Τρίτη 10 Αυγούστου 2021

COVID-19 pandemic and reasons to prioritize the needs of the health care system to ensure its sustainability: A scoping review from January to October 2020 (Review)

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Exp Ther Med. 2021 Sep;22(3):1039. doi: 10.3892/etm.2021.10471. Epub 2021 Jul 21.

ABSTRACT

The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led the World Health Organization to characterize the pandemic as a public health emergency of international concern. National health care systems in countries during the initial surge of the pandemic were unable to handle the sanitarian crisis that had emerged. Thus, the prevention and control of future global health emergencies must be a priority. The present scoping review aimed to retrieve articles that summarize the current experience on issues related to historical knowledge, and epidemiology, clinical features and overall burden of SARS-CoV-2 on health care services. In summary, a comprehensive overview of the information that has been learnt during this period is presented in the current review. Furthermore, taking into account the global experience, the need for planning cohesive and functional health services before similar pandemic events occur in the future is highlighted. The next public health issue should be prevented rather than treated. In spite of the vaccination benefits, a number of sporadic cases of SARS-CoV-2infections will persist. Information collected remains relevant for appraising how similar threats can be faced in the future. Overall, collaborative health care plans need to be rethought to increase preparedness.

PMID:34373725 | PMC:PMC8343896 | DOI:10.3892/etm.2021.10471

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Musculoskeletal adverse reactions after immunotherapy for cancer: A case series

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Exp Ther Med. 2021 Sep;22(3):1027. doi: 10.3892/etm.2021.10459. Epub 2021 Jul 16.

ABSTRACT

Immunotherapy has revolutionized cancer treatment. Immune checkpoint inhibitors (ICIs) including antibodies targeting cytotoxic T lymphocyte associated antigen-4 and programmed cell death 1 have been shown to be effective in the treatment of certain types of cancer. The benefit of these therapies is to prolong life expectancy in the case of metastatic malignancies. Rheumatic adverse events are not very common. In the present study, 9 patients were monitored between November 2018 and January 2020. The oncologist, who identified the occurrence of rheumatic toxicities after the treatment with ICIs, evaluated the patients. Only oncological patients with rheumatic manifestations after the start of immunotherapy were included. Toxicity grading was performed by both the oncologist and the rheumatologist, on a scale from 1 to 5 (1, mild; 2, moderate; 3, severe; 4, life-threatening; 5, death related to toxicity). The results showed that rheumatoid factor, which was sampled in each patient, was negative in all cases. Patients were treated with nonsteroidal anti-inflammatory drugs or prednisone depending on the severity of the adverse events. The results varied with the severity of the adverse events. In conclusion, as the number of patients treated with ICIs increases, so will the number of patients presenting with immune-related adverse events (irAEs). The collaboration between oncologists and rheumatologists should be intimate to provide optimal treatment to patients. Musculoskeletal manifestations secondary to ICIs are slightly different from other rheumatologically conditions making diagnosis, treatment and monitoring difficult. Thus, irAEs are new and challenging for oncologists, thus understanding of the pathogenesis and clinical characteristics must be improved for better treatment guidelines.

PMID:34373713 | PMC:PMC8343871 | DOI:10.3892/etm.2021.10459

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Autonomic regulation of imbalance-induced myocardial fibrosis and its mechanism in rats with cirrhosis

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Exp Ther Med. 2021 Sep;22(3):1040. doi: 10.3892/etm.2021.10472. Epub 2021 Jul 21.

ABSTRACT

The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system.

PMID:34373726 | PMC:PMC8343770 | DOI:10.3892/etm.2021.10472

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Ellagic acid inhibits high glucose-induced injury in rat mesangial cells via the PI3K/Akt/FOXO3a signaling pathway

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Exp Ther Med. 2021 Sep;22(3):1017. doi: 10.3892/etm.2021.10449. Epub 2021 Jul 15.

