Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research.

First seen as a storage organ, the white adipose tissue (WAT) is now considered as an endocrine organ. WAT can produce an array of bioactive factors known as adipokines acting at physiological level and playing a vital role in energy metabolism as well as in immune response. The global effect of adipokines in metabolic activities is well established, but their impact on the physiology and the pathophysiology of the central nervous system (CNS) remains poorly defined. Adipokines are not only produced by the WAT but can also be expressed in the CNS where receptors for these factors are present. When produced in periphery and to affect the CNS, these factors may either cross the blood brain barrier (BBB) or modify the BBB physiology by acting on cells forming the BBB. Adipokines could regulate neuroinflammation and oxidative stress which are two major physiological processes involved in neurodegeneration and are associated with many chronic neurodegenerative diseases. In this review, we focus on four important adipokines (leptin, resistin, adiponectin, and TNFα) and one lipokine (lysophosphatidic acid-LPA) associated with autotaxin, its producing enzyme. Their potential effects on neurodegeneration and brain repair (neurogenesis) will be discussed. Understanding and regulating these adipokines could be an interesting lead to novel therapeutic strategy in order to counteract neurodegenerative disorders and/or promote brain repair.

Autotaxin downregulates LPS-induced microglia activation and pro-inflammatory cytokines production.

Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death, and survival. We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A +) microglia were treated with LPS. Tumor necrosis factor α (TNFα), interleukin (IL)-6, and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1, and B7.2) were determined by flow cytometry. ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFα and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1, and B7.2 expressions were reduced in A+ cells. Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation.

Fecal prevalence of Campylobacter spp. in house dogs in Lebanon: A pilot study.

Background and Aim: Campylobacter spp. are Gram-negative bacilli that are widely recognized as a primary cause of bacterial gastroenteritis worldwide. Campylobacteriosis is the disease caused by this pathogen. Recently, greater attention has been given to the prevalence of campylobacteriosis in different animals, including pets. These animals are considered to be significant reservoirs for this zoonosis. In Lebanon, the occurrence of Campylobacter infection is high. Our first-of-its-kind pilot study in Lebanon aimed to estimate the fecal prevalence of Campylobacter species in house dogs. Materials and Methods: Thirty-five rectal swabs were collected from male and female house dogs of different ages, both with or without diarrhea. Samples obtained from the dogs were subjected to qualitative microbiological culture testing and molecular diagnosis by polymerase chain reaction assays after bacterial DNA extraction. Results: Fecal prevalence of Campylobacter spp. in house dogs in this study was 17%. There was a relatively higher prevalence among young females and a significant difference between healthy dogs and those suffering from diarrhea. Conclusion: Campylobacteriosis was found to be prevalent among house dogs in Lebanon, making them potential carriers of Campylobacter species.

Prevalence of Campylobacter spp. in broilers in North Lebanon.

Background and Aim: Great attention has been given recently to the prevalence of different Campylobacter spp. in poultry since the latter are considered the major contributing reservoir of human campylobacteriosis. In Lebanon, the occurrence of campylobacteriosis in humans is high. The aim of our first-of-its-kind study in the country was to estimate the prevalence of Campylobacter spp. in broilers from a convenient sample of farms in North Lebanon. Materials and Methods: One hundred twenty-five fecal samples were collected from 25 broiler farms, which were selected, examined, and classified according to their biosecurity level and rearing system. All samples were subjected to qualitative microbiological culture testing and polymerase chain reaction (PCR) assays to detect Campylobacter spp. Results: Despite the reported use of antibiotics, cell culture and PCR were positive for 44% and 88%, respectively. This implies that this bacterium is resistant to antibiotics used on the farms. Furthermore, Campylobacter infection rate was higher in open (92%) than in closed (85%) system farms. All farms with poor biosecurity measures, and 82% of farms with good biosecurity measures had Campylobacter infections, and the difference was significant (p < 0.05). Conclusion: Our results show that campylobacteriosis was found prevalent among broilers in North Lebanon, making them potential carriers of Campylobacter spp. Future studies should include antibiotic susceptibility testing to check the susceptibility pattern of isolates.

