Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, fibrosis, and dysregulation of the immune system. The therapeutic options available for SSc have limited efficacy, and there is a clear need for new pharmacological alternatives. Thiazolidinediones (TZD) are molecules that have therapeutic potential for SSc due to their pharmacological properties. In this study, we aimed to evaluate the immunomodulatory activity of a new TZD analogue (LPSF/CR-35) in peripheral blood mononuclear cells (PBMC) from SSc patients.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular antioxidant response, playing an important role in protecting neurons from ischemic injury. The hippocampus exhibits region-specific vulnerability to ischemia, with CA1 neurons being highly susceptible, while CA2-3 and dentate gyrus (DG) neurons demonstrate greater resistance. Our previous work revealed higher basal and post-ischemia/reperfusion (I/R) Nrf2 activity in the resistant CA2-3,DG region compared to CA1. This study aimed to identify potential Nrf2-regulated genes that contribute to this regional neuroprotection in a gerbil model of global cerebral ischemia.

Premenstrual disorders (PMD) are a prevalent health issue and often co-occur with mood disorders. The pathophysiology of PMD has not yet been thoroughly described. Two mechanisms appear to be crucial in PMD: (1) lower estrogen levels during the luteal phase, leading to a subsequent decrease in serotonin (5-HT) transmission, and (2) reduced sensitivity to allopregnanolone, resulting in an imbalance in γ-aminobutyric acid (GABA)/glutamate signaling and an increase in hypothalamic-pituitary-adrenal (HPA) activation. The roles of zinc (Zn), copper (Cu), and magnesium (Mg) in mood disorders are well-established, and they appear to be associated with PMD through similar pathways. Therefore, this narrative review provides background information on the roles of Zn, Cu, and Mg in mood regulation and discusses the impact of these trace elements on this process. The results presented, summarizing data from studies: (1) exploring the associations between Zn, Cu, and Mg levels and PMD, and (2) verifying the effects of Zn, Cu, and Mg supplementation on PMD symptoms. Finally, the caveats of current PMD research and the implications of the available data for everyday clinical practice are discussed. : Not applicable.

The gut microbiome has been increasingly recognized for its potential role in schizophrenia through gut-brain interactions involving immune, neural, and metabolic pathways. This pilot study evaluated the impact of fecal microbiota transplantation (FMT) on the abundance and variability of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.

Taxol (Tx) is widely used in cancer therapy due to its ability to disrupt microtubule dynamics, inhibiting cell division and tumor proliferation. However, multidrug resistance (MDR) mechanisms, including enhanced drug efflux, altered metabolism, mutations in tubulin, and inhibition of apoptosis, challenge its efficacy. Peptide-based therapies have emerged as promising and significant solutions to overcome Tx resistance. These peptides offer high specificity, lower toxicity, and acceptable cell membrane penetration, enhancing precision medicine capabilities. Recent advancements focus on peptides that modulate drug efflux, stabilize microtubules, and promote apoptosis in cancer cells. The ATP synthase (ATP)-binding cassette transporters (ABC) transporter ABCB1, tubulin subunits, and anti-apoptotic proteins such as Bcl-2 show potential in restoring Tx effectiveness against MDR. Combining peptides with nanoparticle delivery systems improves tumor penetration and reduces side effects. Despite challenges like protease degradation and immunogenicity, peptide treatment addresses limitations. Peptide cancer therapies could revolutionize anticancer treatment by providing targeted, less toxic alternatives, especially for MDR. phenotype.

Alzheimer’s disease (AD) is the most common form of dementia, and its incidence is projected to triple worldwide over the next 25 years. The most prevalent form, late-onset Alzheimer’s disease (LOAD), develops in genetically predisposed individuals exposed to environmental risk factors. Hallmarks of AD include accumulation of amyloid-β (Aβ), neurofibrillary tangles (NFTs), neuroinflammation, and mitochondrial dysfunction, resulting in oxidative stress, impaired glucose metabolism, and cognitive decline. Such metabolic disruptions result in early cerebral glucose hypometabolism and other metabolic disruptions, including altered lipid and branched-chain amino acid profiles. Recent evidence suggests that gut microbiota alterations, although individually variable, are a consistent and influential factor in AD progression inflammatory and metabolic pathways. This narrative review explores therapeutic interventions targeting the gut-brain axis, including fecal microbiota transplantation (FMT), probiotic and antibiotic treatments, and dietary strategies such as the ketogenic and Mediterranean diets, as well as nutritional compounds such as omega-3 fatty acids. The aim is to evaluate the latest findings in both preclinical and clinical studies to identify multi-targeted, microbiota-based approaches for the prevention and management of AD.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.

