The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis. We aimed to determine the effects and mechanism of IL-33 on the development and severity of pulmonary fibrosis in murine bleomycin-induced fibrosis. Lung fibrosis was induced by bleomycin in wild-type or Il33r (St2)(-/-) C57BL/6 mice treated with the recombinant mature form of IL-33 or anti-IL-33 antibody or transferred with type 2 innate lymphoid cells (ILC2s). The development and severity of fibrosis was evaluated based on lung histology, collagen levels, and lavage cytology. Cytokine and chemokine levels were quantified by using quantitative PCR, ELISA, and cytometry. IL-33 is constitutively expressed in lung epithelial cells but is induced in macrophages by bleomycin. Bleomycin enhanced the production of the mature but reduced full-length form of IL-33 in lung tissue. ST2 deficiency, anti-IL-33 antibody treatment, or alveolar macrophage depletion attenuated and exogenous IL-33 or adoptive transfer of ILC2s enhanced bleomycin-induced lung inflammation and fibrosis. These pathologic changes were accompanied, respectively, by reduced or increased IL-33, IL-13, TGF-β1, and inflammatory chemokine production in the lung. Furthermore, IL-33 polarized M2 macrophages to produce IL-13 and TGF-β1 and induced the expansion of ILC2s to produce IL-13 in vitro and in vivo. IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner.

The nucleotide-binding domain, leucine-rich repeat containing family caspase recruitment domain containing 4 (NLRC4) inflammasome can be activated by pathogenic bacteria via products translocated through the microbial type III secretion apparatus (T3SS). Recent work has shown that activation of the NLRP3 inflammasome is downregulated by autophagy, but the influence of autophagy on NLRC4 activation is unclear. We set out to determine how autophagy might influence this process, using the bacterium Pseudomonas aeruginosa, which activates the NLRC4 inflammasome via its T3SS. Infection resulted in T3SS-dependent mitochondrial damage with increased production of reactive oxygen intermediates and release of mitochondrial DNA. Inhibiting mitochondrial reactive oxygen release or degrading intracellular mitochondrial DNA abrogated NLRC4 inflammasome activation. Moreover, macrophages lacking mitochondria failed to activate NLRC4 following infection. Removal of damaged mitochondria by autophagy significantly attenuated NLRC4 inflammasome activation. Mitochondrial DNA bound specifically to NLRC4 immunoprecipitates and transfection of mitochondrial DNA directly activated the NLRC4 inflammasome; oxidation of the DNA enhanced this effect. Manipulation of autophagy altered the degree of inflammasome activation and inflammation in an in vivo model of P. aeruginosa infection. Our results reveal a novel mechanism contributing to NLRC4 activation by P. aeruginosa via mitochondrial damage and release of mitochondrial DNA triggered by the bacterial T3SS that is downregulated by autophagy.

This study investigated for the first time a simple bio-synthesis approach for the synthesis of copper oxide nanoparticles (CuO NPs) using Annona muricata L (A. muricata) plant extract to test their anti-cancer effects. The presence of CuONPs was confirmed by UV–visible spectroscopy, Scanning electron microscope (SEM), and Transmission electron microscope (TEM). The antiproliferative properties of the synthesized nanoparticles were evaluated against (AMJ-13), (MCF-7) breast cancer cell lines, and the human breast epithelial cell line (HBL-100) as healthy cells. This study indicates that CuONPs reduced cell proliferation for AMJ-13 and MCF-7. HBL-100 cells were not significantly inhibited for several concentration levels or test periods. The outcomes suggest that the prepared copper oxide nanoparticles acted against the growth of specific cell lines observed in breast cancer. It was observed that cancer cells had minor colony creation after 24 h sustained CuONPs exposure using (IC₅₀) concentration for AMJ-13 was (17.04 µg mL⁻¹). While for MCF-7 cells was (18.92 µg mL⁻¹). It indicates the uptake of CuONPs by cancer cells, triggering apoptosis. Moreover, treatment with CuONPs enhanced Lactate dehydrogenase (LDH) production, probably caused by cell membrane damage, creating leaks comprising cellular substances like lactate dehydrogenase. Hence, research results suggested that the synthesized CuONPs precipitated anti-proliferative effects by triggering cell death through apoptosis.

Background: Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. Methods: In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. Results: The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn’s disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Conclusions: Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5‐hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic–pituitary–adrenal axis and increase circulating cortisol levels, which triggers IR and T2D.

Annona muricata is one of the most important traditional medicinal plants which contains numerous chemicals that exhibit various pharmacological properties. In this study, silver nanoparticles were prepared using A. muricata peel extract as a reducing agent and the effect was enhanced through A. muricata like pharmaceutical activity. AgNPs formation was confirmed by color changes, UV-visible spectroscopy, SEM, DLS, and XRD. The anti-proliferative activity of AgNPs against THP-1, AMJ-13, and HBL cell lines was studied. Apoptotic markers were tested using AO/EtBr staining assay, cell cycle phases using flowcytometry, and the expression of P53. Autophagy takes an essential part in controlling inflammasome activation by primary bone marrow-derived macrophages (BMDMs). We report novel functions for AgNPs-affected autophagy, represented by the control of the release of IL-1β, caspase-1, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and NLRP3 in BMDMs following treatment with LPS+ATP. The current study revealed that the AgNPs inhibited THP-1 and AMJ-13 cell proliferation. Meanwhile, the AgNPs significantly increased autophagy and reduced IL-1b and NLRP3 levels in both in vivo and in vitro models. The secretion of IL-1β was reduced whereas the degradation of NLRP3 inflammasome was enhanced. These findings propose that AgNPs apply an anti-proliferative activity against THP-1 and AMJ-13 cells through the stimulation of apoptosis via mitochondrial damage and induction of p53 protein pathway. In addition, AgNP-induced autophagy reduced the levels of IL-1β and NLRP3 inflammasome activation. This indicated that the AgNPs augment autophagy controlled by the IL-1β pathway via two different novel mechanisms. The first one is regulating activation of the IL-1 β, caspase-1, and ASC, while the second is NLRP3 targeting for lysosomal degradation. Overall, this study suggests that AgNPs could be a potent therapy for various types of cancer and an alternative treatment for preventing inflammation via enhancing autophagy.