Density Of Collagen Fibers Research Articles

Dermal Fibroblast-Derived Exosomes Promotes Bone-to-Tendon Interface Healing of Chronic Rotator Cuff Tear in Rabbit Model.

To investigate the efficacy of exosomes derived from dermal fibroblasts (DF-Ex) on bone-to-tendon interface (BTI) healing in a chronic rotator cuff tear (RCT) model of rabbit. After extraction of DF-Ex, the characterization of DF-Ex was identified in the in vitro study. In the in vivo experiment, forty-eight rabbits were randomly allocated into three groups. To create chronic RCT models, transected tendons were left untreated for 6 weeks, and then were repaired in a transosseous manner. Different materials were injected into repair site according to the allocated group (group A: saline, group B: fibrin glue only, group C: DF-Ex with fibrin glue; n = 16 for each). Genetic and immunofluorescence analyses were conducted at 4 weeks post-surgery. Furthermore, genetic, histologic, and biomechanical analyses were conducted at 12 weeks post-surgery. In vitro analyses revealed the exosomal marker proteins, CD9, CD63, and ALIX were positively expressed in DF-Ex, while negative control Calnexin was nearly absent. In vivo analyses showed that group C had the highest mRNA expression levels of COL1A1, COL3A1, and ACAN among all groups (P < 0.001, P = 0.007, and P = 0.002, respectively) at 4 weeks post-surgery. Meanwhile, there were more preliminary fibrocartilaginous matrix (aggrecan+/collagen II+) formation in group C. At 12 weeks post-surgery, group C demonstrated better collagen fiber continuity and orientation, denser collagen fibers, more mature bone-to-tendon junction, and greater fibrocartilage layer formation compared to the other groups (all P < 0.05). Moreover, group C also demonstrated higher load-to-failure value (53.3 ± 6.1 N/kg, P < 0.001). Topical DF-Ex administration effectively promoted BTI healing by upregulating the COL1A1, COL3A1, and ACAN mRNA expression levels at an early stage and enhancing the structural and biomechanical properties at 12 weeks after surgical repair of a chronic RCT model of rabbit. The study could be a transitional study to investigate the efficacy of DF-Ex on BTI healing for surgical repair of chronic RCTs as a powerful biological agent in humans.

Assembly of collagen fibers into contiguous dense and loose regions of subcutaneous fascia

ABSTRACT Objective This study aimed to investigate the collagen fiber structure of the subcutaneous fascia, a connective tissue layer between the skin and epimysium. Methods Fascia samples with varying extensibility were examined using biochemical and microscopic methods Results Loose fascia, the more extensibletype, displayed sparsely distributed collagen fibers, while dense fascia showed tightly packed collagen fiber bundles. Elastase treatment, after urea pretreatment, caused the loosening of collagen fiber bundles and increased collagen fiber generation as the treatment time increased. This suggests that elastic fibers contribute to collagen fiber bundle formation. Additionally, elastase treatment stretched the fascia, indicating the presence of twodimensional tensile stress generated by elastic fibers. Either enzymes capable of cleaving elastic fibers may be activated or the stretching of elastic fibers accompanying tissue deformationmay increase the enzyme sensitivity to elastic fibers, leading to the formation of localized collagen fibers in vivo. Tissue staining confirmed that loose and dense fascia corresponded to areas with sparse and dense collagen fibers, respectively. Some dense collagen fibers appeared to migrate and disperse into loose areas. Conclusion These findings provide insights into the structural organization and functional significance of collagen fibers within the subcutaneous fascia. They particularly highlight the role of elastic fibers in maintaining tissue integrity and facilitating dynamic remodeling.

Bone Marrow Aspirate Concentrate Combined With an Appropriate Carrier Effectively Promotes Bone-Tendon Interface Healing in a Rabbit Model of Chronic Rotator Cuff Tear.

