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Various diabetic drugs have been developed as the number of patients with type 2 diabetes has increased. Sodium-glucose cotransporter (SGLT)-2 inhibitors have been developed as novel therapeutic agents. However, SGLT-2 inhibitors cause skin dryness. The mechanism through which SGLT-2 inhibitors cause skin dryness is unknown. The purpose of this study was to investigate the mechanism through which dapagliflozin, a SGLT-2 inhibitor, induces skin dryness. Specific pathogen-free KK-Ay/TaJcl (type 2 diabetes model) mice were orally administered with SGLT-2 inhibitor (dapagliflozin) daily for 4 weeks at a dose of 1 mg/kg/d. Skin dryness induced in KK-Ay/TaJcl mice became severe after dapagliflozin administration. Dapagliflozin treatment decreased collagen type I and hyaluronic acid levels in mice; additionally, it affected the transforming growth factor (TGF)-β/hyaluronan synthase pathway, further reducing hyaluronic acid levels. The results indicate that the reduction in hyaluronic acid levels plays an important role in the occurrence of dry skin in diabetes.

Cyclooxygenase (COX)-1-selective inhibitors have side effects such as itching and dryness of the skin. In this study, the degree of skin dryness and the onset mechanism of this condition were investigated by comparing the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) in mice. Mice were orally administered either indomethacin, loxoprofen sodium, or celecoxib (n = 5 per group) once daily for four consecutive days, and blood samples as well as skin and jejunal tissues were isolated on day 5. In the mice treated with indomethacin, transepidermal water loss was significantly increased, and dry skin was observed. In addition, the expression of matrix metalloproteinase (MMP)-I, mast cells, CD163, CD23, CD21, histamine, and peroxisome proliferation-activated receptor (PPAR)γ in the skin and jejunum was increased, and the blood levels of interleukin-10 and immunoglobulin E were also increased. In contrast, the expression of collagen type I in the skin was decreased. These results show that indomethacin activates PPARγ in the skin and jejunum, changes the polarity of macrophages, increases the secretion of MMP-1 from mast cells, and decomposes collagen type I, leading to dry skin.

Various side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in analgesia have been reported. Among the NSAIDs, celecoxib has fewer side effects and is often used in therapeutic applications. However, the effect of celecoxib on aged skin is unknown. In this study, we investigated the effects of celecoxib administration on the skin of aged mice. We analyzed a 40-week-old mouse model and a 10-week-old mouse as the control group. The animals were orally administered celecoxib for four consecutive days and then killed and dissected the day after the last dose. In aged mice treated with celecoxib, the water content of the stratum corneum, which is one of the markers of dry skin, was lower than that in the control and young mice groups. In addition, serum hyaluronic acid, creatinine, and inflammatory cytokines in the collected blood samples of aged mice were elevated compared to those in other mice groups, suggesting the onset of acute renal injury. Therefore, it was considered that acute renal injury occurred from the administration of celecoxib to aged mice, whereas dry skin developed by the promotion of inflammatory cytokine secretion and release into the bloodstream in this group.

Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs. Following B16 melanoma cell injection, mice were orally administered glycyrrhizin once every two days over 2 weeks; lung samples were then obtained and analyzed. Blood samples were collected on the final day, and cytokine plasma levels were determined. We found that glycyrrhizin ameliorated the extravasation of melanoma cells into the lungs and suppressed the plasma levels of interleukin-6, tumor necrosis factor-α, and transforming growth factor-β. Furthermore, glycyrrhizin ameliorated the lung tissue expression of high mobility group box-1 protein (HMGB1), receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-4, RAS, extracellular signal-related kinase, NF-κB, myeloid differentiation primary response 88, IκB kinase complex, epithelial-mesenchymal transition markers, and vascular endothelial growth factor-A. Our study demonstrates that glycyrrhizin ameliorates melanoma metastasis by regulating the HMGB1/RAGE and HMGB1/TLR-4 signal transduction pathways.

Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 106 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.

