Targeted pH-responsive delivery of rosmarinic acid via phenylboronic acid functionalized mesoporous silica nanoparticles for liver and lung cancer therapy.

Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. In vitro, drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC50 values of (1.70 ± 0.01 µg/mL and 3.25 ± 0.14 µg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 µg/mL and 29.10 ± 0.25 µg/mL), respectively. The cellular morphology before and after treatment was further confirmed via inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Synthesis and characterization of honey based hybrid dental implants with enhanced antibacterial activity.

Dental implants are commonly used for tooth replacement tools due to their good oral rehabilitation and reconstruction capacities. Dental implants treatment for natural teeth is desired to achieve successful implants treatment with improved osseointegration through promotion of mammalian cell activity and prevention of bacterial activity. Honey is potentially known for its antimicrobial and antibacterial potential, specifically for burns and wound healing. In this study, honey based silver nanoparticles were synthesized using various concentrations of honey. The synthesized HNY-AgNPs, MSN and HNY-AgMSN were characterized for their surface Plasmon resonance using UV spectroscopy, Hydrodynamic diameter using Zetasizer. Morphology using AFM. Furthermore, surface functional groups were characterized using FTIR spectroscopy at 4cm-1 resolutions. The developed hybrid nanoparticles were tested for their anti-bacterial activity at concentration of 3000µg/mL. It was found HNY-AgNPs was active against both bacterial strains i.e, Streptococcus mutans and streptococcus aureus. HNY-AgNPs-MSN hybrid implant demonstrated potential new type of dental implants, which can offer an effective design for the fabrication of advanced dental implants.

Antimicrobial and antioxidant activity on Pakistan origin Launaea nudicaulis (L.) Hook f.: A promising halophyte.

Facultative type of Halophytes is those which can easily grow on both saline and non-saline soil conditions Launaea nudicaulis (L.) Hook f. belongs to family compositae [Asteraceae] is facultative halophyte with great medicinal values. The main objective of this study is to explore anti-oxidant and anti-bacterial potential on different morphological parts of Launaea nudicaulis (L.) Hook f. The results of the antibacterial activity of methanolic extracts of leaves stem and roots of Launaea nudicaulis (L.) Hook f. showed that the potent antibacterial activity observed in all three morphological parts against Staphylococcus aureus. DPPH scavenging activity of extracts of root, stem, leaves against standard i.e., ascorbic acid at different concentrations of 20, 40, 60, 80 and 100 showed that root extract have more significant activity when compared to the ascorbic acid. Documented potentials of halophytes are elevating its prominence which motivates scientist to further explore with extensive research.

Galactosylated iron oxide nanoparticles for enhancing oral bioavailability of ceftriaxone.

The current study focuses on the development, characterization, biocompatibility investigation and oral bioavailability evaluation of ceftriaxone (CFT)-loaded lactobionic acid (LBA)-functionalized iron oxide magnetic nanoparticles (MNP-LBA). Atomic force microscopy and dynamic light scattering showed that the developed CFT-loaded MNP-LBA is spherical, with a measured hydrodynamic size of 147 ± 15.9 nm and negative zeta potential values (-35 ± 0.58 mV). Fourier transformed infrared analysis revealed interactions between the nanocarrier and the drug. Nanoparticles showed high drug entrapment efficiencies of 91.5 ± 2.2%, and the drug was released gradually in vitro and shows prolonged in vitro stability using simulated gastrointestinal (GI) fluids. The formulations were found to be highly biocompatible (up to 100 µg/mL) and hemocompatible (up to 1.0 mg/mL). Using an albino rabbit model, the formulation showed a significant enhancement in drug plasma concentration up to 14.46 ± 2.5 µg/mL in comparison with its control (1.96 ± 0.58 µg/mL). Overall, the developed MNP-LBA formulation was found promising for provision of high-drug entrapment, gradual drug release and was appropriate for enhancing the oral delivery of CFT.

