Synthesis, characterization, pharmacological and computational evaluation of hyaluronic acid modified chebulinic acid encapsulated chitosan nanocomposite for cancer therapy.

The purpose of this study was to produce hyaluronic acid customized nanoparticles with chitosan for the delivery of chebulinic acid (CLA) to enhance its anticancer potential against breast cancer. A significant portion of CLA was encapsulated (89.72 ± 4.38 %) and loaded (43.15 ± 5.61 %) within hybrid nanoparticles. The colloidal hybrid nanoparticles demonstrated a polydispersity index (PDI) of about 0.379 ± 0.112, with zeta capacitance of 32.69 ± 5.12 (mV), and an average size of 115 ± 8 (nm). It was found that CLA-CT-HA-NPs had stronger anticancer effects on MCF-7 cells (IC50 = 8.18 ± 3.02 µM) than pure CLA (IC50 = 17.15 ± 5.11 µM). The initial cytotoxicity findings were supported by additional investigations based on comet assay and flow cytometry analysis. Tumor remission and survival were evaluated in five separate groups of mice. When juxtaposed with pure CLA (3.17 ± 0.419 %), CLA-CT-HA-NPs improved survival rates and reduced tumor burden by 3.76 ± 0.811(%). Furthermore, in-silico molecular docking investigations revealed that various biodegradable polymers had several levels of compatibility with CLA. The outcomes of this study might potentially served as an effective strategy for delivering drugs in the context of breast cancer therapy.

Fabrication and evaluation of anticancer potential of diosgenin incorporated chitosan-silver nanoparticles; in vitro, in silico and in vivo studies.

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 µg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.

Preparation and investigation of a novel combination of Solanum nigrum-loaded, arabinoxylan-cross-linked ß-cyclodextrin nanosponges for the treatment of cancer: in vitro, in vivo, and in silico evaluation.

Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability. Methods: In this study, Solanum nigrum, an effective medicinal plant, loaded arabinoxylan cross-linked ß-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters. Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, -29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 µg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that ß-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = -10.1 Kcal/mol). Conclusion: Therefore, findings of current study elucidated the therapeutic potential of ß-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs.

Cryopreservation of bioflavonoid-rich plant sources and bioflavonoid-microcapsules: emerging technologies for preserving bioactivity and enhancing nutraceutical applications.

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids' shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids' bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

An Unfortunate Incident Of A Surgical Swab Left In The Sphenoid Sinus For Eight Years.

Retained foreign bodies are foreign materials which are left accidentally inside a patient's body after a procedure. In this report we present the case of a 57 year old man who presented to the ENT clinic with a history of symptoms stretching over 8 years back to when he underwent a hypophysectomy through the transsphenoidal approach. These symptoms included cacosmia, ageusia, altered taste at times, foul smelling discharge, nasal discharge and dizziness. He had undergone multiple radiological examinations as well as antibiotic courses. It was only after the examination of the nose under general anaesthesia, conducted by the corresponding author that a swab was found in the sphenoid sinus which was left behind from his surgery 8 years ago. Cases of retained foreign bodies are very rare and are easily preventable. This case highlights the importance of adherence to health and safety protocols to prevent such an avoidable complication.

Fabrication and Evaluation of Anticancer Potential of Eugenol Incorporated Chitosan-Silver Nanocomposites: In Vitro, In Vivo, and In Silico Studies.

The expanding global cancer burden necessitates a comprehensive strategy to promote possible therapeutic interventions. Nanomedicine is a cutting-edge approach for treating cancer with minimal adverse effects. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Eugenol (EGN) were synthesized and evaluated for their anticancer activity against breast cancer cells (MCF-7). The physical, pharmacological, and molecular docking studies were used to characterize these nanoparticles. EGN had been effectively entrapped into hybrid NPs (84 ± 7%). The EGN-ChAgNPs had a diameter of 128 ± 14 nm, a PDI of 0.472 ± 0.118, and a zeta potential of 30.58 ± 6.92 mV. Anticancer activity was measured in vitro using an SRB assay, and the findings revealed that EGN-ChAgNPs demonstrated stronger anticancer activity against MCF-7 cells (IC50 = 14.87 ± 5.34 µg/ml) than pure EGN (30.72 ± 4.91 µg/ml). To support initial cytotoxicity findings, advanced procedures such as cell cycle analysis and genotoxicity were performed. Tumor weight reduction and survival rate were determined using different groups of mice. Both survival rates and tumor weight reduction were higher in the EGN-ChAgNPs (12.5 mg/kg) treated group than in the pure EGN treated group. Based on protein-ligand interactions, it might be proposed that eugenol had a favorable interaction with Aurora Kinase A. It was observed that C9 had the highest HYDE score of any sample, measuring at -6.8 kJ/mol. These results, in conjunction with physical and pharmacological evaluations, implies that EGN-ChAgNPs may be a suitable drug delivery method for treating breast cancer in a safe and efficient way.

Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies.

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of -39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA-NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.

Bone Cement Cranioplasty Reduces Cerebrospinal Fluid Leak Rate after Microvascular Decompression: A Single-Institutional Experience.

Background Microvascular decompression (MVD) is a common surgical treatment for cranial nerve compression, though cerebrospinal fluid (CSF) leak is a known complication of this procedure. Bone cement cranioplasty may reduce rates of CSF leak. Objective To compare rates of CSF leak before and after implementation of bone cement cranioplasty for the reconstruction of cranial defects after MVD. Methods Retrospective chart review was performed of patients who underwent MVD through retrosigmoid craniectomy for cranial nerve compression at a single institution from 1998 to 2017. Study variables included patient demographics, medical history, type of closure, and postoperative complications such as CSF leak, meningitis, lumbar drain placement, and ventriculoperitoneal shunt insertion. Cement and noncement closure groups were compared, and predictors of CSF leak were assessed using a multivariate logistic regression model. Results A total of 547 patients treated by 10 neurosurgeons were followed up for more than 20 years, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Baseline comorbidities were not significantly different between groups. CSF leak rate was significantly lower in the cement group than in the noncement group (4.5 vs. 14.3%; p < 0.001). This was associated with significantly fewer patients developing postoperative meningitis (0.7 vs. 5.2%; p = 0.003). Multiple logistic regression model demonstrated noncement closure as the only independent predictor of CSF leak (odds ratio: 3.55; 95% CI: 1.78-7.06; p < 0.001). Conclusion CSF leak is a well-known complication after MVD. Bone cement cranioplasty significantly reduces the incidence of postoperative CSF leak and other complications. Modifiable risk factors such as body mass index were not associated with the development of CSF leak.

Microvascular Decompression for Trigeminal Neuralgia in Patients with Multiple Sclerosis: Predictors of Treatment Success.

BACKGROUND: Microvascular decompression (MVD) is highly effective in managing the neuropathic facial pain of trigeminal neuralgia (TN). Its utility in patients with TN and concurrent multiple sclerosis (MS) has been a subject of debate. The goal of this study was to identify demographic and perioperative variables associated with favorable outcome after MVD over the past 20 years in patients from our institution. METHODS: A retrospective analysis of our cohort of 33 patients diagnosed with MS and TN who underwent MVD between 1997 and 2017 to treat neuropathic facial pain was performed. Perioperative variables included MS disease burden, findings on preoperative magnetic resonance imaging (MRI), TN pain severity, and the presence of intraoperative neurovascular compression. MS disease burden was quantified using the Expanded Disability Status Scale. Preoperative and postoperative pain severity was quantified using the Barrow Neurological Institute (BNI) pain severity scale. RESULTS: A total of 33 patients with TN and MS were treated with MVD at our institution (out of the 632 total MVDs performed) between 1997 and 2017. Twenty-two patients (67%) maintained a reduction in pain at a mean follow-up of 53.5 months. Higher preoperative BNI pain intensity score was associated with unfavorable outcome after MVD (P = 0.006). No associations were identified between MS disease burden, presence of neurovascular compression or pontine demyelinating plaques on MRI, or intraoperative findings of neurovascular compression and treatment outcomes. CONCLUSIONS: MVD is a reasonable treatment option for patients with TN and MS, although the rate of freedom from pain is lower than that for the general TN population. Preoperative pain severity may be a predictor of treatment success.

Synthesis of novel (E)-1-(2-(2-(4(dimethylamino) benzylidene) hydrazinyl)-4-methylthiazol-5-yl)ethanone derivatives as ecto-5'-nucleotidase inhibitors.

Ecto-5'-nucleotidase (e5'NT), a membrane-bound enzyme and an essential member of ecto-nucleotidases which regulates extracellular purinergic signalling. Their upregulation results in various disease conditions, for example, inflammation, hypoxia and cancer. Therefore, efforts have been made to synthesize potent and selective inhibitors of e5'NT. Here we have synthesized, characterized and evaluated six thiazole derivatives (3a-3f) as potent e5'NT inhibitors. Among all derivatives, the compound (E)-1-(4-methyl-2-(2-(pyridin-3-ylmethylene)hydrazinyl) thiazol-5-yl)ethanone (3a) exhibited maximum inhibition towards both human and rat enzymes. However, their potency against h-e5'NT was 24-fold higher than r-e5'NT. Only two compounds exhibited inhibitory behaviour towards r-e5'NT. The molecular structures of these derivatives were confirmed with the help of solid-state characterization through NMR (1H and 13C), FTIR and elemental analysis. Additionally, molecular docking was also implemented to explain putative bonding interaction between the active site of an enzyme and potent inhibitors.

Antioxidant activity and nutritional assessment of under-utilized medicinal plants.

