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1.
Front Cell Dev Biol ; 12: 1406830, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946798

RESUMO

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

2.
Int J Med Robot ; 20(3): e2655, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38922786

RESUMO

BACKGROUND: Up to 20% of patients remain unsatisfied after total knee arthroplasty (TKA), prompting the development of new implants. Bi-Cruciate Retaining (BCR) TKA preserves both the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL), with the ACL beneficial for its proprioceptive qualities. The Bi-Cruciate Stabilised (BCS) TKA substitutes the ACL and PCL with a unique dual cam-post mechanism. Robotics improve accuracy and facilitate technically demanding TKA. METHODS: This was a retrospective case-control study recruited from two centres. Measured outcomes included kinematic analysis, proprioception, and functional outcomes. RESULTS: There was a significantly larger maximum flexion angle and range of flexion to extension in sit-to-stand and stairs in BCR when compared to BCS. Further analysis revealed more similarities between BCR and normal native knees. Proprioception and functional scores did not have any statistical difference. CONCLUSION: BCR TKA demonstrated better knee flexion in weight-bearing active range of motion and showed similarities with normal knee kinematics.


Assuntos
Ligamento Cruzado Anterior , Artroplastia do Joelho , Articulação do Joelho , Ligamento Cruzado Posterior , Amplitude de Movimento Articular , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Fenômenos Biomecânicos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Ligamento Cruzado Posterior/cirurgia , Estudos de Casos e Controles , Articulação do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Ligamento Cruzado Anterior/cirurgia , Ligamento Cruzado Anterior/fisiopatologia , Prótese do Joelho , Resultado do Tratamento , Propriocepção
3.
Scand J Immunol ; : e13390, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769661

RESUMO

Inflammation is an important pathophysiological process in many diseases; it has beneficial and harmful effects. When exposed to various stimuli, the body triggers an inflammatory response to eliminate invaded pathogens and damaged tissues to maintain homeostasis. However, uncontrollable persistent or excessive inflammatory responses may damage tissues and induce various diseases, such as metabolic diseases (e.g. diabetes), autoimmune diseases, nervous system-related diseases, digestive system-related diseases, and even tumours. Aldo-keto reductase 1B10 (AKR1B10) is an important player in the development and progression of multiple diseases, such as tumours and inflammatory diseases. AKR1B10 is upregulated in solid tumours, such as hepatocellular carcinoma (HCC), non-small cell lung carcinoma, and breast cancer, and is a reliable serum marker. However, information on the role of AKR1B10 in inflammation is limited. In this study, we summarized the role of AKR1B10 in inflammatory diseases, including its expression, functional contribution to inflammatory responses, and regulation of signalling pathways related to inflammation. We also discussed the role of AKR1B10 in glucose and lipid metabolism and oxidative stress. This study provides novel information and increases the understanding of clinical inflammatory diseases.

4.
Trials ; 25(1): 251, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605374

RESUMO

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Músculo Quadríceps , Humanos , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Reconstrução do Ligamento Cruzado Anterior/métodos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Força Muscular , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D , Vitaminas , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
5.
BMJ Nutr Prev Health ; 6(1): 21-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37559968

