Δευτέρα 7 Φεβρουαρίου 2022

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells

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Exp Ther Med. 2022 Mar;23(3):209. doi: 10.3892/etm.2022.11132. Epub 2022 Jan 7.

ABSTRACT

The overall outcomes for patients with advanced liver cancer are far from satisfactory, and the development of more effective therapeutic strategies for liver cancer is required. Sulforhodamine blue and colony formation assays were performed to detect the proliferation of liver certain cancer cells, including HepG2 and Hep3B. Western blotting was also preformed to detect the expression of indicated proteins, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, dual-specificity tyrosine phosphorylation kinase 1A (DYRK1A), PARP-1/2, GAPDH, myeloid cell leukemia-1, phosphorylated-AKT (Ser473), caspase-3, α-tubulin and AKT. PI staining was used to detect cell death. In the present study, DYRK1A knockdown significantly enhanced the anti-liver cancer effect of regorafenib in vitro. Furthermore, DYRK1A inhibitor harmine together with regorafenib provided synergistic anti-liver cancer activity by suppressing cell proliferation. In addition, harmine significantly enhanced regorafenib-induced cell death in liver cancer cells. It has been reported that AKT signaling is activated in regorafenib-resistant cancer cells and plays a crucial role in the regulation of cellular sensitivity to regorafenib. In the present study, AKT was activated in regorafenib-treated cells, and harmine could suppress the activation of AKT and reinforce the anti-cancer effects of regorafenib via regulating AKT in liver cancer cells. These data indicated that harmine enhanced the anti-cancer effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells via regulating the activation of AKT, and harmine plus regorafenib may be a potential therapeutic regimen for treating patients with liver cancer.

PMID:35126712 | PMC:PMC8796640 | DOI:10.3892/etm.2022.11132

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Benefits and adverse events of melatonin use in the elderly (Review)

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Exp Ther Med. 2022 Mar;23(3):219. doi: 10.3892/etm.2022.11142. Epub 2022 Jan 14.

ABSTRACT

Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin a nd β-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area.

PMID:35126722 | PMC:PMC8796282 | DOI:10.3892/etm.2022.11142

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Insulin-like growth factor-1: A potential target for bronchopulmonary dysplasia treatment (Review)

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Exp Ther Med. 2022 Mar;23(3):191. doi: 10.3892/etm.2022.11114. Epub 2022 Jan 5.

ABSTRACT

Bronchopulmonary dysplasia (BPD) is a common respiratory disorder among preterm infants, particularly low-birth-weight infants (LBWIs) and very-low-birth-weight infants (VLBWIs). Although BPD was first reported 50 years ago, no specific drugs or efficient measures are yet available for prevention or treatment. Insulin-like growth factor-1 (IGF-1) belongs to the insulin family. It promotes mitosis and stimulates cell proliferation and DNA synthesis, the primary factors involved in pulmonary development during the fetal and postnatal periods. Several studies have reported that IGF-1 exerts certain effects on BPD genesis and progression by regulating BPD-related biological processes. In addition, exogenous addition of IGF-1 can alleviate lung inflammation, cell apoptosis and eliminate alveolar development disorders in children with BPD. These findings suggest that IGF-1 could be a new target for treating BPD. Here, we summarize and analyze the definition, pathogenesis, and research status of BPD, as well as the pathogenesis of IGF-1 in BPD and the latest findings in related biological processes.

PMID:35126694 | PMC:PMC8794548 | DOI:10.3892/etm.2022.11114

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Efficiency of platelet-rich plasma therapy for healing sports injuries in young athletes

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Exp Ther Med. 2022 Mar;23(3):215. doi: 10.3892/etm.2022.11139. Epub 2022 Jan 11.

ABSTRACT

In recent years, platelet-rich plasma (PRP) therapy has been a subject of controversy in orthopedics field. Our objective was to assess the efficiency of PRP therapy for patients who have suffered grade 2 meniscal lesions and grade 2 anterior cruciate ligament (ACL) lesions, graded by magnetic resonance imaging (MRI). A retrospective observational study was conducted, which included 72 young recreational athletes who had been diagnosed with grade 2 meniscal injury, graded using MRI, that benefited from PRP therapy as an enhancement of the primary treatment, after cast immobilization. The Lysholm score, the pain intensity and the resuming of the physical activity before the PRP treatment and one month after were analyzed. Our study revealed that patients had an improved subjective perception of pain after PRP therapy and an improvement of the Lysho lm score. Concurrently, 83.3% of patients could return to sports and daily physical activity. It can be concluded that PRP therapy is a safe, easy to manage treatment, efficient for pain relief and in resuming of sports activities for young recreational athletes who have sustained partial meniscal or ACL tears. In terms of pain relief, it appears that the PRP therapy could be more efficient for young patients with ACL injuries.

PMID:35126718 | PMC:PMC8796279 | DOI:10.3892/etm.2022.11139

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Identification of key pathways and genes in vestibular schwannoma using bioinformatics analysis

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Exp Ther Med. 2022 Mar;23(3):217. doi: 10.3892/etm.2022.11141. Epub 2022 Jan 13.

ABSTRACT

The aim of the present study is to identify novel promising marks and targets of diagnosis, therapy and prognosis for patients with vestibular schwannoma at the molecular level. The gene expression profiles of GSE54934, GSE39645 and GSE56597 datasets were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by comparing between gene expression profiles of the vestibular schwannoma tissues and normal tissues. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were performed. The function and pathway enrichment analysis were performed for DEGs with DAVID. Reverse transcription-quantitative PCR were conducted to confirm the expression of BCL2, AGT, IL6 and ITGA2 in human Schwann cells and vestibular schwannoma cells. A total of 4,025, 1,1291 and 1,513 DEGs were identified from GSE54934, GSE56597 and GSE39645 datasets, respectively. GO and KEGG analysis showed that the mutual upregulated genes were mainly enriched in cell division, mitotic nuclear division, and transition of mitotic cell cycle, whilst mutual downregulated genes were enriched in chemical synaptic transmission, neurotransmitter transport, and synaptic vesicle membrane. Subsequently, 20 genes, including BCL2, AGT, IL6 and ITGA2 were selected as hub genes with high degrees after PPI network analysis. The significant differential expression of those genes were detected among vestibular schwannoma tissues compared with normal nerve tissues. In conclusion, BCL2, AGT, IL6 and ITGA2 are significantly higher expressed in vestibular schwannoma tissues compared with human Schwann tissues. The DEGs identified in the present study provide novel targets for the diagnosis and treatment of vestibular schwannoma.

PMID:35126720 | PMC:PMC8796280 | DOI:10.3892/etm.2022.11141

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Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review)

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Exp Ther Med. 2022 Mar;23(3):197. doi: 10.3892/etm.2022.11120. Epub 2022 Jan 5.

ABSTRACT

Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enz yme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required.

PMID:35126700 | PMC:PMC8794551 | DOI:10.3892/etm.2022.11120

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Cytokines and Inflammation in Meniere Disease

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Clin Exp Otorhinolaryngol. 2022 Feb 8. doi: 10.21053/ceo.2021.00920. Online ahead of print.

ABSTRACT

Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evide nce to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.

PMID:35124944 | DOI:10.21053/ceo.2021.00920

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