Search results for: hepatic metabolites

Authors: Ashu Rastogi, Uttam Thakur, Jimmy Pathak, Rajesh Gupta, Anil Bhansali

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Introduction: Liraglutide is known to induce weight loss and metabolic benefits in obese individuals. However, its effect after sleeve gastrectomy are not known. Methods: People with obesity (BMI>27.5 kg/m2) underwent LSG. Subsequently, participants were randomized to receive either 0.6mg liraglutide subcutaneously daily from 6 week post to be continued till 24 week (L-L group) or placebo (L-P group). Patients were assessed before surgery (baseline) and 6 weeks, 12weeks, 18weeks and 24weeks after surgery for height, weight, waist and hip circumference, BMI, body fat percentage, HbA1c, fasting C-peptide, fasting insulin, HOMA-IR, HOMA-β, GLP-1 levels (after standard OGTT). MRI abdomen was performed prior to surgery and at 24weeks post operatively for the estimation of intrapancreatic and intrahepatic fat content. Outcome measures: Primary outcomes were changes in metabolic variables of fasting and stimulated GLP-1 levels, insulin, c-peptide, plasma glucose levels. Secondary variables were indices of insulin resistance HOMA-IR, Matsuda index; and pancreatic and hepatic steatosis. Results: Thirty-eight patients undergoing LSG were screened and 29 participants were enrolled. Two patients withdrew consent and one patient died of acute coronary event. 26 patients were randomized and data analysed. Median BMI was 40.73±3.66 and 46.25±6.51; EBW of 49.225±11.14 and 651.48±4.85 in the L-P and L-L group, respectively. Baseline FPG was 132±51.48, 125±39.68; fasting insulin 21.5±13.99, 13.15±9.20, fasting GLP-1 2.4± .37, 2.4± .32, AUC GLP-1 340.78± 44 and 332.32 ± 44.1, HOMA-IR 7.0±4.2 and 4.42±4.5 in the L-P and L-L group, respectively. EBW loss was 47± 13.20 and 65.59± 24.20 (p<0.05) in the placebo versus liraglutide group. However, we did not observe inter-group difference in metabolic parameters between the groups in spite of significant intra-group changes after 6 months of LSG. Intra-pancreatic fat prior to surgery was 3.21±1.7 and 2.2±0.9 (p=0.38) that decreased to 2.14±1.8 and 1.06±0.8 (p=0.25) at 6 months in L-P and L-L group, respectively. Similarly, intra-pancreatic fat was 1.97±0.27 and 1.88±0.36 (p=0.361) at baseline that decreased to 1.14±0.44 and 1.36±0.47 (p=0.465) at 6 months in L-P and L-L group, respectively. Conclusion: Liraglutide augments extra body weight loss after sleeve gastrectomy. A decrease in intra-pancreatic and intra-hepatic fat is noticed after bariatric surgery without additive benefit of liraglutide administration.

Keywords: sleeve gastrectomy, liraglutide, intra-pancreatic fat, insulin

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Nneka Augustina Akwu, Yougasphree Naidoo

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Molecular advancement in technology has created a means whereby the atoms and molecules (solid forms) of certain materials such as plants, can now be reduced to a range of 1-100 nanometres. Green synthesis of silver nanoparticles (AgNPs) was carried out at room temperature (RT) 25 ± 2°C and 80°C, using the metabolites in the aqueous extracts of the leaves and stem bark of Grewia lasiocarpa as reductants and stabilizing agents. The biosynthesized AgNPs were characterized by UV-Vis spectrophotometry, attenuated total reflectance - Fourier transforms infrared (ATR-FTIR) spectroscopy, nanoparticle tracking analysis (NTA), Energy Dispersive X-ray fluorescence scanning electron microscope (SEM-EDXRF) and high-resolution transmission electron microscopy (HRTEM). The AgNPs were biologically evaluated for antioxidant, antibacterial and cytotoxicity activities. The phytochemical and FTIR analyses revealed the presence of metabolites that act as reducing and capping agents, while the UV-Vis spectroscopy of the biosynthesized NPs showed absorption between 380-460 nm, confirming AgNP synthesis. The Zeta potential values were between -9.1 and -20.6 mV with a hydrodynamics diameter ranging from 38.3 to 46.7 nm. SEM and HRTEM analyses revealed that AgNPs were predominately spherical with an average particle size of 2- 31 nm for the leaves and 5-27 nm for the stem bark. The cytotoxicity IC50 values of the AgNPs against HeLa, Caco-2 and MCF-7 were >1 mg/mL. The AgNPs were sensitive to all strains of bacteria used, with methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) being more sensitive to the AgNPs. Our findings propose that antibacterial and anticancer agents could be derived from these AgNPs of G. lasiocarpa, and warrant their further investigation.

