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Wisam Nabeel Ibrahim,1,2 Luqman Muizzuddin Bin Mohd Rosli,2 Abd Almonem Doolaanea2 1Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, MalaysiaCorrespondence: Wisam Nabeel Ibrahim Tel +97444036025Email w.ibrahim@qu.edu.qa; Abd Almonem Doolaanea Tel +6013-6238628Email abdalmonemdoolaanea@yahoo.comIntroduction: Thymoquinone (TQ) is the main active compound extracted from Nigella sativa a traditional herb with wide therapeutic applications and recognizable anticancer properties. This study aimed to formulate and characterize TQ-nanoparticles using PLGA as a biocompatible coating material (TQ-PLGA NPs) with the evaluation of its therapeutic properties in human melanoma cancer cells.Methods: The TQ-PLGA NPs were prepared and characterized for size, zeta potential, encapsulation efficiency, and release profile.Results: The particle size was 147.2 nm, with 22.1 positive zeta potential and 96.8% encapsulation efficiency. The NPs released 45.6% of the encapsulated TQ within 3 h followed by characteristic sustained release over 7 days with a total of 69.7% cumulative release. TQ-PLGA NPs were taken up effectively by the cells in a time-dependent manner up to 24 h. Higher cell toxicity was determined within the first 24 h in melanoma cells due to the rapid release of TQ from the NPs and its low stability in the cell culture media.Conclusion: TQ-PLGA NPs is a potential anticancer agent taking advantage of the sustained release and tailored size that allows accumulation in the cancer tissue by the enhanced permeability and retention effect. However, stability problems of the active ingredient were address in this study and requires further investigation.Keywords: microencapsulation, thymoquinone, PLGA, nanoparticles, melanoma

Objective: Perinatal mortality is an important indicator of obstetric and neonatal services and socio-economic status of a country. This study reviewed perinatal mortality in Pasir Mas district for year 1999 to 2003 and its causes and related obstetric and foetal factors.Design: Retrospective studyMaterials and Methods: We retrospectively examined data obtained from the Perinatal Reporting System in Pasir Mas district.Results: The overall five-year perinatal mortality rate was 16.32 per 1,000 births. The causes of perinatal deaths included macerated stillbirth (26.8%), asphyxia (21.9%), congenital malformation (19.6%), immaturity (10.9%) and infection (4.2%). The mean (SD) age of mother was 31.5 (7.2) years with 65.3% aged less than 35 years, 96.6% Malays, 21.1% primigravida and 23.1% grandmultigravida. The rates of maternal morbidity were: 15.8% hypertension, 13.2% anaemia, 7.5% diabetes mellitus, 6.8% ante partum haemorrhage and 3.4% prolonged rupture of membrane. The providers of antenatal care were: 71.3% health clinics, 8.3% hospitals, 1.9% private clinics, 0.8% none and 17.7% several. The foetus was delivered by doctors (56.6%), nurses (27.5%) and midwives (15.5%). The places of delivery were: 92.1% hospital, 5.7% home, 0.8% health clinic, 0.8% private clinic and 0.8% in transit. The mean (SD) gestational age was 33.7 (4.9) weeks with 65.7% preterm. The gestational age was determined by last menstrual period (68.7%), ultrasound (27.2%) and neonatal condition (4.2%). The mean (SD) of birth weight was 1952.8 (1051.7) grams with 65.3% were < 2500 grams.Conclusion: Perinatal mortality rate in Pasir Mas district was moderate compared to other districts in Kelantan but higher than the average Kelantan and Malaysia rates. The causes of perinatal deaths were similar to other areas. There were still unsafe deliveries in terms of attendant and place. This perinatal registry system gives a good overview of local perinatal related problems. [ABSTRACT FROM AUTHOR]

Cancer remains one of the leading causes of death worldwide. Despite advances in medical treatments, current therapeutic strategies, including radiotherapy, chemotherapy, targeted therapy, and surgical resection, have not significantly reduced the global incidence and mortality rates of cancer. Oncologists face considerable challenges in devising effective treatment plans due to the adverse side effects associated with standard therapies. Therefore, there is an urgent need for more effective and well-tolerated cancer treatments. Curcumin, a naturally occurring compound, has garnered significant attention for its diverse biological properties. Both preclinical studies and clinical trials have highlighted curcumin's potential in cancer treatment, demonstrating its ability to inhibit the proliferation of various cancer cell types through multiple cellular and molecular pathways. This paper examines the antineoplastic properties, and the therapeutic mechanisms including cell signalling pathways targeted by curcumin that are implicated in cancer development and explores the challenges in advancing curcumin as a viable anticancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ameer, Mohamed, Elzubair, Sharif and Ibrahim.)

Introduction: Many factors contribute to the risk of cardiovascular disease (CVD), an umbrella term for several different heart diseases, including inflammation. Macrophage migration inhibitory factor (MIF) is an important immune modulator that has been shown to be involved in the pathogenesis of different heart diseases, so understanding pathogenic variants of the MIF gene is important for risk stratification. We therefore conducted a meta-analysis to investigate whether the MIF -173G/C (rs755622) polymorphism is associated with CVD., Methods: The PubMed, Science Direct, and Embase databases were searched from inception to June 2023 for case-control studies of the MIF -173G/C polymorphism and its relationship to any type of CVD. Correlations between the MIF -173G/C polymorphism and CVD were estimated by pooling the odds ratios (ORs) with 95% confidence intervals in allelic, dominant, and recessive models using random-effects meta-analysis., Results: A total of 9,047 participants (4141 CVD cases and 4906 healthy controls) from 11 relevant studies were included. In the total population, there was no significant association between the MIF -173G/C (rs755622) polymorphism and the risk of developing CVD in the three different models. In a stratified analysis by ethnicity, the allelic model (C vs G) was significantly associated with CVD in the Arab and Asian populations (OR = 0.56, CI 0.42 -0.75 and OR = 1.28, CI 1.12 -1.46, respectively); the dominant model (CC+CG vs GG) was significantly associated with CVD in the Arab population (OR = 0.42, CI 0.30 -0.61); while the recessive model (GG+GC vs CC) was associated with CVD susceptibility in the Arab population (OR = 3.84, CI 1.57 -9.41). There were no significant associations between the MIF -173 G/C polymorphism and CVD risk in the European population. Conclusion, the MIF -173G/C polymorphism is associated with CVD in some populations., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42023441139)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Fouda, Ibrahim, Shi, Alahmadi, Almohammadi, Al-Haidose and Abdallah.)

