Nanoparticle-based delivery of harmine: A comprehensive study on synthesis, characterization, anticancer activity, angiogenesis and toxicity Evaluation.

The effective treatment of cancer presents numerous challenges, including drug resistance and the risk of detrimental effects on normal tissues. Harmine, a beta-carboline alkaloid, has demonstrated diverse biological properties. This study aimed to synthesize and characterize harmine encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (Ha-PLGA-NPs) to investigate their potential as agents against cancer and angiogenesis. The synthesized Ha-PLGA-NPs were thoroughly characterized, exhibiting a connected rod-shaped crystal which some retaining the spherical shape of nanoparticles with an average size of 302.96 nm. Furthermore, the nanoparticles demonstrated a dispersion index of 0.23 and a surface charge of -16.51 mV. In vitro cytotoxicity assays conducted on the breast cancer cell line (MCF-7) revealed that Ha-PLGA-NPs possessed significant cytotoxic properties, with an observed IC50 value of 87.74 µg/mL. Notably, no substantial cytotoxicity was observed in human foreskin fibroblasts, indicating a favorable selectivity towards cancer cells. Evaluation of the anti-angiogenic activity of Ha-PLGA-NPs demonstrated a concentration-dependent inhibition of angiogenesis. Mechanistic investigations indicated that the observed inhibition was mediated through the regulation of key genes involved in angiogenesis, including caspase 3, caspase 9, VEGF, and VEGF-R. In vivo studies involving dietary administration of Ha-PLGA-NPs in mice revealed improvements in weight gain, feed intake, liver enzyme levels, and redox potential. These findings underscore the potential of Ha-PLGA-NPs as a promising therapeutic agent for cancer treatment. The observed effects are attributed to their ability to induce programmed cell death and inhibit angiogenesis, thus offering a multifaceted approach to combat cancer.

Measurement of polychlorinated biphenyls in different high consumption canned foods, using the QuEChERS/GC-MS method.

Polychlorinated biphenyls (PCBs) are organic pollutants containing chlorine, which can be carcinogenic to humans. The current research focused on the heart risk and determination of PCBs levels in canned foods using the modified QuEChERS (fast, easy, cheap, effective, resistant and safe) method and gas chromatograph/mass spectrometer (GC-MS) technique. In this study, LOD (limit of detection), LOQ (limit of quantification), and recovery ranged from 0.06 to 0.32, 0.18 to 1.07 ng/g, and 97.05 to 102.5 %, respectively. In canned foods, the highest median of PCBs was PCB 52 (0.27 ± 0.20 ng/g fat) and the lowest median were PCB 28 and 138 (not detected in samples). Also, the maximum median of PCB 28, 52, 101, 138, 153, and 180 were detected in eggplant samples (0.06 ng/g), haricot samples (0.49 ng/g), eggplant samples (0.36 ng/g), eggplant samples (0.19 ng/g), eggplant samples (0.11 ng/g) and lentiform samples (0.66 ng/g), respectively. The median PCBs levels of oral exposure were estimated to be in the range of 9.80E-07to 4.30E-05 ng/g.d for all population groups, which were meaningfully lesser than the Tolerable daily intake value. The Monte Carlo simulation (MCS) outcomes indicated that the rank order of PCBs in adults based on incremental lifetime cancer risk (ILCR) was Lentiform (7.05E-8) > canned fish (5.73E-8) > Eggplant (5.38E-8) > Haricot (4.33E-8) > pasta source (2.06E-8); and in children was Lentiform (3.40E-7) > canned fish (2.72E-7) > Eggplant (2.44E-7) > Haricot (2.06E-7) > pasta source (9.83E-8). The median values of the ILCR induced oral exposure for all groups were within safe limits (lower than 10-6). The heat map and multivariate principal component analysis (PCA) showed significantly different contributions of PCBs profile in samples as the PCA axis scores were correlated with the type of cans. Based on the obtained outcomes, it can be concluded that the PCBs of canned food do not potential health risks to Iranian consumers.

