The association between healthy eating index-2015 with anthropometric, cardiometabolic and hepatic indices among patients with non-alcoholic fatty liver disease.

BACKGROUND: Obesity, cardiovascular diseases, and metabolic disorders are common problems among participants with non-alcoholic fatty liver disease (NAFLD). However, the association between these problems and the healthy eating index-2015 (HEI-2015) remains unknown. Although the HEI-2015 originated from American dietary guidelines, its comprehensive evaluation of diet quality provides valuable insights for various populations, including Iranians. Therefore, the objective of this study was to investigate the association between anthropometric, hepatic, and cardio-metabolic indices with HEI-2015 scores in participants with NAFLD. METHODS: We conducted a cross-sectional analysis of data from the Hoveyzeh Cohort Study, which included adults aged 35 to 70 years between 2016 and 2018. A total of 664 participant with NAFLD (452 females and 212 males) were included in the analysis. The HEI-2015 was assessed using the Food Frequency Questionnaire (FFQ). Various indices, including the body shape index (ABSI), atherogenic index of plasma (AIP), visceral adiposity index (VAI), lipid accumulation product (LAP), cardiometabolic index (CMI), lipoprotein combine index (LCI), AST/ALT ratio, ALD/NAFLD index, and hepatic steatosis index (HSI), were calculated. RESULTS: No significant differences were observed in anthropometric, cardio-metabolic, and hepatic indices across the quartiles of HEI-2015. However, among participants with NAFLD, men had significantly higher AIP and LCI levels, while women had significantly higher BMI, ABSI, VAI, LAP, and CMI levels. Additionally, women with NAFLD exhibited higher AST/ALT and HSI levels but lower ALD/NAFLD levels compared to men with NAFLD. Linear regression analysis among men with NAFLD revealed a significant negative correlation between HEI-2015 score and HSI in both the unadjusted model (ß=-0.131, SE = 0.058, p = 0.024) and the adjusted model for energy intake (ß=-0.129, SE = 0.058, p = 0.028). CONCLUSION: The present study demonstrated a correlation between lower HEI-2015 scores and an increased risk of steatosis in men with NAFLD. Moreover, our findings highlighted gender-related differences in NAFLD and cardio-metabolic disorders.

The association between dietary inflammatory index with some cardio-metabolic risk indices among the patients with type 2 diabetes from Hoveyzeh cohort study: a cross-sectional study.

BACKGROUND: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. METHODS: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. RESULTS: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). CONCLUSION: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications.

Kidney stones and dietary intake in adults: a population-based study in southwest Iran.

BACKGROUND: The prevalence of kidney stones is on the rise globally. Several risk factors, including lifestyle, contribute to the formation of kidney stones. Nevertheless, there is a contentious debate about the relationship between diet and kidney stones. Therefore, our study aimed to assess the relationship between macronutrients and micronutrients and the formation of kidney stones. METHODS: This population-based cross-sectional study was conducted in the baseline phase of the Hoveyzeh Cohort Study, focusing on adults aged 35-70 in southwest Iran. The information on demographic characteristics, anthropometrics, kidney stone history, and food frequency was collected. Chi-square and t-tests were utilized to assess the relationship between categorical and numerical variables with kidney stones. The ANCOVA and logistic regression models were used to evaluate the relationships while controlling for confounding factors. RESULTS: Among 10,009 participants, the overall prevalence of kidney stones was 18.77% (95% CI: 17.99-19.53). A higher intake of carbohydrates [OR = 1.02 (95% CI:1.002-1.03), p = 0.026] and copper [OR = 1.04 (95% CI:1.01-1.09), p = 0.025] were found to be associated with kidney stones. No associations were found between the other assessed macronutrients or micronutrients and kidney stones (p-tvalues > 0.05). CONCLUSION: Our study's findings indicate a correlation between diet and the formation of kidney stones. However, the relationship between dietary factors and kidney stones is complex, and further research is needed.

Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions.