Evaluation of nephroprotective activity of Musa paradisiaca L. in gentamicin-induced nephrotoxicity.

The objective of the study was to investigate the nephroprotective activity of methanolic extract of different morphological parts (bract, flower, trachea and tracheal fluid) of Musa paradisiaca L. (Family: Musaceae) against gentamicin-induced nephrotoxicity in mice. Gentamicin produced significant changes in biochemical (increased levels of blood urea nitrogen level, blood urea, and serum creatinine), and histological parameters in mice. Treatment with methanolic extract of bract (100 and 250mg/kg, b.w) and flowering stalk (trachea) (250 and 500mg/kg, b.w) significantly prevented biochemical and histological changes produced by gentamicin toxicity. The extracts of M. paradisiaca (bract and flowering stalk) could contribute a lead to discovery of a new drug for the treatment of drug-induced nephrotoxicity.

Pharmacognostic studies on Taxus baccata L.: A brilliant source of Anti-cancer agents.

The present investigation was undertaken to establish standardization profile of Taxus baccata L. with the help of pharmacognostic parameters, which is not done before. T. baccata(Taxaceae), is native to Europe, is an evergreen needle-leaved tree, growing up to 28 m high. A large number of phytochemicals like taxoids viz. taxusin, baccatin, baccatin, lignans, flavanoids, steroids, paclitaxel and sugar derivatives have been isolated from it. For the treatment of different types of cancer like ovarian and breast cancers, Kaposi's sarcoma and lung cancers Paclitaxel (taxol) has been approved. Paclitaxel is also under clinical trial for remedy of number of other cancers in combination with other chemotherapeutic medications. Pharmacognostical and preliminary phytochemical screening of T. baccata will be useful to authenticate and avoid adulteration in the raw material. The diagnostic microscopic characters, physiochemical data and FTIR will be useful in the development of monograph.

Antimalarial and insecticidal activities of newly synthesized derivatives of Benzimidazole.

The bioactive benzimidazole and corresponding substituted phenacyl halides has been synthesized (11) new derivatives out of three compounds 8, 10 and 11 were found to inhibit the Plasmodium falciparum moderately after 72 hours of incubation hence acting as antimalarial agents. While these derivatives were exhibited negligible insecticidal activity too when analyzed by impregnated filter paper method.

Hematological screening of heavy metals among patients of asthma using medicinal herbs in Karachi, Pakistan.

Prevalence and concentration of some toxic (Pb, Cd, and As) and essential metals (Zn, Cu, Cr, Ni, and Co) were determined in the blood samples collected from asthmatic patients in Karachi, Pakistan using atomic absorption spectrophotometer. All selected patients were habitual of taking crude drugs and home remedy as self medication to treat and prevent asthma. We detected large proportion of the patients with detectable levels of heavy metals. The percentage prevalence of Pb, Cr, Ni, and Co, were found 100% while that of As and Cd were 55% and 60% respectively. Atomic absorption spectroscopic data showed the presence of metals in the analyzed samples in the range of 0.00-37.08 µg/dl for As, 8.1-41.4µg/dl for Pb, 0.0-9.6µg/l for Cd, 2.0-55.6µg/l for Cr, 20.0-85.9µg/l for Ni, and 0.15-3.6 µg/l for Co. The study will be helpful in creating awareness regarding the use of quality herbal medicines in asthma. It is suggested that along with avoidance of other risk factors, reliance on the use of quality traditional medicines free from heavy metal contamination is very essential especially incase of bronco asthmatic conditions.

Antihyperglycemic and hypolipidemic effects of Hibiscus schizopetalus (Mast) Hook in alloxan-induced diabetic rats.