Milk thistle nano-micelle formulation promotes cell cycle arrest and apoptosis in hepatocellular carcinoma cells through modulating miR-155-3p /SOCS2 /PHLDA1 signaling axis.

BACKGROUND: Hepatocellular Carcinoma (HCC) is a prevalent form of liver cancer that causes significant mortality in numerous individuals worldwide. This study compared the effects of milk thistle (MT) and nano-milk thistle (N-MT) on the expression of the genes that participate in apoptosis and cell cycle pathways in Huh-7 and HepG2 cells. METHODS: IC50 values of MT and N-MT were determined using the MTT assay. Huh-7 and HepG2 cell lines (containing mutant and wild-type TP53 gene, respectively) were incubated with MT and N-MT for 24h and 48h and the impact of MT and N-MT on the proliferation of these cell lines was evaluated through a comparative analysis. Cell cycle and apoptosis were assessed by flow cytometry after 24h and 48h treatment in the cell lines mentioned. Real-time PCR was used to analyze miR-155-3p, PHLDA1, SOCS2, TP53, P21, BAX, and BCL-2 expression in the cell lines that were being treated. RESULTS: N-MT reduces cancer cell growth in a time and concentration-dependent manner, which is more toxic compared to MT. Huh-7 was observed to have IC50 values of 2.35 and 1.7 µg/ml at 24h and 48h, and HepG2 was observed to have IC50 values of 3.4 and 2.6 µg/ml at 24 and 48h, respectively. N-MT arrested Huh-7 and HepG2 cells in the Sub-G1 phase and induced apoptosis. N-MT led to a marked reduction in the expression of miR-155-3p and BCL-2 after 24h and 48h treatments. Conversely, PHLDA1, SOCS2, BAX, and P21 were upregulated in the treated cells compared to untreated cells, which suggests that milk thistle has the potential to regulate these genes. N-MT reduced the expression of TP53 in Huh-7 cells after mentioned time points, while there was a significant increase in the expression of the TP53 gene in HepG2 cells. No gene expression changes were observed in MT-treated cells after 24h and 48h. CONCLUSION: N-MT can regulate cancer cell death by arresting cell cycle and inducing apoptosis. This occurs through the alteration of apoptotic genes expression. A reduction in the expression of miR-155-3p and increase in the expression of SOCS2 and PHLDA1 after N-MT treatment showed the correlation between miR-155-3p and PHLDA1/SOCS2 found in bioinformatics analysis. While N-MT increased TP53 expression in HepG2, reduced it in Huh-7. The findings indicate that N-MT can function intelligently in cancer cells and can be a helpful complement to cancer treatment.

The Effects of Covid-19 on Financial-Economic and Performance Efficiency of Hospitals.

Background: During the pandemic of COVID-19, the function and performance of hospitals have been affected by various economic-financial and management aspects. The aim of the current study was to assess the process of therapeutic care delivery and also the economic-financial functions of the selected hospitals before and after COVID-19. Methods: This research is a descriptive-analytical study and a cross-sectional-comparative study in terms of time, and it was conducted in several selected teaching hospitals of Iran University of Medical Sciences. A purposeful and convenient sampling method was used. The data has been collected using the standard research tool (standard checklist of the Ministry of Health) in the two areas of financial-economic and healthcare performance (such as Data of financial and economic indicators such as direct and indirect costs, liquidity ratio and profitability index as well as key performance indicators of hospitals such as bed occupancy ratio (BOR; %), average length of stay (ALOS), bed turnover rate (BTR), bed turnover distance rate (BTIR) and hospital mortality rate (HMR), physician-to-bed ratio and nurse-to-bed ratio) of hospitals in two times before and after the outbreak of COVID-19 (time period 2018 to 2021). The data was collected from 2018 to 2021. Pearson/Spearman regression was used for the evaluation of the relationship between variables using SPSS 22. Results: This research showed the admission of COVID-19 patients caused a change in the indicators we evaluated. ALOS (-6.6%), BTIR (-40.7%), and discharge against medical advice (-7.0%) decreased from 2018 to 2021. BOR; % (+5.0%), occupy bed days (+6.6%), BTR (+27.5%, HMR (+50%), number of inpatients (+18.8%), number of discharges (+13.1%), number of surgeries (+27.4%), nurse-per-bed ratio (+35.9%), doctor-per-bed ratio (+31.0%) increased in the same period of time. The profitability index was correlated to all of the performance indicators except for the net death rate. Higher length of stay and turnover interval had a negative effect on the profitability index while higher bed turnover rate, bed occupancy ratio, bed day, number of inpatient admission, and number of surgery had a positive effect on the profitability index. Conclusion: It has been shown from the beginning of the COVID-19 pandemic, the performance indicators of the studied hospitals were negatively affected. As a consequence of the COVID-19 epidemic, many hospitals were not able to deal with the negative financial and medical outcomes of this crisis due to a significant decrease in income and a double increase in expenses.