RESUMO

Objectives: Even though disinfectants are commonly used in clinical practice and daily life, there are few studies on their antibacterial ability and cytotoxicity, which are closely related to the safety and effectiveness of their use. To provide a basis for the use of disinfectants, the cytotoxicity and antibacterial activity of three most commonly used disinfectants, povidone-iodine, chlorhexidine acetate and polyhexamethylene biguanide (PHMB), were investigated. Design: A CCK-8 assay was used to measure the activities of human fibroblasts (HF) and keratinocytes (HaCat), the two most important cells in wound healing, following their exposure to disinfectants. The effects of different times and concentrations were included. The antibacterial activity of disinfectants against Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae was reflected by their minimum inhibitory concentration and minimum bactericidal concentration. Results: All three disinfectants showed strong cytotoxicity in direct contact with HF and HaCat cells. Cytotoxicity increased with increasing exposure time and concentration. S. aureus, A. baumannii and K. pneumoniae comprised 70%, 55% and 85% of the strains sensitive to povidone iodine; 50%, 45% and 80% of the strains sensitive to chlorhexidine acetate; and 60%, 45% and 80% of the strains sensitive to PHMB, respectively. Conclusions: All three disinfectants were cytotoxic; therefore, it is necessary to pay attention to the use time and concentration in the clinical setting. All three disinfectants were cytotoxic, with povidone-iodine being the most cytotoxic even at low concentrations. PHMB had better antibacterial efficacy against S. aureus and is suitable for the treatment of shallow wounds primarily. All three tested bacteria were significantly more sensitive to PHMB than to the other disinfectants.

6.
Nat Commun ; 14(1): 2241, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37193694

RESUMO

The "death cap", Amanita phalloides, is the world's most poisonous mushroom, responsible for 90% of mushroom-related fatalities. The most fatal component of the death cap is α-amanitin. Despite its lethal effect, the exact mechanisms of how α-amanitin poisons humans remain unclear, leading to no specific antidote available for treatment. Here we show that STT3B is required for α-amanitin toxicity and its inhibitor, indocyanine green (ICG), can be used as a specific antidote. By combining a genome-wide CRISPR screen with an in silico drug screening and in vivo functional validation, we discover that N-glycan biosynthesis pathway and its key component, STT3B, play a crucial role in α-amanitin toxicity and that ICG is a STT3B inhibitor. Furthermore, we demonstrate that ICG is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival. Together, by combining a genome-wide CRISPR screen for α-amanitin toxicity with an in silico drug screen and functional validation in vivo, our study highlights ICG as a STT3B inhibitor against the mushroom toxin.


Assuntos
Hexosiltransferases , Micotoxinas , Humanos , Masculino , Animais , Camundongos , Alfa-Amanitina/farmacologia , Verde de Indocianina/farmacologia , Antídotos , Amanita , Proteínas de Membrana
7.
Medicine (Baltimore) ; 102(15): e33502, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37058074

RESUMO

To investigate the clinical phenotype-genotype correlations of a family with Kennedy disease (KD) and improve our understanding of the disease. KD was confirmed after clinical phenotypic analyses, laboratory tests, polymerase chain reaction assays for cytosine-adenine-guanine (CAG) repeats, and neuro-electrophysiological tests. The disease was assessed using the KD1234 scale and the spinal and bulbar muscular atrophy functional rating scale. The average age of disease onset was 30.8 ± 2.85 years. Clinically diagnosed members had 48 CAG repeats (≥35 is abnormal) in the androgen receptor gene. The patients exhibited gynecomastia and testicular dysfunction. The lesions mainly involved the medulla oblongata and spinal cord. Progesterone and serum creatine kinase levels were significantly high. Electromyography showed chronic neurogenic damage and abnormal sensory and motor conduction in family members who did not participate in sports, exercise, or physical hobbies. Our study showed that this family had a stable inheritance of CAG repeats, and the genotype was consistent with the clinical phenotype. Gynecomastia was the first symptom, with progressive androgen resistance resulting in testicular atrophy, infertility, and sexual dysfunction. Changes in serum creatine kinase may indicate the progression or relief of symptoms, and rehabilitation may delay the progression of muscle atrophy.


