Transcriptomic and Lipidomic Profiles in Nasal Polyps of Glucocorticoid Responders and Non-Responders: Before and After Treatment

Background: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and mechanisms underlying different responses to systemic glucocorticoids (GC) remain unclear. The major aim of this study was to explore the transcriptomic and oxidative lipidomic signatures and the effects of GC in patients with different clinical responses.Methods: Nasal polyp biopsies were obtained before and after 14-day oral GC treatment from 16 patients with CRSwNP, and normal nasal mucosa specimens were collected from 12 control subjects. RNA sequencing and oxidative lipidomics were performed, and differential gene expression analysis was conducted in the Responder and Non-responder groups at baseline and after treatment.Results: In the Responder group, GC significantly improved clinical symptoms and reduced tissue eosinophil infiltration. Meanwhile, GC led to a pronounced transcriptomic reversion with robust suppression of inflammatory responses and abnormal metabolism of extracellular matrix, as well as restoration of cilia function. However, non-responders were mainly characterized by epithelial hyperplasia and keratinization, with much less transcriptomic improvement after GC treatment. Higher expression of type 2 inflammatory molecules (CCL13, IGHE, CCL18, CCL23, CCR3, and CLC) with lower levels of LACRT, PPDPFL, DES, C6, MUC5B, and SCGB3A1 were related to a stronger clinical response to GC. Besides decreased prostaglandins and increased leukotrienes, increased dysregulation in other oxylipid mediators derived from polyunsaturated fatty acids was determined in nasal polyps, which was ameliorated by GC treatment.Conclusion: Systemic GC exert anti-inflammatory effects, improve tissue remodeling, restore cilia function, and ameliorate dysregulation of oxylipid mediator pathway in CRSwNP. GC-responders exhibited different transcriptomic signatures from non-responders.

Download Full-text

Functional Evaluation of a “Lingual Ring” Oral Device Applied on Patients Affected by Temporo-Mandibular Disorders TMDs: A Comparative Clinical Trial

Applied Sciences ◽

10.3390/app11114832 ◽

2021 ◽

Vol 11 (11) ◽

pp. 4832

Author(s):

Giuseppe Currò ◽

Mario Ferlisi ◽

Alessandro Rampello ◽

Alessio Rampello ◽

Gianfranco Albergo

Keyword(s):

Clinical Trial ◽

Minimally Invasive ◽

Clinical Symptoms ◽

Functional Evaluation ◽

Clinical Symptomatology ◽

Therapeutic Protocol ◽

Before And After ◽

Clinical Responses ◽

Surgery Department ◽

Articular Pain

This study aims to evaluate the functional variations of the electromyographic response and clinical symptomatology in TMD patients. This study has been performed and compared before and after the application of a therapeutic protocol based on the use of an oral device working on the proper mandibular repositioning through the proprioceptive-based lingual re-education called “Lingual Ring”. Between January to December 2016, 32 TMD patients have been recruited out of a series of 321 individuals recruited at the Neurosensorial and Motorial Surgery Department, in Palermo (Italy). All the patients underwent the Surface Electromyography (sEMG) of Masseter and Temporal muscles, with different registrations at T0, T1, T2, and T3; to evaluate the variations of the Electromyographic values, it was assigned the application of the Lingual Ring as the only therapy. The study demonstrated a neat rebalancing of the EMG tracks and important improvements with the TMD related issues. The clinical responses, due to the treatment at the end of the therapeutic protocol, were: absence or reduction of muscular or articular pain; absence or reduction of articular noises; absence or reduction of the cephalalgia. Hence, significant results, both clinical and in terms of instrumental EMG, were assessed. We can affirm that the adopted methodology allowed the monitoring of the Electromyographic variation and clinical symptoms. Moreover, the usage of the “Lingual Ring device” allowed to carry out a simple and immediate therapeutic protocol that is minimally invasive, ensuring a clear rebalancing of the EMG tracks as well as the TMD related pain.

Download Full-text

Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

The Cerebellum ◽

10.1007/s12311-021-01313-z ◽

2021 ◽

Author(s):

Angela Sanna ◽

Paolo Follesa ◽

Paolo Tacconi ◽

Mariangela Serra ◽

Maria Giuseppina Pisu ◽

...

Keyword(s):

Spinocerebellar Ataxia ◽

Rating Scale ◽

Clinical Symptoms ◽

Therapeutic Use ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Motor Cortex Excitability ◽

Before And After ◽

Theta Burst ◽

Serum Bdnf

AbstractSpinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.

Download Full-text

Fucoxanthin Ameliorates Oxidative Stress and Airway Inflammation in Tracheal Epithelial Cells and Asthmatic Mice

Cells ◽

10.3390/cells10061311 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1311

Author(s):

Shu-Ju Wu ◽

Chian-Jiun Liou ◽

Ya-Ling Chen ◽

Shu-Chen Cheng ◽

Wen-Chung Huang

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Airway Inflammation ◽

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Eosinophil Infiltration ◽

Tracheal Epithelial Cells ◽

Tracheal Epithelial ◽

And Oxidative Stress

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.

Download Full-text

Endoscopically controlled surgery with open hemilaminectomy for the treatment of intradural extramedullary tumors: an operative technique and short-term outcomes of 20 consecutive cases

Chinese Neurosurgical Journal ◽

10.1186/s41016-020-00222-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xiaorong Yan ◽

Huiqing Wang ◽

Cai Li ◽

Yuanxiang Lin ◽

Lin Lin ◽

...

