Tissue Contraction Research Articles

Human Tendon-on-a-Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis.

Understanding the myofibroblast microenvironment is critical to developing therapies for fibrotic diseases. Here the development of a novel human tendon-on-a-chip (hToC) is reported to model this crosstalk in peritendinous adhesions, which currently lacks biological therapies. The hToC facilitates cellular and paracrine interactions between a vascular component, which contains endothelial cells and monocytes, and a tissue hydrogel component that houses tendon cells and macrophages. It is found that the hToC replicates some aspects of in vivo inflammatory and fibrotic phenotypes in preclinical and clinical samples, including activated mTOR signaling, vascular inflammation, tissue contraction induced by myofibroblast activation, inflammatory cytokines secretion, and transendothelial migration of monocytes to the tissue hydrogel. Transcriptional analysis demonstrates significant overlap in enriched pathways in the hToC with human tenolysis samples, including the activation of mTOR signaling. Rapamycin suppresses the vascular inflammation and fibrotic phenotype in the hToC, which provides proof-of-concept of its utility as an in vitro tool for investigating multicellular crosstalk in fibrosis and testing therapeutics to mitigate it.

Tissue Contraction With Helium-Based Plasma Radiofrequency Technology: A Preliminary Report of Initial Ultrasound Findings

Abstract Background Application of helium-based plasma radiofrequency (RF; Renuvion, Apyx Medical, Clearwater, Florida, USA) in the subcutaneous plane results in tissue coagulation and contraction. While traditionally, impact of thermal devices on skin laxity is assessed by measuring changes in skin surface area, this indirect measure does not permit intraoperative assessment or differentiation of effects from various treatments. Objectives To determine the amount of soft tissue contraction achieved by multiple passes of helium plasma RF energy to the subcutaneous connective tissues following power-assisted liposuction (PAL). Methods In this single-center study, 4 subjects were assessed using real-time ultrasound measurements at baseline and following both PAL and each pass with helium plasma RF. Results Based on changes in the distance from the skin (dermal basement membrane) to Scarpa’s fascia, PAL produced an average reduction of 36.7% (SD 14.6, range 24.7%-58.6%) due to the fat removal. Contraction observed with helium plasma RF was greatest for the first pass, with a mean decrease of 27.0% (SD 19.6, range 4.5%-52.1%) in distance relative to distance measured following liposuction. Subsequent passes resulted in additional incremental contraction relative to prior treatment pass: 17.0% (5.1) for pass 2, 7.7% (17.5) for pass 3, and 7.1% (5.5) for pass 4. Overall, helium plasma RF resulted in an average contraction of 44.0% (SD 17.2, range 27.1%-59.4%) in the skin-to-Scarpa-fascia measurement. Conclusions Helium plasma RF improved tissue contraction following PAL by an average of 44% and data suggest that the greatest increase in tissue contraction is obtained by the first treatment pass.

Understanding of Polydopamine Formulation for Oral Therapeutic Delivery in Ulcerative Colitis Treatment

AbstractOral therapeutic delivery remains challenged by gastrointestinal tract (GI) barriers, which hinders the successful transition of therapeutic candidates into clinical treatments. Polydopamine (PDA), with its versatile ability to overcome GI barriers, offers a promising drug formulation technology to address the challenge. Nevertheless, many critical questions remain unanswered regarding the practicality of PDA‐based formulations. Building on the previous research, which tackled multiple physicochemical aspects, the current study aims to address another three outstanding issues, including the quantification of residual dopamine (DA) in PDA‐based formulations, the examination of these formulations stimulatory effects on colon tissue, and the potential anti‐inflammatory properties. To facilitate this investigation, a curcumin‐containing nanomedicine (CP@CCS) is prepared as a representative PDA‐based formulation. The results reveal a marked decrease of residual DA within the formulation. In the treatment of ulcerative colitis (UC), the formulation do not provoke the substantial contractions in colon tissue typically induced by DA. Furthermore, in vivo evaluation verified the supplementary anti‐UC benefits of PDA. These outcomes add evidence for the practicality of PDA‐based formulations in terms of safety and therapeutic efficacy. Finally, a conceptual framework is proposed for understanding the role of PDA in oral therapeutic delivery, thereby providing insightful directions for subsequent research.

