Molecular detection of ruminal micro-flora and micro-fauna in Saudi Arabian camels: Effects of season and region.

This study investigated and explored the availability of micro-flora and micro-fauna in the ruminal contents of Arabian camel (Camelus dromedarius) from three different regions in Saudi Arabia along with two seasons. Samples were prepared and tested by conventional polymerase chain reaction (PCR). This study confirmed that the bacterial flora were dominating over other microbes. Different results of the availability of each microbe in each region and season were statistically analyzed and discussed. There was no significant effect of season on the micro-flora or micro-fauna however, the location revealed a positive effect with Ruminococcus flavefaciens (p < 0 0.03) in the eastern region. This study was the first to investigate the abundance of micro-flora and micro-fauna in the ruminal contents of camels of Saudi Arabia. This study underscores the significance of camel ruminal micro-flora and micro-fauna abundance, highlighting their correlation with both seasonality and geographic location. This exploration enhances our comprehension of camel rumination and digestion processes. The initial identification of these microbial communities serves as a foundational step, laying the groundwork for future in-depth investigations into camel digestibility and nutritional requirements.

Detection of Avian Orthoavulavirus-1 genotypes VI.2.1 and VII.1.1 with neuro-viscerotropic tropism in some backyard pigeons (Columbidae) in Eastern Saudi Arabia.

Introduction: Avian orthoavulavirus-1 (AOAV1) has a wide host range, including domestic and wild birds. The present study aimed to identify the currently circulating AOAV1 strains from some outbreaks in some backyard pigeons in the eastern region of Saudi Arabia (ERSA). Methods: Tracheal/cloacal swabs and tissue specimens were collected from eight backyards in Al-Ahsa, ERSA, between January 2021 and March 2023. Samples were tested for the presence of AOAV1 using commercial real-time RT-PCR. Part of the fusion gene was also amplified by gel-based RT-PCR, and the obtained amplicons were sequenced. Results and discussion: AOAV1 was detected in samples from the eight flocks. The retrieved sequences from samples of 6/8 pigeon backyards are reported. Phylogenetic analysis based on the obtained sequences from these backyard pigeons showed the segregation of the obtained sequences in AOAV1 genotypes VI.2.1 and VII.1.1. Clinically, nervous manifestations were dominant in pigeons infected with both genotypes. Respiratory manifestations and significantly higher overall mortality rate were induced by genotype VI.2.1. The deduced amino acid sequences of the fusion protein cleavage site (FPCS) showed that all the detected isolates belong to velogenic strains. Differences in clinical profiles induced by the natural infection of pigeons with AOAV1 genotypes VI.2.1 and VII.1.1 were reported. The present findings highlight the potential roles of some backyard pigeons in the long-distance spread and cross-species transmission of the reported AOAVI genotypes. Further research is required to perform biotyping and pathotyping of the reported strains.

Isolation of chromium resistant bacteria from tannery waste and assessment of their chromium reducing capabilities - A Bioremediation Approach.

Every year different industries generate numerous toxic environmental polluting agents throughout the world. Among the polluting agents, chromium (Cr) toxicity is a great concern nowadays. It is continuously released in soil and water, causing environmental and health problems thereby raising several public health issues in developing countries like Bangladesh. The primary goal of this study was to provide a bioremediation option to reduce toxic hexavalent chromium to a less toxic trivalent form by isolating chromium resistant bacteria from Cr contaminated environments. Bacterial isolates were obtained from seven tannery waste samples collected from Hazaribag and Hemayetpur, Savar, Dhaka. Twenty morphologically distinct colonies were screened, of which six showed the highest resistance. These were designated as A1, A2, B1, F1, K1, and P1. Their maximum tolerance to Cr (VI) was determined through growth assays in varying chromium concentrations up to 8000 mg/L on LB agar media. Strains A2 and B1 exhibited the highest resistances to chromium at 7700 mg/L and 7200 mg/L respectively. Bacterial strains A2 and B1 were identified through several biochemical tests and after PCR analysis finally identified as Bacillus sp. and Micrococcus sp. respectively. Their Cr (VI) reduction capabilities were assessed quantitatively using the diphenylcarbazide colorimetric assay. Both strains exhibit approximately 100% reduction of chromium from 100 mg/L concentration to non-toxic form within 48 h using accurate analytical methods. This study demonstrates the isolation of highly chromium-resistant bacteria from tannery waste that can efficiently bioremediate Cr (VI) pollution, thus providing an eco-friendly and cost-effective bioremediation approach.