In vitro anti-Toxoplasma gondii activity of Ganoderma lucidum extracts.

OBJECTIVE: Ganoderma extracts have the potential to be used as anti-cancer, anti-inflammatory, immunomodulator, and antimicrobial agents, as evaluated in numerous studies. This study was aimed to determine the lethal and inhibitory effects of aqueous, hydroalcoholic, and alcoholic extracts of Ganoderma lucidum on Toxoplasma gondii RH strain tachyzoites, in vitro. RESULTS: All three types of extracts showed toxoplasmacidal effects. The highest percentage of mortality was related to hydroalcoholic extract. The EC50 of Ganoderma extracts for tachyzoites were 76.32, 3.274, and 40.18 for aqueous, hydroalcoholic and alcoholic extracts, respectively. The selectivity index obtained for hydroalcoholic extract was 71.22, showing the highest activity compared to other extracts. According to our findings, the hydroalcoholic part was the most effective substance among the extracts. This basic study showed obvious anti-toxoplasma effect of Ganoderma lucidum extracts. These extracts can be used as candidates for further in-depth and comprehensive studies especially In vivo experiments to prevent toxoplasmosis.

Fampridine in multiple sclerosis patients with acute phase of cervical transverse myelitis: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Fampridine is a potassium channel blocker drug used to improve walking ability in patients with multiple sclerosis (MS). We evaluated the effect of fampridine in patients with MS in the acute phase of transverse myelitis. METHODS: In a randomized, placebo-controlled trial, 30 patients who had their first episode of cervical myelitis with quadriparesis presentation, with the final diagnosis of MS, were randomly divided into two equal groups. The intervention group received intravenous methylprednisolone (IVMP) for 7 days plus fampridine. The placebo group received IVMP for 7 days plus placebo. To compare the treatment results, we compared the Barthel index (BI) scores of the groups at the start of the trial and the 21st day after the start of treatment. RESULTS: There was no significant difference in baseline characteristics between the intervention and placebo groups in terms of mean age, sex, and mean admission BI (p > 0.05). Mean (SD) admission BI in placebo and intervention groups was 27.20 (7.341) and 27.87(5.78), respectively (p = 0.784). The measured mean (SD) BI after treatment was 48.73 (15.54) in the placebo and 64.93 (11.81) in the intervention group (p = 0.003) after 3 weeks. CONCLUSION: Using fampridine plus IVMP in the acute phase of transverse myelitis in MS patients improved the disease's symptoms and increased the daily activity ability of patients.

Vascular Endothelial Growth Factor as a Predictive and Prognostic Biomarker for Multiple Sclerosis.

