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The influence of erythropoietin on apoptosis and fibrosis in the early phase of chronic pancreatitis in rats

Arch Med Sci. 2020 Oct 12;17(4):1100-1108. doi: 10.5114/aoms.2020.99800. eCollection 2021.

ABSTRACT

INTRODUCTION: Chronic pancreatitis (CP) is a continuing, inflammatory process of the pancreas, characterised by irreversible morphological changes. The identification of pancreatic stellate cells resulted in the development of research on the pathogenesis of CP. Erythropoietin (Epo) regulates the interaction between apoptosis and inflammation of the brain, kidney, and heart muscle. Erythropoietin receptors were also found in the pancreas, in particular on the islet cells. Our objective was to evaluate the influence of Epo on fibrosis and apoptosis in experimental CP.

MATERIAL AND METHODS: The experiments were performed on 48 male Wistar rats (250-350 g). The animals were divided into six equal groups (I – control, II – chronic cerulein – induced pancreatitis, III – 1 ml of Epo sc, IV – 0.5 ml of Epo sc, V – CP treated with 1 ml Epo, VI – CP treated with 0.5 ml Epo). The blood for gelatinases and pancreata for the morphological examinations and immunohistochemistry were collected.

RESULTS: A slight reduction of interstitial oedema and less severe fibrosis were noticed in the groups treated with Epo. Reduced expression of caspase-3 and α-actin, and a lack of Bcl-2 expression were observed in areas with inflammation. There was no expression of caspase-9 observed in all groups. There were no statistically significant differences between the groups in the activity of gelatinases.

CONCLUSIONS: Erythropoietin seems to have the effect of reducing fibrosis and apoptosis in an experimental model of CP.

PMID:34336038 | PMC:PMC8314426 | DOI:10.5114/aoms.2020.99800

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lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p

Dis Markers. 2021 Jul 17;2021:2217663. doi: 10.1155/2021/2217663. eCollection 2021.

ABSTRACT

BACKGROUND: Long noncoding RNA (lncRNA) critically impacts the modulation of tumor developments and progressions. Our study is aimed at investigating the expressing patterns, clinical significance, and biological roles of lncRNA TSPEAR-AS2 (TSPEAR-AS2) in oral squamous cell carcinoma (OSCC). Material and Approach. The expressing states achieved by TSPEAR-AS2 were examined in OSCC specimens and cell lines by RT-PCR. The clinical significance of TSPEAR-AS2 was statistically analyzed. OSCC proliferating, invading, and migrating processes were examined with the use of wound healing assays, transwell, colony formation, and cell counting kit-8. Additionally, the downstream molecular mechanism of TSPEAR-AS2 in OSCC was explored.

RESULTS: TSPEAR-AS2 was overexpressed in OSCC tumors and cells. High TSPEAR-AS2 was associated with advanced TNM stage. Patients with high TSPEAR-AS2 expression displayed a shorter disease-free survival and total survival of OSCC patients than those with low TSPEAR-AS2 expressing level. It was found that knockdown of TSPEAR-AS2 could inhibit the proliferating, invading, and migrating processes pertaining to OSCC cells. Luciferase reporter tests and RNA pull-down results revealed that TSPEAR-AS2 enhanced the expressions of PPM1A by regulating miR-487a-3p, and TSPEAR-AS2 could be adopted as a miR-487a-3p sponge to inhibit PPM1A expression.

CONCLUSION: Our study highlighted the significance of the TSPEAR-AS2/miR-487a-3p/PPM1A axis within OSCC progression and offered a novel biomarker and novel strategies for OSCC treatments.

PMID:34336002 | PMC:PMC8313349 | DOI:10.1155/2021/2217663

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Long-term predictions of current confirmed and dead cases of COVID-19 in China by the non-autonomous delayed epidemic models

Cogn Neurodyn. 2021 Jul 26:1-10. doi: 10.1007/s11571-021-09701-1. Online ahead of print.

