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Lower eyelid aging is a complicated process, and for that reason, a comprehensive assessment of the lower eyelid is important before treatment.This study was conducted to analyze and assess the lower eyelid aging process between different age groups of Asian women.The authors developed the comprehensive lower eyelid age rating scale (CLEARS). The rating scale contains 3 domains and each composed of 3 items. Individuals were evaluated by the age group starting with the third decade (20-29 years) through the seventh decade (60-69 years) by 2 dermatologists working independently.A total of 114 cases were evaluated. The total scores of CLEARS increased significantly between each adjacent age group. The scores of the snap test and the severity of fine lines, nasojugal groove, midcheek furrow, and eye bags increased significantly from the 3rd decade. The scores of the distraction test and the severity of palpebromalar groove and malar mound begin to increase with the 4th decade. Kappa coefficients of all items achieved moderate to substantial agreement.This study describes the lower eyelid aging process among Asian women by CLEARS assessment. Lower eyelid aging becomes progressively more notable beginning with the third decade.

Many Oriental eyes feature single eyelid fold and ptotic eyelid. Performing the double eyelid blepharoplasty (DEB) in a minimally invasive manner with simultaneous blepharoptosis correction (BPC) is important to achieve an aesthetic pleasing outcome.To demonstrate an effective mini-invasive transcutaneous and transconjunctival dual approach technique for simultaneous DEB and BPC. Furthermore, to compare the outcome of BPC in dual approach, transcutaneous procedure and transconjunctival procedure.This is a retrospective study reviewing 159 eyelids that underwent mini-invasive DEB with BPC from November 2018 to May 2019, including the technical description and the surgical outcomes. To investigate the efficacy, the pre- and postoperative margin reflex distance 1 (MRD1) and levator function (LF) corresponding to the different surgical procedures and preoperative severity was analyzed.Statistically, the dual approach group has significant improvement in MRD1 and LF (47 eyelids, p0.05) corresponding to patients with ptosis of any severity. Under the same tucking amount, dual approach can achieve 1.6±0.7 mm of MRD1 improvement, which is nearly twice the amount compare with transconjunctival approach alone. No revision nor complication noted in the dual approach group by 6-month follow-up.The dual approach technique is a method with a wide range of applications, effective, and low revision rate that simultaneously correct blepharoptosis and create a double eyelid.

Proinflammatory mediators such as interleukin (IL)-1β cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1β-induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1β induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.

Olive (Olea europaea Linn) leaves contain a phenolic compound oleuropein (Ole) has antioxidant, anti-inflammatory, and immunomodulatory activities. However, whether Ole might be an effective treatment for atopic dermatitis (AD) remains unknown.This study investigated the functional role of oleuropein in a 2,4-dinitrochlorobenzene-induced AD-like mouse model, with a focus on allergic inflammation.We evaluated cytokine gene expression, COX-2 inflammatory protein production, and Th2 related cytokine regulation of mast cells and eosinophils that infiltrated AD-like skin lesions.A topical application of Ole significantly reduced Th2-related cytokine gene expression (IL-4 and IL-5) and inflammatory COX-2 protein production in AD-like skin lesions. Additionally, Ole suppressed serum IgE levels. Furthermore, Ole effectively reduced ear swelling and epidermal and dermal thickening.These results suggested that, mechanistically, Ole treatment improved allergic inflammation by blocking the Th2-driven inflammatory axis. In conclusion, our findings indicated that Ole showed promise in treating AD by regulating serum IgE and Th2 cytokine levels. Although the effects of Ole on AD in humans require clinical trials, our results provided insights into how AD treatments might be improved.

Retinoic acid (RA) is an approved treatment for skin photoaging induced by ultraviolet (UVA). Topically applied RA is mainly located in the stratum corneum (SC) with limited diffusion into the deeper strata. A delivery system capable of facilitating dermal delivery and cellular internalization for RA is critical for a successful photoaging therapy. Two delivery approaches, namely nanoparticles and laser ablation, were combined to improve RA's absorption efficacy and safety. The nanoparticle absorption enhancement by the lasers was compared between full-ablative (Er:YAG) and fractional (CO

