Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-κB signalling pathway

Abstract

Aim

The aim of the present study is to investigate the anti-inflammatory effect of melatonin in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis through the inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signalling pathway and activation of melatonin receptor.

Methods

Colitis was induced in Wistar rats by administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50% ethanol solution using a flexible plastic rubber catheter into the colon via the anus. This resulted in incidence of colitis on the first day, and all treatments were conducted for 10 days after induction of colitis. Melatonin was administered intraperitoneally (i.p.) at doses of 1, 5, and 10 mg/kg/day. Luzindole (non-selective MT1/MT2 receptor antagonist) was administered i.p. at dose of 5 mg/kg/day 15 min prior to melatonin injection. During the experiment, animals were monitored for the appearance of diarrhoea, body weight loss, and rectal bleeding. Myeloid peroxidase enzyme and tumour necrosis factor-α (TNF-α) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB p65, and inhibitor of kappa B (I-κB) were detected by western blotting analysis.

Results

Treatment with melatonin improved weight loss, mucosal, and histological damage compared with TNBS group. In addition, melatonin decreased TNBS-induced up-regulation of TLR4, MyD88, and NF-κB p65, and increased down-regulation of I-κB proteins. On the other hand, the administration of luzindole resulted in the inhibition of melatonin effects.

Conclusions

It seems that the inhibition of TLR4/NF-κB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced rat colitis.

Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress

Abstract

Rutin, found widely in traditional Chinese medicine materials, is used to treat eye swelling and pain, hypertension, and hyperlipidemia. In the present study, a mouse mastitis model induced by lipopolysaccharide (LPS) was established to explore rutin's inhibitory mechanism on mastitis via nuclear factor kappa B (NF-κB) inflammatory signaling and the relationship between NF-κB signaling and endoplasmic reticulum (ER) stress. Mice were divided into six groups: Control group, LPS model group, LPS + rutin (25, 50, and 100 mg/kg) and LPS + dexamethasone (DEX) group. DEX, rutin, and PBS (control and LPS groups) were administered 1 h before and 12 h after perfusion of LPS. After LPS stimulation for 24 h, to evaluate rutin's therapeutic effect on mastitis, the mammary tissues of each group were collected to detect histopathological injury, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 mRNA and protein levels; and glucose-regulated protein, 78 kDa (GRP78) protein levels. The protein and mRNA levels of TNF-α, IL-1β, and IL-6 in the LPS + rutin group were significantly lower than those in the LPS model group. Similarly, p50/p105, phosphorylated (p)-p65/p65 and p-inhibitor of nuclear factor kappa b kinase subunit beta (p-IKKβ)/IKKβ ratios in the LPS + rutin group (50 mg/kg) and LPS + rutin group (100 mg/kg) decreased significantly. GRP78 protein expression was significantly higher in LPS + rutin group (100 mg/kg). The structure of mammary tissue became gradually more intact and vacuolization of acini decreased as the rutin concentration increased. The nuclear quantity of p65 in the LPS + rutin group decreased significantly in a rutin dose-dependent manner. Rutin had an anti-inflammatory effect in the LPS-induced mouse mastitis model, manifested by inhibition of NF-κB pathway activation and attenuation of ER stress.

SB203580 attenuates acute lung injury and inflammation in rats with acute pancreatitis in pregnancy

