BK Channels in Tail Artery Vascular Smooth Muscle Cells of Normotensive (WKY) and Hypertensive (SHR) Rats Possess Similar Calcium Sensitivity But Different Responses to the Vasodilator Iloprost.

It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively low efficacy has been established, whereas downstream BK currents seem to be increased. Thus, the overall performance of this signaling pathway in SHR is elusive. For a better understanding, we focused on one aspect, the direct targeting of the BK channel by the G-protein/AC pathway and tested the hypothesis that the comparatively low AC pathway efficacy in SHR results in a reduced agonist-induced stimulation of BK currents. This hypothesis was investigated using freshly isolated smooth muscle cells from WKY and SHR rat tail artery and the patch-clamp technique. It was observed that: (1) single BK channels have similar current-voltage relationships, voltage-dependence and calcium sensitivity; (2) BK currents in cells with a strong buffering of the BK channel activator calcium have similar current-voltage relationships; (3) the iloprost-induced concentration-dependent increase of the BK current is larger in WKY compared to SHR; (4) the effects of activators of the PKA pathway, the catalytic subunit of PKA and the potent and selective cAMP-analogue Sp-5,6-DCl-cBIMPS on BK currents are similar. Thus, our data suggest that the lower iloprost-induced stimulation of the BK current in freshly isolated rat tail artery smooth muscle cells from SHR compared with WKY is due to the lower efficacy of upstream elements of the G-Protein/AC/BK channel pathway.

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.

Interleukin-6 induced activation of a non-selective outward cation conductance in human cardiac fibroblasts.

BACKGROUND: It has been demonstrated that cardiac fibroblasts of the human heart have several myocyte-like features, induced by inflammation. OBJECTIVES: This study analyzed the changes of the expressed currents in the basal condition and in the presence of interleukin-6 in cultured human cardiac fibroblasts. METHODS: Human cardiac fibroblasts were cultured as monolayers from earlier passages (2-4). Whole-cell voltage clamp experiments were performed on single culture human cardiac fibroblasts. RESULTS: The cultured human cardiac fibroblasts had a membrane resistance of Rm of 412±91MΩ, and a resting membrane potential of -68.1±3.2mV. Among different cells, we have been analyzed these at which depolarizing clamp steps induced outward currents that reached peak within approx. 20ms and then slowly decayed. Gd3+ decreased the current amplitudes at depolarizing steps. Superfusion with interleukin-6 caused increasing of the outward membrane currents. The changes in the membrane currents continued up to 6min of interleukin-6 perfusion, by reaching their maximum at 3min and slowly decreasing to the level of control recordings at 6min. In the presence of 8µmol/l Gd3+, interleukin-6 does not modify the membrane currents. CONCLUSION: The involvement of mechano sensitive channels in interleukin-6 induced electrical property of fibroblast was proposed. This report presents one particular model of action of interleukin-6, that can open new insights for a deeper understanding of the relationships between interleukin-6 and different ion channels into the fibroblast.

Insulin treatment corrects hepcidin but not YKL-40 levels in persons with type 2 diabetes mellitus matched by body mass index, waist-to-height ratio, C-reactive protein and Creatinine.

BACKGROUND: It has been shown that hepcidin and YKL-40 levels change in persons with insulin resistance in different circumstances. However, variations of the levels of these parameters through the stages of prediabetes and type 2 diabetes mellitus are unclear. We hypothesized that hepcidin levels will decrease in persons with prediabetes, while these levels will tend to correct when persons with diabetes are treated with insulin. Finally we sought to determine the levels of YKL-40 in all groups of participants included in the study. METHODS: Serum hepcidin levels and YKL-40 levels were measured in control group (n = 20), persons with prediabetes (n = 30) and persons with diabetes on insulin therapy (n = 30) using ELISA method. Patients in all three groups were matched by Body Mass Index, Waist-to-Height Ratio, C-Reactive Protein and creatinine levels. RESULTS: Hepcidin levels were lower in persons with prediabetes compared to control, while persons with diabetes on insulin therapy had higher values than those with prediabetes (p = 0,00001). YKL-40 levels showed no significant changes. CONCLUSIONS: Serum hepcidin levels in matched persons with prediabetes are a stronger marker of early changes in glucose metabolism compared to YKL-40 levels. Also, treatment with insulin corrects hepcidin levels, but not YKL-40 levels. Correcting levels of hepcidin is important for reducing iron-overload, which is a risk factor for diabetes.

