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1.
Br J Cancer ; 130(7): 1206-1220, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310186

RESUMO

BACKGROUND: Na+,HCO3--cotransporter NBCn1/Slc4a7 accelerates murine breast carcinogenesis. Lack of specific pharmacological tools previously restricted therapeutic targeting of NBCn1 and identification of NBCn1-dependent functions in human breast cancer. METHODS: We develop extracellularly-targeted anti-NBCn1 antibodies, screen for functional activity on cells, and evaluate (a) mechanisms of intracellular pH regulation in human primary breast carcinomas, (b) proliferation, cell death, and tumor growth consequences of NBCn1 in triple-negative breast cancer, and (c) association of NBCn1-mediated Na+,HCO3--cotransport with human breast cancer metastasis. RESULTS: We identify high-affinity (KD ≈ 0.14 nM) anti-NBCn1 antibodies that block human NBCn1-mediated Na+,HCO3--cotransport in cells, without cross-reactivity towards human NBCe1 or murine NBCn1. These anti-NBCn1 antibodies abolish Na+,HCO3--cotransport activity in freshly isolated primary organoids from human breast carcinomas and lower net acid extrusion effectively in primary breast cancer tissue from patients with macrometastases in axillary lymph nodes. Inhibitory anti-NBCn1 antibodies decelerate tumor growth in vivo by ~50% in a patient-derived xenograft model of triple-negative breast cancer and pH-dependently reduce colony formation, cause G2/M-phase cell cycle accumulation, and increase apoptosis of metastatic triple-negative breast cancer cells in vitro. CONCLUSIONS: Inhibitory anti-NBCn1 antibodies block net acid extrusion in human breast cancer tissue, particularly from patients with disseminated disease, and pH-dependently limit triple-negative breast cancer growth.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/genética , Apoptose , Concentração de Íons de Hidrogênio , Simportadores de Sódio-Bicarbonato/genética , Simportadores de Sódio-Bicarbonato/metabolismo
2.
Sports Med Open ; 10(1): 10, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240903

RESUMO

BACKGROUND: Climbing is an intricate sport composed of various disciplines, holds, styles, distances between holds, and levels of difficulty. In highly skilled climbers the potential for further strength-specific adaptations to increase performance may be marginal in elite climbers. With an eye on the upcoming 2024 Paris Olympics, more climbers are trying to maximize performance and improve training strategies. The relationships between muscular strength and climbing performance, as well as the role of strength in injury prevention, remain to be fully elucidated. This narrative review seeks to discuss the current literature regarding the effect of resistance training in improving maximal strength, muscle hypertrophy, muscular power, and local muscular endurance on climbing performance, and as a strategy to prevent injuries. MAIN BODY: Since sport climbing requires exerting forces against gravity to maintain grip and move the body along the route, it is generally accepted that a climber`s absolute and relative muscular strength are important for climbing performance. Performance characteristics of forearm flexor muscles (hang-time on ledge, force output, rate of force development, and oxidative capacity) discriminate between climbing performance level, climbing styles, and between climbers and non-climbers. Strength of the hand and wrist flexors, shoulders and upper limbs has gained much attention in the scientific literature, and it has been suggested that both general and specific strength training should be part of a climber`s training program. Furthermore, the ability to generate sub-maximal force in different work-rest ratios has proved useful, in examining finger flexor endurance capacity while trying to mimic real-world climbing demands. Importantly, fingers and shoulders are the most frequent injury locations in climbing. Due to the high mechanical stress and load on the finger flexors, fingerboard and campus board training should be limited in lower-graded climbers. Coaches should address, acknowledge, and screen for amenorrhea and disordered eating in climbers. CONCLUSION: Structured low-volume high-resistance training, twice per week hanging from small ledges or a fingerboard, is a feasible approach for climbers. The current injury prevention training aims to increase the level of performance through building tolerance to performance-relevant load exposure and promoting this approach in the climbing field.

