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Neurobiology of Aging Nov 2023Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in...
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-β and phosphorylated tau. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging.
Topics: Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Alzheimer Disease; Atrophy; Brain; Biomarkers
PubMed: 37549446
DOI: 10.1016/j.neurobiolaging.2023.05.012 -
Journal of Cosmetic Dermatology Apr 2024Botulinum toxin has been widely and mainly used for the treatment of conditions affecting the upper and middle face; however, recent efforts have expanded the... (Review)
Review
BACKGROUND
Botulinum toxin has been widely and mainly used for the treatment of conditions affecting the upper and middle face; however, recent efforts have expanded the indications of botulinum toxin injection to the lower face and neck areas for cosmetic and medical purposes.
AIMS
We have reviewed the latest updates on using botulinum toxin in the lower face and neck focusing on cosmetic purposes and have discussed the existing concerns as well as the adverse sequelae of these newer indications.
PATIENTS/METHODS
A comprehensive literature search was performed using the following keywords [[botulinum] AND [[Toxin] OR [Neurotoxin]]] AND [[Lower AND Face] AND/OR [Neck]] within the main databases including Web of Science, PubMed, Embase and gray literature on and before February 2023. The data were screened using titles and abstracts and those relevant to the topic were included in the paper.
RESULTS
Botulinum toxin injection has considerable cosmetic and therapeutic effect on facial contouring, masseteric hypertrophy, lower face and neck scars, gummy smile, drooping lip corner and even skin rejuvenation.
CONCLUSION
BNT injection has been widely used for the treatment of different medical and cosmetic purposes. Low rates of side effects, which were self-limited in most cases, have been reported in the literature, making BNT a safe therapeutic medication in most cases. However, regulatory status needs to be updated and more accurately revised in many countries and more comprehensive research is required to address the existing gaps in this area including the site, dosage, and method of injection in each case.
Topics: Humans; Botulinum Toxins, Type A; Esthetics, Dental; Gingiva; Smiling; Neurotoxins; Neuromuscular Agents
PubMed: 38059697
DOI: 10.1111/jocd.16116 -
In Vivo (Athens, Greece) 2023As the largest organ of the human body, the skin serves as a critical barrier against environmental damage. However, many factors, such as genetics, sun exposure, and...
BACKGROUND/AIM
As the largest organ of the human body, the skin serves as a critical barrier against environmental damage. However, many factors, such as genetics, sun exposure, and lifestyle choices can lead to skin damage creating wrinkles, sagging, and loss of elasticity. The use of skincare products containing natural ingredients has become increasingly popular as a way to combat the signs of aging. Caviar oil is one such ingredient that has gained attention due to its rich composition of fatty acids, vitamins, and minerals. The objective of this study was to investigate the potential anti-aging effects of caviar oil and to develop a product, Cavi Balm, which could potentially reduce wrinkles and skin sagging.
MATERIALS AND METHODS
An in vitro model using the 3T3-L1 cell line was employed to assess the effect of caviar oil on adipocyte differentiation. An ex vivo study using human skin tissue was conducted to investigate the impact of caviar oil on collagen and elastin formation and the expression of matrix metalloproteinase-1,2,9 (MMP-1, MMP-2, MMP-9). Furthermore, 102 participants were enrolled in five clinical studies to evaluate the anti-aging efficacy of our product, "Cavi Balm", in facial and neck wrinkles, facial and eye area lifting, and various skin parameters, such as skin moisture, skin elasticity, skin density, skin tightening relief, skin clarity, and skin turnover.
RESULTS
In vitro, caviar oil enhanced adipocyte differentiation, and increased lipid accumulation inside the cells. The ex vivo analysis revealed that caviar oil reduced the expression levels of MMP-1, MMP-2, and MMP-9, and increased the formation of elastin and collagen I, III. Moreover, in the clinical study, Cavi Balm improved skin parameters after one-time use, with more significant effects observed after four weeks of usage.
CONCLUSION
Caviar oil has a substantial impact on mitigating skin aging and holds potential for application in anti-aging products.