Evaluation of Bone Healing After Osteotomies Prepared With Er:YAG Laser in Contact and Noncontact Modes and Piezosurgery--An Animal Study.

PURPOSE: To analyze the healing of bone tissue treated with Er:YAG laser contact and noncontact modes of and piezosurgery in a rat model using triangular laser profilometry. MATERIALS AND METHODS: Twenty-four 10-week-old adult male Wistar rats were used in the study. Three osteotomies on the medial part of tibia were performed in each animal, 1 in the right tibia and 2 in the left tibia. The osteotomies were performed with a piezoelectric device set at maximal power and the Er:YAG laser in contact mode (power, 7.5 W; pulse energy, 375 mJ; repetition rate, 20 Hz; MSP mode) and noncontact mode (power, 7.5 W; pulse energy, 750 mJ; repetition rate, 10 Hz; QSP mode) with a novel type of circular, digitally controlled handpiece (x-Runner). After surgery, 6 animals were immediately euthanized (group 1), and the others were euthanized after 1 week (group 2, n = 6), 2 weeks (group 3, n = 6), and 3 weeks (group 4, n = 6). Bone healing after osteotomy was analyzed using a 3-dimensional laser scanning technique (ie, laser triangulation profilometry). RESULTS: The volume reduction rates are similar for all 3 techniques (0.2 to 0.25 mm(3) per week). Greater volume reduction of 0.25 mm3 per week was observed for the Er:YAG laser in noncontact mode (x-Runner). After 3 weeks, almost complete healing of the prepared osteotomy was observed. CONCLUSION: Within the limitations of this study, the osteotomies performed by the Er:YAG laser in digitally controlled noncontact mode healed the fastest.

Bone Healing Following Different Types of Osteotomy: Scanning Electron Microscopy (SEM) and Three-Dimensional SEM Analyses.

The aim of the present study was to compare dynamics of the bone healing process after different types of osteotomies. In total, 24 Wistar rats were subjected to different types of osteotomy performed with standard steel bur, piezosurgery, contact, and non-contact Erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation. The animals were randomly divided into four groups, to be euthanized immediately after the procedure, or at 1, 2, or 3 weeks after surgery. The obtained bone samples were analyzed by scanning electron microscopy (SEM). Immediately after surgery, there were significant differences in the appearance of the bone defects, with presence of bone fragments and debris after standard steel bur preparation, compared with the clean smooth walls and relatively sharp edges in all other groups. The initial bone formation in defects prepared by piezosurgery was observed to be the most rapid. After 3 weeks, all bone defects were completely restored; although, differences in the healing pattern were noted, with a modest initial delay in healing after laser preparation. The first stage of the bone healing process was delayed when contact and non-contact Er:YAG laser modes were used and accelerated by piezosurgery; however, the results after 3 weeks demonstrated similar restitution of defects in all tested groups.

Cystathionine gamma-lyase of perivascular adipose tissue with reversed regulatory effect in diabetic rat artery.