Exposure to an organometal compound stimulates adipokine and cytokine expression in white adipose tissue.

OBJECTIVE: White adipose tissue (WAT) is now considered a defined tissue capable of interactions with other organ systems. WAT role in elevating the level of systemic chronic inflammation suggests that alterations in this tissue as the result of disease or environmental factors may influence the development and progression of various obesity-related pathologies. This study investigated WAT cell-specific responses to an organometal compound, trimethyltin (TMT), to determine possible contribution to induced inflammation. METHODS: Human primary mature adipocytes and macrophage differentiated THP-1 cells were cultured in TMT presence and relative toxicities and different adipokine levels were determined. The inflammatory response was examined in TMT presence for primary cells from obese ob/ob mice WAT, and after TMT injection in ob/ob mice. RESULTS: Both adipocytes and macrophages were resistant to cell death induced by TMT. However, adipocytes cultured in TMT presence showed increased expression of TNFα and IL-6, and modified leptin levels. In macrophage cultures, TMT also increased TNFα and IL-6, while MCP-1 and MIP-1α were decreased. In vivo, a single injection of TMT in ob/ob mice, elevated TNFα, MIP-1α and adiponectin in WAT. CONCLUSIONS: Elevation of the inflammatory related products can be induced by chemical exposure in adipocytes and macrophages, as well as murine WAT. These data suggest that numerous factors, including a systemic chemical exposure, can induce an inflammatory response from the WAT. Furthermore, when characterizing both chemical-induced toxicity and the progression of the chronic inflammation associated with elevated WAT content, such responses in this target tissue should be taken into consideration.

Food shopping and food hygiene related knowledge and practices during the COVID-19 pandemic: The case of a developing country.

The aim of this study was to assess the level of food hygiene and food shopping knowledge and practices among residents of Lebanon during the COVID-19 pandemic, and to identify their socio-demographic determinants. A cross-sectional study was conducted through an online questionnaire composed of 13 questions about demographics, and 25 questions related to knowledge and practices in terms of hand maintenance, mask placing, and food shopping. A total of 1337 participants filled the survey. On average, participants scored 73±15 and 67±17% on food hygiene and knowledge and practices, respectively. In terms of best practices by section, they scored 77±22, 51±42, and 65±23% on hand maintenance, mask placing and shopping, respectively. Hand maintenance best practices score was significantly (p<0.05) affected by gender; mask placing best practices score was significantly affected by age and major of study; shopping best practices score was significantly affected by gender; overall best practices score was significantly affected by gender and major of study; food hygiene knowledge score was significantly affected by gender, age, marital status, educational level, and major of study. Food hygiene practices and knowledge scores were significantly (p<0.001) related with a weak correlation coefficient (R=0.114). No study has determined the food hygiene and shopping knowledge and practices during the COVID-19 pandemic in a developing country before.

Repressive effect of Rhus coriaria L. fruit extracts on microglial cells-mediated inflammatory and oxidative stress responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhus coriaria L. represents a herbal shrub that is used widely in traditional medicine in the Middle East region to treat different diseases including inflammation-related disorders. R. coriaria extracts have been well characterized in terms of their biological activities, pharmacological potential and phytochemical components. However, the effect of R. coriaria on neuro-inflammation has not been studied previously in detail. AIM OF THE STUDY: In the present study, we performed a qualitative phytochemical analysis and investigated the antioxidant and anti-neuro-inflammatory potential of R. coriaria extracts on BV-2 microglial cells. MATERIALS AND METHODS: R. coriaria extracts were prepared using two different solvents: distilled water and ethanol. Phytochemical screening was performed to determine the principal bioactive components. The radical scavenging activity was assessed by DPPH method (2,2-diphenyl-1-picrylhydrazyl). The effect of R. coriaria on neuro-inflammation was studied upon measuring the production of oxidative stress and inflammatory factors using DCF (2',7'-dichlorofluorescein) and Nitric oxide (NO) assays respectively, and by analyzing the mRNA (TNFα, IL-10, iNOS and COX-2) and protein (NFκß) levels of genes involved BV-2 microglia cells-mediated inflammation using quantitative Real Time PCR and Western blot, respectively. RESULTS: We found that R. coriaria extracts contain high phenolic and flavonoid contents. Interestingly, the ethanolic extract exerted a potent anti-inflammatory potential on insulted BV-2 cells manifested by: i) inhibition of Reactive Oxygen species (ROS) production and nitric oxide (NO) release; ii) suppressing TNFα, iNOS and COX-2 mRNA levels; iii) reducing NFκß activation; and iiii) enhancing IL-10 transcription levels. CONCLUSION: Our results indicate that the neuro-inflammation inhibitory activity of R. coriaria extracts involves the inhibition of NF-κB signaling pathway. These findings suggest that R. coriaria might carry therapeutic potential against neurodegenerative diseases.

