Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer ...cells. CAR‐natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti‐cancer functions. Importantly, CAR‐NK cells can be utilized as universal cell‐based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor‐associated antigens (TAAs). Indeed, CAR‐NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR‐NK cell anti‐cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the “off‐the‐shelf” anti‐cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR‐NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.
In the current review, we focus on the therapeutic efficacy of CAR‐NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.
We compared the prevalence, awareness, treatment, and control of hypertension in Iran based on two hypertension guidelines; the 2017 ACC/AHA -with an aggressive blood pressure target of 130/80 mmHg- ...and the commonly used JNC8 guideline cut-off of 140/90 mmHg. We shed light on the implications of the 2017 ACC/AHA for population subgroups and high-risk individuals who were eligible for non-pharmacologic and pharmacologic therapies.
Data was obtained from the Iran national STEPS 2016 study. Participants included 27,738 adults aged ≥25 years as a representative sample of Iranians. Regression models of survey design were used to examine the determinants of prevalence, awareness, treatment, and control of hypertension.
The prevalence of hypertension based on JNC8 was 29.9% (95% CI: 29.2-30.6), which soared to 53.7% (52.9-54.4) based on the 2017 ACC/AHA. The percentage of awareness, treatment, and control were 59.2% (58.0-60.3), 80.2% (78.9-81.4), and 39.1% (37.4-40.7) based on JNC8, which dropped to 37.1% (36.2-38.0), 71.3% (69.9-72.7), and 19.6% (18.3-21.0), respectively, by applying the 2017 ACC/AHA. Based on the new guideline, adults aged 25-34 years had the largest increase in prevalence (from 7.3 to 30.7%). They also had the lowest awareness and treatment rate, contrary to the highest control rate (36.5%) between age groups. Compared with JNC8, based on the 2017 ACC/AHA, 24, 15, 17, and 11% more individuals with dyslipidaemia, high triglycerides, diabetes, and cardiovascular disease events, respectively, fell into the hypertensive category. Yet, based on the 2017 ACC/AHA, 68.2% of individuals falling into the hypertensive category were eligible for receiving pharmacologic therapy (versus 95.7% in JNC8). LDL cholesterol< 130 mg/dL, sufficient physical activity (Metabolic Equivalents≥600/week), and Body Mass Index were found to change blood pressure by - 3.56(- 4.38, - 2.74), - 2.04(- 2.58, - 1.50), and 0.48(0.42, 0.53) mmHg, respectively.
Switching from JNC8 to 2017 ACC/AHA sharply increased the prevalence and drastically decreased the awareness, treatment, and control in Iran. Based on the 2017 ACC/AHA, more young adults and those with chronic comorbidities fell into the hypertensive category; these individuals might benefit from earlier interventions such as lifestyle modifications. The low control rate among individuals receiving treatment warrants a critical review of hypertension services.
The use of repurposing drugs that may have neoplastic and anticancer effects increases the efficiency and decrease resistance to chemotherapy drugs through a biochemical and mechanical transduction ...mechanisms through modulation of fibroblast/fibrosis remodeling in tumor microenvironment (TME). Interestingly, fibroblast/fibrosis remodeling plays a vital role in mediating cancer metastasis and drug resistance after immune chemotherapy. The most essential hypothesis for induction of chemo-immunotherapy resistance is via activation of fibroblast/fibrosis remodeling and preventing the infiltration of T cells after is mainly due to the interference between cytoskeleton, mechanical, biochemical, metabolic, vascular, and remodeling signaling pathways in TME. The structural components of the tumor that can be targeted in the fibroblast/fibrosis remodeling include the depletion of the TME components, targeting the cancer-associated fibroblasts and tumor associated macrophages, alleviating the mechanical stress within the ECM, and normalizing the blood vessels. It has also been found that during immune-chemotherapy, TME injury and fibroblast/fibrosis remodeling causes the up-regulation of inhibitory signals and down-regulation of activated signals, which results in immune escape or chemo-resistance of the tumor. In this regard, repurposing or neo-adjuvant drugs with various transduction signaling mechanisms, including anti-fibrotic effects, are used to target the TME and fibroblast/fibrosis signaling pathway such as angiotensin 2, transforming growth factor-beta, physical barriers of the TME, cytokines and metabolic factors which finally led to the reverse of the chemo-resistance. Consistent to many repurposing drugs such as pirfenidone, metformin, losartan, tranilast, dexamethasone and pentoxifylline are used to decrease immune-suppression by abrogation of TME inhibitory signal that stimulates the immune system and increases efficiency and reduces resistance to chemotherapy drugs. To overcome immunosuppression based on fibroblast/fibrosis remodeling, in this review, we focus on inhibitory signal transduction, which is the physical barrier, alleviates mechanical stress and prevents mechano-metabolic activation.
