Effects of Melatonin and Propolis Supplementation on Inflammation, Oxidative Stress, and Clinical Outcomes in Patients with Primary Pneumosepsis: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVE: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis. MATERIALS AND METHODS: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded. RESULTS: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/mL) and C-reactive protein (-21.656 mg/L) levels, while increasing gavage intake (326.680 mL/day) and improving some clinical outcomes (APACHE II, SOFA, and NUTRIC scores) compared to the control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, there was no significant difference in the 28-day survival rate between the groups (p = 0.07). CONCLUSION: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings.

Preparation of Chitosan Nanoparticles as a Capable Carrier for Antigen Delivery and Antibody Production.

Background: Chitosan (CS) nanoparticles have attracted considerable attention as a non-viral and cationic carrier for delivery of therapeutic proteins and antigens and offer non-invasive routes of administration such as oral, nasal and ocular routes, and also show adjuvant characteristics for vaccines. Objectives: Preparation and formulation of CS nanoparticles as a capable carrier with immunoadjuvant properties to enhance the bioavailability of antigen and produce antibody with high affinity. Materials and Methods: CS nanoparticles were produced by ionic gelation process of sodium tripolyphosphate (TPP) with CS. Particle size and morphology of nanoparticles were determined using Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM) and also direct observation under light microscope. The influence of the initial BSA concentration and CS concentration on loading efficiency and release behavior was evaluated. The ε-toxin (derived from Clostridium perfringens type D) was loaded on CS nanoparticles and the complex was injected hypodermically into the rabbits for once. The anti ε-toxin antibody level in blood serum was evaluated using Dot Blot and ELISA methods. Results: The CS nanoparticles in different groups have a particle diameter (Z-average) in approximate ranges of 200-400, 300-600, 450-800 nm and a positive Zeta potential (32.4 - 48.6 mv). Optimum loading efficiency was achieved for CS at a concentration of 0.5 mg.mL-1 and TPP of 1.0 mg.mL-1. The results showed that the toxin-CS complex produces antitoxin at levels more than twice as high the control. Conclusion: The CS nanoparticles can be used as a good biodegradable carrier for protein and antigen delivery.

Topical propolis improves wound healing in patients with diabetic foot ulcer: a randomized controlled trial.

In this randomized controlled trial, diabetic patients with foot ulcers (Wagner grades 1 and 2) were randomly assigned to conventional therapies for diabetic foot ulcer plus topical propolis ointment (5%; twice daily) or conventional therapies alone. The process of ulcer healing was observed during 4 weeks and compared between the two groups regarding the size, erythema, exudates, white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). The process of ulcer size reduction during the four-week period of study was significantly different between the groups. However, this difference was not significant between the third and fourth weeks. There was no significant difference between two groups regarding erythema and exudate reduction as well as WBC count and ESR. Administration of topical propolis ointment in addition to the conventional treatments of diabetic foot ulcer could reduce the size of ulcers with Wagner grades 1 and 2.

Preventing and Therapeutic Effect of Propolis in Radiotherapy Induced Mucositis of Head and Neck Cancers: A Triple-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Mucositis is one of the acute complications of radiotherapy which can ulcerate oral mucosa and cause severe pain and discomfort which can affect oral normal function. Propolis is a natural source of flavenoid which has antiulcer, antibacterial, antifungal, healing and anti-inflammatory effects. Using such an affordable compound without any bad smell or taste that has reasonable price can help the radiotherapy undergoing patients. OBJECTIVES: Our goal is assessing the preventing and therapeutic effect of propolis in radiotherapy induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: In a randomized triple blind clinical trial, 20 patient were selected randomly to swish and swallow 15 ml of water based extract of propolis mouth wash 3 times a day in the case group (n = 10) and 15 ml placebo mouth wash in control group (n = 10). we use NIC-CTC scale for determining mucositis grading. RESULTS: We use T-test, Man-Whitney, Chi-square, and Friedman as analyzing tests. Case group had significantly (P < 0.05) lower grade of mucositis in all of the follow-ups, but xerostomia is not significantly different in two groups (P > 0.05). CONCLUSIONS: This is a pilot study which shows water based extract of propolis efficiently prevents and heals radiotherapy induced mucositis.