The Role of the Vascular System in Degenerative Diseases: Mechanisms and Implications.

Degenerative diseases, encompassing a wide range of conditions affecting various organ systems, pose significant challenges to global healthcare systems. This comprehensive review explores the intricate interplay between the vascular system and degenerative diseases, shedding light on the underlying mechanisms and profound implications for disease progression and management. The pivotal role of the vascular system in maintaining tissue homeostasis is highlighted, as it serves as the conduit for oxygen, nutrients, and immune cells to vital organs and tissues. Due to the vital role of the vascular system in maintaining homeostasis, its dysfunction, characterized by impaired blood flow, endothelial dysfunction, and vascular inflammation, emerges as a common denominator of degenerative diseases across multiple systems. In the nervous system, we explored the influence of vascular factors on neurodegenerative diseases such as Alzheimer's and Parkinson's, emphasizing the critical role of cerebral blood flow regulation and the blood-brain barrier. Within the kidney system, the intricate relationship between vascular health and chronic kidney disease is scrutinized, unraveling the mechanisms by which hypertension and other vascular factors contribute to renal dysfunction. Throughout this review, we emphasize the clinical significance of understanding vascular involvement in degenerative diseases and potential therapeutic interventions targeting vascular health, highlighting emerging treatments and prevention strategies. In conclusion, a profound appreciation of the role of the vascular system in degenerative diseases is essential for advancing our understanding of degenerative disease pathogenesis and developing innovative approaches for prevention and treatment. This review provides a comprehensive foundation for researchers, clinicians, and policymakers seeking to address the intricate relationship between vascular health and degenerative diseases in pursuit of improved patient outcomes and enhanced public health.

Effect of high-fat diet on cerebral pathological changes of cerebral small vessel disease in SHR/SP rats.

Cerebral small vessel diseases (CSVD) are neurological disorders associated with microvessels, manifested pathologically as white matter (WM) changes and cortical microbleeds, with hypertension as a risk factor. Additionally, a high-fat diet (HFD) can affect peripheral vessel health. Our study explored how HFD affects cerebral small vessels in normotensive WKY, hypertensive SHR, and SHR/SP rats. The MRI results revealed that HFD specifically increased WM hyperintensity in SHR/SP rats. Pathologically, it increased WM pallor and vacuolation in SHR and SHR/SP rats. Levels of blood-brain barrier (BBB) protein claudin 5 were decreased in SHR and SHR/SP compared to WKY, with HFD having minimal impact on these levels. Conversely, collagen IV levels remained consistent among the rat strains, which were increased by HFD. Consequently, HFD caused vessel leakage in all rat strains, particularly within the corpus callosum of SHR/SP rats. To understand the underlying mechanisms, we assessed the levels of hypoxia-inducible factor-1α (HIF-1α), Gp91-phox, and neuroinflammatory markers astrocytes, and microglia were increased in SHR and SHR/SP compared to WKY and were further elevated by HFD in all rat strains. Gp91-phox was also increased in SHR and SHR/SP compared to WKY, with HFD causing an increase in WKY but little effect in SHR and SHR/SP. In conclusion, our study demonstrates that HFD, in combined with hypertension, intensifies cerebral pathological alterations in CSVD rats. This exacerbation involves increased oxidative stress and HIF-1α in cerebral vessels, triggering neuroinflammation, vascular basement membrane remodeling, IgG leakage, and ultimately WM damage.

