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Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.
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Antígenos CD5 , Imunoterapia Adotiva , Linfócitos T , Animais , Imunoterapia Adotiva/métodos , Antígenos CD5/imunologia , Camundongos , Humanos , Linfócitos T/imunologia , Linfócitos T/transplante , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Linhagem Celular Tumoral , Sistemas CRISPR-Cas , FemininoRESUMO
The 5-factor modified Frailty Index (mFI-5) is a risk-stratification tool utilized to predict complications and mortality following major lower extremity (LE) amputation. However, its prognostic value for long-term mortality is unknown. The study aim was to assess whether a high mFI-5 score relates to long-term mortality following major LE amputation for chronic wounds. Patients ≥60 years who underwent major LE amputation from 2017 to 2021 were retrospectively reviewed. Data regarding demographics, comorbidities, perioperative factors, amputation type, and postoperative complications was collected and mFI-5 was calculated. Survival analysis was performed with Kaplan-Meier curves and differences were assessed with Log-Rank test. A total of 172 patients were identified. Mean age was 70.7 ± 8.0 years. Median time to ambulation was 3.7 months (IQR 4.0). By final follow-up of 17.5 ± 15.9 months, ambulatory rate was 51.7% (n = 89), overall mortality 36.0% (n = 62), 1-year mortality 14.0% (n = 24), and 3-year mortality 27.9% (n = 48). Patients with an mFI-5 of ≥4 (26.7%, n = 46) compared with patients with mFI-5 <4 (73.3%, n = 126) had a higher rate of prolonged postoperative LOS (34.8% vs 19.8%, p = .042), overall mortality (52.2% vs 30.2%, p = .008), 1-year mortality (23.9% vs 10.3%, p = .023), and 3-year mortality (45.7% vs 21.4%, p = .002). Multivariate analysis demonstrated mFI-5 was an independent predictor of 3-year mortality (OR 2.35, p = .043). At a threshold ≥4, the mFI-5 demonstrated utility in predicting long-term mortality. The value of this prognostic indicator is in its preoperative application of assessing risk of mortality, which should be utilized in conjunction with other measures.
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Amputação Cirúrgica , Fragilidade , Extremidade Inferior , Humanos , Masculino , Feminino , Amputação Cirúrgica/mortalidade , Idoso , Estudos Retrospectivos , Fragilidade/mortalidade , Fragilidade/complicações , Extremidade Inferior/cirurgia , Medição de Risco , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Prognóstico , Idoso de 80 Anos ou mais , Estimativa de Kaplan-MeierRESUMO
Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor microenvironment. With this rapid clinical and scientific progress, the field of cancer immunotherapy is currently at a critical inflection point, with potential for exponential growth over the next decade. Recognizing this, the Society for Immunotherapy of Cancer convened a diverse group of experts in cancer immunotherapy representing academia, the pharmaceutical and biotechnology industries, patient advocacy, and the regulatory community to identify current opportunities and challenges with the goal of prioritizing areas with the highest potential for clinical impact. The consensus group identified seven high-priority areas of current opportunity for the field: mechanisms of antitumor activity and toxicity; mechanisms of drug resistance; biomarkers and biospecimens; unique aspects of novel therapeutics; host and environmental interactions; premalignant immunity, immune interception, and immunoprevention; and clinical trial design, endpoints, and conduct. Additionally, potential roadblocks to progress were discussed, and several topics were identified as cross-cutting tools for optimization, each with potential to impact multiple scientific priority areas. These cross-cutting tools include preclinical models, data curation and sharing, biopsies and biospecimens, diversification of funding sources, definitions and standards, and patient engagement. Finally, three key guiding principles were identified that will both optimize and maximize progress in the field. These include engaging the patient community; cultivating diversity, equity, inclusion, and accessibility; and leveraging the power of artificial intelligence to accelerate progress. Here, we present the outcomes of these discussions as a strategic vision to galvanize the field for the next decade of exponential progress in cancer immunotherapy.
