Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review.

The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes of morbidity and mortality worldwide. According to current knowledge, the heart-brain axis is more than a theoretical concept, with many common pathophysiological mechanisms involved in the onset and evolution of both coronary and cerebral ischemia. Moreover, the focus is on the prevention and early intervention of risk factors in searching for targeted and personalized medical treatment. In this context, this narrative review aims to offer, in a didactic and practice-oriented manner, an up-to-date overview of the role played by lipid-derived biomarkers (from low-density lipoprotein cholesterol to oxylipin and apolipoproteins) in chronic coronary syndrome and ischemic stroke. Firstly, the authors highlight, via relevant epidemiological data, the significant burden of chronic coronary syndrome and ischemic stroke in the general population, thus explaining the need for updated information on this topic. Subsequently, the most important lipid-derived biomarkers and their multiple roles in the pathogenesis of these two disorders are listed. Currently available and experimental targeted therapies based on these lipid-derived biomarkers are presented in the final part of this paper, representing this manuscript's original and novel input.

Influence of Education, Cognition, and Physical Disability on Quality of Life of Romanian Patients with Multiple Sclerosis-A Cohort Study.

Background and Objectives: objective measures of disability and neurological impairmentare used to search for disease activity and monitor disease evolution in multiple sclerosis (MS). These are sometimes in disagreement with subjective quality-of-life measures. We aimed to establish the relations between the Multiple Sclerosis Quality of Life instrument (MSQOL-54) and objective measures of neurological impairment. Materials and Methods: 107 patients with MS were evaluated with the Single Digit Modalities Test (SDMT) for cognition, Nine Holes Peg Test (9HPT) for upper limb function, 25 Feet Walk Test (25FWT) for gait, and EDSS for global disability in a cohort study. Age and education level were recorded as sociodemographic factors. Results: the median EDSS was 3.5 (IQR 2.5); average SDMT score was 30.38 ± 13.54; and 9HPT speed was significantly higher for the dominant upper limb (0.3 ± 0.1 pegs/s versus 0.28 ± 0.11 pegs/s) (p = 0.016). The mental health composite score of the MSQOL-54 correlated with the SDMT, education level, and EDSS. Education level correlated with cognition and quality of life. The physical health composite score of the MSQOL-54 correlated with motor-function parameters and with SDMT. The motor-function parameters correlated well among themselves. A linear regression model found an important influence of SDMT and education level on the mental health composite score of the MSQOL-54. Although the linear regression model predicting the physical health composite score from physical disability parameters was statistically sound, none of the determinants had a significant individual influence. Conclusions: the subscores of the MSQOL-54 correlated well with the objective parameters. The strongest correlations were those with the cognitive function. Correlations with physical disability were less powerful, probably reflecting their indirect and more limited influence on quality of life compared to cognition and perception of disability.

Lidocaine-Liposomes-A Promising Frontier for Transdermal Pain Management.

(1) Background: We aim to develop novel gel formulations for transdermal drug delivery systems in acute and inflammatory pain therapy. (2) Methods: We induced inflammation by the injection of λ-carrageenan on the hind paw of 80 Wistar male rats. The animals were randomized into eight groups of 10 rats each: C (placebo gel), E (EMLATM), L (lidocaine 2%), L-CD (lidocaine + cyclodextrin 2.5%), L-LP (lidocaine + liposomes 1.7%), L-CS (lidocaine + chitosan 4%), L-CSh (lidocaine + chitosan hydrochloride), and L-CS-LP (lidocaine + chitosan + liposomes). The behavior response was determined with a hot plate, cold plate, and algesimeter, each being performed at 30, 60, 120, 180, and 240 min after pain induction. At the end of the experiment, tissue samples were collected for histological assessment. (3) Results: L-LP had the greatest anesthetic effects, which was proven on the cold plate test compared to placebo and EMLATM (all p ≤ 0.001). L-CS-LP had a significant effect on cold plate evaluation compared to placebo (p ≤ 0.001) and on hot plate evaluation compared to EMLATM (p = 0.018). (4) Conclusions: L-LP is a new substance with a substantial analgesic effect demonstrated by the cold plate in the first 120 min. Further studies with more animals are needed to determine the maximum doses that can be applied for a better analgesia with minimum side effects.

Inflammatory Pathways in Overweight and Obese Persons as a Potential Mechanism for Cognitive Impairment and Earlier Onset Alzeihmer's Dementia in the General Population: A Narrative Review.

