Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights.

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion.

Several ABC exporters carry a degenerate nucleotide binding site (NBS) that is unable to hydrolyze ATP at a rate sufficient for sustaining transport activity. A hallmark of a degenerate NBS is the lack of the catalytic glutamate in the Walker B motif in the nucleotide binding domain (NBD). The multidrug resistance transporter ABCB1 (P-glycoprotein) has two canonical NBSs, and mutation of the catalytic glutamate E556 in NBS1 renders ABCB1 transport-incompetent. In contrast, the closely related bile salt export pump ABCB11 (BSEP), which shares 49% sequence identity with ABCB1, naturally contains a methionine in place of the catalytic glutamate. The NBD-NBD interfaces of ABCB1 and ABCB11 differ only in four residues, all within NBS1. Mutation of the catalytic glutamate in ABCB1 results in the occlusion of ATP in NBS1, leading to the arrest of the transport cycle. Here we show that despite the catalytic glutamate mutation (E556M), ABCB1 regains its ATP-dependent transport activity, when three additional diverging residues are also replaced. Molecular dynamics simulations revealed that the rescue of ATPase activity is due to the modified geometry of NBS1, resulting in a weaker interaction with ATP, which allows the quadruple mutant to evade the conformationally locked pre-hydrolytic state to proceed to ATP-driven transport. In summary, we show that ABCB1 can be transformed into an active transporter with only one functional catalytic site by preventing the formation of the ATP-locked pre-hydrolytic state in the non-canonical site.

Vitamin D status and its correlation to depression.

BACKGROUND: Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression. METHODS: Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects. RESULTS: Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency. CONCLUSIONS: The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.

In vitro anticancer and antioxidant potential of Cestrum species.

The methanolic extract of leaves and stem of Cestrum nocturnum and Cestrum diurnum were investigated for their antioxidant and anticancer attribute through standard methods. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was carried out to estimate the antioxidant activity of the extracts. Whereas, anticancer potential of extracts were tested against colon cancer cell line, HCT 116 and acute myeloid leukemia (AML) cell lines, THP-1. Results showed that extracts of both plants exhibited a very strong antioxidant activity in a dose dependent manner. In addition, both extracts efficiently increased the cell death in two different cancer cell lines. Moreover, DNA fragmentation analysis further strengthens the anticancer potential of extracts of both types of plants. Current study, therefore, provide a preliminary data highlighting the antioxidant and anticancer activities of methanolic extract of leaves and stem of Cestrum nocturnum and Cestrum diurnum.

Screening and computational analysis of colorectal associated non-synonymous polymorphism in CTNNB1 gene in Pakistani population.

BACKGROUND: Colorectal cancer (CRC) is categorized by alteration of vital pathways such as ß-catenin (CTNNB1) mutations, WNT signaling activation, tumor protein 53 (TP53) inactivation, BRAF, Adenomatous polyposis coli (APC) inactivation, KRAS, dysregulation of epithelial to mesenchymal transition (EMT) genes, MYC amplification, etc. In the present study an attempt was made to screen CTNNB1 gene in colorectal cancer samples from Pakistani population and investigated the association of CTNNB1 gene mutations in the development of colorectal cancer. METHODS: 200 colorectal tumors approximately of male and female patients with sporadic or familial colorectal tumors and normal tissues were included. DNA was extracted and amplified through polymerase chain reaction (PCR) and subjected to exome sequence analysis. Immunohistochemistry was done to study protein expression. Molecular dynamic (MD) simulations of CTNNB1WT and mutant S33F and T41A were performed to evaluate the stability, folding, conformational changes and dynamic behaviors of CTNNB1 protein. RESULTS: Sequence analysis revealed two activating mutations (S33F and T41A) in exon 3 of CTNNB1 gene involving the transition of C.T and A.G at amino acid position 33 and 41 respectively (p.C33T and p.A41G). Immuno-histochemical staining showed the accumulation of ß-catenin protein both in cytoplasm as well as in the nuclei of cancer cells when compared with normal tissue. Further molecular modeling, docking and simulation approaches revealed significant conformational changes in the N-terminus region of normal to mutant CTNNB1 gene critical for binding with Glycogen synthase kinase 3-B (GSK3) and transducin containing protein1 (TrCp1). CONCLUSION: Present study on Pakistani population revealed an association of two non-synonymous polymorphisms in the CTNNB1 gene with colorectal cancer. These genetic variants led to the accumulation of the CTNNB1, a hallmark of tumor development. Also, analysis of structure to function alterations in CTNNB1 gene is crucial in understanding downstream biological events.

