Coffea arabica Extract Attenuates Atopic Dermatitis-like Skin Lesions by Regulating NLRP3 Inflammasome Expression and Skin Barrier Functions.

Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of Coffea arabica extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1ß and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.

Correlation between the quality of cartilage repair tissue and patellofemoral osteoarthritis after matrix-induced autologous chondrocyte implantation at three-year follow-up: a cross-sectional study.

PURPOSE: To investigate whether the quality of cartilage repair tissue is associated with patellofemoral osteoarthritis (PFOA) at a three year follow-up after matrix-induced autologous chondrocyte implantation (MACI). METHODS: This retrospective study included 32 patients who underwent MACI between October 2014 and May 2018 at our institute. The Lysholm score and Visual Analog Scale (VAS) score were assessed. The magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and T2* relaxation time of repair tissue were used to evaluate cartilage repair tissue quality. A modified MRI Osteoarthritis Knee Score (mMOAKS) was used to evaluate PFOA. RESULTS: Compared with pre-operative scores, the final Lysholm score (50.71 ± 2.22 vs 89.70 ± 1.18; t = 15.5, P < 0.0001) and VAS score (4.67 ± 0.47 vs 0.92 ± 0.64; t = 22.62, P < 0.0001) were improved at 3 years after MACI. At the three year follow-up, the mean MOCART 2.0 score was 61.56 ± 18.11, and the T2* relaxation time of the repair tissue was significantly lower than that in the healthy control region (24.11 ± 6.38 vs 34.39 ± 1.33, t = - 8.635, P < 0.0001). The mean mMOAKS score was 9.16 ± 4.51. On univariate analysis, the MOCART 2.0 score and T2* relaxation time were negatively associated with the mMOAKS score. CONCLUSION: MACI can lead to significant pain relief and restoration of knee joint function, and good quality cartilage repair tissue was a protective factor against PFOA at the three year follow-up.

Protective Effect of Djulis (Chenopodium formosanum) Extract against UV- and AGEs-Induced Skin Aging via Alleviating Oxidative Stress and Collagen Degradation.

Skin aging is a complex process involving photoaging and glycation stress, which share some fundamental pathways and have common mediators. They can cause skin damage and collagen degradation by inducing oxidative stress and the accumulation of reactive oxygen species (ROS). Chenopodium formosanum (CF), also known as Djulis, is a traditional cereal in Taiwan. This study investigated the protection mechanisms of CF extract against ultraviolet (UV) radiation and advanced glycation end products (AGEs)-induced stress. The results indicated that CF extract had strong antioxidant and free radical scavenging effects. It could reduce UV-induced intracellular ROS generation and initiate the antioxidant defense system by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in human skin fibroblasts. CF extract modulated mitogen-activated protein kinase (MAPK) and transformed growth factor-beta (TGF-ß) signaling pathways to alleviate oxidative stress-induced skin aging. Moreover, the results revealed that CF extract not only promoted collagen synthesis but also improved aging-induced collagen degradation. CF extract attenuated AGEs-induced ROS production and the upregulation of receptor for AGEs (RAGE). The overall results suggest that CF extract provides an effective anti-aging strategy by preventing skin damage from oxidative stress and collagen loss with potent antioxidant, anti-photoaging, and antiglycation activities.

The Anti-Melanogenesis Effect of 3,4-Dihydroxybenzalacetone through Downregulation of Melanosome Maturation and Transportation in B16F10 and Human Epidermal Melanocytes.

The biosynthesis pathway of melanin is a series of oxidative reactions that are catalyzed by melanin-related proteins, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Reagents or materials with antioxidative or free radical-scavenging activities may be candidates for anti-melanogenesis. 3,4-Dihydroxybenzalacetone (DBL) is a polyphenol isolated from fungi, such as Phellinus obliguus (Persoon) Pilat and P. linteus. In this study, we investigated the effects and mechanisms of DBL on antioxidation and melanogenesis in murine melanoma cells (B16F10) and human epidermal melanocytes (HEMs). The results indicated that DBL scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, and exhibited potent reducing power, indicating that it displays strong antioxidative activity. DBL also inhibited the expression of TYR, TRP-1, TRP-2, and microphthalmia-related transcription factor (MITF) in both the cells. In addition, DBL inhibited hyperpigmentation in B16F10 and HEMs by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3 beta (GSK3ß), and mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK) signaling pathways. DBL not only shortened dendritic melanocytes but also inhibited premelanosome protein 17 (PMEL17) expression, slowing down the maturation of melanosome transportation. These results indicated that DBL promotes anti-melanogenesis by inhibiting the transportation of melanosomes. Therefore, DBL is a potent antioxidant and depigmenting agent that may be used in whitening cosmetics.

