Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BACKGROUND: Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies. MAIN BODY: CIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKs-based therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content of T cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings. CONCLUSION: CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies.

Self-Management among Stroke Survivors in the United States, 2016 to 2021.

Background: Self-management among stroke survivors is effective in mitigating the risk of a recurrent stroke. This study aims to determine the prevalence of self-management and its associated factors among stroke survivors in the United States. Methods: We analyzed the Behavioral Risk Factor Surveillance System (BRFSS) data from 2016 to 2021, a nationally representative health survey. A new outcome variable, stroke self-management (SSM = low or SSM = high), was defined based on five AHA guideline-recommended self-management practices, including regular physical activity, maintaining body mass index, regular doctor checkups, smoking cessation, and limiting alcohol consumption. A low level of self-management was defined as adherence to three or fewer practices. Results: Among 95,645 American stroke survivors, 46.7% have low self-management. Stroke survivors aged less than 65 are less likely to self-manage (low SSM: 56.8% vs. 42.3%; p < 0.0001). Blacks are less likely to self-manage than non-Hispanic Whites (low SSM: 52.0% vs. 48.6%; p < 0.0001); however, when adjusted for demographic and clinical factors, the difference was dissipated. Higher education and income levels are associated with better self-management (OR: 2.49, [95%CI: 2.16-2.88] and OR: 1.45, [95%CI: 1.26-1.67], respectively). Further sub-analysis revealed that women are less likely to be physically active (OR: 0.88, [95%CI: 0.81-0.95]) but more likely to manage their alcohol consumption (OR: 1.57, [95%CI: 1.29-1.92]). Stroke survivors residing in the Stroke Belt did not self-manage as well as their counterparts (low-SSM: 53.1% vs. 48.0%; p < 0.001). Conclusions: The substantial diversity in self-management practices emphasizes the need for tailored interventions. Particularly, multi-modal interventions should be targeted toward specific populations, including younger stroke survivors with lower education and income.

Prevalence and Determinants of Long-Term Post-COVID Conditions in the United States: 2022 Behavioral Risk Factor Surveillance System.

BACKGROUND: A significant proportion of COVID survivors experience lingering and debilitating symptoms following acute COVID-19 infection. According to the national research plan on long COVID, it is a national priority to identify the prevalence of post-COVID conditions and their associated factors. METHOD: We performed a cross-sectional analysis of the Prevention Behavioral Risk Factor Surveillance System (BRFSS) 2022, the largest continuously gathered health survey dataset worldwide by the Centers for Disease Control. After identifying individuals with a positive history of COVID-19, we grouped COVID-19 survivors based on whether they experienced long-term post-COVID conditions. Using survey-specific R packages, we compared the two groups' socio-demographics, comorbidities, and lifestyle-related factors. A logistic regression model was used to identify factors associated with post-COVID conditions. RESULTS: The overall estimated prevalence of long-term post-COVID conditions among COVID survivors was 21.7%. Fatigue (5.7%), dyspnea (4.2%), and anosmia/ageusia (3.8%) were the most frequent symptoms. Based on multivariate logistic regression analysis, female sex, body mass index (BMI)≥25, lack of insurance, history of pulmonary disease, depression, and arthritis, being a former smoker, and sleep duration <7 h/d were associated with higher odds of post-COVID conditions. On the other hand, age >64 y/o, Black race, and annual household income ≥$100k were associated with lower odds of post-COVID conditions. CONCLUSION: Our findings indicate a notable prevalence of post-COVID conditions, particularly among middle-aged women and individuals with comorbidities or adverse lifestyles. This high-risk demographic may require long-term follow-up and support. Further investigations are essential to facilitate the development of specified healthcare and therapeutic strategies for those suffering from post-COVID conditions.

Imaging the post-treatment pelvis with gynecologic cancers.

Gynecological malignancies, such as ovarian cancers, cervical cancers, and endometrial cancers, have a significant global impact. Women with gynecologic malignancies may receive a single or a combination of treatments, including surgery, chemotherapy, and radiation-based therapies. Radiologists utilize various diagnostic imaging modalities to provide the surgeon with relevant information about the diagnosis, prognosis, optimal surgical strategy, and prospective post-treatment imaging. Computerized Tomography (CT) and magnetic resonance imaging (MRI) may be used initially to evaluate and detect post-treatment complications. Although CT is primarily used for staging, MRI is commonly used for a more accurate evaluation of a tumor's size and detection of local invasion. Complications such as hematoma, abscess, inclusion cyst, seroma, tumor thrombosis, anorectovaginal fistula, and gossypiboma may occur after the three primary treatments, and systems such as the genitourinary, gastrointestinal, neurological, and musculoskeletal may be affected. In order to distinguish between early-onset and late-onset complications following gynecological treatment, radiological findings of the most common post-treatment complications will be presented in this review.

The Hepatoprotective Effects of Ginsenoside from Ginseng: A Review of Molecular Mechanisms and Therapeutic Potentials.

