Correction: Abbas et al. Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies. Antioxidants 2022, 11, 1160.

In the original publication [...].

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis.

Background: Ulcerative colitis is a chronic immune-mediated inflammatory bowel disease that involves inflammation and ulcers of the colon and rectum. To date, no definite cure for this disease is available. Objective: The objective of the current study was to assess the effect of Calliandra haematocephala on inflammatory mediators and oxidative stress markers for the exploration of its anti-ulcerative colitis activity in rat models of acetic acid-induced ulcerative colitis. Methods: Methanolic and n-hexane extracts of areal parts of the plant were prepared by cold extraction method. Phytochemical analysis of both extracts was performed by qualitative analysis, quantitative methods, and high-performance liquid chromatography (HPLC). Prednisone at 2 mg/kg dose and plant extracts at 250, 500, and 750 mg/kg doses were given to Wistar rats for 11 days, which were given acetic acid on 8th day through the trans-rectal route for the induction of ulcerative colitis. A comparison of treatment groups was done with a normal control group and a colitis control group. To evaluate the anti-ulcerative colitis activity of Calliandra haematocephala, different parameters such as colon macroscopic damage, ulcer index, oxidative stress markers, histopathological examination, and mRNA expression of pro and anti-inflammatory mediators were evaluated. mRNA expression analysis was carried out by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: The phytochemical evaluation revealed polyphenols, flavonoids, tannins, alkaloids, and sterols in both extracts of the plant. Results of the present study exhibited that both extracts attenuated the large bowel inflammation and prevented colon ulceration at all tested doses. Macroscopic damage and ulcer scoreswere significantly decreased by both extracts. Malondialdehyde (MDA) levels and nitrite/nitrate concentrations in colon tissues were returned to normal levels while superoxide dismutase (SOD) activity was significantly improved by all doses. Histopathological examination exhibited that both extracts prevented the inflammatory changes, cellular infiltration, and colon thickening. Gene expression analysis by RT-qPCR revealed the downregulation of pro-inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) whereas the anti-inflammatory cytokines including Interleukin-4 (IL-4) and Interleukin-10 (IL-10) were found to be upregulated in treated rats. Conclusion: It was concluded based on study outcomes that methanolic and n-hexane extracts of Calliandra haematocephala exhibited anti-ulcerative colitis activity through modulation of antioxidant defense mechanisms and the immune system. In this context, C. haematocephala can be considered as a potential therapeutic approach for cure of ulcerative colitis after bioassay-directed isolation of bioactive phytochemicals and clinical evaluation.

Integrated virtual screening and molecular dynamics simulation approaches revealed potential natural inhibitors for DNMT1 as therapeutic solution for triple negative breast cancer.

Triple negative breast cancers (TNBC) are clinically heterogeneous but mostly aggressive malignancies devoid of expression of the estrogen, progesterone, and HER2 (ERBB2 or NEU) receptors. It accounts for 15-20% of all cases. Altered epigenetic regulation including DNA hypermethylation by DNA methyltransferase 1 (DNMT1) has been implicated as one of the causes of TNBC tumorigenesis. The antitumor effect of DNMT1 has also been explored in TNBC that currently lacks targeted therapies. However, the actual treatment for TNBC is yet to be discovered. This study is attributed to the identification of novel drug targets against TNBC. A comprehensive docking and simulation analysis was performed to optimize promising new compounds by estimating their binding affinity to the target protein. Molecular dynamics simulation of 500 ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between compound and binding pockets of DNMT1. In a nutshell, our study uncovered that Beta-Mangostin, Gancaonin Z, 5-hydroxysophoranone, Sophoraflavanone L, and Dorsmanin H showed maximum binding affinity with the active sites of DNMT1. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with TNBC, but, experimental validation is needed to ensure their safety.Communicated by Ramaswamy H. Sarma.

Structural insights into the mechanism of resistance to bicalutamide by the clinical mutations in androgen receptor in chemo-treatment resistant prostate cancer.

