P53-associated lncRNAs regulate immune functions and RNA-modifiers in gastric cancer.

TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.

In vitro and in silico evaluation of bioactivities and chemical composition of the aerial parts of Anchusa officinalis L. methanol extract.

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R2 = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R2 = 0.999). The IC50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 µg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 µg/mL). The IC50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities.

New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease MPro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies.

New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.

Lamiales epidermal dynamics: Unveiling antimicrobial resilience in a structural symphony.

This research on Lamiales epidermal anatomy not only provides in-depth understanding of their structural traits but also highlights the significance of uncovering the inherent antimicrobial resilience embedded within these plants. Such insights hold promise for advancing natural product-based approaches in medicine, potentially contributing to the development of novel antimicrobial agents inspired by Lamiales unique biological defense mechanisms. Scanning microscopic tools were utilized to conduct foliar epidermal anatomy of nine species that belong to seven genera and four families within the Lamiales order, Plantaginaceae, Scrophulariaceae, Verbenaceae, and Lamiaceae. This approach aimed to gather both qualitative and quantitative data, facilitating the assessment of taxonomic microanatomical significance. The shape of epidermal cells and their anticlinal walls; number of epidermal cells, stomata, and trichomes; type of stomata and trichomes; length and width of epidermal cells, trichomes, stomatal pore, guard cells, and subsidiary cells; and stomatal index were determined statistically. Most of the species examined were amphistomatous and showed extensive array of trichomes diversity. The exploration of Lamiales epidermal micromorphology and their antimicrobial potential were significant for their implications in multidisciplinary fields. The pharmacological research to utilize sustainable agricultural practices prompts avenues to strengths of Lamiales order for the development of novel antimicrobial solutions and ecological benefits. RESEARCH HIGHLIGHTS: Diverse trichome morphometry reveals a wide array of trichome structures across Lamiales species. Epidermal microscopic architecture variability of epidermal cell shapes and sizes signifies the interspecies variability. Secondary metabolite localization within microanatomical structures elucidates potential hotspots for antimicrobial compound production.

Biological and molecular characterization of citrus bent leaf viroid.

Background and aim: Citrus bent leaf viroid (CBLVd) is one of the emerging and widely distributed viroids in citrus-growing areas of the world, including Pakistan. Previously, CBLVd has been reported in Pakistan for the first time in 2009. Therefore, characterization of CBLVd is required to monitor the viroid status in the citrus orchards concerning citrus decline. Methods: Biological and molecular characterization of CBLVd was studied through biological indexing and confirmation through RT-PCR, followed by phylogenetic analysis of selected CBLVd isolates. Among four citrus cultivars viz., Kinnow (Citrus nobilis × Citrus deliciosa), Mosambi (C. sinensis), Futrell's Early (C. reticulata) and Lemon (C. medica) used as indicator plants for two transmission trials viz., graft inoculation and mechanical inoculation. Graft inoculation was more efficient than mechanical inoculation. Results: Symptoms such as mild mosaic, slight backward leaf bending, and leaf curling were observed after eight months' post-inoculation. Citrus nobilis × Citrus deliciosa, C. reticulata and C. sinensis were more sensitive to CBLVd as compared to C. medica. Inoculated plants were reconfirmed through RT-PCR amplicons of 233 bp. The phylogenetic tree of submitted sequences showed more than 90% relevance of CBLVd in Pakistan compared to the rest of the world. Conclusions: There was slight genetic variability, but more than 90% relevance was found among the submitted and already reported CBLVd isolate from Pakistan. Scanty literature is available regarding the biological and molecular studies of CBLVd in Pakistan. Therefore, the transmission and molecular characterization of CBLVd in Pakistan were studied for the first time.

Chemical Composition, Antioxidant, Anticancer, and Antibacterial Activities of Roots and Seeds of Ammi visnaga L. Methanol Extract.

For centuries, plants and their components have been harnessed for therapeutic purposes, with Ammi visnaga L. (Khella) being no exception to this rich tradition. While existing studies have shed light on the cytotoxic and antimicrobial properties of seed extracts, there remains a noticeable gap in research about the antimicrobial, antioxidant, and anticancer potential of root extracts. This study seeks to address this gap by systematically examining methanol extracts derived from the roots of A. visnaga L. and comparing their effects with those of seed extracts specifically against breast cancer cells. Notably, absent from previous investigations, this study focuses on the comparative analysis of the antimicrobial, antioxidant, and anticancer activities of both root and seed extracts. The methanol extract obtained from A. visnaga L. seeds demonstrated a notably higher level of total phenolic content (TPC) than its root counterpart, measuring 366.57 ± 2.86 and 270.78 ± 2.86 mg GAE/g dry weight of the dry extract, respectively. In the evaluation of antioxidant activities using the DPPH method, the IC50 values for root and seed extracts were determined to be 193.46 ± 17.13 µg/mL and 227.19 ± 1.48 µg/mL, respectively. Turning our attention to cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231), both root and seed extracts displayed similar cytotoxic activities, with IC50 values of 92.45 ± 2.14 µg/mL and 75.43 ± 2.32 µg/mL, respectively. Furthermore, both root and seed extracts exhibited a noteworthy modulation of gene expression, upregulating the expression of caspase and Bax mRNA levels while concurrently suppressing the expression of anti-apoptotic genes (Bcl-xL and Bcl-2), thereby reinforcing their potential as anticancer agents. A. visnaga L. seed extract outperforms the root extract in antimicrobial activities, exhibiting lower minimum inhibitory concentrations (MICs) of 3.81 ± 0.24 to 125 ± 7.63 µg/mL. This highlights the seeds' potential as potent antibacterial agents, expanding their role in disease prevention. Overall, this study underscores the diverse therapeutic potentials of A. visnaga L. roots and seeds, contributing to the understanding of plant-derived extracts in mitigating disease risks.