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Background: This study investigated the wound-healing potential of hispolon, a polyphenolic pigment derived from medicinal mushrooms, under diabetic conditions using both in vitro and in vivo models. Methods: In the in vitro assays, L929 fibroblast cells exposed to high glucose (33 mmol/L) were treated with hispolon at concentrations of 2.5, 5, 7.5, or 10 μmol/L. In the in vivo assays, streptozotocin-induced diabetic rats with excision wounds received daily topical applications of 0.2 g of 5% (w/w) hispolon ointment. Results: Hispolon improved cell viability; suppressed oxidative stress by reducing reactive oxygen species, lipid peroxidation, and oxidative DNA damage; and restored the reduced glutathione/oxidized glutathione ratio. The scratch assay demonstrated that hispolon at 10 μmol/L enhanced fibroblast migration impaired by high-glucose conditions. Treatment with 5% (w/w) hispolon ointment accelerated wound contraction, reduced the epithelialization time, and enhanced tissue regeneration with an efficacy comparable to that of Fespixon® cream, as shown by histological findings of increased fibroblast activity, collagen deposition, and capillary growth. Hispolon ointment also modulated macrophage polarization in diabetic wounds by reducing M1 markers and enhancing M2 markers. In a diabetic rat dead-space-wound model, 5% (w/w) hispolon ointment reduced the levels of pro-inflammatory cytokines, increased those of anti-inflammatory cytokines and growth factors, and stimulated Type I and III collagen synthesis, effectively promoting wound healing. In incisional wounds, hispolon ointment improved the wound-breaking strength, showing results comparable to that of Fespixon® cream. Safety assessments confirmed that hispolon ointment showed no acute dermal toxicity. These findings underscore hispolon's potential as a promising candidate for diabetic wound management by mitigating oxidative stress, enhancing tissue regeneration, and accelerating wound healing. [ABSTRACT FROM AUTHOR]

ABSTRACT Background/Aim Methods Results Conclusion Pseudoxanthoma elasticum (PXE) is a genetic connective tissue disorder that affects the skin with limited treatment options. A recent technology employing particle‐free polycaprolactone (PCL) has shown promising results in treating inner thighs and kness of a 27‐year‐old female patient. This article provides a case report along with our detailed treatment protocol based on the efficacy of PCL in reversing skin laxity that can be easily incorporated into the therapeutic approaches for patients with PXE.The pinch test for clinical assessment, photographic documentation as well as satisfaction questionnaire were used in order to evaluate the improvement observed in skin laxity.After the finish of the protocol, the Pinch test score was diminished from 4 to 2, and the depth of the wrinkles was obviously improved in the photos. All the above, together with the high score of the patient satisfaction questionnaire, verified the efficacy of this novel PCL protocol in reversing PXE‘s skin laxity.Fully liquid PCL appears to outperform other bio‐stimulators in improving skin quality in PXE, offering longer‐lasting results and a high safety profile. However, further clinical trials with long‐term follow‐up are required to confirm its efficacy in PXE‘s skin laxity. [ABSTRACT FROM AUTHOR]

Background: Recent advancements in dermatological therapeutics have highlighted the need for treatments that enhance skin regeneration and healing. Diamond‐Augmented Zinc Oxide (ND‐ZnO) technology combines zinc oxide with diamond particles in a unique core‐shell structure, offering a multifaceted approach to overall skin health. Aims: This study evaluates the efficacy of ND‐ZnO in promoting human dermal fibroblast migration and growth, enhancing total collagen synthesis, and improving transdermal delivery of active ingredients as a daily comprehensive skin regeneration topical therapy. Patients/Methods: In vitro assays assessed wound healing, collagen production, and skin absorption. Human Dermal Fibroblasts (HDFs) were used in scratch wound assays. Collagen synthesis was quantified using enzyme‐linked immunosorbent assays (ELISA). Permeation tests were performed on reconstructed human epidermal tissues to evaluate niacinamide absorption. Clinical case studies validated ND‐ZnO efficacy in post‐CO₂ laser treatments and Actinic Keratosis removal recovery. Results: ND‐ZnO increased HDF migration by 198% compared to controls. Collagen synthesis assays showed a 71.3% restoration of collagen production in aged HDFs. Skin permeation studies revealed a 203% increase in niacinamide skin absorption with ND‐ZnO. Clinical case studies demonstrated faster and more effective healing post‐ablative CO₂ laser and significant improvements in Actinic Keratosis recovery. Conclusions: ND‐ZnO technology enhances wound healing, collagen synthesis, and active ingredient delivery, offering substantial benefits for daily skin regeneration and other dermatological applications. This innovative approach holds promise for advancing dermatological therapeutics, providing comprehensive skin care solutions that address both protective and regenerative needs. [ABSTRACT FROM AUTHOR]