The present study investigates the nutritive and anti-nutritive composition of six species (Allium porrum, Amaranthus spinosis, Apium graveolens, Caralluma edulis, Chenopodium album, Urtica dioica). The studied species contained considerable amount of crude protein (4.53-11.41%), crude fat (1.25-3.74%), vitamin C (7.85-28.09mg 100-1 g) and ß-Carotene (18.29-169.33mg 100-1g). The mineral profile of Chenopodium album is considered as potential source of Zn (14.51±1.14mg 100-1g), Mn (67.71±0.85mg 100-1g), Se (8.45±0.49mg 100-1g) and Fe (182.08±1.52mg 100-1g) and Caralluma edulis as potential source of Fe (7.28± 0.03mg 100-1g). Ca and P content ranged 63-306mg 100-1 g and 12-392mg 100-1 g in all studied plants with exceptionally high level was found in Chenopodium album (1084mg 100-1g) and (3924mg 100-1g), respectively. Similarly, total phenol, tannin and phytic acid were found in the range of 105-354, 5-90 and 10-85mg 100-1g, respectively. Total oxalates and soluble oxalates contents were below 200mg 100-1g in five examined plants with the exception of Chenopodium album (413mg 100-1g). Antioxidant activity of Caralluma edulis was found maximum while the rest of the examined plants had moderate levels.

A novel example of double 6-exo-trig heterocyclization: nitrile conversion to new anticancer active (HeLa cells) primary amine ionic liquids.

Conversion of nitriles under mild conditions leads to a new class of primary amines, including room temperature ionic liquids, acting as efficient anticancer agents.

Cytotoxicity and enzyme inhibition studies of polyoxometalates and their chitosan nanoassemblies.

Polyoxometalates (POMs) have become very significant in biomedical research for their structural diversity which renders them highly active against bacterial, viral and cancer diseases. In this study three different POMs were synthesized and nanoassemblies were made with chitosan (CTS), a natural biodegradable polymer with excellent drug carrier properties. The compounds were tested on two isoenzymes of alkaline phosphatases including tissue specific calf intestine alkaline phosphatase (CIAP) and tissue non-specific alkaline phosphatase (TNAP). Compound [TeW6O24]6- (TeW6) showed the highest activity (45.4 ± 11.3 nM) among tested compounds against TNAP. Similarly, chitosan-[TeW6O24]6- (CTS-TeW6) was proved to be a potent inhibitor of CIAP with Ki value of 22 ± 7 nM. A comparative study was made to evaluate their cytotoxic potential against HeLa cells. Among all tested compounds, Chitosan-[NaP5W30O110]14- (CTS-P5W30) has showed higher percent cytotoxicity (88 ± 10%) at 10 µM when compared with the standard anticancer drug vincristine (72 ± 7%). The study revealed that selected POMs proved excellent anticancer potential and were equally effective against alkaline phosphatase enzyme, an increased level of which may indicate cancer metastasis.

Preparation of high purity nickel film from industrial effluent by the distribution of charge over microelectrodes using newly designed free electrolytic diffusion approach.

The present work deals with the development of a newly designed free electrolytic diffusion approach (the distribution of charge over microelectrodes) for the purification of metals and was successfully applied for the purification of nickel from the industrial effluent containing high proportion of nickel. Atomic absorption spectrophotometer (AAS) analyzed the purified nickel deposited on working microelectrodes. The results obtained show that the purity of nickel was enhanced from 95% to 99.9% with traces of copper etc. It was concluded that distribution of charge over the microcathodes at a rate of 50 cycles per second (cps) shows better results for the production of high purity (HP) nickel as compared to 25 cycles per second (cps).

Comparative studies on storage stability of ferrous iron in whole wheat flour and flat bread (naan).

Whole wheat flour was fortified with premix containing ferrous sulfate, ethylenediamine tetraacetic acid and folic acid (20.0:20.0:1.5 ppm) and was stored at ambient temperature for 60 days. Naans (flat bread) were prepared from 0 ppm, 25 ppm, 50 ppm and 75 ppm ferrous iron-fortified flour samples at 10-day intervals and were analyzed for physicochemical constants and sensory evaluation. It was observed that flour containing 75 ppm ferrous sulfate contained the highest iron residues. The total iron in flour samples showed no significant difference, while ferrous iron significantly decreased in fortified flour (0.53-3.08%) and in the naans (0.42-3.48%) because of its oxidation to ferric iron during storage. The phytic acid content decreased (0.886-0.810%) significantly during the same storage period. Iron levels affected some sensory characteristics significantly (P < or =0.05), including color, texture, flexibility, chewability and overall acceptability of the naans, but not taste and flavor. The sensory attributes of naans illustrated that naans containing 50 ppm ferrous iron are more acceptable than those prepared with 75 ppm ferrous iron.