Artificial neural network-assisted prediction of radiobiological indices in head and neck cancer.

Background and purpose: We proposed an artificial neural network model to predict radiobiological parameters for the head and neck squamous cell carcinoma patients treated with radiation therapy. The model uses the tumor specification, demographics, and radiation dose distribution to predict the tumor control probability and the normal tissue complications probability. These indices are crucial for the assessment and clinical management of cancer patients during treatment planning. Methods: Two publicly available datasets of 31 and 215 head and neck squamous cell carcinoma patients treated with conformal radiation therapy were selected. The demographics, tumor specifications, and radiation therapy treatment parameters were extracted from the datasets used as inputs for the training of perceptron. Radiobiological indices are calculated by open-source software using dosevolume histograms from radiation therapy treatment plans. Those indices were used as output in the training of a single-layer neural network. The distribution of data used for training, validation, and testing purposes was 70, 15, and 15%, respectively. Results: The best performance of the neural network was noted at epoch number 32 with the mean squared error of 0.0465. The accuracy of the prediction of radiobiological indices by the artificial neural network in training, validation, and test phases were determined to be 0.89, 0.87, and 0.82, respectively. We also found that the percentage volume of parotid inside the planning target volume is the significant parameter for the prediction of normal tissue complications probability. Conclusion: We believe that the model has significant potential to predict radiobiological indices and help clinicians in treatment plan evaluation and treatment management of head and neck squamous cell carcinoma patients.

Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents.

Benzimidazole-based pyrrole/piperidine analogs (1-26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1-13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC50 = 16.11 ± 0.33 µM) and galantamine (IC50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14-26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC50 = 20.01 ± 0.12 µM) and galantamine (IC50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of -10.50, -9.3, -7.73 and -7.8 for AChE and -8.97, -8.2, -8.20 and -7.6 for BuChE, respectively.

Biochemical Investigation of Therapeutic Efficacy of Berberine-Enriched Extract in Streptozotocin-Induced Metabolic Impairment.

Metabolic disorders pose significant global health challenges, necessitating innovative therapeutic approaches. This study focused on the multifaceted therapeutic potential of berberine-enriched extract (BEE) in mitigating metabolic impairment induced by streptozotocin (STZ) in a rat model and compared the effects of BEE with berberine (BBR) and metformin (MET) to comprehensively evaluate their impact on various biochemical parameters. Our investigation reveals that BEE surpasses the effects of BBR and MET in ameliorating metabolic impairment, making it a promising candidate for managing metabolic disorders. For this, 30 male Wistar rats were divided into five groups (n = 6): control (CN), STZ, STZ + MET, STZ + BBR, and STZ + BEE. The treatment duration was extended over 4 weeks, during which various biochemical parameters were monitored, including fasting blood glucose (FBG), lipid profiles, inflammation, liver and kidney function biomarkers, and gene expressions of various metabolizing enzymes. The induction of metabolic impairment by STZ was evident through an elevated FBG level and disrupted lipid profiles. The enriched extract effectively regulated glucose homeostasis, as evidenced by the restoration of FBG levels, superior to both BBR and MET. Furthermore, BEE demonstrated potent effects on insulin sensitivity, upregulating the key genes involved in carbohydrate metabolism: GCK, IGF-1, and GLUT2. This highlights its potential in enhancing glucose utilization and insulin responsiveness. Dyslipidemia, a common occurrence in metabolic disorders, was effectively managed by BEE. The extract exhibited superior efficacy in regulating lipid profiles. Additionally, BEE exhibited significant anti-inflammatory properties, surpassing the effects of BBR and MET in lowering the levels of inflammatory biomarkers (IL-6 and TNF-α), thereby ameliorating insulin resistance and systemic inflammation. The extract's superior hepatoprotective and nephroprotective effects, indicated by the restoration of liver and kidney function biomarkers, further highlight its potential in maintaining organ health. Moreover, BEE demonstrated potent antioxidant properties, reducing oxidative stress and lipid peroxidation in liver tissue homogenates. Histopathological examination of the pancreas underscored the protective effects of BEE, preserving and recovering pancreatic ß-cells damaged by STZ. This collective evidence positions BEE as a promising therapeutic candidate for managing metabolic disorders and offers potential benefits beyond current treatments. In conclusion, our findings emphasize the remarkable therapeutic efficacy of BEE and provide a foundation for further research into its mechanisms, long-term safety, and clinical translation.