Correction: Shibly et al. Analysis of Cerebral Small Vessel Changes in AD Model Mice. Biomedicines 2023, 11, 50.

In the original publication [...].

Integrating phytoremediation and mycoremediation with biosurfactant-producing fungi for hydrocarbon removal and the potential production of secondary resources.

Treatment of petroleum-contaminated soil to a less toxic medium via physical and chemical treatment is too costly and requires posttreatment. This review focuses on the employment of phytoremediation and mycoremediation technologies in cleaning hydrocarbon-contaminated soil which is currently rare. It is considered environmentally beneficial and possibly cost-effective as it implements the synergistic interaction between plants and biosurfactant producing mycorrhiza to degrade hydrocarbon contaminants. This review also covers possible sources of hydrocarbon pollution in water and soil, toxicity effects, and current technologies for hydrocarbon removal and degradation. In addition to these problems, this review also discusses the challenges and opportunities of transforming the resultant treated sludge and treating plants into potential by-products for a higher quality of life for future generations.

Beneficial probiotic bacteria prevalence in different lactating dromedary camel milk of Saudi Arabia.

Dromedary camel or Arabian camel (Camelus dromedarius) has great economic importance due to its milk and byproducts. Its milk has high nutrition along with healthy bacteria such as Lactic acid bacteria helpful in the fermentation process. The aim was to compare the probiotic bacteria from one week of lactating camel milk vs one year lactating camel milk to differentiate the potential probiotics. This study analyzed the microbiomes of one year lactating raw camel milk M1, M2 (A) (n = 10) and one week of lactating camel milk M3, M4 (B) (n = 10) through metagenomic analysis of 16S rRNA. In total, 276 species were found in two groups (A and B) and they shared 55 genes. Group B showed a higher number of species (2 2 0) than group A (56). The statistical data on functional annotations such as Card, COG, NOG and Swiss-prot revealed at least one or more contributions from this study sample database. The phylum Proteobacteria contributed largely up to 75 % in group B. In contrast, Ascomycota and Verrucomicrobia existed in higher quantity in group A than in group B and Firmicutes were slightly higher in group A than in group B. Actinobacteria were higher in group B whereas Bacteroidetes dominated in group A than group B. The potential probiotic bacteria found in camel milk including Enterococcus faecalis, Enterococcus faecium, Propionibacterium, Streptococcus thermophilus, Solibacillus silvestris and Akkermansia muciniphila. Despite the probiotic bacteria some pathogenic microbes also resided in the studied samples, hence it is strongly recommended proper sterilization before consumption. This proposed research is to get an efficient microbial consortium of beneficial bacteria and their functional roles.

Attenuation of Immunogenicity in MOG-Induced Oligodendrocytes by the Probiotic Bacterium Lactococcus Sp. PO3.

Background and Objectives: Milk is healthy and includes several vital nutrients and microbiomes. Probiotics in milk and their derivatives modulate the immune system, fight inflammation, and protect against numerous diseases. The present study aimed to isolate novel bacterial species with probiotic potential for neuroinflammation. Materials and Methods: Six milk samples were collected from lactating dairy cows. Bacterial isolates were obtained using standard methods and were evaluated based on probiotic characteristics such as the catalase test, hemolysis, acid/bile tolerance, cell adhesion, and hydrophobicity, as well as in vitro screening. Results: Nine morphologically diverse bacterial isolates were found in six different types of cow's milk. Among the isolates, PO3 displayed probiotic characteristics. PO3 was a Gram-positive rod cell that grew in an acidic (pH-2) salty medium containing bile salt and salinity (8% NaCl). PO3 also exhibited substantial hydrophobicity and cell adhesion. The sequencing comparison of the 16S rRNA genes revealed that PO3 was Lactococcus raffinolactis with a similarity score of 99.3%. Furthermore, PO3 was assessed for its neuroanti-inflammatory activity on human oligodendrocyte (HOG) cell lines using four different neuroimmune markers: signal transducer and activator of transcription (STAT-3), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and GLAC in HOG cell lines induced by MOG. Unlike the rest of the evaluated neuroimmune markers, STAT-3 levels were elevated in the MOG-treated HOG cell lines compared to the untreated ones. The expression level of STAT-3 was attenuated in both PO3-MOG-treated and only PO3-treated cell lines. On the contrary, in PO3-treated cell lines, MBP, GFAP, and GLAC were significantly expressed at higher levels when compared with the MOG-treated cell lines. Conclusions: The findings reported in this article are to be used as a foundation for further in vivo research in order to pave the way for the possible use of probiotics in the treatment of neuroinflammatory diseases, including multiple sclerosis.