Keywords: antioxidant, cytotoxicity, Grewia lasiocarpa, silver nanoparticles, Zeta potentials

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Authors: Joshua Russell, Omar Zubair, Reuben Ndegwa

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Introduction: Mesenteric ischemia is an uncommon condition that can be challenging to diagnose in the acute setting, with the potential for significant morbidity and mortality. Very rarely has acute acalculous cholecystitis been described in the setting of mesenteric ischemia. Case: This was the case in a 78-year-old male, who initially presented with clinical and radiological evidence of small bowel obstruction, thought likely secondary to malignancy. The patient had a 6-week history of anorexia, worsening lower abdominal pain, and ~30kg of unintentional weight loss over a 12-month period and a CT- scan demonstrated a transition point in the distal ileum. The patient became increasingly hemodynamically unstable and peritonitic, and an emergency laparotomy was performed. Intra-operatively, however, no obvious transition point was identified, and instead, the gallbladder was markedly gangrenous and oedematous, consistent with acalculous cholecystitis. An open total cholecystectomy was subsequently performed. The patient was admitted to the Intensive Care Unit post-operatively and continued to deteriorate over the proceeding 48 hours, with two re-look laparotomies demonstrating progressively worsening bowel ischemia, initially in the distribution of the superior mesenteric artery and then the coeliac trunk. On review, the patient was found to have an aberrant right hepatic artery arising from the superior mesenteric artery. The extent of ischemia was considered non-survivable, and the patient was palliated. Discussion: Multiple theories currently exist for the underlying pathophysiology of acalculous cholecystitis, including biliary stasis, sepsis, and ischemia. This case lends further support to ischemia as the underlying etiology of acalculous cholecystitis. This is particularly the case when considered in the context of the patient’s aberrant right hepatic artery arising from the superior mesenteric artery, which occurs in 11-14% of patients. Conclusion: This case report adds further insight to the debate surrounding the pathophysiology of acalculous cholecystitis. It also presents acalculous cholecystitis as a complication of mesenteric ischemia that should always be considered, especially in the elderly patient and in the context of relatively common anatomical variations. Furthermore, the case brings to attention the importance of maintaining dynamic working diagnoses in the setting of evolving pathophysiology and clinical presentations.

Keywords: acalculous cholecystitis, anatomical variation, general surgery, mesenteric ischemia

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Authors: Patricia M. B. Saint-Vincent, Anna Furches, Stephanie Galanie, Erica Teixeira Prates, Piet Jones, Nancy Engle, David Kainer, Wellington Muchero, Daniel Jacobson, Timothy J. Tschaplinski

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Uridine diphosphate-glycosyltransferases (UGTs) are enzymes that catalyze sugar transfer to a variety of plant metabolites. UGT substrates, which include plant secondary metabolites involved in lignification, demonstrate new activities and incorporation when glycosylated. Knowledge of UGT function, substrate specificity, and enzyme products is important for plant engineering efforts, especially related to increasing plant biomass through lignification. UGTs in Populus trichocarpa, a biofuel feedstock, and model woody plant, were selected from a pool of gene candidates using rapid prioritization strategies. A functional genomics workflow, consisting of a metabolite genome-wide association study (mGWAS), expression of synthetic codon-optimized genes, and high-throughput biochemical assays with mass spectrometry-based analysis, was developed for determining the substrates and products of previously-uncharacterized enzymes. A total of 40 UGTs from P. trichocarpa were profiled, and the biochemical assay results were compared to predicted mGWAS connections. Assay results confirmed seven of 11 leaf mGWAS associations and demonstrated varying levels of substrate specificity among candidate UGTs. P. trichocarpa UGT substrate processing confirms the role of these newly-characterized enzymes in lignan, flavonoid, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress responses.

Keywords: Populus, metabolite-gene associations, GWAS, bio feedstocks, glycosyltransferase

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Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

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There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

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Authors: Feiyu Yang, Chunfang Ni, Rong Wang, Yun Zou, Wenbin Liu, Chenggong Zhang, Fenjin Sun, Chun Wang

