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Background IL-19 and IL-24 induce proinflammatory cytokine production through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. The primary objective of this study was to investigate any changes in IL-19 and IL-24 expression between inflammatory bowel disease (IBD) patients and healthy controls, as well as before and after the initiation of biologics. The secondary objective was to investigate any relation between their expression and disease phenotype and activity. Methods IL-19 and IL-24 expression was measured in intestinal tissue samples from 121 patients with moderate to severe IBD versus healthy controls using immunohistochemistry. Their expression was then measured 12 months after treatment on the patient group treated with biologics. The disease activity was measured before and after treatment using the Harvey Bradshaw Index (HBI) for Crohn's disease (CD) patients and the Mayo Score (MS) for ulcerative colitis (UC) patients. Data were analyzed using SPSS (IBM Inc., Armonk, New York). Results IL-19 expression was raised in the IBD group versus healthy controls. In the CD group, the IL-19 expression was related with the disease activity score post-biologic treatment. IL-24 was also highly expressed in patients with active UC and CD and was increased post-treatment. Its expression in UC was statistically related with the MS. Conclusions IL-24 and IL-19 are key factors in IBD-related intestinal inflammation and this is one of the few human studies to suggest that. An immunosuppressive role of IL-24 was demonstrated in the UC group. A future use as biomarkers of disease activity and response to treatment might be feasible.
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Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.
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Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in the tumor immune microenvironment (TIME) across different TNBC molecular subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling and bioinformatic analyses to classify TNBC samples into molecular subtypes, as well as immunohistochemistry and cell deconvolution methods to characterize the TIME. Results revealed significant heterogeneity in immune cell composition among TNBC subtypes, with the immunomodulatory (IM) subtype demonstrating robust immune infiltration, composed mainly of adaptive immune cells along with an increased density of CTLA-4+ and PD-1+ TILs, high PD-L1 tumor cell expression, and upregulation of FOXP3+ Tregs. A more immunosuppressive TIME with a predominance of innate immune cells and lower levels of tumor-infiltrating lymphocytes (TILs) was observed in luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, the TIME was mainly composed of innate immune cells, with a high number of M2 tumor-associated macrophages (TAMs), while the BL and M tumors displayed poor adaptive and innate immune responses, indicating an "immune-cold" phenotype. Differential activation of signaling pathways, genomic diversity, and metabolic reprogramming were identified as contributors to TIME heterogeneity. Understanding this interplay is crucial for tailoring therapeutic strategies, especially regarding immunotherapy.
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BACKGROUND: Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance. METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. A comprehensive search of the PubMed/MEDLINE, SCOPUS, and Cochrane databases was performed until 12 January 2022 utilizing the PICO (Patient, Intervention, Comparison, Outcome) tool. Fifteen English-language studies focusing on isotretinoin-treated acne patients were included. Serum levels of insulin, glucose, and adiponectin were evaluated before and after treatment, and insulin sensitivity was assessed using the HOMA-IR. A meta-analysis was conducted using RevMan 5.4.1 software, and a quality assessment was undertaken using the ROBINS-I tool. RESULTS: The meta-analysis unveiled a statistically significant rise in the post-treatment levels of adiponectin, an anti-inflammatory agent, which inhibits liver glucose production while enhancing insulin sensitivity (SMD = 0.86; 95% confidence interval (95% CI) = 0.48-1.25, p-value < 0.0001; I2 = 58%). Our subgroup analysis based on study type yielded consistent findings. However, no statistically significant outcomes were observed for insulin, glucose levels, and the HOMA-IR. CONCLUSIONS: There is not a clear association between isotretinoin and insulin resistance, but it appears to enhance the serum levels of adiponectin, which participates in glucose metabolism.
