Role of Momordica charantia in preventing the natural aging process of skin and sexual organs in mice.

Although various methods for improving the natural aging of skin have been examined, an effective method is currently unavailable. Therefore, in this study, we investigated the effects of Momordica charantia on the natural aging of skin of mice and how sex differences influenced these effects. To this end, we bred female and male hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered 50 mg/kg/day Momordica charantia fruit extract, three times per week. The characteristics of naturally aging skin, in terms of moisture retention, hydration, thickness, and reduced wrinkle score, improved after Momordica charantia treatment in both male and female mice. Furthermore, reduced cell apoptosis was observed in the female ovaries and male testes, and the levels of testosterone and 17ß-estradiol in blood were maintained. After treatment with Momordica charantia, the expression of matrix metalloprotease (MMP)-1 and hyaluronidase (HAYL)2 decreased in the skin of female mice, whereas the serum levels of interleukin (IL)-33 increased in the male mice. These results indicated that the natural aging of the skin was decelerated by Momordica charantia via regulation of the 17ß-estradiol/mast cell/MMP-1/HAYL2 and testosterone/mast cell/IL-33 signaling pathways in female and male mice, respectively.

Ameliorative effect of green odor against UVB-induced immunosuppression of contact hypersensitivity.

Ultraviolet (UV) irradiation to the eye induces photoimmunosuppression. In here, we examined the effect of green odor against immunosuppression of contact hypersensitivity in the eye induced by ultraviolet B (UVB) irradiation. Systemic immunosuppression was induced in ICR mice sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive green odor treatment significantly counteracted UVB irradiation-induced immunosuppression of the contact hypersensitivity (CHS) response. The green odor treatment increased dopamine and ß-endorphin levels in the brain and the plasma, respectively, and decreased the plasma corticosterone concentration in the oxazolone-sensitized mice after UVB irradiation to the eye, in contrast with that in acetone-treated mice (treatment negative control). Green odor prevented UVB irradiation-induced photoimmunosuppression of the CHS response by regulating the dopamine/ß-endorphin/corticosterone pathway.

Ameliorative Effect of Hochu-ekki-to on Natural Skin Aging.

INTRODUCTION: Although it is beneficial to protect the skin from natural aging, especially in an aging society, the approach by which this can be achieved is still not well known. Hochu-ekki-to, a Chinese natural medicine, has various advantageous effects; however, there is no report about its influence on skin aging. OBJECTIVE: Therefore, we examined the effect of hochu-ekki-to against natural aging. METHODS: Hairless mice, bred without ultraviolet ray irradiation and physical stress, were orally administered huchu-ekki-to 3 times per week for 2 years. After that period, degree of skin hydration and permeability were measured. Furthermore, hematoxylin and eosin histochemistry was performed to determine the morphology and condition of the tissues. Lastly, levels of vitamin A, vitamin C, and reactive oxygen species (ROS) in plasma and skin, as well as concentration of hyaluronic acid in the skin, were measured. RESULTS: Signs of skin aging were ameliorated by administration of hochu-ekki-to, such as moisture retention, skin hydration, and the generation of wrinkles. Furthermore, vitamin A, vitamin C, collagen type I, collagen type III, fibroblasts, and hyaluronic acid levels in the skin increased, while levels of ROS decreased after hochu-ekki-to treatment. CONCLUSION: These results indicated that natural skin aging was ameliorated by treatment with hochu-ekki-to, specifically moisture retention, and skin hydration, and thickening, via the regulation of the vitamin C/fibroblast, collagen type III/collagen type I, and vitamin A/hyaluronic acid signaling pathways.

Genome-wide analysis of spatiotemporal gene expression patterns during early embryogenesis in rice.

Embryogenesis in rice is different from that of most dicotolydonous plants in that it shows a non-stereotypic cell division pattern, formation of dorsal-ventral polarity, and endogenous initiation of the radicle. To reveal the transcriptional features associated with developmental events during rice early embryogenesis, we used microarray analysis coupled with laser microdissection to obtain both spatial and temporal transcription profiles. Our results allowed us to determine spatial expression foci for each expressed gene in the globular embryo, which revealed the importance of phytohormone-related genes and a suite of transcription factors to early embryogenesis. Our analysis showed the polarized expression of a small number of genes along the apical-basal and dorsal-ventral axes in the globular embryo, which tended to fluctuate in later developmental stages. We also analyzed gene expression patterns in the early globular embryo and how this relates to expression in embryonic organs at later stages. We confirmed the accuracy of the expression patterns found by microarray analysis of embryo subdomains using in situ hybridization. Our study identified homologous genes from Arabidopsis thaliana with known functions in embryogenesis in addition to unique and uncharacterized genes that show polarized expression patterns during embryogenesis. The results of this study are presented in a database to provide a framework for spatiotemporal gene expression during rice embryogenesis, to serve as a resource for future functional analysis of genes, and as a basis for comparative studies of plant embryogenesis.

