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Κυριακή 4 Ιουλίου 2021

New Onset Vertigo After COVID-19 Infection. A Case Report

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Abstract

In addition to the known pathophysiological sequelae of the SARS-COV-2 virus and its related respiratory symptoms, several studies have recently reported cardiovascular, gastrointestinal, and neurological symptoms of new-onset after a history of infection. Vertigo is a symptom indicating dysfunction of the vestibular system and this report of a 60-year-old female patient points out the possible association between new-onset vertigo and SARS-COV-2 infection. A 60-year-old diabetic and hypertensive female patient with a 9-days history of COVID-19 symptoms presented to the emergency department with acute vertigo attack without nausea or vomiting. A full physical examination showed no other auditory or neurological symptoms and she never experienced vertigo before. Laboratory findings confirmed a current COVID-19 infection. The patient was managed with antihypertensive, anti-vertigo medications, and COVID-19 protocol for mild cases. After discharge, the patient was advised to continue the anti-vertigo drugs and COVID-19 medications. SARS-COV-2 may lead to vestibular neuritis causing vertigo and other related symptoms, but more well-designed observational studies with a large sample size are needed to establish a definite association between COVID-19 and vertigo.

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Knockdown of enhancer of rudimentary homolog expression attenuates proliferation, cell cycle and apoptosis of melanoma cells

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Early stage or localized melanoma can be surgically resected with satisfactory outcome, whereas advanced malignant melanoma responds to treatment poorly and has a negative prognosis even after surgery, radiotherapy and other comprehensive treatments. Gene therapy targeting various biological signaling pathwa ys has become an increasingly popular area in melanoma research. However, for gene therapy success, it is important to reveal the molecular mechanisms of melanoma tumorigenesis and development. The present study examined the effects of downregulating enhancer of rudimentary homolog (ERH) expression on the proliferation, metastasis and cell cycle of melanoma cells. ERH expression levels in melanoma tissues and cells were determined. Then, ERH gene expression in melanoma cell lines was downregulated or overexpressed by the lentiviral RNA interference technique. Furthermore, we performed cell counting kit-8, clone formation, scratch, transwell migration, subcutaneous tumorigenesis and venous metastasis assays as well as carried out flow cytometry analysis to explore the effects of ERH expression on cell proliferation, cell cycle, apoptosis and metastasis. We found that ERH expression in melanoma tissues and cells was markedly higher than in normal melanin nevus. Suppressing ERH express ion by RNA interference in melanoma A375, WM35 and SK28 cell lines inhibited their proliferation and induced cell apoptosis. The cell cycle was also found to be blocked in the G1 phase. However, the metastatic properties of melanoma cells in vitro and in vivo remained largely unaltered by ERH knockdown. Our results show that ERH expression is increased in melanoma. Meanwhile, the proliferation and cell cycle transformation abilities are impaired potentially by downregulating the ERH expression in melanoma cells. Therefore, targeting ERH might serve as a novel therapeutic approach for malignant melanoma. Received 30 May 2020 Accepted 18 April 2021 Correspondence to Dr. Jianda Zhou, Department of Plastic Surgery, The Third Xiangya Hospital, Tong zi po Road 172, Changsha 410083, Hunan, China, Tel: +86 135 0849 3668; fax: +86 731 88618015; e-mail: zhoujianda@csu.edu.cn Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma

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Immunotherapy has revolutionized the treatment of melanoma, yet survival remains poor for patients with metastatic disease. The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe adjuvant therapy for patients with resected stage III/IV melanoma who complete the primary vaccine series. Here, we describe an open-label trial of patients with metastatic melanoma treated with TLPLDC vaccine in addition to standard of care (SoC) therapies. The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles, which are phagocytosed by autologous dendritic cells ex vivo. Patients who recurred while enrolled in a phase IIb trial of adjuvant TLPLDC vaccine (crossover cohort) and patients with measurable metastatic melanoma cohort were offered TLPLDC vaccine along with SoC therapies. Tumor response was measured by RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by intention-to-treat analysis. Fifty-four patients were enrolled (28 in crossover cohort; 26 in metastatic melanoma cohort). The vaccine was well-tolerated with no grade ≥3 adverse events when given with SoC therapies to include checkpoint inhibitors, BRAF/MEK inhibitors, tyrosine kinase inhibitors, intralesional therapy and/or radiation. In the crossover arm, OS was 76.5% and PFS was 57.1% (median follow-up of 13.9 months). In the metastatic melanoma arm, OS was 85.7% and PFS was 52.2% (median follow-up 8.5 months). The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma. Received 16 February 2021 Accepted 21 May 2021 Correspondence to Alexandra M. Adams, Department of Surgery, Brooke Army Medical Center, 3551 Roger Brooke Dr., Fort Sam Houston, TX 78234, USA Tel: xxx; e-mail: lexy.adams16@gmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Πέμπτη 1 Ιουλίου 2021