The efficacy of bone marrow aspirate concentrate (BMAC) in promoting bone-tendon interface (BTI) healing without any carriers remains a subject of debate. To evaluate BMAC effects with different carriers on tendon regeneration in a rabbit model of chronic rotator cuff tear. Controlled laboratory study. In vitro, the amount of growth factor and the differentiation potential of BMAC with different carriers (polydeoxyribonucleotide [PDRN] and atelocollagen [ATC]) were assessed. In vivo, 64 rabbits were randomly allocated into 4 groups. Different materials were injected into the repair site according to the allocated group: control, saline; BMAC, BMAC and saline; BMAC-PDRN, BMAC with PDRN; BMAC-ATC, BMAC with ATC (n = 16 in each). Genetic and histologic analyses were conducted at 4 and 12 weeks after repair, while biomechanical evaluations were performed at 12 weeks after repair. In vitro, the degree of multilineage differentiation was much stronger using BMAC with ATC as compared with administration of BMAC alone or BMAC with PDRN (P < .001). In vivo, the BMAC-ATC group had the highest levels of aggrecan expression, bone morphogenetic protein 2, and collagen type I alpha 1 among all groups (all P < .001) at 4 weeks after repair. Furthermore, the BMAC-ATC group showed collagen fiber continuity, denser collagen fibers, and more mature BTI as compared with the other groups (all P < .001) at 12 weeks after repair. Concurrently, the BMAC-ATC group also demonstrated significantly higher load-to-failure versus the remaining groups (all P < .001) at 12 weeks after repair. Local application of BMAC without appropriate carriers could not enhance BTI healing. However, BMAC with 2 different carriers effectively accelerated BTI healing, particularly in the ATC environment. Therefore, the combination of BMAC and ATC may act as a powerful biological agent to promote healing after rotator cuff repair in a chronic rotator cuff tear model using rabbits. Local application of BMAC without appropriate carriers could not enhance BTI healing. However, the combination of BMAC and ATC may synergistically promote rotator cuff tendon healing.

Kangfuxin solution alleviates esophageal stenosis after endoscopic submucosal dissection: A natural ingredient strategy.

Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection (ESD). Excessive fibrotic repair is a typical pathological feature leading to stenosis after ESD. To examine the effectiveness and underlying mechanism of Kangfuxin solution (KFX) in mitigating excessive fibrotic repair of the esophagus post-ESD. Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential ESD. Endoscopic examinations occurred on days 7 and 21 post-ESD. In vitro, recombinant transforming growth factor (TGF)-β1 (5 ng/mL) induced a fibrotic microenvironment in primary esophageal fibroblasts (pEsF). After 24 hours of KFX treatment (at 1.5%, 1%, and 0.5%), expression of α-smooth muscle actin-2 (ACTA2), fibronectin (FN), and type collagen I was assessed. Profibrotic signaling was analyzed, including TGF-β1, Smad2/3, and phosphor-smad2/3 (p-Smad2/3). Compared to the Control group, the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis, lower weight loss rates, and improved food tolerance 21 d after ESD. After treatment, Masson staining revealed thinner and less dense collagen fibers in the submucosal layer. Additionally, the expression of fibrotic effector molecules was notably inhibited. Mechanistically, KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1, Smad2/3, and p-Smad2/3. In vitro, pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity, which was reversed by KFX treatment, leading to reduced activation of ACTA2, FN, and collagen I. The 1.5% KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated pEsF. KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures, potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.

Mitochondrial transplantation reconstructs the oxidative microenvironment within fibroblasts to reverse photoaging.

Fibroblast-mediated oxidative stress is a pivotal factor in the pathogenesis of skin photoaging, predominantly induced by UVA radiation. Diverging from traditional strategies that concentrate on the reduction of reactive oxygen species (ROS), the present study implements mitochondrial transplantation as an innovative therapeutic approach. The objective of this study is to reestablish the oxidative microenvironment and to effectively rejuvenate cellular functionality through the direct introduction of healthy and vibrant mitochondria. In vitro assays have illustrated that the seamless incorporation of exogenous mitochondria into fibroblasts ameliorates UVA radiation perturbations in membrane potential and oxidative stress, while simultaneously reestablishing the oxidative microenvironment. These interventions exert salutary influences on cellular proliferation and migratory capabilities. Subsequent in vivo analyses reveal a mitigation in dermal collagen depletion, alongside an enhancement in collagen fiber density and tissue architecture post-mitochondrial transplantation, thus ameliorating the manifestations of skin photoaging. Collectively, the study underscores the potential of mitochondrial transplantation as a promising therapeutic intervention for the reversal of skin photoaging by modulating the oxidative microenvironment within fibroblasts.

