Identification of a Single Nucleotide Polymorphism of Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP) Gene and Its Dysregulated Pathway Through VDR-VDBP Interaction Network Analysis in Vitamin D-Deficient Infertile Females.

INTRODUCTION: The prevalence of female infertility in Pakistan is currently estimated at 22%, and emerging research suggests that vitamin D (VD) deficiency (VDD) may play a significant role in influencing female fertility. The focus of this study was to investigate the single nucleotide polymorphism (SNP) patterns within the VD binding protein (VDBP). The study aimed to explore dysregulated pathways and gene enrichment through an interaction network analysis, specifically focusing on the interplay between the VD receptor (VDR) and VDBP in females experiencing unexplained infertility (UI) coupled with VDD. METHODS: A cross-sectional study was conducted on VD-deficient, fertile, and UI female subjects. VDBP and VDR were assessed by enzyme-linked immunoassay and genotyping performed. FunRich (version 3.1.3; http://funrich.org/index.html) was employed for analysis of the identified proteins: VDR and VDBP and with their mapped gene datasets, gene enrichment, and protein-protein interaction (PPI) network. RESULTS: The mean VD and VDR values of infertile females were significantly lower than those of fertile females. VDBP in infertile females (median (IQR)): 296.05 (232.58-420.23)) was lower than that of fertile females (469.9 (269.57-875.55), (p=0.01)). On sequence analysis, a mutation rs 4588 SNP (Thr 436 Lys) was found in exon 11 of the VDBP gene of UI females, but no mutation in exons 8 and 9 of the VDR gene, with some insignificant intronic variants, was observed. The proteins such as plasma membrane estrogen receptor signaling pathway (p < 0.001), VDR, SMAD3, NCOR1, CREBBP, NCOA1, STAT1, GRB2, PPP2CA, TP53, and NCOA2 were enriched after biological pathway grouping when VDR was made the focused gene and directly interacting with VDBP. CONCLUSION: The females with UI exhibited significantly low VD, VDBP, and VDR. The plasma membrane estrogen receptor signaling pathway was enriched in VDD infertile females.

Optimal Enzyme-Assisted Extraction of Phenolics from Leaves of Pongamia pinnata via Response Surface Methodology and Artificial Neural Networking.

This research work seeks to evaluate the impact of selected enzyme complexes on the optimised release of phenolics from leaves of Pongamia pinnata. After preliminary solvent extraction, the P. pinnata leaf extract was subjected to enzymatic treatment, using enzyme cocktails such as kemzyme dry-plus, natuzyme, and zympex-014. It was noticed that zympex-014 had a greater extract yield (28.0%) than kemzyme dry-plus (17.0%) and natuzyme (18.0%). Based on the better outcomes, zympex-014-based extract values were subsequently applied to several RSM parameters. The selected model is suggested to be significant by the F value (12.50) and R2 value (0.9669). The applicability of the ANN model was shown by how closely the projected values from the ANN were to the experimental values. In terms of total phenolic contents (18.61 mg GAE/g), total flavonoid contents (12.56 mg CE/g), and DPPH test (IC50) (6.5 g/mL), antioxidant activities also shown significant findings. SEM analysis also revealed that the cell walls were damaged during enzymatic hydrolysis, as opposed to non-hydrolysed material. Using GC-MS, five potent phenolic compounds were identified in P. pinnata extract. According to the findings of this study, the recovery of phenolic bioactives and subsequent increase in the antioxidant capacity of P. pinnata leaf extract were both positively impacted by the optimisation approaches suggested, including the use of zympex-014.

Comparison of pre and post Foley catheter Bishop's Score: A retrospective record review at Aga Khan University Hospital Karachi, Pakistan.