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Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Neoplasias/imunologia , Sociedades MédicasRESUMO
Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment for hematological malignancies, but its adaptation to solid tumors is impeded by multiple challenges, particularly T cell dysfunction and exhaustion. The heterogeneity and inhospitableness of the solid tumor microenvironment (TME) contribute to diminished CAR T cell efficacy exhibited by reduced cytotoxicity, proliferation, cytokine secretion, and the upregulation of inhibitory receptors, similar to the phenotype of tumor-infiltrating lymphocytes (TILs). In this review, we highlight recent advances in T cell therapy for solid tumors, particularly brain cancer. Innovative strategies, including locoregional delivery and 'armoring' CAR T cells with cytokines such as interleukin (IL)-18, are under investigation to improve efficacy and safety. We also highlight emerging issues with toxicity management of CAR T cell adverse events. This review discusses the obstacles associated with CAR T cell therapy in the context of solid tumors and outlines current and future strategies to overcome these challenges.
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Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Linfócitos T , Microambiente Tumoral , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microambiente Tumoral/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Animais , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
In Escherichia coli, many environmental stressors trigger polyphosphate (polyP) synthesis by polyphosphate kinase (PPK1), including heat, nutrient restriction, toxic compounds, and osmotic imbalances. PPK1 is essential for virulence in many pathogens and has been the target of multiple screens for small molecule inhibitors that might serve as new anti-virulence drugs. However, the mechanisms by which PPK1 activity and polyP synthesis are regulated are poorly understood. Our previous attempts to uncover PPK1 regulatory elements resulted in the discovery of PPK1* mutants, which accumulate more polyP in vivo, but do not produce more in vitro. In attempting to further characterize these mutant enzymes, we discovered that the most commonly-used PPK1 purification method - Ni-affinity chromatography using a C-terminal poly-histidine tag - altered intrinsic aspects of the PPK1 enzyme, including specific activity, oligomeric state, and kinetic values. We developed an alternative purification strategy using a C-terminal C-tag which did not have these effects. Using this strategy, we were able to demonstrate major differences in the in vitro response of PPK1 to 5-aminosalicylic acid, a known PPK1 inhibitor, and observed several key differences between the wild-type and PPK1* enzymes, including changes in oligomeric distribution, increased enzymatic activity, and increased resistance to both product (ADP) and substrate (ATP) inhibition, that help to explain their in vivo effects. Importantly, our results indicate that the C-terminal poly-histidine tag is inappropriate for purification of PPK1, and that any in vitro studies or inhibitor screens performed with such tags need to be reconsidered in that light.
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Escherichia coli , Histidina , Fosfotransferases (Aceptor do Grupo Fosfato) , Escherichia coli/genética , Escherichia coli/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/genética , Histidina/metabolismo , Histidina/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Polifosfatos/metabolismo , CinéticaRESUMO
Anti-CD19 CAR T cells were among the last decade's scientific breakthroughs, achieving remarkable remissions in patients with B cell leukemias and lymphomas. Now, the engineered cell therapies are traversing disease indications into autoimmunity and resolving disease symptoms in patients with systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis.1.
