The effects of Fasciola hepatica recombinant proteins (peroxiredoxin and cathepsin L1) on Crohn's disease experimental model.

The immunomodulatory potential of the excretory-secretory (E/S) proteins of the helminths has been shown in previous investigations. This study evaluated the effects of the recombinants and excretory-secretory proteins of the Fasciola hepatica on induced colitis in Balb/c mice. The F. hepatica Recombinant proteins, Cathepsin L1 and Peroxiredoxin, and E/S proteins were intraperitoneally injected into the three mice groups as the case groups, while the control groups received PBS. Colitis was induced in mice by intraluminal administration of the 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS). After 8 h, the case groups received the second dosage of the treatments, and it was repeated 24 h later. The immunological, pathological, and macroscopic changes were evaluated 3 days after colitis induction. The macroscopic evaluation revealed significantly lower inflammatory scores in the mice treated with recombinant Peroxiredoxin (rPRX) and recombinant Cathepsin L1 (rCL1). Despite the macroscopic observation, the pathological finding was insignificant between the groups. IFN-γ secretion was significantly lower in splenocytes of the groups that received rPRX, rCL1, and E/S than the controls. IL-10 showed significantly higher levels in groups treated with rPRX and rCL1 than controls, whereas the level of IL-4 was not statistically significant. Excretory-secretory proteins of the F. hepatica showed immunomodulatory potency and the main effects observed in this study were through the reduction of inflammatory cytokine and inflammation manifestation as well as induction of anti-inflammatory cytokines.

Ageism and lookism as stereotypes of health disparity in intensive care units in Iran: a critical ethnography.

BACKGROUND: The intensive care unit presents structural complexities, and the prevailing power imbalance between patients and staff can lead to health disparities. Hence, unveiling the underlying factors that give rise to and reinforce these disparities can contribute to their prevention. This study aims to shed light on the stereotypes linked to ageism and lookism, which perpetuate health disparities within the intensive care unit setting in Iran. METHODS: This critical ethnographic study employed Carsepkan's approach and was carried out in intensive care units in the west of Iran from 2022 to 2023. The data collection and analysis were conducted through three interconnected stages. In the initial stage, more than 300 h of observations were made at the research site. In the subsequent stage, a horizon analysis was performed. Conversations with 14 informants were conducted in the final stage to enrich the dataset further. Then the analysis process was carried out as in the previous step to uncover an implicit culture of health disparity. To verify the validity and reliability of the study, credibility, conformability, dependability, and transferability were all taken into account. FINDINGS: The ageism and lookism stereotypes emerged from seven main themes; youth-centric; negative ageism; age-friendliness; age-related priority; centered care for pediatric patients and families; appearance-centeredness; and a contradiction between belief and behavior. CONCLUSION: This critical study showed that ageism and lookism stereotypes permeated the intensive care unit's culture. These stereotypes have the potential to influence equality dynamics, as well as to foster and support health disparity in the intensive care unit.

Tic disorder in allergic rhinitis children and adolescents: a case-control study.

BACKGROUND: Allergic rhinitis is the most common allergic disease. It can accompany psychological disorders such as tic disorders due to the prolonged course of the symptoms of allergic rhinitis. This pioneer case-control study aims to investigate tic disorders in children and adolescents under 18 years of age diagnosed with allergic rhinitis. METHOD: The case group in this study consisted of patients who had both allergic rhinitis and tic disorders. Patients with allergic rhinitis without tic disorders were also enrolled as the control group with matched gender and age. Demographic characteristics, tic classifications, and contributing factors for allergic rhinitis and tic disorders were studied among the cases. Tic disorders were evaluated using DSM-5 criteria for the classification of tic disorders. RESULTS: 47 patients in the case group and 47 patients in the control group were included in this study. 53.2% and 46.8% were males and females in the case group, respectively. The mean age of the patients was 10.46 ± 3.97 years old. Sound tics were more common among the patients compared to motor tics. Patients with concomitant AR and tic disorders had more days per week with AR symptoms (P-value ≤ 0.001; OR (every day vs. three days a week = 11.02(2.98, 40.76))). Most patients with sound tick were women (p: 0.026), and most patients with motion tic were in the Provisional tic disorder group (p: 0.001). The history of infantile eczema was seen more in patients without sound tic (p: 0.025), and otitis media was significantly less common among patients with sound tics (p: 0.026). Provisional tic disorder was the most common class among the patients. In the case group (coexistence between allergic rhinitis and tic) compared to the control group, patients had significantly more days with AR symptoms per week. CONCLUSION: This preliminary study indicates that Provisional tic disorder was the most common classification of tic among patients with allergic rhinitis, especially in patients with motor tics. Asthma in motor tics, a history of food allergy in infancy, and a history of infantile eczema were also common among patients with vocal tics. Also, patients with allergic rhinitis and tic had more severe disease (more symptoms per week) than those with rhinitis alone. These findings emphasize the association of tic disorders with immunological pathways.