Kinin B1- and B2-Receptor Subtypes Contract Isolated Bovine Ciliary Muscle: Their Role in Ocular Lens Function and Intraocular Pressure Reduction

Background: Bradykinin is an endogenously produced nonapeptide with many physiological and pathological functions that are mediated by two pharmacologically defined receptor subtypes, B1- and B2-receptors. Current studies sought to characterize the functional bradykinin (BK) receptors present in freshly isolated bovine ciliary muscle (BCM) using an organ-bath tissue contraction system. Methods: Cumulative longitudinal isometric tension responses of BCM strips (4–5 mm) were recorded before and after the addition of test compounds to BCM strips hooked up to an isometric strain gauge transducer system. Results: BK and its analogs (7–11 concentrations) contracted BCM in a biphasic concentration-dependent manner. The first high affinity/potency phase accounted for 40–60% of the maximal contraction by each of BK (potency, EC50 = 0.9 ± 0.3 nM), Lys-BK (EC50 = 0.7 ± 0.1 nM), Met-Lys-BK (EC50 = 1 ± 0.1 nM), Hyp3-BK (EC50 = 1 ± 0.2 nM), RMP-7 (EC50 = 3.5 ± 0.5 nM), and Des-Arg9-BK (EC50 = 10 ± 0.4nM) (mean ± SEM, n = 3–8). The second lower activity phase of contraction potency values for these peptides ranged between 100 nM and 3 µM. In the presence of a selective B1-receptor antagonist (R715; 0.1–10 µM), the concentration–response curves to Des-Arg9-BK (B1-receptor agonist) were still observed, indicating activation of B2-receptors by this kinin. Likewise, when B2-receptors were completely blocked by using a B2-selective antagonist (WIN-64338; 1–10 µM), BK still induced BCM contraction, now by stimulating B1-receptors. Conclusions: This agonist/antagonist profile of BCM receptors indicated the presence of both B1- and B2-receptor subtypes, both being responsible for contracting this smooth muscle. The BCM kinin receptors may be involved in changing the shape of the ocular lens to influence accommodation, and since the ciliary muscle is attached to the trabecular meshwork through which aqueous humor drains, endogenously released kinins may regulate intraocular pressure.

Design of an Innovative Method for Measuring the Contractile Behavior of Engineered Tissues.

Hypertrophic scarring is a common complication in severely burned patients who undergo autologous skin grafting. Meshed skin grafts tend to contract during wound healing, increasing the risk of pathological scarring. Although various technologies have been used to study cellular contraction, current methods for measuring contractile forces at the tissue level are limited and do not replicate the complexity of native tissues. Self-assembled skin substitutes (SASSs) were developed at the "Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX" and are used as permanent full-thickness skin grafts. The autologous skin substitutes are produced using the self-assembly method, allowing the cultured cells to produce their extracellular matrix leading to a tissue-engineered substitute resembling the native skin. The level of contraction of the SASSs during the fabrication process is patient-dependent. Thus, because of its architecture and composition, SASS is an interesting model to study skin contraction in vitro. Unfortunately, standard measurement methods are unsuited for SASS contraction assessment, mainly due to incompatibilities between the SASS manufacturing process and the current contraction force measurement methods. Here, we present an innovative contraction measurement method specifically designed to quantify the contractile behavior of tissue-engineered substitutes, without disrupting the protocol of production. The method uses C-shape anchoring frames that close at different speeds and magnitudes according to the tissue contractile behavior. A finite element analysis model is then used to associate the frame deformation to a contractile force amplitude. This article shows that the method can be used to measure the contraction force of tissues produced with cells displaying different contractile properties, such as primary skin fibroblasts and myofibroblasts. It can also be used to study the effects of cell culture conditions on tissue contraction, such as serum concentration. This protocol can be easily and affordably applied and tuned to many regenerative medicine applications or contraction-related pathological studies. Impact Statement The protocol presented in this article is a new and simple method to quantify contraction forces present in tissue-engineered substitutes. Using finite element analysis, it allows for the measurement of a contraction force rather than a surface reduction as usually provided by other tissue contraction measurement methods. The results shown are in correlation with the current literature relevant to tissue contraction. It can be easily implemented, and hence, this method will open up new avenues to study tissue contraction of living substitutes engineered with various cell types and to optimize culture conditions.

