HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway

xlomafota13 shared this article with you from Inoreader HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):705. doi: 10.3892/etm.2021.10137. Epub 2021 May 2. ABSTRACT Chemotherapy resistance is a main obstacle in the clinical chemotherapeutic treatment of multiple myeloma (MM). High-mobility group box 1 (HMGB1) has been revealed to be associated with the sensitivity of MM cells to chemotherapy, but how HMGB1 regulates chemotherapy resistance in MM has yet to be fully elucidated. In the present study, the exact molecular mechanism underlying HMGB1-mediated drug resistance in MM was explored using three chemotherapy-resistant MM cells (RPMI8226/ADR, RPMI8226/BOR and RPMI8226/DEX) that were successfully established. Reverse transcription-quantitative polymerase chain reaction revealed that the three chemotherapy-resistant MM cells exhibited a higher release of HMGB1 compared with the parental RPMI8226 cells. Interference with endogenous HMGB1 increased the sensitivity of drug-resistant MM cells to chemotherapy, whi ch was supported by the low IC50 value and the enlargement of cell apoptosis. Furthermore, short hairpin (sh)RNA-transfected MM cells showed an obvious elevation in phosphorylated (p)-IKKα/β, p-IκBα and p-p65 in whole cell lysate and/or nucleus, and treatment of nuclear factor (NF)-κB activator reversed the effect of shHMGB1-mediated cell viability and apoptosis in MM cells. In conclusion, HMGB1 regulates drug resistance in MM cells by regulating NF-κB signaling pathway, suggesting that HMGB1 has the potential to serve as a target for MM treatment. PMID:34007314 | PMC:PMC8120504 | DOI:10.3892/etm.2021.10137 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hedgehog signaling modulates cigarette-induced COPD development

xlomafota13 shared this article with you from Inoreader Hedgehog signaling modulates cigarette-induced COPD development Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):729. doi: 10.3892/etm.2021.10161. Epub 2021 May 4. ABSTRACT Hedgehog (Hh) signaling is involved in early embryogenesis and maintains quiescence in the adult lungs. The interruption of Hh signaling may lead to the development of chronic obstructive pulmonary disease (COPD). The current study aimed to assess whether the Hh pathway affects cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines. C57BL/6J mice were randomized into control, cigarette smoke (CS) or CS + cyclopamine (CSC) groups. Control mice were exposed to normal room air, CS mice were exposed to tobacco smoke and CSC mice were exposed to CS and received cyclopamine treatment. Histopathological examination of lung tissues was performed, and the expression of sonic hedgehog (HH), glioma-associated oncogene homolog 1 (Gli1), hedgehog-interacting protein (HIP) and several inflammatory mediators (intracellular adhesi on molecule-1, IL-6, IL-8 and TNF-α) were compared using reverse transcription-quantitative PCR and western blotting. The emphysema of lung tissues by histopathological examination demonstrated partial amelioration in the CSC group compared with that in the CS group. Additionally, expression levels of SHH, Gli1 and inflammatory mediators were significantly higher in the CS group compared with the control group but were significantly decreased in the CSC group. The expression of HIP was decreased in the CS group, but significantly increased in the CSC group. Hh signaling may serve an important role in cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines in animal models. Therefore, diminishing the activation of the Hh signal may serve as a novel therapeutic strategy for patients suffering from smoking-related COPD. PMID:34007338 | PMC:PMC8120645 | DOI:10.3892/etm.2021.10161 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Features of a simvastatin-loaded multi-layered co-electrospun barrier membrane for guided bone regeneration

