Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.058
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36662259

RESUMO

In this study, rational design and saturation mutagenesis efforts for engineering phenylalanine ammonia-lyase from Petroselinum crispum (PcPAL) provided tailored PALs active towards challenging, highly valuable di-substituted substrates, such as the L-DOPA precursor 3,4-dimethoxy-L-phenylalanine or the 3-bromo-4-methoxy-phenylalanine. The rational design approach and saturation mutagenesis strategy unveiled identical PcPAL variants of improved activity, highlighting the limited mutational variety of the substrate specificity-modulator residues, L134, F137, I460 of PcPAL. Due to the restricted catalytic efficiency of the best performing L134A/I460V and F137V/I460V PcPAL variants, we imprinted these beneficial mutations to PALs of different origins. The variants of PALs from Arabidopsis thaliana (AtPAL) and Anabaena variabilis (AvPAL) showed higher catalytic efficiency than their PcPAL homologues. Further, the engineered PALs were also compared in terms of catalytic efficiency with a novel aromatic ammonia-lyase from Loktanella atrilutea (LaAAL), close relative of the metagenome-derived aromatic ammonia-lyase AL-11, reported recently to possess atypically high activity towards substrates with electron-donor aromatic substituents. Indeed, LaAAL outperformed the engineered Pc/At/AvPALs in the production of 3,4-dimethoxy-L-phenylalanine; however, in case of 3-bromo-4-methoxy derivatives it showed no activity, with computational results supporting the occurrence of steric hindrance. Transferring the unique array of selectivity modulator residues from LaAAL to the well-characterized PALs did not enhance their activity towards the targeted substrates. Moreover, applying the rational design strategy valid for these well-characterized PALs to LaAAL decreased its activity. These results suggest that distinct tailoring rationale is required for LaAAL/AL-11-like aromatic ammonia-lyases, which might represent a distinct PAL subclass, with natural reaction and substrate scope modified through evolutionary processes. KEY POINTS: • PAL-activity for challenging substrates generated by protein engineering • Rational/semi-rational protein engineering reveals constrained mutational variability • Engineered PALs are outperformed by novel ALs of distinct catalytic site signature.

2.
Biogerontology ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662374

RESUMO

Hydrogen sulfide (H2S) is one of the most important gasotransmitters that affect lifespan and provide resistance to adverse environmental conditions. Here we investigated geroprotective effects of the individual and simultaneous overexpression of genes encoding key enzymes of H2S biosynthesis - cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE) on D. melanogaster model. Simultaneous overexpression of CBS and CSE resulted in additive (in males) and synergistic (in females) beneficial effects on median lifespan. Individual overexpression of CBS was associated with increased thermotolerance and decreased transcription level of genes encoding stress-responsive transcription factors HIF1 and Hsf, while individual overexpression of CSE was associated with increased resistance to paraquat. Simultaneous overexpression of both genes increased resistance to hyperthermia in old females or paraquat in old males. The obtained results suggest sex-specific epistatic interaction of CBS and CSE overexpression effects on longevity and stress resistance.

3.
Development ; 150(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36628974

RESUMO

Src kinases are important regulators of cell adhesion. Here, we have explored the function of Src42A in junction remodelling during Drosophila gastrulation. Src42A is required for tyrosine phosphorylation at bicellular (bAJ) and tricellular (tAJ) junctions in germband cells, and localizes to hotspots of mechanical tension. The role of Src42A was investigated using maternal RNAi and CRISPR-Cas9-induced germline mosaics. We find that, during cell intercalations, Src42A is required for the contraction of junctions at anterior-posterior cell interfaces. The planar polarity of E-cadherin is compromised and E-cadherin accumulates at tricellular junctions after Src42A knockdown. Furthermore, we show that Src42A acts in concert with Abl kinase, which has also been implicated in cell intercalations. Our data suggest that Src42A is involved in two related processes: in addition to establishing tension generated by the planar polarity of MyoII, it may also act as a signalling factor at tAJs to control E-cadherin residence time.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Junções Aderentes/metabolismo , Caderinas/genética , Caderinas/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Junções Intercelulares/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo
4.
Biomedicines ; 11(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36672624