The intricate interplay between the brain and gut, often referred to as the gut-brain axis, has emerged as a cornerstone of health and disease. This bidirectional communication network, mediated by neural, hormonal, immune, and microbial signals, plays a pivotal role in maintaining homeostasis and influencing both neurological and gastrointestinal functions. Dysregulation of the gut-brain axis is implicated in various neurological and gastrointestinal disorders, highlighting the need to explore novel therapeutic strategies targeting this axis. Uridine, an endogenous pyrimidine nucleoside that is also obtained through dietary sources, has recently gained increasing attention for its neuroprotective and gut-modulating properties. Known for its critical role in RNA synthesis, membrane phospholipid production, and neurotransmitter regulation, uridine has demonstrated potential in enhancing synaptic plasticity, reducing inflammation, and supporting neuronal survival. Emerging evidence also suggests that uridine may influence gut health by promoting epithelial integrity, modulating the gut microbiota, and reducing intestinal inflammation. Given the interconnected nature of the gut and brain, uridine's dual actions present a compelling opportunity to explore its role in modulating the gut-brain axis as a means of achieving neuroprotection. This review aims to provide a comprehensive overview of the effect of uridine on brain and gut health, with a particular focus on its potential to influence the gut-brain axis.

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, characterized by debilitating motor and non-motor symptoms. Its complex pathogenesis involves dopaminergic neuron degeneration, α-synuclein aggregation, neuroinflammation, oxidative stress, and mitochondrial dysfunction. Current symptomatic treatments offer limited symptom improvement, highlighting the urgent need for new strategies, including lifestyle modifications. The ketogenic diet (KD), a dietary approach that shifts the body's primary energy source from glucose to ketone bodies (KBs) like β-hydroxybutyrate (β-HB), has demonstrated significant therapeutic potential. This review explores KD as a promising, multifaceted intervention for PD. The potential beneficial impact of KD on PD stems from several key mechanisms. β-HB exhibits potent anti-inflammatory properties, reducing pro-inflammatory cytokines and microglial activation by inhibiting pathways such as NF-κB and NLRP3 inflammasome. The diet also improves mitochondrial function by enhancing electron transport chain activity and increasing ATP synthesis, which is crucial given the mitochondrial deficits observed in PD. Furthermore, KBs directly alleviate oxidative stress through enhanced antioxidant defenses. KD offers neuroprotection for dopaminergic neurons, provides an alternative fuel source to the brain, and optimizes cerebral glucose metabolism. It also boosts levels of essential neurotrophic factors, including brain-derived neurotrophic factor (BDNF). Beyond direct neurological effects, KD may enhance levodopa efficacy by improving its bioavailability and appears to play a crucial role in modulating gut microbiota dysbiosis, a frequently observed and potentially contributing factor in PD. While further research is essential, the comprehensive effects of KD on PD-related pathophysiology position it as a promising non-pharmacological strategy.

Colorectal cancer (CRC) remains a major global health challenge, with increasing incidence, particularly among individuals under 50 years of age. Cathelicidin LL-37, a multifunctional antimicrobial peptide, has shown promise in cancer treatment, particularly for its anti-inflammatory effects.

Separation and encapsulation provide a practical and effective strategy for the targeted delivery of bioactive components in formulation technologies. This study aimed to develop an inorganic Pickering-mediated formulation, Solcumin™, for food-derived tetrahydrocurcumin (THC), and to evaluate its long-term storage stability and in vitro bioactivity.

Heart regeneration, or the replacement or restoration of damaged myocardium, remains one of the most challenging areas in regenerative medicine, primarily due to the limited regenerative capacity of the adult human heart. Unlike the embryonic heart, which exhibits robust cardiomyocyte proliferation, postnatal cardiac muscle cells permanently exit the cell cycle, resulting in minimal regenerative potential following injury such as myocardial infarction. This limitation contributes significantly to the progression of heart failure, a leading cause of morbidity and mortality worldwide. Recent breakthroughs in understanding the molecular and cellular mechanisms that govern cardiomyocyte proliferation have revealed that targeting signaling pathways (e.g., Hippo-YAP), cell cycle regulators, epigenetic modulators, and extracellular components may be a promising strategy for stimulating heart repair. Despite these advances, cardiac regeneration still faces significant obstacles in replacing damaged tissue and ensuring the regenerated muscle functions effectively within the complex heart system. This review aims to provide a comprehensive analysis of emerging regulatory mechanisms involved in cardiomyocyte proliferation and myocardial regeneration. It critically evaluates current strategies for promoting heart regeneration, with particular emphasis on the most promising molecular pathways and therapeutic approaches with translational potential. Ongoing research, as summarized in this review, continues to expand the potential of regenerative medicine to repair heart damage, offering hope for more effective treatments for heart disease.

Urinary tract infection (UTI) is a serious problem in the healthcare system. It is caused by bacteria from the gastrointestinal tract. The risk factors that impact the UTI incidence include administration of certain drugs (flozins), sex, use of urinary catheter, and diabetes. This is a retrospective study of the records of 76 patients from a Nursing and Treatment Facility at County Hospital in Drezdenko (Poland) aimed to assess the factors that may have an impact on the incidence of UTI.

