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Functioning as the human body's most extensive organ, the skin exhibits an intricate, stratified architecture. This architecture consists of distinct layers: the epidermis, dermis, and hypodermis. Collectively, these layers play a crucial role in safeguarding the body and upholding its general well-being. The aging process of the skin is complex and is influenced by a wide range of internal and external factors. The loss of skin elasticity and firmness is a consequence of these factors, which ultimately contribute to signs of aging such as wrinkles, skin discoloration, and diminished radiance as people get older. A comprehensive understanding of these factors and their impact on the skin can lead to the development of more effective methods and products for skin care, capable of slowing down this process and improving skin quality. Recent advances in nanotechnology, driven by increasing consumer demand for beauty products, have prompted the development of novel methods of skincare that are aimed at minimizing the appearance of symptoms of aging. Therefore, nanotechnology in skin care has emerged as a recognized novel and effective approach that can provide efficient solutions for combating skin aging. Nano lipid carriers have been introduced as one of the key innovations in this field. These carriers can effectively enhance the penetration of active cosmetic and skincare ingredients through the branched layers of the epidermis, which serve as the main barrier to the penetration of substances into the skin. These nanocarriers enhance the stability of active ingredients present in cosmetic and skincare formulations. When it comes to cosmetics and skincare products, nano lipid carriers have several distinctive qualities that add to their potential to improve efficacy while simultaneously minimizing side effects. They facilitate controlled release and long-term diffusion of active ingredients, ensuring continuous and uniform distribution of active compounds in the skin. Hence, they improve the biocompatibility of ingredients, thereby reducing skin irritation and enhancing skin tolerance to active substances. A wide range of nanocarriers is utilized in the dermal delivery of cosmetic and skincare products. These include nanoemulsions, liposomes, lipid nanoparticles, ethosomes, niosomes, transferosomes, nanocrystals, as well as polymeric and mineral nanocarriers. Each of these nanocarriers exhibits specific properties and mechanisms of action that effectively improve the penetration and efficacy of active ingredients into the deeper layers of the skin. In the present article, various types of nano lipid carriers have been examined as effective vehicles for delivering active compounds into the skin layers, along with their mechanisms of action. Furthermore, the latest anti-aging and anti-wrinkle products containing these nanocarriers have been discussed. Scientific investigations have demonstrated that the use of nano lipid carriers in the formulation of anti-aging products can significantly improve skin rejuvenation and regeneration. These products, by enhancing the permeability and stability of active compounds, exhibit better efficacy in reducing wrinkles and fine lines, increasing skin firmness and elasticity. It is also anticipated that with further advancements in this field, more innovative products will be introduced to the market to meet diverse consumer needs.

Background and purpose: Methamphetamine is one of the stimulant drugs that leads to the occurrence of cognitive and behavioral dysfunctions. Among the disorders that occur after methamphetamine abuse are learning and memory disorders as well as social interactions and anxiety. On the other hand, the function of sex steroids in the development of brain regions involved in reproduction has been the subject of extensive research over the years. In this context, testosterone plays an important role in neuronal and glial organization in prenatal and postnatal periods. Recent studies showed the effect of sex hormones on the nervous system and highlight the brain as a main target tissue for androgens. On the other hand, studies have shown that testosterone has neuroprotective effects against cognitive and behavioral disorders. Clinical manifestations of testosterone-related brain changes include cognitive impairments such as reduced memory efficiency related to the frontal cortex, as well as reduced long-term memory related to the hippocampus and other temporal regions of the midbrain. Androgens, especially testosterone, play an important role in memory function whereby the decrease and absence of testosterone leads to cognitive impairment and also neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Therefore, in this study, the role of testosterone hormone in social memory, novel object recognition memory, as well as anxiety-like behavior and brain edema induced by a neurotoxic regimen of methamphetamine were investigated. Materials and methods: This study was conducted on 48 gonadectomized rats in 6 groups including control groups, methamphetamine (6mg/kg), solvent (sesame oil), methamphetamine + testosterone (0.25mg /kg), methamphetamine + testosterone (0.5 mg/kg) and methamphetamine + testosterone (1 mg/kg) were performed. At first, mice were anesthetized and gonadectomy surgery was performed. After 2 weeks of recovery, the evaluation of social memory was done using the three-chamber social interaction test, and anxiety-like behavior index using the open field test. Finally, the animals were killed and the brain tissue was evaluated for brain edema. Results: The findings of the study showed that social memory was significantly impaired in rats that received methamphetamine compared to the control group (P

