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SERPINA3: Stimulator or Inhibitor of Pathological Changes.

ABSTRACT: SERPINA3, also called α-1-antichymotrypsin (AACT, ACT), is one of the inhibitors of serine proteases, one of which is cathepsin G. As an acute-phase protein secreted into the plasma by liver cells, it plays an important role in the anti-inflammatory response and antiviral response. Elevated levels of SERPINA3 have been observed in heart failure and neurological diseases such as Alzheimer's disease or Creutzfeldt-Jakob disease. Many studies have shown increased expression levels of the SERPINA3 gene in various types of cancer, such as glioblastoma, colorectal cancer, endometrial cancer, breast cancer, or melanoma. In this case, the SERPINA3 protein is associated with an antiapoptotic function implemented by adjusting the PI3K/AKT or MAPK/ERK 1/2 signal pathways. However, the functions of the SERPINA3 protein are still only partially understood, mainly in the context of cancerogenesis, so it seems necessary to summarize the available information and describe its mechanism of action. In particular, we sought to amass the existing body of research focusing on the description of the underlying mechanisms of various diseases not related to cancer. Our goal was to present an overview of the correct function of SERPINA3 as part of the defense system, which unfortunately easily becomes the "Fifth Column" and begins to support processes of destruction.

SUBMITTER: de Mezer M

PROVIDER: S-EPMC9856089 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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SERPINA3: Stimulator or Inhibitor of Pathological Changes.

de Mezer Mateusz M Rogaliński Jan J Przewoźny Stanisław S Chojnicki Michał M Niepolski Leszek L Sobieska Magdalena M Przystańska Agnieszka A

Biomedicines 20230107 1

SERPINA3, also called α-1-antichymotrypsin (AACT, ACT), is one of the inhibitors of serine proteases, one of which is cathepsin G. As an acute-phase protein secreted into the plasma by liver cells, it plays an important role in the anti-inflammatory response and antiviral response. Elevated levels of SERPINA3 have been observed in heart failure and neurological diseases such as Alzheimer's disease or Creutzfeldt-Jakob disease. Many studies have shown increased expression levels of the <i>SERPINA ...[more]

PMID: 36672665

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Project description:Proteases facilitate a number of steps in cancer progression. The serine protease inhibitors (serpins) are a protein superfamily with inhibitory activity against proteases. One of these proteases, serpinA3, appears to have a multifaceted role and is associated with inflammatory reactions, Alzheimer's disease, malignant melanoma and gastric cancer. To gain insight into the potential effect of serpinA3 on colorectal cancer (CRC) we determined whether serpinA3 is altered in colorectal tissue or plasma in CRC patients. Collectively, by using ELISA we noted a significantly lower serpinA3 level in cancer tissue compared to paired normal tissue. Moreover, the tumour serpinA3 level tended to be higher in disseminated disease as compared to localised disease. No significant difference in the plasma levels of serpinA3 was noted in the patients when compared to the controls. However, plasma serpinA3 and C-reactive protein (marker of inflammation) in the CRC patients and controls were significantly positively correlated. To confirm and detect localization of serpinA3 expression, immunohistochemistry was performed. Immunohistochemistry showed heterogeneous immunoreactivity in epithelial cells in the cancer and normal tissue and extracellular staining within bands of stroma as well as in some stromal cells. A Taq Man system was used to investigate a single nucleotide polymorphism (rs4934) in the serpinA3 signal sequence gene with supposed effect on serpinA3 secretion and expression. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions, nor were associations noted between clinical characteristics and serpinA3 levels. In conclusion, an altered serpinA3 concentration in CRC tissue may be a potential biomarker in CRC progression. SerpinA3 concentrations in plasma appear to be correlated with systemic inflammation, but do not appear to be specific to CRC patients. Further studies are warranted to improve our understanding of the role of serpinA3 in CRC.

