Lipid‐Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT‐133 towards CRTH2 in the Treatment of Type‐2 Inflammation Dependent Diseases

Chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTH2) has been involved in several inflammation dependent diseases by mediating the chemotaxis of pro‐inflammatory cells in response to allergy and other responses through PGD2 ligation. This CRTH2‐PGD2 signaling pathway has become a target for treating allergic and type 2 inflammation dependent diseases, with many inhibitors developed to target the PGD2 binding pocket. One of such inhibitors is the ramatroban analog, CT‐133, which exhibited therapeutic potency cigarette smoke‐induced acute lung injury in patients. Nonetheless, the molecular mechanism and structural dynamics that accounts for its therapeutic prowess remain unclear. Employing computational tools, this study revealed that although the carboxylate moiety in CT‐133 and the native agonist PGD2 aided in their stability within the CRTH2 binding pocket, the tetrahydrocarbazole group of CT‐133 engaged in strong interactions with binding pocket residues which could have formed as the basis of the antagonistic advantage of CT‐133. Tetrahydrocarbazole group interactions also enhanced the relative stability CT‐133 within the binding pocket which consequently favored CT‐133 binding affinity. CT‐133 binding also induced an inactive or ‘desensitized’ state in the helix 8 of CRTH2 which could conversely favor the recruitment of arrestin. These revelations would aid in the speedy development of small molecule inhibitors of CRTH2 in the treatment of type 2 inflammation dependent diseases.     

A Two-Level Computation Model Based on Deep Learning Algorithm for Identification of piRNA and Their Functions via Chou’s 5-Steps Rule

International Journal of Peptide Research and Therapeutics - Piwi interacting RNA (piRNA) molecules belong to a largest class of small non coding RNA molecules which are originally discovered in...     

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma(28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total Ig E level(P \ 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However,removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever(DHF) rather than dengue fever(DF). In comparison with DF, DHF was associated with Ig E positivity. Furthermore, specific-Ig E level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.     

Condensation of heptaminol hydrochloride for its spectrofluorimetric determination in pure form and tablets: application in human plasma

A sensitive, simple, accurate and less expensive fluorimetric method was designed and validated for analysis of heptaminol HCl in both its pure and dosage forms, as well as in human plasma. The main principle used in the proposed approach was the condensation reaction between heptaminol's primary amino moiety and ethyl acetoacetate/formaldehyde reagents, giving a derivative that was highly fluorescent at 416 nm after excitation at 350 nm. Various experimental parameters that affected either the product's development or its stability were evaluated and optimized. The constructed calibration curve was linear over the range 0.2–2 μg/ml, with a good correlation coefficient (0.9996). Both the calculated limit of detection and limit of quantitation were 0.06 and 0.18 μg/ml, respectively. The presented approach was a success when used to determine Corasore® tablets and was validated according to International Council for Harmonisation guidelines.     

Overtaking Collisions of Electrostatic N-Soliton in Electron–Hole Quantum Plasmas

Plasma Physics Reports - The effects of overtaking collisions of electrostatic multisolitons (i.e., N-soliton) in an electron–hole dense semiconductor plasma are examined employing the...     

Synthesis,Reactions, and Antimicrobial Activity of Novel Heterocyclic Compounds Containing Cyclopenta[d]thieno[2,3-b]pyridine Moiety and Related Fused Heterocycles

Russian Journal of Bioorganic Chemistry - We describe a simple method to synthesize novel 4-cyano-1-morpholin-4-yl-6,7-dihydro-5H-cyclopenta[c]pyridine-3-thione by the reaction of...     

Boosted Growth Performance,Mucosal and Serum Immunity,and Disease Resistance Nile Tilapia ( Oreochromis niloticus ) Fingerlings Using Corncob-Derived Xylooligosaccharide and Lactobacillus plantarum CR1T5

The present work, herein, studied the effects of corncob-derived xylooligosaccharides (CDXOS) and Lactobacillus plantarum CR1T5 (LP) integrated into fish d     

Broad diversity of Mycobacterium tuberculosis complex strains isolated from humans and cattle in Northern Algeria suggests a zoonotic transmission cycle

Mycobacterium tuberculosis complex (MTBC) comprises closely related species responsible for human and animal tuberculosis (TB). Efficient species determination is useful for epidemiological purposes, especially for the elucidation of the zoonotic contribution. In Algeria, data on MTBC genotypes are largely unknown. In this study, we aimed to investigate the occurrence and diversity of MTBC genotypes causing human and bovine TB in Northern Algeria. During a two-year sampling period (2017–2019) in two regions of Northern Algeria, we observed an overall prevalence of 6.5% of tuberculosis (TB) among slaughtered cattle, which is higher than previous Algerian data yet comparable to neighboring countries. A total of 296 Mycobacterium tuberculosis complex (MTBC) isolates were genotyped by spoligotyping: 181 from tissues with TB-like lesions collected from 181 cattle carcasses and 115 from TB patients. In human isolates, we identified 107 M. tuberculosis, seven M. bovis and one “M. pinnipedii-like”, while for bovine samples, 174 isolates were identified as M. bovis, three as M. caprae, three as “M. pinnipedii-like” and one as “M. microti-like”. The majority of isolates (89.2%) belonged to 72 different known Shared International Types (SIT) or M. bovis spoligotypes (SB), while we also identified seven new SB profiles (SB2695 to SB2701). Twenty-eight of the SB profiles were new to Algeria. Our data suggest zoonotic transmission in Sétif, where significantly more TB was observed among cattle (20%) compared to the slaughterhouses from the three other regions (5.4%–7.3%) (p < 0.0001), with the isolation of the same M. bovis genotypes from TB patients. The present study showed a high genetic diversity of MTBC isolated from human and cattle in Northern Algeria. Even though relatively small in terms of numbers, our data suggest the zoonotic transmission of TB from cattle to humans, suggesting the need for stronger eradication strategies for bovine TB.     

Inflammatory markers in chronic kidney disease and end stage renal disease patients

Molecular Biology Reports - Chronic kidney disease (CKD) is condition characterized by a gradual loss of kidney function, patient with CKD suffering from a variety of immune system defects. This...