The undesirable inflammation and the excessive M1 macrophage activity may lead to inflammatory diseases. Corticosteroids and stem cell therapy are used in clinical practice to promote anti-inflammatory responses. However, this protocol has limitations and is associated with numerous side effects. In this study, the synergistic anti-inflammatory effects of dexamethasone (Dex) and mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) were evaluated to enhance the polarization of M1 inflammatory macrophages into the anti-inflammatory (M2) phenotype. Hence, we designed different combinations of Dex and EVs using three methods, including EVs isolated from Dex-preconditioned MSCs (Pre-Dex-EVs), EVs loaded with Dex (L-Dex-EVs), and EVs and Dex co-administration (Dex + EVs). All designed EVs had a significant effect on reducing the expression of M1-related genes (iNOS, Stat1, and IRF5), cytokines (IL6 and TNF-a), and CD markers (CD86) in lipopolysaccharide-stimulated macrophages. On the other hand, these combinations promoted the expression of alternative-activated M2-related genes (Arg-1, Stat6, and IRF4), cytokine (IL10), and CD markers (CD206).The combination of Dex and MSC-EVs enhances the effectiveness of both and synergistically promotes the conversion of inflammatory macrophages into an anti-inflammatory state.

Reduction of ovarian reserves and activation of necroptosis to in vivo air pollution exposures.

We investigated the association between air pollution and changes in ovarian follicles, anti-mullerian hormone (AMH) levels, the occurrence of necroptosis cell death by activation of receptor-interacting protein kinase 3 (RIPK3) and, the activation of mixed lineage kinase domain-like (MLKL) proteins. Forty-two female Wistar rats were divided into three groups of 14 each, which were exposed to real-ambient air, filtered air and purified air (control) in two periods of 3 and 5 months. The results showed that the number of ovarian follicles decreased in the group exposed to real-ambient air versus the control group (P < 0.0001). The trend of age-related AMH changes with respect to exposure to air pollutants was affected and its levels decreased after 3 months of exposure. The MLKL increased in the group exposed to the real-ambient air compared to the control group (P = 0.033). Apparently long-term exposure to air pollution can reduce ovarian reserves.

Application of multi-criteria group decision-making for water quality management.

As waste discharge into numerous river systems escalates, the pollution of water bodies typically rises. Given the limited capacity of rivers to withstand pollution and their constrained self-cleaning capabilities, treated pollutants from waste discharge must be released into the river. Despite numerous models and algorithms proposed for managing river water quality to meet standards, literature, to our awareness, lacks the utilization of a comprehensive multi-criteria group decision-making approach for water quality management, particularly in river systems. Therefore, this research introduces a new, comprehensive multi-criteria group decision-making for the management of water quality in the Haraz River basin, located in Iran. To do so, the water quality of the basin, a one-dimensional water quality model, QUAL2Kw, was employed to simulate and calibrate the water quality along the river. The simulation results revealed that the downstream water quality violates the water quality standards. To mitigate this issue, various scenarios for waste load allocation (WLA) were evaluated, including no wastewater treatment, primary wastewater treatment, advanced secondary wastewater treatment utilizing the activated sludge (AS) method, and advanced wastewater treatment via the membrane bioreactor (MBR) method. Utilizing the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and Fuzzy TOPSIS group decision-making model, it was determined that the optimal solution was the implementation of secondary wastewater treatment utilizing the activated sludge method for the 11 PS of pollution, while still adhering to Iranian water quality standard. In addition, the findings of the present study indicate that the implementation of primary wastewater treatment, advanced secondary wastewater treatment utilizing AS, and advanced wastewater treatment through MBR within the study area led to a significant enhancement in water quality. This enhancement ranged from 35 to 105% across various scenarios when compared to conditions where no actions were taken to the treatment of water.

Immunophenotyping characteristics of COVID-19 patients: Peripheral blood CD8+ HLA-DR+ T cells as a biomarker for mortality outcome.

INTRODUCTION: The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID-19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID-19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA-DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID-19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA-DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8-HLA-DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA-DR+ T, CD8- HLA-DR+ T, and CD8+ HLA-DR+ T cells was associated with mortality in COVID-19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA-DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA-DR+ T cells in COVID-19 patients may be helpful to identify high-risk patients. However, further studies with larger sample size are needed.