Leishmaniasis is one of the most common parasitic diseases in tropical and subtropical regions worldwide and poses a threat to public health. According to the World Health Organization (WHO), the number of leishmaniasis cases worldwide is estimated at 12 million, and the number of people at risk is 350 million. However, leishmaniasis therapies have their limitations, and today nanoparticle delivery systems such as liposomes are used. Liposomes are bilayered structures made of phospholipids and cholesterol, which contain hydrophilic and hydrophobic components in their structure and enable the uptake of hydrophobic, hydrophilic, or amphiphilic compounds. Since the leishmaniasis parasite is predominantly found in macrophages, drug delivery systems improve the therapeutic index of anti-leishmaniasis drugs and reduce the effective dose and toxic off-target effects of non-specific biodistribution. Targeted liposomal drug delivery systems are achieved by utilizing their different structural features such as particle size and surface charge and attaching other ligands to the surface of liposomes for targeted drug delivery. Today, sugar-coated liposomes, cationic liposomes, arsenoliposomes and peptide-targeted liposomes are used to deliver traditional anti-leishmaniasis drugs to Leishmania, and due to the importance of nanoliposomes and their many benefits, research continues in this field.

Abstract 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

Background and purpose: Cancer is one of the causes of mortality worldwide. Evidence suggests that iron depletion by a chelator agent suppresses the development of some cancer cells. Deferasirox is shown to have anticancer properties. This research aims to synthesize and evaluate the effects of deferasirox nanoparticles on human breast cancer cells (SKBR3) and mouse breast cancer cells (4T1) compared with the drug form. Materials and methods: Deferasirox nanoparticles were synthesized by Poly lactic-co-glycolic acid (PLGA) moiety with emulsion formation and solvent evaporation. Cytotoxicity was evaluated using the MTT assay and their 50% inhibitory concentration (IC50) were assessed in SKBR3 and 4T1. Results: Findings showed that IC50 of nano-deferasirox for SKBR3 and 4T1 were 9.09±0.011 µg/ml and 6.6±0.032 µg/ml, respectively and the IC50 of the deferasirox drug form for SKBR3 and 4T1 IC50 were 21.07±0.003 µg/ml and 11.08±0.013 µg/ml, respectively. Conclusion: The anticancer effects of deferasirox were confirmed on the cell lines, and the improved properties and efficacy were also confirmed on two cancer cell lines. Nanoparticle delivery systems improve absorption and drug properties and increase the effectiveness of the drug.

Olanzapine (2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno [2, 3-b][1, 5]benzodiazepine) is an antipsychotic drug with poor water-solubility that has a suitable affinity to some receptors. This benzodiazepine derivative is a new (atypical) antipsychotic drug and has a wide range of efficacy, especially in treatment of patients with negative psychiatric symptoms of schizophrenia. Olanzapine is used in psychotic disorders, mood disorders, and acute restlessness in bipolar patients. Its oral absorption is low and about 40% of the drug is metabolized in first-pass hepatic metabolism. This drug has low permeability into the brain related to remove by p-glycoprotein efflux and blood-brain-barrier (BBB) existence. Emerging nanotechnology during recent years demonstrated the tremendous ability of nanoparticles as versatile nanocarrier systems. This emerging technology has raised promising attempts to address the significant impact on decreasing side effects of drugs and their associated defects. Olanzapine can be administrated by different routes. Intranasal delivery of olanzapine to the brain due to lack of blood-brain-barrier in the olfactory system has facilitated its delivery. In this review article, several olanzapine nano-drug delivery systems are listed by reviewing their results, including nanosuspensions, nanoemulsions, solid lipid nanoparticles (SLN), niosomes, transfersomes, nanostructured lipid carriers (NLC), polymeric nanoparticles (PNP), etc.

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.