Despite advanced diagnosis and detection technologies, prostate cancer (PCa) is the most prevalent neoplasms in males. Dysregulation of the androgen receptor (AR) is centrally involved in the tumorigenesis of PCa cells. Acquisition of drug resistance due to modifications in AR leads to therapeutic failure and relapse in PCa. An overhaul of comprehensive catalogues of cancer-causing mutations and their juxta positioning on 3D protein can help in guiding the exploration of small drug molecules. Among several well-studied PCa-specific mutations, T877A, T877S and H874Y are the most common substitutions in the ligand-binding domain (LBD) of the AR. In this study, we combined structure as well as dynamics-based in silico approaches to infer the mechanistic effect of amino acid substitutions on the structural stability of LBD. Molecular dynamics simulations allowed us to unveil a possible drug resistance mechanism that acts through structural alteration and changes in the molecular motions of LBD. Our findings suggest that the resistance to bicalutamide is partially due to increased flexibility in the H12 helix, which disturbs the compactness, thereby reducing the affinity for bicalutamide. In conclusion, the current study helps in understanding the structural changes caused by mutations and could assist in the drug development process.Communicated by Ramaswamy H. Sarma.

Detection of high-risk human papillomavirus infected cervical biopsies samples by immunohistochemical expression of the p16 tumor marker.

Cervical cancer is the fourth most common type of cancer in women worldwide. It is widely accepted that the main cause of cervical cancer, especially in underdeveloped countries like Pakistan, is the infection caused by the human papillomavirus (HPV). The current screening and diagnostic methods face several challenges in accurately detecting the various types of lesions caused by HPV. Therefore, the present study was conducted to assess the effectiveness of p16 immunohistochemistry (IHC) analysis as a diagnostic method in samples of cervical biopsies. One hundred cervical biopsy samples were obtained from female patients across various age groups (> 20- ≤ 30, > 31- ≤ 40, > 41- ≤ 50, > 51- ≤ 60 years). These samples were subsequently prepared for subsequent examination. All samples were analyzed using automated tissue processing followed by Hematoxylin and Eosin (H & E) staining, and p16 IHC tumour marker staining. The H & E slides showed changes in normal cervical tissues, while four cervical abnormalities were identified statistically significant using p16 marker including chronic cervicitis, nabothian cyst formation, cervical intraepithelial neoplasia, and cervical cancers (P value 0.014). Furthermore, among females of different age groups (> 31- ≤ 40, > 41- ≤ 50, > 51- ≤ 60 years) were found statistically significant suffering from cervical cancer (P value 0.04), HPV with cervical cancer (P value 0.01), HPV with cervical intraepithelial neoplasia (P value 0.01). Based on the available data, it can be inferred that the incorporation of the p16 tumor marker may be a valuable method for detecting high-risk HPV in cervical biopsies samples.

The Use of Trimodality Treatment in Patients With Locally Advanced Oesophageal Squamous Cell Carcinoma: An Experience From a Large Cancer Centre in Pakistan.

Introduction Esophageal cancer is one of the most common cancers worldwide. Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for locally advanced squamous cell carcinoma (SCC). Pathological complete response (pCR) after surgery is associated with better outcomes in terms of overall survival and disease-free survival. We aim to determine the effectiveness of neoadjuvant chemoradiotherapy in patients with locally advanced SCC at our institute, the largest purpose-built cancer center in Pakistan. We also aim to identify various factors influencing pCR, such as chemotherapy regimen, total radiation dose, clinical stage at presentation, and gender. Materials and methods This is a retrospective review of all patients with esophageal SCC presented between January 2019 and 2021 to the institute for treatment. Patients received neoadjuvant chemoradiotherapy (nCRT) as per the CROSS trial protocol, followed by surgery. We assessed the pCR rate. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York). pCR was studied alongside associated factors such as age, gender, stage of disease, chemotherapy regimen, and total dose of radiotherapy. A p-value of <0.05 was considered statistically significant. The chi-square test was used to compare categorical variables. Univariate and multivariate logistic regression was employed to evaluate factors affecting pCR. Results A total of 218 patients were included in the study. pCR was achieved in 64.2% of the patients. The female gender was associated with better outcomes, as 70.4% (n=81) of female patients achieved a complete pathological response, compared to 57.3% (n=59) of males, with a p-value of 0.03. On univariate analysis, the complete pathological response was 69.6% (n=94) in the age group of 45 years and below, whereas it was 55.4% (n=46) in the age group above 45 years, with a p-value of 0.024. Though statistically insignificant, outcomes were slightly better for those with node-negative disease, as 67.2% (n=41) achieved complete pathological response compared to those with node-positive disease at 63.1% (n=99). Univariate logistic regression analysis identified gender (p=0.044, OR=1.77, 95% CI: 1.016-3.108) and age group (p=0.034, OR=1.844, 95% CI: 1.046-3.252) as significantly associated with pCR. Female patients were 77% more likely to achieve pCR compared to male patients (OR=1.77, 95% CI: 1.016-3.108). Younger patients (≤45 years) were 84.4% more likely to achieve pCR compared to the older age group (OR=1.844, 95% CI: 1.046-3.252). However, these did not maintain significance in multivariate logistic regression analysis. Conclusion Our study indicated a high rate of pCR with nCRT in patients with esophageal SCC compared to other studies. The achievement of pCR was higher among females and younger patients, which was statistically significant on univariate logistic regression analysis. Our study also concluded that a higher dose of RT (50Gy/25#) is not superior to a lower dose (45Gy/25#) in terms of pCR achievement but was statistically insignificant. Similarly, CARBO/PAC was not superior to CIS/CAP in terms of pCR achievement and was also statistically insignificant.

