Diabetes mellitus is a chronic metabolic disease which is a serious global problem. In 2010 an estimated 285 million people had diabetes and within the next 20 years this value is expected to almost double. Many antidiabetic therapies focus on improving insulin sensitivity, increasing insulin production, and/or decreasing the level of blood glucose. Although a number of synthetic medicines are available, drugs of natural origin have aroused great interest. Triterpenes seem to demonstrate adequate properties. Many experiments have shown that these compounds have several antidiabetic mechanisms. They can inhibit enzymes involved in glucose metabolism, prevent the development of insulin resistance and normalize plasma glucose and insulin levels. These natural compounds, in contrast to synthetic drugs, apart from producing a hypoglycemic effect have also been found to manifest hypolipidemic and anti-obesity activity. Triterpenes are also promising agents in the prevention of diabetic complications. They have strong antioxidant activity and inhibit the formation of advanced glycation end products, implicated in the pathogenesis of diabetic nephropathy, embryopathy, neuropathy or impaired wound healing. Until now very few clinical studies have been concerned with the application of triterpenes in treating diabetes. However, due to their great therapeutic potential, these compounds deserve special attention.

The prevention or alleviation of neurodegenerative diseases, including Alzheimer’s disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious disturbances in the functioning of the whole organism. The Mediterranean diet is characterized by a high consumption of fruits and vegetables, cereals, nuts, olive oil, and seeds as the major source of fats, moderate consumption of fish and poultry, low to moderate consumption of dairy products and alcohol, and low intake of red and processed meat. The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life.

Cancer cells have developed a number of adaptation mechanisms involving the signal activation of the transduction pathways, which promotes the progression and metastasis. Our results showed that the percentage of apoptotic MCF-7 cells incubated in the low glucose medium for 48 h was lower in comparison to those cultured in the high glucose medium, despite the high expression of the proapoptotic transcription factor—CHOP. Furthermore, the MCF-7 cells incubated in the low glucose medium for 48 h showed a higher expression of NF-κB p100/p52 subunits compared to cells incubated in the high glucose medium. Moreover, our findings demonstrated that the shortage of glucose strongly induces autophagy in MCF-7 cells. The activation of this process is not associated with the changes in the expression of mTOR kinase. We suggest, that the antiapoptotic chaperone ORP150 induction, transcription factor NF-κB2 activation, and increased autophagy constitute mechanisms protecting the MCF-7 cells against apoptosis.

L-carnitine plays an important role in the functioning of the central nervous system, and especially in the mitochondrial metabolism of fatty acids. Altered carnitine metabolism, abnormal fatty acid metabolism in patients with autism spectrum disorder (ASD) has been documented. ASD is a complex heterogeneous neurodevelopmental condition that is usually diagnosed in early childhood. Patients with ASD require careful classification as this heterogeneous clinical category may include patients with an intellectual disability or high functioning, epilepsy, language impairments, or associated Mendelian genetic conditions. L-carnitine participates in the long-chain oxidation of fatty acids in the brain, stimulates acetylcholine synthesis (donor of the acyl groups), stimulates expression of growth-associated protein-43, prevents cell apoptosis and neuron damage and stimulates neurotransmission. Determination of L-carnitine in serum/plasma and analysis of acylcarnitines in a dried blood spot may be useful in ASD diagnosis and treatment. Changes in the acylcarnitine profiles may indicate potential mitochondrial dysfunctions and abnormal fatty acid metabolism in ASD children. L-carnitine deficiency or deregulation of L-carnitine metabolism in ASD is accompanied by disturbances of other metabolic pathways, e.g., Krebs cycle, the activity of respiratory chain complexes, indicative of mitochondrial dysfunction. Supplementation of L-carnitine may be beneficial to alleviate behavioral and cognitive symptoms in ASD patients.

