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Cellular and Molecular Life Sciences :... Oct 2023Although the pro-tumorigenic functions of hyaluronan (HA) are well documented there is limited information on the effects and targets of different molecular weight HA....
Although the pro-tumorigenic functions of hyaluronan (HA) are well documented there is limited information on the effects and targets of different molecular weight HA. Here, we investigated the effects of 27 kDa, 183 kDa and 1000 kDa HA on ES-2 ovarian cancer cells overexpressing the stem cell associated protein, Notch3. 1000 kDA HA promoted spheroid formation in ES-2 cells mixed with ES-2 overexpressing Notch3 (1:3). We report disabled-2 (DAB2) as a novel protein regulated by 1000 kDa HA and further investigated its role in ovarian cancer. DAB2 was downregulated in ovarian cancer compared to normal tissues but increased in metastatic ovarian tumors compared to primary tumors. High DAB2 expression was associated with poor patient outcome and positively correlated with HA synthesis enzyme HAS2, HA receptor CD44 and EMT and macrophage markers. Stromal DAB2 immunostaining was significantly increased in matched ovarian cancer tissues at relapse compared to diagnosis and associated with reduced survival. The proportion of DAB2 positive macrophages was significantly increased in metastatic ovarian cancer tissues compared to primary cancers. However, DAB2 overexpression significantly reduced invasion by both A2780 and OVCAR3 cells in vivo. Our research identifies a novel relationship between HA signalling, Notch3 and DAB2. We highlight a complex relationship of both pro-tumorigenic and tumor suppressive functions of DAB2 in ovarian cancer. Our findings highlight that DAB2 has a direct tumor suppressive role on ovarian cancer cells. The pro-tumorigenic role of DAB2 may be mediated by tumour associated macrophages and requires further investigation.
Topics: Female; Humans; Apoptosis; Cell Line, Tumor; Hyaluronan Receptors; Hyaluronic Acid; Molecular Weight; Ovarian Neoplasms; Tumor Suppressor Proteins
PubMed: 37815603
DOI: 10.1007/s00018-023-04972-9 -
Macromolecular Rapid Communications Dec 2023Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman...
Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman imaging, given their ultrastrong Raman scattering intensity. However, the relationship between the structure, especially the molecular length of polydiacetylenes, and their Raman scattering intensity remains unclear. In this work, a series of water-soluble polydiacetylenes, namely poly(deca-4,6-diynedioic acid) (PDDA) with different molecular weights (MWs), is prepared through controlled polymerization and degradation. The ultraviolet-visible (UV-vis) absorption spectroscopic and Raman spectroscopic studies on these polymers reveal that the Raman scattering intensity of PDDA increases nonlinearly with the MW. The MW-Raman scattering intensity relationship in the polymerization process is completely different from that in the degradation process. In contrast, the Raman scattering intensity increases more linearly with the maximal absorbance of the polymer, and the relationship between the Raman scattering intensity and the maximal absorbance of PDDA in the polymerization process is consistent with that in the degradation process. The Raman scattering intensity of PDDA hence exhibits a better dependence on the effective conjugation length of the polymer, which should guide the future design of conjugated polymers for Raman imaging applications.
Topics: Polymers; Spectrum Analysis, Raman; Polyacetylene Polymer; Molecular Weight
PubMed: 37713720
DOI: 10.1002/marc.202300412 -
Skin Research and Technology : Official... Apr 2024Hyaluronic acid (HA) is a widely used active cosmetic ingredient. Its multiple skin care benefits are modulated by its molecular weight. Low molecular weight (LMW) HA... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hyaluronic acid (HA) is a widely used active cosmetic ingredient. Its multiple skin care benefits are modulated by its molecular weight. Low molecular weight (LMW) HA can penetrate the skin, but high molecular weight (HMW) HA remains at the surface. Here, we assessed how vectorization of HMW HA with bentonite clay-achieved with an innovative technology-enhances its cosmetic and hydrating properties.
MATERIALS AND METHODS
The two HA forms were applied to skin explants; their penetration and smoothing effects were monitored by Raman spectroscopy and scanning electron microscopy. The two forms were biochemically characterised by chromatography, enzyme sensitivity assays, and analysis of Zeta potential. Cosmetics benefits such as, the smoothing effect of vectorised-HA was assessed in ex vivo experiments on skin explants. A placebo-controlled clinical study was finally conducted applying treatments for 28 days to analyse the final benefits in crow's feet area.
