GLUT5-overexpression-related tumorigenic implications.

Glucose transporter 5 (GLUT5) overexpression has gained increasing attention due to its profound implications for tumorigenesis. This manuscript provides a comprehensive overview of the key findings and implications associated with GLUT5 overexpression in cancer. GLUT5 has been found to be upregulated in various cancer types, leading to alterations in fructose metabolism and enhanced glycolysis, even in the presence of oxygen, a hallmark of cancer cells. This metabolic shift provides cancer cells with an alternative energy source and contributes to their uncontrolled growth and survival. Beyond its metabolic roles, recent research has unveiled additional aspects of GLUT5 in cancer biology. GLUT5 overexpression appears to play a critical role in immune evasion mechanisms, which further worsens tumor progression and complicates therapeutic interventions. This dual role of GLUT5 in both metabolic reprogramming and immune modulation highlights its significance as a potential diagnostic marker and therapeutic target. Understanding the molecular mechanisms driving GLUT5 overexpression is crucial for developing targeted therapeutic strategies that can disrupt the unique vulnerabilities of GLUT5-overexpressing cancer cells. This review emphasizes the complexities surrounding GLUT5's involvement in cancer and underscores the pressing need for continued research to unlock its potential as a diagnostic biomarker and therapeutic target, ultimately improving cancer management and patient outcomes.

Adipose Tissue Dysfunction Related to Climate Change and Air Pollution: Understanding the Metabolic Consequences.

Obesity, a global pandemic, poses a major threat to healthcare systems worldwide. Adipose tissue, the energy-storing organ during excessive energy intake, functions as a thermoregulator, interacting with other tissues to regulate systemic metabolism. Specifically, brown adipose tissue (BAT) is positively associated with an increased resistance to obesity, due to its thermogenic function in the presence of uncoupled protein 1 (UCP1). Recently, studies on climate change and the influence of environmental pollutants on energy homeostasis and obesity have drawn increasing attention. The reciprocal relationship between increasing adiposity and increasing temperatures results in reduced adaptive thermogenesis, decreased physical activity, and increased carbon footprint production. In addition, the impact of climate change makes obese individuals more prone to developing type 2 diabetes mellitus (T2DM). An impaired response to heat stress, compromised vasodilation, and sweating increase the risk of diabetes-related comorbidities. This comprehensive review provides information about the effects of climate change on obesity and adipose tissue, the risk of T2DM development, and insights into the environmental pollutants causing adipose tissue dysfunction and obesity. The effects of altered dietary patterns on adiposity and adaptation strategies to mitigate the detrimental effects of climate change are also discussed.

Positive Tetrahydrocurcumin-Associated Brain-Related Metabolomic Implications.

Tetrahydrocurcumin (THC) is a metabolite of curcumin (CUR). It shares many of CUR's beneficial biological activities in addition to being more water-soluble, chemically stable, and bioavailable compared to CUR. However, its mechanisms of action have not been fully elucidated. This paper addresses the preventive role of THC on various brain dysfunctions as well as its effects on brain redox processes, traumatic brain injury, ischemia-reperfusion injury, Alzheimer's disease, and Parkinson's disease in various animal or cell culture models. In addition to its strong antioxidant properties, the effects of THC on the reduction of amyloid ß aggregates are also well documented. The therapeutic potential of THC to treat patterns of mitochondrial brain dysmorphic dysfunction is also addressed and thoroughly reviewed, as is evidence from experimental studies about the mechanism of mitochondrial failure during cerebral ischemia/reperfusion injury. THC treatment also results in a dose-dependent decrease in ERK-mediated phosphorylation of GRASP65, which prevents further compartmentalization of the Golgi apparatus. The PI3K/AKT signaling pathway is possibly the most involved mechanism in the anti-apoptotic effect of THC. Overall, studies in various animal models of different brain disorders suggest that THC can be used as a dietary supplement to protect against traumatic brain injury and even improve brain function in Alzheimer's and Parkinson's diseases. We suggest further preclinical studies be conducted to demonstrate the brain-protective, anti-amyloid, and anti-Parkinson effects of THC. Application of the methods used in the currently reviewed studies would be useful and should help define doses and methods of THC administration in different disease conditions.

