A CULTURAL AND SOCIAL PERUSAL OF REPORTAGE “SHEHER”

Ibrahim Jalees’ reportage “Sheher” is a masterpiece of non-fictional literature. The cultural and traditional life of Bombay city is the main subject. The writer has tried to represent the helpless and miserable urban life probing from its artificial brightness. Also, it is the sorrowful lamentation of the valuelessness of ancient literature, culture, values and social life in the artificial glittering capitalist civilization. All the above issues have been addressed with a literary spell and beauty. The struggle for livelihood can be observed in this reportage. This “Reportage” is a literary and historical document about the multicultural civilization and society’s representation of the city’s development

Psychological Concept of Iqbal’s Ideal Society

Iqbal’s thoughts paved the way for a progressive society in the Indo-Pak subcontinent. We would not be wrong in saying that it was the essence of Iqbal’s work which was evident in the voice of the progressive writers who rose for change, equality, and literature for all. There is no doubt that they have been anti against some of Iqbal’s thought processes but it is also true that Iqbal’s work was not only speculation but an epitome of change which many scholars themselves followed. Iqbal was in favor of such a society where all the humanity could collaborate and progress together where he did not want such a society for the Muslim world only but the whole world. It is this philosophical landmark of his that makes him a leading international poet. His concept of an ideal society based on human psychology is based on the knowledge of the Quran and Hadith. It is due to this reason that his teachings are misinterpreted before the third world as being controversial to demoralize them and hence affecting their courage and confidence while on the other hand, the developing world follows the same ideology for their existence and perseverance. Along with Iqbal’s work on the progressive society, in this article, it would also be inspected how much these rules and regulations of Iqbal are introduced for such societies implementable. Is Iqbal’s vision a fictitious marvel or following the ground realities? We will also throw light on the facts that If Iqbal’s knowledge, rules, and regulations introduced by him can bring actual happiness to a person or all his work has only been for the sole purpose of getting fame

Anti-Cholinesterase Combination Drug Therapy as a Potential Treatment for Alzheimer’s Disease

Alzheimer’s disease (AD) is a burgeoning social and healthcare problem. Cholinesterase inhibitors (ChEIs) are employed for symptomatic treatment of AD, but often elicit adverse drug reactions (ADRs). Herein, the potency of the ChEIs, donepezil, tacrine, berberine, and galantamine to inhibit human or Torpedo californica acetylcholinesterase (tcAChE) proteins were evaluated. The efficacy of dual-drug combinations to inhibit human AChE directly and within differentiated neurons was also quantified. ChEI potency was in the order: donepezil > tacrine > berberine > galantamine for both AChEs. Dual-drug combinations of berberine and tacrine (BerTac), berberine and galantamine (BerGal), and tacrine and donepezil (TacDon) all produced synergistic outcomes for AChE inhibition. Donepezil and berberine (DonBer) and tacrine and galantamine (TacGal) elicited antagonistic responses. Donepezil and galantamine (DonGal) was synergistic for human AChE but antagonistic for tcAChE. After application of dual-drug combinations to neuronal cells, BerTac, BerGal, DonGal, and DonBer all showed synergistic inhibition of AChE, TacDon additive, and TacGal antagonistic effects. BerGal produced the most potent synergism and reduced total drug dose by 72%. Individual ChEIs or dual-drug combinations were relatively non-toxic to neuronal cells, and only reduced cell viability at concentrations two–three orders of magnitude greater than that required to inhibit AChE. In summary, dual-drug combinations of ChEIs potentially represent a novel means of AD patient treatment, with reduced and more cost-effective drug dosing, and lowered likelihood of ADRs

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity

Potential Nutraceutical Properties of Leaves from Several Commonly Cultivated Plants

