High shear wet granulation is commonly applied technique for commercial manufacturing of tablets. Granulation process for tablets manufacturing is generally optimized by hit and trial which involves ...preparation of granules under different processing parameters, compression of granules and evaluation of the resultant tablets; and adjustment is made in granulation process on the basis of characteristics of tablets. Objective of the study was to optimize the process of high shear wet granulation and prediction of characteristics of tablets on the basis of properties of granules. Atenolol granules were prepared by high shear wet granulation method, using aqueous solution of polyvinyl pyrrolidone (PVP k-30) as binder. Concentration of binder solution and granulation time were taken as process variables, both studied at three levels. Different combinations of process variables were determined by Design Expert software. Granules were evaluated for different parameters on the basis of SeDeM-ODT (Sediment Delivery Model-Oro Dispersible Tablets) expert system. Granules from all the trials were compressed using round (10.5 mm) flat faced punches at compression weight of 250 mg/tablet. Tablets were evaluated of different quality control parameters as per USP. Results showed that both the process variables had positive effect on mechanical strength of tablets and negative effect on disintegration and dissolution rate. Granule prepared with highest level of binder concentration (15%) and highest granulation time (60 sec) resulted in tablets with highest crushing strength (11.8 kg), specific crushing strength (0.328 kg/mm2), tensile strength (0.208 kg/mm2), lowest value of friability (0.19%) and highest disintegration time (10.9 min), as predicted from granules characteristics on the basis of SeDeM-ODT expert system. Drug release from Trial-13 (processed under highest level of both process parameters) was also lower than rest of the trials. It is concluded from the study that quality characteristics of tablets can be predicted from granules characteristics using SeDeM-ODT expert system. Furthermore, SeDeM-ODT expert system can also be used for optimization of the process of high shear wet granulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study was conducted to investigate the concentrations of heavy metals in soil and vegetables, and human health risks through ingestion of contaminated vegetables. Soil and vegetable samples were ...collected from different locations in Gilgit, northern Pakistan, and analyzed for Cd, Cu, Ni, Pb and Zn. Plant transfer factors (PTF), daily intake of metals (DIM) and health risk index (HRI) were also calculated. The concentrations of Cd, Cu and Zn exceeded their respective permissible limits in soil samples. The highest concentrations of Cu, Ni, Pb and Zn were observed in the edible parts of
Malva neglecta,
Brassica oleracea,
Mintha sylvestris and
Brassica campestris, respectively. PTF values were lower for all the selected heavy metals, except for Cd. Furthermore, the HRI values were within the safe limit (<1) except for Pb; therefore, the health risks of metals through ingestion of vegetables were of great concern in the study area.
Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the
gene located on long ...arm of chromosome 17. The primary gene product undergoes several modifications, such as the removal of introns and signal peptides, and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing inactive proMPO by the insertion of a heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into the extracellular fluid after oxidative stress and different inflammatory responses. Myeloperoxidase is the only type of peroxidase that uses H₂O₂ to oxidize several halides and pseudohalides to form different hypohalous acids. So, the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and the pathogenesis of several other major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants. Thus, the enhanced level of MPO activity is one of the best diagnostic tools of inflammatory and oxidative stress biomarkers among these commonly-occurring diseases.
Image processing plays a major role in neurologists' clinical diagnosis in the medical field. Several types of imagery are used for diagnostics, tumor segmentation, and classification. Magnetic ...resonance imaging (MRI) is favored among all modalities due to its noninvasive nature and better representation of internal tumor information. Indeed, early diagnosis may increase the chances of being lifesaving. However, the manual dissection and classification of brain tumors based on MRI is vulnerable to error, time‐consuming, and formidable task. Consequently, this article presents a deep learning approach to classify brain tumors using an MRI data analysis to assist practitioners. The recommended method comprises three main phases: preprocessing, brain tumor segmentation using k‐means clustering, and finally, classify tumors into their respective categories (benign/malignant) using MRI data through a finetuned VGG19 (i.e., 19 layered Visual Geometric Group) model. Moreover, for better classification accuracy, the synthetic data augmentation concept i s introduced to increase available data size for classifier training. The proposed approach was evaluated on BraTS 2015 benchmarks data sets through rigorous experiments. The results endorse the effectiveness of the proposed strategy and it achieved better accuracy compared to the previously reported state of the art techniques.
