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Wound healing is a dynamic process that requires an optimal extracellular environment, as well as an accurate synchronization between various cell types. Over the past few years, great efforts have been devoted to developing novel approaches for treating and managing burn injuries, sepsis, and chronic or accidental skin injuries. Multifunctional smart-polymer-based dressings represent a promising approach to support natural healing and address several problems plaguing partially healed injuries, including severe inflammation, scarring, and wound infection. Naturally derived compounds offer unique advantages such as minimal toxicity, cost-effectiveness, and outstanding biocompatibility along with potential anti-inflammatory and antimicrobial activity. Herein, the main driving idea of the work was the design and development of konjac glucomannan d-glucono-1,5-lactone (KG) films bioactivated by tannic acid and d-glucono-1,5-lactone (GL) addition. Our analysis, using attenuated total reflectance-Fourier transform infrared, atomic force microscopy, and surface energy measurements demonstrated that tannic acid (TA) clearly interacted with the KG matrix, acting as its cross-linker, whereas GL was embedded within the polymer structure. All developed films maintained a moist environment, which represents a pivotal property for wound dressing. Hemocompatibility experiments showed that all tested films exhibited no hemolytic impact on human erythrocytes. Moreover, the presence of TA and GL enhanced the metabolic and energetic activity in human dermal fibroblasts, as indicated by the MTT assay, showing results exceeding 150%. Finally, all films demonstrated high antibacterial properties as they significantly reduced the multiplication rate of both Staphylococcus aureusand Escherichia coliin bacterial broth and created the inhibition zones for S. aureusin agar plates. These remarkable outcomes make the KG/TA/GL film promising candidates for wound healing applications.

Increased activity of blood platelets contributes to vascular complications in patients with diabetes. The aim of this work was to investigate whether persisting hyperglycemia in diabetic patients generates excessive accumulation of ATP/ADP, which may underlie platelet hyperactivity. Platelet ATP and ADP levels, thiobarbituric acid-reactive species synthesis, and aggregation of platelets from patients with diabetes were 18-82% higher than in platelets from healthy participants. In patients with diabetes, platelet stimulation with thrombin caused about two times greater release of ATP and ADP than in the healthy group while decreasing intraplatelet nucleotide content to similar levels in both groups. This indicates that the increased content of adenylate nucleotides in the releasable pool in the platelets of diabetic patients does not affect their level in metabolic cytoplasmic/mitochondrial compartments. Significant correlations between platelet ATP levels and plasma fructosamine, as well as between platelet ATP/ADP and platelet activities, have been found in diabetic patients. In conclusion, chronic hyperglycemia-evoked elevations of ATP/ADP levels and release from blood platelets of patients with diabetes may be important factors underlying platelet hyperactivity in the course of the disease., Atherosclerosis and microanglopathy are common complications of long-lasting, insulin-dependent and -independent diabetes. Several factors contribute to the serf-propelling mechanism of atheromatic lesions in the course of the disease, including dyslipoproteinemia; [...]

Recent years have brought new developments in interventional chronic pain management, namely regenerative orthopedics utilizing platelet‐rich plasma (PRP) as well as further evolution of pulsed radiofrequency neuromodulation (PRF). Both methods have been used separately. Here, we investigated whether PRF may potentiate the activation of platelets in PRP samples when both these techniques are combined together in in vitroconditions. Studies were performed on concentrated PRP samples (PRPs) obtained from acid citrate dextrose‐treated blood taken from 11 healthy volunteers. PRPs were divided into four groups: 1) nonactivated PRP; 2) thrombin‐activated PRP as a positive control for maximal platelets activation; 3) PRF‐treated PRP exposed for 20 min to PRF energy generated by neurotherm radio frequency generator at 500 kHz, with a voltage of 40 V and maximal temperature of 42°C; and 4) a combination of groups 2 and 3. PRF‐induced platelet activation measured by platelet factor 4 (PF4) and ATP release from PRPs was significantly higher compared to nonactivated PRPs, and similar to PF4 and ATP release from thrombin‐activated PRPs. Thrombin activation did not potentiate PF4 release in PRF samples and even reduced ATP level. Additionally, PRF neither induced any platelet membrane damage measured by lactic dehydrogenase release from PRP nor modified any platelets viability or metabolism measured by MTT. We confirmed that PRF may activate PRP without additional platelet activators. So, a combination of both methods PRF and PRP application may provide a more effective opportunity for tissue regeneration in dentistry, surgery, dermatology, or in orthopedics.