A multi-institutional joint study of contact dermatitis related to hair colouring and perming agents in Japan.

BACKGROUND: In Japan, allergic contact dermatitis caused by hair colouring agents is a considerable problem for those occupationally exposed and also for consumers. Over the last 20 years, p-phenylenediamine (PPD) has been a common allergen, with ∼7% positive patch test reactions. OBJECTIVES: To investigate which ingredients caused allergic contact dermatitis related to hair dye and perming solutions in Japan, to assess whether PPD is suitable for screening for hair dye allergy, and to propose allergens for a Japanese hairdresser series. METHODS: We selected 19 hair cosmetic allergens, including PPD, Bandrowski's base, cysteamine HCl, and ammonium thioglycolate. Altogether 203 patients (26 males and 177 females) with suspected contact allergy to hair colouring or perming solutions at 14 hospitals in Japan were included. RESULTS: The highest prevalence of positive reactions (35.1%) was for PPD. p-Methylaminophenol and o-aminophenol were often positive, both in the PPD-positive and in the PPD-negative patients. Moreover, cysteamine HCl often yielded positive test reactions. CONCLUSIONS: PPD is insufficient to diagnose contact allergy caused by to hair dyes. We recommend 13 allergens to be included in a Japanese hairdresser series.

Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell-extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein-tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG-induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG-induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis.

Spatial and temporal control of laminin-332 and -511 expressions during hair morphogenesis.

Hair is one of the smallest organs, but has many important functions to mammals. Hair morphogenesis occurs through the reciprocal exchange of epithelial and mesenchymal signals. There are some reports about the expression of laminin-511 and -332 during hair morphogenesis, but are no reports of the chronological expression and function of laminin-511 and its counter regulator laminin-332 during hair morphogenesis. Our results of immunoblotting revealed that laminin-332 proteins were detected at stage 0 and downregulated during stage 1 to stage 2, and then recovered at stage 3. However, laminin α5 expression was constant throughout stages 0-3. According to the results of semi-quantitative RT-PCR, the mRNA expression of all laminin-332 subunits increased gradually from stage 0 to stage 2, while the mRNA expression of all laminin-511 subunits remained constant from stage 0 to stage 3. Our results suggest that the proper expression of laminin-332 and laminin-511 may regulate appropriate hair morphogenesis.

Design, synthesis, and biological evaluation of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives as novel androgen receptor antagonists.

We designed and synthesized a series of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives D and evaluated their potential as novel androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a methyl group at the 2-position (R(2)) of the pyrrolidine ring increased the AR binding affinity. The (2S,3R) configuration of the pyrrolidine ring was favorable for the AR antagonistic activity. It was found that introduction of an amide substituent (R(1)) and a pyridin-3-yl group (Q) was effective for reducing the AR agonistic activity which appeared during the optimization of lead compound 6. Compound 54 showed potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft, in which bicalutamide exhibited only partial suppression of tumor growth. Thus, the pyrrolidine derivatives such as 54 are novel AR antagonists, and their properties having efficacy against CRPC are distinct from those of a representative first-generation antagonist, bicalutamide.

Performance Improvement of a Return Channel in a Multistage Centrifugal Compressor Using Multiobjective Optimization.

