Locoregional therapy containing surgery in metastatic breast cancer: Systematic review and meta-analysis.

INTRODUCTION: The role of locoregional therapy (LRT) containing surgery and systematic therapy in metastatic breast cancer patients remains controversial. This study investigated the effect of LRT in patients who were initially diagnosed with metastatic breast cancer (MBC) on overall survival (OS), locoregional progression-free survival (PFS), and distant systemic PFS. METHODS: The related keywords were searched in MEDLINE/PubMed, SCOPUS, and Web of Science databases up to August 15th, 2022. Hazard ratios (HR) with 95% confidence intervals (CIs) were pooled by the random-effects model. RESULTS: Seven articles with 1626 participants compared LRT with only systemic therapy (ST) for patients with de novo MBC. LRT did not improve (p = 0.28) OS compared to ST (HR: 0.83, 95% CI: 0.60, 1.16). LRT significantly improved locoregional PFS outcomes compared to ST (HR: 0.31, 95% CI: 0.15, 0.60, p = 0.001). LRT significantly (p = 0.001) improved OS in patients with solitary bone metastases (HR: 0.48; 95% CI: 0.35-0.67). CONCLUSION: LRT improves locoregional PFS. Furthermore, LRT improves OS in patients with solitary bone metastases.

Association between nutritional status and biochemical markers among hematopoietic stem cell transplant candidates: a cross-sectional study.

AIM: Candidates of Hematopoietic Stem Cell Transplantation (HSCT) may be at nutritional risk due to decreased oral intake, high nutritional requirements and nutrient malabsorption. The aim of this study was to evaluate the association between nutritional status and blood biomarkers in candidates of HSCT. METHODS: A total of 278 patients aged 18-65 years old were recruited and their baseline demographic and clinical characteristics were recorded. All subjects underwent nutritional status analysis using Nutritional Risk Screening (NRS-2002). Blood biomarkers including C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), hemoglobin, albumin and total protein as well as CRP-albumin ratio (CAR) and Body Mass Index (BMI) were measured and compared between two groups based on Nutritional Risk Screening (NRS-2002) within 24 h of admission in Bone Marrow Transplant ward. RESULTS: The results showed that undernourished patients (NRS ≥ 3) had significantly higher inflammatory markers including ESR, CRP and CAR as well as lower BMI and serum albumin and hemoglobin concentrations (P < 0.05); however, no significant association was observed in terms of total protein even after adjusting for confounders (P > 0.05). CONCLUSIONS: This study revealed that BMI combined with biochemical markers are the appropriate parameters for assessment of nutritional status in HSCT candidates. Furthermore, the nutritional status was verified to be significantly associated with systematic inflammation.

The effect of anamorelin (ONO-7643) on cachexia in cancer patients: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cachexia is associated with increased morbidity and mortality rates in patients with cancer. This meta-analysis aims to explore the effect of anamorelin on cancer cachexia markers. METHODS: We searched MEDLINE/PubMed, SCOPUS, and WOS from their inception until 5 June 2022. A systematic search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We included trials investigating the effect of anamorelin on body weight, lean body mass, fat mass, insulin-like growth factor 1 (IGF-1), handgrip, quality of life insulin-like growth factor-binding protein 3 (IGFBP-3), and in patients with cancer. A random-effects model was run to pooled results. RESULTS: Five articles providing 1331 participants were analyzed in this study. Pooled analysis revealed a significant increase in body weight (weighted mean difference (WMD): 1.56 kg, 95% confidence interval (CI): 1.20, 1.92; I2= 0%), lean body mass (WMD: 1.36 kg, 95% CI: 0.85, 1.86; I2= 53.1%), fat mass (WMD: 1.02 kg, 95% CI: 0.51, 1.53; I2= 60.7%), IGF-1 (WMD: 51.16 ng/mL, 95% CI: 41.42, 60.90, I2= 0%), and IGFBP-3 (WMD: 0.43 µg/mL, 95% CI: 0.17, 0.68, I2= 98.6%). Results showed no significant increase in appetite when analysis run on all studies without considering different doses 0.29 (95% CI: -0.30, 0.89, I2= 73.8%), however, there was a significant increase in appetite without heterogeneity and inconsistency 0.59 (95% CI: 0.32, 0.86; I2= 0%) in the 100 mg/day group compared to anamorelin non-user. CONCLUSIONS: Patients with cancer who receive anamorelin as a treatment for cachexia showed a significant increase in body weight, lean body mass, fat mass, IGF-1, and IGFBP-3.