Myocardial infarction and oxidative damage in animal models: objective and expectations from the application of cysteine derivatives.

Reactive oxygen species (ROS) and associated oxidative stress are the main contributors to pathophysiological changes following myocardial infarction (MI), which is the principal cause of death from cardiovascular disease. The glutathione (GSH)/glutathione peroxidase (GPx) system appears to be the main and most active cardiac antioxidant mechanism. Hence, enhancement of the myocardial GSH system might have protective effects in the setting of MI. It follows that by increasing antioxidant capacity, the heart will be able to reduce the damage associated with MI and even prevent/weaken the occurrence of oxidative stress, which is highly ranked among the factors responsible for the occurrence of acute MI. For these reasons, the primary goal of future investigations should be to address the effects of different antioxidative compounds and especially cysteine derivatives like N-acetyl cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) as precursors responsible for the enhancement of the GSH-related antioxidant system's capacity. It is assumed that this will lay down the basis for elucidation of the mechanisms throughout which applicable doses of OTC will manifest a potentially positive impact in the reduction of adverse effects of acute MI. The inclusion of OTC in the models for prediction of the distribution of oxygen in infarcted animal hearts can help to upgrade existing computational models. Such a model would be based on computational geometries of the heart, but the inclusion of biochemical redox features in addition to angiogenic therapy, despite improvement of the post-infarcted oxygenated outcome could enhance the accuracy of the predictive values of oxygenation.

Serum redox markers in uncomplicated type 2 diabetes mellitus accompanied with abnormal iron levels.

OBJECTIVES: This study aimed at evaluating the serum redox status in type 2 diabetes mellitus (T2DM) accompanied with an imbalance in iron concentrations. METHODS: Diabetic patients were grouped according to serum iron levels [normal (DNFe), low (DLFe), and high (DHFe)], and their clinical and redox parameters [total sulfhydryl groups (tSH), uric acid (UA), and total bilirubin (tBILI) as non-enzymatic antioxidants, and malondialdehyde (MDA) and advanced oxidation products of proteins (AOPP) as markers of oxidative stress] were determined. RESULTS: Glucose and HbA1c levels in the T2DM patients did not differ in function of serum iron. T2DM was associated with reduced tSH levels. In the diabetic patients, tSH, UA, and tBILI negatively correlated with MDA, as well as HbA1c with UA. Accordingly, AOPP and MDA were higher in the diabetic groups compared to the controls. The reduced antioxidant capacity was particularly pronounced in the DLFe group, which was further characterized by lower levels of UA and tBILI compared to the other groups. Subsequently, the level of MDA in the DLFe group was higher compared to the DNFe and DHFe groups. The positive correlation between serum iron levels and the antioxidants UA and tBILI, in conjunction with the negative correlation between serum iron levels and the markers of oxidative stress in the diabetic patients, corroborated the indication that comparatively higher level of oxidative stress is present when T2DM coexists with decreased iron levels. CONCLUSIONS: T2DM-associated redox imbalance is characterized by a decrease in serum total sulfhydryl groups and low serum iron-associated reduction in uric acid and total bilirubin levels, accompanied by increased oxidative stress markers. The relatively noninvasive and simple determination of these parameters may be of considerable interest in monitoring the pathophysiological processes in T2DM patients, and may provide useful insights into the effects of potential therapeutic or nutritional interventions.

Efficacy of the monocarbonyl curcumin analog C66 in the reduction of diabetes-associated cardiovascular and kidney complications.