Purpose Although the onset mechanism of Alzheimer's disease, which co-occurs with aging, has been extensively studied, no effective methods that improve the decline in memory and learning abilities following aging have been developed. Tranexamic acid provided promising results for ameliorating photo-aging and extending the natural lifespan. However, it is unknown whether it affects the decline in memory and learning abilities due to aging. In this study, we examined the effect of tranexamic acid on memory and learning abilities of naturally aging mice. Methods ICR mice were orally administered with tranexamic acid (12 mg/kg/day) three times weekly for 2 years, and their memory and learning abilities were compared between the tranexamic acid-treated and non-treated groups. Results The decline in memory and learning abilities due to aging was ameliorated by tranexamic acid administration. The expression of plasmin and amyloid-β decreased following the treatment with tranexamic acid. Furthermore, the number of M1-type brain macrophages diminished and that of M2 macrophages increased. In addition, administration of tranexamic acid decreased the concentrations of interleukin (IL)-1β and tumor necrosis factor-α, while it increased the levels of IL-10 and transforming growth factor-α in the brain. Conclusion These results indicated that tranexamic acid suppressed the secretion of the inflammatory cytokines aging M1-type macrophages, thereby improving age-related memory and learning abilities.

Sparassis crispa (SC; Japanese name: Hanabiratake) is a mushroom with high β(1-3)-glucan content. We here studied the effects of SC and lactic acid bacteria-fermented SC (SCL) on innate immunity. In in vivo studies using mice, oral administration of SC or SCL enhanced the accumulation of macrophages, neutrophils, natural killer (NK) cells, and C-C chemokine receptor type 2- or phospho-Syk-expressing cells in the jejunum epithelial villi and spleen, with significantly higher cell numbers in the SCL group than in the SC group. In addition, mRNA levels of genes encoding tissue factor (TF) and tumor necrosis factor (TNF)-α were increased in monocytes/macrophages from the peritoneal cavity of mice orally administered SCL. In in vitro studies using cultured human monocytes, SC and SCL enhanced the expression of gees involved in blood coagulation and inflammation, as well as those encoding various innate immune-related factors, such as TF, TNF-α, plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1β, IL-8, IL-12β, and IL-17, in a dose-dependent manner. In particular, the expression levels of all these factors in monocytes were significantly higher with SCL treatment than with SC treatment. SCL significantly enhanced the phagocytosis of pH-sensitive fluorescent dye-labeled Escherichia coli by human monocytes compared to SC. The effect of SCL on phagocytosis was significantly reduced to approximately 30% by pre-digestion of SCL with β-glucanase, suggesting that β(1-3)-glucan in SCL is a major contributor to the effect. These data suggest that oral administration of SCL significantly enhances innate immunity in mice and possibly humans.

Objective: Atopic dermatitis (AD) symptoms are altered with exercise. However, no study has investigated the association between testosterone and AD. The aim of this study was to investigate the role of testosterone by which the strength and weakness of exercise affects the skin symptoms of AD. Methods: Specific pathogen-free (SPF) and conventional NC/Nga mice were used. NC/Nga mice spontaneously developed dermal symptoms similar to AD patients. Two exercises, mild (20 m/min, 60 min) and rigorous (25 m/min, 90 min), were carried out using a treadmill four times every alternate day. Furthermore, we administered testosterone (0, 5, 50, 500, and 5000 pg/mice) to non-exercised conventional NC/Nga mice. On the final day of this experiment, we analyzed the plasma levels of immunoglobulin E (IgE), interleukin (IL)-6, IL-4, IL-13, testosterone and α-melanocyte-stimulating hormone (α-MSH) by ELISA kit. Results: Symptoms manifested by NC/Nga mice were strongly exacerbated upon severe exercise but were ameliorated during mild exercise. Between mild and severe exercised conventional mice, the plasma level of IgE was not changed. On administering an equivalent amount of testosterone, depending on the exercise, AD-like symptoms in non-exercising NC/Nga mice were ameliorated with mild exercise and exacerbated through rigorous exercise. Plasma IL-6, IL-4, and IL-13 levels remained unchanged between +50 pg (mild) and +500 pg (severe) testosterone administration. Plasma α-MSH levels were elevated with +500 pg testosterone but decreased with +50 pg testosterone administration. Conclusion: The present results suggest that exercise largely mimics AD symptoms depending on the α-MSH and testosterone levels.