Background: Nonablative lasers are popular alternatives for atrophic acne scar treatment in Asia. Objectives: We aimed to compare the efficacy and safety between 1550-nm nonablative fractional laser (NAFL) and 755-nm picosecond laser with diffractive lens array (DLA) in Asian patients. Methods: Twenty-three patients with atrophic acne scars received three sessions of split-face treatment with 1550-nm NAFL on one side and 755-nm picosecond laser with DLA on the other side. Sessions were applied at 8-week interval. Blinded dermatologists assessed efficacy through baseline and follow-up photographs. Results: A greater improvement in atrophic facial acne scars was observed on the 1550-nm NAFL side than on the 755-nm picosecond laser side (P < 0.05). Pain was significantly more severe on the 1550-nm NAFL side than the 755-nm picosecond laser side (P < 0.05). Adverse effects on the 1550-nm NAFL side included prolonged erythema, acneiform eruptions, superficial crusting, and postinflammatory hyperpigmentation. Only transient erythema was observed on the 755-nm picosecond laser side. Conclusion: Although the 1550-nm NAFL showed superior efficacy to the 755-nm picosecond laser with DLA for the treatment of atrophic facial acne scars, the latter was associated with fewer adverse effects and may be the best choice for those who request “little-to-no down-time” treatments.

Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.

Vitiligo is a common, psychologically devastating pigmentary disorder. Surgical graftings are used to treat stable vitiligo when medical treatment fails. An automated epidermal micrograft harvesting (AEMH) system was first designated to treat wounds, and very few studies investigated the application of AEMH in vitiligo. In this study, we investigated the efficacy and safety of the AEMH system in patients with stable segmental and nonsegmental vitiligo. The rate of repigmentation and adverse events was recorded bimonthly for at least 12 months. We analyzed the efficacy based on patient characteristics, vitiligo subtypes, and different anatomical locations. A total of 56 depigmented lesions from 34 patients were included. 95.50% of the automated epidermal micrografts were successfully grafted at the recipient sites. There was a significant improvement in Vitiligo Area Scoring Index (VASI) and Dermatologic Life Quality Index (DLQI) in patients treated with AEMH (p < 0.001). The rate of repigmentation by VASI score improves from 96.25 ± 8.59 to 48.30 ± 28.16 after the treatment (p < 0.001). Treatment outcomes were comparable between the patients of segmental and stable nonsegmental vitiligo. The face and neck region achieved a better outcome, followed by the trunk (chest, abdomen, back, and axilla), limbs, and the worse outcome was found in the acral region (p < 0.014). Conclusively, AEMH is an effective treatment procedure with limited adverse events in patients with stable vitiligo. This harvesting method may be a feasible option for vitiligo surgical treatment.

BACKGROUND AND OBJECTIVES The picosecond (PICO) laser has been a new and promising device. But, so far, there have not been many prospective studies investigating the efficacy in acne scar treatment. This study evaluated the efficacy and safety of the dual-wavelength picosecond laser in the treatment of acne scar. STUDY DESIGN/MATERIALS AND METHODS A total of 20 patients with skin type III-IV were enrolled in this study. Eighteen patients completed the study. All patients completed six treatment sessions within a 1-month interval. All patients were treated using both 532 and 1,064 nm fractionated dual-wavelength picosecond handpieces. In evaluation, Goodman and Baron's quantitative global acne scarring grading system (GSS) was scored by two physicians. Patients also judged the results themselves by Visual Analog Scale (VAS) and pain score. RESULTS The average baseline score of GSS quantity and quality were 15.22 and 3.00, respectively. The final scores were 10.61 and 2.33. The average baseline of patient VAS score was 4.28. The final score was 2.00. All scores achieved statistical significance (P

Q-Switched laser devices have been a standard treatment modality for dermal pigmentary disorders since the 1990s. However, the adverse events are sometimes intolerable even if the efficacy has been well accepted. These adverse events stop the patient from continuing the treatment and cause other cosmetic issues. Since 2012, the first picosecond laser for cosmetic applications was approved; it seems promising for treating pigmentary disorders in a new way, but lack strong evidence. We evaluated the efficacy and safety of a 755-nm picosecond laser for treatment of dermal pigmentary disorders in Asians. This is a 2-year retrospective study. We reviewed 36 female cases, including 8 cases of nevus of Ota and 28 cases of acquired bilateral nevus of Ota-like macules. Institutional Review Board (IRB) approval was granted by the Chang Gung Memorial Hospital medical research ethics committee (IRB 201900833B0). The epidemiologic data was collected. These patients have been treated with the 755-nm picosecond laser for 1 to 4 sessions at variable treatment interval. Our parameter settings were fluence of 2.73–3.98 J/cm2, with a spot size of 2.9 to 2.4 mm under the 650-ps mode. The pulse duration is 650 ps and fluence range is from 2.73 to 3.98 J/cm. Photographs were taken prior to every treatment and 1 month following the treatment. Two dermatologists conducted the clinical evaluation independently. Clinical improvement was observed in all with a minimal side effect. A total of 88.89% of patients had moderate to marked improvement in following 1 to 4 sessions. Transient swelling and erythema were observed in all patients but resolved within 24 h. Only one patient (2.78%) developed hypopigmentation and two patients (5.56%) had hyperpigmentation temporarily. Faster clearance could be achieved by the picosecond 755-nm laser for treating dermal pigmentary disorders in Asians. The treatment course is well tolerable and has minimal side effects.

