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Πέμπτη 22 Απριλίου 2021

Dl-butylphthalide inhibits rotenone-induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO-1 signaling pathway

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Exp Ther Med. 2021 Jun;21(6):597. doi: 10.3892/etm.2021.10029. Epub 2021 Apr 9.

ABSTRACT

Activated microglia are a source of superoxide which often increases oxidative stress in the brain microenvironment, increase production of reactive oxygen species (ROS) and directly or indirectly lead to dopaminergic neuronal death in the substantia nigra. Thus superoxide contributes to the pathogenesis of Parkinson's disease (PD). Evidence suggests that mitochondria are the main source of ROS, which cause oxidative stress in cells. Levels of ROS are thus associated with the function of the mitochondrial complex. Therefore, protecting the mitochondrial function of microglia is important for the treatment of PD. Dl-butylphthalide (NBP), a compound isolated from Chinese celery seeds, has been approved by the China Food and Drug Administration for the treatment of acute ischemic stroke. Recently, NBP demonstrated therapeutic potential for PD. However , the mechanism underlying its neuroprotective effect remains unclear. The present study aimed to investigate the effect of NBP on rotenone-induced oxidative stress in microglia and its underlying mechanisms. The results demonstrated that NBP treatment significantly increased mitochondrial membrane potential and decreased ROS level in rotenone-induced microglia. Western blot analysis showed that NBP treatment promoted entry of nuclear respiratory factor-2 (Nrf2) into the nucleus, increased heme oxygenase-1 (HO-1) expression and decreased the level of the Nrf2 inhibitory protein, Kelch-like ECH-associated protein 1. Overall, the findings indicated that NBP inhibited rotenone-induced microglial oxidative stress via the Keap1/Nrf2/HO-1 pathway, suggesting that NBP may serve as a novel agent for the treatment of PD.

PMID:33884035 | PMC:PMC8056112 | DOI:10.3892/etm.2021.10029

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Interferon-τ regulates the expression and function of bovine leukocyte antigen by downregulating bta-miR-204

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Exp Ther Med. 2021 Jun;21(6):594. doi: 10.3892/etm.2021.10026. Epub 2021 Apr 8.

ABSTRACT

IFN-τ is a pregnancy recognition factor that regulates embryo implantation in ruminants. IFN-τ has been suggested to be involved in the expression of microRNA (miRNA/miR) and bovine leukocyte antigen (BoLA), which is an analog of the human major histocompatibility complex class I. However, little is known about whether the miRNAs are involved in the expression of BoLA in ruminants. The present study firstly verified that bta-miR-204 was downregulated and that BoLA was upregulated in the uterine tissues of dairy cows during early pregnancy. Subsequently, luciferase reporter assays, reverse transcription-quantitative PCR and western blot analysis were used to validate BoLA as the target gene of bta-miR-204. Moreover, BoLA was markedly upregulated and bta-miR-204 was downregulated in bovine endometrial epithelial cells (bEECs) treated with IFN-τ. I n addition, the results indicated that when the expression level of BoLA was increased by IFN-τ, the expression level of programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) was also increased. Furthermore, when BoLA was silenced in bEECs by small interfering RNA, the expression of PD-L1 and PD-L2 was not affected by IFN-τ. The expression level of PD-L1 and PD-L2 was also increased in the uterine tissues of pregnant dairy cattle. In conclusion, IFN-τ may function by suppressing the expression of bta-miR-204 to increase the expression of BoLA during the embryo implantation period in cattle. IFN-τ may induce PD-L1 and PD-L2 transcription by regulating BoLA, which may influence the T cell immune response, thereby regulating pregnant cattle immunization.

PMID:33884032 | PMC:PMC8056107 | DOI:10.3892/etm.2021.10026

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Intra-articular injections of platelet-rich plasma vs. hyaluronic acid in patients with knee osteoarthritis: Preliminary follow-up results at 6-months

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Exp Ther Med. 2021 Jun;21(6):598. doi: 10.3892/etm.2021.10030. Epub 2021 Apr 11.

