Upregulation of the long noncoding RNA GJA9-MYCBP and PVT1 is a potential diagnostic biomarker for acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of blood cancer in children. Aberrant expression of long noncoding RNAs (lncRNAs) may set stages for ALL development. LncRNAs are emerging as a novel diagnostic and prognostic biomarker for ALL. Herein, we aimed to evaluate the expression of lncRNA GJA9-MYCBP and PVT1 in blood samples of ALL and healthy individuals. METHODS: As a case-control study, 40 pairs of ALL and healthy individual samples were used. The expression of MYC and each candidate lncRNA was measured using quantitative real-time PCR. Any possible association between the expression of putative noncoding RNAs and clinicopathological characteristics was also evaluated. RESULTS: LncRNA GJA9-MYCBP and PVT1 were significantly upregulated in ALL samples compared with healthy ones. Similarly, mRNA levels of MYC were increased in ALL samples than control ones. Receiver operating characteristic curve analysis indicated a satisfactory diagnostic efficacy (p-value <.0001), suggesting that lncRNA GJA9-MYCBP and PVT1 may serve as a diagnostic biomarker for ALL. Linear regression analysis unveiled positive correlations between the expression level of MYC and lncRNA GJA9-MYCBP and PVT1 in ALL patients (p-values <.01). CONCLUSIONS: In this study, we provided approval for the clinical diagnostic significance of lncRNA GJA9-MYCBP and PVT1that their upregulations may be a diagnostic biomarker for ALL.

Ex vivo expansion of hematopoietic stem cells in two/ three-dimensional co-cultures with various source of stromal cells.

The ex vivo expansion of hematopoietic stem cells, with both high quantities and quality, is considered a paramount issue in cell and gene therapy for hematological diseases. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells reveal the importance of using 2D and 3D coculture as a physiological system simulator in the proliferation, differentiation, and homeostasis of HSCs. Herein, the capacity of mesenchymal stem cells derived from different sources to support the expansion and maintenance of HSPC was compared with each other. We evaluated the fold increase of HSPC, CD34 marker expression, cytokine secretion profile of different MSCs, and the frequency of hematopoietic colony-forming unit parameters. Our results show that there was no significant difference between adipose tissue-MSC, Wharton jelly-MSC, and Endometrial-MSCs in HSPC expansion (fold increase: 34.74±4.38 in Wj-MSC, 32.22±5.07 in AD-MSC, 25.9±1.27 in En-MSCs); However, there were significantly more than the expansion media alone (4.4±0.69). The results obtained from the cytokine secretion analysis also confirm these results. Also, there were significant differences in the clonogenicity of Wj-MSC, En-MSCs, and expansion media (CFU-GEMM: 7±1.73, 2.3±1.15, and 2.3±1.52), which indicated that Wj-MSC could significantly maintain the primitive state. As a result, using Wj-mesenchymal stem cells on a 3D coculture system effectively increases the HSPC expansion and maintains the colonization potential of hematopoietic stem cells.

Case Report: Challenges for the Diagnosis and Treatment of Strongyloides stercoralis in Chronic Obstructive Pulmonary Disease Patients.

Strongyloidiasis, a neglected tropical disease (NTD), which is caused by Strongyloides stercoralis, can be fatal in immunocompromised patients. In most chronic cases, infections most frequently are asymptomatic, and eosinophilia might be the only clinical characteristic of this disease. The use of corticosteroids in some diseases like chronic obstructive pulmonary disease (COPD) may lead to the development of the life-threatening S. stercoralis hyperinfection syndrome. In the present research, we presented five cases of strongyloidiasis with a history of COPD and receiving corticosteroids from Abadan County, southwestern Iran. By performing the direct smear stool examinations, two cases were identified and the other three cases were diagnosed using the agar plate culture method. Despite reporting eosinophilia in previous patients' hospitalizations, the fecal examination was not performed for parasitic infections. Moreover, pulmonary symptoms were similar, but gastrointestinal symptoms were varied, including nausea, vomiting, abdominal pain, epigastric pain, constipation, and diarrhea. All the included patients were treated with albendazole, which is the second-line drug for S. stercoralis, and relapse of infection was observed in two patients by passing few months from the treatment. The increased blood eosinophil count was shown to play important roles in both the management of COPD and diagnosis of helminthic infections. In COPD patients who are receiving steroids, screening and follow-up for strongyloidiasis should be considered as priorities. In addition, ivermectin, which is the first-line drug for strongyloidiasis, should be available in the region.

