RESUMO
PURPOSE: To systematically review and meta-analyse the efficacy of resistance training on quality of life (QOL), fatigue, physical function, and muscular strength in people diagnosed with cancer undergoing chemotherapy. METHODS: Electronic databases PubMed, Cochrane Central, CINAHL, SCOPUS and Web of Science were systematically searched for randomised controlled trials (RCTs) that compared the effects of resistance training to control on QOL, fatigue, physical function, and lower-body and upper-body muscular strength in adults undergoing chemotherapy. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assess using the risk of bias tool for randomised trials (RoB 2). RESULTS: Seven RCTs encompassing 561 participants were included. The pooled results of seven RCTs showed that resistance training during chemotherapy significantly improved lower-body strength (n = 555, SMD 0.33, 95% CI 0.12 to 0.53, moderate-quality evidence, I2 = 23%) compared to control. There was no evidence for an effect of resistance training on QOL (n = 373, SMD 0.13, 95% CI -0.15 to 0.42, low-quality evidence, I2 = 0%), fatigue (n = 373, SMD -0.08, 95% CI -0.37 to 0.22, low-quality evidence, I2 = 20%), physical function (n = 198, SMD 0.61, 95% CI -0.73 to 1.95, very low-quality evidence, I2 = 83%), or upper-body strength (n = 413, SMD 0.37, 95% CI -0.07 to 0.80, very low-quality evidence, I2 = 69%). CONCLUSIONS: Resistance training may improve lower-body strength in patients undergoing chemotherapy treatment compared to control.
Assuntos
Fadiga , Força Muscular , Neoplasias , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Força Muscular/fisiologia , Neoplasias/tratamento farmacológico , Fadiga/etiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagemRESUMO
Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still pose a considerable risk in modern-day procedures and are highly undesirable. We have developed a novel mouse peritoneal strip ex vivo adhesion model which may serve to bridge the gap between single cell culture systems and in vivo animal drug testing for the assessment of potential anti-adhesion agents, and study of causality of the process. We investigated the optimal conditions for adhesion formation with mouse peritoneal tissue strips by modifying an existing ex vivo rat model of peritoneal adhesions. We assessed the impact of the following conditions on the formation of adhesions: contact pressure, abrasions, and the presence of clotted blood. Macroscopic adhesions were detected in all mouse peritoneal strips exposed to specific conditions, namely abrasions and clotted blood, where peritoneal surfaces were kept in contact with pressure using cotton gauze in a tissue cassette. Adhesions were confirmed microscopically. Interestingly, connexin 43, a gap junction protein, was found to be upregulated at sites of adhesions. Key features of this model were the use of padding the abraded tissue with gauze and the use of a standardised volume of clotted blood. Using this model, peritoneal strips cultured with clotted blood between abraded surfaces were found to reproducibly develop adhesion bands at 72 h. Our goal is to develop a model that can be used in genetically modified mice in order to dissect out the role of particular genes in adhesion formation and to test drugs to prevent adhesion formation.
Assuntos
Conexina 43/metabolismo , Modelos Biológicos , Peritônio/metabolismo , Aderências Teciduais/metabolismo , Animais , Conexina 43/genética , Camundongos , Camundongos Transgênicos , Ratos , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/genéticaRESUMO
OBJECTIVES: Connexins are building blocks of membranous channels that form gap junctions and hemichannels. These channels are essential portals for information exchange and coordination during inflammation. Pathologic levels of these conduits may result in excessive inflammation and collateral destruction. This study aimed to analyse temporospatial levels of connexin 43 (Cx43) during pulpitis in extracted human teeth and in a rodent model. A specific interest was directed at the pulpal stroma as it is conserved during vital pulp therapy. MATERIALS AND METHODS: Pulpal tissues were attained from human extracted teeth of various pulpal inflammatory stages and fixed for cryosections. Pulpal exposures were created in bilateral maxillary molars in Sprague-Dawley rats. Rats were sacrificed at days 1 to 5 post-exposure. Immunofluorescence histology was performed to detect Cx43, markers for inflammation, and cell death. Immunofluorescent levels in the pulpal stroma at 3 sites (wound/near/far) were matched to pulpal condition (human) or days post-exposure (rodent). RESULTS: Cx43 upregulation was observed with increased severity of pulpitis both in humans and rodent model. The upregulation appeared to be global and included distant regions. Elevated levels of neutrophils were present in advanced pulpitis. Apoptosis and necroptosis seem to be upregulated in human samples as Cx43 levels rose. CONCLUSIONS: We observed a disseminated upregulation of Cx43 throughout the pulpal stroma as inflammation became advanced. This observation may facilitate cell death signal transfer or represent overt levels of purinergic signalling that leads to pro-inflammatory conditions. CLINICAL RELEVANCE: Cx43 downregulation may represent a potential therapeutic approach to enable resolution of pulpal inflammation.
