davood bashash

Despite therapeutic advancements, treatment failure in hepatocellular carcinoma (HCC) continues to pose a significant obstacle. Given the vital role of the tumor immune microenvironment (TIM) in HCC and the promising effectiveness of immune therapies, we aimed to elucidate potential predictive biomarkers by developing a prognostic model based on immune-related genes (IRGs). After obtaining data, differentially expressed IRGs were identified, and prognostic models were developed using Cox regression analyses. Key contributors of the model were identified and the results were validated by experimental assays in HCC cell lines. Our eight-IRG signature can serve as an independent prognostic factor in HCC. The low-risk group exhibited superior overall survival and lower tumor mutation burden (TMB). The high-risk group showed elevated proportions of immune cells, including regulatory T cells and resting CD4+ memory T cells. We found that the NEAT1-C1/miR-542-5p/BIRC5 regulatory network may serve as a potential target in HCC. The experimental investigations showed that BIRC5 inhibition reduced the metabolic activity in four HCC cell lines. The results of this study facilitate patient stratification and the development of more effective treatment strategies, particularly for high-risk HCC patients.

The importance of the gut microbiota in human health and disease has been known for a long time. Current investigations involving preclinical and clinical studies have presented numerous lines of evidence indicating that gut microbiota can influence the effectiveness of cancer immunotherapies, particularly immune checkpoint inhibitors (ICIs). The gut microbiota can alter the immune response in the tumor microenvironment (TME) by engaging with innate and adaptive immune cells. Notably, one of the primary methods by which the gut microbiota modulates antitumor immunity is through the production of metabolites, which are small molecules capable of traveling from the gut to other parts of the body and influencing local and systemic antitumor immune responses. This exploration of mechanisms has yielded valuable insights for developing microbiota-based therapeutic strategies such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites. In this review, we explored several possible interventions that could enhance the efficacy of ICIs, thereby potentially restoring or augmenting patient responses to these therapeutic agents.

Multiple myeloma (MM) is a malignancy of plasma cells, terminally differentiated B cells, with complications like hypercalcemia, renal failure, anemia, and bone disease, which are also known as CRAB criteria. MM develops from monoclonal gammopathy of unknown significance (MGUS), a pre-malignant plasma cell dyscrasia. Over some time, MGUS has the potential to progress into smoldering multiple myeloma (SMM), which can evolve into MM. MM rarely progresses into plasma cell leukemia (PCL), a condition in which malignant plasma cells no longer stay in the bone marrow niche and circulate in the peripheral blood. In MM, various soluble factors play important roles, and  interleukin-6 has different vital roles. Interleukin-6, an inflammatory cytokine, has significant roles in the growth, survival, angiogenesis, metastasis, and apoptosis resistance in MM. Interleukin-6 is produced and secreted by both autocrine from myeloma cells and paracrine from bone marrow stromal cells. To tackle MM, various therapeutic approaches were applied over many years, and according to the results, most patients with MM can respond well to first-line treatment. However, the majority of patients may relapse as conventional treatment may not be curative. So, there is an urgent need for novel cell-based and cell-free therapeutic strategies, such as mesenchymal stem cell-based therapies and their products to offer new therapeutic strategies for MM.

In the present study, we investigated the impacts of exosomes derived from human placental mesenchymal stem cells (hPMSCs) on apoptosis and interleukin-6 expression in a myeloma cell line, U-266, for the first time. hPMSCs were isolated from the human placenta and cultured in a DMEM medium. After characterizing the cells and acknowledging their identity, they underwent several passages and their supernatant was collected to harvest exosomes. The exosomes were isolated by ultracentrifugation and characterized by DLS and TEM, and their concentration was measured by BCA protein assay. U266 cells were treated with different concentrations of exosomes and then MTT and annexin/propidium iodide flow cytometry tests were performed to evaluate cell viability. Afterward, a real-time PCR test was performed to evaluate interleukin-6 gene expression.

According to our findings, treatment of U-266 cells with hPMSCS-derived exosomes led to the preservation of myeloma cells without changes in their cell cycle. Surprisingly, treatments did not hinder the expression of interleukin-6 in the myeloma cells.