COVID-19-associated pulmonary aspergillosis (CAPA) in Iranian patients admitted with severe COVID-19 pneumonia.

PURPOSE: Bacterial or virus co-infections with SARS-CoV-2 have been reported in many studies; however, the knowledge on Aspergillus co-infection among patients with COVID-19 was limited. This study was conducted to identify and isolate fungal agents and to evaluate the prevalence of pulmonary aspergillosis (CAPA) as well as antifungal susceptibility patterns of Aspergillus species in patients with COVID-19 admitted to Shahid Beheshti Hospital, Kashan, Iran. METHODS: The study involved 119 patients with severe COVID-19 pneumonia referred to the Shahid Beheshti Hospital, Kashan, Iran. A total of 17 Aspergillus spp. that were isolated from COVID-19 patients suspected of CAPA were enrolled in the study. CAPA was defined using ECMM/ISHAM consensus criteria. The PCR amplification of the ß-tubulin gene was used to identify the species. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B against Aspergillus spp. were evaluated according to the Clinical and Laboratory Standards Institute manual (M38-A3). RESULTS: From the 119 patients with severe COVID-19 pneumonia, CAPA was confirmed in 17 cases (14.3%). Of these, 12 (70.6%) were males and 5 (29.4%) were females; the mean age at presentation was 73.8 years (range: 45-88 years; median = 77; IQR = 18). Aspergillus fumigatus (9/17; 52.9%), Aspergillus flavus (5/17; 29.4%), Aspergillus oryzae (3/17, 17.6%), were identified as etiologic agents of CAPA, using the molecular techniques. Voriconazole and amphotericin B showed more activity against all isolates. Moreover, the MIC of fluconazole, itraconazole varied with the tested isolates. For 3 clinical isolates of A. fumigatus, 2 isolate of A. flavus and 3 A. oryzae, the MIC of fluconazole and itraconazole were ≥ 16 µg/mL. CONCLUSIONS: We observed a high incidence (14.3%) of probable aspergillosis in 119 patients with COVID-19, which might indicate the risk for developing IPA in COVID-19 patients. When comparing patients with and without CAPA regarding baseline characteristics, CAPA patients were older (p =0 .024), had received more frequent systemic corticosteroids (p = 0.024), and had a higher mortality rate (p = 0.018). The outcome of CAPA is usually poor, thus emphasis shall be given to screening and/or prophylaxis in COVID-19 patients with any risk of developing CAPA.

Sequence variation of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene in chronic lymphocytic leukemia and healthy volunteer subjects.

Epstein-Barr virus-related malignancies have been linked to variations in the sequences of EBV genes, notably EBNA1. Therefore, the purpose of this study was to examine the DBD/DD domain and USP7 binding domain sequences at the C-terminus of the EBNA1 gene in patients with chronic lymphocytic leukemia (CLL). This study included 40 CLL patients and 21 healthy volunteers. Using commercial kits, total DNA was extracted from buffy coat samples, and each sample was tested for the presence of the EBV genome. The C-terminus of EBNA1 was then amplified from positive samples, using nested PCR. Sanger sequencing was used to identify mutations in the PCR products, and the results were analyzed using MEGA11 software. The mean ages of CLL patients and healthy individuals were 61.07 ± 10.2 and 59.08 ± 10.3, respectively. In the EBNA-1 amplicons from CLL patients and healthy individuals, 38.5% and 16.7%, respectively, harbored mutations in the DBD/DD domain of the C-terminal region of the EBNA1 gene (P = 0.378). The mutation frequency at locus 97,320 was significantly higher in CLL patients than in healthy individuals (P = 0.039). Three EBV subtypes based on residue 487 were detected. The frequency of alanine, threonine, and valine in both groups was 88, 8, and 4 percent, respectively (P = 0.207). Moreover, all of the isolates from healthy donors had alanine at this position. The findings indicated that the presence of threonine or valine at residue 487 as well as a synonymous substitution at residue 553 in the C-terminal region of EBNA1 might be involved in the pathogenesis of EBV in CLL patients.

