UNASSIGNED: Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis.
UNASSIGNED: We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period.
UNASSIGNED: Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function.
UNASSIGNED: These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function.

Cutibacterium acnes is an opportunistic pathogen in acne vulgaris. C. acnes produces autoinducer-2 (AI-2）, a signaling molecule used for communication known as quorum sensing (QS）. In C. acnes, QS reportedly upregulates biofilm formation leading to resistance against bactericidal agents. In this study, we analyzed how heparinoid affected QS and biofilm formation of the opportunistic pathogen C. acnes. We also verified whether heparinoid would suppress biofilm formation and enhance the efficacy of the bactericidal agent 4-isopropyl-3-methylphenol (IPMP) against C. acnes biofilms. We ran an AI-2 bioassay using Vibrio harveyi ATCC BBA-1121. Heparinoid exhibited inhibitory activity against AI-2 at concentrations of 0.003-0.005%, suggesting an AI-2 analog-derived or C. acnes culture supernatant-derived inhibition of the AI-2 activity. To evaluate how heparinoid suppresses biofilm formation in C. acnes, we completed a biofilm assay in 96-well plates. We also evaluated the bactericidal activity of IPMP against the C. acnes biofilm prepared with or without heparinoid. Heparinoid inhibited C. acnes biofilm formation and IPMP bactericidal efficacy increased upon heparinoid-mediated suppression of biofilm formation. In this study, we clarified that heparinoid inhibits the AI-2-mediated QS of C. acnes, thereby suppressing biofilm formation and increasing IPMP bactericidal efficacy, potentially suppressing acne vulgaris.

Crude anionic polysaccharides extracted from the Pacific starfish Lethasterias fusca were purified by anion-exchange chromatography. The main fraction LF, having MW 14.5 kDa and dispersity 1.28 (data of gel-permeation chromatography), was solvolytically desulfated and giving rise to preparation LF-deS with a structure of dermatan core [→3)-β-d-GalNAc-(1→4)-α-l-IdoA-(1→]n, which was identified according to NMR spectroscopy data. Analysis of the NMR spectra of the parent fraction LF led to identification of the main component as dermatan sulfate LF-Derm →3)-β-d-GalNAc4R-(1→4)-α-l-IdoA2R3S-(1→ (where R was SO3 or H), bearing sulfate groups at O-3 or both at O-2 and O-3 of α-l-iduronic acid, as well as at O-4 of some N-acetyl-d-galactosamine residues. The minor signals in NMR spectra of LF were assigned as resonances of heparinoid LF-Hep composed of the fragments →4)-α-d-GlcNS3S6S-(1→4)-α-l-IdoA2S3S-(1→. The 3-O-sulfated and 2,3-di-O-sulfated iduronic acid residues are very unusual for natural glycosaminoglycans, and further studies are needed to elucidate their possible specific influence on the biological activity of the corresponding polysaccharides. To confirm the presence of these units in LF-Derm and LF-Hep, a series of variously sulfated model 3-aminopropyl iduronosides were synthesized and their NMR spectra were compared with those of the polysaccharides. Preparations LF and LF-deS were studied as stimulators of hematopoiesis in vitro. Surprisingly, it was found that both preparations were active in these tests, and hence, the high level of sulfation is not necessary for hematopoiesis stimulation in this particular case.