In MM patients, interleukin-6 plays different roles, and it is a desirable target to design new therapeutic strategies. To evaluate the effects of new therapeutic strategies, we designed and performed our study to estimate the effects of cell-free therapeutic strategy.  In the present study, the impacts of hPMSCS-derived exosomes on the viability of MM cells and interleukin-6 gene expression were evaluated. The results showed that hPMSCS-derived exosomes resulted in the perseverance of myeloma cells without changes in the cell cycle.  Furthermore, the interleukin-6 gene expression level showed no significant change.

Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees’ royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells.

The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes. 

RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells’ transition to the S phase of the cell cycle through p21 up-regulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells.

Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells’ programmed cell death. However, further studies are required to examine this compound’s pharmaceutical application.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with atherosclerosis servingas a primary factor in their development. Platelets, leukocytes, and their interactions play a crucial role ininitiating and amplifying atherosclerosis. This study aims to evaluate the levels of platelet-monocyte aggregates (PMA)and specific integrins involved in leukocyte recruitment, including macrophage-1 antigen (Mac-1) and lymphocytefunction-associated antigen-1 (Lfa-1), in patients with acute coronary syndrome (ACS). In this case-control study, thirty-two subjects with ACS and 30 healthy individuals participated.It aimed to evaluate PMA expression and the median fluorescence intensity (MFI) of Mac-1 and Lfa-1 using flowcytometry. Dot plots and Pearson correlation coefficient were employed to examine the relationship between PMA,Mac-1, and Lfa-1. Multilevel model analysis was used to explore the effects and relationships of various parameters,including Mac-1 and Lfa-1, on PMA. Finally, receiver operating characteristic (ROC) curves were utilized to assessthe diagnostic accuracy of PMA, Mac-1, and Lfa-1 markers. It was observed that patients had higher PMA levels compared to the control group (58.99 ± 16.27 vs.29.99 ± 4.19 in controls, P<0.001), which correlated with PLT (ρ=0.512, P=0.035). Additionally, CD18 and CD11bexpression on monocytes were significantly elevated in patients (P<0.001) and were positively associated with PMA(β=19.09, P<0.001; β=6.90, P=0.022), but no significant relationship between CD11a and PMA was observed (β=5.06,P=0.315). PMA and Mac-1 were identified as better markers for differentiating patients from healthy individuals.(respectively, AUC=0.94, Sensitivity= 0.84, specificity=0.98; AUC=0.84, Sensitivity= 0.93, specificity=0.70). The study results indicated an increase in both Mac-1 and PMA levels in patients with ACS. Additionally,the significant association observed between Mac-1 and PMA in the patient group suggests a potential relationshipbetween these markers and ACS.

CD4+/CD8+ double-positive (DP) thymocytes are normal cells within the thymus. However, the presence of mature DP T cells is indicative of cancer and abnormality in peripheral blood. Philadelphia+ (Ph+) T-ALL is extremely rare, but it holds significant therapeutic and prognostic implications. The incidence and outcomes of BCR-ABL+ T-ALL remain uncertain, and distinguishing it from T-cell lymphoblastic crises of CML can be challenging. The current document discussed a rare case of CD4+/CD8+ BCR-ABL+ T-ALL in an 11-year-old Iranian male, detailing his medical conditions, laboratory findings, and treatment. The patient presented with enlarged lymph nodes, splenomegaly, anemia, leukocytosis, and severe thrombocytopenia. The blood smear was nearly filled with irregular/convoluted and cleaved nuclear blasts with fine chromatin. The patient received imatinib with induction chemotherapy. After two months, the patient achieved complete remission with undetectable Minimal/Measurable Residual Disease (MRD). By detailing the patient's characteristics and the required tests, the manuscript contributes to a deeper understanding of this complex disease subtype. Furthermore, by examining and comparing the current case with other available cases, the study lays the groundwork for better characterizing the disease and developing more effective therapeutic strategies.

