Collagen Synthesis Research Articles

The potential therapeutic applications and mechanisms of action of Cryptomphalus aspersa (snail) extracts in dermatology and wound healing

Cryptomphalus aspersa, commonly known as the garden snail, has emerged as a promising therapeutic agent in the fields of dermatology and wound healing. This review explores the diverse therapeutic applications and underlying mechanisms of action of Cryptomphalus aspersa extracts. With a rich history in traditional medicine and growing scientific evidence supporting their efficacy, snail extracts offer multifaceted benefits including anti-inflammatory, antioxidant, collagen-stimulating, and immunomodulatory activities. In dermatology, snail extracts have shown promise in managing conditions such as acne vulgaris, atopic dermatitis, photoaging, and hyperpigmentation, while also demonstrating efficacy in promoting wound healing in various types of wounds, including full-thickness and chronic wounds. Mechanistically, snail extracts modulate inflammatory pathways, neutralize oxidative stress, stimulate collagen synthesis, and regulate immune responses, contributing to their therapeutic effects. While the potential of Cryptomphalus aspersa extracts is vast, further research and clinical trials are warranted to establish their efficacy and safety profiles for specific dermatological conditions and wound types. Overall, Cryptomphalus aspersa extracts represent a novel and promising approach in dermatology and wound healing, offering a natural and multifaceted solution for improving skin health and promoting tissue repair.

DYNAMIC CHANGES IN HISTOLOGICAL AND MORPHOMETRIC INDICATORS OF THE LUNGS IN SEXUALLY IMMATURE RATS DURING SIMULATION OF PARTIAL TRACHEAL STENOSIS

Introduction. The morphological features of the respiratory system in laryngomalacia remain insufficiently understood, particularly regarding structural, cytological, and functional alterations. The aim of this study is to investigate the morphological characteristics of the respiratory compartment in the lungs of sexually immature rats, conduct a morphometric assessment of lung tissue density, analyze the dynamics of erythrocyte mass and collagen accumulation, and identify correlations between these parameters. Materials and Methods: The study involved sexually immature male Wistar rats aged 25-28 days and weighing 40-55 g. Partial tracheal stenosis was induced in experimental animals using a developed method, restricting the tracheal lumen by 20-25%. The stenosis was maintained for 7 and 21 days in different groups. In one group, tracheal stenosis was relieved after 7 days by removing the compressive ligature. Histological, histochemical, and morphometric methods were employed to study changes in lung tissue. Results. Pathological changes in lung tissue during hypoxia were characterized by an increase in the number of different types of cells and erythrocyte mass, especially on the 21st day of the experiment and the removal of ligatures from the trachea in experimental animals. Disturbances in the microcirculation of the lung acini were manifested by a sharp increase in blood filling of the microvessels and expansion of their lumen. In this case, the process of erythrocyte penetration into the lumen of the alveoli was sometimes noted. The results of histochemical detection of collagen indicate that in the lung tissue of experimental animals there is no activation of fibrogenetic processes, which would be accompanied by a simultaneous increase in the specific density of collagen. Indicators characterizing the lung tissue (number of cells, their specific density) made it possible to evaluate the corresponding correlations. At the same time, they were not associated with the level of collagen or erythrocyte density in the studied loci of the respiratory system of experimental sexually immature rats. A significant increase in the specific density of erythrocyte mass in lung tissue did not depend on the duration of the experiment. Removal of the ligature and restoration of the tracheal lumen did not significantly affect the restoration of alveolar acini and the spectrum of identified cells. In addition, an increase in the specific density of lung tissue was observed. Conclusion. The findings of this study contribute to deeper understanding of lung damage in children with laryngomalacia and associated respiratory system ventilation impairment. The observed reactive changes in lung connective tissue and collagen synthesis during hypoxia do not necessarily indicate the development of respiratory system fibrosis. However, longer exposure to hypoxic conditions may increase the risk of fibrosis in children.