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC's heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in the tumor microenvironment. Therapeutic modalities, including immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4, are explored in preclinical and clinical trials. Promising results emerge from combining ICIs with anti-TGF-β and VISTA, hindering TNBC tumor growth. TNBC cells employ complex evasion strategies involving interactions with stromal and immune cells, suppressing immune recognition through various cytokines, chemokines, and metabolites. The recent focus on unraveling humoral and cellular components aims to disrupt cancer crosstalk within the tumor microenvironment. This review identifies TNBC's latest resistance mechanisms, exploring potential targets for clinical trials to overcome immune checkpoint resistance and enhance patient survival rates.

In this study, we investigated the effects of an ethanolic extract of Mangifera indica L. kernel on the viability and proliferation of human lung cancer cells. We utilized MTT and BrdU cell proliferation assays, morphological assessments, cell cycle analyses, and apoptosis assays to investigate the extract's effects on lung cancer (A549 and NCI-H292) and normal lung (MRC-5) cells. The extract demonstrated a toxicity toward cancer cells compared to normal cells with dose-dependent anti-proliferative effect on lung cancer cells. The extract also caused differential effects on the cell cycle, inducing G0/G1 arrest and increasing the Sub-G1 population in both lung cancer and normal lung cells. Notably, the extract induced loss of membrane integrity, shrinkage, membrane blebbing, and apoptosis in lung cancer cells, while normal cells exhibited only early apoptosis. Furthermore, the extract exhibited higher toxicity towards NCI-H292 cells, followed by A549 and normal MRC-5 cells in decreasing order of potency. Our results suggest that the ethanolic extract of M. indica L. kernel has significant potential as a novel therapeutic agent for treating lung cancer cells, given its ability to induce apoptosis in cancer cell lines while causing minimal harm to normal cells., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Rheumatic heart disease (RHD) represents a serious cardiac sequela of acute rheumatic fever, occurring in 30-45% of patients. RHD is multifactorial, with a strong familial predisposition and known environmental risk factors that drive loss of immunological tolerance. The gut and oral microbiome have recently been implicated in the pathogenesis of RHD. Disruption of the delicate balance of the microbiome, or dysbiosis, is thought to lead to autoimmune responses through several different mechanisms including molecular mimicry, epitope spreading, and bystander activation. However, data on the microbiomes of RHD patients are scarce. Therefore, in this comprehensive review, we explore the various dimensions of the intricate relationship between the microbiome and the immune system in RHD and other rheumatic diseases to explore the potential effect of microbiota on RHD and opportunities for diagnosis and treatment.

Background: Uric acid is the final product of purine metabolism and is a potent plasma antioxidant but with pro-inflammatory effects. At high levels, it may increase the risk of developing multiple chronic diseases, such as gout, atherosclerosis, hypertension, and renal diseases. The aim of this study was to assess the sex-specific association between serum bicarbonate and uric acid levels among healthy adults., Methodology: This retrospective cross-sectional study included 2,989 healthy Qatari adults (36.4 ± 11.1  years) from the Qatar Biobank database. Serum uric acid and bicarbonate levels were estimated alongside other serological markers. Participants free from chronic diseases were divided into four quartiles based on serum bicarbonate levels. The sex-specific relationship between serum bicarbonate and uric acid levels was assessed through univariate and multivariate analyses., Results: In men, low serum uric acid levels were significantly associated with higher quartiles of serum bicarbonate levels after adjusting for age. The association remained significant after further adjustment for BMI, smoking, and renal function. The subgroup analysis using the restricted cubic spline method confirmed a significant dose-response association between the variation coefficients of uric acid by serum bicarbonate level in men with adjustments for age, BMI, smoking, and renal function. In women, no significant association was found between quartiles of serum bicarbonate and uric acid levels following the same adjustments. However, using the restricted cubic spline method, a significant bidirectional relation was demonstrated between serum bicarbonate and the variation coefficients of uric acid that were positive for serum bicarbonate levels below 25 mEq/L and negative at higher levels., Conclusion: Serum bicarbonate levels are linearly associated with reduced serum uric acid levels among healthy adult men, which may be a potential protective factor against hyperuricemia-related complications. Further research is needed to determine the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ibrahim, Shi, Abdallah and Abu-Madi.)

Background: Hemophilia A, an X-linked bleeding disorder, is caused by a complete or partial deficiency in factor VIII. Multiple factors engage in the development and progression of bleeding episodes in hemophilia patients, especially arthropathy., Objectives: Detection of macrophage migration inhibitory factor (MIF)-173 G/C polymorphism in people with hemophilia A (PWH) and the possible associations between the type of MIF gene polymorphism and selected disease-related variables., Patients and Methods: This case-control study included 95 male patients with hemophilia A and 95 non-hemophiliac subjects, all aged from 2 months to 63 years. An allele-specific polymerase chain reaction (AS-PCR) with a multiplex technique was used to detect MIF polymorphisms., Results: A significantly higher frequency of GG polymorphism was reported in the control group (81, 85.3%) compared to PWH (64, 67.4%), while a significantly higher frequency of GC polymorphism was found in PWH (21, 22.1%) than that in healthy subjects (10, 10.5%), P < 0.05. The G allele polymorphism was detected in 90.0% of the control group compared to 78.4% of PWH (149 subjects), while the C allele frequency was higher in PWH (41, 21.6%) compared to that in healthy individuals (18, 10.0%), P < 0.05. The frequencies of varied MIF-173 polymorphisms did not show significant differences among patients with different clinical presentations or in relation to presence of inhibitors, P > 0.05., Conclusions: MIF-173 GC polymorphism is seen in PWH more than that in healthy individuals. Further studies are required to detect additional SNPs through sequencing of the MIF gene and to detect MIF serum levels during bleeding episodes.

The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl 2 ), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl 2 from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl 2 toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Infertility of unknown etiology is considered a significant medical and health problem. This study focused on the role of the estrogen receptor alpha ( ESRα ) gene polymorphism, PvuII (rs2234693), and its effect on the amount of ESRα in the blood of women who cannot get pregnant for unknown reasons. A total of 184 females were evaluated, including 102 with unexplained infertility (UI) and 82 age-matched control females (with at least one living child and no history of infertility). Blood samples were collected, genomic DNA was isolated from blood samples, and the genotyping of the ESRα gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ESRα expression levels were assessed by the ELISA. The study revealed that the mean serum level of ESRα was significantly higher in the case group than in the control group ( P <0.05). Furthermore, the genotypes (TT, TC, and CC) and alleles (T and C) significantly influenced the plasma level of ESRα in the study population. Moreover, the presence of the C allele was considered a risk factor, and the polymorphism had a significant effect on ESRα expression level in women with UI., Competing Interests: The authors declare that they have no conflict of interest.