МОРФОЛОГИЧЕСКОЕ ИССЛЕДОВАНИЕ ПОЧЕК И БЕЛКОВОГО ОТДЕЛА ЯЙЦЕВОДА У ГУСЕОБРАЗНЫХ ПТИЦ

The purpose of research is to study the features of the macro- and microscopic structure of the kidneys and the protein section in Peking duck and Italian goose. The object of the study is the carcasses of adult poultry. In the studied species of birds, the presence of paired dark brown kidneys located in the renal fossae of the pelvic bone retroperitoneally is noted. The kidneys consist of cranial, middle and caudal lobes, with microscopy of which the cortical and cerebral zones are noted. The relative weight of the kidneys to body weight is 0.36 % (Peking duck) and 0.29 % (Italian goose). In the studied species of birds, the protein section represents the longest part of the oviduct, forming 5–6 bends along its entire length, making up the cranial, middle, and caudal parts. The folds have different shapes and linear indicators. The mucous membrane of the protein section is covered with multi-row ciliated epithelium with the presence of goblet, ciliated and argyrophilic cells. A well-developed muscular coat is represented by longitudinal and circular layers of smooth muscle fibers. The serous membrane is covered on the outside with a layer of mesothelial cells that lie in loose fibrous connective tissue. In relation to the wall thickness of the protein section, the mucous membrane occupies from 65.1 to 68.1 %, the muscular one – from 21.5 to 25.3 % and the outer one – from 9.6 to 10.4 %. In the folds of the mucous membrane at the base of the lamina propria there are dense collagen and thin loose elastic fibers resembling a grid structure with the presence of epithelial and glandular cells that are part of the tubular glands.

Collagen Density Is Associated With Pathological Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

The tumor-associated stroma is an essential compartment in breast cancer, and collagen fiber organization in the stroma has been reported to be correlated with prognosis. In this study, we sought to evaluate collagen fiber characteristics in relation to pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 388 breast cancer patients receiving NAC were enrolled. The stroma type was manually assessed on pretreatment hematoxylin and eosin (HE)-stained slides, and the collagen fiber features were quantified by a computer tool. The relationship between syndecan-1 expression and collagen fibers and its correlation with treatment efficacy were detected by immunohistochemistry. The pCR rate of patients with collagen-dominant stroma was lower than that of patients with lymphocyte-dominant stroma (19.6% vs. 40.0%, p = 0.001). Patients who achieved pCR had straighter and less dense fibers in pretreatment biopsied tissue than non-pCR patients (p = 0.031, p = 0.044). Additionally, the pCR group had greater syndecans-1 expression on the tumor epithelium than the non-pCR group (p < 0.001), while there was no statistically significant difference in the stroma (p = 0.333). Collagen fiber density was the only factor associated with pCR after correction for other clinicopathological variables in triple-negative breast cancer (TNBC)patients (OR 0.466, 95% CI 0.227-0.956, p = 0.037); patients with lower fiber density had a greater pCR rate (37.5% vs. 12.5%, p = 0.021). Collagen fiber density was associated with pCR in patients with breast cancer, and it could be a potential candidate for discriminating between responders and nonresponders for TNBC patients receiving NAC.

Boric Acid Protects the Uterus and Fallopian Tubes from Cyclophosphamide-Induced Toxicity in a Rat Model.

Background/Objectives: Cyclophosphamide (CP) is widely used for treating various cancers and autoimmune diseases, but it causes damage to reproductive organs due to oxidative stress (OS) and inflammation. Boric acid (BA) has antioxidant properties that may help reduce OS, which is critical for preserving uterine functionality, particularly for cancer patients considering pregnancy after cryopreservation. This study aimed to determine whether BA could diminish CP-induced toxicity in the uterus and fallopian tubes (FT) using CP-induced toxicity in a rat model. Methods: Forty female Wistar rats, aged 18-20 weeks, were divided into four groups as follows: control, oral BA (OBR), CP, and CP plus OBR (CP + OBR). The toxicity was induced in the CP and CP + OBR groups with an initial dose of 200 mg/kg CP, followed by 8 mg/kg daily for 14 days. Rats in the OBR and CP + OBR groups received 20 mg/kg/day of BA. After the 16-day experiment, tissues were collected for analysis. Results: Histopathological and immunohistochemical assessments of IL-6 and HIF-1α expressions were used to evaluate inflammation and OS. The control, OBR, and CP + OBR groups maintained normal tissue features, while the CP group showed epithelial cell shedding, vacuolization, degenerative endometrial glands, lymphocyte infiltration, and reduced collagen fiber density. Elevated HIF-1α and IL-6 expressions in the uterus and FT indicated significant OS and inflammation. Conclusions: The study concluded that BA supplementation in CP-treated rats effectively reduced CP-induced uterine and FT damage, suggesting the potential protective role of BA in managing CP-associated toxicity.