Chronic dietary ingestion of suitable phytochemicals may assist with limiting or negating neurodegenerative decline. Current therapeutics used to treat Alzheimer’s disease elicit broad adverse drug reactions, and alternative sources of cholinesterase inhibitors (ChEIs) are required. Herein, we have screened methanolic extracts from seven commonly cultivated plants for their nutraceutical potential; as an ability to inhibit acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), and provision of antioxidant activity through their 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging capabilities. Potential neurotoxicity of plant extracts was examined via application to SHSY-5Y neuroblastoma cells and quantitation of cell viability. Methanolic extracts of Citrus limon (Lemon), Bombax ceiba (Red silk-cotton), Lawsonia inermis (Henna), Eucalyptus globulus (Eucalyptus), Ocimum basilicum (Basil), Citrus reticulata (Mandarin orange), and Mentha spicata (Spearmint) all displayed concentration dependent inhibition of AChE and BuChE. The majority of extracts inhibited AChE and BuChE to near equipotency; with Henna and Eucalyptus extracts the two most potent ChEIs. All plant extracts were able to scavenge free radicals in a concentration dependent manner, with Eucalyptus the most potent antioxidant. Toxicity of plant extracts to neuronal cells was concentration dependent, with Eucalyptus also the most toxic extract. Fractionation of plant extracts and analysis by mass spectrometry identified a number of plant polyphenols that might have contributed to the cholinesterase inhibition: 3-caffeoylquinic acid, methyl 4-caffeoylquinate, kaempferol-acetyl-glycoside, quercetin 3-rutinoside, quercetin-acetyl-glycoside, kaempferol 3-O-glucoside, and quercetin 3-O-glucoside. In silico molecular modelling of these polyphenols demonstrated their improved AChE and BuChE binding affinities than the current FDA approved dual ChEI, galantamine. Collectively, all of the plant extracts contained neutraceutical agents as antioxidants and ChEIs, and therefore their chronic consumption may provide beneficial to combat the pathological deficits that accrue in Alzheimer’s disease

Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma

Neurokinin-1 receptor (NK-1R) induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues is dependent on receptor signalling. Substance P (SP) has a high affinity for the NK-1R, to which it binds preferentially. We aimed to investigate the expression of NK-1R in World Health Organization (WHO) grade 4 astrocytomas as well as in oral squamous cell carcinoma (OSCC) and urothelial carcinoma, and its association with disease progression.The study included tissue samples from 19 brain astrocytomas, 40 OSCCs and 10 urothelial carcinomas. NK-1R expression was quantitatively assessed in the tumour cells using immunohistochemistry. The relationship between NK-1R expression in astrocytomas and recurrence-free interval has been explored.The results showed that the NK-1R was intensely expressed in patients with WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. However, cases clinically diagnosed as a low-grade cancer showed reduced NK-1R expression.NK-1R is overexpressed in all cases of WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. The ubi-quitous presence of SP/NK-1R complex during tumour development and progression suggests a possible therapeutic key strategy to use NK-1R antagonist as an adjuvant therapy in the future

رضا علی عابدی کے ادبی نشر ئیے اُردو سفر نامے کی روایت کا ایک نیا زاویہ

Raza Ali Abidi is a famous writer and a retired BBC broadcaster. His BBC documentaries received much appreciation and great popularity among masses. Here we discuss social and civilized aspects of his documentaries which include Jernali Sarrak, Sher Darya and Rail Kahani. It has been noticed that all his documentaries have been published in a form of book.

Computed tomography findings in bilateral perinephric lymphangiomatosis

Perinephric lymphangioma is rare disorder that may be confused with various forms of renal cystic diseases and urinomas. In this disorder a developmental malformation results in failure of developing lymphatic tissue to establish normal communication with the rest of lymphatic system. Once there is restricted drainage of lymphatic fluid the lymphatic channels dilate to form cystic masses that may be unilocular or multilocular and may be seen unilaterally or bilaterally .This condition presents with various signs and symptoms or can be just an incidental finding which in presence of misleading clinical history may be confused with other diseases. CT scan with delayed cuts and USG guided aspiration with biochemical analysis of fluid will help us in arriving to final diagnosis

Early-stage endometrial carcinoma; risk factors for recurrence

Background: Endometrial carcinoma (EC) is the most common gynecological malignancy in developed countries. The overall prognosis is excellent, as most cases are diagnosed at an early stage with low-grade histology, but once the recurrence occurs, the median survival decreases severely. Aims and Objectives: The aim of this study was to identify the risk factors associated with recurrence in early-stage EC and explore their impact on overall survival (OS) after recurrence. Materials and Methods: Records from patients diagnosed with EC were retrospectively reviewed. 220 patients were identified as early-stage, low-risk EC who underwent primary surgical treatment between January 2010 and December 2022, and their baseline characteristics were analyzed. Cox regression analysis was used to identify various factors for tumor recurrence. Survival analysis was done using the Kaplan-Meier method. Results: In a cohort of 220 patients, we observed tumor recurrence in 44 (20%) patients and 34 (15.45%) deaths over a median follow-up of 72 months (range, 12–144 months). Multivariate analysis confirmed two risk factors: myometrial invasion (MMI) of any depth and lymphovascular invasion (LVI) as independent predictors of recurrence. The prognosis was worse for patients with recurrence than for those without. The OS for the recurrent group was 38.6%, compared to 96.0% in the non-recurrent group. In our study, the median time to recurrence was 19 months (confidence interval 18–30) months. Conclusion: The presence of MMI and LVI are important predictors for recurrence in early-stage low-risk EC