Silver-doped magnesia nanoparticles (Ag/MgO) were synthesized using the precipitation method and characterized by various techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), Brunner-Emmett-Teller (BET) surface area measurements, and dispersive X-ray spectroscopy (EDX). The morphology of Ag/MgO nanoparticles was determined by transmission and scanning electron microscopy, which revealed cuboidal shaped nanoparticles with sizes ranging from 31 to 68 nm and an average size of 43.5 ± 10.6 nm. The anticancer effects of Ag/MgO nanoparticles were evaluated on human colorectal (HT29) and lung adenocarcinoma (A549) cell lines, and their caspase-3, -8, and -9 activities, as well as Bcl-2, Bax, p53, cytochrome C protein expressions were estimated. Ag/MgO nanoparticles showed selective toxicity towards HT29 and A549 cells while remaining relatively innocuous towards the normal human colorectal, CCD-18Co, and lung, MRC-5 cells. The IC 50 values of Ag/MgO nanoparticles on the HT29 and A549 cells were found to be 90.2 ± 2.6 and 85.0 ± 3.5 μg/mL, respectively. The Ag/MgO nanoparticles upregulated caspase-3 and -9 activities, downregulated Bcl-2, upregulated Bax and p53 protein expressions in the cancer cells. The morphology of the Ag/MgO nanoparticle treated HT29 and A549 cells was typical of apoptosis, with cell detachment, shrinkage, and membrane blebbing. The results suggest that Ag/MgO nanoparticles induce apoptosis in cancer cells and exhibit potential as a promising anticancer agent., Competing Interests: The authors declare no conflict of interest.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Cancer immunotherapy is a type of treatment that harnesses the power of the immune systems of patients to target cancer cells with better precision compared to traditional chemotherapy. Several lines of treatment have been approved by the US Food and Drug Administration (FDA) and have led to remarkable success in the treatment of solid tumors, such as melanoma and small-cell lung cancer. These immunotherapies include checkpoint inhibitors, cytokines, and vaccines, while the chimeric antigen receptor (CAR) T-cell treatment has shown better responses in hematological malignancies. Despite these breakthrough achievements, the response to treatment has been variable among patients, and only a small percentage of cancer patients gained from this treatment, depending on the histological type of tumor and other host factors. Cancer cells develop mechanisms to avoid interacting with immune cells in these circumstances, which has an adverse effect on how effectively they react to therapy. These mechanisms arise either due to intrinsic factors within cancer cells or due other cells within the tumor microenvironment (TME). When this scenario is used in a therapeutic setting, the term "resistance to immunotherapy" is applied; "primary resistance" denotes a failure to respond to treatment from the start, and "secondary resistance" denotes a relapse following the initial response to immunotherapy. Here, we provide a thorough summary of the internal and external mechanisms underlying tumor resistance to immunotherapy. Furthermore, a variety of immunotherapies are briefly discussed, along with recent developments that have been employed to prevent relapses following treatment, with a focus on upcoming initiatives to improve the efficacy of immunotherapy for cancer patients.

Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1 H -pyrrol-2-yl)prop-2-en-1-one (compound 8 ) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABA A , -8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Herein, magnetic polyaniline was modified with lanthanum nanoparticles (MPANI@La) as adsorbent, aiming to the treatment of high phosphate-containing aquatic solutions. High valent lanthanum doped with polyaniline was a promising adsorbent to uptake phosphate ions with possible electrostatic interaction and cation exchange process. The functional groups, composition, surface morphology, and magnetic property of the adsorbent were investigated using Fourier Transform-Infrared Spectroscopy (FTIR), Energy Dispersive X-ray (EDX), Scanning Electron Microscopic (SEM), and Vibrating Sample Magnetometer (VSM), respectively. During the experimental process, MPANI@La has removed phosphate ions from water >90%, with 80 mg adsorbent, and shaking for 150 min at room temperature. In this regard, the process was fitted with the Pseudo-second-order kinetic model (R2 > 0.999) and the Langmuir isotherm (R2 > 0.99). The proposed nanoparticles provided an appropriate adsorption capacity (qm) of 45.24 mg.g-1 at pH 4 for phosphate ions. Besides, the adsorbent can be used with an efficiency of 92.49% up to three times that reduced to 52.89% after ten times. In addition, the adsorption process was justified by thermodynamics which confirmed the proposed adsorption mechanism. Hence, the models were provided surface adsorption, monolayer pattern, and the physical mechanism of the phosphate removal process using MPANI@La. Hence the proposed adsorbent can be used as an alternative adsorbent in environmental water remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, a magnetic solid-phase extraction method was developed based on multi-wall carbon nanotubes decorated by magnetic nanoparticles (Fe 3 O 4 ) and cadmium sulfide nanoparticles (Fe 3 O 4 @MWCNT-CdS) for trace extraction of cefixime and tetracycline antibiotics from urine and drug company wastewater. The adsorbent features were characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), and energy dispersive X-ray analysis (EDX). Various effective parameters on the sorption and desorption cycle, such as sorption time, the mass of adsorbent, pH, salt addition, and material ratio, were investigated and optimized. The data were evaluated using isotherm models, and experimental data were well-fitted to both Langmuir (R 2 = 0.975) and Freundlich (R 2 = 0.985) models. Moreover, kinetic of reaction was agreement with pseudo-second-order (R 2 = 0.999) as compared pseudo-first-order (R 2 = 0.760). The maximum adsorption capacity for tetracycline and cefixime was achieved at 116.27 and 105.26 mg·g -1 , respectively. Hence, the prepared adsorbent can be used as an alternative material for enhanced determination of pharmaceutical substances in biological fluids., Competing Interests: The authors declare no conflict of interest.

Despite the wide distribution of COVID-19 vaccines, refugees remain last in line for the intake of vaccines. Syrian refugees in Jordan reach up to 700,000 registered and almost up to 700,000 unregistered refugees. This study aims to assess the willingness of Syrian refugees in Jordan to take the COVID-19 vaccine. Participants in the Zaatari refugee camp in Jordan were invited through social media to complete the survey between January and March 2022. A total of 230 refugees participated in our study, with almost half the participants of male gender. The majority of the participants had secondary school as their highest education level and were unemployed, being below the social poverty line. Interestingly, Syrian refugees showed a high vaccine acceptance rate, as 89.6% were willing to take the vaccine. Moreover, they showed high knowledge regarding the vaccine, the disease, and the virus. Our findings highlight the importance of knowledge and awareness of the COVID-19 vaccine to increase the acceptance rate. This is very important as refugees represent a vulnerable group to infection and complications and require close attention, especially with their significant numbers in Jordon and challenges of providing adequate vaccine supplies at their camps. We hope that, with proper dissemination of knowledge and awareness and with easy accessibility to the vaccines, it will ensure high immunization to reach herd immunity in Jordan.

