Impacts of epidural electrical stimulation on Wnt signaling, FAAH, and BDNF following thoracic spinal cord injury in rat.

Electrical stimulation (ES) has been shown to improve some of impairments after spinal cord injury (SCI), but the underlying mechanisms remain unclear. The Wnt signaling pathways and the endocannabinoid system appear to be modulated in response to SCI. This study aimed to investigate the effect of ES therapy on the activity of canonical/noncanonical Wnt signaling pathways, brain-derived neurotrophic factor (BDNF), and fatty-acid amide hydrolase (FAAH), which regulate endocannabinoids levels. Forty male Wistar rats were randomly divided into four groups: (a) Sham, (b) laminectomy + epidural subthreshold ES, (c) SCI, and (d) SCI + epidural subthreshold ES. A moderate contusion SCI was performed at the thoracic level (T10). Epidural subthreshold ES was delivered to upper the level of T10 segment every day (1 hr/rat) for 2 weeks. Then, animals were killed and immunoblotting was used to assess spinal cord parameters. Results revealed that ES intervention for 14 days could significantly increase wingless-type3 (Wnt3), Wnt7, ß-catenin, Nestin, and cyclin D1 levels, as well as phosphorylation of glycogen synthase kinase 3ß and Jun N-terminal kinase. Additionally, SCI reduced BDNF and FAAH levels, and ES increased BDNF and FAAH levels in the injury site. We propose that ES therapy may improve some of impairments after SCI through Wnt signaling pathways. Outcomes also suggest that BDNF and FAAH are important players in the beneficial impacts of ES therapy. However, the precise mechanism of BDNF, FAAH, and Wnt signaling pathways on SCI requires further investigation.

The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats.

BACKGROUND: The manipulation of gut microbiota as a target has been suggested to reduce the risks for a number of diseases such as type 2 diabetes mellitus (T2DM). Conversely, T2DM is associated with complications such as gut and brain disorders. Furthermore, the impact of probiotics and prebiotics to improve T2DM complications are reported. Thus, the present study seeks to investigate the therapeutic and neuropsychological effects of L. plantarum and inulin in diabetic rats. METHODS: Throughout the investigation, L. plantarum, inulin or their combination (synbiotic) was administered to diabetic rats. in the end, fecal samples were collected to evaluate the gut microbial composition. Then behavioral tests were conducted. Subsequently, the obtainment of the prefrontal cortex (PFC) and hippocampal samples. RESULTS: Our data demonstrated that administration of L. plantarum and inulin could improve gut dysbiosis and oxidative stress status. In addition, it could ameliorate serotonin and BDNF/TrkB signaling pathway. Notably, a strong correlation between the gut microbiota changes and cognition responses was observed. Interestingly, synbiotics intake exploited a rather powerful effect on oxidative stress markers. CONCLUSION: The findings confirm that there is a beneficial therapeutic potential of supplements, especially symbiotic. Moreover, neuropsychological improvement associated with balanced gut microbiome.

Immunomodulatory and anti-inflammatory effects of probiotics in multiple sclerosis: a systematic review.

Multiple sclerosis (MS) is an inflammatory and autoimmune neurological disorder which leads to demyelination. Although the etiology of MS is yet to be known, it appears that regulating the immune system and suppressing inflammatory pathways may possibly have a favorable effect on the healing of this disease. Evidence suggests that probiotics consumption via gut microbiome alteration devises beneficial effects in improving immune and inflammatory responses in MS. All articles were systematically searched (in the main databases) for this paper. Two investigators independently scrutinized full texts of the potentially eligible articles. The quality of the study was evaluated using standardized tools. The methodological quality of seven studies included in this review ranged from fair to good. The findings illustrated that there were statistically significant improvements in the static and dynamic balance in patients and animals with MS. In the paper in hand, the effects of probiotics administration on immune and inflammatory markers in MS disease are evaluated. In addition, the limitations and knowledge gaps were reported while proposing a possible mechanism of probiotics therapy in modulating immune and inflammatory responses. This systematic review indicated that the probiotics could improve immune and inflammatory parameters, the cytokines and cells in MS disease. Probiotics may have efficient effects in management and treatment of MS. More studies are required to clarify the effect of supplementation with probiotics and their mechanisms in MS disease.