Effect of bariatric surgery on atherogenicity and insulin resistance in patients with obesity class II: a prospective study.

OBJECTIVE: Enormous efforts have been made to evaluate reliable, simple and practical indicators for predicting patients at risk of progression of cardiovascular disease events, whereby bariatric surgery has remained understudied. Thus, we performed this study to assess the effect of bariatric surgery procedures on atherogenicity and insulin resistance indicators. DESIGN: Cohort study. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Four hundred and forty-three class II obese (severely obese) patients who underwent sleeve gastrectomy, Roux-en-Y gastric bypass, or one anastomosis gastric bypass were followed up for 12 months after surgery. Atherosclerosis-related indicators were evaluated at baseline, as well as 6 and 12 months after surgery. RESULTS: Atherogenic index of plasma, lipoprotein combine index, atherogenic coefficient, cholesterol index, Castelli's risk indices I and II, and triglyceride to high-density lipoprotein-cholesterol ratio (p<0.01) improved after 12 months. Additionally, bariatric surgery yielded a significantly reduced triglyceride glucose index. There was no significant difference between procedures in terms of indicators. The Spearman correlation test showed a significant inverse correlation between weight plus fat mass and atherosclerosis-related indicators as well as a positive correlation between percentage of excess weight loss and these indicators. CONCLUSIONS: This study demonstrated three bariatric surgery procedures' ability to improve atherogenicity and insulin resistance in patients with obesity class II. The anti-atherogenicity effects can be partly assigned to the reduction of body weight and adipose tissue. Nevertheless, further studies with larger sample sizes and longer follow-ups are required to confirm our results.

Tamoxifen use and risk of endometrial cancer in breast cancer patients: A systematic review and dose-response meta-analysis.

BACKGROUND: Worse prognosis of endometrial cancers (EC) in tamoxifen-treated women compared to non-tamoxifen-treated women been proposed. The relationship between tamoxifen treatment of breast cancer (BC) and the risk of EC is controversial and there is no agreement between publication results on this issue (the answer to all comments provided in the page 2 of manuscript). The aim of this study is investigation the association between tamoxifen treatment and the risk of EC in patients with BC. METHODS AND RESULTS: We conducted a comprehensive search with related keywords in MEDLINE/PubMed, SCOPUS, and Web of Science databases until April 16, 2022. Random-effects model (DerSimonian and Laird) was used to pool risk ratios (RRs) with 95% confidence intervals (CIs) of EC. Dose, cumulative dose, and duration-response analysis were performed in linear and non-linear states. Twenty-six studies reported a relation between tamoxifen treatment and risk of EC in patients with BC. Results showed a direct relationship between tamoxifen use and EC (RR: 2.03, 95% CI: 1.68-2.45; I2:76%). By increase the age of participants, the risk of EC was decrease (coef = -.0206), although this was not statistically significant (p = .37). Linear dose-response model indicated a direct significant association between dose and duration use of tamoxifen and EC (dose: exe(b) = 1.019, p = .001; duration: exe(b) = 1.014, p = .001). Non-linear dose-response analysis confirmed linear analysis. CONCLUSION: This study highlights that tamoxifen use is a significant risk factor related to the incidence of EC in patients with BC.

The impact of bariatric surgery procedures on the modulation of cardiometabolic risk factors in patients with severe obesity: a 12-month follow-up.