Arsenic trioxide (As 2 O 3 ) is a ubiquitous heavy metal in the environment. Exposure to this toxin at low concentrations is unremarkable in developing organisms. Nevertheless, understanding the underlying mechanism of its long-term adverse effects remains a challenge. In this study, embryos were initially exposed to As 2 O 3 from gastrulation to hatching under semi-static conditions. Results showed dose-dependent increased mortality, with exposure to 30-40 µM As 2 O 3 significantly reducing tail-coiling and heart rate at early larval stages. Surviving larvae after 30 µM As 2 O 3 exposure showed deficits in motor behavior without impairment of anxiety-like responses at 6 dpf and a slight impairment in color preference behavior at 11 dpf, which was later evident in adulthood. As 2 O 3 also altered locomotor function, with a loss of directional and color preference in adult zebrafish, which correlated with changes in transcriptional regulation of adsl , shank3a , and tsc1b genes. During these processes, As 2 O 3 mainly induced metabolic changes in lipids, particularly arachidonic acid, docosahexaenoic acid, prostaglandin, and sphinganine-1-phosphate in the post-hatching period of zebrafish. Overall, this study provides new insight into the potential mechanism of arsenic toxicity leading to long-term learning impairment in zebrafish and may benefit future risk assessments of other environmental toxins of concern.

The World Health Organization (WHO) recorded approximately 350 million people worldwide have suffered from mental health disorders, such as depression, anxiety, schizophrenia, and addictive behaviors. The search for new drugs from nature has drawn on many biological resources and human practices. In this study, leaves of Polygonum minus standardized extract (Biokesum®), 1 and 100 mg/L were used to evaluate the anti-stress effect in the chronic unpredictable stress (CUS) zebrafish model. Five groups of zebrafish were manipulated in this study, comprising control, chronic unpredictable stress (CUS), CUS + Biokesum® 1 mg/L (4 days, 20 min/day, immersion) CUS + Biokesum® 100 mg/L (4 days, 20 min/day, immersion) and CUS + fluoxetine 0.6 mg/L (4 days, 20 min/day, immersion). Four different behavioral tests were used, i.e. open-field test, social interaction test, light and dark test, and exploratory test. After four consecutive days of treatment, the zebrafish were sacrificed for whole-body cortisol analysis. The exploratory test showed a significant change upon P. minus treatment (one-way ANOVA; p = 0.0011). Cortisol analysis showed a decrease of cortisol level after treatment with the extract and fluoxetine, without significant difference. These results showed that zebrafish is a reliable model to study the anti-stress effect of compounds or herbal extract., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Clitoria ternatea Linn. (CT), or butterfly pea, is an Ayurvedic plant traditionally used as a brain tonic. Recently, it was reported to be of use in treating central nervous system (CNS) disorders, i.e., as an antistress treatment and antidepressant. In the present study, we report a detailed phytochemical profile of the ethyl acetate fraction of the flower of CT (CTF&#95;EA) with significant neuroprotective and anti-neuroinflammatory properties in both LPS-activated BV-2 and SK-N-SH cells. Concurrently, the molecular network (MN) derived from the CTF&#95;EA metabolome allows putative identification of flavonol 3- O -glycosides, hydrocinnamic acids, and primary metabolites. Molecular docking studies suggest that CTF&#95;EA preferentially targets iNOS, resulting in a decrease in nitric oxide (NO). Furthermore, no toxic effects on normal embryonic development, blood vessel formation, and apoptosis are observed when CTF&#95;EA is tested for in vivo toxicity in zebrafish models. The overall preliminary results suggest the anti-neuroinflammatory and neuroprotective effects of CT and provide scientific support for the efficacy of this medicinal plant at local and traditional levels. However, studies on the targeted isolation of bioactive metabolites, in-depth pharmacological efficacy, and safety in mammalian models are urgently needed to expand our understanding of this plant before it is developed into a promising therapeutic agent for brain-related diseases.

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Overexpression of c-Myc plays an essential role in leukemogenesis and drug resistance, making c-Myc an attractive target for cancer therapy. However, targeting c-Myc directly is impossible, and c-Myc upstream regulator pathways could be targeted instead. This study investigated the effects of thymoquinone (TQ), a bioactive constituent in Nigella sativa, on the activation of upstream regulators of c-Myc: the JAK/STAT and PI3K/AKT/mTOR pathways in HL60 leukemia cells. Next-generation sequencing (NGS) was performed for gene expression profiling after TQ treatment. The expression of c-Myc and genes involved in JAK/STAT and PI3K/AKT/mTOR were validated by quantitative reverse transcription PCR (RT-qPCR). In addition, Jess assay analysis was performed to determine TQ’s effects on JAK/STAT and PI3K/AKT signaling and c-Myc protein expression. The results showed 114 significant differentially expressed genes after TQ treatment (p < 0.002). DAVID analysis revealed that most of these genes’ effect was on apoptosis and proliferation. There was downregulation of c-Myc, PI3K, AKT, mTOR, JAK2, STAT3, STAT5a, and STAT5b. Protein analysis showed that TQ also inhibited JAK/STAT and PI3K/AKT signaling, resulting in inhibition of c-Myc protein expression. In conclusion, the findings suggest that TQ potentially inhibits proliferation and induces apoptosis in HL60 leukemia cells by downregulation of c-Myc expression through inhibition of the JAK/STAT and PI3K/AKT signaling pathways.

