Electrical transport properties of [(1 - x)succinonitrile:xpoly(ethylene oxide)]-LiCF3SO3-Co[tris-(2,2'-bipyridine)]3(TFSI)2-Co[tris-(2,2'-bipyridine)]3(TFSI)3 solid redox mediators.

A solid redox mediator (solid electrolyte) with an electrical conductivity (σ25°C) greater than 10-4 S cm-1 is an essential requirement for a dye-sensitized solar cell in the harsh weather of Gulf countries. This paper reports the electrical properties of solid redox mediators prepared using highly dissociable ionic salts: Co[tris-(2,2'-bipyridine)]3(TFSI)2, Co[tris-(2,2'-bipyridine)]3(TFSI)3, and LiCF3SO3 as a source of Co2+, Co3+, and Li+ ions, respectively, in a solid matrix: [(1 - x)succinonitrile:xpoly(ethylene oxide)], where x = 0, 0.5, and 1 in weight fraction. In the presence of large size of cations (Co2+ and Co3+) and large-sized and weakly-coordinated anions (TFSI- and CF3SO3-), only the succinonitrile-poly(ethylene oxide) blend (x = 0.5) resulted in highly conductive amorphous regions with σ25°C of 4.7 × 10-4 S cm-1 for EO/Li+ = 108.4 and 3.1 × 10-4 S cm-1 for EO/Li+ = 216.8. These values are slightly lower than 1.5 × 10-3 S cm-1 for x = 0 and higher than 6.3 × 10-7 S cm-1 for x = 1. Only blend-based electrolytes exhibited a downward curve in the log σ-T-1 plot, a low value of pseudo-activation energy (0.06 eV), a high degree of transparency, and high thermal stability, making it useful for device applications.

Global epidemiology of breast cancer based on risk factors: a systematic review.

Background: Numerous reviews of the epidemiology and risk factors for breast cancer have been published previously which heighted different directions of breast cancer. Aim: The present review examined the likelihood that incidence, prevalence, and particular risk factors might vary by geographic region and possibly by food and cultural practices as well. Methods: A systematic review (2017-2022) was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, reporting on epidemiological and risk factor reports from different world regions. Medical Subject Heading (MeSH) terms: "Breast neoplasm" "AND" country terms such as "Pakistan/epidemiology", "India/epidemiology", "North America/epidemiology", "South Africa/epidemiology" were used to retrieve 2068 articles from PubMed. After applying inclusion and exclusion terms, 49 papers were selected for systematic review. Results: Results of selected articles were summarized based on risk factors, world regions and study type. Risk factors were classified into five categories: demographic, genetic and lifestyle risk factors varied among countries. This review article covers a variety of topics, including regions, main findings, and associated risk factors such as genetic factors, and lifestyle. Several studies revealed that lifestyle choices including diet and exercise could affect a person's chance of developing breast cancer. Breast cancer risk has also been linked to genetic variables, including DNA repair gene polymorphisms and mutations in the breast cancer gene (BRCA). It has been found that most of the genetic variability links to the population of Asia while the cause of breast cancer due to lifestyle modifications has been found in American and British people, indicating that demographic, genetic, and, lifestyle risk factors varied among countries. Conclusion: There are many risk factors for breast cancer, which vary in their importance depending on the world region. However, further investigation is required to better comprehend the particular causes of breast cancer in these areas as well as to create efficient prevention and treatment plans that cater to the local population.

An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats.

Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity.

Curative potential of Populus ciliata Wall ex. Royle extract against adjuvant-induced arthritis and peripheral neuropathy in Wistar rats.