Disruption of anchoring junctions in the testes of experimental varicocele rats

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Exp Ther Med. 2021 Aug;22(2):887. doi: 10.3892/etm.2021.10319. Epub 2021 Jun 16.

ABSTRACT

Varicocele is a common disease of the male reproductive system and is the main cause of male infertility; however, the pathological mechanisms of varicocele remain unclear. The anchoring junctions (AJs) in the testies are located between Sertoli cells, or between Sertoli cells and germ cells. Intact and functional AJs are crucial for spermatogenesis. In the present study, the histomorphology, ultrastructure of AJ, cell cycle, expression of AJ structural proteins, and the level of AJ-associated signaling molecules were investigated in the left testes of experimental varicocele rats at 8 and 12 weeks after surgery. The results revealed that varicocele induced the loss of premature germ cells from the seminiferous epithelium. Furthermore, the results of the present study also revealed damage to the AJ ultrastructure, disorientation of the spermatid h ead, deregulation of the cell cycle, downregulation of AJ structural proteins, enhanced phosphorylation of focal adhesion kinase (FAK) at Tyr397 and its downstream adapter Src at Tyr416, and activation of the extracellular signal-regulated protein kinase 1 (ERK1) signaling pathway. Thus, the present study demonstrated that varicocele disrupted the structure and function of AJs in the left testes of rats, and that enhancement of FAK phosphorylation may contribute to AJ damage by activating ERK1 signaling, disrupting actin-based filament networks, and altering the balance of the apical ectoplasmic specialization-blood testis barrier functional axis. These findings provide important insights into the pathological mechanisms through which varicocele contributes to male infertility and could help to identify new therapeutic targets for varicocele.

PMID:34194565 | PMC:PMC8237278 | DOI:10.3892/etm.2021.10319

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Curcumin sensitizes Epstein-Barr-immortalized lymphoblastoid cell lines to inorganic arsenic toxicity

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Exp Ther Med. 2021 Aug;22(2):872. doi: 10.3892/etm.2021.10304. Epub 2021 Jun 14.

ABSTRACT

Chronic exposure to inorganic arsenic (iAs) through contaminated drinking water is an important health problem in certain countries. The use of phytochemicals such as curcumin has recently emerged as an alternative strategy for preventing cellular damage caused by iAs. The Epstein-Barr virus (EBV) affects ~90% of the population and experimental evidence suggested that curcumin mediates cytotoxicity against EBV-infected cells. Due to the potential for an interaction of these factors, the aim of the present study was to evaluate the effect of this phytochemical on iAs-related toxicity in EBV-infected cells. Two independent EBV-immortalized human lymphoblastoid cell lines (LCLs) were used as the model. The cell lines were first incubated with increasing concentrations of curcumin or iAs for 24 and 15 h, respectively, to determine the individual effec ts of each exposure on cell death. In the next experiment, cell cultures were pre-incubated with 5 µM curcumin for 9 h prior to treatment with 10 µM iAs for 15 h, followed by evaluation of cell death and the cell cycle profile via flow cytometry. The results indicated that individual treatment with either curcumin or iAs induced cell death in a concentration-dependent manner. Furthermore, curcumin pre-treatment enhanced iAs-induced cell death and promoted cell cycle arrest in G1 phase. Taken together, these results suggested that curcumin sensitizes EBV-positive LCLs to the cytotoxic effects of iAs.

PMID:34194550 | PMC:PMC8237405 | DOI:10.3892/etm.2021.10304

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Actualities in immunological markers and electrochemical sensors for determination of dopamine and its metabolites in psychotic disorders (Review)

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Exp Ther Med. 2021 Aug;22(2):888. doi: 10.3892/etm.2021.10320. Epub 2021 Jun 17.