Due to the restrictions in accessing research laboratories and the challenges in providing proper storage and transportation of cells during the COVID-19 pandemic, having an effective and feasible mean to solve these challenges would be of immense help. Therefore, we developed a 3D culture setting of cancer cells using alginate beads and tested its effectiveness in different storage and transportation conditions. The viability and proliferation of cancer cells were assessed using trypan blue staining and quantitative CCK-8 kit, respectively. The developed beads allowed cancer cells survival up to 4 weeks with less frequent maintenance measures such as change of the culture media or subculture of cells. In addition, the recovery of cancer cells and proliferation pattern were significantly faster with better outcomes in the developed 3D alginate beads compared to the standard cryopreservation of cells or the 2D culture conditions. The 3D alginate beads also supported the viability of cells while the shipment at room temperature for a duration of up to 5 days with no humidity or CO 2  support. Therefore, 3D culture in alginate beads can be used to store or ship biological cells with ease at room temperature with minimal preparations., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Molecularly imprinted polymers (MIPs) are synthetic polymers with a predetermined selectivity for a particular analyte or group of structurally related compounds, making them ideal materials for separation processes. Hence, in sample preparation, MIPs are chosen as an excellent material to provide selectivity. Moreover, its use in solid-phase extraction, also referred to as molecular imprinted solid phase extraction (MISPE), is well regarded. In recent years, many papers have been published addressing the utilization of MIPs or MISPE as sorbents in natural product applications, such as synthesis. This review describes the synthesis and characterization of MIPs as a tool in natural product applications.

Abstract: This study aimed to investigate evidence of gray matter brain lesions in multiple sclerosis (MS) patients by evaluating the resting state alpha rhythm of brain electrical activity.The study included 50 patients diagnosed with MS recruited from the MS clinic with 50 age and gender-matched control participants. The study investigated parameters of posterior dominant rhythm (PDR) in the electroencephalography (EEG) recordings including wave frequency and amplitude. Functional disability among the patients was evaluated according to the expanded disability status scale. Univariate statistical analysis was completed using one-way analysis of variance and t test with a P value of less than .05 to indicate statistical significance.Patients with MS had significantly lower PDR frequency and amplitude values compared to the controls (P value < .01) and 34% of the MS patients had a PDR frequency of less than 8.5 Hz. The PDR frequency was negatively associated with the level of functional disability among the patients (P value <.001) and 4% of the patients had abnormal epileptiform discharges.Background slowing of resting alpha rhythms and epileptiform discharges are suggestive of gray matter degeneration and may help in the prediction and follow-up of cortical damage and functional disabilities among MS patients. Therefore, electroencephalography monitoring of the PDR spectrum may serve as an alternative or complementary tool with other imaging techniques to detect and monitor cerebral cortical lesions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa , TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.

The second most prevalent neurodegenerative disorder in the elderly is Parkinson's disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish ( Danio rerio ) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans . The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Razali, Othman, Mohd Nasir, Doolaanea, Kumar, Ibrahim, Mohamed Ibrahim and Mohamed.)

Background: Oxidative stress has been implicated as a fundamental mechanism in the decline of bone mass. Although serum uric acid (SUA) has potent antioxidant properties, the findings of many epidemiological and experimental studies couldn't draw a clear conclusion on the relation between SUA and bone health. We aim to investigate the association between SUA and bone mineral density (BMD) at different skeletal sites among healthy Qataris., Methodology: A cross-sectional analysis including total-body and site-specific bone mineral density scores and other serological markers of 2981 healthy Qatari adults (36.4 ± 11.1 years) from the Qatar biobank database was conducted. The study participants were divided into quartiles based on the level of SUA, and the BMD was measured using dual-energy X-ray absorptiometry (DXA). Multiple regression analyses were applied to investigate the association between SUA and BMD adjusting for multiple confounding factors., Results: High levels of SUA were significantly associated with the increased bone mineral density of the total body and at site-specific skeletal locations after adjusting for age and gender (p-value < 0.001). Further adjustment for body mass index (BMI), smoking, vitamin D, alkaline phosphatase, and estimated glomerular filtration rate (eGFR) levels attenuated the association but the association remained significant for individuals with high SUA levels (p-value ≤ 0.01).The association between SUA and BMD was not significant in non-obese, females, young adults, and smokers. However, no interaction was found between SUA and age, gender, BMI and smoking., Conclusion: Higher SUA levels are associated with a high bone density among healthy Qatari adults. However, such observation demands further investigations to outline the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ibrahim, Younes, Shi and Abu-Madi.)

Objective: The natural compound, thymoquinone (TQ) has demonstrated potential anticancer properties in inhibiting cell proliferation and promoting apoptosis in myeloid leukemia cells, breast cancer cells, and others. However, the effect mechanism of TQ on AML cells still not fully understood. In this study, the authors examined the effects of TQ on the expression of JAK/STAT-negative regulator genes SOCS-1, SOCS-3, and SHP-1, and their consequences on cell proliferation and apoptosis in HL60 leukemia cells., Methods: MTT and trypan blue exclusion tests were conducted to determine the 50% inhibitory concentration (IC50) and cell proliferation. FITC Annexin and Guava® reagent were used to study the cell apoptosis and examine the cell cycle phases, respectively. The expression of JAK/STAT-negative regulator genes, SOCS-1, SOCS-3, and SHP-1, was investigated using reverse transcriptase- quantitative PCR (RT-qPCR)., Results: TQ demonstrated a potential inhibition of HL60 cell proliferation and a significant increase in apoptotic cells in dose and time-dependent manner. TQ significantly induced cycle arrest at G0-G1 phase (P < 0.001) and enhanced the re-expression of JAK/STAT-negative regulator genes., Conclusion: TQ potentially inhibited HL60 cell proliferation and significantly increased apoptosis with re-expression of JAK/STAT-negative regulator genes suggesting that TQ could be a new therapeutic candidate for leukemia therapy., .

Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1 H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1 H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), β-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.

Diseases caused by oxidative stress can be prevented by antioxidant. Current treatments for those neurodegenerative diseases are not effective and cause many side effects. Thus, the search for alternative medicines is in high demand. Therefore, the main purposed of this study is to evaluate the neuroprotective effects of Curcuma longa (rhizome) 80% methanol extract. Antioxidant using dichlorofuoresence diacetate (DCF-DA) assay on SH-SY5Y cells revealed high activities of Curcuma longa (rhizome) extract with IC50 of 105.9±0.8 µg/mL. Sub-acute and chronic toxicity tests of the plant extract on adult Javanese medaka (Oryzias javanicus) showed high toxicity effect with LC 50 of 24.15±0.8 mg/L and 13.69±0.7 mg/L respectively. Neuroprotective tests using cholinesterase assay disclose significant differences at P<0.05 between the group that are exposed to arsenic and treated with the crude extract and the group that are exposed to only arsenic. Identification of vitexin and isovitexin justified the high antioxidant potential of this plant leaf and it highest benefit to be used as medicinal supplement.