Curcumin is a polyphenolic compound derived from turmeric that has potential beneficial properties for cardiovascular and renal diseases and is relatively safe and inexpensive. However, the application of curcumin is rather problematic due to its chemical instability and low bioavailability. The experimental results showed improved chemical stability and potent pharmacokinetics of one of its analogs - (2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66). There are several advantages of C66, like its synthetic accessibility, structural simplicity, improved chemical stability (in vitro and in vivo), presence of two reactive electrophilic centers, and good electron-accepting capacity. Considering these characteristics, we reviewed the literature on the application of C66 in resolving diabetes-associated cardiovascular and renal complications in animal models. We also summarized the mechanisms by which C66 is preventing the release of pro-oxidative and pro-inflammatory molecules in the priming and in activation stage of cardiomyopathy, renal fibrosis, and diabetic nephropathy. The cardiovascular protective effect of C66 against diabetes-induced oxidative damage is Nrf2 mediated but mainly dependent on JNK2. In general, C66 causes inhibition of JNK2, which reduces cardiac inflammation, fibrosis, oxidative stress, and apoptosis in the settings of diabetic cardiomyopathy. C66 exerts a powerful antifibrotic effect by reducing inflammation-related factors (MCP-1, NF-κB, TNF-α, IL-1ß, COX-2, and CAV-1) and inducing the expression of anti-inflammatory factors (HO-1 and NEDD4), as well as targeting TGF-ß/SMADs, MAPK/ERK, and PPAR-γ pathways in animal models of diabetic nephropathy. Based on the available evidence, C66 is becoming a promising drug candidate for improving cardiovascular and renal health.

Tetrahydrocurcumin-Related Vascular Protection: An Overview of the Findings from Animal Disease Models.

Tetrahydrocurcumin (THC), one of the major metabolites of CUR, possesses several CUR-like pharmacological effects; however, its mechanisms of action are largely unknown. This manuscript aims to summarize the literature on the preventive role of THC on vascular dysfunction and the development of hypertension by exploring the effects of THC on hemodynamic status, aortic elasticity, and oxidative stress in vasculature in different animal models. We review the protective effects of THC against hypertension induced by heavy metals (cadmium and iron), as well as its impact on arterial stiffness and vascular remodeling. The effects of THC on angiogenesis in CaSki xenografted mice and the expression of vascular endothelial growth factor (VEGF) are well documented. On the other hand, as an anti-inflammatory and antioxidant compound, THC is involved in enhancing homocysteine-induced mitochondrial remodeling in brain endothelial cells. The experimental evidence regarding the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion injury and the therapeutic potential of THC to alleviate mitochondrial cerebral dysmorphic dysfunction patterns is also scrutinized and explored. Overall, the studies on different animal models of disease suggest that THC can be used as a dietary supplement to protect against cardiovascular changes caused by various factors (such as heavy metal overload, oxidative stress, and carcinogenesis). Additionally, the reviewed literature data seem to confirm THC's potential to improve mitochondrial dysfunction in cerebral vasculature during ischemic stroke through epigenetic mechanisms. We suggest that further preclinical studies should be implemented to demonstrate THC's vascular-protective, antiangiogenic, and anti-tumorigenic effects in humans. Applying the methods used in the presently reviewed studies would be useful and will help define the doses and methods of THC administration in various disease settings.

Antioxidant and anti-inflammatory effects of the monocarbonyl curcumin analogs B2BRBC and C66 in monocrotaline-induced right ventricular hypertrophy.

For 22 days after monocrotaline injection two groups of rats received either of the monocarbonyl curcumin analogs (2E,6E)-2,6-bis(2-bromobenzylidene)cycloxehanone (B2BrBC) and (2E,6E)-2,6-bis([2-trifluoromethyl]benzylidene)cyclohexanone (C66), and their right ventricle parameters were compared to those from the control and the monocrotaline injected animals. B2BrBC and C66 treatments did not prevent the monocrotaline-induced right ventricular hypertrophy but attenuated the changes in antioxidant enzyme activities and reduced inflammation. The level of thiol-based nonenzymatic antioxidants did not change in the function of monocrotaline or curcumin analogs treatment. However, due to its stronger antioxidant properties, only B2BrBC treatment was effective in the reduction of monocrotaline-associated lipid peroxidation. The obtained results suggest that increasing the levels of antioxidant enzymes may not be sufficient to reduce oxidative stress and chronic inflammation optimally and our current study supports the potential of compounds with more than one beneficial biological activity as a promising treatment against the progression of cardiac hypertrophy.

