Background:The clinical and methodological diversity observed in national and regional diabetes surveys, emphasized on the need of the weighted average prevalence of diabetes. Objective: To measure the pooled prevalence of type 2 diabetes mellitus in the adult population of Pakistan. Methods: The prospective cross-sectional studies reporting adult diabetes in Pakistan and published on any date were retrieved from PubMed, ScienceDirect and PakMediNet databases. In the meta-analysis, PRISMA guidelines were used for reporting; the AXIS tool for assessing quality and risk of bias within studies; I 2 statistics for measuring heterogeneity between studies and subgroups; and Tableau Public 10.4 for geographic mapping of included studies. Using Meta-Analyst 3.13 βeta, overall and subgroup pooled estimates were measured by random effects model. Results: The pooled sample of twelve studies included 42,051 adults (≥20 years) comprised of both sexes from urban and rural Pakistan. The pooled prevalence of diabetes was 13.7% (95% CI, 10.7-17.3). None of the twelve studies was of poor quality (<10 scores). Ten studies were published in ISI indexed journals, and nine of them were indexed for Medline. The level of heterogeneity observed across studies and between subgroups was moderate (<50%). The subgroup analysis revealed a higher pooled estimate of diabetes in males than in females (13.1 vs. 12.4%). It was also higher in urban than in rural patients (15.1 vs. 1.6%), and in HbA1c than in OGTT tests (23.9 vs. 14.4%). However, pooled estimates of the WHO and the ADA criteria were similar (13.8 vs. 13.5%). Conclusions:The prevalence of diabetes is on the rise in the adult population of Pakistan. The heterogeneity across studies observed in the meta-analysis suggested that the design of future diabetes surveys should be efficient and purposeful, and that valid tools and methods should be used to generate more precise data. Moreover, harmony between the stakeholders is much needed to seek a true picture of the diabetes burden in the country.

Fagonia indica is a widely known medicinal plant. The extracts of Fagonia species contain secondary metabolites such as flavonoids, phenolic compounds, and terpenoids. Silver nanoparticles are known for antibacterial properties. In this study, AgNPs were synthesized using the callus extract of F. indica as a reducing agent. Characterization through different techniques suggests that the AgNPs absorbed light and gave SPR peaks at 414 nm while in case of ciprofloxacin supplemented callus mediated AgNPs the peak were recorded at 419 nm. Furthermore, FTIR analysis revealed the role of amides, acyl group, nitro group of callus extract of F. indica , and some functional groups of the ciprofloxacin in the reduction process as well as the capping and stabilization of AgNPs. Similarly, X-Ray Diffraction analysis indicate the structure of AgNPs as face-centered cubic crystalline particles. The antibacterial activity of AgNPs and ciprofloxacin and callus extract as control against resistant bacteria such as Escherichia coli, Citrobacter amalonaticus , Shigella sonnei , and Salmonella typhi was studied. The combination of AgNPs and antibiotic showed better antibacterial activity as compared to AgNPs alone and ciprofloxacin alone. Maximum inhibition zone of E. coli , C. amalonaticus , S. sonnei , and S. typhi in response to AgNPs and ciprofloxacin was 38.5 mm, 35.5 mm, 33 mm, and 35.5 mm, respectively. It can, therefore, be suggested that the AgNPs along with Ciprofloxacin might have worked in interaction and resulted in better antibacterial activity against all the tested pathogens.

Development of multidrug resistance (MDR) to antimicrobial, antiparasitic and chemotherapeutic agents is a global challenge for the scientific community. Despite of the emergence of MDR pathogens, the development of novel and more effective drugs is slow and scientist even speculate that we are going back the pre-antibiotic era. This work aims to study and evaluate the preliminary antibacterial, anthelmintic and cytotoxic potentials of ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoates. Among all of the four compounds, compound 2 has displayed remarkable potency with MIC values of 0.125, 0.083, 0.073, and 0.109 mg/ml against E. sakazakii, E. coli. S. aureus, and K. pneumonia, respectively. Compared to etoposide (LC50 9.8 μg/ml), the compounds demonstrated LC50 values from 280 to 765 μg/ml. For anthelmintic assay, three concentrations of each compound and standard drug were studied in determination of time of death of the two species. Excellent anthelmintic activity was observed by all four compounds against P. posthuma and A. galli better than standard albendazole. High GOLD fitness score data from docking analysis toward the targets represent better protein–ligand binding affinity and thus indicate a high propensity for all the active compounds to bind to the active site. The promising in-vitro antimicrobial, anthelmintic activity, and cytotoxicity data conclusively revealed that these compounds may serve as viable lead compounds for the treatment of bacterial and parasitic infections, and therefore, could help the medicinal chemists to design future chemotherapeutic agents to avoid rapid drug resistance.

