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Αλέξανδρος Γ. Σφακιανάκης

Monday, March 28, 2022

New ORL Abstracts

The association between inflammatory biomarkers and statin use among patients with head and neck squamous cell carcinoma
2d
by
Kayla R. Getz, Emily Bellile, Katie R. Zarins, Steven B. Chinn, Jeremy M. G. Taylor, Laura S. Rozek, Gregory T. Wolf, Alison M. Mondul
via
Head & Neck
Abstract
Background
Tumor-infiltrating lymphocytes (TILs) and cytokines are associated with prognosis among patients with head and neck squamous cell carcinoma (HNSCC). Statins (cholesterol-lowering drugs) may improve HNSCC prognosis, particularly in human papillomavirus (HPV)-positive cases, but the mechanism remains unclear.

Methods
Statin use was collected from medical records for HNSCC cases (2008–2014). TILs were counted in tumor tissue, and a total weighted score (TILws) was created. Cytokines were measured in blood. The associations between statins and biomarkers were estimated using logistic (biomarker categories: <median, ≥median) and linear regression models (log-transformed continuous biomarkers) adjusted for age, smoking, and comorbidities.

Results
We observed a positive association between statins and TILs among HPV-positive patients (TILws odds ratio [OR] = 2.80; 95% CI = 1.03–7.61), but no association among HPV-negative patients. We observed no association between statins and cytokines.

Conclusions
Statins may influence TILs in HPV-positive patients. This may be the mechanism through which they improve prognosis in HPV-positive HNSCC patients.

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Oral metastasis as the first indication of undiscovered malignancy at a distant site: A systematic review of 413 cases
2d
by
Talita Carvalho Kimura, Flávia Akemi Nakayama Henschel, Mailon Cury Carneiro, Gabriela Cristina Santin, Vanessa Cristina Veltrini
via
Head & Neck
Abstract
This systematic review is the first to provide evidence regarding demographic, clinical, and imaging characteristics, as well as information related to survival, of patients with oral and maxillofacial metastases of occult primary tumors. Case reports, case series, and cross-sectional studies were included. Ten databases were searched. The risk of bias was assessed using the Joanna Briggs Institute appraisal tools. Overall, 353 articles (413 patients) were included. Statistically significant associations between survival and multiplicity of metastatic foci, and between each of the main primary sites and some features of the oral lesions were observed. Some clinical and imaging characteristics can help dentists in raising diagnostic suspicions and also in relating to plausible primary sites. Early diagnosis of oral and maxillofacial metastases can positively affect the survival rate when they are the only focus of dissemination, conferring an important role on the dentist.



Glial Choristoma of Epitympanum and Mastoid Cavity
2d
by
Konstantinos Garefis
via
ear nose throat
pubmed-meta-image.png

Ear Nose Throat J. 2022 Mar 25:1455613221087944. doi: 10.1177/01455613221087944. Online ahead of print.

NO ABSTRACT

PMID:35337189 | DOI:10.1177/01455613221087944

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Cholecalciferol pretreatment ameliorates ischemia/reperfusion-induced acute kidney injury through inhibiting ROS production, NF-κB pathway and pyroptosis
2d
by
Wangyu Wu
via
histochem
pubmed-meta-image.png

Acta Histochem. 2022 Mar 22;124(4):151875. doi: 10.1016/j.acthis.2022.151875. Online ahead of print.

ABSTRACT

Acute kidney injury (AKI) is a common complication in patients with potentially life-threatening diseases, and it is also usually associated with unacceptable morbidity and mortality rates. Therefore, new and efficient therapies are urgently required to relieve AKI. It is well known that, reactive oxygen species (ROS), the NF-κB signaling pathways and pyroptosis are involved in AKI induced by ischemia/reperfusion (I/R). The present study seeks to further confirm the internal relationship between vitamin D deficiency and I/R-induced AKI in patients, and to explore the underlying mechanisms of ROS, NF-κB signaling pathways and pyroptosis in the renal ischemia-reperfusion injury, as well as investigating the protective role of cholecalciferol. Patients with vitamin D deficiency show worse renal function reflected by postoperative glomerular filtration rate (GFR) and more release of proinflammatory cytokine IL-1β and IL-18. Renal cell injury and renal dysfunction induced by I/R surgery were attenuated in the ICR mice administered with cholecalciferol. Cholecalciferol reduced ROS production, suppressed activated NF-κB signaling, and inhibited gasdermin D (GSDMD, a pyroptosis execution protein)-mediated pyroptosis. Cholecalciferol therefore has potential, as a clinical drug, to protect renal function in I/R-induced AKI through reducing ROS production, NF-κB activation and GSDMD-mediated pyroptosis.

PMID:35334282 | DOI:10.1016/j.acthis.2022.151875

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Measurements of The Pediatric Cartilaginous Eustachian Tube: Implications for Balloon Dilation
2d
by
Yuan Yu, Brent Geffen, Hilary McCrary, Gabriel Dunya, John Rampton, Chong Zhang, Angela P. Presson, Dennis Poe, Albert H. Park
via
The Laryngoscope
Objectives
(1) Measure the cartilaginous Eustachian tube (ET) length using a computed tomography (CT) scan and (2) develop a prediction model to measure this length without the need of a CT scan.

