The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

Depression and obesity are amongst the most serious global health challenges. Each of them is associated with high morbidity, chronicity, and socioeconomic burden. Increasing evidence suggests that these conditions are not merely comorbid but share convergent biological pathways (e.g., hypothalamic–pituitary–adrenal axis dysregulation, chronic inflammation, gut dysbiosis, and mitochondrial dysfunction). All these components contribute together to the development and persistence of depressive symptoms as well as to an increase in adiposity. Within this framework, adipose tissue has emerged as an essential endocrine organ that has a deep impact on neuroimmune signalling and mood regulation through its secreted molecules, such as leptin, adiponectin, resistin, omentin, apelin, chemerin, and visfatin. The current management of depression involves a comprehensive, multidisciplinary approach that includes pharmacological treatment and psychotherapeutic support, alongside lifestyle changes. Here we highlight the molecular crosstalk between adipose tissue and the brain, summarising the evidence of adipokines’ dysregulation role in connecting metabolic dysfunction to depressive neurobiology. By integrating metabolic, immunological, and neuroendocrine perspectives, this narrative review underscores the need to reconceptualise depression as an immunometabolic disorder. Understanding adipokine-mediated pathways may reveal new biomarkers and therapeutic targets, fostering interdisciplinary approaches. This would allow for the development of new treatment strategies, which include recombinant adipokines, anti-inflammatory agents, and microbial modulation. These new strategies might provide a significant benefit in selected patients, in addition to conventional antidepressants.

Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive therapies targeting immune modulation. Fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator originally approved for multiple sclerosis, has shown promising effects in both preclinical and early clinical studies of acute ischemic stroke. Methods: We conducted a structured narrative review of preclinical and clinical studies published between 2015 and 2024, using PubMed, Scopus, and Web of Science databases. Inclusion criteria were original studies evaluating fingolimod in ischemic stroke models or human patients, either as monotherapy or in combination with reperfusion therapies. Exclusion criteria included conference abstracts without peer review, studies lacking mechanistic insight, and non-English publications. Results: Preclinical evidence demonstrates that fingolimod reduces infarct size, preserves blood–brain barrier integrity, and modulates neuroinflammation through multiple mechanisms, including T cell sequestration, microglial polarization, and mitochondrial protection. Clinical trials, though limited in size, suggest improved short- and long-term outcomes when fingolimod is used in combination with intravenous thrombolysis or endovascular therapy, with a manageable safety profile. Novel nanotechnology-based delivery systems further enhance central nervous system (CNS) targeting and reduce systemic side effects. Conclusions: Fingolimod represents a promising multi-targeted adjunctive strategy for ischemic stroke, acting at the intersection of immune modulation, vascular protection, and neuroprotection. While current findings are encouraging, larger randomized controlled trials and biomarker-driven patient selection are needed to validate its clinical utility. This review highlights the translational potential of fingolimod and outlines key directions for future research.

Embolic stroke of undetermined source (ESUS) was proposed in 2014 as a clinical category to subgroup non-lacunar cryptogenic ischemic strokes that appear embolic but lack an identifiable cause despite thorough investigation. The initial hypothesis was that anticoagulation might offer superior secondary prevention compared to antiplatelet therapy, prompting several large clinical trials. This review synthesizes current knowledge on ESUS. ESUS represents about 17% of ischemic strokes and often affects younger patients with fewer traditional risk factors. Although these patients lack major cardioembolic sources (e.g., atrial fibrillation) or significant arterial stenosis, many have covert embolic substrates. Major trials—NAVIGATE ESUS, RE-SPECT ESUS, and the atrial cardiopathy-focused ARCADIA—found no benefit of anticoagulants over aspirin, challenging the original ESUS framework. These results highlight the heterogeneity within ESUS and underscore the need for individualized diagnostic and therapeutic strategies.

Traumatic brain injury (TBI) is one of the leading causes of death worldwide, particularly in young people. Diffuse axonal injuries (DAI) are the result of strong rotational and translational forces on the brain parenchyma, leading to cerebral oedema and neuronal death. DAI is typically characterized by coma without focal lesions at presentation and is defined by localized axonal damage in multiple regions of the brain parenchyma, often causing impairment of cognitive and neuro-vegetative function. Following TBI, axonal degeneration has been identified as a progressive process that begins with the disruption of axonal transport, leading subsequently to axonal swelling, axonal ballooning, axonal retraction bulges, secondary disconnection and Wallerian degeneration. The objective of this paper is to report on a series of patients who have suffered fatal traumatic brain injury, in order to verify neurological outcomes in dynamics, relative to the time of injury, using antibodies for neurofilament (NFL), spectrin II, beta-amyloid (β-APP), glial fibrillary acidic protein (GFAP) and cluster of differentiation 68 (CD68). From the studied cases, a total of 50 cases were chosen, which formed two study groups. The first study group comprises 30 cases divided according to survival interval. The control group comprises 20 cases with no history of traumatic brain injury. Cardiovascular disease and history of stroke, cases suffering from loss of vital functions, a post-traumatic survival time of less than 15 min, autolysis and putrefaction were established as criteria for exclusion. Based on their expression, we tested for diagnosis and degree of DAI as a strong predictor of mortality. Immunoreactivity was significantly increased in the DAI group compared to the control group. The earliest changes were recorded for GFAP and CD68 immunolabeling, followed by β-APP, spectrin II and NFM. The most intense changes in immunostaining were recorded for spectrin II. Comparative analysis of brain apoptosis, reactive astrocytosis and inflammatory reaction using specific immunohistochemical markers can provide important information on diagnosis of DAI and prognosis, and may elucidate the timing of the traumatic event in traumatic brain injury.

Introduction: The global spread of the SARS-CoV-2 pandemic led to a serious health, social and economic global crisis. This pandemic was and remains the most important health emergency worldwide, for which all professionals have been called to provide diagnosis and treatment support. Despite early concerns about safety, forensic medicine has contributed to a better understanding of the pathological mechanisms involved. Objective: This study aims to describe and analyze the postmortem pathological findings in confirmed SARS-CoV-2 cases, emphasizing the contribution of forensic autopsies to elucidating the mechanisms of death and associated comorbidities. Methods: A retrospective study was conducted on 279 autopsies between 2020 and 2022. Demographic, clinical, and pathological data were collected and statistically analyzed. Results: Following the descriptive analysis of the cases included in the study, as well as the analysis of the relevant scientific literature, the major impact of the COVID-19 pandemic was highlighted in terms of the death mechanisms involved, occurring consequences and induced changes. Conclusions: Autopsies remain the essential tools for investigating COVID-19-related deaths. The findings confirm that SARS-CoV-2 primarily affects the pulmonary and cardiovascular systems. However, the overlap between “death from” and “death with” COVID-19 highlights the need for standardized postmortem diagnostic criteria and comprehensive clinical–pathological correlation.