Possible influence of vitamin D on male reproduction

Publication date: Available online 28 September 2016
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Ida Marie Boisen, Lasse Bøllehuus Hansen, Li Juel Mortensen, Beate Lanske, Anders Juul, Martin Blomberg Jensen
Vitamin D is a versatile signaling molecule with an established role in the regulation of calcium homeostasis and bone health. In recent years the spectrum of vitamin D target organs has expanded and a reproductive role is supported by the presence of the vitamin D receptor (VDR) and the vitamin D metabolizing enzymes in the gonads, reproductive tract, and human spermatozoa. Interestingly, expression levels of VDR and the vitamin D inactivating enzyme CYP24A1 in human spermatozoa serve as positive predictive markers of semen quality and are higher expressed in spermatozoa from normal than infertile men. VDR mediates a non-genomic increase in intracellular calcium concentration, sperm motility, and induces the acrosome reaction. Furthermore, functional animal model studies have shown, that vitamin D is important for sex steroid production, estrogen signaling, and semen quality. Cross-sectional clinical studies have supported the notion of a positive association between serum 25-hydroxyvitamin D (25-OHD) level and semen quality in both fertile and infertile men. However, it remains to be determined whether this association reflects a causal effect. The VDR is ubiquitously expressed and activated vitamin D is a regulator of insulin, aromatase, and osteocalcin. Hence, it is plausible that the influence of vitamin D on gonadal function may be mediated indirectly through other vitamin D regulated endocrine factors. Recent studies have indicated that vitamin D supplementation may be beneficial for couples in need of assisted reproductive techniques as high serum vitamin D levels were found to be associated with a higher chance of achieving pregnancy. Randomized clinical trials are needed to determine whether systemic changes in vitamin D metabolites can influence semen quality, fertility, and sex steroid production in infertile men. In this review known and possible future implications of vitamin D in human male reproduction function will be discussed.



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ENDOGENOUSLY PRODUCED NONCLASSICAL VITAMIN D HYDROXY-METABOLITES ACT AS “BIASED” AGONISTS ON VDR AND INVERSE AGONISTS ON RORα AND RORγ.

Publication date: Available online 28 September 2016
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Andrzej T. Slominski, Tae-Kang Kim, Judith V. Hobrath, Allen S.W. Oak, Edith K.Y. Tang, Elaine W. Tieu, Wei Li, Robert C. Tuckey, Anton M. Jetten
The classical pathway of vitamin D activation follows the sequence D3→25(OH)D3→1,25(OH)2D3 with the final product acting on the receptor for vitamin D (VDR). An alternative pathway can be started by the action of CYP11A1 on the side chain of D3, primarily producing 20(OH)D3, 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3 and 17,20,23(OH)3D3. Some of these metabolites are hydroxylated by CYP27B1 at C1α, by CYP24A1 at C24 and C25, and by CYP27A1 at C25 and C26. The products of these pathways are biologically active. In the epidermis and/or serum or adrenals we detected 20(OH)D3, 22(OH)D3, 20,22(OH)2D3, 20,23(OH)2D3, 17,20,23(OH)3D3, 1,20(OH)2D3, 1,20,23(OH)3D3, 1,20,22(OH)3D3, 20,24(OH)2D3, 1,20,24(OH)3D3, 20,25(OH)2D3, 1,20,25(OH)3D3, 20,26(OH)2D3 and 1,20,26(OH)3D3. 20(OH)D3 and 20,23(OH)2D3 are non-calcemic, while the addition of an OH at C1α confers some calcemic activity. Molecular modeling and functional assays show that the major products of the pathway can act as "biased" agonists for the VDR with high docking scores to the ligand binding domain (LBD), but lower than that of 1,25(OH)2D3. Importantly, cell based functional receptor studies and molecular modeling have identified the novel secosteroids as inverse agonists of both RORα and RORγ receptors. Specifically, they have high docking scores using crystal structures of RORα and RORγ LBDs. Furthermore, 20(OH)D3 and 20,23(OH)2D3 have been tested in cell model that expresses a Tet-on RORα or RORγ vector and a RORE-LUC reporter (ROR-responsive element), and in a mammalian 2-hybrid model that test interactions between an LBD-interacting LXXLL-peptide and the LBD of RORα/γ. These assays demonstrated that the novel secosteroids have ROR-antagonist activities that were further confirmed by the inhibition of IL17 promoter activity in cells overexpressing RORα/γ. In conclusion, endogenously produced novel D3 hydroxy-derivatives can act both as "biased" agonists of the VDR and/or inverse agonists of RORα/γ. We suggest that the identification of large number of endogenously produced alternative hydroxy-metabolites of D3 that are biologically active, and of possible alternative receptors, may offer an explanation for the pleiotropic and diverse activities of vitamin D, previously assigned solely to 1,25(OH)2D3 and VDR.