Prevalence, Laboratory Findings and Clinical Characteristics of Campylobacteriosis Agents among Hospitalized Children with Acute Gastroenteritis in Lebanon.

PURPOSE: Campylobacter species are currently the most common cause of bacterial gastroenteritis. In Lebanon, Campylobacter infection occurrence is underdiagnosed owing to the lack of specific culture and rapid test kits, particularly among children. This study aimed to evaluate the prevalence, laboratory findings, and clinical characteristics of Campylobacter infection in hospitalized children with acute gastroenteritis in South Lebanon. METHODS: We conducted a 6-month retrospective cohort study between January and June 2018, including 291 children aged between 1 month and 12 years, who were admitted to a tertiary healthcare center in South Lebanon. The medical files of the patients were reviewed to retrieve the required clinical information, including clinical and laboratory data. RESULTS: The prevalence of campylobacteriosis agents in pediatric patients with acute gastroenteritis is 12.02%. Patients infected with Campylobacter had more severe acute gastroenteritis than Campylobacter-negative patients and often presented with high-grade fever, diarrhea episodes more than six times per day, diarrhea lasting for more than five days, and dehydration. Indeed, children with high-grade fever (≥38.5°C) were five times more likely to test positive for Campylobacter than those with low-grade fever. In addition, the results showed a higher Vesikari score for the majority of Campylobacter-positive patients with severe acute gastroenteritis compared to a moderate profile for Campylobacter-negative patients. CONCLUSION: The present study findings highlight that Campylobacter infection is frequent among children with acute gastroenteritis. Therefore, the detection of Campylobacter should be carried out for the diagnosis of human gastroenteritis in Lebanon, along with the detection of routine enteropathogens.

Seroprevalence of Brucella abortus in cattle in Southern Lebanon using different diagnostic tests.

BACKGROUND AND AIM: Brucellosis is endemic zoonotic and highly contagious bacterial disease. Recently, several brucellosis cases were reported in Lebanon, causing significant economic losses; however, no study was done so far on farms located in the southern part of the country. Thus, the aim of our study was to estimate the prevalence of Brucella abortus in South Lebanon using three different serological tests in the diagnosis of brucellosis in cattle. MATERIALS AND METHODS: Seventeen farms from 14 locations in Southern Lebanon were selected. Two hundred and three bovine blood samples of different ages, and 121 milk samples collected from older than 2 years cattle were tested using different serological tests: Rose Bengal test (RBT), milk ring test (MRT), indirect enzyme-linked immunosorbent assay (I-ELISA), and confirmed with competitive ELISA (C-ELISA). RESULTS: Results revealed that approximately 15.3% (confidence interval [CI] 95 10.3-20.2%) and 15.7% (CI 95 9.2-22.2%) of samples were positive using RBT and MRT, respectively. This percentage was significantly higher when using I-ELISA (18.3%) (CI 95 12.9-23.5%) and C-ELISA (18.7%) (CI 95 9.8-27.5%). Among used diagnostic tests, our results showed that ELISA was more accurate for the detection of brucellosis, especially since it detects the late stages of the infection, which is characterized by the presence of immunoglobulin G. The seroprevalence of brucellosis was higher among females. All positive tests were of cattle Holstein breed older than 2 years. Tyre and Jezzine cities had a higher significance in bovine brucellosis than Saida. A positive correlation between human and cattle brucellosis was found. CONCLUSION: Our results showed that bovine brucellosis is prevalent in southern Lebanon. Lack of research, in addition to little feedback of occurring illness or symptoms, creates a gap in helping to control the spread of the disease.

