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1.
Biomed Mater ; 18(6)2023 10 24.
Article in English | MEDLINE | ID: mdl-37827172

ABSTRACT

Recently, photodynamic therapy (PDT) has received a lot of attention for its potential use in cancer treatment. It enables the therapy of a multifocal disease with the least amount of tissue damage. The most widely used prodrug is 5-aminolevulinic acid, which undergoes heme pathway conversion to protoporphyrin IX, which acts as a photosensitizer (PS). Additionally, hematoporphyrin, bacteriochlorin, and phthalocyanine are also studied for their therapeutic potential in cancer. Unfortunately, not every patient who receives PDT experiences a full recovery. Resistance to different anticancer treatments is commonly observed. A few of the resistance mechanisms by which cancer cells escape therapeutics are genetic factors, drug-drug interactions, impaired DNA repair pathways, mutations related to inhibition of apoptosis, epigenetic pathways, etc. Recently, much research has been conducted to develop a new generation of PS based on nanomaterials that could be used to overcome cancer cells' multidrug resistance (MDR). Various metal-based, polymeric, lipidic nanoparticles (NPs), dendrimers, etc, have been utilized in the PDT application against cancer. This article discusses the detailed mechanism by which cancer cells evolve towards MDR as well as recent advances in PDT-based NPs for use against multidrug-resistant cancers.


Subject(s)
Neoplasms , Photochemotherapy , Humans , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use
2.
BMJ Glob Health ; 8(8)2023 08.
Article in English | MEDLINE | ID: mdl-37558269

ABSTRACT

Management of COVID-19 in Africa is challenging due to limited resources, including the high cost of vaccines, diagnostics, medical devices and routine pharmaceuticals. These challenges, in addition to wide acceptability, have resulted in increased use of herbal medicines based on African traditional medicines (ATMs) by patients in Africa. This is in spite of the often-significant gaps in evidence regarding these traditional medicines as to their efficacy and safety for COVID-19. African scientists, with some support from their governments, and guidance from WHO and other bodies, are addressing this evidence gap, developing and testing herbal medicines based on ATMs to manage mild-to-moderate cases of COVID-19. Such efforts need further support to meet public health needs.


Subject(s)
COVID-19 , Humans , Medicine, African Traditional , Pandemics , Africa , Plant Extracts
3.
Front Cell Infect Microbiol ; 12: 865814, 2022.
Article in English | MEDLINE | ID: mdl-36583107

ABSTRACT

Introduction: After being used vigorously for the previous two decades to treat P. falciparum, chloroquine and sulfadoxine-pyrimethamine were replaced in 2009 with an artemisinin-based combination therapy (artesunate-sulfadoxine-pyrimethamine) in an effort to combat multidrug-resistant parasites. Methods: We set out to assess the genetic variants of sulfadoxine-pyrimethamine resistance and the effectiveness of its treatment in eastern India prior to, during, and 6 to 8 years following the introduction of the new pharmacological regime. In 2008-2009, 318 P. falciparum-positive patients got the recommended doses of sulfadoxine-pyrimethamine. We used 379 additional isolates from 2015 to 2017 in addition to the 106 isolates from 2010. All 803 isolates from two study sites underwent in vitro sulfadoxine-pyrimethamine sensitivity testing and genomic characterisation of sulfadoxine-pyrimethamine resistance (pfdhfr and pfdhps). Results: In Kolkata and Purulia, we observed early treatment failure in 30.7 and 14.4% of patients, respectively, whereas recrudescence was found in 8.1 and 13.4% of patients, respectively, in 2008-2009. In 2017, the proportion of in vitro pyrimethamine and sulfadoxine resistance steadily grew in Kolkata and Purulia despite a single use of sulfadoxine-pyrimethamine. Treatment failures with sulfadoxine-pyrimethamine were linked to quintuple or quadruple pfdhfr- pfdhps mutations (AICII-AGKAT, AICII-AGKAA, AICII-SGKGT, AICII-AGKAA, AICNI-AGKAA) in 2008-2009 (p < 0.001). The subsequent spread of mutant-haplotypes with higher in vitro sulfadoxine-pyrimethamine resistance (p < 0.001), such as the sextuple (dhfr-AIRNI+dhps-AGEAA, dhfr-ANRNL+dhps-AGEAA) and septuple (dhfr-AIRNI+dhps-AGEAT), mutations were observed in 2015-2017. Discussion: This successive spread of mutations with high in vitro sulfadoxine-pyrimethamine resistance confirmed the progressive increase in antifolate resistance even after an 8-year withdrawal of sulfadoxine-pyrimethamine.


