Evaluation of the local and systemic pattern of sensitization to allergens in patients with adenotonsillar hypertrophy.

PURPOSE: Adenotonsillar hypertrophy (ATH) is a medical condition characterized by the enlargement or swelling of the tonsils. The role of allergy in ATH has not been persuasively evidenced. Therefore, we investigated the state of humoral immunity and the presence of specific immunoglobulin E (sIgE) in tissues and sera in children suffering from TH. METHODS: According to the skin prick test (SPT) result, 44 ATH children were divided into the atopic and non-atopic groups. The level of sIgE against 30 inhalants and food allergens in the sera and tissue homogenates was measured by a commercial allergy immunoblotting kit. In addition, we evaluated the following variables in both tonsillar tissue homogenates and serum: total IgE, IgA, IgM, IgG, and tissue eosinophil counts. RESULTS: Our results showed that 21 (47.7%) of patients with ATH were sensitized to at least one allergen in the adenotonsillar sample and/or sera. Only two patients were negative for sIgE in the atopic group, but in the non-atopic group, only one had positive sIgE results. In the atopic group, 19 (86.4%) patients had positive sIgE in tonsillar tissues, and 18 (81.8%) had sensitized serum. There were no statistical differences in the case of other antibodies except IgE levels between the two groups. The average eosinophilic count was significantly higher in atopic patients than in the non-atopic group. CONCLUSION: The results of this study support the role of allergy in the pathogenesis of ATH and confirmed local allergic inflammation in tonsillar tissue.

Evaluation of SARS-CoV-2 Specific Antibodies in Recovered Patients by Different ELISA Kits.

Background: The coronavirus disease 2019 (COVID-19) was first reported in December 2019 in Wuhan, Hubei Province of China. As long as the 27th of December 2021, approximately 280 million people have been infected with coronavirus, resulting in more than 5,418,421 deaths worldwide. Since the beginning of the COVID-19 pandemic, different methods were introduced for diagnosing coronavirus-infected patients and evaluating the immune response, following the vaccination. Objective: The current study aimed to compare the level of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) specific IgG in a group of patients who recovered from COVID-19, measured by three different enzyme-linked immunosorbent assay (ELISA) kits. Methods: This cross-sectional study was conducted on sera from patients who recovered from a real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 in Birjand, South Khorasan, Iran. SARS-CoV-2 anti-nucleocapsid (N) and spike (S) protein IgG levels were measured using commercial ELISA kits. Comparison between groups was made using one-way ANOVA and Tukey post hoc tests. Results: The mean titer of anti-N IgG was significantly higher for the PishtazTeb Diagnostics kit than the Ideal Tashkhis Atieh kit (p<0.05). There was no correlation between the titer of anti-N IgG (PishtazTeb Diagnostics and Ideal Tashkhis Atieh) and anti-S IgG (Chemobind Company) antibodies. Conclusion: This study indicates that the domestic ELISA kits have variable but acceptable sensitivity for detecting SARS-CoV-2 specific IgG antibodies.

Single-cell RNA sequencing uncovers heterogeneous transcriptional signatures in tumor-infiltrated dendritic cells in prostate cancer.

Prostate cancer (PCa) is one of the two solid malignancies in which a higher T cell infiltration in the tumor microenvironment (TME) corresponds with a worse prognosis for the tumor. The inability of T cells to eliminate tumor cells despite an increase in their number reinforces the possibility of impaired antigen presentation. In this study, we investigated the TME at single-cell resolution to understand the molecular function and communication of dendritic cells (DCs) (as professional antigen-presenting cells). According to our data, tumor cells stimulate the migration of immature DCs to the tumor site by inducing inflammatory chemokines. Many signaling pathways such as TNF-α/NF-κB, IL2/STAT5, and E2F up-regulated after DCs enter the tumor location. In addition, some molecules such as GPR34 and SLCO2B1 decreased on the surface of DCs. The analysis of molecular and signaling alterations in DCs revealed some suppression mechanisms of tumors, such as removing mature DCs, reducing the DC's survival, inducing anergy or exhaustion in the effector T cells, and enhancing the differentiation of T cells to Th2 and Tregs. In addition, we investigated the cellular and molecular communication between DCs and macrophages in the tumor site and found three molecular pairs including CCR5/CCL5, CD52/SIGLEC10, and HLA-DPB1/TNFSF13B. These molecular pairs are involved in the migration of immature DCs to the TME and disrupt the antigen-presenting function of DCs. Furthermore, we presented new therapeutic targets by the construction of a gene co-expression network. These data increase our knowledge of the heterogeneity and the role of DCs in PCa TME.