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Cocaine is the most frequently used illegal drug globally, with the global annual prevalence of cocaine used ranging from 0.3% to 0.4 % of the adult population aged 15–64 years. Growing consumption trend of abused cocaine and drug crimes are a great concern, therefore urine sample testing has become an important noninvasive sampling whereas cocaine and its metabolites (COCs) are usually present in high concentrations and relatively long detection windows. However, direct analysis of urine samples is not feasible because urine complex medium often causes low sensitivity and selectivity of the determination. On the other hand, presence of low doses of analytes in urine makes an extraction and pretreatment step important before determination. Especially, in gathered taking drug cases, the pretreatment step becomes more tedious and time-consuming. So developing a sensitive, rapid and high-throughput method for detection of COCs in human body is indispensable for law enforcement officers, treatment specialists and health officials. In this work, a new automated magnetic dispersive solid-phase extraction (MDSPE) sampling method followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) was developed for quantitative enrichment of COCs from human urine, using prepared magnetic nanoparticles as absorbants. The nanoparticles were prepared by silanizing magnetic Fe3O4 nanoparticles and modifying them with divinyl benzene and vinyl pyrrolidone, which possesses the ability for specific adsorption of COCs. And this kind of magnetic particle facilitated the pretreatment steps by electromagnetically controlled extraction to achieve full automation. The proposed device significantly improved the sampling preparation efficiency with 32 samples in one batch within 40mins. Optimization of the preparation procedure for the magnetic nanoparticles was explored and the performances of magnetic nanoparticles were characterized by scanning electron microscopy, vibrating sample magnetometer and infrared spectra measurements. Several analytical experimental parameters were studied, including amount of particles, adsorption time, elution solvent, extraction and desorption kinetics, and the verification of the proposed method was accomplished. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.1 ng·mL-1 with recoveries ranging from 75.1 to 105.7%. Compared to traditional sampling method, this method is time-saving and environmentally friendly. It was confirmed that the proposed automated method was a kind of highly effective way for the trace cocaine and cocaine metabolites analyses in human urine.

Keywords: automatic magnetic dispersive solid-phase extraction, cocaine detection, magnetic nanoparticles, urine sample testing

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Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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Authors: S. Mamoucha, N.Tsafantakis, T. Ioannidis, S. Chatzipanagiotou, C. Nikolaou, L. Skaltsounis, N. Fokialakis, N. Christodoulakis

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Introduction: Pistacia lentiscus L. (well known as Mastic tree) is an evergreen sclerophyllous shrub that extensively thrives in the eastern Mediterranean area yet only the trees cultivated in the southern region of the Greek island Chios produces mastic resin. Different parts of P. lentiscus L. var. chia have been used in folk medicine for various purposes, such as tonic, aphrodisiac, antiseptic, antihypertensive and management of dental, gastrointestinal, liver, urinary, and respiratory tract disorders. Several studies have focused on the antibacterial activity of its resin (gum) and its essential oil. However, there is no study combining anatomy of the plant organs, phytochemical profile, and antibacterial screening of the plant. In our attempt to discover novel bioactive metabolites from the mastic tree, we screened its antibacterial activity not only against ATCC strains but also against clinical, resistant strains. Materials-methods: Leaves were investigated using Transmission (ΤΕΜ) and Scanning Εlectron Microscopy (SEM). Histochemical tests were performed on fresh and fixed tissue. Extracts prepared from dried, powdered leaves using 3 different solvents (DCM, MeOH and H2O) the waste water obtained after a hydrodistillation process for essential oil production were screened for their phytochemical content and antibacterial activity. Μetabolite profiling of polar and non-polar extracts was recorded by GC-MS and LC-HRMS techniques and analyzed using in-house and commercial libraries. The antibacterial screening was performed against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853 and against clinical, resistant strains Methicillin-resistant S. aureus (MRSA), Carbapenem-Resistant Metallo-β-Lactamase (carbapenemase) P. aeruginosa (VIM), Klebsiella pneumoniae carbapenemases (KPCs) and Acinetobacter baumanii resistant strains. The antibacterial activity was tested by the Kirby Bauer and the Agar Well Diffusion method. The zone of inhibition (ZI) of each extract was measured and compared with those of common antibiotics. Results: Leaf is compact with inosclereids and numerous idioblasts containing a globular, spiny crystal. The major nerves of the leaf contain a resin duct. Mesophyll cells showed accumulation of osmiophillic metabolites. Histochemical treatments defined secondary metabolites in subcellular localization. The phytochemical investigation revealed the presence of a large number of secondary metabolites, belonging to different chemical groups, such as terpenoids, phenolic compounds (mainly myricetin, kaempferol and quercetin glycosides), phenolic, and fatty acids. Among the extracts, the hydrostillation wastewater achieved the best results against most of the bacteria tested. MRSA, VIM and A. baumanii were inhibited. Conclusion: Extracts from plants have recently been of great interest with respect to their antimicrobial activity. Their use emerged from a growing tendency to replace synthetic antimicrobial agents with natural ones. Leaves of P. lentiscus L. var. chia showed a high antimicrobial activity even against drug - resistant bacteria. Future prospects concern the better understanding of mode of action of the antibacterial activity, the isolation of the most bioactive constituents and the clarification if the activity is related to a single compound or to the synergistic effect of several ones.