Despite the advances in treatment, breast cancer (BC) remains a major cause of death in women. Thisstudy aims to evaluate the prognostic significance of detecting circulating tumor cells (CTCs) and disseminated tumorcells (DTCs) in paired peripheral blood (PB) and bone marrow (BM) samples obtained both before and after adjuvantchemotherapy from patients with operable BC. In this experimental study, from 160 patients with primary BC, we collected 160 PB and BM samplesbefore and we could be able to collect PB and BM samples from 100 of them after adjuvant chemotherapy. The expressionlevel of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin 1 (MGB1), mucin 2 (MUC2) and trefoil factor1 (TFF1) mRNAs in the PB/BM samples were analyzed by quantitative real-time polymerase chain reaction (PCR). Multivariate Cox regression analyses indicated that the detection of CK19 mRNA-positive CTCs/DTCs eitherbefore or after adjuvant chemotherapy was an independent factor for prognosis associated with decreased diseasefreesurvival (DFS). Patients with tumor cells detected in both PB and BM and patients with persistent detection oftumor cells before and after chemotherapy had worse outcomes compared to those with tumor cells detected in one orneither of the compartments. This study suggests that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvantchemotherapy could be an independent predictor of DFS in operable BC patients.

The emergence of technology has long been a defining characteristic of human civilization, and in our current era, artificial intelligence (AI) stands as one of the most advanced innovations. Through the integration of AI into machines, the aim has been to unlock unprecedented levels of convenience. However, we now find ourselves at a crucial juncture where a significant question arises: Do humans continue to hold dominion, or have AI-equipped machines taken the reins? With its profound ability to reshape human capabilities, it is not surprising to propose that AI may represent the next stage of evolution. As we delve deeper into the potential of AI, it becomes imperative to ponder whether the emergence of AI as a form of evolved human beings is inevitable, and if so, what implications it may hold for the future of humanity. Taken together, it is essential for society to ensure the development and deployment of AI in a manner that prioritizes the safety and well-being of humanity while also giving careful consideration to ethical and legal concerns.

The field of cancer research has been profoundly impacted by the utilization of artificial intelligence (AI), particularly through the analysis of medical records encompassing genomics, transcriptomics, proteomics, and imaging data. Subdomains of AI, such as machine learning (ML) and deep learning (DL), possess the capability to analyze intricate patterns within these records. This allows for groundbreaking advancements in cancer diagnosis, prognosis, and treatment by extracting valuable insights from sources such as histology and radiology imaging. The integration of AI-based models has led to improved prediction, diagnosis, and even treatment of various types of cancer, resulting in enhanced performance within the field of oncology. However, AI also faces challenges including ethical and legal considerations, data quality and accessibility, and issues pertaining to model interpretability. It is crucial to develop and evaluate AI-based systems in collaboration with clinicians and researchers to ensure their safety, reliability, and validity in cancer research.

Severe congenital neutropenias (SCNs) are the rare heterogenous group of preleukemia bone marrow failure syndromes characterized by impaired differentiation of neutrophilic granulocytes and, as a result, severe chronic neutropenia. Patients with SCN are predisposed to recurrent, often life-threatening bacterial and/or fungal infections beginning in the first months of life. Molecular abnormalities in 10 genes have been identified that are responsible for SCNs. The pathophysiological mechanisms of SCNs are the subject of extensive investigation and are not fully known. The current review aims to summarize the studies exploring the biological role of SCN-associated genes and the effects of mutant genes in neutropenia pathogenesis. We mainly focus on the genetic mutations that lead to SCN1 to SCN9 and X-linked SCN (XSCN) to shed more light on the pathophysiology of these diseases.

The identification of long non-coding RNAs (lncRNAs) in the pathogenesis of acute myeloid leukemia (AML) has marked a new era in the molecular understating of the disease. This study investigated the correlation between the changes in the expression of lncRNAs, including HOTAIR, PVT-1, and CRNDE, and the alteration in the expression profile of FLT-3, c-Myc, STAT3, STAT5, and p27 in AML patients.

