Association of polymorphisms in TLR3 and TLR7 genes with susceptibility to COVID-19 among Iranian population: a retrospective case-control study.

Background and Objectives: Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main factors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibility to COVID-19 in a sample of the Iranian population. Materials and Methods: This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was genotyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a significant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P<0.0001; adjusted OR: 6.818; 99% CI: 3.149-14.134) were determined. The polymorphism frequency of TLR3 rs3775291 and rs3775296 genotypes were not significantly different between the case and control groups (P> 0.004167). Conclusion: SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population.

Added γ-oryzanol boosted anti-inflammatory effects of canola oil in adult subjects with type 2 diabetes: a randomized controlled clinical trial.

PURPOSE: This study was conducted to examine the effects of daily intake of γ-oryzanol (ORZ)-fortified canola oil, as compared with plain canola and sunflower oils, on certain inflammatory and oxidative stress biomarkers in adult subjects with Type 2 Diabetes (T2D). METHODS: We randomly allocated 92 adult subjects with T2D from both sexes to one of the following groups to receive: (a) ORZ-fortified canola oil (ORZO; n1 = 30); (b) unfortified canola oil (CANO; n2 = 32); or (c) sunflower oil (SUFO; n3 = 30) for 12 weeks. Dietary and laboratory evaluations were performed initially and finally. RESULTS: Serum hs-CRP concentrations significantly decreased in ORZO group (from 3.1 ± 0.2 to 1.2 ± 0.2 mg/L), as compared with CANO (p = 0.003) and SUFO (p < 0.001) groups. Serum IL-6 significantly decreased just in ORZO (- 22.8%, p = 0.042) and CANO groups (- 19.8%, p = 0.038). However, the between-group differences were not significant. Serum IL-1ß slightly decreased in ORZO (- 28.1%, p = 0.11) and increased in SUFO (+ 20.6%, p = 0.079) but between-group difference was statistically significant (p = 0.017). Serum IFN-γ concentrations decreased significantly only in ORZO (from 3.3 ± 0.08 to 2.9 ± 0.21 IU/mL, p = 0.044). Salivary IgA concentrations increased significantly in all three intervention groups. Notwithstanding, only the difference between ORZO and CANO groups was statistically significant (p = 0.042). Similarly, circulating malondialdehyde concentrations significantly decreased in all three groups but with no between-group significant difference. CONCLUSIONS: Daily consumption of ORZ-fortified canola oil, compared with unfortified canola and sunflower oils, for 12 weeks resulted in boosting of certain anti-inflammatory effects of canola oil. These findings may have preventive implications for both clinicians and policy makers. This clinical trial was registered at clinicaltrials.gov (03.08.2022; NCT05271045).

Daily consumption of γ-oryzanol-fortified canola oil, compared with unfortified canola and sunflower oils, resulted in a better improvement of certain cardiometabolic biomarkers of adult subjects with type 2 diabetes: a randomized controlled clinical trial.

BACKGROUND: This study was undertaken to examine the effects of daily consumption of γ-oryzanol (ORZ)-fortified canola oil, as compared with plain canola and sunflower oils, on certain cardiometabolic indicators. METHODS: Ninety-two adult subjects from both sexes with T2D were randomly assigned to one of the three groups to receive: (a) ORZ-fortified canola oil (Group 1; n1 = 30); (b) unfortified canola oil (Group 2; n2 = 32); or (c) sunflower oil (Group 3; n3 = 30) for 12 weeks. The participants were instructed to use only the given oils for all cooking (but frying) purposes. Anthropometric, dietary and biochemical assessments were done initially and finally. RESULTS: Though body mass index (BMI) significantly decreased in all three groups, only in Groups 1 and 2 waist circumference (WC) showed a significant decrement (-2.6 ± 0.1 and -2.2 ± 0.1 cm in Groups 1 and 2 respectively, p < 0.001 for both) which was accompanied by a significant reduction of blood pressure just in Group 1. Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) showed a significant decrease only in ORZ-fortified canola oil group (-7.7 ± 0.4 mg/dL, p = 0.039 and -0.7 ± 0.1%, p < 0.001, respectively). However, insulin resistance, as judged by HOMA-IR, did not change significantly. In addition, serum triglyceride (TG) concentrations decreased in all three groups but only in ORZ-fortified canola oil was this decrement statistically significant (-17.9 ± 2.1 mg/dL, p = 0.005). Other components of serum lipid profile did not change significantly in either group. CONCLUSIONS: Consumption of either sunflower or canola oils for 12 weeks improved certain studied biomarkers. However, only ORZ-fortified canola oil resulted in a significant decrease of blood pressure, WC, FBG, HbA1c and TG. These findings can help both clinicians and public health authorities for dietary recommendations to subjects with T2D and presumably the whole community. TRIAL REGISTRATION: number at clinicaltrials.gov (NCT05271045).