xlomafota13 shared this article with you from Inoreader Features of a simvastatin-loaded multi-layered co-electrospun barrier membrane for guided bone regeneration Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):713. doi: 10.3892/etm.2021.10145. Epub 2021 May 3. ABSTRACT A novel tri-layer membrane consisting of polycaprolactone (PCL) fibrous sheets and structured nanofibers with a gelatin (Gt) shell and a simvastatin-containing PCL core (PCL-Gt/PCL-simvastatin membrane) was prepared. The soft external layer comprised of Gt/PCL-simvastatin, the external layer of PCL and the middle layer of both microfilaments, interwoven together. The membrane was designed to promote osteoinduction and act as a barrier against cells but not against water and molecules in order to promote guided bone regeneration. The structure of the membrane was characterized by scanning electronic microscopy. The in vitro release rates of simvastatin over 32 days were determined by high-performance liquid chromatography. For in vitro biological assays, bone marrow mesenchymal stem cells and human fibroblasts were cultured on the diff erent surfaces of the membrane. Cell adhesion, proliferation, distribution, and differentiation were examined. For in vivo testing, cranial defects were created in rabbits to assess the amount of new bone formed for each membrane. The results revealed that membranes with multi-layered structures showed good cell viability and effective osteoinductive and barrier properties. These results suggest that the novel multi-layered PCL-Gt/PCL-simvastatin membranes have great potential for bone tissue engineering. PMID:34007322 | PMC:PMC8120663 | DOI:10.3892/etm.2021.10145 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Preclinical study analysis of massive magnesium alloy graft for calcaneal fractures

xlomafota13 shared this article with you from Inoreader Preclinical study analysis of massive magnesium alloy graft for calcaneal fractures Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):731. doi: 10.3892/etm.2021.10163. Epub 2021 May 7. ABSTRACT The highly comminuted calcaneal fractures represent a challenge for surgeons and require bone grafts for a good clinical outcome. Postoperative results are generally associated with increased morbidity and long periods of inactivity. The biomedical community promotes the use of artificial materials for grafts in order to achieve improved results. In an era when cosmetic concerns as well as the satisfaction of patients are mandatory and the use of autologous bone grafts is not without complications, an artificial replacement appears to be a favorable option. Synthetic bone grafts are known to fail under stress shield or are associated with systemic side effects. The purpose of the present study was to investigate and determine an already commercially available magnesium (Mg) alloy whose design is most suitable for long-term use. The mechanical prope rties of Mg1Ca and MgYREZr compared with normal cortical and cancellous bone were assessed. Another discussed aspect was the influence of the alloy in the graft fixation. The results revealed that Mg1Ca and MgYREZr alloys had a low tensile strength of 75 and 250 MPa, respectively. For this reason, it was surmised that MgYREZr alloy could be an optimal choice with favorable corrosion resistance. Since calcaneal fractures are prone to skin necrosis and septic complications, the need for antibacterial procedures and antibiotic prophylaxis is highlighted. Thus, an in vivo attempt was also made to identify the relationship between Mg alloy products and bacterial load. However, the most important feature of the present study was the creation of a 3D model grafting, with an anti-sliding design, which can be potentially used with the preferred Mg alloy in this type of fractures. In conclusion, artificial materials are the future in medicine, replacing the body-limiting capabilities o f grafts. They are safe and incur less comorbidities. This method could pave the way for reducing patient discomfort and increasing patient satisfaction. Although further testing is required, this research represents a great starting point for calcaneal fractures. PMID:34007339 | PMC:PMC8120552 | DOI:10.3892/etm.2021.10163< /p> View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dihydroartemisinin inhibits endothelial cell migration via the TGF-β1/ALK5/SMAD2 signaling pathway

xlomafota13 shared this article with you from Inoreader Dihydroartemisinin inhibits endothelial cell migration via the TGF-β1/ALK5/SMAD2 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):709. doi: 10.3892/etm.2021.10141. Epub 2021 May 3. ABSTRACT Anti-angiogenesis therapy is a novel treatment method for malignant tumors. Endothelial cell (EC) migration is an important part of angiogenesis. Dihydroartemisinin (DHA) exhibits strong anti-angiogenic and anti-EC migration effects; however, the underlying molecular mechanisms are yet to be elucidated. The TGF-β1/activin receptor-like kinase 5 (ALK5)/SMAD2 signaling pathway serves an important role in the regulation of migration. The present study aimed to explore the effects of DHA treatment on EC migration and the TGF-β1/ALK5/SMAD2 signaling pathway. The effects of DHA on human umbilical vein EC migration were assessed using wound healing and Transwell assays. The effects of DHA on the TGF-β1/ALK5/SMAD2 signaling pathway were detected using western blotting. DHA exhibited an inhibitory effect on EC migration in the wound healing and Transwell assays. DHA treatment upregulated the expression levels of ALK5 and increased the phosphorylation of SMAD2 in ECs. SB431542 rescued the inhibitory effect of DHA during EC migration. DHA inhibited EC migration via the TGF-β1/ALK5/SMAD2-dependent signaling pathway, and DHA may be a novel drug for the treatment of patients with malignant tumors. PMID:34007318 | PMC:PMC8120513 | DOI:10.3892/etm.2021.10141 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cis-acting: A pattern of lncRNAs for gene regulation in induced pluripotent stem cells from patients with Down syndrome determined by integrative analysis of lncRNA and mRNA profiling data