OBJECTIVE: To evaluate the effects of one anastomosis gastric bypass (OAGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) on cardiometabolic risk factors (CMRFs) in patients with severe obesity. METHODS: This retrospective cohort study included patients with severe obesity who had undergone OAGB, RYGB, or SG between 2015 and 2017 and follow-up assessments over 12-months. RESULTS: Among 485 included patients, anthropometric measurements, body composition, fasting blood glucose (FBG), lipid profile, and comorbidities were significantly improved for all three procedures throughout the follow-up period. Weight, % total weight loss (%TWL), body mass index, fat mass and fat mass to fat-free mass ratio improvements were higher with RYGB and OAGB than SG. There were no significant differences between procedures in all other variables. A significant trend toward remission rate of dyslipidemia and type 2 diabetes mellitus was observed with all three procedures, with no significant difference between the three groups. %TWL statistically correlated with fat mass, FBG, and triglycerides. CONCLUSIONS: OAGB, RYGB, and SG had a beneficial impact on CMRFs and comorbidities during 12 months of follow-up. Of note, RYGB and OAGB may result in better outcomes, particularly anthropometric and body composition indices. Further large-sample, long-term follow-up studies are required to expand on the present findings.

Zingiber officinale essential oil-loaded chitosan-tripolyphosphate nanoparticles: Fabrication, characterization and in-vitro antioxidant and antibacterial activities.

Zingiber officinale essential oil (ZEO) was encapsulated in chitosan nanoparticles at different concentrations using the emulsion-ionic gelation technique and its antioxidant and antibacterial effects were investigated. The results indicated that ZEO level had a significant effect on encapsulation efficiency (EE), loading capacity (LC), particle size and zeta potential. The value obtained for EE, LC, mean particle size and zeta potential were 49.11%-68.32%, 21.16%-27.54%, 198.13-318.26 nm and +21.31-43.57 mV, respectively. According to scanning electron micrographs, the nanoparticles had a spherical shape with some invaginations due to the drying process. The presence of essential oil within the chitosan nanoparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. In vitro release studies in simulated gastrointestinal fluid (SGF) and simulated intestinal fluid (SIF) indicated an initial burst effect followed by slow release with higher release rate in acidic medium of SGF. ZEO-loaded nanoparticles showed DPPH radical scavenging activity of 20%-61% which increased by raising the ZEO level. Moreover, results of antibacterial activity revealed that Staphylococcus aureus (with inhibition zones of 19-35.19 mm2) and Salmonella typhimurium (with inhibition zones of 9.78-17.48 mm2) were the most sensitive and resistant bacteria to ZEO, respectively. Overall, chitosan nanoparticles can be considered as suitable vehicles for ZEO and improve its stability and solubility.

Effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral or parenteral feeding.

BACKGROUND: Glutamine plays an important role in acute catabolic conditions in critically ill patients. This meta-analysis aimed to investigate the effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral feeding (EN) or parenteral feeding (PN). METHODS: PubMed, Web of Science, Scopus, and Embase were explored to identify the studies investigating the effect of glutamine on serum inflammatory markers in intensive care unit patients. All randomized clinical trials that assessed the effect of glutamine supplementation on "inflammatory markers" in EN or PN were included in the study. Because a small number of studies were included, SE was adjusted for overall effect size by using the Knapp-Hartung method. RESULTS: In this study, 2728 eligible studies were initially included, and 10 eligible case-control studies were finally enrolled for further investigations. There was a statistical reduction between preintervention and postintervention CRP levels (standardized mean difference [SMD] = -0.38 mg/L; 95% CI, -0.72 to -0.03). No significant association was found between L-glutamine supplementation in the EN/PN and interleukin 6 (IL-6) (SMD = -0.58 pg/ml; 95% CI, -2.15 to 0.99) and tumor necrosis factor alpha (TNF-α) (SMD = 2.69 pg/ml; 95% CI, -9.66 to 15.03) compared with the control group. CONCLUSIONS: This study identified that glutamine supplementation might have an important effect on CRP in acute conditions and no significant effect on IL-6 and TNF-α in acute conditions.

