Anna Paola Capra

In post-mortem genetic identification, teeth represent one of the most reliable sources of nuclear DNA when other biological samples are unavailable, owing to their ability to protect genetic material from autolysis, microbial degradation, and environmental insults. The present study describes a forensic veterinary case report involving a Staffordshire Bull Terrier litter in which the appearance of blue-coated offspring from a phenotypically black sire and a blue dam prompted parentage verification. The sire died before formal ante-mortem sampling could be carried out. In accordance with Regulation (EC) No. 1069/2009, Article 15, the carcass was interred in the owner’s garden. Before burial, two teeth were collected as the sole biological material available for identification by the official veterinarian, ensuring an unambiguous chain of custody from death certification to laboratory analysis. DNA extraction was performed using two independent protocols: Method A, a silica-membrane-based purification (QIAamp DNA Kit, Qiagen), applied to dental pulp, and Method B, a decalcification-based workflow (T-Bone Ex Kit) followed by DNA extraction using EZ2 Connect Instruments (Qiagen). Quantification of the DNA samples obtained were done by fluorometry. Short Tandem Repeat (STR) genotyping was performed using the Canine Genotypes™ Panel 1.1 by Applied Biosystems (Thermo Fisher Scientific, Waltham, MA, USA) targeting the 18 autosomal ISAG-recommended microsatellite loci. Parentage assignments were carried out against reference STR profiles obtained from peripheral blood of the dam and offspring. The two methods, considering a different biological matrix and different operating conditions, allowed us to obtain the STR profile, but Method B showed quality electropherograms, improving the confidence and interpretation of all the markers analyzed. The differences observed between the two approaches may reflect a combination of factors, including the different dental matrices analysed, the quantity and quality of the starting material, tooth identity and tissue preservation, and differences inherent to the extraction procedures themselves; therefore, in this case, the more complete and clearer STR profile obtained with Method B should be considered a case-specific observation rather than evidence of a direct effect of the extraction method. Overall, regardless of the DNA extraction method used, the results did not exclude the biological paternity of the blue-mantled offspring. Furthermore, this case report provides practical methodological guidance for DNA recovery from canine teeth and supports their use as a reliable source of post-mortem DNA for STR-based parentage testing.

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation, immune dysregulation, oxidative stress, and impaired epidermal barrier function. In the present study, we investigated the protective effects of Tempol, a membrane‐permeable nitroxide with antioxidant and anti‐inflammatory properties, using several psoriasiform models. In HaCaT keratinocytes, stimulation with a cytokine mixture significantly induced inflammatory responses. Tempol (0.5 and 1 mM) showed no cytotoxic effects and markedly reduced the mRNA and protein levels of proinflammatory cytokines, including TNF‐α, IL‐1β, and IL‐6. Tempol was associated with reduced expression of TLR4, MyD88, TRAF6, and nuclear factor‐kappa B (NF‐κB), together with restoration of IκBα expression, findings consistent with modulation of the TLR4/NF‐κB signaling pathway. In parallel, Tempol was associated with activation of the nuclear factor erythroid 2‐related factor 2 (Nrf2)/HO‐1 antioxidant axis, as evidenced by increased expression of Nrf2, HO‐1, and MnSOD, along with a reduction in the pro‐oxidant enzymes NOX2 and NOX4. These effects were associated with decreased oxidative damage, including reduced lipid peroxidation and nitric oxide production. Furthermore, Tempol exerted cytoprotective effects by restoring the balance between pro‐ and antiapoptotic markers, as indicated by increased Bcl‐2 levels, decreased Bax and p53 expression, and a reduced Bax/Bcl‐2 ratio. The anti‐inflammatory activity of Tempol was further confirmed in an imiquimod (IMQ)‐stimulated HaCaT/THP‐1 coculture model, where it significantly reduced the release of key immune mediators, including TLR4, IL‐8, IL‐17A, and IL‐23, highlighting its ability to modulate immune‐epithelial crosstalk. In a reconstructed human epidermis (RHE) model, Tempol preserved tissue viability under psoriasiform conditions and significantly reduced Staphylococcus aureus ( S. aureus ) adhesion. Importantly, Tempol restored epidermal barrier integrity, as demonstrated by increased levels of tight junction and differentiation markers, including ZO‐1, Occludin, Claudin‐1, and Filaggrin, even under infection‐associated conditions. Taken as a whole, these findings support the potential of Tempol as a promising therapeutic strategy for psoriasis and related inflammatory skin disorders.

The gut–brain axis refers to the bidirectional communication network linking the gut microbiota and the central nervous system (CNS). Recent research has highlighted the critical role of gut microbiota in influencing brain health, neurogenesis, and neuroinflammation. In the context of brain tumors, especially gliomas, the gut–brain axis plays a significant role in tumor development, progression, and response to therapy. Gut dysbiosis, characterized by an imbalance in microbiota composition, has been linked to chronic inflammation, immune suppression, and altered blood–brain barrier (BBB) permeability, key factors in glioma pathogenesis. Gut-derived metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters can either promote or inhibit tumor growth, impacting the tumor microenvironment (TME) and immune responses. Emerging evidence suggests that microbiome modulation, through strategies such as probiotics, prebiotics, and dietary interventions, may enhance anti-tumor immunity and improve the efficacy of conventional treatments like chemotherapy, radiotherapy, and immunotherapy. This review examines the interactions between gut microbiota and brain tumors, focusing on how microbiota alterations may influence tumor biology and therapeutic outcomes. Understanding the mechanisms of the gut–brain axis could lead to novel adjunctive therapies in neuro-oncology, offering new prospects for personalized treatment strategies in brain tumor management.