Study Design
CT measurements in children.

Setting
Children's Hospital.

Methods
CT scans were reformatted to project the cranial and caudal limits of the cartilaginous ET. The length was measured in 193 children who underwent a neck CT scan for nonotologic indications. Five physicians independently reviewed all or some of these measures. Four different models based on age, age ranges, weight, and height were created and compared to predict ET length.

Results
The cartilaginous ET length was 25.3 ± 3.1 mm for the right and for the left ear. The mean ET length for the females was statistically significantly less than the length in males. The lower ET lengths in children as old as 5 years of age were less than the 2 cm adult criteria used for catheter insertion. All 4 models performed equally well in predicting ET length. Model number 4, which is based on height, was the easiest to calculate ET length.

Conclusion
The cartilaginous portion of the pediatric ET can be measured with good precision using reformatted CT images. We caution against using the "adult" criteria of 2 cm for catheter insertion in children, especially those younger than 5 years of age. We recommend using a model utilizing height measures to estimate ET length or direct measurements from a reformatted CT scan.

Level of Evidence
NA Laryngoscope, 2022

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Treatment of sleep apnoea with tonsillectomy: a retrospective analysis using long-term follow-up data
2d
by
Henrik M Sjöblom
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 Mar 25. doi: 10.1007/s00405-022-07350-6. Online ahead of print.

ABSTRACT

PURPOSE: This single-group, retrospective, pre-test-post-test study was performed to examine clinical outcomes in treating obstructive sleep apnoea (OSA) with tonsillectomy alone and had the longest follow-up periods to date.

METHODS: We analysed 151 tonsillectomies in our district between the years 2004 and 2018 that had either sleep apnoea or snoring listed as a diagnosis. Twenty-one patients met our criteria and were included. Patient records were analysed for home sleep apnoea test and Epworth Sleepiness Scale (ESS) scores.

RESULTS: We defined success as a > 50% reduction of the Apnoea-Hypopnea Index (AHI) and a total AHI of < 20 post-surgery. The averages before surgery were an AHI of 22.3 and an ESS of 7.22. The success rate was 47.6% after tonsillectomy as the sole treatment for obstructive sleep apnoea in our adult population. Eleven patients were non-responders. The average ESS score reduction was 0.69 and did not reach statistical significance. With follow-up times ranging from 1.8 to 171 months, this study had the longest follow-up period compared to other existing studies. No patient with a follow-up longer than one year was a responder.

CONCLUSION: Our results support that tonsillectomy is an effective treatment for obstructive sleep apnoea in adults with tonsillar hypertrophy. With less severe OSA than those reported on previously, our patients also had less severe daytime sleepiness before surgery, and daytime sleepiness score reductions did not reach statistical significance. In the future, long-term results should be further analysed.

PMID:35338397 | DOI:10.1007/s00405-022-07350-6


Relative Value Units and Operative Time in Plastic and Reconstructive Surgery
21h
by
Joshua B Cadwell
via
Journal of plastic, reconstructive & aesthetic surgery : JPRAS
J Plast Reconstr Aesthet Surg. 2022 Mar 2:S1748-6815(22)00125-5. doi: 10.1016/j.bjps.2022.02.045. Online ahead of print.

ABSTRACT

BACKGROUND: Work relative value units (wRVUs) are linked to clinical reimbursements and physician compensation in the USA and thus should consider the time of the physician providing care. The primary goal of this study is to assess whether wRVUs appropriately consider operative time in plastic and reconstructive surgery.

METHODS: The 2015-2018 National Surgical Quality Improvement Program was queried for the 50 most performed plastic surgery cases with assigned wRVUs and a recorded operative time. Linear regressions were used to assess the relationships between operative time, assigned wRVUs, and wRVUs per hour. The procedures with the highest and lowest assigned wRVUs relative to their operative time were identified.

RESULTS: A total of 31,156 cases were included in this analysis. Among the 50 most performed procedures, the median (range) for assigned wRVUs was 10.0 (1.0-42.6), operative time was 61 min (21-441), and wRVUs per hour was 8.7 (2.2-16.2). There was a strong positive linear correlation between assigned wRVUs and median operative time (R2=0.78), with each additional operative hour being associated with an increase of 5.3 wRVUs (p<0.001). The procedures earning the most wRVUs relative to their operative times were breast reconstruction with other techniques and tissue expander placement in breast reconstruction. However, excisional debridements of the muscle/fascia and subcutaneous tissue had the lowest earned wRVUs relative to their operative times.

CONCLUSION: Although wRVUs and operative time are correlated in plastic surgery, numerous outliers from this trend exist. This suggests that wRVUs may not be optimally assigned across the range of plastic surgery procedures.