Exosome-mediated miR-200a delivery into TGF-ß-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression.

Exosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential regulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miR-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miR-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-ß for EMT induction and then, these cells cultured with miR-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading efficiency of 5.92 ± 4.6%. The TGF-ß treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miR-200a expression in AGS cells. Mechanistically, miR-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of ß-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01), leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miR-200a delivery that is of importance for preventing migration and invasion of GC cells.

Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity.

The identification of agents that can reverse drug resistance in cancer chemotherapy, and enhance the overall efficacy is of great interest. Paclitaxel (PTX) belongs to taxane family that exerts an antitumor effect by stabilizing microtubules and inhibiting cell cycle progression. However, PTX resistance often develops in tumors due to the overexpression of drug transporters and tumor-promoting pathways. Noncoding RNAs (ncRNAs) are modulators of many processes in cancer cells, such as apoptosis, migration, differentiation, and angiogenesis. In the present study, we summarize the effects of ncRNAs on PTX chemotherapy. MicroRNAs (miRNAs) can have opposite effects on PTX resistance (stimulation or inhibition) via influencing YES1, SK2, MRP1, and STAT3. Moreover, miRNAs modulate the growth and migration rates of tumor cells in regulating PTX efficacy. PIWI-interacting RNAs, small interfering RNAs, and short-hairpin RNAs are other members of ncRNAs regulating PTX sensitivity of cancer cells. Long noncoding RNAs (LncRNAs) are similar to miRNAs and can modulate PTX resistance/sensitivity by their influence on miRNAs and drug efflux transport. The cytotoxicity of PTX against tumor cells can also be affected by circular RNAs (circRNAs) and limitation is that oncogenic circRNAs have been emphasized and experiments should also focus on onco-suppressor circRNAs.

The effect of IGF-1 plasma concentration on COVID-19 severity.

BACKGROUND: The severity and fatality of Coronavirus disease 2019 (COVID-19) infection are not the same in the infected population. The host immune response and Immune-stimulating factors appear to play a role in COVID-19 infection outcome. insulin-like growth factor-1 (IGF-1) affects the immune system by controlling the endocrine system. Recently, the effect of IGF-1 levels on COVID-19 prognosis has been considered. OBJECTIVE: To investigate the difference between circulating IGF-1 and inflammatory cytokines concentration among COVID-19 patients, infected patients admitted to the Intensive Care Unit (ICU) (n = 40; 35 ± 5 y) and patients with mild cases of COVID-19 (n = 40; 35 ± 5 y) were screened prior to participation in the study. There was no significant difference between the groups in terms of gender and preexisting inflammatory state. Collected samples were evaluated by ELISA for IGF-1 and IL-6. RESULTS: The study outcomes included a significant decrease in IGF-1 and an increase in IL-6 serum concentration, as an inflammatory marker, for infected patients admitted to the Intensive Care Unit (ICU) (P ≤ 0.001). Finally, there was a significant increase in the IGF-1 and a decrease in the IL-6 serum concentration of hospitalized patients. DISCUSSION: it appears that inflammatory cytokines (IL-6) serum concentration in the severe form of corona virus-based infections causes reduced defenses because of suppressed IGF-1. CONCLUSIONS: Our findings show that lower IGF-1 concentrations are associated with a Severe form of COVID-19 disease. It seems, IGF-1 supplementation or anti-inflammatory treatment rescued the severe form of COVID-19 infection. Further studies are required to determine how to design COVID-19 therapeutic strategies targeting the IGF-1 pathway.

