Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

Sirtuins (SIRTs), enzymes from the family of NAD⁺-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.     

Amination of biochar surface from watermelon peel for toxic chromium removal enhancement

Watermelon peel residues were used to produce a new biochar by dehydration method. The new biochar has undergone two methods of chemical modification and the effect of this chemical modification on its ability to adsorb Cr(VI) ions from aqueous solution has been investigated. Three biochars, Melon-B, Melon-BO-NH_2 and Melon-BO-TETA, were made from watermelon peel via dehydration with 50% sulfuric acid to give Melon-B followed by oxidation with ozone and amination using ammonium hydroxide to give Melon-BO-NH_2 or Triethylenetetramine(TETA) to give Melon-BO-TETA. The prepared biochars were characterized by BET, BJH,SEM, FT-IR, TGA, DSC and EDAX analyses. The highest removal percentage of Cr(VI) ions was 69% for Melon-B,98% for Melon-BO-NH_2 and 99% for Melon-BO-TETA biochars of 100 mg·L~(-1) Cr(VI) ions initial concentration and 1.0 g·L~(-1) adsorbents dose. The unmodified biochar(Melon-B) and modified biochars(Melon-BO-NH_2 and Melon-BO-TETA) had maximum adsorption capacities(Qm) of 72.46, 123.46, and 333.33 mg·g~(-1), respectively.The amination of biochar reduced the pore size of modified biochar, whereas the surface area was enhanced.The obtained data of isotherm models were tested using different error function equations. The Freundlich,Tempkin and Langmuir isotherm models were best fitted to the experimental data of Melon-B, Melon-BO-NH_2 and Melon-BO-TETA, respectively. The adsorption rate was primarily controlled by pseudo-second–order rate model. Conclusively, the functional groups interactions are important for adsorption mechanisms and expected to control the adsorption process. The adsorption for the Melon-B, Melon-BO-NH_2 and Melon-BO-TETA could be explained for acid–base interaction and hydrogen bonding interaction.     

Effect of hyperbranched poly(citric polyethylene glycol) with various polyethylene glycol chain lengths on starch plasticization and retrogradation

A series of hyperbranched poly(citric polyethylene glycol) (PCPEG) materials with varied polyethylene glycol (PEG) chain lengths as plasticizers were mixed with maize starch (MS) via cooking and film‐forming. The structure, pasting property, plasticization, aging property, moisture absorption and compatibility of plasticized starches were studied by means of Fourier transform infrared spectroscopy, X‐ray diffraction, rapid viscosity analysis, tension testing, moisture absorption measurements and scanning electron microscopy. Compared with PEG and citric acid, PCPEG was more effective in promoting starch chain movement and inhibiting the retrogradation of starch film. Also, PCPEG/MS had smaller moisture content. The longer the plasticizer chain, the better were the aging resistance and moisture resistance of starch. But with an increase of PEG chain length, mechanical properties of PCPEG/MS deteriorated and the compatibility between PCPEG and MS decreased. The hyperbranched derivative of PEG with longer chain exhibited improved plasticization and compatibility with starch. © 2019 Society of Chemical Industry     

TiO2/MXene-Assisted LDI-MS for Urine Metabolic Profiling in Urinary Disease

Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO₂/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO₂/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.     

Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Harmful effects of pyrethroid ester insecticide on the male reproductive system mainly through affecting testicular function and inflammatory markers

Pyrethroid esters are widely used as insecticides worldwide. In this study, we aimed to evaluate the harmful effect of deltamethrin on the male reproductive system through the assessment of reproductive hormones, inflammatory markers, and testicular function. To achieve our aim, eighty male 7-9-week-old, Wistar rats were taken, weighed, and divided into four experimental groups. The first group was kept as a control group, and the other three groups were given deltamethrin orally at different concentrations (0.87, 8.7, and 17.4 mg/kg body weight) for nine weeks. The results indicated that deltamethrin administration associated with a significant decrease in reproductive hormones, especially FSH, LH, and significant elevation in the interleukin 2 (IL2), interleukin 6 (IL6), histamine, and cortisol levels. Also, the significance of inhibition of sperm motility and viability, decreased testis weights, sperm count, and fructose in semen were noted. These findings clarify the harmful effect of deltamethrin on the male reproductive system by producing a significant alteration in reproductive hormones, inflammatory markers as well as testicular function.