D-galactose induced inflammation lipid peroxidation and platelet activation in rats.

BACKGROUND: To investigate events possibly related to the development of D-galactose induced senescence, we examined whether 8-iso PGF(2α) formation, a marker of in vivo lipid peroxidation is altered and whether its biosynthesis is associated with 11-dehydro-TXB(2) excretion rate, as a marker of in vivo platelet activation. In this setting, we also investigated the relationship between proinflammatory mediators (IL-6 and TNF-α from one, and lipid peroxidation and platelet activation, from another aspect. METHODS AND RESULTS: Forty animals were divided, depending on treatment with d-galactose into: placebo and D-galactose treated rats. 8-iso-PGF(2α), IL-6 and TNF-α were measured in plasma, while 11-dehydro-TXB(2) was determined in the urine after a six week treatment with d-galactose. Compared to placebo, d-galactose treated animals showed significantly higher levels of all measured parameters. CONCLUSIONS: D-galactose induced changes in the rate of F(2)-isoprostane formation are associated with the changes in the excretion rate of 11-dehydro-TXB(2).

Monocarbonyl analogs of curcumin C66 and B2BrBC modulate oxidative stress, JNK activity, and pancreatic gene expression in rats with streptozotocin-induced diabetes.

The pathogenesis of type 1 diabetes mellitus (T1DM) involves oxidative stress and inflammation. Curcumin, a natural polyphenolic compound found in turmeric, known to exhibit antioxidative and anti-inflammatory properties, is characterized by poor chemical stability, low bioavailability, and rapid metabolism. Monocarbonyl analogs of curcumin (MACs) with a structural absence of ß-diketone and enhanced stability and bioavailability present a potential solution to the challenges associated with the use of curcumin. This study aimed to evaluate the effect of two MACs, C66 and B2BrBC, on oxidative stress markers, antioxidant enzyme activity, expression of diabetes-associated genes, and signaling pathway proteins in the context of T1DM. Streptozotocin (STZ)-induced male Wistar rats or rat pancreatic RIN-m cells were used for in vivo and in vitro experiments, respectively. C66 or B2BrBC were given either before or after STZ treatment. Oxidative stress markers and antioxidant enzyme activities were determined in various tissues. Expression of diabetes-associated genes was assessed using RT-qPCR, and the activity of signaling pathway proteins in the pancreas was determined through Western blot analysis. Treatment with C66 and B2BrBC significantly reduced oxidative stress markers and positively influenced antioxidant enzyme activities. Moreover, both compounds inhibited JNK activity in the pancreas while enhancing the expression of genes crucial for ß-cell survival and glucose and redox homeostasis. The findings highlight the multifaceted potential of C66 and B2BrBC in ameliorating oxidative stress, influencing gene expression patterns linked to diabetes, and modulating key signaling pathways in the pancreas. The findings suggest that these compounds can potentially address diabetes-related pathological processes.

The Role of KACh Channels in Atrial Fibrillation.

This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (KACh) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of KACh channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of KACh activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.4 and K2P3.1, significantly influence the electrophysiological remodeling associated with AF. Furthermore, this manuscript identifies the crucial role of the KACh-mediated current, IKACh, in sustaining arrhythmia through facilitating shorter re-entry circuits and stabilizing the re-entrant circuits, particularly in response to vagal nerve stimulation. Experimental findings from animal models, which could not induce AF in the absence of muscarinic activation, highlight the dependency of AF induction on KACh channel activity. This is complemented by discussions on therapeutic interventions, where KACh channel blockers have shown promise in AF management. Additionally, this study discusses the broader implications of KACh channel behavior, including its ubiquitous presence across different cardiac regions and species, contributing to a comprehensive understanding of AF dynamics. The implications of these findings are profound, suggesting that targeting KACh channels might offer new therapeutic avenues for AF treatment, particularly in cases resistant to conventional approaches. By integrating genetic, cellular, and pharmacological perspectives, this manuscript offers a holistic view of the potential mechanisms and therapeutic targets in AF, making a significant contribution to the field of cardiac arrhythmia research.

