Sensitizing TRAIL response via differential modulation of anti- and pro-apoptotic factors by AZD5582 combined with ER nanosomal TRAIL in neuroblastoma

xlomafota13 shared this article with you from Inoreader Sensitizing TRAIL response via differential modulation of anti- and pro-apoptotic factors by AZD5582 combined with ER nanosomal TRAIL in neuroblastoma Via histochem Acta Histochem. 2022 Jan 22;124(2):151856. doi: 10.1016/j.acthis.2022.151856. Online ahead of print. ABSTRACT Neuroblastoma is a metastatic brain tumor particularly common in children. The cure rate is below 50% for patients of high-risk condition. Novel therapeutic agents and approaches are needed to improve the cure rate. Tumor necrosis factor-related and apoptosis-inducing ligand (TRAIL) is a promising proapoptotic factor that rapidly induces apoptosis preferentially in t ransformed and cancerous cells. Unfortunately, the common TRAIL resistance in cancers has hampered the clinical application of the ligand. Previously we prepared a novel TRAIL-armed ER derived nanosomal agent (ERN-T) that overcomes TRAIL resistance in some cancer lines when combined with a synthetic antagonist of inhibitors of apoptosis proteins (IAPs), AZD5582. However, how AZD5582 sensitizes cancer cells to ERN-T remains not well understood. In this study we continued to test the therapeutic efficacy of the combinatory therapy of ERN-T and AZD5582 on neuroblastoma, aiming to reveal the molecular mechanism underlying the synergism between AZD5582 and ERN-T. The obtained data revealed that ERN-Ts overcame TRAIL resistance and showed significant cytotoxicity on the resistant neuroblastoma line SH-SH5Y when combined with AZD5582 whilst sparing normal cells. The combination of low doses of ERN-Ts and AZD5582 induced intensive apoptosis in SH-SY5Y but not in normal skin fibroblasts (NSF s). Importantly we discovered that TRAIL sensitization in SH-SY5Y was associated with the concomitant downregulation of antiapoptotic factors cFLIP, MCL-1 and IAPs and upregulation of proapoptotic protein BAX and the death receptor 5 (DR5) by the cotreatment of ERN-T and AZD5582. In vivo study demonstrated that the combination of ERN-T and AZD5582 constituted a highly effective and safe therapy for subcutaneous SH-SY5Y xenograft neuroblastoma in nude mice. In conclusion, we identified that the concomitant regulation of both antiapoptotic and proapoptotic factors and DR5 is an essential molecular mechanism for overcoming TRAIL resistance in SH-SY5Y and the combination of ERN-T and AZD5582 potentially constitutes a novel therapeutic strategy, which is highly effective and safe for neuroblastoma. PMID:35077998 | DOI:10.1016/j.acthis.2022.151856 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morphology of the ligaments located on the medial side of the ankle and on the plantar surface of the foot

xlomafota13 shared this article with you from Inoreader Morphology of the ligaments located on the medial side of the ankle and on the plantar surface of the foot Via radiol anat Surg Radiol Anat. 2022 Jan 25. doi: 10.1007/s00276-021-02872-w. Online ahead of print. ABSTRACT To have biodynamic features, the feet have bones located in a special posture, the joints that keep together those bones, the ligaments that provide linkage to those joints, and tendons of muscles particularly which end the foot. This study aimed to research the morphology of the medial side and plantar ligaments. The study was conducted on a total of 30 feet belonging to 2 women and 13 men cadavers that exist at the Anatomy Department of the Medical Faculty of Uludag University. After the dissections, 61 parameters that belonging to the ligaments and general features of the foot, were evaluated. The statistical analysis of the collected data was evaluated by SPSS 20.0. According to the findings, while the descriptive statistics of the foot and the ligaments related to the foot, the statistically significant difference of any of the parameters wasn't observed when they were compared between the right and left sides of the foot. In terms of the correlative relations, the parameters that showed high correlation were chosen and 28 formulas were developed using regression analysis. We foresee that our findings of the features belonging to normal anatomic structures will deepen our knowledge besides providing important benefits before or during orthopedic and plastic surgery operations related to the region. Also, our findings were discussed by comparing the find ings of similar studies belonging to many other researchers in literature, and our study's contribution to the literature was evaluated. PMID:35075567 | DOI:10.1007/s00276-021-02872-w View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effectiveness of submucosal turbinoplasty in refractory obstructive rhinitis: a prospective comparative trial