Blood samples were collected from forty-one newly diagnosed AML patients and ten healthy individuals to evaluate the expression levels of the study genes using qRT-PCR analysis. The probable correlation between the gene expressions was determined using Pearson’s correlation test.

The results showed that while there was a significant elevation in the expression of FLT3, c-Myc, STAT3, and HOTAIR, p27 expression remarkably diminished in AML patients compared to the control group. Also, a correlation was found between the expression of FLT-3 and p27 and the expression of HOTAIR and STAT3. It was assumed that FLT-3 had a role in increasing the proliferative and survival capacity of AML cells, at least partly, through c-Myc-mediated suppression of p27. Moreover, lncRNA HOTAIR showed to be involved in leukemia proliferation assumably by enhancing the expression of STAT3.

Overall, the results of gene profile analysis suggested that studying the expression of HOTAIR, FLT-3, c-Myc, STAT3, and p27 could be helpful to AML patients, and each of these genes could be a valuable target for pharmaceutic intervention.

 Acute myeloid leukemia (AML) is described by the clonal expansion of myeloid blasts with abnormal differentiation. Considering the role of Toll-like receptors (TLRs) in inflammation induction and the effect of chronic inflammation on cancer development, investigating the state of TLRs’ expression in human malignancies has attracted scientists’ attention.

 In this study, 36 newly-diagnosed AML patients and 36 control samples were examined. The mRNA expression levels of TLR1/2/4/7/8 were measured in both groups using real-time PCR. The student’s t-test was utilized to compare gene expression levels between the two populations and the one-way ANOVA test was used to compare data among multiple subtypes.

All TLR gene expression levels were significantly up-regulated in patients compared to the control group (p<0.05). Positive correlations between different TLRs were observed as well. AML patients under the age of 55 showed significantly higher TLR1/2/4 expression in comparison with healthy individuals of the same age; a similar comparison in people above 55 also showed an elevated expression of TLR1/2/4/8. Male patients overexpressed almost all genes compared to healthy subjects; the levels of TLR1/2/4 were also higher in female patients. No difference was observed comparing blast percentages and FAB subtypes.

 By considering the results of this experiment, it seems that TLRs up-regulation in AML patients may contribute to the pathogenesis and development of the disease; however, more investigations are required to elucidate the exact roles of these receptors in AML. 

Although Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), not all patients reach complete remission and a considerable proportion of the patients develop resistance to Imatinib.

In an attempt to increase the tail on the survival curve, we conducted a Phase I/II study of PR1/BCR-ABL multipeptides vaccination trial in CML patients with at least 15 months of Imatinib treatment and 5 months of persistent molecular residual disease.

One month after the completion of the vaccinations, 4 patients nearly developed a 1-log fall in their BCR-ABL transcript level, with 4 patients achieving a major molecular response (MMR). Nine patients were followed for more than a period of 7 years. The vaccinations were associated with a MMR in five patients and a complete molecular response (CMR) in one patient. The removal of Imatinib in two patients who achieved MMR after the vaccinations led to a resurgence of the leukemia population and relapse.

Our study suggests that a combination of immunotherapy with Imatinib targeted therapy keeps the leukemia population under control, improving the long-lasting clinical and molecular response of CML patients, for at least 7 years.

Minimal residual disease (MRD) is considered the greatest prognostic factor in acute lymphoblastic leukemia(ALL). MRD is a valuable tool for anticipating impending relapse and treatment response assessment. The objective ofthe present study was to investigate whether the detection of IgH gene rearrangement using polymerase chain reaction(PCR)-based GeneScan analysis could be a complementary method to monitor MRD along with the quantitative realtimePCR (qPCR). In this cross-sectional study, we valued the MRD levels, based on the GeneScanning analysis(GSA), and then compared the data with quantitative real-time polymerase chain reaction at different time points inperipheral blood (PB) samples of adult B-lineage ALL patients (n=35). The specific polymerase chain reaction (PCR)primers for IGH gene FR-1 and fluorescence-labeled J-primer were used and analyzed by capillary gel electrophoresison a sequencer. The results of this study were compared with the previously reported MRD results obtained by the IGHrearrangements allele-specific oligonucleotide (ASO) -qPCR methods. The total concordance rate was 86.7%, with a P<0.001. MRD results obtained by GSA and ASO-qPCR methodswere concordant in all diagnostic samples and samples on the 14th and 28th days of induction therapy. The results of these 2.5years’ follow-ups demonstrated a significant correlation between the two techniques (r=0.892, P<0.001). It seems that the PCR-based GeneScan analysis of IGH gene rearrangement detection may be a valuablemolecular technique to distinguish monoclonality from polyclonality. And also, it may be a precise tool to detect theresidual leukemic DNA in the PB follow-up samples of patients.

