Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies.

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation, followed by deleterious effects at the cellular and systemic levels, is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders, including metabolic syndrome, diabetes mellitus, and cardiovascular diseases. In this review, an interplay between pathways leading to MGO generation and scavenging is addressed in regard to this system's impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases, are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

Modulatory Impact of Lamiaceae Metabolites on Apoptosis of Human Leukemia Cells.

Lamiaceae species are rich sources of biologically active compounds which have been applied in medicine since ancient times. Especially their antineoplastic properties have been thoroughly studied with respect to their putative application in chemoprevention and adjuvant therapy of cancer. However, the most known biological effects of Lamiaceae have been ascribed to their essential oil fractions, whereas their (poly)phenolic metabolites being also abundant in these plants, are much less recognized, nevertheless contributing to their beneficial properties, such as anti-cancer actions. The aim of this study was to evaluate the impact of dried aqueous extracts from common thyme (Thymus vulgaris L.) (ExTv), wild thyme (Thymus serpyllum L.) (ExTs), sweet marjoram (Origanum majorana L.) (ExOm), and peppermint (Mentha × piperita L.) (ExMp), as well as (poly)phenolic compounds: caffeic acid (CA), rosmarinic acid (RA), lithospermic acid (LA), luteolin-7-O-ß-glucuronide (Lgr), luteolin-7-O-rutinoside (Lr), eriodictyol-7-O-rutinoside (Er), and arbutin (Ab), on unstimulated Jurkat cells, in comparison with their effect on staurosporine-stimulated Jurkat cells. Jurkat T cells were incubated with different concentrations of ExTv, ExTs, ExOm, ExMp, Lgr, LA, Er, Lr, RA, CA, or Ab. Subsequently, staurosporine was added to half of the samples and flow cytometry combined with fluorescence-activated cell sorting analysis was conducted, which allowed for the selection of early and late apoptotic cells. Both ExTs and ExOm stimulated apoptosis of Jurkat cells and enhanced the proapoptotic effect of staurosporine. Conversely, ExTv and ExMp demonstrated no clear effect on apoptosis. CA and RA raised the staurosporine-induced apoptotic effect. The impact of Er and Lgr on Jurkat cells showed fluctuations depending on the compound concentration. Neither Er nor Ab altered staurosporine-induced apoptosis in Jurkat cells, whereas Lgr seemed to weaken the proapoptotic action of staurosporine. The most evident observation in this study was the pro-apoptotic action of ExTs and ExOm observed both in staurosporine-unstimulated and stimulated Jurkat cells. Additionally, an enhancement of staurosporine-induced apoptosis by caffeic and rosmarinic acids was reported. Therefore, it might be concluded that these are the mixtures of biologically active polyphenols which often exert more pronounced beneficial effects than purified molecules.

HDL Accessory Proteins in Parkinson's Disease-Focusing on Clusterin (Apolipoprotein J) in Regard to Its Involvement in Pathology and Diagnostics-A Review.

Parkinson's disease (PD)-a neurodegenerative disorder (NDD) characterized by progressive destruction of dopaminergic neurons within the substantia nigra of the brain-is associated with the formation of Lewy bodies containing mainly α-synuclein. HDL-related proteins such as paraoxonase 1 and apolipoproteins A1, E, D, and J are implicated in NDDs, including PD. Apolipoprotein J (ApoJ, clusterin) is a ubiquitous, multifunctional protein; besides its engagement in lipid transport, it modulates a variety of other processes such as immune system functionality and cellular death signaling. Furthermore, being an extracellular chaperone, ApoJ interacts with proteins associated with NDD pathogenesis (amyloid ß, tau, and α-synuclein), thus modulating their properties. In this review, the association of clusterin with PD is delineated, with respect to its putative involvement in the pathological mechanism and its application in PD prognosis/diagnosis.

Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis - with impact on gastrointestinal tract.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seems to employ two routes of entrance to the host cell; via membrane fusion (with the cells expressing both angiotensin converting enzyme 2 (ACE2) and transmembrane peptidase/serine subfamily member 2/4 (TMPRSS2/4)) or via receptor-mediated endocytosis (to the target cells expressing only ACE2). The second mode is associated with cysteine cathepsins (probably cathepsin L) involvement in the virus spike protein (S protein) proteolytic activation. Also furin might activate the virus S protein enabling it to enter cells. Gastrointestinal tract (GIT) involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019 (COVID-19) patients exhibiting GIT symptoms, such as diarrhea, and presenting viral-shedding in feces. Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT (especially brush-border enterocytes), these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract. Additionally, in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT. However, also furin and cysteine cathepsins (cathepsin L) might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT. Moreover, cathepsin L (due to its involvement in extracellular matrix components degradation and remodeling, the processes enhanced during SARS-CoV-2-induced inflammation) might be responsible for the dysregulation of absorption/ digestion functions of GIT, thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.

Punicalagin in Cancer Prevention-Via Signaling Pathways Targeting.

The extract of pomegranate (Punica granatum) has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, and antineoplastic properties. Anticancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reviewed. However, less is known about punicalagin (Pug), a prevailing compound in pomegranate, seemingly responsible for its most beneficial properties. In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized and discussed. Its attenuating effect on signaling circuits promoting cancer growth and invasion is depicted. The Pug-induced redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence, and autophagy (thus compromising neoplastic progression) is delineated. Considerations presented in this review are based mainly on data obtained from in vitro cell line models and concern the influence of Pug on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types.

Upregulated sulfatase and downregulated MMP-3 in thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) formation is accompanied by degradation of extracellular matrix components (EMC). Numerous matrix metalloproteinases (MMPs) have been implicated in the process, but the involvement of MMP-3 remains unclear. Additionally, the changes in proteoglycan (PG) structure can alter the signal transduction pathways in TAA, though the enzymatic systems which originate them are not fully understood. OBJECTIVES: To measure MMP-3 and sulfatase levels in aneurysmal tissue, comparing them with non-aneurysmal vessels, and to investigate possible correlations with patients' serum levels in order to evaluate their potential usefulness in aiding aneurysm detection and monitoring. MATERIAL AND METHODS: The study included 74 patients (TAA: n = 42; control group: n = 32). Sulfatase activity was measured colometrically and MMP-3 levels were measured immunoenzymatically. RESULTS: Sulfatase activities were higher (p = 0.03) and MMP-3 concentrations lower (p = 0.014) in aneurysmal tissue than in normal aortic tissue. Medium-sized dilatations were associated with lower tissue MMP-3 concentrations than small dilatations (p = 0.033). No differences in sulfatase activity or MMP-3 concentration in the serum of TAA patients were observed in comparison with the controls. The serum and tissue levels of MMP-3 were correlated (r = 0.41; p < 0.001). The serum levels of MMP-3 were significantly lower in the female patients than in the male patients (p = 0.006). CONCLUSIONS: Our studies confirmed the lower MMP-3 levels in aneurysmal tissue, but the lack of a statistically confirmed reduction of MMP-3 in the blood serum seems to preclude its usefulness for diagnostic purposes. Our study points to the differences in MMP-3 behavior between TAA and abdominal aortic aneurysms. Significantly higher sulfatase activity in TAA tissue suggests a possible impact of sulfatase on signal transduction pathways involved in aneurysm formation.

Paraoxonase 1 decline and lipid peroxidation rise reflect a degree of brain atrophy and vascular impairment in dementia.

