Glutathione S‒transferases (GSTs) are multifunctional enzymes that play an important role in detoxification, cellular signalling, and the stress response. Camelus dromedarius is well-adapted to ...survive in extreme desert climate and it has GSTs, for which limited information is available. This study investigated the structure-function and thermodynamic properties of a mu-class camel GST (CdGSTM1) at different pH. Recombinant CdGSTM1 (25.7 kDa) was expressed in E. coli and purified to homogeneity. Dimeric CdGSTM1 dissociated into stable but inactive monomeric subunits at low pH. Conformational and thermodynamic changes during the thermal unfolding pathway of dimeric and monomeric CdGSTM1 were characterised via a thermal shift assay and dynamic multimode spectroscopy (DMS). The thermal shift assay based on intrinsic tryptophan fluorescence revealed that CdGSTM1 underwent a two-state unfolding pathway at pH 1.0-10.0. Its Tm value varied with varying pH. Another orthogonal technique based on far-UV CD also exhibited two-state unfolding in the dimeric and monomeric states. Generally, proteins tend to lose structural integrity and stability at low pH; however, monomeric CdGSTM1 at pH 2.0 was thermally more stable and unfolded with lower van't Hoff enthalpy. The present findings provide essential information regarding the structural, functional, and thermodynamic properties of CdGSTM1 at pH 1.0-10.0.
Guava (
) leaves are commonly used in the treatment of diseases. They are considered a waste product resulting from guava cultivation. The leaves are very rich in essential oils (EOs) and volatiles. ...This work represents the detailed comparative chemical profiles of EOs derived from the leaves of six guava varieties cultivated in Egypt, including Red Malaysian (RM), El-Qanater (EQ), White Indian (WI), Early (E), El-Sabahya El-Gedida (ESEG), and Red Indian (RI), cultivated on the same farm in Egypt. The EOs from the leaves of guava varieties were extracted by hydro-distillation and analyzed with GC-MS. The EOs were categorized in a holistic manner using chemometric tools. The hydro-distillation of the samples yielded 0.11-0.48% of the EO (
). The GC-MS analysis of the extracted EOs showed the presence of 38 identified compounds from the six varieties. The sesquiterpene compounds were recorded as main compounds of E, EQ, ESEG, RI, and WI varieties, while the RM variety attained the highest content of monoterpenes (56.87%). The sesquiterpenes,
-caryophyllene (11.21-43.20%), and globulol (76.17-26.42%) were detected as the major compounds of all studied guava varieties, while
-nerolidol (0.53-10.14) was reported as a plentiful compound in all of the varieties except for the RM variety. A high concentration of D-limonene was detected in the EOs of the RM (33.96%), WI (27.04%), and ESEG (9.10%) varieties. These major compounds were consistent with those reported for other genotypes from different countries. Overall, the EOs' composition and the chemometric analysis revealed substantial variations among the studied varieties that might be ascribed to genetic variability, considering the stability of the cultivation and climate conditions. Therefore, this chemical polymorphism of the studied varieties supports that these varieties could be considered as genotypes of
. It is worth mentioning here that the EOs, derived from leaves considered to be agricultural waste, of the studied varieties showed that they are rich in biologically active compounds, particularly
-caryophyllene,
-nerolidol, globulol, and D-limonene. These could be considered as added value for pharmacological and industrial applications. Further study is recommended to confirm the chemical variations of the studied varieties at a molecular level, as well as their possible medicinal and industrial uses.
The impact of biochar and chitosan on barley plants under drought stress conditions was investigated during two field experiments. Our results confirmed that drought stress negatively affected ...morphological and physiological growth traits of barley plants such as plant height, number of leaves, chlorophyll concentrations, and relative water content. However, electrolyte leakage (EL%), lipid peroxidation (MDA), soluble sugars, sucrose and starch contents significantly increased as a response to drought stress. Additionally, 1000 grain weight, grains yield ha−1 and biological yield significantly decreased in stressed barley plants, also anatomical traits such as upper epidermis, lower epidermis, lamina, and mesophyll tissue thickness as well as vascular bundle diameter of flag leaves significantly decreased compared with control. The use of biochar and chitosan led to significant increases in plant height, number of leaves, and chlorophyll concentrations as well as relative water content; nevertheless these treatments led to significant decreases in electrolyte leakage (EL%) and lipid peroxidation (MDA) in the stressed plants. Moreover, anatomical and yield characters of stressed barley plants were improved with application of biochar and chitosan. The results proved the significance of biochar and chitosan in alleviating the damaging impacts of drought on barley plants.