Assuntos
Atrofia Bulboespinal Ligada ao X , Ginecomastia , Atrofia Muscular Espinal , Humanos , Masculino , Atrofia Bulboespinal Ligada ao X/genética , Atrofia Bulboespinal Ligada ao X/diagnóstico , Genótipo , Fenótipo , Atrofia Muscular , Creatina Quinase , Receptores Androgênicos/genética , Atrofia Muscular Espinal/genética
8.
Aging Ment Health ; 27(8): 1627-1635, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724006

RESUMO

OBJECTIVE: The present study explores how and when lifetime discriminatory experience moderates the mediation effect of early life adversities and social activity on loneliness among older European adults over eight years. METHOD: The study analyzed 13,699 respondents aged 50 years and over who were interviewed in 2009 and re-interviewed in 2017 in the European Survey of Health, Ageing, Retirement. Conditional process analysis using the PROCESS model 15 was applied to examine the moderated mediation effect of lifetime discriminatory experience in 2009 (W) on early life adversities in 2009 (X) and social activity at 2017 (M) to loneliness in 2017 (Y). RESULTS: Our moderated mediation models found that early life adversities (X) are associated with loneliness (Y) (Coeff X→Y=-0.0501, p<.001), but social activity (M) reduces its effect on loneliness (Y) (Coeff X→M→Y=-1.6391, p<.001). However, lifetime discriminatory experience (W) hampers social activity (Coeff M*W→Y = 0.0955, p<.05) and increases loneliness (Coeff X*M→Y = 0.6069, p<.05). CONCLUSION: Older adults experiencing early life adversities may not necessarily develop later life loneliness. However, lifetime discriminatory experience due to political beliefs, religion, ethnicity, sexual orientation/background etc. may reverse the positive effect of social engagement on the relationship between early life adversities and loneliness. Early interventions should address discrimination and social inequalities and increase social participation across the life course to prevent the development of later-life loneliness among older adults.


Assuntos
Solidão , Análise de Mediação , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Envelhecimento , Europa (Continente) , Discriminação Social
9.
MedComm (2020) ; 4(2): e207, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36818016

RESUMO

Anti-obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti-obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti-obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high-fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet-induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously.

10.
Trials ; 23(1): 771, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096886

RESUMO

BACKGROUND: The ultimate goal of anterior cruciate ligament reconstructions (ACLR) is to fulfil the return-to-play (RTP) criteria. Quadriceps muscle strength is one of the key determinants for a patient's successful return-to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the postoperative period on quadriceps muscle strength in ACL injured patient. Adult patients (aged 18-30) with a unilateral ACL injury, total quadriceps muscle volume is equal or more than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, and both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, and Xtreme CT for bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be drawn before and after intervention. DISCUSSION: This is the first trial evaluating the effects of PEMF on quadriceps muscle recovery after ACLR. The proposed study addresses a huge research gap by evaluating practical use of PEMF as part of rehabilitation. The proposed study will provide much needed scientific support in the use of this noninvasive treatment modality to facilitate recovery of quadriceps strength after PEMF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05184023. Registered on 5 January 2022.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Adulto , Lesões do Ligamento Cruzado Anterior/diagnóstico , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Reconstrução do Ligamento Cruzado Anterior/métodos , Campos Eletromagnéticos , Humanos , Força Muscular/fisiologia , Músculo Quadríceps/fisiologia
11.
J Hazard Mater ; 440: 129698, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35952428

RESUMO

The health concerns of microplastics (MPs) and nanoplastics (NPs) surge, but the key indicators to evaluate the adverse risks of MPs/NPs are elusive. Recently, MPs/Ps were found to disturb glucose and lipid metabolism in rodents, suggesting that MPs/NPs may play a role in obesity progression. In this study, we firstly demonstrated that the distribution of fluorescent polystyrene nanoplastics (nPS, 60 nm) white adipose tissue (WAT) of mice. Furthermore, nPS could traffic across adipocytes in vitro and reduced lipolysis under ß-adrenergic stimulation in adipocytes in vitro and ex vivo. Consistently, chronic oral exposure to nPS at the dietary exposure relevant concentrations (3 and 223 µg/kg body weight) impaired fasting-induced lipid mobilization in obese mice and subsequently contributed to larger adipocyte size in the subcutaneous WAT. In addition, the chronic exposure of nPS induced macrophage infiltration in the small intestine and increased lipid accumulation in the liver, accelerating the disruption of systemic metabolism. Collectively, our findings highlight the potential obesogenic role of nPS via diminishing lipid mobilization in WAT of obese mice and suggest that lipolysis relevant parameters may be used for evaluating the adverse effect of MPs/NPs in clinics.