PMID:35339421 | DOI:10.1016/j.bjps.2022.02.045

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Masseteric-to-facial nerve transfer combined with static suspension: Evaluation and validation of facial symmetry in patients with different levels of asymmetry
21h
by
Hao Ma
via
Journal of plastic, reconstructive & aesthetic surgery : JPRAS
J Plast Reconstr Aesthet Surg. 2022 Feb 20:S1748-6815(22)00082-1. doi: 10.1016/j.bjps.2022.02.011. Online ahead of print.

ABSTRACT

One-stage combined dynamic reanimation with static suspension has obvious advantages of improving facial symmetry. In clinical observation, patients with different levels of oral commissure drooping achieve different symmetry outcomes, despite undergoing the same surgical procedure. Patients with slight asymmetry obtain better outcomes than those with severe asymmetry. The mechanisms influencing postoperative outcomes have not been systematically explored. We retrospectively analyzed 44 patients performed with masseteric-to-facial nerve transfer combined with static suspension. Patients were divided into two groups according to the level of oral commissure drooping: slight-asymmetry group (n = 24) and severe-asymmetry group (n = 20). Static and dynamic symmetry were assessed with FACE-gram software pre and postoperatively. The symmetry of the oral commissures at rest and during smiling significantly improved postoperatively in all patients. The differences of the bilateral oral commissure positions were significantly smaller in slight-asymmetry group than that in severe-asymmetry group (p<0.001), indicating that slight-asymmetry group achieved better symmetry. Furthermore, these differences were caused by the oral commissures position on the unaffected side, both pre and postoperatively (p<0.001), but not the paralyzed side's (p>0.05). In conclusion, masseteric-to-facial nerve transfer combined with static suspension achieved dynamic and static symmetry in patients with different levels of asymmetry. Patients with slight asymmetry obtained better postoperative symmetry than those with severe asymmetry. Postoperative facial asymmetry might be influenced by the hypertonicity of facial muscles on the unaffected side.

PMID:35339422 | DOI:10.1016/j.bjps.2022.02.011

T2-weighted MRI defines critical compression in the distal carpal tunnel that is relieved after decompressive surgery
17h
by
S Tullie
via
Journal of plastic, reconstructive & aesthetic surgery : JPRAS
J Plast Reconstr Aesthet Surg. 2022 Feb 26:S1748-6815(22)00113-9. doi: 10.1016/j.bjps.2022.02.039. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite carpal tunnel syndrome (CTS) being the most common entrapment neuropathy, its pathophysiology remains debated. Sub-synovial connective tissues (SSCT) within the carpal tunnel are thought to play a role but are poorly characterised. MRI analysis offers potentially novel insights into SSCT characteristics.

METHODS: A pilot study of T2-weighted MRI was performed in healthy controls (n = 7), and in CTS patients (n = 16) pre- and 6 months post-surgical decompression. Image analysis was performed to quantify SSCT cross-sectional area, SSCT signal intensity ratio, and wrist index (depth/width) at distal, middle, and proximal wrist landmarks.

RESULTS: Median SSCT signal intensity was lower in the distal carpal tunnel of CTS patients pre-operatively (0.96) compared to controls (1.13; P = 0.008) and normalised post-operatively (1.13, P = 0.001). Median wrist index was also lower in CTS patients pre-operatively (0.60) than in controls (0.67, P = 0.022), and again normalised post-operatively (0.74, P = 0.001). This was attributed to changes in carpal depth in the anteroposterior axis with decompression surgery.

CONCLUSION: This pilot study successfully demonstrated MRI assessment of SSCT in patients with CTS. The decreased SSCT signal intensities suggest predominant changes at the distal tunnel, potentially indicating reduced SSCT perfusion pre-surgery which normalised post-surgery. Our preliminary findings merit further investigation in a larger cohort.

PMID:35341704 | DOI:10.1016/j.bjps.2022.02.039

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Evaluation of the inflammatory process, collagen production, and MMP-2 and MMP-9 expressions produced by Luffa aegyptiaca Mill using the subcutaneous rat implanted model
17h
by
Daniele Hneda
via
histochem
pubmed-meta-image.png

Acta Histochem. 2022 Mar 24;124(4):151882. doi: 10.1016/j.acthis.2022.151882. Online ahead of print.

ABSTRACT

The subcutaneous rat implanted model is a preclinical approach used in studies to characterize the histocompatibility of materials that could be used as biomaterials. Biomaterials are obtained synthetically or from the environment, and they can be used to treat or replace any tissues or organs that the body has lost. To execute their roles, the biomaterials must present any level of histocompatibility and a lower level of inflammatory reaction. This work aimed to evaluate some aspects of histocompatibility, such as the inflammatory process, collagen production, and MMP-2 and 9 expression as responses to the Luffa aegyptiaca Mill using the subcutaneous rat implanted model. Luffa fragments were implanted into the dorsal subcutaneous region of twelve male Wistar rats, and the number of eosinophils, mast cells, the production of collagen to form the fibrous capsule, and the expression of MMP-2 and MMP-9 were evaluated on the 15th, 45th, and 90th days. Results showed statistical differences (p < 0.05) in the number of eosinophils and mast cells present inside and outside the fibrous capsule among the days evaluated. The permanent presence of macrophages and giant foreign body cells circumjacent to all implants was also observed. A progressive increase in the production of collagen was also detected, along with a significant reduction on day 90 (p < 0.05). The expression of MMP-9 was detected as being specifically expressed in the giant foreign body cells on all days evaluated, while the expression of MMP-2 was detected in fat cells present around the implants, mainly on day 90. Taken together, these results indicate a general reduction level for the inflammatory process during the days evaluated, which allows us to conclude that Luffa, being a natural product that is simple to obtain, could be a potential candidate to become a biomaterial to be tested in further approaches.