Screening of Strongyloides stercoralis infection in high-risk patients in Khuzestan Province, Southwestern Iran.

BACKGROUND: Strongyloidiasis, one of the neglected tropical diseases (NTDs), can be fatal in immunocompromised patients. Available data on Strongyloides stercoralis infection in high-risk patients in Iran are limited. The aim of the present study was to determine the prevalence of S. stercoralis infection and associated risk factors among high-risk patients as well as to evaluate the sensitivity of the diagnostic tests used in the diagnose of S. stercoralis infection. METHODS: This cross-sectional study was performed from 2019 to 2020 among 300 high-risk patients in Khuzestan Province, southwestern Iran. Patients with autoimmune diseases, uncontrolled diabetes, HIV/AIDS, cancer, organ transplant, hematological malignancy, asthma and chronic obstructive pulmonary disease (COPD) were examined using direct smear examination, formalin-ether concentration, Baermann funnel technique, agar plate culture, and ELISA test. Since agar plate culture was considered the reference diagnostic test, culture-positive samples were confirmed by PCR amplification and the sequencing of the nuclear 18S rDNA (SSU) hypervariable region (HVRIV) of the parasite. RESULTS: The prevalence of S. stercoralis infection was 1%, 1.3%, 2%, 2.7%, and 8.7% using direct smear examination, formalin-ether concentration, Baermann funnel technique, agar plate culture, and ELISA test, respectively. All culture-positive samples were confirmed by SSU-PCR. According to the results, the most sensitive test was ELISA, with 100% sensitivity, followed by the Baermann funnel technique with the sensitivity of 75%. Direct smear examination, formalin-ether concentration technique, and Baermann funnel technique had the highest PPV (100%) while the ELISA test had the highest NPV (100%). Significant eosinophilia was observed in the patients whose culture test was positive (7/8; P < 0.05). In the present study, the majority of the positive cases by the agar plate culture had a history of prolonged exposure to soil and of asthma and COPD and were > 60 years old. CONCLUSIONS: Given that the ELISA test had the highest NPV, the screening of all high-risk patients for S. stercoralis infection in endemic areas is recommended prior to starting corticosteroid therapy with the ELISA test. The results indicate the importance of paying attention to patients with unknown eosinophilia in endemic areas. Ivermectin should be available to strongyloidiasis patients in the endemic areas.

COVID-19: A Case for Inhibiting NLRP3 Inflammasome, Suppression of Inflammation with Curcumin?

Curcumin is the effective ingredient of turmeric, sometimes used as a painkiller in traditional medicine. It has extensive biological properties such as anti-inflammatory and antioxidant activities. SARS-CoV-2 is a betacoronavirus developing severe pneumonitis. Inflammasome is one of the most important components of innate immunity, which exacerbates inflammation by increasing IL-1ß and IL-18 production. Studies on viral infections have shown overactivity of inflammasome and thus the occurrence of destructive and systemic inflammation in patients. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The proliferation of SARS-CoV-2 in a wide range of cells can be combined with numerous observations of direct and indirect activation of inflammasome by other coronaviruses. Activation of the inflammasome is likely to be involved in the formation of cytokine storm. Curcumin regulates several molecules in the intracellular signal transduction pathways involved in inflammation, including IBB, NF-kBERK1,2, AP-1, TGF-ß, TXNIP, STAT3, PPARγ, JAK2-STAT3, NLRP3, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Due to anti-inflammatory and anti-inflammasome properties without any special side effects, curcumin can potentially play a role in the treatment of COVID-19 infection along with other drug regimens.

Intestinal Parasites Infection in Children with Cancer in Ahvaz, Southwest Iran.