The aim of this study is to reveal the regulatory role of cystathionine gamma-lyase (CSE), the main source of hydrogen sulphide (H2S) in perivascular adipose tissue (PVAT), of diabetic rats. Diabetes was induced in male rats by a single intraperitoneal injection of streptozotocin. Animals with glucose levels above 20 mmol/L were determined as diabetic. The rat gracilis arteries (a. gracilis) were dissected with or without PVAT. In all in vitro experiments endothelium-denuded preparations were used for isometric contraction measurements. Increasing concentrations of 5-hydroxytryptamine (5-HT) from 10-10 to 10-5 mol/L were applied to induce gradual increase in force of contractions of circular artery segments. The relaxing effect of CSE was inhibited by DL-propargyl glycine (PGG). The presence of PVAT decreases the contractile response to 5-HT of a. gracilis from control rats. This response is reversed in contraction studies in the same rat artery from diabetic rats. DL-PPG (1 mmol/L) induced significant increase of the force of contraction in artery preparations with PVAT from control rats in the whole range of 5-HT. In contrast, PGG had a relaxing effect in high concentrations of 5-HT (10-6 and 10-5 mol/L) in diabetic rat arteries with PVAT. It is concluded that in skeletal muscle artery from diabetic rats, a mediator related to H2S is released from PVAT. This paracrine mediator increases the maximal force of contraction of endothelium-denuded preparations at higher concentrations of 5-HT.

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).

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.

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.

Interfacial properties of three different bioactive dentine substitutes.

Three different bioactive materials suitable as dentine substitutes in tooth repair have been studied: glass-ionomer cement, particulate bioglass, and calcium-silicate cement. On 15 permanent human molars, Class V cavities were prepared and the bottom of each cavity was de-mineralized by an artificial caries gel. After the de-mineralization, the teeth were restored with: (1) Bioglass®45S5 and ChemFil® Superior; (2) Biodentine™ and ChemFil® Superior; and (3) ChemFil® Superior for a complete repair. The teeth were stored for 6 weeks in artificial saliva, then cut in half along the longitudinal axis: the first half was imaged in a scanning electron microscope (SEM) and the other half was embedded in resin and analyzed by SEM using energy-dispersive X-ray analysis. The glass-ionomer and the bioglass underwent ion exchange with the surrounding tooth tissue, confirming their bioactivity. However, the particle size of the bioglass meant that cavity adaptation was poor. It is concluded that smaller particle size bioglasses may give more acceptable results. In contrast, both the glass-ionomer and the calcium-silicate cements performed well as dentine substitutes. The glass-ionomer showed ion exchange properties, whereas the calcium silicate gave an excellent seal resulting from its micromechanical attachment.

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.

Kv2.1 Channels Prevent Vasomotion and Safeguard Myogenic Reactivity in Rat Small Superior Cerebellar Arteries.

Vascular smooth muscle voltage-gated potassium (Kv) channels have been proposed to contribute to myogenic autoregulation. Surprisingly, in initial experiments, we observed that the Kv2 channel inhibitor stromatoxin induced vasomotion without affecting myogenic tone. Thus, we tested the hypothesis that Kv2 channels contribute to myogenic autoregulation by fine-tuning the myogenic response. Expression of Kv2 channel mRNA was determined using real-time PCR and 'multiplex' single-cell RT-PCR. Potassium currents were measured using the patch-clamp technique. Contractile responses of intact arteries were studied using isobaric myography. Expression of Kv2.1 but not Kv2.2 channels was detected in intact rat superior cerebellar arteries and in single smooth muscle cells. Stromatoxin, a high-affinity inhibitor of Kv2 channels, reduced smooth muscle Kv currents by 61% at saturating concentrations (EC50 36 nmol/L). Further, stromatoxin (10-100 nmol/L) induced pronounced vasomotion in 48% of the vessels studied. In vessels not exhibiting vasomotion, stromatoxin did not affect myogenic reactivity. Notably, in vessels exhibiting stromatoxin-induced vasomotion, pressure increases evoked two effects: First, they facilitated the occurrence of random vasodilations and/or vasoconstrictions, disturbing the myogenic response (24% of the vessels). Second, they modified the vasomotion by decreasing its amplitude and increasing its frequency, thereby destabilizing myogenic tone (76% of the vessels). Our study demonstrates that (i) Kv2.1 channels are the predominantly expressed Kv channels in smooth muscle cells of rat superior cerebellar arteries, and (ii) Kv2.1 channels provide a novel type of negative feedback mechanism in myogenic autoregulation by preventing vasomotion and thereby safeguarding the myogenic response.