Graphical abstract

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Clinical practice guidelines for vitamin D in the United Arab Emirates

Publication date: Available online 28 September 2016
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Afrozul Haq, Sunil J. Wimalawansa, Pawel Pludowski, Fatme Al Anouti
In the UAE and the Gulf region in general, there are several intricate public health issues in the context of vitamin D deficiency that needs to be addressed. Changes in lifestyle such as diet, lack of exercise, cultural habits, avoiding sun exposure due to excessive heat, and other risk factors predispose those who live in GULF countries, such as Emiratis likely to becoming vitamin D deficient. Consequently, the prevalence of vitamin D deficiency is high, and new guidelines are needed to overcome this major public health issue. Peer-reviewed papers related to guidelines and those vitamin D-related papers relevant to the Middle-Eastern region were extracted from multiple research databases using key words according to the general guidelines from the Preferred Reporting Items for Systematic Analysis. This guideline was prepared focusing on the United Arab Emirate and the Gulf populations, to overcome the high incidence of vitamin D deficiency and to improve overall health. We recommend the following vitamin D supplementations for different groups of people: (A) Breastfed infants supplement with 400 IU/day up to age 6 months, and 400–600 IU/day between 6 and 12 months, depending on daily intake of total vitamin D and sun exposure; (B) For children and adolescents of age 1–18 years supplement with 600–1000 IU/day depending on the body weight; (C) Adults greater than 18 years', supplementation with 1000–2000 IU/day is recommended, while, (D) the elderly (over 65 years) should be supplemented with 2000 IU/day, throughout the year; (E) Pregnant and breast feed women, 2000 IU/day from the first trimester of pregnancy. (F) Premature infants, supplementation of 400–800 IU/daystart from the first days of life. (G) For obese, individuals and those with metabolic syndrome, supplementation of 2000 IU/day (H) For individuals with dark skin complexions and for night workers, supplementation of 1000–2000 IU/day (25–50μg/day), throughout the year, depending on body weight. The goal of supplementation is to achieve and longer term maintenance of serum 25(OH)D concentration of 30–50ng/mL.



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Screening Sunscreens: Protecting the Biomechanical Barrier Function of Skin from Solar Ultraviolet Radiation Damage

Abstract

Objective

Solar ultraviolet (UV) radiation is ubiquitous in human life and well-known to cause skin damage that can lead to harmful conditions such as erythema. Although sunscreen is a popular form of protection for some of these conditions, it is unclear if sunscreen can maintain the mechanical barrier properties of skin. The objective of this study is to determine if in vitro thin film mechanics techniques adapted for biological tissue are able to characterize the efficacy of commonly used UV inhibitors and commercial sunscreens to protect the biomechanical barrier properties of stratum corneum (SC) from UV exposure.

Methods

The biomechanical properties of SC samples were assayed through measurements of the SC's drying stress profile and delamination energy. The drying stresses within SC were characterized from the curvature of a borosilicate glass substrate onto which SC had been adhered. Delamination energies were characterized using a double-cantilever beam (DCB) cohesion testing method. Successive DCB specimens were prepared from previously separated specimens by adhering new substrates onto each side of the already tested specimen in order to probe delamination energies deeper into the SC. These properties of the SC were measured before and after UV exposure, both with and without sunscreens applied, to determine the role of sunscreen in preserving the barrier function of SC.

Results

The drying stress in SC starts increasing sooner and rises to a higher plateau stress value after UVA exposure as compared to a non-UV exposed control specimens. For specimens that had sunscreen applied, the UVA exposed and non-exposed SC had similar drying stress profiles. Additionally, specimens exposed to UVB without protection from sunscreen exhibited significantly lower delamination energies than non-exposed controls. With commercial sunscreen applied, the delamination energy for UVB exposed and non-exposed tissue was consistent, even up to large doses of UVB.

Conclusion

In vitro thin film mechanics techniques can readily characterize the effects of SC's exposure to UV radiation. The methods used in this study demonstrated commercial sunscreens were able to preserve the biomechanical properties of SC during UV exposure, thus indicating the barrier function of SC was also maintained.

This article is protected by copyright. All rights reserved.