Preparation and characterization of Pistacia atlantica oleo-gum-resin-loaded electrospun nanofibers and evaluating its wound healing activity in two rat models of skin scar and burn wound.

A growing body of research is dedicated to developing new therapeutic agents for wound healing with fewer adverse effects. One of the proceedings being taken today in wound healing research is to identify promising biological materials that not only heal wounds but also vanish scarring. The effectiveness of nanofibers like polyvinyl alcohol (PVA), in improving wound healing can be related to their unique properties. Pistacia atlantica Desf. subsp. kurdica (Zohary) Rech. f. (PAK) [Anacardiaceae], also known as "Baneh" in traditional Iranian medicine, is one of the most effective herbal remedies for the treatment of different diseases like skin injuries due to its numerous pharmacological and biological properties, including anti-inflammatory, antioxidant, and anti-bacterial effects. Our study aimed to evaluate the wound-healing activity of nanofibers containing PVA/PAK oleo-gum-resin in two rat models of burn and excision wound repair. PVA/PKA nanofibers were prepared using the electrospinning method. Scanning electron microscope (SEM) images and mechanical properties of nanofibers were explored. Diffusion and releasing experiments of nanofibers were performed by the UV visible method at different time intervals and up to 72h. The animal models were induced by excision and burn in Wistar rat's skin and the wound surface area was measured during the experiment for 10 and 21days, respectively. On the last day, the wound tissue was removed for histological studies, and serum oxidative factors were measured to evaluate the antioxidant properties of the PVA/PKA. Data analysis was performed using ImageJ, Expert Design, and statistical analysis methods. PVA/PKA nanofibers were electrospun at different voltages (15, 18, and 20kV). The most suitable fibers were obtained when the nozzle was positioned 15cm away from the collector, with a working voltage of 15kV, and an injection rate of 0.5mm per hour, using the 30:70 w/v PKA gum. In the SEM images, it was found that the surface tension of the polymer solution decreased by adding the gum and yield thinner and longer fibers at a voltage of 15kV with an average diameter of 96 ± 24nm. The mechanical properties of PVA/PKA nanofibers showed that the presence of gum increased the tensile strength and decreased the tensile strength of the fibers simultaneously. In vivo results showed that PVA/PKA nanofibers led to a significant reduction in wound size and tissue damage (regeneration of the epidermal layer, higher density of dermal collagen fibers, and lower presence of inflammatory cells) compared to the positive (phenytoin and silver sulfadiazine) and negative control (untreated) groups. Wound contraction was higher in rats treated with PVA/PKA nanofibers. Additionally, antioxidative serum levels of catalase and glutathione were higher in the PVA/PKA nanofiber groups even in comparison to positive control groups. Pistacia atlantica oleo-gum-resin-loaded electrospun nanofibers potentially improve excision and burn models of skin scars in rats through antioxidative and tissue regeneration mechanisms.

Comparative evaluation of collagen modifications in breast cancer in human and canine carcinomas

New diagnostic and therapeutic approaches have been increasingly demanded due to the high morbidity and mortality associated with breast cancer. Recently, changes in the collagen fibres in mammary neoplasms have been shown to provide information that can be helpful for more accurate diagnosis. We aimed to conduct a comparative analysis of the tumour stroma in human and canine mammary neoplasms to assess the relationship between collagen modifications and the behaviour of carcinomas in both species, by multiphoton microscopy. We present a retrospective study of 70 cases of human mammary tumour and 74 cases of canine mammary tumour. We analysed sections stained with haematoxylin and eosin from 1,200 representative areas of normal mammary tissue, fibroadenoma, grade I invasive carcinoma, grade III invasive carcinoma and invasive micropapillary carcinoma in human species and 1,304 representative areas of normal mammary tissue, benign mixed tumour, mixed carcinoma, carcinosarcoma, invasive micropapillary carcinoma and solid carcinoma in canine species. We obtained that both human and canine mammary carcinomas present lower density of collagen fibres, higher density of cells and the collagen fibres are more aligned than in normal tissue. For human mammary carcinomas, the collagen fibres are more linear as compared to normal tissue. In addition, we demonstrated that the carcinomas with unfavourable prognosis present shorter collagen fibres, and these collagen changes correlate with the clinical and pathological data in human and canine species. For dogs, there is a correlation between the mean fibre length with the specific survival times. Thus, we demonstrate that dogs provide an excellent comparative perspective for studying how changes in the tumour stroma affect patient survival.