Objective: To compare pre and post Foley's catheter Bishop Score during labour induction. Methods: This study was a retrospective study conducted at the Aga Khan University Hospital Karachi, Pakistan after approval from ethical review board. All women who underwent induction of labour with Foley's Catheter at gestation of 37 weeks or more from September 2014-October 2015 were included. Data was entered and analyzed in Statistical Package for Social Sciences (SPSS) version 19.0. The comparison between pre and post Foley's catheter Bishop Score during labour induction will be calculated by Wilcoxon sign test. Results: There were 981 cases of inductions of labour, 749 (76.3%) received Foley's catheter, in combination with prostaglandins and oxytocin. About 68% were vaginal deliveries while 32% underwent C-section. Two third of women had bishop <4. Overall, Bishop score improved significantly in all patients with the catheter however, maximum benefit was seen in patients where the catheter was placed for 10-12 hours. Conclusion: Foley's is the better and safer option. In view of our results, It has been recommended to keep the Foley's for 10-12 hours to get significant improvement in bishop score.

Design and development of new inhibitors against breast cancer, Monkeypox and Marburg virus by modification of natural Fisetin via in silico and SAR studies.

The natural Fisetin and its derivatives have been shown to have effective bioactivity and strong pharmacological profile, which is continuously drawing the interest of therapeutic applications to the development of new biomolecules against Breast cancer and Monkeypox, and Marburg viral infection, while computational approaches and the study of their structure-activity relationship (SAR) are the most eloquent and reliable platform for performing their hypothetical profile renovation. So, the main perspective of this investigation is to evaluate dual function of Fisetin and its derivatives against both virus and cancerous target. First and foremost, the prediction of activity spectra for materials (PASS) valuation has provided preliminary data on the antiviral, antibacterial, antiparasitic, and anti-cancer possibilities of the mentioned compounds. According to the evidence, PASS predicted scores were shown to perform better in antineoplastic and antiviral than antibacterial, and antiparasitic efficiency; as evidenced by their higher PASS scores in antineoplastic and antiviral drug tests. Breast cancer, Monkeypox, and Marburg virus have been selected as targeted pathogens, and different in silico studies were conducted to determine the dual function of mention derivatives. The "Lipinski five rules," on the other hand, has been subjected to extensive testing for drug-like characteristics. Molecular docking against Breast cancer, Monkeypox, and Marburg virus have been accomplished after confirmation of their bioactivity. The molecular docking evaluation against targeted disease displayed re-markable binding affinity and non-bonding engagement, with most of the results indicating that derivatives are more effective than the FDA approved standard antiviral, and antineoplastic drugs. Finally, the ADMET characteristics have been computed, and they indicate that the substance is suitable to use and did not have any chance to produce adverse effects on aquatic or non-aquatic environment, as well as having a highly soluble capacity in water medium, high G.I absorption rate, with outstanding bioavailability index. Therefore, these mentioned Fisetin derivatives could be suggested as potential medication against Breast cancer and newly reported Monkeypox, and Marburg virus, and may further proceed for laboratory experiment, synthesis, and clinical trials to evaluate their practical value.

Stigmatization, panic disorder, and death anxiety among patients of Covid-19: Fourth wave of pandemic in Pakistan.

BACKGROUND: In Pakistan, the fourth wave of COVID-19 is causing an increasing number of positive cases. This fourth wave may be a risky aspect of mental health issues for COVID-19 patients. This quantitative study is designed to understand the stigmatization, and panic disorder and to explore the mediating role of death anxiety among patients of COVID-19 during the fourth wave of novel coronavirus. METHODS: The study was conducted using a correlational research design. The survey was carried out by utilizing a questionnaire with a convenient sample technique. The sample of the study was comprised of 139 patients with COVID-19. Data were collected through Stigma Scale for Chronic Illnesses (SSCI), The Panic Disorder Severity Scale (PDSS), and Death Anxiety Inventory. RESULTS: Results show that stigma is significantly positively related to panic disorder and death anxiety. Furthermore, panic disorder is also significantly positively related to death anxiety. Results also indicate that stigmatization is a significant positive predictor for death anxiety and panic disorder. Moreover, results indicate that death anxiety has a mediating role in the relationship between stigmatization and panic disorder with age and gender as covariates. CONCLUSION: This study would be helpful for people around the world to understand this threatening contagious virus so they wouldn't stigmatize infected ones. Additional research is required for the sustainable improvement of anxiety over time.