Suturing techniques

The act of suturing wounds on the skin has been done for thousands of years. Closing dead space, supporting and strengthening wounds until healing increases their tensile strength, approximating skin edges for an esthetically pleasing and functional result, and minimizing the risks of bleeding and infection remain the primary goals of suture techniques, even though suture materials and techniques have changed. A well-planned closure or flap may have its post-operative appearance jeopardized if the wrong suture technique is used or if the procedure is not performed well. On the other hand, poor surgical skills cannot entirely be made up for by careful suturing. Poor incision placement with respect to relaxed skin tension lines, excessive removal of tissue, or inadequate undermining may limit the surgeon’s options in wound closure and suture placement. Gentle handling of the tissue is also important to optimize wound healing. The choice of suture technique depends on the type and anatomic location of the wound, thickness of the skin, degree of tension, and desired cosmetic result. Proper placement of sutures enhances the precise approximation of the wound edges, which helps minimize and redistribute skin tension. Wound eversion is essential to maximize the likelihood of good epidermal approximation. Eversion is desirable to minimize the risk of scar depression secondary to tissue contraction during healing. Usually, inversion is not desirable, and it probably does not decrease the risk of hypertrophic scarring in an individual with a propensity for hypertrophic scars. To maximize the esthetic and functional outcomes, dead space must be removed, natural anatomic shapes must be restored, and stitch marks must be minimized. This page describes the methods for placing sutures for different kinds of stitches, goes over why certain suture techniques are better than others and goes over the benefits and drawbacks of each suture technique. For the best possible closure of a wound, multiple suture techniques are frequently required. After reading this article, the reader ought to comprehend the basic techniques for inserting each type of suture as well as how and why specific sutures are selected.

CHANGES IN THE CONTENT AND ACTIVITY OF MUSCLE PROTEINS AS A MARKER IN THE CASE OF EXPOSURE TO IONIZING RADIATION IN ANIMALS

Objective. To find out the specifics of muscle tissue contraction under the conditions of exposure to low doses of ionizing radiation in parents and their irradiated offspring by evaluating changes in the content of contractile proteins and ATPase activity of skeletal and cardiac muscles. Methods. Experimental studies were conducted on 50 rats. Animals were randomized as follows: group 1 — intact sexually mature rats; 2 — sexually mature animals irradiated with a dose of 1.0 Gy; group 3 — monthold rats obtained from intact individuals; group 4 — month-old rat pups obtained from parents irradiated with a dose of 1.0 Gy; group 5 — month-old rats obtained from animals irradiated with a dose of 1.0 Gy, which were irradiated at the same dose. The results. Muscle dysfunction in irradiated offspring and parents is manifested by a decrease in the content of contractile proteins, functional dysfunction of the actomyosin bridge, and a decrease in the ATPase activity of contractile proteins. Marked muscle dysfunctions during the post-radiation time period may be the reason for the formation of orthopedic pathology in a significant contingent of irradiated persons. Conclusions. The expression of muscle dysfunction in the offspring of irradiated animals, which were also exposed to ionizing radiation, is greater than the corresponding processes in their irradiated parents, which indicates the mediation of muscle dysfunction in the second generation of irradiated animals by epigenetic mechanisms. Marked muscle dysfunctions during the post-radiation time period may be the reason for the formation of orthopedic pathology in a significant contingent of irradiated persons

Maxillectomy and its ophthalmic implications: A comprehensive analysis over 20 years