Subject(s)
Antimalarials , Malaria, Falciparum , Humans , Plasmodium falciparum/genetics , Antimalarials/pharmacology , Antimalarials/therapeutic use , Sulfadoxine/pharmacology , Sulfadoxine/therapeutic use , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Drug Resistance/genetics , Mutation , Genomics , Treatment Outcome , Tetrahydrofolate Dehydrogenase/genetics , Drug Combinations
4.
Molecules ; 27(11)2022 May 30.
Article in English | MEDLINE | ID: mdl-35684442

ABSTRACT

Background: This study comparatively assessed seven indigenous traditional tea plants on several attributes that included antioxidant, nutritional, caffeine contents, and cyclooxygenase activity. Methodology: Nutritional content of all tea plants were determined for energy, fat, carbohydrates, total sugars, dietary fiber and amino acids. Antioxidant potential and the antioxidant potentiating secondary metabolites were also measured and compared. Further, we investigated the tea plants for any role they would have on cyclooxygenase (COX) activity on cobalt chloride (CoCl2) induced human glioma cell lines (U87MG). Results: The tea plants were found non-cytotoxic at concentrations tested against the human Chang liver and HeK 293 kidney cells and were found to be naturally caffeine free. The lowest and highest extraction yield among the tea plants was 7.1% for B. saligna and 15.48% for L. scaberrimma respectively. On average, the flavonol content was 12 to 8 QE/g, ORAC 800 µmol TE/g, TEAC 150 µmol TE/g, FRAP 155 µmol AAE/g, polyphenols 40 mg GAE/g, flavanols 0.35 mg CE/g, flavonols 12 mg QE/g and total flavonoid content (TFC) 180 µg QE/mg. The COX activity has been found to be inhibited by a dose-dependent manner by L. scaberrimma, B. saligna and L. javanica. Conclusion: The results further support competitive value of tea plants and need for improved and further development.


Subject(s)
Antioxidants , Teas, Herbal , Antioxidants/chemistry , Caffeine , Cell Hypoxia , Cyclooxygenase Inhibitors , Flavonols , HEK293 Cells , Humans , Nutritive Value , Polyphenols/chemistry , Prostaglandin-Endoperoxide Synthases , South Africa
5.
Molecules ; 27(4)2022 Feb 11.
Article in English | MEDLINE | ID: mdl-35209008

ABSTRACT

A South African traditional formulation, PHELA®, is consumed by the traditional people for severe chest problems with coughing, diarrhea, oral ulcers etc. The present study focused on establishing the anti-infective properties of a safe and standardized poly-herbal formulation through a series of criteria and specifications.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Biofilms/drug effects , Medicine, African Traditional , Plant Extracts/chemistry , Plant Extracts/pharmacology , Anti-Infective Agents/isolation & purification , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Humans , Mass Spectrometry , Microbial Sensitivity Tests , Plant Extracts/isolation & purification
6.
Aging Dis ; 13(1): 29-36, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35111360

ABSTRACT

Presently, the second wave of COVID-19 pandemic is driving the world towards a devastating total failure of the healthcare system. The purpose of the review is to search for the studies reporting on the implication of herd immunity into a naïve population through age specific mass vaccination. This review is based on selected publications on the effect herd immunity to COVID 19 in communities. We searched published scientific articles, review articles, reports, published in 2020 as well as read some basic, cult publications related to establishment of indirect immunity to a population. We have focused on use of application of vaccine induced herd immunity into community to confer indirect immunity against COVID-19 and searched on electronic databases, including PubMed (http://www.pubmed.com), Scopus (http://www.scopus.com), Google Scholar (http://www.scholar.google.com), Web of Science (www.webofscience.com) and Science Direct by using key words such as Herd immunity, indirect or passive immunization, Coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), and immune-technique. This review proposes the implication of mass vaccination-induced herd immunity in a population to curb the infection, and to every individual in a given population irrespective of their age.

