Involvement of gut microbiota in multiple sclerosis-review of a new pathophysiological hypothesis and potential treatment target.

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood-brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS.

The Clock Drawing Task reveals executive dysfunction in the dialysis population - an underrecognized and underestimated problem.

AIM OF THE STUDY: The study aimed to assess the prevalence of executive function impairment among patients with chronic kidney disease (CKD) undergoing dialysis, with no subjective cognitive problems and with normal global cognition on the Mini-Mental State Examination (MMSE). We also investigated the relationship between cardiovascular risk factors and cognitive test results. RATIONALE FOR THE STUDY: Patients with CKD, including those undergoing renal replacement therapy, are at a higher risk of developing cognitive impairment (CI) than the general population. Recent research has shown CI to be a growing problem among CKD patients worldwide. Yet, it remains underdiagnosed, even though it may significantly influence the lives of patients. MATERIALS AND METHODS: In this cross-sectional, prospective study, 58 dialysis patients with no cognitive decline on the MMSE screening were assessed for executive function impairment using the Executive Clock-Drawing Task (CLOX). Moreover, past medical history, demographic data, and laboratory test results were collected. RESULTS: The mean patient age was 59.47 ± 14.98 years, and the mean duration of dialysis was 45.93 ± 48.49 months. The prevalence of executive function impairment amounted to 8.6%. Moreover, remarkably similar pattern of clock drawing was observed, with numbers written outside the clock face in the CLOX1 test. CONCLUSIONS: Executive dysfunctions in dialysis patients may manifest itself before the onset of global cognitive impairment. There appear to be a deficit in the spatial domain as well. Better education may play a protective role.

Current progress, strategy, and prospects of PD-1/PDL-1 immune checkpoint biosensing platforms for cancer diagnostics, therapy monitoring, and drug screening.

Recent technological advancements in testing and monitoring instrumentation have greatly contributed to the progress in cancer treatment by surgical, chemotherapeutic and radiotherapeutic interventions. However, the mortality rate still remains high, calling for the development of new treatment strategies with higher efficacy. Extensive efforts driven in this direction have included broadening of early cancer screening and applying innovative theranostic nanotechnologies. They have been supported by platforms introduced to enable the detection and monitoring of cancer biomarkers, inhibitors, and other agents, able to slow down cancer progression and prevent metastasis. Despite of the well-recognized principles of the immune checkpoint blockade, the efficacy of immunotherapy achieved so far does not meet the well-founded expectations. For a successful cancer treatment, highly sensitive, robust, and inexpensive multiplex biosensors have to be designed to aid in the biomarkers monitoring and in the development of new inhibitors. In this review, we provide an overview of the efforts undertaken to aid in the development and monitoring of anticancer immunotherapy, based on the programmed cell-death immune checkpoint (PD-1/PDL-1) blockade, by designing biosensors for the detection of relevant cancer biomarkers and their inhibitors screening. This review also emphasizes alternative targets made by exosomes carrying PD-L1 overexpressed in cancer cells and passed into the excreted exosomes. Evaluated are also novel targeted drug delivery nanocarriers, providing simultaneous biosensing, thereby contributing to the emerging immune checkpoint cancer therapy. On the basis of the current trends and the emerging technologies, future perspectives of cancer diagnostics and treatment monitoring using biosensing platforms are projected.

Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes.

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS). When they're not functioning correctly, becoming fragmented and losing their membrane potential, they contribute to these diseases. In this review, we explore how mitochondria fuse and undergo fission, especially in the context of NDs. We discuss the genetic and protein mutations linked to these diseases and how they impact mitochondrial dynamics. We also look at the key regulatory proteins in fusion (MFN1, MFN2, and OPA1) and fission (DRP1 and FIS1), including their post-translational modifications. Furthermore, we highlight potential drugs that can influence mitochondrial dynamics. By unpacking these complex processes, we aim to direct research towards treatments that can improve life quality for people with these challenging conditions.

Cognitive Impairment and Anxiety Are Prevalent in Kidney Transplant Recipients.