Correlation between the subchondral bone marrow lesions and cartilage repair tissue after matrix-associated autologous chondrocyte implantation in the knee: a cross-sectional study.

BACKGROUND: The contribution of the subchondral bone in the development and progression of osteoarthritis (OA) has long been recognized, but its role in cartilage repair procedures has only recently attracted more attention. PURPOSE: To explore the correlation between the cartilage repair tissue (RT) and the subchondral bone marrow lesions (BMLs) after matrix-associated autologous chondrocyte implantation (MACI) in the knee joint. MATERIAL AND METHODS: A total of 30 patients who underwent MACI in the knee from January 2015 to June 2018 and follow-up magnetic resonance imaging (MRI) scan were recruited in this study. The MRI results of cartilage RT were evaluated using T2* relaxation time. Subchondral BMLs were also qualitatively evaluated by use of the two-dimensional proton density-weighted fat-suppressed (2D-PD-FS) and three-dimensional dual-echo steady-state (3D-DESS) sequences. RESULTS: The univariate analysis displayed a significant negative correlation between subchondral BMLs and cartilage RT (P < 0.01). In the minimally adjusted model (only age, sex, and body mass index [BMI] adjusted), the results did not show obvious changes (ß = -6.54, 95% confidence interval [CI] = -10.99 to -2.09; P = 0.008). After adjustment for the full models (age, sex, BMI, defect size, combined injury, and preoperative duration of symptoms adjusted), the connection was also detected (ß = -6.66, 95% CI -11.82 to -1.50; P = 0.019). CONCLUSION: After MACI, the subchondral BMLs are significantly correlated with cartilage RT-T2* relaxation time. The role of subchondral bone in cartilage repair procedures should not be underestimated.

Oral intake of Streptococcus thermophil us improves knee osteoarthritis degeneration: A randomized, double-blind, placebo-controlled clinical study.

This preliminary clinical study demonstrates the possibility of a new species of probiotic for improvement of the degeneration of knee osteoarthritis (KOA). TCI633 (Streptococcus thermophil us) is a newly founded bacterium from human breast milk, and it is able to produce hyaluronate (HA) in gastrointestinal (GI) tract. A recent study has proved that TCI633 can substantially alleviate synovial tissue inflammation and cartilage damage in the animal models, but so far it has never been applied in clinical intervention. In this study, we recruited 80 subjects and conducted 12 weeks clinical trial to validate the efficacy of TCI633 for improvement of the progression of KOA. TCI633 could improve serum collagen type II C-telopeptide (sCTX-II) and serum C-reactive protein (sCRP) by 41.58% and 39.58%, respectively, after the study. The improvement rates for sCTX-II and sCRP in TCI633 group were 54% and 57%, respectively, at 12 weeks. Compared to the results of placebo, the indistinct improvement progresses of sCTX-II and sCRP might be caused by the uneventful distribution of K/L populations between the TCI633 and placebo groups, a short term of study period, and few recruited subjects. Moreover, the results of Western Ontario and McMaster Universities (WOMAC) questionnaires show that TCI633 might retard the progression and development of KOA after the trial. In brief, this preliminary research may provide an alternative approach to the improvement of KOA by probiotics although more detailed investigations should be conducted for solid conclusions.

Efficacy and Safety of Percutaneous Argon-Helium Cryoablation for Hepatocellular Carcinoma Abutting the Diaphragm.