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The objective of this study was to assess the effects of sodium dodecyl sulphate (SDS) on the hen egg white lysozyme (HEWL) at pH 9.0. We employed several spectroscopic (light ...scattering, intrinsic fluorescence, dynamic light scattering (DLS), and circular dichroism (CD)) techniques to evaluate the role of SDS in prevention of aggregation and imparting stability to HEWL. From the spectroscopic measurements, it was observed that the secondary as well as tertiary structures were modified in the presence of SDS. Thermal stability of HEWL with or without SDS was also evaluated. In the absence of SDS, HEWL starts unfolding at transition temperature 54.0 ± 0.22 °C. However, in the presence of 2.0 mM SDS, the HEWL unfolded at slightly higher temperature, and transition temperature was found to be around 59.77 ± 0.27 °C. In this study, we also found that thermal unfolding of HEWL led to simultaneous aggregation at temperatures above 55 °C as confirmed by light scattering measurements but no aggregation was seen in the presence of SDS. In the absence of SDS, the hydrodynamic radii of HEWL increased at higher temperature. However, the hydrodynamic radii remained unchanged in the presence of SDS up to 90 °C. The overall results suggested that SDS provided extra stability to and simultaneously prevented aggregation of HEWL. The possible interactions found in SDS-stabilized HEWL are electrostatic and hydrophobic.
The present study aims to develop a biodegradable polymer blend that is environmentally friendly and has comparable tensile and thermal properties with synthetic plastics. In this work, ...microcrystalline cellulose (MCC) extracted from bamboo-chips-reinforced poly (lactic acid) (PLA) and poly (butylene succinate) (PBS) blend composites were fabricated by melt-mixing at 180 °C and then hot pressing at 180 °C. PBS and MCC (0.5, 1, 1.5 wt%) were added to improve the brittle nature of PLA. Field emission scanning electron microscopy (FESEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscope (FTIR), thermogravimetric analysis (TGA), differential thermogravimetry (DTG), differential scanning calorimetry (DSC)), and universal testing machine were used to analyze morphology, crystallinity, physiochemical, thermal, and tensile properties, respectively. The thermal stability of the PLA-PBS blends enhanced on addition of MCC up to 1wt % due to their uniform dispersion in the polymer matrix. Tensile properties declined on addition of PBS and increased with MCC above (0.5 wt%) however except elongation at break increased on addition of PBS then decreased insignificantly on addition of MCC. Thus, PBS and MCC addition in PLA matrix decreases the brittleness, making it a potential contender that could be considered to replace plastics that are used for food packaging.
Background
Splice-disrupt genomic variants are one of the causes of cancer-causing errors in gene expression. Little is known about splice-disrupt genomic variants.
Methods and results
Here, pattern ...of splice-disrupt variants was investigated using 21,842,764 genomic variants in different types of prostate cancer. A particular attention was paid to genomic locations of splice-disrupt variants on target genes.
HLA-A
in prostate cancer,
MSR1
in familial prostate cancer, and
EGFR
in both castration-resistant prostate cancer and metastatic castration-resistant had the highest allele frequencies of splice-disrupt variations. Some splice-disrupt variants, located on coding sequences of
NCOR2
,
PTPRC
, and
CRP
, were solely present in the advanced metastatic castration-resistant prostate cancer. High-risk splice-disrupt variants were identified based on computationally calculated Polymorphism Phenotyping (PolyPhen), Sorting Intolerant From Tolerant (SIFT), and Genomic Evolutionary Rate Profiling (GERP) + + scores as well as the recorded clinical significance in dbSNP database of NCBI. Functional annotation of damaging splice-disrupt variants highlighted important cancer-associated functions, including endocrine resistance, lipid metabolic process, steroid metabolic process, regulation of mitotic cell cycle, and regulation of metabolic process. This is the first study that profiles the splice-disrupt genomic variants and their target genes in prostate cancer. Literature mining based variant analysis highlighted the importance of rs1800716 variant, located on the
CYP2D6
gene, involved in a range of important functions, such as RNA spicing, drug interaction, death, and urotoxicity.
Conclusions
This is the first study that profiles the splice-disrupt genomic variants and their target genes in different types of prostate cancer. Unravelling alternative splicing opens a new avenue towards the establishment of new diagnostic and prognostic markers for prostate cancer progression and metastasis.
In this study six unsymmetrical thiourea derivatives, 1-isobutyl-3-cyclohexylthiourea (1), 1-tert-butyl-3-cyclohexylthiourea (2), 1-(3-chlorophenyl)-3-cyclohexylthiourea (3), ...1-(1,1-dibutyl)-3-phenylthiourea (4), 1-(2-chlorophenyl)-3-phenylthiourea (5) and 1-(4-chlorophenyl)-3-phenylthiourea (6) were obtained in the laboratory under aerobic conditions. Compounds 3 and 4 are crystalline and their structure was determined for their single crystal. Compounds 3 is monoclinic system with space group P21/n while compound 4 is trigonal, space group R3:H. Compounds (1–6) were tested for their anti-cholinesterase activity against acetylcholinesterase and butyrylcholinesterase (hereafter abbreviated as, AChE and BChE, respectively). Potentials (all compounds) as sensing probes for determination of deadly toxic metal (mercury) using spectrofluorimetric technique were also investigated. Compound 3 exhibited better enzyme inhibition IC50 values of 50, and 60 µg/mL against AChE and BChE with docking score of −10.01, and −8.04 kJ/mol, respectively. The compound also showed moderate sensitivity during fluorescence studies.