ABSTRACT

The pathological damage of mesangial cells serves an important role in the occurrence and development of diabetic nephropathy. Ellagic acid has been reported to possess antioxidant, antitumor, antiviral and anti-inflammatory properties in several diseases, but the roles of ellagic acid in diabetic nephropathy are unclear. The main aim of the present study was to investigate the effect of ellagic acid on high glucose-induced mesangial cell damage. The results revealed that high glucose could induce the hyperproliferation of mesangial cells, decrease the activity of superoxide dismutase, increase the malondialdehyde content, the level of reactive oxygen species, the secretion of inflammatory factors (TNF-α, IL-1β and IL-6) and the synthesis of extracellular matrix (Fibronectin, MMP-9 and TIMP-1) and activate the PI3K/Akt/FOXO3a signaling pathway. Ellagic acid could attenuate the injury of mesangial cells induced by high glucose in a concentration-dependent manner and its effect was consistent with that of a PI3K inhibitor (LY294002). Moreover, a PI3K agonist (740Y-P) reversed the protective effect of ellagic acid on mesangial cells induced by high glucose. In conclusion, ellagic acid protected mesangial cells from high glucose-induced injury in a concentration-dependent manner. The mechanism may be associated with ellagic acid inhibiting the activation of the PI3K/Akt signaling pathway and reducing the expression levels of downstream transcription factor FOXO3a.

PMID:34373703 | PMC:PMC8343806 | DOI:10.3892/etm.2021.10449

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MicroRNA-934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf-related protein 2

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Exp Ther Med. 2021 Sep;22(3):1041. doi: 10.3892/etm.2021.10473. Epub 2021 Jul 21.

ABSTRACT

Increasing evidence demonstrates that dysregulation of microRNAs (miRNAs/miRs) is implicated in the development of colorectal cancer. However, the biological functions of several differentially expressed miRNAs remain unknown. In the present study, a bioinformatic analysis of a previously published microarray data and reverse transcription-quantitative PCR analysis demonstrated that miR-934 expression was upregulated in colorectal cancer samples collected from patients. Mechanistically, Dickkopf-related protein 2 (DDK2) was identified as a novel target gene of miR-934 in colorectal cancer cells. Knockdown of DDK2 reversed the inactivation of Wnt signaling pathway induced using miR-934 inhibitor in colorectal cancer cells. In addition, DDK2 silencing reversed miR-934 inhibitor-induced cell proliferation inhibition and elevation of cell apoptosis. The results demonstrated that DDK2 mRNA expression was negatively associated with miR-934 expression in colorectal tumors. Collectively, the results of the present study demonstrated that the miR-934/DDK2 axis regulated colorectal cancer cell proliferation, suggesting that miR-934 may be a biomarker for patients with colorectal cancer.

PMID:34373727 | PMC:PMC8343583 | DOI:10.3892/etm.2021.10473

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Lidocaine liposome modified with folic acid suppresses the proliferation and motility of glioma cells via targeting the PI3K/AKT pathway

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Exp Ther Med. 2021 Sep;22(3):1025. doi: 10.3892/etm.2021.10457. Epub 2021 Jul 15.

ABSTRACT

Glioma is life-threatening tumor of the central nervous system. Although lidocaine is usually used as local anesthetic, it also has antitumor effects. However, its clinical application in glioma is hampered by limited distribution to the brain. The aim of the present study was to enhance the ability of lidocaine to penetrate the blood-brain barrier (BBB) to target glioma and investigate its antitumor mechanism. A folic acid (FA)-modified lidocaine-carrying liposome (Lid-FA-Lip) was prepared, and its particle size, ζ potential, encapsulation efficiency, release profile stability and hemolytic effect were characterized in vitro. The targeting capacity and antitumor activities of Lid-FA-Lip were also investigated in vitro and in vivo. The results indicated that the modification of liposomes with FA significantly improved the ab ility of lidocaine to cross the BBB in an in vitro model and increased its uptake by U87 cells. Additionally, Lid-FA-Lip significantly suppressed the motility of U87 glioma cells and stimulated apoptosis. Furthermore, the results confirmed that Lid-FA-Lip targeted the PI3K/AKT pathway and suppressed the growth of glioma xenografts in mice. In summary, the study demonstrated that Lid-FA-Lip is a promising liposomal formulation of lidocaine that may provide improved therapeutic effects on glioma, mediated via the PI3K/AKT pathway.

