Physiology international最新文献

Background: The most prevalent form of lung cancer, lung adenocarcinoma (LUAD), has significant incidence and fatality rates worldwide. When treating LUAD, osimertinib resistance is a typical problem. Thus, it is imperative to address the concerns of clarifying the mechanism of osimertinib resistance in LUAD and enhancing medication sensitivity.

Methods: Using bioinformatics techniques, expression and possible biological roles of BMP8A in LUAD were examined, and predictions were made about upstream regulatory variables and binding locations. H1975 cell line, resistant to osimertinib, was created. Western blot and RT-qPCR were instrumental to determine mRNA and protein expression of FABP5, ACC1, and FASN associated to lipid metabolism. A fluorescent lipid synthesis test kit was utilized to detect amount of triglycerides present in culture medium. BMP8A and RUNX2 mRNA levels were assayed using RT-qPCR. Utilizing CCK-8 and ANNEXIN V-FITC/PI flow cytometry, cell viability was assessed. Through the use of dual luciferase assays, whether RUNX2 could regulate BMP8A was confirmed. CHIP was further employed to confirm whether the two were bound together.

Results: BMP8A and fatty acid metabolism (FAM) have a strong association, as revealed by bioinformatics investigation, and RUNX2 is its upstream transcription factor. Osimertinib-resistant H1975 cell lines were successfully created, and these cell lines showed a significant upregulation of BMP8A expression. The drug sensitivity of the resistant cell lines was decreased, and their FAM level was considerably enhanced by overexpressing BMP8A. Changes in drug sensitivity and FAM were reversed by using FAM inhibitors. An efficient binding of RUNX2 to the BMP8A promoter region was demonstrated by experimental validation, hence activating the production of the BMP8A gene. Lowering LUAD cell survival rates, lipid metabolism levels, and BMP8A expression were all caused by RUNX2 knockdown.

Conclusion: RUNX2 activated BMP8A-mediated FAM to facilitate osimertinib resistance in LUAD.

Purpose: Osteosarcoma (OS) is the most common primary bone tumor. Insulin Growth Factor-2 Binding Protein 3 (IGF2BP3) regulates mRNA stability and is a potential oncogene in many cancers, but its role in OS remains unknown.

Methods: The CCK-8 assay was used to evaluate the cell viability. Cell cycle and apoptosis were determined using flow cytometry. Real-time PCR and western blot were performed to measure gene expression.

Results: Silencing IGF2BP3 weakened cell proliferation and inhibited cell cycle progression. Mechanistically, we demonstrated the regulation of E3 ubiquitin ligase ubiquitination factor E4A (UBE4A) by IGF2BP3. The RIP, MeRIP, and RNA decay assays showed that IGF2BP3 bound to the m6A-modified UBE4A mRNA, thereby enhancing its stability and subsequently promoting the malignant proliferation of OS. Overexpression of UBE4A reversed the decrease in cell viability and induction of apoptosis caused by IGFBP3 knockdown. Furthermore, UBE4A promoted the ubiquitination modification of Natriuretic Peptide Receptor 3 (NPR3), a previously known tumor suppressor in OS. High expression of NPR3 significantly inhibited proliferation and promoted apoptosis in UBE4A-overexpressing cells.

Conclusions: IGF2BP3 is upregulated in OS and promotes the malignant phenotype of OS cells. Mechanistically, IGF2BP3 stabilizes UBE4A mRNA to increase UBE4A expression, thereby facilitating the ubiquitination and proteasomal degradation of tumor-suppressor NPR3 to exert pro-tumor functions in OS.

Background: Among genetic variants associated with physical performance, ACTN3 R577X and ACE I/D are among the most studied. However, their prevalence and functional significance in combat sports like Taekwondo remain underexplored.

Objective: To evaluate the prevalence of ACTN3 R577X and ACE I/D polymorphisms in Taekwondo athletes and controls, and to investigate their association with competitive level and belt ranking.

Methods: A total of 204 individuals (119 athletes and 85 controls) were genotyped via PCR using DNA from buccal cells. Genotype distributions were analyzed for Hardy-Weinberg equilibrium (HWE). Associations with performance level and belt ranking were tested. A "two loci profile" variable was created by combining genotypes into power-, endurance-, or mixed-oriented categories.

Results: ACE I/D genotypes in athletes deviated from HWE due to a higher prevalence of the DD genotype (32.2%, P = 0.017). In contrast, controls were in HWE for ACE but not for ACTN3. The DD genotype was more common among national-level competitors and black belts. The ACTN3 RR genotype also showed higher frequency among black belts but without statistical significance. When combining ACE DD and/or ACTN3 RR genotypes, black belts showed significantly greater prevalence than other ranks (37.5% vs. 14.3%, P = 0.038).