Mitochondrial DNA sequencing of Kehilan and Hamdani horses from Saudi Arabia.

The Arabian horse breed is well known for its purity and played a key role in the genetic improvement of other horses worldwide. The mitochondrial genome plays a vital role in maternal inheritance and it's helpful to evaluate its genetic diversity and conservation. It has higher mutation rates than nuclear DNA in vertebrates and therefore reveals phylogenetic relationships and haplotypes. In this study, the mitochondrial genome mutations in two Saudi horse strains, Kehilan and Hamdani demonstrated various changes in the gene and amino acid levels and included two other Saudi horses (Hadban and Seglawi) from the previous study for phylogenetic comparison. The whole mitochondrial genome sequencing resulted in intra and inter mtDNA variations between the studied horses. Interestingly, the Hamdani horse has nucleotide substitutions similar to those of the Hadban horse, which is reflected in the phylogenetic tree as a significantly close relationship. This type of study provides a better understanding of mitogenome structure and conservation of livestock species genetic data.

Bacillus subtilis PM5 from Camel Milk Boosts Chicken Immunity and Abrogates Salmonella entertitidis Infections.

With the practice of a successful livestock industry using antibiotics, which has continued for more than five decades, researchers have long been interested in finding alternatives to antibiotics for poultry production. Probiotics can potentially reduce enteric diseases in livestock and enhance their productivity. The aim of this study was to isolate putative probiotics from camel milk and test them against Salmonella infection as well as host immune development. Thirteen different isolates were obtained from six different camel milk samples from dairy farms in Saudi Arabia. Three of the six isolates (PM1, PM2, PM3, PM4, PM5, and PM6) that showed Gram-positive characters reacted negatively to catalase and hemolytic assays. PM1, PM5, and PM6 showed significant nonpolar surface properties (>51% hydrophobic) and potent antimicrobial activities against avian pathogens, namely S. enterica, S. typhi, S. aureus, and E. coli. PM5 exhibited substantial probiotic traits; therefore, further focus was given to it. PM5 was identified as Bacillus subtilis OQ913924 by the 16S rRNA sequencing method and showed similarity matrix > 99%. An in vivo chicken model was used to access the health benefits of probiotics. After salmonella infection, the mucosal immune response was significantly increased (p < 0.01), and none of the challenge protocols caused mortality or clinical symptoms after infection in intestinal contents. S. enterica organ infiltration in the spleen, thymus, and small intestine was significantly reduced in the B. subtilis PM5-fed chickens. The S. enterica load in chicken feces was reduced from CFU 7.2 to 5.2 in oral-fed B. subtilis PM5-fed chickens. Probiotic-fed chickens showed buffered intestinal content and positively regulated the level of butyric acid (p < 0.05), and intestinal interleukin 1 beta (IL1-ß), C-reactive protein (CRP), and interferon gamma (IFN-γ) levels were reduced (p < 0.05). In addition, B. subtilis PM5 showed significant binding to peritoneal macrophages cells and inhibited S. enterica surface adhesion, indicating co-aggregation of B. subtilis PM5 in macrophage cells. It could be concluded that supplementation with probiotics can improve the growth performance of broilers and the quality of broiler chickens against enteric pathogens. The introduction of this probiotic into the commercial poultry feed market in the near future may assist in narrowing the gap that now exists between chicken breeding and consumer demand.