Keywords: antibacterial screening, leaf anatomy, phytochemical profile, Pistacia lentiscus var. chia

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Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

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Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Cliff Shunsheng Han

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Identifying the direct allergy cause that can be easily mitigated is the foundation to stop the allergy epidemic that has been started in the seventies. It has confirmed that the personal and social hygiene practices are associated with the allergy prevalence. But direct causes have been found, and proposed translational measures have not been effective. This study, assisted by a particular case of allergies, has seen the direct cause of allergies, developed a valid test resulted in lasting relief for allergies, and constructed theory describing general relationship between microbiota and host immune system. Saliva samples were collected from a subject for three years during which time the person experienced yearlong allergy, seasonal allergy, and remission of allergy symptoms. Bacterial DNA was extracted and 16S rRNA genes were profiled with Illumina sequencing technology. The analyzing results indicate that the possible direct cause of allergy is the lacking probiotic bacteria in the oral cavity, such as genera Streptococcus and Veilonella, that can produce metabolites to pacify immune system. Targeted promotion of those bacteria with a compound designed for them, has led to lasting remissions of allergic rhinitis. During the development of the translational measure, the subject's oral biofilm was completely destructed by a moderate fever due to an unrelated respiratory infection. The incident not only facilitated the development of the heat based microbiota reseeding procedure but also indicated a possible natural switch that subsequently increases the efficacy of the immune system previously restrained by metabolites from microbiota. These results lead to the proposal of a Theory of Negative Trigger (TNT) to describe the relationship between oral probiotics and immune system, in which probiotics are the negative trigger that will release the power of immune system when removed by fever or modern lifestyles. This study could open doors leading to further understanding of how the immune system functions under the influence of microbiota as well as validate simple traditional practices for healthy living.

Keywords: oral microbiome, allergy, immune system, infection

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Authors: Yi-Shuan ShaoShao, Yen-An Tsai, Chia-Huang Chang, Kai-Wei Liao, Ming-Song Tsai, Mei-Lien Chen

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Organophosphate pesticides (OPs) is an environmental hormone with proven endocrine-disrupting effects that may affect the growth and development in human. A large amount of organophosphate pesticides (OPs) is used throughout Taiwan, and human may be exposed through dietary intake or residential use. During pregnancy, OPs can be transferred to the blood stream reaching the fetus through the placenta. The aim of this study was to explore the association between maternal OPs exposure levels and fetal developments and birth outcomes. A birth cohort was follow-up. Maternal urine sample were collected at the first, second, and third gestational trimester. Fetal growth characteristics were measured by ultrasonic scan and birth outcomes were assessed by pediatrician. Urinary metabolite of organophosphate pesticides were assessed using gas chromatography-mass spectrometry. The analytes included dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphates (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP). We found that all of urine samples in each trimester were detected at least one metabolite for dialkyl phosphate (DAP). The detection rate range of OP urinary metabolites were from the lowest 22% DEDTP to the highest 100% DMP and DMTP. And to compared geometric means (GM) of urinary metabolites with three trimesters, that third trimester had the highest concentration for DMPs, DEPs, and DAPs in pregnant women were 368.01, 169.85 and 543.75 nmol/g creatinine, respectively. We observed that DAPs concentration in first and second trimester were significantly negative association with head circumference. DMPs in first trimester was significantly negative association with thoracic circumference (p=0.05) by spearman correlation. Our results support associations with prenatal OPs exposure with fetal head circumference and thoracic circumference. It provided that maternal OPs exposure might affect birth outcomes. Thus, prenatal exposure to OPs and health risk worthy of attention and concern.

Keywords: DAPs, birth outcomes, organophosphate pesticides, prenatal

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Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

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Authors: Hannah S. Elizabeth, D. Gnanasekaran, M. R. Manju Gowda, Antony George