PMID:35339777 | DOI:10.1016/j.acthis.2022.151882

Omentin inhibits the resistin-induced hypertrophy of H9c2 cardiomyoblasts by inhibiting the TLR4/MyD88/NF-κB signaling pathway
16h
by
Xiaoliang Yan
via
Experimental and therapeutic medicine
Exp Ther Med. 2022 Apr;23(4):292. doi: 10.3892/etm.2022.11222. Epub 2022 Feb 17.

ABSTRACT

The recently identified adipocytokine omentin was previously found to be expressed mainly in human omental and visceral adipose tissues. As such, reduced plasma concentrations of omentin were revealed to be associated with increased risks of cardiovascular diseases. Omentin has also been previously demonstrated to exert anti-inflammatory effects. By contrast, resistin is a protein that has been associated with obesity and type-2 diabetes mellitus, and the serum concentration of resistin is increased significantly in these populations. Resistin is involved in mediating inflammation development, where they can promote cardiac hypertrophy in humans through toll-like receptor 4 (TLR4)-related signaling. In the present study, the potential effects of omentin on resistin-induced hypertrophy in H9c2 cardiomyoblasts were investigated. In the absence/presence of omentin, H9c2 cardiomyoblasts were treated with resistin. Omentin was found to significantly inhibit resistin-induced increases in the surface area of H9c2 cardiomyoblasts as determined by immunofluorescence. In addition, omentin significantly inhibited resistin-induced increases in the mRNA expression of atrial natriuretic factor, brain natriuretic peptide, β-myosin heavy chain (which is a characteristic feature of cardiac hypertrophy) and TLR4, which was determined using reverse-transcription-quantitative PCR. According to western blotting results, omentin significantly inhibited resistin-induced ERK phosphorylation, which is an important mediator of cardiomyoblast hypertrophy. Furthermore, omentin significantly inhibited resistin-induced protein expression of TLR4, myeloid differentiation factor 88 (MyD88) and NF-κB phosphorylation, both of which are important members of inflammatory signaling. To conclude, data from the present study suggest that omentin can inhibit resistin-induced H9c2 cardiomyoblast hypertrophy through inhibition of the TLR4/MyD88/NF-κB signaling pathway. Therefore, omentin serve as an attractive therapeutic target against resistin-induced cardiac hypertrophy.

PMID:35340867 | PMC:PMC8931589 | DOI:10.3892/etm.2022.11222

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Assessing the anti-inflammatory effects of quercetin using network pharmacology and <em>in vitro</em> experiments
16h
by
Jingwen Zhang
via
Experimental and therapeutic medicine
Exp Ther Med. 2022 Apr;23(4):301. doi: 10.3892/etm.2022.11230. Epub 2022 Feb 22.

ABSTRACT

The present study aimed to investigate the anti-inflammatory effects of quercetin and the associated mechanisms involved. ELISA, reverse transcription-quantitative PCR and western blot analysis were performed to determine the anti-inflammatory effects of quercetin in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The molecular mechanisms of quercetin were investigated using network pharmacology, molecular docking technology and in vitro experiments. The results revealed that quercetin reduced the LPS-induced production of TNF-α, IL-6 and IL-1β in RAW264.7 macrophages. Protein-protein interaction network topology analysis indicated that Akt was the target of quercetin. Kyoto Encyclopedia of Genes and Genomes analysis indicated that quercetin may regulate the PI3K/Akt signaling pathway to exert its anti-inflammatory effects. Furthermore, the molecular docking results indicated that quercetin had a good affinity for the active sites of Akt. Western blot analysis confirmed that quercetin inhibited the phosphorylation of Akt, with an efficacy stronger than that of an Akt inhibitor. Taken together, Akt served as a target as part of the mechanism of the anti-inflammatory effect of quercetin. This result lays a foundation for the clinical application of quercetin in the treatment of inflammatory diseases.

PMID:35340883 | PMC:PMC8931623 | DOI:10.3892/etm.2022.11230

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Tilianin attenuates MPP<sup>+</sup>-induced oxidative stress and apoptosis of dopaminergic neurons in a cellular model of Parkinson's disease
15h
by
Jie Li
via
Experimental and therapeutic medicine
Exp Ther Med. 2022 Apr;23(4):293. doi: 10.3892/etm.2022.11223. Epub 2022 Feb 17.