Long-term eye exposure to ultraviolet (UV)A can effect memory and learning ability. However, the underlying mechanism behind these effects remain unknown. In this study, we used HR-1 mice to study effects of long-term UVA eye irradiation. The eyes or dorsal skin of the mice were exposed to UVA at the dose of 110kj/m2 using an FL20SBLB-A lamp three times a week over 12 months. We measured the levels of reactive oxygen species, corticotropin-releasing hormone (CRH), urocortin 2, and CRH type 2 receptor (CRHR-2) in the brain of treated and control animals. Their memory and learning ability following exposure to UVA was analyzed by the standard water maze test. Our results showed that the levels of reactive oxygen species, CRH, urocortin 2, and CRHR-2 increased significantly following long-term UVA irradiation, and the effects were more pronounced in animals subjected to eye irradiation than those subjected to dorsal skin irradiation. Furthermore, the UVA exposure led to an increase in the levels of β-amyloid and microglia in the brain. These results indicated that UVA eye irradiation potentially mediated a decline in memory and learning ability via enhancing levels of urocortin 2, microglia, and β-amyloid in the brain.

In this data file, the synthetic procedures for the preparation of a series of anticancer tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]n+ (n = 1 or 2, tetrazolato-bridged complexes)) and of the bridging ligands of 5-substituted 1H-tetrazoles (5-R-1H-tetrazoles) are described. These compounds were characterized by 1H-, 13C-, 19F- and 195Pt-NMR spectroscopy and mass spectrometry.

Cyclooxygenase (COX)-1-selective inhibitors have side effects such as itching and dryness of the skin. In this study, the degree of skin dryness and the onset mechanism of this condition were investigated by comparing the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) in mice. Mice were orally administered either indomethacin, loxoprofen sodium, or celecoxib (n = 5 per group) once daily for four consecutive days, and blood samples as well as skin and jejunal tissues were isolated on day 5. In the mice treated with indomethacin, transepidermal water loss was significantly increased, and dry skin was observed. In addition, the expression of matrix metalloproteinase (MMP)-I, mast cells, CD163, CD23, CD21, histamine, and peroxisome proliferation-activated receptor (PPAR)γ in the skin and jejunum was increased, and the blood levels of interleukin-10 and immunoglobulin E were also increased. In contrast, the expression of collagen type I in the skin was decreased. These results show that indomethacin activates PPARγ in the skin and jejunum, changes the polarity of macrophages, increases the secretion of MMP-1 from mast cells, and decomposes collagen type I, leading to dry skin.

Tranexamic acid (TA) has been reported to exhibit antitumor effects in various mouse models of cancer. However, the mechanism underlying its antitumor effects against endometrial cancer remains to be elucidated. This study was aimed at investigating the efficacy of TA against chronic inflammation-associated endometrial cancer induced by

Background Vitamin C plays a part in various roles in the human body. In this study, we examined the effect of oral administration of high-dose vitamin C on the skin dryness induced by irinotecan. Methods To establish the experimental model of irinotecan-induced skin dryness, the drug was intraperitoneally administered for four consecutive days. Simultaneously, oral administration of high-dose vitamin C (4 g/kg) was continued for 4 days. Results High-dose vitamin C administration ameliorated the skin dryness induced by irinotecan. The expression of caspase-3 and caspase-9, reactive oxygen species, and the number of TUNEL-positive cells increased in the skin of irinotecan-treated mice but were lowered by high-dose vitamin C administration. In contrast, fibroblasts and collagen type I decreased in the skin of the irinotecan-treated mice but was increased by high-dose vitamin C administration. Conclusion These results suggested that high-dose vitamin C administration can improve the skin dryness induced by irinotecan.

Skin dryness is a characteristic of rheumatoid arthritis (RA) model mice. However, the mechanism underlying the induction of dry skin by RA is unclear. We hypothesized that T helper (Th)2 and Th17 cells mediate this process. A mouse model of DBA/1JJmsSlc collagen-induced arthritis was treated with Th2 or Th17 cell inhibitor, and transepidermal water loss (TEWL) and the expression of markers associated with allergic reaction and inflammation were evaluated. TEWL and plasma levels of thymic stromal lymphopoietin, interleukin (IL)-6 and -17, and tumor necrosis factor (TNF)-α were increased in the arthritis mouse model compared to that in control mice. Administration of Th2 cell inhibitor abolished the increase in TEWL, IL-6, and TNF-α levels, whereas Th17 cell inhibitor reversed TEWL and decreased IL-17 level. Th2 and Th17 cells contribute to the induction of dry skin, but via distinct mechanisms.