Assessment of antimicrobial, antioxidant and cytotoxicity properties of Camellia sinensis L.

The phytochemical screening, antimicrobial, antioxidant and cytotoxic properties of Camellia sinensis were evaluated in the present study. The phytochemical screening revealed the presence of an applicable amount of lycopene, ß-carotenes, flavonoids and tannins in C. sinensis. Among the phytochemicals, tannin was found to be significantly higher in tea plant. The antimicrobial activity of plant extracts against selected bacterial strains namely, Escherichia coli, Staphylococcus aurous, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Marginella morganii and Haemophilus influenzae was investigated. The results showed that the stem part of C. sinensis presented greater antimicrobial potential than the leaf and root. Antioxidant activity (assessed through % inhibition of linoleic acid per oxidation test) was the highest (89.22%) in n-hexane extract of root part as compared to other extracts. Finally, the cytotoxicity analysis (haemolytic activity against human erythrocytes) of plant extract showed the negligible (%) lysis of RBCs ranging from 1.73 to 4.01%. In conclusion, it can be suggested that C. sinensis is the potential source to obtain bioactive phenolic compounds with high antimicrobial and antioxidant properties, which could possibly be exploited for the treatment of various infectious diseases.

Evaluation of antioxidant, anti-inflammatory, analgesic and antipyretic activities of the stem bark of Sapindus mukorossi.

BACKGROUND: Saponins are the main constituents of genus Sapindus and have the therapeutic potential for inflammatory disorders. In this study the antioxidant, anti-inflammatory, analgesic and antipyretic potential of the stem bark of soap nut (Sapindus mukorossi) methanol extract and its derived fractions has been investigated. METHODS: Powder of stem bark of the S. mukorossi was extracted with methanol (SMM) and fractionated in order of n-hexane (SMH), chloroform (SMC), ethyl acetate (SME), n-butanol (SMB) and the remaining as aqueous fraction (SMA). Quantitative estimation for the total phenolic and total flavonoid content was carried out in all the extract/fractions. Further, various in vitro antioxidant assays were also performed. Anti-inflammatory (Carrageenan induced paw edema), analgesic (hot plate latency test) and antipyretic (rectal temperature) were determined in Sprague-Dawley rat. RESULTS: Quantitative estimation of total phenolic contents in extract/fractions varied between 252.3 ± 2.41 mg of GAE/g - 594.16 ± 4.3 mg of GAE/g while the total flavonoids estimated were from 11.02 ± 1.3 mg of RUE/g to 96.9 ± 3.2 mg of RUE/g. Standard antioxidant assays such as scavenging of DPPH, hydroxyl radical, nitric oxide, phosphomolybdenum assay, reducing power, inhibition of ß-carotene bleaching, iron chelation activity and inhibition of heat induced protein denaturation indicated the antioxidant potential of the extract/fractions. Carrageenan induced paw edema of rat was effectively inhibited by SMA at 300 mg/kg administration to rat (84.19 ± 1.48%) after 3 h and analgesia (latency time) in hot plate test (55.78 ± 1.22%) after 120 min. SMA at 300 mg/kg distinctly decreased the rectal temperature in brewer's yeast (Saccharomyces cerevisiae) induced pyrexia in rat. CONCLUSION: The resulted obtained in this study suggested the therapeutic importance of stem bark of S. mukorossi in inflammatory related disorders.