In vitro treatment of murine splenocytes with extracellular vesicles derived from mesenchymal stem cells altered the mRNA levels of the master regulator genes of T helper cell subsets.

INTRODUCTION: The purpose of the current study was to evaluate the effect of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) on the production of cytokines and expression of genes, which are corresponded to the subsets of T helper cells. MATERIALS AND METHODS: The supernatant of the second passage of MSCs that had been isolated from C57BL/6 mice abdominal adipose tissue was used to collect the MSC-EV. Splenocytes of healthy mice were activated using anti-CD3 and anti-CD28 antibodies and simultaneously were treated using the MSC-EVs. The proliferation rate of lymphocytes and the frequency of regulatory T cells were measured using flow cytometry. In addition, the expressions of T helper cell subset-specific transcription factors were evaluated using a real-time PCR assay. To appraise the effects of MSC-EV on splenocytes, the levels of IFN-γ, IL-17A, IL-10, and TGF-ß were measured using ELISA. RESULTS: The results showed that the treatment of the CD3/CD28-activated splenocytes with MSC-EV did not statistically change the proliferation of CD3+ splenocytes. However, after the treatment, the mRNA levels of Foxp3 and Elf4 as well as the frequency of regulatory T cells was significantly higher when compared to the control group. The expression levels of Gata3, Rorc, and Tbx21 were down-regulated while, the corresponding cytokines levels did not alter. CONCLUSION: The results revealed that the in vitro treatment of MSC-EV was associated with the increase in the frequency of CD4+CD25+FOXP3+ T cells and upregulation of Foxp3 mRNA level.

In vitro naive CD4+ T cell differentiation upon treatment with miR-29b-loaded exosomes from mesenchymal stem cells.

BACKGROUND: Gene regulation by microRNA (miRNA) is central in T lymphocytes differentiation processes. Here, we investigate miRNA-29b (miR-29b) roles in the reprogramming of T cell differentiation, which can be a promising therapeutic avenue for various types of inflammatory disorders such as rheumatoid arthritis and multiple sclerosis. METHODS AND RESULTS: Adipose Mesenchymal Stem Cell-derived exosomes (AMSC-Exo) enriched with miR-29b were delivered into naive CD4+ T (nCD4+) cells. The expression level of important transcription factors including RAR-related orphan receptor gamma (RORγt), GATA3 binding protein (GATA3), T-box transcription factor 21, and Forkhead box P3 was determined by quantitative Real-Time PCR. Moreover, flow cytometry and Enzyme-linked Immunosorbent Assay were respectively used to measure the frequency of T regulatory cells and the levels of cytokines production (Interleukin 17, Interleukin 4, Interferon-gamma, and transforming growth factor beta. This study indicates that the transfection of miR-29b mimics into T lymphocytes through AMSC-Exo can alter the CD4+ T cells' differentiation into other types of T cells. CONCLUSIONS: In conclusion, AMSC-Exo-based delivery of miR-29b can be considered as a new fascinating avenue for T cell differentiation inhibition and the future treatment of several inflammatory disorders.

Sleep duration and Framingham´s cardiovascular risk score: results from the Hoveyzeh Cohort Study (HCS).

BACKGROUND: Cardiovascular diseases (CVDs) are the leading causes of global deaths. So, it is necessary to know the possible risk factors for each region. We aimed to assess the relationship between the risk of CVDs and sleep duration in the Iranian Arab population. METHODS: In this cross-sectional study, data from 8362 participants aged between 35 and 70 from the Hoveyzeh Cohort Study enrollment phase between 2016 and 2018 was analyzed. This study evaluated the association between ten-year CVD risk using the Framingham risk score and sleep duration. Self-reported sleep duration was categorized as short duration (equal to or less than 5 h), standard duration (6-8 h), or prolonged duration (equal to or greater than 9 h). Multivariable logistic regression to adjust for conventional CVD risks was used. RESULTS: Among the assessed participants, 4892 (58.50%) were female, and the mean age was 47.93 (9.01). The average sleep duration was 7.59 (1.56) hours. The low, intermediate-to-high, and high CVD risk individuals were 6461 (77.27%), 1185 (14.17%), and 716 (8.56%), respectively. There was a significant relationship between prolonged sleep duration and lower odds of intermediate-to-high CVD risk in males (OR 0.66, 95% CI: 0.49-0.87, P-value: 0.004). CONCLUSION: The results of our study showed that longer sleep duration has a protective association with the intermediate to high risk of cardiovascular diseases in males. However, long and short sleep durations have no significant relationship with females' risk of cardiovascular disease.