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Phytoremediation a new technology of remediating the contaminated soil, water and air using plants and serves as a green technology with environmental friendly approach. The main aim of this technique is cleansing and detoxifying of organic compounds, organo-phosphorous pesticides, heavy metals like arsenic, iron, cadmium, gold, radioactive elements which cause teratogenic and life threatening diseases to mankind and animal kingdom when consume the food crops, vegetables, fruits, cerals, and millets obtained from the contaminated soil. Also, directly they may damage the genetic materials thereby alters the biosynthetic pathways of secondary metabolites and other phytoconstituents which may have different pharmacological activities which lead to lost their efficacy and potency as well. It would reflect in mutagenicity, drug resistance and affect other antagonistic properties of normal metabolism. Is the technology for real clean-up of contaminated soils and the contaminants which are potentially toxic. It reduces the risks produced by a contaminated soil by decreasing contaminants using plants as a source. The advantages are cost-effectiveness and less ecosystem disruption. Plants may also help to stabilize contaminants by accumulating and precipitating toxic trace elements in the roots. Organic pollutants can potentially be chemically degraded and ultimately mineralized into harmless biological compounds. Hence, the use of plants to revitalize contaminated sites is gaining more attention and preferred for its cost-effective when compared to other chemical methods. The introduction of harmful substances into the environment has been shown to have many adverse effects on human health, agricultural productivity, and natural ecosystems. Because the costs of growing a crop are minimal compared to those of soil removal and replacement, the use of plants to remediate hazardous soils is seen as having great promise.

Keywords: cost effective, eco-friendly, phytoremediation, secondary metabolites

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Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w.day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation.

Keywords: antioxidants, doxorubicin, hepatotoxicity, purslane

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Authors: Rashmi Tomar, A. Srinivasan, Nayan K. Mohanty, Arun K. Jain

Abstract:

Phthalates have been used as additives in industrial products since the 1930s, and are universally considered to be ubiquitous environmental contaminants. The general population is exposed to phthalates through consumer products, as well as diet and medical treatments. Animal studies showing the existence of an association between some phthalates and testicular toxicity have generated public and scientific concern about the potential adverse effects of environmental changes on male reproductive health. Unprecedented declines in fertility rates and semen quality have been reported during the last half of the 20th century in developed countries and increasing interest exists on the potential relationship between exposure to environmental contaminants, including phthalates, and human male reproductive health Studies. Phthalates may be associated with altered endocrine function and adverse effects on male reproductive development and function, but human studies are limited. The aim of the present study was detection of phthalate compounds, estimation of their metabolites in infertile & fertile male. Blood and urine samples were collected from 150 infertile patients & 75 fertile volunteers recruited through Department of Urology, Safdarjung Hospital, New Delhi. Blood have been collected in separate glass tubes from the antecubital vein of the patients, serum have been separate and estimate the phthalate level in serum samples by Gas Chromatography / Mass Spectrometry using NIOSH / OSHA detailed protocol. Urine of Infertile & Fertile Subjects was collected & extracted using solid phase extraction method, analysis by HPLC. In conclusion, to the best of our knowledge the present study based on human is first to show the presence of phthalate in human serum samples and their metabolites in urine samples. Significant differences were observed between several phthalates in infertile and fertile healthy individuals.

Keywords: Gas Chromatography, HPLC, male infertility, phthalates, serum, toxicity, urine

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Authors: Aidan Ryan, Nahima Miah, Sahaj Kaur, Imogen Sutherland, Mohamed Saleh

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Pulmonary symptoms are a common presentation to the emergency department. Due to a lack of understanding of the underlying pathophysiology, chronic liver disease is not often considered a cause of dyspnea. We present three patients who were admitted with significant respiratory distress secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. The first is a 27-year-old male with a 6-month history of progressive dyspnea. The patient developed a severe type 1 respiratory failure with a PaO₂ of 6.3kPa and was escalated to critical care, where he was managed with non-invasive ventilation to maintain oxygen saturation. He had an agitated saline contrast echocardiogram, which showed the presence of a possible shunt. A CT angiogram revealed significant liver cirrhosis, portal hypertension, and large para esophageal varices. Ultrasound of the abdomen showed coarse liver echo patter and enlarged spleen. Along with these imaging findings, his biochemistry demonstrated impaired synthetic liver function with an elevated international normalized ratio (INR) of 1.4 and hypoalbuminaemia of 28g/L. The patient was then transferred to a tertiary center for further management. Further investigations confirmed a shunt of 56%, and liver biopsy confirmed cirrhosis suggestive of alpha-1-antitripsyin deficiency. The findings were consistent with a diagnosis of hepatopulmonary syndrome, and the patient is awaiting a liver transplant. The second patient is a 56-year-old male with a 12-month history of worsening dyspnoea, jaundice, confusion. His medical history included liver cirrhosis, portal hypertension, and grade 1 oesophageal varices secondary to significant alcohol excess. On admission, he developed a type 1 respiratory failure with PaO₂ of 6.8kPa requiring 10L of oxygen. CT pulmonary angiogram was negative for pulmonary embolism but showed evidence of chronic pulmonary hypertension, liver cirrhosis, and portal hypertension. An echocardiogram revealed a grossly dilated right heart with reduced function, pulmonary and tricuspid regurgitation, and pulmonary artery pressures estimated at 78mmHg. His biochemical markers showed impaired synthetic liver function with an INR of 3.2, albumin of 29g/L, along with raised bilirubin of 148mg/dL. During his long admission, he was managed with diuretics with little improvement. After three weeks, he was diagnosed with portopulmonary hypertension and was commenced on terlipressin. This resulted in successfully weaning off oxygen, and he was discharged home. The third patient is a 61-year-old male who presented to the local ambulatory care unit for therapeutic paracentesis on a background of decompensated liver cirrhosis. On presenting, he complained of a 2-day history of worsening dyspnoea and a productive cough. Chest x-ray showed a large pleural effusion, increasing in size over the previous eight months, and his abdomen was visibly distended with ascitic fluid. Unfortunately, the patient deteriorated, developing a larger effusion along with an increase in oxygen demand, and passed away. Without underlying cardiorespiratory disease, in the presence of a persistent pleural effusion with underlying decompensated cirrhosis, he was diagnosed with hepatic hydrothorax. While each presented with dyspnoea, the cause and underlying pathophysiology differ significantly from case to case. By describing these complications, we hope to improve awareness and aid prompt and accurate diagnosis, vital for improving outcomes.