Seasonal variations of vitamin A, D and E levels in serum of female camels (Camelus dromedarius) and their calves raised in five geographic regions of Saudi Arabia.

The aim of this study was to investigate the serum level of fat-soluble vitamins A, D and E in clinically healthy lactating female camel (Camelus dromedarius) and suckling calf > one-year-old during winter and summer seasons in five main regions of Saudi Arabia. 60 sera samples were collected and tested for vitamins A, D and E levels and the results were statistically analyzed. The statistical mean value of vitamin A was within the reported range but for D and E, there were minor variations. The effect of season was insignificant (p > 0.05) for vitamins A and E in the combined results of the dam and newborn together. This seasonal effect was highly significant in dam serum (p < 0.05). Region effect was significant for vitamin A in the northern area (p < 0.05) and for vitamin E in the southern region (p < 0.05). Correlations analysis revealed significant results in the season vs vitamin A and E p < 0.05. Mean values of vitamins A, D and E in dam and newborn did not observe significant variations however, in the season and regions there were significant variations which can be attributed to the climate difference, availability of balanced rations and camel management in each location of the five main regions of Saudi Arabia. There is a great need for further studies and the consequent development of supplementation programs and camel feed manufacturers awareness of such results is highly recommended.

A review of the treatment technologies for hexavalent chromium contaminated water.

The toxicity of hexavalent chromium (Cr(VI)) present in the environment has exceeded the current limits or standards and thus may lead to biotic and abiotic catastrophes. Accordingly, several treatments, including chemical, biological, and physical approaches, are being used to reduce Cr(VI) waste in the surrounding environment. This study compares the Cr(VI) treatment approaches from several areas of science and their competence in Cr(VI) removal. As an effective combination of physical and chemical approaches, the coagulation-flocculation technique removes more than 98% of Cr(VI) in less than 30 min. Most membrane filtering approaches can remove up to 90% of Cr(VI). Biological approaches that involve the use of plants, fungi, and bacteria also successfully eliminate Cr(VI) but are difficult to scale up. Each of these approaches has its benefits and drawbacks, and their applicability is determined by the research aims. These approaches are also sustainable and environmentally benign, thus limiting their effects on the ecosystem.

Synthesis, molecular docking, and biological evaluation of [3,2-b]indole fused 18ß-glycyrrhetinic acid derivatives against skin melanoma.

Melanoma, the most serious yet uncommon type of cancer, originates in melanocytes. Risk factors include UV radiation, genetic factors, tanning lamps and beds. Here, we described the synthesis and selective anti melanoma activity of [3,2-b]indole fused 18ß-glycyrrhetinic acid, a derivative of 18ß-glycyrrhetinic acid in murine B16F10 and A375 human melanoma cell lines. Among the 14 molecules, GPD-12 showed significant selective cytotoxic activity against A375 and B16F10 cell lines with IC50 of 13.38 µM and 15.20 µM respectively. GPD 12 induced the formation of reactive oxygen species in A375 cells that could trigger oxidative stress mediated cell death as is evident from the increased expression of apoptosis related proteins such as caspase-9 and caspase-3 and the increased ratio of Bax to Bcl2. The results showed that GPD 12 can be used as an effective therapeutic agent against melanoma.

Probiotic-Fermented Camel Milk Attenuates Neurodegenerative Symptoms via SOX5/miR-218 Axis Orchestration in Mouse Models.