Regulation of the Th17/Treg balance by human umbilical cord mesenchymal stem cell-derived exosomes protects against acute experimental colitis.

Increasing evidence suggests that mesenchymal stem cells (MSCs) have immunosuppressive properties mediated by MSC-derived small extracellular vesicles (sEV). Exosomes are small extracellular vesicles that contain components that regulate immune cell function. We investigated the immunomodulatory effects of MSC-derived Exosome (MSC-Exo) on the severity of colitis using the dextran sulfate sodium (DSS)-induced colitis model. Exosomes were administrated intraperitoneally. Daily changes in body weight, stool consistency, and bleeding were assessed to determine the impact of MSC-Exos on colitis. Several measurements were taken, including the colon weight, length, and histological analysis of the colon tissues. The percentage of regulatory T cells and IL-10, TGF-ß, IL-17, TNF-α, and IFN-γ levels were calculated in the mesenteric lymph node (MLN) and spleen. The results showed MSC-Exos improved clinical manifestations of colitis. Colon macroscopic and histological observations also showed improvement in tissue destruction. The results illustrated that MSC-Exos might attenuate colitis by regulating Treg/Th17 balance, increasing anti-inflammatory, and decreasing pro-inflammatory cytokines expression. As a result, MSC-Exos could be used as an immunomodulatory approach to treating bowel inflammation.

Exosomes derived from rapamycin-treated 4T1 breast cancer cells induced polarization of macrophages to M1 phenotype.

M2 macrophages are the most prevalent type in the tumor microenvironment and their polarization to M1 type can be used as a potential cancer immunotherapy. Here, we investigated the role of tumor microenvironment and particularly purified exosomes in M2 to M1 macrophage polarization. Rapamycin treatment on triple-negative breast cancer cells (TNBC) was performed. Tumor cells-derived exosomes (called texosomes) were isolated and characterized using scanning electron microscopy, transmission electron microscopy, dynamic light scattering, high-performance liquid chromatography, Fourier transform infrared, and Western blot assays. M2 mouse peritoneal macrophages were treated with rapamycin or rapamycin-texosome. Then, M1/M2 phenotype-specific marker genes and proteins were measured to assess the degree of M2 to M1 polarization. Finally, nitric oxide (NO) production, phagocytosis, and efferocytosis assays were assessed to verify the functionality of the polarized macrophages. Purified rapamycin-texosomes significantly increased the expression of the M1 markers (Irf5, Nos2, and CD86) and decreased M2 markers (Arg, Ym1, and CD206). In addition, the levels of M1-specific cytokines tumor necrosis factor alpha and interleukin 1ß (IL-1ß) were increased, whereas the levels of M2 specific cytokines IL-10 and transforming growth factor beta were declined. Furthermore, texosome treatment increased NO concentration and phagocytosis and decreased efferocytosis indicating M1 polarization. These findings suggest rapamycin-texosomes can induce M2 to M1 macrophages polarization as a potential immunotherapy for TNBC.

Association between oral contraceptives with lipid profile: results from Hoveyzeh cohort study (HCS).

