RESUMEN
BACKGROUND: Extensive evidence has suggested the cardio-protective properties of the polyphenol curcumin. The aim of this study was to investigate the effects of a highly bioavailable curcumin supplement on cardiometabolic risk factors, health-related quality of life, and depression in patients with coronary slow flow phenomenon (CSFP). METHODS: This randomized double-blind placebo-controlled clinical trial was conducted in 42 patients with CSFP (age 35-70 years, 25 ≤ body mass index < 40 kg/m2). Patients received either 80 mg/day nano-curcumin or placebo for 12 weeks. Serum levels of visfatin, high-sensitivity C-reactive protein (hs-CRP), and glycemic indices were measured before and after the intervention. The short form 36-item quality of life (SF-36) and Beck's Depression Inventory-II (BDI-II) questionnaires were assessed, as well. RESULTS: No significant improvements were observed in circulating hs-CRP and visfatin following the intervention. A significant increase was observed in pre- to post-fasting blood glucose (- 0.9 ± 12.2 vs. 7.7 ± 12.4 mg/dl, p = 0.02) and hemoglobin A1C (- 0.1 ± 0.8 vs. 0.5 ± 0.8%, p = 0.04) levels, in the placebo compared with the intervention group. Physical (8.2 ± 8.1 vs. - 1.2 ± 6.5, p < 0.001) and mental (6.8 ± 11.8 vs. - 1.1 ± 10.4, p = 0.02) component summary scores were significantly improved in the nano-curcumin than the placebo group. Additionally, the number of patients with lower degrees of depression was significantly better in the intervention than the placebo group following the supplementation (p = 0.046). CONCLUSION: Curcumin supplementation prevented deterioration of glycemic control and improved physical and psychological quality of life and depression in patients with CSFP. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20131125015536N8), June 19, 2019.
Asunto(s)
Factores de Riesgo Cardiometabólico , Curcumina , Depresión , Suplementos Dietéticos , Calidad de Vida , Humanos , Curcumina/administración & dosificación , Método Doble Ciego , Persona de Mediana Edad , Masculino , Depresión/psicología , Depresión/tratamiento farmacológico , Depresión/prevención & control , Femenino , Anciano , Adulto , Resultado del Tratamiento , Circulación Coronaria/efectos de los fármacos , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisisRESUMEN
BACKGROUND: Cardiovascular events and poor quality of life are frequently observed in patients with coronary slow flow phenomenon (CSFP). This trial evaluated the effect of nano-curcumin supplement containing curcuminoids, as multifunctional nutraceuticals, on angina status, and some traditional and novel cardiovascular risk factors in overweight or obese patients with CSFP. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 42 overweight or obese patients with CSFP received either 80 mg/day of nano-curcumin or placebo for 12 weeks. Seattle angina questionnaire (SAQ) as a clinical measure of angina status, circulating endocan, adropin, homocysteine, lipid profile, and the novel scores of visceral adiposity index (VAI) and waist-triglyceride index (WTI) were assessed before and after the intervention. The independent samples t-test, Mann-Whitney test, analysis of covariance, Chi-square, and Fisher's exact tests were used where appropriate. RESULTS: All domains of SAQ including physical limitation, angina stability, angina frequency-severity, treatment satisfaction, and disease perception and quality of life improved significantly in the nano-curcumin compared with the placebo group. No significant changes were observed in serum endocan, adropin, and homocysteine following the intervention. Triglycerides, triglyceride/high-density lipoprotein cholesterol ratio, WTI and VAI values improved significantly only within the nano-curcumin group. CONCLUSIONS: Supplementation with 80 mg/day nano-curcumin (containing curcuminoids) for 12 weeks significantly improved clinically important disease-specific aspects of health in patients with CSFP. Some traditional and novel cardiovascular risk factors improved significantly only compared with the baseline values, which need further investigation. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1398.794). The study protocol was registered at Iranian Registry of Clinical Trials by IRCT20131125015536N8 registration ID at 19.06.2019.
RESUMEN
Objectives: Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= 54.5 ºC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC, Tm= - 2 ºC). Materials and Methods: Nanoliposomes with different percentages of PEG (3% and 5%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done. Results: The results revealed that the formulations are in the 80-120 nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately 87%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. Conclusion: The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).
RESUMEN
INTRODUCTION: In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. METHOD: The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. RESULTS: Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1 . BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α). CONCLUSION: Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.