INTRODUCTION: Cognitive impairment (CI) is common in end-stage kidney disease (ESKD), including kidney transplant recipients. Patients with cognitive problems may find it difficult to comply with medical recommendations after kidney transplantation (KT), which can be the cause of many complications, poorer prognosis, and increased hospitalization rates after transplantation. Additionally, some patients after KT may experience depression and anxiety, which are prevalent comorbidities in patients with ESKD. METHODS: In this single-center, cross-sectional study, we included 56 consecutive adult patients after KT. Cognitive function was assessed using the Addenbrooke Cognitive Test III (ACE III). In addition, all patients were screened for depression and anxiety using the Hospital Anxiety and Depression Scale (HADS). The impact of immunosuppressive therapy and other disease-related variables on cognitive function was also assessed. RESULTS: A total of 56 KT patients, with a mean age of 50.3 ± 11.7 years, transplanted ≤35 months ago were included in the study. The prevalence of CI was 30%. Compared with cognitively unimpaired patients, patients with CI scored significantly lower in all cognitive domains. Furthermore, better cognitive functioning after KT was significantly associated with more years of schooling. We found no significant correlation between CI and age at assessment, duration of dialysis before KT, creatinine levels, creatinine clearance, uric acid levels, hemoglobin levels, comorbid cardiovascular diseases, and immunosuppressive therapy. In addition, the prevalence of depression and anxiety in screening tests was 12.5% and 27%, respectively, and patients receiving higher daily dose of prednisone had higher HADS scores on both the depression and anxiety subscales (not statistically significant). DISCUSSION: Cognitive disorders are a relevant issue in kidney transplant recipients. There might be many factors, both before and after KT, that have a negative impact on cognition. Therefore, further research is needed to increase knowledge about the course and profile of cognitive function after KT.

Patterns of Cognitive Impairment in Hemodialysis Patients and Related Factors including Depression and Anxiety.

INTRODUCTION: Hemodialysis patients are at higher risk of developing cognitive impairment, but the pattern of affected cognitive domains is still undetermined. Little is also known about the symptoms of depression and anxiety in hemodialysis patients. METHODS: In this cross-sectional study, we included 74 consecutive adult patients undergoing hemodialysis. Cognitive functions were assessed using the Addenbrooke Cognitive Test III. In addition, all patients were screened for symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale. RESULTS: The mean age of hemodialysis patients was 65.69 ± 14 years. Among the patients, there were 27% and 31% of patients with mild cognitive impairment and suspected dementia, respectively. In the group of patients with suspected dementia, all cognitive functions had significantly lower values compared to these functions in incognitively unimpaired and mild cognitive impairment patients. The most impaired domain was verbal fluency, which reflects impairments in executive function. Depression and anxiety symptoms were observed in 28% and 22% of patients, respectively. Patients with anxiety symptoms had higher levels of endogenous creatinine, parathyroid hormone, and hemoglobin, as well as decreased creatinine clearance, being younger and less educated. No factors contributing to the occurrence of depressive symptoms were found. CONCLUSION: Cognitive dysfunction is a significant problem in hemodialysis patients. Our study showed that the prevalence of cognitive impairment and depression and anxiety symptoms in hemodialysis patients was high. The domain of executive functions was most affected. Furthermore, creatinine, parathyroid hormone, hemoglobin levels, creatinine clearance, and education affected the anxiety scale score.

Prevalence of Cognitive Impairment in Peritoneal Dialysis Patients and Associated Factors.

BACKGROUND: Cognitive impairment (CI) in patients with chronic kidney disease, including those treated with renal replacement therapy, is a growing problem worldwide. OBJECTIVES: The study aimed to assess the prevalence of CI and associated factors in patients undergoing peritoneal dialysis (PD). METHODS: In this cross-sectional study, 18 consecutive patients with PD therapy and 15 controls were evaluated for CI using the Addenbrooke's Cognitive Examination III (ACE III) test. RESULTS: The prevalence of CI was 33% in patients and 27% in the control group and was not statistically significant. A higher prevalence of CI was found in subjects aged ≥65 years old than in those <65 years old (p = 0.02), but only in the control group. The prevalence of CI in PD patients over and under 65 years of age did not differ statistically significantly (p = 0.12). Memory and verbal fluency were the most affected cognitive domain in PD patients with CI (p = 0.00, p = 0.04, respectively). There was a significant correlation between higher educated PD patients and the ACE III test results. The duration of dialysis did not affect the results of the cognitive screening test. CONCLUSIONS: CI is a growing problem in the course of chronic kidney disease and dialysis therapy. It seems that cognitive problems may occur in patients undergoing PD at a younger age than in the general population with particularly affected memory and verbal fluency. Higher educated patients score better on the cognitive screening test.