A comprehensive insight into effects of green tea extract in polycystic ovary syndrome: a systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS), as the most common endocrine disorder in reproductive-aged women, is characterized by oxidative stress and ovarian tissue inflammation. Green tea extract (GTE) potentially possesses therapeutic effects for PCOS because of the antioxidant and anti-inflammatory compounds. This systematic review evaluates the potential roles of GTE on metabolic variables, hormone levels, and ovarian function in PCOS. METHODS: A systematic review was conducted of published studies reporting the effects of GTE on PCOS. Several major databases, including PubMed, SCOPUS, and Google Scholar, were searched up from inception to April 2021. Clinical trials and animal studies that assessed the effects of GTE on PCOS were eligible for inclusion. RESULTS: Of 314 articles found in the search, four human studies and four animal studies were included. All studies in humans showed the effects of GTE on weight loss. GTE's effect on decreasing testosterone levels in humans and LH levels in animals were also reported. In addition, increases in FSH and progesterone levels in animal models were observed. Although GTE improved fasting blood sugar and insulin levels, the effect of GTE on inflammatory parameters, such as TNF-alpha and IL-6 and antioxidant status, was limited to animal studies. CONCLUSION: Therefore, this review suggests that GTE could be considered a potential agent to attenuate PCOS complications mainly due to its effect on weight loss and glycemic levels. However, more studies are needed to formulate conclusions about the effects and mechanisms of GTE in PCOS.

Cell therapy in patients with COVID-19 using Wharton's jelly mesenchymal stem cells: a phase 1 clinical trial.

BACKGROUND: Mesenchymal stem cells (MSCs) have received particular attention because of their ability to modulate the immune system and inhibit inflammation caused by cytokine storms due to SARS-CoV-2. New alternative therapies may reduce mortality rates in patients with COVID19. This study aimed to assess the safety and efficacy of injecting intravenous Wharton's jelly-derived MSCs in patients with COVID-19 as a treatment. METHODS: In this study, five patients with severe COVID-19 were treated with Wharton's jelly-derived mesenchymal stem cells (150 × 106 cells per injection). These patients were subject to three intravenous injections 3 days apart, and monitoring was done on days 0, 3, 6, and 14 in routine tests, inflammatory cytokines, and flow cytometry of CD4 and CD8 markers. A lung CT scan was performed on base and days 14 and 28. In addition, IgM and IgG antibodies against SARS-CoV-2 were measured before and after treatment. RESULTS: The results showed that IL-10 and SDF-1 increased after cell therapy, but VEGF, TGF-ß, IFN-γ, IL-6, and TNFα decreased. Routine hematology tests, myocardial enzyme tests, biochemical tests, and inflammation tests were performed for all patients before and after cell therapy on base and days 3, 6, and 14, which indicated the improvement of test results over time. COVID-19 antibody tests rose in 14 days after WJ-MSC injection. The total score of zonal involvement in both lungs was improved. CONCLUSIONS: In patients, the trend of tests was generally improving, and we experienced a reduction in inflammation. No serious complications were observed in patients except the headache in one of them, which was resolved without medication. In this study, we found that patients with severe COVID-19 in the inflammatory phase respond better to cell therapy. More extensive clinical trials should be performed in this regard. TRIAL REGISTRATION: IRCT, IRCT20190717044241N2 . Registered April 22, 2020.

Effects of curcuminoids on inflammatory and oxidative stress biomarkers and clinical outcomes in critically ill patients: A randomized double-blind placebo-controlled trial.

Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU-admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL-6, TNF-α, MCP-1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short-term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.

Efficacy, safety, and tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients. METHOD: This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8). RESULTS: A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey). CONCLUSION: Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.

Nutritional status in kidney transplant patients before and 6-month after transplantation: Result of PNSI study.

