Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force which supports effective healing. A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds. In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy. Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance. The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing. The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology. The study also defines how and what mechanical changes influence tissue regeneration and wound healing. The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study.

PurposeThis prospective, randomized and single-blinded study assesses the influence of radial extracorporeal shock wave therapy (rESWT) in patients with low back pain (LBP).MethodsA total of 52 patients with LBP were enrolled in the study, out of which a homogeneous group of 40 patients with mean age of 53.45±4.9 years was included. Patients were randomized into group A (n=20) treated with rESWT (2000 pulses; 2.5 bars; 5 Hz, 7 mins) performed twice a week for five weeks (10 sessions) and stabilization training, as well as group B (n=20) treated with sham rESWT and stabilization training. To analyze the therapeutic progress, the following tests were performed (before and after therapy; 1 and 3 months follow-up) to assess pain and functional efficiency: (1) Visual Analog Scale (VAS), (2) Laitinen Pain Scale (LPS), and (3) Oswestry Disability Index (ODI).ResultsThe control group had a statistically significant advantage over the rESWT group (4.4 vs. 3.1 points on the VAS; p=0.039). However, in long-term observations, group A gradually experienced more pain relief than group B (2.7 vs. 3.5 points, p>0.05, at one month and 2.0 vs. 4.4 points at three months after treatment; p<0.0001). Similar findings can be seen in the analysis of changes in pain sensations measured with the LPS. The functional state (ODI) was better in rESWT group, especially in follow-up observation (9.3 vs. 14.6 points, p=0.033, at one month and 9.3 vs. 17.8 points, p=0.004, at three months after treatment).ConclusionThe rESWT combined with stabilization training is particularly effective in the long-term and achieves a stable beneficial effect for patients with LBP. The use of rESWT has a significant long-term influence on the reduction of pain and the improvement of the general functional state in relation to the conventional motor improvement program.

BackgroundMaspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. Several studies have suggested potential anti-proliferative activity of maspin as well as sensitizing activity of maspin for therapeutic cytotoxic agents in breast cancer tissue culture and animal models. All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. In this study, the effect of maspin cytoplasmic and nuclear location and expression level on breast cancer proliferation and patient survival was studied.MethodsTissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. The localization and expression level of maspin were correlated with estimated patient overall survival and percent of Ki-67-positive cells. In further studies, we created constructs for transient transfection of maspin into breast cancer cells with targeted cytoplasmic and nuclear location. We analyzed the effect of maspin location in normal epithelial cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR-3 - by immunofluorescence and proliferation assay.ResultsWe observed a strong positive correlation between moderate and high nuclear maspin level and survival of patients. Moreover, a statistically significant negative relationship was observed between nuclear maspin and Ki-67 expression in patients with invasive ductal breast cancer. Spearman’s correlation analysis showed a negative correlation between level of maspin localized in nucleus and percentage of Ki-67 positive cells. No such differences were observed in cells with cytoplasmic maspin. We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. The anti-proliferative effect of nuclear maspin on breast cancer cells was statistically significant in comparison to cytoplasmic maspin.ConclusionsOur results suggest that nuclear maspin localization may be a prognostic factor in breast cancer and may have a strong therapeutic potential in gene therapy. Moreover, these data provide a new insight into the role of cytoplasmic and nuclear fractions of maspin in breast cancer.

Purpose: This systematic review examines intervention studies using extracorporeal shock wave therapy (ESWT) application in post-stroke muscle spasticity with particular emphasis on the comparison of two different types of radial (rESWT) and focused shock waves (fESWT). Methods: PubMed, PEDro, Scopus, and EBSCOhost databases were systematically searched. Studies published between the years 2000 and 2019 in the impact factor journals and available in the English full-text version were eligible for inclusion. All qualified articles were classified in terms of their scientific reliability and methodological quality using the PEDro criteria. The PRISMA guidelines were followed and the registration on the PROSPERO database was done. Results: A total of 17 articles were reviewed of a total sample of 303 patients (age: 57.87 ±10.45 years and duration of stroke: 40.49±25.63 months) who were treated with ESWT. Recent data confirm both a subjective (spasticity, pain, and functioning) and objective (range of motion, postural control, muscular endurance, muscle tone, and muscle elasticity) improvements for post-stroke spasticity. The mean difference showing clinical improvement was: Δ=34.45% of grade for fESWT and Δ=34.97% for rESWT that gives a slightly better effect of rESWT (Δ=0.52%) for spasticity (p<0.05), and Δ=38.83% of angular degrees for fESWT and Δ=32.26% for rESWT that determines the more beneficial effect of fESWT (Δ=6.57%) for range of motion (p<0.05), and Δ=18.32% for fESWT and Δ=22.27% for rESWT that gives a slightly better effect of rESWT (Δ=3.95%) for alpha motor neuron excitability (p<0.05). The mean PEDro score was 4.70±2.5 points for fESWT and 5.71±2.21 points for rESWT, thus an overall quality of evidence grade of moderate ("fair" for fESWT and "good" for rESWT). Three studies in fESWT and four in rESWT obtained Sackett's grading system's highest Level 1 of evidence. Conclusion: The studies affirm the effectiveness of ESWT in reducing muscle spasticity and improving motor recovery after stroke.

P-glycoprotein (P-gp) is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q), manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR) phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB) through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1) was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp.

