In this dissertation, Monotheca buxifolia and Bosea amherstiana were assessed for isolation and structural elucidation of their compounds. The phytochemical investigations of Monotheca buxifolia includes lauric acid (1), oleanolic acid (2) and bis (2-ethylhexyl) phthalate (3) while Bosea amherstiana incudes quercetin (4), gallic acid (5) and cinnamic acid (6). The pharmacological and biological activities of crude extract, different fractions thereof, and some compounds isolated in reasonable quantity from Monotheca buxifolia and Bosea amherstiana were investigated. The plants exhibited moisture, fat, fiber, nitrogen, and protein contents. Biological investigation shows significant antibacterial and phytotoxic activity exhibited by the secondary metabolites of Monotheca buxifolia and Bosea amherstiana against L. minor plants and cytotoxicity activity in brine shrimps. Moreover, Monotheca buxifolia and Bosea amherstiana showed moderate inhibition against urease and carbonic anhydrase. The potency of Monotheca buxifolia and Bosea amherstiana for inhibiting the growth of laryngeal cancer cells was determined by MTT assay at concentrations of 200 μg/ml and 150 μg/ml. The IC50 values of Monotheca buxifolia ranged from 80.6214 ± 1.89 μg/ml to 244.506 ± 2.43 μg/ml, while the IC50 values of Bosea amherstiana ranged from 108.564 ± 1.28 μg/ml to 206.053 ± 1.54 μg/ml. A comet assay was performed for the determination of DNA damage and the protective activity of the plant extracts against H2O2-induced human lymphocytes. The maximum protective effect of lymphocyte pretreatment was observed with the dichloromethane fraction of Monotheca buxifolia, which was 5.21 ± 0.030% tail DNA, while the Olive tail moment was 0.61 ± 0.03 compared with the rest of the treated Monotheca buxifolia samples. In Bosea amherstiana, the methanolic fraction had more protective effects against H2O2-induced lymphocytes, with 6.36 ± 2.23% tail DNA and an Olive tail moment of 0.84 ± 0.40. Antioxidant enzymes of lymphocytes were assessed. MB has an effective role in decreasing lipid peroxidase (TBAR) enzymes. The methanol, dichloromethane, and ethyl acetate fractions of MB were more effective (2.3, 2.4, and 2.7, respectively), while the aqueous fraction of MB increased the LPO slightly to 8.1. Both MB and MA had slight effects on the catalase (CAT) enzymes. The dichloromethane fraction of Bosea amherstiana increased the CAT enzymes slightly, while the aqueous fraction of Monotheca buxifolia lowered the concentration of CAT enzymes compared with the control. The dichloromethane fraction of MB slightly increased the peroxidase (POD) enzymes’ value to 31.2, while the aqueous extract of MB lowered the POD enzymes to 20.51. MB had no effect on decreasing or increasing superoxide dismutase (SOD), while BA contributed to lowering the SOD values. In terms of acute toxicity in vivo, both plants were found to be safe at all the test doses (500, 1,000, 1,500, and 2,000 mg/kg. Monotheca buxifolia and Bosea amherstiana (50, 100, and 150 mg/kg) dose dependently reduced abdominal constrictions in mice. Both plants exhibited significant (p < 0.0001) sedative effects at doses of 50, 150, and 150 mg/kg; however, they should be considered mild to moderate sedatives, as the sedation induced was for the less standard drug diazepam. Both plants markedly (p < 0.0001) reduced yeast-induced hyperthermia. CCl4 treatment considerably increased (p < 0.01) the activity of liver serum marker enzymes, such as liver LDH, serum LDH, ALP, AST, and ALT compared with the control group. The protective effect of Monotheca buxifolia was assessed by measuring the serum markers, assays of antioxidant enzymes, genotoxicity, and DNA damage. Monotheca buxifolia inverted the activities of the serum marker enzymes, and the cholesterol profile was damaged by CCl4 treatments. Activities of antioxidant enzymes of the liver tissue homogenates were assessed; CAT, SOD, and peroxidase (POD) were reduced with CCl4 administration, and they were retained with Monotheca buxifolia. The administration of Monotheca buxifolia and Bosea amherstiana reduced hepatic damage, with fewer or no fatty changes, expansion of blood vessels, or constant morphology of the hepatocytes in the control group. The isolated compounds of lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of laryngeal cancer cells, as determined by MTT assay. The IC50 value for lauric acid was 56.4584 ± 1.20 μg/ml, that for oleanolic acid was 31.9421 ± 1.03 μg/ml, and that for bis(2-ethylhexyl) phthalate was 83.8019 ± 2.18 μg/ml. After 24 h of treatment, 29.5% of Hep G2 cells treated with lauric acid, 52.1% of those treated with oleanolic acid, and 22.4% of those treated with bis(2-ethylhexyl) phthalate were apoptotic.