xlomafota13 shared this article with you from Inoreader Effectiveness of submucosal turbinoplasty in refractory obstructive rhinitis: a prospective comparative trial Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2022 Jan 25. doi: 10.1007/s00405-022-07267-0. Online ahead of print. ABSTRACT OBJECTIVE: Refractory inferior turbinate hypertrophy requires a surgical approach to address symptomatic complaints. Submucosal approaches demonstrated their efficacy in restoring respiratory function and respecting the nasal mucosa. Microdebrider-assisted turbinoplasty (MAT) tools effectively reduces the soft tissue, exploiting a very different principle from the kinetic energy of radiofrequency. Thus, we aimed to compare the microdebrider-assisted turbinoplasty and the quantum molecular resonance (QMR) to assess patients' perspectives and respiratory outcomes. METHODS: Subjects with persistent bilateral nasal blockage due to inferior turbinates hypertrophy were prospectively recruited from the University Medical Center. We randomly assigned the patients to each treatment and performed symptom evaluation via the visual analog score and endoscopic assessment at baseline and 30-, 90-, and 180-day post-treatment. RESULTS: Seventy participants completed the evaluations, 35 in MAT and 35 in the QMR group. Nasal complaints were significantly reduced after 1 month using both methods. Although the MAT group reported higher postoperative bleeding and edema than QMR group, similar significant reductions were seen for turbinate size at long-term follow-up. Conversely, the MAT group reported greater VAS outcomes than QMR from the first postoperative month. In addition, MAT showed a longer operating time, although this difference was not statistically significant (p < 0.05). CONCLUSION: MAT allows effective control of nasal symptoms by reducing the size of turbinates in patients with lower turbinate hypertrophy. Although QMR may cause fewer postoperative complications, functional results are comparable to long-term follow-up. PMID:35076746 | DOI:10.1007/s00405-022-07267-0 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A study of 285 cases of cranial vault suture closure in Chinese adults

xlomafota13 shared this article with you from Inoreader A study of 285 cases of cranial vault suture closure in Chinese adults Via radiol anat Surg Radiol Anat. 2022 Jan 25. doi: 10.1007/s00276-021-02854-y. Online ahead of print. ABSTRACT PURPOSE: To examine the presence and characteristics of cranial vault suture closure in Chinese adults and to explore whether craniosacral therapy (CST) manipulation is rational from the anatomical perspective. METHODS: Anthropological non-metric observation and craniometry were used to study 285 dry skull specimens of Chinese adults. RESULTS: A total of 91 specimens w ith closed extracranial sutures were observed, with an occurrence rate of 31.93%. Based on the mode of closure, there were 32 cases of single type closure, with sagittal suture closure predominating with 20 cases (21.98%); 59 cases of composite closure, with a partial closure of coronal suture + sagittal suture + lambdoid suture predominating with 26 cases (28.57%). In terms of the degree of closure, there were 13 cases (14.28%) of sagittal suture grade 0 closure and 78 cases (85.72%) of grade 1 - 4 closure; 34 cases (37.36%) of coronal suture grade 0 closure and 57 cases (62.64%) of grade 1 - 4 closure; 47 cases (51.65%) of lambdoid suture grade 0 closure and 44 cases (48.35%) of grade 1 - 4 closure. The segment and degree of coronal suture closure (46, 80.7%) and lambdoid suture (31, 70.45%) were mostly left-right symmetrical. The bone surfaces on either side of the cranial vault sutures are embedded in each other, forming a rough, complex and interlocking bone-suture-bone structu re. CONCLUSION: This study observed the closure of the cranial vault suture, summarized its characteristics, and explored the irrationality of the CST manipulation. The anatomical characteristics of the cranial suture dictate that manipulation cannot push the cranial suture at will. PMID:35076751 | DOI:10.1007/s00276-021-02854-y View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Adult female acne: Clinical and therapeutic particularities (Review)

xlomafota13 shared this article with you from Inoreader Adult female acne: Clinical and therapeutic particularities (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2022 Feb;23(2):151. doi: 10.3892/etm.2021.11074. Epub 2021 Dec 16. ABSTRACT Acne is a chronic inflammatory condition affecting the pilosebaceous unit that was traditionally viewed as a disease of the adolescence. However, over the past several years, an increasing number of adult women have been reported to suffer from this condition. The prevalence of adult female acne ranges between 12 and 54%. Two clinical types can be distinguished in this population, a 'retentional' and an 'inflammatory' type, which usually tend to overlap. In terms of evolution, three main subtypes can be identified: Persistent acne, which is the most frequent subtype, late-onset acne and recurrent acne. This type of acne is mainly mild-to-moderate in severity and may be refractory to conventional treatment. The etiopathogenesis is complex and has yet to be fully elucidated. It appears to involve an interaction among genetic predisposition, hormonal factors, and chronic activation of the innate immune system overlapping with external factors, such as daily stress, Western-type diet, use of tobacco and cosmetics. The treatment may be challenging and a holistic approach is required, with special attention to the individual needs and particularities of adult women. Both topical and systemic treatments are available, with hormonal therapies being of special value in this population. The aim of the present article was to provide up-to-date, evidence-based information on the clinical presentation, etiopathogenesis and treatment of adult female acne. PMID:35069832 | PMC:PMC8753972 | DOI:10.3892/etm.2021.11074 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Silencing CoREST inhibits the viability and migration of fibroblast-like synoviocytes in TNF-α-induced rheumatoid arthritis

