اردو افسانہ۔۔۔ موضوعات و ارتقا
ادب کا انسانی زندگی سے گہرا تعلق ہے۔ادب صرف معاشرتی زندگی کا عکاس ہی نہیں بلکہ اس میں زندگی کی نا ہمواریوں کا دکھ اور شخصی اور اجتماعی زندگی کا عکس بھی ملتا ہے۔’’ادب‘‘زندگی سے جنم لیتا ہے۔ ایک کے بغیر دوسرے کا تصور نا ممکن ہے۔ معاشرے میں رو نما ہونے والے سارے عناصر ادب پر اثرانداز ہوتے ہیں۔افسانے میں ایک طرف تخلیق کار کی ذات کا پتہ چلتا ہے تو دوسری طرف اس سے انسانیت کی اعلیٰ اقدار بھی جھلکتی ہیں۔ادب معاشرے کی تعمیر و ترقی میں اہم کردار ادا کرتا ہے اور سماجی، تہذیبی اور فکری رجحانات و میلانات پر اثر انداز بھی ہوتا ہے۔ ادب معاشرے کا آئینہ اور ترجمان ہے جوتمام حقیقتوں کو من وعن پیش کرتا ہے۔ یعنی ادب ہی کے ذریعہ سے کسی بھی بستی، علاقے،خطے،یا ملک و قوم کے باشندوں کی ثقافت،رہن سہن، اطواراور ان کی بودوباش کا علم ہوتا ہے۔ یہ ادب ہی ہے کہ جس کی بدولت کسی بھی قوم کے رہنے والوں کے مجموعی انداز فکر کا اندازہ لگایا جا سکتا ہے۔ ادب اور زندگی ایک دوسرے کے لئے لازم و ملزوم ہیں۔دونوں کو ایک دوسرے سے جدا نہیں کیا جا سکتا۔ابولخیر کشفی ادب کے متعلق لکھتے ہیں:
’’ادب کے وسیلے سے مختلف سماجوں اور معاشروں نے اپنے مجموعی اندازِ فکر،مختلف رویوں اپنی ثقافت اور اپنے شعور کا اظہار کیا ہے۔ادب کو ہر مہذب معاشرے نے نہ صرف گہری توجہ کا مستحق ہی نہیں سمجھا بلکہ ادب کے آئینے میں اپنے بطون کو پیش کیا ہے۔‘‘(1)
افسانہ جدید ادب کی ایک صنف ہے۔جس میں افسانوی انداز میں حقیقی واقعات کو بیان کیا جاتا ہے۔یہ ناول کے مقابلے میںخاصا مختصر ہوتا ہے۔افسانے میں ناول کی طرح کہانی کو پھیلایا نہیں جاتا بلکہ مختصر طور پر پیش کیا جاتا ہے۔ افسانے سے...
Since the Arab spring, youth have been politically active in Asia through various modes. Regime revolution or failed takeover on 15 July 2016, in Turkey is its vibrant example. However, it’s unfortunate that the political perception, intention or attitude of youth towards democracy have not been included in the process of policy making. As a result, youth activism in politics remained unrecognized. Therefore, present work is an effort to explore democratic attitude of youth in Pakistan. The state of Pakistan has been selected because 64 % of her population comprises youth. Current study examines democratic attitude through four major independent variables: economic growth, democratic values, public participation and political stability. Data was collected from the respondents who were in between 18-35 years of age by distributing a survey questionnaire which was adopted from the literature. Data was analyzed through SPSS version 24.0. Result of the study suggests that all the developed hypotheses were accepted. Additionally, study finds that despite massive corruption, social injustice, favoritism, nepotism, political instability, economic crisis and many other problems, Pakistani youth overwhelmingly considers democracy, as the potential form of government and dislike any alternative of it. Current study may be the first stone in the stagnant water not only in measuring democratic attitude of young generation but it will also help them to understand what sort of democracy is needed in Pakistan.
