Surface-Phosphided Metal Oxide Microspheres as Catalytic Host of Sulfur to Enhance the Performance of Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are one of the most promising high-energy density secondary batteries due to their high theoretical energy density of 2600 Wh kg-1. However, the sluggish kinetics and severe "shuttle effect" of polysulfides are the well-known barriers that hinder their practical applications. A carefully designed catalytic host of sulfur may be an effective strategy that not only accelerates the conversion of polysulfides but also limit their dissolution to mitigate the "shuttle effect." Herein, in situ surface-phosphided Ni0.96Co0.03Mn0.01O (p-NCMO) oxide microspheres are prepared via gas-phase phosphidation as a catalytic host of sulfur. The as-prepared unique heterostructured microspheres, with enriched surface-coated metal phosphide, exhibit superior synergistic effect of catalytic conversion and absorption of the otherwise soluble intermediate polysulfides. Correspondingly, the sulfur cathode exhibits excellent electrochemical performance, including a high initial discharge capacity (1162 mAh gs-1 at 0.1C), long cycling stability (491 mAh gs-1 after 1000 cycles at 1C), and excellent rate performance (565 mAh gs-1 at 5C). Importantly, the newly prepared sulfur cathode shows a high areal capacity of 4.0 mAh cm-2 and long cycle stability under harsh conditions (high sulfur loading of 5.3 mg cm-2 and lean electrolyte/sulfur ratio of 5.8 µL mg-1). This work proposes an effective strategy to develop the catalytic hosts of sulfur for achieving high-performance Li-S batteries via surface phosphidation.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS: TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Lc-pPG-612-OmpU-CTB: A promising oral vaccine for protecting Carassius auratus against Vibrio mimicus infection.

Vibrio mimicus (V. mimicus) is known to cause severe bacterial diseases with high mortality rates in fish, resulting in significant economic losses in the global aquaculture industry. Therefore, the objective of this study was to develop a safe and effective vaccine for protecting Carassius auratus (C. auratus) against V. mimicus infection. Recombinant Lactobacillus casei (L. casei) strains, Lc-pPG-612-OmpU and Lc-pPG-612-OmpU-CTB (surface-displayed), were constructed using a L. casei strain (ATCC 393) as an antigen delivery carrier and the cholera toxin B subunit (CTB) as an adjuvant. The two recombinant strains of L. casei were administered to C. auratus via oral immunization, and the protective efficacy of the oral vaccines was assessed. The results demonstrated that oral immunization with the two strains significantly increased the levels of nonspecific immune indicators in C. auratus, including alkaline phosphatase (AKP), lysozyme (LYS), acid phosphatase (ACP), complement 3 (C3), complement 4 (C4), lectin, and superoxide dismutase (SOD). Moreover, the experiment groups exhibited significant increases in specific immunoglobulin M (IgM) antibodies against OmpU, as well as the transcription of immune-related genes (ie., IL-1ß, TNF-α, IL-10, and TGF-ß), when compared to the control groups. Following infection of C. auratus with V. mimicus, the mortality rate of the recombinant L. casei-treated fish was observed to be lower compared to the control group. This finding suggests that recombinant L. casei demonstrates effective protection against V. mimicus infection in C. auratus. Furthermore, the addition of the immune adjuvant CTB was found to induce a more robust adaptive and innate immune response in C. auratus, resulting in reduced mortality after infection with V. mimicus.

Oral vaccination with recombinant Lactobacillus casei with surface displayed OmpK fused to CTB as an adjuvant against Vibrio mimicus infection in Carassius auratus.

