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Rice is known to accumulate arsenic (As) in its grains, posing serious health concerns for billions of people globally. We studied the effect of nanoscale sulfur (NS) on rice seedlings and mature plants under As stress. NS application caused a 40% increase in seedling biomass and a 26% increase in seed yield of mature plants compared to untreated control plants. AsIII exposure caused severe toxicity to rice; however, coexposure of plants to AsIII and NS alleviated As toxicity, and growth was significantly improved. Rice seedlings treated with AsIII + NS produced 159 and 248% more shoot and root biomass, respectively, compared to plants exposed to AsIII alone. Further, AsIII + NS-treated seedlings accumulated 32 and 11% less As in root and shoot tissues, respectively, than the AsIII-alone treatment. Mature plants treated with AsIII + NS produced 76, 110, and 108% more dry shoot biomass, seed number, and seed yield, respectively, and accumulated 69, 38, 18, and 54% less total As in the root, shoot, flag leaves, and grains, respectively, compared to AsIII-alone-treated plants. A similar trend was observed in seedlings treated with AsV and NS. The ability of sulfur (S) to alleviate As toxicity and accumulation is clearly size dependent as NS could effectively reduce bioavailability and accumulation of As in rice via modulating the gene expression activity of As transport, S assimilatory, and glutathione synthesis pathways to facilitate AsIII detoxification. These results have significant environmental implications as NS application in agriculture has the potential to decrease As in the food chain and simultaneously enable crops to grow and produce higher yields on marginal and contaminated lands.

Tuberculosis (TB) is a slow growing, potentially debilitating disease that has plagued humanity for centuries and has claimed numerous lives across the globe. Concerted efforts by researchers have culminated in the development of various strategies to combat this malady. This review aims to raise awareness of the rapidly increasing incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, highlighting the significant modifications that were introduced in the TB treatment regimen over the past decade. A description of the role of pathogen-host immune mechanisms together with strategies for prevention of the disease is discussed. The struggle to develop novel drug therapies has continued in an effort to reduce the treatment duration, improve patient compliance and outcomes, and circumvent TB resistance mechanisms. Herein, we give an overview of the extensive medicinal chemistry efforts made during the past decade toward the discovery of new chemotypes, which are potentially active against TB-resistant strains.

Aims This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827–839.

The aim of this study was to evaluate the toxicological profile of biosurfactant encapsulated polymeric nanoparticles of Polylactic acid-Polyethylene glycol (PLA-PEG) in mice. Hematological, biochemical and histopathological samples of rodents were evaluated. Mice were selected randomly and divided into 3 treatment groups and one control group. Group I mice served as a control group, Group II were administrated with biosurfactant, Group III were treated with Polymeric nanoparticles of PLA-PEG. Group IV mice were injected with biosurfactant loaded polymeric nanoparticles of PLA-PEG. The formulations were administered intravenously via tail vein with 20 μg/mL dose concentration of biosurfactant. The normal control group was injected with only PBS. Blood samples were collected on 7th, 14th and 21st day and hematological and biochemical assays were performed. After the blood collection, mice were sacrificed for histopathological examination. The results showed that there were no significant difference in hematology parameter between the control and treated group. Some minute, non-significant changes were found in biochemical parameters which were not considered. Histopathological result of selected vital organs revealed that the biosurfactant and/or PLA-PEG polymeric nanoparticles can be considered as safe as no toxicological features were observed in histopathology of tissues. Hence, it can be deliberated that the biosurfactant encapsulated in PLA-PEG copolymeric nanoparticles are non toxic and can provide a safe, suitable platform for biomedical applications in future.