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Imunoterapia Adotiva , Lúpus Eritematoso Sistêmico , Neoplasias , Humanos , Autoimunidade/imunologia , Lúpus Eritematoso Sistêmico/terapia , Linfócitos T , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T/uso terapêuticoRESUMO
Objective: This study evaluated the relationship between physical literacy (PL) and muscular fitness (MF) as well as muscle-strengthening activities (MSA) in adolescents. Methods: A secondary cross-sectional study included 823 adolescents (45.1% boys) from the Eating Healthy and Daily Life Activities Study. The Spanish Perceived Physical Literacy Instrument for Adolescents (S-PPLI) assessed the participants' perceived PL. The evaluation of MF in the young population was conducted using the Assessing the Levels of Physical Activity and Fitness (ALPHA-FIT) test battery. MSA were assessed by the following question: 'In the past week, how many days did you exercise to strengthen or tone the muscle, such as through push-ups, sit-ups or lifting weights?' To examine the associations between S-PPLI scores and handgrip strength, standing long jump and MSA days in adolescents, we employed generalised additive models. Results: Participants with high perceived physical literacty (PPL) had the highest handgrip strength (mean=25.1; PPL had the highest handgrip strength (mean=25.1; bias-corrected and accelerated (BCa) bootstrapped 95% CI 24.2 to 26.0) and standing long jump (mean=149.7; confidence interval (CI) 24.2 to 26.0) and standing long jump (mean=149.7; 24.2 to 26.0) and standing long jump (mean=149.7; BCa bootstrapped 95% CI 145.8 to 153.5). Conversely, those adolescents with low PPL had the lowest handgrip strength (mean=23.1; BCa bootstrapped 95% CI 22.3 to 23.8) and standing long jump (mean=137.3; BCa bootstrapped 95% CI 133.9 to 140.6). For MSA, adolescents with high PPL had the highest mean of MSA days (mean=3.0; BCa bootstrapped 95% CI 2.8 to 3.3), while the lowest mean was observed for those with low PPL (mean=2.0; BCa bootstrapped 95% CI 1.8 to 2.2). Conclusion: A high level of PL was associated with higher levels of MF and MSA among Spanish adolescents.
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Thyroid chondroplasty (TC) in facial gender-affirming surgery (FGAS) is aimed at modifying the thyroid cartilage to achieve a more feminine laryngeal appearance. This study evaluated open versus endoscopic techniques to TC and associated outcomes and complications. A systematic review (SR) of articles pertaining to TC was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twelve articles representing 368 patients were included for analysis. Nine articles described open approaches, and three articles described endoscopic techniques. The rate of total complications was 4.3% (n = 12) in the open approach compared to 15% (n = 13) in the endoscopic approach. Positive esthetic results were reported in 92% of cases performed with the open approach and 90% with the endoscopic approach. In the open approach, seven (2.5%) patients requested additional removal of cartilage, and three (1.1%) requested scar revision. In the endoscopic approach, three (3.7%) patients requested additional cartilage removal. In addition, data of individuals who underwent "cervical tracheoplasty" for gender dysphoria from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed, and there was no incidence of wound or major complications among patients who underwent tracheoplasty alone. Although the advantage of the endoscopic approach is a scarless neck incision, the rate of complications is higher with the open approach. Endoscopic approaches are still not widely used, and continued investigations are warranted to improve familiarity with this approach and reduce postoperative complications.
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Cartilagem Tireóidea , Humanos , Cartilagem Tireóidea/cirurgia , Endoscopia/métodos , Cirurgia de Readequação Sexual/métodos , Cirurgia de Readequação Sexual/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estética , Feminino , Masculino , Resultado do Tratamento , Disforia de Gênero/cirurgiaRESUMO
AIM: To determine the prevalence of adolescents who meet muscle-strengthening activities (MSA) recommendation and their associations with anthropometric variables, physical fitness, and lifestyle behaviours in a sample of Spanish adolescents aged 12-17 years. METHODS: This was a cross-sectional study using data from The Eating Healthy and Daily Life Activities (EHDLA) Study. Participants reported the days on which they engaged in MSA (≥3 days per week were considered to meet World Health Organization recommendation). Physical fitness was assessed with the ALPHA fitness battery. Additionally, body mass index, waist circumference, skinfolds and body fat percentage were assessed. Lifestyle variables were recreational screen time, sleep time and adherence to the Mediterranean diet. The associations between MSA and outcome variables were tested with linear and logistic regressions. RESULTS: Of the 852 participants, 48% met MSA recommendation. Meeting MSA recommendation was associated with lower adiposity and higher performance in the shuttle run test, maximal oxygen consumption, standing long jump, speed-agility, flexibility, lower screen time (in weekdays) and higher adherence to the Mediterranean diet. CONCLUSION: Engaging in MSA once or twice a week was linked with more desirable health outcomes than not engaging in such activities. However, meet with MSA recommendation (i.e., at least 3 days per week) reinforced these benefits.