Heparinoid, a type of compound that has structures similar to heparin, has been found in marine organisms such as shrimp head. This shrimp waste products were used to prepare, characterize, and evaluate the antithrombotic effect of heparinoid. Two heparinoid compounds were obtained from shrimp head, and the main fraction F1 was →4)-GlcA-(1→3)-GalNAc-(1→ with Ara, while the minor fraction F2 composed mainly of the backbone as →4)-β-D-GlcA (or IdoA)-(1→4)-β-D-GlcN (or GlcNAc)-(1→. Both F1 and F2 could extend activated partial thromboplastin time and thrombin time concentration-dependently, and F2 has stronger activity than F1 at the same concentration. The potential anticoagulant mechanism of F1 and F2 may relate to their combination with more antithrombin III, which binds to and potentiates the action of antithrombin as well as inhibiting coagulation factors Xa and IIa, preventing blood clot formation. Furthermore, heparinoid F1 and F2 were found to have high fibrinolytic capability in vitro and in vivo via activating the self-fibrinolytic system. In conclusion, heparinoids (F1 and F2) derived from shrimp head wastes could be used as candidate compounds to prevent thrombosis while posing a lower hemorrhagic risk.

Heparinoid, a sulfate polysaccharide derived from marine organisms was attracted largely attention due to its versatile activities. A naturally occurring heparinoid (M2) that was extracted from the mollusk Meretrix lusoria and used in this investigation shown strong antithrombotic action. UV-Vis, FT-IR, SAX-HPLC, and NMR were used to explore the structural characteristics of M2, results indicated that M2 similar with heparin, its average molecular weight was 22.58 kDa. Which was primarily made up of→4)-α-IdoA2S-(1→4)-α-GlcNS6S-(1→ (31.19%), →4)-β-GlcA-(1→4)-α-GlcNAc (1→ (23.21%), →4)-β-GlcA-(1→4)-α-GlcNS (1→ (13.87%), →4)-α-IdoA2S-(1→4)-α-GlcNS (1→ (8.95%), →4)-β-GlcA-(1→4)-α-GlcNAc6S (1→ (7.39%) and →4)-β-GlcA-(1→4)-α-GlcNS6S (1→ (7.63%). The antithrombotic activity of M2 was evaluated using measurements of the anticoagulant effect in vitro and the fibrinolytic capability in vitro and in vivo, and M2 has 122.4 U/mg of anticoagulant activity and 1.41 U/mg of fibrinolytic activity, respectively. Additionally, a mouse tail-cutting model was used to assess the bleeding effect in real time, it found that M2 had a reduced hemorrhagic risk than heparin. Consequently, M2 could be exploited to develop functional foods or medications with antithrombotic properties.

Tight junctions (TJs) play important roles in epidermal barrier function and their dysfunction is involved in the pathogenesis of various skin diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is the active ingredient of a moisturizing agent used to treat xerosis in patients with AD; however, its mechanism of action on TJ barrier function remains unclear. To elucidate the effects of MPS on TJs, adult human epidermal keratinocyte (HEKa) cells were exposed to MPS, subjected to Western blotting and quantitative PCR analyses for the investigation of TJ-related factors. MPS treatment significantly increased the mRNA and protein expression of claudin-1 (CLDN1) and zonula occludens-1, and significantly increased transepithelial electrical resistance (TEER), which indicates TJ integrity. Conversely, the sulphated and non-sulphated glycosaminoglycans, chondroitin sulphate and hyaluronic acid, respectively, had little effect on TEER or the expression of mRNAs or TJ-related proteins. Interestingly, MPS treatment also inactivated the extracellular signal-regulated kinase signalling pathway, which is known to negatively regulate CLDN1 expression. Furthermore, MPS notably improved the reduction in CLDN1 expression and TEER caused by histamine, which is upregulated in the skin of patients with AD and is known to disrupt the TJ barrier function. Taken together, these findings demonstrate that treatment with the moisturizing agent, MPS, can repair TJ dysfunction and could therefore represent a new therapeutic option for treating patients with AD.