Correction to: The novel insight into anti-inflammatory and anxiolytic effects of psychobiotics in diabetic rats: possible link between gut microbiota and brain regions.

The original version of this article unfortunately contained a mistake in the order of the author list.

The novel insight into anti-inflammatory and anxiolytic effects of psychobiotics in diabetic rats: possible link between gut microbiota and brain regions.

PURPOSE: Type 2 diabetes mellitus (T2DM) was associated with gut microbial impairment (dysbiosis) and neurological and behavioral disorders. The role of the gut-brain axis in the management of many diseases including T2DM has been the focus of much research activity in the recent years. However, a wide knowledge gap exists about the gut microbial effects on the function of glia cells. Hence, the present study was aimed to examine the effects of psychobatics on dysbiosis and glia cells function in enteric and central nervous system with an inflammatory insight in T2DM. METHODS: Thirty rats were treated by Lactobacillus (L.) plantarum, inulin, or their combination (synbiotic) for 8 weeks after inducing T2DM. Fecal sample was collected to evaluate gut microbial composition. Then, the rats were sacrificed, and the colon, amygdala, and prefrontal cortex (PFC) were studied. RESULTS: T2DM resulted in dysbiosis and increased levels of glial cell-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), and inflammatory markers (IL-17, IL-6, and TLR-2) in the colon and brain. However, concurrent supplementation of L. plantarum and inulin could improve the gut microbial composition as well as reduce the levels of inflammatory cytokines. While the administration of L. plantarum led to a significant decrease in TLR-2 as well as GDNF and GFAP only in the amygdala, the synbiotic intake could make such changes in the colon, amygdala, and PFC. CONCLUSIONS: Our findings demonstrated an innovative approach to the beneficial effects of psychobiotics in neuroinflammation and behavioral performance through gut microbiota changes, focusing on possible role of glial cells in gut-brain axis.

Apoptosis and myocardial infarction: role of ncRNAs and exosomal ncRNAs.

ncRNAs, particularly miRNAs, lncRNAs and circRNAs, are a group of RNAs which, although they do not encode proteins (however, recent evidence shows that certain circRNAs are translatable), play a major role in regulating gene expression and, therefore, affect multiple cellular processes, in particular apoptosis. Apoptosis is proven to mediate myocardial infarction physiopathology in addition to ischemic necrosis and, therefore, has recently gained great interest as a target to improve MI outcomes. The current work reviews studies that have assessed ncRNAs with the ability to promote or suppress apoptosis in the process of MI and, therefore, may introduce new therapeutic targets for MI treatment.

From the gut to the heart: L. plantarum and inulin administration as a novel approach to control cardiac apoptosis via 5-HT2B and TrkB receptors in diabetes.