Background Lower blepharoplasty is a common cosmetic operation that relies on minimal postoperative scarring, but Asian patients are at higher risk than Caucasians for hypertrophic and/or widened scars. Botulinum toxin type A (BTX) injections are widely employed to alleviate dynamic facial rhytids and also can improve scar quality by reducing scar tension. The authors assessed whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. Objectives The objective of this study was to assess whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. Methods This is a prospective, randomized, vehicle-controlled, double-blinded clinical trial. Between May 2015 and May 2018, 40 adults who underwent bilateral transcutaneous lower blepharoplasties were randomized to receive BTX (n = 20) or vehicle (normal saline; n = 20) injections into the lateral orbicularis oculi muscle immediately after wound closure. Vancouver Scar Scale, Visual Analogue Scale, and photographic scar width measurements at 3 reference points were recorded at the final clinical follow-up. Results Thirty-seven patients completed the trial. Vancouver Scar Scale and Visual Analogue Scale scores in the experimental and vehicle control groups were similar, but scar widths in the experimental group at all measured points were significantly narrower than in the vehicle control group (P < 0.001, P = 0.027, and P < 0.001 at each measured point, respectively). Conclusions Transcutaneous lower blepharoplasty scars in Asians can be significantly narrowed by simultaneous BTX injections without additional complications. Level of Evidence 4

Objectives and designPro-inflammatory mediators such as interleukin (IL)-1b cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1b–induced inflammation have not been examined in the adult RPE cell line ARPE-19.Materials/methodsHere, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1β induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Result The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. ConclusionsThese results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.

BackgroundIsorhapontigenin, a resveratrol analogue, isolated from Iris domestica can induce apoptosis in tumor cells. Here, we designed to explore whether isorhapontigenin reduced inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.MethodsIsorhapontigenin treated with RAW 264.7 cells, and then with LPS to stimulate inflammatory response. Proinflammatory cytokine expressions were measured using ELISA, and protein expressions were detected using western blots. ResultsIsorhapontigenin significantly inhibited the proinflammatory cytokine expressions. Isorhapontigenin also decreased cyclooxygenase-2 and inducible nitric oxide synthase productions and promoted heme oxygenase-1 expression in LPS-stimulated RAW264.7 cells. Isorhapontigenin could significantly inhibit NF-κB subunit p65 protein localization to the nucleus and reduced MAPK signal pathway activation. Isorhapontigenin also decreased reactive oxygen species production. ConclusionThus, isorhapontigenin has potential anti-inflammation and anti-oxidative stress that inhibits inflammatory mediators and cytokines expressions through suppressing the MAPK and NF-κB pathways.

