Testosterone as a regulator of immune system via modulation of toll-like receptor 4/extracellular signal-regulated kinase signaling pathway

There is a growing body of evidence supporting the immunomodulation effects of testosterone. Previous researches have focused on its direct blunt inflammatory effect on mediation of cytokines secretion through down-regulated expression of toll-like receptor 4 (TLR4). However, how testosterone modulates immune responses via mechanisms of TLR4 downstream molecules has not yet been elucidated. Recently, we have firstly confirmed that testosterone deficiency is the main reason that caused the exacerbate inflammation status in rat spleen. Orchidectomy in rats resulted in a markedly enhance of spleen weight (splenomegaly) and basal production of nitric oxide (NO) from splenocytes. Moreover, lipopolysaccharide (LPS) amplified proliferation rate of splenocytes and the production of tumor necrosis factor-alpha (TNF-α) following castration. Extracellular signal-regulated kinase (ERK) is a critical mediator of TLR4 cascades, and we further examined whether absence of endogenous testosterone affects ERK expression. As anticipated, orchidectomized rats manifested an increased phosphorylation of ERK. Furthermore, testosterone administration was demonstrated to be associated with a diminished LPS-evoked TNF-α and NO secretion in a dose-dependent manner. In the present study, we answered how testosterone withdrawal affects downstream signaling cascades of TLR4 and supports that testosterone might potentially ameliorate inflammatory responses. Our findings mention the possibility that testosterone functions might serve as a useful endogenous regulator of immune responses

Revisiting "integrating a cost-reduction shipment plan into a single-producer multi-retailer system with rework" using an alternative approach

This study revisits a single-producer multi-retailer system with a cost-reduction shipment plan and rework [1] using an alternative approach. Unlike the conventional method that uses differential calculus on system cost function to prove its convexity and derive the optimal production-shipment policy, we proposed an algebraic solution procedure to the problem. Such a straightforward approach may enable the practitioners with little knowledge of calculus to understand real supply chain systems more easily

Down regulation of acrolein on corticosterone secretion in male rats

Acrolein is a small unsaturated aldehyde and can be found in a wide range of resources including all types of smoke and exhaust gases from gasoline engines. Although the toxicity and damage of acrolein have been recognized, the action mechanisms of acrolein, especially that of acrolein on the response of stresshormones are still unclear. The present study hypothesized that administration of acrolein altered the secretion of both adrenocorticotropin (ACTH) and corticosterone via the regulation of steroid biosynthetic pathway in rat zona fasciculata-reticularis (ZFR) cells. Both in vivo and in vitro approaches were uased. In the in vivo study, intraperitonal injection of acrolein (2 mg/ml/kg) once daily for 1 or 3 days resulted in a reduction of plasma levels of ACTH and corticosterone as well as the intracellular cAMP and ACTH-induced secretion of corticosterone. The protein expression of ACTH receptor (ACTHR) in rat ZFR cells was also reduced by 40-60% after treatment of acrolein for 1 day and 3 days, respectively. In the in vitro study, rat ZFR cells were prepared and chanllenged with ACTH (10-9 M), forskolin (an adenylyl cyclase activitior, 10-5 M), 8-Br-cAMP (a permeable synthetic cAMP, 5x10-5 M), 25-OH-cholesterol (10-5 M) ± trilostane (an inhibitor of 3?-hydroxysteroid dehydrogenase, 3?-HSD, 10-5 M). The evoked release of corticosterone by ACTH, forskolin, 8-Br-cAMP and the induced release of pregnenolone in response to 25-OH-cholesterol plus triolostane were decreased. Since the accumulation of pregnenolone after blocking 3?-HSD by trilostane represents the activity of P450scc, therate-limiting step of steroid biosynthesis, we suggest that not only the cAMP pathway was inhibited, but also the enzyme activity of P450scc was attenuated following administration of acrolein. Although insignificant, the protein expression of steroidogenic acute regulatory protein (StAR) was decreased by 40% in ZFR cells after treatment of acrolein in vivo. Incubation of ZFR cells with acrolein (10-9~10-7 M) also decreased the in vitro release of corticosterone. These results suggest that administration of acrolein inhibited corticosterone production via the attenuation of cAMP pathway, StAR protein expression, and the enzyme activity of P450scc. The attenuation of protein expression of ACTHR (also named melanocortin 2 receptor, MC2R) and reduced secrection of ACTH indicated that the hypothalamus-pituitary-adrenal (H-P-A) axis was also down- regulated by the administration of acrolein

The joint influence of quality assurance and postponement on a hybrid multi-item manufacturing-delivery decision-making

The present research explores the collective influence of quality assurance and postponement on a hybrid multiproduct replenishing-delivery decision-making. Assume the required multiproduct has a standard (common) component, and our replenishing-delivery model has incorporated a two-phase postponement strategy. The first phase makes all standard components and hires an external supplier to partially provide the required parts to cut short the needed uptime. In contrast, the second phase fabricates the finished multiproduct in sequence. To ensure the desired merchandise quality, we apply a quality-assurance action to the in-house processes to screen and remove scrap items and rework the repairable defects in both stages. Upon completing each merchandise, these products are transported to the customer in n fixed-quantity shipment in fixed-time intervals. We employ math modeling and formulating approaches to gain the overall supply-chain operating expenses comprising subcontracting, fabricating, stock holding, transportation, and customer holding costs. By minimizing system operating expenses, this research determines the optimal replenishing-delivery policy. Lastly, we give a numerical example to demonstrate our study’s applicability and usefulness/capability for facilitating managerial decision-making

Taxonomy of the family Arenaviridae and the order Bunyavirales : update 2018

In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.Peer reviewe

Anti-inflammatory mechanism of moderate aerobic exercise in spleen: focus on TLR4/PI3K/Akt signaling pathway