حافظ فضل حق آزادؔ عظیم آبادی ۲۷؍ شعبان ۱۳۶۱ھ کو صوبہ بہار کے مشہور و ممتاز کہنہ مشق شاعر حافظ فضل حق آزاد عظیم آبادی نے اس دنیائے دوں کو الوادع کہا، مرحوم کی عمر اس وقت غالباً اسّی (۸۰) سے زیادہ ہوگی، کانوں سے اونچا سننے لگے تھے، مگر اس سن و سال میں بھی ان کی شاعری کے شباب کا وہی عالم تھا، غزلوں کے کہنے کا اتفاق کم ہوتا تھا، مگر قومی و علمی و اخلاقی اور فلسفیانہ نظموں کا شوق زیادہ تھا، زیادہ تر اردو میں اور کبھی کبھی فارسی میں کہتے تھے اور شاذو نادر عربی میں بھی طبع آزمائی کی نوبت آجاتی تھی۔ پٹنہ میں سرسید مرحوم کی تعلیمی و قومی تحریک کے علمبردار قاضی رضا حسین صاحب مرحوم تھے، یہ ان کے حیدرآباد کے وفد کے ایک رکن بھی تھے، قاضی صاحب مرحوم کی فیض بخش علمی صحبتوں میں بہار کے جو چند نوجوان ابھرے، بڑھے اور پھیلے، ان میں ایک نام حافظ آزاد مرحوم کا بھی ہے، چنانچہ سرسید مرحوم کے اس ۱۸۹۱ء والے حیدرآبادی وفد میں جس کے دوسرے ممبر مولانا شبلی نعمانی اور مولانا حالی وغیرہ تھے، قاضی رضا حسین صاحب کیساتھ آزاد مرحوم بھی تھے۔ میں نے ان کو سب سے پہلے ۱۹۰۰ء میں جب میری نوعمری تھی ندوہ کے اجلاس پٹنہ میں اپنا ترکیب بند پڑھتے سنا، بلند قد، اونچی آواز، خود اعتمادی کے تیور، لہجہ پر جوش، کٹہرے میں شیر کی گرج سی سنائی دیتی تھی، سامنے علماء اور مشائخ کی صفیں تھیں، جن کی تعداد کئی سو سے کم نہ ہوگی، اکثر کی نورانی شکلوں کی یاد اب بھی دل کو منور کرتی ہے، شاعر نے جب ان کی طرف ہاتھ سے اشارہ کرکے یہ شعر پڑھا ہے: نشانِ کاروان رفتہ ہیں دل کے اجالے ہیں غنیمت ہی غنیمت ہیں کہ سب اﷲ...
Misunderstanding of Westerner about Islam. Islam originates from the word "Salam" which means peace, submission and tolerance. Islam has never preached for intolerance, hatred and violence. It has despised violence and bloodshed and having no place for extremism. Islam is a religion of moderation rather than extremism. The Holy Quran enshrines benign treatment and attitude even towards non-believers, who are residing in Muslim state and to guarantee them all their basic rights of life and property. It negates hatred and fundamentalism and stands for universality. There arises question that how this situation has been muddled and the real soul of Islam is distorted? How incendiary norms have been infested in federally administered tribal areas of Pakistan? There is a need for implementation of anti-terror laws and to condemn terrorism in all its manifestations.