3.
Breast Cancer Res ; 25(1): 46, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098526

RESUMO

BACKGROUND: Carbonic anhydrases catalyze CO2/HCO3- buffer reactions with implications for effective H+ mobility, pH dynamics, and cellular acid-base sensing. Yet, the integrated consequences of carbonic anhydrases for cancer and stromal cell functions, their interactions, and patient prognosis are not yet clear. METHODS: We combine (a) bioinformatic analyses of human proteomic data and bulk and single-cell transcriptomic data coupled to clinicopathologic and prognostic information; (b) ex vivo experimental studies of gene expression in breast tissue based on quantitative reverse transcription and polymerase chain reactions, intracellular and extracellular pH recordings based on fluorescence confocal microscopy, and immunohistochemical protein identification in human and murine breast cancer biopsies; and (c) in vivo tumor size measurements, pH-sensitive microelectrode recordings, and microdialysis-based metabolite analyses in mice with experimentally induced breast carcinomas. RESULTS: Carbonic anhydrases-particularly the extracellular isoforms CA4, CA6, CA9, CA12, and CA14-undergo potent expression changes during human and murine breast carcinogenesis. In patients with basal-like/triple-negative breast cancer, elevated expression of the extracellular carbonic anhydrases negatively predicts survival, whereas, surprisingly, the extracellular carbonic anhydrases positively predict patient survival in HER2/ErbB2-enriched breast cancer. Carbonic anhydrase inhibition attenuates cellular net acid extrusion and extracellular H+ elimination from diffusion-restricted to peripheral and well-perfused regions of human and murine breast cancer tissue. Supplied in vivo, the carbonic anhydrase inhibitor acetazolamide acidifies the microenvironment of ErbB2-induced murine breast carcinomas, limits tumor immune infiltration (CD3+ T cells, CD19+ B cells, F4/80+ macrophages), lowers inflammatory cytokine (Il1a, Il1b, Il6) and transcription factor (Nfkb1) expression, and accelerates tumor growth. Supporting the immunomodulatory influences of carbonic anhydrases, patient survival benefits associated with high extracellular carbonic anhydrase expression in HER2-enriched breast carcinomas depend on the tumor inflammatory profile. Acetazolamide lowers lactate levels in breast tissue and blood without influencing breast tumor perfusion, suggesting that carbonic anhydrase inhibition lowers fermentative glycolysis. CONCLUSIONS: We conclude that carbonic anhydrases (a) elevate pH in breast carcinomas by accelerating net H+ elimination from cancer cells and across the interstitial space and (b) raise immune infiltration and inflammation in ErbB2/HER2-driven breast carcinomas, restricting tumor growth and improving patient survival.


Assuntos
Anidrases Carbônicas , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Anidrases Carbônicas/genética , Anidrases Carbônicas/metabolismo , Acetazolamida/farmacologia , Microambiente Tumoral/genética , Proteômica , Concentração de Íons de Hidrogênio , Antígenos de Neoplasias/genética , Receptor ErbB-2
5.
Sci Rep ; 13(1): 3287, 2023 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-36841900

RESUMO

This study compared perceptional and physiological responses of finger flexor exercise performed with free flow and blood flow restriction (BFR). Thirteen male advanced climbers completed three sessions of finger flexor resistance exercise at (1) 40% of MVC (Low) and (2) 75% of MVC (High) and (3) BFR at 40% of MVC (Low + BFR) in a randomized and counterbalanced order. Rate of perceived exertion for effort (RPE) and discomfort (RPD), session pleasure/displeasure (sPDF), exercise enjoyment (EES), lactate concentration and oxygen saturation were recorded after the last set. Both low-intensity sessions induced higher RPD than High (p = 0.018-0.022, ES = 1.01-1.09) and High was perceived as more enjoyable than Low-BFR (p = 0.031, ES = 1.08). No differences were found for RPE or sPDF (p = 0.132-0.804). Lactate was elevated more after High than the Low-sessions (p < 0.001, ES = 1.88-2.08). Capillary oxygen saturation was lower after Low + BFR compared to the other sessions (p = 0.031, ES = 1.04-1.27). Finally, the exercise volume was greater in Low compared to High (p = 0.022, ES = 1.14) and Low + BFR (p = 0.020, ES = 0.77). In conclusion, among advanced male climbers, performing Low + BFR led to a similar exercise volume but was perceived as more discomforting and less enjoyable compared to High. The Low session yielded similar responses as the Low + BFR but required a much greater exercise volume.