Pore-exposed tyrosine residues of P-glycoprotein are important hydrogen-bonding partners for drugs.

The multispecific efflux transporter, P-glycoprotein, plays an important role in drug disposition. Substrate translocation occurs along the interface of its transmembrane domains. The rotational C2 symmetry of ATP-binding cassette transporters implies the existence of two symmetry-related sets of substrate-interacting amino acids. These sets are identical in homodimeric transporters, and remain evolutionary related in full transporters, such as P-glycoprotein, in which substrates bind preferentially, but nonexclusively, to one of two binding sites. We explored the role of pore-exposed tyrosines for hydrogen-bonding interactions with propafenone type ligands in their preferred binding site 2. Tyrosine 953 is shown to form hydrogen bonds not only with propafenone analogs, but also with the preferred site 1 substrate rhodamine123. Furthermore, an accessory role of tyrosine 950 for binding of selected propafenone analogs is demonstrated. The present study demonstrates the importance of domain interface tyrosine residues for interaction of small molecules with P-glycoprotein.

Synthesis, biological evaluation and 3D-QSAR studies of new chalcone derivatives as inhibitors of human P-glycoprotein.

P-glycoprotein (P-gp) is an ATP-dependent multidrug resistance efflux transporter that plays an important role in anticancer drug resistance and in pharmacokinetics of medicines. Despite a large number of structurally and functionally diverse compounds, also flavonoids and chalcones have been reported as inhibitors of P-gp. The latter share some similarity with the well studied class of propafenones, but do not contain a basic nitrogen atom. Furthermore, due to their rigidity, they are suitable candidates for 3D-QSAR studies. In this study, a set of 22 new chalcone derivatives were synthesized and evaluated in a daunomycin efflux inhibition assay using the CCRF.CEM.VCR1000 cell line. The compound 10 showed the highest activity (IC50=42nM), which is one order of magnitude higher than the activity for an equilipohillic propafenone analogue. 2D- and 3D-QSAR studies indicate the importance of H-bond acceptors, methoxy groups, hydrophobic groups as well as the number of rotatable bonds as pharmacophoric features influencing P-gp inhibitory activity.

Pap smear, an important screening tool to detect precancerous stage of carcinoma of cervix.

BACKGROUND: Many women can be saved from carcinoma of cervix by detecting and treating its precancerous stage. Pap smear is cheap and easily available in majority of institutes. The objective of this study is to determine the frequency of abnormal Pap smear and role of Pap smear in detecting precancerous stage of cancer cervix in women. METHODS: This is retrospective descriptive study was conducted in gynaecology outpatient department of Isra University Hospital, Hyderabad, Sind from Nov 2006 to Oct 2009. All women who presented in OPD with gynaecological complaints were included in the study. Pregnant women were excluded from the study. Smear was collected with an Aryes spatula and relevant information was obtained from the patient's record and recorded on pre-designed Performa. Slides were then sent to pathology department. Data were analysed through SPSS-15 and presented as frequency and percentage. RESULTS: Total 981 women underwent Pap smear screening. Majority (63.3%) of the patients belonged to age group of 31-40 years. One hundred and eighty (18.34%) smears were normal and 792 (80.7%) were abnormal. Among these abnormal smears, 739 (75.33%) smears were inflammatory while 4 (0.40%) women had Ca in situ and 4 (0.40%) had squamous cell carcinoma. CONCLUSION. Pap smear is an important screening tool to detect precancerous stage of carcinoma of cervix. It should be done periodically in all married and high risk women for early detection of a precancerous stage.

Vaginal breech delivery: still a safe option.