BACKGROUND & AIMS: Type 2 diabetes mellitus, as a metabolic disorder, can lead to diabetic cardiomyopathy, identified by cardiomyocyte apoptosis and myocardial fibrosis. Brain-derived neurotrophic factor (BDNF) and serotonin are two neurotransmitters that can control cardiomyocyte apoptosis and myocardial fibrosis through their cardiac receptors. In the present study, we investigated the impacts of L. plantarum and inulin supplementation on the inhibition of cardiac apoptosis and fibrosis by modulating intestinal, serum, and cardiac levels of serotonin and BDNF as well as their cardiac receptors. METHODS: Diabetes was induced by a high-fat diet and streptozotocin in male Wistar rats. Rats were divided into six groups and were supplemented with L. plantarum, inulin or their combination for 8 weeks. Finally, the rats were killed and levels of intestinal, serum, and cardiac parameters were evaluated. RESULTS: Concurrent administration of L. plantarum and inulin caused a significant rise in the expression of cardiac serotonin and BDNF receptors (P < 0.001) as well as a significant fall in cardiac interstitial and perivascular fibrosis (P < 0.001, both) and apoptosis (P = 0.01). Moreover, there was a strong correlation of cardiac 5-Hydroxytryptamine 2B (5-HT2B) and tropomyosin receptor kinase B (TrkB) receptors with interstitial/perivascular fibrosis and apoptosis (P < 0.001, both). CONCLUSIONS/INTERPRETATION: Results revealed beneficial effects of L. plantarum, inulin or their combination on intestinal, serum, and cardiac serotonin and BDNF accompanied by higher expression of their cardiac receptors and lower levels of cardiac apoptotic and fibrotic markers. It seems that L. plantarum and inulin supplementation could be considered as a novel adjunct therapy to reduce cardiac complications of type 2 diabetes mellitus.

Antioxidative and Metabolic Effects of Lactobacillus plantarum, Inulin, and Their Synbiotic on the Hypothalamus and Serum of Healthy Rats.

Nowadays, much attention has been paid to the link between gut microbiota and brain. The beneficial metabolic effects of probiotics and prebiotics in several diseases such as diabetes and obesity have been reported. However, studies bridging the association of gut microbiome with brain function in healthy states are rare. Therefore, it was hypothesized that the administration of Lactobacillus plantarum (L plantarum) and inulin may affect serum and hypothalamic metabolic parameters as well as oxidative markers in healthy male rats. Daily L plantarum (107 CFU/mL) and inulin (5% of daily food weight) or their combination (synbiotic) was given to healthy rats. Then, serum and hypothalamic levels of leptin, insulin, and oxidative markers were measured. Administration of synbiotic for 8 weeks led to significant changes in serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, low-density lipoprotein/high-density lipoprotein ratio, triglyceride, and total cholesterol. The intake of synbiotic also resulted in a significantly reduced hypothalamic level of malondialdehyde and increased hypothalamic superoxide dismutase (SOD). Also, L plantarum could significantly increase hypothalamic SOD level. Furthermore, synbiotic administration insignificantly increased the hypothalamic and serum levels of insulin and leptin. These findings suggest that the synbiotic could significantly improve oxidative markers and lipid profile in healthy rats. Therefore, simultaneous intake of L plantarum and inulin appears to be more effective in the amelioration of metabolic and oxidative parameters.

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives.

BACKGROUND & AIMS: In our previous study, a Seesaw model was proposed for the fluctuation of crucial anti- (IL-10) and pro-inflammatory (Il-6 & IL-17A) cytokines through vitamin D3. In this paper, however, it is intended to extend the mentioned model by assessing the expression mRNA levels of IL-27 and TGF-ß1 as well as the changes of plasma levels of IL-27, TGF-ß1, IL-17A, IL-10, and IL-6 after treatment by vitamin D3. METHOD: Venous blood samples were drawn from Healthy Participants (HP, n = 25) and First-Degree Relative Participants (FDRP, n = 25) as control groups and Multiple Sclerosis Participants (MSP, n = 25) before and after eight weeks of supplementation with 50000 IU vitamin D3. The mRNA expression and plasma concentrations were gauged by using Real-Time PCR and ELISA assay, respectively. RESULTS: The mRNA surfaces of IL-27, as well as TGF-ß1, were up-regulated. However, the plasma levels of TGF-ß1, IL-17A, and IL-6 were significantly different among the three groups. In addition, the plasma levels of IL-27, TGF-ß1, IL-10, IL-17A, and IL-6 significantly changed following the administration of vitamin D3. CONCLUSION: The findings of this paper illustrate that anti-inflammatory cytokines could have a key role in immunomodulatory functions due to their anti-inflammatory functions. To conclude, this might contribute to preventing the pathophysiological process of MS. Also, the proposed model could be used as a preventive way on disposed people to multiple sclerosis, particularly in first degree relatives of these patients.