7.
Article in English | MEDLINE | ID: mdl-33618651

ABSTRACT

BACKGROUND: There are anecdotal claims on the use of Cannabis sativa L. in the treatment of Alzheimer's disease, but there is a lack of scientific data to support the efficacy and safety of Cannabis sativa L. for Alzheimer's disease. AIM: The aim of the study was to evaluate the effect of aerial parts of Cannabis sativa L. on the cholinesterases and ß-secretase enzymes activities as one of the possible mechanisms of Alzheimer's disease. METHODS: The phytochemical and heavy metal contents were analysed. The extracts were screened for acetylcholinesterase, butyrylcholinesterase and ß-secretase activity. Cytotoxicity of extracts was performed in normal vero and pre-adipocytes cell lines. The extracts were characterized using high-performance thin layer chromatography and high-performance liquid chromatography for their chemical fingerprints. Alkaloids, flavonoids and glycosides were present amongst the tested phytochemicals. Cannabidiol concentrations were comparatively high in the hexane and dichloromethane than in dichloromethane: methanol (1:1) and methanol extracts. RESULTS: Hexane and dichloromethane extracts showed a better inhibitory potential towards cholinesterase activity, while water, hexane, dichloromethane: methanol (1:1) and methanol showed an inhibitory potential towards ß-secretase enzyme activity. All extracts showed no cytotoxic effect on pre-adipocytes and vero cells after 24- and 48-hours of exposure. CONCLUSION: Therefore, this may explain the mechanism through which AD symptoms may be treated and managed by Cannabis sativa L. extracts.


Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases , Cannabis , Cholinesterase Inhibitors , Plant Extracts , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/metabolism , Animals , Butyrylcholinesterase/metabolism , Cannabis/chemistry , Chlorocebus aethiops , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Flowers/chemistry , Hexanes , Methanol , Methylene Chloride , Phytochemicals/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Vero Cells
8.
Curr Opin Pharmacol ; 60: 261-267, 2021 10.
Article in English | MEDLINE | ID: mdl-34481336

ABSTRACT

Ebola virus infection results in the fast onset of severe acute haemorrhagic fever with high mortality. The Ebola virus is labelled as a category A pathogen. Vaccines against the Ebola virus (EBOV) are essential for everyone, and an expansion in the arena of vaccine synthesis; especially, plant-based vaccine development has drawn attention. To express the heterologous protein for plant-based vectors, both RNA and DNA viruses have been adapted. Among the different approaches of plant-based vaccine technologies, the agroinfiltration method, which was initially established to investigate plant-virus interactions, has been considered an effective method to produce monoclonal antibodies against EBOV. The effectiveness of plants as bioreactors of vaccine/monoclonal antibodies development could be well-thought-out to attend the obligatory mandate. The review confers recent progress in the production of plant-based vaccines and antibody treatments against the Ebola virus disease, thereby alleviating public health alarms associated with EBOV.


Subject(s)
Ebola Vaccines , Ebolavirus , Hemorrhagic Fever, Ebola , Antibodies, Neutralizing , Antibodies, Viral , Hemorrhagic Fever, Ebola/prevention & control , Humans
9.
Cytokine ; 144: 155555, 2021 08.
Article in English | MEDLINE | ID: mdl-33992538

ABSTRACT

Emergence and spread of resistant parasites to the newest chemotherapeutic anti-malarial agents are the biggest challenges against malaria control programs. Therefore, developing a novel effective treatment to reduce the overgrowing burden of multidrug resistant malaria is a pressing need. Herein, we have developed a biocompatible and biodegradable, non-toxic chitosan-tripolyphosphate-chloroquine (CS-TPP CQ) nanoparticle. CS-TPP CQ nanoparticles effectively kill the parasite through redox generation and induction of the pro- and anti-inflammatory cytokines in both sensitive and resistant parasite in vitro. The in vitro observations showed a strong inhibitory effect (p < 0.01) on pro-inflammatory cytokines more specifically on TNF-α and IFN-γ whereas CS-TPP CQ nanoparticles significantly elevated the anti-inflammatory cytokines- IL-10 and TGF-ß. In addition, CS-TPP CQ nanoparticle significantly increased NO generation (p < 0.01) and altered the GSH/GSSG ratio 72 h after parasite co-culture with peripheral blood mononuclear cells culminating in the free radical induced parasite killing. CS-TPP CQ nanoparticle had an effective dose of 100 ng/ml against CQ-sensitive parasite lines (p < 0.001) whereas effective dose against CQ-resistant parasite line was 200 ng/ml CS-TPP CQ with an effective duration of 72 h (p < 0.001). Our studies suggest that CS-TPP CQ nanoparticle has a potential to modulate the pro- and anti-inflammatory responses, and to trigger the redox-mediated parasite killing. It can be a novel nano-based futuristic approach towards malaria control.