Several studies have been conducted to investigate the anti-cancer effects of vitamin C (VC). However, the effect of high-dose VC administration on tumor angiogenesis remains unclear. Focusing on our high-dose VC, our study investigated the effect of high-dose VC (4 g/kg) on vascular endothelial growth in mice with xenografts of a rectal cancer cell line referred to as Colon 26. Male mice harboring Colon 26 tumors were established, and high-dose VC solution was orally administered once daily for 14 d. On the final day of the study, the lower limb tumor tissues and serum samples were collected and analyzed for the expression of tumor angiogenesis related proteins as well as the levels of reactive oxygen species (ROS). Oral VC administration decreased tumor volumes and increased p53 and endostatin levels. In addition, plasma and in tumor part ROS levels and tissue hypoxia inducible factor-1α (HIF-1α) were reduced by VC administration. In addition, the levels of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor D (VEGFD) were decreased by VC administration. These results suggest that VC exerts its anti-cancer effects by suppressing angiogenesis.

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

Inflammation is a primary risk factor for cancer. Epidemiological studies previously demonstrated that aspirin decreased the incidence of cancer and specifically reduced the risk of colorectal cancer. However, the number of animal studies that have confirmed the efficacy of aspirin remains limited. Therefore, the purpose of the present study was to investigate the mechanisms by which aspirin prevents colorectal cancer in mice. ICR mice were treated with azoxymethane and the ulcerative colitis inducer, dextran sodium sulfate, to induce colorectal tumors. Aspirin was orally administered three times per week for 12 weeks. Aspirin significantly reduced the number and size of colorectal tumors. Aspirin also significantly decreased tumor necrosis factor alpha and reactive oxygen species (ROS) levels in the plasma. Immunohistochemical analyses and western blots showed that cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), and the active form of Yes-associated protein 1 (YAP1), and cytosolic high mobility group box 1 (HMGB1) were strongly expressed at colorectal tumor sites and clearly suppressed by aspirin. An indicator of inflammation-related DNA damage, 8-nitroguanine, also accumulated in the colorectal tissues and was suppressed by aspirin. The present results suggest that the ingestion of aspirin suppressed carcinogenesis caused by inflammation through decreases in COX2 and ROS levels, resulting in reductions in DNA damage and oncogenic YAP1.

High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.

Photoaging can be induced by long-term ultraviolet (UV)A eye irradiation, but an ameliorating method for such photoaging is not known. In this study, we examined the effects of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) on photoaging of the skin induced by UVA eye irradiation. We used the C57BL/6 j female mice and locally exposed their eyes to UVA at a dose of 110 kJ/m2 using an FL20SBLB-A lamp multiple times a week for one year. The plasma urocortin 2, β-endorphin, methionine enkephalin (OGF), and histamine content, as well as the expression of the corticotropin-releasing hormone receptor (CRHR) type 2, μ-opioid receptor, opioid growth factor receptor (OGFR), T-bet, and GATA3 increased in the mice subjected to UVA eye irradiation. However, the increased levels of urocortin 2, methionine enkephalin, histamine, OGFR, T-bet, and GATA3 were suppressed by tranexamic acid treatment. Conversely, the levels of β-endorphin and μ-opioid receptor increased with tranexamic acid treatment. In addition, the expression of the estrogen receptor-β on the surface of mast cells was increased by tranexamic acid. These results indicate that photoaging induced by UVA eye irradiation can be ameliorated by tranexamic acid through the regulation of hypothalamo-pituitary hormones. Furthermore, this ameliorative effect on photoaging may be due to an increase in estrogen receptor-β after tranexamic acid treatment.

Ultraviolet (UV) irradiation is a well known photo-immunosuppressant. To determine the effect of Eucommia ulmoides leaf extract (ELE) components (chlorogenic acid, geniposidic acid, and asperuloside) on UVB induced immunosuppression, we examined mice that were contact hypersensitized. Systemic immunosuppression was induced in the C57BL/6j mice that were sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive oral administration of ELE, chlorogenic acid, or geniposidic acid significantly reduced UVB-induced suppression of the contact hypersensitivity (CHS) response. The treatment with chlorogenic acid or geniposidic acid decreased the serum interleukin-10 levels in the sensitized mice after UVB irradiation. Additionally, the level of plasma reactive oxygen species and the expression of skin mast cells decreased in the chlorogenic acid-treated mice. Contrarily, the expression of regulatory T cell in the skin decreased in the geniposidic acid-treated mice. These results suggest that chlorogenic and geniposidic acids prevent the photo-immunosuppression of the CHS response.