Clinical Experts' Opinion Improves the Attitude of Medical Students Toward |Basic Sciences' Courses.

The medical curriculum consists of basic pre-clinical and clinical parts. Basic sciences are required for diagnostic and clinical reasoning but students do not have a positive attitude toward basic sciences, mostly because of the lack of clinical relevancy. Basic sciences have many applications in the prevention, diagnosis, and treatment of a broad range of diseases but do not attract the attention of medical students. The aim of this study was to investigate the influence of clinical experts' opinions on the attitude of medical students toward basic sciences, particularly immunology. The opinion of six clinical specialists in different fields was recorded in a video clip, presenting the application of basic sciences and immunology in their routine practice. The attitude of second-year medical students toward the basic science courses was evaluated by a questionnaire containing four ranking questions and one short answer. The video clip was streamed and after that, students were answering the same questions. In total, 188 students including 129 s-year students (M/F ratio: 0.92) and 59 third-year students M/F ratio: 0.90) participated in the study. For all ranking questions, the mean score was significantly increased after watching the interviews' film streaming. Before watching the video clip, only 14.9% of students considered immunology as an important course but after that, the percentage significantly increased to 58.5% (P < 0.001). The results of this study showed that knowing clinical specialists' opinions about basic sciences significantly improved the attitude of students toward basic science courses, in particular immunology.

Reactogenicity within the first week after Sinopharm, Sputnik V, AZD1222, and COVIran Barekat vaccines: findings from the Iranian active vaccine surveillance system.

BACKGROUND: This study aimed to evaluate the reactogenicity effects of COVID-19 vaccines, used in Iran. METHODS: At least 1000 people were followed up with phone calls or self-report in a mobile application within 7 days after vaccination. Local and systemic reactogenicities were reported overall and by subgroups. RESULTS: The presence of one or more local and systemic adverse effects after the first dose of vaccines was 58.9% [(95% Confidence Intervals): 57.5-60.3)] and 60.5% (59.1-61.9), respectively. These rates were reduced to 53.8% (51.2-55.0) and 50.8% (48.8-52.7) for the second dose. The most common local adverse effect reported for all vaccines was pain in the injection site. During the first week after the first dose of vaccines, the frequency of the pain for Sinopharm, AZD1222, Sputnik V, and Barekat was 35.5%, 86.0%, 77.6%, and 30.9%, respectively. The same rates after the second dose were 27.3%, 66.5%, 63.9%, and 49.0%. The most common systemic adverse effect was fatigue. In the first dose, it was 30.3% for Sinopharm, 67.4% for AZD1222, 47.6% for Sputnik V, and 17.1% for Barekat. These rates were reduced to 24.6%, 37.1%, 36.5%, and 19.5%, in the second dose of vaccines. AZD1222 had the highest local and systemic adverse effects rates. The odds ratio of local adverse effects of the AZD1222 vaccine compared to the Sinopharm vaccine were 8.73 (95% CI 6.93-10.99) in the first dose and 4.14 (95% CI 3.32-5.17) in the second dose. Barekat and Sinopharm had the lowest frequency of local and systemic adverse effects. Compared to Sinopharm, systemic adverse effects were lower after the first dose of Barekat (OR = 0.56; 95% CI 0.46-0.67). Reactogenicity events were higher in women and younger people. Prior COVID-19 infection increased the odds of adverse effects only after the first dose of vaccines. CONCLUSIONS: Pain and fatigue were the most common reactogenicities of COVID-19 vaccination. Reactogenicities were less common after the second dose of the vaccines. The adverse effects of AZD1222 were greater than those of other vaccines.

Crimean-Congo hemorrhagic fever virus in Central, Eastern, and South-eastern Asia.

