Obesity induces gut leakage and elevates serum lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria, through gut translocation. Because Candida albicans is prominent in human gut but not in mouse, C. albicans, a source of (1→3)-β-D-glucan (BG) in gut contents, was administered in high-fat diet (HFD)-induced obese mice at 1 week before sepsis induction by cecal ligation and puncture (CLP). As such, sepsis in Candida-administered obese mice was more severe than obese mice without Candida as determined by mortality, organ injury (liver and kidney), serum cytokines, gut leakage, endotoxemia, serum BG, and fecal Gram-negative bacteria (microbiome analysis). Mice subjected to CLP and fed a HFD, but not treated with Candida demonstrated a similar mortality to non-obese mice with more severe gut leakage and higher serum cytokines. In vitro experiments demonstrated that LPS plus BG (LPS + BG) induced higher supernatant cytokines from hepatocytes (HepG2) and macrophages (RAW264.7), compared with the activation by each molecule alone, and were amplified by palmitic acid, a representative saturated fatty acid. The energy production capacity of HepG2 cells was also decreased by LPS + BG compared with LPS alone as evaluated by extracellular flux analysis. However, Lactobacillus rhamnosus L34 (L34) improved

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviors and cognitive deficits; the effects of adverse childhood experiences (ACE) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalences of gut microbiome phyla, genera, and species by analyzing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namely Hungatella and Fusicatenibacter (positive associations) and Butyricicoccus, Clostridium, Parabacteroides merdae, and Desulfovibrio piger (inverse association). This profile (labeled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to suicidal behaviors. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, and Romboutsia were positively associated, while Proteobacteria and Clostridium sensu stricto were negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current suicidal behaviors. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and suicidal behaviors, and possibly for the prevention of future episodes.

No abstract

A previous study reported that lamin A/C (LMNA) expression was increased in renal tubular cells adhered with calcium oxalate monohydrate (COM) crystals; however, its functional significance in kidney stone disease remained unknown. In the present study, increased levels of LMNA and its partner, nesprin-1 (SYNE1), in Madin-Darby canine kidney cells upon COM crystal adhesion were confirmed by Western blotting and immunofluorescence staining. LMNA was then knocked down by small interfering RNA. Immunofluorescence staining confirmed the efficiency of small interfering RNA of LMNA (si-LMNA), which also reduced expression of its partner, SYNE1. Scratch assay and total cell count revealed defects in tissue repair and cell proliferation, respectively, whereas cell death quantitation showed no cytotoxicity in si-LMNA-transfected cells. Crystal-binding assay highlighted the role of LMNA in crystal adhesion, whereas protein network analysis revealed interactions between LMNA and potential COM crystal receptors. Their associations were confirmed by reduced levels of these proteins, including vimentin, tubulin, enolase, S100, and annexin A2, in si-LMNA-transfected cells. These data have demonstrated for the first time, to our knowledge, that LMNA in renal tubular cells is important for tissue repair, cell proliferation, and COM crystal adhesion and is associated with potential COM crystal receptors. Therefore, LMNA may serve as a potential target for prevention of kidney stone disease and its recurrence.-Pongsakul, N., Vinaiphat, A., Chanchaem, P., Fong-ngern, K., Thongboonkerd, V. Lamin A/C in renal tubular cells is important for tissue repair, cell proliferation, and calcium oxalate crystal adhesion, and is associated with potential crystal receptors.

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours and cognitive deficits; the effects of adverse childhood experiences (ACE) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalences of gut microbiome phyla, genera, and species by analysing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namely Hungatella and Fusicatenibacter (positive associations) and Butyricicoccus, Clostridium, Parabacteroides merdae, and Desulfovibrio piger (inverse association). This profile (labeled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to suicidal behaviours. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, and Romboutsia were positively associated, while Proteobacteria and Clostridium sensu stricto were negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current suicidal behaviours. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and suicidal behaviours, and possibly for the prevention of future episodes.