Satisfaction of online students is one of the important issues of online education, and identifying the predictors of satisfaction can improve the effectiveness and success of online education. This ...study thus aimed to investigate online students’ and instructors’ perceptions of the influential factors such as motivation, e-readiness, and barriers for online satisfaction and to determine the contribution of these factors to satisfaction. The participants were 114 online graduate students of TEFL and 5 online instructors at Iran University of Science and Technology. Four questionnaires on learning barriers, motivation, e-readiness, and satisfaction along with 4 open-ended questions were administered in this descriptive study. The results revealed that most of online students were satisfied with the online graduate program of TEFL as online instructors provided students with lesson summary and class material prior to the session, had interaction with students through social networks, and held the online classes after office hours. The results also showed that online students' motivation was mostly instrumental, and some were not completely ready for online education. The results of multiple regression analysis also indicated that the contribution of motivation to satisfaction was higher than that of readiness and barriers. Online instructors need to solve students’ educational problems to make them ready for online instruction and to foster students’ motivation, which are influential in enhancing their satisfaction with online learning programs.
HIF-1α and STAT3 are two of the critical factors in the growth, proliferation, and metastasis of cancer cells and play a crucial role in inhibiting anti-cancer immune responses. Therefore, we used ...superparamagnetic iron oxide (SPION) nanoparticles (NPs) coated with thiolated chitosan (ChT) and trimethyl chitosan (TMC) and functionalized with hyaluronate (H) and TAT peptide for delivery of siRNA molecules against STAT3 and HIF-1α to cancer cells both in vivo and in vitro. The results indicated that tumor cell transfection with siRNA-encapsulated NPs robustly inhibited proliferation and migration and induced apoptosis in tumor cells. Furthermore, simultaneous silencing of HIF-1α and STAT3 significantly repressed cancer development in two different tumor types (4T1 breast cancer and CT26 colon cancer) which were associated with upregulation of cytotoxic T lymphocytes and IFN-γ secretion. The findings suggest inhibiting the HIF-1α/STAT3 axis by SPION-TMC-ChT-TAT-H NPs as an effective way to treat cancer.
Concurrent inhibition of HIF-1α and STAT3 suppresses cancer development. Hyperactivity of HIF-1α and STAT3 leads to tumor growth by increasing the expression of factors involved in proliferation (Ki-67), metastasis (MMP2/9), etc. SPION-TMC-ChT-TAT-H NPs loaded with HIF-1α/STAT3 siRNAs effectively suppress tumor growth. Display omitted
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with a mortality rate of up to 50% in humans. To avoid safety concerns associated with the use of live virus in virus neutralization ...assays and to detect human serum neutralizing antibodies, we prepared lentiviral particles containing the CCHF glycoprotein (lenti-CCHFV-GP). Incorporation of the GP into the lentiviral particle was confirmed by electron microscopy and Western blotting. Lenti-CCHFV-GP was found to be able to infect a wide range of cell lines, including BHK-21, HeLa, HepG2, and AsPC-1 cells. In addition, lenti-CCHFV-GP was successfully used as an alternative to CCHFV for the detection of neutralizing antibodies. Sera collected from CCHF survivors neutralized lenti-CCHFV-GP particles in a dose-dependent manner. Our results suggest that the lenti-CCHFV-GP pseudovirus can be used as a safe tool for neutralization assays in low-containment laboratories.