Azithromycin (AZM), a macrolide antibiotic used for the treatment of Chlamydial conjunctivitis, is less effective for the treatment of this disease due to its poor bioavailability (38%). Various alternatives have been developed for improving the physico-chemical properties (i.e., solubility) of the AZM without much success. To overcome the problems associated with AZM, an inclusion complex employing a modified cyclodextrin i.e., sulfobutylether-β-cyclodextrin (SBE-β-CD) was prepared and characterized by phase solubility studies, pXRD and FTIR techniques. The results portrayed the formation of the inclusion complex of AZM with sulfobutylether β-cyclodextrin (SBE-β-CD) in 1:2 molar stoichiometric ratios. This inclusion complex was later incorporated into a polymer matrix to prepare anin situgel. Various combinations of carbopol 934P and hydroxypropyl methylcellulose (HPMC K4M) polymers were used and evaluated by rheological andin vitrodrug release studies. The optimized formulation (F4), containing carbopol 934P 0.2% (w/v) and HPMC K4M 0.2% (w/v), was evaluated for clarity, pH, gelling capacity, drug content, rheological properties,in vitrodrug release pattern, ocular irritation test and antimicrobial efficacy. Finally, owing to the improved antimicrobial efficacy and increased residence time, AZM:SBE-β-CDin situgel was found to be a promising formulation for the efficient treatment of bacterial ocular disease.

Graphene oxide is graphene-based two dimensional material and structure based on single sheet of carbon atoms arranged in hexagonal lattice or honeycomb framework. Graphene oxide is better than graphene in terms of dispersion in polar solvents due to oxygen-containing functional groups attached with carbon sheets, results as researchers to get indulged in this molecule. Graphene oxide has been attracted researchers in different fields like chemistry, physics and materials science. Graphene oxide has endless potential applications in building materials, environmental protection, electronics, medicine, pharmaceutical industries etc. In medicinal industry, graphene oxide used as antibacterial, antimicrobial and antifungal agent. Its potential activity with other nanoparticles as antifungal agent has come in light and became the main focus of going on works on graphene oxide. The antifungal property of GO-Ag composites was investigated. Furthermore, nanoparticles show great potential in the fields of biomedical, because of their antifungal properties. The GO-Ag composites act as alternative antifungal material. Moreover, antifungal activity of Reduced Graphene Oxide (rGO) nanosheets is also researched.

Background Biosurfactants are amphipathic molecules of microbial origin that reduce surface and interfacial tension at gas-liquid-solid interfaces. Earlier, the biosurfactant was isolated and characterized in our laboratory from Candida parapsilosis. The property of the biosurfactant is further explored in this study by using quantum dots (QDs) as nanocarrier. Materials and methods Graphene quantum dots (GQDs) were synthesized by bottom-up approach through pyrolysis of citric acid. GQDs were conjugated with both biosurfactant and folic acid (FA) using carbodiimide chemistry. The prepared GQD bioconjugate was studied for diagnostic and therapeutic effects against cancer cells. Results and discussion Photoluminescence quantum yield (QY) of plain GQDs was measured as 12.8%. QY for biosurfactant conjugated GQDs and FA-biosurfactant conjugated GQDs was measured as 10.4% and 9.02%, respectively, and it was sufficient for targeting cancer cells. MTT assay showed that more than 90% of cells remained viable at concentration of 1 mg/mL, hence GQDs seemed to be non-toxic to cells. Biosurfactant conjugated GQDs caused 50% reduction in cellular viability within 24 hours. FA conjugation further increased the specificity of bioconjugated GQDs toward tumor cells, which is clearly evident from the drug internalization studies using confocal laser scanning microscopy. A higher amount of drug uptake was observed when bioconjugated GQDs were decorated with FA. Conclusion The ability of GQD bioconjugate could be used as a theranostic tool for cancer. It is foreseen that in near future cancer can be detected and/or treated at an early stage by utilizing biosurfactant conjugated GQDs. Therefore, the proposed study would provide a stepping stone to improve the life of cancer patients.

Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of β-cyclodextrin, i.e. hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) and to investigate enhanced cellular uptake of inclusion complexed drug. Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (−1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation. Results: SBEβCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPβCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M−1) for DXT-SBEβCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPβCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug . Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo.