Characterization of Encapsulated Berberine in Yeast Cells of Saccharomyces cerevisiae.

Berberine was loaded in yeast cells of Saccharomyces cerevisiaeas a novel pharmaceutical carrier to improve the treatment ofmany diseases. The yeast-encapsulated active materialsshowedhigh stability and bioavailability due to the enhanced solubility and sustained releasing. In this study, different characteristics of prepared berberine loaded yeast cells (loading capacity, release kinetic order, MIC and stability) were evaluatedby different analytical methods (fluorescence spectroscopy, HPLC and SEM).The loading capacity was about 78% ± 0.6%.Berberine release patterns of microcapsules happened in two different stages and followed by zero and first-order kinetic,respectively. About 99% of all active material released during 34 h. MIC was improved by berberine loaded microcapsules in comparison withberberine powder. The microcapsules were completely stable. Berberine loaded Sac. Cerevisiae could be considered as a favorite sustained release drug delivery system. The yeast would be applied as an efficient carrier to improve various properties of different active materials.

Evaluation of Immune Response Against Inactivated Avian Influenza (H9N2) Vaccine, by Using Chitosan Nanoparticles.

BACKGROUND: Influenza A is a virus that affects a wide range of animals and also human beings. Avian influenza virus (AIV) subtype H9N2 has the potential to create influenza pandemic and vaccination is a common solution for this problem. The vaccine, used for rapid intervention, should be safe to use and highly effective, after a single administration. Chitosan nanoparticles (CNP) have already been recommended as a new adjuvant for inactivated AIV H9N2 vaccine immunization. OBJECTIVES: This study aimed at the evaluation and better understanding of optimum concentration of CNP preparations and also, assessment of loading capacity of AIV into CNP, as an adjuvant in specific pathogen-free (SPF) chickens. MATERIALS AND METHODS: For measurement of vaccine-antibody response, different types of CNP were injected intramuscularly, in a single dose, to 21-day-old specific pathogen-free chickens. Chickens were monitored for the efficacy of the nanoparticles and, also, their immune response, during a follow up of 7 weeks, by using hemagglutination-inhibition (HI) test. The CNP were prepared according to modified ionic gelation method and inactivated antigen was loaded in four hemagglutinin units (HAU) concentrations. Loading capacity of nanoparticles was determined by hemagglutination (HA) method. Inactivated A/H9N2 AIV was mixed with chitosan of low molecular weight. RESULTS: The CNP did not cause any mortality or side effects, when chickens were administered the prepared vaccine. The results strongly showed that this novel vaccine significantly enhances the immunogenicity of inactivated AIV, comparing with ISA70 (SEPPIC, Puteaux, France) adjuvant that is used routinely in the Razi Serum and Vaccine Research and Production Institute, Karaj, Iran, to reduce ISA70's side effects. CONCLUSIONS: The AIV loaded into CNP vaccines induce appropriate antibody titers, after a single immunization, while requiring a low dose of antigen. The CNP also represent an interesting new platform for antigen delivery and a promising adjuvant candidate for H9N2 inactivated influenza vaccine.

Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study.

In the present study, water extract of dried fruit of Zyzyphus Jujube was tested for its possible anticancer effect and induction of apoptosis on human tumor cell lines, HEp-2, HeLa and Jurkat cell lines. The inhibitory effect of water extract of this fruit on cell proliferation was assessed by MTT colorimetric assay. The induction of apoptosis of this extract was analyzed by DNA fragmentation analysis. Zyzyphus Jujube extract showed inhibitory effects on mentioned cell lines. Jurkat leukemic line was found the most sensitive cells with IC50 of 0.1 mug mL(-1). Our study also showed a typical DNA laddering in this cell line. The present study showed cytotoxic activity of Zyzyphus Jujube on tumor cells. Although Zyzyphus Jujube has useful compounds for medical applications.