Real-time fluorescent monitoring of phase I xenobiotic-metabolizing enzymes.

This article explores the intricate landscape of advanced fluorescent probes crafted for the detection and real-time monitoring of phase I xenobiotic-metabolizing enzymes. Employing state-of-the-art technologies, such as fluorescence resonance energy transfer, intramolecular charge transfer, and solid-state luminescence enhancement, this article unfolds a multifaceted approach to unraveling the dynamics of enzymatic processes within living systems. This encompassing study involves the development and application of a diverse range of fluorescent probes, each intricately designed with tailored mechanisms to heighten sensitivity, providing dynamic insights into phase I xenobiotic-metabolizing enzymes. Understanding the role of phase I xenobiotic-metabolizing enzymes in these pathophysiological processes, is essential for both medical research and clinical practice. This knowledge can guide the development of approaches to prevent, diagnose, and treat a broad spectrum of diseases and conditions. This adaptability underscores their potential clinical applications in cancer diagnosis and personalized medicine. Noteworthy are the trifunctional fluorogenic probes, uniquely designed not only for fluorescence-based cellular imaging but also for the isolation of cellular glycosidases. This innovative feature opens novel avenues for comprehensive studies in enzyme biology, paving the way for potential therapeutic interventions. The research accentuates the selectivity and specificity of the probes, showcasing their proficiency in distinguishing various enzymes and their isoforms. The sophisticated design and successful deployment of these fluorescent probes mark significant advancements in enzymology, providing powerful tools for both researchers and clinicians. Beyond their immediate applications, these probes offer illuminating insights into disease mechanisms, facilitating early detection, and catalyzing the development of targeted therapeutic interventions. This work represents a substantial leap forward in the field, promising transformative implications for understanding and addressing complex biological processes. In essence, this research heralds a new era in the development of fluorescent probes, presenting a comprehensive and innovative approach that not only expands the understanding of cellular enzyme activities but also holds great promise for practical applications in clinical settings and therapeutic endeavors.

Comprehensive analysis of MAPK gene family in upland cotton (Gossypium hirsutum) and functional characterization of GhMPK31 in regulating defense response to insect infestation.

KEY MESSAGE: The transcriptomic, phenotypic and metabolomic analysis of transgenic plants overexpressing GhMPK31 in upland cotton revealed the regulation of H2O2 burst and the synthesis of defensive metabolites by GhMPK31. Mitogen-activated protein kinases (MAPKs) are a crucial class of protein kinases, which play an essential role in various biological processes in plants. Upland cotton (G. hirsutum) is the most widely cultivated cotton species with high economic value. To gain a better understanding of the role of the MAPK gene family, we conducted a comprehensive analysis of the MAPK gene family in cotton. In this study, a total of 55 GhMPK genes were identified from the whole genome of G. hirsutum. Through an investigation of the expression patterns under diverse stress conditions, we discovered that the majority of GhMPK family members demonstrated robust responses to abiotic stress, pathogen stress and pest stress. Furthermore, the overexpression of GhMPK31 in cotton leaves led to a hypersensitive response (HR)-like cell death phenotype and impaired the defense capability of cotton against herbivorous insects. Transcriptome and metabolomics data analysis showed that overexpression of GhMPK31 enhanced the expression of H2O2-related genes and reduced the accumulation of defensive related metabolites. The direct evidence of GhMPK31 interacting with GhRBOHB (H2O2-generating protein) were found by Y2H, BiFC, and LCI. Therefore, we propose that the increase of H2O2 content caused by overexpression of GhMPK31 resulted in HR-like cell death in cotton leaves while reducing the accumulation of defensive metabolites, ultimately leading to a decrease in the defense ability of cotton against herbivorous insects. This study provides valuable insights into the function of MAPK genes in plant resistance to herbivorous insects.

Effect of Maternal and Newborn Care Service Package on Perinatal and Newborn Mortality: A Cluster Randomized Clinical Trial.