Topics: Humans; Animals; Guinea Pigs; Matrix Metalloproteinase 1; Elastin; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Skin; Collagen; Aging
PubMed: 37652485
DOI: 10.21873/invivo.13305 -
International Journal of Molecular... Jul 2023When stimulated by proinflammatory mediators, endothelial cells release ultra-large von Willebrand factor (ULVWF) multimers that are hyperactive in activating and...
When stimulated by proinflammatory mediators, endothelial cells release ultra-large von Willebrand factor (ULVWF) multimers that are hyperactive in activating and aggregating platelets. These ULVWF multimers can accumulate in the circulation and on the inflamed endothelium because they are insufficiently cleaved by the metalloprotease ADAMTS-13, which becomes moderately deficient under conditions of systemic inflammation. This moderate ADAMTS-13 deficiency may lead to thrombotic complications that contribute to ischemic tissue injury and organ failure that are associated with severe infections. To test this hypothesis, we investigated whether recombinant ADAMTS-13 improves the pathological course of endotoxemia in lipopolysaccharide (LPS)-treated mice. C57BL/J6 mice received a bolus infusion of either 5 µg/mouse of ADAMTS-13 or vehicle control 30 min after LPS challenge and were monitored for seven-day survival. During the monitoring period, platelet counts, VWF antigen, and ADAMTS-13 activity were measured. Thrombosis was also examined by the immunohistochemistry in the liver. We found that ADAMTS-13 reduced mortality from 66% to 34.9%. The improved survival was associated with a greater recovery from thrombocytopenia, higher plasma ADAMTS-13 activity, and less thrombotic vascular occlusion. These results suggest that systemic inflammation could result in deficient ULVWF proteolysis by ADAMTS-13 and that ADAMTS-13 improves the outcomes of endotoxemia-induced inflammation.
Topics: Animals; Mice; ADAM Proteins; Endothelial Cells; ADAMTS13 Protein; Endotoxemia; Lipopolysaccharides; Mice, Inbred C57BL; von Willebrand Factor
PubMed: 37511541
DOI: 10.3390/ijms241411782 -
Journal of Ethnopharmacology Jan 2024Dendrobium officinale Kimura & Migo is traditionally used to treat skin diseases, gastrointestinal diseases, and other diseases. Dendrobium officinale polysaccharides...
ETHNOPHARMACOLOGICAL RELEVANCE
Dendrobium officinale Kimura & Migo is traditionally used to treat skin diseases, gastrointestinal diseases, and other diseases. Dendrobium officinale polysaccharides (DOP) are the main component of Dendrobium officinale that accounts for its bioactivity, which shows a variety of effects such as moisturizing, antioxidant and anti-fatigue. However, there is no comprehensive study on the effect of DOP on skin photoaging combined with in vitro and in vivo models, and its specific mechanism is still unclear.
AIM OF THE STUDY
Our study aimed to explore the effect and underlying mechanism of DOP on skin photoaging, as well as to improve the stability and transdermal absorption of DOP.
MATERIALS AND METHODS
DOP was extracted, purified and structurally characterized. In vitro HaCaT cell photoaging model was used to examine the photoprotection effect of DOP. Cell viability was detected by CCK-8; Intracellular reactive oxygen species were determined by DCFH-DA; DNA damage, cell apoptosis and cell cycle arrest were examined by flow cytocytometry. For autophagy flux detection, the adenovirus loaded with mRFP-GFP-LC3 was introduced into cells. Further, to enhance the stability and absorption of DOP, we designed and prepared the W/O/W type DOP multilayer emulsions (ME) by a two-step emulsification method. The emulsion stability, drug loading and encapsulation rate, DOP stability and DOP transdermal rate were detected. In vivo photoaging animal model was applied to compare the difference of photoaging protection effect between DOP solution and DOP ME. Specifically, skin appearance, histological change, antioxidant system, proinflammatory indicators, matrix metalloproteinases and autophagy level of skin tissues were examined and compared.