Assuntos
Treinamento Resistido , Humanos , Masculino , Ácido Láctico , Músculo Esquelético/fisiologia , Esforço Físico/fisiologia , Fluxo Sanguíneo Regional/fisiologia
6.
Front Psychol ; 13: 1010596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248475

RESUMO

The aim of this study was to compare the acute effects of performing a lower body resistance training program in one long or two shorter sessions in 1 day on training volume and affective measures. Employing a randomized-crossover design, 23 resistance-trained women (22 ± 2 years, 166 ± 6 cm, and 66.4 ± 7.5 kg) performed two training days consisting of (i) one long (46 min) or (ii) two short sessions (total of 43 min) separated by 3.5-5 h. Each training day was separated by 4-6 days and consisted of three sets to failure for six exercises. Training volume (number of repetitions lifted) were recorded during the sessions. Rating of perceived exertion for effort (RPE), rating of perceived exertion for discomfort (RPD), session displeasure/pleasure (sPDF) and exercise enjoyment (EES) were measured 10 min after each session. Participants also completed a readiness to train questionnaire (7 questions), 24 h after each session, and which training protocol they preferred, 48 h after the last session. The long session led to higher RPE (+1 point, p < 0.001, ES = 1.07), RPD (+1 point, p = 0.043, ES = 0.53) and sPDF (p = 0.010, ES = 0.59) compared to the short sessions. There was no difference in EES (p = 0.118, ES = 0.33). The short sessions had 3% higher training volume than the long session (p = 0.002, ES = 0.42). There were no differences in perceived readiness to train 24 h after the sessions (range: p = 0.166-0.856 and ES = 0.08-0.32). Twenty-two participants preferred the long session, while one preferred the short sessions. In conclusion, performing a longer, lower body, resistance training session led to greater perceptions of effort, discomfort and session pleasure than splitting the same program into two shorter sessions among resistance-trained women. However, two shorter sessions led to a greater training volume.

7.
J Sci Med Sport ; 25(12): 1023-1032, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36130847

RESUMO

OBJECTIVES: The aim of the study was to aggregate different effects between variable resistance training and traditional resistance training on maximal muscle strength and muscle power and identify potential sex- and training program-related moderator variables. DESIGN: Meta-analysis. METHODS: A systematic literature search was conducted in SPORTDiscus, PubMed, and Web of Science. Interventions were included if they compared variable resistance training and traditional resistance training in healthy adults and examined the effects on measures of maximal muscle strength and/or muscle power of the lower and/or upper body. A random-effects model was used to calculate weighted and averaged standardized mean differences. Additionally, univariate sub-group analyses were independently computed for sex and training-related moderator variables. RESULTS: Seventeen studies comprising a total of 491 participants (341 men and 150 women, age 18-37 years) were included in the analyses. In terms of maximal muscle strength, there were no statistically significant differences between variable resistance training and traditional resistance training for the lower (p = 0.46, standardized mean difference = -0.10) or the upper body (p = 0.14, standardized mean difference = -0.17). Additionally, there were no significant training-related differences in muscle power for the lower (p = 0.16, standardized mean difference = 0.21) or upper body (p = 0.81, standardized mean difference = 0.05). Sub-group analyses showed a significant moderator effect for training period and repetitions per set for maximal muscle strength in the lower body (p = 0.03-0.04) with larger strength gains following traditional resistance training when performing more repetitions per set (p = 0.02, standardized mean difference = 0.43). No other significant sub-group effects were found (p = 0.18-0.82). CONCLUSIONS: Our results suggest that variable resistance training and traditional resistance training are equally effective in improving maximal muscle strength and muscle power in healthy adults.


Assuntos
Treinamento Resistido , Adulto , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Força Muscular , Distúrbios Menstruais , Projetos de Pesquisa , Músculos
8.
Front Psychol ; 13: 912368, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783742