Implementation of an In-House Platform for Rapid Screening of SARS-CoV-2 Genome Variations.

BACKGROUND: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. METHODS: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. RESULTS: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. CONCLUSION: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.

The combined effect of fish oil containing Omega-3 fatty acids and Lactobacillus plantarum on colorectal cancer.

Colorectal cancer (CRC) is one of the deadliest malignancies. Recent attempts have indicated the role of diet in the etiology of CRC. Natural dietary compounds such as probiotics and Omega-3 fatty acids that act synergistically can be beneficial in finding a tremendous solution against CRC. To date, the combined effect of fish oil containing Omega-3 fatty acids (Omega-3) and Lactobacillus plantarum (L. plantarum) on CRC has been left behind. We here evaluated the effects of co-encapsulation of Omega-3 and probiotic bacteria on CRC cell lines compared to normal cells. Omega-3 and L. plantarum bacteria were co-encapsulated in three ways, including gelatin-gum Arabic, gelatin-chitosan, and chitosan-gum Arabic complex coacervate microcapsules. After treatment of cells (Normal [L929] and colorectal [C26]) by L. plantarum, Omega-3, and microcapsules, viability and growth capacity of cell lines were measured using the MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Isolated total RNA was used to evaluate the expression profile of BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and Caspase-3 (CASP3) genes by real-time polymerase chain reaction (PCR). Statistical analysis was performed with SPSS 25 software. A value of p < .05 was considered statistically significant. The results indicated a significant reduction in cell viability of C26 in a concentration-dependent manner in the treated cells with all treatments, except gelatin-gum Arabic microcapsules. The messenger RNA (mRNA) expression level of the BAX and CASP3 genes in C26 cells being treated with all treatments significantly increased than in untreated cells, and the expression level of the anti-apoptotic factor of the BCL-2 gene decreased in C26 cells simultaneously (p < .05). Although, the combined effect of Omega-3 and L. plantarum and microcapsulated treatments had no more effect on viability and apoptosis gene expression of cancer cells compared to Omega-3 or L. plantarum. In conclusion, combination therapy with fish oil containing Omega-3 and L. plantarum does not improve the anticancer effect of each alone.

Texture and viscoelastic characteristics of silver carp (Hypophthalmichthys molitrix) surimi affected by combination of washing regimes and hydrogen peroxide.