Objective(s): Toxoplasma gondii, an obligate intracellular protozoan parasite, is widespread across the world. It causes congenital disease and abortion in humans and domestic animals. One of the major concerns in parasitology, thus, is an effective vaccine development to control Toxoplasmosis. Materials and Methods: In the present research, a nano-liposomal vaccine containing soluble antigens (SA) was designed to evaluate the immunity and protective efficacy against T. gondii infection in BALB/c mice. Soluble antigens (SA) were achieved from tachyzoites, encapsulated in the liposome, and investigated via scanning electron microscope. Three times with 2-week intervals, BALB/c mice were immunized subcutaneously with different formulations. The level of protection against infection was assessed through the percent survival survey of BALB/c mice after challenge with tachyzoites of T. gondii RH strain; also, the type of generated immune response was determined by evaluating the generation of cytokine (IFN-γ, IL-4) and titration of IgG isotypes.Results: The immunization with liposome DSPC+ SA and liposome DSPC+ Imiquimod + SA induced a substantial increase in anti-Toxoplasma IgG antibody as compared to the PBS group (p

Global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, epilepsy, and multiple sclerosis is steadily increasing, but, there is still no effective delivery system to deliver therapeutic amounts of drug into the central nervous system (CNS). The blood-brain barrier ​​is the major component to control the entrance of drugs into the brain. Recent studies introduced intranasal drug delivery as a suitable method of drug delivery for bypassing blood-brain barrier and treatment of neurological diseases. The nasal route has been repeatedly examined in several preclinical models to investigate the delivery of drug to the brain via nanoparticles. Among various carriers utilized for drug delivery via nasal route, chitosan is widely used due to being effective in modulating drug charge. Key features of drug delivery systems through nasal route include easy drug delivery, higher stability in nasal cavity, increased penetration ability of drugs through nasal epithelium, and decreased drug metabolism. The present review investigated novel nano-formulations for drug delivery via nose to brain in treatment of major neurological disorders. In preclinical studies, intransaal nanoparticle-based drug delivery systems are found to be more promising, effective, and targeted. However, more preclinical studies are needed to confirm their non-toxicity and beneficial effects.

Objective(s): 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. Nasal administration is significantly effective in case of oral administration of drug gives an undesirable side effect. So, the purpose of the present study was to develop intranasal delivery systems of Sumatriptan succinate using nanoliposomes as container of a water-soluble drug and chitosan as a mucoadhesive polymer.Materials and Methods: Liposomal formulations containing Sumatriptan as well as chitosan-coated liposomal formulations with different phospholipids and different concentrations were prepared. The formulations were evaluated for their physicochemical properties, stability and Cytotoxicity on BEAS-2B cells.Results: The prepared liposomal formulations coated with chitosan containing Sumatriptan had a size range of 165±9.4to 258±6.4 nm, and the surface charge of the obtained formulations was measured between 32±6 and 40±5 mV. Also, the encapsulation efficiency of the formulations was also observed between 14.2±2.7% and 19±3.4%. Based on the obtained results of physicochemical studies, liposomes F2 was also tested for stability and toxicity and showed that the F2 liposomes retained its physicochemical properties for up to 3 months. Finally, the toxicity test of the mentioned formulation showed relatively low toxicity on BEAS-2B cells.Conclusion: In the presents study, stable liposomal formulations coated with chitosan containing Sumatriptan were prepared and studied. Based on the obtained, these formulations can be used in preclinical and animal studies for the nasal administration of Sumatriptan.

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.

Cutaneous fungal infections are the fourth most common health problem, which involves approximately 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.

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.

Leishmaniasis is a vector-borne zoonotic disease caused by various species of the genus Leishmania, (trypanosomatidae family) that is transmitted by phlebotomine sandflies. The disease can present in a range of clinical forms, including dermal lesions, metastasis mucocutaneous forms, and fatal visceral forms. In this non-systematic review, we aimed at introducing the role of kinetoplast DNA (kDNA) and dependent topoisomerases (TPI) as potential chemotherapeutic targets for treatment of leishmaniasis. The Leishmania parasite has a mitochondrial DNA located in the attached circles. KDNA replication process is very complex and a large number of proteins are involved. Some of them are classified as topoisomerases, which play major biological roles in the effective cell processes in the topology, synthesis, and organization of kDNA and constitute the main drug target in kinetoplast for leishmaniasis cure. Several studies have shown that the inhibitors of TPI exchange these enzymes into intracellular cell toxins and provide an appropriate tool for killing the parasite in the host. DNA binding drugs have also been reported as therapeutic agents against leishmanial infections.