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Chronic ear disease with cholesteatoma is characterized by an intrusion of keratinizing stratified squamous epithelium into the middle ear manifesting bone resorption at the interface of the perimatrix. The aim of our study was to investigate the markers of a catabolic process associated with several chronic inflammatory states. We assessed the level of catabolism of glycoconjugates in assays of cholesteatoma extracts, quantifying two lysosomal exoglycosidases: alpha-mannosidase (alpha-MAN) and beta-galactosidase (beta-GAL). Cholesteatomas (n = 15) and normal adult postauricular skin served as controls (n = 15) were collected from the patients during surgery owing to chronic otitis media. To assess exoglycosidase activity, release of p-nitrophenol from p-nitrophenol derivatives of alpha-mannose and beta-galactose was used. In 13 of 15 specimens, we observed significantly higher activity of investigated enzymes in cholesteatoma tissue compared with control tissue (postauricular skin). The mean activity of alpha-MAN from the cholesteatoma cells was 1.76 +/- 1.10 nkat/g wet tissue and 0.61 +/- 0.21 nkat/g wet tissue in the control probes. The mean activity of beta-GAL from the cholesteatoma cells was 1.77 +/- 1.07 nkat/g wet tissue and 0.87 +/- 0.20 nkat/g wet tissue in the control probes. Catabolic reactions involving glycoproteins, glycolipids, and proteoglycans may play a role in cholesteatoma-related bone resorption. The present data indicating that the lysosomal exoglycosidases alpha-MAN and beta-GAL are significantly and consistently elevated suggest the need to further correlations assessment between levels of alpha-MAN and beta-GAL and cholesteatoma behavior. Further research should also evaluate the relative importance of these particular exoglycosidases in manifesting bone resorption in considering the spectrum of identified inflammatory mediators.

Cholesteatoma is a destructive disease characterized by the progressive expansion of keratinizing squamous epithelium in the middle ear and mastoid, and chronic inflammatory reaction of the subepithelial connective tissue. N-Acetyl-beta-d-hexosaminidase (HEX) catalyzes the release of terminal non-reducing N-acetyl-d-hexosamine residues acting on glucosides and galactosides in glycoproteins, G(M2)-gangliosides and glycosaminoglycans (GAGs). In this study the activities of HEX were measured in cholesteatoma tissue and in normal skin to demonstrate a possible role of HEX in bone resorption in the area adjacent to cholesteatoma. Cholesteatomas (n = 21) and normal adult retroauricular skin (controls, n = 21), were collected from patients during surgery due to chronic otitis media. In 20 of 21 specimens a significantly higher activity of HEX was observed in cholesteatoma tissue compared with that in normal skin. Mean release of HEX from the activated cells was 68.55 +/- 30.77 nkat/g wet tissue in cholesteatoma and 31.79 +/- 10.02 nkat/g wet tissue in skin specimens. It may explain the process of bone resorption in the area adjacent to cholesteatoma, i.e. ossicles or temporal bone. This study suggests that drugs inhibiting HEX activity, such as iminocyclitols, may be useful in cholesteatoma treatment.

BackgroundLysosomal exoglycosidases, such as α-mannosidases (MAN) and β-galactosidases (GAL), are found in different glycoside hydrolase sequence-based families. Considerable research has proved plays the role of MAN, which play a key role in the modification and diversification of hybrid N-glycans, processes with strong cellular links to cancer. Therefore the study aim was to investigate the activities of MAN and GAL in larynx cancer compared to controls.Material and methodsLarynx cancer (n = 21) and normal healthy tissue (n = 21) were collected from patients during total laryngectomy. A biopsy of macroscopically healthy tissue in the area of the lower 1/3 of omohyoid muscle was taken for frozen sections in each case and these served as controls. The release of p-nitrophenol from p-nitrophenol derivatives of MAN and GAL was used.ResultsIn all specimens we observed significantly higher activity of investigated enzymes in larynx cancer compared with controls. The mean release of MAN from activated cells was 3.702 ±1.3245 nkat/g wet tissue compared to controls (1.614 ±0.8220 nkat/g wet tissue). The mean release of GAL from the activated cells was 3.383 ±2.1980 nkat/g wet tissue compared to controls (2.137 ±1.3685 nkat/g wet tissue). Differences in observed activity were statistically significant.ConclusionThe present data indicate that MAN and GAL are significantly and consistently elevated in larynx cancer growth. It also means that catabolic reactions involving glycoproteins, glycolipids and proteoglycans may play a role in larynx cancer. Further research should also evaluate the relative importance of these particular exoglycosidases in indicating the progress of the disease in considering the spectrum of identified marker mediators.