Botryocladia leptopoda is a red macroalga known for its bioactive compounds with antioxidant, anti-inflammatory, and skin-regenerative properties. The study aimed to examine their effects on UV protection, collagen synthesis, fibroblast proliferation, and pigmentation modulation. Bioactive compounds were extracted using two solvents, producing ethanol extract (FE) and alkaline extracts (AE). Methods involved characterizing extracts using mass spectrometry and assessing their effects on human fibroblasts under UVB-induced damage. UV absorbance, ROS production, and collagen synthesis were evaluated. The FE extract, which comprised 4-hydroxyquinoline, phytosphingosine, and docosapentaenoic acid, reinstated procollagen type I synthesis to 113% of baseline levels and reduced TGF-β1-mediated fibroblast proliferation to 87.78%. FE also suppressed Smad2 and α-SMA by 71% and 68%, respectively, indicating modulation of fibrosis-associated pathways. AE, containing 4-hydroxyquinoline and phenylalanine betaine, demonstrated dose-responsive cellular repair, reducing fibroblast proliferation to 97.86% and collagen Type I expression by 73% at 1000 μg/mL. Both extracts decreased ROS production, with FE and AE reducing levels by 21.4% and 19.7%, respectively, under UVB-induced oxidative stress. FE showed superior scar inhibition, while AE excelled in skin regeneration and pigmentation management. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a long-term autoimmune condition marked by persistent inflammation of the joints and various systemic complications, including endothelial dysfunction, atherosclerosis, and pulmonary fibrosis. Oxidative stress is a key contributor to the pathogenesis of RA, potentially exacerbating vascular damage and promoting pro-angiogenic and profibrotic processes. Objective: This study aims to investigate the effects of sera from RA patients on human umbilical vein endothelial cells (HUVECs), focusing on the induction of oxidative stress, endothelial cell proliferation, migration, and collagen type I synthesis. Methods: Twenty-eight serum samples were collected from RA patients and healthy donors (HDs). HUVECs were exposed to these sera, and intracellular reactive oxygen species (ROS) levels were fluorescently detected using H2DCF-DA. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was evaluated through a scratch wound assay, and collagen type I synthesis was measured using a lentiviral vector expressing the green fluorescent protein (GFP) under the control of the human COL1A1 gene promoter. Results: Exposure to RA sera resulted in a significant increase in intracellular ROS levels in HUVECs compared to HD sera, indicating an elevated state of oxidative stress. RA sera also promoted endothelial cell proliferation and migration, suggesting a pro-angiogenic stimulus. Additionally, RA sera significantly increased collagen type I synthesis in HUVECs, implicating a potential role in profibrotic processes associated with RA. Conclusion: The results of this study emphasize the importance of circulating factors in RA sera in promoting oxidative stress, endothelial dysfunction, and pro-angiogenic and profibrotic phenotypes in endothelial cells. These processes may contribute to the vascular and fibrotic complications observed in RA, highlighting the necessity for additional research into focused therapeutic approaches to alleviate these effects. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a debilitating vascular disorder characterized by abnormal pulmonary artery smooth muscle cell (PASMC) proliferation and collagen synthesis, contributing to vascular remodeling and elevated pulmonary vascular resistance. This study investigated the critical role of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) in cell proliferation and collagen synthesis in PASMCs in PAH. Here we show that ATIC levels are significantly increased in the lungs of monocrotaline (MCT)-induced PAH rat model, hypoxia-induced PAH mouse model, and platelet-derived growth factor (PDGF)-stimulated PASMCs. Inhibition of ATIC attenuated PDGF-induced cell proliferation and collagen I synthesis in PASMCs. Conversely, overexpression or knockdown of ATIC causes a significant promotion or inhibition of Ras and ERK activation, cell proliferation, and collagen synthesis in PASMCs. Moreover, ATIC deficiency attenuated Ras activation in the lungs of hypoxia-induced PAH mice. Furthermore, Ras inhibition attenuates ATIC overexpression- and PDGF-induced collagen synthesis and PASMC proliferation. Notably, we identified that transcription factors MYC, early growth response protein 1 (EGR1), and specificity protein 1 (SP1) directly binds to promoters of Atic gene and regulate ATIC expression. These results provide the first evidence that ATIC promotes PASMC proliferation in pulmonary vascular remodeling through the Ras signaling pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: The worth of sea urchin gonads in the market is determined by their specific features connected to size and texture. Compared with wild counterparts, farmed sea urchins fed formulated feeds showed faster gonad growth but worse gonad texture traits, such as adhesiveness, cohesiveness, hardness, springiness, chewiness, and gumminess. Thus, it is pressing to enunciate the underlying mechanisms and find solutions to solve this problem. As the most abundant collagen, collagen type I is momentous for improving the hardness, springiness, and chewiness of muscle as verified. Vitamin C is vital for participating in the regulation of hydroxyproline biosynthesis, which is an essential component of collagen. However, the effects of vitamin C addition on the collagen synthesis and underlying mechanisms remain poorly understood in any sea urchin species. Therefore, this study aims to investigate the impact of vitamin C on the gonad growth, texture, collagen content, and the expression of genes involved in the collagen synthesis of sea urchin (Mesocentrotus nudus). These results could contribute to precisely quantify the vitamin C addition in the diets to produce gonads with high texture quality in sea urchin. The market value of sea urchin gonads is determined by the specific characteristics associated with gonad size and texture. Formulated feeds can effectively promote the gonad growth of sea urchins but cannot assure essential gonad texture traits. The objective of this study was to investigate the impact of vitamin C (VC) on the gonad growth, texture, collagen content, and the expression of genes involved in the collagen synthesis of sea urchins (Mesocentrotus nudus). Graded amounts of VC (0, 3000 and 6000 mg/kg) were supplemented to make three formulated feeds. Fresh kelp (Saccharina japonica) was used as the control diet. Each diet was randomly distributed to three tanks of M. nudus. The results indicated that the gonadosomatic index (GSI) and texture traits of M. nudus fed C3000 were significantly greater than those fed C0 and C6000. Collagen type I (Col I) in the gonads of M. nudus fed C3000 showed significantly greater areas than those fed C0 and C6000. Consistently, the expression levels of collagen alpha-1 (colp1α) of M. nudus fed C3000 were significantly higher than those fed C0 and C6000. As for the transforming growth factor beta (tgf-β)/Smads pathway, the expression levels of collagen synthesis genes (tgf-β receptor 1 and 2, smad nuclear-interacting protein 1 (snip1) and prolyl 4-hydroxylase subunit beta (p4hβ)) in the C3000 group were significantly greater than those in the C0, C6000 and kelp groups. On the contrary, the expression levels of collagen degradation genes (lysyl oxidase-like 2 (loxl2) and matrix metalloproteinase 14 (mmp14)) in the C3000 group were significantly lower than those in the C0, C6000 and kelp groups. In conclusion, VC at an addition level of 3000 mg/kg significantly increased the gonad texture and collagen contents of M. nudus, which could be accomplished by increasing collagen synthesis and inhibiting collagen degradation through the tgf-β/Smads pathway. These results could contribute to better understanding the beneficial effects of VC addition on the gonad texture quality of M. nudus. [ABSTRACT FROM AUTHOR]

Objectives: A diabetic ulcer, or delayed wound recovery, is a significant complication of diabetes mellitus (DM), with its prevalence having risen steadily in recent decades. With the advancement of technology, nanoparticles have been used to treat wounds. Nanoparticles derived from pumpkin leaves (CmAgNPs) are abundant in antioxidants and vitamins and possess antimicrobial and antiviral properties. This study highlighted the effectiveness of CmAgNPs in accelerating wound healing. Methods: Twenty-four male albino rats with partial-thickness wounds were assigned to four groups: the control group (NN), the untreated diabetes group (DN), the diabetic group treated with (CmAgNPs), and the group treated with silver sulfadiazine (SSD) cream. Morphological, histopathological, and physiological assessments of inflammation were conducted on all rats at 0-, 7-, 14-, and 21-days post-treatment. Results: On days 0, 7, 14, and 21, histological examination was conducted. Also, the activities of glutathione (GSH) and superoxide dismutase (SOD) were assessed. Histological analysis demonstrated that CmAgNPs significantly increased collagen content in the wound tissue and facilitated re-epithelialization. On days 7, 14, and 21, the group treated with CmAgNPs exhibited higher GSH levels compared to the DN and SSD groups. However, CmAgNPs did not have a significant effect on SOD levels. Conclusion: By stimulating re-epithelialization and collagen synthesis, (Cucurbita maxima) demonstrated superior efficacy in treating diabetic wound compared to silver sulfadiazine ointment. [ABSTRACT FROM AUTHOR]

Background Emodin is a traditional medicine that has been shown to exert anti-inflammatory and anti-oxidative effects. Previous research has indicated that emodin can alleviate myocardial remodeling and inhibit myocardial hypertrophy and fibrosis. However, the mechanism by which emodin affects myocardial fibrosis (MF) has not yet been elucidated.Methods Fibroblasts were treated with ANGII, and a mouse model of MF was established by ligation of the left anterior descending coronary artery. Cell proliferation was examined by a Cell Counting Kit-8 (CCK8) assay. Dihydroethidium (DHE) was used to measure reactive oxygen species (ROS) levels, and Masson and Sirius red staining were used to examine changes in collagen fiber levels. PI3K was over-expressed by lentiviral transfection to verify the effect of emodin on the PI3K/AKT/mTOR signaling axis. Changes in cardiac function in each group were examined by echocardiography.Results Emodin significantly inhibited fibroblast proliferation, decreased intracellular ROS levels, significantly upregulated collagen II expression, downregulated α-SMA expression, and inhibited PI3K/AKT/mTOR pathway activation in vitro. Moreover, the in vivo results were consistent with the in vitro. Emodin significantly decreased ROS levels in heart tissue and reduced collagen fibrillogenesis. Emodin could regulate the activity of PI3K to increase the expression of collagen II and downregulate α-SMA expression in part through the PI3K/AKT/mTOR pathway, and emodin significantly improved cardiac structure and function in mice.Conclusions This study revealed that emodin targeted the PI3K/AKT/mTOR pathway to inhibit the development of myocardial fibrosis and may be an antifibrotic agent for the treatment of cardiac fibrosis.

The article published in the Journal of Physiology explores the role of the circadian clock in regulating collagen homeostasis in tendons, particularly in chronic tendinopathy. The study by Yeung et al. reveals time-dependent gene expression patterns in healthy and tendinopathic human patellar tendons, highlighting disruptions in circadian gene expression and collagen composition in diseased tendons. The findings suggest potential implications for physical training, therapeutic interventions, and the early diagnosis and treatment of tendinopathy, offering new insights into the pathogenesis of this condition. [Extracted from the article]

Hypertension (HTA) is commonly treated with medications that can cause drug-induced gingival overgrowth (DIGO). This study investigates the mechanisms behind DIGO in hypertensive patients, focusing on the effects of calcium channel blockers, immunosuppressants, and anticonvulsants. We explore the cellular and molecular pathways involved, such as collagen synthesis, inflammation, and the role of integrins. Clinical implications include challenges in oral hygiene, periodontal health, and patient quality of life. Management strategies discussed include drug substitution, enhanced oral hygiene, and surgical options. Understanding the link between HTA treatment and gingival overgrowth can help healthcare providers better diagnose and manage this condition, improving patient outcomes and periodontal health.