Integrated omics and machine learning-assisted profiling of cysteine-rich-receptor-like kinases from three peanut spp. revealed their role in multiple stresses.

Arachis hypogaea (peanut) is a leading oil and protein-providing crop with a major food source in many countries. It is mostly grown in tropical regions and is largely affected by abiotic and biotic stresses. Cysteine-rich receptor-like kinases (CRKs) is a family of transmembrane proteins that play important roles in regulating stress-signaling and defense mechanisms, enabling plants to tolerate stress conditions. However, almost no information is available regarding this gene family in Arachis hypogaea and its progenitors. This study conducts a pangenome-wide investigation of A. hypogaea and its two progenitors, A. duranensis and A. ipaensis CRK genes (AhCRKs, AdCRKs, and AiCRKs). The gene structure, conserved motif patterns, phylogenetic history, chromosomal distribution, and duplication were studied in detail, showing the intraspecies structural conservation and evolutionary patterns. Promoter cis-elements, protein-protein interactions, GO enrichment, and miRNA targets were also predicted, showing their potential functional conservation. Their expression in salt and drought stresses was also comprehensively studied. The CRKs identified were divided into three groups, phylogenetically. The expansion of this gene family in peanuts was caused by both types of duplication: tandem and segmental. Furthermore, positive as well as negative selection pressure directed the duplication process. The peanut CRK genes were also enriched in hormones, light, development, and stress-related elements. MicroRNA (miRNA) also targeted the AhCRK genes, which suggests the regulatory association of miRNAs in the expression of these genes. Transcriptome datasets showed that AhCRKs have varying expression levels under different abiotic stress conditions. Furthermore, the multi-stress responsiveness of the AhCRK genes was evaluated using a machine learning-based method, Random Forest (RF) classifier. The 3D structures of AhCRKs were also predicted. Our study can be utilized in developing a detailed understanding of the stress regulatory mechanisms of the CRK gene family in peanuts and its further studies to improve the genetic makeup of peanuts to thrive better under stress conditions.

Network pharmacology based virtual screening of Flavonoids from Dodonea angustifolia and the molecular mechanism against inflammation.

Inflammation is a nonspecific immune response against injury caused by a harmful agent that strives to restore tissue function and homeostasis. Dodonaea angustifolia L.f. (Sapindaceae) is a medium-sized shrub used to treat a variety of diseases in traditional medicine. In the current study, integrated network-pharmacology and molecular docking approaches were used to identify the active constituents, their possible targets, signaling pathways, and anti-inflammatory effects of flavonoids from D.angustifolia. D. angustifolia active ingredients were acquired from the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT), and Traditional Chinese Medicine System Pharmacology (TCMSP) databases. The screening included the ten most prevalent D. angustifolia components, and the SwissTargetPrediction database was utilized to anticipate the targets of these compounds. Anti-inflammatory genes were found using the GeneCards database. The 175 overlapping genes were discovered as prospective D. angustifolia anti-inflammatory targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation, such as response to organonitrogen compound, protein kinase activity, phosphotransferase activity, pI3k-Akt signaling pathway, metabolic pathways, and chemical carcinogenesis. Compound-target-pathway, and protein-protein interaction networks revealed 6-Methoxykaempferol and 5-Hydroxy-7,8 dimethoxyflavone as key compounds, and AKT1, VEGFA, and EGFR as key targets. Furthermore, molecular docking followed by molecular dynamic (MD) simulation of D. angustifolia active ingredients with core proteins fully complemented the binding affinity of these compounds and indicated stable complexes at the docked site. These findings reveal D. angustifolia 's multi-target, multi-compound, and multi-pathway strategies against inflammation. Our study paved the way for further research into the mechanism for developing D. angustifolia -based natural products as alternative therapies for inflammation.

