Evaluation of anticancer effect of colchicum autumnale L. Corm on breast cancer cell.

BACKGROUND: Breast cancer is the most common malignancy in women, and medicinal plants can prevent and play an inhibitory role for cancer. This study aims to evaluate the anticancer effect of colchicum autumnale L. Corm on breast cancer cell models. METHODS: In this study, the alkaloid-rich extract was prepared using the percolation method and with methanol/water solvent (70:30). HFF2 normal cell line and MCF-7 breast cancer cell line were cultured in microplates (96 wells). Then cells were treated with concentrations of 62.5 to 2000 ng/ml of extract and concentrations of 62 to 1000 ng/ml of doxorubicin at regular intervals of 48 and 72 h, and the percentage of cell growth inhibition was calculated. Cytotoxicity of drugs was measured by the MTT assay method. IC50 values were calculated by Calcusyn software. Also, the P-value of < 0.05 was considered significant. RESULTS: Alkaloid-rich extract of Colchicum autumnale plant inhibited breast cancer cell growth (MCF-7). The IC50 parameter showed more cytotoxic effects of Colchicum autumnale plant extract on the MCF-7 cancer cell line than HFF2 normal cell line for 48 and 72 h. In addition, with higher concentrations of the extract, cytotoxicity, and growth inhibitory effect increased significantly and in comparison to the doxorubicin was almost the same as cytotoxic. CONCLUSION: This research provides a novel view into the development of new drugs for the treatment of cancer diseases. Colchicum autumnale plant extract had a significant cytotoxic effect like Doxorubicin drug on breast cancer cell line (MCF-7), which can alternatively treat and prevent breast cancer.

Engineering HEK293T cell line by lentivirus to produce miR34a-loaded exosomes.

BACKGROUND: RNA (ribonucleic acid) antisense is developing as a possible treatment option. As an RNA, miR-34a is involved in P53 function and cancer cell apoptosis. Although the therapeutic applications of miRNAs have several limitations, such as structural instability and susceptibility to nucleases. To resolve these issues, this study aims to apply exosomes as a delivery vehicle for miR-34a. AIMS: This study aims to create a cell factory to generate miR34a-enriched exosomes. The produced nanoparticles act as a delivery system and improve the structural stability of miR34a. METHODS: First exosome specific sequences were inserted into miR34a. The resulting miR34a oligonucleotide was transduced HEK293T cells genome with a lentiviral system. In the structure of miR34a oligonucleotide, six nucleotides were substituted to increase its packaging rate into exosomes. To maintain the secondary structure, stability, and expression of the miRNA gene, changes to the miR34a oligonucleotide were made using PCR (polymerase chain reaction) Extension. The forward-34a (5-TGGGGAGAGGCAGGACAGG-3) and Reverse-34a primers (5-TCCGAAGTCCTGGCGTCTCC-3) were used for amplification of the miR34a gene from DNA. RESULTS: The results confirmed that the changes in miR34a oligonucleotide do not affect its secondary structure. The energy level of the manipulated miR34a oligonucleotide was kept the same compared to the original one. Moreover, the loading of miR34a to the exosomes was increased. CONCLUSION: Our findings revealed that normal HEK293T did not express miR34a. However, lentiviral transduced miR34a oligonucleotide induced the loading of miR34a into the exosome. Moreover, replacing six nucleic acids in the 3' end of miR34a increased the loading of miR34a to exosome.

Potential Inhibitory Effect of Miltefosine against Terbinafine-Resistant Trichophyton indotineae.

Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine's in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063-0.5 µg/mL and 0.125-0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy.

Antifungal activity of miltefosine against both azole-susceptible and -resistant Aspergillus strains.