Subject(s)
Antimalarials/pharmacology , Cytokines/metabolism , Malaria/drug therapy , Nanoparticles/administration & dosage , Oxidation-Reduction/drug effects , Parasites/drug effects , Animals , Cells, Cultured , Chitosan/administration & dosage , Chitosan/analogs & derivatives , Chloroquine/pharmacology , Drug Resistance/drug effects , Humans , Inflammation/drug therapy , Inflammation/metabolism , Leukocytes, Mononuclear/metabolism , Malaria/metabolism , Parasites/metabolism , Plasmodium falciparum/drug effects
10.
Transfus Clin Biol ; 28(1): 123-127, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33285298

ABSTRACT

Since December 2019, the human populations of the 195 global countries continue experiencing grave health and life threats due to the current COVID-19 pandemic. As a result of the novelty of the pathogen, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at present there is lack of preventive as well as therapeutic options for treating and managing the infection. The use of ancient immunotherapeutic technique - the convalescent plasma (CP) therapy, may act as an immediate and available option to control the COVID-19 pandemic. This review provides a concept and understanding on the CP therapy, its potential to control SARS-CoV-2 pandemic. The CP therapy might act as an immediate saviour for society from the virus. Although the CP therapy has exert affirmative result against COVID-19 it has not been recommended for long time use in COVID-19 and this review gives support for its possible application.


Subject(s)
Antibodies, Viral/therapeutic use , COVID-19/therapy , Pandemics , SARS-CoV-2 , Antibodies, Viral/blood , COVID-19/blood , Clinical Trials as Topic , Convalescence , Disease Management , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Plasmapheresis , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Virulence , COVID-19 Serotherapy
11.
Int J Antimicrob Agents ; 56(2): 106028, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32450198

ABSTRACT

Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/metabolism , Chloroquine/pharmacology , Coronavirus Infections/drug therapy , Drug Repositioning , Hydroxychloroquine/pharmacology , Pandemics , Pneumonia, Viral/drug therapy , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/metabolism , Humans , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , SARS-CoV-2
12.
Biol Trace Elem Res ; 195(1): 82-94, 2020 May.
Article in English | MEDLINE | ID: mdl-31309447

ABSTRACT

Biogenic silver nanoparticles (AgNPs) continue captivating researchers in biomedicine field of research. Dicoma anomala Sond. plant, locally known as hloenya, hlonya, maagbossie, inyongwana, is widely recommended by South African traditional health practitioners (THPs) to treat against different health issues. The antiplasmodial effects of novel sesquiterpene molecules (C30H36O7; MW: 509.25) isolated from D. anomala Sond. have been reported by us (Patent US 8,586,112 B2). The aim of the study was to determine the anticancer activity of AgNPs synthesized using D. anomala plant root extract and the antiparasitic potency of AgNP-conjugated sesquiterpene. Nanoparticles have been characterized using different methods. Anticancer activity of AgNPs was evaluated against the MCF-7. This study also revealed that the AgNP-conjugated sesquiterpene has shown better antiparasitic activity against Plasmodium falciparum NF54 strain. One-pot synthesized AgNPs using Dicoma anomala Sond. root extract caused oxidative damage in breast cancer cells. These findings indicate the need for more in-depth research in the use of the AgNPs and sesquiterpene for development into potential leads as an antimalarial candidates and to improve the bioavailability of these sesquiterpenes.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antiparasitic Agents/pharmacology , Asteraceae/chemistry , Metal Nanoparticles/chemistry , Plant Extracts/pharmacology , Sesquiterpenes/pharmacology , Silver/pharmacology , 3T3 Cells , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antiparasitic Agents/chemistry , Antiparasitic Agents/isolation & purification , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Mice , Parasitic Sensitivity Tests , Particle Size , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Roots/chemistry , Plasmodium falciparum/drug effects , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Silver/chemistry , Surface Properties , Tumor Cells, Cultured
13.
Int J Parasitol Drugs Drug Resist ; 7(3): 251-261, 2017 12.
Article in English | MEDLINE | ID: mdl-28692943

