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Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the accumulation of α-Synuclein aggregates and the degeneration of dopaminergic neurons in substantia nigra in the midbrain. Although the exact mechanisms of neuronal degeneration in PD remain largely elusive, various pathogenic factors, such as α-Synuclein cytotoxicity, mitochondrial dysfunction, oxidative stress, and pro-inflammatory factors, may significantly impair normal neuronal function and promote apoptosis. In this context, neuroinflammation and autophagy have emerged as crucial processes in PD that contribute to neuronal loss and disease development. They are regulated in a complex interconnected manner involving most of the known PD-associated genes. This review summarizes evidence of the implication of neuroinflammation and autophagy in PD and delineates the role of inflammatory factors and autophagy-related proteins in this complex condition. It also illustrates the particular significance of plasma and serum immune markers in PD and their potential to provide a personalized approach to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is a disturbance of neurodevelopment with a complicated pathogenesis and unidentified etiology. Many children with ASD have a history of "allergic symptoms", often in the absence of mast cell (MC)-positive tests. Activation of MCs by various stimuli may release molecules related to inflammation and neurotoxicity, contributing to the development of ASD. The aim of the present paper is to enrich the current knowledge on the relationship between MCs and ASD by discussing key molecules and immune pathways associated with MCs in the pathogenesis of autism. Cytokines, essential marker molecules for MC degranulation and therapeutic targets, are also highlighted. Understanding the relationship between ASD and the activation of MCs, as well as the involved molecules and interactions, are the main points contributing to solving the enigma. Key molecules, associated with MCs, may provide new insights to the discovery of drug targets for modeling inflammation in ASD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation play a crucial role as a pathogenetic mechanism in PD. The glycoprotein YKL-40 (CHI3L1) is a potential biomarker involved in inflammation and tumor processes. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship between cellular bioenergetics and YKL-40. The study included 18 naïve PD patients and an age-matched control group (HC, n = 7). Patients were diagnosed according to the MDS-PD, the UPDRS, and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. New data are reported revealing changes in the mitochondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in PD compared to HC. The protein levels of YKL-40 were threefold higher in PD. We found a correlation between the YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that the YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD. [ABSTRACT FROM AUTHOR]

At present it is well-defined that autophagy is a fundamental process essential for cell life but its pro-viral and anti-viral role has been stated out with the COVID pandemic. However, viruses in turn have evolved diverse adaptive strategies to cope with autophagy driven host defense, either by blocking or hijacking the autophagy machinery for their own benefit. The mechanisms underlying autophagy modulation are presented in the current review which summarizes the accumulated knowledge on the crosstalk between autophagy and viral infections, with a particular emphasizes on SARS-CoV-2. The different types of autophagy related to infections and their molecular mechanisms are focused in the context of inflammation. In particular, SARS-CoV-2 entry, replication and disease pathogenesis are discussed. Models to study autophagy and to formulate novel treatment approaches and pharmacological modulation to fight COVID-19 are debated. The SARS-CoV-2—autophagy interplay is presented, revealing the complex dynamics and the molecular machinery of autophagy. The new molecular targets and strategies to treat COVID-19 effectively are envisaged. In conclusion, our finding underline the importance of development new treatment strategies and pharmacological modulation of autophagy to fight COVID-19. [ABSTRACT FROM AUTHOR]

The prognosis for patients with relapsed childhood acute lymphoblastic leukaemia (cALL) remains poor. The main reason for treatment failure is drug resistance, most commonly to glucocorticoids (GCs). The molecular differences between prednisolone-sensitive and -resistant lymphoblasts are not well-studied, thereby precluding the development of novel and targeted therapies. Therefore, the aim of this work was to elucidate at least some aspects of the molecular differences between matched pairs of GC-sensitive and -resistant cell lines. To address this, we carried out an integrated transcriptomic and metabolomic analysis, which revealed that lack of response to prednisolone may be underpinned by alterations in oxidative phosphorylation, glycolysis, amino acid, pyruvate and nucleotide biosynthesis, as well as activation of mTORC1 and MYC signalling, which are also known to control cell metabolism. In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-α-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs. Among other druggable targets that were identified in this study, inhibition of glutamine metabolism presents a potential therapeutic approach in GC-sensitive, but more importantly, in GC-resistant cALL cells. Lastly, these findings may be clinically relevant in the context of relapse—in publicly available datasets, we found gene expression patterns suggesting that in vivo drug resistance is characterised by similar metabolic dysregulation to what we found in our in vitro model. [ABSTRACT FROM AUTHOR]

