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1.
Arthroscopy ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33812917

RESUMO

PURPOSE: This study seeks to evaluate the biomechanical relationship between the severity of rotator cable tears and the function of the rotator cuff. METHODS: Twelve cadaveric shoulders with intact rotator cuff, existing rotator cable and a critical shoulder angle below 35° were included. For each shoulder, a posterosuperior rotator cuff tear (PSRCT) [model 2] in the crescent area was formed. Then anterior insertion detached [model 3], anterior insertion detached together with the middle cable tear [model 4] and the whole rotator cable tear [model 5] were subsequently created. The rotator cuff that lay above the humeral head rotation centre was detached as a global tear control [model 6], along with the primitive status as the intact control [model 1]. Glenohumeral abduction was initiated by simulating deltoid and remaining rotator cuff force. Functioning of the remaining rotator cuff was evaluated using the middle deltoid force (MDF), as required for abduction. RESULTS: No statistically- significant differences in peak MDF values were seen between the four PSRCT statuses (44.10 ± 7.30 N [model 2], P = 0.96; 45.50 ± 9.55 N [model 3], P = 0.86; 45.90 ± 3.53 N [model 4], P = 0.30; 44.20 ± 8.19N [model 5], P = 0.80) and intact control status (39.79 ± 7.65 N [model 1]). However, significant differences in peak MDF values were found between the four PSRCT statuses and the global tear control status (54.53 ± 7.46 N [model 6], P<0.01). CONCLUSION: The PSRCT, regardless of how severe the rotator cable tear, does not induce functionally-significant biomechanical impairment. Tear extension involving all rotator cuff tissue above the geometric rotation centre of the humeral head results in obvious functional impairment. CLINICAL RELEVANCE: For PSRCT, the remaining rotator cuff tissue above the geometric rotation centre may contribute to the preservation of shoulder function in RCT patients.

2.
Molecules ; 26(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804903

RESUMO

Sweet potato (Ipomoea batatas) is one of the most important food crops worldwide and its leaves provide a dietary source of nutrients and various bioactive compounds. These constituents of sweet potato leaves (SPL) vary among varieties and play important roles in treating and preventing various diseases. Recently, more attentions in health-promoting benefits have led to several in vitro and in vivo investigations, as well as the identification and quantification of bioactive compounds in SPL. Among them, many new compounds have been reported as the first identified compounds from SPL with their dominant bioactivities. This review summarizes the current knowledge of the bioactive compositions of SPL and their health benefits. Since SPL serve as a potential source of micronutrients and functional compounds, they can be further developed as a sustainable crop for food and medicinal industries.

3.
Cancers (Basel) ; 13(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805354

RESUMO

BACKGROUND: Few studies have evaluated long-term medical monetary cost in patients with prostate cancer (PC) receiving open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), or robot-assisted radical prostatectomy (RARP). To the best of our knowledge, this is the largest and longest follow-up study to examine medical monetary cost in patients with PC undergoing ORP, LRP, or RARP. After adjustment for confounders, the medical monetary cost in the RARP group was the least compared with that in the ORP and LRP groups. PURPOSE: To estimate long-term medical resource consumption among patients with prostate cancer (PC) receiving open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), or robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Participants were men enrolled in the Taiwan Cancer Registry with localized PC diagnosis who received radical prostatectomy. After adjustment for confounders, a generalized linear mixed model was used to determine significant differences in the number of urology outpatient clinic visits required, proportion of patients being hospitalized for urinary diseases or surgical complications, and medical reimbursement for urinary diseases or surgical complications following ORP, LRP, or RARP in the first, second, and third years. Results: No differences were observed in the median number of urology outpatient clinic visits between the three types of surgical modalities up to the second year after ORP, LRP, and RARP (median: 15, 10, and seven visits, respectively; p < 0.001), but significant differences were observed in the third year. Similarly, with RARP (10.9% versus 18.7% in ORP and 9.8% in LRP; p = 0.0014), the rate of hospitalization for urinary diseases or surgical complications decreased in the third year. Medical reimbursement for urinary diseases or surgical complications reduced after RARP compared with that for ORP and LRP, with approximately 22% reduction in the first year (p = 0.0052) and 20-40% reduction in the third year (p value = 0.0024). CONCLUSIONS: Medical resource consumption in the RARP group was less compared with those in the ORP and LRP groups.