Keyword(s):

Surgical Technique ◽

Spinal Deformity ◽

Tumor Recurrence ◽

Clinical Symptoms ◽

Short Term ◽

Before And After ◽

Intradural Extramedullary ◽

Controlled Surgery

Abstract Background To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique. Methods In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis. Results All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity. Conclusion The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

Download Full-text

Peptide VSAK maintains tissue glucose uptake and attenuates pro-inflammatory responses caused by LPS in an experimental model of the systemic inflammatory response syndrome: a PET study

Scientific Reports ◽

10.1038/s41598-021-94224-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ismael Luna-Reyes ◽

Eréndira G. Pérez-Hernández ◽

Blanca Delgado-Coello ◽

Miguel Ángel Ávila-Rodríguez ◽

Jaime Mas-Oliva

Keyword(s):

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Glucose Uptake ◽

Inflammatory Responses ◽

Serum Levels ◽

Systemic Inflammatory Response ◽

Positron Emission ◽

Inflammatory Molecules ◽

Circulating Levels ◽

Lps Treatment

AbstractThe present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.

Download Full-text

Perturbations in Eosinophil Homeostasis following Treatment of Lymphatic Filariasis

Infection and Immunity ◽

10.1128/iai.68.1.93-99.2000 ◽

2000 ◽

Vol 68 (1) ◽

pp. 93-99 ◽

Cited By ~ 12

Author(s):

Ramya Gopinath ◽

L. E. Hanna ◽

V. Kumaraswami ◽

V. Perumal ◽

V. Kavitha ◽

...

Keyword(s):

Clinical Symptoms ◽

Wuchereria Bancrofti ◽

Activation Markers ◽

Interleukin 5 ◽

Hla Dr ◽

Before And After ◽

Early Peak ◽

Eosinophil Activation ◽

Later Phase ◽

Second Peak

ABSTRACT Treatment of patients with patent Wuchereria bancroftiinfection results in an acute clinical reaction and peripheral eosinophilia. To investigate the dynamics of the eosinophil response, changes in eosinophil activation and degranulation and plasma levels of eosinophil-active chemokines and cytokines were studied in 15 microfilaremic individuals in south India by sequential blood sampling before and after administration of 300 mg of diethylcarbamazine (DEC). Clinical symptoms occurred within 24 h. Plasma interleukin-5 (IL-5) and RANTES levels peaked 1 to 2 days posttreatment, preceding a peak peripheral eosinophil count at day 4. Major basic protein secretion from eosinophils paralleled IL-5 secretion, while levels of eosinophil-derived neurotoxin peaked at day 13 after treatment. Expression of the activation markers HLA-DR and CD25 on eosinophils rose markedly immediately after treatment, while expression of VLA-4 and α4β7 showed an early peak within 24 h and a second peak at day 13. Thus, the posttreatment reactions seen in filarial infections can be divided into an early phase with killing of microfilariae, clinical symptomatology, increases in plasma IL-5 and RANTES levels, and eosinophil activation and degranulation and a later phase with expression of surface integrins on eosinophils, recruitment of eosinophils from the bone marrow to tissues, and clearance of parasite antigen.

Download Full-text

Adjuvant corticosteroid therapy in hepatosplenic candidiasis-related IRIS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2012.018 ◽

2012 ◽

Vol 4 (1) ◽

pp. e2012018 ◽

Cited By ~ 3

Author(s):

Cengiz Bayram ◽

Ali Fettah ◽

Nese Yarali ◽

Abdurrahman Kara ◽

Fatih Mehmet Azik ◽

...

Keyword(s):

Corticosteroid Therapy ◽

Immune Reconstitution ◽

Inflammatory Responses ◽

Clinical Symptoms ◽

Lymphoblastic Leukemia ◽

Laboratory Findings ◽

Hepatosplenic Candidiasis ◽

Cell Acute Lymphoblastic Leukemia ◽

Inflammatory Syndrome ◽

Standard Risk

Hepatosplenic candidiasis (HSC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy and requires protracted antifungal therapy. Immune reconstitution inflammatory syndrome (IRIS) is best characterized as a dysregulated inflammatory responses triggered by rapid resolution of immunosuppression.We present a child diagnosed with standard-risk precursor B cell-acute lymphoblastic leukemia who developed HSC and Candida-related IRIS during recovery of neutropenia associated with induction chemotherapy. Addition of corticosteroid therapy to antifungal treatment is associated with the resolution of the clinical symptoms and laboratory findings

Download Full-text

CD4+ CD25+ Foxp3+ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

Infection and Immunity ◽

10.1128/iai.00578-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4763-4772 ◽

Cited By ~ 55

Author(s):

Raquel M. Gonçalves ◽

Karina C. Salmazi ◽

Bianca A. N. Santos ◽

Melissa S. Bastos ◽

Sandra C. Rocha ◽

...

Keyword(s):

Dendritic Cells ◽

Parasite Species ◽

Inflammatory Responses ◽

Clinical Symptoms ◽

Clinical Manifestations ◽

Surface Expression ◽

Interleukin 10 ◽

Treg Cells ◽

Experimental Models ◽

Necrosis Factor Alpha

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.

Download Full-text