PURPOSE: To evaluate the efficacy and safety of percutaneous argon-helium cryoablation (CA) for hepatocellular carcinoma (HCC) abutting the diaphragm (<5 mm). MATERIALS AND METHODS: A total of 61 consecutive patients (50 men, 11 women; mean age, 56.3 ± 12.1 years old; range, 32-83 years) with 74 HCC tumors (mean size, 3.3 ± 1.7 cm; range, 0.8-7 cm) who were treated with percutaneous argon-helium CA were enrolled in this retrospective study. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Local tumor progression (LTP) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. The risk factors associated with OS and LTP were evaluated using univariate and multivariate Cox regression analysis. RESULTS: No periprocedural (30-day) deaths occurred. A total of 29 intrathoracic adverse events occurred in 24 of the 61 patients. Major adverse events were reported in 5 patients (pleural effusion requiring catheter drainage in 4 patients and pneumothorax requiring catheter placement in 1 patient). Median follow-up was 18.7 months (range, 2.3-60.0 months). Median time to LTP after CA was 20.9 months (interquartile range [IQR], 14.1-30.6 months). Median times of OS after CA and diagnosis were 27.3 months (IQR, 15.1-45.1 months) and 40.9 months (interquartile range, 24.8-68.6 months), respectively. Independent prognostic factors for OS included tumor location (left lobe vs right lobe; hazard ratio [HR], 2.031; 95% confidence interval [CI], 1.062-3.885; P = .032) and number of intrahepatic tumors (solitary vs multifocal; HR, 2.684; 95% CI, 1.322-5.447; P = .006). Independent prognostic factors for LTP included age (HR, 0.931; 95% CI, 0.900-0.963; P  < .001), guidance modality (ultrasound vs computed tomography and US; HR, 6.156 95% CI, 1.862-20.348; P  =   .003) and origin of liver disease. CONCLUSIONS: Percutaneous argon-helium CA is safe for the treatment of HCC abutting the diaphragm, with acceptable LTP and OS.

Retrospective analysis of CT-guided percutaneous cryoablation for treatment of painful osteolytic bone metastasis.

This study aimed to evaluate the safety and effectiveness of CT-guided percutaneous cryoablation for treatment of painful osteolytic bone metastases. A total of 26 patients (36 bone metastases) treated with CT-guided percutaneous cryoablation between May 2012 and June 2016 were enrolled in this retrospective study. All procedures were performed under local anesthesia. A visual analog scale (VAS) was used to evaluate pain before the procedure and at 1 day, 1 month, 3 months, and 6 months after the procedure. Complications during and after the procedure were recorded and graded by the Clavien-Dindo classification. The mean VAS pain score was 7.1 ± 1.1 (range, 4-10) before cryoablation. It was significantly lower at all timepoints after treatment: 2.1 ± 1.7 (P < 0.0001) at 1 day after treatment, 1.3 ± 1.8 (P < 0.0001) at 1 month, 1.6 ± 1.7 (P < 0.0001) at 3 months, and 1.8 ± 1.3 (P < 0.0001) at 6 months. The response rates were 91.7%, 94.4%, 91.7%, and 94.4%, respectively, at 1 day, 1 month, 3 months, and 6 months after cryoablation; the complete response rates were 22.2%, 41.7%, 36.1%, and 22.2%, respectively. Adverse events (skin frostbite, nerve injury, pathologic fracture) occurred in 3 patients. CT-guided percutaneous cryoablation under local anesthesia appears to be a safe and effective treatment for painful osteolytic bone metastases. Prospective clinical trials on large samples needed to confirm this conclusion.

Protective Effects and Mechanisms of N-Phenethyl Caffeamide from UVA-Induced Skin Damage in Human Epidermal Keratinocytes through Nrf2/HO-1 Regulation.

The skin provides an effective barrier against physical, chemical, and microbial invasion; however, overexposure to ultraviolet (UV) radiation causes excessive cellular oxidative stress, which leads to skin damage, DNA damage, mutations, and skin cancer. This study investigated the protective effects of N-phenethyl caffeamide (K36) from UVA damage on human epidermal keratinocytes. We found that K36 reduced UVA-induced intracellular reactive oxygen species (ROS) production and induced the expression of the intrinsic antioxidant enzyme heme oxygenase-1 (HO-1) by increasing the translocation of nuclear factor erythroid 2⁻related factor 2 (Nrf2). K36 could inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) and reduce UVA-induced matrix metalloproteinase (MMP)-1 and MMP-2 overexpression; it could also elevate the expression of tissue inhibitors of metalloproteinases (TIMP). In addition, K36 ameliorated 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by UVA irradiation. Furthermore, K36 could downregulate the expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) and the subsequent production of nitric oxide (NO) and prostaglandin E2 (PGE2). Based on our findings, K36 possessed potent antioxidant, anti-inflammatory, antiphotodamage, and even antiphotocarcinogenesis activities. Thus, K36 has the potential to be used to multifunctional skin care products and drugs.

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin's antiphotodamage and antiphotoinflammation activities.