Treatment of hepatic diseases presents a significant challenge due to their diverse nature. Ginsenosides, bioactive compounds derived from the root of Panax ginseng and widely used in traditional Chinese medicine, offer multifaceted protection to various organs in the body. Their versatile effects, including antioxidant, anti-inflammatory, anti-apoptotic and more, make them a promising approach for addressing hepatic disorders. This review explores the intricate molecular mechanisms and properties of ginsenosides in the prevention and treatment of liver ailments, from mild conditions to severe damage and liver fibrosis. Given the increasing prevalence of hepatic disorders, this article sheds light on the significant pharmaceutical potential of ginsenosides in the realm of hepatic disease management.

Modulatory Effects of Hydatid Cyst Fluid on a Mouse Model of Experimental Autoimmune Encephalomyelitis.

The reduced burden of helminth parasites in industrialized countries is probably one of the reasons for the increased prevalence of autoimmune disorders such as multiple sclerosis (MS). The current study aimed to evaluate the potential preventive effects of hydatid cyst fluid (HCF) on the disease severity in an EAE mouse model of MS. EAE-induced mice were treated with HCF before and after EAE induction. An RT-PCR-based evaluation of IFN-γ, IL-1ß, TNF, T-bet, IL-4, GATA3, IL-17, RoRγ, TGF-ß, and FOXP3 expression levels in splenocytes and an ELISA-based analysis of IFN-γ and IL-4 levels in cell culture supernatant of splenocytes were performed. Histopathological examinations of mice during the study were also conducted. The expression levels of T-bet, IL-4, GATA3, TGF-ß, and FOXP3 in EAE + HCF mice were significantly higher compared to EAE + PBS mice. In the EAE + HCF group, the expression levels of IFN-γ, IL-1ß, and TNF were significantly lower than in the EAE + PBS group. The histopathological results showed significantly reduced inflammation and demyelination in EAE + HCF mice compared to EAE + PBS mice. Our study provides proof-of-concept in the EAE mouse model of MS that helminth-derived products such as HCF have a potential prophylactic effect on MS development and present a novel potential therapeutic strategy.

Combined systemic inflammatory indexes as reflectors of outcome in patients with COVID­19 infection admitted to ICU.

INTRODUCTION: The principal etiology of mortality in COVID-19 patients is the systemic pro-inflammatory processes which may lead to acute respiratory distress syndrome. Hematologic indices are reachable representatives of inflammation in patients with COVID-19 infection. The purpose of the current study was to evaluate the potential predictive value of these inflammatory indices in the in-hospital mortality of ICU-admitted COVID-19 patients. The studied indexes included AISI, dNLR, NLPR, NLR, SII, and SIRI. METHOD: 315 COVID-19 patients admitted to ICU managed in Imam Khomeini Hospital of Urmia, Iran, during the last 6 months of 2020 were retrospectively enrolled in the study and divided into two subgroups based on their final outcome, discharge or death. RESULTS: Total leucocyte count (TLC), absolute neutrophil count (NLC), urea, Cr, RDW, AISI, dNLR, NLPR, NLR, SII, and SIRI were drastically elevated in the dead patients (P < 0.05). The optimal cut-off points for AISI (378.81), dNLR (5.66), NLPR (0.03), NLR (5.97), SII (1589.25), and SIRI (2.31) were obtained using ROC curves. NLR and SII had the highest sensitivity (71.4%) and specificity (73.6%), respectively. Patients with above-cut-off levels of ISI, dNLR, NLPR, NLR, and SII had lower average survival time. Age (OR = 1.057, CI95%: 1.030-1.085, p < 0.001) and dNLR (OR = 1.131, CI95%: 1.061-1.206, p < 0.001) were the independent predictors for mortality in the studied COVID-19 patients based on multivariate logistic regression. CONCLUSION: Age and dNLR are valuable predictive factors for in-hospital death of ICU-admitted COVID-19 patients. Besides, other indices, AISI, NLPR, NLR, SII, and SIRI, may have an additional role that requires further investigation.

Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.

BACKGROUND: Targeting influential factors in resistance to chemotherapy is one way to increase the effectiveness of chemotherapeutics. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway overexpresses in chronic lymphocytic leukemia (CLL) cells and appears to have a significant part in their survival and chemotherapy resistance. Here we produced novel nanoparticles (NPs) specific for CD20-expressing CLL cells with simultaneous anti-Nrf2 and cytotoxic properties. METHODS: Chitosan lactate (CL) was used to produce the primary NPs which were then respectively loaded with rituximab (RTX), anti-Nrf2 Small interfering RNA (siRNAs) and Cyclophosphamide (CP) to prepare the final version of the NPs (NP-Nrf2_siRNA-CP). All interventions were done on both peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMNCs). RESULTS: NP-Nrf2_siRNA-CP had satisfying physicochemical properties, showed controlled anti-Nrf2 siRNA/CP release, and were efficiently transfected into CLL primary cells (both PBMCs and BMNCs). NP-Nrf2_siRNA-CP were significantly capable of cell apoptosis induction and proliferation prevention marked by respectively decreased and increased anti-apoptotic and pro-apoptotic factors. Furthermore, use of anti-Nrf2 siRNA was corresponding to elevated sensitivity of CLL cells to CP. CONCLUSION: Our findings imply that the combination therapy of malignant CLL cells with RTX, CP and anti-Nrf2 siRNA is a novel and efficient therapeutic strategy that was capable of destroying malignant cells. Furthermore, the use of NPs as a multiple drug delivery method showed fulfilling properties; however, the need for further future studies is undeniable. Video Abstract.