BACKGROUND: Molecular targeted therapies (MTTs) cause skin disorders in patients with cancer, and moisturizers are useful treatments; however, their actual use and costs are unknown. Our purpose was to examine the use and costs of moisturizers prescribed for xerosis (asteatosis) in patients with cancer treated with MTTs.
METHODS: We used data from a Japanese hospital-based claims database. The index date was the first date of MTT prescription from October 2011 to April 2018 (selection period), and the follow-up period was 1 year from the index date. Patients treated with MTTs during the selection period and who were not prescribed moisturizers in the 6 months before the index date were included as the study cohort. Timing, duration, amount, and costs of the prescribed moisturizers and total medical costs were analyzed.
RESULTS: Among the 78,190 patients in the study cohort, 27,906 patients (35.7%) were prescribed moisturizers during follow-up. Moisturizer prescription timing, duration, and volume were inconsistent. The average annual total medical costs for treating patients with MTT who were prescribed moisturizers was JPY 6.165 million (USD 53,797) per patient, and the moisturizer costs were JPY 6033 (USD 53). The number of patients who used moisturizers showed an increasing trend.
CONCLUSIONS: No consistent patterns were observed for the timing or duration of moisturizer use, which suggests various developmental patterns of skin disorders. Furthermore, medical costs for moisturizers accounted for only a small proportion of the total medical costs required for cancer treatment.

OBJECTIVE: Atopic dermatitis (AD) is characterized by chronic inflammation, which frequently recurs, is exacerbated, and enters remission. A maintenance remission period is important for AD patients. We developed a formulation for use during AD remission, containing heparinoid and pseudo-ceramide that forms a lamellar structure. We evaluated the allergen permeability and examined the formulation\'s efficacy in maintaining remission in patients with AD.
METHODS: Seventeen AD patients applied a cream containing 0.3% heparinoid and pseudo-ceramide (test cream group, n = 10), or a general cream containing 0.3% heparinoid (control cream group, n = 7) to their arm for four weeks after inducing remission with the application of a steroid cream for two weeks.
RESULTS: The lamellar structure of the test cream was confirmed with small- and wide-angle x-ray scattering analysis and observation by transmission electron microscopy. The test cream inhibited the penetration of V8 protease significantly compared to the control cream in vitro. According to AD severity score by dermatologists, the effects remission maintenance of the test cream group were comparable to those of the control cream group. However, the test cream group had a significantly increased skin hydration value compared to the control cream group. A significant decrease in transepidermal water loss, an indicator of skin barrier function, was shown in the test cream group compared to the control cream group.
CONCLUSIONS: The cream with lamellar structures containing heparinoid and pseudo-ceramides may inhibit allergen penetration. Moreover, skin properties improved during the remission period; thus, the formulation we developed was suitable for use during the AD remission period.

Recently, heparin-induced thrombocytopenia (HIT) after vaccination with the vaccines manufactured by AstraZeneca and Pfizer-BioNTech has been published in the New England Journal of Medicine. These reports state that heparin was not used around the vaccination period in all cases. HIT after vaccination is more common in women; thus, heparinoid use can be suspected to induce HIT.

The autoimmune disorder rheumatoid arthritis (RA) is a relapsing and chronic inflammatory disease that affects the synovial cells, cartilage, bone, and muscle. It is characterised by the accumulation of huge numbers of polymorphonuclear neutrophils (PMNs) and macrophages in the synovia. Auto-antibodies are deposited in the joint via the activity of highly cationic histones released from neutrophil extracellular traps (NETs) in a phenomenon termed NETosis. The cationic histones function as opsonic agents that bind to negatively charged domains in autoantibodies and complement compounds via strong electrostatic forces, facilitating their deposition and endocytosis by synovial cells. However, eventually the main cause of tissue damage is the plethora of toxic pro-inflammatory substances released by activated neutrophils recruited by cytokines. Tissue damage in RA can also be accompanied by infections which, upon bacteriolysis, release cell-wall components that are toxic to tissues. Some amelioration of the damaged cells and tissues in RA may be achieved by the use of highly anionic heparins, which can neutralize cationic histone activity, provided that these polyanions are co-administrated with anti-inflammatory drugs such as steroids, colchicine, or methotrexate, low molecular weight antioxidants, proteinase inhibitors, and phospholipase A2 inhibitors.