4.
Plants (Basel) ; 10(3)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805801

RESUMO

Tea (Camellia sinensis), a globally cultivated beverage crop, is sensitive to drought, which can have an adverse effect on the yield and quality of tea. Azoxystrobin (AZ) is one kind of fungicide considered as an agent to relieve damage caused by stress. Initially, the response of tea plant to osmotic-gradient stress was evaluated using leaf disc assays with PEG-induced osmotic stress. The decline of the maximum quantum yield of PSII (Fv/Fm), actual photosynthetic efficiency of PS II (Y(II)), total chlorophylls, carotenoids, DPPH radical scavenging capacity, reducing power, total phenols, and the increase in MDA was observed in leaf discs treated with a gradient of PEG solutions (22.8, 33.2, 41.1% PEG, and blank). These results revealed that efficiency of photosystem II (PSII), photosynthetic pigments, and antioxidant ability in leaf discs were inhibited with an aggravated lipid peroxidation under PEG-induced osmotic stress, and indicated leaf disc assay with moderate PEG iso-osmotic condition would reflect a portion of tea plant response to drought stress. Therefore, the protective effect of AZ (0.125 and 1.25 g a.i. L-1) on tea plants suffering from drought was evaluated using leaf disc assays with 22.8% PEG iso-osmotic condition. Pretreatment of AZ (0.125 a.i. g L-1) reversed Fv/Fm, Y(II), DPPH radical scavenging capacity, and reducing power with reduced MDA in PEG-treated leaf discs, but photosynthetic pigments, total phenols, and ascorbate peroxidase activity were irresponsive to AZ. An Alleviated physiological damage in tea leaf with AZ applying was preliminarily revealed in this study. A Rapid screening of agents for tea plants against drought was developed to assist in the selection of protective agents.

5.
Cancers (Basel) ; 13(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806181

RESUMO

PURPOSE: To estimate the oncologic outcomes of radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) with short-term androgen-deprivation therapy (ADT) in relatively young men with unfavorable intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network (NCCN-UIR-PC). PATIENTS AND METHODS: We enrolled relatively young men (≤65 years) from the Taiwan Cancer Registry who had been diagnosed as having NCCN-UIR-PC and who had received RP or high-dose IMRT (at least ≥72 Gy) with short-term ADT (4-6 months). After propensity score matching of the confounders, Cox proportional regression was used to model the time from the index date (i.e., date of diagnosis) to all-cause death, biochemical failure (BF), locoregional recurrence (LRR), and distant metastasis (DM). RESULTS: The corresponding adjusted hazard ratios (95% confidence intervals) of the risk of all-cause death, BF, LRR, and DM were 2.76 (1.36-5.60, p = 0.0050), 2.74 (1.72-4.84, p < 0.0001), 1.28 (1.09-1.90, p = 0.0324), and 2.11 (1.40-4.88, p = 0.0052), respectively. CONCLUSIONS: RP is superior to high-dose IMRT with short-term ADT in terms of oncologic outcomes for relatively young men with UIR-PC.

6.
J Cell Mol Med ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811439

RESUMO

The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour invasion and migration, but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus. In this study, we aim to explore its role in trophoblast development and placenta-related pregnancy complications and the potential mechanism. Levels of FoxO3a and its phosphorylated form (p-FoxO3a) in placental tissue from healthy pregnant women and pre-eclampsia patients were first compared. Then, HTR-8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit-8, wound-healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT-PCR and ChIP-qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p-FoxO3a was increased in pre-eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule-1 (ICAM1) gene in ChIP assays and led to reduced invasion and migration of trophoblast cells, arrested cell cycle in G1 phase and increased apoptosis under oxidative stress. Our results suggested that FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.