The overweight status or obesity can be confirmed through classical methods such as the body mass index (BMI) and the waist-to-hip ratio (WHR). Apart from metabolic issues such as atherosclerosis, liver steatosis, or diabetes mellitus, long-term obesity or overweight status can pose a risk for cardiovascular and neurovascular complications. While some acute adverse events like coronary syndromes of strokes are well-documented to be linked to an increased body mass, there are also chronic processes that, due to their silent onset and evolution, are underdiagnosed and not as thoroughly studied. Through this review, we aimed to collect all relevant data with regard to the long-term impact of obesity on cognitive function in all ages and its correlation with an earlier onset of dementia such as Alzheimer's disease (AD). The exact mechanisms through which a decline in cognitive functions occurs in overweight or obese persons are still being discussed. A combination of factors has been acknowledged as potential triggers, such as a sedentary lifestyle and stress, as well as a genetic predisposition, for example, the apolipoprotein E (ApoE) alleles in AD. Most research highlights the impact of vascular dysfunction and systemic inflammation on the nervous system in patients with obesity and the subsequent neurological changes. Obesity during the early to mid-ages leads to an earlier onset of cognitive dysfunction in various forms. Also, lifestyle intervention can reverse cognitive dysfunction, especially dieting, to encourage weight loss.

Autoimmune myasthenia gravis and COVID-19. A case report-based review.

A potential relationship between COVID-19 infection and new onset myasthenia gravis (MG) has been suggested by the coexistence of these two diseases in a number of reports. This study aimed to assess their relationship by reviewing case studies of COVID-19 followed by new onset MG published between 01 December 2019 and 30 June 2023 identified by a search of PubMed/Medline database. In addition, we reviewed evidence in favour and against a potential cause and effect association, and described possible mechanisms that would underpin such a relationship. We identified 14 publications that reported 18 cases. Analysis showed the following features: age 19-83 years; 10 men/8 women; median time interval between COVID-19 and MG (17, 5-56 days); autoimmune comorbidities (4); generalised MG (14); ocular MG (4); thymoma (3); antiacetylcholine receptor antibody (16); antimuscle-specific kinase antibodies (2). All patients improved following treatment. Proof of direct causality between the two conditions can only be established in time by confirming epidemiological increase in the incidence of MG or elucidating pathogenic mechanisms to substantiate a possible cause-effect association, or both.

Electrolyte contact changes nano-Li4Ti5O12 bulk properties via surface polarons.

It is of general interest to combine the faradaic processes based high energy density of a battery with the non-faradaic processes based high power density of a capacitor in one cell. Surface area and functional groups of electrode materials strongly affect these properties. For the anode material Li4Ti5O12 (LTO), we suggest a polaron based mechanism that influences Li ion uptake and mobility. Here we show electrolytes containing a lithium salt induce an observable change in the bulk NMR relaxation properties of LTO nano particles. The longitudinal 7Li NMR relaxation time of bulk LTO can change by almost an order of magnitude and, therefore, reacts very sensitively to the cation and its concentration in the surrounding electrolyte. The reversible effect is largely independent of the used anions and of potential anion decomposition products. It is concluded that lithium salt containing electrolytes increase the mobility of surface polarons. These polarons and additional lithium cations from the electrolyte can now diffuse through the bulk, induce the observed enhanced relaxation rate and enable the non-faradaic process. This picture of a Li+ ion equilibrium between electrolyte and solid may help with improving the charging properties of electrode materials.

Correlations between Cognitive Evaluation and Metabolic Syndrome.

One of the most common medical diseases is metabolic syndrome (MetS), which encompasses diabetes and obesity. It has a systemic effect, which has long-lasting consequences on the body that are still not fully understood. The objectives of the study were to investigate the association between the severity of metabolic imbalances, insulin resistance, leptin concentration, and the presence of cognitive disorders and to assess the possible protective role of some classes of drugs used in the treatment of type 2 diabetes mellitus (T2D) and dyslipidemia in order to identify a viable target in the near future. The study included 148 diabetic patients. Standardized tests for the evaluation of cognition, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), were applied to all study participants. Serum concentrations of leptin and insulin were determined using the enzyme-linked immunosorbent assay method (ELISA), and insulin resistance was calculated using the homeostatic model assessment for insulin resistance (HOMA-IR). We found that MMSE and MoCA scores were associated with anthropometric parameters, and MoCA was associated with glycemic control parameters and leptin levels. Further research is needed in order to establish the magnitude of the relationship between metabolic syndrome components and cognitive decline in diabetic patients.

Chemical and Antimicrobial Characterization of Mentha piperita L. and Rosmarinus officinalis L. Essential Oils and In Vitro Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells.

