Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy.

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson's trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor ß1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines' tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.

Serum interleukin-23 levels: relation to depression, anxiety, and disease activity in psoriatic arthritis patients.

OBJECTIVES: Assessment of serum levels of IL-23 in PsA patients and its correlation with depression, anxiety, and disease activity. METHODS: Eighty psoriatic arthritis (PsA) patients and eighty healthy volunteers matched for age and gender were included in this observational case-control study. All participants suspected to detailed history, clinical assessment, PsA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI), and ultrasonographic assessments of the entheses were examined according to the Madrid Sonographic Enthesitis Index (MASEI). Depression and anxiety were assessed by Hospital Anxiety and Depression Scale (HADS). Serum IL-23 was measured and correlated with disease activity, depression, and anxiety. RESULTS: There was no significant difference between patients and controls regarding demographic data. Thirty-six PsA patients (45%) had anxiety and 28 patients (35%) had depression, while in the control group, 16 persons (20%) had anxiety and 12 (15%) had depression, with significant differences between the 2 groups (p < 0.0001). There were significant differences in HADS anxiety and depression scores between patients and controls with significant positive correlations between HADS depression, anxiety scores and IL-23, DAPSA, PASI, and MASEI scores (p < 0.05). IL-23 was positively correlated with DAPSA, PASI, and HADS scores; we observed that interleukin 23, higher DAPSA, and PASI were independently associated with depression and anxiety. CONCLUSION: Serum interleukin-23 levels were elevated in PsA patients and were found to be correlated with depression, anxiety, and disease activity. Key Points • Psoriatic arthritis is a multidimensional disorder with psychiatric drawbacks. • Interleukin-23 is a proinflammatory cytokines that was correlated with depression and anxiety in PsA patients. • Interleukin-23 was correlated with disease activity in PsA. • Depression and anxiety were positively correlated with disease activity in PsA.

BAFF rs9514828 gene polymorphism and the risk of the development of inhibitors in children with severe haemophilia A.

INTRODUCTION: Haemophilia A (HA) is an x-linked recessive disease due to deficiency of coagulation factor VIII (FVIII). The development of neutralizing antibodies (inhibitors) against infused FVIII is a major concern. B cell activating factor (BAFF) has been implicated in several autoimmune diseases. AIM: We aimed to evaluate the possible association of BAFF rs9514828 gene polymorphism and the risk of the development of FVIII inhibitor in children with severe HA. METHODS: This cohort study was carried out on 100 newly diagnosed boys with severe HA who were never treated before with FVIII concentrate. Assessment of serum levels of BAFF and BAFF rs9514828 genotyping at first diagnosis was performed and the patients were followed up for the completion of a total of 50 exposure days or the development of inhibitors whichever occurred first. The patients were divided as positive or negative according to the presence or absence of inhibitors. RESULTS: The risk allele for BAFF rs9514828 (T) was significantly more frequent in the inhibitor positive patients than the inhibitor negative patients (P = .003). In addition, CT+TT genotypes were associated with increased risk of FVIII inhibitor development. Receiver operating characteristics (ROC) analysis showed that BAFF levels could predict the development of FVIII inhibitors at a cut-off value of ≥ .92 with a sensitivity of 85.9% and a specificity of 80.2%. CONCLUSION: BAFF rs9514828 gene polymorphism could be independent risk factor and elevated BAFF levels might be useful prognostic marker for the development of FVIII inhibitor in newly diagnosed children with severe HA.

Impact of CD105 Flow-Cytometric Expression on Childhood B-Acute Lymphoblastic Leukemia.

BACKGROUND: CD105 (Endoglin) is a receptor of the transforming growth factor-Beta (TGF- ß) superfamily. It is expressed in angiogenic endothelial cells and is considered a powerful marker of angiogenesis and a potential main player in the pathogenesis of vascular diseases as well as tumor progression. CD105 expression was correlated with poor prognosis in many types of solid malignancies, however, its influence on hematological neoplasms is still an area of interest. PURPOSE: To assess the flow-cytometric expression of CD105 in childhood B-acute lymphoblastic leukemia (B-ALL) and its relation to disease response after the induction chemotherapy. SUBJECTS AND METHODS: Eighty children newly diagnosed with B-ALL were screened for flow-cytometric expression of CD105 at time of diagnosis, then they were followed up to detect their response to induction therapy. RESULTS: CD105 was expressed in 41.2% of B-ALL patients. Higher expression of CD105 was observed in high and very high-risk groups. The multivariate analysis considered CD105 positivity as an independent prognostic marker for response to induction therapy. Values higher than 2.5 Specific fluorescence indices (SFIs) and 35% expression were sensitive predictors to induction failure. CONCLUSION: CD105 can be considered as a potential prognostic marker for the detection of response to induction therapy in childhood B-ALL, and it can serve to optimize treatment decisions.