Background: Varicose veins are a common problem worldwide. Although it was reported that varicose veins have cosmetic and symptomatic effects and can also lead to an increased risk of incident deep venous thrombosis, pulmonary embolism, and peripheral artery disease, whether varicose vein treatment prevents those serious complications is unknown. Methods: This retrospective cohort study used claims data extracted from the Chang Gung Research Database and National Health Insurance Research Database in Taiwan. The study subjects were patients aged ≥20 years who underwent endovenous thermal ablation (ETA) from 2005 to 2016 and a group of untreated subjects who were matched by sex and year of birth. All patients were followed from the index date to the earliest occurrence of peripheral artery disease, deep venous thrombosis, or pulmonary embolism or death or the end of the study. To avoid possible selection bias, 1:4 propensity score matching was implemented and a Cox proportional-hazards model was applied while controlling for potential confounders. We also collected data on complications within 28 days of ETA. Results: In total, data on 1323 ETA-treated patients with varicose veins were extracted from the Chang Gung Research Database, while data on 149 586 untreated patients with varicose veins were extracted from the National Health Insurance Research Database. Compared with the untreated group, ETA-treated patients had decreased risks of deep venous thrombosis and peripheral artery disease (adjusted hazard ratio, 0.49 [95% CI, 0.32–0.75] and 0.64 [95% CI, 0.49–0.85]). The incidence rates of deep venous thrombosis and pulmonary embolism after ETA (≤28 days) were 0.296% and 0.074%, respectively. Conclusions: ETA treatment of varicose veins was associated with a substantial decrease in the subsequent incidence of thromboembolism and peripheral artery disease compared with that in the absence of treatment. In addition, the incidence rate of postprocedural thromboembolic complications after ETA was low in the Asian population. We suggest that improved disease awareness and appropriate early treatment may help reduce the risk of serious complications.

A pronounced epicanthal fold is a common feature that presents in 50-90% of the Asian population; it will not only cause the eyes to look small but will also cause a deformity when a double eyelid blepharoplasty is performed, restricting the formation of a preferable outer-type double eyelid. Moreover, the wide intercanthal distance (ICD) arising from the epicanthal fold would diminish the aesthetic appearance, giving the impression of a collapsed nasal bridge.

Ludwigia octovalvis extract (LOE) is a widely used traditional Chinese herbal medicine. To date, few studies have demonstrated the effect of LOE supplementation on exercise performance, physical fatigue and biochemical profile. The purpose of this study is to evaluate the potential beneficial effects of LOE extract on fatigue and ergogenic functions following physiological challenge. Male ICR mice from 3 groups (n=8 per group) were orally administered LOE for 4 weeks at 0 (vehicle), 61.5 (LOE-1X) or 307.5 (LOE-5X) mg/kg/day. LOE supplementation was able to dose-dependently increase endurance swimming time (P

Background The follicular unit transplantation strip harvesting surgery is one of the gold standard methods of hair transplantation; the counting follicular unit ratio and hair density is a major step in donor site evaluation. Aims We conducted the study for analyzing the preoperative donor site evaluation and comparison of the actual harvested and estimated follicular units in hair transplantation. Patients/methods In this retrospective study, we enrolled 65 male patients with androgenetic alopecia who underwent follicular unit transplantation. Before the donor strip harvesting procedure, we counted the follicular unit density and calculated the percentage of each follicular unit. And then, we compared them to actual harvesting grafts. Result The number of actual harvested transplanted hairs (3162.22 ± 958.30) were less than estimated transplanted hairs (3319.25 ± 1007.86). Both the number and percentage of actual harvested 1-hair follicular unit were more than estimated 1-hair follicular unit. In contrast, the number and percentage of actual harvested 3-hair follicular unit was less than estimated 3-hair follicular unit. The follicular unit density was lower in older patients. Those received more than one session of hair transplantation tended to have lower follicular and hair density (P = 0.007 and 0.01, respectively). The scalp laxity was lower in older patients and those received multiple sessions of hair transplantation. Conclusion The actual harvested grafts yield more 1-hair follicular units and less 3-hair follicular units than estimation. Old age and multiple sessions of hair transplantation caused more limitation of harvesting donor scalp.

The 595-nm pulsed dye laser (PDL) has been used to treat vascular anomalies for about 30 years; however, there are insufficient data in Chinese patients concerning therapeutic efficacy, optimized parameters, and procedure techniques.To study the efficacy and relevant factors in PDL therapy for vascular anomalies in Chinese patients.We enrolled 431 patients with 8 different vascular anomalies and no previous treatment in this retrospective study. A detailed classification of vascular anomalies and various parameters and techniques of PDL were studied. The clinical outcomes were analysed using the Investigator Global Assessment.Improvements were significantly correlated with infantile haemangioma (IH) subtypes (p 0.05). A significant correlation between efficacy and lesion colour, anatomical sites, and hypertrophic-type port-wine stain (PWS) was found (p 0.05). There was no significant correlation between efficacy and age or sex (p 0.05).PDL is an effective and safe therapeutic modality for managing vascular anomalies in Chinese patients. We determined that differentiating and identifying IH subtypes prior to treatment could be a useful parameter for predicting therapeutic results. Lesion colour, sites, and hypertrophic changes in PWS are relevant therapeutic factors. PDL parameters and techniques differ according to the various vascular anomalies to achieve optimal results.