ABSTRACT

The flavonoid tilianin is derived from the leaves of Dracocephalum moldavica L. amiales and has been proven to serve a neuroprotective role in cerebral ischemia. Therefore, the aim of the present study was to determine whether tilianin could prevent oxidative stress and the apoptosis of dopaminergic neurons in Parkinson's disease (PD). The dopaminergic neuron MES23.5 cell line was treated with 1-methyl-4-phenylpyridinium (MPP+) to construct a PD cell model. Following pretreatment with tilianin, the Cell Counting Kit-8 assay was used to assess cell viability. The protein and mRNA expression levels of tyrosine hydroxylase were determined using immunofluorescence, reverse transcription-quantitative PCR (RT-qPCR) and western blotting. mRNA and protein expression levels of inflammatory cytokines IL-6, IL-1β and TNF-α and oxidative stress-related enzymes manganese superoxide dismutase and catalase were also quantified using RT-qPCR and western blotting, respectively. Cell apoptotic rate was analyzed using the TUNEL assay and the expressions of apoptosis-related proteins Bcl-2, Bax and cleaved caspase-3 were detected by western blotting. MAPK signaling pathway-related protein expression levels were assessed via western blotting in MPP+-stimulated MES23.5 cells with or without tilianin pretreatment. Tilianin was demonstrated to exert no cytotoxic effects on MES23.5 cells and was able to prevent MPP+-induced reductions in cell viability. Pretreatment with tilianin also inhibited MPP+-induced inflammatory cytokine secretion, oxidative stress and apoptosis of MES23.5 cells. In addition, the protein expression levels of MAPK signaling pathway-related proteins were upregulated by MPP+, whereas pretreatment with tilianin downregulated these in a dose-dependent manner. The results of the present study indicated that tilianin may exert anti-inflammatory and antioxidant effects and inhibit the MAPK signaling pathway, which may ameliorate injury to dopaminergic neurons induced by PD.

PMID:35340873 | PMC:PMC8931633 | DOI:10.3892/etm.2022.11223

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Sevoflurane preconditioning prevents acute renal injury caused by ischemia-reperfusion in mice via activation of the Nrf2 signaling pathway
16h
by
Wen-Xi Wang
via
Experimental and therapeutic medicine
Exp Ther Med. 2022 Apr;23(4):303. doi: 10.3892/etm.2022.11232. Epub 2022 Feb 22.

ABSTRACT

Oxidative stress, caused by renal ischemia reperfusion (IR)/hypoperfusion, is one of the main causes of acute kidney injury (AKI). Previous studies have demonstrated that sevoflurane (SEV) protects organs from the damage caused by oxidative stress. In the present study, mice were randomly assigned to a sham operation group (Sham), IR-vehicle group (IR+ vehicle), IR + SEV low-dose preconditioning group and an IR + SEV high-dose preconditioning group. The effect of SEV on nuclear factor E2-related factor 2 (Nrf2), a key regulatory protein of the endogenous antioxidant defense system and, consequently oxidative stress, inflammation and apoptosis-related factors, were all quantified using commercial kits or by western blotting. SEV preconditioning was demonstrated to ameliorate kidney injury as a result of decreased blood urine nitrogen and serum creatinine levels, activated Nrf2 expression in the kidney and decreased oxidative stress and inflammatory index levels an AKI mouse model. SEV preconditioning also protected injured kidney via the downregulation of caspase-3 protein expression levels. In addition, using the Nrf2 inhibitor, Brusatol, significantly abolished the SEV preconditioning renal protective effect. Using an in vitro HK-2 cell model of hypoxia/reoxygenation, it was also demonstrated that Nrf2 pathway activation was necessary for SEV to exert its beneficial effect for tubular cell injury caused by hypoxia/reoxygenation. These results indicated that SEV may protect against renal injury caused by IR via Nrf2 upregulation.

PMID:35340877 | PMC:PMC8931593 | DOI:10.3892/etm.2022.11232

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Bone resorption improvement by conditioned medium of stem cells from human exfoliated deciduous teeth in ovariectomized mice
16h
by
Ayako Maeda
via
Experimental and therapeutic medicine
Exp Ther Med. 2022 Apr;23(4):299. doi: 10.3892/etm.2022.11228. Epub 2022 Feb 21.

ABSTRACT

Stem cells from human exfoliated deciduous teeth (SHED) are mesenchymal stem cells with multipotent differentiation potential present in the dental pulp tissue of the deciduous teeth. SHED produce secretions that have immunomodulatory and regenerative functions. In the present study, we investigated the effects of SHED-conditioned medium (SHED-CM) on osteopenia induced by the ovariectomy (OVX) phenotype and its corresponding immunological changes. Eleven-week-old female C3H/HeJ mice were subjected to OVX. SHED-CM was administered intraperitoneally in these mice for 4 weeks starting immediately after OVX. SHED-CM improved bone mass after OVX and elevated the polarization of M2 macrophages in the peritoneal cavity. SHED-CM also suppressed an OVX-induced increase in interferon-γ (INF-γ) and interleukin-17 (IL-17) concentrations in the peripheral blood. Inhibition of M2 macrophage polarization with neutralizing antibodies did not reduce the concentration of IFN-γ and IL-17 in peripheral blood, which were increased by OVX, and did not alleviate osteopenia induced by the OVX phenotype. Mechanistically, these findings suggest that SHED-CM alleviates bone resorption by suppressing the activation of IFN-γ and IL-17 cells by polarizing M2 macrophages. In conclusion, our data indicate that SHED-CM contains active secretions that may have promising efficacy to ameliorate OVX-induced osteopenia. We suggest that SHED-CM has the potential to be used as a novel therapeutic agent to inhibit osteoporosis.