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T hromboxane A2 promotes the dev elopment of imiquimod-induced mouse psoriasis model via TP receptor

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Yuri Tanada-Ueharaguchi, Tetsuya Honda, Teruasa Murata, Makoto Arita, Yoshiki Miyachi, Kenji Kabashima




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The air exposure of normal human keratinocytes induces release of ATP and IL-1beta

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Kaori Inoue, Masashi Miyai, Toshihiko Hibino




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Editors Choice

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1





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Suppressed psoriatic inflammation in interferon regulatory factor-8 knockout mouse treated with imiquimod

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Tomoya Watanabe, Yukie Yamaguchi, Tomohiko Tamura, Michiko Aihara




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Hypoxia inducible factor-1α of Langerhans cell plays a critical role in a murine irritant dermatitis model

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Saeko Nakajima, Catharina Moniaga, Yoshiki Miyachi, Kenji Kabashima




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Analysis of spinal neurotransmitters in histaminergic and non-histaminergic itch

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Mitsutoshi Tominaga, Tasuku Akiyama, Mirela I. Carstens, Earl Carstens, Kenji Takamori




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Expression of nitric oxide-containing structures in the rat carotid body

Publication date: Available online 28 September 2016
Source:Acta Histochemica
Author(s): Dimitrinka Y. Atanasova, Nikolay D. Dimitrov, Nikolai E. Lazarov
The carotid body (CB) is a major peripheral arterial chemoreceptor organ that evokes compensatory reflex responses so as to maintain gas homeostasis. It is dually innervated by sensory fibers from petrosal ganglion (PG) neurons, and autonomic fibers from postganglionic sympathetic neurons of the superior cervical ganglion (SCG) and parasympathetic vasomotor fibers of intrinsic ganglion cells in the CB. The presence of nitric oxide (NO), a putative gaseous neurotransmitter substance in a number of neuronal and non-neuronal structures, was examined in the CB, PG and SCG of the rat using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) immunohistochemistry and retrograde tracing. One week after injecting the retrograde tracer Fast Blue (FB) in the CB, we found that a subset of perikarya in the caudal portions of the PG and SCG were FB-labeled. Histochemistry and immunohistochemistry revealed that the majority of large- and medium-sized PG and SCG cells were NADPH-d positive and displayed a strong NOS immunostaining. We also observed that many varicose nerve fibers penetrating the CB and enveloping the glomus cells and blood vessels were NADPH-d reactive and expressed the constitutive isoforms of NOS, nNOS and eNOS. In addition, some autonomic microganglion cells embedded within, or located at the periphery of the CB, and not glomus or sustentacular cells were nNOS-immunopositive while CB microvasculature expressed eNOS. The present results suggest that NO is a transmitter in the autonomic nerve endings supplying the CB and is involved in efferent chemoreceptor inhibition by a dual mechanism.



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Epitope-dependent pathogenicity of antibodies to collagenXVII/BP180 for blister formation

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Mayumi Wada, Wataru Nishie, Hideyuki Ujiie, Kentaro Izumi, Hiroaki Iwata, Ken Natsuga, Yoshimasa Kitagawa, Hiroshi Shimizu




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Bioactive molecules derived from umbilical cord mesenchymal stem cells

Publication date: Available online 28 September 2016
Source:Acta Histochemica
Author(s): Lipeng Bai, Danting Li, Jie Li, Zhengzhong Luo, Shumin Yu, Suizhong Cao, Liuhong Shen, Zhicai Zuo, Xiaoping Ma
Umbilical cord mesenchymal stem cells (UCMSCs) retain their intrinsic stem cell potential while at the same time displaying high proliferation rates, powerful differentiation capacity, and low immunogenicity. They can also secrete multiple bioactive molecules that exert specific physiological functions. Thus, UCMSCs represent excellent candidates for cell therapy in regenerative medicine and tissue engineering. Abundant preclinical research on different disease models has shown that UCMSCs can accelerate wound or nerve damage recovery and suppress tumor progression. In fact, UCMSCs are thought to possess a higher therapeutic potential than MSCs derived from other tissues. Increasing evidence suggests that the mechanism underlying UCSMCs efficacy depends mostly on cell secretions, in contrast to the early paradigm of cell replacement and differentiation. In this review, we discuss UCMSCs biological characteristics, their secretome-based therapeutic mechanism, and potential applications.



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Editorial board

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1





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NADPH-diaphorase reactivity and Fos-immunoreactivity within the ventral horn of the lumbar spinal cord of cats submitted to acute muscle inflammation induced by injection of carrageenan

