The Association between Brain-Derived Neurotrophic Factor (BDNF) Protein Level and Body Mass Index.

Background and Objectives: Obesity is a major health concern worldwide. Many studies emphasize the important role of brain-derived neurotrophic factor (BDNF) in regulating appetite and body weight. We aimed to investigate the association between BDNF protein serum levels and body mass index (BMI). Materials and Methods: We conducted a cross-sectional study among 108 healthy adult participants divided into six categories depending on their body mass index (BMI). The ages of the participants ranged between 21 to 45 years. The BDNF serum level was measured using the enzyme-linked immunosorbent assay (ELISA) technique. Results: A Kruskal−Wallis test showed a significant difference in BDNF between the different BMI categories, χ2(2) = 24.201, p < 0.001. Our data also showed that BDNF levels were significantly lower in people with obesity classes II and III than those of normal weight (p < 0.05). The Spearman rank correlation test was statistically significant with negative correlations between the BMI and BDNF (r) = −0.478, (p < 0.01). Moreover, we observed a negative dose-dependent relationship pattern between BMI categories and the levels of circulating BDNF protein. Conclusions: In this study, our data support the hypothesis that low serum levels of BDNF are associated with high BMI and obesity in Saudi adults.

Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide.

Development of a Chlamydia trachomatis vaccine has been a formidable task partly because of an ineffective delivery system. Our laboratory has generated a recombinant peptide of C. trachomatis major outer membrane protein (MOMP) (rMOMP-187) and demonstrated that it induced at 20 µg ml(-1) maximal interleukin (IL)-6 and IL-12p40 Th1 cytokines in mouse J774 macrophages. In a continuous pursuit of a C. trachomatis effective vaccine-delivery system, we encapsulated rMOMP-187 in poly(d,l-lactic-co-glycolic acid) (PLGA, 85:15 PLA/PGA ratio) to serve as a nanovaccine candidate. Physiochemical characterizations were assessed by Fourier transform-infrared spectroscopy, atomic force microscopy, Zetasizer, Zeta potential, transmission electron microcopy and differential scanning calorimetry. The encapsulated rMOMP-187 was small (∼200 nm) with an apparently smooth uniform oval structure, thermally stable (54 °C), negatively charged ( - 27.00 mV) and exhibited minimal toxicity at concentrations <250 µg ml (-1) to eukaryotic cells (>95% viable cells) over a 24-72 h period. We achieved a high encapsulation efficiency of rMOMP-187 (∼98%) in PLGA, a loading peptide capacity of 2.7% and a slow release of the encapsulated peptide. Stimulation of J774 macrophages with a concentration as low as 1 µg ml (-1) of encapsulated rMOMP-187 evoked high production levels of the Th1 cytokines IL-6 (874 pg ml(-1)) and IL-12p40 (674 pg ml(-1)) as well as nitric oxide (8 µM) at 24 h post-stimulation, and in a dose-response and time-kinetics manner. Our data indicate the successful encapsulation and characterization of rMOMP-187 in PLGA and, more importantly, that PLGA enhanced the capacity of the peptide to induce Th1 cytokines and NO in vitro. These findings make this nanovaccine an attractive candidate in pursuit of an efficacious vaccine against C. trachomatis.

The anti-inflammatory cytokine, interleukin-10, inhibits inflammatory mediators in human epithelial cells and mouse macrophages exposed to live and UV-inactivated Chlamydia trachomatis.

Chlamydia trachomatis infects macrophages and epithelial cells evoking acute and chronic inflammatory conditions, which, if not controlled, may put patients at risk for major health issues such as pelvic inflammatory disease, chronic abdominal pain, and infertility. Here we hypothesized that IL-10, with anti-inflammatory properties, will inhibit inflammatory mediators that are produced by innate immune cells exposed to C. trachomatis. We used human epithelial (HeLa) cells and mouse J774 macrophages as target cells along with live and UV-inactivated C. trachomatis mouse pneumonitis (MoPn) as stimulants. Confocal microscopy employing an anti-Chlamydia antibody confirmed cells infectivity by day 1, which persisted up to day 3. Kinetics studies revealed that live C. trachomatis induced TNF, IL-6, and IL-8, as a function of time, with day-2 infection inducing the highest cytokine levels. Exogenous IL-10 inhibited TNF, IL-6, and IL-8 as secreted by day-2 infected cells. Similarly, IL-10 diminished cytokine levels as produced by macrophages exposed to UV-inactivated Chlamydia, suggesting the IL-10-mediated inhibition of cytokines is not restricted to live organisms. Our data imply that IL-10 is an important regulator of the initial inflammatory response to C. trachomatis infection and that further investigations be made into IL-10 use to combat inflammation induced by this bacterium.

Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine.

We recently demonstrated by in vitro experiments that PLGA (poly D, L-lactide-co-glycolide) potentiates T helper 1 (Th1) immune responses induced by a peptide derived from the recombinant major outer membrane protein (rMOMP) of Chlamydia trachomatis, and may be a promising vaccine delivery system. Herein we evaluated the immune-potentiating potential of PLGA by encapsulating the full-length rMOMP (PLGA-rMOMP), characterizing it in vitro, and investigating its immunogenicity in vivo. Our hypothesis was that PLGA-rMOMP triggers Th1 immune responses in mice, which are desirable prerequisites for a C. trachomatis candidate nanovaccine. Physical-structural characterizations of PLGA-rMOMP revealed its size (approximately 272 nm), zeta potential (-14.30 mV), apparent spherical smooth morphology, and continuous slow release pattern. PLGA potentiated the ability of encapsulated rMOMP to trigger production of cytokines and chemokines by mouse J774 macrophages. Flow cytometric analyses revealed that spleen cells from BALB/c mice immunized with PLGA-rMOMP had elevated numbers of CD4+ and CD8+ T cell subsets, and secreted more rMOMP-specific interferon-gamma (Th1) and interleukin (IL)-12p40 (Th1/Th17) than IL-4 and IL-10 (Th2) cytokines. PLGA-rMOMP-immunized mice produced higher serum immunoglobulin (Ig)G and IgG2a (Th1) than IgG1 (Th2) rMOMP-specific antibodies. Notably, sera from PLGA-rMOMP-immunized mice had a 64-fold higher Th1 than Th2 antibody titer, whereas mice immunized with rMOMP in Freund's adjuvant had only a four-fold higher Th1 than Th2 antibody titer, suggesting primarily induction of a Th1 antibody response in PLGA-rMOMP-immunized mice. Our data underscore PLGA as an effective delivery system for a C. trachomatis vaccine. The capacity of PLGA-rMOMP to trigger primarily Th1 immune responses in mice promotes it as a highly desirable candidate nanovaccine against C. trachomatis.