RESUMO

Medullary thyroid carcinoma (MTC) accounts for only 2-5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims to identify criteria that could predict increased aggressiveness. We analyzed 59 consecutive MTC cases. We focused on the relationships among clinicopathological characteristics, parameters of aggressiveness (extrathyroidal extension, lymphovascular invasion, and lymph node metastasis), and parameters for MTC grading. Statistically significant correlations were found for tumor size, lymphovascular invasion, and lymph node metastasis and tumor focality and lymph node metastasis. Our results showed, in tumors larger than 40 mm, odds ratios (ODs) of 13.695 and 6 for lymphovascular invasion and lymph node metastasis, respectively; in multifocal tumors, we registered an OD of 9.42 for lymph node metastasis. No significant correlation was found for the parameters of the MTC grading system when assessed individually and integrated by reporting low-grade and high-grade risk groups. Although our data indicate that lymphovascular invasion and lymph node metastasis remain significant markers for aggressiveness, studies on larger series of cases are mandatory to detect and validate new factors responsible for the variable course of MTC.

5.
J Orthop Sports Phys Ther ; : 1-27, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688716

RESUMO

OBJECTIVE: To describe age-, sex-, and graft source-specific reference values for patient-reported, physical function, and strength outcome measures in adolescents at 5-7 months after anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional study METHODS: Data were collected at 3 universities and 2 children's hospitals. Participants completed at least one of the International Knee Documentation Committee (IKDC) Subjective Evaluation Form, Pediatric IKDC (PEDI-IKDC), Knee Injury and Osteoarthritis Outcomes Score (KOOS), and ACL Return to Sport after Injury Scale (ACL-RSI). Participants also completed single leg hop tests and/or isokinetic quadriceps and hamstrings strength assessments (at 60°/s). Reference values were summarized using descriptive statistics and stratified for age, sex, and graft source. RESULTS: Reference values were reported for common patient-reported outcomes and measures of physical function and strength from 783 participants (56% females, age=16.4±2.0 years) who were in early adolescence (12-14 years, N=183, 52% females), mid-adolescence (15-17 years, N=456, 58% females), or late adolescence (18-20 years, N=144, 55% females). 379 participants (48.4%) received a bone-patellar tendon-bone autograft, 292 (37.3%) hamstring tendon autograft, and 112 (14.3%) autograft or allograft from an alternative source. CONCLUSION: Reference values for common patient-reported outcomes and measures of physical function and strength differed depending on a patient's age, sex, and graft source. Using patient-specific reference values, in addition to previously described age-appropriate cutoff values, may help clinicians monitor and progress patients through rehabilitation and return to physical activity after ACLR.

6.
PeerJ ; 11: e14672, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36684676

RESUMO

Background: The goal of this study was to assess the reliability of electromyography and range of motion measurements obtained using a knee exercise monitoring system. This device was developed to collect data on knee exercise activities. Methods: Twenty healthy individuals performed isotonic quadriceps exercises in this study. The vastus medialis surface electromyography (sEMG) and range of motion (ROM) of the knee were recorded during the exercise using the isotonic knee exercise monitoring device, the Mobi6-6b, and a video camera system. Each subject underwent a second measuring session at least 24 h after the first session. To determine reliability, the intraclass correlation coefficients (ICCs) and standard error of measurement (SEM) at the 95% confidence interval were calculated, and a Bland-Altman analysis was performed. Results: For inter-rater reliability, the ICCs of the mean absolute value (MAV) and root mean square (RMS) of sEMG were 0.73 (0.49, 0.86) and 0.79 (0.61, 0.89), respectively. ROM had an ICC of 0.93 (0.02, 0.98). The intra-rater reliability of the MAV of the sEMG was 0.89 (0.71, 0.96) and the intra-rater reliability of RMS of the sEMG was 0.88 (0.70, 0.95). The ROM between days had an intra-rater reliability of 0.82 (0.54, 0.93). The Bland-Altman analysis demonstrated no systematic bias in the MAV and RMS of sEMG, but revealed a small, systematic bias in ROM (-0.8311 degrees). Conclusion: For sEMG and range of motion measures, the isotonic knee exercise monitoring equipment revealed moderate to excellent inter- and intra-rater agreement. However, the confidence interval of ROM inter-rater reliability was quite large, indicating a small agreement bias; hence, the isotonic knee exercise monitor may not be suitable for measuring ROM. This isotonic knee exercise monitor could detect and collect information on a patient's exercise activity for the benefit of healthcare providers.