A series of (
)-2-(nitroheteroarylmethylene)-3(2
)-benzofuranones possessing nitroheteroaryl groups of nitroimidazole, nitrofuran, and nitrothiophene moieties was screened for antiplasmodium activity ...against a drug-sensitive strain (3D7 strain) and a multidrug-resistant (chloroquine CQ and pyrimethamine) strain (K1 strain) of Plasmodium falciparum. 5-Nitroimidazole and 4-nitroimidazole analogs were highly selective and active against resistant parasites, while 5-nitrofuran and 5-nitrothiophene derivatives were more potent against the 3D7 strain than against the K1 strain. Among the synthetic analogues, (
)-6-chloro-2-(1-methyl-5-nitroimidazol-2-ylmethylene)-3(2
)-benzofuranone (compound 5h) exhibited the highest activity (50% inhibitory concentration IC
, 0.654 nM) against the K1 strain and (
)-7-methoxy-2-(5-nitrothiophen-2-ylmethylene)-3(2
)-benzofuranone (10g) showed the highest activity (IC
, 0.28 μM) against the 3D7 strain in comparison with the activities of CQ (IC
s of 3.13 and 206.3 nM against 3D7 and K1 strains, respectively). The more active compounds, with IC
s lower than 5 μg/ml (∼20 μM), were further studied for their cytotoxicity responses using KB cells. From these studies, 5-nitroimidazole, 4-nitroimidazole, and 5-nitrofuran analogues were shown to be cytotoxic against KB cells, while 5-nitrothiophene analogues were shown to have the least cytotoxic effects. To gain some insight into their potential contributing mechanisms of action, three derivatives, 10e, 10g, and 10h (from the nitrothiophene subgroup, possessing 6-methoxy, 7-methoxy, and 6,7-dimethoxy substituents, respectively, on their benzofuranone moieties), showing the least toxicity and highest selectivity indices were assessed for their β-hematin formation inhibition activity. Compound 10g demonstrated the highest inhibition activity (IC
, 10.78 μM) in comparison with that of CQ (IC
, 2.63 μM) as the reference drug. Finally, these three analogues (10e, 10g, and 10h) were further evaluated for their
activities against the Plasmodium berghei/albino mouse model (Peter's test). The tested analogues were shown to be active, reducing the percentages of erythrocytes that contained parasites by 53.4, 48.8, and 32.4%, respectively.
Background: Hypothermia is usually used during cardiac surgery to further protect against cardiac and cerebral ischemia. However, cognitive impairment could be a common complication after open heart ...surgery. This study aims to determine the effect of rewarming on the cognitive status of patients after open heart surgery. Methods: The present study was conducted as a double-blind, randomized clinical trial at Tehran Heart Center, Tehran, Iran. In this clinical trial, 80 patients referred for open heart surgery were selected and randomly assigned into the intervention (n=40) and control (n=40) groups. In the intervention group, rewarming the mattress was started after the patient entered the intensive care unit. Warming continued until the patient’s body temperature reached the normothermia level (37°C to 37.5°C). The data were collected by demographic-clinical questionnaire and Mini-Mental State Examination at three time points: before, 7 days, and 1 month after the surgery. The data were analyzed in SPSS software, version 16 using descriptive statistics, independent t test, chi-square test, repeated measure ANOVA, and paired t test. The significance level was considered less than 0.05. Results: The difference between the mean±SD scores of cognitive status in the intervention group before the surgery (28.73±0.87), 7 days (27.63±1.03), and 1 month after the surgery (28.93±1.21) was significant (P=0.008). The difference between the mean±SD scores of cognitive status in the control group before the surgery (28.42±1.02), 7 days (26.61±0.86), and 1 month after the surgery (27.85±1.06) was also significant (P=0.042). The results indicated that the mean score of cognitive status improves after 1 month, and it is greater in the intervention group (F=20.37, df=2, P<0.001). Significant differences were observed between the first and second time of measurements (P<0.0001) and also the second and third time of measurements (P<0.0001). Conclusion: Rewarming patients after open heart surgery improves their cognitive status. Therefore, this procedure can be used as a safe and non-invasive method to prevent cognitive complications by nurses after open heart surgery.
Intimate partner violence (IPV) is a neglected public health issue in Iran. This study was conducted among married women residing in urban Rasht (northern Iran), to estimate the prevalence and ...frequency of different forms of IPV from husband and their associations with socio-demographic factors. We carried out a population-based cross-sectional survey with cluster sampling design from February to October 2015. The samples consisted of married women aged ≥ 18 years with total household in Rasht city (north Iran) as the sample frame. We administered the Revised Conflict Tactics Scale (CTS-2) to estimate prevalence of past-year IPV. Of 2091 women, 57.1% had suffered psychological aggression, 27.6% physical abuse, 26.6% sexual abuse, and 6.9% injury. A significant association with IPV was found for women with, age ≤ 40 years, unemployed, low education, husband's addiction and rented-householders. Women who experienced physical abuse, had less age at marriage than women without violence. Also women with sexual coercion had less length of marriage than other non-abused women. On logistic regression, the strongest predictor of psychological, physical and sexual abuse was unemployment of spouse, whereas for injury it was low educational level (<12 years) of women. Our findings suggest that risk of IPV is high in our population. There is an obvious need of preventive and treatment activities. Our findings point at that various forms of abuse are different from each other in terms of differing characteristics of the perpetrators and it might be that also different strategies are needed to reduce and prevent these violence. Confirmation by further research is needed.
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