RESUMEN
mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Animales , Humanos , Ratones , Conejos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/epidemiología , COVID-19/prevención & control , Sueroterapia para COVID-19 , Vacunas contra la COVID-19/efectos adversos , Macaca mulatta/genética , Pandemias/prevención & control , ARN Mensajero/genética , SARS-CoV-2 , Vacunas ViralesRESUMEN
Cancer is a major cause of death worldwide. Cancer-resistant to chemo or radiotherapy treatment is a challenge that could be overcome by a nanotechnology approach. Providing a theranostic nano-platform for different cancer treatment strategies could be revolutionary. Here we introduce a multifunctional theranostic nanostructure which has the capacity for improving cancer diagnosis and treatment through better chemo and radiotherapy and current x-ray imaging systems through co-encapsulation of a small gold cluster and anticancer drug doxorubicin. 2 nm gold clusters represent good heating under radio frequency electric field (RF-EF) exposure and have been used for in vitro hyperthermia treatment of cancerous cells. Liposomal doxorubicin (169 ± 19.8 nm) with gold clusters encapsulation efficiency of 13.2 ± 3.0% and doxorubicin encapsulation efficiency of 64.7 ± 0.7% were prepared and studied as a theranostic agent with a high potential in different cancer treatment modalities. Exposure to a radiofrequency electric field on prepared formulation caused 20.2 ± 2.1% drug release and twice decreasing of IC50 on colorectal carcinoma cells. X-ray attenuation efficiency of the liposomal gold cluster was better than commercial iohexol and free gold clusters in different concentrations. Finally, treatment of gold clusters on cancerous cells results in a significant decrease in the viability of irradiated cells to cobalt-60 beam. Based on these experiments, we concluded that the conventional liposomal formulation of doxorubicin that has been co-encapsulated with small gold clusters could be a suitable theranostic nanostructure for cancer treatment and merits further investigation.
Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Liposomas/química , Medicina de Precisión , Oro/química , Doxorrubicina/farmacología , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
BACKGROUND & AIMS: This study investigated the effects of collagen hydrolysate and omega-3 fatty acids (FAs) on the rate and quality of wound healing, metabolic disorders, and adipose-derived peptides in patients with major burns. METHODS: In this randomized clinical trial, 66 patients with 20-45% deep partial or full-thickness burns were randomly assigned to three groups to receive either a beverage containing collagen (40 gr/d), collagen (40 gr/d) plus 3 gr/d omega-3 (ω-3) FAs, or placebo for four weeks. Wound healing rate, Vancouver scar scale (VSS), as well as baseline, weeks two and three serum concentrations of adiponectin, fibroblast growth factor 21 (FGF21), neuregulin 4 (NRG4), transforming growth factor (TGF)-ß1, and pre-albumin/hs-CRP ratio were assessed. RESULTS: The wound healing rate during the weeks post-burn (p = 0.006 and p = 0.01), and days of 95% (21.3 ± 6.8 and 22.9 ± 8.7 vs. 34.3 ± 14.8 days, p = 0.003 and p = 0.03) and complete (26 ± 7.7 and 27.4 ± 9.4 vs. 41.1 ± 16.6 days, p = 0.003 and p = 0.01) wound healing were significantly better with Collagen and Collagen. ω-3 compared to the placebo group. The VSS was significantly lower, indicated better scar status, in the both intervention groups compared to the placebo (p = 0.02 and p = 0.01). Wound healing outcomes were not statistically different between the Collagen and Collagen. ω-3 groups. Hs-CRP/pre-albumin ratio was significantly lower in the Collagen. ω-3 than the placebo group at week three (1.2 ± 1.9 vs. 4.8 ± 7.7 dl/l, p = 0.03). The significant decrease in serum adiponectin seen during the trial course within the placebo (10 ± 8.8 to 5.8 ± 4.9 mg/l, p = 0.03) and Collagen (11.8 ± 14 to 8.6 ± 11.7 mg/l, p = 0.03) groups was prevented in the Collagen. ω-3 group (p = 0.4). Circulating FGF21 decreased significantly within the Collagen (p = 0.005) and Collagen. ω-3 (p = 0.02) groups at the end of week three compared to the baseline. CONCLUSIONS: Adding collagen hydrolysate as part of adjunctive therapy improved wound healing rate and quality. These findings as well as the efficacy of omega-3 FAs need to be further confirmed in larger populations. This study was registered with the Iranian Registry of Clinical Trials (IRCT20090901002394N42).