ABSTRACT

In this paper, we make long-term predictions based on numbers of current confirmed cases, accumulative dead cases of COVID-19 in different regions in China by modeling approach. Firstly, we use the SIRD epidemic model (S-Susceptible, I-Infected, R-Recovered, D-Dead) which is a non-autonomous dynamic system with incubation time delay to study the evolution of the COVID-19 in Wuhan City, Hubei Province and China Mainland. According to the data in the early stage issued by the National Health Commission of China, we can accurately estimate the parameters of the model, and then accurately predict the evolution of the COVID-19 there. From the analysis of the issued data, we find that the cure rates in Wuhan City, Hubei Province and China Mainland are the approximately linear increasing functions of time t and their death rates are the piecewisely decreasing functions. These can be estimated by finite difference method. Secondly, we use the delayed SIRD epidemic model to study the evolution of the COVID-19 in the Hubei Province outside Wuhan City. We find that its cure rate is an approximately linear increasing function and its death rate is nearly a constant. Thirdly, we use the delayed SIR epidemic model (S-Susceptible, I-Infected, R-Removed) to predict those of Beijing, Shanghai, Zhejiang and Anhui Provinces. We find that their cure rates are the approximately linear increasing functions and their death rates are the small constants. The results indicate that it is possible to make accurate long-term predictions for numbers of current confirmed, accumulative dead cases of COVID-19 by modeling. In this paper the results indicate we can accurately obtain and predict the turning points, the end time and the maximum numbers of the current infected and dead cases of the COVID-19 in China. In spite of our simple method and small data, it is rather effective in the long-term prediction of the COVID-19.

PMID:34335995 | PMC:PMC8312358 | DOI:10.1007/s11571-021-09701-1

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Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19

Theranostics. 2021 Jul 6;11(16):8008-8026. doi: 10.7150/thno.61832. eCollection 2021.

ABSTRACT

Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. Results: By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. Conclusion: The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.

PMID:34335977 | PMC:PMC8315065 | DOI:10.7150/thno.61832

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Corneal endothelial changes induced by pars plana vitrectomy with silicone oil tamponade for retinal detachment

Exp Ther Med. 2021 Sep;22(3):961. doi: 10.3892/etm.2021.10393. Epub 2021 Jul 7.

ABSTRACT

Silicone oils are effective intraocular tamponade agents in the treatment of severe retinal detachments, because they maintain the adhesion between neurosensory retina and retinal pigment epithelium, thanks to their ability to remove aqueous humor from the surface of the retina. To understand their effectiveness, it is important to know the characteristics of silicone oils. Patients should be closely monitored due to many complications associated with intraocular silicon oil, such as inflammatory reaction, raised intraocular pressure, refraction disorders, cataract, and emulsification. This study presents corneal endothelial changes and some intraocular complications caused by silicone oil used as an intraocular tamponade agent in the case of vitrectomy for complex retinal detachments. The aim of the study was to demonstrate the damage of corneal endothelial cells after the use of silicone oil in patients with retinal detachment surgery. Endothelial specular microscopy measurements were performed and the changes of the following parameters demonstrated the corneal damage: Mean cell density, coefficient of variation, average cell area, percentage of hexagonal cells, and corneal thickness. Three months postoperatively, a statistically significant decrease was observed in the following analyzed parameters: Mean cell density (P=0.04), and percentage of hexagonal cells (P=0.002); the remaining parameters also had a linear decrease (coefficient of variation, average cell area), but were statistically insignificant. Three months postoperatively, the corneal thickness presented a slight increase. Silicone oils are powerful tools when used wisely and within the limits of their use. These are often recommended in cases of severe detachment of the retina in patients at high risk of experiencing intraoperative complications.

PMID:34335903 | PMC:PMC8290465 | DOI:10.3892/etm.2021.10393

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Attitude of the surgical approach in hyperparathyroidism: A retrospective study

Exp Ther Med. 2021 Sep;22(3):959. doi: 10.3892/etm.2021.10391. Epub 2021 Jul 7.