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is endemic in Africa, Asia, and Europe, but CCHF epidemiology and epizootiology is only rudimentarily defined for most regions. Here we summarize what is known about CCHF in Central, Eastern, and South-eastern Asia. Searching multiple international and country-specific databases using a One Health approach, we defined disease risk and burden through identification of CCHF cases, anti-CCHFV antibody prevalence, and CCHFV isolation from vector ticks. We identified 2313 CCHF cases that occurred in 1944-2021 in the three examined regions. Central Asian countries reported the majority of cases (2,026). In Eastern Asia, China was the only country that reported CCHF cases (287). In South-eastern Asia, no cases were reported. Next, we leveraged our previously established classification scheme to assign countries to five CCHF evidence levels. Six countries (China, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) were assigned to level 1 or level 2 based on CCHF case reports and the maturity of the countries' surveillance systems. Two countries (Mongolia and Myanmar) were assigned to level 3 due to evidence of CCHFV circulation in the absence of reported CCHF cases. Thirteen countries in Eastern and South-eastern Asia were categorized in levels 4 and 5 based on prevalence of CCHFV vector ticks. Collectively, this paper describes the past and present status of CCHF reporting to inform international and local public-health agencies to strengthen or establish CCHFV surveillance systems and address shortcomings.

Analysis and comparison of anti-RBD neutralizing antibodies from AZD-1222, Sputnik V, Sinopharm and Covaxin vaccines and its relationship with gender among health care workers.

BACKGROUND: Vaccine efficiency has a significant role in the public perception of vaccination. The current study was designed to evaluate the efficacy of COVID-19 vaccines (AZD-1222, Sputnik-V, Sinopharm, and Covaxin) and the effect of gender on vaccine efficacy. We evaluated the efficacy of these vaccines among 214 health care employees in Iran. Blood samples were taken from all participants on day 0 and 14 days after the second dose. Humoral responses were evaluated by the PT-SARS-CoV-2-Neutralizing-Ab-96. RESULTS: The frequency of immunized individuals in the Sputnik V and AZD-1222 groups was 91% and 86%, respectively. This rate was 61% and 67% for Sinopharm and Covaxin vaccines. A comparison of the results obtained from the effectiveness of the vaccines between female and male groups did not demonstrate a significant difference. CONCLUSION: According to the results, Sputnik V and AZD-1222 vaccines were more effective than Sinopharm and Covaxin vaccines. Moreover, the effectiveness of these vaccines is not related to gender.

The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors.

Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection.

CHAC1 as a novel biomarker for distinguishing alopecia from other dermatological diseases and determining its severity.

Alopecia Areata (AA) is characterised by an autoimmune response to hair follicles (HFs) and its exact pathobiology remains unclear. The current study aims to look into the molecular changes in the skin of AA patients as well as the potential underlying molecular mechanisms of AA in order to identify potential candidates for early detection and treatment of AA. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules, hub genes, and mRNA-miRNA regulatory networks associated with AA. Furthermore, Chi2 as a machine-learning algorithm was used to compute the gene importance in AA. Finally, drug-target construction revealed the potential of repositioning drugs for the treatment of AA. Our analysis using four AA data sets established a network strongly correlated to AA pathogenicity based on GZMA, OXCT2, HOXC13, KRT40, COMP, CHAC1, and KRT83 hub genes. Interestingly, machine learning introduced these genes as important in AA pathogenicity. Besides that, using another ten data sets, we showed that CHAC1 could clearly distinguish AA from similar clinical phenotypes, such as scarring alopecia due to psoriasis. Also, two FDA-approved drug candidates and 30 experimentally validated miRNAs were identified that affected the co-expression network. Using transcriptome analysis, suggested CHAC1 as a potential diagnostic predictor to diagnose AA.

COVID-19 cases, hospitalizations and deaths after vaccination: a cohort event monitoring study, Islamic Republic of Iran.