xlomafota13 shared this article with you from Inoreader Cis-acting: A pattern of lncRNAs for gene regulation in induced pluripotent stem cells from patients with Down syndrome determined by integrative analysis of lncRNA and mRNA profiling data Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):701. doi: 10.3892/etm.2021.10133. Epub 2021 May 2. ABSTRACT Down syndrome (DS), caused by the trisomy of chromosome 21, is one of the common chromosomal disorders, the main clinical manifestations of which are delayed nervous development and intellectual disability. Long non-coding RNAs (lncRNAs) have critical roles in various biological processes, including cell growth, cell cycle regulation and differentiation. The roles of abnormally expressed lncRNAs have been previously reported; however, the biological functions and regulatory patterns of lncRNAs in DS have remained largely elusive. The aim of the present study was to perform a whole-genome-wide identification of lncRNAs and mRNAs associated with DS. In addition, global expression profiling analysis of DS-induced pluripotent stem cells was performed and differentially expressed (DE) lncRNAs and mRNAs were screened. Furthermore, the target genes and fu nctions of the DE lncRNAs were predicted using Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis. The results revealed that the majority of the lncRNAs exerted functions in DS via cis-acting target genes. In addition, the results of the enrichment analysis indicated that these target genes were mainly involved in nervous and muscle development in DS. In conclusion, this integrative analysis using lncRNA and mRNA profiling provided novel insight into the pathogenesis of DS and it may promote the diagnosis and development of novel therapeutics for this disease. PMID:34007310 | PMC:PMC8120638 | DOI:10.3892/etm.2021.10133 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Differentiation capacity of dental pulp stem cell into inner ear hair cell using an in vitro assay: a preliminary step toward treating sensorineural hearing loss