BACKGROUND: Paraoxonase 1 (PON1) is an enzyme with the capability to protect against lipid oxidation and atherosclerotic lesions formation. Impaired antioxidative capacity and enhanced lipid peroxidation (reflected by malondialdehyde rise) accompany dementias. OBJECTIVES: The aim of this study was to discern the possible differences in the activity and phenotype distribution of PON1, and lipid peroxidation level in dementias of neurodegenerative and vascular pathology, to assess whether they reflect structural changes in the brain, and to evaluate their potential as dementia markers. MATERIAL AND METHODS: Paraoxonase 1 arylesterase activity and polymorphisms (dual-substrate method), and malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS) levels were determined spectrophotometrically in 257 serum samples derived from 136 dementive patients (with Alzheimer's disease (AD; n = 63), vascular dementia (VaD; n = 40) and mixed-type dementia (MD; n = 33), as well as from 121 non-dementive individuals. The results were analyzed with reference to dementia type and severity (assessed with Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scales), structural brain changes (estimated with magnetic resonance imaging (MRI) - Global Cortical Atrophy (GCA), Medial Temporal lobe Atrophy (MTA) and Fazekas scales)) and brain ischemia (Hachinski Ischemic Scale (HIS) index), and evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Malondialdehyde/thiobarbituric acid reactive substances were increased in dementia (more in VaD than AD). In patients with vascular involvement, MDA/TBARS elevation reflected a degree of global cortical atrophy. Paraoxonase 1 activity was decreased in patients with dementia, especially in patients with severe cognitive deficits. In VaD, a drop in PON1 reflected a degree of MTA and brain ischemia. MDA/TBARS displayed 75% accuracy as a general dementia marker, but, similarly to PON1, were a poor differential marker. CONCLUSIONS: Both indices were more associated with vascular involvement and the severity of brain atrophy or ischemia rather than with degree of cognitive decline.

Systemic hepcidin quantified with LC-MS/MS in dementia in association with disease pathology and severity and with structural changes in the brain.

Hepcidin is a peptide hormone regulating iron metabolism, the dyshomeostasis of which has been implicated in dementia. Yet, data on hepcidin status in dementia are scanty, limited to Alzheimer's disease (AD) and inconsistent due to methodological problems with its determination using immunoassays and/or lack of homogeneity of evaluated groups. Hepcidin association with vascular dementia (VaD) remains unknown. We proposed a mass spectrometry method of hepcidin quantification in sera and aimed at determining hepcidin systemic status in patients with dementia of AD, VaD, or mixed (MD) pathology, with reference to the degree of cognitive loss and structural changes in the brain as well as at evaluating the diagnostic potential of hepcidin as a biomarker. We found that hepcidin concentrations were significantly elevated in VaD and insignificantly so in AD or MD and that they positively correlated with the Clinical Dementia Rating and inversely with the Mini Mental State Examination. Hepcidin tended to be more pronouncedly elevated in patients with advanced cortical atrophy and white matter lesions. It displayed a biphasic relationship with the Hachinski Ischemic Scale and a good accuracy as dementia but not differential marker. Taken together, our results demonstrated that dementia of vascular and not neurodegenerative pathology is associated with significant elevation of systemic hepcidin. Hepcidin elevation reflects the degree of cognitive loss as well as the severity of structural changes in the brain. If confirmed in a prospective study, hepcidin quantification may hold promise as a diagnostic marker; its accuracy as a differential marker of VaD is insufficient.

Cytotoxic impact of phenolics from Lamiaceae species on human breast cancer cells.

The aim of this study was to evaluate the cytotoxicity of dried aqueous extracts from Thymus serpyllum (ExTs), Thymus vulgaris (ExTv), Majorana hortensis (ExMh), and Mentha piperita (ExMp), and the phenolic compounds caffeic acid (CA), rosmarinic acid (RA), lithospermic acid (LA), luteolin-7-O-glucuronide (Lgr), luteolin-7-O-rutinoside (Lr), eriodictiol-7-O-rutinoside (Er), and arbutin (Ab), on two human breast cancer cell lines: Adriamycin-resistant MCF-7/Adr and wild-type MCF-7/wt. In the MTT assay, ExMh showed the highest cytotoxicity, especially against MCF-7/Adr, whereas ExMp was the least toxic; particularly against MCF-7/wt cells. RA and LA exhibited the strongest cytotoxicity against both MCF-7 cell lines, over 2-fold greater than CA and Lgr, around 3-fold greater than Er, and around 4- to 7-fold in comparison with Lr and Ab. Except for Lr and Ab, all other phytochemicals were more toxic against MCF-7/wt, and all extracts exhibited higher toxicity against MCF-7/Adr. It might be concluded that the tested phenolics exhibited more beneficial properties when they were applied in the form of extracts comprising their mixtures.

