Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

Aristolochia manshuriensis has been used for centuries in Chinese medicinal system for their versatile medicinal uses. Recent studies have revealed two new aristolactames (compound A and B) with γ-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). Studies on aristolactames and related compounds claim for their CDK2 inhibition without delineating the involved mechanism and structural basis of interaction. Molecular structural model was used to we propose a structural basis of CDK2 inhibition. We showed that these compounds (A and B) can successfully dock into the inhibitor binding pockets of human CDK2. Predicted binding affinities are comparable to known inhibitors of CDK2. Results were in agreement with the earlier biochemical studies. Hence, suggest that studied compounds A and B can be a promising scaffold for rational design of novel and potential drugs against cancer. ABBREVIATIONS: CDK2 - cyclin-dependent kinase 2, OLO - Olomoucine, NW1 - Cyclohexylmethyloxy-5-Nitroso-Pyrimidine- 2, 4-Diamine, CMG - 6-O-Cyclohexylmethyl Guanine.     

FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway

The Fanconi anemia (FA) core complex plays a central role in the DNA damage response network involving breast cancer susceptibility gene products, BRCA1 and BRCA2. The complex consists of eight FA proteins, including a ubiquitin ligase (FANCL) and a DNA translocase (FANCM), and is essential for monoubiquitination of FANCD2 in response to DNA damage. Here, we report a novel component of this complex, termed FAAP100, which is essential for the stability of the core complex and directly interacts with FANCB and FANCL to form a stable subcomplex. Formation of this subcomplex protects each component from proteolytic degradation and also allows their coregulation by FANCA and FANCM during nuclear localization. Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability. Our study identifies FAAP100 as a new critical component of the FA-BRCA DNA damage response network.     

The mechanism of liposome accumulation in infarction

This paper explores the mechanism(s) whereby liposomes accumulate in chronically ischaemic myocardium and intestine. Plasma prepared from venous blood obtained at sites of myocardial and intestinal infarction does not promote the lysis of positively and negatively charged liposomes in vitro. Albumin-bound lysophosphatidylcholine (≥ 2 mM) lyses positively and negatively charged liposomes in vitro at similar rates. [^99mTc]Diethylenetriamine pentaacetic acid (DTPA) entrapped in positively charged liposomes was accumulated in ischaemic rat caecum/colon 6 and 24 h after mesenteric ligation. Presumably allied to the accumulation of liposomal components, necrotic caecum/colon showed marked Ca²⁺ accumulation and phospholipid depletion. It is postulated that Ca²⁺ and Ca²⁺-activated membrane phospholipases may be implicated in the mechanism of liposome accumulation in chronic ischaemia.     

Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging in vivo, leading to decreased ability to form and maintain bone homeostasis with age. In this review we summarize evidence of MSC involvement in age related bone loss and suggest new emerging targets for intervention.     

Green synthesis of zinc nanoparticles using Lavandula angustifolia Vera. Extract by microwave method and its prophylactic effects on Toxoplasma gondii infection

BackgroundToday, a suitable vaccine has not yet been discovered to prevent Toxoplasma gondii infection. Therefore, prophylaxis can be suggested as the preferred approach to prevent toxoplasmosis. This study aims to evaluate the prophylactic effects of synthesized zinc nanoparticles (ZnNPs) using Lavandula angustifolia Vera., by microwave method on chronic toxoplasmosis in mice.MethodsBALB/c Mice orally administrated with ZnNPs the doses of 32.5, 75, 150 mg/kg/day for two weeks. On the 15th day, the mice were intraperitoneally infected with the Tehran strain of T. gondii (25 tissue cysts). The mean diameter and the numbers of brain tissue cysts, as well as the mRNA levels of inducible nitric oxide synthesize (iNOs), and interferon-gamma (IFN-γ) in mice of each experimental group were evaluated.ResultsThe synthesized ZnNPs represent a spherical form with a size ranging from 30 to 80 nm. The results revealed that oral administration of Zn NPs at the doses of 32.5 (p < 0.001) and 75 mg/kg/day (p < 0.001) for 14 days significantly reduced the mean number and diameter of the brain tissue cysts in tested mice. No T. gondii tissue cyst was observed after oral administration of Zn NPs at the doses of 150 mg/kg. Based on the results of Real-time PCR analysis, the expression level of IFN-γ and iNOs was significantly increased (p < 0.001) in mice treated with 32.5, 75, 150 mg/kg/day for two weeks.ConclusionThe obtained findings of the current investigation exhibit the significant prophylactic effects of ZnNPs against chronic toxoplasmosis in mice; so that oral administration of ZnNPs the doses 32.5, 75, 150 mg/kg reduced the parasite load and even completely controlled the infection in mice. The results show that the ZnNPs had strengthened the innate immune system which could be the reason for its strong prophylactic effects. However, further in vivo and clinical investigations are required to confirm these results as well as other possible mechanisms that can trigger these pharmacological properties.     

Midden site selection in Dorcas gazelle: Larger is not always better

Dorcas gazelles are believed to use middens to mark their territories and transmit information. Given the commitment to maintaining a midden, it is believed that middens are not placed randomly. We examined how the habitat (tree height and maximum canopy) and anthropogenic disturbance (camel and human presence) influenced the selection of midden sites by Dorcas gazelles in South Sinai, Egypt. Our results showed that Dorcas gazelles did not place middens at larger trees, while favoring relatively smaller trees and shrubs where the anthropogenic disturbance and perceived hunting risk are less. Our results, in light of the previous findings, suggest that selection of midden sites is species context‐dependent behavior. In areas with less anthropogenic disturbance and hunting, Dorcas gazelles have been shown to select the largest trees of the same species as midden sites. In contract, in our study site with high anthropogenic disturbance and no protection from hunting, gazelles did not utilize the presumably optimum landmarks for midden sites. Our study showed that Dorcas gazelles instead utilized smaller trees and some shrubs that are less conspicuous and presumably less effective as advertisement sites, but safer.     

Assessment of bio-contaminants during COVID-19 outbreak from the indoor environment of Hail city,Kingdom of Saudi Arabia

Biocontaminants are minute particles derived from different biological materials. Indoor biocontaminants are associated with major public health problems. In Gulf countries, it is more precarious due to the harsh climatic conditions, including high ambient temperatures and relative humidity. In addition, due to COVID-19 pandemic, most of the time public is inside their home. Therefore, the aim of the study was to determine the load of biocontaminants in the indoor environment of Hail city. The results showed that most of the bacteria are gram-positive and higher in polymicrobial (87.1%) than monomicrobial (62.7%) association. There was no significant association with sample collection time and types of isolates. The most abundant microbes found in all samples were Staphylococcus aureus followed by Bacillus spp. Among Gram-negative bacterial isolates, E. coli was most common in tested indoor air samples. The study will be useful to find the biocontaminants associated with risk factors and their impact on human health in indoor environment, especially during the COVID-19 pandemic. These results indicate the need to implement health care awareness programs in the region to improve indoor air quality.