xlomafota13 shared this article with you from Inoreader Silencing CoREST inhibits the viability and migration of fibroblast-like synoviocytes in TNF-α-induced rheumatoid arthritis Via Experimental and therapeutic medicine Exp Ther Med. 2022 Feb;23(2):148. doi: 10.3892/etm.2021.11071. Epub 2021 Dec 15. ABSTRACT Fibroblast-like synoviocytes (FLSs) have functions in the pathogenesis of rheumatoid arthritis (RA) through the onset of synovitis, the growth of pannus and the destruction of cartilage and bone. The significant increase in the proliferation, migration and invasion of FLSs induces the onset and advancement of RA. To date, the exact function of corepressor element-1 silencing transcription factor (CoREST) in RA remains unclear, but its expression has been determined in RA synovial tissues. In this study, the effects of CoREST were investigated in a TNF-α-induced FLS activation model. Following the silencing of CoREST expression with small interfering (si)RNA, the viability and migration of FLSs were evaluated. Furthermore, the possible molecular mechanisms were explored by detecting the expression of key factors, including matrix metalloproteinase s (MMPs), lysine-specific histone demethylase 1 (LSD1) and associated cytokines, via reverse transcription-quantitative PCR and western blotting. CoREST expression increased not only in the RA synovial tissues, but also in the TNF-α-induced FLS activation model. Following the silencing of CoREST in the FLSs treated with TNF-α, cell viability was inhibited, and the migratory capacity of FLSs was suppressed, which was accompanied by the reduced expression of MMP-3 and MMP-9. The expression of LSD1 was also downregulated. There was a notable decrease in the synthesis of interferon-γ and interleukin (IL)-17, while IL-10 expression was increased. The knockdown of CoREST inhibited the viability and migration of FLSs stimulated with TNF-α. Thus, the suppression of CoREST may have crucial roles in the occurrence and development of RA. PMID:35069829 | PMC:PMC8756401 | DOI:10.3892/etm.2021.11071 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Potential biomarkers of acute myocardial infarction based on co-expression network analysis

xlomafota13 shared this article with you from Inoreader Potential biomarkers of acute myocardial infarction based on co-expression network analysis Via Experimental and therapeutic medicine Exp Ther Med. 2022 Feb;23(2):162. doi: 10.3892/etm.2021.11085. Epub 2021 Dec 21. ABSTRACT Acute myocardial infarction (AMI) is a common cause of death in numerous countries. Understanding the molecular mechanisms of the disease and analyzing potential biomarkers of AMI is crucial. However, specific diagnostic biomarkers have thus far not been fully established and candidate regulatory targets for AMI remain to be determined. In the present study, the AMI gene chip dataset GSE48060 comprising blood samples from control subjects with normal cardiac function (n=21) and patients with AMI (n=26) was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the AMI and control groups were identified with the online tool GEO2R. The co-expression network of DEGs was analyzed by calculating the Pearson correlation coefficient of all gene pairs, mutual rank screening and cutoff threshold screening. Subsequently, the Gene Ontology (GO) database was used to analyze the genes' functions and pathway enrichment of genes in the most important modules was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) Disease and BioCyc were used to analyze the hub genes in the module to determine important sub-pathways. In addition, the expression of hub genes was confirmed by reverse transcription-quantitative PCR in AMI and control specimens. In the present study, 52 DEGs, including 26 upregulated and 26 downregulated genes, were identified. As key hub genes, three upregulated genes (AKR1C3, RPS24 and P2RY12) and three downregulated genes (ACSL1, B3GNT5 and MGAM) were identified from the co-expression network. Furthermore, GO enrichment analysis of all AMI co-expression network genes revealed functional enrichment mainly in 'RAGE receptor binding' and 'negative regulation of T cell cytokine production'. In addition, KEGG Disease and BioCyc analysis indicated functional enrichment of the genes RPS24 a nd P2RY12 in 'cardiovascular diseases', of AKR1C3 in 'cardenolide biosynthesis', of MGAM in 'glycogenolysis', of B3GNT5 in 'glycosphingolipid biosynthesis' and of ACSL1 in 'icosapentaenoate biosynthesis II'. In conclusion, the hub genes AKR1C3, RPS24, P2RY12, ACSL1, B3GNT5 and MGAM are potential markers of AMI, and have potential application value in the diagnosis of AMI. PMID:35069843 | PMC:PMC8753964 | DOI:10.3892/etm.2021.11085 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.