UNRAVELING GENDER DISPARITIES AND PROGNOSTIC INSIGHTS IN MODERATE AORTIC STENOSIS: A RETROSPECTIVE STUDY

Abstract Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries, associated with reduced survival if severe AS remains untreated. Recent reports note unfavorable outcomes in moderate AS (mAS) patients, challenging optimal intervention timing. Variations in pathophysiology linked to sex differences, involving sex hormones, activation of the renin–angiotensin–aldosterone system, and dysregulation in collagen synthesis, have been observed. Yet, limited data exists on sex–specific differences in mAS outcomes. This single–center, retrospective study included 150 patients (median age 79±13 years, female sex 48%) diagnosed with mAS who underwent comprehensive echocardiography in IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico of Milan from July 2022 to October 2023. Clinical data, encompassing demographics details and therapy, were obtained via record reviews and phone interviews. Death verification relied on the ‘Sistema Informativo Socio–Sanitario Regione Lombardia’ database. Echocardiographic records were digitally stored and post–processed by four independent investigators using Medimatic ComPACS workstation. Men were significantly younger than women (75±10 vs 79±9.7 years, p= 0.016). They exhibited lower left ventricular (LV) ejection fraction, larger LV end–systolic volume and stroke volume compared to women (54±7 vs 59±10%; p=0.028. 55±36 vs 31±13 ml; p<0.001. 83±18 vs 75±18 ml; p=0.030). Men had significantly smaller aortic valve (AV) area index to body surface area (BSA) (0.6±0.09 vs 0.7±0.1 cmq/mq; p<0.001) and lower doppler velocity index (0.32±0.07 vs 0.38±0.11; p<0.001) than women. Coronary artery disease and smoking were more frequent in men (53.3 vs 46.7%; p=0,002. 52.6 vs 47.4%; p<0.001). In survival analysis, 15% of women and 30.8% of men experienced events, with male gender independently associated with the composite outcome (all–cause mortality and AV replacement) over a mean follow–up time of 200 ± 133 days, showing a median survival of 244±16 vs 255±15 days for females (p–value=0.025). In multivariable analysis including relevant clinical variables (hemoglobin and AV index to BSA), male sex remained independently associated with the composite outcome (hazard ratio 2,01; CI 1.0–4.17; p=0.05). Women diagnosed with mAS exhibited a lower incidence of AV replacement and all–cause mortality. These findings may suggest the existence of different clinical and echocardiographic phenotypes among patients with AS.

Wall Shear Stress Measured with 4D Flow CMR Correlates with Biomarkers of Inflammation and Collagen Synthesis in Mild-to-Moderate Ascending Aortic Dilation and Tricuspid Aortic Valves.

Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic hemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow CMR), and circulating biomarkers in aortic dilation. Forty-seven cases with aortic dilation (diameter ≥40 mm) and 50 sex-and age-matched controls (diameter <40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D Flow CMR, and biomarkers including interleukin-6, collagen type I α1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared to controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between hemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, p < 0.001), and maximum oscillatory shear index and collagen type I α1 chain (r = -0.575, p < 0.001 in cases). Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between hemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.

Comparative evaluation of oxygenating agent “blue m gel” and traditional periodontal dressing “Coe-Pak” on patient preference parameters (Pain and wound healing) after surgical depigmentation – A split mouth study

Individuals with high lip line and gummy smile when accompanied withdark colored gingiva have an esthetic concern while smiling. For the management of gingival hyperpigmentation surgical technique with scalpel is still considered the gold standard, although healing may occur by secondary intension and oxygen is one of the essential nutrients for cellular metabolism and production of energy through ATP. It is also involved in collagen synthesis, oxygenative killing of bacteria and angiogenesis. To clinically evaluate and compare the effectiveness of oxygenating agent (Blue M Gel) and traditional periodontal dressing COE-PAK on patient preference parameters (pain and wound healing) after surgical depigmentation. This split-mouth randomized clinical trial was conducted on 5 non-smoking individuals aged 20–40 years irrespective of gender with maxillary or mandibular physiologic gingival pigmentation class (III) and (IV) according to the Dummett–Gupta Oral Pigmentation Index (10 treated sites) who had requested an esthetic treatment for gingival hyperpigmentation of the maxillary or mandibular gingiva. The maxilla or the mandible was randomly divided into two symmetrical parts i.e. from the right second premolar to the midline and from the midline to the left second premolar—to receive either Blue M gel or Coe-Pak as a periodontal dressing after surgical depigmentation with a scalpel. Patient preference parameters such as pain was assessed after 24 hours and 7 days of intervention and re-epithelisation index with toluidine blue was assessed after 1 week and 1 month of intervention. The result of the study demonstrated that pain score and re-epithelisation score was less in Test group (Blue M Gel) as compared to control group (COE-PAK) and was found to be statistically significant. :It can be concluded that Blue M gel can also be a better alternative as a periodontal dressing compared to COE-PAK due to its properties of better healing and decreasing post-operative pain.

Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro.

Bone is increasingly recognized as a target for diabetic complications. In order to evaluate the direct effects of high glucose on bone, we investigated the global transcriptional changes induced by hyperglycemia in osteoblasts in vitro. Rat bone marrow-derived mesenchymal stromal cells were differentiated into osteoblasts for 10days, and prior to analysis, they were exposed to hyperglycemia (25 mM) for the short-term (1 or 3days) or long-term (10 days). Genes and pathways regulated by hyperglycemia were identified using mRNA sequencing and verified with qPCR. Genes upregulated by 1-day hyperglycemia were, for example, related to extracellular matrix organization, collagen synthesis and bone formation. This stimulatory effect was attenuated by 3days. Long-term exposure impaired osteoblast viability, and downregulated, for example, extracellular matrix organization and lysosomal pathways, and increased intracellular oxidative stress. Interestingly, transcriptional changes by different exposure times were mostly unique and only 89 common genes responding to glucose were identified. In conclusion, short-term hyperglycemia had a stimulatory effect on osteoblasts and bone formation, whereas long-term hyperglycemia had a negative effect on intracellular redox balance, osteoblast viability and function.

Vitamin C: Is it Relevant or Obsolete in the Modern Era?

Abstract Purpose In this review, we discuss the historic background of vitamin C, vitamin C’s physiology, its dietary sources, and how deficiency can manifest. We also discuss modern studies investigating the role of Vitamin C in immunity, in cardiovascular disease, and in chronic conditions. Summary In the body, vitamin C acts as an essential cofactor in several enzymatic reactions including, but not limited to, neurotransmitter synthesis, hormone amidation, collagen synthesis, hypoxic transcription factor modification, and epigenetic modifications. Scurvy, caused by severe vitamin C deficiency, is an infamous disease recorded in historical documents, with patients presenting with joint ache, bleeding gums, depression, and hysteria. Since humans are unable to naturally synthesize ascorbic acid, they must rely on dietary sources such as fruits and vegetables in order to maintain their vitamin C levels and avoid such manifestations. Maintaining stable vitamin C levels remains increasingly important in the modern era, particularly for the vulnerable pediatric patient with chronic conditions or critical illness. Regulating vitamin C levels could decrease morbidity and mortality in the chronic and critically ill pediatric population. Moving forward, there is a need for more head-to-head trials pertaining to vitamin C’s role in improving immunity, modifying cardiovascular risk, and altering cancer prognosis.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial

ObjectiveHeart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine...

Human Adipose-Derived Mesenchymal Stem Cells Colonize and Promote Healing of Leprosy Ulcer by Inducing Neuro-Vascularization.

Leprosy ulcer is a chronic and recurrent disease resulting from nerve injury. While existing treatments partially facilitate ulcer healing, they exhibit limited ability to address localized nerve repair, leading to a risk of recurrence. Moreover, there is a dearth of animal models to evaluate the preclinical efficacy and safety of novel therapeutic approaches. Over the years, adipose-derived mesenchymal stem cells have been extensively employed in regenerative medicine as an optimal cell therapy source for fostering skin ulcer healing. They have also demonstrated the capacity to enhance nerve regeneration in in vitro experiments and clinical trials. In this study, we established a NU/NU mouse foot pad leprosy ulcer model, transplanted human adipose-derived stem cells (hADSCs) into leprosy ulcers via local injection, and conducted subsequent follow-up. Our findings revealed that hADSCs persisted in the leprosy ulcer and facilitated the healing process. In this respect, gross observation and histological analysis revealed increased granular formation, collagen synthesis, and re-epithelialization in the local ulcer area. RNA-Seq data revealed that the upregulated differential genes resulting from the transplantation intervention were not only enriched in pathways related to re-epithelialization and collagen synthesis but also contributed to local nerve regeneration. Furthermore, immunofluorescence assays revealed the increased expression of angiogenesis markers-CD31 and VEGFa, cell proliferation markers-Ki67 and TGF-β, and nerve regeneration markers-β3-tubulin, SOX10, NGF, and NT-3. These results underscore the potential of hADSCs in promoting the healing of leprosy ulcers and offer valuable preclinical data for their prospective clinical application.

Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway

BackgroundSimvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms.MethodsThe rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway.ResultsSim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions.ConclusionsSim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.

Mechanical properties, collagen and glycosaminoglycan content of equine superficial digital flexor tendons are not affected by training.

Physical activity can activate extracellular matrix (ECM) protein synthesis and influence the size and mechanical properties of tendon. In this study, we aimed to investigate whether different training histories of horses would influence the synthesis of collagen and other matrix proteins and alter the mechanical properties of tendon. Samples from superficial digital flexor tendon (SDFT) from horses that were either (a) currently race trained (n = 5), (b) previously race trained (n = 5) or (c) untrained (n = 4) were analysed for matrix protein abundance (mass spectrometry), collagen and glycosaminoglycan (GAG) content, ECM gene expression and mechanical properties. It was found that ECM synthesis by tendon fibroblasts invitro varied depending upon the previous training history. In contrast, fascicle morphology, collagen and GAG content, mechanical properties and ECM gene expression of the tendon did not reveal any significant differences between groups. In conclusion, although we could not identify any direct impact of the physical training history on the mechanical properties or major ECM components of the tendon, it is evident that horse tendon cells are responsive to loading invivo, and the training background may lead to a modification in the composition of newly synthesised matrix.

Developing and Assessing a Cream Designed to Remove Stretch Marks from “Prunus armeniaca” and “Centella asiatica”

Stretch marks (Striae distensae) are visible lines on the outer skin located usually on abdomen, breats, thighs. Stretch marks which develop on pregnant women known as striae gravidarum. Almost 50-90% of pregnant women may develop striae distensae. It is caused due to sudden increase in weight during pregnancy, due to rapid weight gain the collagen fibres present between dermis and epidermis layer of skin gets break down and stretch marks appears. Because of various side effects of synthetic medications, the use of herbal medications has increased. To avoid side effect, oil obtained from the leaves of Centella asiatica linn i.e. Gotukola and the fruits of Prunus armeniaca i.e. Apricot was incorporated into the formulation stimulates collagen synthesis by energizing dermal fibroblast and regenerate the skin cells. The main active ingredient found in gotukola is triterpenoids (saponin) and Apricot is glycosides, it increases collagen production in body and regenerate the skin cells this may help to prevent new stretch marks from forming as well as help to heal any existing marks. The objective of the present study was to developing the cream for the removal of stretch marks. Creams was prepared by oil-in-water emulsion by changing the concentration of active ingredients. Total 3 formulation were prepared among these F3 batch. In this (1.5% and 2%) concentration of oil was added and some butters were added. The final formulation shows pH (8.9), No skin irritancy, better spreadability, consistency and antimicrobial testing.