RESUMO

The aim of the study was to compare the acute effects of traditional resistance training and superset training on training duration, training volume and different perceptive measures. Twenty-nine resistance-trained participants (27 ± 7 years, 173 ± 9 cm, and 70 ± 14 kg) performed a whole-body workout (i) traditionally and (ii) as supersets of exercises targeting different muscle groups, in a randomized-crossover design. Each session was separated by 4-7 days, and consisted of eight exercises and three sets to failure. Training duration and number of repetitions lifted were recorded during the sessions. Rate of perceived exertion for effort (RPE), rate of perceived exertion for discomfort (RPD), session displeasure/pleasure (sPDF), and exercise enjoyment (EES) were measured 15 min after each session. Forty-eight hours after the final session participants reported which session they preferred. The superset session led to significantly higher values for RPE (1.3 points, p < 0.001, ES = 0.96) and RPD (1.0 points, p = 0.008, ES = 0.47) and tended to be higher for sPDF, i.e., more pleasurable, (p = 0.059, ES = 0.25) compared to the traditional session. There was no difference in EES (p = 0.661, ES = 0.05). The traditional session led to significantly increased training volume (4.2%, p = 0.011, ES = 0.34) and lasted 23 min (66%, p < 0.001, ES = 7.78) longer than the superset session. Eighteen of the participants preferred the superset session, while 11 preferred the traditional session. In conclusion, performing a whole-body workout as a superset session was more time-efficient, but reduced the training volume and was perceived with greater exertion for effort and discomfort than a traditional workout.

9.
Int J Cancer ; 151(7): 1150-1165, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35657342

RESUMO

Intracellular Ca2+ dynamics shape malignant behaviors of cancer cells. Whereas previous studies focused on cultured cancer cells, we here used breast organoids and colonic crypts freshly isolated from human and murine surgical biopsies. We performed fluorescence microscopy to evaluate intracellular Ca2+ concentrations in breast and colon cancer tissue with preferential focus on intracellular Ca2+ release in response to purinergic and cholinergic stimuli. Inhibition of the sarco-/endoplasmic reticulum Ca2+ ATPase with cyclopiazonic acid elicited larger Ca2+ responses in breast cancer tissue, but not in colon cancer tissue, relative to respective normal tissue. The resting intracellular Ca2+ concentration was elevated, and ATP, UTP and acetylcholine induced strongly augmented intracellular Ca2+ responses in breast cancer tissue compared with normal breast tissue. In contrast, resting intracellular Ca2+ levels and acetylcholine-induced increases in intracellular Ca2+ concentrations were unaffected and ATP- and UTP-induced Ca2+ responses were smaller in colon cancer tissue compared with normal colon tissue. In accordance with the amplified Ca2+ responses, ATP and UTP substantially increased proliferative activity-evaluated by bromodeoxyuridine incorporation-in breast cancer tissue, whereas the effect was minimal in normal breast tissue. ATP caused cell death-identified with ethidium homodimer-1 staining-in breast cancer tissue only at concentrations above the expected pathophysiological range. We conclude that intracellular Ca2+ responses are amplified in breast cancer tissue, but not in colon cancer tissue, and that nucleotide signaling stimulates breast cancer cell proliferation within the extracellular concentration range typical for solid cancer tissue.


Assuntos
Neoplasias da Mama , Neoplasias do Colo , Acetilcolina , Trifosfato de Adenosina/farmacologia , Animais , Cálcio , Proliferação de Células , Feminino , Humanos , Camundongos , Uridina Trifosfato/farmacologia
10.
BMC Sports Sci Med Rehabil ; 14(1): 87, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568897

RESUMO

BACKGROUND: The aim of this study was to assess the efficacy of a 12-week upper/lower split- versus a full-body resistance training program on maximal strength, muscle mass and explosive characteristics. Fifty resistance untrained women were pair-matched according to baseline strength and randomized to either a full-body (FB) routine that trained all of the major muscle groups in one session twice per week, or a split-body program (SPLIT) that performed 4 weekly sessions (2 upper body and 2 lower body). Both groups performed the same exercises and weekly number of sets and repetitions. Each exercise was performed with three sets and 8-12 repetition maximum (RM) loading. Study outcomes included maximal strength, muscle mass, jump height and maximal power output. RESULTS: No between-group differences were found in any of the variables. However, both FB and SPLIT increased mean 1-RM from pre- to post-test in the bench press by 25.5% versus 30.0%, lat pulldown by 27.2% versus 26.0% and leg press by 29.2% versus 28.3%, respectively. Moreover, both FB and SPLIT increased jump height by 12.5% versus 12.5%, upper-body power by 20.3% versus 16.7% and muscle mass by 1.9% versus 1.7%, p < 0.01, respectively. CONCLUSIONS: This study did not show any benefits for split-body resistance-training program compared to full-body resistance training program on measures of maximal- and explosive muscle strength, and muscle mass. TRIAL REGISTRATION: ISRCTN81548172, registered 15. February 2022.