ABSTRACT

Psychotic disorders represent a serious health concern. At this moment, anamnestic data, international criteria for diagnosis/classification from the Diagnostic and Statistical Manual of Mental Disorders-5 and the International Classification of Diseases-10 and diagnostic scales are used to establish a diagnosis. The most commonly used biomarkers in psychotic illnesses are those regarding the neuroimmune system, metabolic abnormalities, neurotrophins and neurotransmitter systems and proteomics. A current issue faced by clinicians is the lack of biomarkers to help develop a more accurate diagnosis, with the possibility of initiating the most effective treatment. The detection of biological markers for psychosis has the potential to contribute to improvements in its diagnosis, prognosis and treatment effectiveness. The mixture of multiple biomarkers may improve the ability to differentiate and classify these patients. In this sense, the aim of this study was to analyze the literature concerning the potential biomarkers that could be used in medical practice and to review the newest developments in electrochemical sensors used for dopamine detection, one of the most important exploited biomarkers.

PMID:34194566 | PMC:PMC8237259 | DOI:10.3892/etm.2021.10320

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Stroke secondary to giant-cell arteritis: A literature review

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Exp Ther Med. 2021 Aug;22(2):876. doi: 10.3892/etm.2021.10308. Epub 2021 Jun 15.

ABSTRACT

Stroke is a leading cause of death and disability worldwide. In addition to the classical etiologies of stroke as atherosclerosis and cardioembolism there are many unusual, rare causes, which require a high level of clinical suspicion and further investigations for correct and early diagnosis and adequate treatment. Giant-cell arteritis or temporal arteritis, the most frequent vasculitis in the elderly population is one of the uncommon causes of stroke. In the setting of giant-cell arteritis, stroke more likely affects the vertebrobasilar territory and is the main cause of mortality. Duplex ultrasound examination is a routine investigation for stroke patients and may be key to the diagnosis if the classical hypoechoic 'halo sign' is recognized at the level of vertebral arteries. In this situation the ultrasound evaluation of temporal arteries and temporal artery biopsy are mandatory. The Giant-cell arteritis-related stroke is a rare condition; therefore, there are no evidence-based guidelines or standard recommendations for the treatment. In the present review, the main characteristics of giant-cell arteritis-related stroke are discussed.

PMID:34194554 | PMC:PMC8237390 | DOI:10.3892/etm.2021.10308

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LGR5 enhances the osteoblastic differentiation of MC3T3-E1 cells through the Wnt/β-catenin pathway

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Exp Ther Med. 2021 Aug;22(2):889. doi: 10.3892/etm.2021.10321. Epub 2021 Jun 17.

ABSTRACT

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is a Wnt-associated gene that contributes to cell proliferation and self-renewal in various organs. LGR5 is expressed in Ewing sarcoma, and LGR5-overexpressing mesenchymal stem cells promote fracture healing. However, the effects of LGR5 on osteoblastic differentiation remain unclear. The aim of the present study was to explore the function of LGR5 in osteoblastic differentiation. LGR5 was overexpressed or knocked down in the MC3T3-E1 pre-osteoblastic cell line via lentiviral transfection and its function in osteoblastic differentiation was investigated. The mRNA expression levels of the osteoblast differentiation markers alkaline phosphatase (ALP), osteocalcin and collagen type I a1 were determined, and ALP and Alizarin red staining were performed. In addition, the effects of LGR5 modulation on β-catenin and the expression of target genes in the Wnt pathway were investigated. The results revealed that the overexpression of LGR5 promoted osteoblastic differentiation. This was associated with enhancement of the stability of β-catenin and its levels in the cell nucleus, which enabled it to activate Wnt signaling. By contrast, the inhibition of LGR5 decreased the osteogenic capacity of MC3T3-E1 cells. These results indicate that LGR5 is a positive regulator of osteoblastic differentiation, whose effects are mediated through the Wnt/β-catenin signaling pathway. This suggests suggesting that the regulation of LGR5/Wnt/β-catenin signaling has potential as a therapy for osteoporosis.