Miltefosine, an alkylphosphocholine, has been approved recently for the treatment of visceral leishmaniasis. Miltefosine has shown promise as a treatment for paracoccidioidomycosis, and has mixed activity against other fungi and yeast. There are limited data on the in-vitro activity of miltefosine against azole-resistant and -susceptible Aspergillus spp. As such, the aim of this study was to determine the in-vitro activity of miltefosine against Aspergillus strains. Miltefosine was tested against 108 azole-susceptible and -resistant Aspergillus strains isolated from Iran and other countries using the broth microdilution method. Miltefosine was found to be effective against azole-resistant Aspergillus isolates, with minimum inhibitory concentrations (MICs) ranging from 1.562 to 6.25 µg/mL. MIC50 and MIC90 were 1.562 and 3.125 µg/mL, respectively. Miltefosine had a higher geometric mean MIC (2.459 µg/mL) for wild-type Aspergillus isolates than itraconazole (0.220 µg/mL) and voriconazole (0.298 µg/mL). No significant difference was found between miltefosine MICs for azole-resistant Aspergillus isolates and azole-susceptible Aspergillus isolates (P>0.05). Miltefosine appears to have good in-vitro activity against azole-resistant Aspergillus strains, according to these findings. Furthermore, the findings suggest that miltefosine could be used to treat infections caused by azole-resistant Aspergillus spp.

Polyethyleneglycol-serine nanoparticles as a novel antidote for organophosphate poisoning: synthesis, characterization, in vitro and in vivo studies.

Acute organophosphate pesticide poisoning causes considerable worldwide mortality and morbidity. In this study, serine was attached to the polyethylene glycol-bisaldehyde (PEG) as a novel antidote for diazinon (DZ) poisoning. Serine and PEG were conjugated with a reductive amination reaction. PEG-serine NPs (PEG-NPs) were purified and their structure was analyzed by 1H NMR, 13 C NMR, IR, and particle size was determined via dynamic light scattering. In vitro studies, including hemolysis assay and cytotoxicity on SK-BR-3 and HFFF2 cell lines, were performed. In vivo studies of PEG-NPs were evaluated on DZ-exposed mice. PEG-NPs were administered (i.p.) 20 min after a single dose of DZ (LD50; 166 mg/kg). Atropine (20 mg/kg, i.p.) with pralidoxime (20 mg/kg, i.p.) was used as the standard therapy compared to PEG-NPs. NMR and IR data confirmed that the conjugation of PEG to serine occurred successfully. The average NP size was 22.1 ± 1.8 nm. The hemolysis of the PEG-NPs was calculated at 0.867%, 50% inhibitory concentration (IC50) was calculated 36 ± 4.5, and 41 ± 3.4 mg/mL on SK-BR-3 and HFFF2 cell lines, respectively. Percentage of surviving significantly improved by 12.5, 25, and 25% through the usage of PEG-NPs at doses of 100, 200, and 400 mg/kg, respectively, when compared with the DZ group. Cholinesterase enzyme activity, lipid peroxidation, and mitochondrial function significantly improved through PEG-NPs when compared with the DZ group. PEG conjugated serine is very biocompatible with low toxicity and can reduce the acute toxicity of DZ as a new combination therapy.

In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains.

Fusarium species are filamentous fungi that cause a variety of infections in humans. Because they are commonly resistant to many antifungal drugs currently available in clinical settings, research into alternative targets in fungal cells and therapeutic approaches is required. The antifungal activity of miltefosine and four comparators, amphotericin B, voriconazole, itraconazole, and caspofungin, were tested in vitro against a collection of susceptible and resistant clinical (n = 68) and environmental (n = 42) Fusarium isolates. Amphotericin B (0.8 µg/mL) had the lowest geometric mean (GM) MICs/MECs values followed by miltefosine (1.44 µg/mL), voriconazole (2.15 µg/mL), caspofungin (7.23 µg/mL), and itraconazole (14.19 µg/mL). Miltefosine was the most effective agent against Fusarium isolates after amphotericin B indicating that miltefosine has the potential to be studied as a novel treatment for Fusarium infections.

Role of the cannabinoid CB1 receptor in methamphetamine-induced social and recognition memory impairment.

Methamphetamine (METH) has been reported to induce social and recognition memory impairment. Evidence suggests that the cannabinoid system has an important modulatory role in cognitive processing and social interaction. Nonetheless, no previous study has investigated the probable role of the cannabinoids system on METH-induced deficits of novel object recognition (NOR) memory and social interaction. Adult male rats were given a neurotoxic METH regimen (four injections of 6 mg/kg, s.c, at 2 h intervals). One week later, they were examined for either NOR or social interaction in different groups. The cannabinoid type 1 receptor (CB1R) antagonist rimonabant (1 or 3 mg/kg, i.p.) improved METH-induced impairment of the acquisition, consolidation, and retrieval, but not reconsolidation, of NOR and also METH-induced impairment of social behavior. Administration of the CB1R agonist WIN 55,212-2 (WIN; 3 or 5 mg/kg, i.p.) did not affect memory deficits or social behavior impairment induced by METH. Our findings may indicate that METH neurotoxicity impairs social and recognition memory. On the other hand, the CB1R antagonist rimonabant, but not the CB1R agonist WIN, prevented these negative effects of METH neurotoxicity. Thus, it seems that the CB1R can be targeted to prevent the adverse effects of METH on cognition and social behavior, at least at experimental levels.