OBJECTIVES: Kidney transplantation is an essential treatment in management of kidney failure patients. The present study evaluated and compared the nutritional status of renal transplant patients before and 6 months after kidney transplantation and in comparison with healthy individuals. METHODS: A multi-center, case-control study was conducted among 40 kidney transplant recipients and 40 healthy adults. Biochemical tests, anthropometric indices, and dietary intake were collected at baseline and 6 months post-transplant and compared with healthy controls. RESULTS: Anthropometric indices of the participants increased in post-transplant period compared to baseline (p < 0.05). The calories, fat, carbohydrates, and selenium intakes also increased in patients compared to before transplantation and healthy controls. The mean score of malnutrition index in patients, before transplantation were: good nutrition status (A) = 42.5%, mild to moderate malnutrition (B) = 52.5%, and severe malnutrition (C) = 5%, that changed to A = 75%, B = 20%, and C = 5% six months after surgery. The mean score of malnutrition index in pre-transplant patients were: A = 42.5%, B = 52.5% and, C = 5%, which changed to A = 75%, B = 20% and C = 5% after 6 months. Experimental results showed that mean plasma levels of albumin, total protein, calcium increased as well as mean plasma levels of magnesium and phosphorus decreased over six months (p < 0.001). CONCLUSION: Kidney transplantation led to improvement in clinical and nutritional status of patients with renal failure. Improving dietary intakes as part of the medical care process can help improve their medical conditions.

Insights to potential antihypertensive activity of berry fruits.

Hypertension is one of the main risk factors for cardiovascular disease and causes widespread morbidity and mortality worldwide. Although several antihypertensive drugs have been proposed for management of high blood pressure, changing lifestyle, including diet, has attracted interest recently. In this sense, consumption of fruits and vegetables, which are rich in vitamins, minerals, and phytochemicals, has been assigned as an efficient therapeutics. Berry fruits contain various bioactive compounds with potential health implications such as antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. The main mechanisms responsible for antihypertensive activity mainly arise from the activity of flavonoids, minerals, and vitamins, as well as fibers. The objective of this review is to provide a summary of studies regarding the effect of berry fruits on the hypertensive animals and humans. The mechanisms involved in reducing blood pressure by each group of compounds have been highlighted. It can be concluded that berries' bioactive compounds are efficient in mitigation of hypertension through improvement of vascular function, angiotensin-converting enzyme's (ACE) inhibitory activity, increasing endothelial nitric oxide synthase (eNOS) activity, and nitric oxide (NO) production, besides anti-oxidative and anti-inflammatory activities. These fruits can be considered as potential sources of invaluable compounds for development of antihypertensive foods and pharmaceuticals.

A comprehensive insight into potential roles of Nigella sativa on diseases by targeting AMP-activated protein kinase: a review.

OBJECTIVES: Nigella sativa (NS) is a known medicinal herb with numerous therapeutic effects such as antidiabetic, anti-proliferative, anti-inflammatory, and anti-cancer activities. It has been indicated that NS can regulate cellular metabolism by adjusting transduction signaling pathways. Adenosine monophosphate-activated protein kinase (AMPK) is one of the main physiological processes, such as energy hemostasis, cellular metabolism, and autophagy regulators. Herb-derived medicines have always been considered as one of the main AMPK activators, and surprisingly recent data has demonstrated that it can be a target for NS and its derivatives. EVIDENCE ACQUISITION: The literature search was conducted in PubMed, SCOPUS, Embase, ProQuest, and Google Scholar electronic resources. Published articles up to September 2020 were considered, and those of which investigated Nigella sativa effects on the AMPK pathway after meeting the inclusion criteria were included. RESULTS: The search was performed on several online databases such as PubMed, Scopus, Embase, ProQuest, and Google Scholar from inception until January 2020. Among the initial search, 245 studies were found. After removing duplicated data and meeting the inclusion criteria, only 14 studies were selected. They included the effects of NS and its bioactive compounds as anti-hyperglycemic (n = 5), on liver function (n = 4), cancers (n = 3), and on Neuroinflammation and Atherosclerosis (n = 2). Most of the included studies are animals or in-vitro investigations. CONCLUSION: In this review, we discuss the latest findings on the molecular mechanism of NS effecting the AMPK signaling pathway. We also focus on the therapeutic effects of NS, including the prevention and treatment of metabolic and pro-inflammatory disease by targeting the AMPK pathway.