Background In modern society, irregular lifestyles are a problem. It is well known that Atopic Dermatitis (AD) occurs during physical stress in people with an irregular lifestyle. We evaluated the influence that day-and-night reversal physical stress has on AD. Methods Six-week-old specific-pathogen-free and conventional NC/Nga male mice were used. For the day-and-night reversal procedure, the mice ran on a treadmill at a slow speed of 10 m/min for 12 h (between 8:00 and 20:00). Then, between 20:00 and 8:00, we put the mice in a dark place. This treatment was repeated every day for two weeks. The behavioral circadian rhythm of the mice was evaluated with the open field test. Then, the mice were sacrificed and histological examinations of the tissues, the expression of peptide hormones, corticosterone, Immunoglobulin E, histamine, and cytokines was performed using an enzyme-linked immunosorbent assay. Results In the treadmill-treated conventional NC/Nga mice, AD symptoms were deteriorated compared with the non-treated conventional NC/Nga mice. The levels of Period (Per) 2, Clock, and brain and muscle arnt-like protein 1 (Bmal1) in the skin were increased constantly in the treadmill-treated conventional mice. Furthermore, the expression of Retinoic Acid-related Orphan Receptor (ROR)α, which activates Bmal1, was increased in the treadmill-treated conventional mice compared with the non-treated conventional mice. In addition, when non-treated conventional mice were administrated by the agonist of RORα, AD symptoms were deteriorated similar to treadmill-treated conventional mice. Conclusion In the day-and-night reversal mice, the clock genes were increased constantly, indicating that this is a factor that deteriorated AD.

Although we previously reported the exacerbation of dextran sodium sulfate (DSS)-induced ulcerative colitis by ultraviolet (UV) B eye irradiation, we do not yet understand the mechanism behind this phenomenon. In this study, we examined the relationship between the deterioration of DSS-induced ulcerative colitis and clock genes. We induced a mouse model of ulcerative colitis by administering DSS for 5 days, and administered UVB eye irradiation on each day of the DSS treatment period. The DSS-induced ulcerative colitis was deteriorated by the UVB eye irradiation. The levels of Clock, brain and muscle arnt-like protein 1 (Bmal1), reverse orientation c-erb A gene (Rev-Erb)α, RAR-related orphan receptor gamma (RORγt), and interleukin (IL)-17 in the colon were increased by UVB eye irradiation in the DSS-treated mice (UVB/DSS-treated mice). Conversely, the nuclear factor, interleukin 3 regulated (NFIL-3) levels in the colon were lower after UVB eye irradiation. The Casein Kinase 1ε/δ inhibitor (PF670462) administration, which is a Clock/Bmal1 inhibitor (PER2 activator), inhibited the deterioration caused by UVB eye irradiation. These results suggest that the UVB eye irradiation-mediated exacerbation of DSS-induced ulcerative colitis depends on IL-17 produced in response to alterations in clock genes.

This study investigated the sex differences of the inflammatory mediator level at the time of itch onset in patients with chronic venous disease (CVD). Twenty-seven CVD patients (nineteen women, eight men) and nine healthy controls (five women, four men) participated. CVD-associated itching was observed in both men and women. Before sclerotherapy, both sexes had elevations in several itch-related mediators. Among these, women had significantly higher tryptase, whereas men had significantly higher β-endorphin and adrenocorticotropic hormone. After sclerotherapy, all levels normalized in both sexes. In this study, itching was increased tryptase in women and increased adrenocorticotropic hormone and β-endorphin in men.

