Moderating Gut Microbiome/Mitochondrial Axis in Oxazolone Induced Ulcerative Colitis: The Evolving Role of ß-Glucan and/or, Aldose Reductase Inhibitor, Fidarestat.

A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). ß-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of ß-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, ß-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa ß (NF-kß), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kß, on the other hand, significantly decreased. Using ß-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness.

Modulating gut dysbiosis and mitochondrial dysfunction in oxazolone-induced ulcerative colitis: the restorative effects of ß-glucan and/or celastrol.

OBJECTIVES: Microbiome-Mitochondria interaction is gaining a significant attention; thus, studying its mechanism emerges as a must to provide restorative lines in managing diseases. The aim is to study the mechanistic effects of ß-Glucan and/or Celastrol in oxazolone-induced ulcerative colitis (UC). METHODS: 75 Wistar rats were allocated into 5 equal groups. Group I: control group. Group II: UC group, Group III: ß-Glucan-treated UC group, Group IV: Celastrol-treated UC group & Group V: mutual treatment group. All groups were subjected to the detection of free fatty acid receptor 2 (FFAR-2) and peroxisome proliferator-activated receptor gamma co-activator1α (PGC-1α) mRNA gene expressions. Citrate synthase (CS) activity, mitochondrial membrane potential (MMP), ATP concentration, reactive oxygen species (ROS) were detected. Trimethylamine N-oxide (TMAO) concentration was measured. RESULTS: After treatment we monitored significant upregulation of FFAR-2 and PGC-1α mRNA expression. Likewise, ATP level and CS activity were significantly increased. On the contrary, there was a significant lessening in ROS and TMAO levels with improvement of MMP. CONCLUSION: Mutual use of ß- Glucan and Celastrol had a greater effect than each alone against UC, which is considered a novel finding highlighting the ameliorative effects of this combined treatment in modulating Microbiome/Mitochondria axis, thus launching promising avenues for UC.

Can immunohistochemistry replace immunofluorescence in diagnosis of skin bullous diseases?

Autoimmune bullous diseases are distressing and sometimes risky bullous dermatoses characterized by the presence of antibodies focused against disease-specific target antigens. Recognition of these antibodies using immunofluorescence is used to be the only sure diagnostic method after reviewing the routine histopathological section. Because of many causes that make the using of immunofluorescence difficult, we tried to evaluate the role of immunohistochemistry in diagnosis of these bullous skin diseases; 40 pemphigus cases (30 pemphigus vulgaris and 10 pemphigus foliaceus) and 37 non-pemphigus cases (35 vesiculobullous skin diseases and 2 normal skin). Skin biopsy was obtained for histopathological diagnosis, immunofluorescence study, and immune-histochemical studying for IgG4 and C3d expression. IgG4 was positive in almost all cases of pemphigus vulgaris and most of pemphigus foliaceus and bullous pemphigoides, while all other diseases were negative. C3d expression was positive in almost all bullous pemphigoides and pemphigus gestationis cases, while it was negative in almost all other cases. Sensitivity and specificity of both markers increase by using them in combination in diagnosis of such bullous diseases. IgG4 and C3d immunohistochemistry could replace DIF in almost all of our cases, so before doing DIF, reliable immunohistochemical detection of IgG4 and C3d on formalin-fixed tissue is advised to be done.

Expression of Beclin-1, an autophagy-related marker, in chronic hepatitis and hepatocellular carcinoma and its relation with apoptotic markers.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in worldwide. Multiple precancerous factors, including infection with hepatitis C virus (HCV), have been studied extensively. Autophagy is a highly regulated process, involved in the turnover of damaged organelles. The relationship between apoptosis and autophagy is still a debated topic especially in HCC. This study aimed to investigate the expression of beclin-1 in chronic hepatitis and HCC and its relation with apoptotic markers. The study included the following: 20 chronic HCV hepatitis cases (first group), 35 HCC cases (second group), and 10 normal tissues as control (third group). All were stained for anti-beclin-1, Bcl-2, Bcl-XL, and Bax antibodies. A significant positive correlation was found between beclin-1 and Bcl-2 among the first group. While a significant inverse correlation was found between them in the second group. A positive correlation was found between beclin-1 and Bcl-XL expression in the first and the second groups. Also positive significant correlations were identified between beclin-1 and Bax in the first and the second groups. Autophagy and apoptosis in the liver are interrelated processes. The high levels of beclin-1 observed in hepatitis may suggest a central role that may limit liver damage and interact with progression to cancer where beclin-1 later on becomes suppressed in aggressive HCC cases. So defective autophagy synergized with defective apoptosis may facilitate tumor progression. Knowledge of the role of autophagic molecules together with apoptotic markers in HCC could lead to improved treatment efficacy and overall prognosis.