Fabrication of novel glutathione-Fe3O4-loaded/activated carbon encapsulated sand bionanocomposites for enhanced removal of diethyl phthalate from aqueous environment in a vertical flow reactor.

The extensive use of plasticizers in various industries has made Diethyl phthalate (DEP), a serious threat to the environment and ecological water security, owing to its complex-structure and low-biodegradability. Thus, the present study aimed to design a sustainable sand-coated nano glutathione (GSH) -Fe3O4-loaded/activated carbon (AC) bionanocomposite (AC-GSH-Fe3O4@sand bionanocomposite) for effective removal of DEP from water. Characterization results suggested bionanocomposites' rough and irregular texture due to the uneven distribution of AC and Fe3O4 nanoparticles over the sand. The XRD spectra indicated high crystallinity of bionanocomposites, while the FTIR spectra confirmed the presence of all individual components, i.e., GSH, AC, Fe3O4, and sand. EDX-mapping, AFM, and TGA further verified its elemental composition, topographical changes and thermal stability. The influence of pH (3, 7, 9), bed height (2, 4, 6) cm, and flow rate (2.5, 3.5, 4.5) mL min-1 were studied in a dynamic system with an initial DEP concentration of 50 mg L-1 to investigate the removal behavior of the bionanocomposites. The best DEP removal efficiency (90.18 %) was achieved over 28-h at pH 9, bed-height-4 cm, and flow-rate-3.5 mL min-1, with an optimum qmax-200.25 mg g-1 as determined through Thomas-model. Breakthrough curves were predicted using various column models, and the corresponding parameters essential for column-reactor process design were calculated. The high reusability up to the 10th cycle (≥83.32%) and the effective treatment in complex matrices (tap-water: 90.11 %, river-water: 89.72 %, wastewater: 83.83%) demonstrated bionanocomposites' prominent sustainability. Additionally, the production cost at 6.64 USD per Kg, underscores its potentiality for industrial application. Phytotoxicity assessment on mung-bean revealed better root (5.02 ± 0.27 cm) and shoot (17.64 ± 0.35 cm) growth in the bionanocomposite-treated DEP samples over the untreated samples. Thus, AC-GSH-Fe3O4@sand bionanocomposites could be considered a highly-sustainable, low-cost technique for the effective removal of DEP and other phthalate-esters from contaminated matrices.

Evaluation of Acute Leukaemias by Flow Cytometry and Its Correlation With Diagnosis Using Morphological and Special Staining Techniques.

BACKGROUND: Leukaemia can be reliably diagnosed and classified by the simultaneous application of multiple techniques. Cytochemical stains that are cheap and do not require any special instruments are very important in developing countries for the diagnosis of acute leukaemia (AL). AIM: To diagnose AL in all suspected cases by flow cytometry and to correlate the diagnosis with morphological and special staining like myeloperoxidase (MPO) and periodic acid-Sciff (PAS) techniques.  Methods and materials: The study participants' peripheral blood smear details and bone marrow aspirate smear morphologic findings, as well as socio-demographic information, were taken from the patients' medical files. In total, 57 newly diagnosed instances of acute leukaemia confirmed by flow cytometry were incorporated into the study, which underwent cytochemical labeling and morphological diagnosis. All patients who gave previous consent had their bone marrow aspirated, and a Wright-stained smear was produced for microscopic inspection, cytochemical staining, and immunophenotyping. In an ethylenediaminetetraacetic acid (EDTA) container, peripheral blood was also drawn for the same purpose. During the entire bone marrow smear examination, we used both MPO and PAS staining techniques. RESULTS:  The study was carried out between July 2019 and June 2020. Out of 57 cases in the study, 29 (50.9%) cases on cytochemical analysis of leukaemia using PAS and MPO were diagnosed with acute myeloid leukaemia (AML) and 28 (49.1%) were diagnosed as acute lymphoid leukaemia (ALL). Cytochemical analysis of leukaemia using PAS and MPO rendered the diagnosis in 92.9% of acute leukaemia cases in our study. A total of 25 out of 25 AML cases and 28 out of 32 cases of ALL were correctly diagnosed based on morphology and cytochemical staining. Morphology and cytochemical analysis alone were unable to correctly diagnose a total of four ALL cases. All AML cases that were wrongly diagnosed as ALL were mostly M0 and M1-AML. CONCLUSION: Morphological staining diagnosis by itself is capable of correctly identifying a large proportion of cases of AL, which comprised 92.98% of total cases. There was also a favorable relationship between findings of diagnosis by flow cytometry and findings of diagnosis by morphology assessment in determining acute leukaemias.

Pharmacological and Pathological Relevance of S100 Proteins in Neurological Disorders.