Populus ciliata (PCCR) is traditionally used to treat muscular swelling, inflammation, pain, and fever. The current study was designed to validate the potential of aqueous ethanolic extract of the plant against inflammation, peripheral neuropathy, and pain in arthritic rats. The PCCR was chemically characterized by gas chromatography-mass spectroscopy and high-performance liquid chromatography. In vitro antioxidant, and in vitro anti-inflammatory assays were carried out on PCCR. For anti-arthritic potential, Wistar rats' rear paws were injected with 0.1 ml Complete Freund's Adjuvant using methotrexate (3 mg/kg/week) as standard control. PCCR at 100, 200, and 400 mg/kg was given orally to arthritic rats for 21 days. The PCCR exhibited significant inhibition of bovine serum albumin denaturation (IC-50: 202.1 µg/ml), egg albumin denaturation (IC-50:553.5 mg/ml) and RBC membrane stabilization (IC-50: 122.5 µg/ml) and antioxidant (IC-50 = 49.43 µg/ml) activities. The PCCR notably decreased the paw diameter and increased body weight of treated arthritic animals as equated to diseased control. The treatment notably (p < 0.05-0.0001) decreased malondialdehyde, and increased superoxide dismutase, reduced glutathione, and catalase in the liver and sciatic nerve homogenate in compared to diseased rats. The PCCR treatment remarkably (p < 0.05-0.0001) regulated the levels of nor-adrenaline and serotonin in sciatic nerve in contrast to diseased rats. Treatment with PCCR improved the motor activity, pain, ligament degeneration, and synovial hyperplasia in arthritic rats. Moreover, PCCR significantly (p < 0.01-0.0001) decreased the IL-6 and TNF-α. It is evident from the current study that PCCR had ameliorated polyarthritis and peripheral neuropathy through reduction of inflammatory markers, and improvement of oxidative stress might be due to presence of phenolic acids, flavonoids, phytosterols, and other fatty acids.

Pterostilbene reduces the progression of atopic dermatitis via modulating inflammatory and oxidative stress biomarkers in mice.

Atopic dermatitis (AD) is one of the most prevalent chronic skin inflammatory disorders requiring continuous treatment and care. Pterostilbene (PTN) belongs to stilbene and is a polyphenolic compound of natural origin. It is similar to resveratrol and has analogous anti-inflammatory, anti-oxidant, and anti-carcinogenic characteristics. This study was intended to evaluate the effect of PTN against atopic dermatitis. The disease was induced by sensitization with 2,4-dinitrochlorobenzene (DNCB) in mice. The standard control group (SCG) received topical 0.1% tacrolimus (TC), whereas three other treatment groups received daily topical PTN at 0.2, 0.6, and 1% w/w for 28 days. Dermatitis scoring, ear thickness, and body weight of animals were weekly determined while other parameters were assessed at the termination of the experiment. PTN reduced the ear weight, skin thickness, and the weight and size of thymus glands and spleen in comparison with diseased animals. PTN also reduced the elevated immunoglobulin E (IgE) level and blood inflammatory cells in diseased mice. The histopathological findings showed a decreased epidermal thickness in PTN-treated groups. Moreover, treatment with PTN improved the amount of oxidative stress markers in the skin of the diseased mice. The expressions of IL-4, IL-6, TNF-α, and NF-κB in the skin of diseased mice were also reduced by PTN. This study concludes that PTN ameliorated the symptoms of atopic dermatitis through the reduction of inflammation, oxidative damage, and inflammatory cytokines in the skin of diseased animals. Therefore, PTN must be further investigated for the treatment of AD complications and other inflammatory skin disorders.

Alternative treatment of polycystic ovary syndrome: pre-clinical and clinical basis for using plant-based drugs.

The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an endocrine disorder that occurs in approximately one in seven women. Among these PCOS patients, two thirds will not ovulate on a regular basis and seek treatment for ovulation induction. The symptoms vary in their severity, namely ovulation disorders, excessive androgen levels, or polycystic ovarian morphology. All these symptoms require a therapeutic approach. Many drugs are used to eradicate PCOS symptoms, like metformin, clomiphene citrate, spironolactone, and pioglitazone. Long-term treatment is required to achieve the desired outcome, which is often accompanied by significant adverse reactions. Some herbs and phytochemicals are equally effective for treating PCOS and produce minimal side effects. Recently, herbal products are gaining popularity due to their wide biological activities, safety, availability, and efficacy. The present review covers aetiology, current treatment, pathophysiology, and detailed pre-clinical and clinical studies on plants and phytochemicals that are proven to be useful for the treatment of symptoms associated with PCOS.

High-Fidelity NIR-II Multiplexed Lifetime Bioimaging with Bright Double Interfaced Lanthanide Nanoparticles.