ABSTRACTObjectives:Zinc excitotoxicity and thiamine pyrophosphate deficiency (TD) are known pathogenic signals contributing to mechanism of different encephalopathies through inhibition of enzymes responsible for energy metabolism such as pyruvate dehydrogenase, aconitase or ketoglutarate dehydrogenase. The aim of this work was to investigate whether subclinical Zn excess and TD, frequent in aging brain, may combine yielding overt neuronal impairment.Results:Clonal SN56 cholinergic neuronal cells of septal origin were used as the model of brain cholinergic neurons, which are particularly susceptible to neurodegeneration in the course of Alzheimer’s disease, hypoxia and other dementia-linked brain pathologies. Neither subtoxic concentration of Zn (0.10 mM) nor mild 20–25% TD deficits alone caused significant negative changes in cultured cholinergic neurons viability and their acetyl-CoA/acetylcholine metabolism. However, cells with mild TD accumulated Zn in excess, which impaired their energy metabolism causing a loss of neurons viability and their function as neurotransmitters. These negative effects of Zn were aggravated by amprolium which is an inhibitor of thiamine intracellular transport.Conclusion:Our data indicate that TD may amplify otherwise non-harmful border-line Zn excitotoxic signals yielding progress of neurodegeneration.

Background: Hyperactivation of blood platelets is an essential factor in the pathomechanism of diabetes-evoked angiopathies. The aim of this work was to investigate whether blood platelets hyperactivation resulting from type 2 diabetic hyperglycaemia-increased pyruvate dehydrogenase complex activity and excessive acetyl-CoA accumulation may be brought to the normal range by the enzyme inhibitors. Methods: Platelets were isolated from the blood of 9 type 2 diabetic patients and 10 healthy donors. Effects of 3-bromopyruvate and 3-nitropropionate on pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase activities, as well as levels of acetyl-CoA, ATP, thiobarbituric acid reactive species and aggregation were assessed in non-activated and thrombin-activated platelets. Results: In type 2 diabetic patients fasting plasma glucose and fructosamine levels were 61 and 64% higher, respectively, than in the healthy group (p?<?0.001). In non-activated diabetic platelets PDHC activity, PDHC-E2, acetyl-CoA and ATP levels were 66, 70, 68 and 60%, higher, respectively, than in platelets from healthy controls (p?<?0.01). 3-bromopyruvate (0.1 mM) decreased pyruvate dehydrogenase activity in healthy and diabetic platelets by 42% and 59%, respectively. Similar inhibitory effects were observed for acetyl-CoA and ATP levels, aggregation and TBARS accumulation rates. Succinate dehydrogenase activity was inhibited by 3-nitropropionate (10 mM) to 38 and 41% of control values in healthy and diabetic platelets, respectively, but affected neither function nor acetyl-CoA metabolism in platelets of both groups. Conclusions: These data indicate that inhibition of pyruvate dehydrogenase excessive activity in diabetic platelets by 3-bromopyruvate may normalise their functional parameters through adjustment of acetyl-CoA/ATP levels to control values. Graphic abstract: Platelets from blood of diabetic patients display higher activities of pyruvate dehydrogenase complex (PDHC), higher levels of dihydrolipoate transacetylase (DLAT, E2 subunit of PDHC) as well as higher levels of acetyl-CoA yielding greater ATP/ADP accumulation than in platelets of normoglycemic subjects. Therefore, in diabetic platelets, thrombin caused higher release of ATP/ADP triggering excessive production of reactive oxygen species (ROS) and stronger aggregation compared to control platelets. In diabetic platelets, relative excess of DLAT in PDHC made them highly susceptible to 3-bromopyruvate (3BrP) inhibition. Resulting limitation of acetyl-CoA provision by 3-BrP normalised activity of diabetic platelets.

The paper describes the age and lithological diversity of floor sediments in the Lower Nidzica Valley in the Ma ł opolska Upland (Southern Poland). Six sections of the valley floor were analyzed based on 29 samples obtained using a core drill. Four basic alluvial series were identified based on texture and sediment structure: (1) Pleistocene sand and gravel sediments that form fossilized erosional horizons, (2) fine-grained carbonate sediments deposited during the warm and humid periods of the Holocene, (3) mineral and organic sediments deposited since about 3794 102 BC, (4) sub-Atlantic mineral overbank deposits. Research has shown that floor aggradation in the Nidzica Valley occurred regularly during the Holocene and was determined primarily by local relief (valley floor width and gradient) and increasing human impact since the Neolithic. Holocene relief development in the studied part of the Nidzica valley floor is the result of both climate conditions and human impact - although their proportions vary over time. The age of the studied alluvial series was compared to that of other sediments analyzed for river valley floors across loess uplands in southern Poland.