Keywords: dyspnea, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary syndrome

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

Abstract:

Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: Rabab Makki, Deputy Chief Dietitian

Abstract:

Malnutrition is commonly seen in Liver Disease patients. Prevalence of malnutrition in cirrhosis, is as high as 65-90%. Protein depletion and reduced muscle function are common. There are many mechanisms of malnutrition in liver cirrhosis e.g. insulin resistance, low respiratory quotient, increased glucogenesis etc. Nutrition support improves outcome in patients unable to maintain an intake of 35-40 Kcal/kg and 1.2-1.5 gm/kg/day. Simple methods of assessment such as subjective global assessment, calorie counting, MMC are useful. The value of BCAAs remains uncertain despite a considerable number of studies. Normal protein diets have been given safely to patients with hepatic encephalopathy. Restriction of protein not more than 48 hours pre- and pro-biotic, glutamine, fish oil etc are all part of the latest advanced techniques used.

Keywords: liver cirrhosis, omega 3 for liver disease, nutrition management, malnutrition

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Authors: Olufemi M. Alabi, Foluke A. Aderemi, Adebayo A. Adewumi, Banwo O. Alabi

Abstract:

General well-being of animals is of paramount interest in some developed countries and of global importance hence the shift onto alternative housing systems for egg-type chickens as replacement for conventional battery cage system. However, there is paucity of information on the effect of this shift on physiological status of the hens to judge their health via the blood profile. Therefore, investigation was carried out on two strains of hen kept in three different housing systems in humid tropics to evaluate changes in their blood parameters. 108, 17-weeks old super black (SBL) hens and 108, 17-weeks old super brown (SBR) hens were randomly allotted to three different intensive systems Partitioned Conventional Cage (PCC), Extended Conventional Cage (ECC) and Deep Litter System (DLS) in a randomized complete block design with 36 hens per housing system, each with three replicates. The experiment lasted 37 weeks during which blood samples were collected at 18th week of age and bi-weekly thereafter for analyses. Parameters measured are packed cell volume (PCV), hemoglobin concentration (Hb), red blood counts (RBC), white blood counts (WBC) and serum metabolites such as total protein (TP), albumin (Alb), globulin (Glb), glucose, cholesterol, urea, bilirubin, serum cortisol while blood indices such as mean corpuscular hemoglobin (MCH), mean cell volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) were calculated. The hematological values of the hens were not significantly (p>0.05) affected by the housing system and strain, so also the serum metabolites except for the serum cortisol which was significantly (p<0.05) affected by the housing system only. Hens housed on PCC had higher values (20.05 ng/ml for SBL and 20.55 ng/ml for SBR) followed by hens on ECC (18.15ng/ml for SBL and 18.38ng/ml for SBL) while hens on DLS had the lowest value (16.50ng/ml for SBL and 16.00ng/ml for SBR) thereby confirming indication of stress with conventionally caged birds. Alternative housing systems can also be adopted for egg-type chickens in the humid tropics from welfare point of view with the results of this work confirming stress among caged hens.

