Inhibitory effects of Gracilaria edulis and Gracilaria salicornia against the MGMT and VEGFA biomarkers involved in the onset and advancement of glioblastoma using in silico and in vitro approaches.

Glioblastoma (GBM), an aggressive primary brain tumor originating from glial cells, poses significant treatment challenges due to its rapid growth and invasiveness. The exact mechanisms of GBM's brain damage remain unclear. This study examines primary molecular markers commonly assessed in GBM patients, including brain-derived neurotrophic factor (BDNF), platelet-derived growth factor receptor A (PDGFRA), O6-methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA) using computational approaches. The study revealed significant differences (p ≤ 0.05) in PDGFRA, EGFR, and VEGFA expression rates, which are particularly interesting. Additionally, MGMT and VEGFA showed higher hazard ratios. Expression levels of MGMT and VEGFA were visualized in immune and malignant cells using single-cell RNA datasets GSE103224 and GSE148842. From a total of 48 compounds in Gracilaria edulis and 86 in Gracilaria salicornia, we identified 15 compounds capable of crossing the blood-brain barrier. Notably, 2-tridecanone (binding affinity [BA] = -4.2 kcal/mol; root mean square deviation [RMSD] = 1.479 Å) and decanoic acid, ethyl ester (BA = -4.2 kcal/mol; RMSD = 1.702 Å) from G. edulis interacted with MGMT via hydrogen bonds. The compound alpha-terpineol interacted with MGMT (BA = -5.7 kcal/mol; RMSD = 0.501 Å) and VEGFA (BA = -4.7 kcal/mol; RMSD = 2.483 Å). Ethanolic and methanolic extracts from G. edulis and G. salicornia demonstrated mild anti-cell proliferation properties in the GBM LN-229 cell line, suggesting potential therapeutic benefits. This study highlights the significance of molecular markers and natural compounds in understanding and potentially treating GBM.

Exploring the adsorption efficacy of Cassia fistula seed carbon for Cd (II) ion removal: Comparative study of isotherm models.

The current study demonstrates the potential of Cassia fistula seed carbon (CFSC), a waste lignocellulosic biomass, to eliminate Cd (II) ion-from saturated liquid samples. The efficient removal of about 93.2% (w/v) of Cd (II) ions from 10 mg/L concentration was achieved within 80 min of treatment. The CFSC dosage of 100 mg/50 mL accounted as optimal for enhanced Cd (II) removal. Cd (II) adsorption onto CFSC was observed to be maximum at pH 6. The investigational trials were assessed with three isotherm models such Dubinin-Radushkevich, Freundlich, and Langmuir. The specifications obtained from this experimental study align well with the Langmuir isotherm model, which describes the maximal adsorption capacity of 68.02 mg/g. Cd (II) adsorption data from this study exhibited the R2 of 0.9 under pseudo-second-order. Maximum desorption (76.3% w/v) was obtained with 0.3 M HCL. This study revealed that thermally activated C. fistula seed carbon (CFSC) can be tuned to be lucrative adsorbent for Cd (II) elimination from water and waste-water.

Daidzein attenuated paclitaxel-induced neuropathic pain via the down-regulation of TRPV1/P2Y and up-regulation of Nrf2/HO-1 signaling.

Paclitaxel (PTX) is an anti-microtubule agent, used for the treatment of various types of cancers; however, it produces painful neuropathy which limits its use. Many neuroprotective agents have been introduced to mitigate PTX-induced neuropathic pain (PINP), but they pose many adverse effects. The purpose of this study was to evaluate the pharmacological characteristics of soy isoflavone, and daidzein (DZ) in attenuating PINP. At the beginning of the investigation, the effect of DZ was confirmed through behavioral analysis, as it reduced pain hypersensitivity. Moreover, changes in the histological parameters were reversed by DZ administration along with vascular permeability. PTX administration upregulated transient receptor potential vanilloid 1 (TRPV1) channels and purinergic receptors (P2Y), contributing to hyperalgesia; but administration of DZ downregulated the TRPV1 and P2Y, thus reducing hyperalgesia. DZ increased nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), playing a pivotal role in the activation of the antioxidant pathway. DZ also decreased neuronal apoptosis by decreasing caspase-3 and Bcl2-associated X-protein (Bax), while simultaneously, increasing Bcl-2. PTX administration produced severe DNA damage, which was mitigated by DZ. Similarly, DZ administration resulted in inhibition of neuroinflammation by increasing antioxidant enzymes and reducing oxidative stress markers. PTX caused increased in production of pro-inflammatory mediators such as the cytokines production, while DZ inhibited the pro-inflammatory mediators. Additionally, in silico pharmacokinetic and toxicodynamic study of DZ was also conducted. In summary, DZ demonstrated significant neuroprotective activity against PTX induced neuropathic pain.

Anti-nociceptive effects of magnolol via inhibition of TRPV1/P2Y and TLR4/NF-κB signaling in a postoperative pain model.