Abstract

Acute pancreatitis in pregnancy (APIP) can lead to multiple maternal and fetal organ injury and mitogen-activated protein kinase (MAPK) signaling pathway may be involved in it; however, whether APIP can result in acute lung injury and P38MAPK signaling pathway is involved in the pathogenesis has not been elucidated. The present study was undertaken to investigate the participation of P38MAPK signaling pathway and the protective effect of SB203580, an inhibitor of P38MAPK on acute lung injury induced by APIP. Twenty-four late-gestation SD rats were randomly assigned to four groups: Sham operation (SO) group, SB302580 (SB) group, APIP group, and SB + APIP group. All the rats were killed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY) and lipase (LIPA) and histopathological changes. Histological assessment of the lung and inflammatory cell infiltration was performed by H&E and immunofluorescence assay. The lung wet/dry (W/D) weight ratio was determined, and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the protein expression of phosphorylated and total P38, tumor necrosis factor (TNF)-α, and intercellular adhesion molecules 1 (ICAM-1) in lung tissues. Obvious pathological changes existed in pancreas and lung after the induction of APIP, and their pathological scores were significantly higher than that of control group. The results showed that the phosphorylation of P38MAPK was elevated in the lung of APIP rats. Compared with APIP group, the intervention of SB203580 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated the secretion of TNF-α, IL-1β, and IL-6 in lung, reduced the inflammatory cells' infiltration and lung W/D ratio and inhibited the activation of P38MAPK signaling pathway. These results suggest that APIP can lead to acute lung injury and inflammation and SB203580 can inhibit the lung injury by inhibiting the P38MAPK signaling pathway and blocking the inflammatory responses.

Troubling Hope: Performing Inventive Connections in Discomforting Times

Abstract

In what follows, we revisit the most promising conceptions of "hope" while following Haraway's admonition to "stay with the trouble." Thirty-five years after Haraway's (1991) opening to the Manifesto for Cyborgs where she states that "irony is about contradictions that do not resolve into larger wholes" (p. 149), we move with her ceaseless task to eschew resolution and certainty, urging instead a radical contingency that is fundamental to thought itself. The radical contingency recognizes the limits of what any one individual or one species is capable of unto itself. Any such exceptionalism is spurned. The possibilities of thinking-with, and making-with, are the necessary path of the troubled present. And there is no escaping the present, a present that is thick with affliction but is still unfinished and ongoing. We enter into the thick presence of our ongoing conversation around hope by revisiting the concepts that help us to think our thoughts, exploring how these conceptions worked and did not work for our collective thinking. We then build on the concepts' appendages, their attachments and detachments to our conversation around hope, by sketching Haraway's materialist challenge to hope (and despair), and her refusal of futurism and contingency that raise some questions about the potentialities of "critical hope." Finally, we situate our work within an understanding of the "pedagogical work of the concept," drawing a line from Haraway to Stengers to Deleuze, which allows us to explore resonance between concepts and posit a "pedadogy of the concept" to situate the limits of hope and potentialities of "staying with the trouble." To work towards a pedagogy that "stays with the trouble," we extend Haraway's critique that it matters "what thoughts think thoughts" by suggesting that it also matters which feelings we feel with, highlighting the vital necessity of feeling to the project of staying with the trouble.

Reinforcement of barrier function – skin repair formulations to deliver physiological lipids into skin

International Journal of Cosmetic Science, Volume 0, Issue ja, -Not available-.

Consensus research priorities for facial palsy: a Delphi survey of patients, carers, clinicians and researchers

Despite the potential negative impact of facial palsy, major gaps in understanding persist surrounding the treatment and care of those affected. This collaborative three-round Delphi process aimed to identify priorities for future facial palsy research, from the perspective of clinicians, researchers, patients and carers. It also determined whether the research priorities of patients and carers aligned with those of health professionals and researchers.In Round one participants (n=85) were asked to generate research questions via focus groups or an online or postal survey.

Granuloma Annulare’s Triangular Association with Malignancy

Effect of iron plaque and selenium on mercury uptake and translocation in rice seedlings grown in solution culture