ABSTRACT

The aim of the present study was to compare the clinical and economic benefits of intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) in Chinese patients with knee osteoarthritis (OA). A total of 86 patients (42 treated with PRP and 44 with HA) were treated with three weekly intra-articular injections. The inclusion criteria included patients between 18 and 75 years of age, with chronic knee pain or swelling lasting >3 months and X-ray findings of degenerative joint alterations according to the Kellgren-Lawrence score grade I-III. Clinical examinations were performed before treatment, at 1- and 6-month post-injection intervals. International Knee Documentation Committee subjective, Western Ontario and McMaster Universities and visual analogue scale scores were determined at each examination. Adverse reactions, aver age cost, treatment time and patient satisfaction were also recorded. Compared with patients injected with HA, PRP was found to be associated with increased and more severe post-injection pain and swelling, where the duration of adverse reactions was greater in the PRP group (P=0.02). During the follow-up evaluations, both groups showed statistically significant improvements in all clinical scores from pre-injection to 1- and 6-month assessments (P<0.05). However, no significant inter-group (PRP vs. HA) differences were observed in the clinical scores between the two follow-up time points. There were also no significant differences in clinical score between the groups with regards to the Kellgren-Lawrence grade I, II or III. The average cost of PRP injections was 22.8X that of HA administration and the average treatment time was 5X that of HA, but there was no significant difference in patient satisfaction. These preliminary results indicate that although PRP injections can signi ficantly improve clinical outcome in patients with knee OA, PRP is not any more effective compared with HA. Furthermore, PRP injections are associated with higher costs and treatment times. Therefore, additional clinical studies are required before PRP injections can be considered as a first-line treatment option for knee OA.

PMID:33884036 | PMC:PMC8056115 | DOI:10.3892/etm.2021.10030

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Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

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Exp Ther Med. 2021 Jun;21(6):601. doi: 10.3892/etm.2021.10033. Epub 2021 Apr 12.

ABSTRACT

[This retracts the article DOI: 10.3892/etm.2018.5710.].

PMID:33884039 | PMC:PMC8056111 | DOI:10.3892/etm.2021.10033

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Role of NGF and its receptors in wound healing (Review)

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Exp Ther Med. 2021 Jun;21(6):599. doi: 10.3892/etm.2021.10031. Epub 2021 Apr 11.

ABSTRACT

Wound healing is an important and complicated process that includes four highly integrated and overlapping phases, haemostasis, inflammation, proliferation and tissue remodelling. Nerve growth factor (NGF) was the first member of a family of neurotrophic factors to be discovered, and is an essential neurotrophic factor for the development and maintenance of the central and peripheral nervous systems. Several studies have proposed that NGF and its receptors, tropomyosin-related kinase receptor 1 and NGF receptor, are involved in the wound healing process, and are important components of the healing of several wounds both in vivo and in vitro. Topical application of NGF significantly promotes the healing of different types of wounds, including diabetic foot ulcers, pressure ulcers and corneal wounds. The present review summarizes the s tatus of NGF and its receptors in current literature, and discusses data obtained in the last few years on the healing action of NGF in cutaneous, corneal and oral wounds.

PMID:33884037 | PMC:PMC8056114 | DOI:10.3892/etm.2021.10031

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Role of Notch, IL-1 and leptin expression in colorectal cancer

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Exp Ther Med. 2021 Jun;21(6):600. doi: 10.3892/etm.2021.10032. Epub 2021 Apr 11.

ABSTRACT

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that inter acts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1β, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were incre ased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

PMID:33884038 | PMC:PMC8056113 | DOI:10.3892/etm.2021.10032

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Comparison of anti-inflammatory effects of Mecasin and its constituents on lipopolysaccharide-stimulated BV2 cells

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Exp Ther Med. 2021 Jun;21(6):591. doi: 10.3892/etm.2021.10023. Epub 2021 Apr 8.

ABSTRACT

Mecasin, a traditional medicine, contains nine herbal constituents: Curcuma longa, Salvia miltio rhiza, Gastrodia elata, Chaenomeles sinensis, Polygala tenuifolia, Paeonia japonica, Glycyrrhiza uralensis, Atractylodes japonica and processed Aconitum carmichaeli. Several biological effects of mecasin have been described both in vivo and in vitro. Previous studies have demonstrated that mecasin has anti-inflammatory effects. The purpose of the present study was to determine anti-inflammatory effects of mecasin and its natural product constituents on lipopolysaccharide (LPS)-stimulated BV2 cells by measuring nitrite and nitric oxide contents. Nitrite production levels in LPS-stimulated BV2 cells incubated with mecasin and each individual constituent of mecasin were measured. The results suggested that C. longa , P. tenuifolia and P. japonica inhibited nitrite production in a pattern similar to that of mecasin. The effect of mecasin was likely a result of synergistic effects of its natural herb constituents.

PMID:33884029 | PMC:PMC8056109 | DOI:10.3892/etm.2021.10023

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A minimum 8-year follow-up comparative study of decompression and coflex stabilization with decompression and fusion

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Exp Ther Med. 2021 Jun;21(6):595. doi: 10.3892/etm.2021.10027. Epub 2021 Apr 9.