The effect of the design parameters of a return channel on the performance of a multistage centrifugal compressor was numerically investigated, and the shape of the return channel was optimized using a multiobjective optimization method based on a genetic algorithm to improve the performance of the centrifugal compressor. The results of sensitivity analysis using Latin hypercube sampling suggested that the inlet-to-outlet area ratio of the return vane affected the total pressure loss in the return channel, and that the inlet-to-outlet radius ratio of the return vane affected the outlet flow angle from the return vane. Moreover, this analysis suggested that the number of return vanes affected both the loss and the flow angle at the outlet. As a result of optimization, the number of return vane was increased from 14 to 22 and the area ratio was decreased from 0.71 to 0.66. The radius ratio was also decreased from 2.1 to 2.0. Performance tests on a centrifugal compressor with two return channels (the original design and optimized design) were carried out using two-stage test apparatus. The measured flow distribution exhibited a swirl flow in the center region and a reversed swirl flow near the hub and shroud sides. The exit flow of the optimized design was more uniform than that of the original design. For the optimized design, the overall two-stage efficiency and pressure coefficient were increased by 0.7% and 1.5%, respectively. Moreover, the second-stage efficiency and pressure coefficient were respectively increased by 1.0% and 3.2%. It is considered that the increase in the second-stage efficiency was caused by the increased uniformity of the flow, and the rise in the pressure coefficient was caused by a decrease in the residual swirl flow. It was thus concluded from the numerical and experimental results that the optimized return channel improved the performance of the multistage centrifugal compressor.

Inducible nitric oxide synthase plays important roles in allergic reactions of pollinosis in mice sensitized with pollen allergy.

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO-synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we analyzed changes in the frequency of sneezing, plasma levels of NO metabolites, α-melanocyte-stimulating hormone (MSH) and immunoglobulin E and tracheal expression of IgA and mast cell tryptase in control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized with Cry j I antigen. After the last intranasal challenge of antigen, changes in the frequency of sneezing and plasma levels of IgE, α-MSH and NO metabolites and tracheal expression of iNOS, IgA and mast cell tryptase were analyzed by ELISA and immunohistochemistry using specific antibodies. The sensitization of mice with Cry j I antigen increased plasma levels of NO metabolites, α-MSH and IgE and tracheal expression of iNOS, IgA and mast cell tryptase in control not but in iNOS(-/-) mice. Administration of N(G)-nitro-L-arginine methyl ester strongly inhibited all these changes occurred in control mice. These results indicate that the symptom of pollinosis including sneezing is enhanced by iNOS derived NO through activation of α-MSH-receptor containing mast cells enriched with tryptase.

Mild exercise suppresses exacerbation of dermatitis by increasing cleavage of the ß-endorphin from proopiomelanocortin in NC/Nga mice.

This study investigated the mechanism by which the strength and weakness of exercise stress affects the skin symptoms of atopic dermatitis (AD). Specific pathogen-free (SPF) and conventional NC/Nga mice were used. Conventional mice, but not the SPF, spontaneously develop dermal symptoms similar to that of patients with AD. There were two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The symptom of the conventional group were strongly exacerbated by strong exercise but ameliorated by mild exercise. The plasma concentrations of α-melanocyte stimulating hormone (α-MSH) and the expression of melanocortin receptor-1 in skin elevated after strong exercise but decreased after mild exercise. The plasma levels of ß-endorphin and the expression of µ-opioid receptor in skin were increased by mild exercise. In addition, the expression of prohormone convertase (PC) 1/3, PC2 and carboxypeptidase E (CPE) in pituitary gland were higher in the conventional group than in the SPF group. The level of PC2 was suppressed by mild exercise in the conventional groups, and elevated further by strong exercise. The level of PC1/3 becomes higher with the increase of the exercise load. On the other hand, the expression of the CPE was further increase by mild exercise but suppressed by strong exercise. These observations suggested that exercise-induced stress significantly affect the symptoms of AD in a pivotal manner depending on the levels of α-MSH and ß-endorphin, and the expression of pituitary PC2 and CPE.

[Outbreak of extensively drug-resistant pulmonary tuberculosis in a hemodialysis facility].