11.
BMC Psychiatry ; 22(1): 157, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232425

RESUMO

Depressive symptoms are prevalent in adolescence, and girls have higher levels of depressive symptoms and depressive disorder than boys. Rumination and especially brooding, seem to be a central maintaining factor of depressive symptoms, where metacognitions about rumination play a prominent role in maintaining depressive rumination. There is a sex difference in adults in depressive disorder. The current investigation of a high school / community sample of adolescents aged 16-20 from Norway (N = 1198, 62.2% women) found that adolescent women had higher scores than men on all relevant measures: Depressive symptoms, negative and positive metacognitions, pondering, and brooding. A path model for predicting depressive symptoms showed that the major factors for both sexes were negative metacognitions and brooding. The predictors of depressive symptoms were invariant across sex and age groups, suggesting similar underlying mechanisms across these groups. The overall findings suggest that metacognitive therapy may be an efficient intervention for depressive symptoms among adolescents.


Assuntos
Comportamento do Adolescente , Metacognição , Adolescente , Comportamento do Adolescente/psicologia , Adulto , Depressão/diagnóstico , Depressão/psicologia , Feminino , Humanos , Masculino , Noruega
12.
Ophthalmol Retina ; 6(2): 139-152, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34256192

RESUMO

TOPIC: To examine the potential role of systemic neurodegeneration, this study aimed to provide an overview of the available evidence on the relationship between diabetic retinopathy (DR) and systemic neurodegeneration. CLINICAL RELEVANCE: The association between DR and systemic neurodegeneration is inconsistent in the literature. A summary estimate on the measures of association is important to establish whether DR may be used as a risk marker of systemic neurodegeneration. METHODS: We searched the literature databases PubMed/MEDLINE, EMBASE, and Cochrane Library on October 3, 2020, for all observational studies on humans evaluating the association between DR and systemic neurodegenerative diseases. Two authors conducted the literature search, study selection, and data extraction in an independent fashion. Studies were reviewed qualitatively in text and quantitatively in meta-analyses. Heterogeneity was evaluated with Cochran's Q and I2, and Funnel plot was used to investigate for skewed results and possible publication bias. RESULTS: We identified 27 eligible studies with a total of 1 398 041 patients with diabetes. Diagnosis of DR was made using fundus photography or examination (n = 20), health registries (n = 4), was self-reported (n = 1), or was not disclosed in the remaining studies. Neurodegenerative conditions studied were cognitive impairment (n = 23), Alzheimer's disease (n = 3), and Parkinson's disease (n = 1). In cross-sectional and longitudinal studies, respectively, presence of any DR was associated with present (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.02-2.43, P = 0.043) and incident (OR, 2.36; 95% CI, 1.50-3.71, P = 0.00021) systemic neurodegeneration, but severity of DR was not associated with differences in systemic neurodegeneration (OR, 0.98; 95% CI, 0.45-2.15, P = 0.96). CONCLUSIONS: In this systematic review, DR appears to be a marker of systemic neurodegeneration. Further studies are warranted to better elucidate the clinical practical implications of this relationship.


Assuntos
Retinopatia Diabética/etiologia , Técnicas de Diagnóstico Oftalmológico , Doenças Neurodegenerativas/complicações , Retinopatia Diabética/diagnóstico , Humanos
13.
J Strength Cond Res ; 36(2): 304-309, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895283