Asunto(s)
Cicatriz , Ácidos Grasos Omega-3 , Humanos , Proteína C-Reactiva , Adipoquinas , Adiponectina , Irán , Cicatrización de Heridas , Colágeno/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , BiomarcadoresRESUMEN
Spinal cord injury (SCI) is a debilitating condition for which no definitive treatment has yet been identified. Notably, it influences other tissues through inflammatory reactions and metabolic disturbances. Therefore, fingolimod (FTY-720), as an FDA-approved inflammatory modulator, would be promising. In the present study, nanocarriers with two distinct monodisperse particle sizes of 60 (nF60) and 190 (nF190) nm were prepared via low-(stirring) and high-energy (probe ultrasound) emulsion oil in water (O/W) methods. Larger nanocarriers showed higher EE% and sustained-release profile than smaller nanocarriers. Neural stem cell (NSC) viability and lactate dehydrogenase (LDH) release were studied in the presence of nanocarriers and free FTY-720. The results indicated that nanocarriers and free FTY-720 enhanced NSC viability compared with the control group. However, nF190 induced significantly less cell membrane damage than nF60. Nanocarriers and free FTY-720 enhanced motor neuron recovery in SCI rats, while body weight and return to bladder reflux by nF190 were significantly higher than those in the nF60 group. Return to bladder reflux might be due to the role of FTY-720 in the regulation of detrusor muscle tone and preservation of the integrity of vessels by acting on endothelial cells. Moreover, nF190 gained higher soleus muscle weight than the free drugs; probably decreasing proinflammatory cytokines in the soleus diminishes muscular atrophy in SCI rats. In summary, it might be said that larger nanocarriers with sustained-release profile and less cell membrane damage seem to be more efficient than smaller ones to manage SCI and enhance bladder reflux. These data will help pharmaceutical companies select the correct particle size for nanodrugs and develop more efficient drug formulations to treat SCI.
Asunto(s)
Clorhidrato de Fingolimod , Traumatismos de la Médula Espinal , Animales , Preparaciones de Acción Retardada/farmacología , Células Endoteliales , Clorhidrato de Fingolimod/farmacología , Tamaño de la Partícula , Ratas , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismoRESUMEN
OBJECTIVES: Metformin has been shown to kill cancer stem-like cells in genetically various types of breast carcinoma. With the aim to simultaneously eradicate the bulk population of tumour cells and the rare population of cancer stem-like cells in breast cancer tissues, we used the combination chemotherapy of docetaxel (DTX) with metformin (MET). Furthermore, we introduce an active loading method based on ammonium sulphate 250 mM (SA) for encapsulating docetaxel into liposomes. METHODS: Docetaxel and metformin encapsulated into PEGylated liposomes with two different methods based on remote or passive loading methods, respectively. The size and surface charge of the liposomes were characterized. DTX content in the nanoliposomes was measured by the high-performance liquid chromatography method. The drug release profiles were evaluated in phosphate-buffered dextrose 5% with the pH of 6.5 and 7.4. We examined the antitumour activity of Taxotere (TAX), and liposomal formulation of DTX and MET as a monotherapy or combination therapy. The biodistribution of liposomes was also investigated using 99mTc hexamethyl propylene amine oxime method in BALB/c mice bearing 4T1 breast carcinoma tumours. KEY FINDINGS: The final formulations were prepared according to the best physicochemical characteristics which were HSPC/mPEG2000-DSPE/Chol (DTX liposomes) and HSPC/DPPG/mPEG2000-DSPE/Chol (MET liposomes), at molar ratios of 85/5/10 and (55/5/5/35), respectively. In vivo experiments showed that when free or liposomal metformin used in combination with liposomal docetaxel, they prolonged median survival time (MST) from 31 in the control group to 46 days, which demonstrates their promising effects on the survival of the 4T1 breast carcinoma mice models. Moreover, combination therapies could significantly increase life span in comparison with phosphate-buffered saline (PBS) and Taxotere groups at the same dose. Furthermore, in the combination therapy study, treatment with DTX liposomes prepared by ammonium sulphate 250 mM buffer alone resulted in similar therapeutic efficacy to combination therapy. The biodistribution study exhibited significant accumulation of DTX liposomes in the tumours due to the Enhanced Permeability and Retention effect. CONCLUSIONS: This study also showed that metformin-based combinatorial chemotherapies have superior efficacy versus their corresponding monotherapy counterparts at same doses. The findings confirm that liposomes based on ammonium sulphate 250 mM could be as a promising formulation for efficient DTX delivering and cancer targeting and therefore merit further investigations.
