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Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms

Authors: James Anderson

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By James Anderson

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (Lepob/ob). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics.

Evaluation of the Nephroprotective Effect of Omega-3 Polyunsaturated Fatty Acids on Gentamicin-Induced Renal Toxicity in Albino Wistar Rats

Authors: Ahon Gnamien Marcel , Ouattara Sitapha , Djyh Bernard Nazaire , Lago Gnonseka Constantin Mederic , Yapi Houphouet Felix , Djaman Allico Joseph

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The kidney performs several important functions in the body. Its failure leads to a dysfunction that deserves a solution. Thus, this study was initiated to investigate the protective effects of omega-3 fatty acids on nephrotoxicity. For this purpose, 48 Albino Wistar rats (male and female) were divided into 8 groups of 6 rats. The first group, serving as a control, received 1 mL/g body weight of distilled water daily by gavage and a 0.9% NaCl solution intraperitoneally one hour later. The second, received gentamicin at a dose of 80 mg/Kg/day by intraperitoneal injection for 7 days, the third, treated with the combination of omega 3 by gavage at a dose of 200 mg/Kg of body weight plus gentamicin by intraperitoneal injection at a dose of 80 mg/Kg for the same period. The fourth, treated with the combination of omega 3 by gavage at a dose of 600 mg/Kg body weight plus gentamycin by intraperitoneal injection at a dose of 80 mg/Kg for 7 days, the fifth, treated with the combination of vitamin E at a dose of 250 mg/kg/day body weight by gavage plus gentamicin by intraperitoneal injection at a dose of 80 mg/Kg for 7 days. The sixth and seventh received 200 mg/kg and 600 mg/kg body weight by gavage of omega-3 for 7 days, respectively. The last group received vitamin E at a dose of 250 mg/kg/day of body weight by gavage. Omega-3 at a dose of 600 mg/kg body weight exerts a protective effect against induced nephrotoxicity in rats (especially females), with a decrease in urea and creatinine levels. The consumption of food rich in omega 3 in the protection of the kidneys advised. Further studies could be envisaged to compare the protective effects of omega-3 with other polyunsaturated fatty acids (omega-6 and 9) on nephrotoxicity.

Productivity and Progesterone Profile of Nulliparous and Second-Parous Rabbits Characterized by Low and High Litter Size

Authors: Mohamed Abdel-Fatah Abo-Farw , Wael Mohamed Nagy , Sherief Mohamed Zayed , George Ezaat Younan , Rehab Fawzy Ismail

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This study aimed to evaluate the effect of the litter size (LS) category on the reproductive performance of nulliparous (NP) and second-parous (SP) NZW rabbits and the performance of their offspring. A total of 39 NP and 33 SP doe rabbits were divided into low (LLS,

Quantitative Production of High Concentration Poly-Ferric Magnesium Sulfate Coagulant Through Ferrous Sulfate Oxidation

Authors: Rufu Wang , Ping Wu , Yong Liu , Rong Wang

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Poly-ferric magnesium sulfate coagulant as another water purifying agent besides poly-aluminum multi-salt can be quantitatively produced through ferrous sulfate oxidation with high product concentration. This article starts with the selection of raw material, then elaborates process flow from a small-scale lab simulate experiment to a large-scale production of this high concentration water purifying agent. According to the corporate technical standard of this product, chemical compositions of the primary material (ferrous sulfate heptahydrate) and auxiliary materials (alkalizing agent, oxidizer, etc.), and the alkalinity of the product (B=8%), this article provides calculation of the raw materials’ input and output for producing 1 ton of the product liquid. The reaction is carried out step-by-step in a heating reactor equipped with acidic mist re-flux tower and filtration devices. The first step: ferrous sulfate oxidation by sodium chlorate; the second step: polymerization, precipitation, and filtration separation; the third step: arsenic and heavy metal check and precipitate separation by flocculating precipitant and metal chelating precipitant; last, use the laboratory test results to back calculating alkalinity (B%), coagulation strength (C%), and molecular formula of the final product liquid. This article not only rationalizes the feasibility with chemical/physical mechanisms this technique, formulation, production method, but also guides through the back calculation to provide data of the properties as a documentation of the certificate of analysis for the product.