Keywords: blood, housing, humid-tropics, layers

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Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

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Authors: Mohammad Nazri Abdul Bahari, Nurshafika Mohd Sakeh, Siti Nor Akmar Abdullah

Abstract:

Basal stem rot (BSR) is the most devastating disease in oil palm. Among the oil palm pathogenic fungi, the most prevalent and virulent species associated with BSR is Ganoderma boninense. Early detection of G. boninense attack in oil palm wherein physical symptoms has not yet appeared can offer opportunities to prevent the spread of the necrotrophic fungus. However, poor understanding of molecular defense responses and roles of antifungal metabolites in oil palm against G. boninense has complicated the resolving measures. Hence, characterization of defense-related molecular responses and production of antifungal compounds during early interaction with G. boninense is of utmost important. Four month-old oil palm (Elaeis guineensis) seedlings were artificially infected with G. boninense-inoculated rubber wood block via sitting technique. RNA of samples were extracted from roots and leaves tissues at 0, 3, 7 and 11 days post inoculation (d.p.i) followed with sequencing using RNA-Seq method. Differentially-expressed genes (DEGs) of oil palm-G. boninense interaction were identified, while changes in metabolite profile will be scrutinized related to the DEGs. The RNA-Seq data generated a total of 113,829,376 and 313,293,229 paired-end clean reads from untreated (0 d.p.i) and treated (3, 7, 11 d.p.i) samples respectively, each with two biological replicates. The paired-end reads were mapped to Elaeis guineensis reference genome to screen out non-oil palm genes and subsequently generated 74,794 coding sequences. DEG analysis of phytohormone biosynthetic genes in oil palm roots revealed that at p-value ≤ 0.01, ethylene and jasmonic acid may act in antagonistic manner with salicylic acid to coordinate defense response at early interaction with G. boninense. Findings on metabolite profiling of G. boninense-infected oil palm roots and leaves are hoped to explain the defense-related compounds elicited by Elaeis guineensis in response to G. boninense colonization. The study aims to shed light on molecular defense response of oil palm at early interaction with G. boninense and promote prevention measures against Ganoderma infection.

Keywords: Ganoderma boninense, metabolites, phytohormones, RNA-Seq

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Authors: Geminne Manzano, Clairecynth Yu, Lilibeth Salvador-Reyes, Viviene Santiago, Porfirio AliñO

Abstract:

The distribution and abundance patterns of many marine sessile organisms such as sponges vary among and within reefs. Determining the factors affecting its distribution is essential especially for organisms that produce secondary metabolites with pharmaceutical importance. In this study, the small-scale distribution patterns of the Philippine blue sponge, Xestospongia sp. in relation to some ecological factors were examined. The relationship between the renieramycin-M production and their benthic attributes were also determined. Ecological surveys were conducted on two stations with varying depth and exposure located in Oriental Mindoro, Philippines. Three 30 by 6m belt transect were used to assess the sponge abundance at each station. The substratum of the sponges was also characterized. Fish visual census observations were also taken together with the photo transect methods benthic surveys. Sponge samples were also collected for the extraction of Renieramycin-M and for further chemical analysis. Varying distribution patterns were observed to be attributed to the combination of different ecological and environmental factors. The amount of Renieramycin-production also varied in each station. The common substratum for blue sponges includes hard and soft corals, as well as, dead coral with algal patches. Blue sponges from exposed habitat frequently grow associated with massive and branching corals, Porites sp., while the most frequent substrate found on sheltered habitats is the coral Pavona sp. Exploring the influence of ecological and environmental parameters on the abundance and distribution of sponge assemblages provide ecological insights and their potential applications to pharmaceutical studies. The results of this study provide further impetus in pursuing studies into patterns and processes of the Philippine blue sponge, Xestospongia sp. distribution in relation to the chemical ecology of its secondary metabolites.

Keywords: distribution patterns, Porifera, Renieramycin-M, sponge assemblages, Xestospongia sp.

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Authors: Jonathan Josephs-Spaulding, Hannah Rettig, Simon Graspeunter, Jan Rupp, Christoph Kaleta

Abstract:

Background: Recurrent urinary tract infections (rUTIs) are a global cause of emergency room visits and represent a significant burden for public health systems. Therefore, metatranscriptomic approaches to investigate metabolic exchange and crosstalk between uropathogenic Escherichia coli (UPEC), which is responsible for 90% of UTIs, and collaborating pathogens of the urogenital microbiome is necessary to better understand the pathogenetic processes underlying rUTIs. Objectives: This study aims to determine the level in which uropathogens optimize the host urinary metabolic environment to succeed during invasion. By developing patient-specific metabolic models of infection, these observations can be taken advantage of for the precision treatment of human disease. Methods: To date, we have set up an rUTI patient cohort and observed various urine-associated pathogens. From this cohort, we developed patient-specific metabolic models to predict bladder microbiome metabolism during rUTIs. This was done by creating an in silico metabolomic urine environment, which is representative of human urine. Metabolic models of uptake and cross-feeding of rUTI pathogens were created from genomes in relation to the artificial urine environment. Finally, microbial interactions were constrained by metatranscriptomics to indicate patient-specific metabolic requirements of pathogenic communities. Results: Metabolite uptake and cross-feeding are essential for strain growth; therefore, we plan to design patient-specific treatments by adjusting urinary metabolites through nutritional regimens to counteract uropathogens by depleting essential growth metabolites. These methods will provide mechanistic insights into the metabolic components of rUTI pathogenesis to provide an evidence-based tool for infection treatment.

