The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Lipidomic changes in mouse oocytes vitrified in PEG 8000-supplemented vitrification solutions.

Cryopreserved oocytes are inevitably exposed to cold stress, which negatively affects the cellular aspects of the oocytes. Lipidomic analysis of the oocytes reveals quantitative changes in lipid classes under conditions of cold stress, leading to potential freezing-vulnerability. We had previously shown that specific phospholipids are significantly downregulated in vitrified-warmed mouse oocytes compared to those in fresh oocytes. In this study, we examined whether supplementation of polyethylene glycol 8000 (PEG 8000) during vitrification influences the lipidome of the oocytes. We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to study the alteration in the lipidome in three groups of mouse oocytes: fresh, vitrified-warmed, and vitrified with PEG 8000-warmed during vitrification. In these groups, we targeted to analyze 21 lipid classes. We profiled 132 lipid species in the oocytes and statistical analyses revealed lipid classes that were up- or downregulated in these groups. Overall, our data revealed that several classes of lipids were affected during vitrification, and that oocytes vitrified with PEG 8000 to some extent alleviated the levels of changes in phospholipid and sphingolipid contents during vitrification. These results suggest that phospholipids and sphingolipids are influenced by PEG 8000 during vitrification and that PEG 8000 can be considered as a potential candidate for preserving membrane integrity during oocyte cryopreservation.

Proteoglycan Combined with Hyaluronic Acid and Hydrolyzed Collagen Restores the Skin Barrier in Mild Atopic Dermatitis and Dry, Eczema-Prone Skin: A Pilot Study.

Dry and eczema-prone skin conditions such as atopic dermatitis and xerotic eczema primarily indicate an impaired skin barrier function, which leads to chronic pruritus. Here, we investigated the effects of a novel emollient containing H.ECMTM liposome, which contains a soluble proteoglycan in combination with hydrolyzed collagen and hyaluronic acid. A prospective, single-arm study was conducted on 25 participants with mild atopic dermatitis or dry skin to assess the hydration and anti-inflammatory effect of the novel emollient applied daily over four weeks. All efficacy parameters, including itching severity, transepidermal water loss, and skin hydration, improved significantly after four weeks. The in vitro and ex vivo studies confirmed the restoration of the skin's barrier function. The study revealed the clinical and laboratory efficacy of H.ECMTM liposome in reducing itching and improving the skin's barrier integrity. Thus, the use of H.ECMTM liposome can be considered a therapeutic option for dry and eczema-prone skin.

Simethicone to prevent colonic bubbles during CT colonography performed with polyethylene glycol lavage and iohexol tagging: a randomized clinical trial.

OBJECTIVE: The purpose of this study was to determine whether the occurrence of numerous colonic bubbles during CT colonography (CTC) performed with polyethylene glycol cleansing and oral iohexol fecal/fluid tagging could be prevented by use of simethicone. SUBJECTS AND METHODS: Adults with suspected colonic neoplasia who had been randomly assigned to control and simethicone intervention groups underwent CTC after cleansing with 4 L of polyethylene glycol, tagging with 50 mL of 350 mg I/mL oral iohexol, and without (control) or with (intervention) oral administration of 200 mg of simethicone. Colonic segments in the control and intervention groups were evaluated for amount of colonic bubbles during CTC. A 6-point grading system was used in which 0 indicated no bubbles and 5 indicated that more than three fourths of the air-distended mucosa was covered with bubbles. The primary endpoint was a per-patient colonic bubble grade, derived as an average of the segmental grades. RESULTS: Eighty adults with suspected colonic neoplasia were randomly assigned to the control (40 patients) and simethicone intervention (40 patients) groups. A total of 659 colonic segments in the control group and 689 segments in the intervention group were evaluated for amount of colonic bubbles during CTC. The per-patient colonic bubble score was significantly lower in the simethicone intervention group than in the control group. The mean score was 0.0±0.1 (SD) versus 1.2±0.8 (p<0.001; 95% CI for the mean difference, -1.4 to -1.0). In the intervention group, 673 (97.7%) segments were grade 0, and 16 (2.3%) were grade 1. In contrast, in the control group, 226 (34.3%) segments were grade 0; 173 (26.3%), grade 1; 175 (26.6%), grade 2; 45 (6.8%), grade 3; 23 (3.5%), grade 4; and 17 (2.6%), grade 5. CONCLUSION: The colonic bubbles associated with fecal/fluid tagging with iohexol can be successfully prevented by adding simethicone to the colonic preparation.