Assuntos
Articulação do Joelho , Joelho , Humanos , Reprodutibilidade dos Testes , Amplitude de Movimento Articular , Extremidade Inferior
7.
Am J Ophthalmol Case Rep ; 29: 101797, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36703903

RESUMO

Purpose: To report the unusual case of a previously stable choroidal nevus, closely followed for over 15 years, which underwent malignant transformation into small choroidal melanoma with massive extrascleral extension. Observations: A 67-year-old Caucasian female was referred to the Stanford Ocular Oncology Service with concern for malignant transformation of a previously stable choroidal nevus in her left eye. Her funduscopic examination demonstrated a dome-shaped choroidal lesion with overlying associated lipofuscin and subretinal fluid, consistent with a diagnosis of small choroidal melanoma. By B-scan ultrasonography, the lesion measured 8.0 × 6.0 mm in base and 2.1 mm in thickness. B-scan ultrasonography also disclosed an associated retroscleral mass, which appeared contiguous with the intraocular melanoma and was confirmed on subsequent orbital magnetic resonance imaging. A decision was made to proceed with enucleation. Under direct endoscopic visualization, the globe and extrascleral mass were fully isolated, mobilized, and removed in toto. At 24 months post-enucleation, the patient remains disease-free without evidence of systemic metastasis or local recurrence. Conclusions/importance: This case describes a small choroidal melanoma hiding massive extrascleral extension, underscoring the value of B-scan ultrasonography. This case also describes the unique management of choroidal melanoma with extrascleral extension using endoscopic enucleation. Performing enucleation under direct endoscopic visualization ensures complete resection and prevents inadvertent transection of the extrascleral component.

8.
Methods Mol Biol ; 2586: 163-173, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36705904

RESUMO

The computational prediction of RNA-RNA interactions has long been studied in RNA informatics. Most of the existing approaches focused on the interaction prediction of short RNAs in small datasets. However, in recent years, two fast prediction methods, RIsearch2 and RIblast, have been developed to predict transcriptome-scale interactions or long RNA interactions. The key idea of the software acceleration of these tools was the integration of a seed-and-extend method, which is used in fast sequence alignment tools, into RNA-RNA interaction prediction. As a result, the two software programs were ten to a thousand times faster than the existing tools; because of this acceleration, detection of genome-wide microRNA target sites or interaction partners of function-unknown long noncoding RNAs has become possible. In this review, we describe the basic concept of the algorithm, its applications, and the future perspectives of the fast RNA-RNA interaction prediction tools.

9.
Int J Cancer ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36691808

RESUMO

Extending screening intervals in ongoing cancer screening programmes can lead to challenging year-on-year variations in the number of screening tests. We explored how such variation could be diminished with a managed transition to the extended interval. We defined three extension scenarios: immediate extension for the entire target population; stepped transition by birth cohort; and gradual transition by reducing the number of available screening appointments. These were compared with a situation in which the interval remains unchanged in a demographic model covering a 15-year period. The model was populated with observed parameters from England, a real-world setting recommending cervical screening with three-year intervals at age 25-49 and five-year intervals at age 50-64. Informed by typical changes currently considered by several European programmes including the programme in England, we explored the effect on screening test numbers of an extension of the three-year interval to five years for women younger than 50. All three extension scenarios resulted in similar cumulative numbers of screening tests, which were about 30% lower compared with a situation in which the interval would remain unchanged. However, the year-on-year variation in the number of screening tests varied between the scenarios. This variation was around four-fold for the immediate scenario. In the stepped scenario, the yearly numbers could differ by around 20%, whereas in the gradual scenario they were virtually constant. A managed interval extension, transitioning different groups of the target population at different times, can substantially reduce the yearly variation in screening workload without increasing the total number of screening tests in the long term.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36692843