RESUMO

ABSTRACT: Saeterbakken, AH, Stien, N, Pedersen, H, and Andersen, V. Core muscle activation in three lower extremity exercises with different stability requirements. J Strength Cond Res 36(2): 304-309, 2022-The aim of the study was to compare core muscle surface electromyography (sEMG) during 3-repetition maximum (3RM) and the sEMG amplitude in the turnover from the descending to ascending phase in leg press, free-weight squats, and squats using the Smith machine. Nineteen women with 4.5 (±2.0) years of resistance training were recruited. After one familiarization session, the subjects performed 3RM in randomized order measuring electromyographic activity in the rectus abdominis, external oblique, and erector spinae. The exercises with the lowest stability requirements (leg press) demonstrated 17-59% and 17-42% lower core muscle sEMG amplitude than free weights and the Smith machine, respectively. No statistically significant differences were observed between the Smith machine and free weights. No statistically significant differences in turnover sEMG amplitude in the rectus abdominis between the exercises was observed, but lower sEMG amplitude was observed in external oblique and erector spinae in leg press compared with the other exercises. The 3RM loads in leg press were 54 and 47% greater than squats using the Smith machine and free weights, with 5% greater loads with the Smith machine than with free weights. In conclusion, lower mean and turnover core muscle sEMG amplitude were observed with the leg press but greater 3RM loads compared with squats with the Smith machine and free weights. The authors recommend that resistance-trained individuals use squats to include the core muscles in the kinetic chain, but there is no evidence that greater stability requirements (free weights instead of the Smith machine) will result in greater core muscle sEMG amplitude.


Assuntos
Treinamento Resistido , Eletromiografia , Feminino , Humanos , Extremidade Inferior , Músculo Esquelético , Músculos Paraespinais , Levantamento de Peso
14.
J Sports Sci Med ; 20(3): 438-447, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34267583

RESUMO

This study examined the effects of two or four weekly campus board training sessions among highly accomplished lead climbers. Sixteen advanced-to-elite climbers were randomly allocated to two (TG2), or four weekly campus board training sessions (TG4), or a control group (CG). All groups continued their normal climbing routines. Pre- and post-intervention measures included bouldering performance, maximal isometric pull-up strength using a shallow rung and a large hold (jug), and maximal reach and moves to failure. Rate of force development (RFD; absolute and 100ms) was calculated in the rung condition. TG4 improved maximal force in the jug condition (effect size (ES) = 0.40, p = 0.043), and absolute RFD more than CG (ES = 2.92, p = 0.025), whereas TG2 improved bouldering performance (ES = 2.59, p = 0.016) and maximal moves to failure on the campus board more than CG (ES = 1.65, p = 0.008). No differences between the training groups were found (p = 0.107-1.000). When merging the training groups, the training improved strength in the rung condition (ES = 0.87, p = 0.002), bouldering performance (ES = 2.37, p = 0.006), maximal reach (ES = 1.66, p = 0.006) and moves to failure (ES = 1.43, p = 0.040) more than CG. In conclusion, a five-week campus board training-block is sufficient for improving climbing-specific attributes among advanced-to-elite climbers. Sessions should be divided over four days to improve RFD or divided over two days to improve bouldering performance, compared to regular climbing training.


Assuntos
Desempenho Atlético/fisiologia , Montanhismo/fisiologia , Condicionamento Físico Humano/métodos , Adulto , Braço/anatomia & histologia , Braço/fisiologia , Dedos/fisiologia , Força da Mão , Humanos , Masculino , Fadiga Muscular/fisiologia , Força Muscular , Fatores de Tempo
15.
Elife ; 102021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34219652

RESUMO

Breast cancer heterogeneity in histology and molecular subtype influences metabolic and proliferative activity and hence the acid load on cancer cells. We hypothesized that acid-base transporters and intracellular pH (pHi) dynamics contribute inter-individual variability in breast cancer aggressiveness and prognosis. We show that Na+,HCO3- cotransport and Na+/H+ exchange dominate cellular net acid extrusion in human breast carcinomas. Na+/H+ exchange elevates pHi preferentially in estrogen receptor-negative breast carcinomas, whereas Na+,HCO3- cotransport raises pHi more in invasive lobular than ductal breast carcinomas and in higher malignancy grade breast cancer. HER2-positive breast carcinomas have elevated protein expression of Na+/H+ exchanger NHE1/SLC9A1 and Na+,HCO3- cotransporter NBCn1/SLC4A7. Increased dependency on Na+,HCO3- cotransport associates with severe breast cancer: enlarged CO2/HCO3--dependent rises in pHi predict accelerated cell proliferation, whereas enhanced CO2/HCO3--dependent net acid extrusion, elevated NBCn1 protein expression, and reduced NHE1 protein expression predict lymph node metastasis. Accordingly, we observe reduced survival for patients suffering from luminal A or basal-like/triple-negative breast cancer with high SLC4A7 and/or low SLC9A1 mRNA expression. We conclude that the molecular mechanisms of acid-base regulation depend on clinicopathological characteristics of breast cancer patients. NBCn1 expression and dependency on Na+,HCO3- cotransport for pHi regulation, measured in biopsies of human primary breast carcinomas, independently predict proliferative activity, lymph node metastasis, and patient survival.