Wound healing is a complex process orchestrated by interactions between a variety of cell types, including keratinocytes, fibroblasts, endothelial cells, inflammatory cells, and bioactive factors such as extracellular matrix (ECM) components, growth factors, and cytokines. Chronic wounds exhibit delayed proliferative phase initiation, reduced angiogenesis, impaired ECM synthesis, and persistent inflammatory response. Chronic wounds are one of the main challenges to the healthcare system worldwide, with a high cost for medical services. Hence, investigation of new approaches to accelerate wound healing is essential. Phytomedicines are considered as potential agents for improving the wound healing by accelerating epithelization, collagen synthesis, and angiogenesis. These natural compounds have various advantages including availability, ease of application, and high effectiveness in wound managment. This study aimed to investigate the biological effects of saffron or Crocus sativus L. (C. sativus) petal extract on cell survival, migration, and angiogenesis using MTT, scratch and in vitro tube formation assays. Moreover, the expression of collagen type I alpha 1 (COL1A1) and vascular endothelial growth factor (VEGF) were evaluated in human dermal fibroblasts (HDF)s and human umbilical vein endothelial cells (HUVEC)s, respectively. The effect of the C. sativus extract on the skin of diabetic mice was also monitored. The results showed that C. sativus petal extract promoted the viability and migration of HDFs and HUVECs. Moreover, C. sativus petal extract enhanced the formation of tube-like structures by HUVECs cultured on the Matrigel basement membrane matrix, indicating its potential to stimulate angiogenesis. Gene expression studies have shown the the C. sativus extract increases wound healing by upregulation of COL1A1 and VEGF, which are crucial factors involved in collagen deposition, epithelialization, and angiogenesis. Histological analysis revealed that C. sativus petal extract enhanced vascularity and increased the number of fibroblasts and collagen synthesis, ultimately accelerating wound closure compared to wounds treated with eucerin and commercial ointment in diabetic mice. Therefore, C. sativus petal extract has potential as a herbal treatment to improve the healing of diabetic wounds. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of interfering with the expression of histone demethylase KDM3A on the proliferation and collagen synthesis of hepatic stellate cells (HSCs). Methods Primary rat HSCs were treated with acetaldehyde, and the expression of KDM3A mRNA was detected using real-time quantitative PCR(RT-PCR). Subsequently. HSCs were transfected with lentivirus to interfere with KDM3A expression for 72 h. After acetaldehyde stimulation, the HSCs were collected and cell proliferation activity was assessed using the thiazolyl blue assay. The content of type III and type I collagen proteins was determined using enzyme-linked immunosorbent assay, while the expression levels of transforming growth factor-beta 2 (TGF-β) were measured by RT-PCR and Western blotting. Results Compared with the control group, the relative expression levels of KDM3A mRNA in the acetaldehyde-treated group increased approximately 4-fold (1.00±0.10 vs. 4.00±0.20), and TGF-ẞ mRNA expression increased approximately 3-fold(1.00±0.40 vs. 3.00±0.50),with both differences being statistically significant (143. 201.44.032.P<0.001). Following interference with KDM3A, the proliferation activity of transfected cells decreased by approximately 43.3% compared to the control group [transfected group optical density (0.38±0.06) lower than control group (0.67±0.08)]. Compared to the control group, the content of type III collagen decreased by approximately 20.00%(1.00±0.10 vs. 0.80±0.04), and type I collagen content decreased by approximately 30.00% (1.00±0.10 vs. 0.70±0.04), the protein and mRNA levels of TGF-ß, also significantly decreased (1.00± 0.10 vs. 0.70±0.10) in the transfected group, with all differences being statistically significant(t=12.272, 12.621,21,369, P<0.001). Conclusion Interfering with histone demethylase KDM3A can partially inhibit the proliferation and collagen synthesis of hepatic stellate cells, possibly by suppressing TGF-ẞ, expression. [ABSTRACT FROM AUTHOR]

Skin aging is an inevitable and intricate process instigated, among others, by oxidative stress. The search for natural sources that inhibit this mechanism is a promising approach to preventing skin aging. The purpose of our study was to evaluate the composition of phenolic compounds in the micellar extract of Phaseolus vulgaris sprouts. The results of a liquid chromatography–mass spectrometry (LC-MS) analysis revealed the presence of thirty-two constituents, including phenolic acids, flavanols, flavan-3-ols, flavanones, isoflavones, and other compounds. Subsequently, the extract was assessed for its antioxidant, anti-inflammatory, anti-collagenase, anti-elastase, anti-tyrosinase, and cytotoxic properties, as well as for the evaluation of collagen synthesis. It was demonstrated that micellar extract from common bean sprouts has strong anti-aging properties. The performed WST-8 (a water-soluble tetrazolium salt) assay revealed that selected concentrations of extract significantly increased proliferation of human dermal fibroblasts compared to the control cells in a dose-dependent manner. A similar tendency was observed with respect to collagen synthesis. Our results suggest that micellar extract from Phaseolus vulgaris sprouts can be considered a promising anti-aging compound for applications in cosmetic formulations. [ABSTRACT FROM AUTHOR]

Poly L-lactic acid (PLLA) fillers stimulate collagen synthesis by activating various immune cells and fibroblasts. Piezo1, an ion channel, responds to mechanical stimuli, including changes in extracellular matrix stiffness, by mediating Ca2+ influx. Given that elevated intracellular Ca2+ levels trigger signaling pathways associated with fibroblast proliferation, Piezo1 is a pivotal regulator of collagen synthesis and tissue fibrosis. The aim of the present study was to investigate the impact of PLLA on dermal collagen synthesis by activating Piezo1 in both an H2O2-induced cellular senescence model in vitro and aged animal skin in vivo. PLLA elevated intracellular Ca2+ levels in senescent fibroblasts, which was attenuated by the Piezo1 inhibitor GsMTx4. Furthermore, PLLA treatment increased the expression of phosphorylated ERK1/2 to total ERK1/2 (pERK1/2/ERK1/2) and phosphorylated AKT to total AKT (pAKT/AKT), indicating enhanced pathway activation. This was accompanied by upregulation of cell cycle-regulating proteins (CDK4 and cyclin D1), promoting the proliferation of senescent fibroblasts. Additionally, PLLA promoted the expression of phosphorylated mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III in senescent fibroblasts, with GsMTx4 treatment mitigating these effects. In aged skin, PLLA treatment similarly upregulated the expression of pERK1/2/ERK1/2, pAKT/AKT, CDK4, cyclin D1, mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III. In summary, our findings suggest Piezo1′s involvement in PLLA-induced collagen synthesis, mediated by heightened activation of cell proliferation signaling pathways such as pERK1/2/ERK1/2, pAKT/AKT, and phosphorylated mTOR/S6K1/4EBP1, underscoring the therapeutic potential of PLLA in tissue regeneration. [ABSTRACT FROM AUTHOR]

Corneal fibroblasts maintain homeostasis of the corneal stroma by mediating the synthesis and degradation of extracellular collagen, and these actions are promoted by transforming growth factor-β (TGF-β) and interleukin-1β (IL-1β), respectively. The cornea is densely innervated with sensory nerve fibers that are not only responsible for sensation but also required for physiological processes such as tear secretion and wound healing. Loss or dysfunction of corneal nerves thus impairs corneal epithelial wound healing and can lead to neurotrophic keratopathy. The sensory neurotransmitter substance P (SP) promotes corneal epithelial wound healing by enhancing the stimulatory effects of growth factors and fibronectin. We have now investigated the role of SP in collagen metabolism mediated by human corneal fibroblasts in culture. Although SP alone had no effect on collagen synthesis or degradation by these cells, it promoted the stimulatory effect of TGF-β on collagen type I synthesis without affecting that of IL-1β on the expression of matrix metalloproteinase-1. This effect of SP on TGF-β-induced collagen synthesis was accompanied by activation of p38 mitogen-activated protein kinase (MAPK) signaling and was attenuated by pharmacological inhibition of p38 or of the neurokinin-1 receptor. Our results thus implicate SP as a modulator of TGF-β-induced collagen type I synthesis by human corneal fibroblasts, and they suggest that loss of this function may contribute to the development of neurotrophic keratopathy. NEW & NOTEWORTHY: This study investigates the role of substance P (SP) in collagen metabolism mediated by human corneal fibroblasts in culture. We found that, although SP alone had no effect on collagen synthesis or degradation by corneal fibroblasts, it promoted the stimulatory effect of transforming growth factor-β on collagen type I synthesis without affecting that of interleukin-1β on the expression of matrix metalloproteinase-1. [ABSTRACT FROM AUTHOR]