PurposeMaxillectomy, a critical surgical intervention for head and neck malignancies, often leads to a comprehensive spectrum of ophthalmic complications due to its impact on orbital structures. This study, conducted over 20 years at a single university hospital, aims to evaluate the extent and severity of these complications, encompassing the entire range of ophthalmological issues encountered in the field. DesignA retrospective, observational cohort study. MethodsAmong the 163 patients who underwent maxillectomy at a single university hospital between January 2003 and December 2022, we analyzed the medical records of 101 patients with over one year of postoperative ophthalmological follow-up. Data on demographics, clinical parameters, surgical details, and ophthalmic complications were collected. Complications were categorized into six groups, with statistical analysis identifying factors influencing these outcomes. ResultsOur findings reveal a predominant occurrence of ophthalmic complications among maxillectomy patients. Only 4.4 % had no complications, while 95.6 % experienced at least one, especially with cornea/conjunctiva (56 %), eyelid (48.4 %), and lacrimal system issues (38.5 %) being the most frequent. Notably, 64.8 % had complications in two or more categories, and 33 % in three or more. Multivariate analysis identified that orbital floor resection was a significant risk factor for complications involving the eyelid and the cornea/conjunctiva (P = 0.008 and P = 0.021, respectively), while radiotherapy specifically emerged as a significant risk factor for cornea/conjunctiva complications (P = 0.009). Surgical management of complications following maxillectomy often involved major tissue transplantation in plastic surgery, particularly for cases of significant tissue contraction or severe orbital dystopia. Common secondary ophthalmic surgeries included dacryocystorhinostomy (DCR) in 14 eyes, tarsorrhaphy in 12 eyes, and lateral tarsal strip procedures in 5 eyes. The study found a high incidence of multiple complications, highlighting the complex nature of postoperative challenges. ConclusionMaxillectomy patients are highly susceptible to a range of ophthalmological complications, primarily influenced by surgical extent and adjuvant therapies. A multidisciplinary approach is essential for comprehensive management and improved quality of life in these patients. The study underscores the need for thorough ophthalmological evaluation and integrated care in treating maxillectomy-related complications.

Individual Joint Distractions Using Ilizarov Mini-Fixator Device for Chronic Simultaneous Dislocation of the Distal and Proximal Interphalangeal Joints in the Same Finger.

Simultaneous dislocation of the distal and proximal interphalangeal joints is an uncommon injury. Treating chronic cases proves challenging due to severe contractures affecting both joints and surrounding soft tissues. Here, we report an unusual chronic contracture case in a 46-year-old man who suffered a dorsal dislocation of the distal and proximal interphalangeal joints of the little finger. The patient underwent primary joint distraction followed by open reduction, leading to stable radiographic restoration and a functional range of motion in the affected finger 6 months postoperatively. Joint distraction was a reliable approach for the treatment of chronic joint dislocation with severe soft tissue contracture, especially for multiple joint contractures. In addition, the Ilizarov mini-fixator device was effective in enabling individualized traction on both the distal and proximal interphalangeal joints.

Electroactive differential growth and delayed instability in accelerated healing tissues

Guided by experiments contrasting electrically accelerated recovery with natural healing, this study formulates a model to investigate the importance of electroactive differential growth and morphological changes in tissue repair. It underscores the clinical potential of leveraging electroactive differential growth for improved healing outcomes. The study reveals that voltage stimulation significantly enhances the healing and growth of biological tissues, accelerating the regeneration process across various growth modalities and steering towards isotropic growth conditions that do not favor any specific growth pathways. Enhancing the electroelastic coupling parameters improves the efficacy of bioelectric devices, initiating contraction and fortification of biological tissues in alignment with the electric field. This process facilitates swift cell migration and proliferation, as well as oriented growth of tissue. In instances of strain stiffening at elevated strains, the extreme critical growth ratio aligns with the predictions of neo-Hookean models. Conversely, for tissues experiencing strain stiffening under moderate to very low strain conditions, the strain stiffening effect substantially delays the onset of electroelastic growth instability, ultimately producing a smooth, hyperelastic surface devoid of any unstable morphologies. Our investigation, grounded in nonlinear electroelastic field and perturbation theories, explores how electric fields influence differential growth and instability in biological tissues. We examine the interactions among dimensionless voltage, internal pressure, electroelastic coupling, radius ratio, and strain stiffening, revealing their effects on promoting growth and delaying instability. This framework offers insights into the mechanisms behind electroactive growth and its instabilities, contributing valuable knowledge to the tissue healing.

Inhibiting Ca2+ channels in Alzheimer's disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia.

