Τετάρτη 29 Σεπτεμβρίου 2021

lncRNA LOC339524 inhibits the proliferation of bladder cancer cells by targeting the miR-875-5p/COPS7A signaling axis

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Exp Ther Med. 2021 Nov;22(5):1202. doi: 10.3892/etm.2021.10636. Epub 2021 Aug 23.

ABSTRACT

It has been reported that long non-coding RNAs (lncRNAs) play a crucial role in the progression of various types of cancer. The role of numerous lncRNAs in a variety of cancer types has been investigated. However, the underlying mechanisms of the majority of lncRNAs in bladder cancer (BCa) remain to be elucidated. In the present study, abnormally expressed lncRNAs in BCa and para-carcinoma tissues were identified through screening the Cancer RNA-Seq Nexus database and were validated using reverse transcription-quantitative PCR. It was found that LOC339524 expression levels were markedly downregulated in BCa tissues and cells (J82, T24, UM-UC-3 and 5637). LOC339524 overexpression was revealed to suppress the proliferation of BCa cells. LOC339524 was also discovered to act as a sponge for microRNA (miR)-875-5p, as identified using dual luciferase r eporter assays and biotin pull-down analysis. LOC339524 downregulated the expression of miR-875-5p and knockdown of miR-875-5p expression inhibited the proliferation of bladder cancer cells. In addition, COP9 signalosome subunit 7A (COPS7A) was identified to be the target gene of miR-875-5p and COPS7A expression level was upregulated following LOC339524 overexpression. lncRNA LOC339524 was proposed to function as a competitive endogenous RNA to facilitate the expression of COPS7A by binding to miR-875-5p. In conclusion, the findings of the present study suggested that LOC339524 may inhibit cell proliferation in BCa by targeting the miR-875-5p/COPS7A signaling axis.

PMID:34584547 | PMC:PMC8422399 | DOI:10.3892/etm.2021.10636

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Neuroendocrine neoplasia and bone (Review)

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Exp Ther Med. 2021 Nov;22(5):1219. doi: 10.3892/etm.2021.10653. Epub 2021 Aug 26.

ABSTRACT

This is a narrative review focusing on neuroendocrine neoplasia (NEN) and bone status, in terms of metastases and osteoporosis/fractures. One fifth of NEN have skeletal dissemination, this affinity being regulated by intrinsic tumor factors such as the C-X-C chemokine receptor 4 (CXCR4). Bone colonization impairs the patient quality of life, representing a surrogate of reduced survival. Patients with NEN without bone metastases may exhibit low bone mineral density, perhaps carcinoid-related osteoporosis, yet not a standardized cause of osteoporosis. Case-finding strategies to address bone health in NEN with a good prognosis are lacking. Contributors to fractures in NEN subjects may include: menopausal status and advanced age, different drugs, induced hypogonadism, malnutrition, malabsorption (due to intestinal resection, carcinoid syndrome), hypo vitaminosis D, impaired glucose profile (due to excessive hormones such as glucagon, somatostatinoma or use of somatostatin analogues), various corticoid regimes, and high risk of fall due to sarcopenia. Pheocromocytoma/paraganglioma involve bone through malignant forms (bone is an elective site) and potential secondary osteoporosis due to excessive hormonal content and increased sympathetic activity which is a key player of bone microarchitecture/quality as reflected by low Trabecular Bone Score. Glucocorticoid osteoporosis is related to NEN-associated ectopic Cushing syndrome. Currently, there are a lack of studies to emphasis that excessive gut-derivate serotonin in NENs with carcinoid syndrome is a specific activator of bone loss thus a contributor to carcinoid-related osteoporosis.

PMID:34584564 | PMC:PMC8422397 | DOI:10.3892/etm.2021.10653

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Prospective evaluation of remifentanil-propofol mixture for total intravenous anesthesia: A randomized controlled study

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Exp Ther Med. 2021 Nov;22(5):1198. doi: 10.3892/etm.2021.10632. Epub 2021 Aug 23.