Assuntos
Conexina 43 , Pulpite , Animais , Conexina 43/metabolismo , Polpa Dentária/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Pairs of magnets were applied to the loose skin on the backs of mice in order to cause ischemia for periods of 1.5, 2, 2.5 and 3 h followed by reperfusion. We found 1.5 h of ischemia resulted in the most reliable outcome of blanched skin but no redness or skin breakdown. Histological analysis at 4 h of reperfusion showed, in the centre of the insult, condensed nuclei in the epidermis and sebaceous glands with a build up of neutrophils in the blood vessels, and a reduction in the number of fibroblasts. At 24 h, spongiosis was seen in the epidermis and pockets of neutrophils began to accumulate under it, as well as being scatted through the dermis. In the centre of the insult there was a loss of sebaceous gland nuclei and fibroblasts. Four days after the insult, spongiosis was reduced in the epidermis at the edge of the insult but enhanced in the centre and in hair follicles. Leukocytes were seen throughout the central dermis. At 8 days, spongiosis and epidermal thickness had reduced and fibroblasts were reappearing. However, blood vessels still had leukocytes lining the lumen. The gap junction protein connexin 43 was significantly elevated in the epidermis at 4 h and 24 h reperfusion. Ischemia of 1.5 h generates a sterile inflammatory reaction causing the loss of some cell types but leaving the epidermis intact reminiscent of a stage I pressure ulcer.
Assuntos
Isquemia/complicações , Úlcera por Pressão/etiologia , Reperfusão/métodos , Pele/fisiopatologia , Animais , Modelos Animais de Doenças , Isquemia/fisiopatologia , Camundongos , Pressão/efeitos adversos , Úlcera por Pressão/fisiopatologia , Reperfusão/normas , Reperfusão/estatística & dados numéricos , Pele/patologiaRESUMO
BACKGROUND AND OBJECTIVES: To investigate the feasibility of delivering a functional exercise-based prehabilitation intervention and its effects on postoperative length of hospital stay, preoperative physical functioning and health-related quality of life in elective colorectal surgery. MATERIALS AND METHODS: In this randomised controlled feasibility trial, 22 elective colorectal surgery patients were randomly assigned to exercise prehabilitation (n = 11) or standard care (n = 11). Feasibility of delivering the intervention was assessed based on recruitment and compliance to the intervention. Impact on postoperative length of hospital stay and complications, preoperative physical functioning (timed up and go test, five times sit to stand, stair climb test, handgrip dynamometry and 6-min walk test) and health-related quality of life were also assessed. RESULTS: Over 42% of patients (84/198) screened were deemed ineligible for prehabilitation due to insufficient time existing prior to scheduled surgery. Of those who were eligible, approximately 18% consented to the trial. Median length of hospital stay was 8 [range 6-27] and 10 [range 5-12] days respectively for the standard care and prehabilitation groups. Patterns towards preoperative improvements for the timed up and go test, stair climb test and 6-min walk test were observed for all participants receiving prehabilitation but not standard care. CONCLUSIONS: Despite prehabilitation appearing to convey positive benefits on physical functioning, short surgical wait times and patient engagement represent major obstacles to implementing exercise prehabilitation programmes in colorectal cancer patients.