Fluorescence lifetime imaging provides more possibility of in vivo multiplexing in second near infrared (NIR-II) window. However, it still faces the obstacle that fluorescent probes with differentiable lifetime often exhibit quite different fluorescence intensity, especially the short lifetime usually accompanies with a weak fluorescence intensity, resulting in the difficulty for simultaneously decoding multiplexed lifetime information due to the interference of background noise. To facilitate high-fidelity lifetime multiplexed imaging, we developed a series of Er3+ doped double interface fluorescent nanoprobes (Er-DINPs): α-NaYF4 @NaErF4 : Ce@NaYbF4 @NaErF4 : Ce@NaYF4 with strong fluorescence intensity and easily distinguishable fluorescence lifetime. Both in vitro and in vivo experimental results confirmed the advantage of these probes with comparable fluorescence intensity for high-fidelity multiplexed lifetime bioimaging.

Construction of AC/DC magnetic syringe device for stimulated drug release, injection and ejection of nanocarriers and testing cytotoxicity in vitro.

Iron nanoparticles are used as a targeted drug delivery system. The nanocarrier itself can be genotoxic, trigger oxidative stress or cell death. Therefore, we developed an AC/DC magnetic syringe for injecting, stimulating drug release and safe removing of the nanocarrier. Alongside we optimized the method for nanoparticles' drug release kinetics and testing cytotoxicity in vitro.•This paper presents detailed instructions for construction of AC/DC magnetic syringe device for stimulated drug release, injection and ejection of magnetic nanoparticles; nanoparticles preparation; adsorbing methylene blue on nanoparticles; determination of drug release kinetics from nanocarriers on the example of methylene blue•Gomori´s Prussian blue reaction for differentiated SH-SY5Y human neuroblastoma cell line; MTT viability assay optimized for differentiated SH-SY5Y human neuroblastoma cell line and antioxidant enzymes activities assay and lipid peroxidation methods are optimized for cell analyses cell cultivation for nanoparticles cytotoxicity testing in vitro.•Those protocols are the first step toward further testing the effect of nanoparticles in vivo, on brain tissue.

Green nanotechnology of MGF-AuNPs for immunomodulatory intervention in prostate cancer therapy.

Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent.

NIR-II cell endocytosis-activated fluorescent probes for in vivo high-contrast bioimaging diagnostics.

Fluorescence probes have great potential to empower bioimaging, precision clinical diagnostics and surgery. However, current probes are limited to in vivo high-contrast diagnostics, due to the substantial background interference from tissue scattering and nonspecific activation in blood and normal tissues. Here, we developed a kind of cell endocytosis-activated fluorescence (CEAF) probe, which consists of a hydrophilic polymer unit and an acid pH-sensitive small-molecule fluorescent moiety that operates in the "tissue-transparent" second near-infrared (NIR-II) window. The CEAF probe stably presents in the form of quenched nanoaggregates in water and blood, and can be selectively activated and retained in lysosomes through cell endocytosis, driven by a synergetic mechanism of disaggregation and protonation. In vivo imaging of tumor and inflammation with a passive-targeting and affinity-tagged CEAF probe, respectively, yields highly specific signals with target-to-background ratios over 15 and prolonged observation time up to 35 hours, enabling positive implications for surgical, diagnostic and fundamental biomedical studies.

Ganoderma lucidum (Reishi) an edible mushroom; a comprehensive and critical review of its nutritional, cosmeceutical, mycochemical, pharmacological, clinical, and toxicological properties.

