Neuroblastoma is one of the most common childhood cancers arising from neural crest cells. It mainly affects sympathetic nervous system but can metastasize to other organs of the body. Therapeutic approaches for neuroblastoma range from multi modal therapy to surgery. Most effective treatment is combinational approach which includes induction of remission using chemotherapeutic drugs followed by consolidation phase using stem cell approach or radiotherapy and then maintenance phase to inhibit relapse of neuroblastoma. Still, with recent researches and advancement in therapy, mortality rate of neuroblastoma is high. Resistance and adverse effects of chemotherapeutic drugs limit their use. Keeping this in mind there is a need of newer molecules that can effectively work against neuroblastoma with less toxicity. Here we study novel molecules belonging to terpenoids and mannich bases for their potential antineoplastic activity against SH-SY5Y neuroblastoma cells. Inhibition of growth was assessed by using MTT assay which presented all the test compounds possessed ability to halt the growth of neuroblastoma cells. PGEA-AN, PGEA-4FAN, 3FB3FA8H and 3NBOABA8H showed IC50 dose of 12.5 µM, 8.5 µM, 3.5 µM and 5 µM respectively. The test compounds were compared to cisplatin which showed the IC50 of 17 µM. Apoptosis is considered more favorable mode of death in cancer cells, we checked for apoptotic involvement in growth inhibition of test compounds. Cells treated with test compounds showed morphological signs of apoptosis and nuclear condensation was evident on microscopy which was also shown by decrease in NAF of cells. Annexin V staining confirmed that apoptosis is induced by our test compounds. On molecular level, test compounds are found to enhance the expression of P53 gene. Increase in the level of BAX gene is also observed with no significant alteration of BCL2. This leads BAX/BCL2 ratio to shift towards pro-apoptotic BAX. Cleaved caspase 3 protein is also observed to be increased which might be consequence of BAX/BCL2 shift. Involvement of P53 pathway is augmented by increase in mitochondrial membrane permeability and reactive oxygen species generation. IX Thus, based on the results of the present study, we conclude that the test compounds modulate P53 gene and induce apoptosis in SH-SY5Y neuroblastoma cell. Therefore, further exploration on these compounds at pre-clinical and clinical levels might give us opportunities to develop of novel potent anticancer agents for treatment against neuroblastoma.
تنقید: تنقید عربی زبان کا لفظ ہے۔ جس کے عام معنی اخراج کے ہیں۔نورالغات میں مولوی نورالحسن نے اس کی تعریف یوں کی ہے: "کھوٹا کھرا پرکھنا یا جانچ کرنا۔ایسی جانچ جو ضعیف اور مشکوک چیزوں کو الگ کردے یعنی اچھے اور برے کی تمیز کرنا" اردو ادب میں اس کے مترادف لفظ تنقید استعمال ہوتا ہے لیکن انگریزی میں اس کے مترادف لفظ Criticism استعمال ہوتا ہے۔بعض اوقات اس کے لیے نقد یا انتقاد کے الفاظ بھی استعمال کیے جاتے ہیں۔حامداللہ افسرنے اسی تناظر میں اپنی کتاب "تنقیدی اصول و نظریے" پہلے نقد الادب کے نام سے شائع کی۔ان کی ایک کتاب" انتقاد" اور دوسری "اصول انتقاد ادبیات" کے نام سے شائع ہوئی لیکن ہمارے معاشرے میں اکثریت کے ساتھ چلنا پڑتا ہے۔لہذا حامداللہ افسر اس نتیجے پر پہنچے کہ چونکہ اکثریت اس طرف جا رہی ہے تو میں چونکہ اس کو نام نقد یا انتقاد دینا چاہ رہا ہوں تو شاید کامیاب نہ ہو سکوں تو انہوں نے اپنی کتاب کا نام تبدیل کیا اور اسی کتاب کو پھر شائع کیا اور اس کا نام رکھا" تنقیدی اصول و نظریے"۔ حامد اللہ افسر کی اس کے بارے میں رائے یہ ہے کہ وہ کیوں اس طرف آئے۔وہ کہتے ہیں : "لفظ تنقید عربی صرف و نحو کے اعتبار سے صحیح نہیں ہے جس کی جگہ نقد یا انتقاد ہونا چاہیئے۔لیکن اردو ادب میں اب یہ لفظ رائج ہو گیا ہے۔اس کی جگہ کسی دوسریلفظ کا استعمال مناسب نہ ہوگا۔جہاں تک اردو زبان کا سوال ہے اسے صحیح سمجھنا چاہیئے۔" ادبی اصطلاحات کا تعارف" کے صفحہ 167 پر مصنف ابوالاعجاز صدیقی کی رائے یہ ہے : "تنقید اصل میں کسی بھی فن پارے کو ذاتی پسندو ناپسند سے بالا ہو کر پرکھنے اور جانچنیکا نام ہے۔تنقید کسی ادب کے فنی محاسن کی پرکھ کا نام ہے"
Due to the significance of Sīrah, Muslim scholars started writing about it from the very beginning of Islam. Pashto language, like other major languages, contains the Sīrah writings. There are two types of Sīrah writings in Pashto language. The first type of books are written for a common man, in a very simple language and style, just to get guidance from the Sīrah of the Holy Prophet (P.B.U.H). This type of books were discussed by Dr. Sa’īdullah Qaḍī in his article “Sīrah books in Pashto Language” published in “Al-Ḥaq” Monthly Journal of Jami’a Dārul Uloom Ḥaqqānia, Akora Khattak. The second type of Sīrah books are written after deep research and criticism of the narrations. But it is worth mentioning that no comprehensive research has been carried out so far which can cover both types of books. Therefore an analysis of the Selected Sīrah writings in Pashto Language has been made, to explore the remarkable Sīrah writings in Pashto Language.