Knowledge, attitudes, and practices (KAP) towards COVID-19 pandemic among pregnant women in a tertiary hospital in Karachi, Pakistan.

BACKGROUND: The aim of this study was to evaluate the knowledge, attitude, and practices (KAP) of the pregnant population during the COVID-19 pandemic in a tertiary care hospital. METHODS: This cross-sectional study was conducted at Aga Khan University Hospital, Karachi, Pakistan. KAP towards COVID-19 was assessed using 21-item questionnaires. A score for each category was calculated and points were summed. The outcome variables of KAP were compared with demographic characteristics. Data were analyzed by using SPSS 19. RESULTS: A total of 377 patients participated in the study. The majority of the patients were multiparous (36.8%) in the age group of 30-40years (42.4%). More than 90% of patients were aware of COVID-19 symptoms and mode of transmission. They were aware of no cure for disease and optimum social distance. Although < 50% of patients truly answered the questions regarding the impact of COVID-19 on the risk of congenital malformation, vertical transmission, and the effect of infection on the mode of delivery. Regarding attitude and practices,> 90% of patients were anxious about fetal and personal safety, they are using a facemask, sanitizing their hands regularly, and avoiding social gatherings. Univariate and multivariable linear regression analysis showed statistically significant results among demographic variables (age, parity, family members, occupational status, and source of information). CONCLUSION: Pregnant patients demonstrated inadequate knowledge regarding the impact of COVID-19 on pregnancy. However positive attitude and practices on preventive measures were good. This highlights the need for health education for pregnant women for COVID-19 to improve knowledge on a constant basis.

Evaluation of the whole proteome to design a novel mRNA-based vaccine against multidrug-resistant Serratia marcescens.

Serratia marcescens, a Gram-negative bacterium, is one of the known disease-causing pathogens. It is resistant to ampicillin, macrolides, cephalosporins, cefotaxime, and ceftazidime. The only antibiotic that has been proven to be effective against S. marcescens is gentamicin. By causing epigenetic alterations, bacteria can also become resistant to all antibiotics. Many epigenetically related proteins were studied, and four proteins were selected in this regard for epitope evaluation and their subsequent use in the development of a messenger ribonucleic acid (mRNA) vaccine. A series of immune-informatics tools used to build this mRNA vaccine elicited cellular and humoral immunity. Molecular docking between epitopes and alleles of the major histocompatibility complex (MHC) was performed. The vaccine was developed using 37 epitopes, an adjuvant that is a TLR-4 agonist known as resuscitation-promoting factor E (RpfE), subcellular trafficking structures, secretion boosters, and linkers. This proposed architecture was found to cover 99.6% of the population during testing. During testing, it was proven that it was both effective and safe. To confirm our idea, we performed an in silico immunological simulation of vaccination. The codon was also optimized to ensure that the mRNA reached the cytoplasm of a human host and underwent efficient translation. TLR-4 and TLR-3 were also docked against the secondary and tertiary structures of the vaccine peptide. Furthermore, the vaccine's stability was confirmed by molecular dynamics simulation. In summary, this vaccine construct can be a potential candidate against S. marcescens and is suitable for in vitro analyses to validate its effectiveness.

Anabasis articulata (Forssk.) Moq: A Good Source of Phytochemicals with Antibacterial, Antioxidant, and Antidiabetic Potential.