7.
Biosci Rep ; 41(4)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33835138

RESUMO

OBJECTIVE: The present study aimed to identify risk factors for overall survival in advanced hepatocellular carcinoma (HCC) patients and establish a scoring system to select patients who would benefit from hepatic resection. METHODS: Survival curves were analyzed using the Kaplan-Meier method and log-rank test. The prognostic scoring system was developed from training cohort using a Cox-regression model and validated in a external validation cohort Results: There were 401 patients in the training cohort, 163 patients in the external validation cohorts. The training cohort median survival in all patients was 12 ± 1.07 months, rate of overall survival was 49.6% at 1 year, 25.0% at 3 years, and 18.0% at 5 years. A prognostic scoring system was established based on age, body mass index, alkaline phosphatase, tumor number and tumor capsule. Patients were classified as low- risk group(≤3.5) or high-risk group(>3.5). High-risk patients had a median survival of 9 months, compared with 23 months in low-risk patients. The area under the receiver operating characteristic curve (AUC) of the prognostic scoring system was 0.747 (0.694-0.801), which is significantly better than AFP, Child-Pugh and ALBI. The AUC of validation cohorts was 0.716 (0.63-0.803). CONCLUSION: A prognostic scoring system for hepatic resection in advanced HCC patients has been developed based entirely on preoperative variables. Patients classified as low risk using this system may experience better prognosis after hepatic resection.

8.
Cell Rep ; 34(13): 108922, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33789111

RESUMO

Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor-/- HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor-/- HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.

9.
Aesthet Surg J ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769461

RESUMO

BACKGROUND: Nanofat is an autologous product that is prepared mechanically from harvested fat. In nanofat grafting, converters are used for mechanical emulsification to facilitate fat injection. To date, the study of different converters has received scant attention whether these affect the characteristics of nanofat, so as the practical applications and indications. OBJECTIVES: This study set out to investigate the influence of different internal diameter of converters on biological functionality of nanofat during shuffling. METHODS: Three-dimensional finite element method was used to simulate the process of mechanical emulsification of fat,and also for researching the stress with five different converters (3.76mm、 2.00mm、 1.20mm 、1.00mm 、0.80mm). Assessment of morphology of emulsified fat was conducted. Isolated stromal vascular fraction was analyzed for cellular components, number and viability through flowcytometry and Live/ Dead staining. Adipocytic and angiogenic differentiation assay allowed assessment of differentiation capacity of stromal vascular fraction. RESULTS: The smaller the aperture of the converter, the greater the mechanical force on adipose tissue during mechanical emulsification, showing the different macroscopic and microscopic structure of the emulsified fat. No difference in viability, ration of endothelial progenitor cells and other cells was found. Angiogenic and adipogenic differentiation capacity of the stromal vascular fraction did show a significant change in five different converters. CONCLUSIONS: The mechanical emulsification from different aperture of converters does exert different effects of adipose tissue structure, cell content and multipotency differentiation while not its viability. Converters with different apertures can be selected according to clinical needs.

