Probiotics for the treatment of depression and its comorbidities: A systemic review

Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities

Secreted Expression of the Cap Gene of Porcine Circovirus Type 2 in Classical Swine Fever Virus C-Strain: Potential of C-Strain Used as a Vaccine Vector

Bivalent vaccines based on live attenuated viruses expressing a heterologous protein are an attractive strategy to address co-infections with various pathogens in the field. Considering the excellent efficacy and safety of the lapinized live attenuated vaccine C-strain (HCLV strain) of classical swine fever virus (CSFV), we proposed that C-strain has the potential as a viral vector for developing bivalent vaccines. To this end, we generated three recombinant viruses based on C-strain, one expressing the capsid (Cap) gene of porcine circovirus type 2 (PCV2) with the nuclear localization signal (NLS) (rHCLV-2ACap), and the other two expressing the PCV2 Cap gene without the NLS yet containing the signal peptide of the prolactin gene (rHCLV-pspCap) or that of the ubiquitin-specific peptidase gene (rHCLV-uspCap). All the recombinant viruses exhibited phenotypes similar to those of the parental virus and produced high-level anti-CSFV neutralizing antibodies (NAbs) in rabbits. Interestingly, rHCLV-uspCap and rHCLV-pspCap, but not rHCLV-2ACap, elicited detectable anti-Cap and -PCV2 NAbs in rabbits. Taken together, our data demonstrate that C-strain can be used as a viral vector to develop bivalent vaccines

Effects of MiR-375-BMPR2 as a Key Factor Downstream of BMP15/GDF9 on the Smad1/5/8 and Smad2/3 Signaling Pathways

Background/Aims: Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), which are secreted by oocytes, are important regulators of follicular growth and development and ovarian function. These two factors can regulate the proliferation and apoptosis of cumulus cells via modulation of the Smad signaling pathway. Studies have shown that BMP15 and GDF9 can affect the level of miR-375, whereas the target gene of miR-375 is BMPR2, the type II receptor of BMP15 and GDF9. However, whether or how the BMP15/ GDF9-miR-375-BMPR2 pathway affects the proliferation and apoptosis of bovine cumulus cells through regulation of the Smad signaling pathway remains unclear. Methods: In this study, cumulus cells were first obtained from cumulus-oocyte complexes (COCs). Appropriate concentrations of BMP15 and GDF9 were added during the in vitro culture process. Cell Counting Kit-8 (CCK-8) analyses and flow cytometry were used to determine the effects of BMP15/GDF9 on bovine cumulus cells proliferation and apoptosis. Subsequently, miR-375 mimics, miR-375 inhibitor and BMPR2 siRNA were synthesized and used for transfection experiments. Western Blot analysis was used to detect changes before and after transfection in the expression levels of the BMP15/GDF9 type I receptors ALK4, ALK5 and ALK6; the phosphorylation levels of Smad2/3 and Smad1/5/8, which are key signaling pathway proteins downstream of BMP15/GDF9; the expression levels of PTX3, HAS2 and PTGS2, which are key genes involved in cumulus cells proliferation; and Bcl2/Bax, which are genes involved in apoptosis. Results: The addition of 100 ng/mL BMP15 or 200 ng/mL GDF9 or the combined addition of 50 ng/mL BMP15 and 100 ng/mL GDF9 effectively inhibited bovine cumulus cell apoptosis and promoted cell proliferation. BMP15/GDF9 negatively regulated miR-375 expression and positively regulated BMPR2 expression. High levels of miR-375 and inhibition of BMPR2 resulted in increased expression of ALK4 and decreased expression of PTX3, HAS2 and PTGS2, whereas miR-375 inhibition resulted in the opposite results. BMP15 and GDF9 significantly activated the levels of p-Smad2/3 and p-Smad1/5/8, whereas miR-375 inhibited the levels of p-Smad2/3 and p-Smad1/5/8 by negatively regulating BMPR2 and also led to apoptosis. Conclusion: BMP15 and GDF9 have synergistic effects and can act through miR-375 to affect the expression levels of type I receptor ALK4 and type II receptor BMPR2 and the activation of Smad signaling pathway, which subsequently affected the proliferation, spread and apoptosis of cumulus cells

The cDNA sequence of <i>AccDpp</i> and its amino acid sequence.

<p>The top line shows the nucleotide sequence of <i>AccDpp</i>, and the second line shows the deduced amino acid sequence. The start codon (ATG) and stop codon (TAG) are boxed. The polyadenylation signal (AATAA) sequence is marked by an oval. The underlined region indicates the signal peptide, and the shaded amino acid sequence denotes the predicted antimicrobial peptide. The sequence was deposited in GenBank, and the GenBank accession no. is KT750952.</p

Phylogenetic analysis and the tertiary structure of <i>AccDpp</i>.

<p>A, phylogenetic analysis of AccDpp from different species. The species source of the above analysis is listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149117#pone.0149117.s005" target="_blank">S4 Table</a>. B, the tertiary structure of AccDpp. Helices, sheets, and coils are presented in different colours.</p

Expression of <i>AccDpp</i> in <i>Transetta</i> (DE3) chemically competent cells.

<p>Recombinant AccDpp was separated by SDS-PAGE, and then stained with Coomassie brilliant blue. Lane 1–4, expression of AccDpp after IPTG induction for 4, 5, 6, and 7 h. Lane 5 and Lane 6, non-induced of recombinant AccDpp and induced overexpression of pET-30a (+) vector for 7 h. The box shows the site of recombinant AccDpp.</p

Expression of <i>AccDpp</i> under different stress conditions.

<p>The transcript levels of <i>AccDpp</i> were analysed via qRT-PCR. Untreated 15-day worker bees and the <i>β-actin</i> gene were used as controls and an internal control, separately. The data are the mean ± SE of three independent experiments. Significant differences (p<0.001) were represented by different letters on the bar based on Duncanʾs multiple range tests.</p

Expression profile of <i>AccDpp</i> and Western blot analysis of <i>AccDpp</i> at different developmental stages and different tissues.

<p>A, and B, the mRNA level of <i>AccDpp</i> at different developmental stages: egg (E), one-day to seven-day larvae (L1-L7), pre-pupal phase pupae (Po), pupae (white-eyed (Pw), pink-eyed (Pp), brown-eyed (Pb) and dark-eyed (Pd) pupae)), 1-day worker bees (A1), 15-day worker bees (A15), and 30-day worker bees (A30), and different tissues: leg (Le), wing (Wi), muscle (Ms), midgut (Mi), haemolymph (He), rectum (Re), poison gland (Pg), honey sac (Hs), antennae (An) and epidermis (Ep), respectively. The data are the mean ± SE of three independent experiments. The letters above the columns suggest significant differences (P<0.0001) according to Duncan’s multiple range tests. C, and D, the expression level of AccDpp protein at different tissues and stages of development, separately.</p

Characterization of <i>Dpp</i> from various species.

<p>The amino acid sequences of Dpp were all downloaded from the NCBI database (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149117#pone.0149117.s005" target="_blank">S4 Table</a>). A, alignment of the deduced <i>AccDpp</i> protein sequence with other Dpp proteins. B, Conserved domain of Dpp. The conserved domains are marked by different shapes.</p