ABSTRACT

Application of total intravenous anesthesia (TIVA) may be considered as unpractical when compared with inhalational anesthesia. Although it is mostly not recommended, mixing intravenous agents is popular in clinical practice. The aim of the present study was to investigate the suitability of using remifentanil-propofol mixture (MIXTIVA) for TIVA. Adult patients with an American Society of Anesthesiologists grade of I-II scheduled for elective thyroidectomy were randomly allocated to 3 groups (n=32 for each) to receive TIVA with remifentanil and propofol infusions separately (control group, Group I) or with MIXTIVA infusion that contained remifentanil/propofol at a proportion of 2/1,000 or 3/1,000 (remifentanil concentration, 20 or 30 µg/ml in 1% propofol in Group II or Group III, respectively). The extubation time (the primary outcome of the stu dy), the orientation time and number of patients in whom intraoperative hypotension, hypertension or bradycardia episodes were encountered during anesthesia were comparable among the groups. The mean remifentanil infusion rate in Group III was significantly higher than that in the other groups. The mean propofol infusion rates and mean bispectral index (BIS) scores during anesthesia were comparable among groups. Hypotension accompanied with a high BIS was encountered in one patient in Group III. In conclusion, compared to the standard TIVA technique using separate drug infusions, MIXTIVA infusion used for thyroidectomies did not result in any statistically significant difference in recovery and clinical outcomes. This technique may be considered as a practical implementation for busy ambulatory centers performing general anesthesia. The present study was retrospectively registered at clinicaltrials.gov (trial registration no. NCT04394897).

PMID:34584543 | PMC:PMC8422392 | DOI:10.3892/etm.2021.10632

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Current research developments of patient-derived tumour xenograft models (Review)

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Exp Ther Med. 2021 Nov;22(5):1206. doi: 10.3892/etm.2021.10640. Epub 2021 Aug 24.

ABSTRACT

Patient-derived tumor xenograft (PDTX) models are established by transferring patient tumors into immunodeficient mice. In these murine models, the characteristics of the primary tumor are retained, including the microenvironment of tumor cell growth and histopathology. Due to this, it has become the most reliable in vivo human cancer model. However, the success rates differ by type of tumor, site of transplantation and tumor aggressiveness. Subcutaneous transplantation is a standard method for PDTX, and subrenal capsule transplantation improves the engraftment rate. Recently, PDTX models are frequently used in the fields of precision medicine, predictive biomarkers, evaluation of drug efficacy and preclinical research on tumor immunotherapeutic drugs. The aim of the present article was to review the establishment, clinical applications an d limitations of the PDTX model in tumor research.

PMID:34584551 | PMC:PMC8422395 | DOI:10.3892/etm.2021.10640

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Aged and Young Mice Differentially Respond to Tape‐Stripping in Epidermal Gene Expression

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Abstract

Disruption of epidermal permeability induces an increase in proinflammatory cytokine expression and release, stimulation of epidermal lipid and DNA synthesis, and expression of antimicrobial peptides. Although alterations in epidermal function in the aged skin are known, whether the epidermal transcriptomic responses to barrier disruption differ between aged and young mice remains unknown. Here we performed RNA sequencing of the epidermis in 2-month- vs. 20-month-old mice following barrier disruption with repeated tape-stripping. At baseline condition, the epidermis of 20-month-old mice displayed an upregulation of inflammation-associated genes and down-regulation of epidermal structure- and development-related genes in comparison to 2-month-old mice. Barrier disruption upregulated expression levels of 327 genes and downregulated 209 genes in 2-month-old mice. In 20-month-old mice, the numbers of upregulated and down-regulated genes were 537 and 299, respectively. In comparison to young mice, the prominent upregulated genes in the 20-month-old mice were associated with IL-17 signaling pathway, while downregulated genes were mainly involved in cytokine-cytokine receptor interaction pathway. These results indicate that inflammation-associated signaling pathways are upregulated, while epidermal structure- and development-related genes are downregulated in the epidermis of aged mice, with further aggravation following barrier disruption, suggesting the importance of improving epidermal function in the elderly.

