SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made ...through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2's spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (
), sulfated polymannuroguluronate (SPMG) (
), sulfated mannan (
), sulfated heterorhamnan (
), and chondroitin sulfate E (CS-E) (
). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.
Epicotripeptin (
), a new cyclic tripeptide along with four known cyclic dipeptides (
-
) and one acetamide derivative (
) were isolated from seagrass-associated endophytic fungus
M13 recovered from ...the Red Sea. Additionally, two new compounds, cyclodidepsipeptide phragamide A (
) and trioxobutanamide derivative phragamide B (
), together with eight known compounds (
-
), were isolated from plant-derived endophyte
13A collected from a saline lake of Wadi El Natrun depression in the Sahara Desert. The structures of the isolated compounds were determined based on the 1D and 2D NMR spectroscopic data, HRESIMS data, and a comparison with the reported literature. The absolute configurations of
and
were established by advanced Marfey's and Mosher's ester analyses. The antimicrobial screening indicated that seven of the tested compounds exhibited considerable (MIC range of 2.5-5 µg/mL) to moderate (10-20 µg/mL) antibacterial effect against the tested Gram-positive strains and moderate to weak (10-30 µg/mL) antibacterial effect against Gram-negative strains. Most of the compounds exhibited weak or no activity against the tested Gram-negative strains. On the other hand, four of the tested compounds showed considerable antibiofilm effects against biofilm forming Gram-positive and Gram-negative strains.
Introduction:
Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common ...feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.
Methods:
We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies.
Results and Discussion:
Two homozygous variants in
ABHD16A
segregated with the disease in the two studied families.
ABHD16A
encodes the main brain phosphatidylserine hydrolase.
In vitro
, we confirmed that
ABHD16A
loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.
Conclusion:
ABHD16A
loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia.
The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal day 7 and the ...mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration.
Flavonoids are a class of bioactive plant-derived natural products that exhibit a broad range of biological activities, including antibacterial ones. Their inhibitory activity toward Gram-positive ...bacterial was found to be superior to that against Gram-negative ones. In the present study, a number of flavonoid-coated gold nanoparticles (GNPs) were designed to enhance the antibacterial effects of chrysin, kaempferol, and quercetin against a number of Gram-negative bacteria. The prepared GNPs were able to conjugate to these three flavonoids with conjugation efficiency ranging from 41% to 80%. Additionally, they were able to exert an enhanced antibacterial activity in comparison with the free flavonoids and the unconjugated GNPs. Quercetin-coated GNPs were the most active nano-conjugates and were able to penetrate the cell wall of
. A number of in silico experiments were carried out to explain the conjugation efficiency and the antibacterial mechanisms of these flavonoids as follows: (i) these flavonoids can efficiently bind to the glutathione linker on the surface of GNPs via H-bonding; (ii) these flavonoids, particularly quercetin, were able to increase the bacterial membrane rigidity, and hence decrease its functionality; (iii) these flavonoids can inhibit
's DNA gyrase (Gyr-B) with IC
values ranging from 0.9 to 3.9 µM. In conclusion, these bioactive flavonoid-based GNPs are considered to be very promising antibiotic candidates for further development and evaluation.
Plasmodium sporozoites are the product of a complex developmental process in the mosquito vector and are destined to infect the mammalian liver. Attention has been drawn to the mosquito stages and ...pre-erythrocytic stages owing to recognition that these are bottlenecks in the parasite life cycle and that intervention at these stages can block transmission and prevent infection. Parasite progression in the Anopheles mosquito, sporozoite transmission to the mammalian host by mosquito bite, and subsequent infection of the liver are characterized by extensive migration of invasive stages, cell invasion, and developmental changes. Preparation for the liver phase in the mammalian host begins in the mosquito with an extensive reprogramming of the sporozoite to support efficient infection and survival. Here, we discuss what is known about the molecular and cellular basis of the developmental progression of parasites and their interactions with host tissues in the mosquito and during the early phase of mammalian infection.
The aim of this study is to investigate friction stir welding (FSW) to join A304 austenitic stainless steel and low carbon steel A283 Gr. C in-lap configuration to clad the carbon steel with highly ...corrosion-resistant stainless steel. Thus, a wide range of FSW parameters were investigated such as FSW tool rotation rate from 200 to 400 rpm, tool traverse speed from 25 to 75 mm/min, and vertical forces of 20 to 32 KN. The FSW parameters combination of high welding rotation rate (400 rpm) and high vertical forces (32 KN) results in rejected joints in terms of surface appearance and clear surface defects. On the other hand, rotation rates of 200 and 300 rpm with different welding speeds and vertical forces resulted in some sound joints that were further investigated for microstructure and mechanical properties. The sound lap joints were examined via optical microstructure, SEM, and EDS investigations. For the mechanical properties, both tensile shear testing and hardness testing were used. The transverse macrographs showed intermixing between the two dissimilar materials with an almost irregular interface. The hardness profile in both materials showed a significant increase across the different regions from the Base Material (BM) to the nugget zone, with a maximum value of 260 Hv in the stainless steel and 245 Hv in the carbon steel. This increase is mainly attributed to the grain refining in the weld region due to the dynamic recrystallization and transformations upon the thermomechanical cycle. The tensile shear load of the joints varied from 20 to 27 KN for the FSWed joints, with the highest joint tensile shear load of 27 KN for that produced at 300 rpm tool rotation and 25 mm/min welding speed.
•Cobalt ferrite defective by vanadium doping was prepared by sol gel method.•The saturation magnetization of doped V samples is less than pure CoFe2O4.•The coercivity increases with increasing ...vanadium amount.•The canted angle in CoFe2-1.67xVxO4 is higher than in CoFe2-xVxO4.
Nanoparticles cobalt ferrite, vacancies defective through vanadium substitution for iron, were synthesized by a sol-gel method. Two systems CoFe2-xVxO4 (0.0≤x≤0.25) and CoFe2-1.67xVxO4 (x=0.1, 0.2) were prepared. The crystal structure, microstructure and magnetic properties were investigated using XRD, SEM and VSM magnetometer. The occupancy of tetrahedral and octahedral sites by different cations was determined by Rietveld analysis and correlated with magnetic measurements. Vanadium resides at octahedral sites up to x=0.10, while for higher values it resides mainly at octahedral sites with a lesser amount at the tetrahedrons. Upon increasing the vanadium content, the cell parameter decreases and the bond lengths of the tetrahedral and octahedral sites change opposite to each other. The change in the coercivity and saturation magnetization is correlated with cation distribution. For the same amount of doping x, the iron deficient samples CoFe2-1.67xVxO4 have saturation magnetization obviously reduced than the corresponding samples in CoFe2-xVxO4. The spin canting between cations in A- and B- sites was discussed in details based on Yafet–Kittel triangular arrangement model.
PDF