Prevalence and prevention of brucellosis in cattle in Lebanon.

BACKGROUND AND AIM: Brucellosis is a zoonotic disease caused by the bacterium of the genus Brucella. This disease is present worldwide, especially in developing and underdeveloped countries, where it is endemic. This first-of-its-kind study in Lebanon aimed to assess the prevalence of brucellosis across the country and to determine the efficacy of a vaccine for reducing losses in herds so that its toll on public health is reduced. MATERIALS AND METHODS: Three hundred and fifty-three blood serum and 261 milk samples were obtained from cows in different areas of Lebanon. The samples were analyzed using serological tests (rose Bengal, milk ring, and indirect enzyme-linked immunosorbent assay [ELISA]) and confirmed with competitive ELISA and polymerase chain reaction. RESULTS: The highest rate of Brucellae was found in the Bekaa region (10%). After vaccination of 5 cows and 13 heifers at different times, the results showed that all the vaccinated animals have developed an immune response to brucellosis 60 days after vaccination. This vaccine can be considered as stable and preventative to protect against brucellosis in animals and thus protect the public from this infection. CONCLUSION: These findings will provide further insight into designing future targeted awareness interventions and adapted policies as efforts toward reducing the prevalence and prevention of brucellosis in cattle in Lebanon.

Pyocyanin, a Metabolite of Pseudomonas Aeruginosa, Exhibits Antifungal Drug Activity Through Inhibition of a Pleiotropic Drug Resistance Subfamily FgABC3.

The fungus Fusarium graminearum is the causative agent of economically significant plant diseases such as Fusarium Healed Blight (FHB) of cereals, its mycotoxins as deoxynivalenol (DON), Nivalenol (NIV) and Zearalenone (ZEN) contaminate wheat and other grains. The objectives of the present study were to determine the mechanism by which the bacterium Pseudomonas aeruginosa inhibits the growth of F. graminearum. Our results indicate that P. aeruginosa metabolites as pyocyanin has effective antifungal properties. Pyocyanin was produced by P. aeruginosa when cultured on mineral salt medium and reached a maximum concentration after 72 h. Pyocyanin significantly decreased mycotoxins of F. graminearum, a 25 mg/ml of pyocyanin for 72 h decreased DON by 68.7% and NIV by 57.7%.Real-Time PCR analysis demonstrated that the antifungal effect is mediated by downregulation of the Pleiotropic Drug Resistance (PDR) subfamily FgABC3. 25 mg/ml of pyocyanin decreased FgABC3-mRNA by 60%, inhibited the fungal growth and decreased the area of mycelial growth at 12, 24, 36 and 72 h post incubation by 40-50%. Deletion of FgABC3 led to enhanced accumulation of DON and NIV by 40 and 60%, respectively.The data presented in this report may have significance in understanding mechanism by which certain bacterial metabolites exert a beneficial effect and for developing antifungal drugs.

Autotaxin protects microglial cells against oxidative stress.

Oxidative stress occurs when antioxidant defenses are overwhelmed by oxygen-reactive species and can lead to cellular damage, as seen in several neurodegenerative disorders. Microglia are specialized cells in the central nervous system that act as the first and main form of active immune defense in the response to pathological events. Autotaxin (ATX) plays an important role in the modulation of critical cellular functions, through its enzymatic production of lysophosphatidic acid (LPA). In this study, we investigated the potential role of ATX in the response of microglial cells to oxidative stress. We show that treatment of a microglial BV2 cell line with hydrogen peroxide (H(2)O(2)) stimulates ATX expression and LPA production. Stable overexpression of ATX inhibits microglial activation (CD11b expression) and protects against H(2)O(2)-treatment-induced cellular damage. This protective effect of ATX was partially reduced in the presence of the LPA-receptor antagonist Ki16425. ATX overexpression was also associated with a reduction in intracellular ROS formation, carbonylated protein accumulation, proteasomal activity, and catalase expression. Our results suggest that up-regulation of ATX expression in microglia could be a mechanism for protection against oxidative stress, thereby reducing inflammation in the nervous system.