PROGRESS STUDY: Progression of chronic kidney disease in children and heat shock proteins

Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12192-021-01239-9.     

Characterization of the native honey bee (Apis mellifera jemenitica) in the south western region of Saudi Arabia using morphometric and genetic (mtDNA COI) characteristics

Apis mellifera jemenitica incorporates a few perceived subspecies that vary in their natural properties and farming qualities. Mitochondrial COI gene sequence (mtCOI) has not been used before for bee identification in the southwestern region of Saudi Arabia. The aim of this work was to study the morphometry and analyzing the mtCOI of all collected bees. The nucleotide sequence of the mtCOI gene was analyzed. Similarity searches and distances between each obtained DNA and sequences available in GenBank were made. Morphometric analysis revealed close similarities among the studied bees, but these similarities are different from those previously indicated in earlier studies of the same region. Molecular studies revealed that the collected bees are similar to each other and some other sequences found in GenBank, but these bees are a new hybrid or subspecies that are different from those previously reported in the same region, indicating the emergence of a new hybrid.     

In silico molecular docking analysis for repurposing approved antiviral drugs against SARS-CoV-2 main protease

Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.     

Naturally occurring thiophenes: isolation,purification, structural elucidation,and evaluation of bioactivities

Phytochemistry Reviews - Thiophenes are a class of heterocyclic aromatic compounds based on a five-membered ring made up of one sulfur and four carbon atoms. The thiophene nucleus is well...     

A Mathematical Framework for Kinetochore-Driven Activation Feedback in the Mitotic Checkpoint

Proliferating cells properly divide into their daughter cells through a process that is mediated by kinetochores, protein–complexes that assemble at the centromere of each sister chromatid. Each kinetochore has to establish a tight bipolar attachment to the spindle apparatus before sister chromatid separation is initiated. The spindle assembly checkpoint (SAC) links the biophysical attachment status of the kinetochores to mitotic progression and ensures that even a single misaligned kinetochore keeps the checkpoint active. The mechanism by which this is achieved is still elusive. Current computational models of the human SAC disregard important biochemical properties by omitting any kind of feedback loop, proper kinetochore signals, and other spatial properties such as the stability of the system and diffusion effects. To allow for more realistic in silico study of the dynamics of the SAC model, a minimal mathematical framework for SAC activation and silencing is introduced. A nonlinear ordinary differential equation model successfully reproduces bifurcation signaling switches with attachment of all 92 kinetochores and activation of APC/C by kinetochore-driven feedback. A partial differential equation model and mathematical linear stability analyses indicate the influence of diffusion and system stability. The conclusion is that quantitative models of the human SAC should account for the positive feedback on APC/C activation driven by the kinetochores which is essential for SAC silencing. Experimental diffusion coefficients for MCC subcomplexes are found to be insufficient for rapid APC/C inhibition. The presented analysis allows for systems-level understanding of mitotic control, and the minimal new model can function as a basis for developing further quantitative–integrative models of the cell division cycle.     

Cloning and characterization of an epoxide hydrolase from Cupriavidus metallidurans-CH34

A putative epoxide hydrolase-encoding gene was identified from the genome sequence of Cupriavidus metallidurans CH34. The gene was cloned and overexpressed in Escherichia coli with His(6)-tag at its N-terminus. The epoxide hydrolase (CMEH) was purified to near homogeneity and was found to be a homodimer, with subunit molecular weight of 36 kDa. The CMEH had broad substrate specificity as it could hydrolyze 13 epoxides, out of 15 substrates tested. CMEH had high specific activity with 1,2-epoxyoctane, 1,2-epoxyhexane, styrene oxide (SO) and was also found to be active with meso-epoxides. The enzyme had optimum pH and temperature of 7.5 and 37°C respectively, with racemic SO. Biotransformation of 80 mM SO with recombinant whole E. coli cells expressing CMEH led to 56% ee(P) of (R)-diol with 77.23% conversion in 30 min. The enzyme could hydrolyze (R)-SO, ～2-fold faster than (S)-SO, though it accepted both (R)- and (S)-SO with similar affinity as K(m)(R) and K(m)(S) of CMEH were 2.05±0.42 and 2.11±0.16 mM, respectively. However, the k(cat)(R) and k(cat)(S) for the two enantiomers of SO were 4.80 and 3.34 s(-1), respectively. The wide substrate spectrum exhibited by CMEH combined with the fast conversion rate makes it a robust biocatalyst for industrial use. Regioselectivity studies with enantiopure (R)- and (S)-SO revealed that with slightly altered regioselectivity, CMEH has a high potential to synthesize an enantiopure (R)-PED, through an enantioconvergent hydrolytic process.     

Real-time PCR in HIV/Trypanosoma cruzi coinfection with and without Chagas disease reactivation: association with HIV viral load and CD4 level

Background

Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed.

Methodology

Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not.

Principal Findings

qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman''s correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4⁺ cells or the CD4⁺/CD8⁺ ratio.

Conclusions

qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4⁺ cells/mm³ and the CD4⁺/CD8⁺ ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy.     

Adjuvant BCG immunotherapy for stage I and II malignant melanoma.

Initial adjuvant immunotherapy trials have demonstrated a greater disease-free interval in patients treated with bacille Calmette-Guérin (BCG) compared with historical controls. In this study 149 patients at high risk of recurrence after surgical treatment of local or regional malignant melanoma were given BCG for 2 years and were followed up for a median of 28 months from the start of immunotherapy. The 36 patients in the comparison group had a higher rate of recurrence than the patients treated with BCG, and the rate in the treatment group was close to that reported from a similar study at the University of California at Los Angeles. The relatively long disease-free interval for the high-risk comparison patients in this study suggests that the control groups at other centres may have included patients with unrecognized additional risk. The rates of survival in the Canadian treatment group were also comparable to those reported by other centres. However, reports of a favourable BCG-mediated pattern of recurrence could not be confirmed. Therefore, the routine use of adjuvant BCG immunotherapy is not recommended.     

Preparation,characterization of silver phyto nanoparticles and their impact on growth potential of Lupinus termis L. seedlings

The current study reports rapid and easy method for synthesis of eco-friendly silver nanoparticles (AgNPs) using Coriandrum sativum leaves extract as a reducing and covering agent. The bio-reductive synthesis of AgNPs was monitored using a scanning double beam UV-vis spectrophotometer. Transmission electron microscopy (TEM) was used to characterize the morphology of AgNPs obtained from plant extracts. X-ray diffraction (XRD) patterns of AgNPs indicate that the structure of AgNPs is the face centered cubic structure of metallic silver. The surface morphology and topography of the AgNPs were examined by scanning electron microscopy and the energy dispersive spectrum revealed the presence of elemental silver in the sample. The silver phyto nanoparticles were collected from plant extract and tested growth potential and metabolic pattern in (Lupinus termis L.) seedlings upon exposure to different concentrations of AgNPs. The seedlings were exposed to various concentrations of (0, 0.1, 0.3 and 0.5 mg L^?1) AgNPs for ten days. Significant reduction in shoot and root elongation, shoot and root fresh weights, total chlorophyll and total protein contents were observed under the higher concentrations of AgNPs. Exposure to 0.5 mg L^?1 of AgNPs decreased sugar contents and caused significant foliar proline accumulation which considered as an indicator of the stressful effect of AgNPs on seedlings. AgNPs exposure resulted in a dose dependent decrease in different growth parameters and also caused metabolic disorders as evidenced by decreased carbohydrates and protein contents. Further studies needed to find out the efficacy, longevity and toxicity of AgNPs toward photosynthetic system and antioxidant parameters to improve the current investigation.