Identification and dynamics of novel scaffolds against Enterococcus faecium serine hydroxymethyltransferase enzyme: a potential target for antibiotics development.

Serine hydroxymethyltransferase enzyme is a significant player in purine, thymidylate, and L-serine biosynthesis and has been tagged as a potential target for cancer, viruses, and parasites. However, this enzyme as an anti-bacterial druggable target has not been explored much. Herein, in this work, different computational chemistry and biophysics techniques were applied to identify potential computational predicted inhibitory molecules against Enterococcus faecium serine hydroxymethyltransferase enzyme. By structure based virtual screening process of ASINEX antibacterial library against the enzyme two main compounds: Top-1_BDC_21204033 and Top-2_BDC_20700155 were reported as best binding molecules. The Top-1_BDC_21204033 and Top-2_BDC_20700155 binding energy value is -9.3 and -8.9 kcal/mol, respectively. The control molecule binding energy score is -6.55 kcal/mol. The mean RMSD of Top-1-BDC_21204033, Top-2-BDC_20700155 and control is 3.7 Å (maximum 5.03 Å), 1.7 Å (maximum 3.05 Å), and 3.84 Å (maximum of 6.7 Å), respectively. During the simulation time, the intermolecular docked conformation and interactions were seen stable despite of few small jumps by the compounds/control, responsible for high RMSD in some frames. The MM/GBSA and MM/PBSA binding free energy of lead Top-2-BDC_20700155 complex is -79.52 and -82.63 kcal/mol, respectively. This complex was seen as the most stable compared to the control. Furthermore, the lead molecules and control showed good druglikeness and pharmacokinetics profile. The lead molecules were non-toxic and non-mutagenic. In short, the compounds are promising in terms of binding to the serine hydroxymethyltransferase enzyme and need to be subjected to experimental studies.Communicated by Ramaswamy H. Sarma.

Advanced network pharmacology study reveals multi-pathway and multi-gene regulatory molecular mechanism of Bacopa monnieri in liver cancer based on data mining, molecular modeling, and microarray data analysis.

Liver cancer is a malignant tumor that grows on the surface or inside the liver. The leading cause is a viral infection with hepatitis B or C virus. Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer. A list of studies evidences the therapeutic efficacy of Bacopa monnieri against liver cancer, but the precise molecular mechanism is yet to be discovered. This study combines data mining, network pharmacology, and molecular docking analysis to potentially revolutionize liver cancer treatment by identifying effective phytochemicals. Initially, the information on active constituents of B. monnieri and target genes of both liver cancer and B. monnieri were retrieved from literature as well as from publicly available databases. Based on the matching results between B. monnieri potential targets and liver cancer targets, the protein-protein interaction (PPI) network was constructed using the STRING database and imported into Cytoscape for screening of hub genes based on their degree of connectivity. Later, the interactions network between compounds and overlapping genes was constructed using Cytoscape software to analyze the network pharmacological prospective effects of B. monnieri on liver cancer. Gene Ontology (GO) and KEGG pathway analysis of hub genes revealed that these genes are involved in the cancer-related pathway. Lastly, the expression level of core targets was analyzed using microarray data (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790). Further, the GEPIA server and PyRx software were used for survival and molecular docking analysis, respectively. In summary, we proposed that quercetin, luteolin, apigenin, catechin, epicatechin, stigmasterol, beta-sitosterol, celastrol, and betulic acid inhibit tumor growth by affecting tumor protein 53 (TP53), interleukin 6 (IL6), RAC-alpha serine/threonine protein kinases 1 (AKT1), caspase-3 (CASP3), tumor necrosis factor (TNF), jun proto-oncogene (JUN), heat shot protein 90 AA1 (HSP90AA1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), and SRC proto-oncogene (SRC). Through, microarray data analysis, the expression level of JUN and IL6 were found to be upregulated while the expression level of HSP90AA1 was found to be downregulated. Kaplan-Meier survival analysis indicated that HSP90AA1 and JUN are promising candidate genes that can serve as diagnostic and prognostic biomarkers for liver cancer. Moreover, the molecular docking and molecular dynamic simulation of 60ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between the compound and binding pockets of HSP90AA1 and JUN. Despite that, in vivo and in vitro studies are mandatory to unveil pharmacokinetics and biosafety profiles to completely track the candidature status of B. monnieri in liver cancer.