Importance: In resource-constrained settings where the neonatal mortality rate (NMR) is high due to preventable causes and health systems are underused, community-based interventions can increase newborn survival by improving health care practices. Objectives: To develop and evaluate the effectiveness of a community-based maternal and newborn care services package to reduce perinatal and neonatal mortality in rural Pakistan. Design, Setting, and Participants: This cluster randomized clinical trial was conducted between November 1, 2012, and December 31, 2013, in district Rahim Yar Khan in the province of Punjab. A cluster was defined as an administrative union council. Any consenting pregnant resident of the study area, regardless of gestational age, was enrolled. An ongoing pregnancy surveillance system identified 12 529 and 12 333 pregnancies in the intervention and control clusters, respectively; 9410 pregnancies were excluded from analysis due to continuation of pregnancy at the end of the study, loss to follow-up, or miscarriage. Participants were followed up until the 40th postpartum day. Statistical analysis was performed from January to May 2014. Intervention: A maternal and newborn health pack, training for community- and facility-based health care professionals, and community mobilization through counseling and education sessions. Main Outcomes and Measures: The primary outcome was perinatal mortality, defined as stillbirths per 1000 births and neonatal death within 7 days per 1000 live births. The secondary outcome was neonatal mortality, defined as death within 28 days of life per 1000 live births. Systematic random sampling was used to allocate 10 clusters each to intervention and control groups. Analysis was conducted on a modified intention-to-treat basis. Results: For the control group vs the intervention group, the total number of households was 33 188 vs 34 315, the median number of households per cluster was 3092 (IQR, 3018-3467) vs 3469 (IQR, 3019-4075), the total population was 229 155 vs 234 674, the mean (SD) number of residents per household was 6.9 (9.5) vs 6.8 (9.6), the number of males per 100 females (ie, the sex ratio) was 104.2 vs 103.7, and the mean (SD) number of children younger than 5 years per household was 1.0 (4.2) vs 1.0 (4.3). Altogether, 7598 births from conrol clusters and 8017 births from intervention clusters were analyzed. There was no significant difference in perinatal mortality between the intervention and control clusters (rate ratio, 0.86; 95% CI, 0.69-1.08; P = .19). The NMR was lower among the intervention than the control clusters (39.2/1000 live births vs 52.2/1000 live births; rate ratio, 0.75; 95% CI, 0.58-0.95; P = .02). The frequencies of antenatal visits and facility births were similar between the 2 groups. However, clean delivery practices were higher among intervention clusters than control clusters (63.2% [2284 of 3616] vs 13.2% [455 of 3458]; P < .001). Chlorhexidine use was also more common among intervention clusters than control clusters (55.9% [4271 of 7642] vs 0.3% [19 of 7203]; P < .001). Conclusions and Relevance: This pragmatic cluster randomized clinical trial demonstrated a reduction in NMR that occurred in the background of improved household intrapartum and newborn care practices. However, the effect of the intervention on antenatal visits, facility births, and perinatal mortality rates was inconclusive, highlighting areas requiring further research. Nevertheless, the improvement in NMR underscores the effectiveness of community-based programs in low-resource settings. Trial Registration: ClinicalTrials.gov Identifier: NCT01751945.

Construction of Host Plant Insect-Resistance Mutant Library by High-Throughput CRISPR/Cas9 System and Identification of A Broad-Spectrum Insect Resistance Gene.

Insects pose significant challenges in cotton-producing regions. Here, they describe a high-throughput CRISPR/Cas9-mediated large-scale mutagenesis library targeting endogenous insect-resistance-related genes in cotton. This library targeted 502 previously identified genes using 968 sgRNAs, generated ≈2000 T0 plants and achieved 97.29% genome editing with efficient heredity, reaching upto 84.78%. Several potential resistance-related mutants (10% of 200 lines) their identified that may contribute to cotton-insect molecular interaction. Among these, they selected 139 and 144 lines showing decreased resistance to pest infestation and targeting major latex-like protein 423 (GhMLP423) for in-depth study. Overexpression of GhMLP423 enhanced insect resistance by activating the plant systemic acquired resistance (SAR) of salicylic acid (SA) and pathogenesis-related (PR) genes. This activation is induced by an elevation of cytosolic calcium [Ca2+ ]cyt flux eliciting reactive oxygen species (ROS), which their demoted in GhMLP423 knockout (CR) plants. Protein-protein interaction assays revealed that GhMLP423 interacted with a human epidermal growth factor receptor substrate15 (EPS15) protein at the cell membrane. Together, they regulated the systemically propagating waves of Ca2+ and ROS, which in turn induced SAR. Collectively, this large-scale mutagenesis library provides an efficient strategy for functional genomics research of polyploid plant species and serves as a solid platform for genetic engineering of insect resistance.