33 1-Carbon metabolism: Methionine and more

Abstract Methionine, via S-adenosylmethionine, has an important role in the post-translational methylation of Arg, Lys, and His in proteins, methylation of DNA and RNA, and methylation of serotonin (to melatonin), noradrenaline (to adrenaline), and guanidinoacetate (to creatine). After the methyl-group of Met is transferred to an acceptor, the resulting homocysteine can transfer its sulfur group to Ser yielding Cys. Homocysteine can also be remethylated back to Met in the so-called Met salvage pathway, which requires betaine or N5-methyl tetrahydrofolate (THF) as a 1-carbon donor. Methionine is, thus, not necessarily the dietary source of 1-carbon in methylation reactions. N5-methyl THF is one of the “1-carbon flavors” of THF and the catabolism of Ser, Gly, His, and formate (e.g., from Trp catabolism) results in the formation of 1-carbon metabolites linked to THF. These amino acids (and choline and betaine) are thus potential dietary sources of 1-carbon groups, of which only Ser and Gly can be synthesized de novo. In recent years, there has been an increased interest in the role of Ser and Gly in 1-carbon metabolism. Glycine has the unique property that it is able to accept and donate 1-carbon groups and the high concentration of Gly in plasma may be indicative for its 1-carbon buffering capacity. Glycine is also one of the few non-essential amino acids for which the retention (e.g., for collagen synthesis) largely exceeds the dietary intake. However, the de novo synthesis of Gly has been considered “a weak link in metabolism” because it is always associated with the synthesis of a 1-carbon group, and the capacity of the animal to dispose of excess 1-carbon groups may be limited. An excess supply of 1-carbon groups may therefore lead to a dietary requirement for Gly.

Urea cycle promotion via ammonia-upregulated CPS1 is involved in arsenite-induced pulmonary fibrosis through enhancing collagen synthesis

Arsenic exposure is connected with lung toxicity and is related to lung fibrotic changes. Idiopathic pulmonary fibrosis (IPF) is characterized by extracellular matrix (ECM) deposition. Various genetic mechanisms and environmental factors induce or exacerbate pulmonary fibrosis. Collagen synthesis induced by sodium arsenite (NaAsO2) is closely associated with IPF. Fibroblasts tend to fine-tune their metabolic networks to support their synthetic requirements in response to environmental stimuli. Alterations in metabolism have an influential role in the pathogenesis of IPF. However, it is unclear how arsenic affects the metabolism in IPF. The urea cycle (UC) is needed for collagen formation, which provides adequate levels of proline (Pro) for biosynthesis of collagen. Carbamoyl phosphate synthetase 1 (CPS1) converts the ammonia to carbamoyl phosphate, which controls the first reaction of the UC. We show that, in arsenite-exposed mice, high amounts of ammonia in the lung microenvironment promotes the expression levels of CPS1 and the Pro metabolism. Reduction of ammonia and CPS1 ablation inhibit collagen synthesis and ameliorate IPF phenotypes induced by arsenite. This work takes advantage of multi-omics data to enhance understanding of the underlying pathogenic mechanisms, the key molecules and the complicated cellular responses to this pollutant, which provide a target for the prevention of pulmonary fibrosis caused by arsenic.

Inhibition of the rapamycin-insensitive mTORC1 /4E-BP1 axis attenuates TGF-β1-induced fibrotic response in human Tenon's fibroblasts

Subconjunctival fibrosis is the major cause of failure in both conventional and modern minimally invasive glaucoma surgeries (MIGSs) with subconjunctival filtration. The search for safe and effective anti-fibrotic agents is critical for improving long-term surgical outcomes. In this study, we investigated the effect of inhibiting the rapamycin-insensitive mTORC1/4E-BP1 axis on the transforming growth factor-beta 1(TGF-β1)-induced fibrotic responses in human Tenon's fibroblasts (HTFs), as well as in a rat model of glaucoma filtration surgery (GFS). Primary cultured HTFs were treated with 3 ng/mL TGF-β1 for 24 h, followed by treatment with 10 μM CZ415 for additional 24 h. Rapamycin (10 μM) was utilized as a control for mTORC1/4E-BP1 signaling insensitivity. The expression levels of fibrosis-associated molecules were measured using quantitative real-time PCR, Western blotting, and immunofluorescence analysis. Cell migration was assessed through the scratch wound assay. Additionally, a rat model of GFS was employed to evaluate the anti-fibrotic effect of CZ415 in vivo. Our findings indicated that both rapamycin and CZ415 treatment significantly reduced the TGF-β1-induced cell proliferation, migration, and the expression of pro-fibrotic factors in HTFs. CZ415 also more effectively inhibited TGF-β1-mediated collagen synthesis in HTFs compared to rapamycin. Activation of mTORC1/4E-BP signaling following TGF-β1 exposure was highly suppressed by CZ415 but was only modestly inhibited by rapamycin. Furthermore, CZ415 was found to decrease subconjunctival collagen deposition in rats post GFS. Our results suggest that rapamycin-insensitive mTORC1/4E-BP1 signaling plays a critical role in TGF-β1-driven collagen synthesis in HTFs. This study demonstrated that inhibition of the mTORC1/4E-BP1 axis offers superior anti-fibrotic efficacy compared to rapamycin and represents a promising target for improving the success rate of both traditional and modern GFSs.