High-quality genome assembly and comparative genomic profiling of yellowhorn (Xanthoceras sorbifolia) revealed environmental adaptation footprints and seed oil contents variations.

Yellowhorn (Xanthoceras sorbifolia) is a species of deciduous tree that is native to Northern and Central China, including Loess Plateau. The yellowhorn tree is a hardy plant, tolerating a wide range of growing conditions, and is often grown for ornamental purposes in parks, gardens, and other landscaped areas. The seeds of yellowhorn are edible and contain rich oil and fatty acid contents, making it an ideal plant for oil production. However, the mechanism of its ability to adapt to extreme environments and the genetic basis of oil synthesis remains to be elucidated. In this study, we reported a high-quality and near gap-less yellowhorn genome assembly, containing the highest genome continuity with a contig N50 of 32.5 Mb. Comparative genomics analysis showed that 1,237 and 231 gene families under expansion and the yellowhorn-specific gene family NB-ARC were enriched in photosynthesis and root cap development, which may contribute to the environmental adaption and abiotic stress resistance of yellowhorn. A 3-ketoacyl-CoA thiolase (KAT) gene (Xso_LG02_00600) was identified under positive selection, which may be associated with variations of seed oil content among different yellowhorn cultivars. This study provided insights into environmental adaptation and seed oil content variations of yellowhorn to accelerate its genetic improvement.

Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications.

Antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs) post-operatively. However, there are concerns with the extent of prophylaxis post-operatively, especially in low- and middle-income countries (LMICs). This increases antimicrobial resistance (AMR), which is a key issue in Pakistan. Consequently, we conducted an observational cross-sectional study on 583 patients undergoing surgery at a leading teaching hospital in Pakistan with respect to the choice, time and duration of antimicrobials to prevent SSIs. The identified variables included post-operative prophylactic antimicrobials given to all patients for all surgical procedures. In addition, cephalosporins were frequently used for all surgical procedures, and among these, the use of third-generation cephalosporins was common. The duration of post-operative prophylaxis was 3-4 days, appreciably longer than the suggestions of the guidelines, with most patients prescribed antimicrobials until discharge. The inappropriate choice of antimicrobials combined with prolonged post-operative antibiotic administration need to be addressed. This includes appropriate interventions, such as antimicrobial stewardship programs, which have been successful in other LMICs to improve antibiotic utilization associated with SSIs and to reduce AMR.

Effect of soil texture and zinc oxide nanoparticles on growth and accumulation of cadmium by wheat: a life cycle study.

Cadmium (Cd) is getting worldwide attention due to its continuous accumulation in agricultural soils which is due to anthropogenic activities and finally Cd enters in food chain mainly through edible plants. Cadmium free food production on contaminated soils is great challenge which requires some innovative measures for crop production on such soils. The current study evaluated the efficiency of zinc oxide nanoparticles (ZnONPs) (0, 150 and 300 mg/kg) on the growth of wheat in texturally different soils including clay loam (CL), sandy clay loam (SCL), and sandy loam (SL) which were contaminated with were contaminated with 25 mg/kg of Cd before crop growth. Results depicted that doses of ZnONPs and soil textures significantly affected the biological yields, Zn and Cd uptake in wheat plants. The application of 300 mg/kg ZnONPs caused maximum increase in dry weights of shoot (66.6%), roots (58.5%), husk (137.8%) and grains (137.8%) in CL soil. The AB-DTPA extractable Zn was increased while Cd was decreased with doses of NPs depending upon soil textures. The maximum decrease in AB-DTPA extractable Cd was recorded in 300 mg/kg of ZnONPs treatment which was 58.7% in CL, 33.2% in SCL and 12.1% in SL soil as compared to respective controls. Minimum Cd concentrations in roots, shoots, husk and grain were found in 300 mg/kg ZnONPs amended CL soil which was 58%, 76.7%, 58%, and 82.6%, respectively. The minimum bioaccumulation factor (0.14), translocation index (2.46) and health risk index (0.05) was found in CL soil with the highest dose of NPs. The results concluded that use of ZnONPs significantly decreased Cd concentration while increased Zn concentrations in plants depending upon doses of NPs and soil textures.

Survival Of Patients With Brain Metastases After Palliative Whole-Brain Radiotherapy - An Experience From A Single Institute.