Identification of Long Noncoding RNA Recognized by RNA-Binding Protein TLS/FUS: Purification of RNAs by Affinity Chromatography of GST-TLS

Authors: Naomi Ueda , Ryoma Yoneda , Riki Kurokawa

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RNA binding protein TLS/FUS binds promoter-associated noncoding RNA-D (pncRNA-D), long noncoding RNA (lncRNA), and inhibits histone acetyltransferase (HAT) activity in cellular nuclei to repress the cyclin-D1 gene transcription. TLS is expressed in neuronal cells and plays pivotal roles in neuronal develop and function. Its precipitation in motor neurons is supposed to cause amyotrophic lateral sclerosis (ALS) one of neurodegenerative diseases. Our preliminary experiments indicate that pncRNA-D should repress the phase separation and the resultant precipitation of TLS in biochemical conditions. This implies that pncRNA-D be a seed for effective drug against ALS. It is conceivable that a pool of lncRNAs bound to TLS should be a competent library screening for an ALS drug. Then, we decided to search for more lncRNAs to regulate phase separation and precipitation. In this manuscript, we develop a simple and swift technology of the affinity purification of unidentified RNAs from HeLa cell total RNA using bacterially expressed glutathione S-transferase-tagged-TLS (GST-TLS). Screening of the GST-TLS bound RNA has been performed with a human lncRNA microarray using a fluorescent dye, the cy3-labeled bound RNA as a probe. 1728 lncRNAs of more than two-fold increase at the fluorescent signals have been identified, compared to those of the input HeLa cell total RNA. The top 25 lncRNAs from the 1728 lncRNAs were expressed at more than 12-fold induction. Tentatively, the top four putative lncRNAs were employed for further analysis. Then, these lncRNAs have been shown to have specific binding to GST-TLS and also cellular TLS. The precipitation based experiment to detect phase separation has shown that these lncRNAs inhibit the phase separation-induced precipitation which is dissolved in 1, 6-hexanediol (1,6-HD). There is no significant sequence homology over these lncRNAs, although a consensus conformation of these lncRNAs is the loops and stems structure based upon the predicted secondary structures of the top 25 lncRNAs selected. These data confirm that the GST-TLS based affinity purification of RNA bound to TLS works well to provide the novel lncRNAs specific to TLS. The method to identify novel lncRNAs recognized by TLS provides a profitable technique for initiating the biology of TLS-bound lncRNAs in cellular programs.

Discussion on Molecular Mechanism of Siwei Xiaoliuyin in Treating Glioma Based on Network Pharmacology and Molecular Docking

Authors: Biaogang Han , Xiaohong Wu , Xiaopei Zhang , Shihua Liu , Yongqing Shen , Aixia Sui

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Background. Siwei Xiaoliuyin, a traditional Chinese medicine, is effective in treating glioma, but its molecular mechanism of action is still unclear. In this paper, we will explore the molecular mechanism of Siwei Xiaoliuyin in the treatment of glioma through network pharmacology. Methods. The potential active components and molecular targets of Siwei Xiaoliuyin were collected through the pharmacological database and analysis platform of traditional Chinese medicine system and TCMID database; glioma-related target genes were obtained through the GenCards database, OMIM database and Disgenet database; the intersection of drug action targets and disease genes was extracted using R software, and Venn diagram was drawn; the key targets were imported into the String database to construct a protein interaction network; the key targets were imported into R software using clusterProfiler for GO and KEGG enrichment analysis; the main components of Siwei Xiaoliuyin were molecularly docked with the Hub gene by AutoDock Vina technology. Results. Siwei Xiaoliuyin consists of four components, which are Curcuma zedoaria, Tianlong, Solanum nigrum and Smilax glabra and a total of 26 potential active components and 56 targets were identified from it, 5750 glioma-related genes and 47 key target genes crossed between Siwei Xiaoliuyin and glioma. The results of enrichment analysis showed that GO entries involved fatty acid metabolic processes, response to steroid hormones and other processes. KEGG analysis identified key genes mainly enriched in PI3K-Akt signaling pathway, estrogen signaling pathway and HIF-1 signaling pathway, etc. The results of molecular docking showed that Diosgenin, the main component of Siwei Xiaoliuyin, docked well with the AHR gene. Conclusions. Through network pharmacology prediction, Siwei Xiaoliuyin may regulate multiple signaling pathways such as PI3K-Akt, estrogen and HIF-1 through multiple targets EGFR, ESR1, VEGFA, AHR and AR, thus affecting the function of multiple cells and playing an important role in the treatment of glioma.

