Foeniculum vulgare Mill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology of Foeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates that Foeniculum vulgare remains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in several in vitro and in vivo pharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property. Foeniculum vulgare has emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.

We show that co-expression of interleukin 15 (IL-15) and IL-15 receptor ␣ (IL-15R␣) in the same cell allows for the intracellular interaction of the two proteins early after translation, resulting in increased stability and secretion of both molecules as a complex. In the absence of co-expressed IL-15R␣, a large portion of the produced IL-15 is rapidly degraded immediately after synthesis. Co-injection into mice of IL-15 and IL-15R␣ expression plasmids led to significantly increased levels of the cytokine in serum as well as increased biological activity of IL-15. Examination of natural killer cells and T lymphocytes in mouse organs showed a great expansion of both cell types in the lung, liver, and spleen. The presence of IL-15R␣ also increased the number of CD44 high memory cells with effector phenotype (CD44 high CD62L؊). Thus, mutual stabilization of IL-15 and IL-15R␣ leads to remarkable increases in production, stability, and tissue availability of bioactive IL-15 in vivo. The in vivo data show that the most potent form of IL-15 is as part of a complex with its receptor ␣ either on the surface of the producing cells or as a soluble extracellular complex. These results explain the reason for coordinate expression of IL-15 and IL-15R␣ in the same cell and suggest that the IL-15R␣ is part of the active IL-15 cytokine rather than part of the receptor. 2 is a pleiotropic cytokine produced in many tissues. It is a member of the four ␣-helix bundle family of cytokines and was initially described as a T cell proliferation factor (1, 2). IL-15 shares with interleukin-2 (IL-2) a common receptor complex, consisting of the IL-2 receptors ␤ and ␥ chains (3). Both IL-2 and IL-15 use an additional private receptor subunit responsible for the specificity of binding, the IL-2 receptor ␣ (IL-2R␣) and IL-15 receptor ␣ (IL-15R␣), respectively. Both molecules have a similar ligand-binding motif (sushi domain) as well as a relatively short intracellular tail (13 amino acids for human IL-2R␣ and 41 amino acids for human IL-15R␣). In contrast to IL-2R␣, which displays a lower affinity for IL-2 (K d ϳ 10 Ϫ8 M) and is expressed mainly on activated T cells, IL-15R␣ has a high affinity for IL-15 (K d ϳ10 Ϫ11 M), and its mRNA has a wide tissue distribution (4). IL-15Ϫ/Ϫ and IL-15R␣ Ϫ/Ϫ mice have profound defects in NK, NK-T, intraepithelial lymphocytes, and memory CD8ϩ T cells, indicating that IL-15 is essential for the homeostatic maintenance and function of these cells (5, 6). In contrast, IL-2 Ϫ/Ϫ and IL-2R␣ Ϫ/Ϫ mice develop autoimmune diseases with increased frequency of activated T and B cells (7,8). Despite the clear results on the positive role of IL-15R␣ for IL-15 function, several investigators have reported inhibitory effects of IL-15R␣ on IL-15 function. Injection in mice of a soluble recombinant form of IL-15R␣ protein (IL-15sR␣) was reported to suppress natural killer (NK) cell proliferation and T-dependent immune responses in vivo (9). Addition of IL-15sR␣ in vitro was reported to block the response of cell lines to IL-1...

We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we combined the SIVmac239 DNA vaccine with protein immunization using inactivated SIVmac239 viral particles as protein source. Twenty-six weeks after the last vaccination, the animals were challenged intrarectally at weekly intervals with a titrated dose of the heterologous SIVsmE660. Two of DNA-protein coimmunized macaques did not become infected after 14 challenges, but all controls were infected by 11 challenges. Vaccinated macaques showed modest protection from SIVsmE660 acquisition compared with naïve controls (P = 0.050; stratified for TRIM5α genotype). Vaccinees had significantly lower peak (1.6 log, P = 0.0048) and chronic phase viremia (P = 0.044), with 73% of the vaccinees suppressing viral replication to levels below assay detection during the 40-wk follow-up. Vaccine-induced immune responses associated significantly with virus control: binding antibody titers and the presence of rectal IgG to SIVsmE660 Env correlated with delayed SIVsmE660 acquisition; SIV-specific cytotoxic T cells, prechallenge CD4 + effector memory, and postchallenge CD8 + transitional memory cells correlated with control of viremia. Thus, SIVmac239 DNA and proteinbased vaccine protocols were able to achieve high, persistent, broad, and effective cellular and humoral immune responses able to delay heterologous SIVsmE660 infection and to provide long-term control of viremia. These studies support a role of DNA and protein-based vaccines for development of an efficacious HIV/AIDS vaccine.T he use of a combination vaccine consisting of the recombinant Canarypox ALVAC-HIV (vCP1521; containing Gag, PR, and Env) together with gp120 Env protein (AIDSVAX B/E) resulted in modest, but statistically significant protection from infection in the RV144 vaccine trial conducted in Thailand (1). The limited efficacy and the fact that the vaccine-induced responses waned over time suggest that improved vaccine designs are needed to achieve long-lasting cross-clade-specific immune responses able to prevent infection. Rhesus macaque simian immunodeficiency virus (SIV) challenge models provide an excellent system to test different vaccine modalities and to compare efficacy using different challenge viruses and infection routes.DNA as priming immunization together with boosting by recombinant viral vectors is a vaccine platform widely used in the HIV/SIV field. DNA as the only vaccine component has been considered poorly immunogenic in humans, although recent results showed that in vivo DNA electroporation (EP) results in more efficient vaccine delivery, a higher frequency of responders, and higher, longer-lasting immunity than needle/syringe delivery (2). Similarly, the inclusion of DNA encoding the cytokine IL-12 as molecular adjuvant has been shown to be advantageous (3). These recent data suggest that DN...

Ficus carica has emerged as a good source of traditional medicine for the treatment of various ailments such as anemia, cancer, diabetes, leprosy, liver diseases, paralysis, skin diseases, and ulcers. It is a promising candidate in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.

Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the detection of systemic IL-12 cytokine in the plasma. Peak levels obtained by day 4-5 post injection were paralleled by a rapid increase of IFN-γ, indicating bioactivity of the IL-12 cytokine. Both plasma IL-12 and IFN-γ levels were reduced to basal levels by day 14, indicating a short presence of elevated levels of the bioactive IL-12. The effect of IL-12 as adjuvant together with an SIVmac239 DNA vaccine was further examined comparing two groups of rhesus macaques vaccinated in the presence or absence of IL-12 DNA. The IL-12 DNA-adjuvanted group developed significantly higher SIV-specific cellular immune responses, including IFN-γ (+) Granzyme B (+) T cells, demonstrating increased levels of vaccine-induced T cells with cytotoxic potential, and this difference persisted for 6 mo after the last vaccination. Coinjection of IL-12 DNA led to increases in Gag-specific CD4 (+) and CD4 (+) CD8 (+) double-positive memory T cell subsets, whereas the Env-specific increases were mainly mediated by the CD8 (+) and CD4 (+) CD8 (+) double-positive memory T cell subsets. The IL-12 DNA-adjuvanted vaccine group developed higher binding antibody titers to Gag and mac251 Env, and showed higher and more durable neutralizing antibodies to heterologous SIVsmE660. Therefore, co-delivery of IL-12 DNA with the SIV DNA vaccine enhanced the magnitude and breadth of immune responses in immunized rhesus macaques, and supports the inclusion of IL-12 DNA as vaccine adjuvant.