Impaired erythrocyte antioxidant defense in active inflammatory bowel disease: impact of anemia and treatment.

BACKGROUND: Oxidative stress contributes to the propagation and exacerbation of inflammatory bowel disease (IBD) but the status of erythrocyte antioxidant defense remains unknown. METHODS: Erythrocyte activities of superoxide dismutase-1 (SOD1), catalase, and glutathione peroxidase-1 (GPx1) were determined in 174 IBD patients and 105 controls and referred to IBD activity, inflammation severity, nutritional status, systemic oxidative stress, anemia, and treatment. RESULTS: Catalase and GPx1 activities were decreased in active IBD, whereas SOD1 became upregulated by IBD-related oxidative stress. In Crohn's disease (CD) corticosteroids decreased SOD1 activity. SOD1 correlated indirectly with CD activity and erythrocyte sedimentation rate (ESR) and directly with transferrin. In ulcerative colitis (UC) anemia downregulated SOD1. Decreases in GPx activity corresponded with IBD activity, anemia, inflammation, and malnutrition. Oxidative stress in UC and corticosteroids in CD also downregulated GPx. Catalase activity was decreased by CD-related anemia, correlating directly with hemoglobin, and indirectly with CD activity, inflammatory and protein oxidative stress markers. When co-analyzed, anemia but not CD activity significantly contributed to catalase downregulation. In UC, catalase activity corresponded indirectly with UC endoscopic activity and inflammation and directly with hemoglobin. UC activity, anemia, and treatment with azathioprine negatively affected catalase. As indicators of active IBD, GPx1 showed a diagnostic accuracy of 73%, whereas catalase showed 63% as compared to 74% of C-reactive protein and ESR. CONCLUSIONS: Erythrocyte antioxidant defense is impaired in active IBD. SOD1, GPx1, and CAT activities are differently affected by the disease type, activity, anemia, inflammation, oxidative stress, and treatment. As an active IBD indicator, GPx1 was comparable to C-reactive protein and ESR.

Paraoxonase-1 status in Crohn's disease and ulcerative colitis.

BACKGROUND: Paraoxonase 1 (PON1) is an extracellular enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, immunomodulator, and/or quorum-quenching factor. There are no data on PON1 activity in Crohn's disease (CD). METHODS: PON1 phenotype and activity were determined spectrophotometrically in 52 subjects with CD, 67 with ulcerative colitis (UC), and 99 healthy individuals, and related to lipid peroxidation and disease phenotype, clinical and biochemical activity, and therapeutic strategy. Diagnostic utility of PON1 was evaluated by ROC analysis and compared with C-reactive protein (CRP). RESULTS: In comparison with controls (166 U), PON1 was reduced only in active CD (110 U, P < 0.0001) and UC (126 U, P < 0.0001), and correlated with disease activity (r = -0.47, P = 0.001 in CD and r = -0.50, P < 0.001 in UC). PON1 significantly correlated with erythrocyte sedimentation rate (ESR) (r = -0.36), platelets (r = -0.35), interleukin-6 (r = -0.45), hemoglobin (r = 0.29), transferrin (r = 0.46), albumin (r = 0.60) in CD, and CRP (r = -0.29), ESR (r = -0.37), platelets (r = -0.43), leukocytes (r = -0.50), interleukin-6 (r = -0.45), hemoglobin (r = 0.34), transferrin (r = 0.54), and albumin (r = 0.50) in UC. PON1 correlated positively with lipids but not with their peroxidation markers (thiobarbituric acid-reactive substances, lipid hydroperoxides, ox-LDL, and ox-LDL autoantibodies). PON1 phenotype B (protective against IBD) tended to be less frequent in IBD patients than controls, and associated with lower concentration of inflammatory indices. PON1 was a poorer indicator of CD or UC than CRP. CONCLUSIONS: PON1 was reduced in IBD, despite treatment with antioxidant 5'-aminosalicylate derivatives. PON1 reflected disease activity, inflammation severity, and anemia but not lipid peroxidation. The diagnostic power of PON1 was insufficient for its clinical application.