SIRT-associated attenuation of cellular senescence in vascular wall.

This review focuses on the vital function that SIRT1 and other sirtuins play in promoting cellular senescence in vascular smooth muscle cells, which is a key element in the pathogenesis of vascular aging and associated cardiovascular diseases. Vascular aging is a gradual process caused by the accumulation of senescent cells, which results in increased vascular remodeling, stiffness, and diminished angiogenic ability. Such physiological alterations are characterized by a complex interplay of environmental and genetic variables, including oxidative stress and telomere attrition, which affect gene expression patterns and trigger cell growth arrest. SIRT1 has been highlighted for its potential to reduce cellular senescence through modulation of multiple signaling cascades, particularly the endothelial nitric oxide (eNOS)/NO signaling pathway. It also modulates cell cycle through p53 inactivation and suppresses NF-κB mediated expression of adhesive molecules at the vascular level. The study also examines the therapeutic potential of sirtuin modulation in vascular health, identifying SIRT1 and its sirtuin counterparts as potential targets for reducing vascular aging. This study sheds light on the molecular basis of vascular aging and the beneficial effects of sirtuins, paving the way for the development of tailored therapies aimed at enhancing vascular health and prolonging life.

Emerging technologies in adipose tissue research.

Technologies are transforming the understanding of adipose tissue as a complex and dynamic tissue that plays a critical role in energy homoeostasis and metabolic health. This mini-review provides a brief overview of the potential impact of novel technologies in biomedical research and aims to identify areas where these technologies can make the most significant contribution to adipose tissue research. It discusses the impact of cutting-edge technologies such as single-cell sequencing, multi-omics analyses, spatial transcriptomics, live imaging, 3D tissue engineering, microbiome analysis, in vivo imaging, and artificial intelligence/machine learning. As these technologies continue to evolve, we can expect them to play an increasingly important role in advancing our understanding of adipose tissue and improving the treatment of related diseases.

The Microbiome in the Obesity-Breast Cancer Axis: Diagnostic and Therapeutic Potential.

A growing body of evidence has demonstrated a relationship between the microbiome, adiposity, and cancer development. The microbiome is emerging as an important factor in metabolic disease and cancer pathogenesis. This review aimed to highlight the role of the microbiome in obesity and its association with cancer, with a particular focus on breast cancer. This review discusses how microbiota dysbiosis may contribute to obesity and obesity-related diseases, which are linked to breast cancer. It also explores the potential of the gut microbiome to influence systemic immunity, leading to carcinogenesis via the modulation of immune function. This review underscores the potential use of the microbiome profile as a diagnostic tool and treatment target, with strategies including probiotics, fecal microbiota transplantation, and dietary interventions. However, this emphasizes the need for more research to fully understand the complex relationship between the microbiome, metabolic disorders, and breast cancer. Future studies should focus on elucidating the mechanisms underlying the impact of the microbiome on breast cancer and exploring the potential of the microbiota profile as a biomarker and treatment target.

Inflammatory and oxidative stress markers in intracerebral hemorrhage: Relevance as prognostic markers for quantification of the edema volume.