Asunto(s)
Antineoplásicos , Metformina , Neoplasias , Sulfato de Amonio , Animales , Antineoplásicos/química , Línea Celular Tumoral , Docetaxel/farmacología , Liposomas/química , Metformina/farmacología , Ratones , Ratones Endogámicos BALB C , Fosfatos , Polietilenglicoles/química , Distribución TisularRESUMEN
This review highlights using nanotechnology in increasing the bioavailability of AP (Apigenin) to enhance its therapeutic efficacy in breast cancer treatment. Breast cancer is one of the most leading causes of cancer death in women both in developed and developing countries. According to several epidemiological and clinical trial studies that indicate progestin-stimulated breast cancer in post-menopausal women; it is necessary to determine compounds to suppress or attenuate the tumor-promoting effects of progestins in breast cells. For this purpose, using the natural anti-progestins, including AP compared with the chemical ones could be significantly effective due to the lack of toxicities and contradiction effects. However, AP is categorized as a Class II drug of Biopharmaceutical Classification System with low solubility in water which limited its therapeutic effects. Therefore, nanotechnology due to the presentation of remarkable properties has overcome this limitation through enhanced the solubility and bioavailability of AP. In this regard, various nanocarriers such as nanocrystals, micelles, liposomes, PLGA, etc., have highlighted the significantly increased bioavailability and therapeutic efficacy of AP. Therefore, we will focus on the anticancer effects of AP in breast cancers, including involved mechanisms, the chemistry of AP and its bioavailability, finally different nanostructure systems to enhance the bioavailability of AP.
RESUMEN
It has been more than a year since the outbreak of COVID-19, and it is still the most critical issue of the healthcare system. Discovering effective strategies to treat infected patients is necessary to decrease the mortality rate. This study aimed to determine the effects of nanocurcumin on the severity of symptoms and length of hospital stay (LOS) in COVID-19 patients. Forty-eight COVID-19 patients were randomly assigned into nanocurcumin (n = 24) and placebo (n = 24) groups receiving 160 mg/day nanocurcumin or placebo capsules for 6 days. Mean differences of O2 saturation were significantly higher in patients who received nanocurcumin supplements (p = 0.02). Also, nanocurcumin treatment significantly reduced the scores of domains 3 and 4 and the total score of Wisconsin Upper Respiratory System Survey (WURSS-24), indicating milder symptoms in the treatment group (p = 0.01, 0.03, and 0.01 respectively). Besides, the LOS in curcumin groups was lower than in the placebo group, although the difference was not statistically significant (6.31 ± 5.26 vs. 8.87 ± 8.12 days; p = 0.416). CBC/differentiate, hs-CRP level and the pulmonary involvement in CT scan were not different between the two groups. As nanocurcumin can be effective in increasing O2 saturation and reducing the severity of symptoms in COVID-19 patients, it could probably be used as a complementary agent to accelerate the recovery of patients.
