Homeodomains are helix-turn-helix type DNA-binding domains that exhibit sequence-specific DNA binding by insertion of their "recognition" alpha helices into the major groove and a short N-terminal arm into the adjacent minor groove without inducing substantial distortion of the DNA. The stability and DNA binding of four representatives of this family, MATalpha2, engrailed, Antennapedia, and NK-2, and truncated forms of the last two lacking their N-terminal arms have been studied by a combination of optical and microcalorimetric methods at different temperatures and salt concentrations. It was found that the stability of the free homeodomains in solution is rather low and, surprisingly, is reduced by the presence of the N-terminal arm for the Antennapedia and NK-2 domains. Their stabilities depend significantly upon the presence of salt: strongly for NaCl but less so for NaF, demonstrating specific interactions with chloride ions. The enthalpies of association of the homeodomains with their cognate DNAs are negative, at 20 degrees C varying only between -12 and -26 kJ/mol for the intact homeodomains, and the entropies of association are positive; i.e., DNA binding is both enthalpy- and entropy-driven. Analysis of the salt dependence of the association constants showed that the electrostatic component of the Gibbs energy of association resulting from the entropy of mixing of released ions dominates the binding, being about twice the magnitude of the nonelectrostatic component that results from dehydration of the protein/DNA interface, van der Waals interactions, and hydrogen bonding. A comparison of the effects of NaCl/KCl with NaF showed that homeodomain binding results in a release not only of cations from the DNA phosphates but also of chloride ions specifically associated with the proteins. The binding of the basic N-terminal arms in the minor groove is entirely enthalpic with a negative heat capacity effect, i.e., is due to sequence-specific formation of hydrogen bonds and hydrophobic interactions rather than electrostatic contacts with the DNA phosphates.
Stroke is the second leading cause of mortality worldwide and one of the main causes of adult disability. Many studies have suggested that combination therapies provide better outcomes in patients with stroke than monotherapies. The combination of botulinum-A toxin (BTX) injection with rehabilitation methods, such as modified constraint-induced movement therapy (BTX-mCIMT), has emerged as a highly promising intervention for promoting motor recovery after stroke. Thus, the present study compared the effectiveness of the combination of BTX with high-dose conventional therapy (BTX-ICT) and BTX-mCIMT for improving motor recovery and reducing spasticity of the upper limb in patients with stroke. This study recruited 64 patients with stroke. The patients were randomly allocated to two groups, namely, BTX-ICT and BTX-mCIMT. Modified Ashworth scale (MAS), Fugl–Meyer assessment (FMA), and Barthel index (BI) assessment scores were determined for the patients in both the groups before and at 4 weeks after the BTX injection. After four weeks of treatment, the MAS, FMA, and BI assessment scores of the patients in both groups were significantly higher than the scores before the treatments (P < 0.05). At the end of 4 weeks, the patients in the BTX-mCIMT group showed significantly higher mean FMA and BI assessment scores than the patients in the BTX-ICT group (P < 0.05). However, no significant statistical difference was observed in the MAS score of the patients in the two groups (P > 0.05). Our results indicated that while both BTX-mCIMT and BTX-ICT promoted motor function recovery in patients with stroke, BTX-mCIMT exerted higher therapeutic effects than BTX-ICT on motor function recovery and in the activities of daily living of patients with stroke.
Objective: The aim of the present study was to systematically evaluate and quantify the effectiveness of dual-task training on gait parameters, motor symptoms and balance in individuals diagnosed with Parkinson’s disease. Data resources: A systematic review of published literature was conducted until May 2020, using PubMed, EMBASE, Cochrane Library, Web of Science, EBSCO and CNKI databases. Methods: We included randomized controlled trials (RCTs) and non-RCTs to evaluate the effects of dual-task training compared with those of non-intervention or other forms of training. The measurements included gait parameters, motor symptoms and balance parameters. Methodological quality was assessed using the PEDro scale. Outcomes were pooled by calculating between-group mean differences using fixed- or random-effects models based on study heterogeneity. Results: A total of 11 RCTs comprising 322 subjects were included in the present meta-analysis. Results showed that dual-task training significantly improved gait speed (standardized mean difference [SMD], −0.23; 95% confidence interval [CI], −0.38 to −0.08; P = 0.002), cadence (SMD, −0.25; 95% CI, −0.48 to −0.02; P = 0.03), motor symptoms (SMD, 0.56; 95% CI, 0.18 to 0.94; P = 0.004) and balance (SMD, −0.44; 95% CI, −0.84 to −0.05; P = 0.03). However, no significant changes were detected in step length or stride length. Conclusion: Dual-task training was effective in improving gait performance, motor symptoms and balance in patients with Parkinson’s disease relative to other forms of training or non-intervention.
Motor dysfunction is a common and severe complication of stroke that affects the quality of life of these patients. Currently, motor function rehabilitation predominantly focuses on active movement training; nevertheless, the role of sensory input is usually overlooked. Sensory input is very important to motor function. Voluntary functional movement necessitates preparation, execution, and monitoring functions of the central nervous system, while the monitoring needs the participation of the sensory system. Sensory signals affect motor functions by inputting external environment information and intrinsic physiological status as well as by guiding initiation of the motor system. Recent studies focusing on sensory input-based rehabilitation training for post-stroke dyskinesia have demonstrated that sensory function has significant effects on voluntary functional movements. In conclusion, sensory input plays a crucial role in motor function rehabilitation, and the combined sensorimotor training modality is more effective than conventional motor-oriented approaches.
Increasing evidence demonstrates that inflammation plays an important role in cerebral ischemia. Carvacrol, a monoterpenic phenol, is naturally occurring in various plants belonging to the family Lamiaceae and exerts protective effects in a mice model of focal cerebral ischemia/reperfusion injury by reducing infarct volume and decreasing the expression of cleaved caspase-3. However, the anti-inflammatory mechanisms by which carvacrol protect the brain have yet to be fully elucidated. We investigated the effects of carvacrol on inflammatory reaction and inflammatory mediators in middle cerebral artery occlusion rats. The results of the present study showed that carvacrol inhibited the levels of inflammatory cytokines and myeloperoxidase (MPO) activity, as well as the expression of iNOS and COX-2. It also increased SOD activity and decreased MDA level in ischemic cortical tissues. In addition, carvacrol treatment suppressed the ischemia/reperfusion-induced increase in the protein expression of nuclear NF-kB p65. In conclusion, we have shown that carvacrol inhibits the inflammatory response via inhibition of the NF-kB signaling pathway in a rat model of focal cerebral ischemia. Therefore, carvacrol may be a potential therapeutic agent for the treatment of cerebral ischemia injury.
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