Rosa spp., commonly known as rosehips, are wild plants that have traditionally been employed as herbal remedies for the treatment of a wide range of disorders. Rosehip is a storehouse of vitamins, including A, B complex, C, and E. Among phytonutrients, vitamin C is found in the highest amount. As rosehips contain significant levels of vitamin C, they are perfect candidates for the development of skincare formulations that can be effectively used in the treatment of different skin disorders (i.e., scarring, anti-aging, hyperpigmentation, wrinkles, melasma, and atopic dermatitis). This research focuses on the vitamin C content of several Rosa sp. by their botanical and geographic origins, which according to research studies are in the following order: R. rugosa > R. montana > R. canina > R. dumalis, with lower levels in R. villosa and R. arvensis, respectively. Among rosehip species, R. canina is the most extensively studied species which also displays significant amounts of bioactive compounds, but also antioxidant, and antimicrobial activities (e.g., against Propionibacterium acnes, Staphylococcus aureus, S, epidermis, and S. haemolyticus). The investigation also highlights the use of rosehip extracts and oils to minimise the harmful effects of acne, which primarily affects teenagers in terms of their physical appearance (e.g., scarring, hyperpigmentation, imperfections), as well as their moral character (e.g., low self-confidence, bullying). Additionally, for higher vitamin C content from various rosehip species, the traditional (i.e., infusion, maceration, Soxhlet extraction) and contemporary extraction methods (i.e., supercritical fluid extraction, microwaveassisted, ultrasonic-assisted, and enzyme-assisted extractions) are highlighted, finally choosing the best extraction method for increased bioactive compounds, with emphasis on vitamin C content. Consequently, the current research focuses on assessing the potential of rosehip extracts as medicinal agents against various skin conditions, and the use of rosehip concentrations in skincare formulations (such as toner, serum, lotion, and sunscreen). Up-to-date studies have revealed that rosehip extracts are perfect candidates as topical application products in the form of nanoemulsions. Extensive in vivo studies have revealed that rosehip extracts also exhibit specific activities against multiple skin disorders (i.e., wound healing, collagen synthesis, atopic dermatitis, melasma, and anti-aging effects). Overall, with multiple dermatological actions and efficacies, rosehip extracts and oils are promising agents that require a thorough investigation of their functioning processes to enable their safe use in the skincare industry. [ABSTRACT FROM AUTHOR]

The aim of this review is to enumerate medicinal plants and their bioactive compounds that may become potential leads in the mitigation of oral submucous fibrosis (OSMF) in the forthcoming future. It is focused on pathophysiology, risk factors, current treatment regimen, potential plant leads, and future therapies for OSMF. Data were extracted from a vast literature survey by using SciFinder, Web of Science, Google Scholar, and PubMed search engines with relevant keywords. Upon literature survey, we found that the phytochemical 'arecoline' present in the areca nut is the main causative agent of OSMF condition. Currently, OSMF is treated by immunomodulatory and anti‐inflammatory agents such as corticosteroids, enzymes (hyaluronidase, chymotrypsin, and collagenase), anti‐inflammatory mediators (isoxsuprine and pentoxifylline), dietary supplements (vitamins, antioxidants, and micronutrients), and anti‐fibrotic cytokines like interferon‐gamma that provides short‐term symptomatic relief to OSMF patients. However, some plant leads have been proven effective in alleviating symptoms and mitigating OSMF, which ultimately improves the quality of OSMF patients' life. We concluded that plant drugs like lycopene, curcumin, Aloe vera, colchicine, and Glycyrrhiza glabra are effective against OSMF in various in vitro and/or clinical studies and are being used by modern and traditional practitioners. [ABSTRACT FROM AUTHOR]

The aim of this study was to comprehensively examine and summarize the available in vitro evidence regarding the relationship between mechanical stimulation and biomarkers of collagen synthesis in human-derived tendon cells. Systematic review with narrative analyses and risk of bias assessment guided by the Health Assessment and Translation tool. The electronic databases MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid) and COMPENDEX (Engineering Village) were systematically searched from inception to 3 August 2023. Inclusion criteria encompassed English language, original experimental, or quasi-experimental in vitro publications that subjected human tendon cells to mechanical stimulation, with collagen synthesis (total collagen, type I, III, V, XI, XII, and XIV) and related biomarkers (matrix metalloproteinases, transforming growth factor β, scleraxis, basic fibroblast growth factor) as outcomes. Twenty-one publications were included. A pervasive definite high risk of bias was evident in all included studies. Owing to incomplete outcome reporting and heterogeneity in mechanical stimulation protocols, planned meta-analyses were unfeasible. Reviewed data suggested that human tendon cells respond to mechanical stimulation with increased synthesis of collagen (e.g., COL1A1, procollagen, total soluble collagen, etc.), scleraxis and several matrix metalloproteinases. Results also indicate that mechanical stimulation dose magnitude may influence synthesis in several biomarkers. A limited number of studies, unfortunately characterized by a definite high risk of bias, suggest that in vitro mechanical stimulation primarily increases type I collagen synthesis by human tendon cells. Findings from this systematic review provide researchers and clinicians with biological evidence concerning the possible beneficial influence of exercise and loading on cellular-level tendon adaptation. [ABSTRACT FROM AUTHOR]

Copper (Cu) is a trace element, essential for fish growth. In the current study, in addition to growth performance, we first explored the effects of Cu on collagen synthesis and myofiber growth and development in juvenile grass carp (Ctenopharyngodon idella). A total of 1080 fish (11.16 ± 0.01 g) were randomly divided into 6 treatments (3 replicates per treatment) to receive five doses of organic Cu, which were Cu citrate (CuCit) at 0.99 (basal diet), 2.19, 4.06, 6.15, and 8.07 mg/kg, and one dose of inorganic Cu (CuSO4·5H2O at 3.15 mg/kg), for 9 weeks. The results showed appropriate Cu level (4.06 mg/kg) enhanced growth performance, improved nutritional Cu status, and downregulated Cu-transporting ATPase 1 mRNA levels in the hepatopancreas, intestine, and muscle of juvenile grass carp. Meanwhile, collagen content in fish muscle was increased after Cu intake, which was probably due to the following pathways: (1) activating CTGF/TGF-β1/Smads signaling pathway to regulate collagen transcription; (2) upregulating of La ribonucleoprotein domain family 6 (LARP6) mRNA levels to regulate translation initiation; (3) increasing proline hydroxylase, lysine hydroxylase, and lysine oxidase activities to regulate posttranslational modifications. In addition, optimal Cu group increased myofiber diameters and the frequency of myofibers with diameter >50 μm, which might be associated with upregulation of cyclin B, cyclin D, cyclin E, proliferating cell nuclear antigen, myogenic determining factor (MyoD), myogenic factor 5, myogenin (MyoG), myogenic regulatory factor 4 and myosin heavy chain (MyHC) and downregulation of myostatin mRNA levels, increasing protein levels of MyoD, MyoG and MyHC in fish muscle. Finally, based on percentage weight gain (PWG), serum ceruloplasmin (Cp) activity and collagen content in fish muscle, Cu requirements were determined as 4.74, 4.37 and 4.62 mg/kg diet (CuCit as Cu source) of juvenile grass carp, respectively. Based on PWG and Cp activity, compared to CuSO4·5H2O, the efficacy of CuCit were 131.80% and 115.38%, respectively. Our findings provide new insights into Cu supplementation to promote muscle growth in fish, and help improve the overall productivity of aquaculture.