Early in Alzheimer's disease (AD), pericytes constrict capillaries, increasing their hydraulic resistance and trapping of immune cells and, thus, decreasing cerebral blood flow (CBF). Therapeutic approaches to attenuate pericyte-mediated constriction in AD are lacking. Here, using in vivo two-photon imaging with laser Doppler and speckle flowmetry and magnetic resonance imaging, we show that Ca2+ entry via L-type voltage-gated calcium channels (CaVs) controls the contractile tone of pericytes. In AD model mice, we identifed pericytes throughout the capillary bed as key drivers of an immune reactive oxygen species (ROS)-evoked and pericyte intracellular calcium concentration ([Ca2+]i)-mediated decrease in microvascular flow. Blocking CaVs with nimodipine early in disease progression improved CBF, reduced leukocyte stalling at pericyte somata and attenuated brain hypoxia. Amyloid β (Aβ)-evoked pericyte contraction in human cortical tissue was also greatly reduced by CaV block. Lowering pericyte [Ca2+]i early in AD may, thus, offer a therapeutic strategy to enhance brain energy supply and possibly cognitive function in AD.

Evaluation of Full Thickness Wounds Following Application of a Visco-Liquid Hemostat in a Swine Model.

Wound healing is a complex dynamic biomechanical process as the body attempts to restore the integrity of traumatized or devitalized tissues. There are four stages of wound of healing that begins with hemostasis followed by inflammation, proliferation and finally weeks later wound remodeling. Full thickness wounds usually are covered with a dressing material after hemostasis, which allows for controlled hydration. We investigated the potential of a visco-liquid hemostat, polyhedral oligomeric silsesquioxane (POSS), for providing hemostasis and to maintain a microenvironment in the wound bed that would maintain moisture content and promote early re-epithelialization. We hypothesized that the hemostatic agent POSS if left in the wound bed would maintain a protective barrier and accelerate wound healing similar to using saline to irrigate the wound to keep the wound moist. We compared the early phase of wound repair (3-7 days) in a porcine full thickness wound model to evaluate the efficacy of the material. Biopsies were taken after 3 and 7 days to determine the acute response of the POSS hemostat or saline on inflammation, cell migration, concentrations of metalloproteinase (MMPs), and tissue inhibitors of metalloproteinase (TIMPs). Accelerated healing was observed in POSS treated wounds by changes in wound contraction, keratinocyte migration, and development of granulation tissue in comparison to saline treated wounds. Increased concentrations at day 3 of MMP-2, MMP-3, and in MMP-1 at day 7 in POSS treated wounds compared to saline coincide with keratinocyte migration observed in the tissue histology and changes in wound contraction. Tissue concentrations of TIMP-1 and TIMP-2 in POSS treated wounds appear to coordinate the sequence of MMP events in the healing tissue. Matrix metalloproteinase-13, a marker for tissue remodeling, was not upregulated in the early wound healing cascade in either POSS or saline treated wounds at 3 or 7 days. Overall, the data suggests POSS treatment contributed to enhanced early cell migration and wound closure compared to saline treatment.

Effect of high blood flow on heat distribution and ablation zone during microwave ablation-numerical approach.

Microwave ablation has become a viable alternative for cancer treatment for patients who cannot undergo surgery. During this procedure, a single-slot coaxial antenna is employed to effectively deliver microwave energy to the targeted tissue. The success of the treatment was measured by the amount of ablation zone created during the ablation procedure. The significantly large blood vessel placed near the antenna causes heat dissipation by convection around the blood vessel. The heat sink effect could result in insufficient ablation, raising the risk of local tumor recurrence. In this study, we investigated the heat loss due to large blood vessels and the relationship between blood velocity and temperature distribution. The hepatic artery, with a diameter of 4 mm and a height of 50 mm and two branches, is considered in the computational domain. The temperature profile, localized tissue contraction, and ablation zones were simulated for initial blood velocities 0.05, 0.1, and 0.16 m/s using the 3D Pennes bio-heat equation, temperature-time dependent model, and cell death model, respectively. Temperature-dependent blood velocity is modeled using the Navier-Stokes equation, and the fluid-solid interaction boundary is treated as a convective boundary. For discretization, we utilized elements for the wave propagation model, elements for the Pennes bio-heat model, and elements for the Navier-Stokes equation, where represents the computational domain. The simulated results show that blood vessels and blood velocity have a significant impact on temperature distribution, tissue contraction, and the volume of the ablation zone.