Background: NGF is a molecule with a pleiotropic role, affecting neuro-immune functions, energy homeostasis, and synaptic plasticity. The mechanisms of NGF-induced neuronal differentiation are well established, but its effect on mitochondria in autism spectrum disorder (ASD) is still unclear. We hypothesize that NGF-induced neuronal development requires large amounts of energy, and mitochondria in ASD are overloaded to meet the new functional requirements. Method: The study includes primary diagnosed ASD children. Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from both patients and typically developing children (TDC). PBMCs were analyzed with Seahorse XFp, and plasma NGF protein levels were measured. Results: We detected nearly 50% higher NGF levels and approximately 40% elevation in spare respiratory capacity in ASD compared to TDC. These findings are consistent with the observed difference in maximal respiration, which was also significantly higher in the patient group. Both mitochondrial respiration and NGF plasma levels exhibit a strong potential to discriminate children with ASD from TDC. Conclusions: This study is the first to link elevated NGF with mitochondrial respiration and altered energy homeostasis in ASD. High NGF correlates with basic bioenergetic signatures that may be used as a screening tool to improve early diagnosis and clinical follow-up in ASD. [ABSTRACT FROM AUTHOR]

Refractory disease and relapse remain the main causes of cancer therapy failure. Refined risk stratification, treatment regimens and improved early diagnosis and detection of minimal residual disease have increased cure rates in malignancies like childhood acute lymphoblastic leukaemia (ALL) to 90%. Nevertheless, overall survival in the context of drug resistance remains poor. The regulatory role of micro RNAs (miRNAs) in cell differentiation, homeostasis and tumorigenesis has been under extensive investigation in different cancers. There is accumulating data demonstrating the significance of miRNAs for therapy outcomes in lymphoid malignancies and some direct demonstrations of the interplay between these small molecules and drug response. Here, we summarise miRNAs' impact on chemotherapy resistance in adult and paediatric ALL and chronic lymphocytic leukaemia (CLL). The main focus of this review is on the modulation of particular signaling pathways like PI3K-AKT, transcription factors such as NF-κB, and apoptotic mediators, all of which are bona fide and pivotal elements orchestrating the survival of malignant lymphocytic cells. Finally, we discuss the attractive strategy of using mimics, antimiRs and other molecular approaches pointing at miRNAs as promising therapeutic targets. Such novel strategies to circumvent ALL and CLL resistance networks may potentially improve patients' responses and survival rates. [ABSTRACT FROM AUTHOR]

Clinically, there is an urgent need to identify new therapeutic strategies for selectively treating cancer cells. One of the directions in this research is the development of biocompatible therapeutics that selectively target cancer cells. Here, we show that novel aminated graphene oxide (haGO-NH2) nanoparticles demonstrate increased toxicity towards human hepatocellular cancer cells compared to pristine graphene oxide(GO). The applied novel strategy for amination leads to a decrease in the size of haGO-NH2 and their zeta potential, thus, assuring easier penetration through the cell membrane. After characterization of the biological activities of pristine and aminated GO, we have demonstrated strong cytotoxicity of haGO-NH2 toward hepatic cancer cells—HepG2 cell line, in a dose-dependent manner. We have presented evidence that the cytotoxic effects of haGO-NH2 on hepatic cancer cells were due to cell membrane damage, mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Intrinsically, our current study provides new rationale for exploiting aminated graphene oxide as an anticancer therapeutic. [ABSTRACT FROM AUTHOR]