Experiences of cancer patients about seeking health information: a qualitative study.

OBJECTIVE: Searching for health information is an important strategy in dealing with cancer that contributed to the improved management of cancer. This qualitative study aimed to explore the experiences of cancer patients seeking health information using the conventional content analysis approach. METHODS: The 18 participants were selected by purposive sampling and data were collected through semi-structured in-depth interviews. Data were analyzed by software MaxQDA 10 based on conventional content analysis. RESULTS: Data analysis led to the emergence of three central categories, including "optimal cancer management," "poor information dissemination system," and "perceived health literacy." CONCLUSION: Knowing how cancer patients obtain health information can form the basis to promote patients' health literacy and design a health information dissemination system tailored to the patients' needs.

Effect of fluoxetine treatment on neurotoxicity induced by lysolecithin in male rats.

Demyelination disorder is an unusual pathologic event, which occurs in the central nervous system (CNS). Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects the CNS, and it is the leading cause of disability in young adults. Lysolecithin (LPC) is one of the best toxin-induced demyelination models. In this study, a suitable model is created, and the effect of fluoxetine treatment is examined on this model. In this case, it was assumed that daily fluoxetine treatment had increased the endogenous remyelination in the LPC model. This study was focused on investigating the influence of the fluoxetine dose of 5 or 10 mg/kg per day for 1 and 4 weeks on LPC-induced neurotoxicity in the corpus callosum region. It was performed as a demyelinating model in male Wistar rats. After 3 days, fluoxetine was injected intraperitoneally (5 or 10 mg/kg per day) for 1 and 4 weeks in each group. After completing the treatment course, the corpus callosum was removed to examine the gene expression and histological analysis was performed. The results of the histopathological study of hematoxylin and eosin staining of the corpus callosum showed that in 1 and 4-week treatment groups, fluoxetine has reduced the level of inflammation at the LPC injection site (5 and 10 mg/kg per day). Fluoxetine treatment in the luxol fast blue (LFB) staining of the corpus callosum has been led to an increase in myelination capacity in all doses and times. The results of the genetic study showed that the fluoxetine has significantly reduced the expression level of tumor necrosis factor-α, nuclear factor κß, and induced nitric oxide synthase in comparison with the untreated LPC group. Also, the fluoxetine treatment has enhanced the expression level of the forkhead box P3 (FOXP3) gene in comparison with the untreated group. Fluoxetine has increased the expression level of myelination and neurotrophic genes such as myelin basic protein (MBP), oligodendrocyte transcription factor 2 (OLIG2), and brain-derived neurotrophic factor (BDNF). The outcomes demonstrated that fluoxetine reduces inflammation and strengthens the endogenous myelination in the LPC-induced demyelination model; however, supplementary studies are required for specifying the details of its mechanisms.

Association between TBXT rs2305089 polymorphism and chordoma in Iranian patients identified by a developed T-ARMS-PCR assay.

BACKGROUND: Chordoma is a locally aggressive bone tumor with a high capability of recurrence. Because chordoma often occurs at critical locations next to neurovascular structures, there is an urgent need to introduce validated biomarkers. T-box transcription factor T (TBXT; OMIM: 601397) plays an important role in the pathogenesis and survival of chordoma cells. METHODS: Herein, we aimed to show whether rs2305089 polymorphism is correlated with chordoma in the Iranian population. In order to detect rs2305089, tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used. In total, 19 chordoma patients and 108 normal healthy individuals were recruited and screened using T-ARMS-PCR. The results were subsequently validated by Sanger sequencing. RESULTS: The genotype distributions and allele frequencies were significantly different among the patient and healthy groups (p-value <0.05). The A allele of rs2305089 showed a significant positive association with chordoma risk (p-value <0.05). DNA sequencing verified the T-ARMS-PCR results as well. This study demonstrated the association between TBXT rs2305089 and chordoma in an Iranian population using a simple, accurate, and cost-effective T-ARMS-PCR assay. CONCLUSIONS: Our results were in line with those of previous studies showing that TBXT rs2305089 is associated with chordoma development. We also developed an efficient T-ARMS-PCR assay to determine the genotype of rs2305089.