Skin is a highly specialized organ system of human body. It is the exterior most part of our body and acts as a boundary between the organs inside the body and environment, facing the external stresses. Genodermatosis is a term used for a congenital skin disease for which the genetic cause is determined. Genodermatoses possessing skin phenotypes without systemic manifestations are excellent models for genetic research because disorders of skin and its appendages make more than one third part of all monogenic diseases. Autozygosity mapping is a powerful statistical technique used for the identification of genes causing recessive disorders in human consanguineous families. In a country like Pakistan, consanguinity or inbreeding is a very common incident due to highly conserved ethnic groups, separated by customs, cultural and geographical barriers. Such population, with high consanguinity in families, experiences rare recessive disorders, which are more likely to be caused by identical-by-descent (IBD) mutations. In the present investigation 11 families (A-K) segregating autosomal recessive disorders of skin or its appendages were ascertained. Ten of these families were identified in the remote areas of Pakistan and one was provided by collaborators from Islamic Republic of Iran. In family A, affected individuals showed characteristic clinical features of cutis laxa syndrome having generalized skin laxity, progeroid appearance, facial anomalies with hypertelorism, sagging cheeks, broaden nasal bridge and hiatal hernia. Human genome scan using 534 microsatellite markers revealed a common homozygous region of 14.6 Mb, flanked by markers D9S1862 and D9S167, on chromosome 9q13-21.32 in the affected individuals of the family. Maximum multipoint LOD of > 3.0 was obtained at recombination fraction zero with several markers on chromosome 9q13-q21.32. Sequencing of the eight selected putative candidate genes (PRKACG, TJP2, ALDH1A1, RFK, GCNT1, GNAQ, PSAT1, CHCHD9) did not reveal any functional sequence variant and therefore their involvement in causing cutis laxa syndrome phenotype at the present novel locus is not supported. In family B, affected individuals showed clinical features of autosomal recessive hypotrichosis (LAH1). The disease equally affected both males and females with sparse Genetic Mapping of Genes Underlying Human Skin Disorders XVII Abstract hair on scalp, sparse to absent eyebrows and eyelashes, and sparse hair on rest of the body. Genotyping data showed linkage of the family to DSG4 gene on chromosome 18q12. Sequence analysis of DSG4 gene revealed a previously reported large intragenic homozygous deletion mutation (Ex5_8del) in all the affected individuals. In family C, affected individuals showed clinical features of autosomal recessive hypotrichosis (LAH2). The patients showed thin fragile hair on scalp, sparse to absent eyebrows and eyelashes, and sparse hair on rest of the body. Genotyping data showed linkage of the family to LIPH gene on chromosome 3q27. Sequence analysis of LIPH gene revealed a novel homozygous two base pairs deletion mutation (c.659_660delTA, p.Ile220ArgfsX25) in all the affected individuals. Three families (D, E, F) showed clinical features of autosomal recessive hypotrichosis (LAH3). All the affected individuals presented an equal intensity of the disease with sparse thin fragile hair on scalp, sparse to absent eyebrows and eyelashes, and arrested hair follicle growth. Genotyping data showed linkage of the families to P2RY5 gene on chromosome 13q14.11-q23.21. Sequence analysis of the P2RY5 gene revealed three novel homozygous mutations including an insertion (c.160insA, p.Thr54AsnfsX5) in family D, and missense (c.436G>A, p.Gly146Arg) in family E and (c.830C>T, p.Lue277Pro) in family F. Two families (G, H) showed clinical features of atrichia with papular lesions. Patients in these families showed complete hair loss of scalp, absent eyebrows and eyelashes, loss of axillary and pubic hair. Genotyping results showed linkage of the two families to human hairless gene (HR) located on chromosome 8p21.3. In family G, sequence analysis revealed a novel sequence variant involving three base pairs homozygous deletion (c.1839-1841delATG, p.Cys614del) in