This study aimed to apply H2 O2 at different concentrations in combination with mince:water (M:W) ratios and different washing cycles (WCs) to produce surimi gel from silver carp without compromising its quality characteristics. Color, texture, microstructure, and rheological properties of surimi gels were investigated. Water holding capacity, texture profile, and gel strength showed a greater dependency on number of WCs than the M:W ratios and percentage of H2 O2 (p < .05), that is, higher WCs, firmer surimi gel. Accordingly, T2 (one WC, 2% H2 O2 , 1:3), T10 (two WC, 1% H2 O2 , 1:2), and T16 (three WC, 1% H2 O2 , 1:2) treatments resulted the most cohesive and resilient surimi compared with the rest (p < .05), confirmed by scanning electron microscopy images. However, all treated fish mince samples with H2 O2 , resulted in a surimi gel with lower texture quality compared with the control surimi prepared by conventional washing process without H2 O2 (p < .05). A temperature sweep test was conducted based on the linear viscoelastic region stress and frequency values and the aforementioned surimi gels exhibited an obvious valley shape pattern at temperature range of 48-62°C. In the creep-recovery test, the Burgers model satisfactorily described the internal structure of the surimi gel samples as the lowest deformation belonged to the control samples followed by T2. However, after 300 s strain, neither of surimi gels were fully recovered their original shape. Altogether, further studies are needed to clarify the effects of H2 O2 in reduction of WCs, without significantly affecting the textural and rheological properties of resultant surimi gel.

Renin-Angiotensin-Aldosterone Axis Inhibition Improves Outcome of Diabetic Patients with Chronic Hypertension and COVID-19: An Iranian Perspective.

Background: Safe use of drugs such as angiotensin-converting enzyme 2 (ACE2) inhibitors and angiotensin receptor blockers (ARBs) in COVID diabetic patients needs comprehensive studies. This study addressed this issue from the Iranian perspective. Materials and Methods: Admitted COVID-19 patients were divided into four groups in this historical cohort study. Group 1 included 740 non-diabetic, non-hypertensive patients. Group 2 included 132 non-hypertensive diabetic patients. Group 3 included 154 non-diabetic hypertensive patients. Group 4 included 183 diabetic patients who were under ACE inhibitors or ARBs. Death, intensive care unit (ICU) admission, and length of hospitalization were compared between the groups. Results: After considering associated factors such as age, gender, dyslipidemia, cardiovascular diseases, rheumatoid arthritis (RA), chronic kidney disease (CKD), history of surgery, and corticosteroid use, diabetic patients (group 2) were associated with increased mortality (CI 95%, OR 1.93 [1.11-3.33]). Presence of diabetes (group 2) and hypertension were associated with an increased need for ICU admission (CI 95%, OR 1.69 [1.04-2.76]; CI 95%, OR 1.71 [1.08-2.71], respectively). Group 4 patients although having a similar rate of ICU admission with group 2 and 3 patients, had significantly better ICU survival. Conclusions: The current study suggests that ACE inhibitors and ARBs are associated with decreased mortality, ICU admission, and better ICU survival in the diabetic subgroup of hypertensive patients.

Disease Waves of SARS-CoV-2 in Iran Closely Mirror Global Pandemic Trends.

BACKGROUND: Complete SARS-CoV-2 genome sequencing in the early phase of the outbreak in Iran showed two independent viral entries. Subsequently, as part of a genome surveillance project, we aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year after emerging. METHODS: We provided 319 SARS-CoV-2 whole-genome sequences used to monitor circulating lineages in March 2020-May 2021 time interval. RESULTS: The temporal dynamics of major SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and represent the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7), leading the second, third and fourth waves, respectively. We observed a mixture of circulating B.1.36, B.1.1.413, B.1.1.7 lineages in winter 2021, paralleled in a fading manner for B.1.36/B.1.1.413 and a growing rise for B.1.1.7, prompting the fourth outbreak. Entry of the Delta variant, leading to the fifth disease wave in summer 2021, was detected in April 2021. This study highlights three lineages as hallmarks of the SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (B.1.1 with the combination of [D138Y-S477N-D614G] spike mutations) as a characterizing lineage in Iran, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. It also designates the renowned combination of G and GR clades' mutations as the top recurrent mutations. CONCLUSION: In brief, we provided a real-time and comprehensive picture of the SARS-CoV-2 genetic diversity in Iran and shed light on the SARS-CoV-2 transmission and circulation on the regional scale.

Influence of non-thermal microwaveradiationon emulsifying properties of sunflower protein.