RESULTS
The results showed that DOP achieve photoaging protection by inhibiting oxidative stress, alleviating cell cycle arrest and apoptosis, and enhancing autophagy flux in photoaged HaCaT cells. The W/O/W type DOP multilayer emulsion (ME) with high encapsulation rate and strong stability was found to significantly improve the stability and transdermal absorption of DOP. In addition, our results showed that DOP (ME) remarkably improved skin condition of photoaged mice. Specifically, DOP (ME) enhanced the expression of antioxidant enzymes and autophagy and decreased the levels of pro-inflammatory factors and matrix metalloproteinases in the skin of photoaged mice as compared with DOP solution.
CONCLUSIONS
In conclusion, DOP was effective in improving skin photoaging, and the DOP multilayer emulsion we designed enhanced the stability and skin absorption of DOP, boosting DOP's protective effect against photoaging.
Topics: Mice; Animals; Antioxidants; Emulsions; Dendrobium; Skin Aging; Polysaccharides; Matrix Metalloproteinases
PubMed: 37517571
DOI: 10.1016/j.jep.2023.116974 -
Molecular Biology Reports Jan 2024Recovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and...
BACKGROUND
Recovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and fibrosis. Phenotypic alterations in both macrophages and fibroblasts have been detected in the diabetic wound. Recently, a fibroblast subpopulation that expresses high matrix metalloproteinase 1 (MMP1), MMP3, MMP11 and Chitinase-3-Like Protein 1 (CHI3L1) was associated with a successful diabetic wound healing. However, it is not known whether these healing-associated fibroblasts are regulated by macrophages.
METHODS AND RESULTS
We used bioinformatic tools to analyze selected public databases on normal and diabetic skin from patients, and identified genes significantly altered in diabetes. In a mouse model for diabetic wound healing, we detected not only a loss of the spatiotemporal changes in interleukin 1β (IL1β), IL6, IL10 and vascular endothelial growth factor A (VEGF-A) in wound macrophages, but also a compromised expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in healing-associated wound fibroblasts in a diabetic status. Co-culture with diabetic macrophages significantly reduced the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from non-diabetic wound. Co-culture with non-diabetic macrophages or diabetic macrophages supplied with IL6 significantly increased the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from diabetic wound. Moreover, macrophage-specific expression of IL6 significantly improved wound healing and angiogenesis in diabetic mice.
CONCLUSIONS
Macrophages may induce the activation of wound-healing-associated fibroblasts, while the defective macrophages in diabetes may be corrected with IL6 treatment as a promising therapy for diabetic foot disease.
Topics: Humans; Animals; Mice; Vascular Endothelial Growth Factor A; Matrix Metalloproteinase 3; Matrix Metalloproteinase 1; Matrix Metalloproteinase 11; Diabetes Mellitus, Experimental; Interleukin-6; Wound Healing
PubMed: 38270651
DOI: 10.1007/s11033-023-09100-1 -
Aesthetic Surgery Journal Oct 2023Treatment of wrinkles and dynamic lines with botulinum toxin has been a routine practice for years in aesthetic clinical settings. The effective treatment of wrinkles... (Review)
Review
Treatment of wrinkles and dynamic lines with botulinum toxin has been a routine practice for years in aesthetic clinical settings. The effective treatment of wrinkles requires a comprehensive understanding of facial expression muscles and their interactions, the mechanism of action of botulinum toxin, and individual patient preferences. The dose adjustment practice and injection technique of physicians are affected by cultural differences; most Asian patients prefer natural-looking results. This article aims to present an expert consensus on the injection sites, doses, and levels of botulinum toxin for various indications in Asians, with the hope of providing guidance to some clinicians. This consensus paper reviews LetibotulinumtoxinA for patient evaluation, dosage, and delivery techniques in Asians from the time LetibotulinumtoxinA was approved up to December 2022. Panelists proposed individualized treatment plans for botulinum toxin type A (BTxA) treatments in 3 areas-wrinkle removal, contour adjustment, and face lifting-for Asians based on their extensive experience and knowledge of facial anatomy. When using a different BTxA, clinicians should start with a conservative dose and carefully individualize the treatment for each patient, and adjust it according to feedback to obtain a higher satisfaction level.