Starch based polyhydroxybutyrate production in engineered Escherichia coli.

Every year, the amount of chemosynthetic plastic accumulating in the environment is increasing, and significant time is required for decomposition. Bio-based, biodegradable plastic is a promising alternative, but its production is not yet a cost effective process. Decreasing the production cost of polyhydroxyalkanoate by utilizing renewable carbon sources for biosynthesis is an important aspect of commercializing this biodegradable polymer. An Escherichia coli strain that expresses a functional amylase and accumulate polyhydroxybutyrate (PHB), was constructed using different plasmids containing the amylase gene of Panibacillus sp. and PHB synthesis genes from Ralstonia eutropha. This engineered strain can utilize starch as the sole carbon source. The maximum PHB production (1.24 g/L) was obtained with 2% (w/v) starch in M9 media containing 0.15% (w/v) yeast extract and 10 mM glycine betaine. The engineered E. coli SKB99 strain can accumulate intracellular PHB up to 57.4% of cell dry mass.

AAPE proliposomes for topical atopic dermatitis treatment.

CONTEXT: Anti-inflammatory effect of advanced adipose stem cell derived protein extract (AAPE) could be improved by minimising protein degradation. OBJECTIVE: To develop a proliposomal formulation of AAPE for the treatment of topical atopic dermatitis. MATERIALS AND METHODS: Proliposomal powder was manufactured by evaporating a solution of soy phosphatidyl choline, AAPE and Poloxamer 407 in ethanol under vacuum on sorbitol powder. Characterisation of proliposomes (zeta potential, diameter, stability and flowability) as well as in vivo efficacy in a dermatitis mouse model was investigated. RESULTS AND DISCUSSION: Reconstitution of the proliposomal powder formed liposomes of 589 ± 3.6 nm diameter with zeta potential of -51.33 ± 0.36 mV. Protein stability was maintained up to 90 days at 25 °C as proliposomes. In vivo studies on atopic dermatitis mouse model showed a significant reduction in IgE levels after topical AAPE proliposome treatment. CONCLUSION: AAPE proliposomes maintained protein stability and showed promising results for atopic dermatitis treatment.

A pilot study evaluating the efficacy and safety of retinaldehyde-loaded niosomes against mild-to-moderate acne.

BACKGROUND: Retinoids are the mainstay of topical therapy for acne. To improve the efficacy and minimize the side effects of retinoids, various novel drug delivery mechanisms, including nanoparticles, have been developed. AIM: To evaluate the efficacy and safety of a retinaldehyde-loaded niosome (RA-N) nanoemulsion against sebum secretion and keratinization on mild-to-moderate acne. PATIENTS/METHODS: Twenty-three participants exhibiting mild-to-moderate acne with both closed and open comedones were included. They applied a 0.05% RA-N nanoemulsion daily for 4 weeks, did not to use any other emollient or topical pharmaceutical, and were asked to report any symptoms and treatment satisfaction. RESULTS: The participants demonstrated significantly fewer closed and open comedones after 2 and 4 weeks of treatment than at baseline (*p < 0.05). The mean sebum secretion, measured using Sebumeter®, was 327.95 ± 90.20 µg cm-2 at baseline and reduced to 282.60 ± 99.70 and 250.65 ± 97.6 µg cm-2 , respectively, after 2 and 4 weeks of treatment (*p < 0.05). The mean desquamation index, determined using Visioscan®, was 10.99 ± 1.69 at baseline and decreased to 9.81 ± 1.10 and 8.89 ± 1.32, respectively, after 2 and 4 weeks of treatment (*p < 0.05). The application of the RA-N nanoemulsion resulted in a significantly lower desquamation level, suggesting that the RA-N nanoemulsion was well-tolerated without any skin irritation. None of the participants reported a serious adverse event during this study. CONCLUSION: Our findings suggest that the RA-N nanoemulsion was effective in improving comedones in acne-prone skin and safe for long-term application. Further studies are necessary to investigate the long-term effects of the application of the RA-N nanoemulsion in participants with inflammatory acne and acne scars.