Rosa spp., commonly known as rosehips, are wild plants that have traditionally been employed as herbal remedies for the treatment of a wide range of disorders. Rosehip is a storehouse of vitamins, including A, B complex, C, and E. Among phytonutrients, vitamin C is found in the highest amount. As rosehips contain significant levels of vitamin C, they are perfect candidates for the development of skincare formulations that can be effectively used in the treatment of different skin disorders (i.e., scarring, anti-aging, hyperpigmentation, wrinkles, melasma, and atopic dermatitis). This research focuses on the vitamin C content of several Rosa sp. by their botanical and geographic origins, which according to research studies are in the following order: R. rugosa > R. montana > R. canina > R. dumalis, with lower levels in R. villosa and R. arvensis, respectively. Among rosehip species, R. canina is the most extensively studied species which also displays significant amounts of bioactive compounds, but also antioxidant, and antimicrobial activities (e.g., against Propionibacterium acnes, Staphylococcus aureus, S, epidermis, and S. haemolyticus). The investigation also highlights the use of rosehip extracts and oils to minimise the harmful effects of acne, which primarily affects teenagers in terms of their physical appearance (e.g., scarring, hyperpigmentation, imperfections), as well as their moral character (e.g., low self-confidence, bullying). Additionally, for higher vitamin C content from various rosehip species, the traditional (i.e., infusion, maceration, Soxhlet extraction) and contemporary extraction methods (i.e., supercritical fluid extraction, microwave-assisted, ultrasonic-assisted, and enzyme-assisted extractions) are highlighted, finally choosing the best extraction method for increased bioactive compounds, with emphasis on vitamin C content. Consequently, the current research focuses on assessing the potential of rosehip extracts as medicinal agents against various skin conditions, and the use of rosehip concentrations in skincare formulations (such as toner, serum, lotion, and sunscreen). Up-to-date studies have revealed that rosehip extracts are perfect candidates as topical application products in the form of nanoemulsions. Extensive in vivo studies have revealed that rosehip extracts also exhibit specific activities against multiple skin disorders (i.e., wound healing, collagen synthesis, atopic dermatitis, melasma, and anti-aging effects). Overall, with multiple dermatological actions and efficacies, rosehip extracts and oils are promising agents that require a thorough investigation of their functioning processes to enable their safe use in the skincare industry.

Background: Emodin is a traditional medicine that has been shown to exert anti-inflammatory and anti-oxidative effects. Previous research has indicated that emodin can alleviate myocardial remodeling and inhibit myocardial hypertrophy and fibrosis. However, the mechanism by which emodin affects myocardial fibrosis (MF) has not yet been elucidated. Methods: Fibroblasts were treated with ANGII, and a mouse model of MF was established by ligation of the left anterior descending coronary artery. Cell proliferation was examined by a Cell Counting Kit-8 (CCK8) assay. Dihydroethidium (DHE) was used to measure reactive oxygen species (ROS) levels, and Masson and Sirius red staining were used to examine changes in collagen fiber levels. PI3K was over-expressed by lentiviral transfection to verify the effect of emodin on the PI3K/AKT/mTOR signaling axis. Changes in cardiac function in each group were examined by echocardiography. Results: Emodin significantly inhibited fibroblast proliferation, decreased intracellular ROS levels, significantly upregulated collagen II expression, downregulated α-SMA expression, and inhibited PI3K/AKT/mTOR pathway activation in vitro. Moreover, the in vivo results were consistent with the in vitro. Emodin significantly decreased ROS levels in heart tissue and reduced collagen fibrillogenesis. Emodin could regulate the activity of PI3K to increase the expression of collagen II and downregulate α-SMA expression in part through the PI3K/AKT/mTOR pathway, and emodin significantly improved cardiac structure and function in mice. Conclusions: This study revealed that emodin targeted the PI3K/AKT/mTOR pathway to inhibit the development of myocardial fibrosis and may be an antifibrotic agent for the treatment of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor–β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10–30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM–DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation. [ABSTRACT FROM AUTHOR]

Sinocyclocheilus grahami is an economically valuable and famous fish in Yunnan Province, China. However, given its slow growth (40 g/2 years) and large growth differences among individuals, its growth performance needs to be improved for sustainable future use, in which molecular breeding technology can play an important role. In the current study, we conducted muscle transcriptomic analysis to investigate the growth gaps among individuals and the mechanism underlying growth within 14 fast- and 14 slow-growth S. grahami. In total, 1,647 differentially expressed genes (DEGs) were obtained, including 947 up-regulated and 700 down-regulated DEGs in fast-growth group. Most DEGs were significantly enriched in ECM-receptor interaction, starch and sucrose metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, amino acids biosynthesis and metabolism, peroxisome, and PPAR signaling pathway. Some genes related to glycogen degradation, glucose transport, and glycolysis (e.g., adipoq, prkag1, slc2a1, agl, pygm, pgm1, pfkm, gapdh, aldoa, pgk1, pgam2, bpgm, and eno3) were up-regulated, while some genes related to fatty acid degradation and transport (e.g., acox1, acaa1, fabp1b.1, slc27a1, and slc27a2) and amino acid metabolism (e.g., agxt, shmt1, glula, and cth) were down-regulated in the fastgrowth group. Weighted gene co-expression network analysis identified col1a1, col1a2, col5a1, col6a2, col10a1, col26a1, bglap, andkrt15 as crucial genes for S. grahami growth. Several genes related to bone and muscle growth (e.g., bmp2, bmp3, tgfb1, tgfb2, gdf10, and myog) were also up-regulated in the fast-growth group. These results suggest that fast-growth fish may uptake adequate energy (e.g., glucose, fatty acid, and amino acids) from fodder, with excess energy substances used to synthesize collagen to accelerate bone and muscle growth after normal life activities are maintained. Moreover, energy uptake may be the root cause, while collagen synthesismay be the direct reason for the growth gap between fast- and slow-growth fish. Hence, improving food intake and collagen synthesis may be crucial for accelerating S. grahami growth, and further research is required to fully understand and confirm these associations. [ABSTRACT FROM AUTHOR]

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Different bone-related diseases are mostly caused by the disruption of bone formation and bone resorption, including osteoporosis. Traditional medicinal literature has reported the possible anti-osteoporotic properties of Glehnia littoralis. However, the chemical compounds in extracts that are responsible for bone metabolism are poorly understood. The present study aimed to explore and compare the coumarin-based compounds present in G. littoralis extracts, the antioxidant activities, and the anti-osteoporotic properties of different extracts of G. littoralis (leaf and stem, fruit, whole plant, and root extracts) on bone metabolism. This study analyzed G. littoralis extract effects on the proliferation and osteoblastic differentiation of MC3T3-E1 osteoblasts. Among the different tested samples, stem extracts had the highest scopoletin (53.0 mg/g), and umbelliferone (1.60 mg/g). The significantly (p < 0.05) highest amounts of imperatorin (31.9 mg/g) and phellopterin (2.3 mg/g), were observed in fruit and whole plant extracts, respectively. Furthermore, the results confirmed alkaline phosphatase activity, collagen synthesis, mineralization, osteocalcin content, and osterix and RUNX2 expression. G. littoralis extracts at concentrations greater than 20 µg/mL had particularly adverse effects on MC3T3-E1 cell viability and proliferation. Notably, cell proliferation was significantly elevated at lower G. littoralis concentrations. Comparatively, 0.5 µg/mL stem had a higher osteocalcin content. Of the four extract types, stem showed a higher collagen synthesis effect at concentrations of 0.5–5 µg/mL. Except for fruit extracts, G. littoralis extract treatment significantly elevated osterix gene expression. All G. littoralis extracts increased RUNX2 gene expression. The results described here indicate that G. littoralis ethanolic extracts can effectively prevent osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Hyaluronic acid presents a valuable cosmetic ingredient that occurs naturally. Its direct links to skin aging has led to its broad application. The aim of this study was to improve the cosmetic efficacy of high molecular weight hyaluronic acid (HMWHA) without chemical modifications and evaluate such improvements through clinical and in vitro studies. Methods: A novel formulation of HMWHA (SCAI‐HA) was prepared and investigated to comparatively assess 6 clinical and 2 in vitro parameters concerning its dermatological cosmetic efficacy and biological properties. The dermatological and cellular parameters examined in this study include skin hydration, transepidermal water loss (TEWL), skin elasticity, wrinkles, facial sagging, dermal density, cytotoxicity, and collagen synthesis. Results: SCAI‐HA exhibited the ability to improve the tested dermatological parameters (hydration, elasticity, wrinkles, and density) to magnitudes comparable to those of HMWHA. In addition, SCAI‐HA showed notably improved capacities for attenuating facial sagging and TEWL and promoting cellular collagen synthesis in normal human dermal fibroblasts. Conclusion: SCAI‐HA presents a novel conformation of HMWHA with improved cosmetic efficacy in mitigating (i) facial sagging, (ii) TEWL, and promoting, and (iii) collagen synthesis. These findings denote the enhancement of SCAI‐HA as a cosmetic ingredient with potential anti‐aging properties. [ABSTRACT FROM AUTHOR]

