CoronaVac (Sinovac) COVID-19 vaccine-induced molecular changes in healthy human serum by infrared spectroscopy coupled with chemometrics

From the beginning of the COVID-19 coronavirus pandemic in December of 2019, the disease has infected millions of people worldwide and caused hundreds of thousands of deaths. Since then, several vaccines have been developed. One of those vaccines is inactivated CoronaVac-Sinovac COVID-19 vaccine. In this proof of concept study, we first aimed to determine CoronaVac-induced biomolecular changes in healthy human serum using infrared spectroscopy. Our second aim was to see whether the vaccinated group can be separated or not from the non-vaccinated group by applying chemometric techniques to spectral data. The results revealed that the vaccine administration induced significant changes in some functional groups belonging to lipids, proteins and nucleic acids. In addition, the non-vaccinated and vaccinated groups were successfully separated from each other by principal component analysis (PCA) and linear discriminant analysis (LDA). This proof-of-concept study will encourage future studies on CoronaVac as well as other vaccines and will lead to make a comparison between different vaccines to establish a better understanding of the vaccination outcomes on serum biomolecules.     

Effects of apelin-13 in mice model of experimental pain and peripheral nociceptive signaling in rat sensory neurons

Objective: Apelin-13 is an endogenous peptide with potential analgesic action, although the sites of its analgesic effects remain uncertain and the results are even controversial with regard to its pain modulating action. This study evaluated the possible pain-modulating action of peripherally administered apelin-13 using heat-induced, withdrawal latency to the thermal stimuli, acute pain model in mice. Involvement of peripheral mechanisms was tested, by using the intracellular calcium concentrations as a key signal for nociceptive transmission, in cultured rat dorsal root ganglion (DRG) neurons. Methods: DRG neurons were cultured on glass coverslips following enzymatic digestion and mechanical agitation, and loaded with the calcium-sensitive dye Fura-2 acetoxymethyl ester (1?µM). Intracellular calcium responses in individual DRG neurons were quantified by ratiometric calcium imaging technique. Results: Peripheral injection of a single dose of apelin-13 (100?mg/kg and 300?mg/kg) significantly decreases the latency to painful stimuli in a dose and time-dependent manner (p?<?0.01, p?<?0.05, respectively, n?=?8 each). Apelin-13 (0.1?µM and 1?µM) did not produce a significant effect on cytoplasmic Ca²⁺ ([Ca²⁺]_i) responses, evoked by membrane depolarization, in cultured rat DRG neurons. Conclusion: Together these results indicate that apelin-13 can cause increased pain sensitivity after peripheral administration, but this effect does not involve calcium mediated signaling in primary sensory neurons.     

Effects of ivermectin treatment of backyard chickens on mosquito dynamics and West Nile virus transmission

BackgroundVector control strategies typically rely on pesticides to target mosquitoes involved in enzootic and zoonotic transmission of West Nile virus (WNV). Nevertheless, increasing insecticide resistance and a desire to reduce pesticide usage provide the impetus for developing alternative strategies. Ivermectin (IVM), an antiparasitic drug which is widely used in human and veterinary medicine, is a potential alternative for targeted control because Culex mosquitoes experience increased mortality following ingestion of IVM in bloodmeals.Methodology/Principal findingsWe conducted a randomized field trial to investigate the impact of treating backyard chicken flocks with IVM in urban neighborhoods across Davis, California on mosquito populations and WNV transmission dynamics. We observed a significant reduction in WNV seroconversions in treated vs. untreated chickens, suggesting a reduction in WNV transmission intensity around treated flocks. We also detected a reduction in parity rates of Cx. tarsalis near treated vs. untreated flocks and increased mortality in wild mosquitoes following a bloodmeal on treated chickens (IVM serum concentration > 5ng/mL) vs. chickens with IVM serum concentrations < 5 ng/mL. However, we did not find a significant difference in abundance or infection prevalence in mosquitoes between treatment groups associated with the reductions in seroconversions. Mosquito immigration from surrounding larval habitat, relatively low WNV activity in the study area, and variable IVM serum concentrations likely contributed to uncertainty about the impact.Conclusions/SignificanceTaken together, our results point to a reduction in WNV transmission due to the impact of IVM on Culex mosquito populations and support the ongoing investigation of oral administration of IVM to wild birds for local control of WNV transmission, although further work is needed to optimize dosing and understand effects on entomological endpoints.     

Novel approaches for COVID-19 diagnosis and treatment: a nonsystematic review

Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.     

Design of novel and potent cPLA2α inhibitors containing an α-methyl-2-ketothiazole as a metabolically stable serine trap

We report the design of novel, potent cPLA₂α inhibitors that possess an α-methyl-2-ketothiazole that acts as a serine-reactive moiety. We describe the optimization of the series for potency and metabolic stability towards ketone reduction. This was achieved by attenuating the reactivity of the ketone using a combination of electronic and steric effects.     

