The impact of fibromyalgia syndrome on obstructive sleep apnea syndrome in terms of pain threshold, daytime symptoms, anxiety, depression, disease severity, and sleep quality: a polysomnographic study

BackgroundCurrent studies have focused on the association of fibromyalgia syndrome (FMS) and obsctructive sleep apnea syndrome (OSAS). Results of these studies on the effect of this association have been inconsistent. The current study aimed to investigate the effect of FMS on OSAS regarding sleep quality, pressure pain threshold, fatigue, daytime symptoms, anxiety, and depression, and also to determine the relationship between OSAS severity and FMS.MethodsIn a cross-sectional design, patients diagnosed with OSAS were evaluated in two groups comparing those with and those without FMS. Data on demographics, headache, morning fatigue, and chronic pain duration were collected. Questionnaires including the Fatigue Severity Scale (FSS), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were completed. Pressure pain threshold, tender points, and polysomnographic data were recorded.ResultsOf 69 patients, 27 were diagnosed with FMS + OSAS and 42 were diagnosed as OSAS only. Statistically significant differences were found between the two groups in VAS, pain duration, morning fatigue, headache, BAI, tender point count, FIQ and FSS scores, and algometer measurements. All polysomnografic data were compared, and no statistically significant differences were found between the two groups. There were no statistically significant differences in the algometer, BDI, BAI, FIQ, and FSS scores when analyzed according to the severity of OSAS.ConclusionThe findings suggest that FMS has no effect on polysomnographic parameters of OSAS. Headache, daytime fatigue, anxiety, depression, pain duration, and pain intensity are higher while the pressure pain threshold is lower when FMS is present. No correlation was found between OSAS severity and FMS, fatigue, pressure pain threshold, depression, and anxiety.Clinical Trial Registration Number: NCT05367167/date: April 8, 2022

NF-κB targeting by way of IKK inhibition sensitizes lung cancer cells to adenovirus delivery of TRAIL

<p>Abstract</p> <p>Background</p> <p>Lung cancer causes the highest rate of cancer-related deaths both in men and women. As many current treatment modalities are inadequate in increasing patient survival, new therapeutic strategies are required. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells but not in normal cells, prompting its current evaluation in a number of clinical trials. The successful therapeutic employment of TRAIL is restricted by the fact that many tumor cells are resistant to TRAIL. The goal of the present study was to test a novel combinatorial gene therapy modality involving adenoviral delivery of TRAIL (Ad5hTRAIL) and IKK inhibition (AdIKKβKA) to overcome TRAIL resistance in lung cancer cells.</p> <p>Methods</p> <p>Fluorescent microscopy and flow cytometry were used to detect optimum doses of adenovirus vectors to transduce lung cancer cells. Cell viability was assessed via a live/dead cell viability assay. Luciferase assays were employed to monitor cellular NF-κB activity. Apoptosis was confirmed using Annexin V binding.</p> <p>Results</p> <p>Neither Ad5hTRAIL nor AdIKKβKA infection alone induced apoptosis in A549 lung cancer cells, but the combined use of Ad5hTRAIL and AdIKKβKA significantly increased the amount of A549 apoptosis. Luciferase assays demonstrated that both endogenous and TRAIL-induced NF-κB activity was down-regulated by AdIKKβKA expression.</p> <p>Conclusions</p> <p>Combination treatment with Ad5hTRAIL and AdIKKβKA induced significant apoptosis of TRAIL-resistant A549 cells, suggesting that dual gene therapy strategy involving exogenous TRAIL gene expression with concurrent IKK inhibition may be a promising novel gene therapy modality to treat lung cancer.</p

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

BACKGROUND: Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). METHODS: TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. RESULTS: MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4 expression. Furthermore, a DcR2 siRNA approach lowered TRAIL-R4 expression on surface and this sensitized MCF7 cells to TRAIL. CONCLUSION: The expression of TRAIL-R4 decoy receptor appeared to be well correlated with TRAIL resistance encountered in breast cancer cells. Both adenovirus mediated IKKβKA expression and a DcR2 siRNA approach sensitized MCF7 breast cancer cells to TRAIL