General Rehabilitation Principles for Patients with Cerebral Palsy After Single-Event Multilevel Surgery (SEMLS)

Single-Event Multilevel Surgery (SEMLS) is the standard for surgical correction of secondary orthopedic deformities in cerebral palsy (CP). SEMLS include simultaneous correction of soft tissue contractures, bone deformities, incomplete and complete joint dislocation to improve the gait and functional activity of patients with CP. The surgery volume determines the need for planned and long-term postoperative rehabilitation, however, there are no confirmed guidelines, neither Russian, nor foreign, on the patient’s management during postoperative period. This review provides an analysis of rehabilitation approaches after SEMLS at CP, offers recommendations on preparation and step-by-step postoperative restoration of motor function, and prevention of any associated complications.

DNA Base Damage Repair Crosstalks with Chromatin Structures to Contract Expanded GAA Repeats in Friedreich's Ataxia.

Trinucleotide repeat (TNR) expansion is the cause of over 40 neurodegenerative diseases, including Huntington's disease and Friedreich's ataxia (FRDA). There are no effective treatments for these diseases due to the poor understanding of molecular mechanisms underlying somatic TNR expansion and contraction in neural systems. We and others have found that DNA base excision repair (BER) actively modulates TNR instability, shedding light on the development of effective treatments for the diseases by contracting expanded repeats through DNA repair. In this study, temozolomide (TMZ) was employed as a model DNA base damaging agent to reveal the mechanisms of the BER pathway in modulating GAA repeat instability at the frataxin (FXN) gene in FRDA neural cells and transgenic mouse mice. We found that TMZ induced large GAA repeat contraction in FRDA mouse brain tissue, neurons, and FRDA iPSC-differentiated neural cells, increasing frataxin protein levels in FRDA mouse brain and neural cells. Surprisingly, we found that TMZ could also inhibit H3K9 methyltransferases, leading to open chromatin and increasing ssDNA breaks and recruitment of the key BER enzyme, pol β, on the repeats in FRDA neural cells. We further demonstrated that the H3K9 methyltransferase inhibitor BIX01294 also induced the contraction of the expanded repeats and increased frataxin protein in FRDA neural cells by opening the chromatin and increasing the endogenous ssDNA breaks and recruitment of pol β on the repeats. Our study provides new mechanistic insight illustrating that inhibition of H3K9 methylation can crosstalk with BER to induce GAA repeat contraction in FRDA. Our results will open a new avenue for developing novel gene therapy by targeting histone methylation and the BER pathway for repeat expansion diseases.

Immunomodulatory imide drugs inhibit human detrusor smooth muscle contraction and growth of human detrusor smooth muscle cells, and exhibit vaso-regulatory functions

BackgroundThe immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC). MethodsCell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, ResultsDepending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization. ConclusionsIMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.

Abnormal genes and pathways that drive muscle contracture from brachial plexus injuries: Towards machine learning approach

In order to clarify the pathways closely linked to denervated muscle contracture, this work uses IoMT-enabled healthcare stratergies to examine changes in gene expression patterns inside atrophic muscles following brachial plexus damage. The gene expression Omnibus (GEO) database searching was used to locate the dataset GSE137606, which is connected to brachial plexus injuries. Strict criteria (|logFC|≥2 & adj.p < 0.05) were used to extract differentially expressed genes (DEGs). To identify dysregulated activities and pathways in denervated muscles, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used. Hub genes were found using Cytoscape software's algorithms, which took into account parameters like as proximity, degree, and MNC. Their expression, enriched pathways, and correlations were then examined. The results showed that 316 DEGs were predominantly concentrated in muscle-related processes such as tissue formation and contraction pathways. Of these, 297 DEGs were highly expressed in denervated muscles, whereas 19 DEGs were weakly expressed. GSEA showed improvements in the contraction of striated and skeletal muscles. In addition, it was shown that in denervated muscles, Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1 were elevated hub genes with enriched pathways such adrenergic signaling and tight junction. These results point to possible therapeutic targets for denervated muscular contracture, including Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1. This highlights treatment options for this ailment which enhances the mental state of patient.

