IntroductionDysregulation of NLRP3 inflammasome complex formation can promote chronic inflammation by increased release of IL-1β. However, the effect of NLRP3 complex formation on tumor progression remains controversial. Therefore, we sought to determine the effect of NLRP3 modulation on the growth of the different types of cancer cells, derived from lung, breast, and prostate cancers as well as neuroblastoma and glioblastoma in-vitro.MethodThe effect of Caspase 1 inhibitor (VX765) and combination of LPS/Nigericin on NLRP3 inflammasome activity was analyzed in A549 (lung cancer), MCF-7 (breast cancer), PC3 (prostate cancer), SH-SY5Y (neuroblastoma), and U138MG (glioblastoma) cells. Human fibroblasts were used as control cells. The effect of VX765 and LPS/Nigericin on NLRP3 expression was analyzed using western blot, while IL-1β and IL-18 secretion was detected by ELISA. Tumor cell viability and progression were determined using Annexin V, cell proliferation assay, LDH assay, sphere formation assay, transmission electron microscopy, and a multiplex cytokine assay. Also, angiogenesis was investigated by a tube formation assay. VEGF and MMPs secretion were detected by ELISA and a multiplex assay, respectively. Statistical analysis was done using one-way ANOVA with Tukey’s analyses and Kruskal–Wallis one-way analysis of variance.ResultsLPS/Nigericin increased NRLP3 protein expression as well as IL-1β and IL-18 secretion in PC3 and U138MG cells compared to A549, MCF7, SH-SY5Y cells, and fibroblasts. In contrast, MIF expression was commonly found upregulated in A549, PC3, SH-SY5Y, and U138MG cells and fibroblasts after Nigericin treatment. Nigericin and a combination of LPS/Nigericin decreased the cell viability and proliferation. Also, LPS/Nigericin significantly increased tumorsphere size in PC3 and U138MG cells. In contrast, the sphere size was reduced in MCF7 and SH-SY5Y cells treated with LPS/Nigericin, while no effect was detected in A549 cells. VX765 increased secretion of CCL24 in A549, MCF7, PC3, and fibroblasts as well as CCL11 and CCL26 in SH-SY5Y cells. Also, VX765 significantly increased the production of VEGF and MMPs and stimulated angiogenesis in all tumor cell lines.DiscussionOur data suggest that NLRP3 activation using Nigericin could be a novel therapeutic approach to control the growth of tumors producing a low level of IL-1β and IL-18.

NLR family pyrin domain containing 3 (NLRP3) inflammasome formation is triggered by the damaged mitochondria releasing reactive oxygen species. Doxycycline was shown to regulate inflammation; however, its effect on NLRP3 in cancer remains largely unknown. Therefore, we sought to determine the effect of doxycycline on NLRP3 regulation in cancer using an in vitro model. NLRP3 was activated in a prostate cancer cell line (PC3) and a lung cancer cell line (A549) before treatment with doxycycline. Inflammasome activation was assessed by analyzing RNA expression of NLRP3, Pro-CASP-1, and Pro-IL1β using RT-qPCR. Additionally, NLPR3 protein expression and IL-1β secretion were analyzed using Western blot and ELISA, respectively. Tumor cell viability was determined using Annexin V staining and a cell proliferation assay. Cytokine secretion was analyzed using a 41Plex assay for human cytokines. Data were analyzed using one-way ANOVA model with Tukey’s post hoc tests. Doxycycline treatment decreased NLRP3 formation in PC3 and A549 cells compared to untreated and LPS only treated cells (p < 0.05). Doxycycline also decreased proliferation and caused cell death through apoptosis, a response that differed to the LPS-Nigericin mediated pyroptosis. Our findings suggest that doxycycline inhibits LPS priming of NLRP3 and reduces tumor progression through early apoptosis in cancer.

The purpose of this rapid review is to investigate the development of the hepatic manifestations and challenges with SARS-COV-2 and multiple viral hepatitis infections. The literature on the most critical viral, genetic and immunological factors between SARS-CoV-2 and viral hepatitis was reviewed, and the most important interactions that occur with the host were identified in addition to the use of antivirals, another drug, and also the potential of defective viral genomes in antiviral inhibitors. This review specified that some types of viral hepatitis in SARS-COV-2 patients may be reduced reactivation and receive immunosuppressive therapy. We concluded from the current review that it is necessary to consider the special care of persons exposed to infection with SARS-CoV-2 to persons infected with viral hepatitis. In particular, advanced cases of the disease and their stages of treatment as it leads to liver dysfunction and life-threatening patient.

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Background: Cancer patients are prescribed antibiotics, such as macrolides and lactamides, for infection treatment. However, the effect of these antibiotics on NLRP3 activation remains largely unknown. Method: Lung cancer (A549) and prostate cancer (PC3) cell lines were primed with lipopolysaccharide (LPS) to activate NLRP3 transcription. Cells were then treated with azithromycin (Az) or ceftriaxone (Cf). NLRP3 activation was analyzed by qPCR, Western blot, and ELISA. Cell growth and viability were assessed by real-time cell analysis and Annexin V expression. Levels of 41 cytokines were also analyzed using a multiplex assay. Results: LPS-Az activated transcription of NLRP3, Pro-CASP-1, and Pro-IL-1β in A549 cells, while failing to upregulate NLRP3 and Pro-IL-1β in PC3 cells. LPS-Az decreased the secretion of pro-inflammatory cytokines while it induced the pro-angiogenic factors in A549 and PC3 cells. In contrast, LPS-Cf suppressed the expression of NLRP3-associated genes, NLRP3 protein expression, the inflammatory cytokine secretion in A549 and PC3 cells. LPS-Az and LPS-Cf had a limited effect on cell growth and viability. Discussion: Our data suggest that Cf could suppress LPS induced NLRP3 ,which should be considered when selecting antibiotics for cancer treatment. In contrast, the effect of Az on LPS primed NLRP3 and the inflammatory cytokines production appears to depend on the cancer cell origin. Therefore, these data indicate that considerations are required when selecting Az for the treatment of cancer patients.

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This study was applied on 90 tuberculosis patients admitted in the Babylon Center of Tuberculosis and Chest Diseases in Hilla, Iraq. They were divided into four   groups; 50 patients with Pulmonary, 40 patients with Extra pulmonary,20 people as healthy contact group and 20 people as healthy control group. Blood samples were collected from patients and control group to estimate Anti Ascrais lumbricoides-IgG   , also Zinc and copper level were also spectrophotometerically estimated. The ages range of all TB cases were ranged from 11 to more than 71 years; TB patients consisted of 51 males and 39 females. The mean of Anti- Ascrais lumbricoides IgG in PTB patient's sera was 0.43±0.17, while in control subjects was 0.20±0.19. The study significantly shows difference between PTB patients and controls, while The mean of anti Ascrais lumbricoides IgG in EPTB patients sera was 0.23±0.02, while in control subjects was0.20±0.19. The study significantly shows no difference between EPTB patients and controls.