Sunflower protein isolate obtained from industrially de-oiled press cake was treated with non-thermal microwave, aiming to investigate how structure and emulsifying properties were affected. Our results indicated that the content of polar amino acids was decreased and solubility and surface hydrophobicity were altered upon exposure to non-thermal microwave. Higher solubility and surface hydrophobicity of the samples treated with defrost mode and also 350 W were accompanied by a smaller size and lower uniformity of the oil droplets compared to the control and other samples. Non-thermal microwave treatment improved the emulsion stability by 1.43 times and defrost mode treated sample had the lowest stability index after 120 min. Interfacial dilatational rheology measurements revealed that 70 and 350 W treated samples created higher elastic, less stretchable solid-like layer at the O/W interface in comparison with defrost mode treated and control samples. Consequently, non-thermal microwave treatment could be considered as a promising simple, fast, and "green" protein modification technique.

SARS-CoV-2 outbreak in Iran: The dynamics of the epidemic and evidence on two independent introductions.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.

A historical cohort study to investigation of statins safety in COVID-19 hospitalized patients.

BACKGROUND AND OBJECTIVES: A notable proportion of COVID-19 patients need statins for their co-existing conditions. Statins possess several anti-inflammatory properties. We have attempted to describe potential association of exposure to statins and severity of COVID symtpoms in a historical study in hospitalized COVID-19 patients. METHODS: This single-center, historical cohort study was performed in Baharloo hospital as a referral hospital for COVID-19 patients in Tehran. Patients were divided into two groups; 163 statins users and 547 non-users. Mortality rate, intensive care unit (ICU) admission and length of hospitalization were compared between studied groups. In addition, during the investigation, pre-existing conditions were evaluated for groups. If a significant difference was observed between groups, the feature was considered in the adjustment of the odds ratio. RESULTS: At the beginning, statistical analysis study showed that statins users had significantly (p<0.0001) higher mortality rate, ICU admission and length of hospitalization. But after implementation of variables such as age, sex, diabetes, hypertension status, stroke, dyslipidemia, cardiovascular diseases, chronic kidney disease (CKD), corticosteroids, renin-angiotensin-aldosterone axis inhibitors and proton pump inhibitors (PPIs) for adjustment of the odds ratio, a considerable alteration appeared in the studied values. Following adjustment of odds ratio it was shown that statins did not change mortality (95% CI, OR 0.71 (0.41-1.22), p=0.22), ICU admission (95% CI, OR 1.05 (0.66-1.66), p=0.835) and length of hospitalization (95% CI, OR 1.30 (0.78-2.17), p=0.311). In addition, we found that statins could not decrease inflammatory markers in COVID-19 infected patients. CONCLUSION: The use of statins did not seem to change outcomes in COVID19.

A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD).

BACKGROUND: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. RESULTS: Of 166 patients, 102 (61%) and 64 (39%) were males and females, respectively. Ninety-six (57.8%) and 70 (42.2%), had moderate and severe conditions, respectively. Thirty (18%) of patients died. The common symptoms were fever (73%), cough (54%), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54% and 56% of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7%) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. CONCLUSIONS: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate.

Viral Coinfection among COVID-19 Patient Groups: An Update Systematic Review and Meta-Analysis.