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PURPOSE: Pancreatic cancer (PC) is a fatal malignancy with an aggressive course derived from the cells of pancreatic tissue. Gestational diabetes mellitus (GDM) is a state of spontaneous hyperglycemia occurring during gestation and has been suggested as a risk factor PC. Women with a history of GDM revealed a risk rate of 7.1% for the development of PC. The current systematic review aims to investigate the correlation between GDM and the degree to the prevalence of PC. METHODOLOGY: For this systematic review, the PICO model was prepared to construct and outline the exact questions of the study, a PRISMA flow diagram was prepared and quality assessment was conducted using the Newcastle Ottawa Scale (NOS) for Cohort Studies, the NIH Quality Assessment Tool-Criteria for Case Reports and the Cochrane quality assessment tool for Systematic Reviews and Meta-analysis studies. RESULT: A total of eight articles were retrieved from the main databases, and a table was created to summarize the information found. Even though the data found were limited, the quality assessment performed revealed that the articles were of high validity. CONCLUSIONS: It can be concluded that GDM has an association with the development of PC and can be considered as a risk factor.
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Lung cancer is a leading cause of cancer-related deaths globally, includes small cell lung cancer (SCLC), characterized by its aggressive nature and advanced disease at diagnosis. However, the identification of reliable biomarkers for SCLC has proven challenging, as no consistent predictive biomarker has been established. Nonetheless, certain tumor-associated antigens, including programmed death-ligand 1 (PDL1) and Delta-Like Ligand 3 (DLL3), show promise for targeted antibody-based immunotherapy. To ensure optimal patient selection, it remains crucial to comprehend the relationship between PDL1 and DLL3 expression and clinicopathological characteristics in SCLC. In this study, we investigated the expression patterns of PDL1 and DLL3 biomarkers in endobronchial samples from 44 SCLC patients, examining their association with clinical characteristics and survival. High PDL1 expression (>1%) was observed in 14% of patients, while the majority the SCLC patients (73%) exhibited high DLL3 expression (>75%). Notably, we found a positive correlation between high PDL1 expression (>1%) and overall survival. However, we did not observe any significant differences in the biomarkers expression concerning age, sex, disease status, smoking status, or distant metastases. Further subgroup analysis revealed that a high co-expression of both PDL1 (>1%) and DLL3 (100%) antigens was associated with improved overall survival. This suggests that SCLC expressing PDL1 and DLL3 antigens may exhibit increased sensitivity to therapy, indicating their potential as therapeutic targets. Thus, our findings provide novel insights into the simultaneous evaluation of PDL1 and DLL3 biomarkers in SCLC patients. These insights have significant clinical implications for therapeutic strategies, survival prediction, and development of combination immunotherapies.
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Purpose: Postpartum psychosis (PPP) is a serious mental health illness affecting women post-parturition. Around 1 in 1000 women are affected by postpartum psychosis, and the symptoms usually appear within 2 weeks after birth. Postpartum mental disorders are classified into 3 main categories starting from the least to most severe types, including baby blues, postpartum depression, and postpartum psychosis. Materials and Methods: In this systematic review, genetic and epigenetic factors associated with postpartum psychosis are discussed. A PRISMA flow diagram was followed, and the following databases were used as main sources: PubMed, ScienceDirect, and Scopus. Additional information was retrieved from external sources and organizations. The time period for the articles extracted was 5 years. Results: Initially, a total of 2379 articled were found. After the stated criteria were applied, 58 articles were identified along with 20 articles from additional sources, which were then narrowed down to a final total of 29 articles. Conclusions: It can be concluded that there is an association between PPP and genetic and epigenetic risk factors. However, based on the data retrieved and examined, the association was found to be greater for genetic factors. Additionally, the presence of bipolar disorder and disruption of the circadian cycle played a crucial role in the development of PPP.
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Interleukins are potential therapeutic targets that can alter the prognosis and progression of inflammatory bowel disease (IBD). The roles of IL-6, IL-10, IL-17, and IL-23 have been extensively studied, setting the stage for the development of novel treatments for patients with IBD. Other cytokines have been less extensively studied. Members of the IL-20 family, mainly IL-19 and IL-24, are involved in the pathogenesis of IBD, but their exact role remains unclear. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of colonic Tregs in animal models of colitis and patients with IBD. IL-21 is involved in the Th1, Th2, and Th17 responses. Data support a promising future use of these interleukins as biomarkers of severe diseases and as potential therapeutic targets for novel monoclonal antibodies. This review aims to summarize the existing studies involving animal models of colitis and patients with IBD to clarify their role in the intestinal mucosa.