Pharmacokinetics study of chitosan-coated liposomes containing sumatriptan in the treatment of migraine.

BACKGROUND: Sumatriptan is a routine medication in the treatment of migraine and cluster headache that is generally given by oral or parental routes. However, a substantial proportion of patients suffer severe side effects. The aim of this study was to investigate the physicochemical characterization and pharmacokinetic parameters of a novel delivery system for sumatriptan succinate (SS) using nanoliposomes (NLs) coated by chitosan (CCLs) to optimize the formulations to enhance its bioavailability. METHODS: The new formulation was used to minimize drug particle size and extend its release and bioavailability. The mean particle size and entrapment efficiency for NLs and CCls were optimized and the formulations with better characteristics were chosen for in vivo studies. The concentration-time profile of intravenous SS, intranasal SS, SS-NLs, and CCLs were examined in a rabbit model. RESULTS: The results demonstrated that CCLs were absorbed more rapidly from nasal drops containing chitosan compared to those of SS and SS-NLs as indicated by a shorter tmax, and a higher Cmax in both states. A comparison of the AUC (0-240 min) values revealed that chitosan improved the extent of SS absorption for CCLs formulation. The results of the present study indicated that loading SS into the liposome and coating with chitosan improves drug absorption and a large amount of the drug can be efficiently delivered into the systemic circulation. CONCLUSION: The liposomal and chitosan formulations of SS had better kinetic behavior than the soluble form in the animal model.

Harnessing Intranasal Delivery Systems of Sumatriptan for the Treatment of Migraine.

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.

Investigation of Structural, Treatment, and Clinical Characteristics of COVID-19 Along with the Challenges Caused by its Prevalence.

In late 2019, a report from China was published stating a disease with an unknown cause. After that, the outbreak of the COVID-19 caused a pandemic in the world. On March 11, 2020, the outbreak of this virus was reported in 100 countries. The virus is currently spreading rapidly around the world. In the past, coronaviruses caused lifethreatening diseases such as SARS and MERS in some areas of the world. Although there is still a debate about the origin of this new coronavirus, it is most likely linked with some animals, including bats, civet, and pangolin. In this review, we try to describe the features of the new coronavirus as well as the recent diagnostic and therapeutic findings.

An overview on liposomal delivery and adjuvant development for leishmaniosis vaccines.

Leishmaniosis is caused by different species of Leishmania parasites. The available treatments for this disease have not provided strong consistent results yet. The weak response of current chemotherapeutics can be attributed to their deficient effects on stealth parasites inside macrophages, rapid clearance from the site of action, and systemic side effects in high doses. To enhance leishmaniosis vaccine efficacy, it is a valuable strategy to use liposomes as vaccine delivery systems due to combined increase in technological advances and understanding of the immune system. Liposomes that contain and deliver immunostimulators and antigens are now being developed to target diseases that require stimulation of both humoral and cell-mediated immune responses. Hence, using particulate adjuvants, like liposomes for effective delivery to the antigen presenting cells (APCs) is important for improving leishmaniosis vaccine efficacy. This study aimed at reviewing liposomal adjuvants in vaccine development with specific accentuation on their adjuvant mechanism and surface charge. It also examined how specific physicochemical qualities of liposomes and the particle size during formulation design can affect the immune response.

In vitro anti-Acanthamoeba activity of the commercial chitosan and nano-chitosan against pathogenic Acanthamoeba genotype T4.