ABSTRACT

The present study constitutes a retrospective study for patients with hyperparathyroidism surgically operated on at the Department of Thoracic Surgery of the Central Military Emergency University Hospital ‘Dr. Carol Davila’, Bucharest, Romania (SUUMC), over a period of 6 years. The study aimed to elucidate the diagnostic and surgical attitude for an effective treatment, practiced at SUUMC, Romania. The study group included 55 patients: 41 women and 14 men, diagnosed at the endocrinology department, who underwent various personalized surgeries (Kocher modified incision) for typical and ectopic locations of parathyroid pseudotumor formations (hyperplasia and parathyroid adenoma), to cure the disease. The recommended protocol was followed by immediate and 30-day postoperative evaluation which showed normalization of the blood tests, and improved clinical and imaging anomalies. In conclusion, the thoracic surgeon has the necessary knowledge to perform surgery at the cervical, thoracic-cervical and mediastinal levels. Postoperative, the results of laboratory tests for calcium (Ca) and parathyroid hormone (PTH) gradually returned to normal, as can be seen from the statistical study.

PMID:34335901 | PMC:PMC8290464 | DOI:10.3892/etm.2021.10391

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A Romanian study on the impact of glypressin in laparoscopic myomectomy

Exp Ther Med. 2021 Sep;22(3):955. doi: 10.3892/etm.2021.10387. Epub 2021 Jul 6.

ABSTRACT

A major myomectomy-associated problem is excessive blood loss. The aim of the present study was to evaluate the effect of glypressin on blood loss during laparoscopic myomectomy (LM) in women with uterine myomas. A total of 188 women scheduled for LM for uterine myomas were divided into two groups. The one group of women (n=64) received a 5-ml intramyometrial injection of glypressin 0.2 mg/ml (glypressin group; group 1). The other group of women (n=124) (group 2) had an LM performed without any other method to reduce blood loss. The decrease in postoperative hemoglobin (Hb), hematocrit (Ht), morbidity and duration of hospital stay were assessed. The results revealed that Hb and Ht (as it was presumed) exhibited similar changes in our study. Statistically significant differences (P<0.05) were obtained between the two groups in terms of Hb and Ht; after LM both Hb and Ht were decreased. In conclusion, the impact of glypressin administration in hemorrhage control in uterine leiomyomas may establish new future perspectives, regarding its administration in gynecological hemorrhagic pathologies.

PMID:34335897 | PMC:PMC8290438 | DOI:10.3892/etm.2021.10387

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Cervical ripening after cesarean section: a prospective dual center study comparing a mechanical osmotic dilator vs. prostaglandin E2

J Perinat Med. 2021 Aug 2. doi: 10.1515/jpm-2021-0157. Online ahead of print.

ABSTRACT

OBEJCTIVES: Worldwide, the overall cesarean section is rising. Trial of labor after cesarean (TOLAC) is an overall safe option with an immediate impact on neonatal and maternal short- and long-term health. Since the use of prostaglandins in cervical ripening is associated with an increased risk of uterine rupture, mechanical methods as balloon catheters or osmotic dilators have been suggested for cervical ripening prior to induction of labour. Here we are analyzing and comparing the VBAC rate, as well as maternal and fetal outcome in cervical ripening prior to TOLAC.

METHODS: This prospective dual center study analyses maternal and neonatal outcomes of TOLAC in women with an unfavorable cervix requiring cervical ripening agent. The prospective application of an osmotic dilator (Dilapan-S, n=104) was analysed in comparison to the retrospective application of off-label dinoprostone (n=102).

RESULTS: The overall fetal and neonatal outcome revealed no significant differences in both groups. Patients receiving cervical ripening with the osmotic dilator delivered vaginally/by ventouse in 52% of cases, compared to 53% when using dinoprostone (p=0.603). The interval between application to onset of labor was significantly higher in the osmotic dilator group (37.9 vs.20.7 h, p=<0.001). However, time from onset of labor to delivery was similar in both groups (7.93 vs. 7.44 h, p=0.758). There was one case of uterine rupture in the dinoprostone group.