Assuntos
Equilíbrio Ácido-Base/fisiologia , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Idoso , Animais , Bicarbonatos/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Pessoa de Meia-Idade , Organoides/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Simportadores de Sódio-Bicarbonato/genética , Simportadores de Sódio-Bicarbonato/metabolismo , Trocador 1 de Sódio-Hidrogênio/genética , Trocador 1 de Sódio-Hidrogênio/metabolismo , Trocadores de Sódio-Hidrogênio , Transcriptoma
16.
Artigo em Inglês | MEDLINE | ID: mdl-34198674

RESUMO

BACKGROUND: This study compared the muscle activity and six repetition maximum (6-RM) loads in bench press with narrow, medium, and wide grip widths with sub-group comparisons of resistance-trained (RT) and novice-trained (NT) men. METHODS: After two familiarization sessions, twenty-eight subjects lifted their 6-RM loads with the different grip widths with measurement of electromyographic activity. RESULTS: Biceps brachii activity increased with increasing grip width, whereas wide grip displayed lower triceps brachii activation than medium and narrow. In the anterior deltoid, greater activity was observed using a medium compared to narrow grip. Similar muscle activities were observed between the grip widths for the other muscles. For the RT group, greater biceps brachii activity with increasing grip width was observed, but only greater activity was observed in the NT group between narrow and wide. Comparing wide and medium grip width, the RT group showed lower triceps activation using a wide grip, whereas the NT group showed lower anterior deltoid activation using a narrow compared to medium grip. Both groups demonstrated lower 6-RM loads using a narrow grip compared to the other grips. CONCLUSION: Grip widths affect both 6-RM loads and triceps brachii, biceps brachii, and anterior deltoid activity especially between wide and narrow grip widths.


Assuntos
Treinamento Resistido , Levantamento de Peso , Eletromiografia , Força da Mão , Humanos , Masculino , Força Muscular , Músculo Esquelético
17.
J Sports Sci Med ; 20(2): 181-187, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948095

RESUMO

The aim of the study was to compare neuromuscular activation in the gluteus maximus, the biceps femoris and the erector spinae from the Romanian deadlift, the 45-degree Roman chair back extension and the seated machine back extension. Fifteen resistance-trained females performed three repetitions with 6-RM loading in all exercises in a randomized and counterbalanced order. The activation in the whole movement as well as its lower and upper parts were analyzed. The results showed that the Romanian deadlift and the Roman chair back extension activated the gluteus maximus more than the seated machine back extension (94-140%, p < 0.01). For the biceps femoris the Roman chair elicited higher activation compared to both the Romanian deadlift and the seated machine back extension (71-174%). Further, the Romanian deadlift activated the biceps femoris more compared to the seated machine back extension (61%, p < 0.01). The analyses of the different parts of the movement showed that the Roman chair produced higher levels of activation in the upper part for both the gluteus maximus and the biceps femoris, compared to the other exercises. There were no differences in activation of the erector spinae between the three exercises (p = 1.00). In conclusion, both the Roman deadlift and the Roman chair back extension would be preferable to the seated machine back extension in regards to gluteus maximus activation. The Roman chair was superior in activating the biceps femoris compared to the two other exercises. All three exercises are appropriate selections for activating the lower back muscles. For overall lower limb activation, the Roman chair was the best exercise.


Assuntos
Quadril/fisiologia , Músculo Esquelético/fisiologia , Treinamento Resistido/métodos , Fenômenos Biomecânicos , Estudos Cross-Over , Eletromiografia , Feminino , Músculos Isquiossurais/fisiologia , Humanos , Músculos Paraespinais/fisiologia , Adulto Jovem
18.
Int J Sports Physiol Perform ; 16(1): 97-102, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120362