10.
J Orthop Surg (Hong Kong) ; 29(1): 23094990211000143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33745383

RESUMO

OBJECTIVE: To investigate the clinical efficacy of one-stage total hip arthroplasty (THA) for treating the advanced hip tuberculosis. METHODS: A retrospective study was conducted from July 2013 to June 2018, including 19 patients with advanced hip tuberculosis. All patients underwent total hip arthroplasty through posterior approach, and the surgical efficacy was evaluated. RESULTS: Nineteen patients were followed up from 24 months to 48 months, the mean follow-up were 32.1 months. All the incisions healed in grade A. There were no aseptic loosening, dislocation or recurrence of hip tuberculosis after operation. At the last follow-up, the Harris score of the patients was (89.3 ± 6.7), which was significantly higher than (38.2 ± 10.5) of the patients before operation (P < 0.05); the flexion-extension range of motion was (93.6° ± 12.1°), which was significantly larger than (38.2° ± 10.5°) of the patients before operation (P < 0.05). CONCLUSION: The one-stage total hip arthroplasty with regular antituberculosis treatment can attain satisfactory clinical efficacy in the treatment of advanced hip tuberculosis, which can relieve the joint pain and improve the joint function, without recurrence of hip tuberculosis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33725069

RESUMO

Cedarwood oil is an essential oil used as a fragrance material and insect repellent. Its main constituents are sesquiterpenes which are potentially bioaccumulative according to the REACH screening criteria. Cedarwood oil is a complex mixture of hydrophobic and volatile organic chemicals. The volatility and limited water solubility of its constituents are a challenge for standard bioconcentration factor (BCF) test methods using aqueous exposure. We used an abbreviated dietary exposure in vivo testing protocol with internal benchmark substances as "internal standards" to derive the BCF of cedarwood oil constituents using rainbow trout (Oncorhynchus mykiss). Internal benchmarking proved to be a useful tool to control for inter-individual variability, enabling us to calculate the BCF for all major cedarwood oil constituents as a mixture. We found that the BCF of two out of six analysed cedarwood oil constituents exceed a BCF of 5000 and two others exceed a BCF of 2000 (90% confidence level) even though we found evidence for biotransformation for individual constituents. The results of this study indicate that more work is warranted to study the bioaccumulation of essential oils and highlights the utility of internal benchmarking in in vivo dietary exposure BCF tests to increase robustness and allow for the BCF measurement of complex mixtures.

12.
Am J Psychiatry ; : appiajp202020070999, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33726525

RESUMO

OBJECTIVE: The heterogeneity of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) preclude definitive identification of neurobiomarkers and biological risks. High clinical overlap suggests multifaceted circuit-level alterations across diagnoses, which remains elusive. This study investigated whether individuals with ADHD or ASD and their unaffected siblings constitute a spectrum of neurodevelopmental conditions in terms of white matter etiology. METHODS: Sex-specific white matter tract normative development was modeled from diffusion MRI of 626 typically developing control subjects (ages 5-40 years; 376 of them male). Individualized metrics estimating white matter tract deviation from the age norm were derived for 279 probands with ADHD, 175 probands with ASD, and their unaffected siblings (ADHD, N=121; ASD, N=72). RESULTS: ASD and ADHD shared diffuse white matter tract deviations in the commissure and association tracts (rho=0.54; p<0.001), while prefrontal corpus callosum deviated more remarkably in ASD (effect size=-0.36; p<0.001). Highly correlated deviance patterns between probands and unaffected siblings were found in both ASD (rho=0.69; p<0.001) and ADHD (rho=0.51; p<0.001), but only unaffected sisters of ASD probands showed a potential endophenotype in long-range association fibers and projection fibers connecting prefrontal regions. ADHD and ASD shared significant white matter tract idiosyncrasy (rho=0.55; p<0.001), particularly in tracts connecting prefrontal regions, not identified in either sibling group. Canonical correlation analysis identified multiple dimensions of psychopathology/cognition across categorical entities; autistic, visual memory, intelligence/planning/inhibition, nonverbal-intelligence/attention, working memory/attention, and set-shifting/response-variability were associated with distinct sets of white matter tract deviations. CONCLUSIONS: When conceptualizing neurodevelopmental disorders as white matter tract deviations from normative patterns, ASD and ADHD are more alike than different. The modest white matter tract alterations in siblings suggest potential endophenotypes in these at-risk populations. This study further delineates brain-driven dimensions of psychopathology/cognition, which may help clarify within-diagnosis heterogeneity and high between-diagnosis co-occurrence.