BACKGROUND: Brain metastases are a common complication of cancer and approximately 20% of cancer patients develop them over time. Presently palliative whole-brain radiotherapy is used as a palliative treatment for brain metastases because of its cost-effectiveness and easy availability, especially in patients with multiple metastases who are not candidates for surgery or Stereotactic radiosurgery. This study aims to determine the survival in patients who have received palliative whole-brain radiotherapy for brain metastases and to evaluate some of the prognostic factors determining survival in patients with brain metastases. METHODS: It was a cross-sectional study conducted in Shaukat Khanum Memorial Cancer Hospital and Research Centre and all the patients with brain metastases who had completed palliative whole-brain radiotherapy between July 2015 and July 2020 were included. Data was retrospectively collected and analyzed using SPSS 21.0. Overall survival was calculated using the Kaplan-Meier method, taking into consideration the period from the date of diagnosis of brain metastases until death or to the date of last follow-up, whichever was applicable. p-value of <0.05 was regarded as statistically significant. RESULTS: Almost half (45%) of the brain metastases were secondary to breast cancer followed by lung and genitourinary cancers at 16.3% and 15.5% respectively. The median overall survival was lowest in breast carcinoma patients at 5 months followed by lung carcinoma at 7 months. The median overall survival was 5 months in patients having extracranial disease as compared to 12 months in those having no extracranial disease or those in whom the disease status was unknown. CONCLUSIONS: Our study revealed that the most common tumour to metastasize to the brain was breast cancer. The younger age group had a poorer prognosis because most of them had breast cancer with triple-negative disease. Controlled extracranial disease significantly prolonged overall survival in patients with brain metastases.

The Clinicopathologic Characteristics and Outcomes of Gastroentero-pancreatic Neuroendocrine Tumors - Experience from A Tertiary Cancer Center.

OBJECTIVE: Gastroentero-pancreatic neuroendocrine tumor (GEP NETs) are a heterogeneous group of tumors with variable behaviors. Our aim was to study the baseline characteristics and outcomes of GEP-NETs and to establish the impact of tumor grade and resectability on the survival. METHODS: A single center retrospective review of patients registered at SKMCH &RC Pakistan with the diagnosis of GEP-NETs was carried out from the Hospital Information System. The baseline characteristics of 134 diagnosed patients from January 2006 to August 2020 were analyzed. Overall survival (OS) and Disease Free Survival (DFS) was calculated using Kaplan-Meier curve. The impact of tumor grade and resectability was seen on the OS and DFS. Data was analyzed through SPSS version 23. Categorical parameters were computed using ChiSquare test, keeping p-value =0.05 significant. RESULT: A large majority had Grade 1 disease (59%) along with localized stage at presentation (73.1%) as compared to Grade 2 (23.9%) and Grade 3 (17.1%) disease with metastatic stage at presentation (26.9%). The 5 year OS according to tumor grade was, 88%, 57% and 0% in low, intermediate and high grade respectively. The 5-year OS was 94%, 79% and 43% in the completele, incomplete and in unresectable disease group, respectively. CONCLUSION: GEP-NETs are rare tumors with good outcomes in Grade I and II and poor outcomes in grade III Neuroendocrine Carcinomas (NEC). Tumor grade and complete surgery of the primary tumor are important predictors of response outcomes and prognosis.

Antioxidant Effect of Ocimum basilicum Essential Oil and Its Effect on Cooking Qualities of Supplemented Chicken Nuggets.

A commonly observed chicken meat issue is its lipid oxidation that leads to deterioration of its organoleptic and nutritional properties and its further-processed products. Basil (Ocimum basilicum L.) is one of the traditional culinary herbs exhibiting food preservation properties. The current study investigated the essential oil composition, antioxidant activity and in vitro cytotoxic capacity of the essential oil of basil indigenous to Pakistan. GC-MS analysis of the essential oil revealed the presence of 59 compounds that constituted 98.6% of the essential oil. O. basilicum essential oil (OB-EO) exhibited excellent antioxidant activity, i.e., IC50 5.92 ± 0.15 µg/mL as assayed by the DPPH assay, 23.4 ± 0.02 µmoL Fe/g by FRAP, and 14.6 ± 0.59% inhibition by H2O2. The brine shrimp lethality assay identified an average mortality of ~18% with OB-EO at 10-1000 µg/mL, while that of the same concentration range of the standard drug (etoposide) was 72%. OB-EO was found to be non-toxic to HeLa and PC-3 cell lines. TBARS contents were significantly decreased with increase of OB-EO in chicken nuggets. The lowest TBARS contents were recorded in nuggets supplemented with 0.3% OB-EO, whereas the highest overall acceptability score was marked to the treatments carrying 0.2% OB-EO. The results suggest OB-EO as a promising carrier of bioactive compounds with a broad range of food preservation properties, and which has a sensory acceptability threshold level for chicken nuggets falling between 0.2-0.3% supplementation. Future research must investigate the antibacterial impact of OB-EO on meat products preserved with natural rather than synthetic preservatives.