Evaluation of co-cultured spermatogonial stem cells encapsulated in alginate hydrogel with Sertoli cells and their transplantation into azoospermic mice.

An in vitro spermatogonial stem cell (SSC) culture can serve as an effective technique to study spermatogenesis and treatment for male infertility. In this research, we compared the effect of a three-dimensional alginate hydrogel with Sertoli cells in a 3D culture and co-cultured Sertoli cells. After harvest of SSCs from neonatal mice testes, the SSCs were divided into two groups: SSCs on a 3D alginate hydrogel with Sertoli cells and a co-culture of SSCs with Sertoli cells for 1 month. The samples were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays and bromodeoxyuridine (BrdU) tracing, haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining after transplantation into an azoospermic testis mouse. The 3D group showed rapid cell proliferation and numerous colonies compared with the co-culture group. Molecular assessment showed significantly increased integrin alpha-6, integrin beta-1, Nanog, Plzf, Thy-1, Oct4 and Bcl2 expression levels in the 3D group and decreased expression levels of P53, Fas, and Bax. BrdU tracing, and H&E and PAS staining results indicated that the hydrogel alginate improved spermatogenesis after transplantation in vivo. This finding suggested that cultivation of SSCs on alginate hydrogel with Sertoli cells in a 3D culture can lead to efficient proliferation and maintenance of SSC stemness and enhance the efficiency of SSC transplantation.

3D in vivo dosimetry of HDR gynecological brachytherapy using micro silica bead TLDs.

PURPOSE: This study aimed to evaluate the feasibility of defining an in vivo dosimetry (IVD) protocol as a patient-specific quality assurance (PSQA) using the bead thermoluminescent dosimeters (TLDs) for point and 3D IVD during brachytherapy (BT) of gynecological (GYN) cancer using 60 Co high-dose-rate (HDR) source. METHODS: The 3D in vivo absorbed dose verification within the rectum and bladder as organs-at-risk was performed by bead TLDs for 30 GYN cancer patients. For rectal wall dosimetry, 80 TLDs were placed in axial arrangements around a rectal tube covered with a layer of gel. Ten beads were placed inside the Foley catheter to get the bladder-absorbed dose. Beads TLDs were localized and defined as control points in the treatment planning system (TPS) using CT images of the patients. Patients were planned and treated using the routine BT protocol. The experimentally obtained absorbed dose map of the rectal wall and the point dose of the bladder were compared to the TPSs predicted absorbed dose at these control points. RESULTS: Relative difference between TPS and TLDs results were -8.3% ± 19.5% and -7.2% ± 14.6% (1SD) for rectum- and bladder-absorbed dose, respectively. Gamma analysis was used to compare the calculated with the measured absorbed dose maps. Mean gamma passing rates of 84.1%, 90.8%, and 92.5% using the criteria of 3%/2 mm, 3%/3 mm, and 4%/2 mm were obtained, respectively. Eventually, a "considering level" of at least 85% as pass rate with 4%/2-mm criteria was recommended. CONCLUSIONS: A 3D IVD protocol employing bead TLDs was presented to measure absorbed doses delivered to the rectum and bladder during GYN HDR-BT as a reliable PSQA method. 3D rectal absorbed dose measurements were performed. Differences between experimentally measured and planned absorbed dose maps were presented in the form of a gamma index, which may be used as a warning for corrective action.