ABSTRACT

Chloroquine (CQ) is highly effective against P. vivax, due to the rapid spread of CQ resistance in P. falciparum parasites; it is no longer the drug of choice against P. falciparum. This study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ susceptibility was tested in 781 patients with P. falciparum mono infections between 2008 and 2013, of which 338 patients had received CQ in 2008-2009. Genotyping of the pfcrt and the pfmdr1 gene was carried out in all isolates. Early treatment failure was detected in 114 patients {43 (31·39%) from Kolkata and 71 (35·32%) from Purulia} while recrudescence was identified in 13 (9.49%) and 17 (8.46%) patients from Kolkata and Purulia respectively. In vivo chloroquine resistance was strongly associated with CVMNT-YYSNY (p < 0.01) and SVMNT-YYSNY (p < 0.05) allele in Kolkata. In Purulia chloroquine resistance was associated with CVMNK-YYSNY (P < 0.005), SVMNT-YYSNY (P < 0.01) allele. The proportion of in vitro chloroquine resistance increased in subsequent years to 87.23% and 93·10% in 2013, in Kolkata and Purulia, respectively. Isolates with SVMNT-YFSND, SVMNT-YFSNY, CVIET-YFSND and CVIET-YYSNY haplotypes increased gradually (p < 0.05) from 2010 to 2013, leading to a rise in IC50 (p < 0.05) of chloroquine. An increase in in vitro chloroquine resistance and candidate gene mutations even after five years of chloroquine withdrawal against P. falciparum calls for synchronized research surveillance and proper containment strategies.


Subject(s)
Antimalarials/pharmacology , Chloroquine/pharmacology , Drug Resistance , Multidrug Resistance-Associated Proteins/genetics , Plasmodium falciparum/genetics , Point Mutation , Adolescent , Adult , Aged , Antimalarials/therapeutic use , Child , Child, Preschool , Chloroquine/therapeutic use , Coinfection/drug therapy , Coinfection/epidemiology , Coinfection/parasitology , Female , Haplotypes , Humans , India/epidemiology , Malaria/drug therapy , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Malaria, Vivax/drug therapy , Male , Membrane Transport Proteins/genetics , Middle Aged , Plasmodium falciparum/drug effects , Protozoan Proteins/genetics , Young Adult
14.
J Biol Inorg Chem ; 22(6): 893-918, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28643149

ABSTRACT

Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system. Ag-NPs released excess Ag+ ions leads to activation of NADPH oxidase and helps in generating the reactive oxygen species (ROS). Silver nanoparticles elicit the production of excess amount of ROS results activation of TNF-α. Ag-NPs activates caspase-3 and 9 which are the signature of mitochondrial pathway. Ag-NPs are responsible to decrease the antioxidant enzymes and imbalance the oxidative status into the cells but functionalization with BSA and PEG helps to protect the adverse effect of Ag-NPs on the cells. This study suggested that Ag-NPs are toxic to normal cells which directly lead with human health. Surface functionalization may open the gateway for further use of Ag-NPs in different area such as antimicrobial and anticancer therapy, industrial use or in biomedical sciences.


Subject(s)
Metal Nanoparticles/toxicity , Silver/chemistry , Silver/toxicity , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Biomarkers/metabolism , Body Weight/drug effects , Cattle , Cell Survival/drug effects , Cytokines/metabolism , Hemolysis/drug effects , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Mice , Oxidative Stress/drug effects , Particle Size , Polyethylene Glycols/chemistry , Serum Albumin, Bovine/chemistry , Structure-Activity Relationship , Surface Properties
15.
Nanotechnology ; 28(9): 095102, 2017 Mar 03.
Article in English | MEDLINE | ID: mdl-28139466