BACKGROUND: Elective caesarean section has replaced vaginal delivery for term breech foetuses due to fear of complications of vaginal breech delivery. This increasing rate of caesarean section worldwide is alarming. It has not only led to increase in adverse consequences in subsequent pregnancies and future fertility but also loss of skills for vaginal breech delivery. This study was conducted to determine the safety of vaginal breech birth in terms of maternal and neonatal complications. METHODS: This cross sectional study was conducted at department of Obstetrics/Gynaecology, Ayub Medical College, Abbottabad from January 2004 to December 2011. One seventy-eight women having successful vaginal breech delivery of singleton term foetuses from 2004-2008 were selected. They were studied for neonatal complications like low Apgar score (AS) < 7 at 5 min, birth trauma, admission to neonatal intensive care units and perinatal mortality. Maternal complications including any genital tract trauma and post-partum haemorrhage (PPH) were also noted. RESULTS: There were 11243 deliveries during this period, including 674 breech presentations at term (incidence of breech 6%). Out of 178 successful vaginal breech deliveries, 8 (4.49%) neonates had AS < 7 at 5 min, and 6 (3.37%) neonates needed NICU admission. There were no cases of birth trauma or perinatal morbidity. Maternal complications occurred in only 5 (2.8%) patients, 2 (1.1%) having perineal tears, 2 (1.12%) retained placenta and one (0.56%) case of post partum haemorrhage. CONCLUSION: Vaginal breech delivery can be safely undertaken without compromising maternal and neonatal outcome if strict criteria are met before and during labour.

Students' Perspective Of An Ideal Medical Teacher - Expectations And Reality.

BACKGROUND: Medical teacher plays an important role in the education of medical students. Medical students always portray their teacher as an ideal. The objective of the study was to find the gap between the best qualities that an ideal medical teacher should have and the best qualities that a medical teacher actually has. METHODS: This cross-sectional survey was conducted at Ayub Medical College Abbottabad from April 2021 to Dec 2021. Consented students of 4th year and Final year MBBS were the participants. Data regarding the qualities of the best medical teacher was collected on Likert scaled validated survey questionnaire. Two closed-ended questionnaires were used. Items were the same in both questionnaires. One questionnaire (Questionnaire A) was regarding expectations of students and what qualities they expected in their ideal medical teacher. The second questionnaire (questionnaire B) was about the qualities that a medical teacher actually had been exhibiting those students had experienced. Data was analyzed using SPSS version 22.0. RESULTS: A total of 210 students participated in this study, 126 students were from 4th year and 84 were from the final year of MBBS. Ninety-one and a half percent of students thought that an ideal medical teacher should be competent in his/her subject but in reality, 48% of students reported that their teachers are competent. Ninety-four percent of students rated that an ideal medical teacher should have excellent communication skills but in reality, only 33% reported that their teachers are having good communication skills. Eighty-three (83%) students expect their teachers should be students friendly but in reality, only 22% of teachers are students caring. Eighty-nine percent of students expect that an ideal medical teacher shall demonstrate clinical skills to students but in reality, only 36% experienced demonstration from their teachers. CONCLUSIONS: There is a big gap between the expected qualities of a medical teacher and the qualities that a teacher has in reality from students' perspectives. Teachers should be trained to bridge this gap.

In Vitro and In Vivo Evaluation of the Antidiabetic Activity of Solidago virgaurea Extracts.

Background: Solidago virgaurea (Asteraceae) has been used for more than 700 years for treating cystitis, chronic nephritis, urolithiasis, rheumatism, and inflammatory diseases. However, the antidiabetic activity of Solidago virgaurea has been rarely studied. Methods: Three extracts of Solidago virgaurea were prepared, and their antidiabetic potentials were evaluated by various cell-free, cell-based, and in vivo studies. Results: We found that the Solidago virgaurea contained multiple bioactive phytochemicals based on the GC-MS analysis. The Solidago virgaurea extracts effectively inhibited the functions of the carbohydrate digestive enzyme (α-glucosidase) and protein tyrosine phosphatase 1B (PTP1B), as well as decreased the amount of advanced glycation end products (AGEs). In the L6 myotubes, the Solidago virgaurea methanolic extract remarkably enhanced the glucose uptake via the upregulation of glucose transporter type 4 (GLUT4). The extract also significantly downregulated the expression of PTP1B. In the streptozotocin-nicotinamide induced diabetic mice, the daily intraperitoneal injection of 100 mg/kg Solidago virgaurea methanolic extract for 24 days, substantially lowered the postprandial blood glucose level with no obvious toxicity. The extract's anti-hyperglycemic effect was comparable to that of the glibenclamide treatment. Conclusion: Our findings suggested that the Solidago virgaurea extract might have great potential in the prevention and treatment of diabetes.