Conclusion: Genotypes related to strength and power appear more frequent among higher-performing Taekwondo athletes. These results contribute to the understanding of a synergetic action of two loci in combat sports and may support future applications in personalized training and talent identification.

Purpose: To investigate the effects of exercise-induced metabolites on the perceptions of pain and fatigue.

Method: Fifty-three adults completed six visits. The first visit involved multiple baseline tests, including a blood-flow-restricted exercise performance test (i.e., 2 sets of knee extension to task-failure at 30% 1RM with 80% arterial occlusion pressure [AOP]). In subsequent visits, participants performed five experimental conditions in a randomized order: 1) time-matched, non-exercise control (Control) and four low-load exercise conditions with either 2) 80%AOP (LL+80%), 3) 40%AOP (LL+40%), 4) intermittent 80%AOP (LL+80%Int), or 5) no blood flow restriction (0 mmHg; LL). Three-minute post-exercise circulatory occlusion (PECO) was employed to assess the effect of pooled muscle metabolites on perceived pain and fatigue and pain sensitivity (via pressure pain threshold). The results from liner mixed model are presented as mean [95% confidence interval].

Results: Condition-by-time interactions were found for perceived pain (P < 0.001) and fatigue (P < 0.001). LL+80% elicited higher increase in thigh pain (2.7 [2.2, 3.1] AU) and fatigue (2.1 [1.7, 2.5] AU) compared to LL+40%, LL+80%Int, and LL. Pain and fatigue did not change differently during PECO but declined three minutes post-PECO in exercise conditions (except fatigue in LL+80%Int). There was evidence of an interaction for pressure pain threshold of the tibialis anterior but not the forearm.

Conclusion: Continuous blood flow restriction with higher pressure (80%AOP) augmented the pain and fatigue perceptions from submaximal unilateral knee extension exercise, arguably through muscle metabolite accumulation (estimated by PECO). Conflicting evidence existed for blood flow restricted exercise-induced hypoalgesia, possibly confounded by PECO.

Purpose: Epilepsy is a widespread, long-term neurological condition triggered by an overabundance of electrical activity from the neurons in the brain. Genistein, a natural isoflavone found in soybeans, can prevent chronic diseases such as cardiovascular disease and osteoporosis. We aimed to investigate the potential protective effects of genistein on epilepsy using rat models through behavior analysis and investigation of key pathways, including antioxidant activity (Nrf2 and HO-1), promoting mitochondrial biogenesis (TFAM), and reducing brain tissue apoptosis (BCL2, BAX, and caspases).

Main methods: PTZ was used to induce epilepsy in rats, and then they were treated with genistein. The hippocampus sections were stained with Nissl stain, and others were stained with anti-TFAM antibodies. Furthermore, TFAM, Nrf2, HO-1, BCL2, BAX, and caspases-3/8/9 gene expression and protein levels were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and complementary biochemical/functional assays.

Results: Rats treated with genistein displayed notable progress in their behavior during behavioral tests. Sections stained with Nissl revealed that genistein increased the staining intensity of Nissl granules in the cerebral cortex. Additionally, genistein increased the expression of TFAM, Nrf2, HO-1, and BCL2, which reduced levels of BAX and caspase-3/8/9.

Conclusions: Genistein safeguards against epilepsy in rats by enhancing their behavior and reinstating normal neuron structure. Its protective benefits may stem from its potential to boost antioxidant activity and promote mitochondrial biogenesis, which in turn decreases cell apoptosis.

Background/aim: This study aimed to compare electrophysiological hearing thresholds in guinea pigs exposed to intra-cochlear trauma using the continuous loop deconvolution averaging method (CLAD) and quasi-auditory steady state responses (QASSR).

Material and methods: Eight guinea pigs were implanted with electrodes at the lambda point. Intra-cochlear trauma was induced via electrode insertion. Hearing thresholds and amplitudes at 0.5, 1, 4, and 16 kHz were recorded using CLAD and QASSR methods. Recordings from the lambda electrode were compared with those from a conventional retro-auricular needle electrode.

Results: The lambda electrode demonstrated significantly lower mean auditory thresholds at all tested frequencies compared to the retro-auricular needle electrode in both trauma and non-trauma groups (P < 0.05). Amplitude comparisons revealed statistically significant differences at 1 kHz in the trauma group, and at 4 and 16 kHz in both trauma and non-trauma groups (P < 0.05).