Vibrio mimicus (V. mimicus) is a pathogenic bacterium that causes diseases in humans and various aquatic animals. A particularly efficient way to provide protection against V. mimicus is through vaccination. However, there are few commercial vaccines against V. mimics, especially oral vaccines. In our study, two surface-display recombinant Lactobacillus casei (L. casei) Lc-pPG-OmpK and Lc-pPG-OmpK-CTB were constructed using L. casei ATCC393 as an antigen delivery vector, outer membrane protein K (OmpK) of V. mimicus as an antigen, and cholera toxin B subunit (CTB) as a molecular adjuvant; furthermore, the immunological effects of recombinant L.casei in Carassius auratus (C. auratus) were assessed. The results indicated that oral recombinant L.casei Lc-pPG-OmpK and Lc-pPG-OmpK-CTB stimulated higher levels of serum-specific immunoglobulin M (IgM) and increased the activity of acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), lysozyme (LYS), lectin, C3, and C4 in C. auratus, compared with control groups (Lc-pPG group and PBS group). Furthermore, the expression of interleukin-1ß (IL-1ß), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-ß (TGF-ß) in the liver, spleen, head kidney, hind intestine and gills of C. auratus was significantly increased, compared with that in the controls. These results demonstrated that the two recombinant L. casei strains could effectively trigger humoral and cellular immunity in C. auratus. In addition, two recombinant L.casei strains were able to survive and colonize the intestine of C. auratus. Importantly, after being challenged with V. mimicus, C. auratus fed Lc-pPG-OmpK and Lc-pPG-OmpK-CTB exhibited greater survival rates than the controls (52.08% and 58.33%, respectively). The data showed that recombinant L. casei could elicit a protective immunological response in C. auratus. The effect of the Lc-pPG-OmpK-CTB group was better than that of the Lc-pPG-OmpK group, and Lc-pPG-OmpK-CTB was found to be an effective candidate for oral vaccination.

Celastrol gel ameliorates imiquimod-induced psoriasis-like dermatitis in mice by targeting Langerhans cells.

BACKGROUND: Psoriasis is an autoimmune disease mediated by T cells. However, treatment remains a clinical challenge because of its frequent recurrence. Celastrol (Cel), the main active ingredient in Tripterygium wilfordii Hook F, is efficacious in treating autoimmune diseases such as psoriasis. OBJECTIVE: To investigate the effect and mechanism of topical Cel in imiquimod (IMQ)-induced psoriasis-like inflammation in mice. METHODS: Female C57BL/6 and Langerin-diphtheria toxin receptor (DTR) mice were divided into Vehicle group and Cel gel groups. IMQ was used induce psoriasis-like inflammation to establish the mouse model of psoriasis. Hematoxylin and eosin staining was used to observe changes in local inflammatory cells in the skin lesions. Enzyme-linked immunosorbent assay was used to detect protein expression levels. Flow cytometry was used to detect the cell number and cytokine expression. Polymerase chain reaction was used to detect cytokine gene expression. RESULTS: Cel gel targeted the Langerhans cells. In IMQ-induced psoriatic dermatitis, Cel gel reduced the secretion of interleukin (IL)- 23 by Langerhans cells, suppressed the interaction between Langerhans cells and γδT cells, and decreased the number of activated γδT cells and related IL-17 secretion, alleviating psoriasis-like inflammation. Furthermore, Cel gel demonstrated a glucocorticoid-like effect that could impede the recurrence of psoriasis. CONCLUSION: Cel gel reduces the secretion of IL-23 from LCs and inhibits the interaction between LCs and γδT cells to alleviate psoriasis. It also shows an effect similar to that of glucocorticoids, which can prevent psoriasis recurrence. These findings provide a new direction for the clinical treatment of psoriasis and contribute to the development of novel drugs.

Sustained Surface ICAM-1 Expression and Transient PDGF-B Production by Phorbol Myristate Acetate-Activated THP-1 Cells Harboring Blau Syndrome-Associated NOD2 Mutations.