The effect of the online flipped classroom on self-directed learning readiness and metacognitive awareness in nursing students during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has initiated digital developments in higher education while closing in-person university classes. As this crisis continues, the need to revive virtual learning opportunities was seriously felt. The present study was conducted to determine the online flipped classroom's effect on nursing students' self-directed learning readiness and metacognitive awareness. METHODS: This quasi-experimental single-group study with pretest-posttest design recruited 34 sophomore students of a nursing school in Lorestan province, Western Iran selected by census according to the inclusion criteria. Online asynchronous learning and online flipped classrooms were used during the semester's first and second eight weeks, respectively. Students filled out self-directed learning readiness scale and metacognitive awareness inventory online before, in the middle of, and at the end of the semester. Data were analyzed using paired t-test in Stata-14 software. RESULTS: There was no significant difference between the mean score of metacognitive awareness before and after Online asynchronous learning (P=0.15), but the mean score of self-directed learning readiness increased significantly after OA (P=0.0004). After applying online flipped classrooms, students' mean (SD) scores of metacognitive awareness and self-directed learning readiness were 272.03 (53.03) and 162.03 (21.77), respectively, which confirmed their significant improvement compared to before the intervention. A comparison of the mean score changes of both methods indicated that their implementation did not lead to significant differences between the mean total score of metacognitive awareness (P=0.15) and the mean total score of self-directed learning readiness (P=0.07). DISCUSSION: Online flipped classroom approach can be used as an effective method in nursing education by improving self-directed learning and metacognitive awareness, which are essential in online education for nursing students.

Effects of a multidisciplinary management program on symptom burden and medication adherence in heart failure patients with comorbidities: A randomized controlled trial.

BACKGROUND: Comorbidities in heart failure (HF) are a complex clinical challenge. There is little data on the benefits of multidisciplinary postdischarge management programs in such patients. This study aimed to examine the effects of a multidisciplinary management program (MMP) on symptom burden and medication adherence in HF patients with comorbidities. METHODS: In this clinical trial study, 94 HF patients with comorbidities were assigned to intervention (n = 47) and control (n = 47) groups by the stratified-random method. The intervention group underwent MMP supervised by a nurse for two months after discharge, including multi-professional visits, telephone follow-ups, and an educational booklet. Medication adherence and symptom burden were assessed using Morisky Medication Adherence Scale (MMAS) and Edmonton Symptom Assessment Scale (ESAS), respectively, on three occasions: Before discharge, six weeks, and eight weeks after discharge. RESULTS: Both groups almost matched at the baseline, and the most frequent comorbidities included myocardial infarction (MI), hypertension, peptic ulcer, and depression, respectively. The interactive effect of time in groups showed that mean changes in total scores of symptom burden and medication adherence were significantly different (P < 0.001) at other time points. A significant increase in medication adherence (P < 0.001) and a significant reduction in the burden of all symptoms were observed in the intervention group compared to the control group from Time 1 to Time 3. CONCLUSIONS: The MMP (targeting comorbidity) is a promising strategy for managing symptoms and medication adherence in HF patients with comorbidities.

Validation of an individualized home-made superficial brachytherapy mold applied for deep nonmelanoma skin cancer.

Background: This study was conducted to evaluate the effect of brachytherapy (BT) customized mold [Condensation silicone elastomer (ProtesilTM)] and its thickness on the dose distribution pattern of deep nonmelanoma skin cancers (NMSC). Materials and methods: Four blocks of mold material were constructed in 5, 10, 15, and 20 mm thickness and 100 × 100 mm2 area by a plastic cast. The high dose rate (HDR) plus treatment planning system (TPS) (Version 3, Eckert & Ziegler BEBIG Gmbh, Berlin, Germany) with a 60Co source (model: Co0.A86, EZAG BEBIG, Berlin, Germany) as an high dose rate brachytherapy (HDR-BT) source was used. Solid phantom and MOSFETTM and GAFCHROMICTM EBT3 film dosimeters were used for experimental dosimetry of the different thicknesses (up to 20 mm) of BT customized mold. Skin dose and dose to different depths were evaluated. Result: The TPS overestimated the calculated dose to the surface. Skin dose can be reduced from 250% to 150% of the prescription dose by increasing mold thickness from 5 mm to 20 mm. There was a 7.7% difference in the calculated dose by TPS and the measured dose by MOSFET. There was a good agreement between film dosimetry, MOSFET detector, and TPS' results in depths less than 5 mm. Conclusion: Each BT department should validate any individualized material chosen to construct the customized surface BT mold. Increasing the mold thickness can treat lesions without overexposing the skin surface. Superficial BT can be recommended as an appropriate treatment option for some deep NMSC lesions (up to 20 mm) with pre-planning considerations employing thicker molds.