RESUMO

Two-dimensional conductive metal-organic frameworks (2D-c-MOFs) have attracted extensive attention owing to their unique structures and physical-chemical properties. However, the planarly extended structure of 2D-c-MOFs usually limited the accessibility of the active sites. Herein, we designed a triptycene-based 2D vertically conductive MOF (2D-vc-MOF) by coordinating 2,3,6,7,14,15-hexahydroxyltriptycene (HHTC) with Cu2+. The vertically extended 2D-vc-MOF(Cu) possesses a weak interlayer interaction, which leads to a facile exfoliation to the nanosheet. Compared with the classical 2D-c-MOFs with planarly extended 2D structures, 2D-vc-MOF(Cu) exhibits a 100% increased catalytic activity in terms of turnover number and a two-fold increased selectivity. Density functional theory (DFT) calculations further revealed that higher activity originated from the lower energy barriers of the vertically extended 2D structures during the CO2 reduction reaction process.

11.
Clin Proteomics ; 20(1): 5, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694116

RESUMO

BACKGROUND: We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays. METHODS: We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman's rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs). RESULTS: For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65-0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77. CONCLUSION: Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.

12.
Knee ; 41: 150-160, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36702049

RESUMO

BACKGROUND: We aimed to evaluate the association between the flexion-extension gap difference and patient-reported outcome measures after total knee arthroplasty (TKA). METHODS: This was a retrospective case-control study of 60 cruciate-retaining single-radius TKAs. Soft tissue balancing was measured using an offset seesaw tensioner and centre-type digital knee balancer under joint distraction forces of 20-50 lbf and 1.5 times body mass index (1.5 BMI). At the last follow up of 2.0-6.5 (mean, 4.5) years postoperatively, patients were asked if they perceived their knee joint as 'natural' (26 knees) or 'artificial' (34 knees). Age, sex, and the flexion-extension gap were compared between the two groups. A receiver operating characteristic curve was used to determine cut-off values of variables predictive of a natural joint perception. RESULTS: Natural joint perception was associated with a greater flexion-extension gap difference under a distraction force of 1.5 BMI (P = 0.016), higher knee function (Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, P = 0.019), and quality of life (EuroQol 5-Dimension, P = 0.029). A gap difference of 0.95 mm under 1.5 BMI distraction predicted a natural joint perception post-TKA (sensitivity, 97.1%; specificity, 88.5%). Using a gap threshold of 1.0 mm under a 1.5 BMI distraction force yielded significant between-group differences in postoperative flexion (P = 0.040), satisfaction (P = 0.043), knee joint function (P < 0.001), quality of life (P = 0.032), and posterior femoral condylar offset (P = 0.037) CONCLUSION: A flexion-extension gap difference ≥1.0 mm under a distraction force of 1.5 BMI predicted superior outcomes, including patient satisfaction, after cruciate-retaining TKA. It was suggested that posterior femoral condylar offset could influence this finding.

13.
J Biol Chem ; : 102938, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36702254

RESUMO

DNA polymerases catalyze DNA synthesis with high efficiency, which is essential for all life. Extensive kinetic and structural efforts have been executed in exploring mechanisms of DNA polymerases, surrounding their kinetic pathway, catalytic mechanisms, and factors that dictate polymerase fidelity. Recent time-resolved crystallography studies on DNA polymerase η (Pol η) and ß have revealed essential transient events during the DNA synthesis reaction, such as mechanisms of primer deprotonation, separated roles of the three metal ions, and conformational changes that disfavor incorporation of the incorrect substrate. DNA-embedded ribonucleotides (rN) are the most common lesion on DNA and a major threat to genome integrity. While kinetics of rN incorporation has been explored and structural studies have revealed that DNA polymerases have a steric gate that destabilizes rNTP binding, the mechanism of extension upon rN addition remains poorly characterized. Using steady-state kinetics, static and time-resolved X-ray crystallography with Pol η as a model system, we showed that the extra hydroxyl group on the primer terminus does alter the dynamics of the polymerase active site as well as the catalysis and fidelity of DNA synthesis. During rN extension, Pol η error incorporation efficiency increases significantly across different sequence contexts. Finally, our systematic structural studies suggest that the rN at the primer end improves primer alignment and reduces barriers in C2´-endo to C3´-endo sugar conformational change. Overall, our work provides further mechanistic insights into the effects of rN incorporation on DNA synthesis.