Objective(s): Attempts to produce vaccines for leishmaniasis need adjuvants to trigger the kind of immune reaction required for protection. In this study, we examined the properties of the TLR7 agonist imiquimod, a vaccine adjuvant, making use of a live model of infection where the immune reactions could be identified prior to and following the challenge of infection. Materials and Methods: The liposomes of EPC containing the imiquimod adjuvant were prepared and characterized for protein concentration, surface charge, and particle size. Vaccination was done using the soluble Leishmania antigen (SLA) as a first-generation vaccine model in the liposomal state to vaccinate BALB/c mice against the challenge of leishmania major. BALB/c mice were vaccinated subcutaneously, three times at a two-week interval. Parasite burden, footpad swelling, IgG isotype, as well as the level of IL-4 and IFN-γ were assessed as the protection criteria.Results: The group of mice vaccinated by Lip+Imiquimod+SLA demonstrated a lower amount of footpad swelling and parasite burden than the buffer group. In addition, the highest level of IFN-γ and the lowest level of IL-4 production was noticed in the splenocytes of the mice vaccinated with the formulation of Lip+Imiquimod+SLA. Conclusion: These results imply that imiquimod added to the formulation of liposomes is able to modulate the immune reaction of the BALB/c mice vaccinated preferably to a Th1 reaction rather than a Th2 reaction which can also lead to partial protection against the challenge of Leishmania.

Objective(s): Protection against leishmaniasis, in the murine model, is dependent on developing a potent CD4+ mediated Th1 type response. Liposomes can be applied as immunoadjuvants to stimulate immune responses to different antigens. In the present study, it was investigated whether DOTAP liposomes having SLA and imiquimod adjuvant, can induce a Th1 response and protect against Leishmania major challenge in BALB/c mice. Materials and Methods: Liposomes were provided applying the lipid film procedure. BALB/C mice were subcutaneously immunized, three times with 2-week intervals, with various formulations. Assessment of lesion development and parasite burden in the foot and spleen after challenge with L. major, assessment of Th1 cytokine (IFN-γ), and titration of IgG isotypes assessed the type of generated immune reaction and the protection extent. Results: The mice immunized with Liposome DOTAP+imiquimod+SLA showed smaller footpad swelling which was meaningfully different (P

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.

Hydrogels have been used for biomedical applications in recent decades. They are a perfect candidate for regenerative medicine as they resemble the extracellular matrix of native tissues. In addition, their highly hydrated structure makes them a suitable choice for drug and other therapeutics delivery. Injectable hydrogels have increasingly gained attention due to their capability for homogeneous mixing with cells and therapeutic agents, minimally invasive administration, and perfect defect filling. In this review, we discuss various mechanisms which facilitate injectability of hydrogels, including in situ gelling liquids, injectable gels, and injectable particles. Then, we explore the biomedical applications of injectable hydrogels, including tissue engineering, therapeutic agent delivery, and medical devices.

Skin is an important organ of the body due to offering an accessible and convenient site for drug administration. One of the disadvantages of transdermal drug delivery is the low penetration rate of drugs through the skin. Over the past decades, nanoparticles have been used as drug delivery systems to increase therapeutic effects or reduce toxicity. Encapsulation of drugs in nanoparticulate vesicles simplifies the transports of drugs into and across the skin. Niosome nanoparticles are among these drug delivery systems, which have numerous applications in drug delivery and targeting. Niosomes are frequently used for loading drugs serving different purposes (e.g., anticancer, antiviral, and antibacterial agents). In recent years, there has been much research on the use of niosomal systems for the delivery of fungal drugs. A review of the literature investigating the advantages of niosomes in antifungal drug delivery can elucidate the efficiency and superiority of this nanocarrier over other nanocarriers.

The gastrointestinal system harbors various microorganisms, known as gut microbiota. Increase in prevalence of inflammatory bowel disease (IBD) in developed countries is associated with changes in the environment, such as decrease in incidence of parasitic infections, especially helminths, and changes in the intestinal flora. Probiotics are useful microbiota for human health. The parasitic worms (helminths) have evolved over the years with their host. Several studies have investigated the capability of helminths and probiotics to alter or control host immune responses in view of the fact that these organisms have immunomodulation effects. Given the contradictory results, further broad studies are needed to confirm the role of probiotics and helminths in the treatment of IBD.