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Adiposidade , Aptidão Física , Humanos , Adolescente , Estudos Transversais , Obesidade , Índice de Massa Corporal , Estilo de Vida , MúsculosRESUMO
ABSTRACT: Today's youth are weaker than previous generations, and measurable reductions in physical fitness are beginning to emerge. Without targeted initiatives that recognize the foundational importance of resistance training, weaker children and adolescents may be more likely to experience the inevitable consequences of neuromuscular dysfunction and less likely to experience the pleiotropic benefits of exercise and sport. Early exposure to strength-building activities is needed to prepare today's youth for ongoing participation in varied physical activities throughout this developmental phase of life. The novel iceberg of physical development is a metaphoric image that illustrates the sequential and cumulative influence of muscular strength on motor skills and physical abilities. Efforts to enhance the physical capacity of youth should include resistive skills that improve basic movement patterns and enhance motoric competence. A shift in our conceptual thinking about youth resistance training is needed to alter the current trajectory toward physical inactivity and related comorbidities.
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Aptidão Física , Esportes , Criança , Humanos , Adolescente , Força Muscular , Exercício Físico , Destreza MotoraRESUMO
Rodentia is the most species-rich order among mammals. The Republic of South Africa harbours a high rodent diversity whose taxonomy and phylogeny have been extensively studied using genetic tools. Such advances have led to the establishment of new faunal lists for the country. Because rodents are frequently recovered from archaeological cave site material and owl pellets, and constitute prime material for studying both past and present environmental conditions, it is necessary to characterize their osteological remains. The skull and teeth are the most useful diagnostic skeletal elements preserved in modern and fossil accumulations. This key provides updated craniodental criteria for identifying rodent genera found in Quaternary deposits, and modern material from the Republic of South Africa, thus facilitating research on past and present rodent diversity.
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Mamíferos , Roedores , Animais , África do Sul , Filogenia , FósseisRESUMO
The advent of chimeric antigen receptor (CAR) T cell therapy has resulted in unprecedented long-term clearance of relapse/refractory hematological malignancies in both pediatric and adult patients. However, severe toxicities, such as cytokine release syndrome and neurotoxicity, associated with CAR T cells affect therapeutic utility; and treatment efficacies for solid tumors are still not impressive. As a result, engineering strategies that modify other immune cell types, especially natural killer (NK) cells have arisen. Owing to both CAR-dependent and CAR-independent (innate immune-mediated) antitumor killing capacity, major histocompatibility complex-independent cytotoxicity, reduced risk of alloreactivity and lack of major CAR T cell toxicities, CAR NK cells constitute one of the promising next-generation CAR immune cells that are also amenable as 'off-the-shelf' therapeutics. In this Review, we compare CAR T and CAR NK cell therapies, with particular focus on immunological synapses, engineering strategies and challenges.
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Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Criança , Células Matadoras Naturais , Imunoterapia Adotiva/métodos , Terapia Baseada em Transplante de Células e TecidosRESUMO
Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in overweight individuals and individuals with obesity and type 2 diabetes (T2DM). A literature search was conducted through databases such as PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. A random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24 h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analyses were conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and the disease status of participants. This study revealed a significantly reduced glucose AUC (Hedges' g = -0.317; SE = 0.057; p < 0.05) and 24 h mean glucose levels (Hedges' g = -0.328; SE = 0.062; p < 0.05) following PPE compared to CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min compared to ≤30 min. The reduction in 24 h mean glucose levels was also greater (p < 0.05) following PPE for ≥60 min compared to <60 min post-meal and in those with T2DM compared to those without T2DM. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE is a promising strategy, particularly for patients with T2DM. This manuscript is registered with Research Registry (UIN: reviewregistry1693).