BACKGROUND: Oral contraceptives (OCs) affect lipid metabolism, which can cause hyperlipidemia, a risk factor for cardiovascular diseases. The study was designed to evaluate the possible changes in lipid profile due to using OCs. METHODS: A cross-sectional study was conducted from April 2016 to August 2018 among women from the baseline phase Hoveyzeh cohort study (HCS). Sociodemographic data, anthropometric measurements, physical activity, and biochemical blood tests were measured for every participant. Multiple logistic regression was used to adjust the potential confounders. RESULTS: Among 2272 participants, 1549 women were OC users, and 723 women were non-user OCs. The mean lipid profile levels were higher in OC users than in non-user OCs. Odds of abnormal Total cholesterol (TC) in OC users were significantly higher than those of non-users OCs [OR = 1.29 (95% CI;1.05 to 1.58)]. Also, the Odds of abnormal low-density lipoprotein (LDL) in OC users was 12% higher than in non-user OCs. However, no significant relationship between abnormal LDL with Oral Contraceptive Pills (OCPs) was observed. CONCLUSIONS: The mean lipid profile was higher in OC users compared to non-user OCs. This finding highlights the need for public health strategies to prevent and detect hyperlipidemia in user OCs.

Coculture of adipose-derived mesenchymal stem cells/macrophages on decellularized placental sponge promotes differentiation into the osteogenic lineage.

BACKGROUND: Several factors like three-dimensional microstructure, growth factors, cytokines, cell-cell communication, and coculture with functional cells can affect the stem cells behavior and differentiation. The purpose of this study was to investigate the potential of decellularized placental sponge as adipose-derived mesenchymal stem cells (AD-MSCs) and macrophage coculture systems, and guiding the osteogenic differentiation of stem cells. METHODS: The decellularized placental sponge (DPS) was fabricated, and its mechanical characteristics were evaluated using degradation assay, swelling rate, and pore size determination. Its structure was also investigated using hematoxylin and eosin staining and scanning electron microscopy. Mouse peritoneal macrophages and AD-MSCs were isolated and characterized. The differentiation potential of AD-MSCs co-cultured with macrophages was evaluated by RT-qPCR of osteogenic genes on the surface of DPS. The in vivo biocompatibility of DPS was determined by subcutaneous implantation of scaffold and histological evaluations of the implanted site. RESULTS: The DPS had 67% porosity with an average pore size of 238 µm. The in vitro degradation assay showed around 25% weight loss during 30 days in PBS. The swelling rate was around 50% during 72 h. The coculture of AD-MSCs/macrophages on the DPS showed a significant upregulation of four differentiation osteogenic lineage genes in AD-MSCs on days 14 and 21 and a significantly higher mineralization rate than the groups without DPS. Subcutaneous implantation of DPS showed in vivo biocompatibility of scaffold during 28 days follow-up. CONCLUSIONS: Our findings suggest the decellularized placental sponge as an excellent bone substitute providing a naturally derived matrix substrate with biostructure close to the natural bone that guided differentiation of stem cells toward bone cells and a promising coculture substrate for crosstalk of macrophage and mesenchymal stem cells in vitro.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: Clinical Features, Antifungal Susceptibility, Management and Outcome in a Tertiary Hospital in Iran.

BACKGROUND: Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs. OBJECTIVES: To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran. PATIENTS/METHODS: A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol. RESULT: A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9 years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31 days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5 µg/ml) demonstrated the highest potency against Mucorales. CONCLUSION: Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.

Ketamine-propofol for total intravenous anaesthesia in rabbits: a comparison of premedication with acepromazine-medetomidine, acepromazine-midazolam or acepromazine-morphine.