Circular RNAs as novel biomarkers in glomerular diseases.

Circular RNAs (circRNAs) regulate gene expression and biological procedures by controlling target genes or downstream pathways by sponging their related miRNA (s). Three types of circRNAs have been identified; exonic circRNAs (ecircRNAs), intronic RNAs (ciRNAs), and exon-intron circRNAs (ElciRNAs). It is clarified that altered levels of circRNAs have dynamic pathological and physiological functions in kidney diseases. Evidence suggests that circRNAs can be considered novel diagnostic biomarkers and therapeutic targets for renal diseases. Glomerulonephritis (GN) is a general term used to refer to a wide range of glomerular diseases. GN is an important cause of chronic kidney diseases. Here, we review the biogenesis of circRNAs, and their molecular and physiological functions in the kidney. Moreover, the dysregulated expression of circRNAs and their biological functions are discussed in primary and secondary glomerulonephritis. Moreover, diagnostic and therapeutic values of circRNAs in distinguishing or treating different types of GN are highlighted.

The effect of Fingolimod on patients with moderate to severe COVID-19.

Hyper-inflammation, cytokine storm, and recruitment of immune cells lead to uncontrollable endothelial cell damage in patients with coronavirus disease 2019 (COVID-19). Sphingosine 1-phosphate (S1P) signaling is needed for endothelial integrity and its decreased serum level is a predictor of clinical severity in COVID-19. In this clinical trial, the effect of Fingolimod, an agonist of S1P, was evaluated on patients with COVID-19. Forty patients with moderate to severe COVID-19 were enrolled and divided into two groups including (1) the control group (n = 21) receiving the national standard regimen for COVID-19 patients and (2) the intervention group (n = 19) that prescribed daily Fingolimod (0.5 mg) for 3 days besides receiving the standard national regimen for COVID-19. The hospitalization period, re-admission rate, intensive care unit (ICU) administration, need for mechanical ventilation, and mortality rate were assessed as primary outcomes in both groups. The results showed that re-admission was significantly decreased in COVID-19 patients who received Fingolimod compared to the controls (p = .04). In addition, the hemoglobin levels of the COVID-19 patients in the intervention group were increased compared to the controls (p = .018). However, no significant differences were found regarding the intubation or mortality rate between the groups (p > .05). Fingolimod could significantly reduce the re-admission rate after hospitalization with COVID-19. Fingolimod may not enhance patients' outcomes with moderate COVID-19. It is necessary to examine these findings in a larger cohort of patients with severe to critical COVID-19.

The role of SF3B1 and NOTCH1 in the pathogenesis of leukemia.

The discovery of new genes/pathways improves our knowledge of cancer pathogenesis and presents novel potential therapeutic options. For instance, splicing factor 3b subunit 1 (SF3B1) and NOTCH1 genetic alterations have been identified at a high frequency in hematological malignancies, such as leukemia, and may be related to the prognosis of involved patients because they change the nature of malignancies in different ways like mediating therapeutic resistance; therefore, studying these gene/pathways is essential. This review aims to discuss SF3B1 and NOTCH1 roles in the pathogenesis of various types of leukemia and the therapeutic potential of targeting these genes or their mutations to provide a foundation for leukemia treatment.

Dysregulation of immunity in COVID-19 and SLE.

The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19.

Evaluation of telomeric KIR genes and their association with CMV infection in kidney transplant recipients.

Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Despite the immunosuppressed state, natural killer (NK) cells remain the major immune defense cells against viral infections in transplanted patients. The present study aimed at elucidating the correlation between the number of inhibitory and activating genes and the incidence of CMV infection in kidney transplanted recipients. Kidney transplanted recipients including 51 CMV+ and 50 CMV- were genotyped for the presence or absence of 4 activating (KIR2DS1, KIR2DS4, KIR2DS5, KIR3DS1) and 2 inhibitory (KIR3DL1, KIR2DL5a) genes using polymerase chain reaction sequence-specific primers (PCR-SSP) assay. Our results showed that CMV infection occurred in 50.49% of kidney allograft recipients. In addition, there was a significant correlation between the presence of the KIR2DS1 activating gene in the CMV- group compared to the CMV+ group (p = 0.033). The other three activating KIR receptors did not show a correlation with CMV infection. Our results suggest that the prevalence of the KIR activating KIR2DS1 gene may reduce the rate of CMV infection after kidney transplantation in our population.