Anabasis articulata is medicinally used to treat various diseases. In this study, A. articulata was initially subjected to extraction, and the resultant extracts were then evaluated for their antimicrobial, antioxidant, and antidiabetic potentials. After obtaining the methanolic extract, it was subjected to a silica gel column for separation, and fractions were collected at equal intervals. Out of the obtained fractions (most rich in bioactive compounds confirmed through HPLC), designated as A, B, C, and D as well hexane fraction, were subjected to GC-MS analysis, and a number of valuable bioactive compounds were identified from the chromatograms. The preliminary phytochemical tests were positive for the extracts where fraction A exhibited the highest total phenolic and flavonoid contents. The hexane fraction as antimicrobial agent was the most potent, followed by the crude extract, fraction A, and fraction D. DPPH and ABTS assays were used to estimate the free radical scavenging potential of the extracts. Fraction C was found to contain potent inhibitors of both the tested radicals, followed by fraction D. The potential antidiabetic extracts were determined using α-glucosidase and amylase as probe enzymes. The former was inhibited by crude extract, hexane, and A, B, C and D fractions to the extent of 85.32 ± 0.20, 61.14 ± 0.49, 62.15 ± 0.84, 78.51 ± 0.45, 72.57 ± 0.92 and 70.61 ± 0.91%, respectively, at the highest tested concentration of 1000 µg/mL with their IC50 values 32, 180, 200, 60, 120 and 140 µg/mL correspondingly, whereas α-amylase was inhibited to the extent of 83.98 ± 0.21, 58.14 ± 0.75, 59.34 ± 0.89, 81.32 ± 0.09, 74.52 ± 0.13 and 72.51 ± 0.02% (IC50 values; 34, 220, 240, 58, 180, and 200 µg/mL, respectively). The observed biological potentials might be due to high phenolic and flavonoid content as detected in the extracts. The A. articulata might thus be considered an efficient therapeutic candidate and could further be investigated for other biological potentials along with the isolation of pure responsible ingredients.

Obstetric triage improvement process using the Donabedian model of quality care: a quality improvement initiative.

Obstetric triage has become one of the most crucial innovations in the field of perinatal care in the past 15 years. In lower- middle- income countries (LMICs), the pregnant patients are seen in a conventional way based on the time of their arrival; this divergent, unbalanced and inequitable approach results in delayed initial evaluation, prolonged length of stay (LOS) and affected clinical outcomes.This project aimed at implementing an effective and efficient obstetric triage system with improved throughput and care processes within six months to facilitate timely decision making according to the individualized needs of pregnant patients.A pre-implementation audit was completed for the core evaluation of existing obstetric triage services, followed by a fishbone analysis. Following the Donabedian model for quality care, a quality improvement project was initiated to redesign the obstetric triage system. The project strategy was implemented as part of six PDSA (Plan- Do -Study- Act) cycles to optimize the structure, processes, and obstetric triage outcomes. The triage paradigm moved from time-based care delivery to priority care, and processes were improved based on Angelini's recommendations of best practices in obstetric triage. During the initial phase of improvement, the identified outcome measures were waiting time of 5 minutes from arrival to initial assessment, LOS of 120 minutes, and acuity-based care for at least 50% of patients. A post-implementation audit was conducted to assess improvements. The results showed that the LOS at triage reduced from 240 min (4 hours) to 60 min (1 hour) within 6 months. Furthermore, wait times for triage decreased significantly to 5 min in 65% of patients, compared with 6% in traditional triage practice.The results indicate that the traditional triage model of the 'order of arrival' process is inefficient in providing adequate obstetric care. This quality initiative facilitated the successful incorporation of the Donabedian model and best practice triage practices and helped achieve desired outcomes of improved LOS and reduced waiting time with acuity-based care. Therefore, the design of an efficient,and the appropriate obstetric triage system can be adopted by other healthcare institutions in a local setting that can facilitate patient centric care.

Subchorionic hematoma and pregnancy outcomes in patients with threatened miscarriage.