Histological and Microscopic Analysis of Fats in Heart, Liver Tissue, and Blood Parameters in Experimental Mice.

The intake of various types and amounts of dietary fats influences metabolic and cardiovascular health. Hence, this study evaluated the impact of routinely consumed Pakistani dietary fats on their cardiometabolic impact. For this, we made four groups of mice, each comprising 5 animals: (1) C-ND: Control mice on a normal diet, (2) HFD-DG: High-fat diet mice on a normal diet plus 10% (w/w) desi ghee, (3) HFD-O: Mice on normal diet plus 10% (w/w) plant oil (4) HFD-BG: Mice on normal diet plus 10% (w/w) banaspati ghee. Mice were fed for 16 weeks, and blood, liver, and heart samples were collected for biochemical, histological, and electron microscopic analysis. The physical factors indicated that mice fed on HFD gained more body weight than the C-ND group. Blood parameters do not show significant differences, but overall, the glucose and cholesterol concentrations were raised in the mice fed with a fat-rich diet, with the highest concentrations in the HFD-BG group. The mice fed with HFD-BG and HFD-O had more lipid droplets in the liver, compared to HFD-DG and C-ND.

Integrative Genomic Analysis of m6a-SNPs Identifies Potential Functional Variants Associated with Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects 35 million people worldwide. However, no potential therapeutics currently are available for AD because of the multiple factors involved in it, such as regulatory factors with their candidate genes, factors associated with the expression levels of its corresponding genes, and many others. To date, 29 novel loci from GWAS have been reported for AD by the Psychiatric Genomics Consortium (PGC2). Nevertheless, the main challenge of the post-GWAS era, namely to detect significant variants of the target disease, has not been conducted for AD. N6-methyladenosine (m6a) is reported as the most prevalent mRNA modification that exists in eukaryotes and that influences mRNA nuclear export, translation, splicing, and the stability of mRNA. Furthermore, studies have also reported m6a's association with neurogenesis and brain development. We carried out an integrative genomic analysis of AD variants from GWAS and m6a-SNPs from m6AVAR to identify the effects of m6a-SNPs on AD and identified the significant variants using the statistically significance value (p-value <0.05). The cis-regularity variants with their corresponding genes and their influence on gene expression in the gene expression profiles of AD patients were determined, and showed 1458 potential m6a-SNPs (based on p-value <0.05) associated with AD. eQTL analysis showed that 258 m6a-SNPs had cis-eQTL signals that overlapped with six significant differentially expressed genes based on p-value <0.05 in two datasets of AD gene expression profiles. A follow-up study to elucidate the impact of our identified m6a-SNPs in the experimental study would validate our findings for AD, which would contribute to the etiology of AD.

Association of APOE (rs429358 and rs7412) and PON1 (Q192R and L55M) Variants with Myocardial Infarction in the Pashtun Ethnic Population of Khyber Pakhtunkhwa, Pakistan.