Active oxygen derived from gp91phox is critical for gestation. However, no reports have evaluated the relationship between reactive oxygen species (ROS) and the number of births in a given pregnancy. In this study, we examined the influence of ROS produced by gp91phox activity on the number of births using C57BL/6j (control) and gp91phox-knockout (gp91phox−/-) mice. The number of births in gp91phox−/- mice was found to be lower than that in control mice. We observed sequential increases in gp91phox, ROS, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-18 (IL-18), followed by increased expression of mucin1 (MUC1), in control mice. However, none of these markers were upregulated in gp91phox−/- mice. In addition, in control mice administered IL-18 or MUC1 inhibitors, the number of births decreased to a number similar to that of gp91phox−/- mice. These results suggest that ROS derived from gp91phox activity altered the inflammato...

Background: Long-term ultraviolet (UV) A eye irradiation in mice initiates the induction of photoaging. However, the changes in the eye due to long-term exposure to UVA radiation are still unclear. Methods: Male C57BL/6j (control) and inducible nitric oxide synthase knockout (iNOS-/-) mice were used in this study. The eyes of the mice were locally exposed to UVA radiation for 12 months. Results: The expression of iNOS, matrix metalloproteinase-2 (MMP-2), MMP-9, vascular endothelial growth factor, β-amyloid, and macrophages in the retina all increased after UVA irradiation. Furthermore, in the iNOS-/- mice, no retinal changes were induced by UVA eye irradiation. Conclusions: These results indicated that long-term UVA eye irradiation led to iNOS-induced denaturation of the retina; however, further studies are needed to confirm these findings.

Background: Ultraviolet (UV) irradiation is well known to promote inflammation and pigmentation of skin. UVB mainly affects dermatitis and pigmentation. Coffee contains a number of polyphenols, such as caffeic acid (CA) and chlorogenic acid (CGA) but their in vivo bioactivity for photobiology remains unclear. Methods: C57BL/6j male mice were irradiated with UVB (1.0 kJ/m2/day) for 3 days. Five days after the final session of UVB irradiation, the dorsal skin, ear epidermis, and blood samples were analyzed to investigate the inflammatory factors, melanogenesis factors and related hormones. Results: After the oral administration of CA (100 mg/day) or CGA (100 mg/day) for 8 days, only CA was found to inhibit dermatitis and pigmentation. The pathway by which CA inhibits dermatitis is related to the mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK)1/2/cAMP response element binding protein (CREB) pathway. Otherwise, the pathway by which CA inhibits pigmentation is related to the activation of the β-endorphin-μ-opioid receptor and suppresses the cAMP-microphthalmia-associated transcription factor (MITF) pathway. Conclusion: It is suggested that the oral administration of CA prevented dermatitis and pigmentation after UVB irradiation in mice.

It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. We developed an AD mouse model (NC/Nga mice) with ulcerative colitis by administering dextran sodium sulfate (DSS) for five days. DSS-induced ulcerative colitis was deteriorated in our conventional AD mouse model compared with specific-pathogen-free (SPF) mice. The plasma levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor-α increased the most in DSS-treated conventional mice. Furthermore, the expression of dendritic cells (DC), retinoid-related orphan receptor (ROR)γt (marker of T helper 17 cells [Th17]), interleukin (IL)-17, GATA binding protein 3 (GATA3) (marker of Th2), and IL-4 increased the most in the colon of the DSS-treated conventional mice compared with DSS-treated SPF mice. In addition, TSLP inhibitor (TSLP neutralizing antibody) did not exacerbate ulcerative colitis in DSS-treated conventional mice. These results indicate that TSLP/DC/Th2 and Th17 play major roles in the exacerbation of ulcerative colitis by AD.

The pathogenic relationship of ulcerative colitis and rheumatoid arthritis is not known. Therefore, we examined dextran sodium sulfate (DSS)-induced colitis separately and in combination with a mouse arthritis model that mimics rheumatoid arthritis and evaluated the deterioration-related factors of each condition. Arthritis was induced in a collagen-induced arthritis mouse model using DBA/1JJmsSlc mice and ulcerative colitis was induced by the administration of drinking water containing 3.0% (w/v) DSS. The arthritis/DSS-treated mice developed worse colitis scores compared to that of the other groups of mice. The arthritis/DSS-treated mice did not demonstrate changes in hind foot volumes or in the concentration of matrix metalloproteinase-3 (MMP-3) in the plasma; however, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were increased. Our results showed that IL-6 and TNF-α may influence the deterioration effect of colitis in arthritic mice.