Objective: To compare maternal and perinatal outcomes in patients with threatened miscarriage with or without subchorionic hematoma (SCH) at a tertiary care hospital. Methods: This retrospective cohort study was conducted at Aga Khan University Hospital. The study included 200 patients of <20 weeks singleton pregnancy with threatened miscarriage from January 2016 till December 2018. These patients were divided into two groups based on the presence (study group) or absence of subchorionic hematoma (control) on ultrasound imaging. Baseline demographic data, and obstetric outcomes were compared for the two groups. Results: The incidence of subchorionic hematoma was observed to be 30.5% (61/200). Most of the patients of SCH and non SCH groups presented in first trimester. Age and BMI were similar for both groups however there were more multigravida patients in the SCH group (63%versus 46.7%, P=0.12). A higher number of patients in the SCH group ended up in spontaneous miscarriage in contrast to patients with no SCH (13%versus6.1%, P=0.07) and also had a greater proportion of small for gestational age (SGA) babies (8.9%versus3.9%) though no statistical significance was observed. There were more preeclamptic patients in SCH group as compared to non SCH group (4.8%versus0.7%) and the trend was statistically significant(P=0.05). However, no significant correlation of hematoma size and adverse pregnancy outcomes was found in SCH group. Conclusion: Our study shows that women with threatened miscarriage having SCH are at a higher risk of having preeclampsia and SGA and hence these pregnancies warrant greater surveillance.

Bio-Molecular analysis of selected food derived Lactiplantibacillus strains for CLA production reveals possibly a complex mechanism.

Lactiplantibacillus is among the most extensively studied bacterial specie belonging to the genus Lactobacillus with proven probiotic and health promoting effects. These beneficial effects are generally strains specific but the underlying molecular mechanisms are still not fully understood. Dissecting the determinants behind probiotic topographies of this bacterium is of particular interest since it would help select strains that stand the best chance of success in clinical trials and potential industrial applications. In the current study, we have compared the oleate hydratase phylogeny of seven selected strains of L. plantarum on the basis of their sequence, physiochemical properties and 3D structures. All the strains were assessed on molecular level visualization to find out the active site residues which take part in binding with linoleic acid (LA) at the time of interactions. From the whole genome sequences, the genes responsible for conjugated linoleic acid (CLA) production were identified by Venn diagrams. Identified genes were further compared phylogenetically by MEGA X and physiochemical parameters were analyzed by utilizing ExPaSy-Protparam. The genes were further analyzed for the secondary structures using PSIPRED and tertiary structure was generated by trRosseta and SWISS-MODEL. For the analysis of molecular interactions, LA was used as a ligand and the docking was performed using AutoDock Vina. The phylogenetic analysis showed a close phylogeny of the strains with publicly available genomes. The best interaction energy with LA was observed as -6.7 kcal/mol. The bacteria perform an important role in the CLA production through LA metabolism. Oleate hydratase genes are involved in the complex mechanism of the saturated conversion of LA in to CLA. The current study provides further insights for CLA production by different strains of L. plantarum. There is an excellent opportunity for future studies to investigate different CLA production mechanisms in different bacterial strains.

A Comprehensive Review on the Medicinal Importance; Biological and Therapeutic Efficacy of Lagenaria siceraria (Mol.) (Bottle Gourd) Standley Fruit.

Herbal remedies have been employed for the treatment and management of different diseases for ages. Herbal medicines are a promising choice over modern synthetic drugs because of their low side effects and are thus considered to be safe and effective in treating human diseases. Lagenaria siceraria (Mol.) Standley fruit (Bottle gourd) belongs to the Cucurbitaceae family that has been used in a different system of traditional medication to treat various diseases. This is a domestic plant that provides food as well as medication. This vegetable have low caloric values and high water contents. The edible portion of it contains phytochemicals like vitamins, proteins, choline, minerals, terpenoids, flavonoids, etc. Several bioactive compounds have been isolated from L. siceraria, including triterpenoids, sterols, cucurbitacins, flavones, C-glycosides and ß-glycosides. Researchers have evaluated various parts of this plant viz. fruit, root, flowers, and leaves for pharmacological activities like antianxiety, antidepressant, diuretic, antimicrobial, cytotoxic, antihyperlipidemic, cardio protective, analgesic, anti-inflammatory, anthelmintic, anti-hyperglycemic, antihepatotoxic, anti-urolithiatic, antistress, antiulcer, anticancer, hepatoprotective, anthelmintic, immunomodulatory, and antioxidant. In this review, an attempt has been made to explore its phytochemical constituents, traditional, medicinal, and pharmacological uses to highlight the therapeutic importance of this well-known plant. This would be helpful in reviving its importance and will highlight its several promising aspects to encourage researchers for further research on L. siceraria.

Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret.

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 µg/mL (against AChE) and 60 µg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 µg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 µg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.

Pharmacological evaluation and in-silico modeling study of compounds isolated from Ziziphus oxyphylla.

Medicines derived from plants are preferred over synthetic therapeutic agents in treating different diseases. Ziziphus oxyphylla (a member of Rhamnaceae family) is a medicinal plant used as a remedy of different diseases in Greek and Ayurveda medical systems. Z. oxyphylla roots were shade dried and then subjected to extraction of bioactive compounds using different solvent systems and silica gel. From ethyl acetate fraction, three compounds viz., p-coumaric acid (V), 3,4-dimethoxy benzoic acid (VI), and 4-heptyloxy benzoic acid (VII) were isolated in pure form. The selection of ethyl acetate fraction for isolation was based on HPLC profiling of crude extract and different fractions. These compounds were characterized by different spectroscopic techniques and evaluated for their in vitro antioxidant, anticholinesterase, α-glucosidase, and α-amylase inhibitory potentials. To find out possible binding interactions of V with AChE and BChE crystals, in-silico docking studies were also carried out. Compound V showed maximum scavenging capabilities of DPPH and ABTS free radicals with IC50 values of 69 and 62 µg/mL respectively. Excellent percent inhibition (83.4 ± 0.5% at highest concentration 1000 µg/mL) of acetylcholinesterase (AChE) was exhibited by compound V (IC50 = 80 µg/mL); whereas, for the mentioned concentration, 83.2 ± 1.1% inhibition (IC50 = 90 µg/mL) of butyrylcholinesterase (BChE) was observed as well. The compound VI exhibited highest % inhibition against α-glucosidase (IC50 = 84 µg/mL) whereas α-amylase was more potently inhibited by compound V (% inhibition = 86.8 % and IC50 = 85 µg/mL). Docking scores of -1.391 Kcal/mol (BChE) and -6.253 Kcal/mol (AChE) were recorded using molecular docking software. Compound V exhibited strong free radical scavenging and anticholinesterase potentials suggesting that it can be effectively used to treat oxidative stress and dementia in human.

Bioavailability and hepatoprotection enhancement of berberine and its nanoparticles prepared by liquid antisolvent method.

The study was devised to prepare berberine nanoparticles by anti-solvent precipitation method and were assessed for their hepatoprotective effect in Male Sprague-Dawley rats against carbon tetrachloride. The pharmacokinetic parameters of the prepared nanoparticles and berberine were evaluated in rabbits. Histopathological studies and blood biochemical analyses were carried out to evaluate the role of both forms of berberine in the experimental animals. Substantial improvement in the liver function test enzymes levels and liver histopathology were achieved in the animals treated with berberine nanoparticles in comparison to the unprocessed berberine whereas, pharmacokinetic parameters for nanoform of berberine were about 3.97 and 3.88 folds higher than that of the unprocessed berberine. The study revealed that the reduction of berberine particle size to nano range improved pharmacokinetic parameters in rabbits. The nano berberine provided better liver protection in experimental rats and high berberine blood concentration. Thus, better hepatoprotective and pharmacokinetics effects were observed for the nano form in comparison to unprocessed form.