We aimed to analyze the inflammatory and oxidative stress (OS) markers after intracerebral hemorrhage (ICH) and their temporal changes, interaction effects, and prognostic values as biomarkers for the prediction of the edema volume. Our prospective, longitudinal study included a cohort group of 73 conservatively treated patients with ICH, without hematoma expansion or intraventricular bleeding, which were initialized with the same treatment and provided with the same in-hospital care during the disease course. Study procedures included multilevel comprehensive analyses of clinical and neuroimaging data, aligned with the exploration of 19 inflammatory and five OS markers. White blood cells (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophilia, and lymphopenia peaked 3 days post-ICH, and they showed much stronger correlations with clinical and neuroimaging variables, when compared to the admission values. An intricate interplay among inflammatory (WBC, CRP, neutrophils, neutrophil-to-lymphocyte ratio [NLR], interleukin (IL)-6, and IL-10) and OS mechanisms (catalase activity and advanced oxidation protein products [AOPP]) was detected operating 3-days post-ICH, being assessed as relevant for prediction of the edema. The overall results suggested complex pathology of formation of post-ICH edema, via: (A) Not additive, but statistically significant synergistic interactions between CRP-ESR, neutrophils-CRP, and neutrophils-IL-6 as drivers for the edema formation; (B) Significant antagonistic effect of high protein oxidation on the CRP-edema dependence, suggesting a mechanism of potential OS-CRP negative feedback loop and redox inactivation of CRP. The final multiple regression model separated the third-day variables NLR, CRP × AOPP, and WBC, as significant prognostic biomarkers for the prediction of the edema volume, with NLR being associated with the highest effect size. Our developed mathematical equation with 3D modeling for prediction and quantification of the edema volume might be beneficial for taking timely adequate strategies for prevention of delayed neurological deteriorations.

Quercetin supplementation attenuates airway hyperreactivity and restores airway relaxation in rat pups exposed to hyperoxia.

Hyperoxia exposure of immature lungs contributes to lung injury and airway hyperreactivity. Up to now, treatments of airway hyperreactivity induced by hyperoxia exposure have been ineffective. The aim of this study was to investigate the effects of quercetin on hyperoxia-induced airway hyperreactivity, impaired relaxation, and lung inflammation. Newborn rats were exposed to hyperoxia (FiO2 > 95%) or ambient air (AA) for seven days. Subgroups were injected with quercetin (10 mg·kg-1·day-1). After exposures, tracheal cylinders were prepared for in vitro wire myography. Contraction to methacholine was measured in the presence or absence of organ bath quercetin and/or Nω-nitro-L-arginine methyl ester (L-NAME). Relaxation responses were evoked in preconstricted tissues using electrical field stimulation (EFS). Lung tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß) levels were measured by enzyme-linked immunosorbent assay (ELISA). A P < 0.05 was considered statistically significant. Contractile responses of tracheal smooth muscle (TSM) of hyperoxic animals were significantly increased compared with AA animals (P < 0.001). Treatment with quercetin significantly reduced contraction in hyperoxic groups compared with hyperoxic control (P < 0.01), but did not have any effect in AA groups. In hyperoxic animals, relaxation of TSM was significantly reduced compared with AA animals (P < 0.001), while supplementation of quercetin restored the lost relaxation in hyperoxic groups. Incubation of preparations in L-NAME significantly reduced the quercetin effects on both contraction and relaxation (P < 0.01). Treatment of hyperoxic animals with quercetin significantly decreased the expression of TNF-α and IL-1ß compared with hyperoxic controls (P < 0.001 and P < 0.01, respectively).The findings of this study demonstrate the protective effect of quercetin on airway hyperreactivity and suggest that quercetin might serve as a novel therapy to prevent and treat neonatal hyperoxia-induced airway hyperreactivity and inflammation.

Anticarcinogenic Potency of EF24: An Overview of Its Pharmacokinetics, Efficacy, Mechanism of Action, and Nanoformulation for Drug Delivery.

EF24, a synthetic monocarbonyl analog of curcumin, shows significant potential as an anticancer agent with both chemopreventive and chemotherapeutic properties. It exhibits rapid absorption, extensive tissue distribution, and efficient metabolism, ensuring optimal bioavailability and sustained exposure of the target tissues. The ability of EF24 to penetrate biological barriers and accumulate at tumor sites makes it advantageous for effective cancer treatment. Studies have demonstrated EF24's remarkable efficacy against various cancers, including breast, lung, prostate, colon, and pancreatic cancer. The unique mechanism of action of EF24 involves modulation of the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, disrupting cancer-promoting inflammation and oxidative stress. EF24 inhibits tumor growth by inducing cell cycle arrest and apoptosis, mainly through inhibiting the NF-κB pathway and by regulating key genes by modulating microRNA (miRNA) expression or the proteasomal pathway. In summary, EF24 is a promising anticancer compound with a unique mechanism of action that makes it effective against various cancers. Its ability to enhance the effects of conventional therapies, coupled with improvements in drug delivery systems, could make it a valuable asset in cancer treatment. However, addressing its solubility and stability challenges will be crucial for its successful clinical application.