Assuntos
Dieta Hiperlipídica , Lipólise , Tecido Adiposo , Adrenérgicos , Animais , Exposição Dietética , Jejum , Glucose , Lipídeos , Camundongos , Camundongos Obesos , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade
12.
Comput Intell Neurosci ; 2022: 2440263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694572

RESUMO

With the vigorous development of higher education in China, many universities have made great progress in various indicators in recent years. As the number of college students increases year by year, the effect of instruction in the classroom is especially important. The high quality of teaching directly affects the efficiency of students' listening to lectures, and more and more universities are receiving attention. However, the traditional dance classroom education and the one-to-many education model cannot adapt to the development trend of higher art education under the changes of the times and cannot effectively guarantee the quality of classroom education. The development of wireless sensor networks provides practical and feasible technical solutions for the development of dance education systems. Compared with general detection methods, image sensors can provide more real-time and more intuitive on-site information and wirelessly send image information to user terminals. This article describes the classic feature extraction algorithm and proposes a new feature extraction algorithm based on chart filling. The effectiveness of each algorithm is verified through several data sets. Image recognition is carried out by computer, including from computer to image processing, through the computer to recognize objects and various different modes of the target technology. The identification process usually includes several steps. First, the preprocessing of the image is required, then the segmentation of the image is performed, and then the feature extraction and matching are performed. In layman's terms, image recognition hopes to imitate the human heart to read photos. By applying the image recognition technology to the dance education system, changes in the methods and forms of dance education can be stimulated.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , China , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estudantes , Ensino , Universidades
13.
Org Biomol Chem ; 19(39): 8507-8515, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34542126

RESUMO

Quinoliziniums, cationic aromatic heterocycles bearing a quaternary bridgehead nitrogen, have been widely used as fluorescent dyes, DNA intercalators, ionic liquids etc. A library of new quinolizinium compounds was synthesized from quinolines and internal alkyne substrates in up to 65% isolated yields. Systematic studies of their photophysical properties were conducted. The quinoliziniums have been used in three visible-light-induced photocatalysis reactions with good yields.


Assuntos
Substâncias Intercalantes
14.
Burns ; 47(3): 634-642, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402311

RESUMO

INTRODUCTION: Allogeneic and xenogeneic skin are recognized as the best coverings for skin burn wounds, but currently face a supply shortage. To solve this problem, our research group developed a standardized manufactured hydrogel dressing based on a new type of highly bioactive recombinant human collagen. STUDY DESIGN: Prospective self-controlled trial. OBJECTIVE: To evaluate the efficacy and safety of recombinant human collagen hydrogel in the treatment of partial burn wounds to the skin compared to those of xenogeneic skin. METHODS: This study included twenty-one patients admitted to Shanghai Changhai Hospital within 48 h after receiving partial-thickness skin burns. The wounds were symmetrically separated along the axis and treated with recombinant human collagen hydrogel (RHCH) or a human-CTLA4-Ig gene-transferred pig skin xenotransplant. The condition of the wound surfaces was recorded on days 0 (of enrollment), 5, 10, 15, and 20, and bacterial drug sensitivity testing, hematuria examination, and electrocardiographic tests were conducted on days 0, 10, 20, or on the day of wound healing. RESULTS: There were no statistically significant differences in wound healing time between the two groups. The median number of days to healing was 11.00 ± 0.56 for xenogeneic skin vs. 11.00 ± 1.72 for RHCH. CONCLUSION: During the observation period, the therapeutic effect of the RHCH developed by our group on partial-thickness burn wounds was not significantly different from that of gene-transferred xenogeneic skin. Thus, our designed RHCH shows potential for clinical use to treat burn wounds on the skin.