Melasma is a common acquired facial hypermelanosis with irregular brownish macules and patches. The clinical course is often fluctuated and refractory to treatment. The present study was conducted to evaluate the efficacy and safety of pulsed alexandrite laser for the treatment of melasma.In the present study, we enrolled Asian patients with melasma. All the patients received four monthly treatments with a pulsed alexandrite laser. The severity of melasma was evaluated by a blinded dermatologist, using the Modified Melasma Area and Severity Index (MMASI), and by patient assessment, using a visual analogue scale, at baseline, before each treatment, and at the 1-month and 3-month follow-up visits after the last treatment.Twenty-three patients completed all treatments and follow-up visits. The MMASI scores decreased significantly from 8.71 ± 5.83 at baseline to 6.07 ± 4.65 after four sessions of treatment (P0.05) and 6.91 ± 4.97 at 3 months after the last laser treatment (P0.05). After 4 sessions of treatment, 10 patients (43.5%) described their improvement as marked and excellent (60% improvement). The treatments were well tolerated with only mild skin reaction.In the present study, we demonstrated that the pulsed alexandrite laser is safe and effective to treat melasma in Asian skin.

Aims The hypoxia-stimulated response of the endocrine system depends on the kind and duration of hypoxia. Hypoxia has been reported to stimulate testosterone (T) production in rats, but the mechanisms remain to be investigated. Materials and methods Male rats were divided into two groups. The rats exposed to chronic intermittent hypoxia (CIH) at 8 h/day were housed in a hypoxic chamber (12% O2) for 14 days. Normoxic rats were used as control animals. T was measured after challenging the rat Leydig cells (LCs) with different stimulators, including hCG (0.01 IU/ml), forskolin (10−5 M), 8-bromo-cAMP (10−4 M), A23187 (10−5 M), cyclopiazonic acid (10−4 M), and androstenedione (10−8 M). Meanwhile, the LCs were incubated with trilostane (10−5 M) and/or 25-OH-hydroxycholesterol (10−5 M); thereafter the media were collected for pregnenolone assay. Key findings In the CIH group, plasma T levels were increased, but the serum luteinizing hormone (LH) was decreased. Furthermore, at several time intervals after hCG injection, plasma T levels were higher in the CIH group. The evoked-release of T and pregnenolone were significantly increased in the CIH group. Compared with the normoxic group, the CIH group had higher mRNA and protein expression levels of the LH receptor and CYP11A1 but not StAR. The plasma and testicular microvasculature VEGF levels were increased in the CIH group. The testicular vessel distribution was more obvious in CIH rats. Significance CIH-induced T secretion might be partially mediated by mechanisms involving the induction of LH receptor expression, testicular angiogenesis, CYP11A1 activity, 17β-HSD activity, and calcium-related pathway.

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

Spilanthol (SP) is a bioactive compound found in Spilanthes acmella, giving the flowers and leaves a spicy taste. Studies found that phyto-ingredients stored in spice plants act against obesity-related diseases. SP has antimicrobial, anti-inflammatory, and analgesic properties, but the effects on obesity are not yet known. We investigated the effects of SP in differentiated adipocytes (3T3-L1 cells) and mice fed a high-fat diet (HFD). SP significantly inhibited intracellular lipid accumulation and significantly reduced the expression of lipogenesis-related proteins, including acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FAS). In contrast, SP increased the expression of carnitine palmitoyltransferase (CPT)1 and AMP-activated protein kinase (AMPK) in adipocytes. However, SP suppressed the levels of cyclooxygenase-2 (COX-2), phospho-p38 (pp38), and phospho-JNK (c‑Jun N-terminal kinase) (pJNK) in LPS (lipopolysaccharide)-stimulated murine pre-adipocytes. SP administered to HFD-induced obese mice via intraperitoneal injections twice a week for 10 weeks decreased body weight gain, visceral adipose tissue weight, and adipocyte size. SP inhibited lipogenic proteins FAS and ACC, and suppressed adipogenic transcription factors, enhancing lipolysis and AMPK protein expression in the liver. SP has anti-obesity effects, upregulating AMPK to attenuate lipogenic and adipogenic transcription factors.

