International Journal of Immunopathology and Pharmacology最新文献

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy with poor survival rates. The efficacy of radiotherapy in ATL needs enhancement with radiosensitizing agents. This study investigated whether umbelliprenin (UMB) could improve the therapeutic effects of ionizing radiation (IR) in ATL cells. UMB, a naturally occurring prenylated coumarin, exhibits anticancer properties and has shown synergistic effects when combined with chemotherapeutic drugs. Despite this promising profile, there is a notable lack of research on its potential combinatorial effects with IR, particularly for ATL treatment. UMB was extracted from Ferula persica using thin layer chromatography. MT-2 cells were treated with UMB alone and in combination with various doses of IR, and cell proliferation was assessed via alamarBlue assay. Flow cytometry with annexin V and PI staining was conducted, and candidate gene expression was analyzed by qPCR. In silico analysis involved identifying pathogenic targets of ATL, constructing protein-protein interaction (PPI) networks, and evaluating CDK6 expression in MT-2 cells. Molecular docking was used to determine the interaction between UMB and CDK6. The alamarBlue assay and flow cytometry showed that pretreating ATL cells with UMB significantly (p < .0001) enhanced anti-proliferative effects of IR. The combination index indicated a synergistic effect between UMB and IR. qPCR revealed significant (p < .0001) downregulation of CD44, CDK6, c-MYC, and cFLIPL, and overexpression of cFLIPS. Computational analysis identified CDK6 as a hub gene in the PPI network, and CDK6 overexpression was confirmed in MT-2 cells. Molecular docking revealed a favorable binding interaction between UMB and the ATP-binding site of CDK6, with a JAMDA score of -2.131, surpassing the control selonsertib. The current study provides evidence that UMB enhances the anti-proliferative effects of IR on ATL cells, and highlights the significance of targeting CDK6 in combinatorial approaches.

Objectives: Exposure of spleen tissues to ionizing radiation during radiotherapy can induce cellular stress and immune-dysfunction leading to cellular senescence.

Introduction: The process of a cancerous development is facilitated by the accumulation of senescent cells. This justifies the incorporation of anti-senescent medications during splenic irradiation (SI).

Methods: In this study senescence was induced in the spleen of male albino rats by radiation exposure (5Gy-single whole body gamma-irradiation) then after 2 weeks, oral astaxanthin regimen was started once daily in a dose of 25 mg/kg for 7 consecutive days. Concurrent control groups were carried out.

Results: the present data reflected that irradiation provoked an increase in the oxidative stress biomarkers (nitric oxide, lipid peroxidation and total reactive oxygen species levels)and the inflammatory biomarkers (Myeloperoxidase and interleukin-6). In addition irradiation led to the over expression of stimulator of interferon genes (cGAS-STING), mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) along with the lactate dehydrogenase (LDH), cyclin-dependent kinase inhibitor 1 (p21) cyclin-dependent kinase inhibitor 2A (p16) increment with elevation of tumor suppressor protein (p53) level. However, reduced glutathione contents and catalase activity were reduced post irradiation in spleen tissues, all these changes reflecting induction of cellular senescence. Astaxanthin treatment showed an improvement in the antioxidant/oxidative stress balance, inflammatory biomarkers, histopathological examination and immunohistochemical expressions of the tested proteins in the irradiated rats.

Conclusion: the current findings offer a new insight into the senomorphic effect of astaxanthin following radiation-induced spleen senescence via STING, mTOR, and TLR4 signalling pathways.

Enzyme Che plays an essential role in cholinergic and non-cholinergic functions. It is present in the fertilized/unfertilized eggs and sperm of different species. Inclusion criteria for data collection from electronic databases NCBI and Google Scholar are enzyme AChE/BChE, cholinergic therapy, genomic organization and gene transcription, enzyme structure, biogenesis, transport, processing and localization, molecular signaling and biological function, polymorphism and influencing factors. Enzyme Che acts as a signaling receptor during hematopoiesis, protein adhesion, amyloid fiber formation, neurite outgrowth, bone development, and maturation, explaining the activity out of synaptic neurotransmission. Polymorphism in the Che genes correlates to various diseases and diverse drug responses. In particular, change accompanies cancer, neurodegenerative, and cardiovascular disease. Literature knowledge indicates the importance of Che inhibitors that influence biochemical and molecular pathways in disease treatment, genomic organization, gene transcription, structure, biogenesis, transport, processing, and localization of Che enzyme. Enzyme Che polymorphism changes indicate the possibility of efficient and new inhibitor drug target mechanisms in diverse research areas.

Objective: To explore the effect of miR-370-3p on LPS triggering, in particular its involvement in disease progression by targeting the TLR4-NLRP3-caspase-1 cellular pyroptosis pathway in macrophages.

Methods: Human macrophage RAW264.7 was divided into 6 groups: control, LPS, LPS + inhibitor-NC, LPS + miR-370-3p inhibitor, LPS + mimics-NC and LPS + miR-370-3p mimics. RT-qPCR was used to detect the expression level of miR-370-3p and analyzed comparatively. CCK-8 and flow cytometry assays were used to detect cell viability and apoptosis. ELISA assay was used to detect the levels of IL-1β and TNF-α in the supernatant of the cells. The WB assay was used to detect TLR4, NLRP3, Caspase-1 and GSDMD levels.