EGCG-enabled Deep Tumor Penetration of Phosphatase and Acidity Dual-responsive Nanotherapeutics for Combinatory Therapy of Breast Cancer.

The presence of dense collagen fibers is a typical characteristic of triple-negative breast cancer (TNBC). Although these fibers hinder drug penetration and reduce treatment efficacy, the depletion of the collagen matrix is associated with tumor metastasis. To address this issue, epigallocatechin-3-gallate (EGCG) is first exploited for disrupting the dense collagenous stroma and alleviate fibrosis by specifically blocking the TGF-β/Smad pathway in fibroblasts and tumor cells when intraperitoneally administrated in TNBC tumor-bearing mice. A methotrexate (MTX)-loaded dual phosphate- and pH-responsive nanodrug (pHA@MOF-Au/MTX) is next engineered by integrating Fe-based metal-organic frameworks and gold nanoparticles for improved chemo/chemodynamic therapy of TNBC. Surface modification with pH (low)-insertion peptide substantially enhanced the binding of the nanodrug to 4T1 cells owing to tumor stroma remodeling by EGCG. High-concentration EGCG inhibited glutathione peroxidase by regulating mitochondrial glutamine metabolism, thus facilitating tumor cell ferroptosis. Furthermore, sequential EGCG and pHA@MOF-Au/MTX treatment showed remarkable anti-tumor effects in a mouse model of TNBC, with a tumor growth inhibition rate of 79.9%, and a pulmonary metastasis rate of 96.8%. Altogether, the combination strategy developed in this study can improve the efficacy of chemo/chemodynamic therapy in TNBC and represents an innovative application of EGCG.

Reactive Stroma and Acinar Morphology in Prostate Cancer: Implications for Progression and Prognostic Assessment.

Prostate cancer (PC) remains a significant global health concern, with prognostic assessments largely reliant on the Gleason Classification System. While it has proven effective, subjectivity in interpretation persists, prompting the need for complementary approaches. Reactive stroma (RS) has emerged as a potential candidate for enhancing PC characterization, as it reflects intricate interactions among stromal, epithelial, and extracellular matrix components. To shed light on this, we conducted a comprehensive study. Two expert pathologists independently analyzed consecutive prostate biopsies (n = 120 patients), categorized into four groups based on Gleason scores. Four acinar patterns were described, denoted as A, B, C, and D. Our study uncovered a noteworthy presence of RS, predominantly within poorly differentiated tumors. Stromogenic tumors, characterized by high RS content, were particularly associated with Gleason scores of 4 + 3 and ≥ 8. Intriguingly, acinar patterns, including the distinctive B and D patterns, exhibited strong correlations with stromogenic tumors. Incorporating quantitative imaging techniques (Second Harmonic Generation and Two-Photon Excitation Fluorescence Microscopy), we examined collagen fiber density within the stroma. Our analysis revealed a direct relationship between RS intensity and collagen fiber counts, particularly prominent in patterns B and D. These findings suggest that the stromal reaction in PC is closely linked to acinar morphology and collagen deposition. Moreover, rudimentary microacini at the tumor periphery, associated with intense RS and patterns B and D, may signify an unfavorable prognosis. Our study highlights the potential of RS as an additional prognostic factor in PC. It underscores the intricate interplay between acinar patterns, RS intensity, and collagen fiber density, providing valuable insights for future prognostic assessments and therapeutic strategies. Further exploration of these relationships is essential for a comprehensive understanding of PC progression and management.