In vivo glucose-6-phosphatase inhibitory, toxicity and antidiabetic potentials of 2-picolylamine thioureas in Swiss albino mice.

The 2-picolylamine is a simplest analogue of the alkaloid that has secondary and tertiary nitrogen function in its cyclic structure like that of alkaloids that can be derivatized to a number of biologically active compounds. In connection to our previous work, in the present work, three thiourea derivatives (I = 1,3-bis(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl) thiourea, II = 1,3-bis (pyridin-2-ylmethyl) thiourea, and III = 1-(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl)-3-phenylthiourea) were synthesized using 2-picolylamine template which is a readily available synthetic analogue of naturally occurring alkaloid. The biological effect of the synthesized derivatives were monitored on the activity of glucose-6-phosphatase in Swiss albino mice (21-days). The derivatives were also tested for their potential toxicity in a 28-days sub-chronic toxicity studies by assessing their effects on different parameters like hematological, serum biochemistry and liver histology. The therapeutic effect of the safe derivative (I) was examined in streptozotocin-induced diabetic mice as well. The derivatives showed inhibition of the enzyme activity from good to an excellent degree. Compound I had the highest inhibition with 21.42 ± 5.113 mg of the released phosphate as compared to that of the positive control group (84.55 ± 3.213 mg). Only I turned out to be safe for use in animals without exerting any toxic or lethal effects on any of the assessed parameters in the used animal model. Compound I efficiently reversed the effects like hyperglycemia, hyperlipidemia and weight loss in the test animals. Out of these three-tested compounds, I was found safe to be use as therapeutic agent in diabetes complications. However, further toxicological studies in other animal models are needed as well.

Dose-Dependent Internalization and Externalization Integrity Study of Newly Synthesized 99mTc-Thymoquinone Radiopharmaceutical as Cancer Theranostic Agent.

Thymoquinone (TQ) is a bioactive phytochemical isolated from Nigella sativa and has been investigated for biochemical and biological activities in both in vitro and in vivo models. It is best known for its anticancer activities. Thymoquinone accomplishes anticancer activities through targeting multiple cancer markers including PPAR-γ, PTEN, P53, P73, STAT3, and generation of reactive oxygen species at the cancer cell surface. The radiolabeling of TQ with γ- and ß-emitter radionuclide could be used as cancer diagnostic or therapeutic radiopharmaceutical, respectively. In this study, we are reporting the radiolabeling of TQ with technetium-99m (99mTc), stability in saline and blood serum, internalization and externalization of 99mTc-TQ using rhabdomyosarcoma cancer cells line. The quality control study revealed more than 95% labeling yield and stable in blood serum up to 4 hours. In vitro internalization rate was recorded 27.08% ± 0.95% at 1 hour post 2 hours internalization period and comparatively slow externalization. The results of this study are quite encourging and could be investigated for further key preclinical parameters to enter phase I clinical trials.

Isolation of Quercetin from Rubus fruticosus, Their Concentration through NF/RO Membranes, and Recovery through Carbon Nanocomposite. A Pilot Plant Study.

In this study, an attempt has been made to devise a method for a large-scale production of quercetin from a medicinal plant. The natural products are first isolated from plants and then synthesized commercially. During their synthesis, a number of impurities or side products are also formed, most of which are carcinogenic. Plant products have limited side effects. Therefore, they are considered safe to be used for systemic uses. In the Rubus fruticosus fruit, the ethyl acetate extract was loaded to 50 optimized silica gel columns. The effluents of columns were passed through the membrane system for concentration. A 100% recovery was achieved from the drain pipe in case of reverse osmosis membrane when the specified rely of the pilot plant was set on 25% rejection. About 95% recovery was achieved through the NF membrane while the 5% loss in permeate was recovered through magnetic carbon nanocomposite (characterized through a bar magnet, SEM, XRD, and EDX). The equilibrium time of adsorption was 83 min and followed by pseudo-first-order kinetics. The adsorption equilibrium data fitted well to the Langmuir isotherm model. Through the devised method, quercetin was successfully concentrated with high efficiencies; however, further studies are needed to validate the method.