Two-dimensional layered transition metal dichalcogenides (TMDs) are fundamentally and technologically intriguing materials. The versatile and tunable properties of these materials make them attractive for compendium of applications. Emerging transition metal dichalcogenides offer unique and hitherto unavailable opportunities to tailor the mechanical, thermal, electronic and optical properties of polyazomethine based composites. Phase conversion of the transition metal dichalcogenides from 2H phase to 2H''/1T was carried out by organolithium treatment of MoS2 and MoSe2 polycrystalline films on the chips. The conversion was done successfully on the particular area yielding a lateral heterostructure concerning the pristine 2H phase and the 2H''/1T co-phase regions. Lateral heterostructure was verified by Raman spectroscopic, X-ray photoelectron spectroscopic studies and X-ray diffraction analysis. Scanning electron (SEM) and atomic force (AFM) microscopies revealed the changes in the surface morphology and work function of the heterostructure in comparison to the pristine films. Phase stability studies of the heterostructure were also studied by Raman spectroscopic studies.Gas sensing and electrical properties were also performed on these chips. Functionalization route was demonstrated that results in ethylene glycol bonded to the MoSe2 surface via covalent C–Se bond. It was based on lithium intercalation, quenching of the negative charges residing on the MoSe2 by electrophiles such as bromo diazonium salts and subsequently proceeding with ethylene glycol via cross coupling reaction.FTIR and (1H and 13C) NMR spectroscopic analyses techniques were used for structure elucidation. Strong evidence for the existence of heterostructure 2H''/1T of MoSe2 after the effective grafting of C– O linkage on the MoSe2 surface was confirmed by wide angle X-ray diffraction (XRD) and Xray photoelectron spectroscopic studies (XPS). Thermal stability of the synthesized product was ensured by the thermogravimetric analysis (TGA). Surface morphology was also probed by scanning electron microscopic studies (SEM). Further strategy of modifying TMDs with amine-terminated polyazomethines (PAs) was successfully offers a scalable platform suitable for tuning the properties of flexible PAs TMDs composite. TMDs (MoS2, MoSe2, WS2 and WSe2) were properly embedded in the polymer matrix. Bifunctional aldehyde monomers containing sulphone linkage were synthesized and subsequently confirmed by FT-IR and (1H and 13C) NMR spectroscopic studies and then treated with two different diamines to prepare six polyazomethines via polycondensation method in acidic media. Synthesized polyazomethines were confirmed by FT-IR and (1H and 13C) NMR spectroscopic analysis. Furthermore, in another attempt, the ethoxy pendant group was also attached to the linear polyazomethines. Synthesized poly- azomethines (PAs) were further doped with TMDs material and characterized by FTIR, Raman and XPS spectroscopic studies. Scanning electron and transmission electron microscopic studies revealed changes in the surface morphology. Energy dispersive X-ray spectroscopy (EDX) was also done using the TEM setup. UV-Visible and fluorescence spectroscopic technique were also performed to study the photophysical behavior. Electrocatalytic activity was also performed on these composite materials. In addition, synthesized polyazomethines were covalently grafted onto acid functionalized MCNTs. The synthesized nanocomposite materials were consequently characterized by spectroscopic studies (FT-IR, Raman spectroscopic studies). X-ray diffraction (XRD) and Xray photoelectron (XPS) spectroscopic studies were also performed. Scanning electron and transmission electron microscopic studies revealed modifications in the surface morphology. A current voltage measurements and electrocatalytic activity were also performed on these PAs-MCNTs composites. This perspective concerns the synthetic strategies that have been used to incorporate PAs into TMDs and grafting onto MCNT’s surface can improve their performance in technological applications.