Asunto(s)
COVID-19 , Suplementos Dietéticos , Método Doble Ciego , Humanos , Tiempo de Internación , SARS-CoV-2 , Resultado del TratamientoRESUMEN
OBJECTIVE: Although several experimental models have suggested promising pharmacological effects of naringenin in the management of obesity and its related disorders, the effects of naringenin supplementation on cardiovascular disorders as one of the main complications of nonalcoholic fatty liver disease (NAFLD) are yet to be examined in humans. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, 44 overweight/obese patients with NAFLD were equally allocated into either naringenin or placebo group for 4 weeks. Cardiovascular risk factors including atherogenic factors, hematological indices, obesity-related parameters, blood pressure, and heart rate were assessed pre- and postintervention. RESULTS: The atherogenic index of plasma value, serum non-HDL-C levels as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, low-density lipoprotein cholesterol/HDL-C, and non-HDL-C/HDL-C ratios were significantly reduced in the intervention group, compared to the placebo group post intervention (P < 0.05). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P = 0.001 and P = 0.039, respectively). Furthermore, naringenin supplementation could marginally reduce systolic blood pressure (P = 0.055). Mean corpuscular hemoglobin increased significantly in the naringenin group compared to the placebo group at the endpoint (P = 0.023). Supplementation with naringenin also resulted in a marginally significant increase in the mean corpuscular hemoglobin concentration when compared with the placebo group (P = 0.050). There were no significant between-group differences for other study outcomes post intervention. CONCLUSION: In conclusion, these data indicate that naringenin supplementation may be a promising treatment strategy for cardiovascular complications among NAFLD patients. However, further trials are warranted.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Suplementos Dietéticos , Método Doble Ciego , Flavanonas , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/complicaciones , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Factores de RiesgoRESUMEN
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease worldwide. Flavonoids, a group of natural compounds, have garnered a great deal of attention in the management of NAFLD because of their profitable effects on glucose and lipid metabolism, inflammation, and oxidative stress which are the pivotal pathophysiological pathways in NAFLD. Naringenin is a citrus-derived flavonoid with a broad spectrum of potential biological effects including anti-inflammatory and antioxidant properties, which may exert protective effects against NAFLD. The present clinical trial aims to examine the efficacy of naringenin supplementation on plasma adiponectin and neurogulin-4 (NRG-4) concentrations, metabolic parameters, and liver function indices in overweight/obese patients with NAFLD. METHODS AND ANALYSIS: This is a double-blind, randomized, placebo-controlled clinical study that will investigate the impacts of naringenin supplementation in overweight/obese patients with NAFLD. Liver ultrasonography will be applied to diagnose NAFLD. Forty-four eligible overweight/obese subjects with NAFLD will be selected and randomly assigned to receive naringenin capsules or identical placebo (each capsule contains 100 mg of naringenin or cellulose), twice daily for 4 weeks. Participants will be asked to remain on their usual diet and physical activity. Safety of naringenin supplementation was confirmed by the study pharmacist. The primary outcome of this study is changes in adiponectin circulating levels. The secondary outcomes include changes in NRG-4 levels, liver function indices, metabolic parameters, body weight, body mass index (BMI), waist circumference (WC), blood pressure, and hematological parameters. Statistical analysis will be conducted using the SPSS software (version 25), and P value less than 0.05 will be regarded as statistically significant. DISCUSSION: We hypothesize that naringenin administration may be useful for treating NAFLD by modulating energy balance, glucose and lipid metabolism, oxidative stress, and inflammation through different mechanisms. The current trial will exhibit the effects of naringenin, whether negative or positive, on NAFLD status. ETHICAL ASPECTS: The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1399.439). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT201311250155336N12 . Registered on 6 June 2020.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Suplementos Dietéticos , Método Doble Ciego , Flavanonas , Humanos , Irán , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Berberine (BBR) is a plant alkaloid that possesses anti-inflammatory and anti-oxidant effects with low oral bioavailability. In this study, micelle formulation of BBR was investigated to improve therapeutic efficacy and examined its effect on the secretion of inflammatory cytokines in cerebral ischemia in the animal model. MATERIAL AND METHODS: Nano formulation was prepared by thin-film hydration method, and characterized by particle size, zeta potential, morphology, encapsulation efficacy, and drug release in Simulated Gastric Fluid (SGF) and Simulated Intestine Fluid (SIF). Then, Wistar rats were pretreated with the drug (100 mg/kg) and nano-drug (25, 50, 75, 100 mg/kg) for 14 days. Then, on the fourteenth day, stroke induction was accomplished by Bilateral Common Carotid Artery Occlusion (BCCAO); after that, Tumor Necrosis Factor - Alpha (TNF-α), Interleukin - 1 Beta (IL-1ß), and Malondialdehyde (MDA) levels were measured in the supernatant of the whole brain, then the anti-inflammatory effect of BBR formulations was examined. RESULT AND DISCUSSION: Micelles were successfully formed with appropriate characteristics and smaller sizes than 20 nm. The Poly Dispersity Index (PDI), zeta potential, encapsulation efficacy of micelles was 0.227, - 22 mV, 81%, respectively. Also, the stability of nano micelles was higher in SGF as compared to SIF. Our outcomes of TNF-a, IL-1B, and MDA evaluation show a significant ameliorating effect of the Berberine (BBR) and BBR-loaded micelles in pretreated groups. CONCLUSION: Our experimental data show that pretreated groups in different doses (nano BBR 100, 75, 50 mg/kg, and BBR 100 mg/kg) successfully showed decreased levels of the inflammatory factors in cerebral ischemia compared with the stroke group and pretreated group with nano BBR in the dose of 25 mg/kg. Nano BBR formulation with a lower dose can be a better candidate than conventional BBR formulation to reduce oxidative and inflammatory factors in cerebral ischemia. Therefore, BBR-loaded micelle formulation could be a promising protective agent on cerebral ischemia.