Multiple sclerosis is an autoimmune-mediated myelin damage disorder in the central nervous system that is widespread among neurological patients. It has been demonstrated that several genetic and epigenetic factors control autoimmune encephalomyelitis (EAE), a murine model of MS, through CD4+ T-cell population quantity. Alterations in the gut microbiota influence neuroprotectiveness via unexplored mechanisms. In this study, the ameliorative effect of Bacillus amyloliquefaciens fermented in camel milk (BEY) on an autoimmune-mediated neurodegenerative model using myelin oligodendrocyte glycoprotein/complete fraud adjuvant/pertussis toxin (MCP)-immunized C57BL6j mice is investigated. Anti-inflammatory activity was confirmed in the in vitro cell model, and inflammatory cytokines interleukins IL17 (from EAE 311 to BEY 227 pg/mL), IL6 (from EAE 103 to BEY 65 pg/mL), IFNγ (from EAE 423 to BEY 243 pg/mL) and TGFß (from EAE 74 to BEY 133 pg/mL) were significantly reduced in BEY-treated mice. The epigenetic factor miR-218-5P was identified and confirmed its mRNA target SOX-5 using in silico tools and expression techniques, suggesting SOX5/miR-218-5p could serve as an exclusive diagnostic marker for MS. Furthermore, BEY improved the short-chain fatty acids, in particular butyrate (from 0.57 to 0.85 µM) and caproic (from 0.64 to 1.33 µM) acids, in the MCP mouse group. BEY treatment significantly regulated the expression of inflammatory transcripts in EAE mice and upregulated neuroprotective markers such as neurexin (from 0.65- to 1.22-fold) (p < 0.05), vascular endothelial adhesion molecules (from 0.41- to 0.76-fold) and myelin-binding protein (from 0.46- to 0.89-fold) (p < 0.03). These findings suggest that BEY could be a promising clinical approach for the curative treatment of neurodegenerative diseases and could promote the use of probiotic food as medicine.

Alzheimer's Amyloid ß Peptide Induces Angiogenesis in an Alzheimer's Disease Model Mouse through Placental Growth Factor and Angiopoietin 2 Expressions.

Increased angiogenesis, especially the pathological type, has been documented in Alzheimer's disease (AD) brains, and it is considered to be activated due to a vascular dysfunction-mediated hypoxic condition. To understand the role of the amyloid ß (Aß) peptide in angiogenesis, we analyzed its effects on the brains of young APP transgenic AD model mice. Immunostaining results revealed that Aß was mainly localized intracellularly, with very few immunopositive vessels, and there was no extracellular deposition at this age. Solanum tuberosum lectin staining demonstrated that compared to their wild-type littermates, the vessel number was only increased in the cortex of J20 mice. CD105 staining also showed an increased number of new vessels in the cortex, some of which were partially positive for collagen4. Real-time PCR results demonstrated that placental growth factor (PlGF) and angiopoietin 2 (AngII) mRNA were increased in both the cortex and hippocampus of J20 mice compared to their wild-type littermates. However, vascular endothelial growth factor (VEGF) mRNA did not change. Immunofluorescence staining confirmed the increased expression of PlGF and AngII in the cortex of the J20 mice. Neuronal cells were positive for PlGF and AngII. Treatment of a neural stem cell line (NMW7) with synthetic Aß1-42 directly increased the expression of PlGF and AngII, at mRNA levels, and AngII at protein levels. Thus, these pilot data indicate that pathological angiogenesis exists in AD brains due to the direct effects of early Aß accumulation, suggesting that the Aß peptide regulates angiogenesis through PlGF and AngII expression.

Response Surface Methodology (RSM) Approach to Optimization of Coagulation-Flocculation of Aquaculture Wastewater Treatment Using Chitosan from Carapace of Giant Freshwater Prawn Macrobrachium rosenbergii.

The major sources of waste from aquaculture operations emanates from fish or shellfish processing and wastewater generation. A simple technique called coagulation/flocculation utilizes biowaste from aquaculture to produce chitosan coagulant for wastewater treatment. A chemical method was applied in the present study for chitin and chitosan extraction from carapace of Macrobrachium rosenbergii and subsequent application for removal of turbidity and salinity from shrimp aquaculture wastewater. Box-Behnken in RSM was used to determine the optimum operating conditions of chitosan dosage, pH, and settling time, after which quadratic models were developed and validated. Results show that 80 g of raw powder carapace yielded chitin and chitosan of 23.79% and 20.21%, respectively. The low moisture (0.38%) and ash (12.58%) content were an indication of good quality chitosan, while other properties such as water-binding capacity (WBC), fat-binding capacity (FBC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscope (SEM) confirmed the structure and the α-group, as well as the rough morphology of chitosan. In addition, the high solubility (71.23%) and DDA (85.20%) suggested good coagulant potentials. It was recorded in this study that 87.67% turbidity was successfully removed at 20 mg/L of chitosan dosage and 6.25 pH after 30 min settling time, while 21.43% salinity was removed at 5 mg/L of chitosan dosage, 7.5 pH, and 30 min settling time. Therefore, the process conditions adopted in this study yielded chitosan of good quality, suitable as biopolymer coagulant for aquaculture wastewater treatment.

Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers.

Multiple sclerosis (MS), a distinct autoimmune neuroinflammatory disorder, affects millions of people worldwide, including Saudi Arabia. Changes in the gut microbiome are linked to the development of neuroinflammation via mechanisms that are not fully understood. Prebiotics and probiotics in camel milk that has been fermented have a variety of health benefits. In this study, Bacillus amyloliquefaciens-supplemented camel milk (BASY) was used to assess its preventive effect on MS symptoms in a myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL6J mice model. To this end, MOG-induced experimental autoimmune encephalomyelitis (EAE) was established and the level of disease index, pathological scores, and anti-inflammatory markers of BASY-treated mice using macroscopic and microscopic examinations, qPCR and immunoblot were investigated. The results demonstrate that BASY significantly reduced the EAE disease index, increased total microbial load (2.5 fold), and improved the levels of the short-chain fatty acids propionic, butyric and caproic acids in the diseased mice group. Additionally, myeloperoxidase (MPO) proinflammatory cytokines (IL-1ß, IL-6, IL-17, TNF-α) and anti-inflammatory cytokines (TGF-ß) were regulated by BASY treatment. Significant suppression of MPO and VCAM levels were noticed in the BASY-treated group (from 168 to 111 µM and from 34 to 27 pg/mL, respectively), in comparison to the EAE group. BASY treatment significantly reduced the expression of inflammatory cytokines, inflammatory progression related transcripts, and inflammatory progression protein markers. In conclusion, BASY significantly reduced the symptoms of EAE mice and may be used to develop a probiotic-based diet to promote host gut health. The cumulative findings of this study confirm the significant neuroprotection of BASY in the MOG-induced mice model. They could also suggest a novel approach to the treatment of MS-associated disorders.

Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults.

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.

Analysis of the time-dependent changes of phospholipids in the brain regions of a mouse model of Alzheimer's disease.

Phospholipid levels are reported to be decreased in Alzheimer's disease (AD). For a better understanding, we investigated the time-dependent changes of phospholipids species in a mouse model of AD. The levels of phospholipids in the hippocampus and prefrontal cortex of wild-type and APP-Tg (J20) mice were measured by LC-ESI-MS/MS. Compared to wild-type, total phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (LPC) were Increased at 3 months but decreased at 6 months in the cortex of J20 mice. Total lysophosphatidylethanolamine (LPE) was decreased both at 3 and 6 months. PC was decreased and LPC was increased at 6 months, resulting in an increased LPC/PC ratio in the hippocampus of J20 mice. At species levels, PCA analysis could discriminate wild-type and J20 based on PC and LPC distribution at 6 months. At 6 months, several highly abundant PC including PC (16:0/16:0), PC (16:0/18:0), PC (16:0/18:1), and PC (18:0/18:1) were decreased in the cortex and hippocampus of J20. Conversely, LPC species including LPC 16:0, LPC 18:1, and LPC 20:4 were increased especially in the hippocampal area. Increased activation of phospholipid-metabolizing enzyme cPLA2 was seen in the hippocampus and cortex of J20 mice at 9 months. On the other hand, ROS levels started to increase as early as 3 months. Compared to 3 months, ROS levels were higher at 6 months in J20 mice. Thus, we demonstrated here a time- and area-dependent alteration of phospholipid composition during the early stage of AD, which could be important in understanding the pathological process.