Use of 532-nm Q-switched Nd:YAG laser for smoker's gingival hyperpigmentation.

Laser treatments using 532-/1064-nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers are popular non-ablative and selective photothermolysis therapies for pigmentary disorders. We treated three male Korean patients (aged 23, 27 and 24 years) for smoker's gingival hyperpigmentation using a 532-nm Q-switched Nd:YAG laser. At each treatment session, the laser was delivered at 1.2 J/cm(2) with a 5-mm spot size and appropriate overlap. Clinical improvement as well as complete healing of the treated gingiva was noted within 2 weeks after each treatment. We also observed that the therapeutic effects lasted more than 6 months.

Increased Tolerance to Furfural by Introduction of Polyhydroxybutyrate Synthetic Genes to Escherichia coli.

Polyhydroxybutyrate (PHB), the most well-known polyhydroxyalkanoate, is a bio-based, biodegradable polymer that has the potential to replace petroleum-based plastics. Lignocellulose hydrolysate, a non-edible resource, is a promising substrate for the sustainable, fermentative production of PHB. However, its application is limited by the generation of inhibitors during the pretreatment processes. In this study, we investigated the feasibility of PHB production in E. coli in the presence of inhibitors found in lignocellulose hydrolysates. Our results show that the introduction of PHB synthetic genes (bktB, phaB, and phaC from Ralstonia eutropha H16) improved cell growth in the presence of the inhibitors such as furfural, 4-hydroxybenzaldehyde, and vanillin, suggesting that PHB synthetic genes confer resistance to these inhibitors. In addition, increased PHB production was observed in the presence of furfural as opposed to the absence of furfural, suggesting that this compound could be used to stimulate PHB production. Our findings indicate that PHB production using lignocellulose hydrolysates in recombinant E. coli could be an innovative strategy for cost-effective PHB production, and PHB could be a good target product from lignocellulose hydrolysates, especially glucose.

Development of novel biocompatible thermosensitive anti-adhesive agents using human-derived acellular dermal matrix.

Postoperative adhesion is a natural phenomenon that occurs in damaged tissue cells. Several anti-adhesion agents are currently used, but there is no leading-edge product with excellent adhesion-preventive effects. The purpose of this study was to develop ideal anti-adhesive agents using human-derived acellular dermal matrix (ADM). We developed 5 new biocompatible thermosensitive anti-adhesion barriers (AABs) using micronized human-derived ADM, hyaluronic acid, and temperature-sensitive and biocompatible synthesized polymers. The biocompatibility, anti-adhesion effect, and biodegradability of these AABs were compared with those of commercial thermosensitive anti-adhesion agents. No cytotoxic effects were observed in vitro and in vivo. Animal testing of adhesion resistance confirmed that the adhesion area, strength, and grade of AAB03 were statistically superior to those of the control group. Factors related to adhesion formation, such as lymphocytes, macrophages, microvessels, and collagen fiber density, were observed using specific staining methods; the results confirmed that AAB03 group exhibited significantly lower macrophage counts, microvessel density, and collagen fiber density than the control groups. Furthermore, AAB03 was completely absorbed by 6 weeks. Thus, AAB03 has the potential to be used as a high-performance anti-adhesion agent.

Clinical manifestations associated with high titer of anti-streptolysin O in Behcet's disease.