BACKGROUND: Infection with intestinal parasites is widespread worldwide, especially in developing countries. Intestinal parasites are known as one of the leading causes of diarrhea in both immunocompetent and immunocompromised subjects, but cancer patients are highly susceptible to contamination, and it can be deadly for them. This study aimed to estimate the prevalence of intestinal parasites in immunocompromised patients in Ahvaz. Material and Methods. In this descriptive cross-sectional pilot case-control study, fecal samples were collected from 52 children with malignancies hospitalized in Baqaei2 hospital in Ahvaz. A questionnaire including demographic information, type of cancer, type of gastrointestinal symptoms, and laboratory diagnosis was completed for each patient. The collected specimens were examined by direct smear, Logul staining, and concentration. RESULT: The 52 stool samples were collected, 46% were female and 54% male. The age range of children enrolled in the study was from 4 months to 16 years. Of these stool samples, 38.38% were infected with a variety of parasitic intestinal infections (helminths and protozoa). In this study, protozoan parasites, Blastocystis (23%), Chilomastix mesnili (1.92%), Endolimax nana (7.7%), and Entamoeba coli (1.92%), and helminth infection, Strongyloides stercoralis (3.84%), were observed and statistical analysis showed that there was a significant relationship between gastrointestinal symptoms and parasitic infection in children with cancer. CONCLUSION: Blastocystis and Endolimax nana are the most prevalent gastrointestinal parasitic protozoans that infect individuals admitted to Baqaei2 Hospital of Ahvaz, Iran. Since parasitic intestinal infections in immunocompromised patients lead to fatal diarrhea, children with parasitic infections must be carefully identified and treated.

MicroRNA-122 in patients with hepatitis B and hepatitis B virus-associated hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is known as a serious problem in the domain of public health and approximately 350 million people across the world are affected with this infectious disease. As well, microRNAs are recognized as a type of small non-coding RNAs that can be widely used as a diagnostic biomarker and prognosis method of special diseases. In this respect, microRNA-122 or miR-122 can play a significant role in the pathogenesis of several hepatic diseases. Given the importance of microRNA-122 in the liver as well as its pathology, this study focused on the potential functions of microRNA-122 in pathogenesis, diagnosis, and treatment of HBV infection. In this regard, the findings of previous studies had indicated that expression of microRNA-122 in patients with HBV infection could be significantly deregulated. The results of this study were consistent with the idea that diagnosis and treatment of this infectious disease using microRNA-122 could be an efficient method.

Long Non-Coding RNAs in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, and Therapy.

Thyroid cancer is a rare malignancy and accounts for less than 1% of malignant neoplasms in humans; however, it is the most common cancer of the endocrine system and responsible for most deaths from endocrine cancer. Long non-coding (Lnc)RNAs are defined as non-coding transcripts that are more than 200 nucleotides in length. Their expression deregulation plays an important role in the progress of cancer. These molecules are involved in physiologic cellular processes, genomic imprinting, inactivation of chromosome X, maintenance of pluripotency, and the formation of different organs via changes in chromatin, transcription, and translation. LncRNAs can act as a tumor suppressor genes or oncogenes. Several studies have shown that these molecules can interact with microRNAs and prevent their binding to messenger RNAs. Research has shown that these molecules play an important role in tumorigenicity, angiogenesis, proliferation, migration, apoptosis, and differentiation. In thyroid cancer, several lncRNAs (MALAT1, H19, BANCR, HOTAIR) have been identified as contributing factors to cancer development, and can be used as novel biomarkers for early diagnosis or even treatment. In this article, we study the newest lncRNAs and their role in thyroid cancer.

Survivin as a diagnostic and therapeutic marker for thyroid cancer.

Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.

Association between gene polymorphisms and clinical features in idiopathic thrombocytopenic purpura patients.

: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which increased platelet destruction and thrombocytopenia are diagnostic features. In fact, the exact pathogenesis of this disease is still unknown, but genetic changes can be a potential factor in the development of ITP. In this study, the relationship between polymorphisms with platelet destruction has been studied, which leads to decreased platelet count. Relevant literature was identified by a PubMed search (2000-2016) of English language papers using the terms 'ITP', 'polymorphism,' and 'immune system'. The majority of genetic changes (polymorphisms) occur in immune system genes, including interferon (IFN)-γ gene. These changes lead to the dysfunction of immune system and production of pathogenic antibodies against platelet surface glycoproteins such as glycoprotein IIb/IIIa, which eventually result in the destruction of platelets and increasing disease severity. In addition, IFN-γ as well as factors and cytokines involved in megakaryopoiesis, including stem cell factor and interleukin-3 (IL-3), leads to the differentiation of megakaryocytes and platelet release. Considering the fact that IFN-γ is a factor of inflammation and thrombocytopenia, coexistence of this cytokine with thrombopoietin, stem cell factor, and IL-3 results in megakaryocytes differentiation and platelet production, which can be effective to reduce disease severity and increase the platelet counts.

The Influence of Polymorphisms in Disease Severity in ß-Thalassemia.