CONCLUSIONS: Our data shows that the application of the osmotic dilator leads to similar outcomes in VBAC rate and time from onset of labor to delivery as well as safety in both groups compared to off-label use dinoprostone. Cervical ripening using the mechanical dilator is a viable and effective option, without the risk of uterine hyperstimulation.

PMID:34333894 | DOI:10.1515/jpm-2021-0157

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Anti – Dense Fıne Speckled (DFS) Antibody: its staınıng pattern in indirect immunofluorescence and its clinical relevance

Rom J Intern Med. 2021 Jul 31. doi: 10.2478/rjim-2021-0029. Online ahead of print.

ABSTRACT

BACKGROUND: Dense fine speckled (DFS) pattern defined by very intense, heterogeneous speckled staining of nucleoplasms of interphase HEp-2 cells and chromosomal areas of metaphase cells. The association of Anti-DFS70 and rheumatologic signs, symptoms, and diagnosis were evaluated.

METHODS: One-hundred-eight anti-DFS70 positives who consecutively admitted Rheumatology clinic between January-June 2020 were analyzed. The clinical and laboratory findings of positives for anti-DFS70 antibody were compared with those with DFS pattern ANA IFA staining rates. Also, anti-DFS70 positivity rates and their correlation with the DFS staining pattern were analyzed retrospectively in 1016 CTD patients.

RESULTS: The most common complaint was joint pain seen in 77(71.3%) and the most common laboratory abnormality was RF-positivity observed in 10/108(9.3%) who had anti-DFS70 positivity. The most common ANA staining pattern was DFS (72/108;66,7%); one-third had other than DFS. No statistical significance was found for the association of any of the rheumatological complaints and laboratory findings with the DFS70 staining pattern. ANA analysis was performed in a total of 964/1016(94.88%) CTD patients and 44 (4.56%) of these positive for anti-DFS70. The correlation coefficient showed good correlations between the DFS pattern staining and anti-DFS70 antibody positivity (r=+0.773, p<0.001).

CONCLUSIONS: Anti-DFS70-positives have a low rate of CTD. A low anti-DFS70 positivity rate was observed in patients with CTD. As such, it can be considered that anti-DFS70 does not predict CTD or even excludes it.

PMID:34333888 | DOI:10.2478/rjim-2021-0029

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The Frailty Phenotype in Hemodialysis Patients and its Association with Biochemical Markers of Mineral Bone Disorder, Inflammation and Nutrition

Rom J Intern Med. 2021 Jul 31. doi: 10.2478/rjim-2021-0030. Online ahead of print.

ABSTRACT

INTRODUCTION: Frailty is a state of increased vulnerability to physical stressors. It is common in patients with end-stage renal disease (ESRD) who are on hemodialysis (HD).The aim of this study was to analyze the presence of frailty phenotype among HD patients and to evaluate their interrelationship with different biochemical markers.

METHODS: For the frailty assessment the Frailty Phenotype by Fried et al. was used, where frailty was reported if three of the following criteria were met: unintentional weight loss, self-reported exhaustion, weakness, slow walking speed and low physical activity. From 281 HD patients, 126 patients were frail, 58 were pre-frail (two criteria were met) and the rest of the study population were robust (97 patients). BMI was calculated for all patients and venous blood samples were taken to determine laboratory parameters for bone alkaline phosphatase (BAP), phosphate (P), potassium (K), C-reactive protein (CRP) and albumin.

RESULTS: Patients who were on HD longer than 60 months have more characters of frailty. (p=0.019). A statistically significant positive correlations between frailty score and BAP (rho = 0.189; p = 0.001), and CRP (rho = 0.233; p < 0.001) were observed, and significant negative correlations between frailty score and albumin (rho = – 0.218; p < 0.001) and K (rho = – 0.198; p = 0.001).

CONCLUSIONS: The associations of frailty with markers of mineral bone disorder, inflammation and nutrition indicate the importance of these parameters in the indirect assessment of the frailty phenotype in HD patients.

PMID:34333883 | DOI:10.2478/rjim-2021-0030