Bacterial lipase-responsive polydopamine nanoparticles for detection and synergistic therapy of wound biofilms infection

Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by π − π stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo, the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections.

Comparative study on the quality of wild and ecologically farmed large yellow croaker through on-site synchronous sampling from the Nanji Archipelago in the East China Sea

With consumers demanding higher quality in fish products, ecologically farmed fish are increasingly favored due to their quality being close to that of wild fish. However, the differences between the ecologically farmed and wild fish remain largely unclear. In the present study, the wild and ecologically farmed large yellow croakers of the same size were captured simultaneously from the same marine area around Nanji islands (27.479°E, 121.052°N). Then, synchronous tests were conducted to evaluate quality to clarify the key quality parameters that differentiate between the wild and farmed fish. We obtained 49 quality parameters after orthogonal partial least squares discriminant analysis (OPLS-DA) with variable importance in projection (VIP) scores >1 and p < 0.05 using 307 indicators related to 121 length ratios, 4 body color indicators, 5 muscle fiber characteristic indicators, 87 nutrition quality parameters, 40 taste parameters, and 50 volatile compounds. Compared to the farmed fish, the wild fish exhibited a more yellow skin color, higher levels of carotenoids, and a more streamlined conical shape. Changes in histology and ultrastructure of muscle fibers were noted, including increased muscle fiber density and the ratio of fiber area to gap, as well as reduced I band width, observed in the wild fish. The wild fish had high nutritional value of fatty acids and minerals and low nutritional value of amino acids, as reflected by higher levels of C22: 6n3 (DHA), Σn-3 PUFA (polyunsaturated fatty acids), Σn-3/Σn-6 PUFA, Na (sodium), K (potassium), Fe (iron), and Se (selenium), and lower values of ΣMUFA (monosaturated fatty acids), Σn-6 PUFA, TI (thrombogenic index), amino acid and chemistry scores of isoleucine, ΣEAA/ΣTAA (essential amino acid/ total amino acid), and ΣTAA/ΣNEAA (total amino acid/non-essential amino acid) in the muscles of the wild fish. The wild fish muscle showed high levels of hydrolyzed glycine and proline and free methionine, and low levels of free glycine and proline, indicating a propensity for collagen synthesis. Despite significant differences in the contents of fourteen flavor substances of free amino acids, 5′-nucleotides, and volatile compounds, their concentrations were notably below the corresponding threshold and contributed minimally to flavor, suggesting that the wild and farmed fish shared similar flavor characteristics. In summary, this study reveals the quality differences between ecologically farmed and wild large yellow croaker based on on-site synchronous sampling, providing a theoretical foundation for further enhancing the quality of this species.

Tanshinone IIA alleviates pulmonary fibrosis by modulating glutamine metabolic reprogramming based on [U-13C5]-glutamine metabolic flux analysis