PMID:34373711 | PMC:PMC8343891 | DOI:10.3892/etm.2021.10457

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Aminophylline modulates the permeability of endothelial cells via the Slit2-Robo4 pathway in lipopolysaccharide-induced inflammation

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Exp Ther Med. 2021 Sep;22(3):1042. doi: 10.3892/etm.2021.10474. Epub 2021 Jul 21.

ABSTRACT

Sepsis and septic shock are the main cause of mortality in intensive care units. The prevention and treatment of sepsis remains a significant challenge worldwide. The endothelial cell barrier plays a critical role in the development of sepsis. Aminophylline, a non-selective phosphodiesterase inhibitor, has been demonstrated to reduce endothelial cell permeability. However, little is known regarding the role of aminophylline in regulating vascular permeability during sepsis, as well as the potential underlying mechanisms. In the present study, the Slit2/Robo4 signaling pathway, the downstream protein, vascular endothelial (VE)-cadherin and endothelial cell permeability were investigated in a lipopolysaccharide (LPS)-induced inflammation model. It was indicated that, in human umbilical vein endothelial cells (HUVECs), LPS downregulated Slit2, Robo4 and VE-cadherin protein expression levels and, as expected, increased endothelial cell permeability in vitro during inflammation. After administration of aminophylline, the protein expression levels of Slit2, Robo4 and VE-cadherin were upregulated and endothelial cell permeability was significantly improved. These results suggested that the permeability of endothelial cells could be mediated by VE-cadherin via the Slit2/Robo4 signaling pathway. Aminophylline reduced endothelial permeability in a LPS-induced inflammation model. Therefore, aminophylline may represent a promising candidate for modulating vascular permeability induced by inflammation or sepsis.

PMID:34373728 | PMC:PMC8343459 | DOI:10.3892/etm.2021.10474

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Kir4.1 may represent a novel therapeutic target for diabetic retinopathy (Review)

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Exp Ther Med. 2021 Sep;22(3):1021. doi: 10.3892/etm.2021.10453. Epub 2021 Jul 15.

ABSTRACT

As the major cause of irreversible loss of vision in adults, diabetic retinopathy (DR) is one of the most serious complications of diabetes. The imbalance of the retinal microenvironment and destruction of the blood-retinal barrier have a significant role in the progression of DR. Inward rectifying potassium channel 4.1 (Kir4.1) is located on Müller cells and is closely related to potassium homeostasis, water balance and glutamate clearance in the whole retina. The present review discusses the functions of Kir4.1 in regulating the retinal microenvironment and related biological mechanisms in DR. In the future, Kir4.1 may represent a novel alternative therapeutic target for DR through affecting the retinal microenvironment.

PMID:34373707 | PMC:PMC8343704 | DOI:10.3892/etm.2021.10453

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Immune thrombocytopenia, severe hematological consequence in a patient with COVID-19: A case report

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Exp Ther Med. 2021 Sep;22(3):1043. doi: 10.3892/etm.2021.10475. Epub 2021 Jul 21.

ABSTRACT

Since the first appearance of coronavirus disease 2019 (COVID-19), multiple studies have focused on this novel coronavirus. Within a few months, the clinical and paraclinical manifestations and the mechanisms by which these changes are induced were elaborated. Clinically, the virus mainly causes the common cold, but can also result in severe or fatal pneumonia/acute respiratory syndrome. Regarding the biological changes, similar to any other virus, it can lead to a reduced lymphocyte count. The second most common change is represented by a reduced thrombocyte count. Furthermore, most patients have blood clotting abnormalities, inflammatory syndrome, raised D-dimer and lactate dehydrogenase levels. Detection of immune thrombocytopenia in asymptomatic patients who tested positive for COVID-19 justifies the need to perform differential diagnosis and testing for COVID-19. Typically, patients with severe forms of COVID-19 develop mild thrombocytopenia, while severe thrombocytopenia is rarely reported. The aim of this case report was to present the situation in which one asymptomatic patient who tested positive for COVID-19 developed severe immune thrombocytopenia.