Results: After LPS induction, macrophage miR-370-3p levels decreased, cell viability decreased, and apoptosis increased. At the same time, the levels of TLR4, NLRP3, Caspase-1 and GSDMD increased in the cells, and the levels of IL-1β and TNF-α increased in the cell supernatant. Compared with the LPS group, the significantly higher expression level of miR-370-3p in the cells of the LPS + miR-370-3p mimics group was accompanied by significantly higher cell viability, significantly lower apoptosis rate, significantly lower levels of TLR4, NLRP3, Caspase-1, and GSDMD in the cells, and significantly lower levels of IL-1β and TNF-α in the cell supernatant.

Conclusion: MiR-370-3p may be involved in anti-infective immune responses by targeting and inhibiting the macrophage TLR4-NLRP3-caspase-1 cellular pyroptosis pathway.

Introduction: Dry eye is a common ocular condition causing discomfort and visual disturbances. Anti-inflammatory agents like Cyclosporine A (CsA) are often used in its treatment. However, the impact of CsA on ocular flora remains understudied. This research aimed to evaluate changes in conjunctival and nasal microflora in patients receiving topical cyclosporine for dry eye. Methods: In this cross-sectional study, conjunctival and nasal samples were collected from two groups of dry eye patients. Group 1 consisted of 38 patients using CsA eye drops, while Group 2 included 34 patients using preservative-free artificial tear drops. Bacterial cultures were grown from the samples, and the identified organisms underwent antibiotic susceptibility testing. Additionally, alpha diversity metrics were employed to assess the diversity of bacterial species in the samples. Results: Bacterial growth was observed in 75% of conjunctival samples and 97.22% of nasal samples. Staphylococcus epidermidis was the predominant organism in both groups. Alpha diversity analysis showed no significant differences in Shannon diversity and OTU richness between the groups for most bacterial species. Antibiotic susceptibility tests revealed no substantial variations in resistance patterns between the groups. Conclusion: This study provides valuable insights into the impact of CsA eye drops on conjunctival and nasal flora in dry eye patients. The findings suggest that CsA does not significantly influence the composition, diversity, or antibiotic resistance patterns of ocular flora. Long-term topical cyclosporine treatment for dry eye does not significantly impact conjunctival microflora or lead to antibiotic resistance. These results have important implications for the safe use of CsA in patients undergoing ocular treatments, particularly those at risk of intraocular infections.

This study primarily aimed to examine the significance of the C-reactive protein to lymphocyte ratio (CLR), a key marker of inflammation, in relation to the disease progression and management of COVID-19 patients admitted to the intensive care unit (ICU). A total of 464 patients aged 18 years or older, diagnosed with COVID-19 and admitted to the ICU between April 1, 2021, and February 1, 2022, were included in the study. Sociodemographic, laboratory, radiological, and clinical data were collected for each patient. The cohort was then divided into two groups-those who survived and those who did not-and analyzed accordingly. Among the patients included in the study, 58.2% were male, and the mean age was 62.39 ± 15.65 years. The mortality rate was 42%. The analysis revealed that the need for high-flow oxygen and mechanical ventilation increased the risk of death by 9.64 times. Furthermore, for each 1-point increase in the SOFA Score, Charlson Comorbidity Index, and Nutric Score, the risk of death increased by 1.27, 1.18, and 1.40 times, respectively. Intravenous immunoglobulin, administered to a select group of patients, reduced the risk of death by 23.8 times. The optimal threshold value for CLR was identified as 103.05, with values above this increasing the risk of death by 1.84 times. Critically ill patients with CLR values exceeding the identified threshold should receive more intensive monitoring and timely adjustments in treatment. Given that CLR is a simple, accessible, and cost-effective marker, it holds particular value in managing aggressive diseases like COVID-19.

Background: One of the most common long-term neurological disorders affecting children is epilepsy. Even with effective antiseizure medications, one-third of epileptic patients develop drug-resistant epilepsy (DRE). Numerous treatments have been offered to these DRE patients, though with varying degrees of effectiveness.

Objectives: This study aimed to evaluate the effectiveness of probiotics in improving the quality of life (QoL) and lowering the severity and frequency of epileptic episodes in DRE patients. As well as to assess the anti-inflammatory effects of probiotics.

Methods: DRE patients were daily supplemented with one probiotic for 4 months. During these 4 months, patients continued their routine anti-epileptics with no change in the doses. Before and following the 4-month trial, patients had their QoL evaluated using the validated Arabic version of QoL in epilepsy-31 inventory (QoLIE-31) questionnaire, an electroencephalogram (EEG) examination, and serum soluble CD14 (sCD14) evaluation by ELISA.