PMID:35340871 | PMC:PMC8931624 | DOI:10.3892/etm.2022.11228

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Ganoderic acid A ameliorates non-alcoholic streatohepatitis (NASH) induced by high-fat high-cholesterol diet in mice

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Exp Ther Med. 2022 Apr;23(4):308. doi: 10.3892/etm.2022.11237. Epub 2022 Feb 24.

ABSTRACT

Non-alcoholic steatohepatitis (NASH) is becoming a huge global health problem. Previous studies have revealed that ganoderic acids have hepatoprotective and hypocholesterolemic effects. In the present study, to evaluate the anti-NASH activity of ganoderic acid A (GAA), male 6-week-old C57BL/6J mice were divided into the following four groups, which were administered different diets: Normal diet (ND group), high-fat high-cholesterol diet (HFHC group), HFHC diet supplemented with 25 mg/kg/day (GAAL group) or 50 mg/kg/day of GAA (GAAH group). After 12 weeks of GAA treatment, histopathological results revealed that compared with that of the HFHC group, GAA significantly inhibited fat accumulation, steatosis, inflammation and fibrosis in the liver. GAA effectively reduced serum aspartate transaminase and alanine transaminase levels compared with the HF HC model. Furthermore, the endoplasmic reticulum (ER) stress-responsive proteins, including glucose-regulated protein 78, phosphorylated (p)-eukaryotic initiation factor-2α and p-JNK, were significantly suppressed by GAA, while ERp57, p-MAPK and p-AKT were significantly increased after GAA treatment. Taken together, it was concluded that GAA could resist HFHC diet-induced NASH. In terms of its underlying mechanism, GAA could improve liver inflammation and fibrosis by inhibiting hepatic oxidative stress and the ER stress response induced by HFHC.

PMID:35340879 | PMC:PMC8931630 | DOI:10.3892/etm.2022.11237

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Pterostilbene attenuates the proliferation and differentiation of TNF-α-treated human periodontal ligament stem cells

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Exp Ther Med. 2022 Apr;23(4):304. doi: 10.3892/etm.2022.11233. Epub 2022 Feb 22.

ABSTRACT

Periodontitis is a common chronic inflammatory oral disease. The objective of periodontal treatment is to control infection whilst regenerating damaged periodontal tissue. The present study aimed to determine the potential effects of pterostilbene (PTE), a representative stilbene compound, on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Different concentrations (1, 5, 10 and 20 µM) of PTE were applied to hPDLSCs, after which Cell Counting Kit-8 and western blotting assays were performed to examine the protein levels of Ki67, PCNA, p-IκBα, IκBα, Bcl-2, Bax, cleaved caspase3. The effect of PTE on the release of inflammatory factors, including IL-1β, IL-6 and IL-10 was assessed by RT-qPCR. The apoptosis of TNF-α-induced hPDLSCs was evaluated by TUNEL assay and western blotting. Additionally, the rol e of PTE in hPDLSC mineralization was evaluated using alizarin red staining. The expression levels of mineralization indices, including RUNX2 and ALP were subsequently determined using western blotting. Subsequently, the target of PTE was predicted using TargetNet database and AutoDock v4.2 software and verified using western blotting. The results of the present study revealed that PTE promoted the proliferation of hPDLSCs in a concentration-dependent manner. Furthermore, PTE treatment decreased the release of inflammatory factors and alleviated the apoptosis of TNF-α-induced hPDLSCs. PTE was also demonstrated to promote the formation of mineral nodules in TNF-α-induced hPDLSCs. The Targetnet database, along with molecular docking, indicated that histone deacetylases (HDACs) were the probable targets of PTE upstream of regulating periodontitis. The results of western blotting implied that TNF-α significantly increased expression levels of HDAC2, 4, 6 and 8, whilst PTE treatment m arkedly decreased HDAC4, 6 and 8 expression in a concentration-dependent manner compared with the TNF-α group, which further confirmed these conclusions. In summary, results of the present study revealed that PTE promoted TNF-α-induced hPDLSC proliferation and differentiation, whilst alleviating inflammation and apoptosis. PTE also inhibited the expression of HDACs, which may be involved in the mechanism of periodontitis.