Conclusion: The QASSR technique, coupled with chronic lambda electrode implantation, provides an effective method for estimating hearing loss induced by intra-cochlear trauma in guinea pigs.

Triathlon is a very complex sport, as the athlete has to master the characteristics of three sports (swimming, cycling and running), and the tasks of coaches are increased by the need to get the most out of all three. This sport improves endurance, has a positive effect on muscle development, movement coordination, breathing, and circulation.For talent identification factors determining the performance in triathlon are essential (physiological, anthropometric, psychosocial and tactical factors).Scientific literature concerning performance in triathlon sport is rather scarce. Although there are some studies in this field, there is little comprehensive literature analyzing training of youth athletes. The aim of our research was (i) to conduct a targeted literature review of the body composition and performance of youth triathletes and (ii) comparing results with those of elite adults, (iii) determining factors playing a prominent role in the selection and performance of triathletes.The results of our research reveal that factors like the appropriate competition age (approx. 28-30 years for both sexes), anthropometric parameters (it is necessary to take into account the distance the athlete covers) and performance criteria (the most important is VO2max) are essential for successful selection and subsequent success.In the world of triathlon constant regulatory changes and the need to adapt new competitive demands necessitate keeping our knowledge up to date.

The mechanical efficiency of the quadriceps femoris muscle-tendon unit likely depends on its structural and mechanical properties. Therefore, the purpose of this study was to assess the mechanical efficiency in vivo under various stretch-shortening cycle conditions and to investigate how the morphological and mechanical properties of the quadriceps femoris influence mechanical efficiency.We used MRI to measure quadriceps femoris muscle and tendon morphological properties in young females (n = 9), and we determined mechanical efficiency during stretch-shortening cycle contractions using computer-controlled dynamometer. Testing protocol included contractions with moderate and maximal pretension level and stretching loads of 20 and 100J.Greater mechanical efficiency was associated with larger knee flexion angles and increased positive work under moderate pretension levels with both 20 J (r = 0.67, P = 0.045; r = 0.82, P = 0.007) and 100 J stretch loads (r = 0.87, P = 0.006; r = 0.82, P = 0.007).These findings suggest that lower stretching loads enhance muscle-tendon interaction efficiency by favoring tendon elongation during muscle-tendon unit lengthening, resulting in higher mechanical efficiency. No morphological or mechanical parameter of the muscle-tendon unit were linked to mechanical efficiency, suggesting that efficiency may depend more on muscle activation patterns than on structure.

Introduction: Fatigue accumulation in the final 100 m of a 400-m sprint impairs neuromuscular coordination and biomechanics, often resulting in performance decline. This study investigated how fatigue affects lower-limb coordination, joint mechanics, and recovery patterns in competitive sprinters.

Methods: A randomized controlled trial was conducted with 30 trained male Chinese 400-m sprinters (age: 29.8 ± 2.7 years), allocated into control (n = 15) and experimental (n = 15) groups. The experimental group completed five 80-m maximal sprints with decreasing rest intervals before running a 400-m sprint; the control group performed only the 400-m sprint. Kinematic and EMG data were recorded during the final 100 m. Recovery measures-Rating of Perceived Exertion (RPE), Jump Height, Peak Force, and Peak Power-were assessed at 30 min, 1 h, 3 h, and 36 h post-sprint. Data were analysed using two-way ANOVA and paired t-tests.

Results: Fatigue significantly increased stride variability in the experimental group from 0.022 ± 0.010 m (Session I) to 0.035 ± 0.012 m (Session II, P < 0.0001), while hip flexion decreased from 33.1 ± 4.5° to 26.7 ± 3.9° (P = 0.0012), and CRP rose from 15.6 ± 2.9° to 24.1 ± 4.2° (P = 0.002). EMG activation declined in key muscles, including Rectus Femoris (0.28 ± 0.05 to 0.23 ± 0.05, P = 0.0035) and Soleus (0.21 ± 0.05 to 0.18 ± 0.04, P = 0.0003). RPE increased from 10.9 ± 2.05 to 19.5 ± 1.20 at 30 min post-sprint (P < 0.0001), with Jump Height decreasing from 49.5 ± 5.02 cm to 34.8 ± 5.10 cm (P < 0.0001), Peak Force from 17.8 ± 1.28 to 15.1 ± 1.42 N kg-1 (P = 0.0012), and Peak Power from 65.7 ± 6.03 to 50.4 ± 4.95 W kg-1 (P < 0.0001).

Conclusion: Fatigue in the final sprint phase significantly impairs joint coordination, muscle activation, and power output. These findings highlight the need for targeted fatigue-resistance training and individualized recovery protocols. A limitation is the all-male sample, which may affect generalizability.