Abstract

A hydroponics experiment was conducted to investigate the effect of iron plaque on root surfaces and selenium (Se) on the uptake and transfer of mercury (Hg) in rice seedlings by adding in the EDTA-Fe (0, 10, 30, 50, 70 mg Fe l⁻¹) into the solution to produce a different amount of iron plaque outside rice root. After 24 h, the red-brown iron plaque was formed on the root surface, and the amount of iron plaques was positively correlated with the amount of Fe in the solution. The iron plaque deposited on the root surface has a strong adsorption effect on the inorganic Hg. The addition of Se could promote the adsorption of Hg²⁺ on the iron plaque of rice, and the introduction of Se could increase the adsorption capacity of Hg on iron plaque on average by 1.42 times. The Hg was extracted by DCB (Dithionite-citrate-bicarbonate) up to between 66.2 and 67.8% of the total Hg when the roots with iron plaque (Fe70) were incubated with the combination of 5 μmol L⁻¹ of HgCl₂ and 5 μmol L⁻¹ of Na₂SeO₃ for an hour. After 3 days, the content of Hg in the iron plaque decreased to 6.3–33.9%, indicating that part of the inorganic Hg adsorbed by the iron plaque could be reabsorbed and used. Besides that, the iron plaque allowed the Hg to stay longer in the iron plaque, which hindered the transfer of Hg to the shoot significantly. Hg adsorbed in the iron plaque can be desorbed by low-molecular-weight organic acids, which was equivalent to desorption of Hg from ferric hydroxide oxides. Hg adsorbed on the iron plaque can be moved back to the rest of the plant. These results suggest that the iron plaque and Se in the root surface might play a role as "physical buffer" in the absorption and transfer of Hg.

Defending stance voluntarism

Abstract

In this paper, I argue that stance voluntarism is a coherent and useful view for understanding debates about the ontological commitments warranted by science. To do so, I first engage in a defensive move: I rescue stance voluntarism from what I take to be the most pressing objection to have emerged in recent literature, which I call the 'irrationality objection'. According to this objection, an agent courts irrationality by simultaneously holding an epistemic stance and believing that stance voluntarism is true. I argue that this objection is based on a misunderstanding of stance voluntarism and the kinds of reasons that agents take themselves to have for their adopted stances. I then make the positive contention that we can expect the idea of stance voluntarism, thus saved, to not only be a defensible, but also a useful framework for understanding ontological disputes within science. I do this by presenting a case study from contemporary cosmology in which it is so. Combining these two claims, I argue that stance voluntarism is a coherent and useful view for understanding some ongoing disputes about ontology within scientific contexts.

Construction of a risk model for the development of metachronous squamous cell carcinoma after endoscopic resection of esopahageal squamous cell carcinoma

Abstract

Background

Previously, we identified that rs1229984 in ADH1B, rs671 in ALDH2, and smoking status were independently associated with the risk of developing metachronous squamous cell carcinoma (SCC) after endoscopic resection (ER) for esophageal SCC (ESCC). However, this analysis included cases with short-term follow-up. In the present study, we investigated the environmental and genetic factors associated with developing metachronous SCC using long-term follow-up observation after ER for ESCC.

Methods

One hundred and thirty ESCC patients who underwent treatment with ER were followed up using endoscopy for ≥ 30 months. We investigated the incidence of, and genetic/environmental factors associated with, metachronous SCC development after ER for ESCC. We also analyzed the potential risk factors for multiple metachronous SCC development using Cox's proportional hazards model. Moreover, we constructed a risk model for the development of metachronous SCC after ER for ESCC.

Results

Male, rs1229984, rs671, alcohol consumption (> 20 g/day), smoking, and multiple Lugol-voiding lesions (LVLs) significantly affected the incidence of multiple metachronous SCCs. Multiple Cox proportional analysis revealed that rs1229984, rs671, alcohol consumption, smoking, and multiple LVLs were independently associated with the risk of developing metachronous SCC. Patients who had ≤ 2 risk factors did not develop metachronous SCC, and the risk of developing metachronous SCC in patients with ≥ 3 risk factors was significantly higher than in patients with ≤ 2 risk factors.

Conclusion

The risk model using these 5 genetic and environmental factors is useful as an indication for multiple metachronous development in ESCC patients.