We experienced an outbreak of extensively drug-resistant pulmonary tuberculosis (XDR-TB) in a hemodialysis facility. The primary case involved a 51-year-old male hemodialysis patient, with a history of treatment for Mycobacterium tuberculosis infection seven years previously. There was no drug resistance, and the patient completely recovered after undergoing treatment with isoniazid (INH), rifampicin (RFP) and ethambutol (EB). He was admitted to another hospital due to a recurrence of pulmonary tuberculosis in June 2006. At first, he was treated with HRS [INH, RFP and streptomycin (SM)]; however, the drug regimen was changed to INH, EB, levofloxacin (LVFX) and kanamycin (KM) in August following the results of a drug susceptibility test. Although the patient was receiving outpatient tuberculous therapy, he was readmitted in June 2007 due to relapse and conversion of a sputum culture to positive status. Additionally, the XDR-TB organism was identified. Following these events, five staff members of the hemodialysis facility and a member of the patient's family were diagnosed with XDR-TB infection. The staffs who were infected with XDR-TB had worked in the same dialysis room, drug resistance was found in all cases and drug resistant gene mutations were found in three cases; therefore, we considered this to be an outbreak. As XDR-TB infection was suspected in all cases, no patients took drugs to treat latent tuberculosis infection (LTBI). Regarding the causes of the outbreak, the first is the delay of four months in making a diagnosis of re-exacerbation of tuberculosis. Second, in Case 2, the patient developed laryngeal and tracheobronchial tuberculosis after first being diagnosed with asthma, and the tuberculosis diagnosis was delayed. Third, the sputum smear of Case 2 was strongly positive. There is only one previously reported outbreak of XDR-TB in Japan; therefore, we consider this outbreak to be educational.

[Family pharmacy participation in homecare medicine].

Creation of social structures for super-aged society is urgent task, because of the advent of a rapidly aging society. In the past, responsibility of pharmacies was only to dispense prescriptions for outpatient in local medical care. However, it is now essential that they participate in home medical care, and they are continuing to search for ways to support elderly people who live alone, people with dementia, and end-of-life care. Therefore we will report field investigations and case of at-home services by group pharmacies at community.

Toward developing care outcome quality indicators for home care for older people: A prospective cohort study in Japan.

INTRODUCTION: Care quality in Japan's long-term care (LTC) agencies, including home care, is the responsibility primarily of individual agencies, and the evaluation of service processes and outcomes is minimal. OBJECTIVES: To describe the development of quality indicators for LTC (QIs-LTC) in Japan. METHODS: QIs-LTC were developed through literature review and expert panel discussions and then were piloted and used in a 2-year longitudinal survey. The survey (launched in September 2019) targeted older people receiving home care (n = 1450), their family members (n = 880), their professional home care providers (n = 577), and managers of home care agencies (n = 122). RESULTS: Across eight domains (maintaining dignity, minimizing symptoms and disease deterioration, maintaining nutritional status, maintaining bladder/bowel control, encouraging physical activities, experiencing sound sleep, maintaining serenity and contentedness, and maintaining family's well-being), 24 care quality objectives were set with 24 outcome QIs-LTC and 144 process QIs-LTC. In the survey, 84.8% of clients were using home care nursing, 26.3% were living alone, and 39.5% had dementia. In the month preceding the data collection, 13.9% of clients had a new disease or worsening of an existing disease, 8.8% were hospitalized at least once, and 47.9% did not participate in activities of interest. About 20% of clients' families were unable to spend time peacefully, and 52.8% were exhausted from the client's care. CONCLUSIONS: The QIs-LTC developed in the current study are generic and client- and family-centered. They encompass objective and subjective information and would facilitate standardized monitoring if adopted and comparison between LTC settings, including home care. In addition, future research directives are outlined. Geriatr Gerontol Int 2023; 23: 383-394.

Intercellular pathway through hyaluronic acid in UVB-induced inflammation.

Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB-induced inflammation was not induced in gp91phox-depleted mice. To test whether gp91phox is directly involved in UVB-induced inflammation, neutrophil- and hyaluronic acid-depleted mice were also irradiated and examined for their response. Hyaluronic acid-depleted mice showed strongly inhibited UVB-induced inflammation, but the neutrophil-depleted mice did not exhibit any suppressed UVB-induced inflammation. To elucidate the pathway by which UVB irradiation induced inflammation, we examined the expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and caspase-1 in the mouse skin. An increase in the expression of NLRP3 and caspase-1 was seen following the UVB irradiation of C57BL mice; however, the UVB-irradiated gp91phox-knockout (gp91phox(-/-)) mice did not have this increase in expression. Furthermore, the plasma IL-1ß level increased after the UVB irradiation in C57BL mice, but there was no change in the gp91phox(-/-) mice. These results clearly indicate that nicotinamide adenine dinucleotide phosphate oxidase is activated by gp91phox, which is expressed on the surface in response to the increased expression of hyaluronic acid induced by UVB irradiation, and as result, the generation of reactive oxygen species (ROS) increases. This ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1ß, thereby finally inducing inflammation. It is thought that this system may play an important role in the damage and ageing of skin, and further studies are necessary to confirm these finding.