Helminths born diseases are related to pitiable management practices and improper control strategies. The medicinal plants contain various phytoconstituents that are liable for their anthelmintic activity. The aerial parts of the Chenopodium album were successively extracted with microwaves assisted extraction using petroleum ether, ethyl acetate, methanol, hydroalcoholic and aqueous solvents to get respective extracts (CAPE, CAEE, CAME, CAHE, and CAAE). All the extracts were analyzed for preliminary phytochemical screening for the identification of phytoconstituents. The anthelmintic activity was analyzed on Indian adult earthworms Eisenia foetida using piperazine citrate (PCT) as a standard drug. All the extracts (apart from CAAE) lead to paralysis and fatality of the earthworms. CAEE extract exhibits highly significant anthelmintic activity at a 10 mg/ml concentration by causing paralysis and fatality of earthworms and was more potent than PCT suspension. At a concentration of 10 mg/ml, paralysis and death time for CAEE was recorded as (10.08 ± 1.11) and (65.28 ± 2.09) respectively, while for standard piperazine citrate, it was recorded as (22.96 ± 1.12) and (65.09 ± 1.23). The CAEE exhibits two major compounds by LC-MS, i.e., NG and DG, that are mainly accountable for the Chenopodium album anthelmintic activity. The plant possesses GABA-mimetic action and thereby leads to flaccid, reversible paralysis of the body wall muscle., Chenopodium album, Eisenia foetida, Piperazine citrate, Anthelmintic activity, LC-MS

CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

Objective: The present work is an attempt to assess the in vitro antimicrobial activity of the leaves of Caesalpinia decapetala (Roth) fabaceae family collected from forest area of Tamilnadu, India. Methods: The crude drug was successively extracted by Soxhlet assembly using Petroleum ether, dichloromethane, ethyl acetate and methanol as solvents. Preliminary phytochemical screening of different extracts was carried out using several colour and precipitative chemical reagents as per described methods. Antimicrobial activity of the extracts was evaluated against fungal strains (Aspergillus fumigatus and Candida albicans), Gram +ve bacteria (Staphylococcus aureus and Streptococcus pyogenes) and Gram –ve bacteria (Escherichia coli and Pseudomonas aeruginosa) using agar wells dilution method. Nutrient agar medium at37 oC and sabouraud dextrose e agar medium at 28 oC were used in antimicrobial activity evaluation and antifungal activity evaluation respectively. Results: Preliminary phytochemical screening of C. decepetala leaves showed the presence of alkaloids, glycosides, phenols, phytosterols, saponins and flavonoids crude drug. C. decapetala leaf extracts exhibited marked dose dependent antibacterial activity in vitro against tested bacteria. Methanolic extract was found to be more potent particularly against Staphylococcus aureus (Gram +ve bacteria) and staphylococcus aeruginosa (Gram -ve bacteria). Conclusion: Various phytochemicals were found to be present in C. decepetala leaves. Methanolic extract of C. decepetala leaves exhibited better antimicrobial activity in vitro and can be used as a good therapeutic approach for infectious disease management and therapy. Further studies on isolation of phyto-constituents and both in vitro and in vivo evaluation of pharmacological activities of isolated bioactive constituents of the crude drug are recommended as future works.

A sensitive and rapid method for the detection of pathogenic bacteria (Salmonella typhi) in water sample was developed using core-shell CdSe / ZnS quantum dots (QDs) as fluorescence label. Surface-functionalized core-shell quantum dots were synthesized by successive ion layer adsorption and reaction (SILAR) technique and were made hydrophilic by ligand exchange method. Developed hydrophobic and hydrophilic QDs were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and spectrofluorimetry. Carboxy- terminated QDs were conjugated with bacteria-specific antibodies (S. typhi-specific IgG) for the preparation of photostable fluorescent label and were characterized by various techniques like spectrofluorimetry and enzyme-linked immunosorbent assay (ELISA) for their photoluminescence and successful bioconjugation. Antibody (Ab)-conjugated QDs were incubated with bacteria-contaminated water for S. typhi detection. Microscopic images and spectral profile of bacteria–Ab conjugated QDs complex were recorded by confocal laser scanning microscopy (CLSM). A sensitivity of 103 organisms/mL of targeted bacteria (S. typhi) could be attained in a period of about 2 h.

CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. Cite this article: Bone Joint J 2015;97-B:917–23.

Lowe syndrome (oculo-cerebro-renal syndrome of Lowe) is a rare X-linked recessive disor- der characterized by the involvement of eyes, brain and kidneys. It is caused by the deficiency of enzyme phosphatidylinositol 4, 5-bisphosphate 5-phosphatase, which is required for the intracellular trafficking, sec- ond messengers and for the other aspects of cellular metabolism. The gene coding for this enzyme, OCRL1, has been localised at Xq25-q26.1 and mutations in it are reported to cause Lowe Syndrome. In this article we report two male siblings, from North India, with Lowe syndrome.

Sjogren Larsson syndrome (SLS) is a rare autosomal disorder that is characterised by congenital ichthyosis, spastic diplegia or qudriplegia and mental retardation. It is caused by the deficiency of the en- zyme, fatty aldehyde dehydrogenase (FALDH) that is required for the oxidation of fatty alcohol to fatty acid. The metabolism of leukotrine B4 (LTB4) has also been reported to be defective in SLS patients. The gene, ADLH3A2, encoding for FALDH has been localised at 17p11.2 and mutations in it cause SLS. The worldwide frequency of SLS is reported to be less than 1: 100,000 births but rarely a case has been reported from India. This article reviews the genetic factors in SLS and re- ports a case of SLS from India, with two similarly af- fected sibs. The management of SLS including genetic counselling and prenatal diagnostic possibilities are also discussed.

The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacologic properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anticancer peptide NuBCP-9, which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles composed of a polyethylene glycol (PEG)–modified polylactic acid (PLA) diblock copolymer (NuBCP-9/PLA-PEG) or PEG-polypropylene glycol-PEG-modified PLA—tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the nanoparticles was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these nanoparticles in vitro triggered apoptosis by NuBCP-9–mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/nanoparticles triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins. Cancer Res; 74(12); 3271–81. ©2014 AACR.

We report the synthesis of core–shell CdSe/ZnS, CdSe/CdS, CdSe/CdS/ZnS nanoparticles. Fluorescent properties of these core/shell nanoparticles depends on the type of ions present on the surface of nanoparticles; a cation-rich surface enhances the emission intensity, while an anion-rich surface leads to deterioration of the fluorescence signal. We used this phenomenon for the synthesis of fluorescent and non-fluorescent quantum dots. We synthesized CdSe/S in which the fluorescence emission is completely quenched, and CdSe/S/Cd and CdSe/S/Zn type of core–shell nanoparticles, which exhibit high fluorescence emission. Although various fluorescence sensors for metal cations based on nanoparticles were previously developed, to the best of our knowledge we first explored the potential application of non-fluorescent quantum dots for the detection of cadmium and zinc in organic medium.

Present work demonstrates the utilization of surface modified polycarbonate (PC) membrane as solid phase and antibody conjugated CdSe/ZnS quantum dots (QDs) as fluorescent label for the sensitive and selective detection of Salmonella typhi (S. typhi) in water in a period of 2.5h. PC membrane was surface modified with glycine and activated by EDC/NHS for immobilization of S. typhi specific IgG. Antibody immobilized porous PC membrane was incubated with bacteria contaminated water for immunocapturing of S. typhi. Antibody conjugated QDs were also prepared by using carbodiimide chemistry. Both modified PC membrane and quantum dots were characterized by using various modern analytical tools. It was estimated that 1.95 molecules of QDs were successfully bio-conjugated per unit of IgG. PC membrane with captured bacteria was incubated with prepared IgG conjugated QDs for the formation of sandwich complex. Analysis of the regions of interest (ROI) in fluorescent micrographs showed that newly developed method based on PC and fluorescent QDs has 100 times higher detection sensitivity (100 cells/mL) as compared with detection using conventional dye (FITC) based methods.