Background: The introduction of immunotherapy has significantly improved survival outcomes in many solid tumors. However, a subset of patients exhibits limited responsiveness to immune checkpoint inhibitors (ICIs). Emerging evidence indicates that the gut microbiota plays a critical role in modulating the effectiveness of immunotherapy. Consequently, the concurrent use of certain medications that disrupt microbial diversity may contribute to reduced treatment efficacy. Among the agents implicated in altering the gut microbiota are antibiotics and proton pump inhibitors (PPIs). Methods: A systematic literature search was conducted in PubMed, Scopus, and EMBASE. Eligible studies assessed the association between PPI use and progression-free survival (PFS) and/or overall survival (OS) in patients with solid tumors receiving ICIs. They reported hazard ratios (HRs) with 95% confidence intervals (CIs). The analysis focused on studies published between November 2022 and January 2025, in continuity with prior comprehensive meta-analyses that included studies up to November 2022. This contiguity-based approach enabled a focused evaluation of recent evidence, minimizing redundancy while allowing for the detection of evolving trends in clinical practice and methodology. Data were synthesized using both fixed-effects and random-effects models and visualized via Forest plots. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and the Newcastle–Ottawa Scale (NOS). Between-study heterogeneity and publication bias were evaluated using I² statistics and funnel plots. Results: From a pool of over 400 screened articles between November 2022 and January 2025, seven studies met the inclusion criteria. The PFS analysis incorporated data from 1367 participants, while the OS analysis included 10,420 individuals. Use of PPIs was linked to a 12% higher risk of disease progression (HR = 1.12; 95% CI: 0.90–1.34) and an 18% increased mortality risk (HR = 1.18; 95% CI: 1.11–1.25). Conclusions: The observed association between PPIs exposure and reduced efficacy of ICIs, as reflected in worsened PFS and OS outcomes, highlights a potential clinical concern that merits further investigation in prospective studies.

The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut–brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases.

Background: The implantation process is complex and involves numerous factors that can affect its success. In artificial reproductive treatments (ARTs), chronic inflammation seems to be associated with implantation failure, largely contributing to reproductive dysfunction. Pentraxin 3 (PTX3) is overexpressed in several pathological conditions by exerting a pivotal role both as a regulator and indicator of inflammatory response. Some literature data have shown that PTX3 could have an impact on follicle growth and development, influencing women’s fertility. This study aimed to detect PTX3 in follicular fluids collected during an ART protocol in relation to implantation outcomes. Methods: The PTX3/NF-kB/TLR4 pathway and other cytokines were assessed in the follicular fluid of 169 subjects, under the age of 40 years, undergoing IVF cycles, including females without achieved implantation (n = 98) and those with implantation (n = 71). Furthermore, subgroup analyses were performed to evaluate PTX3 values according to age difference. Results: From our data, PTX3 emerged as a strong predictor, more than TNFα and IL-1β, of implantation failure and related inflammatory follicular state. Overall, the results point to PTX3 as a potential biomarker for ART success, and their testing may be helpful in women whose successful implantation remains unexplained. Conclusions: Therefore, PTX3 could constitute a reliable biomarker and a valuable target to improve ART outcomes.

Myocardial ischemia–reperfusion injury (MI/R) is a negative and adverse cardiovascular outcome following myocardial ischemia, cardiac surgery, or circulatory arrest. Prolyl endopeptidase (PREP) appears to be involved in inflammatory responses, so it could be a possible therapeutic target for counteracting ischemia injury. This study aimed to investigate the role of PREP inhibitor, KYP-2047 (4-phenylbutanoyl-l-prolyl-2(S)-cyanopyrolidine), in the modulation of molecular and biochemical processes involved in MI/R. MI/R was induced through coronary artery occlusion (15 min), followed by reperfusion (2 h). KYP-2047 was intraperitoneally administrated at doses of 2.5 mg/kg and 5 mg/kg 24 h before the surgical procedures. The hearts were removed and processed for analysis. KYP-2047 treatment limited ischemic myocardial-induced histological damage and neutrophil accumulation, limiting inflammation, fibrosis, and apoptosis processes. Additionally, KYP-2047 was able to modulate p-38 and p-ERK expression, suggesting an improving role in recovering cardiac function. These findings highlighted the protective effects of KYP-2047 pretreatment in MI/R injury, suggesting PREP as a potential target therapy for the pathogenesis of MI/R. Although the molecular mechanisms underlying the action of KYP-2047 are still to be explored, these results suggested that the regulation of NF-κB, apoptosis, and MAPK pathways by KYP-2047 treatment could preventatively limit the damage caused by MI/R.

Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder characterized by recurrent fevers and inflammation of the serous membranes in the abdomen, lungs, and joints. Currently, the standard treatment of FMF includes colchicine, which is an alkaloid, derived from Colchicum autumnale. Colchicine’s efficacy in FMF is well-established as it is used both to prevent acute attacks and reduce the risk of long-term complications. However, despite these available treatments, 5–10% of patients exhibit resistance to the drug. It has been demonstrated that polymorphisms in several genes involved in inflammation can influence treatment outcomes and the risk of FMF complications like amyloidosis. Among them, some research focused on polymorphism affecting adenosine triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1) gene encoding for P-glycoprotein. P-glycoprotein is considered a key transporter protein as it regulates the absorption, distribution, and excretion of several drugs, including colchicine. In diseases like FMF, ABCB1 polymorphisms have been shown to affect the response to colchicine, potentially leading to treatment resistance or altered toxicity. Based on this evidence, this systematic review aims to analyze available evidence on ABCB1-mediated colchicine transport and its clinical implications in FMF, showing how relevant ABCB1 variants are in response to therapy.