Nanostructural catalyst: metallophthalocyanine and carbon nano-onion with enhanced visible-light photocatalytic activity towards organic pollutants.

Metallophthalocyanine (MPc) and carbon nano-onion (CNO) derivatives were synthesized and characterized by using ultraviolet-visible spectroscopy, infrared and Raman spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy and X-ray powder diffraction. The unmodified CNOs and MPc-CNO derivatives were used as photocatalysts for rhodamine B (RhB) degradation under visible-light irradiation. The photocatalytic studies revealed that the MPc-CNO nanostructural materials simultaneously exhibited a high absorption capacity and an excellent visible-light-driven photocatalytic activity towards RhB. These nanostructures possess great potential for use as active photocatalysts for organic pollutant degradation.

Opening the internal structure for transport of ions: improvement of the structural and chemical properties of single-walled carbon nanohorns for supercapacitor electrodes.

We investigated the electrochemical performance of single-walled carbon nanohorns (SWCNHs) for use as supercapacitor electrodes. For the first time, we used acid-treatment for oxidation of SWCNHs and hole creation in their structure. A detailed study was performed on the correlation between the oxidation of SWCNHs via acid treatment and variable acid treatment times, the structural properties of the oxidized carbon nanostructures, and the specific capacitance of the SWCNH electrodes. We showed that simple functionalization of carbon nanostructures under controlled conditions leads to an almost 3-fold increase in their specific capacitance (from 65 to 180 F g-1 in 0.1 M H2SO4). This phenomenon indicates higher accessibility of the surface area of the electrodes by electrolyte ions as a result of gradual opening of the SWCNH internal channels.

Onion-Like Carbon Nanostructures: An Overview of Bio-Applications.

This article presents a brief review of the knowledge concerning onion-like carbons (OLCs). These nanostructures are some of the most fascinating carbon forms due to their unusual structure and physico-chemical properties. Generally, OLCs consist of a hollowspherical fullerene core surrounded by concentric graphitic layers with increasing diameter. Nevertheless, they can have different size, shape and type of core, which determine their physicochemical properties. In this article, we review the most important literature reports in this area and briefly describe these nanostructures, their physical and chemical properties and their potential uses with a focus on biomedicine.

Nanoforest: Polyaniline Nanotubes Modified with Carbon Nano-Onions as a Nanocomposite Material for Easy-to-Miniaturize High-Performance Solid-State Supercapacitors.

This article describes a facile low-cost synthesis of polyaniline nanotube (PANINT)⁻carbon nano-onion (CNO) composites for solid-state supercapacitors. Scanning electron microscopic (SEM) analyses indicate a uniform and ordered composition for the conducting polymer nanotubes immobilized on a thin gold film. The obtained nanocomposites exhibit a brush-like architecture with a specific capacitance of 946 F g-1 at a scan rate of 1 mV s-1. In addition, the nanocomposites offer high conductivity and a porous and well-developed surface area. The PANINT⁻CNO nanocomposites were tested as electrodes with high potential and long-term stability for use in easy-to-miniaturize high-performance supercapacitor devices.

Tight and uniform layer of covalently bound aminoethylophenyl groups perpendicular to gold surface for attachment of biomolecules.

Strongly adhered layers of the compound with the primary amino group directed toward the solution were obtained at the gold surface by chronoamperometric electroreduction of 4-aminoethylobenzenodiazonium salt (AEBD) in acetonitrile solution at appropriately selected potential. The used techniques (EQCM, AFM, EIS, PM, IRRAS) showed that the nature and thickness of formed aminoethylophenyl layer strongly depend on the potential applied to the electrode. Electroreduction of AEBD salt at a potential more negative than -0.6 V (vs Ag/AgCl) leads to about monolayer on the gold surface. Additionally, such a layer was very tight and uniform. The electrochemical measurements indicate that the efficient and precise attachment of biomolecules to the aminoethylophenyl layer is only possible when this layer is formed at appropriate potential. This was shown for ss- and dsDNA.