Asthma and COPD Overlap Syndrome (ACOS): Risk Factors and Contributing Factors.

Background:The exact description of asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS) is uncertain. This study aims to determine the frequency and symptoms of ACOS and to verify certain risk factors associated with ACOS. Methods:Severe asthmatic patients with and without ACOS above 40 years old participated in this cross-sectional study. The receiver operating curve analysis (ROC) was used to assess the best cutoff values of age, body mass index (BMI), and spirometric data to distinguish asthma patients with overlap syndrome from asthma patients without overlap syndrome. Univariable and multivariable binary logistic regression was used to determine demographic and clinical factors that were associated with ACOS and asthma. Results:Of the 88 patients, 46 (52.2%) had ACOS and 42 (47.7%) had just severe asthma. The mean age of ACOS patients (Sd) was 54.91(12.57) years and in asthma-only patients was 48.69 (13.51). The ROC analysis for age and BMI showed that age ⩾ 49 years and BMI ⩾ 27 kg/m2were the best predictors of ACOS in this study. Spirometry data showed that the forced vital capacity (FVC) (lit) > 2.16, forced expiratory volume in the first second (FEV1) > 69, FEV1 / FVC > 96.5, and FVC (%) > 63 cut points could be used to determine the diagnostic criteria between ACOS and asthma only, respectively. Multivariate modeling showed that among the demographic and clinical variables, only age over 49 years (odds ratio [OR], 3.53 [95% CI, 1.07-11.63]p= 0.025) and living in a big city (OR, 7.42 [95% CI, 1.75-31.49]p= 0.007) were significant. Conclusion:Age over 49 and BMI above 27 have a significant association with ACOS. Also, living in a big city is considered to be another risk factor for ACOS compared with asthma. Spirometry can help distinguish ACOS from severe asthma in this study.

Graphene-Assisted Synthesis of 2D Polyglycerols as Innovative Platforms for Multivalent Virus Interactions.

2D nanomaterials have garnered widespread attention in biomedicine and bioengineering due to their unique physicochemical properties. However, poor functionality, low solubility, intrinsic toxicity, and nonspecific interactions at biointerfaces have hampered their application in vivo. Here, biocompatible polyglycerol units are crosslinked in two dimensions using a graphene-assisted strategy leading to highly functional and water-soluble polyglycerols nanosheets with 263 ± 53 nm and 2.7 ± 0.2 nm average lateral size and thickness, respectively. A single-layer hyperbranched polyglycerol containing azide functional groups is covalently conjugated to the surface of a functional graphene template through pH-sensitive linkers. Then, lateral crosslinking of polyglycerol units is carried out by loading tripropargylamine on the surface of graphene followed by lifting off this reagent for an on-face click reaction. Subsequently, the polyglycerol nanosheets are detached from the surface of graphene by slight acidification and centrifugation and is sulfated to mimic heparin sulfate proteoglycans. To highlight the impact of the two-dimensionality of the synthesized polyglycerol sulfate nanosheets at nanobiointerfaces, their efficiency with respect to herpes simplex virus type 1 and severe acute respiratory syndrome corona virus 2 inhibition is compared to their 3D nanogel analogs. Four times stronger in virus inhibition suggests that 2D polyglycerols are superior to their current 3D counterparts.

MicroRNAs regulating SOX2 in cancer progression and therapy response.