Schizophrenia and related psychotic disorders represent a major cause of global disability, while patients show wide variability in their response to antipsychotic therapy. Genetic variants in one-carbon metabolism (folate and vitamin B12-dependent), catecholamine degradation, and methylation pathways may influence symptom severity and treatment outcomes. This study aimed to assess whether polymorphisms in these pathways are associated with baseline symptomatology and treatment response in a naturalistic setting.

Treatment-resistant depression (TRD) continues to pose a major challenge in clinical practice, as a large proportion of patients fail to achieve remission despite multiple antidepressant drugs. Growing evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, together with epigenetic alterations, neuroinflammation, and kynurenine pathway metabolism, plays a central role in the pathophysiology of TRD. Particularly, prolonged stress-induced glucocorticoid receptor (GR) resistance, persistent hypercortisolaemia, and elevated pro-inflammatory cytokines contribute to neurotoxicity, hippocampal atrophy, and impaired neuroplasticity, aggravating depressive symptoms and reducing treatment response. Additionally, dysregulated tryptophan metabolism and the shift towards neurotoxic kynurenine metabolites further impair neuronal function and resulting in TRD. This review integrates recent findings on the complex interplay between HPA axis dysfunction, neuroimmune responses, and metabolic disturbances in TRD while highlighting novel therapeutic avenues such as ketamine, GR modulators, and anti-inflammatory agents. Further, disruption in the blood-brain barrier as one of the mechanisms of TRD was also reviewed. A deeper understanding of these mechanisms will enable the development of personalized treatment strategies to enhance clinical outcomes for TRD patients.

Methotrexate (MTX) is a widely used chemotherapeutic agent in pediatric oncology, where high-dose protocols (HDMTX; ≥500 mg/m) are standard for treating hematological and central nervous system malignancies. Due to its narrow therapeutic index and potential for severe toxicity, therapeutic drug monitoring (TDM) of plasma MTX concentrations is essential to guide leucovorin rescue therapy and prevent adverse effects.

Acute severe ulcerative colitis (ASUC) and acute severe Crohn's disease (CD) flare are potentially life-threatening conditions, for which treatment remains a clinical challenge. Currently available therapeutic options present limited efficacy, with a high rate of colectomy as the final-line treatment method. Therefore, new alternatives of rescue therapy in inflammatory bowel diseases (IBD) are constantly sought. Upadacitinib (UPA), a selective Janus kinase-1 (JAK1) inhibitor, has been approved for the treatment of moderate-to-severe ulcerative colitis (UC) and CD. Interestingly, the most recent data show an increasing off-label use of this medication in the management of acute severe colitis. We present a comprehensive review focusing on rescue therapy with UPA in IBD, both UC and CD. The article examines the outcomes of recent studies evaluating the effectiveness, safety, and tolerability of UPA treatment in adult patients with ASUC and severe CD flare, a new treatment strategy.

Renal inflammation, oxidative stress, and fibrosis are hallmarks of kidney diseases, including diabetic nephropathy, acute kidney injury (AKI), and chronic kidney disease (CKD). The global prevalence of kidney diseases is increasing, posing a substantial public health challenge. The pathophysiology of kidney diseases is complex and multifactorial, involving a dynamic interplay of oxidative stress, inflammation, and fibrosis. Persistent inflammation in CKD is driven by elevated levels of proinflammatory mediators such as interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). Elevated C-reactive protein (CRP) levels are commonly associated with AKI and CKD. Moreover, oxidative stress, due to increased reactive oxygen species (ROS) and diminished antioxidant defenses, further damages renal tissues. Additionally, renal fibrosis mediated by transforming growth factor beta (TGF-β) signaling contributes to progressive structural deterioration, ultimately leading to end-stage kidney disease. Given the multifactorial nature of kidney disease, driven by the complex interplay of various mediators, there is a need for compounds with multitargeting potential. Formononetin (7-hydroxy-4'-methoxyisoflavone) is a naturally occurring isoflavone known for its broad pharmacological profile, including anti-inflammatory, antioxidant, renoprotective, cardioprotective, and antidiabetic activity. Various studies have demonstrated the significant potential of formononetin in mitigating kidney diseases through the modulation of multiple molecular mediators, including p38-mitogen-activated protein kinase (p38-MAPK), janus kinase (JNK), TGF-β, nuclear factor kappa B (NF-κB), CRP, sirtuin 1 (SIRT1), proinflammatory cytokines, nuclear factor erythroid 2-related factor 2 (Nrf-2), kelch-like ECH-associated protein 1 (Keap1), antioxidants, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). Given formononetin's ability to modulate key molecular mediators involved in kidney disease, this review aims to explore the underlying mechanisms driving its renoprotective effects. By examining these complex and interconnected pathways, the review seeks to provide essential insights that will guide future research and help bridge existing knowledge gaps regarding formononetin's potential in renal disorders.