Alzheimer\'s disease (AD) is a severe progressive neurodegenerative condition associated with neuronal damage and reduced cognitive function that primarily affects the aged worldwide. While there is increasing evidence suggesting that mitochondrial dysfunction is one of the most significant factors contributing to AD, its accurate pathobiology remains unclear. Mitochondrial bioenergetics and homeostasis are impaired and defected during AD pathogenesis. However, the potential of mutations in nuclear or mitochondrial DNA encoding mitochondrial constituents to cause mitochondrial dysfunction has been considered since it is one of the intracellular processes commonly compromised in early AD stages. Additionally, electron transport chain dysfunction and mitochondrial pathological protein interactions are related to mitochondrial dysfunction in AD. Many mitochondrial parameters decline during aging, causing an imbalance in reactive oxygen species (ROS) production, leading to oxidative stress in age-related AD. Moreover, neuroinflammation is another potential causative factor in AD-associated mitochondrial dysfunction. While several treatments targeting mitochondrial dysfunction have undergone preclinical studies, few have been successful in clinical trials. Therefore, this review discusses the molecular mechanisms and different therapeutic approaches for correcting mitochondrial dysfunction in AD, which have the potential to advance the future development of novel drug-based AD interventions.

Parkinson\'s Disease (PD) is a prevalent neurodegenerative disorder characterized by motor and non-motor symptoms. Emerging evidence suggests that gut microbiota alterations, specifically involving short-chain fatty acids (SCFAs) like butyrate, may influence PD pathogenesis and symptomatology. This Systematic Review aims to synthesize current research on the role of butyrate in modulating motor symptoms and its neuroprotective effects in PD, providing insights into potential therapeutic approaches. A systematic literature search was conducted in April 2024 across databases, including ScienceDirect, Scopus, Wiley, and Web of Science, for studies published between 2000 and 2024. Keywords used were \"neuroprotective effects AND butyrate AND (Parkinson disease OR motor symptoms)\". Four authors independently screened titles, abstracts, and full texts, applying inclusion criteria focused on studies investigating butyrate regulation and PD motor symptoms. A total of 1377 articles were identified, with 40 selected for full-text review and 14 studies meeting the inclusion criteria. Data extraction was performed on the study population, PD models, methodology, intervention details, and outcomes. Quality assessment using the SYRCLE RoB tool highlighted variability in study quality, with some biases noted in allocation concealment and blinding. Findings indicate that butyrate regulation has a significant impact on improving motor symptoms and offers neuroprotective benefits in PD models. The therapeutic modulation of gut microbiota to enhance butyrate levels presents a promising strategy for PD symptom management.

Humoral immunity is a major waypoint towards chronic allograft dysfunction in lung transplantation (LT) recipients. Though allo-immunization and antibody-mediated rejection (AMR) are well-known entities, some diagnostic gaps need to be addressed. Morphological analysis could be enhanced by digital pathology and artificial intelligence-based companion tools. Graft transcriptomics can help to identify graft failure phenotypes or endotypes. Donor-derived cell free DNA is being evaluated for graft-loss risk stratification and tailored surveillance. Preventative therapies should be tailored according to risk. The donor pool can be enlarged for candidates with HLA sensitization, with strategies combining plasma exchange, intravenous immunoglobulin and immune cell depletion, or with emerging or innovative therapies such as imlifidase or immunoadsorption. In cases of insufficient pre-transplant desensitization, the effects of antibodies on the allograft can be prevented by targeting the complement cascade, although evidence for this strategy in LT is limited. In LT recipients with a humoral response, strategies are combined, including depletion of immune cells (plasmapheresis or immunoadsorption), inhibition of immune pathways, or modulation of the inflammatory cascade, which can be achieved with photopheresis. Altogether, these innovative techniques offer promising perspectives for LT recipients and shape the 21st century\'s armamentarium against AMR.

Gastrointestinal (GI) cancers represent a significant global health challenge, driving relentless efforts to identify innovative diagnostic and therapeutic approaches. Recent strides in microbiome research have unveiled a previously underestimated dimension of cancer progression that revolves around the intricate metabolic interplay between GI cancers and the host\'s gut microbiota. This review aims to provide a comprehensive overview of these emerging metabolic interactions and their potential to catalyze a paradigm shift in precision diagnosis and therapeutic breakthroughs in GI cancers. The article underscores the groundbreaking impact of microbiome research on oncology by delving into the symbiotic connection between host metabolism and the gut microbiota. It offers valuable insights into tailoring treatment strategies to individual patients, thus moving beyond the traditional one-size-fits-all approach. This review also sheds light on novel diagnostic methodologies that could transform the early detection of GI cancers, potentially leading to more favorable patient outcomes. In conclusion, exploring the metabolic interactions between host gut microbiota and GI cancers showcases a promising frontier in the ongoing battle against these formidable diseases. By comprehending and harnessing the microbiome\'s influence, the future of precision diagnosis and therapeutic innovation for GI cancers appears more optimistic, opening doors to tailored treatments and enhanced diagnostic precision.

Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. TP53 is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress. In AML, TP53 alterations occur in 5%-12% of de novo AML cases. These mutations form an important molecular subgroup, and patients with these mutations have the worst prognosis and shortest overall survival among patients with AML, even when treated with aggressive chemotherapy and allogeneic stem cell transplant. The frequency of TP53-mutations increases in relapsed and recurrent AML and is associated with chemoresistance. Progress in AML genetics and biology has brought the novel therapies, however, the clinical benefit of these agents for patients whose disease is driven by TP53 mutations remains largely unexplored. This review focuses on the molecular characteristics of TP53-mutated disease; the impact of TP53 on selected hallmarks of leukemia, particularly metabolic rewiring and immune evasion, the clinical importance of TP53 mutations; and the current progress in the development of preclinical and clinical therapeutic strategies to treat TP53-mutated disease.

Diabetic cardiomyopathy (DbCM) is a common complication in individuals with type 2 diabetes mellitus (T2DM), and its exact pathogenesis is still debated. It was hypothesized that chronic hyperglycemia and insulin resistance activate critical cellular pathways that are responsible for numerous functional and anatomical perturbations in the heart. Interstitial inflammation, oxidative stress, myocardial apoptosis, mitochondria dysfunction, defective cardiac metabolism, cardiac remodeling, hypertrophy and fibrosis with consequent impaired contractility are the most common mechanisms implicated. Epigenetic changes also have an emerging role in the regulation of these crucial pathways. The aim of this review was to highlight the increasing knowledge on the molecular mechanisms of DbCM and the new therapies targeting specific pathways.

This review explores the pivotal role of angiogenesis in breast cancer progression and treatment. It covers biomarkers, imaging techniques, therapeutic approaches, resistance mechanisms, and clinical implications. Key topics include Vascular Endothelial Growth Factors, angiopoietins, microRNA signatures, and circulating endothelial cells as biomarkers, along with Magnetic Resonance Imaging, Computed Tomography Angiography, Ultrasound, and Positron Emission Tomography for imaging. Therapeutic strategies targeting VEGF, tyrosine kinase inhibitors, and the intersection of angiogenesis with immunotherapy are discussed. Challenges such as resistance mechanisms and personalized medicine approaches are addressed. Clinical implications, prognostic value, and the future direction of angiogenesis-targeted therapies are highlighted. The article concludes with reflections on the transformative potential of understanding angiogenesis.

Traditional medication and alternative therapies have long been used to treat breast cancer. One of the main problems with current treatments is that there is an increase in drug resistance in the cancer cells owing to genetic differences such as mutational changes, epigenetic changes and miRNA (microRNA) alterations such as miR-1246, miR-298, miR-27b and miR-33a, along with epigenetic modifications, such as Histone3 acetylation and CCCTC-Binding Factor (CTCF) hypermethylation for drug resistance in breast cancer cell lines. Certain forms of conventional drug resistance have been linked to genetic changes in genes such as ABCB1, AKT, S100A8/A9, TAGLN2 and NPM. This review aims to explore the current approaches to counter breast cancer, the action mechanism, along with novel therapeutic methods endowing potential drug resistance. The investigation of novel therapeutic approaches sheds light on the phenomenon of drug resistance including genetic variations that impact distinct forms of oestrogen receptor (ER) cancer, genetic changes, epigenetics-reported resistance and their identification in patients. Long-term effective therapy for breast cancer includes selective oestrogen receptor modulators, selective oestrogen receptor degraders and genetic variations, such as mutations in nuclear genes, epigenetic modifications and miRNA alterations in target proteins. Novel research addressing combinational therapies including maytansine, photodynamic therapy, guajadiol, talazoparib, COX2 inhibitors and miRNA 1246 inhibitors have been developed to improve patient survival rates.

Spinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen-activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post-SCI. Modulating this pathway post-injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway\'s characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies.

The pervasive presence of Staphylococcus epidermidis and other coagulase-negative staphylococci on the skin and mucous membranes has long underpinned a casual disregard for the infection risk that these organisms pose to vulnerable patients in healthcare settings. Prior to the recognition of biofilm as an important virulence determinant in S. epidermidis, isolation of this microorganism in diagnostic specimens was often overlooked as clinically insignificant with potential delays in diagnosis and onset of appropriate treatment, contributing to the establishment of chronic infection and increased morbidity or mortality. While impressive progress has been made in our understanding of biofilm mechanisms in this important opportunistic pathogen, research into other virulence determinants has lagged S. aureus. In this review, the broader virulence potential of S. epidermidis including biofilm, toxins, proteases, immune evasion strategies and antibiotic resistance mechanisms is surveyed, together with current and future approaches for improved therapeutic interventions.