Development, characterization and in vitro antioxidant activity of chitosan-coated alginate microcapsules entrapping Viola odorata Linn. extract.

Viola odorata Linn or sweet violet has several biological activities due to the presence of flavonoids, tannins, alaloid, glycoside, and saponins. However, susceptibility of these compounds to harsh conditions and low solubility is a great challenge for their incorporation into food products. Therefore, encapsulation can be an effective approach in this respect. In the present study, chitosan-coated microcapsules loaded with Viola extract were prepared for the first time and the effects of independent variables (sodium alginate: 1-1.5%, calcium chloride: 0.6-1.5% and extract concentrations: 5-10%) on encapsulation efficiency (EE%) were investigated. After evaluation of the model, the optimum condition for preparation of microcapsules was selected as 1.47% sodium alginate, 5.02% extract and 1.42% CaCl2 with EE% of 83.21%. The microcapsules developed at this condition had an acceptable spherical shape and the results obtained in Fourier transform-infrared spectroscopy (FTIR) indicated the presence of the extract within the microcapsules. The mean diameters of the uncoated and chitosan-coated microcapsules were 73 and 141 µm, respectively. The in vitro release in acidic medium (pH 1.5) and phosphate buffer saline (pH 7) were 43.21% and 95.39%, respectively. The prepared extract-loaded microcapsules have potential to be used in food products providing acceptable antioxidant activity.

Therapeutic effects of supplementation with Curcuminoids in critically ill patients receiving enteral nutrition: a randomized controlled trial protocol.

BACKGROUND: Curcuminoids are dietary polyphenols that can improve health indices through different mechanisms such as anti-inflammatory, antioxidant and immunoregulatory properties. Due to the lack of evidences on the efficacy of curcuminoids in critically ill patients, this study was designed to investigate the effects of short-term curcuminoids supplementation on inflammatory, oxidative stress and adipokine indices as well as nutritional and clinical status in Traumatic Brain Injury (TBI) patients admitted in the Intensive Care Unit (ICU). METHODS: The present trial will be performed in the ICU of Sina and Shohadaye Tajrish hospitals of Tehran, Iran. Sixty-two critically ill patients with TBI will be enrolled based on the eligibility criteria. The patients will be randomly assigned into two groups. For 7 days, they will received either 500 mg curcuminoids in combination with 5 mg piperine or matched placebo. A general questionnaire, consent form as well as NUTRIC, SOFA and APACHEII scoring system and anthropometrics will be assessed at baseline. The inflammatory markers including TNF-α, IL-6, MCP-1 and CRP, oxidative stress indices (GPx and SOD) and adipokines (leptin and adiponetctin) will be measured at baseline and at the end of the study. In addition, dietary intake, concomitant drugs and laboratory tests will be recorded daily. DISCUSSION: To the best of our knowledge, this is the first clinical trial investigating the effect of curcuminoids supplementation in critically ill patient with TBI. The findings of the present study will provide evidence on the efficacy and safety of curcuminoids in these patients. TRIAL REGISTRATION NUMBER: (http://www.irct.ir, identifier: IRCT20180619040151N1), Registration date:18.09.2018.

Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma.

BACKGROUND: one of the promising approaches for treatment of some cancers is adoptive cell therapy using natural killer (NK) cells. Various methods have been investigated for ex vivo expansion of NK cells in large-scale, but most of them involved cancer or genetically modified cells as feeder layer and also some of them have the risk of T cell contamination and graft-versus-host disease (GVHD). METHOD: In this study, irradiated autologous peripheral blood mononuclear cells (PBMCs) as feeder layer with an anti-CD3 monoclonal antibody (mAb) were used. For activation and expansion of NK cells, human recombinant IL2 and IL15 were used. After co-culturing of expanded NK cells (eNKC) and isolated NK cells (iNKC) with hepatocellular carcinoma (HCC) cells, the viability of eNKC in compared to iNKC were analyzed by CCK-8 assay and degranulation of NK cells after co-culturing was assayed by measuring CD107a expression. Enzyme-Linked Immunosorbent Assay (ELISA) assay was used for the ability of NK cells to secretion of IFN-γ (interferon-γ) and TNF-α (Tumor Necrosis Factor-α) after co-culture with HCC cells. Real Time PCR analysis was used for expression of human Perforin and Granzyme B genes in the NK cells exposed to target HepG2 cells. RESULT: This method strongly expanded highly purified NK cells with powerful cytotoxicity against HCC cells. The expanded NK cells showed high level of expression of degranulation marker and human Perforin and Granzyme B genes, and also was secreted larger amounts of TNF-α and IFN-γ compared with fresh isolated NK cells. CONCLUSION: we proposed an effective method for expansion of cytotoxic NK cells using irradiated autologous PBMC as feeder layer for more successful transfer of allogeneic NK cell in immuno cell therapy of HCC.