Topics: Humans; Botulinum Toxins, Type A; Neuromuscular Agents; Consensus; Asian People; Esthetics; Skin Aging
PubMed: 37220644
DOI: 10.1093/asj/sjad151 -
Toxins Jun 2024The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products.... (Review)
Review
The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products. Given that BoNTs are biological medications, their characteristics are heavily influenced by their manufacturing methods, leading to unique products with distinct clinical characteristics. The manufacturing and formulation processes for each BoNT are proprietary, including the potency determination of reference standards and other features of the assays used to measure unit potency. As a result of these differences, units of BoNT products are not interchangeable or convertible using dose ratios. The intrinsic, product-level differences among BoNTs are compounded by differences in the injected tissues, which are innervated by different nerve fiber types (e.g., motor, sensory, and/or autonomic nerves) and require unique dosing and injection sites that are particularly evident when treating complex therapeutic and aesthetic conditions. It is also difficult to compare across studies due to inherent differences in patient populations and trial methods, necessitating attention to study details underlying each outcome reported. Ultimately, each BoNT possesses a unique clinical profile for which unit doses and injection paradigms must be determined individually for each indication. This practice will help minimize unexpected adverse events and maximize efficacy, duration, and patient satisfaction. With this approach, BoNT is poised to continue as a unique tool for achieving individual goals for an increasing number of medical and aesthetic indications.
Topics: Humans; Botulinum Toxins; Animals; Neurotoxins
PubMed: 38922160
DOI: 10.3390/toxins16060266 -
Archives of Biochemistry and Biophysics Sep 2023Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover...
Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.
Topics: Humans; Matrix Metalloproteinase 9; Biomarkers; Computational Biology; Gene Expression Profiling; Thyroiditis
PubMed: 37543352
DOI: 10.1016/j.abb.2023.109713 -
Scientific Reports Oct 2023The premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer...
The premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer cells. We investigated several extracellular matrix (ECM) structural proteins, ECM degrading enzymes, and ECM processing proteins involved in the ECM remodeling of the premetastatic niche. Our in vitro model consisted of lung fibroblasts, which were exposed to factors secreted by nonmalignant breast epithelial cells, nonmetastatic breast cancer cells, or metastatic breast cancer cells. We assessed ECM remodeling in vivo in premetastatic lungs of female mice growing orthotopic primary breast tumor xenografts, as compared to lungs of control mice without tumors. Premetastatic lungs contained significantly upregulated Collagen (Col) Col4A5, matrix metalloproteinases (MMPs) MMP9 and MMP14, and decreased levels of MMP13 and lysyl oxidase (LOX) as compared to control lungs. These in vivo findings were consistent with several of our in vitro cell culture findings, which showed elevated Col14A1, Col4A5, glypican-1 (GPC1) and decreased Col5A1 and Col15A1 for ECM structural proteins, increased MMP2, MMP3, and MMP14 for ECM degrading enzymes, and decreased LOX, LOXL2, and prolyl 4-hydroxylase alpha-1 (P4HA1) for ECM processing proteins in lung fibroblasts conditioned with metastatic breast cancer cell media as compared to control. Taken together, our data show that premetastatic priming of lungs by primary breast tumors resulted in significant ECM remodeling which could facilitate metastasis by increasing interstitial fibrillar collagens and ECM stiffness (Col14A1), disruptions of basement membranes (Col4A5), and formation of leaky blood vessels (MMP2, MMP3, MMP9, and MMP14) to promote metastasis.
Topics: Humans; Female; Mice; Animals; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase 14; Matrix Metalloproteinase 3; Lung; Extracellular Matrix; Mammary Neoplasms, Animal; Extracellular Matrix Proteins; Breast Neoplasms
PubMed: 37903851
DOI: 10.1038/s41598-023-45832-7