OBJECTIVES: Blau syndrome is a distinct class of autoinflammatory syndrome presenting with early-onset systemic granulomatosis. Blau syndrome-causing NOD2 mutations located in the central nucleotide-oligomerization domain induce ligand-independent basal NF-κB activation in an in vitro reporter assay. However, the precise role of this signaling on granuloma formation has not yet been clarified. METHODS: Blau syndrome-causing NOD2 mutations were introduced into human monocytic THP-1 cells, and their morphological and molecular changes from parental cells were analyzed. Identified molecules with altered expression were examined in the patient's lesional skin by immunostaining. RESULTS: Although the production of proinflammatory cytokines was not altered without stimulation, mutant NOD2-expressing THP-1 cells attached persistently to the culture plate after stimulation with phorbol myristate acetate. Sustained surface ICAM-1 expression was observed in association with this phenomenon, but neither persistent ICAM-1 mRNA expression nor impaired ADAM17 mRNA expression was revealed. However, the transient induction of PDGF-B mRNA expression was specifically observed in stimulated THP-1 derivatives. In the granulomatous skin lesion of a Blau syndrome patient, ICAM-1 and PDGF-B were positively immunostained in NOD2-expressing giant cells. CONCLUSIONS: Sustained surface ICAM-1 expression and transient PDGF-B production by newly differentiating macrophages harboring mutant NOD2 might play a role in granuloma formation in Blau syndrome.

Antidepressant-like effects of helicid on a chronic unpredictable mild stress-induced depression rat model: Inhibiting the IKK/IκBα/NF-κB pathway through NCALD to reduce inflammation.

We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms.

Background: Psoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis. Objective: To assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis. Methods: Six databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE's risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism. Results: One randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): -6.80; 95% confidence interval (CI): -8.23 to -5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: -0.95; 95% CI: -1.26 to -0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3+ T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05). Conclusions: S1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.

Fire Needle Therapy for the Treatment of Psoriasis: A Quantitative Evidence Synthesis.

Background: Fire needle therapy is a method of quickly piercing into acupoints with red-hot needles to treat diseases. Recently, multiple studies have reported that fire needle therapy is effective in the treatment of psoriasis; however, there are few articles systematically evaluating the effect of this therapy. Therefore, this systematic and meta-analysis study is conducted to estimate the efficacy and safety of fire needle therapy for psoriasis. Methods: PubMed, Embase, CNKI, VIP, CBM, CENTRAL, and Wan Fang databases were systematically searched from the dates of construction of these databases to August 24, 2019, and randomized controlled trials assessing patients with psoriasis who were treated with fire needle therapy alone or in combination with other drugs were also evaluated. Results: Fire needle therapy was effective in treating psoriasis (p = 0.0002; risk ratio [RR], 1.20; 95% confidence interval [CI], 1.09-1.33) with a lower recurrence rate (p = 0.005; RR, 0.48; 95% CI, 0.29-0.80). Adverse events after fire needle treatment were similar to those without fire needle treatment (p = 0.38; RR, 0.67; 95% CI, 0.28-1.63). After fire needle treatment, the number of cluster of differentiation (CD)8+T cells, type 1 helper cells, interleukin (IL)-2, and interferon (IFN)-γ decreased, whereas the number of CD4+T cells, type 2 helper cells, IL-4, IL-10, and the proportion of CD4+T cells and CD8+T cells increased. Conclusions: Fire needle therapy, specifically in combination with oral medicines, is effective in treating patients with psoriasis with low recurrence rates.

Association Between Psoriasis and Dementia: Current Evidence.

Background: Psoriasis and dementia are both inflammatory diseases. The association between psoriasis and dementia has rarely been investigated, and the existing results are conflicting. Thus, we conducted this study to evaluate whether an association exists between psoriasis and dementia. Methods: We searched for studies from six databases from inception to July 30, 2020, using subject and free words. RevMan 5.4 was used to calculate the risk ratio (RR) of dementia in the subjects with psoriasis. When heterogeneity was present, a random-effects model was used. Subgroup, sensitivity, and meta-regression analyses were performed using Stata 15.1. Results: Nine studies were identified and included in the study, of which seven that involved a total of 3,638,487 participants were included in the meta-analysis. We found that among the patients with psoriasis (RR: 1.14, 95% confidence interval [CI]: 1.06-1.24, p = 0.0009) and psoriatic arthritis (RR: 2.20, 95% CI: 1.29-3.78, p = 0.004), the proportions of those with non-vascular dementia (RR: 1.13, 95% CI: 1.11-1.15, p < 0.00001) and vascular dementia (RR: 1.41, 95% CI: 1.09-1.82, p = 0.009) were higher than that among the patients without psoriasis. Those with dementia were also more likely to develop psoriasis, and those with severe psoriasis were less likely to die from dementia (RR: 1.88, 95% CI: 0.72-4.90, p = 0.020). The meta-regression analysis did not show any significant sources of heterogeneity. Conclusions: The patients with psoriasis and psoriatic arthritis show high prevalence of different types of dementia. Based on the findings of this study, dementia may not be considered a high-risk factor of death from severe psoriasis. However, identification of this potential risk allows for early intervention, thereby reducing comorbidities and deaths.