Acanthamoeba keratitis (AK) is a rare but serious infection of the eye and can lead to blindness. The effective and safe medical therapy remains unclear for AK until present. Antimicrobial activity and biological characteristic of chitosan encourage screening of it against Acanthamoeba. Thus, in vitro anti-amoebic activities of commercial chitosan and nano-chitosan were tested on pathogenic Acanthamoeba genotype T4, a causative agent of human AK. The Acanthamoeba spp. was isolated from the keratitis patient. The Acanthamoeba genotype T4 was approved using PCR method followed by sequencing technique. Chitosan nanoparticles was prepared using ionic gelation method and characterized by their physicochemical properties. In the present study, the in vitro activity of serial dilutions (12.5, 25, 50, 100, and 200 µL/mL) of commercial chitosan and nano-chitosan were evaluated against Acanthamoeba trophozoites and cysts. The finding of nano-chitosan particle size by DLS was 118 nm with a PDI of about 0.134. Zeta potential value was found to be 42.7 mV. The obtained results showed that the tested chitosan and nano-chitosan presented anti-amoebic activities dependent to time and concentration. The inhibitory effect of the chitosan and nano-chitosan is enhanced by increasing the concentration and incubation time. The inhibitory effect of nano-chitosan on both trophozoites and cyst was more than chitosan. According to the results, nano-chitosan shows the potent activity against Acanthamoeba T4 and could be used for the development of novel and safe therapeutic approaches in the future.

Nanoliposome-loaded antifungal drugs for dermal administration: A review.

Cutaneous fungal infections are the fourth most common health problem, which involves approximately one billion people worldwide. Drug delivery to the skin seems to be the best choice for superficial fungal infections. Topical formulations can release a sufficient amount of drug in therapeutical concentrations and permeate higher layers of the skin like the stratum corneum. As the outermost layer of the epidermis, the stratum corneum prevents the drug from penetrating the skin. Liposomes, especially nanosized as topical drug delivery systems to the skin, can show various functions depending on their size, lipids and cholesterol components, the percent of ingredients, lamellarity, and surface charge. Nanoliposomes can increase permeation through the stratum corneum, decrease systemic effects with their localizing actions, and overcome many dermal drug delivery obstacles. Antifungal drugs, such as croconazole, econazole, fluconazole, ketoconazole, terbinafine hydrochloride, tolnaftate, and miconazole entrapped in liposomes have indicated improved skin penetration and localizing effects. According to the literature review summarized in this paper, many studies have identified liposomes as a powerful carrier for topical antifungal drug delivery to the skin. However, a few studies introduced new generations of liposomes like ethosomes and transfersomes. This paper was conducted on almost all liposomal studies of antifungal drugs with dermal application.

pH-Sensitive PEGylated Liposomal Silybin: Synthesis, In Vitro and In Vivo Anti-Tumor Evaluation.

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.

Synthesis and characterization of magnetite nanoparticles by co-precipitation method coated with biocompatible compounds and evaluation of in-vitro cytotoxicity.

Recent advances in the use of magnetite nanoparticles for biomedical applications have led to special attention to these nanoparticles. The unique properties of magnetite nanoparticles such as superparamagnetism, low toxicity, and the ability to bond with biological molecules, are suitable for drug delivery, diagnostic methods and therapeutic approaches. The aim of this study was to synthesize magnetite nanoparticles with different biocompatible coatings and investigate their cytotoxicity. Magnetite nanoparticles were synthesized by co-precipitation method and the cytotoxicity of these nanoparticles was investigated with Hepatoma G2 cell using the MTT assay. Treated cells, did not showed any evident cell cycle arrest. The Fourier Transmission Infrared (FTIR) spectroscopy, X- ray powder Diffraction (XRD), Transmission Electron Microscopy (TEM) were evaluated. The results of XRD showed the coated magnetite nanoparticles were 10-12 nm and this size also achieved with TEM images. Synthesized magnetite nanoparticles with SiO2 and oleic acid coatings had lower cytotoxicity than other coatings.

Preparation and Characterization of A Nanoliposomal Vaccine of pcLACK Candidate Against Cutaneous Leishmaniasis.