The accumulation of oxidized LDL (ox-LDL) in macrophages in association with platelet activity leads to the formation of foam cells, which play a key role in the pathophysiology of atherosclerosis and coronary artery diseases (CAD). Here, in this study, we aimed to investigate the simultaneous effect of ox-LDL and platelets on foam cell formation, as well as modification in cell markers. 

First, the U937, a human monocytic cell line,  was cultured in RPMI-1640. Then, isolated platelets were co-cultured with the U937 and exposed to ox-LDL (80 µg/ml) to evaluate the impact of ox-LDL on foam cell formation using Oil red O (ORO) staining. Also, the expression of foam cells’ surface markers and CD36, ABCA1, SR-B1, ACAT1, and LXRα genes, which are involved in macrophage metabolism and ox-LDL uptake, was measured by flow cytometry and real-time PCR, respectively. 

Our findings suggest that platelets promoted foam cell formation (ORO-positive cells), accompanied by a higher level of CD163+ M2 macrophages. Furthermore, the expression of CD36, ABCA1, SR-B1, ACAT1, and LXRα genes, which are implicated in cholesterol accumulation in macrophages, was significantly upregulated in the ox-LDL+ platelets group compared to the control (P < 0.05). Moreover, the up-regulation of CD36, ABCA1, and SR-B1 genes in the ox-LDL+ platelets group was more accentuated compared to the ox-LDL group (P < 0.05).

Owing to the positive effector role of platelets in the formation of foam cells and CD163+ cells, it could be assumed that platelets play a dual role in the development of these cells.

The latest treatments have improved outcomes for patients with hematological malignancies, but relapse, treatment resistance and particularly side effects still remain as common limitations of these treatments. Given the disadvantages of the existing conventional therapeutic methods, developing more effective drugs with less toxicity and side effects is of paramount importance. Medicinal herbs have historically proven their worth as a pool of potential therapeutic agents for leukemia and lymphoma, and today they still represent a rich source for the recognition of new drug leads. The role of the positive synergistic effects of plant-derived natural products and common chemotherapeutic drugs is also considered as one of the rational reasons for paying attention to the medicinal plants in recent chemoprevention and chemotherapeutic investigations. Noteworthy, targeted delivery of plant-derived natural products via the incorporation of nanoparticles or antibodies would be a major step to improve their bioavailability and then to increase their therapeutic effects. In this study, we reviewed plant-derived agents approved and/or under investigation for hematological malignancies.

Therapeutic approaches for acute myeloid leukemia (AML) have remained largely unchanged for over 40 years and cytarabine and an anthracycline (e.g., daunorubicin) backbone is the main induction therapy for these patients. Resistance to chemotherapy is the major clinical challenge and contributes to short-term survival with a high rate of disease recurrence. Given the established efficacy of nanoparticles in cancer treatment, this study was designed to evaluate the anticancer property of our novel nanocomposite in the AML-derived KG1 cells.

To assess the anti-leukemic effects of our nanocomposite on AML cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of nanocomposite on cell cycle and apoptosis.

Our results outlined that ZnO/CNT@Fe3O4 decreased viability and metabolic activity of KG1 cells through induction of G1 arrest by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors and decreasing c-Myc transcription. Moreover, ZnO/CNT@Fe3O4 markedly elevated the percentage of apoptotic cells which was coupled with a significant alteration of Bax and Bcl-2 expressions. Synergistic experiments showed that ZnO/CNT@Fe3O4 enhances the cytotoxic effects of Vincristine on KG1 cells.