A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC 50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Melanocyte survival is mediated by diverse signaling pathways. However, the molecular mechanisms they use and molecules that they target are incompletely understood. Here, we show that melanocyte survival is mediated by diverse, nonredundant signaling pathways, including ERK1/2, AKT, PKA, and PKC. Each of these pathways is exerting prosurvival effects by phosphorylating the BAD. While Ser112-BAD phosphorylation is regulated by pERK, pPKA and pPKC, Ser136 and Ser155 phosphorylation are exclusively controlled by pAKT and pPKA, respectively. Inhibition of these pathways individually resulted in only modest apoptosis; however, most significant apoptosis, as a result of BAD dephosphorylation, was seen when all pathways were inhibited concurrently. BAD phosphorylation was essential for survival of melanocytes as cells expressing phosphorylation-deficient BAD were not rescued by any of the identified pathway. Furthermore, melanocytes became insensitive to kinase inhibitor-induced apoptosis when BAD expression was knocked down by BAD-shRNA. Overexpression of BAD in melanocytes stimulated faster apoptosis in response to kinase inhibitors. Taken together, our results show that BAD is acting as a convergence point for diverse survival pathways in melanocytes. Understanding the molecular mechanisms of melanocyte survival provides fundamental new insights into physiological mechanisms involved in the development of various melanocyte pathologies such as melanoma and vitiligo., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Gallic acid (GA) is a natural phenolic compound with therapeutic effects that are often challenged by its rapid metabolism and clearance. Therefore,  GA was encapsulated using gum arabic into nanoparticles to increase its bioavailability. The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. The GANPs were further evaluated for the in vitro cytotoxicity, cell uptake and cell migration in four types of human cancer cell lines including (MCF-7, MDA-MB231) breast adenocarcinoma, HepG2 hepatocellular cancer, HT-29 colorectal adenocarcinoma, and MCF-10A breast epithelial cell lines. The GANPs demonstrated potent antioxidant effects and have shown promising anti-cancer properties in a dose-dependent manner with a predilection toward HepG2 and MCF7 cancer cells. The uptake of GANPs was successful in the majority of cancer cells with a propensity to accumulate in the nuclear region of the cells. The HepG2 and MCF7 cancer cells also had a significantly higher percentage of apoptosis and were more sensitive to gallic acid nanoparticle treatment in the cell migration assay. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing  the antioxidant properties. The formulated nanoparticles also had remarkably low toxicity in normal cells. Based on these findings, GANPs may have promising therapeutic applications towards the development of more effective treatments with a probable targeting precision in cancer cells.

Background: Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed., Methods: The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka ( Oryzias javanicus ). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC)., Results: The result shows activities with high significant differences at P < 0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method., Conclusion: The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Ibrahim Hassan et al.)

The approach of drug delivery systems emphasizes the use of nanoparticles as a vehicle, offering the optional property of delivering drugs as a single dose rather than in multiple doses. The current study aims to improve antioxidant and drug release properties of curcumin loaded gum Arabic-sodium alginate nanoparticles (Cur/ALG-GANPs). The Cur/ALG-GANPs were prepared using the ionotropic gelation technique and further subjected to physico-chemical characterization using attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), size distribution, and transmission electron microscopy (TEM). The size of Cur/ALG-GANPs ranged between 10 ± 0.3 nm and 190 ± 0.1 nm and the zeta potential was -15 ± 0.2 mV. The antioxidant study of Cur/ALG-GANPs exhibited effective radical scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) at concentrations that ranged between 30 and 500µg/mL. Cytotoxicity was performed using MTT assay to measure their potential in inhibiting the cell growth and the result demonstrated a significant anticancer activity of Cur/ALG-GANPs against human liver cancer cells (HepG2) than in colon cancer (HT29), lung cancer (A549) and breast cancer (MCF7) cells. Thus, this study indicates that Cur/ALG-GANPs have promising anticancer properties that might aid in future cancer therapy.

This work describes the development of a new methodology based on magnetic nanoparticles assisted dispersive liquid-liquid microextraction (DLLME-MNPs) for preconcentration and extraction of chloramphenicol (CAP) antibiotic residues in water. The approach is based on the use of decanoic acid as the extraction solvent followed by the application of MNPs to magnetically retrieve the extraction solvent containing the extracted CAP. The coated MNPs were then desorbed with methanol, and the clean extract was analysed using ultraviolet-visible spectrophotometry. Several important parameters, such as the amount of decanoic acid, extraction time, stirring rate, amount of MNPs, type of desorption solvent, salt addition and sample pH, were evaluated and optimized. Optimum parameters were as follows: amount of decanoic acid: 200 mg; extraction time: 10 min; stirring rate: 800 rpm; amount of MNPs: 60 mg; desorption solvent: methanol; salt: 10%; and sample pH, 8. Under the optimum conditions, the method demonstrated acceptable linearity ( R 2 = 0.9933) over a concentration range of 50-1000 µg l -1 . Limit of detection and limit of quantification were 16.5 and 50.0 µg l -1 , respectively. Good analyte recovery (91-92.7%) and acceptable precision with good relative standard deviations (0.45-6.29%, n = 3) were obtained. The method was successfully applied to tap water and lake water samples. The proposed method is rapid, simple, reliable and environmentally friendly for the detection of CAP., Competing Interests: All authors declare that there is no conflict of interest., (© 2020 The Authors.)

Outbreaks of edwardsiellosis have severe impact on the aquaculture production of African catfish Clarias gariepinus. In this study, feed supplemented with apple mangrove Sonneratia caseolaris extract was evaluated for its protective effect against Edwardsiella tarda infection in African catfish. Results showed an increase in growth performance and higher survival rate in the treatment groups in a dose dependent manner. Haematological analyses showed an increase in white blood cell count in the treatment groups. Histopathological analysis revealed degenerative changes and regeneration of liver tissue architecture in both the control and treatment groups. However, the presence of inflammatory cells was found exclusively in the kidney of T3 treatment group that was supplemented with the highest dose of extract at 3.17 mg/ml, which inferred the activation of immune response in the fish. Contrast to the deteriorative alteration observed in the kidney of the control group due to E. tarda infection, treatment group exhibited tissue regeneration and well-defined kidney tissue architecture at 3 dpi. Taken together, these results demonstrated that supplementation with the methanol extract of S. caseolaris possesses protective effect in African catfish against the infection of E. tarda., (Copyright © 2018. Published by Elsevier Ltd.)