xlomafota13 shared this article with you from Inoreader Differentiation capacity of dental pulp stem cell into inner ear hair cell using an in vitro assay: a preliminary step toward treating sensorineural hearing loss 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. 2021 May 19. doi: 10.1007/s00405-021-06864-9. Online ahead of print. ABSTRACT PURPOSE: Sensorineural hearing loss (SNHL) is commonly caused by the death or dysfunction of cochlear cell types as a result of their lack of regenerative capacity. However, regenerative medicine, such as stem cell therapy, has become a promising tool to cure many diseases, including hearing loss. In this study, we determined whether DPSCs could differentiate into cochlear hair cell in vitro. METHODS: DPSCs derived from human third molar dental pulp were induced into NSCs using a medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) for 7 days, and then into cochlear hair cell using a medium containing EGF and IGF-1 for the next 14 days. We used the neuroepithelial protein marker nestin and cochlear hair cell marker myosin VIIa as the markers for cells differentiation. Cells expressing the p ositive markers under the microscope were confirmed to have differentiated into cochlear hair cell. RESULTS: DPSCs were successfully induced to differentiate into NSCs, with mean 24% nestin-positive cells. We found that DPSC-derived NSCs have a great capacity in differentiating into inner ear hair cell-like cells with an average of 81% cells presenting myosin VIIa. Thus, DPSCs have high potential to serve as a good resource for SNHL treatment. CONCLUSION: We found the high potential of DPSCs to differentiate into NSC. The ability of DPSCs in differentiating into neural lineage cell made them a good candidate for regenerative therapy in neural diseases, such as SNHL. PMID:34008035 | DOI:10.1007/s00405-021-06864-9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma Via Head and neck cancers by Fumisato Sasaki, Shuji Kanmura, Kohei Oda, Hidehito Maeda, Masayuki Kabayama, Hiromichi Iwaya, Yuga Komaki, Shiho Arima, Shiroh Tanoue, Shinichi Hashimoto, Hiroshi Fujita, Akio Ido Patients with inactive acetaldehyde dehydrogenase 2 (ALDH2) are at high risk for esophageal squamous cell carcinoma (ESCC) and hypopharyngeal squamous cell carcinoma (HPSCC). The acetaldehyde breath test (ABT) may demonstrate ALDH2 gene polymorphisms. We evaluated the usefulness of the ABT in patients with ESCC and HPSCC. The squamous cell carcinoma (SCC) group consisted of 100 patients who were treated with endoscopic submucosal dissection (ESD) for ESCC or HPSCC, and the control group (HC) consisted of 275 healthy subjects. The SCC group comprised the "single subgroup" (n = 63), in which a single lesion was initially treated with ESD, and the "multiple subgroup" (n = 31), in which multiple lesions were initially treated with ESD. First, we compared the groups' risk factors for carcinogenesis and measured the acetaldehyde-to-ethanol (A/E) ratio. Then we tested the groups' differences in the abovementioned carcinogenic risk factors. We found that the proport ion of individuals in the SCC group with inactive ALDH2 (A/E ratio ≥ 23.3) was significantly higher than that in the HC group (p = 0.035), as was the A/E ratio (p p = 0.015), as was the A/E ratio (p = 0.008). In conclusion, ABT may be a potential screening tool for detecting people at risk of ESCC and HPSCC. In addition, it could be a useful tool in detecting patients at risk of multiple or double carcinomas among patients with ESCC and HPSCC. Trial registration: Trial Registration number: UMIN000040615 [https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000040615], Data of Registration: 01 46 June 2020, retrospectively registered. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma Via Head and neck cancers by Fumisato Sasaki, Shuji Kanmura, Kohei Oda, Hidehito Maeda, Masayuki Kabayama, Hiromichi Iwaya, Yuga Komaki, Shiho Arima, Shiroh Tanoue, Shinichi Hashimoto, Hiroshi Fujita, Akio Ido Patients with inactive acetaldehyde dehydrogenase 2 (ALDH2) are at high risk for esophageal squamous cell carcinoma (ESCC) and hypopharyngeal squamous cell carcinoma (HPSCC). The acetaldehyde breath test (ABT) may demonstrate ALDH2 gene polymorphisms. We evaluated the usefulness of the ABT in patients with ESCC and HPSCC. The squamous cell carcinoma (SCC) group consisted of 100 patients who were treated with endoscopic submucosal dissection (ESD) for ESCC or HPSCC, and the control group (HC) consisted of 275 healthy subjects. The SCC group comprised the "single subgroup" (n = 63), in which a single lesion was initially treated with ESD, and the "multiple subgroup" (n = 31), in which multiple lesions were initially treated with ESD. First, we compared the groups' risk factors for carcinogenesis and measured the acetaldehyde-to-ethanol (A/E) ratio. Then we tested the groups' differences in the abovementioned carcinogenic risk factors. We found that the proport ion of individuals in the SCC group with inactive ALDH2 (A/E ratio ≥ 23.3) was significantly higher than that in the HC group (p = 0.035), as was the A/E ratio (p p = 0.015), as was the A/E ratio (p = 0.008). In conclusion, ABT may be a potential screening tool for detecting people at risk of ESCC and HPSCC. In addition, it could be a useful tool in detecting patients at risk of multiple or double carcinomas among patients with ESCC and HPSCC. Trial registration: Trial Registration number: UMIN000040615 [https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000040615], Data of Registration: 01 46 June 2020, retrospectively registered. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Der Nasen- oder Rachenabstrich in der COVID-19-Pandemie – Aspekte für den HNO-Arzt/die HNO-Ärztin – SARS-CoV-2, Coronavirus, Nasenabstrich, Rachenabstrich, Komplikationen