Project description:ObjectiveDeep brain stimulation (DBS) is an effective treatment for motor symptoms of advanced Parkinson's disease (PD). Currently, DBS programming outcome is based on a clinical assessment. In an optimal situation, an objectively measurable feature would assist the operator to select the appropriate settings for DBS. Surface electromyographic (EMG) measurements have been used to characterise the motor symptoms of PD with good results; with proper methodology, these measurements could be used as an aid to program DBS.MethodsMuscle activation measurements were performed for 13 patients who had advanced PD and were treated with DBS. The DBS pulse voltage, frequency, and width were changed during the measurements. The measured EMG signals were analysed with parameters that characterise the EMG signal morphology, and the results were compared to the clinical outcome of the adjustment.ResultsThe EMG signal correlation dimension, recurrence rate, and kurtosis changed significantly when the DBS settings were changed. DBS adjustment affected the signal recurrence rate the most. Relative to the optimal settings, increased recurrence rates (median ± IQR) 1.1 ± 0.5 (-0.3 V), 1.3 ± 1.1 (+0.3 V), 1.7 ± 0.4 (-30 Hz), 1.7 ± 0.8 (+30 Hz), 2.0 ± 1.7 (+30 μs), and 1.5 ± 1.1 (DBS off) were observed. With optimal stimulation settings, the patients' Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) score decreased by 35% on average compared to turning the device off. However, the changes in UPRDS-III arm tremor and rigidity scores did not differ significantly in any settings compared to the optimal stimulation settings.ConclusionAdjustment of DBS treatment alters the muscle activation patterns in PD patients. The changes in the muscle activation patterns can be observed with EMG, and the parameters calculated from the signals differ between optimal and non-optimal settings of DBS. This provides a possibility for using the EMG-based measurement to aid the clinicians to adjust the DBS.

Project description:ObjectiveBy analyzing the pathological characteristics and clinical data of renal biopsy in our hospital in the past 20 years, to further understand the epidemic characteristics and pathological changes of primary glomerular disease, and to provide regional data for the big data of kidney disease in my country.MethodsA retrospective analysis of 9448 patients with primary glomerular disease who were hospitalized in our hospital from January 1, 2000 to December 31, 2019, aged 18 years or older, and undergoing renal biopsy. Divided every 5 years into a group, a total of 4 groups (first group 2000.1.1-2004.12.31, second groups 2005.1.1-2009.12.31; third groups 2010.1.1-2014.12.31, fourth groups 2015.1.1-2019.12.31).Results① There were more males than females, and male: female vs 1.53:1. The proportion of men in the past five years has increased compared with the previous 15 years. ② Mostly middle-aged, with a median age of 41.39 years old. The age is increasing over time. There are differences between the four groups, P <0.001; ③ The most common clinical manifestations are nephrotic syndrome, followed by chronic glomerulonephritis. Occult glomerulonephritis, the proportion of patients with nephrotic syndrome increases over time, first to fourth group (40.08%< 42.64% < 47.08%< 53.69%); ④ The most common pathology type from 2000 to 2009 was mesangial proliferative glomerulonephritis. IgA nephropathy was the most common type from 2010 to 2014, but the proportion of membranous nephropathy increased year by year, and it became the most common pathological type from 2015 to 2019; ⑤ The clinical and pathological manifestations of different genders are different, but there is no statistical difference.ConclusionIn the past 20 years, the primary glomerular disease is mainly middle-aged. There are more men than women. The most common type of clinical manifestation is nephrotic syndrome. The pathological type is mesangial proliferative glomerulonephritis. Over time, the average age is increasing, and the proportion of patients with renal syndrome is increasing. IgA nephropathy is the most common pathological type from 2010 to 2014, and membranous nephropathy has become the main pathological type in the past 5 years.

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SERPINA3: Stimulator or Inhibitor of Pathological Changes.

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SERPINA3: Stimulator or Inhibitor of Pathological Changes.

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