The antihyperglycemic and hypolipidemic activities of Hibiscus schizopetalus (Mast) Hook (Malvaceae) flower and leaves extracts were investigated in alloxan-induced diabetic rats. The hypoglycemic activity of both the extracts (100mg/kg, body weight) was tested in fasting normal rat, glucose loaded rats. Observation on body weight was also recorded. The extracts showed a significant (p<0.001) reduction in blood glucose level in normal fasting rats. In glucose tolerance test, significant (p<0.01) decreased observed in all glucose loaded animals. While in alloxan induced diabetic rats, the percent blood glucose reduction was 59.94% and 45.14% in extracts treated groups. The results obtained were compared with the reference standard drug Tolbutamide (100mg/kg, body weight). The diabetic rats showed sign of decreased in their body weight during the treatment period. Cholesterol and triglycerides levels were significantly decreased (p<0.001) by HFE. The results obtained demonstrated the potential hypoglycemic activity of methanolic extracts of H. schizopetalus. There is need of bioassay-directed assay of the active principles responsible for the anti-diabetic activity. The methanolic extracts showed the presence of carbohydrates, alkaloids, steroids, terpenes, saponins and glycosides.

Antidepressant activity of ethanolic extract of Hibiscus rosa sinenesis Linn.

The present study was undertaken to assess the antidepressant effect of crude ethanolic extract of floral part of Hibiscusrosa sinensis (HRS) at doses 100mg/kg, 250mg/kg and 500mg/kg using three parameters which are forced induced swimming test (FST), tail suspension test (TST) and open field test(OFT). Flouxetine (15mg/kg, body weight) was used as standard. Significant dose dependent decline in immobility time was observed in all the three doses in FST and TST while in case of OFT none of the dose of HRS exhibited effectual results. To determine MAO"A" and MAO"B" activity HRS extract was used and the results revealed that each dose of this plant exhibited marked effect on MAO"A", while on MAO"B" only 250mg/kg dose was found significant.

Synthesis of gold and silver nanoparticles by use of arabinoglucan from Lallemantia royleana.

Highly stable gold and silver nanoparticles were synthesized by use of an arabinoglucan from Lallemantia royleana seeds without additional use of reducing or stabilizing agents. The mechanism involved the reduction potential of the hemicellulose as verified by cyclic voltammetry. The arabinoglucan used was substantially free from ferulic acid and phenolic content, suggesting the inherent reducing potential of arabinoglucan for gold and silver ions. The synthesized nanoparticles exhibited surface plasmon resonance maxima at 515 nm (gold) and 397 nm (silver) corresponding to sizes of 10 nm and 8 nm, respectively. The zeta potential values were -24.1 mV (gold) and -22.3 mV (silver). The silver nanoparticles showed potential for application in surface-enhanced Raman spectroscopy. Gold nanoparticles were found to be non-toxic, whereas silver nanoparticles exhibited dose-dependent biological activities and found to be cytotoxic against brine shrimps and HeLa cell lines and the tumours caused by A. tumefaciens.

Enhancement in Oral Absorption of Ceftriaxone by Highly Functionalized Magnetic Iron Oxide Nanoparticles.

The present study aims at the development, characterization, biocompatibility investigation and oral bioavailability evaluation of ceftriaxone (CFT)-loaded N'-methacryloylisonicotinohydrazide (MIH)-functionalized magnetic nanoparticles (CFT-MIH-MNPs). Atomic force microscopy (AFM) and dynamic light scattering (DLS) showed that the developed CFT loaded MIH-MNPs are spherical, with a measured hydrodynamic size of 184.0 ± 2.7 nm and negative zeta potential values (-20.2 ± 0.4 mV). Fourier transformed infrared spectroscopic (FTIR) analysis revealed interactions between the nanocarrier and the drug. Nanoparticles showed high drug entrapment efficiency (EE) of 79.4% ±1.5%, and the drug was released gradually in vitro and showed prolonged in vitro stability using simulated gastrointestinal tract (GIT) fluids. The formulations were found to be highly biocompatible (up to 100 µg/mL) and hemocompatible (up to 1.0 mg/mL). Using an albino rabbit model, the formulation showed a significant enhancement in drug plasma concentration up to 14.4 ± 1.8 µg/mL in comparison with its control (2.0 ± 0.6 µg/mL). Overall, the developed CFT-MIH-MNPs formulation was promising for provision of high drug entrapment, gradual drug release and suitability for enhancing the oral delivery of CFT.