AIMS: The current study explored the anti-nociceptive activity of magnolol in post-incisional inflammatory nociceptive pain. MAIN METHODS: Preliminary, the anti-inflammatory, antioxidant, and cytoprotective potential of magnolol were confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. Next, an in-vivo model of planter incision surgery was established in BALB/c mice. Tramadol 50 mg/kg intraperitoneal (i.p.) and magnolol (0.1, 1, 10 mg/kg i.p. + 10 mg/kg intra planter) were administered after plantar incision surgery and behavior parameters were measured. KEY FINDINGS: The results indicate that magnolol significantly suppressed post-incision-induced mechanical allodynia, thermal hyperalgesia, and paw edema. Magnolol promisingly inhibited post-incision induces nitric oxide (NO), malondialdehyde (MDA), eosinophil peroxidase (EPO), and neutrophil infiltration. Magnolol strongly attenuated post-incision inducing the release of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and inhibited deoxyribonucleic acid (DNA) fragmentation. Magnolol markedly reverses post-incisional histopathological changes and biochemical composition of the incised paw. Magnolol markedly down-regulated post-incisional increase expression of transient receptor potential vanilloid 1 (TRPV1), purinergic (P2Y) nociceptors as well as toll-like receptor 4 (TLR4), nuclear factor kappa light chain enhancer of activated B cell (NF-κB), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) while upregulating the expression of inhibitor of nuclear kappa B alpha (IκB-α). SIGNIFICANCE: The present study strongly suggests that magnolol significantly suppressed post-incisional inflammatory nociceptive pain by targeting TRPV1/P2Y and TLR4/NF-κB signaling.

Root system architecture of historical spring wheat cultivars is associated with alleles and transcripts of major functional genes.

We evaluated root system architecture (RSA) of a set of 58 historical spring wheat cultivars from Pakistan representing 105 years of selection breeding. The evaluations were carried out under control and water-limited conditions using a high-throughput phenotyping system coupled with RhizoVision Explorer software. The cultivars were classified into three groups based on release year as cultivars released pre-1965, released between 1965 and 2000, and cultivars released post-2000. Under water-limited conditions a decline in 20 out of 25 RSA component traits was observed in pre-1965 cultivars group. Whereas cultivars released after the 1965, so-called green revolution period, showed a decline in 17 traits with significant increments in root length, depth, and steep angle frequency which are important root traits for resource-uptake under water-limited conditions. Similarly, cultivars released after 2000 indicated an increase in the number of roots, depth, diameter, surface area, and steep angle frequency. The coefficient of correlation analysis showed a positive correlation between root depth and yield-related traits under water-limited conditions. We also investigated the effects of green-revolution genes (Rht1) and some phenology-related genes such as DRO1, TaMOR, TaLTPs, TaSus-2B on RSA and identified significant associations of these genes with important root traits. There was strong selection pressure on DRO1 gene in cultivated wheat indicating the allele fixed in modern wheat cultivars is different from landraces. The expression of DRO1, and TaMOR were retrieved from an RNAseq experiment, and results were validated using qRT-PCR. The highest expression of DRO1 and TaMOR was found in Chakwal-50, a rainfed cultivar released in 2008, and MaxiPak-65 released in 1965. We conclude that there is a positive historic change in RSA after 1965 that might be attributed to genetic factors associated with favored RSA traits. Furthermore, we suggest root depth and steep angle as promising traits to withstand water-limited environments and may have implications in selection for breeding.

Genome-wide association for heat tolerance at seedling stage in historical spring wheat cultivars.

Increasing global temperature has adverse effects on crop health and productivity at both seedling and reproductivity stages. It is paramount to develop heat tolerant wheat cultivars able to sustain under high and fluctuating temperature conditions. An experiment was conducted to characterize 194 historical wheat cultivars of Pakistan under high temperature at seedling stage to identify loci associated with heat tolerance using genome-wide association studies (GWAS). A quantitative trait locus, TaHST1, on chr4A was also characterized to identify the haplotypes at this locus associated with heat tolerance in wheat from Pakistan. Initially, the diversity panel was planted under control conditions (25°C/20°C day and night temperature) in a glass house. At three leaf stage, plants were subjected to heat stress (HS) by increasing temperature (40°C/35°C day and night), while one treatment was kept at control condition. After 7 days of HS, data were collected for seedling morphology. Heat stress reduced these traits by 25% (root weight) to 40% (shoot weight), and shoot biomass was largely affected by heat stress. A GWAS model, fixed and random model circulating probability unification (FarmCPU), identified 43 quantitative trait nucleotides (QTNs) on all chromosomes, except chr7B, were associated under both HS and control conditions. Thirteen QTNs were identified in control, while 30 QTNs were identified in HS condition. In total, 24 haplotypes were identified at TaHST1 locus, and most of the heat tolerant genotypes were assigned to Hap-20 and Hap-21. Eleven QTNs were identified within 0.3-3.1 Mb proximity of heat shock protein (HSP). Conclusively, this study provided a detailed genetic framework of heat tolerance in wheat at the seedling stage and identify potential genetic regions associated with heat tolerance which can be used for marker assisted selection (MAS) in breeding for heat stress tolerance.