Publication date: Available online 28 September 2016
Source:Acta Histochemica
Author(s): Vladimir A. Maisky, Olena P. Mankivska, Andriy V. Maznychenko, Oleh V. Vlasenko, Olexandr V. Dovgan', Eike D. Schomburg, Heinz Steffens
The NADPH-diaphorase activity and Fos-immunoreactivity within the ventral horn of the lumbar spinal cord were studied in cats with acute unilateral myositis following injection of carrageenan into the m.m. gastrocnemius-soleus. In carrageenan-injected cats maximum in the mean number of intensely stained NADPH-diaphorase reactive (NADPH-dr) neurons was found in lamina VII (+100%) and VIII (+33%) of the contralateral ventral horn of the L6/L7 segments as compared with control animals. The maximumal level of Fos-immunoreactivity was registered in the same laminae with ipsilateral predominance (39.3±4.6 and 7.6±0.9 cells), in comparison with the contralateral side (13.6±0.8 and 5.5±0.6 cells, respectively; P<0.05). We also visualized low-intensely stained and double labelled (Fos immunoreactive+low-intensely stained NADPH-dr) multipolar and fusiform Renshaw-like cells (RLCs) within the ventral horn on both sides of the L6/L7 segments in carrageenan-injected cats. We visualized the double labelled (Fos-ir+NADPH-dr) multipolar and fusiform Renshaw-like cells (RLCs) within the ventral horn on both sides of the L6/L7 segments in carrageenan-injected cats. A significant difference in the mean number of RLCs was recorded between the ipsi- and contralateral sides in the lamina VII (13.6±2.5 vs. 4.9±0.7 cells, respectively). We suppose that activation of inhibitory RLCs in ipsilateral lamina VII could be directed on attenuation of activation of motoneurons during muscle pain development. Our study showed that a significant contralateral increase in the number of NADPH-dr cells is accompanied by an ipsilateral increase in c-Fos expression in lamina VII. These data may suggest that NADPH-dr neurons of the contralateral ventral horn through commissural connections also involved in the maintenance of the neuronal activity associated with acute muscle inflammation. It is also hypothesized, that during acute myositis, plastic changes in the ventral horn activate the processes of disinhibition due to an increase in the number of NADPH-d-reactive neurons in the spinal gray matter.



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IL36RN mutations underlie impetigo herpetiformis and CARD14 c.526G>C is a risk factor for pustular psoriasis with psoriasis vulgaris

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Kazumitsu Sugiura, Naoki Oiso, Shin Iinuma, Hiromasa Matsuda, Masako Minami-Hori, Akemi Ishida-Yamamoto, Akira Kawada, Hajime Iizuka, Masahiko Muto, Masashi Akiyama




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Gain-of-function mutation in PIK3R1 in a patient with a narrow clinical phenotype of respiratory infections

Publication date: Available online 28 September 2016
Source:Clinical Immunology
Author(s): María Teresa Martínez-Saavedra, Sonia García-Gomez, Ana Domínguez Acosta, Juan Jesús Mendoza Quintana, Jesús Poch Páez, Eduardo J. García-Reino, Gracián Camps, Rubén Martinez-Barricarte, Yuval Itan, Bertrand Boisson, Silvia Sánchez-Ramón, José Ramón Regueiro, Jean-Laurent Casanova, Carlos Rodríguez-Gallego, Rebeca Pérez de Diego
Antibody deficiencies can be caused by a variety of defects that interfere with B-cell development, maturation, and/or function. Using whole-exome sequencing we found a PIK3R1 mutation in a patient with hypogammaglobulinemia and a narrow clinical phenotype of respiratory infections. Early diagnosis is crucial; careful analysis of B and T-cells followed by genetic analyses may help to distinguish activated PI3K-delta syndrome (APDS) from other, less severe, predominantly antibody deficiencies.



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IRF7 controls the production of autoantibodies against theDNA- and RNA-containing autoantigens in murine lupus

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Fumi Miyagawa, Hideo Asada




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Genetics of human lupus nephritis

Publication date: Available online 28 September 2016
Source:Clinical Immunology
Author(s): Taro Iwamoto, Timothy B Niewold
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by immune complex formation with multi-organ manifestations. Lupus nephritis (LN) is one of the most severe types of organ damage in SLE, and it clearly contributes to increased morbidity and mortality due to SLE. LN occurs more frequently and is more severe in non-European ancestral backgrounds, although the cause of this disparity remains largely unknown. Genetic factors play an important role in the pathogenesis of SLE. Although many SLE susceptibility genes have been identified, the genetic basis of LN is not as well understood. While some of the established general SLE susceptibility genes are associated with LN, recent discoveries highlight a number of genes with renal functions that are specifically associated with LN. Some of these genes associated with LN help to explain the disparity in the prevalence of nephritis between individuals with SLE, and also partially explain differences in LN between ancestral backgrounds. Moreover, not only the gene mutations, but also post-translational modifications seem to play important roles in the pathogenesis of LN. Overall it seems likely that a combination of general SLE susceptibility genes cooperate with LN specific risk genes to result in the genetic propensity for LN. In this review, we will outline the genetic contribution to LN and describe possible roles of LN susceptibility genes.



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T cell expansion study using the lesional skin provides evidence for the role of drug-specific Tc1 and Th17 cells in severe drug eruptions

Publication date: October 2016
Source:Journal of Dermatological Science, Volume 84, Issue 1
Author(s): Toshiharu Fujiyama, Hideo Hashizume, Takatsune Umayahara, Kazuki Tatsuno, Taisuke Ito, Yoshiki Tokura




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