We describe the preparation, characterization, and application of a composite film adsorbent based on blended agarose-chitosan-multiwalled carbon nanotubes for the preconcentration of selected nonsteroidal anti-inflammatory drugs in aqueous samples before determination by high performance liquid chromatography with ultraviolet detection. The composite film showed a high surface area (4.0258 m 2 /g) and strong hydrogen bonding between the multiwalled carbon nanotubes and agarose/chitosan matrix, which prevent adsorbent deactivation and ensure long-term stability. Several parameters, such as sample pH, addition of salt, extraction time, desorption solvent, and concentration of multiwalled carbon nanotubes in the composite film were optimized using a one-factor-at-time approach. The optimum extraction conditions obtained were as follows: isopropanol as conditioning solvent, 10 mL of sample solution at pH 2, extraction time of 30 min, stirring speed of 600 rpm, 100 μL of isopropanol as desorption solvent, desorption time of 5 min under ultrasonication, and 0.4% w/v of composite film. Under the optimized conditions, the calibration curve showed good linearity in the range of 1-500 ng/mL (r 2  = 0.997-0.999), and good limits of detection (0.89-8.05 ng/mL) were obtained with good relative standard deviations of < 4.59% (n = 3) for the determination of naproxen, diclofenac sodium salt, and mefenamic acid drugs., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two-phase micro-electrodriven membrane extraction (EME) procedure for the pre-concentration of selected non-steroidal anti-inflammatory drugs (NSAIDs) in aquatic matrices was investigated. Agarose film was used as interface between donor and acceptor phase in EME which allowed for selective extraction of the analytes prior to high performance liquid chromatography-ultraviolet detection. Charged analytes were transported from basic aqueous sample solution through agarose film into 1-octanol as an acceptor phase at 9 V potential. Response surface methodology in conjunction with the central composite design showed good correlations between extraction time and applied voltage (R2 > 0.9358). Under optimized extraction conditions, the method showed good linearity in the concentration range of 0.5-500 μg L-1 with coefficients of determination, r2≥ 0.9942 and good limits of detection (0.14-0.42 μg L-1) and limits of quantification (0.52-1.21 μg L-1). The results also showed high enrichment factors (62-86) and good relative recoveries (72-114%) with acceptable reproducibilities (RSDs ≤ 7.5% n = 3). The method was successfully applied to the determination of NSAIDs from tap water and river water samples. The proposed method proved to be rapid, simple and requires low voltage and minute amounts of organic solvent, thus environmentally friendly., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Objective: YB-1 is a transcription and oncogenic factor capable of binding to DNA and RNA performing versatile functions within normal and cancer cells. Some studies reported the binding of YB-1 with a collagenases gene promoter and influencing their expression. In addition, the role of YB-1 in malignant melanoma was not elucidated. Thus, in this study, the aim was to knock down the expression of YB-1 in A375 malignant melanoma cancer cell using the shRNA approach and study its effect on cancer cell proliferation, migration, and expression of collagenases. Methods: A375 malignant melanoma cell lines were grown in standard conditions and were transfected with three plasmids containing a retroviral pGFP-V-RS vector, two of them containing targeting sequences for YB-1 mRNA. The third plasmid contained a scrambled mRNA sequence as a negative control. Expression of YB-1 was validated using immune-fluorescence staining, RT-PCR and western blotting. The cancer cell proliferation was determined using MTT assay, serial trypan blue cell counting and cell cycle flow-cytometry analysis. Expression of collagenases (MMP1, MMP8, and MMP13) was evaluated using RT-PCR and western blotting analysis. In addition, a wound-healing assay was used to assess cell migration potential. Statistical analysis was performed using one-way ANOVA test with Bonferroni post hoc analysis to compare the quantitative results among samples. Results: The established silenced cell strains (P1 and P2) had nearly 70% knockdown in the expression of YB-1. These YB-1 silenced strains had a significant cell cycle-specific reduction in cell proliferation ( p < 0.05 in serial cell counting and cell cycle flow cytometry analysis, p < 0.001 in MTT assay). In addition, YB-1 silenced strains had a remarkable reduction in cell migration potential. Expression of MMP13 was significantly reduced in YB-1 silenced strains. Conclusion: YB-1 oncoprotein is a promising target in the treatment of malignant melanoma. Silencing of this protein is associated with significant anti-proliferative, anti-invasive and MMP13 insulating properties in A375 malignant melanoma cancer cell lines., Competing Interests: The authors declare no conflict of interest.