[[abstract]]Although exercise offers a promising nonpharmacological effect on the anti-inflammatory action, few studies have precisely identified the signaling transduction pathways required for the immunomodulatory properties of exercise. Participation of toll-like receptor 4 (TLR4)-dependent signaling pathway in immunosuppressive reactions via triggered phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) expression is now well documented. However, the anti-inflammatory molecular mechanisms of moderate aerobic exercise involve PI3K/Akt signaling have not been largely defined. Here we have demonstrated that aerobic exercise training suppresses the secretion of inflammatory molecules, e.g. tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and nitric oxide in lipopolysaccharide (LPS)-stimulated primary splenocytes, while simultaneously attenuating the proliferation of splenocytes. To confirm the amelioration effects of exercise in the above aspects, dexamethasone was shown to reduce the LPS-elicited TNF-α and IL-6 secretion in a dose-dependent manner in the splenocytes of trained rats. On the other hand, the expressions of TLR4 and its known cascades target proteins, phospho-nuclear factor-κB (phospho-NF-κB), were diminished following aerobic exercise training, whereas PI3K/phospho-Akt expressions were up-regulated in rat spleen. However, we did not find a significant difference in the phospho-p38 expression after exercise training. In the present study, we provide novel lines of evidence to suggest that anti-inflammatory responses are due to the impairment of TLR4, NF-κB and exaltation of PI3K/Akt expressions by exercise training. Our work proposes the possibility that moderate aerobic exercise training may serve as an efficacious regulator of the immune cell biology through the TLR4-dependent pathway in spleen

Testosterone as a regulator of immune system via modulation of toll-like receptor 4/extracellular signal-regulated kinase signaling pathway: DOI: 10.14800/ics.1407

There is a growing body of evidence supporting the immunomodulation effects of testosterone. Previous researches have focused on its direct blunt inflammatory effect on mediation of cytokines secretion through down-regulated expression of toll-like receptor 4 (TLR4). However, how testosterone modulates immune responses via mechanisms of TLR4 downstream molecules has not yet been elucidated. Recently, we have firstly confirmed that testosterone deficiency is the main reason that caused the exacerbate inflammation status in rat spleen. Orchidectomy in rats resulted in a markedly enhance of spleen weight (splenomegaly) and basal production of nitric oxide (NO) from splenocytes. Moreover, lipopolysaccharide (LPS) amplified proliferation rate of splenocytes and the production of tumor necrosis factor-alpha (TNF-?) following castration. Extracellular signal-regulated kinase (ERK) is a critical mediator of TLR4 cascades, and we further examined whether absence of endogenous testosterone affects ERK expression. As anticipated, orchidectomized rats manifested an increased phosphorylation of ERK. Furthermore, testosterone administration was demonstrated to be associated with a diminished LPS-evoked TNF-? and NO secretion in a dose-dependent manner. In the present study, we answered how testosterone withdrawal affects downstream signaling cascades of TLR4 and supports that testosterone might potentially ameliorate inflammatory responses. Our findings mention the possibility that testosterone functions might serve as a useful endogenous regulator of immune responses

Down regulation of acrolein on corticosterone secretion in male rats

Acrolein is a small unsaturated aldehyde and can be found in a wide range of resources including all types of smoke and exhaust gases from gasoline engines. Although the toxicity and damage of acrolein have been recognized, the action mechanisms of acrolein, especially that of acrolein on the response of stresshormones are still unclear. The present study hypothesized that administration of acrolein altered the secretion of both adrenocorticotropin (ACTH) and corticosterone via the regulation of steroid biosynthetic pathway in rat zona fasciculata-reticularis (ZFR) cells. Both in vivo and in vitro approaches were uased. In the in vivo study, intraperitonal injection of acrolein (2 mg/ml/kg) once daily for 1 or 3 days resulted in a reduction of plasma levels of ACTH and corticosterone as well as the intracellular cAMP and ACTH-induced secretion of corticosterone. The protein expression of ACTH receptor (ACTHR) in rat ZFR cells was also reduced by 40-60% after treatment of acrolein for 1 day and 3 days, respectively. In the in vitro study, rat ZFR cells were prepared and chanllenged with ACTH (10-9 M), forskolin (an adenylyl cyclase activitior, 10-5 M), 8-Br-cAMP (a permeable synthetic cAMP, 5x10-5 M), 25-OH-cholesterol (10-5 M) ± trilostane (an inhibitor of 3β-hydroxysteroid dehydrogenase, 3β-HSD, 10-5 M). The evoked release of corticosterone by ACTH, forskolin, 8-Br-cAMP and the induced release of pregnenolone in response to 25-OH-cholesterol plus triolostane were decreased. Since the accumulation of pregnenolone after blocking 3β-HSD by trilostane represents the activity of P450scc, therate-limiting step of steroid biosynthesis, we suggest that not only the cAMP pathway was inhibited, but also the enzyme activity of P450scc was attenuated following administration of acrolein. Although insignificant, the protein expression of steroidogenic acute regulatory protein (StAR) was decreased by 40% in ZFR cells after treatment of acrolein in vivo. Incubation of ZFR cells with acrolein (10-9~10-7 M) also decreased the in vitro release of corticosterone. These results suggest that administration of acrolein inhibited corticosterone production via the attenuation of cAMP pathway, StAR protein expression, and the enzyme activity of P450scc. The attenuation of protein expression of ACTHR (also named melanocortin 2 receptor, MC2R) and reduced secrection of ACTH indicated that the hypothalamus-pituitary-adrenal (H-P-A) axis was also down- regulated by the administration of acrolein

Dynamic Simulation and Analysis of a LowVoltage Micro-Grid

Abstract-Thi