The S100 protein is one of the calcium-binding proteins associated with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. S100 proteins are expressed in the central nervous system by oligodendrocytes, astrocytes and neurons during both normal and disease conditions. Although amyloid-beta aggregation and hyperphosphorylated tau plaques are the main pathological hallmarks of Alzheimer's disease, the S100 protein family is closely associated with neuroinflammation in several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis in addition to various types of cancer and other brain diseases. This review aims to present the key role of S100 proteins and their different relevant isoforms, along with the various approaches used for the regulation of these proteins in several neurodegenerative disorders.

Zirconia-based nanomaterials: recent developments in synthesis and applications.

In the last decade, the whole scientific community has witnessed great advances and progress in the various fields of nanoscience. Among the different nanomaterials, zirconia nanomaterials have found numerous applications as nanocatalysts, nanosensors, adsorbents, etc. Additionally, their exceptional biomedical applications in dentistry and drug delivery, and interesting biological properties, viz. anti-microbial, antioxidant, and anti-cancer activity, have further motivated the researchers to explore their physico-chemical properties using different synthetic pathways. With such an interest in zirconia-based nanomaterials, the present review focuses systematically on different synthesis approaches and their impact on the structure, size, shape, and morphology of these nanomaterials. Broadly, there are two approaches, viz., chemical synthesis which includes hydrothermal, solvothermal, sol-gel, microwave, solution combustion, and co-precipitation methods, and a greener approach which employs bacteria, fungus, and plant parts for the preparation of zirconia nanoparticles. In this review article, the aforementioned methods have been critically analyzed for obtaining specific phases and shapes. The review also incorporates a detailed survey of the applications of zirconia-based nanomaterials. Furthermore, the influence of specific phases, morphology, and the comparison with their counterpart composites for different applications have also been included. Finally, the concluding remarks, prospects and possible scope are given in the last section.

Fabrication of glutathione functionalized self-assembled magnetite nanochains for effective removal of crystal violet and phenol red dye from aqueous matrix.

A novel fabrication of magnetite (Fe3O4) nanochains, surface functionalized with glutathione (GSH), has been attempted through a basic wet reduction method, coalesced with oxidative etching for the removal of crystal violet (CV) and phenol red (PR) from an aqueous solution. The structural and functional characterizations of GSH@Fe3O4 MNPs were performed using SEM-EDX, DLS, XRD, and FTIR. The nanochain-structured adsorbent was found to have an average size of 24 ± 1.29 nm and a zeta potential value of - 6.44 mV. The batch experiments showed that GSH@Fe3O4 MNPs have a brilliant removal efficiency of 97% and 79% for CV and PR dyes, respectively, within a period of 60 min. The influence of different operational parameters like adsorbent dosage, pH, temperature, reaction time, and initial dye concentration on the removal behaviour of the adsorbent was studied in detail. The adsorbate-adsorbent reaction was tested over isotherm models, and the reaction fitted well for Langmuir isotherm with an excellent qmax value of 1619.5 mg/g and 1316.16 mg/g for CV and PR dye, respectively. The experimental results were also validated using different reaction kinetics, and it was found that the pseudo-first-order model fits well for PR dye adsorption (R2 = 0.91), while adsorption of CV dye was in best agreement with the pseudo-second-order kinetic model (R2 = 0.98). Thermodynamic studies revealed that the adsorption reaction was spontaneous and endothermic in nature. Furthermore, GSH@Fe3O4 MNPs can be reused effectively up to 5 cycles of dye removal. Major mechanisms involved in the adsorption reaction were expected to be electrostatic attraction, hydrogen bonding, and π-interactions. The efficiency of GSH@Fe3O4 MNPs in real water samples suggested that it has a high potential for dye removal from complex aqueous systems and could be used as an effective alternative for remediation of dyes contaminated water.

Biostimulation of Anaerobic Digestion Using Iron Oxide Nanoparticles (IONPs) for Increasing Biogas Production from Cattle Manure.

The effect of synthesised IONPs employing a nontoxic leaf extract of Azadirachta indica as a reducing, capping, and stabilizing agent for increasing biogas and methane output from cattle manure during anaerobic digestion (AD) was investigated in this study. Furthermore, the UV-visible spectra examination of the synthesized nanoparticles revealed a high peak at 432 nm. Using a transmission electron microscope, the average particle size of IONPs observed was 30-80 nm, with irregular, ultra-small, semi-spherical shapes that were slightly aggregated and well-distributed. IONPs had a polydisparity index (PDI) of 219 nm and a zeta potential of -27.0 mV. A set of six bio-digesters were fabricated and tested to see how varying concentrations of IONPs (9, 12, 15, 18, and 21 mg/L) influenced biogas, methane output, and effluent chemical composition from AD at mesophilic temperatures (35 ± 2 °C). With 18 mg/L IONPs, the maximum specific biogas and methane production were 136.74 L/g of volatile solids (VS) and 64.5%, respectively, compared to the control (p < 0.05), which provided only 107.09 L/g and 51.4%, respectively. Biogas and methane production increased by 27.6% and 25.4%, respectively using 18 mg/L IONPs as compared to control. In all treatments, the pH of the effluent was increased, while total volatile fatty acids, total solids, volatile solids, organic carbon content, and dehydrogenase activity decreased. Total solid degradation was highest (43.1%) in cattle manure + 18 mg/L IONPs (T5). According to the results, the IONPs enhanced the yield of biogas and methane when compared with controls.