Lactobacillus plantarum And Inulin: Therapeutic Agents to Enhance Cardiac Ob Receptor Expression and Suppress Cardiac Apoptosis in Type 2 Diabetic Rats.

BACKGROUND: T2DM may cause increased levels of oxidative stress and cardiac apoptosis through elevated blood glucose. The present study investigated the effects of Lactobacillus plantarum (L. plantarum) as a probiotic strain and inulin as a prebiotic supplement on cardiac oxidative stress and apoptotic markers in type 2 diabetes mellitus (T2DM) rats. METHODS: A high-fat diet and a low dose of streptozotocin were used to induce type 2 diabetes. The rats were divided into six groups which were supplemented with L. plantarum, inulin, or their combination for 8 weeks. RESULTS: The results showed improved activity of cardiac antioxidant parameters including total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (P < 0.001, P < 0.01, and P < 0.01, respectively) and decreased level of cardiac malondialdehyde (MDA) concentration (P < 0.05). These changes were accompanied with increased protein expression of cardiac obesity receptor (Ob-R) (P = 0.05) and reduced apoptotic markers such as tumor necrosis factor-alpha (TNF-α), Fas ligand (FasL), and caspase proteins (P < 0.001, P = 0.003, and P < 0.01, respectively) in T2DM rats after concurrent L. plantarum and inulin supplementation. Moreover, a remarkable correlation of cardiac Ob-R and oxidative stress parameters with cardiac apoptotic markers was observed (P < 0.01). CONCLUSION: The concurrent use of L. plantarum and inulin seems to be beneficial, as they can lead to decreased heart complications of T2DM via reducing cardiac apoptotic markers.

Preventive and Tumor-Suppressive Effects of Lactobacillus Paracasei X12 in Rat Model of Colorectal Cancer.

The paper in hand seeks to evaluate the tumor-suppressive and apoptotic effects of L. paracasei X12 in 1, 2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. The rats were divided into three groups (n = 8-12 per group); L. paracasei X12 was administrated to these animals for forty weeks. The findings of this study indicated that L. paracasei X12 administration prevented severe weight loss in DMH-treated rats. It was also determined that L. paracasei X12 administration could prevent the neoplasia incidence, cell proliferation and it also could suppress the tumors' growth. Additionally, a significant improvement was observed in apoptosis indexes and cell proliferation in probiotic-treated rats. In conclusion, this study provides insights into the therapeutic potential of L. paracasei X12 with emphasis on the issue that modulation of apoptosis pathway could leave beneficial effects in the prevention and suppression of colorectal cancer (CRC). However, further studies are in support to clarify the mechanisms involved in the tumor-suppressive effect of probiotics.

The potential therapeutic effects of Lactobacillus plantarum and inulin on serum and testicular reproductive markers in diabetic male rats.

BACKGROUND: It is well established that diminished reproductive health is one of the notable long-term outcomes of type 2 diabetes mellitus (T2DM), especially among males. Due to the global increasing rate of T2DM and infertility, we aimed to investigate the impact of Lactobacillus plantarum (L. plantarum), inulin, and their combinatory supplementation on fertility markers as well as testicular kisspeptin and androgen receptor (AR)'s expression in diabetic male rats. METHODS: Thirty-five Male Wistar rats with Streptozotocin-induced T2DM were supplemented with L. plantarum, inulin, or their combination for 8 weeks. At the end-point, the animals were sacrificed and serum, testicular, and seminal parameters were studied. RESULTS: Administration of L. plantarum and inulin in diabetic male rats improved sperm motility and viability (P < 0.001, both) as well as testicular tissue development via increasing leydig cell number, testicular spermatid count, and diameter of seminiferous tubules (P < 0.001, all). Testicular expression of Kisspeptin was elevated by inulin supplementation (P = 0.01). L. plantarum administration increased testicular AR expression (P = 0.01). The expression of Kisspeptin showed a remarkable correlation with fertility markers (P < 0.001). CONCLUSION: Supplementation with either L. plantarum, inulin, or their combination can prevent infertility caused by T2DM in male rats via improving testicular kisspeptin and AR expression, leydig cell count, and effectively increasing epididymal sperm motility and viability.