Moderate exercise diminishes proinflammation cytokine production in various types of immune cells, but the intracellular signaling pathways involved are not completely understood. Phosphoinositide 3-kinase (PI3K)/Akt, a crucial downstream protein of toll-like receptor 4 (TLR4), may modulate inflammation. The present study aimed to investigate the effects of exercises on lipopolysaccharide (LPS)-stimulated inflammatory response in splenocytes and to explore potential mechanisms of the PI3K/Akt pathway. Male rats were divided into sedentary and exercise groups. Animals in the exercise group underwent endurance training 30 min/day, 7 days/wk, at the speed of 20 m/min on a treadmill for 1 wk. Here, we showed that exercise 1) attenuated TLR4, 2) increased PI3K/phospho-Akt (p-Akt), and 3) diminished phospho-nuclear factor-κB (p-NF-κB) expression. In addition, administration of splenocytes isolated from trained rats with LPS in vitro showed 1) reduced tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and nitric oxide secretion and 2) decreased splenocyte proliferation. The plasma corticosterone (CCS) level in the exercise group was higher than that in the sedentary group. We confirmed that CCS down-regulated TNF-α and IL-6 secretion in response to LPS in rat splenocytes. Dexamethasone also significantly attenuated LPS-evoked release of TNF-α and IL-6 in a dose-dependent manner. These findings suggested that exercise dampened the secretion of inflammation mediators probably through partial inhibition of TLR4 and p-NF-κB and activation of PI3K/p-Akt expression in the spleen.

Acrolein, an α, β-unsaturated aldehyde, exists in a wide range of sources. Acrolein can be not only generated from all types of smoke but also produced endogenously from the metabolism by lipid peroxidation. The cellular influence of acrolein is due to its electrophilic character via binding to and depleting cellular nucleophiles. Although the toxicity of acrolein has been extensively studied, there is relatively little information about its impact on hormone release. This study aimed at the effect of acrolein on hypothalamic-pituitary-adrenal (H-P-A) axis. In an in vivo study, male rats were administrated with acrolein for 1 or 3days. The plasma corticosterone in response to a single injection of adrenocorticotropic hormone (ACTH) increased slowly in acrolein-pretreated rats than in control rats. Further investigating the steroidogenic pathway, the protein expressions of steroidogenic acute regulatory protein (StAR) and the upper receptor-melanocortin 2 receptor (MC2R) were attenuated in acrolein-treated groups. Another experiment using trilostane showed less activity of P450scc in zona fasciculata-reticularis (ZFR) cells in acrolein-treated groups. In addition to the suppressed ability of corticosterone production in ZFR cells, acrolein even had extended influence at higher concentrations. The lower ACTH was observed in the plasma from acrolein-pretreated rats. In an in vitro study, ZFR cells were incubated with acrolein and the results showed that corticosterone concentrations in media were decreased in a dose-dependent manner. Acrolein also desensitized the response of the ZFR cells to ACTH. These results suggested that acrolein decreased the releasing ability of corticosterone via an inhibition on the response of ZFR cells to ACTH and the reduction of protein expressions of StAR and MC2R as well as the activity of P450scc in rat ZFR cells. The present evidences showed that the H-P-A axis was affected by the administration of acrolein.

Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young+mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14pg/ml, 3.14pg/ml, and 6.85pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64pg/ml, 5.86pg/ml, and 5.38pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30-50) were 7.00pg/ml, 10.64pg/ml, and 31.73pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48pg/ml, 33.36pg/ml, and 97.77pg/ml in young males (aged 20-22), respectively. Also, significantly elevated plasma cortisol concentration was noted in betel nut-chewing (median 727.2ng/ml) and oral cancer patients (561.9ng/ml) compared to the mid-aged (176.8ng/ml) and young males (173.4ng/ml), respectively. In addition, lower plasma testosterone concentrations were found in betel nut-chewing subjects compared with young males (2.6±3.3ng/ml vs 6.2±2.9ng/ml). To summarize, the inflammatory cytokines and steroid hormones may reflect the degree of inflammation in betel nut-chewing males and the oral cancer subjects. The above findings suggest that betel nut-chewing or oral cancer inhibits plasma cytokines and regulates steroid hormones concentrations compared to mid-aged or young normal subjects. It is also indicated that betel nut-chewing causes decreased inflammatory cytokines as the same levels as in oral cancer subjects.