14.
Am J Sports Med ; : 3635465221141876, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625427

RESUMO

BACKGROUND: Noncontact anterior cruciate ligament (ACL) injuries typically occur during deceleration movements such as landing or cutting. However, conflicting data have left the kinematic mechanisms leading to these injuries unclear. Quantifying the influence of sagittal and coronal plane knee kinematics on in vivo ACL strain may help to elucidate noncontact ACL injury mechanisms. PURPOSE/HYPOTHESIS: The purpose of this study was to measure in vivo sagittal and coronal plane knee kinematics and ACL strain during a single-leg jump. We hypothesized that ACL strain would be modulated primarily by motion in the sagittal plane and that limited coronal plane motion would be measured during this activity. STUDY DESIGN: Descriptive laboratory study. METHODS: Seventeen healthy participants (8 male/9 female) underwent magnetic resonance imaging (MRI) followed by high-speed biplanar radiography, obtained as participants performed a single-leg jump. Three-dimensional models of the femur, tibia, and associated ACL attachment site footprints were created from the MRIs and registered to the radiographs to reproduce the position of the knee during the jump. ACL strain, knee flexion/extension angles, and varus/valgus angles were measured throughout the jump. Spearman rank correlations were used to assess relationships between mean ACL strain and kinematic variables. RESULTS: Mean ACL strain increased with decreasing knee flexion angle (ρ = -0.3; P = .002), and local maxima in ACL strain occurred with the knee in a straight position in both the sagittal and the coronal planes. In addition, limited coronal plane motion (varus/valgus angle) was measured during this activity (mean ± SD, -0.5°± 0.3°). Furthermore, we did not detect a statistically significant relationship between ACL strain and varus/valgus angle (ρ = -0.01; P = .9). CONCLUSION: ACL strain was maximized when the knee was in a straight position in both the sagittal and coronal planes. Participants remained in <1° of varus/valgus position on average throughout the jump. As a ligament under elevated strain is more vulnerable to injury, landing on a straight knee may be an important risk factor for ACL rupture. CLINICAL RELEVANCE: These data may improve understanding of risk factors for noncontact ACL injury, which may be useful in designing ACL injury prevention programs.

15.
World Dev ; 161: 106089, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36597414

RESUMO

Despite enthusiasm around applications of information and communications technologies (ICTs) to smallholder agriculture in many lower-income countries, there are still many questions on the effectiveness of ICT-based approaches. This study assesses the impacts of video-mediated agricultural extension service provision on farmers' adoption of improved agricultural technologies and practices in Ethiopia using data from a two-year randomized experiment. Our results show that the video-mediated extension approach significantly increases uptake of recommended technologies and practices by improving extension access and farmer knowledge. Specifically, we find that video-mediated extension reaches a wider audience than the government's conventional extension approach and leads to higher levels of farmer understanding and uptake of the subject technologies in those locations randomly assigned to the program. While our results also point to greater extension access and greater knowledge among female spouses in locations where both male and female spouses were targeted by the program, we do not find clear evidence that a more inclusive approach translates into higher uptake of the subject technologies. Finally, we find that the video-mediated approach becomes less costly as the scale of operation increases.

16.
Psychol Sci ; : 9567976221140341, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608172

RESUMO

Boundary extension is a classic memory illusion in which observers remember more of a scene than was presented. According to predictive-processing accounts, boundary extension reflects the integration of visual input and expectations of what is beyond a scene's boundaries. According to normalization accounts, boundary extension rather reflects one end of a normalization process toward a scene's typically experienced viewing distance, such that close-up views give boundary extension but distant views give boundary contraction. Here, across four experiments (N = 125 adults), we found that boundary extension strongly depends on depth of field, as determined by the aperture settings on a camera. Photographs with naturalistic depth of field led to larger boundary extension than photographs with unnaturalistic depth of field, even when distant views were shown. We propose that boundary extension reflects a predictive mechanism with adaptive value that is strongest for naturalistic views of scenes. The current findings indicate that depth of field is an important variable to consider in the study of scene perception and memory.