Results: Of the 21 DRE patients who completed the study, 42.9% achieved the therapeutic goal, which was a ≥50% reduction in seizures. After probiotic, there was a significant increase in time elapsed since the last seizure (p = 0.001) and a decrease in seizure duration (p = 0.038), frequency (p = 0.002), and severity by Chalfont Seizure Severity Score (p < 0.001), as compared to pre-probiotic data. Moreover, there was a significant decrease in serum levels of sCD14 (p < 0.001) and a significant improvement in QoL (p < 0.05).

Conclusion: Probiotics may be used as a DRE adjuvant treatment. They can lessen the number and severity of seizures, alleviate the associated inflammation, and enhance the QoL for DRE patients.

We aimed to evaluate the expression profiles of five circulating lncRNAs (HOTAIR, MALAT-1, XIST, SNHG15, and H19) in DLBCL patients and explore potential associations between their expression and different clinicopathological features. Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma (NHL), exhibits marked genetic and clinical heterogeneity, emphasizing the need for improved tools for risk stratification. Long non-coding RNAs (lncRNAs) emerged as regulators in different cellular processes and have been linked to cancer pathogenesis. Real-time quantitative PCR (qRT-PCR) was used to evaluate lncRNA expression in the plasma of 65 newly diagnosed adult DLBCL patients and 30 age-matched controls. HOTAIR expression was significantly elevated in DLBCL patients, while SNHG15 was significantly downregulated. Interestingly, both HOTAIR and SNHG15 demonstrated robust discriminatory power between DLBCL and healthy individuals, achieving area under the curve (AUC) values of 69% and 71%, respectively. H19 expression displayed a significant association with early-stage (stage I) DLBCL. While upregulated HOTAIR was a significant independent predictor of poor prognosis, high SNHG15 expression appeared to have a protective effect on mortality rates. Our findings suggest that circulating lncRNA expression patterns are promising tools as non-invasive biomarkers for diagnosis of DLBCL. Specific lncRNAs, such as HOTAIR, SNHG15, and H19, could offer potential for disease staging and patient prognosis. Long-term follow-up studies are recommended to further elucidate the interplay between these lncRNAs and survival rates, as well as their interactions with other genetic and pathological features of DLBCL.

Background: Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified into one category, particularly in mucosal areas that are in contact with the external environment.Aims: To explore the morphology, immunophenotype, and molecular changes of Non-neoplastic B-cell predominant lymphoid proliferations (NBPLP) in pathological areas that are exposed to external surroundings which mimicked lymphoma.Methods and Results: 18 cases of Atypical lymphoid hyperplasia (AtLP)  were retrieved in this study. The biopsy samples were mucosal samples obtained from areas exposed to external surroundings, including intestines, urethra, cervix, tonsils, and tongue. Microscopically, there is a different level of B cell hyperplasia accompanied by morphological atypia. We categorized the morphology into 4 groups: type A (7/18), type B (3/18), type C (3/18), type D (5/18). Part of the AtLP was found positive for BCR gene rearrangement (6/15), and TCR gene rearrangement (1/4). The follow-up period ranged from 14.2 to 70 months. No evidence of lymphoma was found. Therefore, we diagnosed all of the presented cases as NBPLP. We illustrated the key differential points and provided valuable diagnostic experience on each subtype.Conclusions: Areas exposed to the external environment are commonly exposed to antigen and easily present with AtLP of NBPLP, accompanying with positive IGH rearrangement. Therefore, a comprehensive evaluation of macroscopic, morphology, immunophenotype, and molecular diagnostics is required to prevent the overdiagnosis of lymphoma.

Objectives: This study aimed to explore the potential correlation between specific single nucleotide polymorphisms (TYK2, IFITM3, IFNAR2, and OAS3 variants) and the severity of COVID-19 in Moroccan patients.

Methods: A genetic analysis was conducted on 109 patients with PCR-confirmed SARS-CoV-2 infection in Morocco. Among these patients, 46% were hospitalized in the intensive care unit, while 59% were not hospitalized. Importantly, all patients lacked known risk factors associated with COVID-19 severity. Genotyping was performed to identify variations in TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079. Statistical analysis was applied using codominant, dominant and recessive logistic regression models to assess correlations with COVID-19 severity.

Results: Our findings revealed no significant correlation between TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079 with COVID-19 severity in Moroccan patients, as indicated in logistic regression models (p > .05). Interestingly, these results may offer insights into the mitigated impact of the COVID-19 pandemic and the reduced severity observed in SARS-CoV-2 infected patients in Morocco. Age, however, exhibited a significant correlation with severity (p < .001), with a trend towards increased likelihood of ICU admission with advancing age. Additionally, In the severe group, a higher proportion of patients were females (54%), indicating a statistically significant correlation with disease severity (p = .04). Nevertheless, female ICU patients aged above 60 years accounted for 37%, compared to 17% for males.

Conclusion: This study underscores the absence of a genetic association between the selected polymorphisms and COVID-19 severity in Moroccan patients. Advanced age emerges as the primary factor influencing the severity of COVID-19 patients without comorbidities. We recommend setting the threshold for advanced age at 60 years as a risk factor for severe forms of COVID-19.