Following preprocessing, ROI extracted using K‐means clustering & finetune VGG19 model for tumor classification (benign/malignant) applied, accuracy improved using synthetic data augmentation.
In the adult brain, Wnt signaling is crucial for neurogenesis, and it also regulates neuronal development, neuronal maturation, neuronal differential, and proliferation. Impaired Wnt signaling ...pathways are associated with enhanced levels of amyloid-β, reduced β-catenin levels, and increased expression of GSK-3β enzyme, suggesting its direct association with the pathogenesis of Alzheimer’s disorder (AD). These findings are consolidated by reports where activation of Wnt signaling by genetic factors and pharmacological intervention has improved the cognitive functions in animals and restored neurogenesis in the adult brain. Various natural and synthetic molecules have been identified that modulate Wnt signaling in the adult brain and promote neurogenesis and alleviate behavioral dysfunction. These molecules include lithium, valproic acid, ethosuximide, selenomethionine, curcumin, andrographolide, xanthoceraside, huperzine A, pyridostigmine, ginkgolide-B, ricinine, cannabidiol, and resveratrol. These molecules are associated with the DKK1 and GSK-3β inhibition and β-catenin stabilization along with their effects on neurogenesis, neuronal proliferation, and differentiation in the hippocampus through modulation of Wnt signaling and thereby could prove beneficial in the management of AD pathogenesis. Although modulation of the Wnt signaling seems to suggest to be promising in the management of AD, unfortunately, most of the literature available for the association of Wnt signaling and AD pathogenesis is either from preclinical studies or post-mortem brain. Therefore, it will be interesting to understand the role of Wnt signaling in AD patients, and a rigorous investigation could provide us with a better understanding of AD pathogenesis and the identification of novel targets for therapeutic interventions.
•Since COVID-19 broke out, there has been renewed interest in understanding the impact of historical and more recent epidemics and pandemics on social conflict.•Evidence suggests that epidemics are ...more likely to lead to social conflict when they are not too lethal, have distressing symptoms, or disproportionately kill young children.•That is also the case for intermediary levels of scientific knowledge, when intergroup tensions are rife, and when authorities adopt heavy-handed policies causing distrust.•Anecdotal evidence of scapegoating during COVID appears consistent with how these channels shaped the epidemic-scapegoating relationship in the past.
Since COVID-19 broke out, there has been renewed interest in understanding the economic and social dynamics of historical and more recent epidemics and pandemics, from the plagues of Antiquity to modern-day outbreaks like Ebola. These events can have significant impacts on the interplay between poverty and social cohesion, i.e. how different groups in society interact and cooperate to survive and prosper. To that effect, this paper provides a theory-driven overview of how social responses to past epidemics and pandemics were determined by the epidemiological and non-epidemiological characteristics of these outbreaks, with a particular focus on the conditions giving rise to scapegoating and persecution of minority groups, including migrants. We discuss existing theories as well as historical and quantitative studies, and highlight the cases where epidemics and pandemics may lead to milder or more severe forms of scapegoating. Finally, we conclude with a summary of priorities for future research on epidemics, pandemics and social conflict and discuss the possible effects and policy implications of COVID-19.
Chitosan-supported; Ciprofloxacin-HCl-Chitosan/Tween/Tri polyphosphate (CIP@CH-TW/TPP) an efficient drug delivery system has been successfully developed using simple sol-gel chemical route. The drug ...encapsulated nanocomposite was interacted with bovine serum albumin (BSA) to deliver the drug at targeted site. Incorporation of tween-80 onto CIP/CH-TPP enhanced loading capacity of nanocomposite and improves drug releasing efficiency up to 61–78% as compared to native chitosan (37%). The CH-TW/TPP nanocomposite has been characterized using FTIR, TGA-DTA, DLS, SEM and XRD analyses. Biophysical properties were performed to achieve optimum interaction of CIP@CH-TW/TPP with BSA that is the novelty of the present study. The effect of surfactant concentration on CIP–BSA interaction was studied using different concentrations of Tween-80 (1 μM and 2 μM) via fluorescence, UV–Vis and circular dichroism (CD) technique. The findings of fluorescence quenching study reveal the binding of CIP with BSA via a static process which results formation of CIP–BSA complex. The results of thermodynamic studies (ΔG, ΔH and ΔS) indicate that the hydrogen bonding and Vander Waals forces play a vital role to achieve optimal CIP-BSA interaction. Molecular modeling calculations and displacement study results confirm the binding of CIP with BSA at site I. Significant results of drug–protein interactions establish the applicability of synthesized CIP@CH-TW/TPP nanocomposite in drug delivery system.