17.
Sci Total Environ ; : 161282, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608819

RESUMO

Despite the adverse effects of pesticides on the environment and human health, they are a key ingredient in boosting agricultural productivity as a way of meeting global food demand. While global levels of pesticides are towering in high-income countries, pesticide use in many parts of Africa remains low, with significant impacts on agricultural productivity and food production. We use a rich longitudinal dataset to examine the relationship between farmer advisory systems and pesticide use in legume-based production systems in Ghana, Mali, and Nigeria. We find that farmers who are advised by private extension systems are approximately 8 % more likely to use pesticides at an extensive level. They are also more likely to use pesticides at an intensive level (41 %). On the other hand, farmers advised by public extension systems are about 5 % more likely to extensively use pesticides. These farmers are observed to reduce the intensive use of pesticides by about 14 %. Furthermore, we also show that farmers advised by joint private-public extension systems are about 4 % more likely to use pesticides as well as reduce their intensity of use by approximately 11 %. At the various country levels, there exists significant heterogeneity in the relationship between advisory systems and pesticide use, suggesting that context matters. Of course, the pesticide regulatory systems and the institutional environments in these countries vary greatly. Given these findings, our study offers key entry and leveraging points for increasing pesticide use at levels that limit their environmental and human effects but may ascertain increased agricultural productivity and food production.

18.
Crit Rev Food Sci Nutr ; : 1-26, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597655

RESUMO

Anti-aging research has become critical since the elderly population is increasing dramatically in this era. With the establishment of frailty phenotype and frailty index, the importance of anti-frailty research is concurrently enlightened. The application of natural phytochemicals against aging or frailty is always intriguing, and abundant related studies have been published. Various models are designed for biological research, and each model has its strength and weakness in deciphering the complex aging mechanisms. In this article, we attempt to show the potential of Caenorhabditis elegans in the study of phytochemicals' effects on anti-aging by comparing it to other animal models. In this review, the lifespan extension and anti-aging effects are demonstrated by various physical, cellular, or molecular biomarkers of dietary phytochemicals, including resveratrol, curcumin, urolithin A, sesamin, fisetin, quercetin, epigallocatechin-3-gallate, epicatechin, spermidine, sulforaphane, along with extracts of broccoli, cocoa, and blueberry. Meanwhile, the frequency of phytochemicals and models studied or presented in publications since 2010 were analyzed, and the most commonly mentioned animal models were rats, mice, and the nematode C. elegans. This up-to-date summary of the anti-aging effect of certain phytochemicals has demonstrated powerful potential for anti-aging or anti-frailty in the human population.

19.
Endocrine ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600104

RESUMO

PURPOSE: The role of adjuvant external-beam radiotherapy (EBRT) in the treatment of locally advanced papillary thyroid carcinoma (PTC) remains controversial due to the lack of prospective data and the conflicting retrospective data. This study aimed to determine the benefits of adjuvant EBRT in patients with PTC and other organ invasions using propensity score matching to reduce the heterogeneity of the patient population. METHODS: Data from patients with PTC with other organ invasions but no distant metastases who underwent surgery and adjuvant radioactive iodine (RAI) alone (Non-EBRT group) or adjuvant EBRT plus RAI (EBRT group) were retrospectively reviewed. Propensity matching was used to reduce heterogeneity. Survival outcomes and toxicities associated with EBRT were evaluated. RESULTS: Between January 2005 and December 2019, 102 patients in the Non-EBRT group and 26 patients in the EBRT group were evaluated. In the 48 propensity score-matched patients, no significant differences in baseline characteristics between the Non-EBRT and EBRT groups were detected. The locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were significantly higher in the EBRT group compared with the rates in the Non-EBRT group (5y-LRRFS: 100% vs. 74%, p = 0.003, 5y-RFS: 91% vs. 74%, p = 0.035). EBRT was well-tolerated, with no grade ≥ 3 toxicity, and all patients completed the therapy as planned. CONCLUSION: Adjuvant EBRT plus RAI exhibited acceptable toxicity and improved LRRFS and RFS in patients with PTC with other organ invasions compared with RAI alone.

20.
Bone Joint Res ; 12(1): 58-71, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36647696

RESUMO

AIMS: As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). METHODS: Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. RESULTS: Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. CONCLUSION: This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies.Cite this article: Bone Joint Res 2023;12(1):58-71.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...