Assessing the potential of GHG emissions for the textile sector: A baseline study.

The carbon footprint (CFP) is a measure of greenhouse gases (GHGs) emitted throughout the lifecycle of a product or activity, while the energy footprint (EFP) and water footprint (WFP) measure energy and water consumption, respectively. These footprints are essential for managing emissions and consumption and promoting low-carbon consumption. A carbon labeling scheme could help consumers make informed choices. Asia is a major textile producer and consumer, so studying textiles' carbon, energy, and water footprints is essential for managing domestic emissions, energy and water consumption, and international trade negotiations. This paper presents a method and framework for assessing CFP, EFP, and WFP at the product level and calculates the footprints for textile products. The results show that the total CFP of all textile products produced is 42,624.12 MT CO2e, with indirect emissions contributing significantly more than direct emissions. The total EFP is 248.38 PJ, with electricity consumption being the main contributor, while the total WFP is 80.71 billion liters. The spinning stage of production has the highest CFP and EFP, and energy consumption is the main contributor to all footprints. These results can help compare different products and reduce the footprints of the textile sector.

Understanding the Radiation Dose Variability in Nasopharyngeal Cancer: An Organs-at-Risk Approach.

Objective This study aims to thoroughly assess the radiation dose distribution to critical organs in patients with nasopharyngeal carcinoma, focusing on the correlation between the radiation dosages for the various organs at risk (OARs) in nasopharyngeal cancer patients. Methods We meticulously analysed a dataset comprising 38 nasopharyngeal carcinoma patients, focusing on radiation dosages measured in Gray (Gy) and volumetric data in cubic centimetres (cc) of critical organs, including the lens, brainstem, spinal cord, optic nerve, optic chiasm, and cochlea. A detailed exploratory data analysis approach encompassed univariate, bivariate, and multivariate techniques. Results Our analysis revealed several key findings. The mean and median values across various dose measurements were closely aligned, indicating symmetrical distributions with minimal skewness. The histograms further corroborated this, showing evenly distributed dose values across different anatomical regions. The correlation matrix highlighted varying degrees of interrelationships between the doses, with some showing strong correlations while others exhibited minimal or no correlation. The 3D scatter plot provided a view of the multi-dimensional dose relationships, with a specific focus on the spinal cord, lens, and brainstem doses. The bivariate scatter plots revealed symmetrical distributions between the right and left lens doses and more complex relationships involving the brainstem and spinal cord, illustrating the intricacies of dose distribution in radiation therapy. Conclusion Our findings reveal distinct radiation exposure patterns to OARs of nasopharyngeal carcinoma. This research emphasises the need for tailored radiation therapy planning to achieve optimal clinical outcomes while safeguarding vital organs.

Exogenous Melatonin Regulates Plant-Disease Interaction by Inducing Maize Resistance and Decreasing the Pathogenicity of Fusarium graminearum.