Asunto(s)
Antiinflamatorios/administración & dosificación , Berberina/administración & dosificación , Isquemia Encefálica/tratamiento farmacológico , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Nanopartículas/administración & dosificación , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Enfermedades de las Arterias Carótidas/metabolismo , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Malondialdehído/metabolismo , Micelas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
INTRODUCTION: Collagen and omega-3 fatty acids (FAs) are suggested to have anti-inflammatory, anti-oxidant, and insulin-sensitizing properties. The aim of this study was to investigate the effect of collagen hydrolysate and omega-3 FAs on inflammation and insulin resistance in patients with major burns. METHODS: In this double-blind randomized clinical trial, 66 patients with 20-45% burns were assigned to either of the three groups of collagen (40 gr/d), collagen (40 gr/d) plus fish oil (10 ml/d), or control. High-sensitivity C-reactive protein (hs-CRP), fasting blood glucose (FBG) and insulin concentrations, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed at baseline, as well as end of weeks two and three. RESULTS: Based on post-hoc analyses, hs-CRP levels were significantly lower in the collagen (p=0.026) and collagen+omega-3 (p=0.044) groups compared to the control group, at week three. However, pre- to post- (week three) changes of hs-CRP were significantly higher only in the collagen+omega-3 group compared to the control group (173.2 vs. 103.7 mg/l, p=0.024). After three weeks of the intervention, insulin (11.3 and 11.9 vs. 22.8 µIU/ml) and HOMA-IR (2.9 and 2.8 vs. 7.9) values seemed to be clinically, but not statistically, lower in both intervention groups compared to the control group. Pre- to post- (week three) values of FBG decreased significantly in the collagen (p=0.002) and collagen+omega-3 (p=0.036) groups. Insulin (p=0.008) and HOMA-IR (p=0.001) decreased significantly only in the collagen+omega-3 group at week three compared to the baseline. CONCLUSIONS: Supplementation with collagen hydrolysate and omega-3 FAs can improve hs-CRP concentration and probably insulin resistance in patients with severe burns. Omega-3 FAs had additional effects on modulating inflammation. Larger clinical trials are needed to confirm the current findings especially in terms of glucose homeostasis.
RESUMEN
The drug delivery systems improve the efficacy of chemotherapeutics through enhanced targeting and controlled release however, biological barriers of tumor microenvironment greatly impede the penetration of nanomedicine within the tumor. We report herein the fabrication of a PEG-detachable silybin (SLB) pH-sensitive liposome decorated with TAT-peptide. For this, Acyl hydrazide-activated PEG2000 was prepared and linked with ketone-derivatized DPPE via an acid-labile hydrazone bond to form mPEG2000-HZ-DPPE. TAT peptide was conjugated with a shorter -PEG1000-DSPE spacer and post-inserted into PEGylated liposome (DPPC: mPEG2000-DSPE: Chol). To prepare nanoliposomes (around 100 nm), first, a novel method was used to prepare SLB-Soya PC (SLB-SPC) complex, then this complex was incorporated into nanoliposomes. The pH-sensitivity and shielding effect of long PEG chain on TAT peptide was investigated using DiI liposome and FACS analysis. Pre-treatment to the lowered pH enhanced cellular association of TAT-modified pH-sensitive liposome due to the cleavage of hydrazone bond and TAT exposure. Besides, TAT-modified pH-sensitive liposomes significantly reduced cell viability compared to the plain liposome. In vivo results were very promising with pH-sensitive liposome by detaching PEG moieties upon exposure to the acidic tumor microenvironment, enhancing cellular uptake, retarding tumor growth, and prolonging the survival of 4T1 breast tumor-bearing BALB/c mice. TAT modification of pH-sensitive liposome improved cancer cell association and cytotoxicity and demonstrated potential intracellular delivery upon exposure to acidic pH. However, in in vivo studies, TAT as a targeting ligand significantly decreased the therapeutic efficacy of the formulation attributed to an inefficient tumor accumulation and higher release rate in the circulation. The results of this study indicated that pH-sensitive liposome containing SLB, which was prepared with a novel method with a significant SLB loading efficiency, is very effective in the treatment of 4T1 breast tumor-bearing BALB/c mice and merits further investigation.