Background and Aim: Recently, several studies have indicated that the central nervous system has the capacity for endogenous repair. But, the proliferation capacity of endogenous neural stem cells (NSCs) isn’t sufficient for the treatment of neurodegenerative diseases. So, it sounds that stimulation of endogenous NSC proliferation is essential for neuroregeneration. The aim of this study was to examine the effects of Sambucus ebulus extract on the proliferation of neonatal rat hippocampus-derived neural stem cells (NSCs) under oxidative stress condition induced by H2O2. Material and Methods: The NSCs were isolated from neonatal rat hippocampus. To confirm neural characteristics of neural stem cells, the expression of neural-specific marker, Nestin was investigated by immunocytochemistry technique. 5×104 cells were cultured in every well of a 96 well plate and H2O2 was added to induce oxidative stress condition. Then NSCs were exposed to 50 µg Sambucus ebulus extract for 24 hours, at various concentrations (25, 50, 100, 200, 400 and 500 μg/ml). The cell proliferation rate was assessed by MTT colorimetry assay before and after treatment with the extract. Results: Immunofluorescent studies showed that neural stem cells expressed specific neural marker; Nestin. The proliferation rate of NSCs increased in the treated groups in comparison to that in the control group. The highest rate of survival was observed when Sambucus ebulus was used at the concentration of 500 μg/ml. (P

Leishmaniasis is a major public health problem, but so far there are no effective commercially available vaccines for this disease. Its control strategy is only reliant on therapy, but currently the drugs available for the treatment of leishmaniasis are also limited and a great concern is the rapid rate of resistance to common drugs. The first step in discovery and development of new drugs is to identify an appropriate drug target. Accordingly, it is important to recognize the metabolic pathways in which the leishmania parasites live and selecting a target in the parasite biological pathway, absent in the host or different from the host homolog. Discovery of new drugs requires high costs and takes a lot of time (up to 15 years). Therefore, choosing the approved drugs in the market for various diseases, including leishmaniasis is very cost-effective considering the mechanism of drug action and other aspects. Miltefosin is an effective anti-cancer agent that is also used for different types of leishmaniasis. In recent years, researchers have focused on the anti-leishmanial effects of pharmaceutical compounds or anticancer drugs to find more effective compounds with lower side effects. The present article mainly reviews the anticancer drugs that have been tested for their anti-leishmanial effects in both in vitro and in vivo conditions.

Metabolic syndrome and its various manifestations are considered to be a significant health epidemic in the developed and developing countries across the world. Metabolic syndrome is characterized by a series of metabolic abnormalities, such as central adiposity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. Patients with metabolic syndrome are at a higher risk of major complications, including fatty liver, type II diabetes mellitus, and cardiovascular diseases. Nuclear receptors are the key regulators of gene transcription, as well as several metabolic pathways. Among these receptors, LXRα and β play a major role in the regulation of lipogenesis, cholesterol/glucose homoeostasis, and inflammatory pathways through the induction or repression of target genes. In addition to metabolic homeostasis and diseases, lipogenesis and hypertriglyceridemia are regarded as the most significant adverse effects of liver X receptor (LXR) activation. Given the importance of lipid and carbohydrate metabolism and inflammation in the development of metabolic disorders, the present study aimed to review the impact of LXR signaling on the risk of metabolic syndrome and its phenotypes, with an emphasis on their potential therapeutic applications in the treatment of metabolic syndrome. In general, growing evidence supports the notion that LXRs may represent the potential drug targets for the treatment of metabolic syndrome.

Toxoplasma gondii is well- known as a common parasite with high proliferative activity in the nucleated cells. This parasite has infected nearly one third of the people worldwide. Infection can result in chorioretinitis in immunocompetent hosts, encephalitis in HIV/AIDS positive patients and abortion and neonatal loss in congenital toxoplasmosis. Development of vaccines for toxoplasmosis infection is very important for decreasing infection transmission routes of the disease in various host species in the world. Live attenuated vaccines are closest to a natural infection; therefore, they are good rescuers of the immune system and often create lifelong immunity with only one or two doses. In this study, the researchers reviewed the current status in the development of live attenuated vaccines on Toxoplasma infection.

