Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that endoplasmic reticulum (ER)-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including a total of 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the unfolded protein response (UPR)-associated genes (p-eIF2, BCL-2, PERK, ATF4, and BAX) were investigated using real-time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression levels of PERK, BCL-2, p-eIF2, ATF4, and BAX were found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056, and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that the targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Exploring the mRNA and Plasma Protein Levels of BDNF, NT4, SIRT1, HSP27, and HSP70 in Multiple Sclerosis Patients and Healthy Controls.

Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease affecting the central nervous system. It is a major cause of non-traumatic neurological disability among young adults in North America and Europe. This study focuses on neuroprotective genes (BDNF, NT4/5, SIRT1, HSP70, and HSP27). Gene expression and protein levels of these markers were compared between MS patients and healthy controls. Blood samples were collected from 42 patients with multiple sclerosis (MS) and 48 control subjects without MS. Quantitative real-time PCR was performed to measure the expression of specific genes. The samples were analyzed in duplicate, and the abundance of mRNA was quantified using the 2-ΔCt method. ELISA assay was used to measure the concentration of specific proteins in the plasma samples. The results show that a 3.5-fold decrease in the gene expression of BDNF corresponds to a 1.5-fold downregulation in the associated plasma protein concentration (p < 0.001). Similar trends were observed with NT-4 (five-fold decrease, slight elevation in protein), SIRT1 (two-fold decrease, two-fold protein decrease), HSP70 (four-fold increase, nearly two-fold protein increase), and HSP27 (four-fold increase, two-fold protein increase) (p < 0.001). This study reveals strong correlations between gene expression and protein concentration in MS patients, emphasizing the relevance of these neuroprotective markers in the disease.

Recent Developments in the Detection of Organic Contaminants Using Molecularly Imprinted Polymers Combined with Various Analytical Techniques.

Molecularly imprinted polymers (MIPs) encompass a diverse array of polymeric matrices that exhibit the unique capacity to selectively identify a designated template molecule through specific chemical moieties. Thanks to their pivotal attributes, including exceptional selectivity, extended shelf stability, and other distinct characteristics, this class of compounds has garnered interest in the development of highly responsive sensor systems. As a result, the incorporation of MIPs in crafting distinctive sensors and analytical procedures tailored for specific analytes across various domains has increasingly become a common practice within contemporary analytical chemistry. Furthermore, the range of polymers amenable to MIP formulation significantly influences the potential utilization of both conventional and innovative analytical methodologies. This versatility expands the array of possibilities in which MIP-based sensing can be employed in recognition systems. The following review summarizes the notable progress achieved within the preceding seven-year period in employing MIP-based sensing techniques for analyte determination.

Association between the Cytosine Hydroxymethylation and the Expression of microRNA in Multiple Sclerosis in Polish Population.

Multiple sclerosis is a chronic demyelinating disorder with an unclear etiology. A key role is thought to be played by Th17 cells and microRNAs associated with Th17, such as miR-155, miR-326 and miR-223. The present study compared the methylation and hydroxymethylation levels of CpG sites within promoters of these microRNA between MS patients and controls using PBMCs and analyzed their relationship with microRNA expression. Significant intergroup differences were found between the levels of 5-hmC within the CpG-1 miR-155 promoter and CpG within the miR-326 promoter; in addition, miR-155-5p and miR-223-3p expression was elevated in MS patients. Correlation analysis showed a positive relationship between the level of 5-hmC of CpG-2 in the miR-223 promoter and miR-223-3p level. As it is possible to pharmacologically modulate the level of epigenetic modifications, our findings cast light on the etiology of MS and support the development of more effective therapies.

Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, although the aetiology of ADHD is not yet understood. One proposed theory for developing ADHD is N-methyl-D-aspartate receptors (NMDARs) dysfunction. NMDARs are involved in regulating synaptic plasticity and memory function in the brain. Abnormal expression or polymorphism of some genes associated with ADHD results in NMDAR dysfunction. Correspondingly, NMDAR malfunction in animal models results in ADHD-like symptoms, such as impulsivity and hyperactivity. Currently, there are no drugs for ADHD that specifically target NMDARs. However, NMDAR-stabilizing drugs have shown promise in improving ADHD symptoms with fewer side effects than the currently most widely used psychostimulant in ADHD treatment, methylphenidate. In this review, we outline the molecular and genetic basis of NMDAR malfunction and how it affects the course of ADHD. We also present new therapeutic options related to treating ADHD by targeting NMDAR.

