The “poisonous water” (mê rʾōš) in Jer 8:14 and the “bewitched water” (mê kaššāpūti) in Maqlû i 103-104: witchcraft in the book of Jeremiah

Some scholars consider the biblical phrase mê rʾōš (“poisonous water”) a metaphor for the venom of a snake, others interpret it as a poisonous substance produced by pressing herbs and still, others believe it to be a metaphor for the destruction of the people Israel and their land. In the book of Jeremiah in particular, the phrase mê rʾōš appears three times (8:14, 9:15, and 23:15) and in all cases, it appears in execratory contexts. Numerous studies have put this phrase in relation to the trial ordeal in Numbers 5:11-31, and have therefore recognized its execratory nature, yet, to my knowledge, no one has ever studied it against the background of the Neo-Assyrian magical tradition. Accordingly, the expression “poisonous water” may have magical nuances attached to it. For example, the ancient Mesopotamians believed that curses could be passed to the victim by means of food or drink. In this analysis, I argue that the expression mê rʾōš may have the function that the Akkadian phrase mê kaššāpūti (“bewitched water”) has in Assyrian anti-witchcraft rituals where the administration of a poisonous drink symbolized the nullification of a curse as it was believed that the bewitched potion given to the evildoer returned to him the evil he had intended for his victim. In my talk, I will analyze the theme of the transfer of the curse through liquids and food in select Assyrian literature. I will then show how the book of Jeremiah redeployed this Assyrian theme to articulate its theological offensive against the harmful effects of the oracular utterances of illegitimate Prophets

Autophagy and rheumatoid arthritis: Current knowledges and future perspectives

Autophagy is a degradation mechanism by which cells recycle cytoplasmic components to generate energy. By influencing lymphocyte development, survival, and proliferation, autophagy regulates the immune responses against self and non-self antigens. Deregulation of autophagic pathway has recently been implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Indeed, autophagy seems to be involved in the generation of citrullinated peptides, and also in apoptosis resistance in RA. In this review, we summarize the current knowledge on the role of autophagy in RA and discuss the possibility of a clinical application of autophagy modulation in this disease

Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus

BACKGROUND: Current evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti-inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect. METHODS: Sixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit. RESULTS: Intracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs. CONCLUSIONS: Our results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity

The role of dietary sodium intake on the modulation of T helper 17 cells and regulatory T cells in patients with rheumatoid arthritis and systemic lupus erythematosus

We aimed at investigating whether the frequency and function of T helper 17 (Th17) and regulatory T cells (Treg) are affected by a restriction of dietary sodium intake in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We enrolled RA and SLE patients not receiving drugs known to increase urinary sodium excretion. Patients underwent a dietary regimen starting with a restricted daily sodium intake followed by a normal-sodium daily intake. The timepoints were identified at baseline (T0), after 3 weeks of low-sodium dietary regimen (T3), after 2 weeks of normal-sodium dietary regimen (T5). On these visits, we measured the 24-hour urinary sodium excretion, the frequency and function of Th17 and Treg cells in the peripheral blood, the serum levels of cytokines. Analysis of urinary sodium excretion confirmed adherence to the dietary regimen. In RA patients, a trend toward a reduction in the frequencies of Th17 cells over the low-sodium dietary regimen followed by an increase at T5 was observed, while Treg cells exhibited the opposite trend. SLE patients showed a progressive reduction in the percentage of Th17 cells that reached a significance at T5 compared to T0 (p = 0.01) and an increase in the percentage of Treg cells following the low-sodium dietary regimen at both T1 and T3 compared to T0 (p = 0.04 and p = 0.02, respectively). No significant apoptosis or proliferation modulation was found. In RA patients, we found a reduction at T5 compared to T0 in serum levels of both TGFβ (p = 0.0016) and IL-9 (p = 0.0007); serum IL-9 levels were also reduced in SLE patients at T5 with respect to T0 (p = 0.03). This is the first study investigating the effects of dietary sodium intake on adaptive immunity. Based on the results, we hypothesize that a restricted sodium dietary intake may dampen the inflammatory response in RA and SLE patients