mRNA-Based Vaccine Designing against Epstein-Barr Virus to Induce an Immune Response Using Immunoinformatic and Molecular Modelling Approaches.

Epstein-Barr Virus (EBV) is a human pathogen that has a morbidity rate of 90% in adults worldwide. Infectious mononucleosis is caused by EBV replication in B cells and epithelial cells of the host. EBV has also been related to autoimmune illnesses, including multiple sclerosis and cancers like nasopharyngeal carcinomas and Burkitt's lymphoma. Currently, no effective medications or vaccinations are available to treat or prevent EBV infection. Thus, the current study focuses on a bioinformatics approach to design an mRNA-based multi-epitope (MEV) vaccine to prevent EBV infections. For this purpose, we selected six antigenic proteins from the EBV proteome based on their role in pathogenicity to predict, extract, and analyze T and B cell epitopes using immunoinformatics tools. The epitopes were directed through filtering parameters including allergenicity, toxicity, antigenicity, solubility, and immunogenicity assessment, and finally, the most potent epitopes able to induce T and B cell immune response were selected. In silico molecular docking of prioritized T cell peptides with respective Human Leukocytes Antigens molecules, were carried out to evaluate the individual peptide's binding affinity. Six CTL, four HTL, and ten linear B cell epitopes fulfilled the set parameters and were selected for MEV-based mRNA vaccine. The prioritized epitopes were joined using suitable linkers to improve epitope presentation. The immune simulation results affirmed the designed vaccine's capacity to elicit a proper immune response. The MEV-based mRNA vaccine constructed in this study offers a promising choice for a potent vaccine against EBV.

Dryopteris juxtapostia Root and Shoot: Determination of Phytochemicals; Antioxidant, Anti-Inflammatory, and Hepatoprotective Effects; and Toxicity Assessment.

An estimated 450 species of Dryopteris in the Dryoperidaceae family grow in Japan, North and South Korea, China, Pakistan, and Kashmir. This genus has been reported to have biological capabilities; however, research has been conducted on Dryopteris juxtapostia. Therefore, with the present study, we aimed to exploring the biological potential of D. juxtapostia root and shoot extracts. We extracted dichloromethane and methanol separately from the roots and shoots of D. juxtapostia. Antioxidant activity was determined using DPPH, FRAP, and H2O2 assays, and anti-inflammatory activities were evaluated using both in vitro (antiurease activity) and in vivo (carrageenan- and formaldehyde-induced paw edema) studies. Toxicity was evaluated by adopting a brine shrimp lethality assay followed by determination of cytotoxic activity using an MTT assay. Hepatoprotective effects of active crude extracts were examined in rats. Activity-bearing compounds were tentatively identified using LC-ESI-MS/MS analysis. Results suggested that D. juxtapostia root dichloromethane extract exhibited better antioxidant (DPPH, IC50 of 42.0 µg/mL; FRAP, 46.2 mmol/g; H2O2, 71% inhibition), anti-inflammatory (urease inhibition, 56.7% at 50 µg/mL; carrageenan-induced edema inhibition, 61.7% at 200 µg/mL; formaldehyde-induced edema inhibition, 67.3% at 200 µg/mL), brine shrimp % mortality (100% at 1000 µg/mL), and cytotoxic (HeLa cancer, IC50 of 17.1 µg/mL; prostate cancer (PC3), IC50 of 45.2 µg/mL) effects than D. juxtapostia root methanol extract. D. juxtapostia shoot dichloromethane and methanol extracts exhibited non-influential activity in all biological assays and were not selected for hepatoprotective study. D. juxtapostia root methanol extract showed improvement in hepatic cell structure and low cellular infiltration but, in contrast the dichloromethane extract, did not show any significant improvement in hepatocyte morphology, cellular infiltration, or necrosis of hepatocytes in comparison to the positive control, i.e., paracetamol. LC-ESI-MS/MS analysis showed the presence of albaspidin PP, 3-methylbutyryl-phloroglucinol, flavaspidic acid AB and BB, filixic acid ABA and ABB, tris-desaspidin BBB, tris-paraaspidin BBB, tetra-flavaspidic BBBB, tetra-albaspidin BBBB, and kaempferol-3-O-glucoside in the dichloromethane extract, whereas kaempferol, catechin, epicatechin, quinic acid, liquitrigenin, and quercetin 7-O-galactoside in were detected in the methanol extract, along with all the compounds detected in the dichloromethane extract. Hence, D. juxtapostia is safe, alongside other species of this genus, although detailed safety assessment of each isolated compound is obligatory during drug discovery.