Assuntos
Curativos Hidrocoloides/normas , Queimaduras/terapia , Colágeno/farmacologia , Adolescente , Adulto , Curativos Hidrocoloides/estatística & dados numéricos , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
RSC Adv ; 11(53): 33294-33299, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-35497514

RESUMO

A novel fluorescent quinolizinium-based turn-off probe has been developed for selective detection of cysteine. The probe showed high selectivity and sensitivity towards cysteine over other amino acids including the similarly structured homocysteine and glutathione with a detection limit of 0.18 µM (S/N = 3). It was successfully applied to cysteine detection in living cells with low cytotoxicity and quantitative analysis of spiked mouse serum samples with moderate to good recovery (96-109%).

16.
J Biol Chem ; 295(41): 13965-13980, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32763976

RESUMO

In addition to acting as a transcriptional co-activator, YAP1 directly mediates translocalization of the pro-oncogenic phosphatase SHP2 from the cytoplasm to nucleus. In the cytoplasm, SHP2 potentiates RAS-ERK signaling, which promotes cell proliferation and cell motility, whereas in the nucleus, it mediates gene regulation. As a result, elucidating the details of SHP2 trafficking is important for understanding its biological roles, including in cancer. YAP1 comprises multiple splicing isoforms defined in part by the presence (as in YAP1-2γ) or absence (as in YAP1-2α) of a γ-segment encoded by exon 6 that disrupts a critical leucine zipper. Although the disruptive segment is known to reduce co-activator function, it is unclear how this element impacts the physical and functional relationships between YAP1 and SHP2. To explore this question, we first demonstrated that YAP1-2γ cannot bind SHP2. Nevertheless, YAP1-2γ exhibits stronger mitogenic and motogenic activities than does YAP1-2α because the YAP1-2α-mediated delivery of SHP2 to the nucleus weakens cytoplasmic RAS-ERK signaling. However, YAP1-2γ confers less in vivo tumorigenicity than does YA1-2α by recruiting tumor-inhibitory macrophages. Mechanistically, YAP1-2γ transactivates and the YAP1-2α-SHP2 complex transrepresses the monocyte/macrophage chemoattractant CCL2 Thus, cell-intrinsic and cell-extrinsic pro-oncogenic YAP1 activities are inversely regulated by alternative splicing of exon 6. Notably, oncogenic KRAS down-regulates the SRSF3 splicing factor that prevents exon 6 skipping, thereby creating a YAP1-2α-dominant situation that supports a "cold" immune microenvironment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Processamento Alternativo , Carcinogênese/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Oncogênicas/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Carcinogênese/genética , Carcinogênese/patologia , Proteínas de Ciclo Celular/genética , Humanos , Camundongos , Células NIH 3T3 , Proteínas Oncogênicas/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
17.
J Interpers Violence ; 35(1-2): 294-318, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-29294623

RESUMO

The aim of the study was to identify the prevalence and perceived helpfulness of a variety of protective strategies that were used by female survivors of domestic abuse and to explore factors that may have influenced strategy usage. Forty participants were recruited from a voluntary sector domestic abuse service, commissioned by an outer London local authority in the United Kingdom, in early 2014. The measurement tools used were the Intimate Partner Violence Strategies Index (IPVSI) and the Coordinated Action Against Domestic Abuse (CAADA) Domestic Abuse, Stalking and "Honour"-Based Violence (DASH) Risk Assessment Checklist. The average age was 33 years (SD = 7.9, range = 20-57); half reported to be of Asian ethnicity, 37.5% White, and 12.5% Black or Mixed ethnicity. The average DASH score was 9.8 (SD = 13.2, range = 0-18), and an average of 18 (SD = 6.7, range = 1-29) protective strategies were utilized by each participant. All of the most commonly used strategies were from the placating category. Although safety planning strategies were rated as the most helpful by all participants, placating strategies were also rated as helpful by two thirds of participants. Stepwise multiple regression showed that placating was the only significant predictor of DASH score (ß = .375, p < .05) and accounted for 14% of the variance of DASH score. Findings showed that women utilized a diverse range of protective strategies with placating strategies being most intensely used and rated as helpful. However, placating strategy usage could be a risk factor as opposed to a protective factor. This study has also demonstrated that greater placating strategies were used by White than South Asian women, and women who were employed used more formal strategies. This research has extended the knowledge base of protective strategies that professionals can draw from to underpin decisions and interventions when working with domestic abuse survivors.