Objective: To investigate the incidence of coronavirus disease 2019 (COVID-19) cases, hospitalizations and deaths in Iranians vaccinated with either AZD1222 Vaxzevria, CovIran® vaccine, SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) or Sputnik V. Methods: We enrolled individuals 18 years or older receiving their first COVID-19 vaccine dose between April 2021 and January 2022 in seven Iranian cities. Participants completed weekly follow-up surveys for 17 weeks (25 weeks for AZD1222) to report their COVID-19 status and hospitalization. We used Cox regression models to assess risk factors for contracting COVID-19, hospitalization and death. Findings: Of 89 783 participants enrolled, incidence rates per 1 000 000 person-days were: 528.2 (95% confidence interval, CI: 514.0-542.7) for contracting COVID-19; 55.8 (95% CI: 51.4-60.5) for hospitalization; and 4.1 (95% CI: 3.0-5.5) for death. Compared with SARS-CoV-2 Vaccine (Vero Cell), hazard ratios (HR) for contracting COVID-19 were: 0.70 (95% CI: 0.61-0.80) with AZD1222; 0.73 (95% CI: 0.62-0.86) with Sputnik V; and 0.73 (95% CI: 0.63-0.86) with CovIran®. For hospitalization and death, all vaccines provided similar protection 14 days after the second dose. History of COVID-19 protected against contracting COVID-19 again (HR: 0.76; 95% CI: 0.69-0.84). Diabetes and respiratory, cardiac and renal disease were associated with higher risks of contracting COVID-19 after vaccination. Conclusion: The rates of contracting COVID-19 after vaccination were relatively high. SARS-CoV-2 Vaccine (Vero Cell) provided lower protection against COVID-19 than other vaccines. People with comorbidities had higher risks of contracting COVID-19 and hospitalization and should be prioritized for preventive interventions.

The Tumor Suppressor Roles and Mechanisms of MiR-491 in Human Cancers.

MicroRNAs (miRNAs) are short non-coding RNAs that bind to the 3' untranslated region (3'' UTR) of target mRNAs to control gene expression post-transcriptionally. Recent indications have highlighted their important roles in a variety of pathophysiological conditions as well as human malignancies. Dysregulated miRNAs act as tumor suppressor genes or oncogenes in a variety of cancers. MiR-491 has been shown to have a major effect on tumorigenesis in multiple malignancies through binding to specific genes and signaling cascades, thereby preventing cancer progression. This review provides an overview of miR-491 expression in regulatory mechanisms and biological procedures of tumor cells, as well as the prospective possible treatment effects of various types of human cancers.

The significance of the SDF-1/CXCR4 signaling pathway in the normal development.

Chemokines are chemoattractants that can regulate cell movement and adhesion. SDF-1 [stromal cell-derived factor-1 (SDF-1)] is a homeostatic CXC chemokine. SDF-1 and its receptors [CXC chemokine receptor 4 (CXCR4)] form a signaling pathway that plays critical roles in different pathological and physiological mechanisms, including embryogenesis, wound healing, angiogenesis, tumor growth, and proliferation. Therefore, the current review aimed to summarize the related studies that addressed the molecular signature of the SDF-1/CXCR4 pathway and to explain how this axis is involved in normal events.

Immunogenicity and Safety of the Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV) in Patients with Malignancy.

OBJECTIVE: To evaluate the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine in cancer patients. MATERIAL AND METHOD: 364 cancer patients who received two doses of vaccine were enrolled. The presence of SARS-CoV-2 anti-Spike protein IgG and neutralizing antibody 2 months following vaccination were measured by ELIZA. RESULTS: Injection site pain and fever were the most common local and systemic side effects. The overall seroconversion rate was 86.9% that was lower in older age, those with hematological malignancies and chemotherapy receivers. CONCLUSION: The result of study confirmed the safety and short-term efficacy of inactivated vaccine in patients with malignancies.

Immunotherapy of cancer in single-cell RNA sequencing era: A precision medicine perspective.

Immunotherapy has revolutionized cancer treatment and brought new aspects into tumor immunology. Effective immunotherapy will require using the suitable target antigens, optimizing the interaction between the antigenic peptide, the APC, and the T cell, and the simultaneous inhibitor of the negative regulatory process that inhibits immunotherapeutic effects and develop resistance. Tumor heterogeneity and its microenvironment is the leading cause of resistance in patients. Recently by emerging the single-cell RNA sequencing technology and its combination with immunotherapy, now we can specifically evaluate the mechanism of tumors in the face of immunotherapy agents at the single-cell resolution by detecting the transcriptional activity of immune checkpoints, screening neoantigens with high transcription levels, identifying rare cells, and other important processes. This review focuses on scRNA-seq, particularly on its application in cancer immunotherapy.