This study relates to the Alteromonas ferment extract, a by-product of a marine bacteria, Alteromonas macleodii, is used in anti-aging cream formulation. Alteromonas ferment extract is an innovative anti-pollution ingredient that chelates heavy metals and has non-toxic anionic polysaccharides, which are used as thickening or structuring agent in tissue engineering, wound management or drug delivery applications. Aging is a physiological process, it is undesirable especially on the skin. Aging leads to weakening of facial muscles and loss of subcutaneous fat and skin laxity, along with wrinkles, prominent lines and sagging skin. Changes in collagen play an important role in reducing skin elasticity. In this case, fibroblast decreases, matrix metalloproteinase increases (responsible for collagen breakdown), and glycosaminoglycans decrease. The objective of the study was to evaluate effects of the anti-aging cosmetic face cream including Alteromonas ferment extract on human dermal fibroblast cells. The outcomes of the characterization analysis have indicated the development of a successful cream formulation with optimum characteristics. No microbial growth was observed. Given the results obtained in the tested conditions, the anti-aging cream is not cytotoxic against fibroblasts 0.5% or less concentration. The dilutions of 0.1% and 0.2% were chosen for evaluation of collagen concentration, because they were the most appropriate concentrations in terms of solubility and lack of cytotoxicity. The treatment with anti-aging cream formulation at 0.1% and 0.2% increased collagen synthesis 57% and 67%, respectively in cell culture. [ABSTRACT FROM AUTHOR]

Abstract Background Nutrient regulation has been proven to be an effective way to improve the flesh quality in fish. As a necessary nutrient for fish growth, protein accounts for the highest proportion in the fish diet and is expensive. Although our team found that the effect of protein on the muscle hardness of grass carp was probably related to an increased collagen content, the mechanism for this effect has not been deeply explored. Moreover, few studies have explored the protein requirements of sub-adult grass crap (Ctenopharyngodon idella). Therefore, the effects of different dietary protein levels on the growth performance, nutritional value, muscle hardness, muscle fiber growth, collagen metabolism and related molecule expression in grass carp were investigated. Methods A total of 450 healthy grass carp (721.16 ± 1.98 g) were selected and assigned randomly to six experimental groups with three replicates each (n = 25/replicate), and were fed six diets with 15.91%, 19.39%, 22.10%, 25.59%, 28.53% and 31.42% protein for 60 d. Results Appropriate levels of dietary protein increased the feed intake, percentage weight gain, specific growth rate, body composition, unsaturated fatty acid content in muscle, partial free amino acid content in muscle, and muscle hardness of grass carp. These protein levels also increased the muscle fiber density, the frequency of new muscle fibers, the contents of collagen and IGF-1, and the enzyme activities of prolyl 4-hydroxylases and lysyloxidase, and decreased the activity of matrix metalloproteinase-2. At the molecular level, the optimal dietary protein increased collagen type I α1 (Colα1), Colα2, PI3K, Akt, S6K1, La ribonucleoprotein domain family member 6a (LARP6a), TGF-β1, Smad2, Smad4, Smad3, tissue inhibitor of metalloproteinase-2, MyoD, Myf5, MyoG and MyHC relative mRNA levels. The levels of the myostatin-1 and myostatin-2 genes were downregulated, and the protein expression levels of p-Smad2, Smad2, Smad4, p-Akt, Akt, LARP6 and Smad3 were increased. Conclusions The appropriate levels of dietary protein promoted the growth of sub-adult grass carp and improved muscle hardness by promoting the growth of muscle fibers, improving collagen synthesis and depressing collagen degradation. In addition, the dietary protein requirements of sub-adult grass carp were 26.21% and 24.85% according to the quadratic regression analysis of growth performance (SGR) and the muscle hardness (collagen content), respectively.

Connective tissue growth factor (Ctgf) is a matricellular protein with diverse biological function. It is regarded as a central regulator of tissue fibrosis and collagen synthesis in mammals. However, its roles in fish remain elusive. Here, a ctgf gene was cloned (NcCtgf), characterized and functionally studied in the chu's croaker (Nibea coibor). NcCtgf encoded a protein containing 346 amino acids, 38 conserved cysteine residues, 4 functional domains and a signal peptide. NcCtgf shared highest identity (99.4 %) to the Larimichthys crocea Ctgf protein. Phylogenetic tree revealed that NcCtgf clustered with the teleost Ctgfa and Ctgf of higher vertebrates, instead of teleost Ctgfb. NcCtgf was expressed with higher level in gonad, spleen, gill and swimming bladder than other tissues, and was up-regulated in swim bladder synchronously with collagen I genes by hydroxyproline and TGF-β1 treatment. NcCtgf knockdown/overexpression inhibited/promoted collagen synthesis in swim bladder cell, respectively. Notably, NcCtgf protein could be secreted to cell culture medium and up-regulated collagen I expression in swim bladder cell. These findings indicate NcCtgf plays vital roles in collagen synthesis in swim bladder of Nibea coibor , and provide basis for further understanding of ctgf evolution and exploring new approach for enhancing collagen deposition in fish products during aquaculture. [ABSTRACT FROM AUTHOR]

Background: Initial lymphatic vessels do not have a continuous basement membrane. Therefore, the ability of lymphatic endothelial cells (LECs) to produce extracellular matrix (ECM) has received little attention. Untreated lymphedema is a chronic disease that progresses to massive fibrosclerosis in advanced stages. Expansion of the intercellular space and fibrosclerosis cause hypoxia, which also affects the LECs. Results: We studied the expression of genes in human LECs in vitro by RNA sequencing, analyzed the effects of hypoxia (1% O2) vs. normoxia (21% O2), and focused on ECM genes. LECs express fibrillin‐1 and many typical components of a basement membrane such as type IV, VIII, and XVIII collagen, laminin β1, β2, and α4, perlecan, and fibronectin. Under hypoxia, we found significant upregulation of expression of genes controlling hydroxylation of procollagen (PLOD2, P4HA1), and also cross‐linking, bundling, and stabilization of collagen fibrils and fibers. Also striking was the highly significant downregulation of elastin expression, whereas fibulin‐5, which controls the assembly of tropoelastin monomers, was upregulated under hypoxia. In the dermis from genital lymphedema, we observed significant PLOD2 expression in initial lymphatics. Conclusions: Overall, hypoxia results in the picture of a dysregulated ECM production of LECs, which might be partly responsible for the progression of fibrosclerosis in lymphedema. Key Findings: Initial lymphatics do not produce a continuous basal lamina, nevertheless, lymphatic endothelial cells (LECs) express numerous ECM genes including collagen IV, V, VIII, XVIII, laminin, perlecan, fibronectin and fibrillin.RNASeq analyses show that LECs express approx. 16.800 genes. We observed significant regulation of 162 genes after 4 days of hypoxia (1% pO2). 13% (21 genes) of the hypoxia‐regulated genes are connected to the ECM.It is very likely that hypoxia is a crucial factor in the development of fibrosis in chronic lymphedema (LE), and our data suggest that hypoxic LECs can contribute to fibrosclerosis during LE progression. [ABSTRACT FROM AUTHOR]

Peroxiredoxin 1 (PRDX1) participates in tumor cell proliferation, apoptosis, migration, invasion, and the epithelial-to-mesenchymal transition (EMT). This study aimed to investigate the effect of PRDX1 on the EMT of airway epithelial cells stimulated with lipopolysaccharide (LPS) and transforming growth factor-beta 1 (TGF-β1). PRDX1 overexpression significantly increased the proliferation and migration of human bronchial epithelial (BEAS-2B) cells, reduced cell apoptosis (p < 0.01), and induced EMT and collagen deposition by upregulating the expression of the matrix metallopeptidase (MMP)2, MMP9, a-smooth muscle actin (α-SMA), N-cadherin, vimentin and twist proteins and inhibiting E-cadherin expression (p < 0.05). PRDX1 overexpression promoted TGF-β1-mediated inhibition of cell proliferation and migration and significantly enhanced the TGF-β1-induced EMT and collagen synthesis (p < 0.05). Knockdown of PRDX1 inhibited cell proliferation, migration, EMT, and collagen synthesis (p < 0.01), reversed LPS-mediated inhibition of cell proliferation and migration, and significantly suppressed LPS-induced EMT and collagen synthesis (p < 0.01). The result indicating that PRDX1 may be involved in LPS/TGF-1-induced EMT and collagen synthesis in human bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