Reishi owes an exceptional value in nutritional, cosmeceutical, and medical treatments; however, none of the studies has provided its future-driven critical assessment. This study documents an up-to-date review (2015-2020, wherever applicable) and provide valuable insights (preclinical and clinical evidence-based) with comprehensive and critical assessments. Various databases 'Google scholar', 'Web of Science', 'ScienceDirect', 'PubMed', 'Springer Link', books, theses, and library resources were used. The taxonomic chaos of G. lucidum and its related species was discussed in detail with solution-oriented emphasis. Reishi contains polysaccharides (α/ß-D-glucans), alkaloids, triterpenoids (ganoderic acids, ganoderenic acids, ganoderol, ganoderiol, lucidenic acids), sterols/ergosterol, proteins (LZ-8, LZ-9), nucleosides (adenosine, inosine, uridine), and nucleotides (guanine, adenine). Some active drugs are explored at an optimum level to make them potential drug candidates. The pharmacological potential was observed in diabetes, inflammation, epilepsy, neurodegeneration, cancer, anxiety, sedation, cardiac diseases, depression, hepatic diseases, and immune disorders; however, most of the studies are preclinical with a number of drawbacks. In particular, quality clinical data are intensely needed to support pharmacological activities for human use. The presence of numerous micro-, macro, and trace elements imparts an essential nutritional and cosmeceutical value to Reishi, and various marketed products are available already, but the clinical studies regarding safety and efficacy, interactions with foods/drinks, chronic use, teratogenicity, mutagenicity, and genotoxicity are missing for Reishi. Reishi possesses many valuable pharmacological activities, and the number of patents and clinical trials is increasing for Reishi. Yet, a gap in research exists for Reishi, which is discussed in detail in the forthcoming sections.

Toxoplasmosis in Pediatric Hematopoietic Stem Cell Transplantation Patients.

Infection due to the protozoa Toxoplasma gondii can be life-threatening in hematopoietic stem cell transplantation (HSCT) recipients. Most cases of toxoplasmosis in HSCT recipients result from reactivation of latent infection in individuals who were Toxoplasma-seropositive before transplantation and did not receive appropriate prophylaxis. Pretransplantation screening with Toxoplasma IgG and IgM antibodies is suggested for all allogeneic HSCT recipients and their donors and all autologous HSCT recipients. Prevention of toxoplasmosis in T. gondii-seropositive HSCT recipients requires primary prophylaxis, preemptive screening, or both. Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred agent for Toxoplasma prophylaxis and should be continued for 6 months or until the patient is no longer receiving immunosuppression, whichever is longer, assuming that immune reconstitution has occurred. Preemptive weekly screening with whole blood Toxoplasma PCR should be considered for seropositive HSCT recipients if prophylaxis cannot be given or if prophylaxis other than TMP-SMX is used. The signs, symptoms, and radiographic findings of toxoplasmosis in HSCT recipients can be nonspecific, and the diagnosis requires a high degree of suspicion. Common presentations include fever, encephalopathy with mental status changes or seizures, and pneumonia. A Toxoplasma PCR analysis from whole blood (and other body fluids/tissues according to clinical symptoms) should be obtained in patients in whom there is a concern for toxoplasmosis. Treatment with oral pyrimethamine, sulfadiazine, and leucovorin for at least 6 weeks is the first-line therapy and should be followed by secondary prophylaxis. In this article, we review the published literature regarding the epidemiology, clinical presentation, treatment, and prevention of toxoplasmosis in HSCT recipients.

Response to Trimethoprim-Sulfamethoxazole in a Pediatric Hematopoietic Stem Cell Transplant Recipient With Disseminated Toxoplasmosis: A Case Report.

We describe the presentation and treatment of a patient who developed ongoing fever and diagnosed with disseminated toxoplasmosis post-hematopoietic stem cell transplantation. He was initially treated with trimethoprim-sulfamethoxazole (TMP-SMX) and there was dramatic improvement in his fever curve. He successfully completed a modified course of therapy.

AC/DC magnetic device for safe medical use of potentially harmful magnetic nanocarriers.

Continuing our previous research work on a drug delivery system based on combined AC/DC magnetic fields, we have developed a prototype AC/DC magnetic syringe device for stimulation of drug release from drug carriers, with the options of injecting/removing drug carriers. The porous Fe3O4 carrier, in a dose-dependent manner, causes acute oxidative damage and reduces the viability of differentiated SH-SY5Y human neuroblastoma cells, indicating the necessity for its removal once it reaches the therapeutic concentration at the target tissue. The working mechanism of the device consists of three simple steps. First, direct injection of the drug adsorbed on the surface of a carrier via a needle inserted into the targeted area. The second step is stimulation of drug release using a combination of AC magnetic field (a coil magnetised needle with AC current) and permanent magnets (DC magnetic lens outside of the body), and the third step is removal of the drug carriers from the injected area after the completion of drug release by magnetising the tip of the needle with DC current. Removing the drug carriers allows us to avoid possible acute and long term side effects of the drug carriers in the patient's body, as well as any potential response of the body to the drug carriers.