Prevalence of COVID-19 vaccines (Sputnik V, AZD-1222, and Covaxin) side effects among healthcare workers in Birjand city, Iran.

BACKGROUND: The prevalence of vaccine side effects plays an important role in public perception about vaccination programs. This study was designed to investigate the side effects of the first dose of COVID-19 vaccine; Sputnik-V, AZD-1222, and Covaxin. METHODS: A study was performed to evaluate the side effects of these vaccine among 503 health care workers in Birjand (Iran). Our study used the questionnaire consisted of 4 main categories including demographic data, previous COVID-19 infection, vaccine information, and local and systemic side effects of vaccines. RESULTS: 81.9%, 88.8%, and 92.9% of people who have been vaccinated with Sputnik-V, AZD1222, and Covaxin vaccines, respectively, have reported at least one side effect. The prevalence of systemic side effects in AZD-1222 vaccine was higher than Sputnik V and Covaxin vaccines. Injection site pain (62.1%), fatigue (43.9%), muscle pain (42.5%), and fever (40.6%) were the most common side effects in all three vaccines. Side effect frequency was higher in the female group (90.6%) than the male group (79.5%). The prevalence of side effects with Sputnik V and Covaxin vaccines was reduced in the elderly. Moreover, the prevalence of side effects was higher in the case of convalescent patients (92.4 %) than in the group with no history of infection. The prevalence of side effects was higher in person with a BMI above 25 in the AZD-1222 and Covaxin vaccines. CONCLUSIONS: The most common side effects of the Sputnik-V, AZD-1222, and Covaxin vaccine among Birjand (Iran) healthcare workers were injection site pain, muscle pain, fatigue, fever, and headache. Age and gender were the most important variables in the prevalence of vaccine side effects.

Evaluation of The Safety and Efficacy of Newly Developed Domestic Allergenic Extracts for Skin Prick Testing.

BACKGROUND: Allergic disorders are common health problems worldwide with significant socio-economic impacts. The best diagnostic method using allergenic extract is the skin prick test. Regarding the effects of geo-climatic factors and allergenic extract source material quality, the aim of study was to determine the safety and efficacy of some in-house-developed allergenic extracts. METHODS: Forty-five different allergenic extracts, including common regional pollen, foods, and dog and cat hair, as well as positive and negative extracts, were prepared from domestic sources using optimum extraction methods. All extracts passed stability and sterility testing, and sterile final products containing 50% glycerin in 10 and 20 w/v concentrations were used. Skin prick testing was performed on volunteers and immediate or late side effects were recorded. RESULTS: In total, 56 students (mean age: 21.2±2.3y, M/F ratio: 1.07) participated in this study. For inhalant allergens, all extracts except dog hair extract caused positive responses. Salsola kali (Russian thistle) and Fraxinus velutina (ash tree) were the most common grass and tree pollen extracts, respectively. Of 18 different food extracts, five, including egg white, tomato, fig, melon, and green pepper caused skin reactivity in only one person. No participant reported any immediate or late side effects, including large local reaction or systemic response. CONCLUSION: The result of the current study confirmed the safety of all our in-house-developed allergenic extracts. Regarding efficacy, almost all inhalant and five food allergens caused positive skin responses.

The high level of adherence to personal protective equipment in health care workers efficiently protects them from COVID-19 infection.

BACKGROUND: The first case of coronavirus disease 2019 (COVID-19) was reported in December 2019 in Wuhan, China. Healthcare workers (HCWs) are at high risk of acquiring and spreading the COVID-19 infection; using personal protective equipment (PPE) reduces the risk of COVID-19 infection in HCWs. OBJECTIVE: Our study aimed to investigate the seroprevalence of COVID-19 IgG, IgM antibodies among HCWs as well as identifying the factors associated with this seroprevalence. METHODS: This cross-sectional study was performed from July to August 2020 on healthcare workers at two COVID-19 referral hospitals of Birjand University of Medical Sciences. The level of COVID-19 IgG and IgM antibodies in sera was measured by commercial qualitative ELISA kits. RESULTS: In total, 192 individuals participated in the study: physicians (31.25%), nurses (30.2%). 84.2% of participants had contact with confirmed COVID-19 cases and among them 42.9 % of had close contact with COVID-19 patients for more than 3 months, and 31% reported close contact with more than 50 confirmed COVID-19 cases. Mask and gloves were the most frequently used personal protective equipment (PPE) with 92.4% and 77.2% of usage. CONCLUSIONS: The results of the current study showed high level of adherence to the use of PPE among HCWs as well as very low prevalence of seropositivity for of COVID-19 antibodies, hence confirming the effectiveness of PPE in protecting HCWs among COVVID-19 and possibly any other similar infections.