Plants cannot avoid environmental challenges and are constantly threatened by diverse biotic and abiotic stresses. However, plants have developed a unique immune system to defend themselves against the invasion of various pathogens. Melatonin, N-acetyl-5-methoxytryptamine has positive physiological effects in plants that are involved in disease resistance. The processes underlying melatonin-induced pathogen resistance in plants are still unknown. The current study explores how melatonin regulates the plant-disease interaction in maize. The results showed that 400 µM melatonin strongly reduced the disease lesion on maize stalks by 1.5 cm and corn by 4.0 cm caused by Fusarium graminearum PH-1. Furthermore, after treatment with melatonin, the plant defense enzymes like SOD significantly increased, while POD and APX significantly decreased compared to the control. In addition, melatonin can also improve maize's innate immunity, which is mediated by melatonin treatments through the salicylic acid signaling pathway, and up-regulate the defense-associated expression of PR1, LOX1, OXR, serPIN, and WIPI genes in maize. Melatonin not only inhibits the disease in the maize stalks and corn, but also down-regulates the deoxynivalenol (DON) production-related expression of genes Tri1, Tri4, Tri5, and Tri6 in maize. Overall, this study sheds new light on the mechanisms by which melatonin regulates antioxidant enzymes and defense-related genes involved in plant immunity to effectively suppress plant diseases.

Agrobacterium-Mediated Genetic Transformation of Withania coagulans (Dunal) with rol A Genes and Its Antioxidant Potential.

In ancient times, Withania coagulans Dunal was used as a therapeutic plant for the treatment of several diseases. This report aims to examine the effect of Agrobacterium tumefactions-mediated transformation of W. coagulans with the rolA gene to enhance secondary metabolite production, antioxidant activity, and anticancer activity of transformed tissues. Before transgenic plant production, the authors designed an efficient methodology for in vitro transformation. In this study, leaf explants were cultured on Murashage and Skoog (MS) media containing different amounts of naphthalene acetic acid (NAA) and benzyl adenine (BA). The best performance for inducing embryogenic callus was in MS medium containing 4 µM NAA and 6.0 µM BA, while the best results for shooting (100%) were obtained at 8 µM benzyl adenine. On the other hand, direct shooting was attained by subculturing leaves on MS medium supplemented with 8 µM benzyl adenine. Prolonged shoots showed excellent in vitro rooting results (80%) with 12 µM indole-3-butyric acid (IBA). The samples were precultivated for 3 days and were followed by 48 h infection with A. tumefaciens strain GV3101 having pCV002. Then, a vector expressed the rol A gene of strain Agrobacterium rhizogenes. Furthermore, three independent transgenic shoot lines and one callus line (T2) were produced and exhibited stable integration of transgene rol A genes, as revealed by PCR analysis. Transgenic strains showed a significant increase in antioxidant potential as compared to untransformed plants. Additionally, LC-MS analysis showed that the transformed strains have a higher withanolide content as compared to untransformed ones. Moreover, the reduced proliferation of prostate cancer cells was observed after treatment with extracts of transgenic plants. Furthermore, these transformed plants exhibited superior antioxidant capability and higher withanolide content than untransformed ones. In conclusion, the reported data can be used to select withanolide-rich germplasm from transformed cell cultures.

Heuristic Approach to Predict the Performance Degradation of a Solid Oxide Fuel Cell Cathode.

The present work aims to predict the degradation in the performance of a solid oxide fuel cell (SOFC) cathode owing to cation interdiffusion between the electrolyte and cathode and surface segregation. Cation migration in the (La0.60Sr0.40)0.95Co0.20Fe0.80O3-x (LSCF)-Gd0.10Ce0.90O1.95 (GDC) composite cathode is evaluated in relation to time up to 1000 h using scanning transmission electron microscopy (STEM)-energy-dispersive X-ray spectroscopy (EDXS). The resulting insulating phase formed within the GDC interlayer is quantified by means of the volume fraction using a two-dimensional (2D) image analysis technique. For the very first time, the amount of the insulating phase in the GDC interlayer is quantified, and the corresponding performance degradation of the LSCF cathode is predicted. Mathematical relationships are established for the estimation of degradation due to surface segregation of the cathode. The ohmic resistance between the cathode and the GDC interlayer/electrolyte interface and the polarization resistance of the cathode, characterized by electrochemical impedance spectroscopy (EIS), show an excellent match with the predicted results. The combined degradation analysis and modeling for the cathode lifetime prediction provide a systematic understanding of the time-dependent cation migration and segregation behavior.

Improving the durability of cobaltite cathode of solid oxide fuel cells - a review.