To evaluate the association of chronic infection with clinical features of Behcet's disease (BD), we studied epidemiological and clinical features of 149 patients with only aphthous ulcer and 294 patients with BD. The incidence of chronic infection history was compared between both groups with age- and sex-matching and clinical manifestations of BD associated with high anti-streptolysin O (ASO) titer were investigated. BD patients had more common history of tonsillitis and dental caries than aphthous ulcer patients (P = 0.002 and P = 0.043, respectively). BD patients with persistently high anti-streptolysin O titers had more frequent history of tonsillitis (P = 0.001, odds ratio [OR] = 2.99, 95% confidence interval [CI] 1.53-5.82) and erythema nodosum (EN)-like lesions (P = 0.001, OR = 3.02, 95% CI 1.54-5.93) and fewer history of genital ulcer (P = 0.027, OR = 0.21, 95% CI 0.05-0.84) than BD patients with normal anti-streptolysin O titer. Our results suggest persistently high ASO titers in BD patients could indicate that streptococcal infections such as tonsillitis are related to BD symptoms such as EN-like lesions. In these patients, ASO titer can be used in the evaluation of BD disease activity and antibiotic treatments might be effective to control the symptoms of BD.

Composite scaffold of micronized porcine cartilage/poly(lactic­co­glycolic acid) enhances anti-inflammatory effect.

The main disadvantage of using poly(lactic­co­glycolic acid) (PLGA), a typical synthetic polymer, as a biomaterial is that it induces inflammation. To overcome this disadvantage, we determined the ability of micronized porcine cartilage (MPC) for alleviating the inflammatory effects of a PLGA scaffold. MPC was analyzed by sodium dodecyl sulfate­polyacrylamide gel electrophoresis and Fourier transform-infrared spectroscopy, and typical collagen components were confirmed. The MPC/PLGA scaffolds were fabricated using various concentrations of MPC and the compressive strength was evaluated to characterize its physical properties. Although the compressive strength decreased with increasing amounts of MPC, the roughness of the surface, assessed by scanning election microscopy, was considered to be suitable for facilitating cell attachment. Notably, in vitro experiments showed that the cell adhesion and proliferation rates increased as the MPC content increased. MPC further reduced gene expression levels of inflammatory cytokines and cellular reactive oxygen species, as determined by real time-polymerase chain reaction and fluorescence-activated cell sorting, respectively. In addition, in vivo experiments confirmed the interaction between tissues and the scaffolds. Overall, these results confirmed that the MPC/PLGA scaffold is superior to the PLGA scaffold in many respects and might be a suitable candidate for resolving the disadvantages of PLGA in tissue engineering applications.

In vitro and in vivo evaluation of N,N,N-trimethylphytosphingosine-iodide (TMP) in liposomes for the treatment of angiogenesis and metastasis.

Phytosphingosine and methyl derivatives are important mediators on cellular processes, and are associated with cell growth and death. The antitumor activity of N,N,N-trimethylphytosphingosine-iodide (TMP) as a novel potent inhibitor of angiogenesis and metastasis was evaluated in B16F10 murine melanoma cells. The results indicated that TMP itself effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors as well as in vivo lung metastasis. However, TMP slightly suppressed in vivo experimental tumor metastasis in its free form and induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP, a liposomal formulation was prepared and tested for its effectiveness. TMP liposomes retained the effectiveness of TMP in vitro while side effects were reduced, and both in vivo experimental and spontaneous tumor metastasis were significantly suppressed. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis as well as in vivo metastasis, and a liposomal formulation is more efficient delivery system for TMP treatment than solution.

Self-assembled nanoparticles based on hyaluronic acid-ceramide (HA-CE) and Pluronic® for tumor-targeted delivery of docetaxel.