Preparation and application of magnetic nitrogen-doped rGO for persulfate activation

Abstract

A heterogeneous catalyst (M-N-rGO) composed of stability enhanced magnetic iron oxide nanoparticles and nitrogen-doped reduced graphene oxide was synthesized and characterized by SEM, XRD, BET, and XPS. It showed excellent catalytic degradation properties in advanced oxidation technology. In the presence of 200 mg/L catalyst and 135 mg/L persulfate at pH 5, 95% of 10–20 mg/L methylene blue could be degraded in 90 min with the TOC removal efficiency of 50%. The rate constant based on pseudo-first-order kinetics ranged from 0.0227 to 0.0488/min in the temperature range of 15 to 32 °C, and the activation energy was 32.5 kJ/mol. Under the optimal operation conditions, 20 mg/L of 2,4-dichlorophneol (2,4-DCP) could be removed almost completely. EPR analysis showed that sulfate and hydroxyl radicals were responsible for degradation of pollutants, and radical quenching experiments indicated that nonradical pathway also played a role in pollutant removal. And a mechanism for M-N-rGO and persulfate system was elucidated. This catalyst was easy for preparation, low-cost, highly effective, convenient for separation, and could be used effectively for four times through 0.1 mol/L H₂SO₄ regeneration. It provided a choice for wastewater treatment in practice.

Orthogonal design-guided preparation of multi-level porous-activated carbon by pyrolysis of waste polyester textiles

Abstract

Multi-level porous amorphous-activated carbon with excellent adsorption performance was prepared by a ZnCl₂-assisted pyrolysis of waste polyester textiles. Experimental parameters were optimized by using orthogonal design. Result of orthogonal design revealed that pyrolysis temperature and pyrolysis time were the dominant individual factors. Samples prepared at the optimal condition were systematically characterized by Brunauer-Emmett-Teller (BET) porosity analyzer, FT-IR spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM). Iodine (I₂), methylene blue (MB) and phenol (PhOH) were selected as target dyes to measure the adsorption performance. Experimental results showed that porous-activated carbon with multi-level pores could be obtained by optimizing experimental parameters. The specific surface area and total pore volume were calculated to be 846.37 m² g⁻¹ and 0.726 cm³ g⁻¹, respectively. Benefit from its multi-level rich porosity, the optimized sample possessed attractive adsorption performance toward different types of dyes. The corresponding adsorption capacity toward I₂, MB, and PhOH were calculated to be 980.48, 384.00, and 300.62 mg g⁻¹, respectively.

Palpebral cutaneous melanomas: a review of 17 cases from a tertiary center

International Journal of Dermatology, EarlyView.

Development of the International Severe Asthma Registry (ISAR): a modified Delphi study

Publication date: Available online 1 September 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Lakmini Bulathsinhala, Nevaashni Eleangovan, Liam G. Heaney, Andrew Menzies-Gow, Peter G. Gibson, Matthew Peters, Mark Hew, Job FM. van Boven, Lauri Lehtimäki, Eric van Ganse, Manon Belhassen, Erin Harvey, Luis Perez de Llano, Anke H. Maitland-van der Zee, Nikolaos Papadopoulos, J. Mark FitzGerald, Celeste Porsbjerg, G. Walter Canonica, Vibeke Backer, Chin Kook Rhee

Abstract

Background

The lack of centralised data on severe asthma has resulted in a scarcity of information about the disease and its management. The development of a common data collection tool for the International Severe Asthma Registry (ISAR) will enable standardised data collection, subsequently enabling data interoperability.

Objectives

To create a standardised list of variables for the first international registry for severe asthma via expert consensus.

Methods

A modified Delphi process was used to reach consensus on a minimum set of variables to capture in ISAR: the core variables. The Delphi panel brought together 27 international experts in the field of severe asthma research. The process consisted of three iterative rounds. In each round, all Delphi panel members were issued an electronic ISAR Delphi workbook to complete and return to the ISAR Delphi administrator. Workbooks and result summaries were anonymously distributed by the Delphi administrator to all panel members at subsequent rounds. Finalisation of the core variable list was facilitated by two face-to-face meetings.

Results

Of the initial 747 selected variables, the Delphi panel reached a consensus on 95. The chosen variables will allow severe asthma to be assessed against patient demographics and medical history, patient-reported outcomes, diagnostic information and clinical characteristics. Physician-reported outcomes such as non-adherence and information about treatment and management strategies will also be recorded.

Conclusion

This is the first global attempt to generate an international severe asthma registry using a common set of core variables to ensure that data collected across all participating countries are standardised.