BACKGROUND: Leishmaniasis is a public health problem and endemic in countries of the tropics and subtropics. An ongoing project with naked LACK (Leishmania homolog of receptors for activated C-kinase) demonstrated that this case of the gene is entirely susceptible to immune response and it does enter the cells effectively. This study aimed at developing a procedure to prepare a type of lipid nanoparticles overloaded with plasmid LACK (pcLACK) for usage as Leishmania major (L. major) nanoliposomal vaccine. MATERIALS AND METHODS: The single-gene expression plasmid of pcLACK was encoded in the LACK antigen. Nanoparticles were set up by thin film procedure using cationic lipids 1, 2-Dioleoyl- 3-Trimethylammonium propane (DOTAP), 1, 2-Dioleoyl-snGlycero-3-Phosphoethanolamine (DOPE), and cholesterol in a molar proportion of 2:1:1 molar ratio. Using dynamic light scattering, the particle diameters of empty and loaded lipoplexes were measured in triplicate. The zeta-potential (ζ) was measured with the same instrument using the zeta potential mode as the average of 20 measurements by diluting the particles into a low salt buffer. RESULTS: The results of the sustainability studies of Liposome-pcLACK formulation showed that there were no significant physical changes up to the 30th day of stability study at the storage condition of 4°C. However, there were significant changes in the formulation content during storage at 25°C for 30 days (204.2±0.90 at Day 30 compared with 207.2±0.26 nm at Day 0). It was observed that the prepared nanoliposomal formulation had more stability under refrigeration. CONCLUSION: Immunostimulatory cationic lipids bearing a pcLACK encapsulation could serve as an effective delivery system.

A Systematic Literature Review of Curcumin with Promising Antileishmanial Activity.

BACKGROUND: Curcumin (CUR) is a bright yellow chemical and it is used as an additive in foods. Recently CUR and its associated bioactive compounds have received much attention in the literature review. The aim of this systematic review is to overview the antileishmanial properties of CUR and its mechanism; perhaps the results of this study will be used for therapeutic and preventive purposes. METHODS: Following the PRISMA guidelines, international databases were systematically searched for studies published until September 2019. Articles related to the subject were selected and included in this systematic review. RESULTS: A total of 15 articles met our eligibility criteria. Then, the effect of CUR and its associated bioactive compounds on Leishmania species was evaluated. In most studies, CUR/derivatives were tested on L. major and in vitro condition. Most investigations were conducted on the promastigote rather than the more relevant intracellular amastigote stage. Our results showed that CUR overcomes the inhibitory effect of nitric oxide (NO) on Leishmania parasites. CONCLUSION: This review indicated that CUR derivatives, instead of CUR alone showed a high potential to serve as an effective herbal drug against leishmaniasis. Moreover, we concluded that the antileishmanial activity of CUR/bioactive compounds is mostly due to increased oxidative stress and apoptosis.

Genetically engineered fusion of allergen and viral-like particle induces a more effective allergen-specific immune response than a combination of them.

Chimeric virus-like particles (VLPs) were developed as a candidate for allergen-specific immunotherapy. In this study, hepatitis B core antigen (HBcAg) that genetically fused to Chenopodium album polcalcin (Che a 3)-derived peptide was expressed in E. coli BL21, purified, and VLP formation was evaluated using native agarose gel electrophoresis (NAGE) and transmission electron microscopy (TEM). Chimeric HBc VLPs were characterized in terms of their reactivity to IgE, the induction of blocking IgG and allergen-specific IgE, basophil-activating capacity, and Th1-type immune responses. Results from IgE reactivity and basophil activation test showed that chimeric HBc VLPs lack IgE-binding capacity and basophil degranulation activity. Although chimeric HBc VLPs induced the highest level of efficient polcalcin-specific IgG antibody in comparison to those induced by recombinant Che a 3 (rChe a 3) mixed either with HBc VLPs or alum, they triggered the lowest level of polcalcin-specific IgE in mice following immunization. Furthermore, in comparison to the other antigens, chimeric HBc VLPs produced a polcalcin-specific Th1 cell response. Taken together, genetically fusion of allergen derivatives to HBc VLPs, in comparison to a mix of them, may be a more effective way to induce appropriate immune responses in allergen-specific immunotherapy. KEY POINTS: • The insertion of allergen-derived peptide into major insertion region (MIR) of hepatitis B virus core (HBc) antigen resulted in nanoparticles displaying allergen-derived peptide upon its expression in prokaryotic host. • The resultant VLPs (chimeric HBc VLPs) did not exhibit IgE reactivity with allergic patients' sera and were not able to degranulate basophils. • Chimeric HBc VLPs dramatically improved protective IgG antibody response compared with those induced by allergen mixed either with HBc VLPs or alum. • Chimeric HBc VLPs induced Th1 responses that were counterparts of Th2 responses (allergic). • Chimeric HBc VLPs increased IgG2a/ IgG1 ratio and the level of IFN-γ compared to those induced by allergen mixed with either HBc VLPs or alum. Graphical Abstract.