In conclusion, this study sheds light on the potent anti-leukemic effects of ZnO/CNT@Fe3O4 and provides evidence for the application of this agent in the treatment of acute myeloid leukemia.

Although the complex structure of acute lymphoblastic leukemia (ALL) andinvolvement of diverse pathways in its pathogenesis have put an obstacle in the way of efficienttreatments, identification of strategies to manipulate the genome of neoplastic cells has madethe treatment prospective more optimistic.

To evaluate whether the transduction of apoptin __a gene encoding a protein thatparticipates in the induction of apoptosis__ could reduce the survival of leukemic cells, wegenerated recombinant lentivirus expressing apoptin, and then, MTT assay, flow cytometricanalysis of DNA content, western blotting, and quantitative reverse transcription polymerasechain reaction (qRT-PCR) were applied.

Transduction of apoptin into different leukemic cells was coupled with the reductionin the viability and proliferative capacity of the cells. Among all tested cell lines, Nalm-6 andC8166 were more sensitive to the anti-leukemic property of apoptin. Moreover, we found thatthe transduction of apoptin in the indicated cell lines not only induced G2/M cell cycle arrestbut also induced apoptotic cell death by altering the balance between pro- and anti-apoptotictarget genes. The efficacy of apoptin transduction was not limited to these findings, as wereported for the first time that the overexpression of this gene could potentiate the anti-leukemicproperty of pan PI3K inhibitor BKM120.

The results of this study showed that the transduction of apoptin into lymphoblasticleukemia cell lines induced cytotoxic effects and enhanced therapeutic value of PI3K inhibition;however, further investigations are demanded to ascertain the safety and the efficacy of apoptintransduction in patients with ALL.

The heterogeneity, high rate of mortality and lack of comprehensive diagnostic methods have categorized primary sarcomas of the thorax as a malignancy with dismal outcomes and unknown etiology. Given the fundamental role of epidemiological analysis in establishing management strategies, we designed a study with focus on the epidemiological characteristics of primary thoracic sarcomas in Iran. 

This national population-based cancer study was conducted on patients with histologically confirmed sarcoma of the thorax referred to the Iranian National Cancer Registry between 2009 and 2014. The incidence was calculated as number of cases per 100,000 person-years and was age-adjusted by the direct method using the weight of the 1960 world standard population. 

Over a 6-year period, 1477 cases with pathologically confirmed thoracic sarcomas were registered in Iran, of which 896 were male and 581 were female. Khuzestan Province had the highest incidence of thoracic sarcomas as compared to other provinces. Malignant mesothelioma was the most common histological subtype (20.85%). Moreover, the age-standardized incidence rate (ASR) of the disease was 1.94 per 100,000 which was more common in males than females with the highest incidence rate in men aged more than 65 years.

Our study provided valuable epidemiologic data on characteristics of thoracic sarcomas. This data can be used for strategizing preventive measures.

Glioblastoma (GBM), the most aggressive and common form of glioma, accounts for over 13,000 death per year in the United States which indicates the importance of developing novel strategies for the treatment of this fatal malignancy. Although Arsenic trioxide (ATO) hinders the growth and survival of GBM cells, the requirement of concentrations higher than 4 μM for triggering apoptotic cell death has questioned its safety profile. Since the NF-κB signaling pathway plays a crucial role in tumorigenesis and chemo-resistance, targeting this oncogenic pathway may sensitize GBM cells to lower concentrations of ATO.

Anti-tumor effects of ATO as monotherapy and in combination with Bay 11-7082 were determined using MTT, crystal violet staining, Annexin V/PI staining and scratch assays. Quantitative reverse transcription-PCR (qRT-PCR) analysis was applied to elucidate the molecular mechanisms underlying the anti-tumor activity of this combination therapy.