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The hair follicle‐psoriasis axis: Shared regulatory mechanisms and therapeutic targets

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Abstract

It has long been known that there is a special affinity of psoriasis for the scalp: Here, it occurs most frequently, lesions terminate sharply in frontal skin beyond the hair line and are difficult to treat. Yet, surprisingly, scalp psoriasis only rarely causes alopecia, even though the pilosebaceous unit clearly is affected. Here, we systematically explore the peculiar, insufficiently investigated connection between psoriasis and growing (anagen) terminal scalp hair follicles (HFs), with emphasis on shared regulatory mechanism and therapeutic targets. Interestingly, several drugs and stressors that can trigger/aggravate psoriasis can inhibit hair growth (e.g. beta-blockers, chloroquine, carbamazepine, interferon-alpha, perceived stress). Instead, several anti-psoriatic agents can stimulate hair growth (e.g., cyclosporine, glucocorticoids, dithranol, UV irradiation), while skin/HF trauma (Köbner phenomenon/depilation) favors the development of psoriatic lesions and induces anagen in "quiescent" (telogen) HFs.

On this basis, we propose two interconnected working models: a) the existence of a bidirectional "hair follicle-psoriasis axis", along which keratinocytes of anagen scalp HFs secrete signals that favor the development and maintenance of psoriatic scalp lesions and respond to signals from these lesions, and b) that anagen induction and psoriatic lesions share molecular "switch-on" mechanisms, which invite pharmacological targeting, once identified. Therefore, we advocate a novel, cross-fertilizing and integrative approach to psoriasis and hair research that systematically characterizes the "HF-psoriasis axis", focused on identification and therapeutic targeting of selected, shared signaling pathways in the future management of both, psoriasis and hair growth disorders.

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Τρίτη 28 Σεπτεμβρίου 2021

The correlation between neonatal parameters and late‐onset inner ear disorders in congenital cytomegalovirus infection: an 10‐year population‐based cohort study

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Abstract

Objective

To evaluate the correlation of neonatal parameters with late-onset sensorineural hearing loss (SNHL) and vestibular dysfunction in individuals with congenital cytomegalovirus (cCMV) infection using the National Health Insurance Research Database (NHIRD) in Taiwan.

Design

Retrospective cohort study.

Setting

The whole Taiwanese population.

Participants

Patients with related diagnostic codes and examinations in their records were regarded as having cCMV infection. Each subject in that group was matched to 10 control individuals with noncongenital CMV infection on the basis of several neonatal parameters, including low gestational age, low birth weight, low Apgar score, maternal history of CMV infection and prolonged cCMV infection. A total of 5,893 and 58,930 participants were enrolled in the study and control groups, respectively.

Main outcome measures

The main outcomes were the development of SNHL and the development of vestibular dysfunction within one year after birth as reflected by diagnostic codes and specific examinations. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of each primary outcome between the two groups.

Results

Overall, 109 and 397 episodes of SNHL developed in the study group and the control group, respectively, and the study group demonstrated a significantly higher incidence of SNHL (adjusted HR: 2.56; 95% CI: 2.07–3.18). In addition, similar incidence rates of vestibular dysfunction were found in the study group and the control group, with 7 and 90 events, respectively (adjusted HR: 0.77; 95% CI: 0.36–1.67). In subgroup analyses, a higher incidence of SNHL was correlated with lower gestational age (GA) (adjusted HR: 2.09; 95% CI: 1.29–3.39), lower birth weight (BW) (adjusted HR: 2.05; 95% CI: 1.28–3.30), and prolonged cCMV infection (adjusted HR: 3.92; 95% CI: 1.95–7.88).

Conclusions

Low GA, low BW and a long disease course are significantly correlated with late-onset SNHL in cCMV infection.

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