This study was designed to investigate in vitro biological activities and phytochemical composition of aqueous and ethanolic extracts from Achillea sintenisii Hub- Mor. (AS). To determine the chemical composition of AS extracts, phytochemical analyses were performed by using HPLC–ESI-Q-TOF-MS-MS. Afterwards, both extracts were investigated in terms of their effect on fibroblast proliferation, collagen synthesis, and hydrogen peroxide-induced damage. In addition to cell culture analysis, antibacterial, antioxidant, hyaluronidase inhibitory activities and total phenolic contents of the extracts were analyzed in cell-free systems. Our results demonstrated that the aqueous and ethanolic extracts did not show cytotoxic activity on fibroblasts, on the contrary, promoted fibroblast proliferation. Both AS extracts potently inhibited hyaluronidase activity and the inhibitory effect of ethanolic extract was comparable with the positive control, especially at high concentrations. The aqueous extract was the potent stimulator of collagen synthesis at 200 µg/mL concentration. Although the ethanolic extract showed antibacterial activity against all gram-positive bacteria, the aqueous extract was only effective against K. pneumoniae and B. subtilis. The ability of AS extracts, which have a rich phenolic compound content (≥50 mg GAE/g), to scavenge free radicals and protect fibroblasts against hydrogen peroxide-induced damage can be considered as a result of their antioxidant potential. Our findings scientifically support the widespread use of this plant, by demonstrating the pharmacological properties of the extracts.

Abstract Introduction Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing. Method A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes. Results The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation. Conclusions Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.

Carpal tunnel syndrome (CTS) is the most common compression neuropathy in the upper limb. Mechanical compression and local ischemia of the median nerve result in paresthesia, pain, and sensory and motoric disturbances. There are some aspects of the disease that suggest the potential role of genetic predispositions. This article presents a review of the literature about the significance of genetic factors in the etiology of CTS. It discusses the effect of selected gene mutations on constitutional and anthropometric features which may predispose to CTS. These genes are involved in the organization of an extracellular matrix architecture, as well as in bone, cartilage, and tendons development pathways. Therefore they may be potentially responsible for the observed relationship between anthropometric/constitutional factors and CTS. The findings from the studies provide reliable information on the association between genetic risk factors and the development of CTS. [ABSTRACT FROM AUTHOR]

Background: Nutrient regulation has been proven to be an effective way to improve the flesh quality in fish. As a necessary nutrient for fish growth, protein accounts for the highest proportion in the fish diet and is expensive. Although our team found that the effect of protein on the muscle hardness of grass carp was probably related to an increased collagen content, the mechanism for this effect has not been deeply explored. Moreover, few studies have explored the protein requirements of sub-adult grass crap (Ctenopharyngodon idella). Therefore, the effects of different dietary protein levels on the growth performance, nutritional value, muscle hardness, muscle fiber growth, collagen metabolism and related molecule expression in grass carp were investigated. Methods: A total of 450 healthy grass carp (721.16 ± 1.98 g) were selected and assigned randomly to six experimental groups with three replicates each (n = 25/replicate), and were fed six diets with 15.91%, 19.39%, 22.10%, 25.59%, 28.53% and 31.42% protein for 60 d. Results: Appropriate levels of dietary protein increased the feed intake, percentage weight gain, specific growth rate, body composition, unsaturated fatty acid content in muscle, partial free amino acid content in muscle, and muscle hardness of grass carp. These protein levels also increased the muscle fiber density, the frequency of new muscle fibers, the contents of collagen and IGF-1, and the enzyme activities of prolyl 4-hydroxylases and lysyloxidase, and decreased the activity of matrix metalloproteinase-2. At the molecular level, the optimal dietary protein increased collagen type I α1 (Colα1), Colα2, PI3K, Akt, S6K1, La ribonucleoprotein domain family member 6a (LARP6a), TGF-β1, Smad2, Smad4, Smad3, tissue inhibitor of metalloproteinase-2, MyoD, Myf5, MyoG and MyHC relative mRNA levels. The levels of the myostatin-1 and myostatin-2 genes were downregulated, and the protein expression levels of p-Smad2, Smad2, Smad4, p-Akt, Akt, LARP6 and Smad3 were increased. Conclusions: The appropriate levels of dietary protein promoted the growth of sub-adult grass carp and improved muscle hardness by promoting the growth of muscle fibers, improving collagen synthesis and depressing collagen degradation. In addition, the dietary protein requirements of sub-adult grass carp were 26.21% and 24.85% according to the quadratic regression analysis of growth performance (SGR) and the muscle hardness (collagen content), respectively. [ABSTRACT FROM AUTHOR]

Background: Salvianolic acid B (SAB) is one of the main active ingredients of Salvia Miltiorrhiza. It has significant skin anti‐aging, whitening, and sun protection properties. Aims: The study aimed at studying the mechanism underlying the effect of salvianolic acid Bon collagen synthesis, which has good anti‐aging efficacy and modulates microcirculation. Methods: This study employed available public databases, bioinformatics methodologies, and the inverse docking approach to explore the effectiveness of SAB in the regulating collagen synthesis, and then used an human dermal fibroblast (HDF)– Human dermal microvascular endothelial cell (HDMEC) in vitro model to validate the predicted mechanism of SAB in influencing collagen synthesis. Results: The results showed that NO production in SAB‐treated HDMEC‐conditioned medium was increased compared to that in control media, and the same tendency was also observed for growth factor production. SAB also upregulated HDMEC cellular eNOS and VEGF. When SAB‐treated HDMEC conditioned medium was transferred to HDFs, the expression of collagen I, collagen III, and elastin in HDFs was upregulated and MMP‐1 was downregulated. Conclusions: The results show that SAB regulates collagen through the HDMEC–HDF pathway. Furthermore, the mechanisms might be closely related to the microcirculation factors NO and VEGF. [ABSTRACT FROM AUTHOR]

Previous studies have noted distinctions between medial meniscus posterior root and horn cells. However, the characteristics of root remnant cells have not been explored in detail. The purpose of this study was to evaluate the gene expression levels, proliferation, and resistance to mechanical stress of remnant and horn cells. Medial meniscus tissue samples were obtained from patients who underwent total or uni-compartmental knee arthroplasty. Cellular morphology, sry-type HMG box 9, type II collagen, and chondromodulin-I gene expression levels were analyzed. Collagen synthesis was assessed by immunofluorescence staining. Proliferation analysis after 4 h-cyclic tensile strain was performed. Horn cells displayed triangular morphology, whereas root remnant cells appeared fibroblast-like. sry-type HMG box 9 mRNA expression levels were similar in both cells, but type II collagen and chondromodulin-I mRNA expressions were observed only in horn cells. The ratio of type II collagen-positive cells in horn cells was about 10-fold higher than that in root remnant cells, whereas the ratio of sry-type HMG box 9-positive cells was similar. A significant increase in proliferation was observed in root remnant cells compared to that in horn cells. Further, under cyclic tensile strain, the survival rate was higher in root remnant cells than in horn cells. Medial meniscus root remnant cells showed higher proliferation and resistant properties to cyclic tensile strain than horn cells and showed no chondromodulin-I expression. Preserving the medial meniscus posterior root remnant during pullout repair surgery might maintain mechanical stress-resistant tissue and support healing. [ABSTRACT FROM AUTHOR]

An eight-week experiment was undertaken to examine the effect of dietary hydroxyproline (Hyp) supplementation on growth performance, collagen synthesis, muscle quality of an improved triploid crucian carp (Carassius auratus Triploid) (ITCC). Six isonitrogenous (340 g/kg diet), isolipidic (60 g/kg diet) and isocaloric (17.80 MJ/kg diet) diets were formulated containing a certain amount of Hyp: 0.09% (the control group), 0.39, 0.76, 1.14, 1.53 and 1.90%. Each diet was randomly assigned to three tanks and each group was fed two times daily until apparent satiation. The results showed that growth performance and feed utilization of ITCC were significantly improved with the dietary Hyp level was increased from 0.09 to 0.76%. Crude protein, threonine and arginine content in the dorsal muscle in 0.76% hydroxyproline group were significantly higher than those in basic diet group (p < 0.05). The muscle textural characteristics increased remarkably with the amount of Hyp in the diet rising from 0.09 to 1.53% (p < 0.05). Meanwhile, the contents of type I collagen (Col I) and Pyridinium crosslink (PYD) in the muscle of fish were significantly increased by dietary Hyp (p < 0.05). The muscle fiber diameter and density of the fish were significantly increased when fed with 0.76% Hyp (p < 0.05). Furthermore, dietary supplementation with an appropriate concentration of Hyp substantially increased the expression of genes involved in collagen synthesis (col1a1 , col1a2 , p4hα1 , p4hβ , smad4 , smad5 , smad9, and tgf-β) and muscle growth (igf-1 , tor , myod , myf5, and myhc) (p < 0.05). In conclusion, dietary supplementation of Hyp can enhance fish growth performance, collagen production, muscle textural characteristics and muscle growth of ITCC. According to the SGR broken-line analysis, the recommended supplementation level of Hyp was 0.74% in the diet for ITCC, corresponding to 2.2% of dietary protein. [ABSTRACT FROM AUTHOR]