Enzyme Inhibitory, Antioxidant And Antibacterial Potentials Of Synthetic Symmetrical And Unsymmetrical Thioureas.

BACKGROUND: In this study, 2 symmetrical and 3 unsymmetrical thioureas were synthesized to evaluate their antioxidant, antibacterial, antidiabetic, and anticholinesterase potentials. METHODS: The symmetrical thioureas were synthesized in aqueous media in the presence of sunlight, using amines and CS2 as starting material. The unsymmetrical thioureas were synthesized using amines as a nucleophile to attack the phenyl isothiocyanate (electrophile). The structures of synthesized compounds were confirmed through H1 NMR. The antioxidant potential was determined using DPPH and ABTS assays. The inhibition of glucose-6-phosphatase, alpha amylase, and alpha glucosidase by synthesized compounds was used as an indication of antidiabetic potential. Anticholinesterase potential was determined from the inhibition of acetylcholinesterase and butyrylcholinesterase by the synthesized compounds. RESULTS: The highest inhibition of glucose-6-phosphatase was shown by compound V (03.12 mg of phosphate released). Alpha amylase was most potently inhibited by compound IV with IC50 value of 62 µg/mL while alpha glucosidase by compound III with IC50 value of 75 µg/mL. The enzymes, acetylcholinesterase, and butyrylcholinesterase were potently inhibited by compound III with IC50 of 63 µg/mL and 80 µg/mL respectively. Against DPPH free radical, compound IV was more potent (IC50 = 64 µg/mL) while ABTS was more potently scavenged by compound I with IC50 of 66 µg/mL. The antibacterial spectrum of synthesized compounds was determined against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Agrobacterium tumefaction and Proteus vulgaris). Compound I and compound II showed maximum activity against A. tumefaction with MIC values of 4.02 and 4.04 µg/mL respectively. Against P. vulgaris, compound V was more active (MIC = 8.94 µg/mL) while against S. aureus, compound IV was more potent with MIC of 4.03 µg/mL. CONCLUSION: From the results, it was concluded that these compounds could be used as antibacterial, antioxidant, and antidiabetic agents. However, further in vivo studies are needed to determine the toxicological effect of these compounds in living bodies. The compounds also have potential to treat neurodegenerative diseases.

Comparison of foeto-maternal outcome in pregnant women with hepatitis E - A review of 12 years.

OBJECTIVE: To compare adverse maternal and foetal outcome in pregnant women with hepatitis E immunoglobulin M reactive versus non-reactive. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised records of pregnant patients at any gestational age with clinical and biochemical evidence of hepatitis E from January 2002 and December 2014. . Maternal and perinatal outcome of the subjects were analysed. SPSS 20 was used for data analysis. RESULTS: Out of the 200 subjects, 168(84 %) were hepatitis E immunoglobulin M reactive and 32(16%) were non-reactive. The overall mean age was 26.7±4.5 years. Also, 12(7%) patients in the immunoglobulin M reactive group were admitted to intensive care unit compared to no one from the non-reactive group. Similarly fulminant hepatic failure was seen in 12(7.1%) patients in the immunoglobulin M reactive group compared to no one in the other group. Post-partum haemorrhage was more frequent in the immunoglobulin M reactive group compared to the non-reactive group. There were 5(3%) maternal deaths in the reactive group compared to no death in the other group. Moreover, 34(20.2%) neonates of the immunoglobulin M reactive group needed neonatal intensive care unit admission compared to none in the non-reactive group. There were 4(2.4%) neonatal deaths in the reactive group. CONCLUSIONS: Participants in the immunoglobulin M reactive group had a higher percentage of adverse foeto-maternal outcomes compared to the non-reactive group.