Hyaluronic acid-ceramide (HA-CE)-based self-assembled nanoparticles were developed for intravenous docetaxel (DCT) delivery. In this study, physicochemical properties, cellular uptake efficiency, and in vivo targeting capability of the nanoparticles developed were investigated. DCT-loaded nanoparticles composed of HA-CE and Pluronic 85 (P85) with a mean diameter of 110-140 nm were prepared and their morphological shapes were assessed using transmission electron microscopy (TEM). DCT release from nanoparticle was enhanced with increasing P85 concentrations in our in vitro model. Blank nanoparticles exhibited low cytotoxicity in U87-MG, MCF-7 and MCF-7/ADR cell lines. From cellular uptake studies, the nanoparticles developed enhanced the intracellular DCT uptake in the CD44-overexpressing cell line (MCF-7). The nanoparticles were shown to be taken up by the HA-CD44 interaction according to DCT and coumarin 6 (C6) cellular uptake studies. The multidrug resistance (MDR)-overcoming effects of DCT-loaded HA-CE/P85-based nanoparticles were also observed in cytotoxicity tests in MCF-7/ADR cells. Following the intravenous injection of DCT-loaded cyanine 5.5 (Cy5.5)-conjugated nanoparticles in MCF-7/ADR tumor-bearing mice, its in vivo targeting for CD44-overexpressing tumors was identified by non-invasive near-infrared (NIR) fluorescence imaging. These results indicate that the HA-CE-based nanoparticles prepared may be a promising anti-cancer drug delivery system through passive and active tumor targeting.

The use of low molecular weight heparin-pluronic nanogels to impede liver fibrosis by inhibition the TGF-ß/Smad signaling pathway.

Low molecular weight heparin (LH) has been reported to have anti-fibrotic and anti-cancer effects. To enhance the efficacy and minimize adverse effects of LH, a low molecular weight heparin-pluronic nanogel (LHP) was synthesized by conjugating carboxylated pluronic F127 to LH. The LHP reduced anti-coagulant activity by about 33% of the innate activity. Liver fibrosis was induced by the injection of 1% dimethylnitrosamine (DMN) in rats, and LH or LHP (1000 IU/kg body weight) was treated once daily for 4 weeks. LHP administration prevented DMN-mediated liver weight loss and decreased the values of aspartate transaminase, alanine transaminase, total bilirubin, and direct bilirubin. LHP markedly reduced the fibrotic area compared to LH. Also, LHP potently inhibited mRNA or protein expression of alpha-smooth muscle actin, collagen type I, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1 compared to LH, in DMN-induced liver fibrosis. In addition, LHP decreased the expression of transforming growth factor-ß(1) (TGF-ß(1)), p-Smad 2, and p-Smad 3, which are all important molecules of the TGF-ß/Smad signaling pathway. The results support an LHP shows anti-fibrotic effect in the liver via inhibition of the TGF-ß/Smad pathway as well as by the elimination of the extracellular matrix.

Vitiligo following intense pulsed light treatment.

Vitiligo is an acquired depigmenting disorder characterized by the progressive loss of melanocytes from the epidermis and epidermal appendages, which results in milky-white macular lesions. Various factors are suspected to affect the induction and progression of vitiligo such as emotional shock, sunburn, pregnancy, physical illness and trauma. The intense pulsed light (IPL) device which mostly affects redness and dyspigmentation has a broad spectrum of emissions of white light with wavelengths between approximately 515 and 1200 nm. Adverse effects such as purpura and pigmentary changes are known to be rare. We present a 41-year-old woman who developed multiple round, hypopigmented macules on both the cheek and mandibular area following the treatment with IPL for lentigines and dyspigmentation. Based on biopsy and Wood's lamp examination, diagnosis as vitiligo was made. She was treated with a 308-nm excimer laser. After 3 months of treatment, almost complete repigmentation was seen but another coin-sized hypopigmented patch was noted after 5 months later. Herein, we report a case of vitiligo which developed after IPL treatment. This is the first case to be reported which vitiligo developed after IPL treatment. Therefore, dermatologists should be aware of unsighted vitiligo lesion before IPL treatment.

A Case of Hand-foot-mouth Disease in an Immunocompetent Adult.

Hand-foot-mouth (HFM) disease is primarily a disease of children, although it can be seen in immunocompromised adults. We describe a case of HFM disease in a 35-year-old immunocompetent male. He presented with multiple, 1~2 mm sized, erythematous vesicular papules on both hands and feet. Histopathological findings of a skin biopsy showed superficial perivascular lymphocytic infiltration, focal keratinocyte necrosis, and reticular degeneration. Because delayed diagnosis can cause spread of the disease to children, dermatologists should be aware that HFM disease can occur in adults with intact immune systems.