Our results revealed that ATO and Bay 11-7082 synergistically inhibited the proliferation and survival of GBM cells. Also, it was revealed that NF-κB inhibition using Bay 11-7082 enhanced the inhibitory effects of ATO on migration of GBM cells via suppressing the expression of NF-κB target genes such as TWIST, MMP2, ICAM-1, and cathepsin B. Furthermore, combination treatment of GBM cells with ATO and Bay 11-7082 significantly induce apoptotic cell death coupled with downregulation of NF-κB anti-apoptotic target genes including Bcl-2 and IAP family members.

Altogether, these findings suggest that combination therapy with ATO and Bay 11-7082 may be a promising strategy for the treatment of GBM.

Since coronary artery disease (CAD) is one of the leading causes of death globally, identifying new risk factors can augment risk assessment. This study aimed to investigate the surface expression of stromal cell-derived factor-1 (SDF-1), CXCR4, and CXCR7 on the platelets of CAD patients and to determine whether there is a correlation between their expressions and left ventricular ejection fraction (LVEF).

Sixty CAD patients and 60 healthy volunteers as normal controls were studied. The mean fluorescence intensity (MFI) of SDF-1 and its receptor expression was evaluated by flow cytometry. Biochemical markers and platelet parameters were investigated with an AutoAnalyzer and a cell counter, respectively.

The platelets of the CAD group expressed SDF-1 and CXCR4 significantly more than those of the control group (MFI=1112±304 vs 943±131; P=0.042 and MFI=23372±6804 vs 20634±3482; P=0.033, respectively). Nevertheless, no significant difference was found in the platelet expression of CXCR7 between the CAD and control groups (MFI=35256±8706 vs 25053±7270; P=0.061). Notably, increased expression levels of SDF-1 and CXCR4 were associated with decreased LVEF (r= −0.388, P=0.003 and r= −0.431, P=0.001).

Our findings demonstrated that the overexpression of SDF-1 and CXCR4 on platelets could be considered a promising candidate indicating that asymptomatic patients with decreased LVEF may be at the risk of CAD. (Iranian Heart Journal 2022; 23(1): 42-53)

The heterogeneous nature of hematopoietic sarcoma has restricted the diagnosis and treatment of this disease to the extent that annually, several patients lose their lives. Given the lack of comprehensive epidemiologic information on the incidence of hematopoietic sarcoma in the Iranian population, we designed the present study to evaluate the distribution pattern of this disease.

In this national population-based cancer registry study, we collected data from patients diagnosed with hematopoietic sarcoma who were registered in the Iran National Cancer Registry (INCR) between 2009 and 2013. For each patient, the variables of age, sex, province, year of diagnosis, site of involvement and morphology were collected.

In 45 cases from 18 provinces of Iran, we found that the incidence rate of the disease was 0.60 (95% CI: 0.44–0.80) per million persons. Among all provinces, Ilam had the highest incidence of hematopoietic sarcoma with a rate of 2 (95% CI: 0.05– 11.14) per million persons, while Isfahan had the lowest incidence with a rate of 0.21 (95% CI: 0.01–1.16) per million persons. The incidence rate of the disease increased with age and the disease was slightly more common in men (0.63 [95% CI: 0.41–0.94] vs. 0.56 [95% CI: 0.35–0.86] per million persons). The frequency of hematopoietic sarcoma in connective and soft tissues was higher than other anatomical sites and we found that myeloid morphology was the most prevalent morphology.

The resulting data provided a valuable perspective on the distribution pattern of hematopoietic sarcoma in Iran; however, further studies are required to confirm these results.

 Acute lymphoblastic leukemia (ALL) is the most frequent form of malignant neoplasia diagnosed in ages 0 to 14 years old. Efforts have not yet converted into a better prospect. Bone marrow relapse is still the leading cause of person-year of life lost in this malignancy.

 This study aimed at identifying the associated risk factors for relapse and mortality for pediatric patients with ALL in standard and high-risk groups.