Assuntos
Neoplasias Colorretais/reabilitação , Neoplasias Colorretais/terapia , Terapia por Exercício/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/reabilitação , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Qualidade de VidaRESUMO
Orange, ST, Metcalfe, JW, Marshall, P, Vince, RV, Madden, LA, and Liefeith, A. Test-retest reliability of a commercial linear position transducer (GymAware PowerTool) to measure velocity and power in the back squat and bench press. J Strength Cond Res 34(3): 728-737, 2020-This study examined the test-retest reliability of the GymAware PowerTool (GYM) to measure velocity and power in the free-weight back squat and bench press. Twenty-nine academy rugby league players (age: 17.6 ± 1.0 years; body mass: 87.3 ± 20.8 kg) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. GYM measured mean velocity (MV), peak velocity (PV), mean power (MP), and peak power at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM). GYM showed good reliability (intraclass correlation coefficient [ICC] and standard error of measurement percentage, respectively) for the measurement of MV at loads of 40 (0.77, 3.9%), 60 (0.83, 4.8%), 80 (0.83, 5.8%), and 90% (0.79, 7.9%) of 1RM in the back squat. In the bench press, good reliability was evident for PV at 40 (0.82, 3.9%), 60 (0.81, 5.1%), and 80% (0.77, 8.4%) of 1RM, and for MV at 80 (0.78, 7.9%) and 90% (0.87, 9.9%) of 1RM. The measurement of MP showed good to excellent levels of reliability across all relative loads (ICC ≥0.75). In conclusion, GYM provides practitioners with reliable kinematic information in the back squat and bench press, at least with loads of 40-90% of 1RM. This suggests that strength and conditioning coaches can use the velocity data to regulate training load according to daily readiness and target specific components of the force-velocity curve. However, caution should be taken when measuring movement velocity at loads <40% of 1RM.
Assuntos
Movimento/fisiologia , Transdutores , Levantamento de Peso/fisiologia , Adolescente , Fenômenos Biomecânicos , Teste de Esforço , Humanos , Masculino , Força Muscular , Reprodutibilidade dos Testes , Treinamento Resistido , Adulto JovemRESUMO
AIMS: To assess whether endothelial microparticles (EMPs), novel surrogate markers of endothelial injury and dysfunction, are differentially produced in response to acute insulin-induced hypoglycaemia in adults with and without type 2 diabetes. MATERIALS AND METHODS: A prospective, parallel study was conducted in individuals with type 2 diabetes (n = 23) and controls (n = 22). Hypoglycaemia (<2.2 mmoL/L: <40 mg/dL) was achieved by intravenous infusion of soluble insulin. Blood samples were collected at baseline and at 0, 30, 60, 120, 240 minutes and 24 hours after hypoglycaemia and analysed for CD31+ (platelet endothelial cell adhesion molecule-1), CD54+ (intercellular adhesion molecule 1), CD62-E+ (E-selectin), CD105+ (endoglin), CD106+ (vascular cell adhesion molecule 1) and CD142+ (tissue factor) EMPs by flow cytometry. The peak elevations (% rise from 0 minutes after hypoglycaemia) in EMP within 240 minutes after insulin-induced hypoglycaemia were modelled using a regression model, with adjustment for relevant covariates. All EMPs were expressed as percentage from 0 minutes hypoglycaemia for each time point and total areas under the curve (AUC0min-24h ) were calculated. RESULTS: Following insulin-induced hypoglycaemia, levels of circulating EMPs were maximal at 240 minutes (P < 0.001) and returned to baseline values within 24 hours for both groups. The peak elevations (% rise from 0 minutes following hypoglycaemia) seen in CD31+ , CD54+ , CD62-E+ , CD105+ and CD142+ EMPs within 240 minutes were associated with diabetes status after adjustments for all relevant covariates. Individuals with type 2 diabetes showed increased CD31+ EMPs AUC0min-24h (P = 0.014) and CD105+ EMPs AUC0min-24h (P = 0.006) compared with controls, but there were no differences for CD54+ (P = 0.91), CD62-E+ (P = 0.14), CD106+ (P = 0.36) or CD142+ (P = 0.77) EMPs AUC0min-24h . CONCLUSIONS: The associations between peak elevations within 240 minutes after insulin-induced hypoglycaemia for CD31+ , CD54+ , CD62-E+ , CD105+ and CD142+ and diabetes status indicate that the assessment of a panel of EMPs within this timeframe would identify a hypoglycaemic event in this population. The greater overall responses over time (AUCs) for apoptosis-induced CD31+ and CD105+ EMPs suggest that hypoglycaemia exerts greater endothelial stress in type 2 diabetes.