ß-Thalassemia is a genetic disorder with a continuum of mild to severe clinical manifestations and requirement of transfusion at different stages of life. The cause(s) of this variety is not clear but genetic alterations could be a potential factor. In this review, the correlation between polymorphisms and different clinical manifestations, including the need for transfusion, was investigated. Relevant articles published in pubmed database from 1982 onwards were studied and compiled. The articles all contained the keywords ß-thalassemia, genetic modifiers, and mutations. Certain polymorphisms and mutations could dictate the severity of symptoms as well as their onset. A significant number of the mentioned genetic alterations appear in beta-globin gene cluster and affect gamma chain. Therefore, hemoglobin F production rate is increased and can affect thalassemia symptoms and can relieve ß-thalassemia symptoms. A number of polymorphisms in catalase and glutathione S transferase genes have also been shown to modify the severity of disease and response to treatment. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients, especially in young ages or before birth to take proper measures in advance and eventually ameliorate the symptoms in the long run.

Immune Thrombocytopenic Purpura in Children and Adults: A Comparative Retrospective Study in IRAN.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease that can cause bleeding disorders in patients, and presents in acute and chronic forms. The acute form is frequently seen in children, but the chronic form mainly inflicts adults. There are differences and similarities in clinical and laboratory findings of the disease between children and adults. We study these differences and similarities in these two groups of patients with ITP. METHODS: In this study, we retrospectively evaluated the clinical and laboratory data of 323 ITP cases within three years. None of our patients had a history of thrombocytopenia. Patients were classified into two groups of children (3 months to 16 years of age) and adults (≥ 16 years). Data analysis was conducted using SPSS software, and the analysis results were compared between the two age groups. RESULTS: Overall, the disease prevalence was higher in women than men, but the prevalence of childhood ITP was higher in males than females. The prevalence of initial symptoms including petechiae, purpura and ecchymosis was 60.5% and 61%, respectively in all patients, but severe bleeding rarely occurred in patients (28.8%). 30.5% of patients had a history of infection before developing ITP, and the children had a higher frequency of infection (80.8%). Before treatment, the mean platelet count in adults and children was 33000/µL and 35000/µL, respectively. CONCLUSION: Comparison of data in children and adults with ITP indicated similarities and differences in clinical and laboratory findings between the two groups with differences in prevalence, bleeding symptoms, initial platelet count and infection history.

T-cell Acute Lymphoblastic Leukemia with del (7) (q11.2q22) and Aberrant Expression of Myeloid Markers.

T cell acute lymphoblastic leukemia (ALL) is an invasive disease with a higher incidence in children and adolescents. In terms of Immunophenotype, T-ALL is positive for CD2, CD7, CD34 and HLA-DR, and the level of these markers is increased with increasing age. In addition, the myeloid markers (CD13, CD33) are sometimes expressed in T-ALL. In this study, we introduce a rare case of a 28-year-old woman with T-ALL with aberrant expression of myeloid markers (CD13), without lymphadenopathy and with 94% blasts in bone marrow specimens. The patient has the rare karyotype of 46,XX del(7)(q11.2q22). The presence of del7 is a rare phenomenon in T-ALL.

The efficacy of zinc supplementation on outcome of children with severe pneumonia. A randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: To compare the clinical outcome of children having severe pneumonia, with and without zinc supplementation by a randomized double-blind placebo controlled trial. METHODS: In this study, 128 children (3-60 months old) admitted to the hospital with severe pneumonia were randomly divided into 2 groups (64 in each) that received either zinc sulfate (2 mg/kg/d, maximum 20 mg in 2 divided doses, for 5 days) or a placebo, along with the standard antimicrobial therapy. Primary outcome measurements included the time taken for clinical symptoms of severe pneumonia such as fever and respiratory distress symptoms to resolve, and the secondary outcome included the duration of hospital stay. RESULTS: The time taken for all the symptoms to resolve in the zinc-supplemented group was significantly lesser then that in the placebo group (42.26 [6.66] vs. 47.52 [7.15] h respectively, p < 0.001). The zinc-treated group had a significantly shorter duration of fever (23.29 [6.67] vs. 26.6 [6.26] h, p = 0.024), respiratory distress (32.87 [7.85] vs. 37.37 [4.43] h, p = 0.001), required a shorter hospital stay (126.74 [12.8] vs. 137.74 [11.52] h, p < 0.001) than did the controls. The zinc supplement was well tolerated by the children. CONCLUSIONS: The results suggest that adjuvant treatment with zinc accelerates recovery from severe pneumonia in young children and significantly reduces the duration of hospital stay. Further studies are required to develop appropriate recommendations for the use of zinc in the treatment of severe pneumonia in other populations.