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•Development of Ciprofloxacin-HCl loaded CH/TW-TPP nanocomposite for drug delivery•The interactions of CIP and NCIP with BSA using biophysical methods and molecular docking•Improvement in clinical efficacy of ciprofloxacin using CH/TW-TPP nanocomposite
Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease, multiple ...sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.
Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains and losses, including ETS gene family fusions, PTEN loss and androgen ...receptor (AR) amplification, which drive prostate cancer development and progression to lethal, metastatic castration-resistant prostate cancer (CRPC). However, less is known about the role of mutations. Here we sequenced the exomes of 50 lethal, heavily pre-treated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment-naive, high-grade localized prostate cancers. We identified low overall mutation rates even in heavily treated CRPCs (2.00 per megabase) and confirmed the monoclonal origin of lethal CRPC. Integrating exome copy number analysis identified disruptions of CHD1 that define a subtype of ETS gene family fusion-negative prostate cancer. Similarly, we demonstrate that ETS2, which is deleted in approximately one-third of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation. Furthermore, we identified recurrent mutations in multiple chromatin- and histone-modifying genes, including MLL2 (mutated in 8.6% of prostate cancers), and demonstrate interaction of the MLL complex with the AR, which is required for AR-mediated signalling. We also identified novel recurrent mutations in the AR collaborating factor FOXA1, which is mutated in 5 of 147 (3.4%) prostate cancers (both untreated localized prostate cancer and CRPC), and showed that mutated FOXA1 represses androgen signalling and increases tumour growth. Proteins that physically interact with the AR, such as the ERG gene fusion product, FOXA1, MLL2, UTX (also known as KDM6A) and ASXL1 were found to be mutated in CRPC. In summary, we describe the mutational landscape of a heavily treated metastatic cancer, identify novel mechanisms of AR signalling deregulated in prostate cancer, and prioritize candidates for future study.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ1–42)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction ...in mice. For the development of an AD mouse model, amyloid-beta (Aβ1–42, 5 μL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice’s brain by using a stereotaxic frame. After that, the mice were treated with Luteolin for two weeks at a dose of 80 mg/kg/day. To monitor the biochemical changes, we conducted western blotting and immunofluorescence analysis. According to our findings, the infusion of amyloid-beta activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental mice; these changes were significantly inhibited in Aβ1–42 + Luteolin-treated mice. Likewise, we also checked the expression of inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB p65 (Ser536), tissue necrosis factor (TNF-α), and Interleukin1-β (IL-1β), in Aβ1–42-injected mice brain, which was attenuated in Aβ1–42 + Luteolin-treated mice brains. Further, we investigated the expression of pro- and anti-apoptotic cell death markers such as Bax, Bcl-2, Caspase-3, and Cox-2, which was significantly reduced in Aβ1–42 + Lut-treated mice brains compared to the brains of the Aβ-injected group. The results also indicated that with the administration of Aβ1–42, the expression levels of β-site amyloid precursor protein cleaving enzyme (BACE-1) and amyloid-beta (Aβ1–42) were significantly enhanced, while they were reduced in Aβ1–42 + Luteolin-treated mice. We also checked the expression of synaptic markers such as PSD-95 and SNAP-25, which was significantly enhanced in Aβ1–42 + Lut-treated mice. To unveil the underlying factors responsible for the protective effects of Luteolin against AD, we used a specific JNK inhibitor, which suggested that Luteolin reduced Aβ-associated neuroinflammation and neurodegeneration via inhibition of JNK. Collectively, our results indicate that Luteolin could serve as a novel therapeutic agent against AD-like pathological changes in mice.
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