RESULTS
Raman spectroscopy analysis revealed native HMW HA to accumulate at the surface of skin explants, whereas vectorised HMW HA was detected in deeper skin layers. This innovative vectorisation process changed the zeta potential of vectorised HMW HA, being then more anionic and negative without impacting the biochemical structure of native HA. In terms of cosmetic benefits, following application of vectorised HMW HA ex vivo, the skin's surface was visibly smoother. This smoothing was clinically confirmed, with a significant reduction in fine lines.
CONCLUSION
The development of innovative process vectorising HMW HA allowed HMW HA penetration in the skin. This enhanced penetration extends the clinical benefits of this iconic cosmetic ingredient.
Topics: Humans; Hyaluronic Acid; Clay; Molecular Weight; Skin; Skin Aging
PubMed: 38591218
DOI: 10.1111/srt.13672 -
Environmental Pollution (Barking, Essex... Nov 2023Lead chromate pigments are commonly used yellow inorganic pigments. They can pose environmental risks as they contain toxic heavy metals lead and chromium. Low molecular...
Lead chromate pigments are commonly used yellow inorganic pigments. They can pose environmental risks as they contain toxic heavy metals lead and chromium. Low molecular weight organic acids (LMWOAs), as widespread dissolved organic matter (DOM), affect the lead and chromium release from the pigment in water. In this work, the role of LMWOAs in the photodissolution of commercial lead chromate pigment was investigated. The pigment underwent significant photodissolution under simulated sunlight exposure with LMWOAs, and subsequently released Cr(III) and Pb(II). The photodissolution process is caused by the reduction of Cr(VI) by photogenerated electrons of the lead chromate pigment. The LMWOAs promoted photodissolution of the pigment by improving the electron-hole separation. The formation of Cr(III)-contained compounds leads to a slower release of chromium than lead. The photodissolution kinetics increase with decreasing pH and increasing LMWOAs concentration. The photodissolution of lead chromate pigment was basically positively related to the total number of hydroxyl and carboxyl groups in LMWOAs. The LMWOAs with stronger affinity to lead chromate pigment, lower adiabatic ionization potential (AIP) and higher energy of the highest occupied molecular orbital (E) are favorable to Cr(VI) reduction by photogenerated electrons and pigment photodissolution. 2.39% of chromium and 10.34% of lead released from the lead chromate pigment in natural conditions during a 6-h sunlight exposure. This study revealed the photodissolution mechanism of lead chromate pigment mediated by LMWOAs with different molecular structures, which helps understand the environmental photochemical behavior of the pigment. The present results emphasize the important role of DOM in the heavy metals release from commercial inorganic pigments.
Topics: Chromates; Lead; Sunlight; Molecular Weight; Chromium; Metals, Heavy; Organic Chemicals; Coloring Agents
PubMed: 37716691
DOI: 10.1016/j.envpol.2023.122553 -
International Journal of Biological... Jun 2024From the perspective of rubber/glass transition, this study clarified that the impact of dextran on retarding hardening behavior and slowing starch retrogradation of...
From the perspective of rubber/glass transition, this study clarified that the impact of dextran on retarding hardening behavior and slowing starch retrogradation of Chinese Steamed Bread (CSB) depended on its molecular weight and concentration level. Guggenheim-Anderson-de Boer (GAB) model was fitted to explore critical behavior changes in rubber/glass transition of CSB. Incorporation of high molecular weight dextran enhanced the elasticity of dough and porosity of CSB, reduced the aging and hardening degree of CSB at appropriate addition levels. CSB hardness showed a growing tendency during storage, while macromolecular dextran reduced the hardness and retrogradation degree by 22.87 % and 67.53 %. Dextran with high molecular weights lowered the glass transition temperature (T) and improved the moisture sorption and molecular mobility of CSB under various relative humidity (RHs) conditions by providing hydrophilic sites or intermolecular space to bind water molecules. Meanwhile, it reinforced the binding between denatured gluten and gelatinized starch. Both of them devoted to starch retrogradation inhibition and stable quality maintenance of CSB. CSB is suggested to maintain stable quality at room temperature with RHs ≤33 % to prevent rubber/glass transition. This work provided theoretical guidance for fractionation application of dextran to regulate the quality and extend the shelf-life of flour products.