Coronary Artery Diseases (CAD) remains the top among Non-communicable Diseases (NCDs). Variations in Apolipoprotein E (APOE) and Paroxonase 1 (PON1) have been associated with Myocardial Infarction (MI) in several populations. However, despite the high prevalence of CAD, no such study has been reported in the Pashtun ethnic population of Pakistan. We have conducted a two-stage (i.e., screening and validation) case-control study in which 200 cases and 100 control subjects have been recruited. In the first stage, Whole Exome Sequencing (WES) was used to screen for pathogenic variants of Myocardial Infarction (MI). In the second stage, selected variants of both APOE and PON1 genes (rs7412, rs429358, rs854560, and rs662) were analyzed through MassARRAY genotyping. Risk Allele Frequencies (RAFs) distribution and association of the selected SNPs with MI were determined using the Chi-square test and logistic regression analysis. WES identified a total of 12 sequence variants in APOE and 16 in PON1. Genotyping results revealed that APOE variant rs429358 (ɛ4 allele and ɛ3/ɛ4 genotype) showed significant association in MI patients (OR = 2.11, p value = 0.03; 95% CI = 1.25-2.43); whereas no significant difference (p˃ 0.05) was observed for rs7412. Similarly, the R allele of PON1 Q192R (rs662) was significantly associated with cases (OR = 1.353, p value = 0.048; 95% CI = 0.959-1.91), with particular mention of RR genotype (OR = 1.523, p value = 0.006; 95% CI = 1.087-2.132). Multiple logistic regression analysis showed that rs429358 (C allele) and rs662 (R allele) have a significantly higher risk of MI after adjustment for the conventional risk factors. Our study findings suggested that the rs429358 variant of APOE and PON1 Q192R are associated with MI susceptibility in the Pashtun ethnic population of Pakistan.

Aspergillus welwitschiae BK Isolate Ameliorates the Physicochemical Characteristics and Mineral Profile of Maize under Salt Stress.

Abiotic stressors are global limiting constraints for plant growth and development. The most severe abiotic factor for plant growth suppression is salt. Among many field crops, maize is more vulnerable to salt, which inhibits the growth and development of plants and results in low productivity or even crop loss under extreme salinity. Consequently, comprehending the effects of salt stress on maize crop improvement, while retaining high productivity and applying mitigation strategies, is essential for achieving the long-term objective of sustainable food security. This study aimed to exploit the endophytic fungal microbe; Aspergillus welwitschiae BK isolate for the growth promotion of maize under severe salinity stress. Current findings showed that salt stress (200 mM) negatively affected chlorophyll a and b, total chlorophyll, and endogenous IAA, with enhanced values of chlorophyll a/b ratio, carotenoids, total protein, total sugars, total lipids, secondary metabolites (phenol, flavonoids, tannins), antioxidant enzyme activity (catalase, ascorbate peroxidase), proline content, and lipid peroxidation in maize plants. However, BK inoculation reversed the negative impact of salt stress by rebalancing the chlorophyll a/b ratio, carotenoids, total protein, total sugars, total lipids, secondary metabolites (phenol, flavonoids, tannins), antioxidant enzyme activity (catalase, ascorbate peroxidase), and proline content to optimal levels suitable for growth promotion and ameliorating salt stress in maize plants. Furthermore, maize plants inoculated with BK under salt stress had lower Na+, Cl- concentrations, lower Na+/K+ and Na+/Ca2+ ratios, and higher N, P, Ca2+, K+, and Mg2+ content than non-inoculated plants. The BK isolate improved the salt tolerance by modulating physiochemical attributes, and the root-to-shoot translocation of ions and mineral elements, thereby rebalancing the Na+/K+, Na+/Ca2+ ratio of maize plants under salt stress.

A novel alpha-amylase inhibitor-based spirooxindole-pyrrolidine-clubbed thiochromene-pyrzaole pharmacophores: Unveiling the [3+2] cycloaddition reaction by molecular electron density theory.