Interpretation of the effect of CYP2C9, VKORC1 and CYP4F2 variants on warfarin dosing adjustment in Turkey

Molecular Biology Reports - It was aimed to underline the importance and explain the meaning of genetic testing in warfarin dosing and investigate and evaluate the contributions of the CYP2C9,...     

Oncogenic ras-induced down-regulation of pro-apoptotic protease caspase-2 is required for malignant transformation of intestinal epithelial cells

Resistance of carcinoma cells to anoikis, apoptosis that is normally induced by loss of cell-to-extracellular matrix adhesion, is thought to be essential for the ability of these cells to form primary tumors, invade adjacent tissues, and metastasize to distant organs. Current knowledge about the mechanisms by which cancer cells evade anoikis is far from complete. In an effort to understand these mechanisms, we found that ras, a major oncogene, down-regulates protease caspase-2 (which initiates certain steps of the cellular apoptotic program) in malignant human and rat intestinal epithelial cells. This down-regulation could be reversed by inhibition of a protein kinase Mek, a mediator of Ras signaling. We also found that enforced down-regulation of caspase-2 in nonmalignant intestinal epithelial cells by RNA interference protected them from anoikis. Furthermore, the reversal of the effect of Ras on caspase-2 achieved by the expression of exogenous caspase-2 in detached ras-transformed intestinal epithelial cells promoted well established apoptotic events, such as the release of the pro-apoptotic mitochondrial factors cytochrome c and HtrA2/Omi into the cytoplasm of these cells, significantly enhanced their anoikis susceptibility, and blocked their long term growth in the absence of adhesion to the extracellular matrix. Finally, the blockade of the effect of Ras on caspase-2 substantially suppressed growth of tumors formed by the ras-transformed cells in mice. We conclude that ras-induced down-regulation of caspase-2 represents a novel mechanism by which oncogenic Ras protects malignant intestinal epithelial cells from anoikis, promotes their anchorage-independent growth, and allows them to form tumors in vivo.     

Diversity of and selection acting on cylindrospermopsin cyrB gene adenylation domain sequences in Florida

Aphanizomenon ovalisporum is the only confirmed cylindrospermopsin producer identified in the United States to date. On the other hand, Cylindrospermopsis raciborskii is a prominent feature of many lakes in Florida and other regions of the United States. To see the variation in cylindrospermopsin cyrB gene adenylation domain sequences and possibly discover new cylindrospermopsin producers, we collected water samples for a 3-year period from 17 different systems in Florida. Positive amplicons were cloned and sequenced, revealing that approximately 92% of sequences were A. ovalisporum-like (>99% identity). Interestingly, 6% of sequences were very similar (>99% identity) to cyrB sequences of C. raciborskii from Australia and of Aphanizomenon sp. from Germany. Neutrality tests suggest that A. ovalisporum-like cyrB adenylation domain sequences are under purifying selection, with abundant low-frequency polymorphisms within the population. On the other hand, when compared between species by codon-based methods, amino acids of CyrB also seem to be under purifying selection, in accordance with the one proposed amino acid thought to be activated by the CyrB adenylation domain.     

The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury

AimsAlthough hyperbaric oxygen (HBO) treatment following spinal cord injury (SCI) have been studied in terms of neurological function and tissue histology, there is a limited number studies on spinal cord tissue enzyme levels.Main methodsThe effect of HBO treatment in SCI was investigated by measuring superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), nitric oxide synthase (NOS) and nitric oxide (NO) activity in the injured tissue. SCI was induced by applying an aneurysm clip extradurally at the level of T9-T11 vertebrae. Preoperative HBO (preopHBO) treatment was applied for 5 days and postoperative HBO (postopHBO) for 7 days.Key findingsIn the preopHBO group, a significant decrease was observed in NOS and NO compared to the SCI group. There was a decrease in SOD, NOS and NO in the postopHBO group when compared to the SCI group. In the pre–postHBO group SOD, GPx, NOS and NO decreased significantly. There was a decrease in SOD in postopHBO compared to preopHBO. In the prepostopHBO, SOD decreased significantly compared to that in the preopHBO group. The prepostopHBO presented a significant decrease in GPx compared to postopHBO (p < 0.05 for all parameters). No significant difference was observed for catalase for all groups. Significant improvement was found in BBB scores for both postopHBO and prepostHBO groups when compared to the SCI group (p < 0.05).SignificanceHBO treatment was found to be beneficial following SCI in terms of biochemical parameters and functional recovery in the postoperative period.