An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry.

Microvirin (MVN) is one of the human immunodeficiency virus (HIV-1) entry inhibitor lectins, which consists of two structural domains sharing 35% sequence identity and contrary to many other antiviral lectins, it exists as a monomer. In this study, we engineered an MVN variant, LUMS1, consisting of two domains with 100% sequence identity, thereby reducing the chemical heterogeneity, which is a major factor in eliciting immunogenicity. We determined carbohydrate binding of LUMS1 through NMR chemical shift perturbation and tested its anti-HIV activity in single-round infectivity assay and its anti-hepatitis C virus (HCV) activity in three different assays including HCVcc, HCVpp, and replicon assays. We further investigated the effect of LUMS1 on the activation of T helper (Th) and B cells through flow cytometry. LUMS1 showed binding to (1-2)mannobiose, the minimum glycan epitope of MVN, potently inhibited HIV-1 and HCV with EC50 of 37.2 and 45.3 nM, respectively, and showed negligible cytotoxicity with CC50 > 10 µM against PBMCs, Huh-7.5 and HepG2 cells, and 4.9 µM against TZM-bl cells. LUMS1 did not activate Th cells, and its stimulatory effect on B cells was markedly less as compared to MVN. Together, with these effects, LUMS1 represents a potential candidate for the development of antiviral therapies.

Noise pollution in the hospital environment of a developing country: A case study of Lahore (Pakistan).

The present study investigates the noise pollution levels in public- and private-sector hospitals of Lahore. The noise pollution parameters were investigated from 20 public and 10 private hospitals. We observed that the equivalent continuous sound level (Leq) values varied significantly in different departments of the hospitals as well as at different times of the day. The public-sector hospitals had significantly higher noise pollution compared to the private-sector hospitals. The Wilcoxon Mann-Whitney two-sample rank-sum test revealed significant difference between noise levels in intensive care unit (ICU) during morning and in emergency, waiting area, intensive care unit (ICU), and reception during daytimes. However, no significant differences were found for any department during the evening. The Leq values were found to be higher than the international norms (WHO standards) for all hospitals, higher than USEPA for 29 hospitals and higher than local standards for 27 hospitals. Overall, significantly lower sound levels were always observed in private hospitals.

Use of Mercury in Dental Silver Amalgam: An Occupational and Environmental Assessment.

The objective of this study was to assess the occupational exposure to mercury in dentistry and associated environmental emission in wastewater of Lahore, Pakistan. A total of ninety-eight blood samples were collected comprising 37 dentists, 31 dental assistants, and 30 controls. Results demonstrate that the dentistry personnel contained significantly higher mean concentration of mercury in their blood samples (dentists: 29.835 µg/L and dental assistants: 22.798 µg/L) compared to that of the controls (3.2769 µg/L). The mean concentration of mercury was found maximum in the blood samples of older age group (62.8 µg/L) in dentists and (44.3 µg/L) in dental assistants. The comparison of mercury concentration among dentists, dental assistants, and controls (pairing based on their ages) revealed that the concentration increased with the age and experience among the dentists and dental assistants. Moreover, the mercury concentration in all the studied dental wastewater samples, collected from twenty-two dental clinics, was found to be exceeding the recommended discharge limit of 0.01 mg/L. Therefore, we recommend that immediate steps must be taken to ensure appropriate preventive measures to avoid mercury vapors in order to prevent potential health hazards to dentistry personnel. Strong regulatory and administrative measures are needed to deal with mercury pollution on emergency basis.