PMID:34373729 | PMC:PMC8343625 | DOI:10.3892/etm. 2021.10475

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Nerve growth factor enhances the therapeutic effect of mesenchymal stem cells on diabetic periodontitis

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Exp Ther Med. 2021 Sep;22(3):1013. doi: 10.3892/etm.2021.10445. Epub 2021 Jul 15.

ABSTRACT

Patients with diabetes frequently suffer from periodontitis, which progresses rapidly and is difficult to cure. Mesenchymal stem cell (MSC) transplantation may effectively treat periodontitis, but high glucose limits its therapeutic effect in diabetes. Nerve growth factor (NGF) has the functions of cell protection, anti-apoptosis and immune regulation, and may have potential application in diabetic periodontitis. In the present study, flow cytometry indicated that NGF inhibited MSC apoptosis induced by high glucose. Of note, high glucose promoted the transformation of MSCs into the proinflammatory type. NGF inhibited this transformation of MSCs under diabetic conditions and further decreased the proportion of T cells and monocytes/macrophages among lymphocytes. An animal model of diabetic periodontitis was constructed and MSC transplantation was demonstrated to reduce alveolar bone loss caused by diabetes. NGF enhanced the therapeutic effect of MSCs and maintained transplanted MSC survival in periodontal tissue of diabetic mice. Immunohistochemical analysis of periodontal tissues suggested that in the NGF group, infiltration of T cells and macrophages was reduced. Neurotrophic receptor tyrosine kinase 1 was indicated to have a key role in these effects of NGF. In conclusion, NGF may enhance the therapeutic effect of MSCs on diabetic periodontitis by protecting the cells and promoting the transformation of MSCs into the immunosuppressive type.

PMID:34373699 | PMC:PMC8343805 | DOI:10.3892/etm.2021.10445

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Modified Xiaochaihu Decoction for gastroesophageal reflux disease: A randomized double-simulation controlled trial

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World J Gastroenterol. 2021 Jul 28;27(28):4710-4721. doi: 10.3748/wjg.v27.i28.4710.

ABSTRACT

BACKGROUND: Gastroesophageal reflux disease (GERD) has a high prevalence worldwide, and its incidence is increasing annually. Modified Xiaochaihu Decoction (MXD) could relieve the symptoms of GERD, but the effects of MXD on GERD manifestations and relapse prevention need to be further explained. Therefore, we performed a prospective, double-blind, and double-simulation study.

AIM: To verify the efficacy of MXD for GERD and its effect on esophageal motility.

METHODS: Using randomization, double-blinding, and a simulation design, 288 participants with GERD were randomized to the treatment group and control group and received herbs (MXD) plus omeprazole simulation and omeprazole plus herbs simulation, respectively, for 4 wk. The GERD-Q scale score and esophageal manometry were measured at baseline, after treatment, and at 1 mo and 3 mo follow -up visits when medication was complete to evaluate recurrence indicators.

RESULTS: The GERD-Q scale score in both groups decreased significantly compared to those before treatment (P < 0.01). However, no significant difference was observed between the two groups (P > 0.05). Esophageal manometry showed that participants with lower esophageal sphincter pressure reduction and the proportion of ineffective swallowing (more than 50%) improved in both groups from baseline (P < 0.01), especially in the treatment group (P < 0.05). The percentage of small intermittent contractions, large intermittent contractions, and increased pre-phase contractions in the treatment group significantly improved compared with baseline (P < 0.05) but did not improve in the control group (P > 0.05). There was no significant difference between the groups after treatment (P > 0.05). The percentage of weak esophageal contractility (dista l contractile integral < 450 mmHg·s·cm), improved in both groups (P < 0.01), but no significant difference was observed between the groups after treatment (P > 0.05). The relapse rate in the treatment group was lower than that in the control group at the 1 mo (P < 0.01) and 3 mo follow-up (P < 0.05).

CONCLUSION: MXD has a similar therapeutic effect to omeprazole in mild-to-moderate GERD. The therapeutic effect may be related to increased pressure in the lower esophageal sphincter and reduced ineffective swallowing.

PMID:34366631 | PMC:PMC8326264 | DOI:10.3748/wjg.v27.i28.4710

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