Monday, February 7, 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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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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Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats

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Exp Ther Med. 2022 Mar;23(3):216. doi: 10.3892/etm.2022.11140. Epub 2022 Jan 11.

ABSTRACT

Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague-Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF-β1, Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also measured by reverse transcription-quantitative PCR, western b lotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF-β1, Collagen I, Collagen III and α-SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB.

PMID:35126719 | PMC:PMC8796288 | DOI:10.3892/etm.2022.11140

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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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From chronic pruritus to neuroendocrine tumor: A case report

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Exp Ther Med. 2022 Mar;23(3):189. doi: 10.3892/etm.2022.11112. Epub 2022 Jan 4.

ABSTRACT

Chronic pruritus is a major and distressing symptom of many diseases of dermatological, neurological, psychogenic or systemic origin. This chronic itch could be a presenting sign of malignancy; therefore, paraneoplastic pruritus has also been associated with neuroendocrine tumors (NETs). This article focuses on a patient presenting with chronic pruritus for the past 12 months and who received numerous treatment schemes with very poor clinical improvement, that presented in the hospital for worsening of the chronic pruritus associated with skin rash and significant weight loss (approximately 6 kg over a 2-month period). The laboratory tests showed iron deficiency anemia, eosinophilia and negative tumor markers. In order to investigate the hypoanabolic and anemic syndromes, upper gastrointestinal endoscopy and colonoscopy, which showed no lesions or tumors, were employed. Skin biopsy was performed and antihistaminic and local steroid treatment was initiated. The patient's status worsened within a week and the patient was started on systemic steroid treatment with poor results. Computer tomography was performed to identify any tumor(s) located either in the pelvis or abdomen. A lesion was found in the terminal ileum, identified as a hypervascularized associating bulky lymphadenopathy. The patient was transferred to the surgical ward where right hemicolectomy with manual ileotransverse anastomosis L-L was performed. The histopathological result confirmed NET G2. The patient clinically improved, the skin lesions resolved and the itchiness disappeared. The general status improved significantly. NET G2 diagnosing was possible due to the atypic paraneoplastic sign: chronic pruritus. This case study highlights the association between itch and malignancy and presents an atypical way of NET presentation when all tumor markers remain neg ative.

PMID:35126692 | PMC:PMC8794552 | DOI:10.3892/etm.2022.11112

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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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Electroacoustic Evaluation of Smartphone-Based Hearing Aid Applications

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Clin Exp Otorhinolaryngol. 2022 Feb 8. doi: 10.21053/ceo.2021.01004. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the electroacoustic characteristics of smartphone-based hearing aid applications (apps).

METHODS: We investigated hearing aid apps based on processing delay measurements, hearing instrument testing, simulated real ear measurements, and a head-and-torso simulator.

RESULTS: Many apps exceeded the recommended level for processing delay. Hearing instrument testing showed the highest amplification characteristics and the best sound quality when a hearing aid was used, followed by the high-end apps and then the low-end apps. The simulated real ear measurements results showed that the high-end apps had a better ability to match the amplification targets than the low-end apps, but there was no consistent pattern among apps when controlling the output. Only a few apps could improve the signal-to-noise ratio in the head-and-torso simulator.

CONCLUSION: Most of the apps showed relatively poor electroacoustic performance in comparison with hearing aids. Generalizing access to hearing care through hearing aid apps induces a wide diversity of hearing performance with no fixed standard for reliability. However, we expect their overall quality to improve over the next few years.

PMID:35124945 | DOI:10.21053/ceo.2021.01004

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Delineating the risk factors of venous congestion: An analysis of 455 deep inferior epigastric perforator flaps with radiographic correlation

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J Plast Reconstr Aesthet Surg. 2022 Jan 16:S1748-6815(22)00017-1. doi: 10.1016/j.bjps.2022.01.003. Online ahead of print.

ABSTRACT

BACKGROUND: Venous congestion occurs in 2-15% of DIEP flaps for breast reconstruction. We previously showed that thicker suprascarpal fat pads are associated with increased SIEV caliber and may, by extension, indicate a dominant superficial venous system. In this study, we aim to provide clinical correlation and to determine the risk factors of venous congestion in order to identify high-risk patients who may benefit from prophylactic SIEV dissection.