Protective Effects of L-2-Oxothiazolidine-4-Carboxylate during Isoproterenol-Induced Myocardial Infarction in Rats: In Vivo Study.

This study aimed to evaluate the cardioprotective effects of L-2-oxothiazolidine-4-carboxylate (OTC) against isoproterenol (ISO)-induced acute myocardial infarction (MI) in rats. Results demonstrated that OTC treatments inhibited ISO-induced oxidative damage, suppressed lipid peroxidation, and increased superoxide dismutase and catalase activity in the hearts of the treated rats compared to those of the untreated controls. The ISO-related NF-κB activation was reduced due to the OTC treatment, and lower degrees of inflammatory cell infiltration and necrosis in the hearts were observed. In summary, OTC treatments exerted cardioprotective effects against MI in vivo, mainly due to enhancing cardiac antioxidant activity.

Antibacterial and Antiviral Properties of Tetrahydrocurcumin-Based Formulations: An Overview of Their Metabolism in Different Microbiotic Compartments.

In this review, the basic metabolic characteristics of the curcuminoid tetrahydrocurcumin (THC) at the level of the intestinal microbiota were addressed. Special attention was given to the bactericidal effects of one of the THC-phospholipid formulations, which has shown greater bioavailability and activity than pure THC. Similarly, quinoline derivatives and amino acid conjugates of THC have also shown antibacterial effects in the gut. The microbial effect of pure THC is particularly pronounced in pathophysiological conditions related to the function of the intestinal microbiota, such as type II diabetes. Furthermore, the antiviral characteristics of Cur compared to those of THC are more pronounced in preventing the influenza virus. In the case of HIV infections, the new microemulsion gel formulations of THC possess high retention during preventive application in the vagina and, at the same time, do not disturb the vaginal microbiota, which is critical in maintaining low vaginal pH. Based on the reviewed literature, finding new formulations of THC which can increase its bioavailability and activity and emphasize its antibacterial and antiviral characteristics could be very important. Applying such THC formulations in preventing and treating ailments related to the microbiotic compartments in the body would be beneficial from a medical point of view.

Cardiomyocytes' prolonged IL-2 incubation induces enhancement in L-type Ca2+ channels mediated by inhibitory-kappaB kinase/nuclear factor-kappaB signalling.

The main objective of this study was to determine the primary intracellular signalling pathway affected by prolonged (2 hours) incubation in interleukin-2 (IL-2). Based on the inflammatory nature of IL-2, priority was given to the involvement of inhibitory-kappaB kinase/nuclear factor-kappaB (IKK/NF-κB) signalling. All of the experiments were performed on freshly prepared cardiomyocytes isolated from rat left ventricles. After isolation, the whole-cell voltage-clamp recordings were performed on single cells. After 2 hours of incubation in IL-2, the current at 0 mV was approximately 100% higher than at the start of the incubation. ACHP, a highly specific kinase ß inhibitor, in a concentration of 10 nmol/L, caused significant reduction in the ICa,L . IL-2 (2 ng/mL) in the presence of 0.1 µmol/L IMD-0354 as a specific inhibitor of IKKß, caused nearly no changes in the ICa,L . IL-2 (3 ng/mL) induced a significant increase in phosphorylated NF-κB p65. The cardiomyocytes incubated in a Kraftbrühe solution containing IL-2 plus PDTC as a specific inhibitor of inducible nitric oxide synthase (iNOS) for 2 hours had a similar ICa,L increase compared to the cells incubated only in IL-2. IL-2-induced enhancement in L-type Ca2+ channels was mediated by IKK/NF-κB signalling, but not via iNOS-mRNA signalling.