Anti-inflammatory effects of dietary vitamin D3 in patients with multiple sclerosis.

OBJECTIVE: To assess the effects of dietary vitamin D3 on proinflammatory (interleukin-17A [IL-17A] and IL-6) and anti-inflammatory (IL-10) cytokines. METHODS: Our study was conducted on 75 participants who were divided into 3 groups: multiple sclerosis participants (MSPs, n = 25), first-degree relative participants (FDRPs, n = 25), and healthy participants (HPs, n = 25). All groups received 50,000 IU vitamin D3/wk for 8 weeks. Serum 25-(OH) vitamin D3 levels and messenger RNA (mRNA) expression levels of ILs were determined using electrochemiluminescence assay and real-time PCR, respectively. RESULTS: Vitamin D3 affected the levels of IL-17A, IL-10, and IL-6 among the 3 groups (p < 0.001 for all). Levels of IL-17A (MSPs: fold change [FC] = 5.9, p = 0.014; FDRPs: FC = 5.2, p = 0.006; HPs: FC = 4.2, p = 0.012) and IL-6 (MSPs: FC = 5.6, p = 0.003; FDRPs: FC = 5.5, p = 0.002; HPs: FC = 5.1, p < 0.001) were downregulated after vitamin D3 treatment. In addition, levels of IL-10 (MSPs: FC = 6.2, p = 0.005; FDRPs: FC = 4.6, p < 0.001; HPs: FC = 5.2, p < 0.001) were upregulated after 8 weeks. CONCLUSIONS: Although supplementation with vitamin D3 reduced the mRNA expression levels of IL-17A and IL-6, it increased the mRNA expression level of IL-10 in all groups. However, these effects were more considerable in the MSP group than in the other groups. Of interest, in a deficiency state of serum vitamin D3, IL-17A expression had a positive feedback effect on the expression of IL-6. Conversely, in the sufficient state, IL-10 expression had a negative feedback effect on the expression of IL-17A and IL-6.

Beneficial psychological effects of novel psychobiotics in diabetic rats: the interaction among the gut, blood and amygdala.

Type 2 diabetes mellitus (T2DM) can lead to major complications such as psychiatric disorders which include depressive and anxiety-like behaviors. The association of the gut-brain axis in the development of such disorders, especially in T2DM, has been elucidated; however, gut dysbiosis is also reported in patients with T2DM. Hence, the regulation of the gut-brain axis, in particular, the gut-amygdala, as a vital region for the regulation of behavior is essential. Thirty-five male Wistar rats were divided into six groups. To induce T2DM, treatment groups received high-fat diet and 35 mg/kg streptozotocin. Then, supplements of Lactobacillus plantarum, inulin or their combination were administered to each group for 8 weeks. Finally, the rats were sacrificed for measurement of blood and tissue parameters after behavioral testing. The findings demonstrated the favorable effects of the psychobiotics (L. plantarum, inulin or their combination) on oxidative markers of the blood and amygdala (superoxide dismutase, glutathione peroxidase, malondialdehyde and total antioxidant capacity), as well as on concentrations of amygdala serotonin and brain-derived neurotrophic factor, in the diabetic rats. In addition, beneficial effects were observed on the elevated plus maze and forced swimming tests with no change in locomotor activity of the rats. There was a strong correlation between the blood and amygdala oxidative markers, insulin and fasting blood sugar with depressive and anxiety-like behaviors. Our results identified L. plantarum ATCC 8014 and inulin or their combination as novel psychobiotics that could improve the systemic and nervous antioxidant status and improve amygdala performance and beneficial psychotropic effects.