TNFα expressed on the surface of microparticles modulates endothelial cell fate in rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is associated with a high prevalence of atherosclerosis. Recently increased levels of microparticles (MPs) have been reported in patients with RA. MPs could represent a link between autoimmunity and endothelial dysfunction by expressing tumor necrosis factor alpha (TNFα), a key cytokine involved in the pathogenesis of RA, altering endothelial apoptosis and autophagy. The aim of this study was to investigate TNFα expression on MPs and its relationship with endothelial cell fate. Methods: MPs were purified from peripheral blood from 20 healthy controls (HC) and from 20 patients with RA, before (time (T)0) and after (T4) 4-month treatment with etanercept (ETA). Surface expression of TNFα was performed by flow cytometry analysis. EA.hy926 cells, an immortalized endothelial cell line, were treated with RA-MPs purified at T0 and at T4 and also, with RA-MPs in vitro treated with ETA. Apoptosis and autophagy were then evaluated. Results: RA-MPs purified at T0 expressed TNFα on their surface and this expression significantly decreased at T4. Moreover, at T0 RA-MPs, significantly increased both apoptosis and autophagy levels on endothelial cells, in a dose-dependent manner. RA-MPs did not significantly change these parameters after 4 months of in vivo treatment with ETA. Conclusions: Our data demonstrate that MPs isolated from patients with RA exert a pathological effect on endothelial cells by TNFα expressed on their surface. In vivo and in vitro treatment with ETA modulates this effect, suggesting anti-TNF therapy protects against endothelial damage in patients with RA

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs)

Well-Come Back! Professional Basketball Players Perceptions of Psychosocial and Behavioral Factors Influencing a Return to Pre-injury Levels

The psychological factors influencing a return to sport has gained increased research attention. In the current investigation, we explored professional basketball players’ perceptions of the psychosocial and behavioral factors facilitating a return to performance equal to or exceeding previous performance standards. We also sought to describe athletes’ experiences – both positive and negative – of returning to sport following injury recovery. Ten Italian professional male basketball players (age range 22–36 years), were retrospectively interviewed in relation to three time-periods: (1) from the commencement of rehabilitation to their first official competition, (2) the first official competition, and (3) the 6-months following the initial competition. Qualitative content analysis of the data revealed numerous themes across the three time periods. In regards to Period 1, participants indicated that social support, investment in rehabilitation and training programs, coping skills and motivation were fundamental in reaching pre-injury performance levels. During their first official game (i.e., Period 2), athletes reported that realistic performance expectations, focusing on the performance, positive emotions, motivation, arousal and social support facilitated their return to sport. Athletes, however, also described a predominance of factors that hindered their return to pre- injury levels (i.e., low confidence in personal abilities, decrements in skill execution and dysfunctional physical sensations). Moreover, participants typically described a substandard level of performance during their first competition back following injury. In recounting experiences during the 6 months following their first official game, basketballers reported improvements in skill execution and highlighted the importance of coping skills, motivation and social support. The process of restoring self-confidence in one’s ability to successfully perform was perceived as crucial in enabling participants to move beyond a mere return to sport to a return to high performance – that is, to reach a level of proficiency equal to or exceeding previous performance standards. Findings support the relevance of cognitive, emotional and behavioral responses highlighted in the Integrated Model and suggest the importance of addressing psychological factors throughout the return-to-sport process. Finally, results from the present study hold a number of practical implications for athletes’ aiming to achieve a return to pre-injury levels

Una complessa eredità: ricordando Fabrizio Frasnedi (1944-2015)

Il volume raccoglie una serie di contributi in ricordo di Fabrizio Frasnedi a cinque anni dalla sua scomparsa. Interventi di Gian Mario Anselmi, Bruno Capaci, Maria Rosaria Catino, Guido Conti, Cristiana De Santis, Yahis Martari, Chiara Panzieri, Michele Prandi, Rocco Ronchi, Alberto Sebastiani, Matteo Vial

Autophagy hijacking in PBMC From COVID-19 patients results in lymphopenia

Autophagy is a homeostatic process responsible for the self-digestion of intracellular components and antimicrobial defense by inducing the degradation of pathogens into autophagolysosomes. Recent findings suggest an involvement of this process in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the role of autophagy in the immunological mechanisms of coronavirus disease 2019 (COVID-19) pathogenesis remains largely unexplored. This study reveals the presence of autophagy defects in peripheral immune cells from COVID-19 patients. The impairment of the autophagy process resulted in a higher percentage of lymphocytes undergoing apoptosis in COVID-19 patients. Moreover, the inverse correlation between autophagy markers levels and peripheral lymphocyte counts in COVID-19 patients confirms how a defect in autophagy might contribute to lymphopenia, causing a reduction in the activation of viral defense. These results provided intriguing data that could help in understanding the cellular underlying mechanisms in COVID-19 infection, especially in severe forms