Berberine is an isoquinoline alkaloid isolated from herb plants, such as Cortex phellodendri (Huangbai) and Rhizoma coptidis (Huanglian). Huanglian and Huangbai have been used as “heat-removing” agents. In addition, berberine has been reported to exert anti-inflammatory effect both in vivo and in vitro, where mitogen-activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) expressions are critically implicated. We herein tested the hypothesis that berberine exerts an anti-inflammatory effect through MAPK and COX-2 signaling pathway in T-cell acute lymphoblastic leukemia (T-ALL). In Jurkat cells, we found that PHA exposure caused elevation on interleukin-2 (IL-2) production in a time-dependent manner. PHA-stimulated reactions were steeply suppressed by berberine, such as IL-2 mRNA expression and protein secretion. However, berberine did not exert any cytotoxic effect at doses of 40 μg/ml. In addition, the possible molecular mechanism of anti-inflammation effect of berberine could be the inhibition of PHA-evoked phosphorylation of p38, since c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinase (ERK) expressions did not alter. Consistent with above results, berberine inhibition on PHA-induced IL-2 secretion could be reversed by treatment of SB203580, a specific inhibitor of p38-MAPK. Interestingly, upregulation of PHA-induced COX-2 expression was also observed following berberine treatment of Jurkat cells. Furthermore, flow cytometry analysis showed berberine-induced cell cycle arrest at G1 phase after PHA stimulation and decreased percentage of G2/M phase. In conclusion, our study demonstrated that the anti-inflammatory effect of berberine largely potentially results from its ability to attenuate p38 MAPK expression, and does not exclude a positive action of berberine on cell cycle arrest. These results provide an innovative medicine strategy to against or treat T-ALL patients.

Gossypol, a natural polyphenolic compound extracted from cottonseed oil, has been reported to possess pharmacological properties via modulation cell cycle and immune signaling pathway. However, whether gossypol has anti-inflammatory effects against phytohemagglutinin (PHA)-induced cytokine secretion in T lymphocytes through similar mechanism remains unclear. Using the T lymphocytes Jurkat cell line, we found that PHA exposure caused dramatic increase in interleukin-2 (IL-2) mRNA expression as well as IL-2 secretion. All of these PHA-stimulated reactions were attenuated in a dose-dependent manner by being pretreated with gossypol. However, gossypol did not show any in vitro cytotoxic effect at doses of 5–20 μM. As a possible mechanism underlying gossypol action, such as pronounced suppression IL-2 release, robust decreased PHA-induced phosphorylation of p38 and c-Jun N-terminal kinase expressions was found with gossypol pretreatment, but not significant phosphorylation of extracellular signal-regulated kinase expression. Furthermore, gossypol could suppress the Jurkat cells’ growth, which was associated with increased percentage of G1/S phase and decreased fraction of G2 phase in flow cytometry test. We conclude that gossypol exerts anti-inflammatory effects probably through partial attenuation of mitogen-activated protein kinase (phosphorylated JNK and p38) signaling and cell cycle arrest in Jurkat cells.

Spilanthol a phytochemical derived from the Spilanthes acmella plant has antimicrobial, antioxidant, and anti-inflammatory properties. This study evaluated its effects on the expression of intercellular adhesion molecule 1 (ICAM-1) and inflammation-related mediators in IL-1β-stimulated human lung epithelial A549 cells. Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3–100 μM) followed by treatment with IL-1β to induce inflammation. The protein levels of pro-inflammatory cytokines, chemokines, and prostaglandin E2 (PGE2) were measured using ELISA. Cyclooxygenase-2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) were measured by immunoblotting. The mRNA expression levels of ICAM-1 and MUC5AC were determined by real-time polymerase chain reaction. Spilanthol decreased the expression of PGE2, COX-2, TNF-α, and MCP-1. It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1β-stimulated A549 cells. Spilanthol also significantly inhibited the phosphorylation of MAPK and I-κB. These results suggest that spilanthol exerts anti-inflammatory effects by inhibiting the expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the NF-κB and MAPK signaling pathways.

