Ali Talha Khalil

Current state and prospects of the phytosynthesized colloidal gold nanoparticles and their applications in cancer theranostics

The design, development, and biomedical applications of phytochemical-based green synthesis of biocompatible colloidal gold nanoparticles (AuNPs) are becoming an emerging field due to several advantages (safer, eco-friendly, simple, fast, energy efficient, low-cost, and less toxic) over conventional chemical synthetic procedures. Biosynthesized colloidal gold nanoparticles are remarkably attractive in several biomedical applications including cancer theranostics due to small size, unusual physico-chemical properties, facile surface modification, high biocompatibility, and numerous other advantages. Of late, several researchers have investigated the biosynthesis and prospective applications (diagnostics, imaging, drug delivery, and cancer therapeutics) of AuNPs in health care and medicine. However, not a single review article is available in the literature that demonstrates the anti-cancer potential of biosynthesized colloidal AuNPs with detailed mechanistic study. In the present review article, we for the first time discuss the biointerface of colloidal AuNPs, plants, and cancer mainly (i) comprehensive mechanistic aspects of phytochemical-based synthesis of AuNPs; (ii) proposed anti-cancer mechanisms along with biomedical applications in diagnostics, imaging, and drug delivery; and (iii) key challenges for biogenic AuNPs as future cancer nanomedicine.

Biosynthesis of iron oxide (Fe2O3) nanoparticles via aqueous extracts of Sageretia thea (Osbeck.) and their pharmacognostic properties

ABSTRACT Sageretia thea (Osbeck.) was used as an effective chelating agent for the biosynthesis of iron oxide nanoparticles (IONPs) and extensively characterized through XRD, FTIR, Raman spectroscopy, Energy Dispersive Spectroscopy, HR-SEM/TEM and SAED. Antibacterial assays against five human pathogenic bacterial strains were carried out and minimum inhibitory concentrations were calculated. Pseudomonas aeruginosa (MIC: 7.4 µg/mL) was the most susceptible strain to biosynthesized IONPs. All of the fungal strains showed susceptibility to the IONPs. MTT cytotoxic assay was carried out against the promastigote and amastigote cultures of Leishmania tropica and their IC50 values were calculated as 17.2 and 16.75 µg/mL. The cytotoxic potential was further assessed using brine shrimps, and the IC50 was calculated as 16.46 µg/mL. Moderate antioxidant activities were reported. Human RBCs and macrophages were found to be biocompatible with biogenic IONPs (IC50 > 200 µg/mL). GRAPHICAL ABSTRACT

Sageretia thea (Osbeck.) modulated biosynthesis of NiO nanoparticles and their in vitro pharmacognostic, antioxidant and cytotoxic potential

Abstract NiO nanoparticles are biosynthesized using Sageretia thea (Osbeck.) aqueous leave extracts and their biological activities are reported. Nanoparticles (∼18 nm) were characterized through XRD, ATR-FTIR, EDS, SAED, HR-SEM/TEM and Raman spectroscopy. Antibacterial activity was investigated against six pathogenic bacterial strains (gram positive and gram negative) and their corresponding minimum inhibitory concentrations (MICs) were calculated. UV-exposed nanoparticles were investigated to have reduced MICs relative to the NiO nanoparticles have not been exposed to UV. Moderate linear fungal growth inhibition was observed while Mucor racemosus (percentage inhibition 64% ± 2.30) was found to be most susceptible. Cytotoxicity was confirmed using brine shrimps lethality assay (IC50 42.60 μg/ml). MTT cytotoxicity was performed against Leishmania tropica-KWH23 promastigotes and amastigotes revealed significant percentage inhibition across the applied concentrations. IC50 values were calculated as 24.13 μg/ml and 26.74 μg/ml for the promastigote and amastigote cultures of Leishmania tropica. NiO nanoparticles were found. Moderate, antioxidant potential was concluded through assays like DPPH, TAP and TAC. Furthermore, protein kinase inhibition and alpha amylase inhibition is also reported. Graphical Abstract

Antibacterial activity of honey in north-west Pakistan against select human pathogens

OBJECTIVE To investigate the antimicrobial activity of commercially available honey and raw honey samples in Khyber Pakhtunkhwa, Pakistan, against pathogenic bacterial strains. METHODS Well diffusion assays were performed to screen pure and diluted honey samples for antibacterial activity against six Gram-negative and six Gram-positive bacterial strains. Zones of inhibition were measured and compared with 10 mg Gentamycin. RESULTS When honey samples were diluted to 20%-70%, the honey samples showed no activity to mild antibacterial activity. The highest antibacterial activity was recorded when 90% and pure undiluted honey samples were tested and compared with a control Gentamycin disc (10 mg). CONCLUSION Commercially processed honey and raw honey samples from north-west of Pakistan possess good antimicrobial potential.

Synergistic antibacterial effect of honey and Herba Ocimi Basilici against some bacterial pathogens.

OBJECTIVE To evaluate the antibacterial activity of the combination of different honey brands and methanolic fraction of Herba Ocimi Basilici using agar well diffusion assay. METHODS The antibacterial activity was determined against thirteen pathogenic bacterial clinical isolates including six gram negative (Klebsiella pneumonia, Pseudomonas aeroginosa, Escherichia coli, Salmonella typhi, Salmonella typhimirium, Xanthomonas campestris) and six gram positive strains (Enterococcus faecalis faecalis, Bacillus subtilis, Staphylococcus aureus, Clostridium perfringens type C, Clostridium perfringens type D, Clostridium chauvoei). Agar well diffusion method was used while zones of inhibition were measured with vernier scale. RESULTS At higher concentration, all the honey brands showed good to significant activity. The highest activity was observed for Hamdard brand honey (27.60 +/- 0.40) against Enterococcus faecalis. CONCLUSION These results revealed that combinations of plant extracts of Herba Ocimi Basilici with honey can be used for the development of potent and novel antibacterial agents.

Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions

Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol‐induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta‐1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.

Evaluation of antileishmanial, antibacterial and brine shrimp cytotoxic potential of crude methanolic extract of Herb Ocimum basilicum (Lamiacea).

OBJECTIVE To collect and screen for ethnopharmacological properties (antileishmanial, antibacterial and brine lethality assays) of medicinal plan Ocimum basilicum from Peshawar region (34.008 latitude and 71.57 altitudes). METHODS In the present study a general antileishmanial activity against Leishmania tropica strair was carried out. The antibacterial potential of the plant was performed against 06 gram positiv and 06 gram negative bacteria. Brine shrimp cyto- toxicity assay at different concentrations were investigated. RESULTS The anti-promastigotes profile of the plant showed good antileishmanial activity exhibited LC50 value 21.67 µg/mL. The result for gram positive antibacterial activity revealed that the O. basilicum leaves extract possesses significant inhibitory activity at highest two concentrations ranging from 20.66 ± 0.31 to 31.86 ± 0.80 for Clostridium perfringens type C and Bacillus subtitilis, respectively, as compared to the gentamycin (27.36 ± 0.55 and 21.80 ± 0.72, respectively). For gram negative bacteria good activity was observed. A highest zone of inhibition was recorded for Pseudomonas aeroginosa (28.83 ± 0.28) at the highest concentration (10 mg/ mL). The LC50 value obtained for brine shrimp lethality assay was 91.56 µg/mL. CONCLUSION The herb basil possesses effective cidal activities which make this plant a good candidate for the isolation of antiprotozoal and antibacterial compounds which may lead to the development of novel drug.

The Study of Structural, Physical and Electrochemical Activity of Zno Nanoparticles Synthesized by Green Natural Extracts of Sageretia Thea

In this contribution an exceptionally simple, cost effective and reliable method for biosynthesis of ZnO nanoparticles through using Sageretia thea natural extracts as an effective chelating agent. The morphological analysis shows ZnO has nanoscale particles size 28.09 nm ± 5 nm, crystalline and possess distinct nanostructure hexagonal wurtzite structure. Effects of heat on ZnO synthesised at room temperature caused bonds with in the molecule to be broken exhibited continuous weight loss with 3 quasi sharp changes and 3 endothermic peaks occurring at 79°C, 228°C and 300°C. A proposed mechanism of reaction for Zn(NO3)2 6H2O precursor with bioactive compounds in Sageretia thea extract such as phenolic acid, flavonoids, natural sterolin and vitamin based compounds to form ZnO nanoparticles. Electrochemically ZnO nanoparticles are electroactive by exhibiting charge transfer resistance (Rct) 82006 Ω and bare GCE 3.7707 × 105 Ω. Showed good catalytic and conductivity which can be applied for pseudo capacitors.

Threats of Agricultural Bioterrorism to an Agro Dependent Economy; What Should be Done?

The economy of Pakistan is primarily dependent on its agricultural resources. Due to the lack of research regarding threat analysis of germ warfare in Pakistan, it is imperative for the agriculturists to understand the potential hazards associated with an attack on the cash crops that contributes heavily to the overall Gross Domestic Product (GDP) growth. Alarming terrorist activities such as 9/11 and many innovative terrorist strategies like Improved Explosive Devices (IED) in different countries, especially in Pakistan, has increased the potential of bioterrorism. Hence there is urgent need of security risk analysis and preparedness. State of the art research labs are not important for the effective production of biological weapons but certainly innovative strategies are required to effectively implement and counter a bioterrorist plan. Bioweapon infection to some staple crops such as wheat and maize can induce a significant loss that can take years to diffuse. This paper is concerned with the vulnerability of certain important crops in Pakistan that can be exposed as soft targets to certain bioterrorists and discusses the preemptive measures that should be undertaken immediately to prevent any sort of nefarious act of bioterrorism.

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges.

Background:The estimated hepatitis C virus (HCV) carriers are approximately 10 million in Pakistan which usually progresses to chronic hepatitis, with rare cases of spontaneous viral eradication. The present article reviews the treatment status of HCV infection in Pakistani population and various factors associated with the treatment response rates. Methods:Literature on anti-HCV therapy was searched in PubMed, Google Scholar and PakMediNet. Thirty three different studies representing different geographic regions of Pakistan published from 2002 to 2016 were included in the present review. Weighted mean, standard error estimates (SE) and standard deviation (SD) were determined for each population group. Results:Mean value for sustained virological response (SVR) for standard IFN plus ribavirin (RBV) combination therapy was 68.38% ± 14.13% (range 33.8%–87.10%; SE 3.08) and pegylated-IFN plus RBV combination therapy 64.38% ± 8.68% (range 55.0%–76.00%; SE 3.88). The lowest value for SVR has been reported to be 24.3% (for genotype 1; administering INF-&agr; 2b 3MU 3 times/week and RBV 1000–1200 mg/day for 48 weeks) while highest of 87.5% (genotype 3a; INF-&agr; 2a 3MU 3 times/week and RBV 1000–1200 mg/day for 24 weeks). The mean value for rapid virological response (RVR) was found to be 48.18% ± 29.20% (SE 9.73). As PEG-interferon and direct acting antivirals (DAAs) are relatively expensive, interferon-alfa (IFN-&agr;) and RBV combination therapy have been used widely to treat HCV infected patients in Pakistan for the last one and half decade. On average, 2.45% of the patients discontinued treatment due to severe side effects. Conclusion:We encourage further studies on understanding host and viral factors associated with specific focus on harder to treat viral variants (relapsers and nonresponders). These variants are currently rising in the country.