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Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a very aggressive cancer. There are various sub-cellular events (both genetic and epigenetic) that get dysregulated leading to tumorigenesis. Methylation in promoters of tumor suppressor genes is one of these epigenetic phenomena contributing to the pathogenesis of cancer. Genes analyzed for promoter methylation status in this study namely SPARC (Secreted Protein Acidic and Rich in Cysteine, UCHL1 (ubiquitin carboxy-terminal hydrolase L1), NPTX2 (neuronal pentraxin 2), PENK (proenkephalin) had been studied in pancreatic cancer, but there is a need to check methylation in these genes as circulatory non-invasive markers. This study analyzed the absolute quantification of methylation levels of SPARC, UCHL1, PENK, and NPTX2 genes promoters in PDAC patients as well as in chronic pancreatitis (CP) patients and healthy subjects (HC) and evaluated its clinical significance in PDAC.Materials and methodsThe study included 65 PDAC patients, 25 CP patients, and 25 healthy controls. DNA was extracted from their plasma samples and subsequently given bisulfite treatment. Absolute quantization of methylated and unmethylated copies of gene promoters of all the four genes was performed using real-time PCR (SYBR green) by the standard curve method. Methylation levels were expressed as methylation index (MI) for each gene in each patient. MI was calculated from absolute copy numbers as follows: MI-methylated copy number/methylated copy number + unmethylated copy number). These indices were used to compare gene methylation levels within different groups and to correlate with clinicopathological features and survival of pancreatic cancer patients. An appropriate statistical analysis was applied.ResultsMethylation indices for all the four genes in PDAC cases were found to be significantly higher as compared to that in healthy individuals. SPARC MI values were found to differentiate early-stage PDAC patients from CP patients. PDAC patients with the metastasized disease and stage IV disease were found to have high MI for the SPARC gene as well as for the NPTX2 gene, while a higher UCHL1 methylation index was found to correlate with an advanced stage of the disease. Higher MI values for SPARC and NPTX2 genes were found to associate with poor survival in patients with PDAC.ConclusionMethylation load in the form of MI for each of the four genes assessed in plasma may emerge as a non-invasive biomarker to differentiate pancreatic cancer from healthy individuals. But only SPARC and NPTX2 hypermethylation were able to distinguish pancreatic cancer from chronic pancreatitis. Association of aberrant methylation in SPARC and NPTX2 gene with metastasis and poor survival of patients suggest the role of methylation in these genes as prognostic markers.

Aconitum chasmanthum Stapf ex Holmes, a highly valued medicinal plant, is a critically endangered plant species with restricted global distribution. Because there is no published report on the in vitro micropropagation of A. chasmanthum, the present study was undertaken to contribute to the development of an efficient micropropagation protocol for its conservation. Seeds collected from the wild showed enhanced germination after being given a chilling treatment (−4 °C and −20 °C) for different durations (10, 20, 30 and 40 days). Seeds given a chilling treatment of −4 °C for 10 days showed enhanced germination rates of 47.59 ± 0.53% with a mean germination time of 10.78 ± 0.21 days compared to seeds kept at room temperature when grown in an MS basal medium. Nodes, leaves and stems, taken from 20–40-day-old seedlings, were used as an explant for micropropagation. An MS medium supplemented with different concentrations of cytokinins (BAP, Kn), auxins (2,4-D, NAA), and an additive adenine sulphate were tested for callusing, direct shoot regeneration and rooting. Only nodal explants responded and showed direct multiple shoot regeneration with 7 ± 0.36 shoots with an elongation of 5.51 ± 0.26 cm in the MS medium supplemented with BAP 0.5 mg/L, and with a response time (RT) of 10.41 ± 0.51 days and a percentage culture response of 77.77 ± 2.77%. Rhizome formation was observed after 8 weeks, with the highest culture response of 36.66 ± 3.33% in the MS basal media with an RT of 43.75 ± 0.50 days. These rhizomes showed a 60% germination rate within 2 weeks and developed into plantlets. The present in vitro regeneration protocol could be used for the large-scale propagation and conservation of A. chasmanthum.

Background & objectives: Inflammation has been studied to be an important contributory factor to carcinogenesis through pro-inflammatory markers such as interleukin (IL)-6 and C-reactive protein (CRP). Furthermore, K-ras mutation is an important genetic alteration in the pathogenesis of pancreatic cancer. This study aimed to compare these inflammatory markers in pancreatic ductal adenocarcinoma (PDAC) with the diseased and healthy controls (HCs) and to check for any association between IL-6 and CRP serum levels with the disease status, survival and K-ras mutation status of PDAC patients. Methods: The study included 135 PDAC, 25 chronic pancreatitis (CP) patients and 25 HCs. The serum levels of IL-6 and CRP were detected by enzyme-linked immunosorbent assay and K-ras mutations were detected by polymerase chain reaction-restriction fragment length polymorphism technique. Results: The serum levels of both these markers were elevated in PDAC cases than that in HCs. High IL-6 levels and higher CRP levels were found to be associated with locally advanced disease, lymphatic invasion, metastasis and advanced stage of the PDAC. In patients with unresectable PDAC, higher IL-6 levels were found to be associated with the presence of K-ras mutations. Interpretation & conclusions: Higher IL-6 and CRP levels in patients with advanced PDAC suggest an important role of these inflammatory markers in tumour progression. Furthermore, the association of mutations in the K-ras gene with serum IL-6 indicates cross-talks that may contribute to the progression of the PDAC.