Increased expression of OCIA domain containing 2 during stepwise progression of ovarian mucinous tumor.

Ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) has been reported to show cancer-specific expression in early invasive lung adenocarcinoma. OCIAD2 shows high homology with OCIAD1, which was originally immunoscreened from ascites of a patient with ovarian cancer and found to be a tumor-specific protein. Therefore, like OCIAD1, OCIAD2 is expected to show high immunoreactivity in ovarian tumors. In this study, we examined the expression pattern of OCIAD2 in 117 ovarian mucinous tumors, and confirmed that it was more highly expressed in borderline tumor and carcinoma (51/74 cases, 69%) than in adenoma (6/43 cases, 14%). The immunoreactivity of OCIAD2 in borderline tumor and carcinoma was more specific than that of OCIAD1 (adenoma, 21/43 cases, 49%), and more sensitive than that of CEA (borderline tumor and carcinoma, 35/74 cases, 47%). Like OCIAD1, OCIAD2 is a cancer-related protein and its expression level increases during the course of malignant progression and is thought to be a very useful marker for evaluating the malignancy of ovarian mucinous tumors.

Erythema dyschromicum perstans in a Japanese child.

Erythema dyschromicum perstans (EDP) is asymptomatic slate-gray to blue-brown macules. Idiopathic eruptive macular pigmentation is asymptomatic brown nonconfluent macules. We describe electron microscopic studies of a 9-year-old Japanese girl with EDP. The ultrastructural figures indicated that the production of immature, small, irregular-shaped melanosomes in melanocytes and peripheral localization of melanosomes in keratinocytes caused the clinical appearance of EDP. The ultrastructural evidence distinguishes EDP from idiopathic eruptive macular pigmentation and suggests a distinct pathogenesis of the disease.

Inducible nitric oxide synthase (iNOS) and α-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice.

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, α-MSH, ACTH, TGF-ß and TNF-α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, α-MSH, ACTH, TGF-ß and TNF-α in control, but not in iNOS(-/-) mice. The administration of l-nitro-arginine-methyl ester (l-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given α-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-ß or TNF-α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α-MSH, which is induced by iNOS-derived NO.

Unilateral eyelid angioedema with congestion of the right bulbar conjunctiva due to loxoprofen sodium.

Angioedema is a variant of urticaria that causes deep dermal and subcutaneous swelling. It frequently is a unilateral reaction and usually lasts for several hours but may persist for several days. We report 2 cases of angioedema that involved the right upper and lower eyelids and was associated with congestion of the right bulbar conjunctiva; the symptoms started approximately 1 to 2 hours after taking loxoprofen sodium. All of the symptoms subsided after oral corticosteroid therapy. In both cases, an oral challenge test with 60 mg of loxoprofen sodium (contained in a tablet) caused swelling of the right upper eyelid within several hours, followed by swelling of the right bulbar conjunctiva. We believe the drug reaction in both patients is angioedema.

Increased alpha-melanocyte-stimulating hormone (alpha-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis.

Patients with a specific subtype of atopic dermatitis (AD) display particular patterns of pigmentation, such as ripple pattern pigmentation on the neck, pigmented macules on the lip and diffuse pigmentation. However, the mechanism underlying these patterns has not been determined. The purpose of our research is to investigate the factors influencing this type of pigmentation in AD. We observed that AD model mice (NC/Nga mice) displayed an increase in the number of 3, 4-dihydroxyphenylalanine (Dopa)-positive melanocytes in the epidermis and intestine (jejunum and colon) while in the inflammatory state. The plasma levels of alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocoticotropin (ACTH) also increased in NC/Nga mice with dermatitis. Furthermore, the expression of melanocortin receptor 5 and melanocortin receptor 1 (MC1R) increased in the skin, and melanocortin receptor 3 (MC3R) expression increased in the intestine. However, the changes in the Dopa-positive cells of conventional NC/Nga mice were not induced by treatment with either agouti (an MC1R antagonist) or agouti-related protein (an MC3R antagonist). These results indicate that the pigmentation of AD is related to increased levels of alpha-MSH, MC1R (in the skin) and MC3R (in the intestines).