13.
Org Lett ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33728923

RESUMO

A new Lewis acid-catalyzed [2 + 2] cycloaddition/retroelectrocyclization (CA-RE)/1,6-addition relay of aurone-derived 1-azadienes and 1-alkynylnaphthalen-2-ols has been reported, leading to the regio- and diastereoselective synthesis of 1,2-dihydrobenzofuro[3,2-b]pyridine with a chiral carbon center and an axial chirality in good yields. This protocol enables the C-C double-bond scission/recombination to rapidly construct aza-heterocyclic architectures and features 100% atom utilization, a wide substrate scope, good compatibility with substituents, and excellent diastereoselectivity.

14.
Plant Dis ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33754863

RESUMO

Wishbone flower (Torenia fournieri L.) is a common ornamental plant for flower bed in Taiwan. In August 2018, root and stem rot of wishbone flower occurred on the flower bed in the campus of National Chung Hsing University, Taichung city, with 100% incidence. Symptoms were dark brown discoloration of basal stems and brown necrosis of roots. Lesions from base of stems were excised into 5 mm long fragments, which were then surface sterilized in 1% sodium hydrochloride for 1 min, rinsed in sterile distilled water, dried on filter paper and thereafter placed onto 2% water agar. After 24 h, hyphae characteristic of Rhizoctonia (Sneh et al. 1991) appeared and dominated in every isolation. Hyphal tips were transferred to potato dextrose agar (PDA). After 5 days of incubation at 28°C, characteristic brown colonies of Rhizoctonia (Sneh et al. 1991) were observed. Hyphal width was 4.29±0.52 µm. No sclerotia were visibly present after 21 days of growth on PDA at 28°C. Hyphae were stained by 0.3% safranin-O and 1% KOH. There were two nuclei in each hyphal compartment, suggesting a binucleate Rhizoctonia fungus. ITS sequence has been used as the best tool to identify specific anastomosis group (AG) of Rhizoctonia as shown by Sharon et al. (2006, 2008). ITS sequence was amplified using the primers Bd1a and ITS4 (Goka et al. 2009; White et al. 1990). Blast search analysis of this acquired sequence (acc. no. LC498494) revealed the highest similarity (98.75 to 99.83%) with the reference sequences (acc. nos. AB286934, AB286933, and AB196653) of binucleate Rhizoctonia AG-L, namely Ceratobasidium sp. AG-L. Pathogenicity test was carried out using seedlings of 4-week-old wishbone flower each grown in a pot of 6.35 cm diameter. To prepare the inoculum, a PDA agar block (6 mm in diameter) excised from the growing front of 5-day-old colony was transferred into a flask with 200 ml of potato dextrose broth (PDB) incubated in a shaker at 26°C and 120 rpm for 6 days. The PDB broth was then blended into slurry. Ten pots each with a seedling were inoculated by pouring 50 ml of slurry onto the potting medium. Five pots were served as the controls by pouring PDB only. Pots were maintained in a greenhouse (26 to 33°C). Three days after inoculation, all inoculated plants exhibited symptom of root and stem rot. The same fungus was reisolated and confirmed by sequencing rDNA-ITS. This is the first report of root and stem rot of wishbone flower caused by binucleate Rhizoctonia AG-L in Taiwan and in the world. Although this is the second cases, since Wang and Hsieh (1993), for binucleate Rhizoctonia AG-L to be pathogenic, this study shows that this fungus has the potential to cause damages and is worth of further investigations.

