity. In addition, the aperture width and body whorl length of the snail was significantly affected by RNAi, suggesting that this gene plays a significant role in promoting the growth of the organism. CONCLUSIONS: These results demonstrated that the GHITM gene was involved in apoptosis and growth in golden apple snail.

14.
Avian Pathol ; : 1-10, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-31951466

RESUMO

Chlamydia psittaci is an important zoonotic pathogen and its oral route of infection plays an important role in the transmission and persistence. Bacillus cereus (B. cereus) strain, a common contaminant of animal feed and feedstuffs, can cause severe diarrhoea and malnutrition in poultry. In our previous study, a B. cereus strain (Dawu C), isolated from the haemorrhagic lungs of infected chickens, was shown to harbour two virulence genes (hblC and cytk) and was able to induce haemorrhagic lesions in the lungs, as well as gizzard erosion and ulceration (GEU) syndrome in broilers. In the present study, we tested the hypothesis that B. cereus-induced GEU would aggravate C. psittaci infection. Our results showed that SPF chickens exposed to B. cereus developed a severe GEU syndrome. More interestingly, prior infection with B. cereus facilitated C. psittaci infection, and aggravated GEU and respiratory distress, which were accompanied by high chlamydial loads in the lungs and severe lesions in respiratory organs. Moreover, levels of local inflammatory cytokines were elevated and T cell responses were impaired in the infected birds. In conclusion, GEU caused by B. cereus may facilitate chlamydial transmission from the ventriculus to the lungs.RESEARCH HIGHLIGHTS Bacillus cereus contributes to the gizzard erosion and ulceration syndrome in chickens.Exposure to Bacillus cereus exacerbates pneumonia in birds following chlamydial infection.Bacillus cereus facilitates persistent chlamydial infection and exacerbates immune responses.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31970856

RESUMO

The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear IrIII -containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine-coupling chemistry between aldehyde end-capped fac-Ir(ppy)3 handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd-even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis-induction upon white-light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA-targeting IrIII -containing metallohelices as PDT agents.

16.
Chem Commun (Camb) ; 56(11): 1693-1696, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31939945

RESUMO

Asymmetric conjugate addition of PhMe2SiBPin to a wide range of N-heteroaryl alkenes proceeded in the presence of a copper catalyst coordinated with an easily accessible chiral phosphoramidite ligand to afford useful ß-silyl N-heteroarenes in high yields (up to 96%) and excellent enantioselectivities (up to 97% ee).

17.
J Bacteriol ; 202(8)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31988079

RESUMO

A critical step in intracellular Chlamydia infection is the production of infectious progeny through the expression of late genes. This differentiation step involves conversion from a reticulate body (RB), which is the replicating form of the bacterium, into an elementary body (EB), which is the developmental form that spreads the infection to a new host cell. EUO is an important chlamydial transcription factor that controls the expression of late genes, but the mechanisms that regulate EUO are not known. We report that a plasmid-encoded protein, Pgp4, enhanced the repressor activity of EUO. Pgp4 did not function as a transcription factor because it did not bind or directly modulate transcription of its target promoters. Instead, Pgp4 increased the ability of EUO to bind and repress EUO-regulated promoters in vitro and physically interacted with EUO in pulldown assays with recombinant proteins. We detected earlier onset of EUO-dependent late gene expression by immunofluorescence microscopy in Pgp4-deficient C. trachomatis and C. muridarum strains. In addition, the absence of Pgp4 led to earlier onset of RB-to-EB conversion in C. muridarum These data support a role for Pgp4 as a negative regulator of chlamydial transcription that delays late gene expression. Our studies revealed that Pgp4 also has an EUO-independent function as a positive regulator of chlamydial transcription.IMPORTANCE Chlamydia trachomatis is an important human pathogen that causes more than 150 million active cases of genital and eye infection in the world. This obligate intracellular bacterium produces infectious progeny within an infected human cell through the expression of late chlamydial genes. We showed that the ability of a key chlamydial transcription factor, EUO, to repress late genes was enhanced by a plasmid-encoded protein, Pgp4. In addition, studies with Chlamydia Pgp4-deficient strains provide evidence that Pgp4 delays late gene expression in infected cells. Thus, Pgp4 is a novel regulator of late gene expression in Chlamydia through its ability to enhance the repressor function of EUO.