Explosives removal and quantification using porous adsorbents based on poly(2-oxazoline)s with various degree of functionalization.

Polymeric porous adsorbents are reported for removal of explosives, namely picric acid, 1,3,5-trinitro-1,3,5-triazinane (RDX), and pentaerythritol tetranitrate (PETN) and their subsequent quantification using direct analysis with ambient plasma mass spectrometry. The adsorbents are obtained by functionalization of short-chain poly(2-oxazoline)s with methyl ester side chains using 4-(aminomethyl)pyridine with a degree of functionalization equal to 0, 5, 10, and 20%. The subsequent step consist of cross-linking using a high internal phase emulsion procedure by further side-chain amidation with diethylenetriamine as crosslinker. Picric acid, RDX, and PETN were chosen as the model compounds as they belong to three different groups of explosives, in particular nitroaromatics, nitroamines, and nitrate esters, respectively. The adsorption isotherms, kinetics, as well as the influence of pH and temperature on the adsorption process was investigated. The porous adsorbents showed the highest maximum adsorption capacity towards picric acid, reaching 334 mg g-1, while PETN (80 mg g-1) and RDX (17.4 mg g-1) were less efficiently adsorbed. Subsequent quantification of the adsorbed explosives is performed by a specially designed ambient mass spectrometry setup equipped with a thermal heater. The obtained limits of detection were found to be 20-times improved compared to direct analysis of analyte solutions. The effectiveness of the proposed analytical setup is confirmed by successful quantification of the explosives in river water samples. The research clearly shows that functional porous adsorbents coupled directly with ambient mass spectrometry can be used for rapid quantification of explosives, which can be, e.g., used for tracking illegal manufacturing sites of these compounds.

RNA-Based Liquid Biopsy in Head and Neck Cancer.

Head and neck cancer (HNC) is a prevalent and diverse group of malignancies with substantial morbidity and mortality rates. Early detection and monitoring of HNC are crucial for improving patient outcomes. Liquid biopsy, a non-invasive diagnostic approach, has emerged as a promising tool for cancer detection and monitoring. In this article, we review the application of RNA-based liquid biopsy in HNC. Various types of RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), circular RNA (circRNA) and PIWI-interacting RNA (piRNA), are explored as potential biomarkers in HNC liquid-based diagnostics. The roles of RNAs in HNC diagnosis, metastasis, tumor resistance to radio and chemotherapy, and overall prognosis are discussed. RNA-based liquid biopsy holds great promise for the early detection, prognosis, and personalized treatment of HNC. Further research and validation are necessary to translate these findings into clinical practice and improve patient outcomes.

Rapid quantification of 2,4-dichlorophenol in river water samples using molecularly imprinted polymers coupled to ambient plasma mass spectrometry.

Rapid quantification of environmental pollutants is important for water quality control and environmental monitoring. In this work, we report the development of molecularly imprinted polymers (MIPs) obtained from poly(methyl vinyl ether-alt-maleic acid) polymer. The synthesized materials were used for selective preconcentration of 2,4-dichlorophenol, a priority pollutant which creates a threat to public health. The structure of poly(methyl vinyl ether-alt-maleic acid) was functionalized with 4-aminomethylpyridine (4-AMP) to incorporate pyridine groups presumably responsible for increased affinity towards 2,4-dichlorophenol. The synthesis was performed with different degree (10%, 20% and 30%) of 4-AMP functionalization to investigate the influence of pyridine group content on the final MIPs properties. The molecular imprinting process was conducted by amidation of polymers' anhydride groups with diethylenetriamine. Moreover, the experimental data indicated that maximum adsorption capacity was observed for the highest 4-AMP functionalization degree. Similarly, MIPs with the highest 4-AMP content proved to possess the highest selectivity towards the analyte. Finally, the functionalized MIPs were used to quantify 2,4-dichlorophenol by their direct introduction into a specially designed ambient mass spectrometry setup. The detection limits were improved significantly over the ones measured for pure analyte solution. The proposed analytical technique was used to quantify 2,4-dichlorophenol in river water and wastewater samples. Good recovery results were obtained, which proves that the method can be used for analysis of complex real-life samples.

Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the widespread accumulation of alpha-synuclein (αSyn) protein aggregates. αSyn aggregation disrupts critical cellular processes, including synaptic function, mitochondrial integrity, and proteostasis, which culminate in neuronal cell death. Importantly, αSyn pathology extends beyond neurons-it also encompasses spreading throughout the neuronal environment and internalization by microglia and astrocytes. Once internalized, glia can act as neuroprotective scavengers, which limit the spread of αSyn. However, they can also become reactive, thereby contributing to neuroinflammation and the progression of PD. Recent advances in αSyn research have enabled the molecular diagnosis of PD and accelerated the development of targeted therapies. Nevertheless, despite more than two decades of research, the cellular function, aggregation mechanisms, and induction of cellular damage by αSyn remain incompletely understood. Unraveling the interplay between αSyn, neurons, and glia may provide insights into disease initiation and progression, which may bring us closer to exploring new effective therapeutic strategies. Herein, we provide an overview of recent studies emphasizing the multifaceted nature of αSyn and its impact on both neuron and glial cell damage.

Poly(2-oxazoline)s as Stimuli-Responsive Materials for Biomedical Applications: Recent Developments of Polish Scientists.

Poly(2-oxazoline)s are the synthetic polymers that are the products of the cationic ring-opening polymerization (CROP) of 2-oxazoline monomers. Due to their beneficial properties, from which biocompatibility, stealth behavior, high functionalization possibilities, low dispersity, stability, nonionic character, and solubility in water and organic solvents should be noted, they have found many applications and gained enormous interest from scientists. Additionally, with high versatility attainable through copolymerization or through post-polymerization modifications, this class of polymeric systems has been widely used as a polymeric platform for novel biomedical applications. The chemistry of polymers significant expanded into biomedical applications, in which polymeric networks can be successfully used in pharmaceutical development for tissue engineering, gene therapies, and also drug delivery systems. On the other hand, there is also a need to create 'smart' polymer biomaterials, responsive to the specified factor, that will be sensitive to various environmental stimuli. The commonly used stimuli-responsive biomedical materials are based mostly on temperature-, light-, magnetic-, electric-, and pH-responsive systems. Thus, creating selective and responsive materials that allow personalized treatment is in the interest of the scientific world. This review article focuses on recent discoveries by Polish scientists working in the field of stimuli-responsive poly(2-oxazoline)s, and their work is compared and contrasted with results reported by other world-renowned specialists.

EGDMA- and TRIM-Based Microparticles Imprinted with 5-Fluorouracil for Prolonged Drug Delivery.

Imprinted materials possess designed cavities capable of forming selective interactions with molecules used in the imprinting process. In this work, we report the synthesis of 5-fluorouracil (5-FU)-imprinted microparticles and their application in prolonged drug delivery. The materials were synthesized using either ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) cross-linkers. For both types of polymers, methacrylic acid was used as a functional monomer, whereas 2-hydroxyethyl methacrylate was applied to increase the final materials' hydrophilicity. Adsorption isotherms and adsorption kinetics were investigated to characterize the interactions that occur between the materials and 5-FU. The microparticles synthesized using the TRIM cross-linker showed higher adsorption properties towards 5-FU than those with EGDMA. The release kinetics was highly dependent upon the cross-linker and pH of the release medium. The highest cumulative release was obtained for TRIM-based microparticles at pH 7.4. The IC50 values proved that 5-FU-loaded TRIM-based microparticles possess cytotoxic activity against HeLa cell lines similar to pure 5-FU, whereas their toxicity towards normal HDF cell lines was ca. three times lower than for 5-FU.

Molecularly Imprinted Polymers as State-of-the-Art Drug Carriers in Hydrogel Transdermal Drug Delivery Applications.

Molecularly Imprinted Polymers (MIPs) are polymeric networks capable of recognizing determined analytes. Among other methods, non-covalent imprinting has become the most popular synthesis strategy for Molecular Imprinting Technology (MIT). While MIPs are widely used in various scientific fields, one of their most challenging applications lies within pharmaceutical chemistry, namely in therapeutics or various medical therapies. Many studies focus on using hydrogel MIPs in transdermal drug delivery, as the most valuable feature of hydrogels in their application in drug delivery systems that allow controlled diffusion and amplification of the microscopic events. Hydrogels have many advantages over other imprinting materials, such as milder synthesis conditions at lower temperatures or the increase in the availability of biological templates like DNA, protein, and nucleic acid. Moreover, one of the most desirable controlled drug delivery applications is the development of stimuli-responsive hydrogels that can modulate the release in response to changes in pH, temperature, ionic strength, or others. The most important feature of these systems is that they can be designed to operate within a particular human body area due to the possibility of adapting to well-known environmental conditions. Therefore, molecularly imprinted hydrogels play an important role in the development of modern drug delivery systems.