Thursday, April 22, 2021

Downregulation of miR-588 is associated with tumor progression and unfavorable prognosis in patients with osteosarcoma

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Exp Ther Med. 2021 Jun;21(6):592. doi: 10.3892/etm.2021.10024. Epub 2021 Apr 8.

ABSTRACT

Osteosarcoma (OS) is a primary malignant tumor characterized by a high metastatic potential and poor prognosis. The dysregulation of miR-588 has been demonstrated to serve crucial roles in the progression of numerous types of cancer. The present study aimed to investigate the expression and function of miR-588 in the development of OS. To do so, clinical samples were collected and analyzed, and in vitro experiments were conducted. A total of 104 patients with OS were recruited between 2012 and 2014. The expression of miR-588 was analyzed by reverse transcription quantitative PCR. The association between miR-588 expression and the clinicopathological characteristics and survival rate of patients with OS was evaluated. Furthermore, Cell Counting Kit-8 and Transwell assays were used to evaluate the effect of miR-588 on the proliferation and the migrat ory and invasive abilities of various OS cell lines. The results demonstrated that miR-588 expression in OS tissues and cells was significantly lower compared with normal tissues and cells. In addition, miR-588 expression was closely associated with the Musculoskeletal Tumor Society (MSTS) staging of patients with OS. miR-588 expression and MSTS staging were therefore considered as independent indicators for the prognosis of patients with OS. In addition, miR-588 downregulation significantly stimulated the proliferation and migratory and invasive abilities of OS cells. Taken together, these findings indicated that miR-588 may serve as an independent prognostic factor and tumor suppressor in OS.

PMID:33884030 | P MC:PMC8056108 | DOI:10.3892/etm.2021.10024

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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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Wednesday, April 21, 2021

Increased salvage rates with early reexploration: A retrospective analysis of 547 free flap cases

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J Plast Reconstr Aesthet Surg. 2021 Mar 19:S1748-6815(21)00089-9. doi: 10.1016/j.bjps.2021.03.001. Online ahead of print.

ABSTRACT

BACKGROUND: Free flap complications are generally rare, but not negligible since they may exert paramount impact on both patients and care providers. The aim of the study was to identify risk factors for reexploration and assess predictors associated with increased salvage rates.

METHODS: A retrospective cohort study was conducted for free flaps performed between 2006 and 2015. Patient demographics, indications and flap types were analyzed together with complications and time to reexploration.

RESULTS: Among 547 consecutive free flaps, 11.5% required acute reexploration. Hematoma together with vascular compromise was the main cause (41.9%) for reexploration, followed by hematoma only (19.4%), venous (16.1%) and arterial (6.5%) thrombosis. Hematoma was associated with an increased risk for concom itant vascular complication (p < 0.02). The incidence of total and partial flap necrosis was 3.5% and 3.7% respectively. There was an overall 71.4% salvage rate. The median time from detection of a compromised flap to reexploration was 3.0 h. Significantly higher salvage rates were observed for cases reexplored within (82.4%) compared to after (57.1%) 3.0 h (OR 3.50 (95% CI 1.10 to 11.13, p = 0.034)).

CONCLUSIONS: The current study highlights the importance of early intervention, including evacuation of hematomas that may lead to vascular compromise. Adequate monitoring of venous outflow was found necessary to improve flap salvage rates, whereas arterial complications were mainly related to persistent arterial injury in traumatized extremities with reduced salvage rates. Free flap surgery requires trained staff and immediate access to operating facilities to ensure high flap survival rates.

PMID:33879412 | DOI:10.1016/j.bjps.2021.03.001

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