Assuntos
Doenças Cardiovasculares/diagnóstico , Micropartículas Derivadas de Células/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/diagnóstico , Endotélio Vascular/patologia , Hipoglicemia/induzido quimicamente , Insulina/efeitos adversos , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Micropartículas Derivadas de Células/fisiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/complicações , Hipoglicemia/fisiopatologia , Insulina/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
This study examined the relationship between sit-to-stand (STS) power and physical function in adults with severe obesity. Thirty-eight adults (age: 44 ± 12 years; body mass index [BMI]: 45.2 ± 7.8 kg/m2) completed evaluations of STS power, strength and functional performance. STS power was measured with a wearable inertial sensor, strength was assessed with the isometric mid-thigh pull, and function was measured with the timed up-and-go (TUG), six-minute walk test (6MWT) and 30-s chair STS. Power and strength (normalised to body mass) entered regression models in addition to age, gender, BMI and physical activity (daily step count). Power displayed large univariate associations with TUG (r = 0.50) and 30-s chair STS (r = 0.67), and a moderate association with 6MWT (r = 0.49). Forward stepwise regression revealed that power independently contributed to TUG (ß = -0.40, p = 0.010), 30-s chair STS (ß = 0.67, p < 0.001) and 6MWT performance (ß = 0.27, p = 0.007). Power also appeared to be a superior determinant of function compared with strength. Power generated via the STS transfer largely underpins the ability to perform functional tasks in adults with severe obesity, although intervention studies are required to investigate a potentially causal relationship.
Assuntos
Atividades Cotidianas , Teste de Esforço/métodos , Força Muscular/fisiologia , Obesidade Mórbida/fisiopatologia , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Humanos , Extremidade Inferior/fisiologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores Sexuais , Teste de Caminhada , Dispositivos Eletrônicos Vestíveis , Adulto JovemRESUMO
Orange, ST, Marshall, P, Madden, LA, and Vince, RV. Short-term training and detraining effects of supervised vs. unsupervised resistance exercise in aging adults. J Strength Cond Res 33(10): 2733-2742, 2019-This study compared the effects of a 4-week supervised (SUP) resistance training program and unsupervised (UNSUP) resistance training program followed by 12 weeks of detraining (DET). Thirty-six healthy aging adults (age: 53.6 ± 3.6 years; body mass index: 28.3 ± 5.1 kg·m) were randomly allocated to an SUP group (n = 17) or a UNSUP group (n = 19). Participants completed 3 training sessions per week using resistance bands and body weight movements. Measures of physical performance were administered at baseline, at the end of the training program, and after the DET period. Function was assessed with the 6-minute walk test (6MWT), timed up-and-go (TUG), 30-second chair sit-to-stand (STS), stair-climb test (SCT), 40-m fast-paced walk test (FPWT) and sit-and-reach test (SRT), whereas the isometric midthigh pull (IMTP) and hand grip test were used to measure muscle strength. After training, improvements in performance were found in the 6MWT, TUG, 30-second chair STS, SCT, FPWT, SRT, and IMTP (p ≤ 0.05), with no significant differences between groups (p > 0.05). In addition, most of the training-induced improvements remained significantly above baseline values after the DET period (p ≤ 0.05). No significant between-group differences were observed after training or DET (p > 0.05). Four weeks of either SUP or UNSUP resistance training is sufficient to substantially improve muscle strength and function in aging adults, and these gains are largely preserved after prescribed exercise cessation. Home-based resistance training seems to be a practical and effective alternative to traditional SUP programs that may help circumvent many barriers to physical activity in aging adults.