RESUMO

PURPOSE: The Nordic hamstring exercise (NHE) has been shown to considerably reduce hamstring injuries among soccer players. However, as the load in the NHE is the person's own bodyweight, it is a very heavy exercise and difficult to individualize. The flywheel inertial leg curl (FLC) could be an alternative since the eccentric overload is based on the amount of work produced in the concentric movement. Therefore, the primary aim of this study was to compare the activation in the hamstrings at long muscle lengths in the NHE and the FLC in amateur soccer players. METHODS: Fifteen male amateur soccer players performed 5 repetitions in each exercise in a randomized and counterbalanced order. The concentric and eccentric movements were divided into lower and upper phases. Surface EMG was measured distally, proximally, and in the middle, at both muscles. RESULTS: In the lower phase in the eccentric movement, there were no significant differences between the 2 exercises (P = .101-.826). In the lower concentric movement, the FLC led to higher activation in all parts of both the biceps femoris (31%-52%, P < .001) and the semitendinosus (20%-35%, P = .001-.023). CONCLUSION: Both exercises activated the hamstrings similarly at long muscle lengths during eccentric contractions (Nordic hamstring, nonsignificantly higher). However, when performing concentric contractions, the FLC induced higher activations. Therefore, the FLC could be a useful alternative to the NHE and particularly suitable for weaker athletes before progressing to NHE.


Assuntos
Músculos Isquiossurais/fisiologia , Contração Muscular , Condicionamento Físico Humano , Futebol , Eletromiografia , Exercício Físico , Humanos , Perna (Membro) , Masculino
19.
Front Sports Act Living ; 2: 598284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33345180

RESUMO

The aim of the study was to compare neuromuscular activation, kinetics and kinematics in three variations of the deadlift: (1) free weights, (2) free weights with elastic bands as resistance (bands anchored to the ground) and (3) free weights with elastic bands as assistance (bands attached above the bar). Sixteen resistance-trained men performed one repetition of the three variations as fast as possible using a 2-repetition maximum load in randomized and counterbalanced order. Muscle activation (gluteus maximus, semitendinosus, biceps femoris, erector spinae, vastus lateralis, and vastus medialis), kinematics (average-, peak-, and time to peak velocity), and kinetics (average-, peak,-and time to peak force) were measured during the ascending movement. Resisted and assisted deadlifts led to higher average and peak force outputs (p < 0.001-0.037, ES = 0.29-0.58), and time to peak velocity was shorter when compared to the free weights deadlift (p = 0.005-0.010, ES = 0.83-1.01). However, peak force was achieved faster when using free weights (p < 0.001, ES = 1.58-2.10) and assisted deadlifts had a lower peak velocity compared to resisted and free weights deadlift (p = 0.004-0.046, ES = 0.43-0.60). There were no significant differences in muscle activation between the different conditions (p = 0.082-1.000). In conclusion, the assisted and resisted deadlift produced higher force when compared to free weights. However, free weight and resisted deadlift seem more favorable for the barbell velocity. These findings are of importance for athletes and coaches which should select exercise depending on the goal of the session.

20.
PLoS One ; 15(9): e0239202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941526

RESUMO

The aim of the study was to compare the EMG amplitude in bench press (stable loads) to bench press using loads moving in anteroposterior and mediolateral directions. Seventeen resistance-trained men, with 9.4±4.7 years of resistance training experience were recruited. After a familiarization session assessing 1 repetition maximum (RM) in the bench press, participants performed: 1) bench press with traditional stable loading 2) bench press with loads (2x5kg) attached as pendulums swinging forward/backwards and 3) left/right in randomized order. The total load was 70% of the 1RM load. Electromyography was measured in the pectoralis major, anterior- and posterior deltoid, biceps brachii, triceps brachii and external obliques. Using stable loads, the pectoralis major demonstrated lower EMG amplitude compared to the two unstable conditions. In the external obliques, the stable conditions demonstrated lower EMG amplitude than the swing in the mediolateral direction, but not the anteroposterior direction. There were no differences between two swinging loads or the three conditions for the triceps brachii, biceps brachii, anterior deltoid or posterior deltoid. In conclusion, swinging in bench press resulted in similar EMG amplitude in the shoulder- and arm muscles, but greater pectoralis and external oblique (only mediolateral swing) activity compared to bench press.


Assuntos
Contração Muscular , Treinamento Resistido/métodos , Adulto , Eletromiografia/métodos , Humanos , Masculino , Músculo Esquelético/fisiologia , Distribuição Aleatória
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