To evaluate efficacy and safety of picosecond 755 nm alexandrite laser as compared to 1064 nm QS-Nd:YAG laser for melasma treatment in Asians. Twelve patients received 4 sessions of treatments at 1-month interval in a split-face manner. The right side of each patient’s face received 755 nm picosecond laser, and the other side received 1064 nm QS-Nd:YAG laser. Zoom handpiece of 755 nm picosecond laser at fluence of 0.88–1.18 J/cm2 was applied. The treatment protocol used for 1064 nm QS-Nd:YAG laser was 8 mm spot size at fluence of 2.0 J/cm2 initially followed by 6 mm spot size at fluence of 3.5 J/cm2, and finishing with 4 mm spot size at 3.2 J/cm2. For both 755 nm picosecond laser and 1064 nm QS-Nd:YAG laser, the endpoint was mild erythema and swelling without petechiae. Objective evaluation with visual analogue score was conducted by two independent physicians. Subject self-assessment for each patient was conducted as well. Statistical results showed that higher pigmentation clearance rate was achieved at the 755 nm picosecond laser side after the second treatment. At the 3 months follow-up, greater clearance was observed at the 755 nm picosecond laser side compared to the 1064 nm QS-Nd:YAG side. 755 nm alexandrite picosecond laser has been observed to achieve a faster and better clearance rate for melasma compared to 1064 nm QS-Nd:YAG laser. We conclude that the 755 nm picosecond laser could be a safe and effective modality for melasma treatment in Asians.

There are versatile modalities to achieve noninvasive fat reduction, and most of them have proven to be effective for circumferential reduction of local fat tissue, without any serious or permanent adverse effects. However, the follow-up time is short, ranging from 1 to 24 weeks. Most of the patients would like to know how long will its effect last and whether there is long-term side effect or not. The aim of this study was to assess the long-term efficacy and safety of combination therapy of focused ultrasound and radio frequency for noninvasive body contouring. Thirty-two Asian subjects received three sequential combination therapies of focused ultrasound and radio-frequency treatments every 2 weeks in the abdominal region and were followed up 1 month and 1 year after the last treatment. After a year, 5 patients were loss follow-up and 2 were pregnant. Finally, 25 healthy Asian subjects (18 females and 7 males) were enrolled in this study. Safety parameters and adverse events were recorded. The mean body weight change remained constant without a significant change 1 year after treatment and was 0.1 ± 1.2 kg (p = 0.513). The mean abdominal circumference change between 1 month and 1 year after the last treatment was 0.4 ± 1.2 cm and was not significant (p = 0.169). The relationships between weight change and circumference change of the 23 patients were tested using Spearman's rho correlation coefficient. There was a correlation between weight change and circumference change (0.73; p = 0.000). The procedure was safe without a recordable long-term adverse event. The combination therapies of nonthermally focused ultrasound and radio-frequency treatments for body contouring in the abdominal region are effective and may show positive results for at least a year if patients can maintain their body weight. The procedure is safe without recordable long-term adverse events in this study.

Background/Objective Tumor necrosis factor-α (TNF-α) antagonists have become increasingly popular in the treatment of psoriasis. However, the increased risk of latent tuberculosis infection (LTBI) reactivation has also become an important issue in clinical practice. The aim of this study was to evaluate serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing for detecting LTBI among a cohort of psoriatic patients vaccinated with bacille Calmette-Guerin in a country with an intermediate burden of TB during long-term treatment with TNF-α antagonists. Methods We enrolled psoriatic patients treated with TNF-α antagonists who also accepted yearly serial QFT-GIT testing and regular chest X-ray examinations before and during the anti-TNF-α treatment from January 2010 to August 2014. Patients diagnosed with LTBI received chemoprophylaxis, and QFT-GIT testing was performed in these patients after completion of chemoprophylaxis. Results In this retrospective study, 101 patients had completed baseline and at least 1 year of follow-up. Among these patients, 60 had continued TNF-α antagonists therapy and received examinations in the 2 nd year, whereas 18 had continued the therapy until the 3 rd year. The conversion rate among these patients was 14.29% (13/91). In this study, 23 patients were diagnosed with LTBI according to the positive results obtained in the QFT-GIT test, with 19 of them having completed chemoprophylactic therapy. Follow-up QFT-GIT testing revealed reversion in 11 patients (57.89%) and decreased interferon-γ (IFN-γ) levels (68.42%) in 13 patients. Patients over 45 years of age tended to have a persistent positive result. Conclusion This study demonstrated that 14.29% of psoriatic patients undergoing long-term TNF-α antagonist therapy had a QFT-GIT conversion. Although a decreased IFN-γ level and QFT-GIT reversion were observed in most cases following prophylactic therapy, the value of QFT-GIT for evaluating the effect of LTBI prophylaxis remains controversial.