Aim To study polymorphisms in glutathione-S-transferases (GST-T1, GST-M1, GST-P1) and uridine-5′-diphosphate-glucuronosyl-transferases (UGT1A7) genes and the risk of developing chronic pancreatitis (CP) associated with these polymorphisms. Methods This study included 49 alcoholic and 51 idiopathic chronic pancreatitis patients, 50 alcohol addicts and 50 healthy controls. Polymorphism(s) in GST-T1 and GST-M1 genes were assessed by multiplex polymerase chain reaction (PCR), while PCR–radiofrequency lesioning (RFLP) was employed to assess the same in GST-P1 and UGT1A7 genes. The differences in polymorphism frequency between groups and the risk of developing pancreatitis were assessed by the odds ratio. Results Strong association of the null genotype of GST-T1 with CP susceptibility was observed. Alcoholics with the Val allele of GST-P1 have higher chances of having pancreatitis. Idiopathic pancreatitis patients with higher age at the onset of pain were found to have the null genotype of GST-M1. Conclusion Alcoholics with the null genotype of the GST-T1 gene and the Valine allele of the GST-P1 gene are at a higher risk of developing CP. Thus, genotyping of these genes may serve as an important screening tool for the identification of high-risk groups among alcoholics.

The ecological activities within the hyporheic zone (HZ) heavily rely on water flow dynamics. The arrangement of the hyporheic community is influenced significantly by the hydrological fluxes occurring within the zone, particularly driven by the dynamics of watercourse surface flow. While there is an ongoing debate, it is suggested that benthic organisms may utilize the HZ as a sanctuary. The ability of stream organisms to colonize the HZ is influenced by their biological characteristics. Lower oxygen levels and reduced pore space in deeper sediment layers restrict the presence of macroinvertebrates while favoring meiofauna and protists. Limited research has been conducted on the overall role of hyporheos in the assembly of entire ecosystems, with most studies focusing on larger species. The metabolism of the hyporheos facilitates the transformation of pollutants and nutrients within the HZ through the action of biofilms that degrade dissolved substances, including contaminants. Lastly, the community that feeds on biofilms and participates in hyporheic exchange flow indirectly contributes to these processes. The aim of this review article is to highlight the critical role of water flow dynamics in the hyporheic zone and its influence on the arrangement of the ecological community within. It emphasizes the potential sanctuary function of the hyporheic zone for benthic organisms, shaped by their biological characteristics.

The present study was carried out to investigate the reasons behind risk taking behavior and interpersonal relationship of adrenaline junkies. Grounded theory method of data analysis was used. The sample included eight people from three cities, i.e., Lahore, Islamabad and Rawalpindi. It consisted of one mountain climber, one person with extreme hobbies, a person who does paragliding and five one wheeling bikers. Interviews were conducted through Skype due to the long distance. Differences as well as similarities were found among them. Four reasons behind risk taking behavior were reported, i.e., happiness, excitement, pleasure, company of friends/siblings, irreplaceable experience and the last reason was; \"it's a hobby\". These factors act as such a strong positive reinforcement for them that they risk their lives to seek bodily sensations caused by them. Interpersonal relations were normal other than arguments with parents regarding extreme activity. It was found that they were less concerned about dying and didn't want to stop doing it despite all the hate speech and condemn they received from the society and their own parents. They were quite comfortable while saying that they would choose extreme sport over loved one if choice will be given.

In this article, the aim of teaching experiment was to investigate the usefulness of role play strategy in the development of critical thinking among elementary students. Evidence was collected in a usual classroom context in the form of observation (audio and video recording), questionnaire. The results of such teaching were evaluated through students discourse emerged during student-student and teacher-student interaction and by the change of their thinking analyzed through pre- and post- questionnaire. Findings suggest that role playing is a productive teaching approach in promoting critical thinking in Pakistani context.

No doubt, across the world, advantages of critical thinking in education motivated educators focus on developing the critical thinking ability and traits among students more than ever before, yet ample evidence from literature has shown the lack of critical thinking skills among students at all level. The purpose of the study was to examine the effectiveness of two teaching strategies questioning and role playing the development of critical thinking attitude among elementary students. This article offers critical thinking as a prelude to developing attitude among students by using case study method and design based approach. Two groups each with 15 students were made using purposive and convenience sampling method. Evidence was collected in a usual classroom context in the form of pre and post questionnaire data. The focus was evaluated through the indirect evidence of its effects on students’ critical thinking attitude by using Paul's intellectual traits model. Findings suggest that critical thinking is a viable tool in influencing critical thinking attitudes of students in Pakistani context.