This work focuses on the study of the drilling performance of bio composites reinforced with date palm fibers (CDPF). It is a new fiber that is characterized in terms of piercing behavior for the ...first time. The experimental study was carried out with three types of drills, with a diameter of 10 mm and feed and spindle speeds of the order of (40, 80 and 200 mm/min) and (560, 1120 and 2240 rpm), respectively. The drilling performance was assessed in terms of delamination and surface quality, such as circularity and cylindricity of the drilled holes. Using the CMM machine, the value of the delamination factor was determined using Image J software. The results showed that the value of the latter increased with the increase in feed rate and decreased with the increase in spindle speed. The delamination factor has maximum and minimum values of approximately 1.98 and 1.01 respectively. For the first time, RSM and ANOVA were used to assess the influence and interaction of input parameters (cutting conditions) on the output parameters (delamination factor Fd) during drilling of CDPF. The results obtained help manufacturers, to choose the most appropriate machining conditions to achieve better machinability for other newly developed NFRCs in the aeronautical and defense industry where the substitution of the synthetic fibers by the natural fibers becomes inevitable for economic reasons.
Abstract Farmers are using municipal wastewater either treated or untreated for irrigation because of limited fresh water resources. Wastewater extensively used for irrigation purposes is enriched ...with many nutrients. The reuse of wastewater is imposing a negative impact on human health and the ecosystem. It is a need of the day to identify and assess issues of the reuse of wastewater. In the current experiment, impact of organic/inorganic amendments was studied to mitigate the toxic effects of pollutants present in wastewater. Soil was brought from the site having consistent use of wastewater and different treatments were applied as per plan. The experiment has 28 treatments with 04 replications. Nine different amendments were used at 3 varying levels. Incubation time of 30 days was given after the addition of all treatments. The results of the study showed the application of FYM @ 5.0% w/w soil reduced soil pH (7.44), EC (2.16 dS m −1 ), SAR (8.14), lead (8.48 mg kg −1 ), cadmium (1.14 mg kg −1 ), nickel (10.55 mg kg −1 ) and arsenic (2.03 mg kg −1 ) when compared with control and other treatments. Usage of compost and horse waste followed FYM. On the basis of this study, it is recommended that wastewater can be used for irrigation purpose after treating with FYM preferably and compost in general.
Background and objectives: Non-small cell lung cancer (NSCLC) is often caused by EGFR mutations, leading to overactive cell growth pathways. Drug resistance is a significant challenge in lung cancer ...treatment, affecting therapy effectiveness and patient survival. However, combining drugs in research shows promise in addressing or delaying resistance, offering a more effective approach to cancer treatment. In this study, we investigated the potential alterations in the apoptotic pathway in A549 cells induced by a combined targeted therapy using tyrosine kinase inhibitors (TKIs) olmutinib and poziotinib, focusing on cell proliferation, differential gene expression, and in silico analysis of apoptotic markers. Methods: A combined targeted therapy involving olmutinib and poziotinib was investigated for its impact on the apoptotic pathway in A549 cells. Cell proliferation, quantitative differential gene expression, and in silico analysis of apoptotic markers were examined. A549 cells were treated with varying concentrations (1, 2.5, and 5 μM) of poziotinib, olmutinib, and their combination. Results: Treatment with poziotinib, olmutinib, and their combination significantly reduced cell proliferation, with the most pronounced effect at 2.5 μM (p < 0.005). A synergistic antiproliferative effect was observed with the combination of poziotinib and olmutinib (p < 0.0005). Quantitative differential gene expression showed synergistic action of the drug combination, impacting key apoptotic genes including STK-11, Bcl-2, Bax, and the Bax/Bcl-2 ratio. In silico analysis revealed direct interactions between EGFR and ERBB2 genes, accounting for 77.64% of their interactions, and 8% co-expression with downstream apoptotic genes. Molecular docking indicated strong binding of poziotinib and olmutinib to extrinsic and intrinsic apoptotic pathway markers, with binding energies of −9.4 kcal/mol and −8.5 kcal/mol, respectively, on interacting with STK-11. Conclusions: Combining poziotinib and olmutinib therapies may significantly improve drug tolerance and conquer drug resistance more effectively than using them individually in lung cancer patients, as suggested by this study’s mechanisms.
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