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor. It accounts for more than 60% of all brain tumors in adults. Treatment options available for malignant gliomas include gross total resection, radiation therapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin. In spite of the variety of modern therapies against GBM, it is still a deadly disease with extremely poor prognosis. Patients usually have a median survival of approximately 14-15 months. The development of new therapeutic strategies for the management of gliomas is therefore crucial. The present study is designed to analyze the therapeutic potentials of anti-inflammatory compound N-(2-hydroxyphenyl) acetamide (NA-2) and anti-hypertensive drug Verapamil (VP) in the treatment of GBM as well as their combine effect with standard drug Temozolomide (TMZ) on U87 human glioblastoma cells. MTT assay was used to determine the growth inhibitory effect of NA-2, VP and TMZ. It was observed that these three drugs inhibited growth of U87 in dose dependent manner. The IC50 doses of NA-2, VP and TMZ were found to be 1.7 mM, 0.45 mM and 0.134 mM respectively. To find out whetherapoptosis is involved in growth inhibition, cells were treated with IC50 doses of these drugs and the effect was observed on morphology, chromatin condensation and DNA fragmentation using phase contrast microscopy, DAPI staining and TUNEL assay respectively. In all three treatment groups cells showed apoptotic morphology, chromatin condensation and DNA fragmentation which are hallmarks of apoptosis. Apoptosis is a process of programmed cell death regulated by pro-apoptotic (Bax) and antiapoptotic genes (Bcl-2). Deregulation of these genes is found to be linked to gliomagenesis. Hence an increase in Bax/Bcl-2 ratio favors the process of apoptosis. Caspase-3 is also an important protein that acts downstream to Bax/Bcl-2 and involved in the execution of apoptosis. Keeping in mind the importance of these apoptotic markers we also studied the effect of NA-2, VP and TMZ on these markers to find out their possible mechanism of action. Cells were treated with IC50 doses of these drugs for 24 hrs and RT-PCR was performed to see the mRNA expression of these markers in vehicle control and the three treatment groups. It was observed that after 24 hrs of treatment both NA-2 and VP downregulated Bcl-2 expression while TMZ has not shown any significant effect on the expression of Bcl-2 as compared to vehicle control. Baxand caspase-3 expression was found to be significantly up-regulated in NA-2, TMZ and VP as compared to control. Beside these proapoptotic and anti-apoptotic proteins we also studied the effect of these drugs on the expression of two other cellular markers that are involved in growth and proliferation of glioma i.e. HIF-1α and VEGF. Both NA-2 and VP inhibited the expression of VEGF and HIF-1α which is a transcriptional regulator of VEGF. While TMZ has not shown any significant effect on these markers. Next, the effect of NA-2 and VP was studied on growth inhibition after combining them with TMZ in various different concentrations. Coefficient of drug interaction (CDI) was also calculated. It was found that combination of 0.33 mMNA-2 with 0.1 mM of TMZ and 0.025 mM of VP with 0.1 mM of TMZ produced synergistic effect on growth inhibition with CDI value < 1. Combination doses that produced synergistic growth inhibitory activity were used for further studies. TUNEL assay was used to detect apoptosis in combination treatment group (TMZ + NA-2 and VP + TMZ) and individual drug treatment groups i.e NA-2 (0.33 mM), TMZ (0.1 mM) and VP (0.025) using doses that produced synergistic effect. Results of TUNEL assay revealed that even low doses (mentioned above) of NA-2, TMZ and VP induced apoptosis and this apoptotic effect was more pronounced in combination treatment groups (TMZ + NA-2 and VP + TMZ) as compared to control and individual drug treatment groups. To determine the possible mechanism of action involved in synergism we studied the effect of NA-2, TMZ and VP individually and in combination (TMZ + NA-2 and VP + TMZ) on the same molecular markers that we studied at IC50doses of these drugs. Expression was analyzed at both mRNA and protein level using RT-PCR and Immunocytochemistry. NA-2, TMZ and VP (non significant mRNA) up-regulated the expression of Bax at both mRNA and protein level andthe expression was more pronounced in combination treatment group TMZ + NA-2 as compared to individual treatment of NA-2 and TMZ. In case of VP + TMZ no further increase in expression was observed as compared to TMZ only. In contrast to BAX, Bcl-2 was found to be down regulated after treatment with NA-2 and VP as compared to control while TMZ had no significant effect on the expression of Bcl-2. Moreover No further significant down-regulation of Bcl-2 was observed at protein level when NA-2 and VP alone treatment groups were compared with TMZ + NA-2 and VP + TMZ respectively. Increase in Bax expression by NA-2, TMZ and VP and down-regulation of Bcl-2 by NA-2 and VP only leads to dramatic increase in Bax/Bcl-2 ratio and shifted the equilibrium of cells towards apoptosis. Apoptosis was further confirmed by analyzing active Caspase-3 expression. NA-2, TMZ and VP treatment also increased active caspase-3 expression and the expression was highest in combination treatment groups where Bax/Bcl-2 ratio and apoptosis was also highest as compared to control and individual treatment of the drugs. Here we concluded that the synergistic growth inhibition that was observed in combination treatment group may in part be related to increase in apoptosis. The expression of HIF-1α and VEGF was alsoanalyzed in combination treatment and found similar results that were observed at IC50 doses. Both NA-2 and VP inhibited the expression of HIF-1α and VEGF while TMZ had no effect on the expression of both these marker. No further significant down-regulation was observed when NA-2 + TMZ and VP + TMZ were compared with NA-2 and VP alone treatment group respectively. In contrast to NA-2 and VP, TMZ did not have any significant effect on the expression of HIF-1α and VEGF, it is possible that increase in efficacy and growth inhibitory activity of TMZ in combination treatment group might also be related to the NA-2 and VP mediated down regulation of HIF- 1α and VEGF as both the markers have role in growth and proliferation also. Based on our observations, we conclude that NA-2, VP and TMZ can inhibit the growth of U87 glioblastoma cells by inducing apoptosis. NA-2 and VP may also inhibit proliferation by down-regulating HIF-1α and VEGF expression. Synergistic growth inhibitory activity of NA-2 and VP with TMZ may in part be related to their apoptotic and anti-proliferative activity. In short NA-2 and VP both have growthinhibitory activity alone which was further refined in combination with TMZ and they can be exploited for therapeutic purposes.