IntroductionGlutamine metabolic reprogramming, mediated by glutaminase (GLS), is an important signal during pulmonary fibrosis (PF) progression. Tanshinone IIA (Tan IIA) is a naturally lipophilic diterpene with antioxidant and antifibrotic properties. However, the potential mechanisms of Tan IIA for regulating glutamine metabolic reprogramming are not yet clear. ObjectivesThis study aimed was to evaluate the role of Tan IIA in intervening in glutamine metabolic reprogramming to exert anti-PF and to explore the potential new mechanisms of metabolic regulation. MethodsFibrotic characteristics was detected via immunofluorescence and western blotting analysis. Cell proliferation was examined with EdU Assay. Cell metabolites were labeled by using stable isotope [U-13C5]-glutamine. By utilizing 100% 13C glutamine tracers and employing network analysis to investigate the activation of metabolic pathways in fibroblasts, as well as evaluating the impact of Tan IIA on these pathways, we accurately quantified the absolute flux of glutaminolysis, proline synthesis, and the TCA cycle pathway using isotopomer network compartmental analysis (INCA), a user-friendly software tool for 13C metabolic flux analysis (13C-MFA). Molecular docking was used for identifying the binding of Tan IIA with target protein. ResultsTan IIA ameliorate TGF-β1-induced myofibroblast proliferation, reduce collagen I and III and α-SMA protein expression in MRC-5 and NIH-3 T3 cells. Furthermore, Tan IIA regulate mitochondrial energy metabolism by modulating TGF-β1-stimulated glutamine metabolic reprogramming in NIH-3 T3 cells and inhibiting GLS1 expression, which reduced the metabolic flux of glutamine into mitochondria in myofibroblasts, and also targeted inhibited the expression of Δ1-pyrroline-5-carboxylate synthase (P5CS), P5C reductase 1 (PYCR1), and phosphoserine aminotransferase 1 (PSAT1), and reduced proline hydroxylation and blocked the collagen synthesis pathway. ConclusionTan IIA reverses glutamine metabolic reprogramming, reduces mitochondrial energy expenditure, and inhibits collagen matrix synthesis by modulating potential targets in glutamine metabolism. This novel perspective sheds light on the essential role of glutamine metabolic reprogramming in PF.

Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts.

Collagen is one of the major proteins of the skin and it is particularly important for its strength and resilience. Skin aging is a natural process that is characterized by the decrease and fragmentation of collagen in the dermis. Oral supplementation with collagen peptides has been clinically shown to have a positive effect on the skin condition. However, the mechanisms of aging-related changes synthesized by cells exposed to collagen are currently not well understood. Therefore, in this in vitro study, the mechanisms associated with collagen, elastin, and versican in human dermal fibroblasts were investigated after exposure to collagen peptides. The effects of different concentrations of collagen peptides on cell viability and metabolism were analyzed. For gene expression analysis, human dermal fibroblasts were treated with collagen peptides. This was then followed by RNA extraction and DNA synthesis. Gene expressions of collagen type 1 (COL1A1), elastin (ELN), and versican (VCAN) were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). In addition, collagen levels were analyzed by confocal scanning laser microscopy using immunostaining. Collagen peptides tested in the study increased the expression of the relevant COL1A1, ELN, and VCAN genes in human dermal fibroblasts (p < 0.005). Furthermore, confocal microscopy showed increased collagen expression in the dermal fibroblast culture after treatment with the collagen peptides (p < 0.005). These data provide cell-based evidence for the beneficial effects of exposure to collagen peptides on the skin's collagen content and on the molecules that provide firmness and elasticity. This may support the hypothesis that collagen peptides are important for maintaining extracellular matrix (ECM) structure and skin regeneration.

Fabrication and characterization of biomineral amphiphilic copolymer hybrid microparticle: Evaluation of storage stability and collagen synthesis property of curcumin

Microencapsulation is an available and effective therapeutic option for entrapping targeted bioactive components. In this study, biomineralization-mediated separation and encapsulation of food-derived bioactive materials in organic materials were conducted, and the storage stability and effectiveness of these materials in the promotion of skin wound healing were assessed. To generate fine-textured and mechanically stable hexagonal particles, the hybrid materials were assembled using CaCO3 mineralized with an amphiphilic copolymer coupled with curcumin (CUR). The synthesized products were characterized using field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and particle size analysis. The hybrid microparticles contained 1.58 wt% of CUR, and 91% of its initial concentration was retained after storage at four different temperatures. Based on the crystallization mechanism, CUR with an amphiphilic copolymer could be the core component that provides the surface for CaCO3 crystal growth, causing independent formation of the organic–inorganic structures and preventing CUR leaching. Furthermore, the induced hybrid particles were found to promote skin wound healing by stimulating collagen synthesis without inducing cytotoxicity. To the best of our knowledge, this is the first study to demonstrate the potential use of bioactive ingredients with an amphiphilic copolymer combined with biomineralization for formulation purposes and to achieve a skin wound healing effect.