Objective(s): Leishmaniasis is a complex parasitic disease that represents a major public health problem. Despite numerous attempts over the past decades, yet there is no effective vaccine against human leishmaniasis probably due to the lack of suitable adjuvants. In this study, a first generation liposomal-based Leishmania vaccine was developed using soluble Leishmania major antigens (SLA) and á, Ü-trehalose6, 6'-dibehenat (TDB) as an immunostimulatory adjuvant. In this liposome structure, the cationic lipid Dimethyldioctadecylammonium (DDA) provides intrinsic adjuvant activity and cholesterol was added as a membrane stabilizer. Liposomes containing SLA were prepared.Materials and Methods: BALB/c mice were subcutaneously (sc) immunized with Lip (DDA/TDB/CHOL)-SLA+, Lip (DDA/TDB)-SLA+, Lip (DDA)-SLA+, Lip (DDA/CHOL)-SLA+, SLA or Tris-HCl buffer. Immunization was done every two weeks for three weeks. The immunized mice were then challenged sc in the left footpad with 1×106 stationary phase L. major promastigotes (50 ìl), at 2 weeks after last booster injection.Results: mice immunized with any of the liposomal formulations containing SLA (Lip-SLA+), substantially increased footpad swelling and parasite loads of foot and spleen with no significant difference compared to Tris-HCl buffer or SLA alone. Lip-SLA+ formulations induced a mixed Th1/Th2 immune response characterized by IFN-ã and IL-4 production as well as high levels of IgG1 anti-Leishmania antibody. Conclusion: immunization with liposomes containing DDA and/or TDB in combination with SLA induces a mixed Th1/Th2 immune response and is not an appropriate strategy for preferential induction of a Th1 response and protection against leishmaniasis.

Leishmaniasis is an infectious disease caused by the protozoan parasites of the genus Leishmania. Leishmaniasis annually affects the socioeconomic status of some societies. Evidence show that vaccination could prevent Leishmania and many studies are done on this, particularly nanovacines. So, this article aimed at reviewing recent developments in this field. In current narrative review article, five English databases including Ebsco, Science Direct, PubMed, Google Scholar, and Scopus and four Persian databases including Magiran, Elm Net, Barakat Knowledge Network System, and the Scientific Information Database (SID) were searched for articles published between 2005 and 2016. Current treatment of leishmaniasis is based on chemical drugs but their application is limited due to high cost, toxicity, side effects, and low efficacy. In addition, vaccines can modulate the immune response in removing Leishmania in favor of the hosts. We attempted to review different types of Leishmania vaccine and their development trends, carriers, vaccine candidates, and strategies and delivery systems in last decade. It was found that nanovaccines consisting of multiple antigens and adjuvant are well developed in conjunction with IL-12 as Leish-111f and MPL-SE, therefore, they could be more successful. Current researches on vaccination clearly indicate the need for more research and investment in developing Leishmania vaccine.

Background and Purpose: Patulin is a mycotoxin produced by some molds,especially Aspergillus and Penicilium, and is responsible for mycotoxicosis in animals and humans.There is still not very detailed data about the anti-cancer potency of patulin, but some reports demonstrated that it induces cellular apoptosis and toxicity. Materials and Methods: To determine the efficacy of patulin as a therapeutic strategy for cervical and colorectal cancers, we investigated its effects on HeLa,SW-48, and MRC-5 cell lines. Cell lines were exposed to various concentrations of patulin (i.e., 0.5, 1, 2, and 4 µM), then using methyl thiazolyl tetrazolium (MTT) and bromo-2′-deoxyuridine (BrdU) assays, the rates of apoptosis and cell viability were determined. Results: The obtained results showed a significant reduction in cell viability and apoptosis induction in a dose-dependent manner. Among all the cell lines, the highest growth inhibition rate was obtained at the 4 μM concentration of patulin.Conclusion: Our results suggested that patulin could significantly decrease tumor growth in human cervical and colorectal cancer models.

Objective(s):Transforming growth factor-β(TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressor-miRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-∆∆CT method through student’s t-test via the GraphPad Prism software. Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b. Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression.

Background: We aimed here to investigate the association between alleles and genotypes of APOE and Age-related macular degeneration (AMD) development. Materials and Methods: After ophthalmological examination, 120 patients with confirmed AMD and 120 healthy controls were enrolled in the study. The polymorphic segment of APOE gene was PCR-amplified and sequenced to determine the frequency distribution of polymorphic alleles and genotypes of this gene in the sample population. Results: The frequency distribution of APOE alleles and genotypes differed significantly between the patients and the control groups (P