Topics: Bread; Dextrans; Flour; Glass; Molecular Weight; Rubber; Starch; Steam; Transition Temperature
PubMed: 38688795
DOI: 10.1016/j.ijbiomac.2024.131887 -
Clinical Science (London, England :... Aug 2023Diabetic cardiomyopathy (DCM) is a chronic metabolic disease with few effective therapeutic options. Immunoproteasome is an inducible proteasome that plays an important...
Diabetic cardiomyopathy (DCM) is a chronic metabolic disease with few effective therapeutic options. Immunoproteasome is an inducible proteasome that plays an important role in the regulation of many cardiovascular diseases, while its role in DCM remains under discussion. The present study aims to demonstrate whether inhibiting immunoproteasome subunit low molecular weight polypeptide 7 (LMP7) could alleviate DCM. Here, we established a type I diabetes mellitus mouse model by streptozotocin (STZ) in 8-week-old male wild-type C57BL/6J mice. We found that immunoproteasome subunit LMP7 was overexpressed in the heart of diabetic mice, while inhibiting LMP7 with pharmacological inhibitor ONX0914 significantly alleviated myocardial fibrosis and improved cardiac function. Besides, compared with diabetic mice, ONX0914 treatment reduced protein levels of mesenchymal markers (Vimentin, α-smooth muscle actin, and SM22α) and increased endothelial markers (VE-cadherin and CD31). In TGFβ1 stimulated HUVECs, we also observed that ONX0914 could inhibit endothelial-mesenchymal transition (EndMT). Mechanistically, we prove that ONX0914 could regulate autophagy activity both in vivo and vitro. Meanwhile, the protective effect of ONX0914 on TGFβ1 stimulated HUVECs could be abolished by 3-methyladenine (3MA) or hydroxychloroquine (CQ). All in all, our data highlight that inhibition of LMP7 with ONX0914 could ameliorate EndMT in diabetic mouse hearts at least in part via autophagy activation. Thus, LMP7 may be a potential therapeutic target for the DCM.
Topics: Animals; Male; Mice; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Mice, Inbred C57BL; Molecular Weight; Peptides
PubMed: 37551616
DOI: 10.1042/CS20230732 -
Carbohydrate Polymers Jan 2024Low-molecular-weight chitosan (LMW chitosan, <10 kDa) have a significant potential for biomedical applications (e.g., antimicrobial and gene/drug delivery) because of...
Low-molecular-weight chitosan (LMW chitosan, <10 kDa) have a significant potential for biomedical applications (e.g., antimicrobial and gene/drug delivery) because of their higher water solubility at pH values ranging from 3.0 to 8.5, compared to that of the high-molecular-weight (>100 kDa) chitosan. A comprehensive understanding of the LMW interaction mechanism with specific functional groups is necessary to predict their binding efficiency to other molecules for effectively utilizing their potential within biological systems. In this study, we used a surface forces apparatus (SFA) to investigate molecular interactions between LMW chitosan and four different functionalized self-assembled monolayers (SAMs) in aqueous solutions at pH values of 3.0, 6.5, and 8.5. Chitosan exhibited the strongest interaction energy with methyl-terminated SAM (CH-SAM), indicating the significance of hydrophobic interaction. Many chitin/chitosan fibers in nature bind polyphenols (e.g., eumelanin) to form robust composites, which can be attributed to the strong attraction between chitosan and phenyl-SAM, presumably caused by cation-π interactions. These findings demonstrate the potential of modulating the magnitude of the interaction energy by controlling the solution pH and types of targeted functional groups to realize the optimal design of chitosan-based hybrid composites with other biomolecules or synthetic materials.
Topics: Chitosan; Molecular Weight; Hydrophobic and Hydrophilic Interactions; Anti-Infective Agents; Water
PubMed: 37985092
DOI: 10.1016/j.carbpol.2023.121504 -
Acta Biomaterialia Jul 2024Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage...
Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.
Topics: Hyaluronic Acid; Liposomes; Animals; Humans; Administration, Cutaneous; Skin; Skin Aging; Mice; Molecular Weight; Keratinocytes; Drug Delivery Systems; HaCaT Cells
PubMed: 38759743
DOI: 10.1016/j.actbio.2024.05.026 -
Marine Environmental Research Feb 2024Ocean acidification has increased due to the enhanced solubility of CO in seawater. Mangrove macroalgae in tropical and subtropical coastal regions can benefit from the...