An eight-week experiment was undertaken to examine the effect of dietary hydroxyproline (Hyp) supplementation on growth performance, collagen synthesis, muscle quality of an improved triploid crucian carp (Carassius auratus Triploid) (ITCC). Six isonitrogenous (340 g/kg diet), isolipidic (60 g/kg diet) and isocaloric (17.80 MJ/kg diet) diets were formulated containing a certain amount of Hyp: 0.09% (the control group), 0.39, 0.76, 1.14, 1.53 and 1.90%. Each diet was randomly assigned to three tanks and each group was fed two times daily until apparent satiation. The results showed that growth performance and feed utilization of ITCC were significantly improved with the dietary Hyp level was increased from 0.09 to 0.76%. Crude protein, threonine and arginine content in the dorsal muscle in 0.76% hydroxyproline group were significantly higher than those in basic diet group (p < 0.05). The muscle textural characteristics increased remarkably with the amount of Hyp in the diet rising from 0.09 to 1.53% (p < 0.05). Meanwhile, the contents of type I collagen (Col I) and Pyridinium crosslink (PYD) in the muscle of fish were significantly increased by dietary Hyp (p < 0.05). The muscle fiber diameter and density of the fish were significantly increased when fed with 0.76% Hyp (p < 0.05). Furthermore, dietary supplementation with an appropriate concentration of Hyp substantially increased the expression of genes involved in collagen synthesis (col1a1, col1a2, p4hα1, p4hβ, smad4, smad5, smad9, and tgf-β) and muscle growth (igf-1, tor, myod, myf5, and myhc) (p < 0.05). In conclusion, dietary supplementation of Hyp can enhance fish growth performance, collagen production, muscle textural characteristics and muscle growth of ITCC. According to the SGR broken-line analysis, the recommended supplementation level of Hyp was 0.74% in the diet for ITCC, corresponding to 2.2% of dietary protein.

The effect of diet on skin aging has become an interesting research topic. Previous studies have mostly focused on the beneficial effects of collagen peptides derived from marine organisms on the aging skin when administered orally, while the beneficial effects of collagen peptides derived from poultry on aging skin have been rarely reported. In this study, collagen peptides were prepared from chicken bone by enzymatic hydrolysis, and the effect and mechanism of action of orally administered collagen peptides on alleviating skin aging induced by UV combined with D-galactose were investigated. The results showed that the chicken bone collagen had typical characteristics of collagen, and the chicken bone collagen peptides (CPs) were mainly small molecular peptides with a molecular weight of <3000 Da. In vivo experiments showed that CPs had a significant relieving effect on aging skin, indicated by the changes in the compostion and structure of the aging skin, improvement of skin antioxidant level, and inhibition of inflammation; the relieving effect was positively correlated with the dose of CPs. Further investigation showed that CPs first reduce the level of skin oxidation, inhibit the expression of the key transcription factor AP-1 (c-Jun and c-Fos), then activate the TGF-β/Smad signaling pathway to promote collagen synthesis, inhibit the expression of MMP-1/3 to inhibit collagen degradation, and inhibit skin inflammation to alleviate skin aging in mice. Moreover, the skin transcriptome found that lysosomes activated after oral administration of CPs may be an important pathway for CPs in anti-skin aging, and is worthy of further research. These results suggested that CPs might be used as a functional anti-aging nutritional component. [ABSTRACT FROM AUTHOR]

Background: Tumor budding is included in the routine diagnosis of colorectal cancer (CRC) and is considered a tumor prognostic factor independent of TNM staging. This study aimed to identify the fibroblast-mediated effect of tumor bud-derived C–C chemokine ligand 5 (CCL5) on the tumor microenvironment (TME). Methods: Recruitment assays and a human cytokine array were used to detect the main cytokines that CRC tumor buds secrete to recruit fibroblasts. siRNA transfection and inhibitor treatment were used to investigate the role of fibroblast CCL5 receptors in fibroblast recruitment. Subsequently, transcriptome sequencing was performed to explore the molecular changes occurring in fibroblasts upon stimulation with CCL5. Finally, clinical specimens and orthotopic xenograft mouse models were studied to explore the contribution of CCL5 to angiogenesis and collagen synthesis. Results: Hematoxylin–eosin staining and immunochemistry revealed a higher number of fibroblasts at the invasive front of CRC tissue showing tumor budding than at sites without tumor budding. In vitro experiments demonstrated that CCL5 derived from tumor buds could recruit fibroblasts by acting on the CCR5 receptors on fibroblasts. Tumor bud-derived CCL5 could also positively regulate solute carrier family 25 member 24 (SLC25A24) expression in fibroblasts, potentially activating pAkt-pmTOR signaling. Moreover, CCL5 could increase the number of α-SMAhigh CD90high FAPlow fibroblasts and thus promote tumor angiogenesis by enhancing VEGFA expression and making fibroblasts transdifferentiate into vascular endothelial cells. Finally, the results also showed that CCL5 could promote collagen synthesis through fibroblasts, thus contributing to tumor progression. Conclusions: At the invasive front of CRC, tumor bud-derived CCL5 can recruit fibroblasts via CCR5-SLC25A24 signaling, further promoting angiogenesis and collagen synthesis via recruited fibroblasts, and eventually create a tumor-promoting microenvironment. Therefore, CCL5 may serve as a potential diagnostic marker and therapeutic target for tumor budding in CRC. [ABSTRACT FROM AUTHOR]

Thai Traditional Medicine believes that human body is composed of four elements. It also mentions that skin problems related to each element can be alleviated by using suitable plants. This study aimed to determine the bioactivities related to skin effects of Aloe vera, Cucumis sativus, Alpinia galanga and Phyllanthus emblica. The plants were extracted with 50% ethanol prior to bioactivity evaluation. The highest anti-oxidant activity (IC50, 14.01 µg/ml) was found for P. emblica. Tyrosinase inhibition was found with P. emblica (41.92% inhibition) and A. vera (26.67% inhibition) at 500 µg/ml concentrations. The cells treated with 500 µg/ml A. vera and 15.62 µg/ml P. emblica had after 48 h increased collagen type-1 production by around 14 and 4 -fold from those of untreated cells. Anti-glycation was found with P. emblica. P. emblica, A. galanga and C. sativus at 62.5 µg/ml exhibited anti-inflammatory activity. This information supports evidence based use of these plants as food and cosmetic ingredients.

Nitric oxide (NO), a potential therapeutic antiaging molecule, modulates various physiological and cellular processes. However, alterations in endogenous NO levels brought on by aging impact multiple organ systems and heighten susceptibility to age-related skin diseases. This correlation underscores the importance of investigating NO-based antiaging interventions. Nonthermal plasma-generated NO is a promising avenue for cosmetic and regenerative medicine due to its capacity to stimulate cellular growth. Herein, we examine the potential of plasma-generated nitric oxide water (NOW) as a bioactive agent in human dermal fibroblasts, emphasizing gene expression patterns linked to extracellular matrix (ECM) breakdown and cellular senescence. The findings of our study indicate that administering NOW at lower dosages enhances cell migration and proliferation. Moreover, the genetic signatures associated with ECM synthesis, antioxidant defense, and antisenescence pathways have been analyzed in NOW-exposed cells. Notably, the downregulation of ECM-degrading enzyme transcripts─collagenase, elastase, and hyaluronidase─suggests NOW's potential in mitigating the intrinsic skin aging phenomena, emphasizing the promise of NO-based interventions in advancing antiaging strategies within regenerative medicine.