Synthesis and Characterization of Polyvinyl Chloride Matrix Composites with Modified Scrap Iron for Advanced Electronic, Photonic, and Optical Systems.

In this study, Fe2O3 powder was synthesized using the co-precipitation method from scrap iron, which was then treated with varying concentrations of copper. Afterwards, the modified Fe2O3 was reinforced in the PVC matrix by using the solution-casting method to synthesize PVC composite films, which were subjected to a UV-visible spectrophotometer, a Fourier transform infrared spectrophotometer, an X-ray diffractometer, and a thermal gravimetric analyzer to evaluate the optical, chemical, structural, and thermal properties. FTIR analysis reveals the formation of the composite through vibrational bands pertaining to both components present, whereas no significant changes in the XRD patterns of PVC were observed after the doping of modified iron oxide, which reveals the compatibility of fillers with the PVC matrix. The optical properties of the copper-doped iron oxide-PVC composites, including absorbance, refractive index, urbach energy, and optical as well as electrical conductivity are measured, and show an increase in optical activity when compared to the pure PVC compound. Moreover, the increased thermal stability of the synthesized composite was also observed and compared with conventional compounds, which, in accordance with all the other mentioned properties, makes the copper-dopped iron oxide-PVC composite an effective material for electronic, photonic, and optical device applications.

Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies.

Tribulus terrestris L. belongs to the family Zygophyllaceae and integral part of various ancient medicinal systems including Chinese, Indian, and European to combat various health ailments. The aim of the present study was to assess the phytochemical constituents, in vitro antioxidant activity using DPPH, FRAP, and H2O2 assays, in vitro anticancer activity using MTT assay, and in vitro and in vivo anti-inflammatory properties of T. terrestris. The acute and sub-acute toxicity of extracts exhibiting most biological potential was examined using murine models. Liquid-liquid partitioning followed by RP-HPLC sub-fraction of crude extract was performed. After that, ESI-MS/MS analysis was done for the timid identification of bioactive metabolites responsible for bioactivities of sub-fractions and HPLC analysis to quantify the compounds using external standards. Among all extracts, T. terrestris methanol extract was noted to hold maximum phenolic (341.3 mg GAE/g) and flavonoid (209 mg QE/g) contents, antioxidant activity in DPPH (IC50 71.4 µg/mL), FRAP (35.3 mmol/g), and H2O2 (65.3% inhibition) assays, anti-inflammatory activities in vitro at 400 µg/mL (heat-induced hemolysis, % inhibition 68.5; egg albumin denaturation, % inhibition 75.6%; serum albumin denaturation, % inhibition 80.2), and in vivo at 200 mg/kg (carrageenan-induced paw edema, % inhibition 69.3%; formaldehyde-induced paw edema, % inhibition 71.3%) and anticancer activity against breast cancer cell (MCF-7) proliferation (IC50 74.1 µg/mL). Acute and sub-acute toxicity studies recorded with no change in body weight, behavior, hematological, serum, and histopathological parameters in treated rats with T. terrestris methanol extracts when compared to control group. Fraction B obtained through liquid-liquid partitioning resulted in more bioactive potential as compared to the parent methanol extract. RP-HPLC analysis of fraction B resulted with four sub-fractions (TBTMF1-TBTMF4), wherein TBTMF3 delineated notable bioactive capabilities as compared to other fractions and parent methanol extract. ESI-MS/MS analysis of TBTMF3 resulted with tentative identification of myricetin, rutin, liquitrigenin, physcion, and protodioscin. It can be stated that T. terrestris is a potential bearing herb and findings of current study further verify the claims made in ancient medicinal systems. However, after investigation of each identified compound, it must be considered for drug discovery.