METHODS: An IRB-approved retrospective study was performed in patients who underwent DIEP flap reconstruction from August 2011 to August 2020. Radiographic measurements of suprascarpal fat pad thickness and SIEV diameter were collected per hemi-abdomen from preoperative imaging. The statistical analysis explored whether certain variables were associated with venous congestion.

RESULTS: A total of 258 patients underwent 455 DIEP flaps. Suprascarpal fat pad thickness was positively correlated with SIEV diameter (r = 0.51, p<0.001), each with a mean caliber of 19.8 mm and 2.5 mm, respectively. Seven flaps (1.5%) developed venous congestion, with five requiring SIEV salvage and secondary venous anastomosis. Congested flaps had significantly thinner suprascarpal fat pads (12.3 vs. 20.0 mm, p = 0.043). All six congested flaps with imaging had suprascarpal thickness less than 18 mm, compared to 182 out of 335 non-congested flaps with imaging (p = 0.035).

CONCLUSIONS: The risk of venous congestion following DIEP flap reconstruction is significantly increased with thinner suprascarpal fat pads, suggesting that the mechanism of venous congestion may not be limited to superficial venous dominance. We recommend prophylactic SIEV dissection in all patients with suprascarpal fat pad thickness less than 18 mm.

PMID:35125307 | DOI:10.1016/j.bjps.2022.01.003

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A comparative analysis of associated injuries in the elderly and youth for facial fractures

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J Plast Reconstr Aesthet Surg. 2022 Jan 16:S1748-6815(22)00016-X. doi: 10.1016/j.bjps.2021.12.006. Online ahead of print.

ABSTRACT

INTRODUCTION: High-velocity and high-impact forces can yield life-threatening injuries that are not only limited to the face but can involve other regions of the body. Associated injuries are more frequent in the elderly impacting management and outcomes. The primary objective was to study the association between associated injuries and age groups by identifying epidemiological trends and differences among the elderly and younger population.

METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Royal Adelaide Hospital, Adelaide. A comparative analysis for elderly and younger controls was assessed for associated injuries, etiology, management, and length of stay.

RESULTS: There were 355 elderly and 1884 younger controls for the study. There were differences betwee n gender, alcohol, socioeconomic status, type of facial fracture, mechanism of injury, and associated injuries (p<0.05). The elderly were 3.6 times more likely to have an associated injury compared to the younger cohort (p<0.05). Total limb injuries were 2.2 times more likely in the elderly compared to the younger cohort, and neurological related injuries were 2.7 times more likely (p<0.05). Neurological injuries were most frequent in fall-related injuries, limb injuries in RTA; and soft-tissue injuries for assault, sport, animal, and work (p<0.001). The elderly had longer hospital stays as compared with younger controls (p<0.05).

CONCLUSIONS: Associated injuries are more frequent in the elderly and impact other bodily systems leading to a longer length of stay. In the assessment and management of facial trauma, anatomical and disciplinary boundaries may cross requiring interdisciplinary care.

PMID:35125309 | DOI:10.1016/j.bjps.2021.12.006

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Eye manifestations in the NSUN2 intellectual disability syndrome

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Int J Mol Epidemiol Genet. 2021 Dec 15;12(6):129-134. eCollection 2021.

ABSTRACT

The NSUN2-intellectual disability syndrome is a rare disorder of the cellular transcriptome that prevents proper t-RNA splicing. This disorder interrupts cellular function and leads to an accumulation of RNA fragments, producing a constellation of symptoms including dysmorphic facies, hypotonia, microcephaly, and short stature. Eye manifestations have been reported but not well characterized. Our study presents a new case involving a 4-year-old boy with novel NSUN2 variants and clinical features consistent with the syndrome. In addition, through a systemic review, we discuss the 24 previously reported cases of the syndrome with an emphasis on the eye and ocular adnexa clinical features.

PMID:35126837 | PMC:PMC8784905

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