Solid oxide fuel cells (SOFCs) are highly efficient, low-emission, and fuel-flexible energy conversion devices. However, their commercialization has lagged due to the lack of long-term durability. Among several performance degradation mechanisms, cathode degradation and elemental inter-diffusion of the electrolyte and cathode has been identified as the predominant factors. In the most common SOFC systems, a cobalt-based perovskite material is used, for example LSC or LSCF. These cobalt-based materials offer mixed conductivity and higher concentration of oxygen vacancies as compared to LSM at lower operating temperature leading to favorable reduction kinetics. However, the presence of cobalt results in higher cost, higher thermal expansion co-efficient (TEC) mismatch and most importantly leads to rapid degradation. Various elements like strontium, cobalt, cerium, chromium, or zirconium accumulate or deposit at the electrode-electrolyte interface, which results in sluggish reaction kinetics of the oxygen reduction reaction (ORR). These elements react to form secondary phases that have lower ionic and electronic conductivity, cover active reaction sites, and eventually lead to cell and system deterioration. Over the past decade, several studies have focused on preventative and protective measures to prolong SOFC lifetime which includes novel fabrication techniques, introduction of new layers, addition of thin films to block the cation transport. Such efforts to prevent the formation of insulating phases and decomposition of the cathode have resulted in a remarkable improvement in long-term stability. In this review paper, current research on leading mechanisms responsible for the degradation of cobaltite cathode of solid oxide fuel cell has been summarized and durability improvement strategies of cobalt-based SOFC cathodes have been discussed.

Drivers of malnutrition among late adolescent and young women in rural Pakistan: a cross-sectional assessment of the MaPPS trial.

OBJECTIVE: This study aimed to characterise the burden of malnutrition and assess how underlying determinants at the structural and intermediary levels contributed to malnutrition among late adolescent and young women in rural Pakistan. DESIGN: Cross-sectional enrolment data assessment. SETTING AND PARTICIPANTS: This study was conducted using data from adolescent and young women (n=25 447) enrolled in the Matiari emPowerment and Preconception Supplementation Trial, collected from June 2017 to July 2018 in Matiari District, Pakistan. The WHO-based cut-offs were applied to anthropometric measures to estimate body mass index (BMI) categories (underweight, overweight, obese) and stunting. Hierarchical models were generated to evaluate the association between the determinants with BMI categories and stunting among late adolescent girls and young women, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes of interest were BMI categories and stunting. Explanatory variables included measures of socioeconomic status, education, occupation, health, well-being, food security, empowerment and food practices. RESULTS: Regardless of age group, the prevalence of underweight was high (36.9%; 95% CI 36.3% to 37.5%). More late adolescent girls were underweight, while more young women were overweight/obese (p<0.001). Stunting affected 9.2% (95% CI 8.9% to 9.6%) of participants, of which 35.7% were additionally underweight and 7.3% overweight/obese. Compared with those in the normal weight category, those underweight were more likely to be impoverished and less empowered. Those overweight/obese were more likely to be from a higher wealth quintile and food secure. Increased education level and food security were associated with reductions stunting risk. CONCLUSIONS: This study informs the data gap and need for comprehensive research on adolescent nutritional status. Findings suggest factors related to poverty played an important, underlying role in undernutrition among participants. Commitment to improving the nutritional status of all adolescent and young women in Pakistan will be critical given the observed burden of malnutrition. TRIAL REGISTRATION NUMBER: NCT03287882.

Fabrication and Characterization of Celecoxib-Loaded Chitosan/Guar Gum-Based Hydrogel Beads.

The aim of this study was to fabricate celecoxib-loaded chitosan/guar gum (CS/GG) single (SC) and dual (DC) crosslinked hydrogel beads using the ionotropic gelation approach. The prepared formulations were evaluated for entrapment efficiency (EE%), loading efficiency (LE%), particle size and swelling studies. The performance efficiency was assessed by in vitro drug release, ex-vivo mucoadhesion, permeability, ex-in vivo swelling and in vivo anti-inflammatory studies. The EE% was found to be ~55% and ~44% for SC5 and DC5 beads, respectively. The LE% was ~11% and ~7% for SC5 and DC5 beads, respectively. The beads showed a matrix-like network with thick fibers. The particle size of beads ranged from ~2.74 to 1.91 mm. About 74% and 24% celecoxib was released from SC and DC hydrogel beads, respectively, within 24 h. The SC formulation showed higher %swelling and permeability than the DC counterpart, while the %mucoadhesion was relatively higher for DC beads. During the in vivo study, a significant decrease in the inflammation of the rat paw and inflammatory markers including C-reactive proteins (CRP) and interleukin-6 (IL-6) was observed following treatment with the prepared hydrogel beads; however, the SC formulation showed better therapeutic efficiency. In conclusion, celecoxib-loaded crosslinked CS/GG hydrogel beads can provide sustained drug release and act as potential candidates for managing inflammatory conditions.