Weighted Gene Co-Expression Network Analysis Combined with Machine Learning Validation to Identify Key Modules and Hub Genes Associated with SARS-CoV-2 Infection.

The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous loss of lives. Various clinical trials of vaccines and drugs are being conducted worldwide; nevertheless, as of today, no effective drug exists for COVID-19. The identification of key genes and pathways in this disease may lead to finding potential drug targets and biomarkers. Here, we applied weighted gene co-expression network analysis and LIME as an explainable artificial intelligence algorithm to comprehensively characterize transcriptional changes in bronchial epithelium cells (primary human lung epithelium (NHBE) and transformed lung alveolar (A549) cells) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study detected a network that significantly correlated to the pathogenicity of COVID-19 infection based on identified hub genes in each cell line separately. The novel hub gene signature that was detected in our study, including PGLYRP4 and HEPHL1, may shed light on the pathogenesis of COVID-19, holding promise for future prognostic and therapeutic approaches. The enrichment analysis of hub genes showed that the most relevant biological process and KEGG pathways were the type I interferon signaling pathway, IL-17 signaling pathway, cytokine-mediated signaling pathway, and defense response to virus categories, all of which play significant roles in restricting viral infection. Moreover, according to the drug-target network, we identified 17 novel FDA-approved candidate drugs, which could potentially be used to treat COVID-19 patients through the regulation of four hub genes of the co-expression network. In conclusion, the aforementioned hub genes might play potential roles in translational medicine and might become promising therapeutic targets. Further in vitro and in vivo experimental studies are needed to evaluate the role of these hub genes in COVID-19.

Overcoming the UCB HSCs -Derived NK cells Dysfunction through Harnessing RAS/MAPK, IGF-1R and TGF-ß Signaling Pathways.

BACKGROUND: The natural killer (NK) cells differentiated from umbilical cord blood (UCB) hematopoietic stem cells (HSCs) may be more suitable for cell-based immunotherapy compared to the NK cells from adult donors. This is due to the possibility to choose alloreactive donors and potentially more robust in vivo expansion. However, the cytotoxicity of UCB-HSC-derived NK cells against cancer cells might be suboptimal. To overcome this obstacle, we attempted to generate NK cells with potent antitumor activity by targeting RAS/MAPK, IGF-1R and TGF-ß signaling pathways using IL-15, IGF-1 and SIS3 respectively. METHODS: The CD34 + cells were isolated from human UCB mononuclear cells through magnetic activation cell sorting (MACS) with purity of (≥ 90%) and were subjected to differentiate into NK cells. After 21 days of induction with SFTG36 (SCF, FLt-3L, TPO, GM-CSF, IL-3 and IL-6), IS721 (IGF-1, SIS3, IL-7 and IL-21) and IL-15/Hsp70 media, NK cells phenotypes were studied and their cytotoxicity against K562 human erythroleukemia cells and SKOV3 ovarian carcinoma cells was analyzed. RESULTS: The NK cells induced in SFTG36/IS721 medium were selected for activation due to their higher expression of CD56 + 16 + CD3 - (93.23% ± 0.75) and mean fluorescence intensity (MFI) of NKG2D + (168.66 ± 20.00) and also a higher fold expansion potential (11.893 ± 1.712) compared to the other groups. These cells once activated with IL-15, demonstrated a higher cytotoxicity against K562 (≥ 90%; P ≤ 0.001) and SKOV3 tumor cells (≥ 65%; P ≤ 0.001) compared to IL-15/Hsp70-activated NK cells. CONCLUSIONS: The differentiation of ex vivo expanded CD34 + cells through manipulation of RAS/MAPK, IGF-1R and TGF-ß signaling pathways is an efficient approach for generating functional NK cells that can be used for cancer immunotherapy.