The role of Killer immunoglobulin-like receptors (KIRs) in the genetic susceptibility to non-celiac wheat sensitivity (NCWS).

OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is an emerging clinical condition characterized by gastrointestinal and extraintestinal symptoms following the ingestion of gluten-containing foods in patients without celiac disease (CD) or wheat allergy. Despite the great interest for NCWS, the genetic risk factors still need to be fully clarified. In this study, we first assessed the possible contribution of KIR genes and KIR haplotypes on the genetic predisposition to NCWS. METHODS: Fifty patients with NCWS, 50 patients with CD, and 50 healthy controls (HC) were included in this study. KIR genes and KIR genotyping were investigated in all subjects by polymerase chain reaction with the sequence oligonucleotide probe (PCR-SSOP) method using Luminex technology. RESULTS: We found a statistically different distribution of some KIR genes among NCWS, CD, and HC. Specifically, NCWS showed a decreased frequency of KIR2DL1, -2DL3, -2DL5, -2DS2, -2DS3, -2DS4, -2DS5, and -3DS1 genes, and an increased frequency of -3DL1 gene respect to both CD and HC. No difference was detected in the KIR haplotype expression. At the multivariate analysis, KIR2DL5, -2DS4, and -2DS5 were independent predictors of NCWS. CONCLUSIONS: Our findings suggest a role of KIR genes in NCWS susceptibility, with KIR2DL5, -2DS4, and -2DS5 having a protective effect. Further large-scale multicentric studies are required to validate these preliminary findings.

Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice.

Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs. Indeed, biomarkers could indicate the pathological mechanisms underpinning NDs. The ideal biofluid for detecting the biomarkers of NDs is cerebrospinal fluid (CSF), which has limitations, hampering its widespread use in clinical practice. However, intensive efforts are underway to introduce high-sensitivity analytical methods to detect ND biomarkers in alternative nonivasive biofluid, such as blood or saliva. This study presents an overview of the ND molecular biomarkers currently used in clinical practice. For some diseases, such as Alzheimer's disease or multiple sclerosis, biomarkers are well established and recommended by guidelines. However, for most NDs, intensive research is ongoing to identify reliable and specific biomarkers, and no consensus has yet been achieved.

Sex and Gender in Ageing and Longevity: Highlights From an International Course.

Gender medicine is a multidisciplinary science and represents an important perspective for pathophysiological and clinical studies in the third millennium. Here, it is provided an overview of the topics discussed in a recent course on the Role of Sex and Gender in Ageing and Longevity. The paper highlights three themes discussed in the course, i.e., the interaction of gender/sex with, i) the pathophysiology of age-related diseases; ii), the role of genetics and epigenetics in ageing and longevity and, iii) the immune responses of older people to pathogens, vaccines, autoantigens, and allergens. Although largely unexplored, it is clear that sex and gender are modulators of disease biology and treatment outcomes. It is becoming evident that men and women should no longer be considered as subgroups, but as biologically distinct groups of patients deserving consideration for specific therapeutic approaches.

Antiviral Activity of Cannabidiolic Acid and Its Methyl Ester against SARS-CoV-2.

In the present study, the antiviral activity of cannabinoids isolated from Cannabis sativa L. was assessed in vitro against a panel of SARS-CoV-2 variants, indicating cannabidiolic acid (CBDA) was the most active. To overcome the instability issue of CBDA, its methyl ester was synthesized and tested for the first time for its antiviral activity. CBDA methyl ester showed a neutralizing effect on all the SARS-CoV-2 variants tested with greater activity than the parent compound. Its stability in vitro was confirmed by ultra-high-performance liquid chromatography (UHPLC) analysis coupled with high-resolution mass spectrometry (HRMS). In addition, the capacity of both CBDA and its derivative to interact with the virus spike protein was assessed in silico. These results showed that CBDA methyl ester can be considered as a lead compound to be further developed as a new effective drug against COVID-19 infection.

Pattern of arterial inflammation and inflammatory markers in people living with HIV compared with uninfected people.

STUDY DESIGN: To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by 18F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET). METHODS: We prospectively enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent 18F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBRmax). The independent relationships between HIV status and both TBRmax and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD). RESULTS: Unadjusted mean TBRmax in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32]) than uninfected people (2.01; IQR 1.85, 2.16]). On multivariable analysis, PLWH had an independent risk of increased mean log-TBRmax in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001). CONCLUSIONS: In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBRmax in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.

Restriction Factors expression decreases in HIV-1 patients after cART.

Activation of interferon (IFN) mediated responses and the consequent expression of restriction factors (RFs) represent an early line of defense against HIV-1 infection. The levels of viral replication and the antiviral are among the determinants influencing RFs' expression pattern. A deeper understanding of the molecular mechanisms regulating RFs activity and their relationship with viral replication factors might lead to new therapeutic strategies based on the enhancement of immune response against the virus. The aim of this study is to perform a longitudinal evaluation of the variations in the levels of a group of selected RFs (APOBEC3G, BST2, TRIM5α, MX2, SAMHD1, SERINC3/5, IFI16 and STING) to determine the impact of cART on their expression in HIV-1 positive patients. Together with RFs expression, immunological and virological parameters (plasma HIV1-RNA load and total HIV1-DNA) were longitudinally evaluated in a cohorts fourteen HIV-1 cART na ve patients, who were evaluated at diagnosis (T0) and followed at 4 (T1) and 8 (T2) months after starting cART. Fourteen long-term treated patients who achieved sustained undetectable viremia for at least 2 years were also included in the study as a reference group. We observed a restoration of immunological conditions during cART, together with a progressive decrease of HIV1-RNA load, which became undetectable at 8 months after starting treatment. On the other hand, despite showing a trend towards decrease, total HIV1-DNA remained detectable after reaching viral suppression, similarly to what observed in long term treated patients. The expression of APOBEC3G, SAMHD1, BST2, IFI16, SERINC3, and SERINC5 was higher at the time of diagnosis and decreased significantly during therapy, reaching levels similar to the ones observed in virally suppressed patients. On the other hand, MX2 and TRIM5a high expression values up to T0, reaching lower levels immediately after the initiation of cART treatment. Correlation analysis showed a positive association between the expression levels of APOBEC3G, IFI16, MX2, SAMHD1, SERINC3 and TRIM5α with the HIV-1 viral load. On the contrary, no significant association was observed for BST2, SERINC5 and STING, even BST2 expression showed a tendency to correlate with viral load. We observed a tendency for a positive association of MX2, SAMHD1 and SERINC5 with the size of viral reservoir and a trend for a negative association for STING. STING appeared also as the only one factor whose expression correlates with the CD4 count and the CD4/CD8 ratio. Our data confirm the correlation between viral replication and expression of RFs, with, the levels of cellular defense proteins decreasing in parallel to the reduction of viral replication.