BACKGROUND: Coinfections have a potential role in increased morbidity and mortality rates during pandemics. Our investigation is aimed at evaluating the viral coinfection prevalence in COVID-19 patients. METHODS: We systematically searched scientific databases, including Medline, Scopus, WOS, and Embase, from December 1, 2019, to December 30, 2020. Preprint servers such as medRxiv were also scanned to find other related preprint papers. All types of studies evaluating the viral coinfection prevalence in COVID-19 patients were considered. We applied the random effects model to pool all of the related studies. RESULTS: Thirty-three studies including 10484 patients were identified. The viral coinfection estimated pooled prevalence was 12.58%; 95% CI: 7.31 to 18.96). Blood viruses (pooled prevalence: 12.48%; 95% CI: 8.57 to 16.93) had the most frequent viral coinfection, and respiratory viruses (pooled prevalence: 4.32%; 95% CI: 2.78 to 6.15) had less frequent viral coinfection. The herpesvirus pooled prevalence was 11.71% (95% CI: 3.02 to 24.80). Also, the maximum and minimum of viral coinfection pooled prevalence were in AMRO and EMRO with 15.63% (95% CI: 3.78 to 33.31) and 7.05% (95% CI: 3.84 to 11.07), respectively. CONCLUSION: The lowest rate of coinfection belonged to respiratory viruses. Blood-borne viruses had the highest coinfection rate. Our results provide important data about the prevalence of blood-borne viruses among COVID-19 patients which can be critical when it comes to their treatment procedure.

Sleep disturbance, psychiatric issues, and employment status of Iranian people living with HIV.

OBJECTIVES: There are limited studies on the psychological issues and sleep problems among the Iranian people living with HIV (HIV). In this study, we aimed to assess sleep disorders, psychiatric characteristics, and employment status among Iranian PLWH. RESULTS: In total, 304 PLWH with a mean age of 40.01 (SD = 9.60) years participated in the study. About 72% of the participants had a global PSQI score of more than 5, with a mean score of 7.71 (SD = 3.31). About 55.6%, 50%, and 67.4% of subjects had abnormal scores for depression, anxiety, and stress. Unemployed participants had 2.13 times more chance (95% CI 1.01-4.53) of having poor sleep quality compared to employed patients, and stress increased its likelihood by 3.18 times (95% CI 1.47-5.88).

Droplet digital PCR of viral DNA/RNA, current progress, challenges, and future perspectives.

High-throughput droplet-based digital PCR (ddPCR) is a refinement of the conventional polymerase chain reaction (PCR) methods. In ddPCR, DNA/RNA is encapsulated stochastically inside the microdroplets as reaction chambers. A small percentage of the reaction chamber contains one or fewer copies of the DNA or RNA. After PCR amplification, concentrations are determined based on the proportion of nonfluorescent partitions through the Poisson distribution. Some of the main features of ddPCR include high sensitivity and specificity, absolute quantification without a standard curve, high reproducibility, good tolerance to PCR inhibitor, and high efficacy compared to conventional molecular methods. These advantages make ddPCR a valuable addition to the virologist's toolbox. The following review outlines the recent technological advances in ddPCR methods and their applications in viral identification.

Biofunctionality of Enzymatically Derived Peptides from Codfish (Gadus morhua) Frame: Bulk In Vitro Properties, Quantitative Proteomics, and Bioinformatic Prediction.

Protein hydrolysates show great promise as bioactive food and feed ingredients and for valorization of side-streams from e.g., the fish processing industry. We present a novel approach for hydrolysate characterization that utilizes proteomics data for calculation of weighted mean peptide properties (length, molecular weight, and charge) and peptide-level abundance estimation. Using a novel bioinformatic approach for subsequent prediction of biofunctional properties of identified peptides, we are able to provide an unprecedented, in-depth characterization. The study further characterizes bulk emulsifying, foaming, and in vitro antioxidative properties of enzymatic hydrolysates derived from cod frame by application of Alcalase and Neutrase, individually and sequentially, as well as the influence of heat pre-treatment. All hydrolysates displayed comparable or higher emulsifying activity and stability than sodium caseinate. Heat-treatment significantly increased stability but showed a negative effect on the activity and degree of hydrolysis. Lower degrees of hydrolysis resulted in significantly higher chelating activity, while the opposite was observed for radical scavenging activity. Combining peptide abundance with bioinformatic prediction, we identified several peptides that are likely linked to the observed differences in bulk emulsifying properties. The study highlights the prospects of applying proteomics and bioinformatics for hydrolysate characterization and in food protein science.

