Heart Fields: Spatial Polarity and Temporal Dynamics

In chick and mouse, heart fields undergo dynamic morphological spatiotemporal changes during heart tube formation. Here, the dynamic change in spatial polarity of such fields is discussed and a new perspective on the heart fields is proposed. The heart progenitor cells delaminate through the primitive streak and migrate in a semicircular trajectory craniolaterally forming the bilateral heart fields as part of the splanchnic mesoderm. They switch their polarity from anteroposterior to mediolateral. The anterior intestinal portal posterior descent inverts the newly formed heart field mediolateral polarity into lateromedial by 125° bending. The heart fields revert back to their original anteroposterior polarity and fuse at the midline forming a semi heart tube by completing their half circle movement. Several names and roles were assigned to different portions of the heart fields: posterior versus anterior, first versus second, and primary versus secondary heart field. The posterior and anterior heart fields define basically physical fields that form the inflow–outflow axis of the heart tube. The first and second heart fields are, in contrast, temporal fields of differentiating cardiomyocytes expressing myosin light chain 2a and undifferentiated and proliferating precardiac mesoderm expressing Isl1 gene, respectively. The two markers present a complementary pattern and are expressed transiently in all myocardial lineages. Thus, Isl1 is not restricted to a portion of the heart field or one of the two heart lineages as has been often assumed. Anat Rec, 297:175–182, 2014. © 2013 Wiley Periodicals, Inc.     

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking,pro-apoptotic,and enzyme inhibition profile

Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies.

The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives.     

In vitro antifungal susceptibility testing of fungi in patients with onychomycosis

Onychomycosis is the most common nail disorder. To examine in vitro antifungal susceptibility of fungi among onychomycosis patients. The study included 68 patients with onychomycosis. Nail specimens were cultured on Sabouraud dextrose agar and Dermasel agar base‐media. Isolated fungi were subjected to antifungal susceptibility tests against terbinafine, itraconazole, fluconazole, and griseofulvin. Candida species (Candida spp.) were detected in 32.4% of the cases of candidal onychomycosis (n = 37), 23.5% of the cases of distal and lateral subungual onychomycosis (n = 17), and 21.4% of the cases of total dystrophic onychomycosis (n = 14). Candida spp. were sensitive to fluconazole in 73.5%, itraconazole in 58.8%, and terbinafine in 5.9% of the cases. Aspergillus spp. were sensitive to itraconazole in all cases, and terbinafine in 87.5% of cases. Penicillium spp. were sensitive to itraconazole and terbinafine in 88.9% and 77.8% of cases, respectively. Trichophyton spp. were sensitive to terbinafine and resistant to itraconazole. Microsporum spp. were sensitive to itraconazole and resistance to terbinafine. All isolated fungi were resistant to griseofulvin. An increasing proportion of Candida spp. was observed among patients with different clinical varieties of onychomycosis. Candida spp. were highly sensitive to fluconazole and a lesser extent to itraconazole.     

Replicating Viral Vector-Based Vaccines for COVID-19: Potential Avenue in Vaccination Arena

The “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” is the third member of human coronavirus (CoV) that is held accountable for the current “coronavirus disease 2019 (COVID-19)” pandemic. In the past two decades, the world has witnessed the emergence of two other similar CoVs, namely SARS-CoV in 2002 and MERS-CoV in 2013. The extent of spread of these earlier versions was relatively low in comparison to SARS-CoV-2. Despite having numerous reports inclined towards the zoonotic origin of the virus, one cannot simply sideline the fact that no animal originated CoV is thus far identified that is considered similar to the initial edition of SARS-CoV-2; however, under-sampling of the diverse variety of coronaviruses remains a concern. Vaccines are proved to be an effective tool for bringing the end to such a devastating pandemic. Many vaccine platforms are explored for the same but in this review paper, we will discuss the potential of replicating viral vectors as vaccine carriers for SARS-CoV-2.     

Antihyperglycemic Activities of Leaves of Three Edible Fruit Plants (Averrhoa Carambola,Ficus Hispida and Syzygium Samarangense) of Bangladesh

Averrhoa carambola L. (Oxalidaceae), Ficus hispida L.f. (Moraceae), and Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae) are three common plants in Bangladesh, the fruits of which are edible. The leaves and fruits of A. carambola and F. hispida are used by folk medicinal practitioners for treatment of diabetes, while the leaves of S. samarangense are used for treatment of cold, itches, and waist pain. Since scientific studies are absent on the antihyperglycemic effects of the leaves of the three plants, it was the objective of the present study to evaluate the antihyperglycemic potential of methanolic extract of leaves of the plants in oral glucose tolerance tests carried out with glucose-loaded mice. The extracts at different doses were administered one hour prior to glucose administration and blood glucose level was measured after two hours of glucose administration (p.o.) using glucose oxidase method. Significant oral hypoglycemic activity was found with the extracts of leaves of all three plants tested. The fall in serum glucose levels were dose-dependent for every individual plant, being highest at the highest dose tested of 400 mg extract per kg body weight. At this dose, the extracts of A. carambola, F. hispida, and S. samarangense caused, respectively, 34.1, 22.7, and 59.3% reductions in serum glucose levels when compared to control animals. The standard antihyperglycemic drug, glibenclamide, caused a 57.3% reduction in serum glucose levels versus control. Among the three plants evaluated, the methanolic extract of leaves of S. samarangense proved to be the most potent in demonstrating antihyperglycemic effects. The result validates the folk medicinal uses of A. carambola and F. hispida in the treatment of diabetes, and indicates that the leaves of S. samarangense can also possibly be used for amelioration of diabetes-induced hyperglycemia.