A novel spirooxindole-pyrrolidine clubbed thiochromene and pyrazole motifs were synthesized by [3+2] cycloaddition (32CA) reactions in one step process starting from the ethylene-based thiochromene and pyrazole scaffolds with the secondary amino-acids and substituted isatins in high yield. The 32CA reaction of AY 10 with ethylene derivative 6 has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, N = 4.39 eV, allows explaining that the most favorable TS-on is 13.9 kcal mol-1 below the separated reagent. This 32CA, which takes place through a non-concerted one-step mechanism, presents a total ortho regio- and endo stereoselectivity, which is controlled by the formation of two intramolecular H… O hydrogen bonds. The design of spirooxindole-pyrrolidines engrafted thiochromene and pyrazole was tested for alpha-amylase inhibition and show a high efficacy in nanoscale range of reactivity. The key interaction between the most active hybrids and the receptor was studied by molecular docking. The physiochemical properties of the designed spirooxindole-pyrrolidines were carried out by in silico ADMET prediction. The newly synthesized most potent hybrid could be considered as a lead compound for drug discovery development for type 2 diabetes mellitus (T2DM).

Dihydropyrazole Derivatives Act as Potent α-Amylase Inhibitors and Free Radical Scavengers: Synthesis, Bioactivity Evaluation, Structure-Activity Relationship, ADMET, and Molecular Docking Studies.

Dihydropyrazole (1-22) derivatives were synthesized from already synthesized chalcones. The structures of all of the synthesized compounds were confirmed by elemental analysis and various spectroscopic techniques. Furthermore, the synthesized compounds were screened against α amylase as well as investigated for antioxidant activities. The synthesized compounds demonstrate good to excellent antioxidant activities with IC50 values ranging between 30.03 and 913.58 µM. Among the 22 evaluated compounds, 11 compounds exhibit excellent activity relative to the standard ascorbic acid IC50 = 287.30 µM. Interestingly, all of the evaluated compounds show good to excellent α amylase activity with IC50 values lying in the range between 0.5509 and 810.73 µM as compared to the standard acarbose IC50 = 73.12 µM. Among the investigated compounds, five compounds demonstrate better activity compared to the standard. In order to investigate the binding interactions of the evaluated compounds with amylase protein, molecular docking studies were conducted, which show an excellent docking score as compared to the standard. Furthermore, the physiochemical properties, drug likeness, and ADMET were investigated, and it was found that none of the compounds violate Lipiniski's rule of five, which shows that this class of compounds has enough potential to be used as a drug candidate in the near future.

Clinical audit of foetomaternal outcome in pregnancies with fibroid uterus.

BACKGROUND: Leiomyoma, myoma, leiomyoma or fibroids are synonymous terms. They may be present in as many as 1 in 5 women over age 35 years. If pregnancy is associated with fibroids, it leads to multiple complications. Objectives of this study were to evaluate the maternal and foetal outcome in women having pregnancy with fibroids in uterus and the complications associated with fibroids during the pregnancy. METHODS: This descriptive study was conducted in the Department of Obstetrics and Gynaecology, Ayub Teaching Hospital Abbottabad from March 2009 to March 2010. Data were collected on performa regarding demographic variables, obstetrical history, mode of delivery, maternal outcome, maternal complications, and foetal outcome. Mean and standard deviation was calculated for age, period of gestation, and obstetrical history. Frequency and percentages was calculated for booking status, maternal outcome, maternal complications and foetal outcome. RESULTS: Thirty patients were included in this study who had pregnancy with fibroid. Normal delivery was achieved in 14 (46.66%) patients. Eight (26.67%) patients had caesarean section and eight (26.67%) had miscarriages. Seven (23.33%) patients had no complications while 8 (26.67%) had miscarriages, 8 (26.67%) had postpartum haemorrhage, 10 (33.33%) had preterm delivery, and 3 patients had ante-partum haemorrhage. Two (10%) patients had premature rupture off membranes and 1 patient (3.33%) had pain abdomen and technical difficulty during caesarean section. There were 12 (40%) healthy babies. Five (16.67%) babies delivered with morbidity but recovered. There were 4 (13.33%) intrauterine deaths and one early neonatal death. CONCLUSION: Fibroid in pregnancy, especially multiple intramural fibroids and fibroids larger than 10 Cm, cause miscarriage and preterm labour.