Keywords: recurrent urinary tract infections, human microbiome, uropathogenic Escherichia coli, UPEC, microbial ecology

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Authors: Prescilla Lambert, Christophe Roos, Mounim Lebrini

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For several years, the Caribbean islands and West Africa have had to deal with the massive arrival of the brown seaweed Sargassum. Overall, this macroalgae, which constitutes a habitat for a great diversity of marine organisms, is also an additional stress factor for the marine environment (e.g., coral reefs). In addition, the accumulation followed by the significant decomposition of the Sargassum spp. biomass on the coast leads to the release of toxic gases (H₂S and NH₃), which calls into question the functioning of the economic, health and tourist life of the island and the other interested territories. Originally, these algae are formed by the eutrophication of the oceans accentuated by global warming. Unfortunately, scientists predict a significant recurrence of these Sargassum strandings for years to come. It is therefore more than necessary to find solutions by putting in place a sustainable management plan for this phenomenon. Martinique, a small island in the Caribbean arc, is one of the many areas impacted by Sargassum seaweed strandings. Since 2011, there has been a constant increase in the degradation of the materials present in this region, largely due to toxic/corrosive gases released by the algae decomposition. In order to protect the structures and the vulnerable building materials while limiting the use of synthetic/petroleum based molecules as much as possible, research is being conducted on molecules of natural origin. Thus, thanks to the chemical composition, which comprise molecules with interesting properties, algae such as Sargassum could potentially help to solve many issues. Therefore, this study focuses on the green extraction and characterization of molecules from the species Sargassum fluitans and Sargassum natans present in Martinique. The secondary metabolites found in these extracts showed variability in yield rates due to local climatic conditions. The tests carried out shed light on the anticorrosive and antibacterial potential of the algae. These extracts can thus be described as natural inhibitors. The effect of variation in inhibitor concentrations was tested in electrochemistry using electrochemical impedance spectroscopy and polarization curves. The analysis of electrochemical results obtained by direct immersion in the extracts and self-assembled molecular layers (SAMs) for Sargassum fluitans III, Sargassum natans I and VIII species was conclusive in acid and alkaline environments. The excellent results obtained reveal an inhibitory efficacy of 88% at 50mg/L for the crude extract of Sargassum fluitans III and efficacies greater than 97% for the chemical families of Sargassum fluitans III. Similarly, microbiological tests also suggest a bactericidal character. Results for Sargassum fluitans III crude extract show a minimum inhibitory concentration (MIC) of 0.005 mg/mL on Gram-negative bacteria and a MIC greater than 0.6 mg/mL on Gram-positive bacteria. These results make it possible to consider the management of local and international issues while valuing a biomass rich in biodegradable molecules. The next step in this study will therefore be the evaluation of the toxicity of Sargassum spp..

Keywords: Sargassum, secondary metabolites, anticorrosive, antibacterial, natural inhibitors

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Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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Authors: Gamal Shiha, Seham Seif, Shahera Etreby, Khaled Zalata, Waleed Samir

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Background: Transient Elastography (TE; FibroScan®) is a non-invasive technique to assess liver fibrosis. Aim: To compare TE and liver biopsy in hepatitis C virus (HCV) patients, genotype IV and evaluate the effect of steatosis and schistosomiasis on FibroScan. Methods: The fibrosis stage (METAVIR Score) TE, was assessed in 519 patients. The diagnostic performance of FibroScan is assessed by calculating the area under the receiver operating characteristic curves (AUROCs). Results: The cut-off value of ≥ F2 was 8.55 kPa, ≥ F3 was 10.2 kPa and cirrhosis = F4 was 16.3 kPa. The positive predictive value and negative predictive value were 70.1% and 81.7% for the diagnosis of ≥ F2, 62.6% and 96.22% for F ≥ 3, and 27.7% and 100% for F4. No significant difference between schistosomiasis, steatosis degree and FibroScan measurements. Conclusion: Fibroscan could accurately predict liver fibrosis.

Keywords: chronic hepatitis C, FibroScan, liver biopsy, liver fibrosis

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Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

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Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

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