Effects of Glycosylation and d-Amino Acid Substitution on the Antitumor and Antibacterial Activities of Bee Venom Peptide HYL.

Glycosylation is a promising strategy for modulating the physicochemical properties of peptides. However, the influence of glycosylation on the biological activities of peptides remains unknown. Here, we chose the bee venom peptide HYL as a model peptide and 12 different monosaccharides as model sugars to study the effects of glycosylation site, number, and monosaccharide structure on the biochemical properties, activities, and cellular selectivities of HYL derivatives. Some analogues of HYL showed improvement not only in cell selectivity and proteolytic stability but also in antitumor and antimicrobial activity. Moreover, we found that the helicity of glycopeptides can affect its antitumor activity and proteolytic stability, and the α-linked d-monosaccharides can effectively improve the antitumor activity of HYL. Therefore, it is possible to design peptides with improved properties by varying the number, structure, and position of monosaccharides. What's more, the glycopeptides HYL-31 and HYL-33 show a promising prospect for antitumor and antimicrobial drugs development, respectively. In addition, we found that the d-lysine substitution strategy can significantly improve the proteolytic stability of HYL. Our new approach provides a reference or guidance for the research of novel antitumor and antimicrobial peptide drugs.

Bioflocs protects copper-induced inflammatory response and oxidative stress in Rhynchocypris lagowski Dybowski through inhibiting NF-κB and Nrf2 signaling pathways.

Copper (Cu) is an essential element in the metabolic process of humans and animals, but it can cause toxicity at high concentrations of exposure. Bioflocs has been proved to have antioxidant, immune-enhancing and anti-inflammatory properties. Here, the purpose of this study was to evaluate potential mechanisms and protective effects of bioflocs and Cu exposure on inflammatory response, oxidative stress and immune-related genes and protein expression in Rhynchocypris lagowski Dybowski. 360 healthy R. lagowski were irregularly distributed among 12 tanks (3 tanks per group, 30 fish per tank). The experiment was divided into two parts: the feeding experiment was carried out in the first eight weeks, followed by acute copper exposure for 96 h. Then we selected the stressed fish for experimental analysis. The results provided evidences that bioflocs protected the R. lagowski by inhibiting the accumulation of copper, the activity of immune enzymes and the expression of NF-κB signaling pathway related genes and proteins, and the activity of antioxidant enzymes and the expression of Nrf2 signaling pathway related genes. Overall, these findings suggest that bioflocs could regulate the activation of Nrf2 and protect acute copper exposure induced inflammatory response by inhibiting the NF-κB signaling pathway in R. lagowski.

Association between physical activity and risk of prevalent psoriasis: A MOOSE-compliant meta-analysis.