Assuntos
Adaptação Psicológica , Violência Doméstica/psicologia , Violência por Parceiro Íntimo/psicologia , Sobreviventes/psicologia , Adulto , Estudos Transversais , Etnicidade , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Proteção , Fatores de Risco , Reino Unido/epidemiologia , Adulto Jovem
18.
Gerontol Geriatr Med ; 5: 2333721419878579, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598541

RESUMO

Objectives: To examine the difference in gender and its impact on selected quality-of-life (QoL) domains of Social Production Function theory among older adults in England. Method: Based on an annual national adult social care service user survey conducted in the United Kingdom in 2016. QoL was assessed by a single-item construct, and independent variables were home design, access to information and local area, self-rated health, perceived pain/discomfort, perceived anxiety/depression, activities of daily living, use and satisfaction of formal and informal care, and demographic variables. Results: A total of 28,955 respondents aged 65+ years were interviewed. Multinomial logistic regression analysis found four interaction effects for predicting a very good/good QoL: (a) Female receiving non-co-residing informal care (odds ratio [OR] = 1.501, p < .01), (b) female feeling safe (OR = 1.499, p < .01), (c) female feeling satisfied with social contact with people (OR = 1.465, p < .05), and (d) female being helped in the use of time (OR = 1.370, p < .05). Conclusion: Findings suggest gender differences in QoL as men and women are heterogeneous with different health and disease patterns, health-/help-seeking behaviors, roles and responsibilities, and levels of resilience, needs, risks, and access and control resources. Practitioners should adopt a gender-specific assessment and personalized interventions to promote gender equality, empowerment, and long-term sustainable development for an aging society.

19.
Burns Trauma ; 7: 19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413962

RESUMO

BACKGROUND: Split-thickness skin grafting is the current gold standard for the treatment of traumatic skin loss. However, for patients with extensive burns, split-thickness skin grafting is limited by donor skin availability. Grafting split-thickness skin minced into micrografts increases the expansion ratio but may reduce wound repair quality. Dermal substitutes such as Pelnac can enhance the healing of full-thickness skin wounds, but their application currently requires two surgeries. The present study investigated whether it is possible to repair full-thickness skin defects and improve wound healing quality in a single surgery using Pelnac as an overlay of minced split-thickness skin grafts in a rat model. METHODS: A full-thickness skin defect model was established using male Sprague-Dawley rats of 10 weeks old. The animals were randomly divided into control and experimental groups in which Vaseline gauze and Pelnac, respectively, were overlaid on minced split-thickness skin grafts to repair the defects. Wound healing rate and quality were compared between the two groups. For better illustration of the quality of wound healing, some results were compared with those obtained for normal skin of rats. RESULTS: We found that using Pelnac as an overlay for minced split-thickness skin grafts accelerated wound closure and stimulated cell proliferation and tissue angiogenesis. In addition, this approach enhanced collagen synthesis and increased the formation of basement membrane and dermis as well as the expression of growth factors related to wound healing while reducing scar formation. CONCLUSIONS: Using minced split-thickness skin grafts overlaid with Pelnac enables the reconstruction of full-thickness skin defects in a single step and can increase the healing rate while improving the quality of wound healing.

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