15.
J Clin Invest ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33690219

RESUMO

Although cancer cells are frequently faced with nutrient- and oxygen-poor microenvironment, elevated hexosamine-biosynthesis pathway (HBP) activity and protein O-GlcNAcylation (a nutrient sensor) contribute to rapid growth of tumor and are emerging hallmarks of cancer. Inhibiting O-GlcNAcylation could be a promising anti-cancer strategy. The gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 (PCK1) was downregulated in hepatocellular carcinoma (HCC). However, little is known about the potential role of PCK1 in enhanced HBP activity and HCC carcinogenesis under glucose-limited conditions. In this study, PCK1 knockout markedly enhanced the global O-GlcNAcylation levels under low glucose condition. Mechanistically, metabolic reprogramming in PCK1-loss hepatoma cells led to oxaloacetate accumulation and increased de novo UTP synthesis contributing to uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis. Meanwhile, deletion of PCK1 also resulted in AMPK-GFAT1 axis inactivation promoting UDP-GlcNAc synthesis for elevated O-GlcNAcylation. Notably, lower expression of PCK1 promoted CHK2 threonine 378 O-GlcNAcylation counteracting its stability and dimer formation, increasing CHK2-dependent Rb phosphorylation and HCC cell proliferation. Moreover, aminooxyacetic acid hemihydrochloride and 6-diazo-5-oxo-L-norleucine blocked HBP-mediated O-GlcNAcylation and suppressed tumor progression in liver-specific Pck1-knockout mice. We reveal a link between PCK1 depletion and hyper-O-GlcNAcylation that underlies HCC oncogenesis and suggest therapeutic targets for HCC that act by inhibiting O-GlcNAcylation.

16.
Pain Res Manag ; 2021: 6660304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688384

RESUMO

Purpose: The occurrence of low back pain (LBP) in marathon runners has been poorly understood. This study aimed to describe the risk factors and identify whether these factors can cause LBP in these athletes. Methods: A self-developed questionnaire was randomly distributed to 850 runners of running a half or a full marathon. Participants responded with the questionnaire focusing on previous training and running conditions after their competitions. Results: On the basis of the remaining 800 valid questionnaires, the incidence of LBP was 4.50% (n = 36). A total of 572 (71.5%) males and 228 (28.5%) females, with an average age range of 33.9 ± 9.0 years, came from different occupations with different physical activity characteristics. However, no significant associations between occupation and runners with LBP (p > 0.05) were found. In the final models, risk factors, including warm-up activities (p=0.012, OR = 2.617), fatigue (p = 0.008, OR = 2.680), running gait posture (p=0.041, OR = 2.273), and environmental temperature (p=0.020, OR = 6.584), were significantly associated with LBP in marathoners. Conclusion: Although LBP was uncommon in marathoners, it was linked to the factors such as insufficient warm-up activities, fatigue, poor running gait posture, and uncomfortable environmental temperature. Future studies need to validate these results. Nevertheless, these findings could still be useful for protecting the lower back area of runners clinically.

17.
Genetics ; 217(1): 1-17, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33683370

RESUMO

Infection with antibiotic-resistant bacteria is an emerging life-threatening issue worldwide. Enterohemorrhagic Escherichia coli O157: H7 (EHEC) causes hemorrhagic colitis and hemolytic uremic syndrome via contaminated food. Treatment of EHEC infection with antibiotics is contraindicated because of the risk of worsening the syndrome through the secreted toxins. Identifying the host factors involved in bacterial infection provides information about how to combat this pathogen. In our previous study, we showed that EHEC colonizes in the intestine of Caenorhabditis elegans. However, the host factors involved in EHEC colonization remain elusive. Thus, in this study, we aimed to identify the host factors involved in EHEC colonization. We conducted forward genetic screens to isolate mutants that enhanced EHEC colonization and named this phenotype enhanced intestinal colonization (Inc). Intriguingly, four mutants with the Inc phenotype showed significantly increased EHEC-resistant survival, which contrasts with our current knowledge. Genetic mapping and whole-genome sequencing (WGS) revealed that these mutants have loss-of-function mutations in unc-89. Furthermore, we showed that the tolerance of unc-89(wf132) to EHEC relied on HLH-30/TFEB activation. These findings suggest that hlh-30 plays a key role in pathogen tolerance in C. elegans.