Psoriasis is a common chronic relapsing immune-mediated inflammatory disease, whose prevalence has increased in recent years. Some physicians believe that physical activity is associated with numerous health-related benefits in adults with dermatoses. While numerous studies have suggested an association between psoriasis and physical activity, others have yielded contradictory results. The aim of our study was to evaluate the association between the level of physical activity and prevalence of psoriasis.A comprehensive search of the literature was performed from January 1970 to February 2017 using EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials electronic databases. Studies published in English were reviewed to identify the contribution of intensity of physical activity on the prevalence of psoriasis.The search strategy yielded 1100 relevant studies, among which 13 observational studies were included. We found that patients with psoriasis exercise significantly less vigorously than controls (relative risk [RR]: 0.76; 95% confidence interval [CI]: 0.67-0.85; P < .00001). Predominantly, these patients exercised at moderate intensity (RR: 0.40; 95% CI: 0.18-0.90; P = .03). Some patients had lesser degree of movement, and some exercised strenuously. There were no significant differences observed in the intensity of exercise performed by controls (RR: 0.90; 95% CI: 0.46-1.77; P = .76). The 3 studies found the frequency of regular exercise differed significantly between patients with psoriasis and controls (RR: 0.88; 95% CI: 0.82-0.95; P = .0007).Different severities of psoriasis have different influences on patients' physical activity levels. Patients with a higher proportion of psoriatic lesions and self-awareness were associated with lower-intensity exercises. Our meta-analysis highlights the fact that intense physical activity may lower the prevalence of psoriasis.

Efficiency and safety of milk feeding rescue for failed chloral hydrate sedation in infants with cyanotic congenital heart disease / 上海交通大学学报（医学版）

Objective·To evaluate the efficiency and safety of milk feeding to rescue failed chloral hydrate sedation in infants with cyanotic congenital heart disease who underwent transthoracic echocardiography.Methods·Clinical data of the infants with known cyanotic congenital heart disease were retrospectively analyzed,who were not adequately sedated after initial dose of chloral hydrate in 2015 in Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine.Vital signs and oxygen saturations were recorded every 5 minutes,and adverse events were noted.For rescue,efficiency and safety of milk feeding were compared with phenobarbital intramuscular injection.Results·A total of 129 infants were enrolled in this study.Fifty-two infants were rescued by intramuscular phenobarbital and the other 77 ones were rescued by milk feeding.The proportion of infants successfully rescued by milk feeding was 55.8％,which was higher than that of intramuscular phenobarbital (30.8％,P=0.005).There was no statistical difference in incidence of adverse events between the two groups (P=0.565).Conclusion·Milk feeding is an effective and safe choice for rescue sedation for infants with cyanotic congenital heart disease undergoing transthoracic echocardiography.

Immune-related adverse events associated with PD-1 and PD-L1 inhibitors for nonsmall cell lung cancer: Protocol for a systematic review and meta-analysis.

INTRODUCTION: Nonsmall cell lung cancer accounts for approximately 80% of all lung cancers, and approximately 75% of cases are diagnosed in the middle and late stages of disease. Unfortunately, limited treatment does not improve the prognosis of advanced disease. Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) represent a new treatment paradigm for nonsmall cell lung cancer. Nevertheless, the immune-related adverse events (irAEs) associated with PD-1 and PD-L1 inhibitors are unique, and early recognition and treatment of these events are essential. METHODS AND ANALYSIS: A systematic literature search will be performed using the EMBASE, MEDLINE, and Cochrane databases to identify relevant articles published in any language. Randomized clinical trials, case series, and case reports of PD-1 and PD-L1 inhibitors in the treatment of nonsmall cell lung cancer will be included. All meta-analyses will be performed using RevMan software. The quality of the studies will be evaluated using the guidelines listed in the Cochrane Handbook. If the necessary data are available, then subgroup analyses will be performed for high-, median-, and low-dose cohorts. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements will be followed until the findings of the systematic review and meta-analysis are reported. CONCLUSIONS: This will be the first systematic review and meta-analysis to describe previously reported irAEs related to PD-1 and PD-L1 inhibitors in the treatment of nonsmall cell lung cancer.

The effect of hydroxychloroquine on lupus erythematosus-like skin lesions in MRL/lpr mice.