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Diabetes Mellitus Tipo 2 , Hiperglicemia , Humanos , Glicemia/análise , Sobrepeso/complicações , Glucose , Obesidade/complicações , Período Pós-Prandial/fisiologia , InsulinaRESUMO
OBJECTIVE: Given the consequences of delayed treatment and diagnosis of craniosynostosis, this study reviews the literature on sociodemographic risk factors and disparities associated with delayed craniosynostosis treatment. DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search of PubMed/Medline and Embase was performed by two independent reviewers. Included studies discussed craniosynostosis health disparities. Demographic characteristics and outcomes were analyzed. SETTING: Not applicable. PATIENTS: Patients with craniosynostosis. INTERVENTIONS: Standard surgical intervention for craniosynostosis. RESULTS: Our literature search yielded 273 studies, of which 18 were included for analysis. Included studies represented data from 31â 256 U.S. patients with craniosynostosis. Sixty percent of patients (n = 16â 510) were White, 13.8% were Hispanic/Latino, 6.2% were Black/African American, 1.3% were Asian, 0.3% were American Indian or Alaska Native, and 0.1% were Native Hawaiian or Pacific Islander. Average age at surgery was 6.36 months for White patients, 10.63 months for Black patients, and 9.18 months for Hispanic patients. Minority racial and/or ethnic status was a risk factor for delayed presentation, and increased incidence of open surgery, complication rates, hospital charges, operative time, anesthesia duration, and hospital length of stay. Government-funded health insurance was associated with delayed intervention and increased complications. CONCLUSIONS: Minority craniosynostosis patients experience delays in intervention and increased complication rates. Our findings highlight the importance of expedited and equitable referrals, screenings, and treatment, and the need for a standardized approach to investigating longitudinal demographic and outcomes data in this population.
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BACKGROUND: The primary aim of our systematic review and meta-analysis was to investigate the effect of resistance training on academic outcomes in school-aged youth. METHODS: We conducted a systematic search of six electronic databases (CINAHL Complete, PsycINFO, SCOPUS, Ovid MEDLINE, SPORTDiscus and EMBASE) with no date restrictions. Studies were eligible if they: (a) included school-aged youth (5-18 years), and (b) examined the effect of resistance training on academic outcomes (i.e., cognitive function, academic achievement, and/or on-task behaviour in the classroom). Risk of bias was assessed using the appropriate Cochrane Risk of Bias Tools, funnel plots and Egger's regression asymmetry tests. A structural equation modelling approach was used to conduct the meta-analysis. RESULTS: Fifty-three studies were included in our systematic review. Participation in resistance training (ten studies with 53 effect sizes) had a small positive effect on the overall cognitive, academic and on-task behaviours in school-aged youth (standardized mean difference (SMD) 0.19, 95% confidence interval (CI) 0.05-0.32). Resistance training was more effective (SMD 0.26, 95% CI 0.10-0.42) than concurrent training, i.e., the combination of resistance training and aerobic training (SMD 0.11, 95% CI - 0.05-0.28). An additional 43 studies (including 211 effect sizes) examined the association between muscular fitness and cognition or academic achievement, also yielding a positive relationship (SMD 0.13, 95% CI 0.10-0.16). CONCLUSION: This review provides preliminary evidence that resistance training may improve cognitive function, academic performance, and on-task behaviours in school-aged youth. PROSPERO REGISTRATION: CRD42020175695.
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The lack of antibodies with sufficient cancer selectivity is currently limiting the treatment of solid tumors by immunotherapies. Most current immunotherapeutic targets are tumor-associated antigens that are also found in healthy tissues and often do not display sufficient cancer selectivity to be used as targets for potent antibody-based immunotherapeutic treatments, such as chimeric antigen receptor (CAR) T cells. Many solid tumors, however, display aberrant glycosylation that results in expression of tumor-associated carbohydrate antigens that are distinct from healthy tissues. Targeting aberrantly glycosylated glycopeptide epitopes within existing or novel glycoprotein targets may provide the cancer selectivity needed for immunotherapy of solid tumors. However, to date only a few such glycopeptide epitopes have been targeted. Here, we used O-glycoproteomics data from multiple cell lines to identify a glycopeptide epitope in CD44v6, a cancer-associated CD44 isoform, and developed a cancer-specific mAb, 4C8, through a glycopeptide immunization strategy. 4C8 selectively binds to Tn-glycosylated CD44v6 in a site-specific manner with low nanomolar affinity. 4C8 was shown to be highly cancer specific by IHC of sections from multiple healthy and cancerous tissues. 4C8 CAR T cells demonstrated target-specific cytotoxicity in vitro and significant tumor regression and increased survival in vivo. Importantly, 4C8 CAR T cells were able to selectively kill target cells in a mixed organotypic skin cancer model having abundant CD44v6 expression without affecting healthy keratinocytes, indicating tolerability and safety.