PMID:35340874 | PMC:PMC8 931590 | DOI:10.3892/etm.2022.11233

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Rosiglitazone ameliorates acute hepatic injury via activating the Nrf2 signaling pathway and inhibiting activation of the NLRP3 inflammasome

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Exp Ther Med. 2022 Apr;23(4):300. doi: 10.3892/etm.2022.11229. Epub 2022 Feb 21.

ABSTRACT

Acute hepatic injury is a common liver disease in clinical practice. Drugs with antioxidant activity exhibit a great potential for alleviating liver injury. The present study aimed to explore the role of rosiglitazone (RSG), a previously reported compound with anti-inflammatory properties, in hepatic injury. Kunming mice were divided into the following four groups: The control group; the RSG group; the carbon tetrachloride (CCl4) group; and the RSG + CCl4 group. Hepatic injury was confirmed by histological examination of the liver. In addition, the serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and those of the biochemical indices superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), NO and reactive oxygen species (ROS) were measured in each group of mice. Addition ally, the levels of inflammatory factors and apoptosis-related proteins, as well as the activity of the related signaling pathways, were evaluated. The results showed that RSG could reverse the CCl4-mediated decrease in the levels of SOD, CAT and GSH, and increase in the levels of ALT, AST, MDA, NO and ROS. Furthermore, treatment with RSG could reduce the expression levels of inflammation- and apoptosis-related proteins, thus suggesting that RSG could attenuate inflammation and liver cell apoptosis. Additionally, treatment with RSG promoted the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, upregulated peroxisome proliferator-activated receptor γ and inhibited activation of the inflammasome NOD-like receptor protein 3 (NLRP3). In conclusion, the current study demonstrated that RSG could ameliorate acute hepatic injury via activating the Nrf2 signaling pathway and inhibiting activation of the NLRP3 inflammasome. The findings of the present study partly uncovered the mechanism underlying the effect of RSG on hepatic injury, thus supporting the application of RSG in clinical practice.

PMID:35340872 | PMC:PMC8931635 | DOI:10.3892/etm.2022.11229

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Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β-catenin signaling following vertical sleeve gastrectomy in obese rats with type-2 diabetes

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Exp Ther Med. 2022 Apr;23(4):302. doi: 10.3892/etm.2022.11231. Epub 2022 Feb 22.

ABSTRACT

Adipogenesis and fat accumulation are closely associated with the development of obesity. Sleeve gastrectomy (SG) is an effective treatment for obesity and associated metabolic disorders. Leptin is downregulated after SG and Src homology phosphatase 2 (Shp2) has an important role in leptin signaling. The role of Shp2 in SG and the mechanisms of fat reduction following SG were further investigated in the current study. Sham and SG operations were performed on obese type-2 diabetes model Sprague-Dawley rats. Primary pre-adipocytes were isolated from the inguinal white adipose tissue (ingWAT) of the rats. Shp2 expression in ingWAT pre-adipocytes was silenced using small interfering RNA transfection. Shp2 function was inhibited using the specific inhibitor, SHP099. In addition, Shp2 was overexpressed using lentivirus. Gene and protein expression analy sis was performed after adipocyte differentiation. Furthermore, Shp2-overexpressing ingWAT pre-adipocytes treated with the β-catenin inhibitor, PNU-74654, were also used for gene and protein expression analysis. Adipogenic markers, including triglycerides, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (Cebpα), adiponectin, fatty acid-binding protein 4 and leptin, were examined. Compared with the sham, triglyceride, leptin, PPARγ and Cebpα levels were significantly reduced in the ingWAT from the SG group. Shp2 expression levels were reduced following leptin treatment. Moreover, genetic analysis demonstrated depot-specific adipogenesis following Shp2 silencing or inhibition in ingWAT pre-adipocytes. Conversely, Shp2 overexpression decreased the expression of adipogenic markers by enhancing β-catenin expression. PNU-74654 treatment abolished the downregulation of adipogenic markers caused by Shp2 overexpression. SG decreased leptin level s in ingWAT, which in turn upregulated Shp2, and Shp2 suppressed fat accumulation and adipogenic differentiation by activating the Wnt/β-catenin signaling pathway. Overall, this may represent a potential mechanism of fat reduction in SG, and Shp2 may serve as a potential therapeutic target for the treatment of obesity and type-2 diabetes.

PMID:35340882 | PMC:PMC8931631 | DOI:10.3892/etm.2022.11231

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Dural Entry Point of the Vertebral Artery: An Overlooked Route of Spinal CSF Leaks

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NMC Case Rep J. 2022 Feb 23;9:1-5. doi: 10.2176/jns-nmc.2021-0265. eCollection 2022.