BACKGROUND: Growing bodies of evidence suggest that angiogenesis plays a crucial role in the development and progression of multiple sclerosis (MS). Vascular endothelial growth factor (VEGF) is one of the key factors involved in angiogenesis. Because of this importance, we investigated the serum levels of VEGF in MS patients according to their clinical phase and subtype of MS in this study. MATERIAL AND METHODS: This case-control study was done on 47 definite MS patients with the first clinical attack and 47 randomly selected individuals without any underlying inflammatory and autoimmune disease as the control group. The total serum VEGF level was measured from the subject's peripheral blood sample by ELISA during the first and second attacks of MS and 6 months after the first attack in the remission phase as well as the control group. In addition, the correlation between these variables and the influence of gender, age, and duration of the remission phase on such associations was evaluated by using the independent t test and Pearson's correlation coefficient. RESULTS: There was an increase in the serum level of VEGF in all phases of MS compared with non-MS individuals (p value <0.0001) and a significant correlation between the serum level of VEGF and the interval between first and second attacks (r = -720, p < 0.0001). A higher serum level of VEGF in the first attack leads to higher VEGF levels in the second and sixth mount of remission phases. CONCLUSION: Rise in the serum VEGF level may be involved in MS's relapsing phases and a shorter remission phase. Therefore, it could be used as a prognostic and predictive biomarker for MS disease.

A case report of rhino-facial mucormycosis in a non-diabetic patient with COVID-19: a systematic review of literature and current update.

BACKGROUND: COVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids. CASE PRESENTATION: A 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealed Rhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis. CONCLUSION: Our report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID-19 cases.

Relationship between antifungal susceptibility profile and virulence factors in Candida albicans isolated from nail specimens

Abstract INTRODUCTION: The aim of this study was to evaluate some virulence factors in Candida albicans isolates from patients with onychomycosis and determine the correlation between these factors and the antifungal resistance profile. METHODS: Seventy species of C. albicans were confirmed using polymerase chain reaction amplification of the HWP1 gene. According to the Clinical & Laboratory Standards Institute guidelines, the susceptibility profile of four antifungal agents was investigated, and the production of aspartyl protease, phospholipase, haemolysin, and biofilm was determined. The correlation between these profiles was also investigated. RESULTS: The isolates indicated different levels of resistance and production of virulence factors. Significant correlations were observed between the minimum inhibitory concentration (MIC) of fluconazole/itraconazole and biofilm production, between phospholipase production and fluconazole/itraconazole MIC, and between fluconazole MIC and hemolytic activity in C. albicans isolates. The results also showed significant correlations between phospholipase activity and biofilm production. CONCLUSIONS: Our findings will contribute to a better understanding of the pathogenesis of C. albicans and characterize the relationship between virulence factors and antifungal resistance, which may suggest new therapeutic strategies considering the possible involvement of the virulence mechanism in the effectiveness of treatment.

Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of the Fungal Genus Fusarium.

Clinically relevant members of the fungal genus, Fusarium, exhibit an extraordinary genetic diversity and cause a wide spectrum of infections in both healthy individuals and immunocompromised patients. Generally, Fusarium species are intrinsically resistant to all systemic antifungals. We investigated whether the presence or absence of the ability to produce biofilms across and within Fusarium species complexes is linked to higher resistance against antifungals. A collection of 41 Fusarium strains, obtained from 38 patients with superficial and systemic infections, and three infected crops, were tested, including 25 species within the Fusarium fujikuroi species complex, 14 from the Fusarium solani species complex (FSSC), one Fusarium dimerum species complex, and one Fusarium oxysporum species complex isolate. Of all isolates tested, only seven strains from two species of FSSC, five F. petroliphilum and two F. keratoplasticum strains, recovered from blood, nail scrapings, and nasal biopsy samples, could produce biofilms under the tested conditions. In the liquid culture tested, sessile biofilm-forming Fusarium strains exhibited elevated minimum inhibitory concentrations (MICs) for amphotericin B, voriconazole, and posaconazole, compared to their planktonic counterparts, indicating that the ability to form biofilm may significantly increase resistance. Collectively, this suggests that once a surface adherent biofilm has been established, therapies designed to kill planktonic cells of Fusarium are ineffective.