Tumor-associated macrophages in cancer: recent advancements in cancer nanoimmunotherapies.

Cancer immunotherapy has emerged as a novel cancer treatment, although recent immunotherapy trials have produced suboptimal outcomes, with durable responses seen only in a small number of patients. The tumor microenvironment (TME) has been shown to be responsible for tumor immune escape and therapy failure. The vital component of the TME is tumor-associated macrophages (TAMs), which are usually associated with poor prognosis and drug resistance, including immunotherapies, and have emerged as promising targets for cancer immunotherapy. Recently, nanoparticles, because of their unique physicochemical characteristics, have emerged as crucial translational moieties in tackling tumor-promoting TAMs that amplify immune responses and sensitize tumors to immunotherapies in a safe and effective manner. In this review, we mainly described the current potential nanomaterial-based therapeutic strategies that target TAMs, including restricting TAMs survival, inhibiting TAMs recruitment to tumors and functionally repolarizing tumor-supportive TAMs to antitumor type. The current understanding of the origin and polarization of TAMs, their crucial role in cancer progression and prognostic significance was also discussed in this review. We also highlighted the recent evolution of chimeric antigen receptor (CAR)-macrophage cell therapy.

In Vitro and In Silico Toxicological Properties of Natural Antioxidant Therapeutic Agent Azimatetracantha. LAM.

Plant-derived antioxidants are a large group of natural products with the capacity to reduce radical-scavenging. Due to their potent therapeutic and preventive actions, these compounds receive a lot of attention from scientists, particularly pharmacologists. The pharmacological activities of the Azima tetracantha Lam. (AT) plant, belonging to the Salvadoraceae family, reported here justifies its traditional use in treating several diseases or disorders. This study aims to look at the propensity of certain plant compounds found in natural AT plant extracts that might play a critical role as a secondary metabolite in cervical cancer treatment. There is a shortage of information on the plant's phytochemical and biological characteristics. Methanol (MeOH) solvent extracts of the dried AT plant were screened phytochemically. Its aqueous extract was tested for antioxidant, antiseptic, anti-inflammatory, and anticancerous properties. Absorption Distribution Metabolism and Excretion (ADME/T), Docking, and HPLC were also performed. In clinical treatment, the plant shown no adverse effects. The antioxidant activity was evaluated and showed the highest concentration at 150 µg/mL (63.50%). MeOH leaf extract of AT exhibited the highest and best inhibitory activity against Staphylococcus aureus (15.3 mm/1000) and displayed a high antiseptic potential. At a 200 µg/mL concentration, MeOH leaves-extract inhibited red blood cells (RBC) hemolysis by 66.56 ± 0.40, compared with 62.33 ± 0.40 from the standard. Albumin's ability to suppress protein denaturation ranged from 16.75 ± 0.65 to 62.35 ± 0.20 inhibitions in this test, providing even more support for its favorable anti-inflammatory properties. The ADME/T studies were considered for a potential cancer drug molecule, and one of our compounds from MeOH extract fills the ADME and toxicity parameters. The forms of compound 4 showed a strong hydrogen-bonding interaction with the vital amino acids (ASN923, THR410, LEU840TRY927, PHE921, and GLY922). A total of 90% of cell inhibition was observed when HeLa cell lines were treated with 300 µg/mL of compound 4 (7-acetyl-3a1-methyl- 4,14-dioxo-1,2,3a,3a1,4,5,5a,6,8a,9b,10,11,11a-tetradecahydro-2,5a epoxy5,6a (methanooxymethano)phenaleno[1',9':5,6,7]indeno[1,7a-b]oxiren-2-yl acetate). The polyphenol compounds demonstrated significant advances in anticancer drug properties, and it could lead to activation of cancer cell apoptosis.

Decreased APE-1 by Nitroxoline Enhances Therapeutic Effect in a Temozolomide-resistant Glioblastoma: Correlation with Diffusion Weighted Imaging.

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI.