This part of work was done to explore the basic understanding of the adsorption chromatography by determining the interaction of selected model proteins (n = 5) to monolithic chromatographic materials, with varying densities of butyl and phenyl ligands. Surface energetics approach was applied to study the interaction behavior. The physicochemical properties of the proteins and monolithic chromatographic materials were explored by contact angle and zeta potential values. These values were used to study protein to monolith interaction under various operating conditions. Surface energetics approach allowed the calculation of interaction energy as a function of distance, i.e. energy minimum values. Calculations were performed at various conditions to analyze the effect of major operating parameters on the interaction strength. The interaction strength exposed the hydrophobic nature of the monoliths which increases with increasing ligand density. Further, interaction energy of proteins were higher with monolith with butyl ligand compared to monolith with phenyl ligand. For instance, lactoferrin interaction to monoliths with butyl represents more interaction, i.e. 24.38 kT as compared to monoliths with phenyl i.e. 23.28 kT, keeping lambda as 0.2 nm and salt concentration as 100 mM of ammonium sulphate. Hence, more energy and time will be consumed for elution of proteins immobilized to monoliths with butyl. Similarly, the effect of solid surface for proteins immobilization, effect of ligand density and effect of lambda showed some interesting insights on the interaction behavior. The knowledge generated from the present work will help in the basic understanding as well as development of an efficient, low cost downstream processing design and may mimic the real chromatographic experiments.

Hydrophobic interaction chromatography, an important and effective purification strategy, is generally used for the purification of variety of biomolecules. A basic understanding of the protein interaction behavior is required to effectively separate these biomolecules. A colloidal type extended Derjaguin, Landau, Verwey, and Overbeek calculations were utilized to study the interactions behavior of model proteins to commercially available hydrophobic chromatographic materials that is, Toyopearl Phenyl 650C and Toyopearl Butyl 650C. Physicochemical properties of selected model proteins were achieved by contact angle and zeta potential measurements. The contact angle of chromatographic materials used was achieved through sessile drop method on disrupted beads and capillary penetration method (CPM) on intact beads. The surface properties were further used to calculate the interactions of the proteins to chromatographic supports. The calculated secondary energy minimum of the proteins with the chromatographic materials (from the contact angle values determined through both methods can be correlated with the retention volumes from the real chromatography. The secondary energy minimum values are higher for each protein to the chromatographic materials calculated from the inputs derived through sessile drop method compared to CPM. For instance, immunoglobulin G has secondary energy minimum value of 0.17 kT compared to 0.11 kT, obtained through sessile drop method and CPM, respectively. Average relative values of the energy minimum calculated for all proteins are as 1.51 kT and 1.29 kT for Toyopearl Butyl 650C and Toyopearl Phenyl 650C, respectively, as a conversion factor for estimation of secondary energy minimum for both methods.

Ion exchange chromatography is one of the most widely used chromatographic technique for the separation and purification of important biological molecules. Due to its wide applicability in separation processes, a targeted approach is required to suggest the effective binding conditions during ion exchange chromatography. A surface energetics approach was used to study the interaction of proteins to different types of ion exchange chromatographic beads. The basic parameters used in this approach are derived from the contact angle, streaming potential, and zeta potential values.The interaction of few model proteins to different anionic and cationic exchanger, with different backbone chemistry, that is, agarose and methacrylate, was performed.Generally, under binding conditions, it was observed that proteins having negative surface charges showed strong to lose interaction (20 kT for Hannilase to 0.5 kT for IgG) with different anionic exchangers (having different positive surface charges). On the contrary, anionic exchangers showed almost no interaction (0-0.1 kT) with the positively charged proteins. An inverse behavior was observed for the interaction of proteins to cationic exchangers. The outcome from these theoretical calculations can predict the binding behavior of different proteins under real ion exchange chromatographic conditions. This will ultimately propose a better bioprocess design for protein separation.

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The present study was designed to measure the mean values of body mass index (BMI), random blood sugar/ fast ing blood sugar (RBS/FBS) tests, and Hb A 1c and to investigate the role of a genetic variant rs1544410 in the VDR gene in a Pakistani cohort. For this purpose, a total of 917 samples including 469 diabetes mellitus type 2 (T2DM), 145 DM type 1 (T1DM), and 303 healthy control were collected. Out of the total sample set, 500 individuals (250 T2DM cases and 250 controls) were genotyped for rs1544410. It was found that 65 (26.0%) cases and 32 (12.8%) controls had homozygous AA, while 69 (27.6%) cases and 139 (55.6%) controls had heterozygous AG, and 116 (46.4%) cases and 79 (31.6%) controls had homozygous GG (χ 2 = 41.81, p = 0.0001). In addition, a similar distribution of allele frequency was determined in cases and controls [p value = 0.866; odds ratio (OR) = 0.967; relative risk (RR) = 1.034]. A significant difference was observed in homozygous dominant [OR = 2.394 (1.501-3.816); RR = 1.46 (1.225-1.740); p = 0.003] and homozygous recessive models [OR = 2.970 (2.086-4.227); RR = 1.798 (1.501-2.154); p = <0.0001] analysis of rs1544410 in the VDR gene. These findings suggest that the VDR gene is associated with T2DM and genotype GG of ge-netic variant rs1544410 is the susceptible genotype in our Pakistani cohort.