Advanced oxidation protein products (AOPPs) in juvenile overweight and obesity prior to and following weight reduction.

OBJECTIVES: To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs. DESIGN AND METHODS: AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin). RESULTS: Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and DeltaAOPPs correlated with DeltaBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%. CONCLUSIONS: Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.

Diagnostic potential of oxidative stress markers in children and adolescents with type 1 diabetes.

OBJECTIVES: To validate the diagnostic utility of oxidative stress markers in the evaluation of young type 1 diabetics, as suggested elsewhere. DESIGN: Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS) and total antioxidant status (TAS) were measured in sera from diabetics, their siblings and controls, with diagnostic potential evaluated by ROC analysis, and related to diabetes clinical parameters. RESULTS: In diabetics AOPP and TBARS were elevated, TAS decreased. Similar alterations were observed for AOPP and TAS in their siblings. AOPP and TAS were good indicators of diabetes. AOPP and TBARS correlated with HbA1C (independent predictor), but were poor markers of non-adequate glycemic control. The cardiovascular disease risk factors were independent predictors of TBARS concentrations. CONCLUSIONS: AOPP accumulation and TAS reduction seem to precede diabetes and might be considered as susceptibility indicators in relatives, but not as diabetes markers in general population (no diabetes specificity has been shown). Application in monitoring of metabolic control is not validated.

Enhanced formation of advanced oxidation protein products in IBD.

BACKGROUND: Advanced oxidation protein products (AOPPs) are new protein markers of oxidative stress with pro-inflammatory properties, accumulated in many pathological conditions. The issue of their enhanced formation in IBD has not been addressed yet. METHODS: The concentration of relative AOPPs (rAOPP; concentration of AOPPs divided by albumin level) were measured in 68 subjects with ulcerative colitis (UC), 50 subjects with Crohn's disease (CD) and 45 healthy volunteers, and related to disease phenotype, clinical and biochemical activity, and therapeutic strategy. Diagnostic utility of rAOPP was evaluated by ROC analysis. RESULTS: In comparison with controls (1.367 micromol/g), rAOPP were increased in inactive (1.778 micromol/g, P = 0.053) and active (1.895 micromol/g, P = 0.013) UC and in active (1.847 micromol/g, P = 0.003) CD. In CD, but not UC, rAOPP correlated with disease activity (r = 0.42, P = 0.013). Significant correlations with the inflammatory/malnutrition indices-erythrocyte sedimentation rate (ESR) (r = 0.53), leukocytes (r = 0.33), platelets (r = 0.38), IL-6 (r = 0.36), and transferrin (r = -0.35) were demonstrated in CD. In UC, rAOPP correlated only with ESR (r = 0.35) and IL-6 (r = 0.30). Instead, associations with antioxidant dismutase (r = 0.29) and catalase (r = 0.22) were observed. The diagnostic power of rAOPP in discriminating diseased from non-diseased subjects was less than that of C-reactive protein (CRP). Simultaneous determination of rAOPP and CRP did not significantly improve the power of single CRP determination. CONCLUSIONS: IBD was associated with enhanced formation of AOPP, which differed between C and UC with respect to the relationship between rAOPP and disease activity, inflammatory and antioxidant response. These differences may reflect divergent ways that oxidative stress develops in CD and UC. The diagnostic power of rAOPP was insufficient for its clinical application.

Maspin and c-erbB-2 expression in correlation with microvessel density in invasive ductal breast cancer.