The proliferation, metastasis and therapy response of tumour cells are tightly regulated by interaction among various signalling networks. The microRNAs (miRNAs) can bind to 3'-UTR of mRNA and down-regulate expression of target gene. The miRNAs target various molecular pathways in regulating biological events such as apoptosis, differentiation, angiogenesis and migration. The aberrant expression of miRNAs occurs in cancers and they have both tumour-suppressor and tumour-promoting functions. On the contrary, SOX proteins are capable of binding to DNA and regulating gene expression. SOX2 is a well-known member of SOX family that its overexpression in different cancers to ensure progression and stemness. The present review focuses on modulatory impact of miRNAs on SOX2 in affecting growth, migration and therapy response of cancers. The lncRNAs and circRNAs can function as upstream mediators of miRNA/SOX2 axis in cancers. In addition, NF-κB, TNF-α and SOX17 are among other molecular pathways regulating miRNA/SOX2 axis in cancer. Noteworthy, anti-cancer compounds including bufalin and ovatodiolide are suggested to regulate miRNA/SOX2 axis in cancers. The translation of current findings to clinical course can pave the way to effective treatment of cancer patients and improve their prognosis.

Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer.

As a phenolic acid compound, caffeic acid (CA) can be isolated from different sources such as tea, wine and coffee. Caffeic acid phenethyl ester (CAPE) is naturally occurring derivative of CA isolated from propolis. This medicinal plant is well-known due to its significant therapeutic impact including its effectiveness as hepatoprotective, neuroprotective and anti-diabetic agent. Among them, anti-tumor activity of CA has attracted much attention, and this potential has been confirmed both in vitro and in vivo. CA can induce apoptosis in cancer cells via enhancing ROS levels and impairing mitochondrial function. Molecular pathways such as PI3K/Akt and AMPK with role in cancer progression, are affected by CA and its derivatives in cancer therapy. CA is advantageous in reducing aggressive behavior of tumors via suppressing metastasis by inhibiting epithelial-to-mesenchymal transition mechanism. Noteworthy, CA and CAPE can promote response of cancer cells to chemotherapy, and sensitize them to chemotherapy-mediated cell death. In order to improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid and p-coumaric acid. Due to its poor bioavailability, nanocarriers have been developed for enhancing its ability in cancer suppression. These issues have been discussed in the present review with a focus on molecular pathways to pave the way for rapid translation of CA for clinical use.

Nrf2 signaling pathway in cisplatin chemotherapy: Potential involvement in organ protection and chemoresistance.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor and its induction is of significant importance for protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) stimulate Nrf2 signaling, enhancing the activity of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. These enzymes are associated with retarding oxidative stress. On the other hand, Nrf2 activation in cancer cells is responsible for the development of chemoresistance due to disrupting oxidative mediated-cell death by reducing ROS levels. Cisplatin (CP), cis-diamminedichloroplatinum(II), is a potent anti-tumor agent extensively used in cancer therapy, but its frequent application leads to the development of chemoresistance as well. In the present study, association of Nrf2 signaling with chemoresistance to CP and protection against its deleterious effects is discussed. Anti-tumor compounds, mainly phytochemicals, retard chemoresistance by suppressing Nrf2 signaling. Upstream mediators such as microRNAs can regulate Nrf2 expression during CP chemotherapy regimens. Protection against side effects of CP is mediated via activating Nrf2 signaling and its downstream targets activating antioxidant defense system. Protective agents that activate Nrf2 signaling, can ameliorate CP-mediated ototoxicity, nephrotoxicity and neurotoxicity. Reducing ROS levels and preventing cell death are the most important factors involved in alleviating CP toxicity upon Nrf2 activation. As pre-clinical experiments advocate the role of Nrf2 in chemoprotection and CP resistance, translating these findings to the clinic can provide a significant progress in treatment of cancer patients.

Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3.

OBJECTIVES: The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count <100 cells/mm3 and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. METHODS: This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count <100 cells/mm3, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). RESULTS: Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (p value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (p < 0.02). CONCLUSIONS: We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count <100 mm3/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.