Prospects for the use of flavonoid substances in pulmonary fibrosis (review of experimental studies)

Pulmonary fibrosis develops both spontaneously and as a result of lung damage by radiotherapy and chemotherapy, infectious diseases, and inhalation of harmful substances and particulate matter. In this case, normal tissue repair is disturbed: instead of regeneration of normal lung cells, the damaged tissue is replaced by fibrotic one consisting of dense collagen fibers. This leads to loss of lung tissue elasticity and impairment of its function, which significantly reduces the quality of patients’ lives. The search for drugs for interstitial fibrotic lung diseases remains an urgent task, since the existing antifibrotic drugs only slow down disease progression and have side effects that significantly reduce the patients’ quality of life. It is believed that natural polyphenolic substances, in particular flavonoids, can be used for the treatment of pulmonary fibrosis. Flavonoids present in various fruits, vegetables, tea and wine show a wide range of biological activities. They have antioxidant, anti-inflammatory and immunomodulatory properties, making them promising for the treatment of various diseases, including pulmonary fibrosis. Some studies have shown that flavonoids can inhibit myofibroblast activation and collagen production, which is directly related to the fibrotic process. Flavonoids are safe and can influence the hallmarks of fibrosis: oxidative stress, inflammation, cell proliferation and differentiation. To date, a large amount of experimental data confirming the antifibrotic effect of flavonoids has been accumulated. In recent years, clinical studies have been conducted to investigate the efficacy and safety of flavonoids in patients with pulmonary fibrosis. For example, quercetin and curcumin are being explored and have shown encouraging results in reducing markers of inflammation and fibrosis in the lung. However, the main obstacle to the widespread introduction of flavonoid substances into clinical practice remains their low oral bioavailability and rapid metabolism. The experimental data on the effect of flavonoids on the development of pulmonary fibrosis is analyzed in this review. The perspectives for improving their bioavailability using modern delivery systems (nanoparticles, liposomes, etc.), as well as dosage forms for topical application, are discussed in this paperwork.

Comparative study of physicochemical properties on corneal stromal lenticules following four decellularization methods

This study compares the physicochemical properties of corneal stromal lenticules following decellularization via four methods. Human corneal stromal lenticules, derived from small incision lenticule extraction surgery, underwent decellularization with sodium dodecyl sulfate (SDS), Triton X-100 (Tx) combined with SDS, trypsin-ethylenediaminetetraacetic acid (TE), or NaCl combined with deoxyribonuclease (DNase), respectively. Lenticule DNA and glycosaminoglycan (GAG) content, immunofluorescence staining of cell nuclei and collagen, transparency, biomechanics, histological structure, and immunogenicity were examined in each group and compared with fresh lenticules. All decellularized groups exhibited effective cell removal, with no significant decrease in GAG content (all P > 0.05). DNA content decreased in all decellularization groups (all P < 0.01), most notably in the SDS and Tx + SDS groups. Additionally, collagen I and IV fluorescence intensity was reduced in the TE group only (P < 0.0001). Histological staining revealed close similarity in collagen arrangement between the Tx + SDS group and fresh lenticules. Collagen fiber density increased while spacing and diameter decreased in all decellularized groups (all P < 0.05), with partial collagen degradation detected in the TE group. Light transmittance remained above 60% in the visible light spectrum in all groups. The Young's modulus or elastic modulus did not decrease significantly among decellularized lenticules (all P > 0.05). Human leukocyte antigen (HLA)-DR, HLA-ABC, and CD45 expression decreased in the Tx + SDS and NaCl + DNase groups (all P < 0.001). Although all four decellularization methods showed varying decellularization efficacy, Tx + SDS effectively removed cells without damaging corneal morphology, extracellular matrix, or biomechanics, indicating its potential for lenticule storage, transplantation, and bio-scaffold fabrication.

Changes associated with dietary beetroot extract on diet-induced damage in the common carotid artery of the albino rat (&lt;i&gt;Rattus norvegicus&lt;/i&gt;)

The high-fat high-fructose diet (HFHFr) has become widespread globally corresponding to a rise in obesity and cardiovascular diseases. Traditionally, these diseases were managed by multiple-drug regimens whose adherence was limited by side effects, hence leading to consideration of natural compounds. Recent studies have exploited the phytochemical properties of numerous plant extracts in ameliorating the histological changes seen in common carotid artery (CCA) damage, however, hardly any studies have investigated the effect of beetroot extract. The CCA were obtained from a biobank of a study that induced HFHFr in 45 male rats. Rats in the control group had received standard rat chow and water, and the positive control group received HFHFr. Those in the experimental group received HFHFr and 200mg/kg beetroot extract. These rats were randomly selected, euthanized and perfused on weeks 4,8,10 and 16. Their CCA were harvested, processed and stereological techniques applied to determine the densities of different histological components of the CCA.The HFHFr fed experimental animals revealed medial vascular thickening with a resultant increase in carotid intima-media thickness, increased vascular smooth muscle density, reduced elastic fiber density, and increased collagen fiber density compared to controls. Beetroot coadministration was protective against most of these structural changes. Dietary administration of beetroot extract has been found to be ameliorative to structural changes on the CCA following administration of HFHFr. Therefore, dietary beetroot extract may be indicated to mitigate harmful changes following long term exposure to a high fat high fructose diet.