Nutritional status of patients hospitalized in the intensive care unit: A comprehensive report from Iranian hospitals, 2018.

INTRODUCTION AND AIM: Malnutrition is a complication of hospitalization in critically ill patients. This event is occurred because of disease and therapeutic processes for curing the patients. Determination of nutritional status helps physicians and clinical nutritionists decide on the best regimen which should be prescribed for a patient. In the current study, we aimed to report the nutritional status ofpatientshospitalizedin the intensive care unit (ICU). METHOD OF STUDY: We used three standard tolls, including Subjective global assessment (SGA), Nutrition Risk in the Critically Ill (NUTRIC) Score and nutrition risk screening (NRS) questionnaires via a multi-stage sampling for different ICU wards of 32 university hospitals in Iran. Frequencies and rates of nutritional scores, comparative studies, and determined agreement of scoring systems and nutritional status in any ward of hospitals were evaluated. RESULTS: There were 771 males and 540 female Cancer and trauma patients had the best and worst nutritional scores, respectively. Using NRS and NUTRIC, the low-risk scores were more frequent than thehigh-riskscores among ICU patients. SGA showed that most patients were in grades A (well nutritional status) or B (moderate nutritional status), andfew caseswere in grade C (poor nutritional status).The high-risk nutritional score wasobtained for older patients. NUTRIC and NRS had better agreement for diagnosis and differentiation of malnutrition than NUTRIC-SGA or NRS-SGA pairs. However, there was no strong agreement between the mentioned pairs. CONCLUSION: Nutritional status of patients hospitalized in ICU wards in Iran wassomewhat better than other countries that this could be due to the highly observed guidelines of patient's care in Iran. Anyway,it is suggested that a more precise tool of nutritional scoresto be validated for patients hospitalized in ICU·In addition, better medical care needs a well evaluation of nutritional insufficiencies and what is necessary for compensation using complementary regimens.

Novel Combination of Mesenchymal Stem Cell-Conditioned Medium with Sorafenib Have Synergistic Antitumor Effect of Hepatocellular Carcinoma Cells

Objective: Hepatocellular carcinoma (HCC) is the most common liver malignancy. Sorafenib is the first-line systemic treatment for advanced HCCs. However, due to safety concerns, researchers are now looking for ways to boost the efficacy of the medication. One approach for reducing toxicity is combining sorafenib with other agents so that a lower dose of sorafenib is required. Mesenchymal stromal cells (MSCs) can have an inhibitory effect on HCC tumor growth. Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) is the substance extracted from MSC culture and contains most of the potential cytokines secreted by MSCs. We, therefore, anticipated a synergistic Antitumor Effect of sorafenib in Combination with MSC-CM. In this study, we used HepG2 as our target cell lines. Methods: HepG2 cells were treated with sorafenib alone and with sorafenib + MSC-CM. CCK-8 assay was used to evaluate and compare the inhibition of cell growth between the two groups with different treatments. Results: The combination treatment of cell lines with sorafenib and MSC-CM had significantly reduced the values of IC50 compared to the use of sorafenib alone (3.4 vs. 2.7 respectively). Conclusion: This study suggests that a combination of sorafenib with MSC-CM can synergistically suppress the growth of HCC cells.