Evaluation of Antiproliferative, Antimicrobial, Antioxidant, Antidiabetic and Phytochemical Analysis of Anogeissus dhofarica A. J. Scott.

In the current study, methanol (ADAM) extracts and their fractions, including chloroform (ADAC), ethyl acetate (ADAE), n-hexane (ADAH), and aqueous (ADAA) fractions, were prepared from aerial parts of Anogeissus dhofarica and evaluated for phytochemical assessment, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analysis, and in vitro bioassays. The qualitative analysis determined that, except alkaloids, all the representative groups were found to be present in the analyzed samples. Samples under quantitative study displayed the highest amount of total phenolic contents in the ADAE fraction, while total flavonoid contents were highest in the ADAM extract. The ADAM extract was subjected to HR-ESI-MS to identify the chemical constituents that presented twenty-two bioactive ingredients, outlined for the first time from A. dhofarica, mainly contributed by sub-class flavanones. In the case of antimicrobial activity, the ADAE extract revealed an effective zone of inhibition (ZOI) against the Gram-positive bacterial strain (Staphylococcus aureus) with an MIC value of 0.78 ± 0.3 mg/mL, while the ADAA extract exhibited higher ZOI (34 ± 0.12 mm) against the fungal strain Candida kruzei with an MIC of 0.78 mg/mL. In the DPPH (2,2-diphenyl-1-picrylhydrazyl) analysis, the ADAE extract exhibited a maximum scavenging potential with an IC50 of 9.8 ± 1.2 µg/mL, succeeded by the ADAM extract with an IC50 of 17.4 ± 0.4 µg/mL free radical scavenging capability. In the antidiabetic assessment, the ADAE extract was the most effective, with an IC50 of 6.40 ± 0.1 µg/mL, while the same extract demonstrated prominent activity with 30.8% viability and an IC50 of 6.2 ± 0.3 µg/mL against breast cancer cell lines. The brine shrimp lethality assay demonstrated a correlation with the in vitro cytotoxicity assay, showing the ADAE extract as the most active, with a 70% mortality rate and an LC50 of 300.1 µg/mL. In conclusion, all the tested samples, especially the ADAE and ADAM extracts, have significant capabilities for the investigated activities that could be due to the presence of the bioactive compounds.

Nanoformulation of Curcuma longa Root Extract and Evaluation of Its Dissolution Potential.

Medicinal plants have been widely used for therapeutic purposes for a long time, but they have been found to have some major issues such as low water solubility and bioavailability. In the present study, the nanoformulation of Curcuma longa L. plant extract was prepared to enhance its dissolution potential and biological activities. For the formulation of the nanosuspension, an ethanolic extract of C. longa was prepared through Soxhlet extraction using the nanoformulation technique. The nanosuspensions were formulated using four different stabilizers, namely sodium lauryl sulfate (SLS), hydroxy propyl methyl cellulose (HPMC), poly(vinyl alcohol) (PVA), and polysorbate-80 (P-80). The scanning electron microscopy (SEM), polydispersity index, and ζ potential were used for characterization of the nanoformulation. Among all of these, the surfactant stabilizer SLS was found to be the best. The average particle size of the selected optimized nanosuspension was found to be 308.2 nm with a polydispersity index (PDI) value of 0.330. The ζ potential value of the optimized nanosuspension was recorded at -33.3 mV. The SEM image indicated that the particles were slightly agglomerated, which may have occurred during lyophilization of the nanosuspension. The highest dissolution rate recorded at pH = 7 was 192.32 µg/mL, which indicates pH = 7 as the most appropriate condition for the dissolution of the C. longa nanosuspension. The antioxidant, antimicrobial, and antifungal activities of the optimized nanosuspension were also determined with regard to the coarse plant extract. The study findings suggested that the nanoprecipitation approach helps in enhancing the dissolution potential and biological activities of C. longa root extract.