OBJECTIVES: To evaluate the effect and safety of hydroxychloroquine (HCQ) on lupus erythematosus (LE)-like skin lesions in the MRL/lpr mouse, a model for systemic LE (SLE). METHODS: We divided the MRL/lpr mice into three groups that were given: (1) drinking water, (2) HCQ at a dose of 4 mg/kg/d, or (3) HCQ at a dose of 40 mg/kg/d. The HCQ was administered to examine the effect and safety of HCQ on skin lesions and the number of infiltrating cells including mast cells in the dermis. RESULTS: Six of 13 mice in the group given drinking water, 3 of 11 mice in the group administered low-dose HCQ (4 mg/kg/d), and 1 of 10 mice in the group administered high-dose HCQ (40 mg/kg/d) presented the skin lesions. The average number of mast cells was 81, 50, and 12 (magnification, ×100), the mortality rate was 24%, 8%, and 9% and the mean body weight gain was 4.6 g, 8.0 g and 5.1 g, respectively. CONCLUSIONS: HCQ was demonstrated to decrease the appearance of LE-like lesions and the number of mast cells in the dermis. Furthermore, there were no obvious systemic adverse effects. This study provides evidence that suggests benefits in human patients.

Severe ulceration with impaired induction of growth factors and cytokines in keratinocytes after trichloroacetic acid application on TRPV1-deficient mice.

Transient receptor potential vanilloid 1 (TRPV1) is a highly polymodal TRP channel activated by various stimuli, including capsaicin, heat and acids. TRPV1 expression can be detected widely but is highest in sensory neurons and its activation alerts the body to noxious signals via neurogenic pain. Although TRPV1 is reportedly localized in the epidermis, it remains unclear how TRPV1 is involved in the chemical peeling processes with cytotoxic acids. Therefore, in this study, the role of TRPV1 on the effects of trichloroacetic acid (TCA) peeling was assessed using TRPV1-deficient mice. Following the confirmation of TRPV1 expression in murine keratinocytes with reverse transcription-polymerase chain reaction and immunohistochemistry, the effects of TCA on TRPV1-deficient mouse skin were compared with those on wild-type mouse skin. Our results indicated that TRPV1 expression was not required for TCA-induced DNA damage, as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, but was indispensable for the TCA-induced production of distinct growth factors and cytokines by keratinocytes. Ulceration after TCA peeling was actually more severe in the absence of TRPV1, suggesting that the TRPV1-mediated epidermal production of growth factors and cytokines affected the damaging and healing processes of TCA-peeled skin to induce rejuvenation.

Poly[diaqua-bis-(nitrato-κ²O,O')bis-(1,10-phenanthroline-κ²N,N')-µ3-succinato-dicadmium].

In the title coordination polymer, [Cd2(C4H4O4)(NO3)2(C12H8N2)2(H2O)2](n), the Cd(II) ion is seven-coordinated within a distorted penta-gonal-bipyramidal O5N2 environment. The succinate anions, located on an inversion centre, adopt a bis-monodentate bridging mode, leading to the formation of rods along [100]. The rods are connected by O-H⋯O hydrogen bonds between the coordinating water mol-ecules and nitrate O atoms of adjacent rods; the same type of hydrogen bonds are also observed between water and carboxyl-ate O atoms within the rods. π-π stacking inter-actions with a minimum plane-to-plane separation of 3.462 (2) Šoccur between phenanthroline ligands.

Influence of chemical peeling on the skin stress response system.

Skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH), a-melanocyte-stimulating hormone (MSH) and b-endorphin that are locally generated in response to locally provided stressors or proinflammatory cytokines. This system would restrict tissue damage and restore local homoeostasis. Trichloroacetic acid (TCA) is one of the most widely used peeling agents and applied for cosmetic treatment of photodamaged skin. However, the biological mechanism responsible for TCA peeling has yet to be fully determined. While our investigation focused on the inflammation and wound healing pathways, in the recent study, we have examined involvement of the SSRS as the third pathway. Mostly depending on our findings that TCA peeling activates the SSRS by inducing the POMC expression of keratinocytes in the CRH-independent manner, together with the results reported by other researchers, we can say that the biological effect of POMC seems to be responsible for the TCA-induced epidermal SSRS activation.