Assuntos
Envelhecimento , Força da Mão , Treinamento Resistido/métodos , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Subida de Escada , Fatores de Tempo , Teste de CaminhadaRESUMO
Orange, ST, Metcalfe, JW, Liefeith, A, Marshall, P, Madden, LA, Fewster, CR, and Vince, RV. Validity and reliability of a wearable inertial sensor to measure velocity and power in the back squat and bench press. J Strength Cond Res 33(9): 2398-2408, 2019-This study examined the validity and reliability of a wearable inertial sensor to measure velocity and power in the free-weight back squat and bench press. Twenty-nine youth rugby league players (18 ± 1 years) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. Repetitions were performed at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM) with mean velocity, peak velocity, mean power (MP), and peak power (PP) simultaneously measured using an inertial sensor (PUSH) and a linear position transducer (GymAware PowerTool). The PUSH demonstrated good validity (Pearson's product-moment correlation coefficient [r]) and reliability (intraclass correlation coefficient [ICC]) only for measurements of MP (r = 0.91; ICC = 0.83) and PP (r = 0.90; ICC = 0.80) at 20% of 1RM in the back squat. However, it may be more appropriate for athletes to jump off the ground with this load to optimize power output. Further research should therefore evaluate the usability of inertial sensors in the jump squat exercise. In the bench press, good validity and reliability were evident only for the measurement of MP at 40% of 1RM (r = 0.89; ICC = 0.83). The PUSH was unable to provide a valid and reliable estimate of any other criterion variable in either exercise. Practitioners must be cognizant of the measurement error when using inertial sensor technology to quantify velocity and power during resistance training, particularly with loads other than 20% of 1RM in the back squat and 40% of 1RM in the bench press.
Assuntos
Força Muscular , Músculo Esquelético/fisiologia , Dispositivos Eletrônicos Vestíveis , Levantamento de Peso , Adolescente , Teste de Esforço , Humanos , Masculino , Reprodutibilidade dos Testes , Treinamento Resistido , Transdutores , Adulto JovemRESUMO
Cancer incidence and mortality have both increased in the last decade and are predicted to continue to rise. Diagnosis and treatment of cancers are often hampered by the inability to specifically target neoplastic cells. Bioimprinting is a promising new approach to overcome shortfalls in cancer targeting. Highly specific recognition cavities can be made into polymer matrices to mimic lock-and-key actions seen in in vivo biological systems. Early studies concentrated on molecules and were inhibited by template size complexity. Surface imprinting allows the capture of increasingly complex motifs from polypeptides to single cell organisms and mammalian cells. Highly specific cell shape recognition can also be achieved by cell interaction with imprints that can be made into polymer matrices to mimic biological systems at a molecular level. Bioimprinting has also been used to achieve nanometre scale resolution imaging of cancer cells. Studies of bioimprint-based drug delivery on cancer cells have been recently trialled in vitro and show that this approach can potentially improve existing chemotherapeutic approaches. This review focuses on the possible applications of bioimprinting with particular regards to cancer understanding, diagnosis and therapy. Cell imprints, incorporated into biosensors can allow the limits of detection to be improved or negate the need for extensive patient sample processing. Similar cell imprinting platforms can be used for nanoscale imaging of cancer morphology, as well as to investigate topographical signalling of cancer cells in vitro. Lastly, bioimprints also have applications as selective drug delivery vehicles to tumours with the potential to decrease chemotherapy-related side effects.
Assuntos
Forma Celular , Impressão Molecular , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Animais , HumanosRESUMO
Enterococcus faecalis is one of the most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics of E faecalis and show that infected wounds result in 2 different states depending on the initial inoculum. Low-dose inocula were associated with short-term, low-titer colonization whereas high-dose inocula were associated with acute bacterial replication and long-term persistence. High-dose infection and persistence were also associated with immune cell infiltration, despite suppression of some inflammatory cytokines and delayed wound healing. During high-dose infection, the multiple peptide resistance factor, which is involved in resisting immune clearance, contributes to E faecalis fitness. These results comprehensively describe a mouse model for investigating E faecalis wound infection determinants, and suggest that both immune modulation and resistance contribute to persistent, nonhealing wounds.