A new facile magnetic micro-solid-phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite-MCM-41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 μg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite-MCM-41 at pH 12. The analyte was desorbed using 100 μL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05-500 μg/L (r 2  = 0.996-0.999). Good limits of detection (0.008-0.010 μg/L) were obtained for the analytes with good relative standard deviations of <8.0% (n = 5) for the determination of 0.1, 5.0, and 500.0 μg/L of antidepressant drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1-115.4%. Results indicate that magnetite micro-solid-phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Agarose-chitosan-immobilized octadecylsilyl-silica (C 18 ) film micro-solid phase extraction (μSPE) was developed and applied for the determination of phenanthrene (PHE) and pyrene (PYR) in chrysanthemum tea samples using high performance liquid chromatography-ultraviolet detection (HPLC-UV). The film of blended agarose and chitosan allows good dispersion of C 18 , prevents the leaching of C 18 during application and enhances the film mechanical stability. Important μSPE parameters were optimized including amount of sorbent loading, extraction time, desorption solvent and desorption time. The matrix match calibration curves showed good linearity (r⩾0.994) over a concentration range of 1-500ppb. Under the optimized conditions, the proposed method showed good limits of detection (0.549-0.673ppb), good analyte recoveries (100.8-105.99%) and good reproducibilities (RSDs⩽13.53%, n=3) with preconcentration factors of 4 and 72 for PHE and PYR, respectively., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate and apply supported ionic liquid membrane (SILM) in two-phase micro-electrodriven membrane extraction combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) for pre-concentration and determination of three selected antidepressant drugs in water samples. A thin agarose film impregnated with 1-hexyl-3-methylimidazolium hexafluorophosphate, [C 6 MIM] [PF 6 ], was prepared and used as supported ionic liquid membrane between aqueous sample solution and acceptor phase for extraction of imipramine, amitriptyline and chlorpromazine. Under the optimized extraction conditions, the method provided good linearity in the range of 1.0-1000μgL -1 , good coefficients of determination (r 2 =0.9974-0.9992) and low limits of detection (0.1-0.4μgL -1 ). The method showed high enrichment factors in the range of 110-150 and high relative recoveries in the range of 88.2-111.4% and 90.9-107.0%, for river water and tap water samples, respectively with RSDs of ≤7.6 (n=3). This method was successfully applied to the determination of the drugs in river and tap water samples. It is envisaged that the SILM improved the perm-selectivity by providing a pathway for targeted analytes which resulted in rapid extraction with high degree of selectivity and high enrichment factor., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chronic exposure to mercury (Hg) can lead to cumulative impairments in motor and cognitive functions including alteration in anxiety responses. Although several risk factors have been identified in recent year, little is known about the environmental factors that either due exposure toward low level of inorganic mercury that may led to the developmental disorders. The present study investigated the effects of embryonic exposure of mercury chloride on motor function and anxiety-like behavior. The embryo exposed to 6 different concentrations of HgCl 2 (7.5, 15, 30, 100, 125, 250nM) at 5hpf until hatching (72hpf) in a semi-static condition. The mortality rate increased in a dose dependent manner where the chronic embryonic exposure to 100nM decreased the number of tail coiling, heartbeat, and swimming activity. Aversive stimulus was used to examine the effects of 100nM interferes with the development of anxiety-related behavior. No elevation in both thigmotaxis and avoidance response of 6dpf larvae exposed with 100nM were found. Biochemical analysis showed HgCl 2 exposure affects proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. These results showed that implication of HgCl 2 on locomotor and biochemical defects affects motor performance and anxiety-like responses. Yet, the potential underlying mechanisms these responses need to be further investigated which is crucial to prevent potential hazards on the developing organism due to neurotoxicant exposure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: The main objective of this study was to emphasize on histopathological examinations and molecular identification of Streptococcus agalactiae isolated from natural infections in hybrid tilapia ( Oreochromis niloticus ) in Temerloh Pahang, Malaysia, as well as to determine the susceptibility of the pathogen strains to various currently available antimicrobial agents., Materials and Methods: The diseased fishes were observed for variable clinical signs including fin hemorrhages, alterations in behavior associated with erratic swimming, exophthalmia, and mortality. Tissue samples from the eyes, brain, kidney, liver, and spleen were taken for bacterial isolation. Identification of S. agalactiae was screened by biochemical methods and confirmed by VITEK 2 and 16S rRNA gene sequencing. The antibiogram profiling of the isolate was tested against 18 standard antibiotics included nitrofurantoin, flumequine, florfenicol, amoxylin, doxycycline, oleandomycin, tetracycline, ampicillin, lincomycin, colistin sulfate, oxolinic acid, novobiocin, spiramycin, erythromycin, fosfomycin, neomycin, gentamycin, and polymyxin B. The histopathological analysis of eyes, brain, liver, kidney, and spleen was observed for abnormalities related to S. agalactiae infection., Results: The suspected colonies of S. agalactiae identified by biochemical methods was observed as Gram-positive chained cocci, β-hemolytic, and non-motile. The isolate was confirmed as S. agalactiae by VITEK 2 (99% similarity), reconfirmed by 16S rRNA gene sequencing (99% similarity) and deposited in GenBank with accession no. KT869025. The isolate was observed to be resistance to neomycin and gentamicin. The most consistent gross findings were marked hemorrhages, erosions of caudal fin, and exophthalmos. Microscopic examination confirmed the presence of marked congestion and infiltration of inflammatory cell in the eye, brain, kidney, liver, and spleen. Eye samples showed damage of the lens capsule, hyperemic and hemorrhagic choroid tissue, and retina hyperplasia accompanied with edema. Brain samples showed perivascular and pericellular edema and hemorrhages of the meninges. Kidney samples showed hemorrhage and thrombosis in the glomeruli and tubules along with atrophy in hematopoietic tissue. Liver samples showed congestion of the sinusoids and blood vessel, thrombosis of portal blood vessel, and vacuolar (fatty) degeneration of hepatocytes. Spleen samples showed large thrombus in the splenic blood vessel, multifocal hemosiderin deposition, congestion of blood vessels, and multifocal infiltration of macrophages., Conclusion: Therefore, it can be concluded that pathological changes in tissues and organs of fish occur proportionally to the pathogen invasion, and because of their high resistance, neomycin and gentamicin utilization in the prophylaxis or treatment of S. agalactiae infection should be avoided.

Recently, there has been considerable interest in the use of miniaturized sample preparation techniques before the chromatographic monitoring of the analytes in unknown complex compositions. The use of biopolymer-based sorbents in solid-phase microextraction techniques has achieved a good reputation. A great variety of polysaccharides can be extracted from marine plants or microorganisms. Seaweeds are the major sources of polysaccharides such as alginate, agar, agarose, as well as carrageenans. Agarose and alginate (green biopolymers) have been manipulated for different microextraction approaches. The present review is focused on the classification of biopolymer and their applications in multidisciplinary research. Besides, efforts have been made to discuss the state-of-the-art of the new microextraction techniques that utilize commercial biopolymer interfaces such as agarose in liquid-phase microextraction and solid-phase microextraction., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The asymmetric unit of the title compound, [Ni(C15H14NO2)2], comprises an Ni(II) cation, lying on an inversion centre, and a Schiff base anion that acts as a bidentate ligand. The Ni(II) cation is in a square-planar coordination environment binding to the imine N and phenolate O atoms of the two Schiff base ligands. The N- and O-donor atoms of the two ligands are mutually trans, with Ni-N and Ni-O bond lengths of 1.9191 (11) and 1.8407 (9) Å, respectively. The plane of the meth-oxy-benzene ring makes a dihedral angle of 84.92 (6)° with that of the phenolate ring. In the crystal, mol-ecules are linked into screw chains by weak C-H⋯O hydrogen bonds. Additional C-H⋯O hydrogen bonds, together with C-H⋯π contacts, arrange the mol-ecules into sheets parallel to the ac plane.

In the title complex, [Pd(C16H16NO2)2]·CHCl3, the Pd(II) cation lies on an inversion center. One Cl atom of the CHCl3 solvent mol-ecule lies on a twofold axis and the C-H group is disordered with equal occupancies about this axis with the other Cl atom in a general position with full occupancy. The Pd(II) cation is four-coordinate and adopts a square-planar geometry via coordination of the imine N and phenolic O atoms of the two bidentate Schiff base anions. The N and O atoms of these ligands are mutually trans. The plane of the benzene ring makes a dihedral angle of 73.52 (10)° with that of the meth-oxy-phenolate ring. In the crystal, mol-ecules of the Pd(II) complex are arranged into sheets parallel to the ac plane, and the chloro-form solvent mol-ecules are located in the inter-stitial areas between the complex mol-ecules. Weak inter-molecular C-H⋯O and C-H⋯π inter-actions stabilize the packing.