ABSTRACT

Drug-resistant bacteria are an increasingly serious threat to global public health. In particular, infections from multidrug-resistant (MDR) Gram-positive bacteria (i.e. Staphylococcus aureus) are growing global health concerns. In this work, we report the first use of nanoscale metal-organic frameworks (NMOFs) coencapsulating an antibiotic (vancomycin) and targeting ligand (folic acid) in one pot to enhance therapeutic efficacy against MDR S. aureus. Zeolitic imidazolate framework (ZIF-8) NMOFs, which have globular morphologies coencapsulating vancomycin and folic acid, are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, ulltraviolet-visible spectroscopy, and dynamic light-scattering techniques. We determined that the presence of folic acid on the surface of the NMOFs is significant in the sense of effective uptake by MDR S. aureus through endocytosis. The functionalized NMOFs transport vancomycin across the cell wall of MDR S. aureus and enhance antibacterial activity, which has been confirmed from studies of the minimum inhibitory concentration, minimum bactericidal concentration, cytotoxicity of bacterial cells, and generation of reactive oxygen species. This work shows that functionalized NMOFs hold great promise for effective treatment of MDR S. aureus.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Metal-Organic Frameworks/chemical synthesis , Nanoparticles/chemistry , Staphylococcus aureus/drug effects , Dynamic Light Scattering , Escherichia coli/drug effects , Escherichia coli/ultrastructure , Folic Acid/pharmacology , Intracellular Space/metabolism , Luminescence , Metal-Organic Frameworks/chemistry , Microbial Viability/drug effects , Reactive Oxygen Species/metabolism , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus/cytology , Staphylococcus aureus/ultrastructure , Vancomycin/pharmacology , X-Ray Diffraction
16.
Carbohydr Polym ; 157: 1657-1665, 2017 Feb 10.
Article in English | MEDLINE | ID: mdl-27987880

ABSTRACT

A water soluble heteroglycan (PS-II) with an average molecular weight∼60kDa was isolated from the hot aqueous extract of an edible mushroom Lentinus fusipes. The structural characterization of PS-II was carried out using total acid hydrolysis, methylation analyses, periodate oxidation, Smith degradation and 1D/2D NMR experiments. Total acid hydrolysis indicated the presence of D-galactose and D-glucose in a molar ratio of approximately 1:1. The chemical and NMR analyses revealed that the proposed repeating unit of the PS-II had a backbone chain consisting of three (1→6)-linked α-d-galactopyranosyl residue and two (1→6)-linked ß-d-glucopyranosyl residues, one of the ß-d-glucopyranosyl residue was branched at O-3 position with a terminal ß-d-glucopyranosyl. The PS-II exhibited significant in vitro splenocyte and macrophage activations with optimum dose of 20µg/ml and 80µg/ml respectively. Flow cytometry study revealed the protective role of the PS-II against nicotine stimulated lymphocytes. Moreover, the ROS scavenging property of PS-II was also established using DPPH radical scavenging assay.


Subject(s)
Immunosuppressive Agents/chemistry , Lentinula/chemistry , Lymphocytes/drug effects , Polysaccharides/chemistry , Agaricales , Free Radical Scavengers/chemistry , Humans , Magnetic Resonance Spectroscopy , Oxidation-Reduction , Polysaccharides/immunology
17.
Int J Biol Macromol ; 95: 833-842, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27932258

ABSTRACT

A water soluble heteroglycan (PCPS) was isolated from the aqueous extract of an edible mushroom Pleurotus cystidiosus. Structural characterization of the heteroglycan was carried out using total hydrolysis, methylation analysis, periodate oxidation, Smith degradation, and 1D/2D NMR experiments. Sugar analysis indicated the presence of glucose, galactose, and mannose in a molar ratio of nearly 6:2:1 respectively. The chemical and NMR analysis of the PCPS indicated the presence of a repeating unit with a backbone consisting of one unit of (1→6)-ß-d-glucopyranosyl, two (1→3)-ß-d-glucopyranosyl, one (1→3)-α-d-glucopyranosyl, one (1→6)-α-d-glucopyranosyl, and two (1→6)-α-d-galactopyranosyl moieties respectively, out of which one (1→3)-ß-d-glucopyranosyl residue was branched at O-6 with terminal ß-d-glucopyranosyl and another (1→6)-α-d-galactopyranosyl residue was branched at O-2 with terminal ß-d-mannopyranosyl moiety. The polysaccharide was found to exhibit cellular activities at different concentrations (10, 25, 50, 100, 200, 400µg/mL) and maintained the redox balance as well as reduced lipid per oxidation which protect the cell destruction.


Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Pleurotus/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Antioxidants/isolation & purification , Antioxidants/toxicity , Carbohydrate Sequence , Dose-Response Relationship, Drug , Humans , Lymphocytes/cytology , Lymphocytes/drug effects , Polysaccharides/isolation & purification , Polysaccharides/toxicity , Water/chemistry
18.
Infect Dis (Auckl) ; 9: 11-9, 2016.
Article in English | MEDLINE | ID: mdl-26917967

ABSTRACT

Due to the indiscriminate use of antibiotics, resistance to antibiotics has increased remarkably in Staphylococcus aureus. Vancomycin is the final drug to treat the S. aureus infection, but nowadays, resistance to this antibiotic is also increasing. So, the investigation of antibiotic resistance pattern is important. As there is already resistance to vancomycin, there is an urgent need to develop a new kind of antimicrobial to treat S. aureus infection. Eugenol may be the new drug of choice. This study was conducted to evaluate the antibacterial activity of eugenol against vancomycin-resistant S. aureus isolated from clinical pus samples. Thirty six pus samples were included in the study. Samples were isolated, identified and antimicrobial susceptibility tests were performed as per routine laboratory protocol. The antimicrobial activity and mechanisms of killing of eugenol were studied. Out of 36 pus samples, only 20 isolates were confirmed as S. aureus strains and 6 isolates exhibited vancomycin resistance. Eugenol successfully destroyed the vancomycin-resistant strains via reactive oxygen species generation and membrane damage. The prevalence of vancomycin resistance is increased day by day in different countries, and necessary steps to prevent the spread and emergence of resistance should be taken. The findings of the study suggested that eugenol might be used to treat vancomycin-resistant S. aureus.

19.
Vaccine ; 34(7): 957-67, 2016 Feb 10.
Article in English | MEDLINE | ID: mdl-26772632

ABSTRACT

In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.


Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines/immunology , Macrophages/immunology , Metal Nanoparticles/administration & dosage , Adjuvants, Immunologic/administration & dosage , Animals , Antibody-Dependent Cell Cytotoxicity , CD4-Positive T-Lymphocytes/immunology , Cobalt , Cytokines/blood , Immunoglobulin G/blood , Mice , Oxides , Phosphonoacetic Acid/analogs & derivatives , Spleen/immunology
20.
J Photochem Photobiol B ; 156: 1-10, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26773494

ABSTRACT

α-Napthoflavone (ANF) microstructures of various morphologies were synthesized using reprecipitation method. Sodium Dodecyl Sulfate (SDS) was used as morphology directing agent. The morphologies of the particles were characterized using optical and scanning electron microscopy (SEM). Single crystal data of ANF suggests that the aromatic units of ANF are in parallel slipped conformation in its aggregated form. Photophysical properties of aggregated ANF hydrosol were studied using UV-Vis absorption, steady state and time resolved spectroscopy. Red shift and broadening of UV-Vis spectra of ANF hydrosol are explained due to strong π-π and H-π interactions among the neighboring ANF molecules within the aggregated microstructures. Though ANF is non-luminescent in good solvent, a strong emission is observed in its aggregated state. This aggregation induced emission (AIE) has been explained due to restriction of intramoleculer rotation and large amplitude vibrational modes of ANF in its aggregated state. Our Photophysical study also reveals that AIE effect decreases after an optimum concentration of ANF and this has been explained due to softening of crystal lattice. Cytotoxicity of ANF hydrosol was examined to get an idea of the toxic level of this hydrosol toward cultured normal human cells. It is observed that ANF hydrosol may draw beneficial effect in biological application as it has no higher toxic activity but has antioxidant property.


Subject(s)
Benzoflavones/pharmacology , Benzoflavones/chemistry , Benzoflavones/toxicity , Crystallography, X-Ray , Fluorescent Dyes , Humans , Molecular Structure , Sodium Dodecyl Sulfate/chemistry , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet
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