Assuntos
Enterococcus faecalis/imunologia , Enterococcus faecalis/patogenicidade , Infecções por Bactérias Gram-Positivas/patologia , Evasão da Resposta Imune , Infecção dos Ferimentos/patologia , Animais , Modelos Animais de Doenças , Enterococcus faecalis/crescimento & desenvolvimento , Infecções por Bactérias Gram-Positivas/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Infecção dos Ferimentos/microbiologiaRESUMO
Chronic wounds are a growing problem worldwide with no effective therapeutic treatments available. Our objective was to understand the composition of the dermal tissue surrounding venous leg ulcers and diabetic foot ulcers (DFU). We used novel 2-photon imaging techniques alongside classical histology to examine biopsies from the edges of two common types of chronic wound, venous leg ulcers and DFU. Compared to normal intact skin, we found that collagen levels are significantly reduced throughout the dermis of venous leg ulcer biopsies and DFU, with a reduction in both fibril thickness and abundance. Both wound types showed a significant reduction in elastin in the upper dermis, but in DFU, the loss was throughout the dermis. Loss of extracellular matrix correlated with high levels of CD68- and CD18-positive leukocytes. 2-photon imaging of the extracellular matrix in the intact tissue surrounding a chronic wound with a hand-held device may provide a useful clinical indicator on the healing progression or deterioration of these wounds.
Assuntos
Derme/diagnóstico por imagem , Pé Diabético/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Matriz Extracelular/ultraestrutura , Úlcera Varicosa/diagnóstico por imagem , Cicatrização/fisiologia , Ferimentos e Lesões/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/fisiopatologiaRESUMO
The aim of this study was to investigate if a pre-exercise alkalosis-mediated attenuation of HSP72 had any effect on the response of the same stress protein after a subsequent exercise. Seven physically active males [25.0 ± 6.5 years, 182.1 ± 6.0 cm, 74.0 ± 8.3 kg, peak aerobic power (PPO) 316 ± 46 W] performed a repeated sprint exercise (EXB1) following a dose of 0.3 g kg(-1) body mass of sodium bicarbonate (BICARB), or a placebo of 0.045 g kg(-1) body mass of sodium chloride (PLAC). Participants then completed a 90-min intermittent cycling protocol (EXB2). Monocyte expressed HSP72 was significantly attenuated after EXB1 in BICARB compared to PLAC, however, there was no difference in the HSP72 response to the subsequent EXB2 between conditions. Furthermore there was no difference between conditions for measures of oxidative stress (protein carbonyl and HSP32). These findings confirm the sensitivity of the HSP72 response to exercise-induced changes in acid-base status in vivo, but suggest that the attenuated response has little effect upon subsequent stress in the same day.
Assuntos
Alcalose/patologia , Exercício Físico/fisiologia , Proteínas de Choque Térmico HSP72/metabolismo , Bicarbonato de Sódio/farmacologia , Adulto , Proteínas de Choque Térmico HSP72/antagonistas & inibidores , Humanos , Masculino , Estresse Oxidativo , Cloreto de Sódio/metabolismoRESUMO
Duramycin, through binding with phosphatidylethanolamine (PE), has shown potential to be an effective antitumour agent. However, its mode of action in relation to tumour cells is not fully understood. PE expression on the surface of a panel of cancer cell lines was analysed using duramycin and subsequent antibody labelling, and then analysed by flow cytometry. Cell viability was also assessed by flow cytometry using annexin V and propidium iodide. Calcium ion (Ca) release by tumour cells in response to duramycin was determined by spectrofluorometry following incubation with Fluo-3, AM. Confocal microscopy was performed on the cancer cell line AsPC-1 to assess real-time cell response to duramycin treatment. Duramycin could detect cell surface PE expression on all 15 cancer cell lines screened, which was shown to be duramycin concentration dependent. However, higher concentrations induced necrotic cell death. Duramycin induced calcium ion (Ca) release from the cancer cell lines also in a concentration-dependent and time-dependent manner. Confocal microscopy showed an influx of propidium iodide into the cells over time and induced morphological changes. Duramycin induces Ca release from cancer cell lines in a time-dependent and concentration-dependent manner.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Bacteriocinas/farmacologia , Cálcio/metabolismo , Peptídeos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas , Neoplasias PancreáticasRESUMO