Hymenoptera Venom Extracts in Clinical Practice

Publication date: Available online 1 September 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): James M. Tracy, David BK. Golden

Abstract

Venom immunotherapy is the only treatment for the prevention of anaphylaxis and remains the prototypical model for its diagnosis and management. Unlike other causes of anaphylaxis, such as foods and drugs, preventative treatment is highly effective and widely available. Hymenoptera venoms are also unique in that the primary allergens are directly measurable in terms of micrograms, rather than labeled based on potency. As such, venoms were the first truly standardized extracts. However, Hymenoptera venom presents unique challenges in collection, processing and stabilization of the venom extract product. Historically, there have been minor variations in insect composition in venom extract content. These differences were in part, based on variation of insect availability and venom collection and have created minor challenges. However, it is a recognized need that venom extracts contain an optimal and complete repertoire of relevant venoms so as to be assured of appropriate diagnosis and treatment. As such, insect availability and collection, as well as storage, stability and sterility of venom extracts have remained critical components to appropriate diagnosis and prevention of venom induced anaphylaxis. In recent years there has been concerns of adequate supplies of venom for appropriate diagnosis and treatment of venom allergy, but these concerns seem to have stabilized, with the movement to a single venom supplier. This movement to a single supplier may provide its own challenges.

Drug Rash Eosinophilia and Systemic Symptoms (DRESS) Syndrome Identified in the Electronic Health Record Allergy Module

Publication date: Available online 31 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Anna R. Wolfson, Li Zhou, Yu Li, Neelam A. Phadke, Ohn A. Chow, Kimberly G. Blumenthal

Abstract

Background

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but severe hypersensitivity reaction that remains poorly characterized in the US.

Objective

We aimed to identify and describe DRESS syndrome cases in an integrated healthcare system using electronic health record (EHR) allergy module free text searches.

Methods

We identified DRESS syndrome cases with rash, absolute eosinophil count ≥500/L, organ involvement, and RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions [SCAR]) to Drugs and Collection of Biological Samples) score ≥2 by reviewing patients from 1980-2016 whose EHR allergic reaction matched DRESS-related keywords. Liver injury required alanine aminotransferase ≥100U/L and renal injury required creatinine increase by ≥0.5mg/dL or 50%. Patient and DRESS characteristics were described, resource use was determined, and cost was estimated.

Results

Among 3,162,562 patients with 3,319,387 million allergy entries, 538 reactions matched keywords, and 69 were DRESS cases (prevalence 2.18 in 100,000). DRESS patients had liver (42%) or renal (42%) injury; 11 (16%) had both liver and renal injury. Primary drug culprits were antibiotics (74%) (vancomycin [39%], beta-lactams [23%], fluoroquinolones [4%], tetracyclines [4%], and sulfonamides [3%]) and anticonvulsants (20%). Of 65 (94%) hospitalized DRESS patients, 43 (66%) were hospitalized for DRESS syndrome management with median length of stay 9 days [IQR, 6-17 days] and cost approximately $17,101 per patient.

Conclusions

Using free text search of the EHR allergy module identified a large US DRESS syndrome cohort. DRESS prevalence was 2.18 per 100,000 patients. Both liver and kidney injury were frequent, and vancomycin was the most common drug culprit. DRESS cases were morbid and resource-intensive.

Routine clinical utility of honeybee venom allergen components

Publication date: Available online 31 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Martina Vachová, Petr Panzner, Peter Kopac, Urska Bidovec Stojkovič, Peter Korošec

Adjuvant treatment for high-risk renal-cell carcinoma: the jury is still out

Larva migrans cutánea facial de origen autóctono en España

Publication date: September 2018

Source: Actas Dermo-Sifiliográficas, Volume 109, Issue 7

Author(s): C. Durán-Vian, I. Vilanova-Udaniz, B. Castro-Gutierrez, M.A. González-López

Enfermedad de Kikuchi-Fujimoto con compromiso de cuero cabelludo

Publication date: September 2018

Source: Actas Dermo-Sifiliográficas, Volume 109, Issue 7

Author(s): A. Combalia, X. Fustà-Novell, A. García-Herrera, J. Ferrando