BackgroundLaser therapy seems to be a beneficial physical agent for chronic low back pain (LBP), and it is commonly used in the clinical rehabilitation practice. However, there are still no indisputable and clearly defined protocols and practical guidelines, and further, the methodology of the previous reports leaves many unsatisfied and raises some reservations.ObjectiveThe aim of this study was to evaluate the effectiveness of low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) in patients with lumbar disc degenerative changes based on the analysis of the short- and long-term results and in comparison with the placebo effect.DesignThis study was a prospective and placebo-controlled clinical trial.Materials and methodsA group of 68 participants were qualified for the therapy and were assigned to four comparative groups in the order they volunteered: HILT of 1,064 nm, 60 J/cm2, 10 minutes (HILT); sham (HILT placebo); LLLT of 785 nm, 8 J/cm2, 8 minutes; and sham (LLLT placebo). The following tests were used to assess the effectiveness of treatment: 1) the visual analogue scale; 2) the Laitinen Questionnaire Indicators of Pain; 3) the Oswestry Disability Index; 4) the Roland–Morris Disability Questionnaire; 5) Lasegue test; and 6) Schober’s test. All measurements were carried out before and after irradiations (3 weeks) and in follow-ups (1 and 3 months).ResultsAfter applying verum or placebo laser irradiation, therapeutic progress was observed in all comparative groups; however, no statistically significant differences were observed among the procedures.ConclusionThe high- and low-energy laser therapy methods used in the present article are ineffective in relation to patients with lumbar disc degenerative changes in both the short- and long-term perspectives and do not show a significant advantage over the placebo effect.

Objective: To evaluate the effect of laser irradiation at different wavelengths on the expression of selected growth factors and inflammatory mediators at particular stages of the wound healing process.Methods: Sixty-seven patients were recruited, treated, and analyzed (group A - 940 nm: 17 patients; group B - 808 nm: 18 patients; group C - 658 nm: 16 patients; group D - sham therapy: 17 patients). Patients received a basic treatment, including repositioning and mobilization, air pressure mattress and bed support surfaces, wound cleansing and drug therapy. Additionally, patients received laser therapy once a day, 5 times a week for 1 month in use of a semiconductor lasers (GaAlAs) which emitted a continuous radiation emission at separate wavelengths of 940 nm (group A), 808 nm (group B) and 658 nm (group C). In group D (sham therapy), laser therapy was applied in the same manner, but the device was off during each session (only the applicator was switched on to scan pressure ulcers using none coherent red visible light).Results: The positive changes in the measured serum (IL-2, IL-6 and TNF-α) and wound tissue (TNF-α, VEGF and TGFβ1) parameters appeared to be connected only with the wavelength of 658 nm. The significant change in pro-inflammatory mediator levels [interleukin 2 (IL-2) with p=0.008 and interleukin 6 (IL-6) with p=0.016] was noticed after two weeks of laser therapy. In the other groups, the inflammation was also reduced, but the process was not as marked as in group C. Similarly, in the case of tumor necrosis factor (TNF-α) concentration, where after two weeks of treatment with irradiation at a wavelength of 658 nm, a rapid suppression was observed (p=0.001), whereas in the other groups, these results were much slower and not as obvious. Interestingly, again in the case of group C, the change in TNF-α concentration in wound tissue was most intensive (≈75% reduction), whereas the changes in other groups were not as obvious (≈50% reduction). After irradiation (658 nm), the VEGF expression increased significantly within the first two weeks, and then it decreased and maintained a stable level. In contrast, the TGFβ1 activity remained level, but always higher in comparison to other groupsConclusions: The effective healing of pressure ulcers is connected with laser irradiation at a wavelength of 658 nm. We believe that this effect is related to the inhibition of inflammatory processes in the wound and stimulation of angiogenesis and fibroblast proliferation at this specific radiation (based both on concentration of interleukins and TNF-α serum level and VEGF, TGFβ1, TNF-α activities in wound biopsies). Laser therapy at wavelengths of 940 and 808 nm does not significantly affect the above-mentioned repair processes, which explains its low effectiveness in the treatment of pressure ulcers.

Laminin-associated polypeptide 2 (LAP2) proteins are alternatively spliced products of a single gene; they belong to the LEM domain family and, in mammals, locate to the nuclear envelope (NE) and nuclear lamina. Isoforms lacking the transmembrane domain also locate to the nucleoplasm. We used new specific antibodies against the N-terminal domain of Xenopus LAP2 to perform immunoprecipitation, identification and localization studies during Xenopus development. By immunoprecipitation and mass spectrometry (LC/MS/MS), we identified the embryonic isoform XLAP2γ, which was downregulated during development similarly to XLAP2ω. Embryonic isoforms XLAP2ω and XLAP2γ were located in close association with chromatin up to the blastula stage. Later in development, both embryonic isoforms and the adult isoform XLAP2β were localized in a similar way at the NE. All isoforms colocalized with lamin B2/B3 during development, whereas XLAP2β was colocalized with lamin B2 and apparently with the F/G repeat nucleoporins throughout the cell cycle in adult tissues and culture cells. XLAP2β was localized in clusters on chromatin, both at the NE and inside the nucleus. Embryonic isoforms were also localized in clusters at the NE of oocytes. Our results suggest that XLAP2 isoforms participate in the maintenance and anchoring of chromatin domains to the NE and in the formation of lamin B microdomains.Electronic supplementary materialThe online version of this article (doi:10.1007/s00441-011-1129-2) contains supplementary material, which is available to authorized users.