Ocean acidification has increased due to the enhanced solubility of CO in seawater. Mangrove macroalgae in tropical and subtropical coastal regions can benefit from the higher availability of CO for photosynthesis and primary production. However, they can be negatively affected by the simultaneously occurring warming and increased salinity in estuaries. Thus, we analyzed the isolated effects of ocean acidification and the interactive effects of increased temperature and salinity on the low molecular weight carbohydrate (LMWC) contents of the mangrove red macroalgae Bostrychia montagnei and Bostrychia calliptera from Brazilian tropical and subtropical populations. Specimens from both climatic niches were tolerant to pH decreased by CO enrichment and enhanced their LMWC contents under increased availability of CO. Specimens from both climatic niches also accumulated their dulcitol and sorbitol contents to cope with warming and salt stress. Nevertheless, temperature of 34 °C was lethal for tropical macroalgae, while 29 °C and 31 °C were lethal for subtropical B. calliptera under salinity of 35. Tropical and subtropical B. montagnei synthesized dulcitol (5-110 mmol kg dry weight) and sorbitol (5-100 mmol kg dry weight) as osmoregulatory, energy and thermal protection compounds, whereas tropical and subtropical B. calliptera synthesized mainly dulcitol (10-210 mmol kg dry weight). Although digeneaside has an energy function in Bostrychia spp., it is not an osmolyte or thermal protection compound. Our data demonstrated that both tropical and subtropical Bostrychia spp. benefit from ocean acidification by CO enrichment, increasing their LMWC contents. However, warming and increased salinity in estuaries will be detrimental to them, even they producing protective metabolites. Multifactorial approaches are recommended to investigate whether negative effects of increased temperature and salinity nullify positive effects of ocean acidification on these Bostrychia species/populations.
Topics: Seawater; Seaweed; Salinity; Hydrogen-Ion Concentration; Carbon Dioxide; Ocean Acidification; Molecular Weight; Temperature; Carbohydrates; Sorbitol; Galactitol; Oceans and Seas; Global Warming
PubMed: 38150789
DOI: 10.1016/j.marenvres.2023.106316 -
Journal of Chromatography. B,... May 2024Adiponectin, a crucial protein hormone originating from adipose tissue, regulates key metabolic processes, including lipid metabolism, mitochondrial activity, and...
Adiponectin, a crucial protein hormone originating from adipose tissue, regulates key metabolic processes, including lipid metabolism, mitochondrial activity, and insulin sensitivity. These pleiotropic roles of adiponectin, along with its inverse correlation with metabolic disorders such as obesity, type II diabetes, and atherosclerosis, establish this protein as a potential therapeutic target. However, due to this complexity, challenges have arisen in its production with a natural conformation in bacterial or mammalian expression systems, hindering clinical translation. Furthermore, while inducers for adiponectin secretion or chemical agonists targeting adiponectin receptors have shown promise in laboratory settings, clinical studies with these agents have not yet been conducted. This study proposes a method for isolating and purifying natural high molecular weight (HMW) adiponectin from discarded plasma fractions during the conventional pharmaceutical protein manufacturing process. The process involved Cohn-Oncley fractionation, initial chromatography using reduced cellufine formyl, and subsequent purification via DEAE Sepharose chromatography. Characterization involved gel electrophoresis and biological assays on a hepatocyte cell-line. The purification process effectively captured adiponectin from the I + III paste, demonstrating that this fraction contained a significant portion of total plasma adiponectin. The two-step chromatography led to highly purified HMW adiponectin, confirmed by native-PAGE showing a 780 kDa multimeric complex. Biological assessments demonstrated normal downstream signaling, with HMW adiponectin inducing AMPK phosphorylation. This study demonstrates the feasibility of obtaining purified HMW adiponectin by repurposing plasma fractionation processes. It offers a promising avenue for the HMW adiponectin production, tapping into HMW adiponectin's therapeutic potential against metabolic disorders while optimizing plasma resource utilization in healthcare.
Topics: Humans; Adiponectin; Molecular Weight; Chromatography, Ion Exchange
PubMed: 38603890
DOI: 10.1016/j.jchromb.2024.124111