Development of Hydrophobic, Anticorrosive, Nanocomposite Polymeric Coatings from Canola Oil: A Sustainable Resource.

A novel hydrophobic Canola oil-based nanocomposite anticorrosive coating material with different contents of fumes silica (FS) was successfully synthesized via an in situ method. Firstly, a Canola oil-based hydroxyl terminated poly (oxalate-amide) was prepared by a two-step process of amidation and condensation. Secondly, the dispersion of fumed silica (1 to 3 wt.%) in hydroxyl terminated poly (oxalate-amide) was carried out, followed by reaction with toluene-2,4- diisocyanate (TDI) in order to form poly (urethane-oxalate-amide)/fumed silica nanocomposite. The structure and properties of nanocomposite were analyzed by FTIR, NMR (1H/13C), TGA/DTA, DSC, contact angle, and SEM. The physico-mechanical and electrochemical tests were performed in order to check the performance of nanocomposite coating. The results reveal that FS is homogenously dispersed in poly (urethane-oxalate-amide) matrix with a loading amount of less than 3 wt.%. The performance of nanocomposite coating improved when compared to virgin polymer. The synthesized nanocomposite coating can be used in the field of hydrophobic anticorrosive coatings.

Mechanically Strong, Hydrophobic, Antimicrobial, and Corrosion Protective Polyesteramide Nanocomposite Coatings from Leucaena leucocephala Oil: A Sustainable Resource.

The aim of this research work is to develop polyesteramide [LMPEA] nanocomposite coating material [LMPEA/Ag] using N,N-bis(2-hydroxyethyl) fatty amide obtained from non-edible Leucaena leucocephala [LL] seed oil [LLO], and maleic anhydride, reinforced with silver nanoparticles [SNPs], biosynthesized in Leucaena leucocephala leaf extract. UV, XRD, TEM, and particle size analyses confirmed the biosynthesis of NP (37.55 nm). FTIR and NMR established the structure of LMPEA formed by esterification reaction, without any solvent/diluent. Coatings were mechanically strong, well adherent to substrate, flexibility retentive, hydrophobic, and antimicrobial as evident from good scratch hardness (2-3 kg), impact resistance (150 lb per inch), bend test (1/8 inch), high water contact angle measurement value (109°) relative to pristine LMPEA coating (89°), and broad-spectrum antimicrobial behavior against MRSA, P. aeruginosa, E. coli, A. baumannii, and C. albicans. LMPEA and LMPEA/Ag exhibited high corrosion protection efficiencies, 99.81% and 99.94%, respectively, in (3.5% w/v) NaCl solution for 20 days and safe usage up to 200 °C. The synthesized nanocomposite coatings provide an alternate pathway for utilization of non-edible Leucaena leucocephala seed oil through a safer chemical synthesis route, without the use/generation of any harmful solvent/toxic products, adopting "Green Chemistry" principles.

Advances in maintenance strategy in newly diagnosed multiple myeloma patients eligible for autologous transplantation.

INTRODUCTION: Multiple myeloma (MM) lacks curative therapy. Therefore, researchers continue to conduct studies in an effort to improve progression-free survival (PFS) and overall survival (OS). Maintenance therapy (MT) after autologous stem cell transplant (ASCT) was extensively studied in the last decade and now considered a standard approach. AREAS COVERED: This review evaluated the evidence and updates on various maintenance agents in newly diagnosed multiple myeloma (NDMM) after ASCT. Articles were searched on PubMed and Embase that were published in last 10 years. Both clinical trials and observational studies were evaluated. EXPERT OPINION: Maintenance strategy after ASCT has consistent PFS benefit but lacks conclusive OS improvement. Lenalidomide is superior to thalidomide given reduced neurotoxicity. OS advantage is controversial for both due to inconsistent evidence. Lenalidomide may confer a PFS advantage even at lower doses due to toxicity with higher doses. Bortezomib-based maintenance has some evidence for OS benefit in high-risk MM (HRMM) and renal dysfunction. Ixazomib has preliminary promising results. Two or three drug combinations for MT are potentially safe and more effective, particularly in HRMM although data on this subject is still evolving. Efficacy of various MT regimens in terms of minimal residual disease status needs to be further investigated.

