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Regenerative Therapy Jun 2024Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury...
BACKGROUND
Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established.
HYPOTHESIS
The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair.
STUDY DESIGN
A controlled laboratory study.
METHODS
: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. : An SMI model was established with Sprague-Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-β1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment.
RESULTS
: The fibroblast migration ability was suppressed by SE added at a concentration of 10⁴ μg/mL in the culture medium. : In the 1-week model, the SE group exhibited significantly lower TGFβ -1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength.
CONCLUSION
Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair.
CLINICAL RELEVANCE
The findings of this study may contribute to the development of an early intervention method for SMIs.
PubMed: 38948131
DOI: 10.1016/j.reth.2024.05.012 -
Theranostics 2024Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung...
Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung fibrosis. Lipofibroblasts (LIFs), on the other hand, are defined by their lipid-storing capacity and are predominantly found in the alveolar regions of the lung. They have been proposed to play a protective role in lung fibrosis. We previously reported that a LIF to MYF reversible differentiation switch occurred during fibrosis formation and resolution. In this study, we tested whether WI-38 cells, a human embryonic lung fibroblast cell line, could be used to study fibroblast differentiation towards the LIF or MYF phenotype and whether this could be relevant for idiopathic pulmonary fibrosis (IPF). Using WI-38 cells, Fibroblast (FIB) to MYF differentiation was triggered using TGF-β1 treatment and FIB to LIF differentiation using Metformin treatment. We also analyzed the MYF to LIF and LIF to MYF differentiation by pre-treating the WI-38 cells with TGF-β1 or Metformin respectively. We used IF, qPCR and bulk RNA-Seq to analyze the phenotypic and transcriptomic changes in the cells. We correlated our transcriptome data from WI-38 cells (obtained via bulk RNA sequencing) with the transcriptomic signature of LIFs and MYFs derived from the IPF cell atlas as well as with our own single-cell transcriptomic data from IPF patients-derived lung fibroblasts (LF-IPF) cultured . We also carried out alveolosphere assays to evaluate the ability of the proposed LIF and MYF cells to support the growth of alveolar epithelial type 2 cells. : WI-38 cells and LF-IPF display similar phenotypical and gene expression responses to TGF-β1 and Metformin treatment. Bulk RNA-Seq analysis of WI-38 cells and LF-IPF treated with TGF-β1, or Metformin indicate similar transcriptomic changes. We also show the partial conservation of the LIF and MYF signature extracted from the Habermann scRNA-seq dataset in WI-38 cells treated with Metformin or TGF-β1, respectively. Alveolosphere assays indicate that LIFs enhance organoid growth, while MYFs inhibit organoid growth. Finally, we provide evidence supporting the MYF to LIF and LIF to MYF reversible switch using WI-38 cells. WI-38 cells represent a versatile and reliable model to study the intricate dynamics of fibroblast differentiation towards the MYF or LIF phenotype associated with lung fibrosis formation and resolution, providing valuable insights to drive future research.
PubMed: 38948058
DOI: 10.7150/thno.93519 -
Cureus May 2024A cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Proper diagnosis and management of CSP are incredibly important secondary to the risk of uterine...
A cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Proper diagnosis and management of CSP are incredibly important secondary to the risk of uterine rupture and life-threatening hemorrhage. Various medical and surgical management have been described previously. This report looks at two cases of CSP diagnosed at an urban hospital in Atlanta, Georgia. The first woman was 30 years old with a history of five prior CS. She was referred from an abortion clinic for CSP at 6 weeks 2 days gestation. She did not desire future fertility and opted for a hysterectomy. The second woman was 38 years old with a history of three prior CS presenting with vaginal bleeding and abdominal pain and found to have a CSP with a gestation sac measuring 5 weeks 1 day. Given the patient's desires for future fertility, she was treated with a two-dose regimen of systemic intramuscular methotrexate (MTX) at 1 mg/kg with successful resolution of CSP and subsequent intrauterine pregnancy. Due to the high risk of uterine rupture and hemorrhage with CSP, it is important to have a high index of suspicion for diagnosis. Due to the rarity of CSP, and thus difficulty creating quality prospective trials, there is no consensus on the best management yet. Although conservative treatment carries high failure risk, shared decision-making incorporating future fertility desires should be considered when determining management of CSP, and when surgical management is considered a minimally invasive approach should be the standard of care in surgical management.
PubMed: 38947697
DOI: 10.7759/cureus.61311 -
Cureus May 2024A 59-year-old woman, who previously underwent surgery on her left long finger A1 pulley and left small finger distal interphalangeal joint for triggering and mallet...
A 59-year-old woman, who previously underwent surgery on her left long finger A1 pulley and left small finger distal interphalangeal joint for triggering and mallet deformity at another medical facility in March 2021, sought evaluation at an Orthopedics Hand clinic. She presented with limited finger movement, a flexion contracture, and difficulty extending her left long finger. Examination revealed an A2 pulley injury with extensive scar tissue. Subsequently, she underwent surgery to remove the scar tissue and reconstruct the A2 pulley using suture tape anchors. This case highlights the negative outcome following A1 pulley release due to an unintended A2 injury, resulting in significant scarring and an intrinsic plus digit posture. Additionally, it underscores the potential effectiveness of using non-absorbable synthetic sutures to minimize scarring and promote an early range of motion in cases where healing leads to excessive scarring around the flexor tendon sheath.