Restoration of Corneal Stiffness in Rabbits Following Withdrawal of Travoprost.

To evaluate if the effect of travoprost on corneal material stiffness could be restored after drug withdrawal. Seventy-two rabbits were randomly allocated into three groups: medicine (M), medicine withdrawal (MW), and blank (B). Within the M and MW groups, treatment with travoprost was administered to the right eyes (MT and MWT) over a period of 12 weeks. Subsequently, the M group was killed, but the MW group underwent an additional 12-week period for treatment withdrawal. No treatment was given to the contralateral eyes (MC and MWC) in the M and MW groups. A separate blank control (BC) group remained untreated for the entire 24-week duration. In each group, corneas from 18 rabbits were tested mechanically under inflation conditions to estimate their tangent modulus (Et). The corneas of the remaining six rabbits underwent electron microscopy analysis, which focused on fibril diameter and interfibrillar spacing. Central corneal thickness (CCT) of the treated eyes (MT and MWT groups) decreased with 12 weeks of travoprost treatment (P < 0.05). The CCT in the MWT group increased after 12 weeks of withdrawal but was still lower than that in the BC group (P < 0.05). The Et of the MT group was significantly lower than that of the MC group at mean tissue stresses of 2, 4, and 6 kPa (P < 0.05). Conversely, no significant difference in Et values was observed between the MWT, MWC, and BC groups, indicating recovery after treatment cessation. Furthermore, the stromal interfibrillar spacing of the treated MT group was significantly larger (P < 0.05) than that of the control MC group, but no disparity was noted among the MWT, MWC, and BC groups following treatment withdrawal. Additionally, there were no significant differences in the mean diameter of collagen fibrils among all groups (all P > 0.05). Travoprost treatment appears to soften corneal tissue, decrease tissue thickness, and reduce the density of stromal collagen fibers by increasing the interfibrillar spacing. These changes were partially reversed after treatment cessation. Travoprost could further inhibit corneal growth, so its use in childhood and adolescence should be carefully considered. Additionally, the effect of travoprost in reducing corneal stiffness may lead to underestimations of intraocular pressure (IOP) measurement and hence overestimations in the effect of treatment in lowering IOP.

The Effects of Eurycoma Longifolia Jack Root Extract on Histological Parameters of Wound Healing.

Introduction: Wound healing involves multiple phases and biological events which are tightly regulated. Eurycoma longifolia Jack has potent activity several potent biological activities that can help in healing of wounds. This study aimed to assess the histological changes of wound healing induced by the topical application of Eurycoma longifolia jack extract hydrogel on wounds. Method: A total of 20 Sprague Dawley rats were grouped into 4 groups, negative control untreated, Hydrocyn® aqua gel, vehicle hydrogel (xanthan), and Eurycoma longifolia Jack (TA) hydrogel. Excisional wound was created in all animals. The gel was applied two time a day starting from wounding day. Granulation tissue samples were collected on day 5 post-wounding and histological sections were stained by H&amp;E for histological observation of the quantity inflammatory cells, fibroblasts, degree of new blood vessel formation, re-epithelialization, and collagen density. Results: TA hydrogel group showed a significantly higher number of fibroblasts and collagen fibre density with P-value ≤ 0.05. It also improved angiogenesis and epithelialization and maintained inflammatory cells at a moderate level. Conclusion: TA hydrogel improved all histological parameters of wound healing.