18.
Oncogene ; 40(10): 1775-1791, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33564074

RESUMO

Metastasis is the fundamental cause of cancer mortality, but there are still very few anti-metastatic drugs available. Endosomal trafficking has been implicated in tumor metastasis, and we have previously found that small chemical vacuolin-1 (V1) potently inhibits autophagosome-lysosome fusion and general endosomal-lysosomal degradation. Here, we assessed the anti-metastatic activity of V1 both in vitro and in vivo. V1 significantly inhibits colony formation, migration, and invasion of various cancer cells in vitro. It also compromises the assembly-disassembly dynamics of focal adhesions (FAs) by inhibiting the recycling and degradation of integrins. In various experimental or transgenic mouse models, V1 significantly suppresses the metastasis and/or tumor growth of breast cancer or melanoma. We further identified capping protein Zß (CapZß) as a V1 binding protein and showed that it is required for the V1-mediated inhibition of migration and metastasis of cancer cells. Collectively, our results indicate that V1 targets CapZß to inhibit endosomal trafficking and metastasis.

19.
Neurobiol Learn Mem ; 179: 107397, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33524570

RESUMO

Human genetic studies established MET gene as a risk factor for autism spectrum disorders. We have previously shown that signaling mediated by MET receptor tyrosine kinase, expressed in early postnatal developing forebrain circuits, controls glutamatergic neuron morphological development, synapse maturation, and cortical critical period plasticity. Here we investigated how MET signaling affects synaptic plasticity, learning and memory behavior, and whether these effects are age-dependent. We found that in young adult (postnatal 2-3 months) Met conditional knockout (Metfx/fx:emx1cre, cKO) mice, the hippocampus exhibits elevated plasticity, measured by increased magnitude of long-term potentiation (LTP) and depression (LTD) in hippocampal slices. Surprisingly, in older adult cKO mice (10-12 months), LTP and LTD magnitudes were diminished. We further conducted a battery of behavioral tests to assess learning and memory function in cKO mice and littermate controls. Consistent with age-dependent LTP/LTD findings, we observed enhanced spatial memory learning in 2-3 months old young adult mice, assessed by hippocampus-dependent Morris water maze test, but impaired spatial learning in 10-12 months mice. Contextual and cued learning were further assessed using a Pavlovian fear conditioning test, which also revealed enhanced associative fear acquisition and extinction in young adult mice, but impaired fear learning in older adult mice. Lastly, young cKO mice also exhibited enhanced motor learning. Our results suggest that a shift in the window of synaptic plasticity and an age-dependent early cognitive decline may be novel circuit pathophysiology for a well-established autism genetic risk factor.

20.
Mol Microbiol ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567149

RESUMO

Enterohemorrhagic Escherichia coli (EHEC), an enteropathogen that colonizes in the intestine, causes severe diarrhea and hemorrhagic colitis in humans by the expression of the type III secretion system (T3SS) and Shiga-like toxins (Stxs). However, how EHEC can sense and respond to the changes in the alimentary tract and coordinate the expression of these virulence genes remains elusive. The T3SS-related genes are known to be regulated by the locus of enterocyte effacement (LEE)-encoded regulators, such as Ler, as well as non-LEE-encoded regulators in response to different environmental cues. Herein, we report that OmpR, which participates in the adaptation of E. coli to osmolarity and pH alterations, is required for EHEC infection in Caenorhabditis elegans. OmpR protein was able to directly bind to the promoters of ler and stx1 (Shiga-like toxin 1) and regulate the expression of T3SS and Stx1, respectively, at the transcriptional level. Moreover, we demonstrated that the expression of ler in EHEC is in response to the intestinal environment and is regulated by OmpR in C. elegans. Taken together, we reveal that OmpR is an important regulator of EHEC which coordinates the expression of virulence factors during gastrointestinal infection in vivo.

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