Asunto(s)
Doxorrubicina , Liposomas , Animales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Humanos , Concentración de Iones de Hidrógeno , Liposomas/química , Ratones , Ratones Endogámicos BALB C , Polietilenglicoles/química , SilibinaRESUMEN
BACKGROUND: Curcumin, a natural polyphenolic compound, is proposed as a potential treatment option for patients with coronavirus disease by inhibiting the entry of virus to the cell, encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. In this study, the efficacy and safety of nanocurcumin oral formulation has been evaluated in patients with mild-moderate Coronavirus disease 2019 (COVID-19) in outpatient setting. METHODS: In this triple-blind randomized placebo-controlled clinical trial, sixty mild to moderate COVID-19 patients in outpatient setting who fulfilled the inclusion criteria were randomly allocated to treatment (n = 30) group to receive oral nanocurcumin formulation (Sinacurcumin soft gel which contains 40 mg curcuminoids as nanomicelles), two soft gels twice a day after food for 2 weeks or placebo (n = 30) group. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period and compared between two groups. RESULTS: All symptoms except sore throat resolved faster in the treatment group and the difference was significant for chills, cough and smell and taste disturbances. The CRP serum level was lower in the treatment group at the end of two weeks and the lymphocyte count was significantly higher in treatment group. No significant adverse reaction reported in the treatment group. CONCLUSION: Oral nanoformulation of curcumin can significantly improve recovery time in patients with mild to moderate COVID-19 in outpatient setting. Further studies with larger sample size are recommended.
RESUMEN
In the present review study, the published articles from 2010-2020 that evaluated the effect of chitosan nanocarrier on the efficacy of amphotericin B (AmB) in the treatment of leishmaniasis, have been considered. Leishmania is a parasitic tropical disease in the world and is treated with AmB as one of the main therapeutic agents. However, the clinical application of AmB is limited due to its toxicity and insolubility issues. Using nanoparticles and, in particular, chitosan, nanocarrier seems a promising approach to overcome these problems. Therefore, various doses of AmB have been loaded in chitosan nanoparticles in different studies and the results of these studies demonstrated that by increasing the drug loading efficiency and decreasing the toxicity, the potency of the nanoformulation to inhibit and to kill the parasite is increased. In this regard, the results of a study performed in 2018, demonstrated that chitosan nanoparticles with the higher dose of drug loading were the most effective formulation to inhibit and kill the parasite. Thus, chitosan nanocarrier can consider as an appropriate candidate in the future to inhibit and kill the Leishmania parasite without causing side effects.
Asunto(s)
Antiprotozoarios , Quitosano , Leishmania , Nanopartículas , Anfotericina B , Portadores de FármacosRESUMEN
AIMS: Liver cirrhosis leads to cirrhotic cardiomyopathy (CCM) and chronotropic incompetence (CI). Heat shock protein 70 (Hsp70) regulates cellular apoptosis and autophagy in stress. Teprenone modulates the Hsp70 and protects against cellular injury. Thus, we aimed to evaluate the effect of teprenone on CI in biliary cirrhotic rats. MAIN METHODS: Liver cirrhosis was induced in male Wistar rats through bile duct ligation (BDL). The chronotropic responses and QT interval were studied through electrocardiography (ECG) in sham, cirrhotic, and cirrhotic/teprenone (100 mg/kg) pre-treated groups. Brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemo-attractant protein-1 (MCP-1), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were investigated in serum. The Hsp70, B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma 2-associated X protein (Bax) expressions were quantified through real-time polymerase chain reaction (Real-time PCR). KEY FINDINGS: The chronotropic responses were decreased significantly in cirrhotic and cirrhotic/teprenone groups. The QT interval and serum BNP, TNF-α, IL-6, ALT, AST, and MCP-1 levels were increased significantly in the cirrhotic and decreased significantly, except BNP, in the cirrhotic/teprenone group. The Hsp70 and Bax expressions increased significantly in cirrhotic and decreased significantly in the cirrhotic/teprenone group while the Bcl-2 decreased significantly in cirrhotic and increased significantly in the cirrhotic/teprenone group. SIGNIFICANCE: Teprenone does not relieve the CI and BNP changes in CCM while other indices are treated. Given that CCM is a multifactorial disease and needs to target other genes and proteins concurrent with Hsp70 to relieve CCM.