ABSTRACT

Spontaneous intracranial hypotension (SIH) is no longer considered rare. Its estimated annual incidence is 5 cases per 100,000 individuals, which is half the incidence of subarachnoid hemorrhage. Epidural blood patch (EBP) is indicated for SIH patients who do not improve with conservative treatment. Accurate determination of the cerebrospinal fluid (CSF) leak site is critical for a successfully targeted EBP. We report the case of a 43-year-old woman with SIH secondary to CSF leakage at the craniovertebral junction dural entry point of the vertebral artery (VA). We treated the patient 2 months after the onset of symptoms. Fat-suppressed T2-weighted spinal magnetic resonance (MR) images revealed a massive epidural fluid collection around the upper thoracic spine. Extravasation of contrast medium through the left VA-dural entry point was clearly visible on computed tomographic myelography. A cervical EBP was injected through the C1-2 interlaminar space. The patient had a smooth recovery and was asymptomatic, with normal spinal MR findings, 6 months after treatment. The possibility of CSF leakage from the dural entry point of the VA should be considered in SIH patients. EBP targeted at the VA entry point is proposed as a safe and effective treatment.

PMID:35340334 | PMC:PMC8906836 | DOI:10.2176/jns-nmc.2021-0265

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3Effect of FFP2+3 masks on voice range profile measurement and voice acoustics in routine voice diagnostics

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Introduction: Voice diagnostics including voice range profile measurement (VRP) and acoustic voice analysis is essential in laryngology and phoniatrics. Due to Covid-19 pandemic, wearing of filtering face masks (FFP2/3) is recommended when high risk aerosol generating procedures like singing and speaking are being performed. Goal of this study was to compare VRP parameters when performed without and with FFP2/3 masks. Further, formant analysis for sustained vowels, singer's formant and analysis of reading standard text samples were performed without/with FFP2/3 masks. Methods: 20 subjects (6 male and 14 female) were enrolled in this study with an average age of 36±16 y (mean ± SD). 14 patients were rated as euphonic/not hoarse and 6 patients as mildly hoarse. All subjects underwent the VRP measurements, vowel and text recordings without/with FFP2/3 mask using the software DiVAS by XION medical (Berlin, Germany). Voice range of singing voice, equivalent of voice extension measure (eVEM), fundamental frequency (F0), sound pressure level (SPL) of soft speaking and shouting were calculated and analyzed. Maximum phonation time (MPT) and jitter-% were included for Dysphonia Severity Index (DSI) measurement. Analyses of singer's formant were performed. Spectral analyses of sustained vowels /a:/, /i:/ and /u:/ (first=F1 and second=F2 formants), intensity of long term average spectrum (LTAS) and alpha-ratio (α-ratio) were calculated using the freeware praat. Results: For all subjects the mean values of routine voice parameters without/with mask were analyzed: no significant differences were found in results of singing voice range, eVEM. SPL and frequency of soft speaking/shouting, except significant lower mean SPL of shouting with FFP2/3 mask, in particular that of the female subjects (p=0.002). Results of MPT, jitter and DSI without/with FFP2/3 mask showed no significant differences. Further mean values analyzed without/with mask were: ratio singer's formant/loud singing, with lower ratio with FFP2/3 mask (p=0.001). F1 and F2 of /a:/, /i:/, /u:/, with no significant differences of the results, with the exception of F2 of /i:/ with lower value with FFP2/3 mask (p=0.005). With the exceptions mentioned, the t-test revealed no significant differences for each of the routine parameters tested in the recordings without and with wearing a FFP2/3 mask. Conclusion: It can be concluded, that VRP measurements including DSI performed with FFP2/3 masks provide reliable data in clinical routine with respect to voice condition/constitution. Spectral analyses of sustained vowel, text and singer's formant will be affected by wearing FFP2/3 masks.
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Tracheobronchial chondritis as an immune-related adverse event occurring during the administration of nivolumab for recurrent hypopharyngeal squamous cell carcinoma

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Ear Nose Throat J. 2022 Mar 27:1455613221081912. doi: 10.1177/01455613221081912. Online ahead of print.

ABSTRACT

Tracheobronchial chondritis is a rare immune-related adverse event (irAE) associated with immune checkpoint inhibitors. We report a case wherein tracheobronchial chondritis occurred while administering nivolumab for recurrent hypopharyngeal squamous cell carcinoma (SCC) in a man diagnosed with T2N3bM0 stage IVB hypopharyngeal SCC. After treatment with cisplatin an d radiotherapy followed by left and right neck dissection, local recurrence was observed in the hypopharynx. Because of the difficulty of salvage surgery, we administered 240 mg/body of nivolumab. After 9 cycles of nivolumab, the patient was judged to have complete response. After 10 cycles, he had cough and sputum, for which prompting us to perform imaging tests. Computed tomography (CT) showed edematous thickening around the trachea and bilateral bronchi and elevated amounts of adjacent subcutaneous fat tissue. Positron emission tomography-CT showed diffuse fluorodeoxyglucose uptake in the trachea and bilateral bronchi, bronchial endoscopy showed redness and swelling throughout the bronchi, and biopsy showed partial mucosal erosion, inflammatory cell (lymphocyte) infiltration, interstitial edema, and desmoplasia. The patient was diagnosed with tracheobronchial chondritis as an irAE resulting from administering anti-programmed death-1 monoclonal antibody. After four-day prednisolon e treatment, his cough and sputum disappeared; after two weeks, tracheobronchial chondritis no longer appeared on CT.

PMID:35343278 | DOI:10.1177/01455613221081912

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