xlomafota13 shared this article with you from Inoreader Der Nasen- oder Rachenabstrich in der COVID-19-Pandemie – Aspekte für den HNO-Arzt/die HNO-Ärztin – SARS-CoV-2, Coronavirus, Nasenabstrich, Rachenabstrich, Komplikationen Via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1498-3549 Seit Beginn der SARS-CoV-2-Pandemie werden zunehmend Abstriche oder andere Beprobungen aus dem oberen Aerodigestivtrakt genommen, da hier vor allen Dingen in frühen Erkrankungsstadien hohe Viruslasten bestehen. Als diagnostische Möglichkeiten sind Abstriche aus der vorderen Nase, dem Nasopharynx oder dem Oropharynx sowie die Gewinnung von Rachenspülwasser oder Speichel möglich. Als Labormethoden stehen in einigen Minuten ablesbare Antigentests oder langwierigere RT-PCR-Methoden zur Verfügung. Abstriche werden von ärztlichem Personal, medizinischem Fachpersonal, Laien und im Eigentest, jeweils nach Instruktionen, durchgeführt. Auf die Aussagekraft und die Sensitivität d es gesamten diagnostischen Prozesses haben somit viele dieser Faktoren einen Einfluss. Die PCR-Labormethode ist sensitiver als die Antigenmethode; der Abstrich aus dem Nasopharynx wird als der valideste Abstrichort angesehen. Eine korrekte Durchführung eines Tests kann auch bei nicht professionellen Personen mit guten Instruktionen erreicht werden. Komplikationen werden bei solchen Abstrichen, gemessen an der anzunehmenden Anzahl durchgeführter Prozeduren, sehr selten berichtet. Kurzfristiges Nasenbluten bei traumatischen Abstrichen ist anzunehmen, ohne dass darüber Publikationen aufgefunden werden konnten. Abgebrochene Abstrichträger mussten HNO-ärztlich entfernt werden. Verletzungen der Schädelbasis mit Liquorrhö wurden bisher sehr vereinzelt berichtet, davon 2-mal bei Anomalien wie Meningozelen. Die Wahl eines geeigneten diagnostischen Mediums hängt von vielen Parametern, wie Verfügbarkeit, zeitlicher Ablauf bis zum Ergebnis, Abstrich durch kundiges Personal oder Eigente st und etlichen anderen praktischen Erwägungen, ab. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Validität präoperativ entnommener SARS-CoV-2-Abstriche bei Kindern

xlomafota13 shared this article with you from Inoreader Validität präoperativ entnommener SARS-CoV-2-Abstriche bei Kindern Via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1494-3341 Hintergrund Aufgrund der eingeschränkten Compliance ist bei Kindern die technisch korrekte Entnahme eines gepoolten Nasopharyngealabstrichs deutlich erschwert. Vor allem bei Operationen im Bereich der oberen Atemwege besteht für alle im Operationssaal Anwesenden infolge der intraoperativen Aerosolbildung ein deutlich erhöhtes Infektionsrisiko für eine Erkrankung an COVID-19. Ziel der Studie ist die Analyse der Validität präoperativ unter im Einzelfall suboptimalen Bedingungen entnommener SARS-CoV-2-Abstriche bei Kindern. Material und Methoden Retrospektiver Vergleich der PCR-Ergebnisse von präoperativ und intraoperativ abgenommenen SARS-CoV-2-Abstrichen bei 62 Kindern im Zeitraum April-Juli 2020. Das Alter der Kinder lag zwischen einem und 14 Jahren (Median 4,49 Jahre). Insgesamt 56 der 62 untersuchten Operationen wurden hinsichtlich des erhöhten Infektionsrisikos als Risikoeingriffe gewertet. Die PCR-Diagnostik erfolgte 1–2 Tage (bei Notfalleingriffen am selben Tag) präoperativ sowie erneut intraoperativ mittels gepooltem Nasopharyngealabstrich. Ergebnisse Alle 62 präoperativ abgenommenen Abstriche waren negativ. Abweichend vom präoperativen Testergebnis war ein intraoperativ gewonnener Abstrich positiv. Schlussfolgerungen Aufgrund eingeschränkter Compliance kann bei Kindern nicht immer von einer korrekten präoperativen Abstrichtechnik (Präanalytik) ausgegangen werden. Infolgedessen sind die Testergebnisse im Hinblick auf eine mögliche SARS-CoV-2-Infektion womöglich inkorrekt. Ausreichende Schutzmaßnahmen für alle im Operationssaal Anwesenden sind daher zwingend erforderlich. Zum Schutz des Personals und zur Prävention möglicher Infektionsketten perioperativ erscheint in dieser Altersgruppe trotz der guten Reproduzierbarkeit der präoperativen Abstrichergebnisse eine erneute intraoperative Testung erwägenswert, falls der präoperative Abstrich unter erschwerten Bedingungen erfolgte oder eine umfassende Anamnese, z. B. vor Notfalleingriffen oder bei Sprachbarriere, nicht möglich ist. [...] Georg Thieme Verlag KG R üdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.