When glioblastoma multiforme (GBM) is treated with anti-vascular endothelial growth factor (VEGF) agents, it commonly exhibits tumor progression due to the development of resistance, which results in a dismal survival rate. GBM tumors contain a large number of monocytes/macrophages, which have been shown to be resistant to the effects of bevacizumab. It has been reported that tumor-associated macrophages (TAMs) promote resistance to bevacizumab treatment. Therefore, it is important to target TAMs in the GBM microenvironment. TAMs, which depend on chemokine ligand 2 (CCL2) for differentiation and survival, induce the expression of proangiogenic factors such as VEGF. Dynamic susceptibility contrast (DSC)-MR imaging is an advanced technique that provides information on tumor blood volume and can potentially predict the response to several treatments, including anti-angiogenic agents such as bevacizumab, in human GBM. In this study, we used a CCL2 inhibitor, mNOX-E36, to suppress the recruitment of TAMs in a CCL2-expressing rat GBM model and investigated the effect of combination therapy with bevacizumab using DSC-MR imaging. We demonstrated that the inhibition of CCL2 blocked macrophage recruitment and angiogenesis, which resulted in decreased tumor volume and blood volume in CCL2-expressing GBM in a rat model. Our results provide direct evidence that CCL2 expression can increase the resistance to bevacizumab, which can be assessed noninvasively with the DSC-MR imaging technique. This study shows that the suppression of CCL2 can play an important role in increasing the efficacy of anti-angiogenic treatment in GBM by inhibiting the recruitment of CCL2-dependent macrophages.

Assessment of Early Therapeutic Response to Nitroxoline in Temozolomide-Resistant Glioblastoma by Amide Proton Transfer Imaging: A Preliminary Comparative Study with Diffusion-weighted Imaging.

Amide proton transfer (APT) imaging is a novel molecular MRI technique to detect endogenous mobile proteins and peptides through chemical exchange saturation transfer. In this preliminary study, the purpose was to evaluate the feasibility of APT imaging in monitoring the early therapeutic response to nitroxoline (NTX) in a temozolomide (TMZ)-resistant glioblastoma multiforme (GBM) mouse model, which was compared with diffusion-weighted imaging (DWI). Here, we prepared TMZ-resistant GBM mouse model (n = 12), which were treated with 100 mg/kg/day of NTX (n = 4) or TMZ (n = 4), or saline (n = 4) for 7 days for the evaluation of short-term treatment by using APT imaging and DWI sequentially. The APT signal intensities and apparent diffusion coefficient (ADC) values were calculated and compared before and after treatment. Moreover, immunohistological analysis was also employed for the correlation between APT imaging and histopathology. The association between the APT value and Ki-67 labeling index was evaluated by using simple linear regression analysis. The short-term NTX treatment resulted in significant decrease in APT value as compared to untreated and TMZ group, in which APT signals were increased. However, we did not observe significantly increased mean ADC value following short-term NTX treatment. The Ki-67 labeling index shows a correlation with APT value. APT imaging could show the earlier response to NTX treatment as compared to ADC values in a TMZ-resistant mouse model. We believe that APT imaging can be a useful imaging biomarker for the early therapeutic evaluation in GBM patients.

Insecticidal effect of plant extracts on Phlebotomus argentipes (Diptera: Psychodidae) in Bihar, India.

BACKGROUND & OBJECTIVES: Phlebotomus argentipes (Diptera: Psychodidae), the established vector for kala-azar is presently being controlled by indoor residual spray of DDT in kala-azar endemic areas in India. Search for non-hazardous and non-toxic biodegradable active molecules from botanicals may provide cost-effective and eco-friendly alternatives to synthetic insecticides. The present study was aimed at evaluating various plant extracts from endemic and non-endemic areas of Bihar for their insecticidal activity against sandfly to identify the most effective plant extract. METHODS: Bio-assay test was conducted with larvae and adult of P. argentipes with different plant extracts collected in distilled water, hexane, ethyl acetate, acetone and methanol. Thin layer chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were conducted for detection of active molecules. RESULTS: Adults and larvae of sandflies exposed to the aqueous extract of Nicotiana tabacum resulted in 100 per cent mortality. The hexane extract of Clerodendrum infortunatum was found to kill 77 per cent adults but was ineffective against larvae. Bio-assay test of the ninth fraction (hexane extract-methanol phase) separated by column chromatography was found to be 63 per cent effective. The purple spot on the TLC of this fraction indicated the presence of a diterpenoid. HPLC of this fraction detected nine compounds with two peaks covering 20.44 and 56.52 per cent areas with retention time of 2.439 and 5.182 min, respectively supporting the TLC results. INTERPRETATION & CONCLUSIONS: The column separated 9 [th] fraction of C. infortunatum extract was found to be effective in killing 63 per cent of adult P. argentipes. Compounds of this fraction need to be evaluated further for identification and characterization of the active molecule by conducting individual bio-assay tests followed by further fractionation and HPLC. Once the structure of the active molecule is identified and validated, it may be synthesized and formulated as a product.