exon 6 of the HR gene in all the affected individuals. In family H, sequence analysis of HR gene failed to detect any functional sequence variant. In family I, affected individuals exhibited characteristic features of alopecia with mental retardation syndrome. Complete loss of scalp hair and, absent eyebrows and eyelashes were observed in the affected individuals. Both the affected individuals were mentally retarded and attending school for special education. Genotyping data showed linkage of the family to APMR1 locus on chromosome 3q26.33-q27.3. The region of homozygousity spanning 11.39 cM (6 Mb) flanked by markers D3S1232 and D3S3686 contains several Genetic Mapping of Genes Underlying Human Skin Disorders XVIII Abstract genes. To search for potential sequence variants, coding exons and splice junction sites of the three genes (LIPH, AADACL1, AHSG) were sequenced in two affected individuals of the family. Sequence analysis of the three genes failed to identify any functional sequence variant, which could be responsible for the disease phenotype. In family J, the patients exhibited hypotrichosis with juvenile macular dystrophy phenotype. The scalp hairs were fine and curly that could easily be pulled out. Eyebrows and eyelashes, pelvic and pubic hair showed normal growth. Fundus examination of the patients disclosed Electrophysiological marked tests degeneration including of the macular electroretinography pigment showed epithelium. severe retinal dysfunction. Sequence analysis of CDH3 gene at chromosome 16q22.1 revealed a novel homozygous splice-acceptor site mutation (IVS10-1G>T) in affected individuals of the family. In family K, affected individuals showed clinical features of ectodermal dysplasia cutaneous syndactyly (EDCS) syndrome. The patients exhibited hypotrichosis with sparse hair on scalp, and sparse to absent eyebrows and eyelashes. Conical and cylindrical shaped teeth with ill-defined surface morphology. Hypoplastic nails, mild keratoderma over the palms and soles and bilateral cutaneous syndactyly of 3-4 digit of hand and 2-3 toe-digit was observed in all patients. Human genome scan mapped the disease locus to chromosome 1q23.1-q23.3. This region corresponds to 5.63 Mb according to the sequenced based physical map (Build 36.2) of the human genome and flanked by markers D1S1653 and D1S1677. A maximum two-point LOD score of 5.05 was obtained with marker D1S484. Sequence analysis revealed a homozygous missense mutation (c.635C>G; p.Pro212Arg) in the recently reported PVRL4 gene causing ectodermal- dysplasia-syndactyly syndrome (EDSS). The data presented here has been published in the following articles. 1 Jelani M, Wasif N, Ali G, Chishti M, Ahmad W (2008) A novel deletion mutation in LIPH gene causes autosomal recessive hypotrichosis (LAH2). Clinical Genetics 74: 184-188 2 Azeem Z, Jelani M, Naz G, Tariq M, Wasif N, Naqvi SK, Ayub M, Yasinzai M, Amin-Ud-Din M, Wali A, Ali G, Chishti MS, Ahmad W (2008) Novel mutations in G Genetic Mapping of Genes Underlying Human Skin Disorders protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). Human Genetics 123: 515-915 3 Jelani M, Salman Chishti M, Ahmad W (2009) A novel splice-site mutation in the CDH3 gene in hypotrichosis with juvenile macular dystrophy. Clinical and Experimental Dermatology 34: 68-73 4 Balighi K, Lajevardi V, Moeineddin F, Jelani M, Tamizifar B, Nikoo A, Javed Q, Ahmad W, Parvaneh N (2009) A novel deletion mutation in the human hairless (HR) gene in an Iranian family with atrichia and papular lesions. Clinical and Experimental Dermatology 34: e498-500 5 Tariq M, Ayub M, Jelani M, Basit S, Naz G, Wasif N, Raza SI, Naveed AK, ullah Khan S, Azeem Z, Yasinzai M, Wali A, Ali G, Chishti MS, Ahmad W (2009) Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families. British Journal of Dermatology 160: 1006-1010 6 Jelani M, Tariq M, Jan IA, Ullah H, Naeem M, Ahmad W (2011) Congenital cutis laxa syndrome maps to a novel locus on chromosome 9q13-q21.32. Journal of Dermatological Science 61:134-136 7 Jelani M, Chishti MS, Ahmad W (2011) Mutation in PVRL4 gene encoding Nectin-4 underlies Ectodermal-dysplasia-cutaneous-syndactyly (EDCS) syndrome. (Accepted to Journal of Human Genetics)" xml:lang="en_US