Colorectal cancer is one of the most frequently diagnosed forms of cancer, and the therapeutic solutions are frequently aggressive requiring improvements. Essential oils (EOs) are secondary metabolites of aromatic plants with important pharmacological properties that proved to be beneficial in multiple pathologies including cancer. Mentha piperita L. (M_EO) and Rosmarinus officinalis L. (R_EO) essential oils are well-known for their biological effects (antimicrobial, antioxidant, anti-inflammatory and cytotoxic in different cancer cells), but their potential as complementary treatment in colorectal cancer is underexplored. The aim of the present study was to investigate the M_EO and R_EO in terms of chemical composition, antioxidant, antimicrobial, and cytotoxic effects in a colorectal cancer cell line-HCT 116. The gas-chromatographic analysis revealed menthone and menthol, and eucalyptol, α-pinene and L-camphor as major compounds in M_EO and R_EO respectively. M_EO exhibited potent antimicrobial activity, moderate antioxidant activity and a low cytotoxic effect in HCT 116 cells. R_EO presented a significant cytotoxicity in colorectal cancer cells and a low antimicrobial effect. The cytotoxic effect on non-cancerous cell line HaCaT was not significant for both essential oils. These results may provide an experimental basis for further research concerning the potential use of M_EO and R_EO for anticancer treatment.

Investigation of Lupeol as Anti-Melanoma Agent: An In Vitro-In Ovo Perspective.

Malignant melanoma (MM) represents the most life-threatening skin cancer worldwide, with a narrow and inefficient chemotherapeutic arsenal available in advanced disease stages. Lupeol (LUP) is a triterpenoid-type phytochemical possessing a broad spectrum of pharmacological properties, including a potent anticancer effect against several neoplasms (e.g., colorectal, lung, and liver). However, its potential as an anti-melanoma agent has been investigated to a lesser extent. The current study focused on exploring the impact of LUP against two human MM cell lines (A375 and RPMI-7951) in terms of cell viability, confluence, morphology, cytoskeletal distribution, nuclear aspect, and migration. Additionally, the in ovo antiangiogenic effect has been also examined. The in vitro results indicated concentration-dependent and selective cytotoxicity against both MM cell lines, with estimated IC50 values of 66.59 ± 2.20 for A375, and 45.54 ± 1.48 for RPMI-7951, respectively, accompanied by a reduced cell confluence, apoptosis-specific nuclear features, reorganization of cytoskeletal components, and inhibited cell migration. In ovo, LUP interfered with the process of angiogenesis by reducing the formation of neovascularization. Despite the potential anti-melanoma effect illustrated in our in vitro-in ovo study, further investigations are required to elucidate the underlying LUP-induced effects in A375 and RPMI-7951 MM cells.

DFTB Modeling of Lithium-Intercalated Graphite with Machine-Learned Repulsive Potential.

Lithium ion batteries have been a central part of consumer electronics for decades. More recently, they have also become critical components in the quickly arising technological fields of electric mobility and intermittent renewable energy storage. However, many fundamental principles and mechanisms are not yet understood to a sufficient extent to fully realize the potential of the incorporated materials. The vast majority of concurrent lithium ion batteries make use of graphite anodes. Their working principle is based on intercalation, the embedding and ordering of (lithium-) ions in two-dimensional spaces between the graphene sheets. This important process, it yields the upper bound to a battery's charging speed and plays a decisive role in its longevity, is characterized by multiple phase transitions, ordered and disordered domains, as well as nonequilibrium phenomena, and therefore quite complex. In this work, we provide a simulation framework for the purpose of better understanding lithium-intercalated graphite and its behavior during use in a battery. To address large system sizes and long time scales required to investigate said effects, we identify the highly efficient, but semiempirical density functional tight binding (DFTB) as a suitable approach and combine particle swarm optimization (PSO) with the machine learning (ML) procedure Gaussian process regression (GPR) as implemented in the recently developed GPrep package for DFTB repulsion fitting to obtain the necessary parameters. Using the resulting parametrization, we are able to reproduce experimental reference structures at a level of accuracy which is in no way inferior to much more costly ab initio methods. We finally present structural properties and diffusion barriers for some exemplary system states.

Mobile Small Polarons Qualitatively Explain Conductivity in Lithium Titanium Oxide Battery Electrodes.

Lithium titanium oxide Li4Ti5O12 is an intriguing anode material promising particularly long-life batteries, due to its remarkable phase stability during (dis)charging of the cell. However, its usage is limited by its low intrinsic electronic conductivity. Introducing oxygen vacancies can be one method for overcoming this drawback, possibly by altering the charge carrier transport mechanism. We use Hubbard corrected density functional theory to show that polaronic states in combination with a possible hopping mechanism can play a crucial role in the experimentally observed increase in electronic conductivity. To gauge polaronic charge mobility, we compute the relative stabilities of different localization patterns and estimate polaron hopping barrier heights.