Overcoming the blood-brain barrier in neurodegenerative disorders and brain tumours.

Drug delivery is one of the major challenges in the treatment of central nervous system disorders. The brain needs to be protected from harmful agents, which are done by the capillary network, the so-called blood-brain barrier (BBB). This protective guard also prevents the delivery of therapeutic agents to the brain and limits the effectiveness of treatment. For this reason, various strategies have been explored by scientists for overcoming the BBB from disruption of the BBB to targeted delivery of nanoparticles (NPs) and cells and immunotherapy. In this review, different promising brain drug delivery strategies including disruption of tight junctions in the BBB, enhanced transcellular transport by peptide-based delivery, local delivery strategies, NP delivery, and cell-based delivery have been fully discussed.

Effects of silver nanoparticles coated with anti-HER2 on irradiation efficiency of SKBR3 breast cancer cells.

Breast cancer is the second cause of death in the world. Ionising radiation is a potent mutagen that can cause DNA damage, chromosomes breakage, and cell death. In the present study, radiotherapy and nanoparticle-antibodies (ABs) have been combined to enhance the efficacy of cancer cell treatment. Silver nanoparticles (SNP) were synthesised, coated with anti-HER2, and then characterised with different techniques such as X-ray diffraction, dynamic light scattering, transmission electron microscopy, Fourier transform infrared, and UV-Vis spectroscopy. SKBR3 cells were irradiated with cobalt-60 in the presence of nanoparticle-AB as the drug. Cell viability was measured using the diphenyltetrazolium bromide assay, and the cellular status was assessed by Raman spectroscopy. Irradiation considerably decreased cell viability proportionate to the dose increase and post-irradiation time. The surface-enhanced Raman spectroscopy increased the signal in the presence of SNP. Increasing the dose to 2 Gy increased the irradiation resistance, and higher dose increases (4 and 6 Gy) enhanced the irradiation sensitivity. Moreover, the cellular changes induced by irradiation in the presence of the drug were stable after 48 h. The authors results introduced the combination of the drug with radiation as an effective treatment for cancer and Raman spectroscopy as a suitable tool to diagnose effective irradiation doses.

Effect of resveratrol on the radiosensitivity of 5-FU in human breast cancer MCF-7 cells.

The aim of this study was to assess the efficacy of resveratrol (Res) on radiosensitivity of 5-fluorouracil (5-FU) in the spheroid culture of MCF-7 breast cancer cell line using colony formation examination. Spheroids on day 9 with 300 µm diameters were treated with 20 µM resveratrol and/or 1 µM 5-FU for one volume doubling time (VDT) (42 hours) and then irradiated with 2 Gy gamma radiation (60 Co) in various groups. Then the viability of the cells and clonogenic ability were acquired by blue dye exclusion and colony formation assay, respectively. The population doubling time in the monolayer culture and the VDT of spheroid culture was 22.48 ± 0.23 hours and 42 ± 0.63 hours respectively. None of the drugs and combination of them had any effect on the viability of cells. The combination treatment of 5-FU+Res+ radiation significantly reduced the colony formation ability of spheroid cells in comparison with each treatment alone. Our results indicated that resveratrol can significantly decrease colony number of breast cancer spheroid cells treated with 5-FU in combination with gamma-rays. Thus, resveratrol as a hypoxia-inducible factor-1-alpha inhibitor increased the radiosensitization of breast cancer spheroid cells.

Role of iron in cancer development by viruses.

Increased levels of iron in body are attributed to higher cancer risk. Given the fact that 16% of all human cancers are caused by viral infections, iron is suggested to play an important role in carcinogenesis particularly those induced by viral infections. The present study provides an updated summary of the literature and the plausible mechanisms of iron involvement in cancer development by viruses. Our understanding about the interplay between viral infections and iron in different settings particularly cancer development is yet to be improved as it may shed a new light in development of new therapeutic strategies.