Correlation of Tree Diameter, Height and Biodiversity with Soil N, P and K

Authors: Shreejana Panthi , Ram Asheshwar Mandal , Ajay Bhakta Mathema

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This research was done to assess effect of soil nutrients (N, P and K) on diameter at breast height (DBH), height and biodiversity. Three transect lines according to altitudinal gradient were established to systematically allocate the plot. Total 45 samples having 20m×25m were established to collect the biophysical data and soil samples. DBH and height of trees were recorded and soil samples were carried out in the lab. The Shannon –Weiner Index, Simpson Index and Evenness Index were analyzed. Nitrogen (N), Phosphorous (P) and Potash (K) was analyzed using Kjeldahl, Olsen’s and Somers and Flame photometric methods respectively. The Pearson’s correlation was performed to show the relation of DBH, height and biodiversity indexes with N, P and K. Descriptive statistics showed that the highest Mean±SE DBH (cm) was 50.75±4.61 in altitude

Biological Parameters of the Red Pandora (Pagellus bellottii Steindachner, 1882) in Soumbedioune, Senegal, West Africa

Authors: Waly Ndiaye , Alassane Sarr , Patrick Diédhiou

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New information on the reproductive biology of Pagellus bellottii (Steindachner, 1882) a Sparid fish in Senegalese waters is provided in this study. Little aspects on the reproductive biology of this fish are reported in Senegal, West Africa. The objective of the study is to examine the length-weight relationship, the condition factor and the reproductive parameters of P. bellottii from the Senegalese waters. A total of 360 specimens (males = 197 and females = 163) bought from fishermen were used for the study. Specimens were collected monthly (thirty individuals per month) from October 2019 to September 2020 from Soumbedioune of Western part of Dakar, Senegal. Each individual was measured with an ichthyometer and weighed with a precision balance. For dissected individuals, sex was determined by macroscopic observation of the gonads. The gonads were extracted to calculate the Gonadosomatic Index. The length-weight relationship gave a negative allometric growth for both sexes. The value of “k” being greater than 1; the species was in good condition in this environment. The sex ratio (1:0.82) was favourable to males. The reproductive period was from March to June with a spawning peak in April for both sexes. Males and females had size at first sexual maturity at 178- and 180-mm total length, respectively. Males matured at smaller sizes than females. The data obtained in this study on some aspects of the reproductive biology of P. bellottii will be essential for better management of fish stocks in Senegal and in the sub-region.

The Effect of Coffee Expansion on Carbon Stock of Natural Forest in Gidame Woreda, West Ethiopia

Authors: Yadesa Akena Dinsa

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The important climate-related functions of forest ecosystems are carbon sequestration, regulating the global carbon cycle and climate change mitigation. About 80% of the terrestrial carbon is stored as forest biomass and soil organic carbon. Deforestation and forest degradation show an alarming high, mainly due to the conversion of natural forest to commercial and cereal crop production. By considering this issue, this study was conducted with the aim to assess the effect of coffee expansion on carbon stock of the natural forest ecosystem in Gidame woreda. The study site was stratified in two strata: undisturbed natural forest and disturbed coffee forest. A total of 71 nested square sample plot was determined, proportionally allocated (29 for undisturbed and 42 for disturbed/coffee forest) and randomly distributed within each stratum. In both cases, the diameter at breast height and tree height were measured; litter sample was collected by harvesting and weighing technique. A total of 72 composite soil samples were also collected from proportionally and randomly selected 24 sample plots; 10 from undisturbed natural forest and 14 from disturbed coffee forest for SOC quantification in three layers (0-15cm, 16-30cm, and 31-45cm). From these forest inventory data, the above-ground biomass carbon stock was estimated by using allometric equations. The below-ground biomass carbon stock was derived from the above-ground carbon stock. The results showed that the biomass carbon stock was 298.758 ± 9.4tc/ha for undisturbed natural forest and 199.895 ± 11tc/ha for disturbed coffee forest and the difference is statistically significant as p < 0.05. This revealed that the disturbance of this natural forest ecosystem, which is associated with the conversion of natural forest to the coffee cultivation area, resulted in the loss of 33.09% of the biomass carbon stock. The SOC is 148.40 ± 12tc/ha for undisturbed forest and 153.80 ± 4.30tc/ha for disturbed coffee forest has no significant difference as p > 0.05. Therefore, maintaining the biomass carbon sequestration potential of this natural forest ecosystem should be required through the implementation of different conservation mechanisms.