18.
Pediatr Cardiol ; 41(1): 38-45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650215

RESUMO

Although isolated congenital ventricular septal defects (VSD) can be repaired with a high degree of success, residual shunts (RS) are commonplace postoperatively. Small RS are relatively innocuous and tend to spontaneously close with time, despite the emotional burden it poses for the patient and family. A large RS, however, needs ongoing surveillance and may necessitate reintervention. Factors influencing the incidence of RS as well as the likelihood and expected timing of its spontaneous closure are discussed in this study. The patient records and relevant data of 362 consecutive patients undergoing cardiac operation with isolated congenital VSD closure as primary procedure between January 2017 and December 2017 were included in the study. Postoperative transthoracic echocardiograms were performed at hospital discharge, and during follow-up, at 1 month, 3 months, 6 months and 1 year postoperatively. Residual defects were measured under echocardiogram at every follow-up. Factors expected to be associated with RS occurrence and spontaneous closure were included for logistic and Cox regression statistical analysis. There were 113 cases where RS occurred according to the first postoperative echocardiograms that were performed at discharge, of which 80 were confirmed closed during subsequent follow-up, with a median follow-up of 96 days. A cutoff of 1.25 mm for the initial RS was found to be the best predictor of spontaneous closure at 6-month follow-up. Small shunts had higher closure rate than larger ones by a follow-up duration of 300 days, at which the two groups tended to reach a similar spontaneous closure rate. Longer surgical bypass time distinguished small from larger residual shunts measured upon discharge. Following repair of isolated congenital VSDs, the incidence of a residual shunt is high. The majority spontaneously close within 300 days following surgery. Longer bypass time predicted a larger residual shunt upon discharge. Larger than 1.25 mm shunts had lower short-term closure rate but seemed not to differ from smaller shunts beyond 300 days postoperatively.

19.
Arch Phys Med Rehabil ; 101(1): 130-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31465758

RESUMO

OBJECTIVE: The purpose of this review was to systematically assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) intervention on gait in individuals with Parkinson disease (PD). DATA SOURCES: We searched online electronic databases up to March 28, 2019, including MEDLINE, Embase, the Cochrane Library, and so on. STUDY SELECTION: The inclusion criteria for this review were randomized controlled trials (RCTs), exploring the effect of rTMS in patients diagnosed with idiopathic PD. DATA EXTRACTION: Data extraction was performed independently by 2 reviewers based on predefined criteria and the methodologic quality of included studies was quantified by the Physiotherapy Evidence Database scale. The outcome measure was walking performance, including walking time (short term and long term), Timed Up and Go (TUG) test, and so on. DATA SYNTHESIS: Among 14 eligible studies, including 298 participants (mean age ± SD [y], 63.24±9.71; 191 [64%] men) were analyzed in this meta-analysis. Walking time was improved with rTMS compared with sham rTMS (standardized mean difference [SMD] -0.30; 95% confidence interval [CI], -0.57 to -0.03; P=.03). The score for the freezing of gait questionnaire did not differ significantly between rTMS and no intervention. Four studies compared TUG between the 2 treatment groups and no significant differences were found between the rTMS and control group (SMD -0.45; 95% CI, -1.32 to 0.41; P=.30). During the off-state, there were no significant differences in estimated effect sizes (SMD=-0.29; 95% CI, -0.79 to 0.21; P=.25), which is significantly different in on-state (SMD -0.98; 95% CI, -1.78 to -0.18; P=.02) evaluation. CONCLUSIONS: The results of the meta-analysis propose the favorable effect of rTMS on walking performance in the short term but not over the long term in individuals with PD.

20.
IEEE Trans Cybern ; 50(3): 1106-1119, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30575553

RESUMO

In evolutionary multiobjective optimization, the Pareto front (PF) is approximated by using a set of representative candidate solutions with good convergence and diversity. However, most existing multiobjective evolutionary algorithms (MOEAs) have general difficulty in the approximation of PFs with complicated geometries. To address this issue, we propose a generic front modeling method for evolutionary multiobjective optimization, where the shape of the nondominated front is estimated by training a generalized simplex model. On the basis of the estimated front, we further develop an MOEA, where both the mating selection and environmental selection are driven by the approximate nondominated fronts modeled during the optimization process. For performance assessment, the proposed algorithm is compared with several state-of-the-art evolutionary algorithms on a wide range of benchmark problems with various types of PFs and different numbers of objectives. Experimental results demonstrate that the proposed algorithm performs consistently on a variety of multiobjective optimization problems.

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