PubMed: 38947663
DOI: 10.7759/cureus.61250 -
Cureus May 2024Facial trauma can cause skin wounds with uneven and discoloured edges that require healing by secondary intention. These wounds often produce excess collagen fibres,...
Facial trauma can cause skin wounds with uneven and discoloured edges that require healing by secondary intention. These wounds often produce excess collagen fibres, leading to fibrosis and hypertrophic scars that can cause discomfort and negatively impact the patient's quality of life. A man suffered facial trauma due to a motor vehicle accident, resulting in a fracture of the left zygomatic-maxillary complex. He underwent surgery to fix the fracture and reconstruct his eyelid but developed a hypertrophic scar during recovery that caused eye dryness and discomfort. To treat the scar, Dermatix silicone gel (SG) (Viatris, Canonsburg, PA) was applied twice a day. After two months of treatment, the scar had improved significantly, and the patient's eyelid function had also improved. This case describes the use of Dermatix SG to treat a patient with a traumatic hypertrophic scar of the eyelid associated with eyelid malposition. Silicone gel is a non-invasive treatment for scars and has been shown to be effective in reducing scar elevation and erythema. However, there is a gap in the literature regarding the routine use of SG to preserve functionality and aesthetics in traumatic hypertrophic scars of complex anatomical structures. Further studies are needed to understand the principles of using SG for these types of scars to improve functional and aesthetic outcomes. Applying Dermatix SG twice a day for 60 days corrected a patient's functional and aesthetic issues. More studies should be conducted to investigate the product's effectiveness further.
PubMed: 38947592
DOI: 10.7759/cureus.61450 -
Clinical Case Reports Jul 2024Cesarean scar pregnancy cases who undergo hysteroscopic suction aspiration could be at higher risk of air emboli due to dilated, low-resistant, high-velocity blood...
Cesarean scar pregnancy cases who undergo hysteroscopic suction aspiration could be at higher risk of air emboli due to dilated, low-resistant, high-velocity blood vessels.
PubMed: 38947538
DOI: 10.1002/ccr3.9060 -
Frontiers in Immunology 2024Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from...
Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.
BACKGROUND
Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression.
METHODS
Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following heme treatment was also examined.
RESULTS
Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response.
CONCLUSIONS
Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.
PubMed: 38947312
DOI: 10.3389/fimmu.2024.1416820 -
Frontiers in Medicine 2024The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging....
BACKGROUND
The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging. Diagnosis often requires the assistance of pathological examination, and dermoscopy can be used as an auxiliary and non-invasive examination method, however, the current findings remain incomplete.
OBJECTIVES
This study aimed to summarize the clinical, histopathological and dermoscopic features of LMDF in the Chinese Han population and aiming to provide practical significance to correct diagnosis.
METHODS
109 patients of LMDF were collected in the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University from August 2015 to August 2023. The clinical and histopathological manifestations of all patients, as well as the dermoscopic image features of 44 cases, including background, follicular findings, vessels, and other structures, were summarized and evaluated.
RESULTS
The most significant histopathological features of LMDF in 109 cases is epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. The most significant dermoscopic features of LMDF in all 44 cases were orange structureless background (30/44), follicular plug (32/44), follicular white scar-like area (32/44), unspecific linear vessels (24/44), linear vessels with branch (24/44) and white streaks (18/44).
CONCLUSION
Histopathologically, LMDF is characterized by the presence of epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. Dermoscopically, it exhibits a distinctive orange structureless background, follicular plug, follicular white scar-like area, nonspecific linear vessels, linear vessels with branches, and white streaks.
PubMed: 38947242
DOI: 10.3389/fmed.2024.1382526 -
Cureus Jun 2024The appearance of scars affects patients' aesthetic and psychological aspects, as atrophic scars can result from previous surgeries or inflammatory/infectious...
The appearance of scars affects patients' aesthetic and psychological aspects, as atrophic scars can result from previous surgeries or inflammatory/infectious conditions. Recently, non-surgical techniques have been introduced to improve scar appearance and enhance patient satisfaction. To our knowledge, there has been limited published medical research evaluating the effectiveness of polydioxanone threads in managing facial scars. This report aims to present three cases where scars were managed using these materials in the facial area with a follow-up of six months post-intervention. Based on the three presented cases, it is shown that there was an improvement in the color and texture of the scar, in addition to its reduced size with no sensation of pain or itching after the procedure. These findings suggest that the materials used are promising for effectively treating facial scars.
PubMed: 38947135
DOI: 10.7759/cureus.63403 -
Stroke Jul 2024GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089...
BACKGROUND
GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown.
METHODS
Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65 and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting.
RESULTS
BTB09089 significantly promoted motor outcomes in WT but not in GPR65 mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65 mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65 mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65 mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice.
CONCLUSIONS
Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.
PubMed: 38946544
DOI: 10.1161/STROKEAHA.124.046954