Genetic Background of Fetal Growth Restriction

Fetal growth restriction (FGR) is one of the most formidable challenges in present-day antenatal care. Pathological fetal growth is a well-known factor of not only in utero demise in the third trimester, but also postnatal morbidity and unfavorable developmental outcomes, including long-term sequalae such as metabolic diseases, diabetic mellitus or hypertension. In this review, the authors present the current state of knowledge about the genetic disturbances responsible for FGR diagnosis, divided into fetal, placental and maternal causes (including preeclampsia), as well as their impact on prenatal diagnostics, with particular attention on chromosomal microarray (CMA) and noninvasive prenatal testing technique (NIPT).     

Zapotin,a Polymethoxyflavone,with Potential Therapeutic Attributes

The use of plants as traditional medicines is common and has prevailed in many different cultures over time. Polymethoxyflavones (PMFs) are natural polyphenols from the group of flavonoids. Zapotin, a member of the PMFs, is found mainly in citrus plants and is almost exclusively limited to their peels. The chemical structure of zapotin has been questioned from the very beginning, since the structure of flavonoids with a single oxygen atom in the C2′ position is extremely rare in the plant kingdom. To clarify this, the structural determination and bio-inspired synthesis of zapotin are discussed in detail in this review. Due to the broad biological potential of PMFs, the complication in the isolation process and characterization of PMFs, as well as their purification, have been estimated by adapting various chromatographic methods. According to available data from the literature, zapotin may be a promising curative agent with extensive biological activities, especially as a chemopreventive factor. Apart from that, zapotin acts as an antidepressant-like, anticancer, antifungal, and antioxidant agent. Finally, accessible studies about zapotin metabolism (absorption, distribution, metabolism, excretion, and toxicity) underline its potential in use as a therapeutic substance.     

Investigation of doped-gadolinium zirconate nanomaterials for high-temperature hydrogen sensor applications

The incorporation of selective nanomaterials, such as common metal oxide semiconductor compositions, into resistive-type gas sensors has been shown by many researchers to lead to very high sensitivities and response rates, especially for micro-sized chemical sensors for room-temperature applications. The same strategy utilizing sensing nanomaterials has not been demonstrated for high-temperature sensors due to the intrinsic instability of typical metal oxide semiconductor nanomaterials at temperatures >500 °C. Within this work, doped Gd₂Zr₂O₇ (GZO) nanomaterial compositions were investigated for H₂ resistive-type sensors for applications between 600 and 1000 °C. This paper investigates the mechanism of H₂ sensing for doped GZO nanomaterials and SnO₂/GZO nanocomposites at the elevated temperatures. By integrating 10 vol.% nano-SnO₂ into yttrium-doped GZO nanomaterials, a sensitivity of 4.15 % was retained for 4000 ppm H₂ levels with a low signal drift of 0.42 %/h at 1000 °C in a 20 % O₂/N₂ gas stream. The signal drift was reduced by more than half of that compared to pure nano-SnO₂ at the same conditions. The nano-GZO limited the grain growth of the nano-SnO₂ particles and also prevented the nano-SnO₂ from fully reducing to Sn at high temperatures in a low oxygen atmosphere. It is among the first resistive-type sensors operating at 1000 °C with sensing times of <5 min. This demonstration provided an example of a strategy of combining traditional metal oxide semiconductor and refractory nanomaterial compositions to form sensing nanocomposites with new sensing mechanisms, as well as, enhanced chemical and microstructural stabilities in high-temperature environments.     

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.     

Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies.     

On the Dependence of Prion and Amyloid Structure on the Folding Environment

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.     

Blockade of Serotonin 5-HT6 Receptor Constitutive Activity Alleviates Cognitive Deficits in a Preclinical Model of Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a common inherited disorder caused by mutations of the NF1 gene that encodes the Ras-GTPase activating protein neurofibromin, leading to overactivation of Ras-dependent signaling pathways such as the mTOR pathway. It is often characterized by a broad range of cognitive symptoms that are currently untreated. The serotonin 5-HT₆ receptor is a potentially relevant target in view of its ability to associate with neurofibromin and to engage the mTOR pathway to compromise cognition in several cognitive impairment paradigms. Here, we show that constitutively active 5-HT₆ receptors contribute to increased mTOR activity in the brain of Nf1^+/− mice, a preclinical model recapitulating some behavioral alterations of NF1. Correspondingly, peripheral administration of SB258585, a 5-HT₆ receptor inverse agonist, or rapamycin, abolished deficits in long-term social and associative memories in Nf1^+/− mice, whereas administration of CPPQ, a neutral antagonist, did not produce cognitive improvement. These results show a key influence of mTOR activation by constitutively active 5-HT₆ receptors in NF1 cognitive symptoms. They provide a proof of concept that 5-HT₆ receptor inverse agonists already in clinical development as symptomatic treatments to reduce cognitive decline in dementia and psychoses, might be repurposed as therapies alleviating cognitive deficits in NF1 patients.     

Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution

Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by favoring the centralization of hydrophobic residues with the simultaneous exposure to polar residues. The degree of compatibility of the residue distribution, with the model of the concentration of hydrophobic residues in the center of the molecule, with the simultaneous exposure of polar residues is determined by the sequence of amino acids in the chain. The fuzzy oil drop model enables the quantification of the degree of compatibility of the hydrophobicity distribution observed in the protein to a form fully consistent with the Gaussian 3D function, which expresses an idealized distribution that meets the preferences of the polar water environment. The varied degrees of compatibility of the distribution observed with the idealized one allow the prediction of preferences to interactions with molecules of different polarity, including water molecules in particular. This paper analyzes a set of proteins with different levels of hydrophobicity distribution in the context of the solubility of a given protein and the possibility of complex formation.