Promising Anti-Protozoan Activities of Propolis (Bee Glue) as Natural Product: A Review.

PURPOSE: Propolis (bee glue) is a resinous mixture of different plant exudates that possesses a wide range of biological and antimicrobial activities and has been used as a food supplement and in complementary medicine for centuries. Some researchers have proposed that propolis could be a potential curative compound against microbial agents such as protozoan parasitic infections by different and occasionally unknown mechanisms due to the immunoregulatory function and antioxidant capacity of this natural product. METHODS: In this review, we concentrate on in vitro and in vivo anti-protozoan activities of propolis extracts/fractions in the published literature. RESULTS: In Leishmania, propolis inhibits the proliferation of promastigotes and produces an anti-inflammatory effect via the inhibition of nitric oxide (NO) production. In addition, it increases macrophage activation, TLR-2, TNF-α, IL-4, IL-17 production, and downregulation of IL-12. In Plasmodium and Trypanosoma, propolis inhibits the parasitemia, improving anemia and increasing the IFN-γ, TNF-α, and GM-CSF cytokines levels, most likely due to its strong immunomodulatory activity. Moreover, propolis extract arrests proliferation of T. cruzi, because it has aromatic acids and flavonoids. In toxoplasmosis, propolis increases the specific IgM and IgG titers via decreasing the serum IFN-γ, IL-1, and IL-6 cytokines levels in the rats infected with T. gondii. In Cryptosporidium and Giardia, it decreases oocysts shedding due to phytochemical constituents, particularly phenolic compounds, and increases the number of goblet cells. Propolis inhibits the growth of Blastocystis, possibly by apoptotic mechanisms like metronidazole. Unfortunately, the mechanism action of propolis' anti-Trichomonas and anti-Acanthamoeba is not well-known yet. CONCLUSION: Reviewing the related literature could highlight promising antimicrobial activities of propolis against intracellular and extracellular protozoan parasites; this could shed light on the exploration of more effective drugs for the treatment of protozoan parasitic infections in the near future.

Photocatalytic study of nanocomposite membrane modified by CeF3 catalyst for pharmaceutical wastewater treatment.

Cerium fluoride (CeF3) nanoparticles (NPs) were synthesized and applied in polysulfone (PS) membrane fabricated by phase inversion method. The produced nanocomposite membranes (PS/CeF3) with different contents of CeF3 NPS (0.25%, 0.5%, 0.75% and 1% w/w) were used to treat pharmaceutical wastewaters. The membranes were characterized by FESEM, EDX, XRD, FTIR, porosity, and water contact angle analyses. Evaluation of the characteristics and performance of the nanocomposite membranes confirmed that utilizing photocatalytic CeF3 NPs in membrane structure could effectively decompose organic contaminants in pharmaceutical wastewaters. It also improves the hydrophilicity and antifouling ability of membrane during filtration especially, in the presence of UV irradiation. The permeate flux of the PS membrane increased from 35.1 to 63.77 l/m2h by embedding 0.75% of CeF3 NPs in membrane structure due to the porosity enhancement from 71.36-78.42% and the decrease in contact angle from 62.9º to 53.73º. Moreover, the flux decline of PS/CeF3-0.75% membrane under UV irradiation was from 63.6 to 46.1 l/m2h that considerably lower than that of the neat PS membrane (from 34.7 to 4.9). On the other hand, the degradation efficiency of PS/CeF3-0.75% membrane was more than 97%, and COD removed was more than 65% while they were 75% and 31%, respectively for the nascent PS membrane. Therefore, applying the appropriate amount of CeF3 NPs in PS membranes not only greatly increased the permeate flux but also significantly enhanced the degradation efficiency and COD removal. This indicates that nanocomposite membranes can be confidently applied for pharmaceutical wastewater treatment UV irradiation.