Optically active neodymium hydroxide surface-functionalized mesoporous silica micro-cocoons for biomedical applications.

Neodymium hydroxide (Nd(OH)3)-surface modified mesoporous silica micro-cocoon microstructures were prepared using a facile single-step sol-gel chemical process. XRD revealed the semi-crystalline nature of the as-prepared materials. TEM and SEM micrographs exhibited highly monodisperse, non-aggregated, typical ordered mesoporous, and irregular sized cocoon-shaped micro-structures with a narrow size distribution. Optical properties, that were examined in the aqueous media, revealed a high colloidal stability and the formation of a semi-transparent colloidal solution. The colloidal solution of Nd(OH)3-surface functionalized micro-structures revealed well characteristics absorption bands of Nd3+ ions in the visible region. thus validating the successful coating of SiO2@Nd(OH)3 layer over the surface silica forming core-shell structures. Zeta potential, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) bromide, and neutral red uptake assays were applied in a dose-dependent manner to investigate the biocompatibility and toxic potential of the designed cocoon-shaped microstructures. Both the assays and the high zeta potential value demonstrated good cell viability even at high concentrations and hydrophilic conditions, indicating excellent biocompatibility and non-toxicity. These highly hydrophilic, optically active, mesoporous, biocompatible, and non-toxic cocoon-shaped microstructures could be potentially suitable candidates for optical bio-probes and drug delivery applications.

The anti-oxidant enzyme, Prdx6 might have cis-acting regulatory sequence(s).

Peroxiredoxin 6 (Prdx6) is a ubiquitously expressed 1-cysteine Peroxiredoxin found throughout all phyla. In mammals, under different physiological conditions, it has evolved from a peroxidase to a multifunctional enzyme. Among the mammalian Prdx6's, human and rat Prdx6's are the most extensively studied. Our study revealed that human and rat Prdx6's exhibit differences in their peroxidase activity. These two Prdx6's have only 8% difference in their primary sequence (with 19 amino acids) with no apparent modification at any of the key conserved residues. In the present communication, we have investigated the roles of thermodynamics, structure and internal flexibility of Prdx6 to account for the difference in their peroxidase activity. We discovered that these amino acid variations have led to structural alterations in human Prdx6 so that it shows enhanced intrinsic dynamics (or flexibility) than the rat protein. We could also identify the gain of intrinsic dynamics of the catalytic site in human Prdx6 due to relocation of an important active site residue (R132) to the loop region as the most plausible reason for high catalytic activity in the human protein as compared to rat variant. Since it is the thioredoxin fold that upholds the peroxidase function, certain structural alteration in the Prdx6 structure might help to regulate the efficiency of thioredoxin folds. Our results hint that Prdx6 might have a cis-acting regulatory sequence(s).

BNCT induced immunomodulatory effects contribute to mammary tumor inhibition.

In the United States, breast cancer is one of the most common and the second leading cause of cancer-related death in women. Treatment modalities for mammary tumor are surgical removal of the tumor tissue followed by either chemotherapy or radiotherapy or both. Radiation therapy is a whole body irradiation regimen that suppresses the immune system leaving hosts susceptible to infection or secondary tumors. Boron neutron capture therapy (BNCT) in that regard is more selective, the cells that are mostly affected are those that are loaded with 109 or more 10B atoms. Previously, we have described that liposomal encapsulation of boron-rich compounds such as TAC and MAC deliver a high payload to the tumor tissue when injected intravenously. Here we report that liposome-mediated boron delivery to the tumor is inversely proportional to the size of the murine mammary (EMT-6) tumors. The plausible reason for the inverse ratio of boron and EMT-6 tumor size is the necrosis in these tumors, which is more prominent in the large tumors. The large tumors also have receding blood vessels contributing further to poor boron delivery to these tumors. We next report that the presence of boron in blood is essential for the effects of BNCT on EMT-6 tumor inhibition as direct injection of boron-rich liposomes did not provide any added advantage in inhibition of EMT-6 tumor in BALB/c mice following irradiation despite having a significantly higher amount of boron in the tumor tissue. BNCT reaction in PBMCs resulted in the modification of these cells to anti-tumor phenotype. In this study, we report the immunomodulatory effects of BNCT when boron-rich compounds are delivered systemically.