OBJECTIVE: To describe ketamine-propofol total intravenous anaesthesia (TIVA) following premedication with acepromazine and either medetomidine, midazolam or morphine in rabbits. STUDY DESIGN: Randomized, crossover experimental study. ANIMALS: A total of six healthy female New Zealand White rabbits (2.2 ± 0.3 kg). METHODS: Rabbits were anaesthetized on four occasions, each separated by 7 days: an intramuscular injection of saline alone (treatment Saline) or acepromazine (0.5 mg kg-1) in combination with medetomidine (0.1 mg kg-1), midazolam (1 mg kg-1) or morphine (1 mg kg-1), treatments AME, AMI or AMO, respectively, in random order. Anaesthesia was induced and maintained with a mixture containing ketamine (5 mg mL-1) and propofol (5 mg mL-1) (ketofol). Each trachea was intubated and the rabbit administered oxygen during spontaneous ventilation. Ketofol infusion rate was initially 0.4 mg kg-1 minute-1 (0.2 mg kg-1 minute-1 of each drug) and was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Ketofol dose and physiological variables were recorded every 5 minutes. Quality of sedation, intubation and recovery times were recorded. RESULTS: Ketofol induction doses decreased significantly in treatments AME (7.9 ± 2.3) and AMI (8.9 ± 4.0) compared with treatment Saline (16.8 ± 3.2 mg kg-1) (p < 0.05). The total ketofol dose to maintain anaesthesia was significantly lower in treatments AME, AMI and AMO (0.6 ± 0.1, 0.6 ± 0.2 and 0.6 ± 0.1 mg kg-1 minute-1, respectively) than in treatment Saline (1.2 ± 0.2 mg kg-1 minute-1) (p < 0.05). Cardiovascular variables remained at clinically acceptable values, but all treatments caused some degree of hypoventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with AME, AMI and AMO, at the doses studied, significantly decreased the maintenance dose of ketofol infusion in rabbits. Ketofol was determined to be a clinically acceptable combination for TIVA in premedicated rabbits.

Exosome engineering in cell therapy and drug delivery.

Cell-derived exosomes have opened new horizons in modern therapy for advanced drug delivery and therapeutic applications, due to their key features such as low immunogenicity, high physicochemical stability, capacity to penetrate into tissues, and the innate capacity to communicate with other cells over long distances. Exosome-based liquid biopsy has been potentially used for the diagnosis and prognosis of a range of disorders. Exosomes deliver therapeutic agents, including immunological modulators, therapeutic drugs, and antisense oligonucleotides to certain targets, and can be used as vaccines, though their clinical application is still far from reality. Producing exosomes on a large-scale is restricted to their low circulation lifetime, weak targeting capacity, and inappropriate controls, which need to be refined before being implemented in practice. Several bioengineering methods have been used for refining therapeutic applications of exosomes and promoting their effectiveness, on the one hand, and addressing the existing challenges, on the other. In the short run, new diagnostic platforms and emerging therapeutic strategies will further develop exosome engineering and therapeutic potential. This requires a thorough analysis of exosome engineering approaches along with their merits and drawbacks, as outlined in this paper. The present study is a comprehensive review of novel techniques for exosome development in terms of circulation time in the body, targeting capacity, and higher drug loading/delivery efficacies.

Rosmarinus officinalis L. Essential Oils Impact on the Microbiological and Oxidative Stability of Sarshir (Kaymak).

This study investigated the effect of Rosmarinus officinalis L. essential oil, REO (one, two and three percent) on the microbiological and oxidative stability of Sarshir during 20 days of refrigerated storage (4 °C). Initially, the chemical composition (gas chromatography/mass spectrometry, GC/MS), antimicrobial (paper disc diffusion) and antioxidant (DPPH) properties of REO were evaluated. Then, the microbial safety, oxidative stability (peroxide and anisidine values) and overall acceptability of the product after addition of REO to Sarshir and the subsequent storage period were determined. According to GC/MS analysis, the major components of REO were α-pinene (24.6%), 1,8-cineole (14.1%), camphor (13.5%), camphene (8.1%) and limonene (6.1%), respectively. Moreover, it was also found that Limosilactobacillus fermentum (inhibition zone (IZ) of 23.5 mm) and Salmonella Typhi (IZ of 16.4 mm) were the most sensitive and resistant spoilage and pathogenic bacteria against REO, respectively. In addition, the half-maximal inhibitory concentration (IC50) of the REO was measured at 24.8 mg/mL, while the IC50 value of butylated hydroxytoluene (BHT) was 16.6 mg/mL. The highest and lowest bacterial populations were detected in the control and the sample containing 3% REO, respectively. The control had the highest extent of lipid oxidation, while the lowest peroxide and anisidine values were measured in Sarshir containing 3% REO.