ABSTRACT

The current study aimed to compare the outcomes of decompression and interlaminar stabilisation with those of decompression and fusion for the treatment of lumbar degenerative disease (LDD) at a minimum 8-year follow-up. The current study also aimed to analyse the risk factors of radiographic adjacent segment degeneration (ASD). A total of 82 consecutive patients with LDD who underwent surgery between June 2007 and February 2011 were retrospectively reviewed. Of these patients, 39 underwent decompression and Coflex interspinous stabilisation (Coflex group) and 43 underwent decompression and posterior lumbar interbody fusion (PLIF) (PLIF group). All patients had a minimum of 8-years of follow-up data. Radiographic and clinical outcomes were compared between the groups, and the risk factors of developing radiographic ASD were also evaluated. The Oswe stry disability index and visual analogue scale leg and back pain scores of both groups significantly improved compared with the baseline (all P<0.05), and no difference were indicated between the two groups at each follow-up time point (P>0.05). The Coflex group exhibited preserved mobility (P<0.001), which was associated with a decreased amount of blood loss (P<0.001), shorter duration of surgery (P=0.001), shorter duration of hospital stay and a lower incidence of ASD (12.8 vs. 32.56%; P=0.040) compared with the fusion group. The current study indicated that coflex and fusion technologies are safe and effective for the treatment of LDD, based on long-term follow-up data. However, Coflex interspinous stabilisation was revealed to reduce ASD incidence. Under strict indications, Coflex interspinous stabilisation is an effective and safe treatment method.

PMID:33884033 | PMC:PMC8056116 | DOI:10.3892/etm.2021.10027

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Cartilaginous bending spring for preventing tympanic membrane graft medialisation in anterior or subtotal tympanic membrane perforations-how I do it

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Eur Arch Otorhinolaryngol. 2021 Apr 21. doi: 10.1007/s00405-021-06814-5. Online ahead of print.

ABSTRACT

BACKGROUND: The reconstruction of anterior or subtotal tympanic membrane perforations is critical due to the risk of anterior graft medialisation and retraction or recurrent perforation.

METHOD: After reconstruction of the tympanic membrane by means of grafting, a rectangular cartilage strut (length 6 mm, breadth 2 mm, thickness 0.1 mm) is prepared using a cartilage knife and scalpel. This strut graft is placed between the cartilage graft and the promontory in the anterior inferior part of the middle ear cavity.

CONCLUSION: Our experience shows that using a U-shaped cartilage strut to sustain the tympanic reconstruction effectively prevents the medialisation of the graft and recurrent perforations.

PMID:33884500 | DOI:10.1007/s00405-021-06814-5

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Τετάρτη 21 Απριλίου 2021

Annual trends in Google searches provides insights related to rhinosinusitis exacerbations

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Eur Arch Otorhinolaryngol. 2021 Apr 20. doi: 10.1007/s00405-021-06806-5. Online ahead of print.

ABSTRACT

PURPOSE: Temporal trends of disease-specific internet searches may provide novel insights into seasonal dynamics of disease burden and, by extension, disease pathophysiology. The aim of this study was to define the temporal trends in rhinosinusitis-specific internet searches.

METHODS: This was a cross sectional analysis of search volume for predefined search terms. Google trends was used to explore the volume of searches for five specific search terms related to rhinosinusitis: nose, mucus, sinus, sinusitis, chronic sinusitis, which were entered into Google web search between 2004 and 2019. Results were analyzed within search "context" which included temporally associated related searches. Relative search volume (RSV) was analyzed for English and non-English speaking countries from the Northern and Southern hemispheres. Analys is of seasonality was performed using the cosinor model.

RESULTS: The five specific search terms were most related to rhinosinusitis-related search contexts, indicating that they were appropriately reflective of internet queries by patients for rhinosinusitis. The RSV for rhinosinusitis-related terms and more general search terms increased with each passing year indicating constant interest in rhinosinusitis. Cosinor time series analysis revealed inquiry peaks in winter months for all five specific rhinosinusitis-related search terms independent from the hemisphere.

CONCLUSION: Over a 15-year period, Google searches with rhinosinusitis-specific search terms consistently peaked during the winter around the world. These findings indirectly support the model of viral infection or exposure as the predominant cause of acute rhinosinusitis and acute exacerbations of chronic rhinosinusitis.

PMID:33877434 | DOI:10.1007/s00405-021-06806-5

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Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study

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Eur Arch Otorhinolaryngol. 2021 Apr 20. doi: 10.1007/s00405-021-06793-7. Online ahead of print.

ABSTRACT

BACKGROUND: Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption.

METHODS: This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43 months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status.

RESULTS: Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival bet ween groups.

CONCLUSION: OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

PMID:33877432 | DOI:10.1007/s00405-021-06793-7

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