 This study included a cohort of pediatric (0 - 16 years old) patients with ALL referred to Sheikh Hospital, Mashhad, Iran from 2007 to 2016. The demographic, clinical, and laboratory information were considered. Hazard ration (HR) with 95% highest posterior density region was obtained, using a Bayesian competing risks model.

 Of 424 patients with a mean age of 5.56 ± 3.75 years, 172 (40%) were female. Median follow-up time was 43.29 months, 10.6% had a relapse, and 17.2% had mortality related to ALL. Relapse-free survival rates at 1, 3, and 5 years were 97, 91, and 88%, respectively. Overall survival rates were 86, 83, and 82%, respectively. In the standard-risk group, tumor lysis syndrome (TLS) significantly increased either the relapse risk [HR: 13.47 (2.05 - 67.54)] or mortality risk [HR: 19.57 (2.24 - 32.18)]. In the high-risk group, the higher level of hemoglobin, platelet, and lactic acid dehydrogenase was significantly associated with higher relapse risk. TLS was associated with a higher risk of mortality in high-risk groups.

 It was suggested that TLS was a predictor for the disease relapse as well as mortality in pediatric patients with ALL. However, further evaluation on the larger population of patients is demanded to ascertain the precision of such parameters in leukemic management strategies.
 

Containment of pandemic infections mainly depends on prompt identification of carriers, achievable through strict surveillance and truthful diagnostic testing. Although molecular identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard method, its low sensitivity and long turnaround time are among major concerns.In this retrospective single-center study, we reviewed the results of the lymphocyte and neutrophil counts of 1450 Iranian patients with coronavirus disease 2019 (COVID-19) recruited at Baqiyatallah Hospital, Tehran, Iran.Of 1450 patients, 439 cases (30.3%) were polymerase chain reaction (PCR) negative; further emphasizing that getting negative molecular testing is not as reliable as a positive result. While the lymphocyte count in cases with less than 50 years old was 1.8×103/µL (1.2-2.5), it was 1.47×103/µL (0.84-2.16) in the older group (p<0.001). Also, men experienced lower lymphocytes as compared to women (1.53×103/µL vs 1.76×103/µL; p=0.002). Of particular interest, the lymphocyte count in the PCR-negative cases was 1.77×103/µL (0.98-2.45) which was significantly higher than its count in their positive counterparts (1.53×103/µL; p=0.004). Unlike lymphocytes, sex and PCR did not significantly affect the number of neutrophils. The odds ratio for neutrophilia in patients aged older than 50, either with a negative or a positive PCR, was 2.46 and 2.23, suggesting old age as the most significant associated factor.The number of lymphocytes along with increased neutrophil count may probably serve as simple, rapid, and economical biomarkers, and are seemingly appropriate items that should be taken into account in the identification of patients with COVID-19, especially those aged more than 50.

Asparagus officinalis (A. officinalis) extract has several bioactive ingredients. This study assessed the healing effects of A. officinalis methanolic extract.

In this experimental study, after preparing the methanolic extract of A. officinalis with a concentration of 100 , its bioactive ingredients were determined using high-performance liquid chromatography (HPLC) and then its cytotoxicity was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Five experimental groups with 25 samples were assessed as follows: (I)human gingival fibroblast(HGFs) cultured in high-glucose Dulbecco’s modified Eagle’s medium (DMEM), (II) same as group Ibut with 10 μg/mL methanolic extract of A. officinalis, (III) same as group Ibut with 25μg/mL methanolic extract of A. officinalis, (IV) same as group Ibut with 50 μg/mL methanolic extract of A. officinalis, and (V)same as group Ibut with 100μg/mL methanolic extract of A. officinalis. Cell motility in the control group and group Vwas examined quantitatively using the cell scratch assay at 24 h. We used one-way ANOVA and t-test to analyzethe cytotoxicity of A. officinalis extract and the motility of HGFs, respectively.

The MTT assay showed no significant difference in cell viability among the experimental groups (P=0.07). A remarkable cellular wound closure equal to 60.85% was noted after 24 h.

The methanolic extract of A. officinalis with a concentration of 100 μg⁄mL showed significant healing effects on an experimental scratch setup of HGFs.