Marine life as a source for breast cancer treatment: A comprehensive review.

Breast cancer, one of the most significant tumors among all cancer cells, still has deficiencies for effective treatment. Moreover, substitute treatments employing natural products as bioactive metabolites has been seriously considered. The source of bioactive metabolites are not only the most numerous but also represent the richest source. A unique source is from the oceans or marine species which demonstrated intriguing chemical and biological diversity which represents an astonishing reserve for discovering novel anticancer drugs. Notably, marine sponges produce the largest amount of diverse bioactive peptides, alkaloids, terpenoids, polyketides along with many secondary metabolites whose potential is mostly therapeutic. In this review, our main focus is on the marine derived secondary metabolites which demonstrated cytotoxic effects towards numerous breast cancer cells and have been isolated from the marine sources such as marine sponges, cyanobacteria, fungi, algae, tunicates, actinomycetes, ascidians, and other sources of marine organisms.

Behavior-based safety program for process industries.

Objectives. This article describes the reduction of unsafe behaviors observed at a fertilizer complex by implementation of a behavior-based safety (BBS) program via a behavior observation form developed by a multidisciplinary team. Methods. Six observation categories, i.e., position of people, reaction of people, personal protective equipment (PPE), tools used, operating procedures and housekeeping, are used to monitor safe and unsafe behaviors for a period of 18 months. Results. Safe behaviors increased from 57 to 70% and unsafe behaviors reduced from 40 to 26%. Behaviors of employees working in various sections of fertilizer complex such as ammonia, urea, utility, bagging/shipping and workshop were also observed. Non-compliance with PPE, housekeeping and standard operating procedures was also monitored in individual sections. Non-operational areas including the administration block, housing colony, maintenance workshop, warehouse, fire station and electrical substation were also observed. Among these, the maximum unsafe behaviors are for the housing colony and minimum for the electrical substation. Conclusion. It has been concluded that working on the housing colony, administration block and fire station areas will address 74% unsafe behaviors of non-operational areas. For practical applications, worldwide industries can implement this BBS program to enhance BBS, thus reducing unsafe behaviors and increasing employee morale.

Risk factors for acute diarrhoea in children between 0 and 23 months of age in a peri-urban district of Pakistan: a matched case-control study.

BACKGROUND: Diarrhoea is a leading cause of preventable childhood morbidity and mortality worldwide. Unfortunately, Pakistan has the third-highest burden of diarrhoea-related deaths in children <5 y of age. Therefore we aimed to evaluate factors associated with diarrhoea among Pakistani children. METHODS: A retrospective 1:2 matched case-control study nested in a baseline cross-sectional survey was conducted from October to December 2018 in Taluka Kotri, a two-thirds urban locality in the Jamshoro district. Children between the ages of 0 and 23 months with a history of diarrhoea in the 2 weeks preceding the survey were labelled as cases. Age-matched controls were children without symptoms of diarrhoea. Univariate and multivariable conditional logistic regression was performed to identify diarrhoea-related factors. RESULTS: A total of 1558 cases were matched with 3116 controls. Factors significantly associated with lower odds of diarrhoea in the multivariate analysis included increasing maternal age (odds ratio [OR] 0.78 [95% confidence interval {CI} 0.67 to 0.90]), breastfeeding (OR 0.77 [95% CI 0.66 to 0.90]), higher paternal education (OR 0.79 [95% CI 0.65 to 0.97]) and belonging to the rich (OR 0.66 [95% CI 0.54 to 0.80]) and richest quintiles (OR 0.54 [95% CI 0.44 to 0.66]). CONCLUSIONS: This study identifies risk factors associated with diarrhoea in children <23 months of age, including younger maternal age, higher paternal education, not breastfeeding and poverty, which has implications for developing preventive programs and strategies that target populations with a higher risk of diarrhoea.