Here we used a 3D human hepatic tumour cell culture model to assess the in vitro efficacy of "active" metformin-loaded nanoparticles (NPs) as anticancer therapeutics. The metformin nanocarrier design was repurposed from previous studies targeting bacterial and fungal biofilms with antimicrobials loaded in protease-coated nanoparticles. These active nanocarriers were constructed with shellac cores loaded with metformin as the anticancer agent and featured a surface coating of the cationic protease lysozyme. The lysozyme's role as a nanocarrier surface coating is to partially digest the extracellular matrix (ECM) of the 3D tumour cell culture which increases its porosity and the nanocarrier penetration. Hep-G2 hepatic 3D clusteroids were formed using a water-in-water (w/w) Pickering emulsion based on an aqueous two-phase system (ATPS). Our specific metformin nano-formulation, comprising 0.25 wt% lysozyme-coated, 0.4 wt% metformin-loaded, 0.2 wt% shellac NPs sterically stabilized with 0.25 wt% Poloxamer 407, demonstrated significantly enhanced anticancer efficiency on 3D hepatic tumour cell clusteroids. We examined the role of the lysozyme surface functionality of the metformin nanocarriers in their ability to kill both 2D and 3D hepatic tumour cell cultures. The anticancer efficiency at high metformin payloads was compared with that at a high concentration of nanocarriers with a lower metformin payload. It was discovered that the high metformin payload NPs were more efficient than the lower metformin payload NPs with a higher nanocarrier concentration. This study introduces a reliable in vitro model for potential targeting of solid tumours with smart nano-therapeutics, presenting a viable alternative to animal testing for evaluating anticancer nanotechnologies.
RESUMO
INTRODUCTION: Biomarker responses to intensive decompression indicate systemic proinflammatory responses and possible neurological stress. To further investigate responses, 12 additional brain and lung biomarkers were assayed.METHODS: A total of 15 healthy men (20 to 50 yr) undertook consecutive same-day ascents to 25,000 ft (7620 m), following denitrogenation, breathing 100% oxygen. Venous blood was sampled at baseline (T0), after the second ascent (T8), and next morning (T24). Soluble protein markers of brain and lung insult were analyzed by enzyme-linked immunosorbent assay with plasma microparticles quantified using flow cytometry.RESULTS: Levels of monocyte chemoattractant protein-1 and high mobility group box protein 1 were elevated at T8, by 36% and 16%, respectively, before returning to baseline. Levels of soluble receptor for advanced glycation end products fell by 8%, recovering by T24. Brain-derived neurotrophic factor rose by 80% over baseline at T24. Monocyte microparticle levels rose by factors of 3.7 at T8 and 2.7 at T24 due to early and late responses in different subjects. Other biomarkers were unaffected or not detected consistently.DISCUSSION: The elevated biomarkers at T8 suggest a neuroinflammatory response, with later elevation of brain-derived neurotrophic factor at T24 indicating an ongoing neurotrophic response and incomplete recovery. A substantial increase at T8 in the ratio of high mobility group box protein 1 to soluble receptor for advanced glycation end products suggests this axis may mediate the systemic inflammatory response to decompression. The mechanism of neuroinflammation is unclear but elevation of monocyte microparticles and monocyte chemoattractant protein-1 imply a key role for activated monocytes and/or macrophages.Connolly DM, Madden LA, Edwards VC, Lee VM. Brain and lung biomarker responses to hyperoxic hypobaric decompression. Aerosp Med Hum Perform. 2024; 95(9):667-674.