Treatment of Full-Thickness Cutaneous Wounds Using a Novel Fish Skin Acellular Dermal Powder as Hydrogel with Gene Expression of Some Growth Factors Genes

The purpose of this study is to evaluate how well fish skin acellular dermal powder hydrogel (FADPH) promotes the healing of cutaneous wounds in Iraqi bucks. 48 of full-thickness cutaneous wounds (3X3 cm) created on the dorsal back of twelve bucks, each two wounds on both sides. Then, divided into two groups according to treatment method (6 bucks /group). The wounds in control group (A), were left without treatment and the wounds in treatment group (B) were treated by topical application of (FADPH). The outcomes were assessed clinically, morphometrically scoring at (7, 14, 35, and 42) days post treatment, and gene expression by RT-PCR of two genes including fibroblast growth factor (FGF) and epidermal growth factor (EGF) at three times periods (0,7 and 14) days and histopathological assessment at (7,14, 35 and 42) days post treatment. The scoring results of group B showed that the percentages of scoring results were significantly higher than that of control wounds at the level of (P&lt;0.001) from the first 7 days until the end of the study. Also, results of gene expression of FGF and EGF was considerably higher in the treated group than control group at the level of (p&lt;0.001). The histopathological results in group B showed faster re- epithelialization of the epidermis, proliferation of fibrin and regenerated epithelia, dense collagen fibers, and finally complete regeneration of the epidermal layer at the end of study in compared with group A which was showed slowly development in wound healing proses and highly inflammatory reaction. In conclusion, FADM hydrogel enhanced and accelerated the healing of skin wounds in male goats.

AGK2, a SIRT2 inhibitor, ameliorates D-galactose-induced liver fibrosis by inhibiting fibrogenic factors.

In our study, we aimed to investigate the effect of SIRT2 inhibition on function, fibrosis and inflammation in liver fibrosis induced by D-Galactose (D-Gal) administration. A total of 32 3-month-old Sprague Dawley rats were used in the study. Rats were divided into 4 groups as Control, d-Gal, Solvent+d-Gal, d-Gal+AGK2+Solvent. d-Gal (150 mg/kg/day), AGK-2 (10 µM/bw) as a specific SIRT2 inhibitor, 4%DMSO + PBS as a solvent was applied to the experimental groups and physiological saline was applied to the control group for 10 weeks. All applications were performed subcutaneously. Histological fibrotic changes were studied in the liver tissues by Masson's trichrome staining, hematoxylin and eosin staining and immunohistochemistry and the levels of selected factors were determined by quantitative reverse transcription-polymerase chain reaction, western blot analysis, and immunohistochemical analysis. Biochemical parameters and Paraoxonase levels were determined in the plasma. d-Galactose administration increased AST, AST-ALT Ratio, APRI, SIRT2 protein expression, IL1β, TGF β, β-catenin, Type I collagen, Type III collagen and α-SMA, collagen fiber density and histopathological score. ALT and lipid panels were not changed and paraxonase plasma level was shown to decrease. These effects were largely blocked by the SIRT2 inhibitor AGK2. These findings suggest that SIRT2 inhibition attenuates d-Gal-induced liver injury and that this protection may be due to its antifibrotic and anti-inflammatory activities.

Immortelle Essential-Oil-Enriched Hydrogel for Diabetic Wound Repair: Development, Characterization, and In Vivo Efficacy Assessment

Background: Alarming data revealed that 19% to 34% of adults with diabetes mellitus develop chronic wounds, which are characterized by impaired healing and a higher risk of infections. Inspired by the traditional use of immortelle for wound healing and the lack of scientific evidence regarding how it thoroughly influences tissue regeneration, we aimed to formulate a hydrogel loaded with immortelle essential oil and assess its effectiveness on diabetic excision wounds. Methods: The rheological properties of the hydrogel, an in vivo safety test, as well as wound healing capacity, were determined in rats with induced diabetes and excision wounds. Diabetic rats were divided into four groups: untreated, treated with 1% silver sulfadiazine ointment, treated with a gel base, and treated with the immortelle essential oil-based hydrogel. Results: It was revealed that the hydrogel exerts pseudoplastic behavior and has no potential to act as an irritant, thus highlighting its suitability for skin application. Moreover, analysis of macroscopic, biochemical, and histopathological data revealed that the immortelle essential oil-based hydrogel significantly improves wound repair. Superior re-epithelialization, scar maturation, and increased collagen fiber density were achieved after immortelle essential oil-based gel application. Conclusions: These findings suggest that the immortelle essential oil-based hydrogel could be a natural, safe, and effective wound-healing dressing.