PMID:341945 67 | PMC:PMC8237272 | DOI:10.3892/etm.2021.10321

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Percutaneous endoscopic transforaminal discectomy for the treatment of L5-S1 lumbar disc herniation and the influence of iliac crest height on its clinical effects

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Exp Ther Med. 2021 Aug;22(2):866. doi: 10.3892/etm.2021.10298. Epub 2021 Jun 13.

ABSTRACT

The present study aimed to explore the clinical effects of percutaneous endoscopic transforaminal discectomy using a transforaminal endoscopic spine system (TESSYS) technique for the treatment of L5-S1 lumbar disc herniation and to analyse the influence of iliac crest height on these clinical effects. The clinical data of 76 patients with L5-S1 single-segment disc herniation treated with TESSYS at The Second Affiliated Hospital and Third Affiliated Hospital of Xi'an Jiaotong University between January and December 2016 were retrospectively analysed. Patients were divided into the following three groups according to the positional relation between the highest point of the iliac crest and the L4 and L5 pedicles in the lateral lumbar, as determined by X-ray: Group I, iliac crest height below the upper edge horizontal line of the L5 pedicle (n=42); gr oup II, iliac crest height between the lower edge horizontal line of the L4 pedicle and the upper edge horizontal line of the L5 pedicle (n=29) and group III, iliac crest height above the lower edge horizontal line of the L4 pedicle (n=5). Changes in the postoperative visual analogue scale (VAS) pain score and Oswestry disability index (ODI) of the lower back and lower limbs were observed, and the effects were compared among the three groups. The mean operating time was 86.5±13.5 min. A single patient experienced cerebrospinal fluid leakage due to a mild tear of the dura mater during the operation, which improved after symptomatic treatment. The same operation was repeated in one patient due to the recurrence of disc herniation. In all patients, the VAS pain score and ODI of the lower back and lower limbs at 1 week and 1, 3 and 12 months following the operation were significantly lower than those before the operation (all P<0.05). Furthermore, the postoperative VAS pain score an d ODI of the lower back and lower limbs were poorer in group III (L5-S1 lumbar disc herniation complicated with high iliac crest) than in groups I and II (P<0.05). These results suggested that TESSYS was effective in treating lumbar disc herniation. Whether the iliac crest is higher than the lower edge horizontal line of the L4 pedicle is suggested to be one of the factors influencing the outcome of the operation.

PMID:34194544 | PMC:PMC8237383< /a> | DOI:10.3892/etm.2021.10298

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IL-6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

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Exp Ther Med. 2021 Aug;22(2):890. doi: 10.3892/etm.2021.10322. Epub 2021 Jun 17.

ABSTRACT

The aim of the present study was to investigate the effect of the IL-6/STAT3 signaling pathway on intestinal epithelial barrier injury in patients with ulcerative colitis (UC). Fifty-two patients with UC and 21 healthy subjects were recruited. The expression level of IL-6 in plasma was determined by ELISA. Normal human colon mucosal epithelial NCM460 cells were treated with IL-6 or plasma from the patients with UC. Then, the transepithelial electrical resistance value, fluorescein yellow permeability and zonulin release were evaluated. Using reverse transcription-quantitative (q)PCR and western blotting, claudin (CLDN) 1 and CLDN2 expression levels were analyzed. Furthermore, western blotting was used to detect phosphorylation of STAT3. Chromatin immunoprecipitation-qPCR was performed to investigate the enrichment of H3K27ac in the promoter region s of CLDN1 and CLDN2. The present study revealed that IL-6 content was elevated in the plasma from patients with UC and increased with the progression of the disease. IL-6 was also observed to induce intestinal epithelial cell barrier injury and regulate barrier function by influencing the expression of tight junction-related proteins, as well as STAT3. The IL-6/STAT3 signaling pathway regulated transcription of CLDN1 and CLDN2 by affecting the enrichment of histone H3K27ac in their promoter regions. Thus, the significantly increased expression level of IL-6 in the peripheral blood of patients with UC indicates a positive association with the development of UC. Furthermore, the IL-6/STAT3 signaling pathway influences the function of the intestinal barrier by affecting the H3K27ac level in intestinal epithelial cells.

PMID:34194568 | PMC:PMC8237277 | DOI:10.3892/etm.2021.10322

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