Assuntos
Biomarcadores , Quimiocina CCL2 , Receptor para Produtos Finais de Glicação Avançada , Humanos , Masculino , Biomarcadores/sangue , Biomarcadores/metabolismo , Adulto , Pessoa de Meia-Idade , Quimiocina CCL2/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Descompressão/métodos , Adulto Jovem , Encéfalo/metabolismo , Pulmão , Doença da Descompressão/sangue , Hiperóxia/sangueRESUMO
OBJECTIVES: Living within a larger body brings unique challenges to exercise participation, which are poorly understood. This qualitative study explored the attitudes towards, and experiences of, exercise participation in adults with class III obesity. DESIGN: Individual semi-structured qualitative interviews. METHODS: We recruited 30 adults with class III obesity (body mass index: 45.8 ± 8.6 kg/m2) from a specialist multidisciplinary weight management service. Participants took part in semi-structured interviews while participating in a 6-month home-based aerobic and resistance exercise intervention. Open-ended questions were used flexibly to explore their views and experiences of exercise, encompassing barriers, motives and perceived benefits. Transcripts were analysed using reflexive thematic analysis. RESULTS: Three themes were developed: (1) a web of barriers; (2) tailored exercise facilitates positive experiences; and (3) a desire to live a normal life. People with class III obesity perceived that they were unable to do exercise; a view that was attributed to perceived judgement, low physical function, pain during everyday activities and failed weight loss attempts. These complex physical and psychosocial barriers to exercise were described as contributing to exercise avoidance. High value was placed on tailored exercise that accommodates the unique needs of moving in a larger body. A desire to carry out everyday tasks underpinned motivations for exercise. CONCLUSIONS: Our findings suggest that multi-component obesity interventions should move away from generic exercise prescriptions designed to maximize energy expenditure, and instead move towards addressing the unique physical and psychosocial needs of people who have class III obesity with tailored person-centred and weight-neutral exercise prescriptions.
RESUMO
Chronic wounds can take months or even years to heal and require proper medical intervention. Normal wound healing processes require adequate oxygen supply. Accordingly, destroyed or inefficient vasculature leads to insufficient delivery to peripheral tissues and impair healing. Oxygen is critical for vital processes such as proliferation, collagen synthesis and antibacterial defense. Hyperbaric oxygen therapy (HBOT) is commonly used to accelerate healing however, this can be costly and requires specialized training and equipment. Efforts have turned to the development of topical oxygen delivery systems. Oxysolutions has developed oxygenated gels (P407, P407/P188, nanocellulose based gel (NCG)) with high levels of dissolved oxygen. This study aims to evaluate the efficacy of these newly developed oxygenated products by assessing their impact on healing rates in a rat perturbed wound model. Here, P407/P188 oxygenated gels demonstrated greater re-epithelialization distances compared to its controls at Day 3. In addition, all oxygenated gels had a higher proportion of wounds with complete wound closure. All three oxygenated gels also minimized further escalation in inflammation from Day 3 to Day 10. This highlights the potential of this newly-developed oxygenated gels as an alternative to existing oxygen therapies.
Assuntos
Hidrogéis , Reepitelização , Ratos , Animais , Cicatrização , Oxigênio , Inflamação/tratamento farmacológicoRESUMO
We have developed a class of selective antimicrobial agents based on the recognition of the shape and size of the bacterial cells. These agents are anisotropic colloid particles fabricated as negative replicas of the target cells which involve templating of the cells with shells of inert material followed by their fragmentation. The cell shape recognition by such shell fragments is due to the increased area of surface contact between the cells and their matching shell fragments which resembles antibody-antigen interaction. We produced such "colloid antibodies" with photothermal mechanism for shape-selective killing of matching cells. This was achieved by the subsequent deposition of (i) gold nanoparticles (AuNPs) and (ii) silica shell over yeast cells, which were chosen as model pathogens. We demonstrated that fragments of these composite AuNP/silica shells act as "colloid antibodies" and can bind to yeast cells of the same shape and size and deliver AuNPs directly onto their surface. We showed that after laser irradiation, the localized heating around the AuNPs kills the microbial cells of matching shape. We confirmed the cell shape-specific killing by photothermal colloid antibodies in a mixture of two bacterial cultures of different cell shape and size. This approach opens a number of avenues for building powerful selective biocides based on combinations of colloid antibodies and cell-killing strategies which can be applied in new antibacterial therapies.