Maspin is a unique member of the serpin family involved in regulation of cell migration, apoptosis and angiogenesis in breast and prostate cancers. In this study maspin expression in comparison with c-erbB-2 (HER2/neu) oncogene expression and microvessel density was investigated. The examined material included specimens of primary invasive ductal breast cancer derived from 69 patients. They were analyzed immunocytochemically to assess maspin and c-erbB-2 expression, as well as microvessel density using endothelium marker CD31. In the studied cancers, maspin expression in cancer cells was detected in more than half of the cases (50.73%). Although statistically insignificant (p=0.27), maspin expression showed decreasing tendency with the increase of tumor grade. C-erbB-2 oncogene expression was observed in 78.26% of the examined cancers. Statistically significant positive correlation was found between c-erbB-2 expression and tumor grade (p<0.005). Analysis of the dependence between maspin and c-erbB-2 expression exhibited statistically significant inverse correlation (p<0.001). Mean microvessel density (MVD) of the studied cancers was 71.64 (SD=19.36). MVD decreased with the increase of maspin expression, whereas in the cases showing c-erbB-2 overexpression MVD was clearly higher. Both correlations were statistically significant (p<0.005). In conclusion, it could be stated that increase in maspin expression is associated with weaker expression of c-erbB-2 oncogene and lower microvessel density, which implies a significant role of maspin in tumor biology. However, the exact mechanism of maspin action (including its potential role in angiogenesis), as well as the assessment of its prognostic significance in breast cancer require further studies.

Cysteine proteases as disease markers.

This review comprises issues concerning cysteine cathepsins (CCs): human peptidases belonging to papain family (C1) of clan CA of cysteine proteases: cathepsins B, L, H, S, K, F, V, X, W, O and C. The involvement of these enzymes in physiological and pathological processes is described, especially with respect to their application as diagnostic and prognostic markers. They participate in precursor protein activation (including proenzymes and prohormones), MHC-II-mediated antigen presentation, bone remodeling, keratinocytes differentiation, hair follicle cycle, reproduction and apoptosis. Cysteine cathepsins upregulation has been demonstrated in many human tumors, including breast, lung, brain, gastrointestinal, head and neck cancer, and melanoma. Besides cancer diseases, they have been implied to participate in inflammatory diseases, such as inflammatory myopathies, rheumatoid arthritis, and periodontitis. Also, certain hereditary disorders are connected with mutations in CCs genes, what is observed in pycnodysostosis resulted from catK gene mutation and Papillon-Lefevre and Haim-Munk syndrome caused by catC gene defect. The potential application of cysteine cathepsins in diagnosis and/or prognosis is discussed in cancer diseases (breast, lung, head and neck, ovarian, gastrointestinal cancers, melanoma), as well as other disorders (periodontitis, rheumatoid arthritis, osteoarthritis).

Activity of cysteine proteases and their inhibitors in the lymph nodes of larynx cancer patients.

BACKGROUND: Cysteine endopeptidases and their inhibitors play an important role in the process of carcinogenesis. Positive correlation has been found between tumor invasiveness, its metastatic potential and the secretion of cysteine endopeptidases. Cysteine protease inhibitory activity is also altered in malignant tumors and various body fluids of patients with cancer. MATERIAL/METHODS: Total cysteine endopeptidase activity and cysteine proteinase inhibitory activity were measured in homogenates of cervical lymph node tissue surgically obtained from the larynx of cancer patients. The tissue samples were histologically examined, and each was divided into two parts: positive (PCN), with mostly cancer cells, and negative (NCN), with no cancer cells. RESULTS: In the PCNs, the levels of the assayed enzymes and their inhibitors were significantly higher than in the NCNs. The mean values of cysteine protease activity were 2.70I2.29 and 1.59I1.28 for PCNs and NCNs, respectively (p<0.005). The mean values of cysteine protease inhibitors were 9.1I8.6 and 6.1I6.3 for PCNs and NCNs, respectively (p<0.02). An altered protease-inhibitor activity ratio was also found in PCN samples compared to NCNs. CONCLUSIONS: These data suggest increased activity of cysteine peptidases and their inhibitors in the case of secondary tumor tissue. The cancer cells metastasized to lymph node tissue produce some alteration in balance between cysteine protease activity and the endogenous inhibitors of the proteases.