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Anticorpos Monoclonais , Neoplasias , Humanos , Anticorpos Monoclonais/farmacologia , Neoplasias/patologia , Glicoproteínas , Epitopos , GlicopeptídeosRESUMO
Appropriate responses to real or potential damaging stimuli to the body (nociception) are critical to an animal's short- and long-term survival. The initial goal of this study was to examine habituation of withdrawal reflexes (whole-body and local shortening) to repeated mechanical nociceptive stimuli (needle pokes) in the medicinal leech, Hirudo verbana, and assess whether injury altered habituation to these nociceptive stimuli. While repeated needle pokes did reduce shortening in H. verbana, a second set of behavior changes was observed. Specifically, animals began to evade subsequent stimuli by either hiding their posterior sucker underneath adjacent body segments or engaging in locomotion (crawling). Animals differed in terms of how quickly they adopted evasion behaviors during repeated stimulation, exhibiting a multi-modal distribution for early, intermediate and late evaders. Prior injury had a profound effect on this transition, decreasing the time frame in which animals began to carry out evasion and increasing the magnitude of these evasion behaviors (more locomotory evasion). The data indicate the presence in Hirudo of a complex and adaptive defensive arousal process to avoid noxious stimuli that is influenced by differences in internal states, prior experience with injury of the stimulated areas, and possibly learning-based processes.
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Hirudo medicinalis , Sanguessugas , Animais , Nociceptividade , Sanguessugas/fisiologia , Comportamento Animal/fisiologia , Reflexo/fisiologiaRESUMO
ABSTRACT: Kang, J, Ratamess, NA, Faigenbaum, AD, Bush, JA, Finnerty, C, DiFiore, M, Garcia, A, and Beller, N. Time-of-day effects of exercise on cardiorespiratory responses and endurance performance-A systematic review and meta-analysis. J Strength Cond Res 37(10): 2080-2090, 2023-The time-of-day effect of exercise on human function remains largely equivocal. Hence, this study aimed to further analyze the existing evidence concerning diurnal variations in cardiorespiratory responses and endurance performance using a meta-analytic approach. Literature search was conducted through databases, including PubMed, CINAHL, and Google Scholar. Article selection was made based on inclusion criteria concerning subjects' characteristics, exercise protocols, times of testing, and targeted dependent variables. Results on oxygen uptake (VÌ o2 ), heart rate (HR), respiratory exchange ratio, and endurance performance in the morning (AM) and late afternoon or evening (PM) were extracted from the chosen studies. Meta-analysis was conducted with the random-effects model. Thirty-one original research studies that met the inclusion criteria were selected. Meta-analysis revealed higher resting VÌ o2 (Hedges' g = -0.574; p = 0.040) and resting HR (Hedges' g = -1.058; p = 0.002) in PM than in AM. During exercise, although VÌ o2 remained indifferent between AM and PM, HR was higher in PM at submaximal (Hedges' g = -0.199; p = 0.046) and maximal (Hedges' g = -0.298; p = 0.001) levels. Endurance performance as measured by time-to-exhaustion or the total work accomplished was higher in PM than in AM (Hedges' g = -0.654; p = 0.001). Diurnal variations in VÌ o2 appear less detectable during aerobic exercise. The finding that exercising HR and endurance performance were greater in PM than in AM emphasizes the need to consider the effect of circadian rhythm when evaluating athletic performance or using HR as a criterion to assess fitness or monitor training.