Management of post-traumatic elbow stiffness in paediatric and adult patients: an update

Posttraumatic elbow stiffness can have a large impact on the ability of a patient to perform activities of daily living. Following a stepwise approach to treatment helps clinicians in this otherwise difficult-to treat condition. Treatment in adults is based on dealing with the involvement of soft tissue contracture, osseous impingement or both. Unlike adults, posttraumatic elbow stiffness in children has distinctly different causes and the thrust of treatment is primarily non-surgical. In skeletally immature children, the skeletal growth potential should be properly assessed and closely followed, observing either progression or natural correction of the deformity. Early active motion aided by physiotherapy is the first step in treatment for both adults and children. Following physiotherapy, brace therapy is a proven cheap and effective therapy for treatment-resistant stiffness. If adequate conservative treatment is unsuccessful, the next step is surgical arthrolysis. This procedure can be performed either open or arthroscopically, with the decision dependent on multiple factors. Early active mobilization after surgery is equally important, with the addition of bracing or continuous passive motion (CPM) in pending contractures following surgery. This paper provides a review of the current literature and a state-of-the-art guidance on the management of posttraumatic elbow stiffness in adult and paediatric patients.

Effects of carvedilol on human prostate tissue contractility and stromal cell growth pointing to potential clinical implications

BackgroundApart from antagonizing ß-adrenoceptors, carvedilol antagonizes vascular α1-adrenoceptors and activates G protein-independent signaling. Even though it is a commonly used antihypertensive and α1-adrenoceptors are essential for the treatment of voiding symptoms in benign prostatic hyperplasia, its actions in the human prostate are still unknown. Here, we examined carvedilol effects on contractions of human prostate tissues, and on stromal cell growth.MethodsContractions of prostate tissues from radical prostatectomy were induced by electric field stimulation (EFS) or α1-agonists. Growth-related functions were examined in cultured stromal cells.ResultsConcentration-response curves for phenylephrine, methoxamine and noradrenaline were right shifted by carvedilol (0.1–10 µM), around half a magnitude with 100 nM, half to one magnitude with 1 µM, and two magnitudes with 10 µM. Right shifts were reflected by increased EC50 values for agonists, with unchanged Emax values. EFS-induced contractions were reduced by 21–54% with 0.01–1 µM carvedilol, and by 94% by 10 µM. Colony numbers of stromal cells were increased by 500 nM, but reduced by 1–10 µM carvedilol, while all concentrations reduced colony size. Decreases in viability were time-dependent with 0.1–0.3 µM, but complete with 10 µM. Proliferation was slightly increased by 0.1–0.5 µM, but reduced with 1–10 µM.ConclusionsCarvedilol antagonizes α1-adrenoceptors in the human prostate, starting with concentrations in ranges of known plasma levels. In vitro, effect sizes resemble those of α1-blockers used for the treatment of voiding symptoms, which requires concentrations beyond plasma levels. Bidirectional and dynamic effects on the growth of stromal cells may be attributed to "biased agonism".

Fabrication of heart tubes from iPSC derived cardiomyocytes and human fibrinogen by rotating mold technology

Due to its structural and functional complexity the heart imposes immense physical, physiological and electromechanical challenges on the engineering of a biological replacement. Therefore, to come closer to clinical translation, the development of a simpler biological assist device is requested. Here, we demonstrate the fabrication of tubular cardiac constructs with substantial dimensions of 6 cm in length and 11 mm in diameter by combining human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human foreskin fibroblast (hFFs) in human fibrin employing a rotating mold technology. By centrifugal forces employed in the process a cell-dense layer was generated enabling a timely functional coupling of iPSC-CMs demonstrated by a transgenic calcium sensor, rhythmic tissue contractions, and responsiveness to electrical pacing. Adjusting the degree of remodeling as a function of hFF-content and inhibition of fibrinolysis resulted in stable tissue integrity for up to 5 weeks. The rotating mold device developed in frame of this work enabled the production of tubes with clinically relevant dimensions of up to 10 cm in length and 22 mm in diameter which—in combination with advanced bioreactor technology for controlled production of functional iPSC-derivatives—paves the way towards the clinical translation of a biological cardiac assist device.