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Acyclovir (ACV) is a potentially effective antiviral medication; however, it has a serious drawback, which is its poor solubility, bioavailability, and short half-life. The goal of this study is to improve its drawbacks through the synthesis of nanogels. In this study, the cross-linked hyaluronic acid-grafted poly(acrylamide- co -itaconic acid) nanogel is synthesized successfully through free radical polymerization and used as a safe pH-responsive carrier for ACV. The nanogels showed pH response in vitro and in vivo. The prepared nanogel C5 (1:1 ratio of acrylamide: itaconic), which had the highest grafting efficiency, showed maximum swelling, drug loading, and release in pH 7.4, higher than pH 1.2. Also, nanogel C5, which had a large surface area, showed good stability, and its matrices shrank in acidic medium and protected the drug, while in basic medium, it expanded and released ACV in a sustained manner and improved the bioavailability and half-life of ACV in vivo.

This study end to develop nanoemulsions of Panax ginseng dry extract and to evaluate the potential impact of these nanoemulsions versus free Panax ginseng dry extract and Vit.E in recovering male infertility induced in rats. Nanoemulsions of Panax ginseng dry extract were prepared by oil in water method. The designed samples were characterized by TEM, zeta sizer, FTIR, and TGA. The in vitro study included DPPH assay to estimate the free radical scavenging activity of the suggested treatments. The in vivo study included 100 adult male Wistar rats which were assigned into 10 equal groups; five groups of young rats weighting (150-200 g) and five groups of aged rats weighting (350-400 g). Group I, negative control. Group II, bisphenol-A (BPA). Group III, BPA+ Panax ginseng dry extract nanoemulsion. Group IV, BPA+ free Panax ginseng dry extract. Group V, BPA +Vit.E. After 40 days, serum total testosterone, free testosterone, MDA, 8-OHdG and AGEs were estimated. Besides, the histological investigation of testicular tissue sections was performed. TEM imaging of Panax ginseng dry extract nanoemulsions indicated spherical shape with diameter range from 2 to 50 nm, and the size distribution was in the range from 62 to 123 d.nm. The zeta potential of the designed nanoemulsions was -32.8 to -38.9 mV. FTIR spectra revealed the common active groups in the prepared nanoemulsions. The thermal stability of the nanoemulsions was up to 207 ºC. The in vitro results of DPPH assay showed % inhibition of DPPH free radical for Panax ginseng nanoemulsions samples was 49.38% (for young-treated group Sample A) and 72.28% (for aged-treated group Sample B), while for free Panax ginseng dry extract samples was 30.27% (for young-treated group Sample C) and 56.76% (for aged-treated group Sample D), for Vit.E samples was 32.36% (for young-treated group Sample E) and 36.39% (for aged-treated group Sample F).Thus the nanoemulsions exhibit free radicals scavenging activity more than free Panax ginseng dry extract and Vit.E. The in vivo findings elucidated that Panax ginseng dry extract nanoemulsions and Vit.E successfully revers the progressive insult of BPA on male fertility by significantly enhance total testosterone (2.87±0.318) and free testosterone (1.63±0.033) serum levels, and significantly decrease MDA (2.77±0.018), 8-OHdG (6.76±0.174) and AGEs (92.60±1.701) serum levels. Interestingly, the most promising outcomes were recorded upon the treatment with Panax ginseng dry extract nanoemulsions. In conclusion the developed Panax ginseng dry extract nanoemulsion could be used as a promising strategy in improving potential male infertility defects by rescuing male sex hormones, neutralizing oxidative stress and retrieving the structural organization of the testes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Ethical Committee for Medical Research of the NRC, Egypt has been granted the final approval for the study under registration number of 13104112022 and all methods were performed in accordance with relevant regulations and guidelines including the ARRIVE guideline., (© 2024. The Author(s).)

Background: The study's primary goal is to ascertain whether there is a relationship between the processed green tea methanolic extract's (GTME) phytochemical components and its potential effectiveness against human liver cancer cells. The GTME's phytochemical composition was identified using gas chromatography-mass spectrometry, and the extract's capacity to lower cellular proliferation and cause apoptosis in HepG2 cancerous liver cell lines was checked., Results: The findings of the gas chromatography-mass chromatogram showed that GTME included bioactive antioxidants and anticancer substances. Additionally, utilizing the MTT, comet assay, and acridine assay, GTME revealed a selective cytotoxic impact with a significant IC50 value (27.3 µg/ml) on HepG2 cells without any harmful effects on WI-38 healthy cells. Also, compared to untreated cells, the extract-treated HepG2 cells had an upsurge in the proportion of cells that have undergone apoptosis and displayed a comet nucleus, which is a sign of DNA damage. In addition, HepG2 cells treated with GTME revealed a stop in the G1 phase and sub-G1 apoptotic cells (37.32%) in a flow cytometry analysis. Furthermore, reactive oxygen species were shown to be responsible for HepG2 apoptosis, and the tested extract significantly reduced their levels in the treated cells. Lastly, compared to untreated cells in treated HepG2 cells, GTME significantly changed protein expression levels linked with cell cycle arrest in the G1 phase and apoptosis., Conclusion: These findings provided information about the processes through which the GTME inhibited the growth of HepG2. Therefore, it has potential as an effective natural therapy for the treatment of human liver cancer. However, to validate these findings, animal models must be used for in vivo studies., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Hanna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Male infertility is identified by the inability of a man to successfully impregnate his fertile female partner, even following a year of regular unprotected sexual intercourse. About half of all infertility cases are attributed to what is known as "male factor" infertility. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common etiological factor due to the ubiquitous presence of the environmental contaminants. Bisphenol A is recognized as an endocrine-disrupting chemical that has adverse effects on both male and female reproductive systems. On the other hand, numerous studies have demonstrated that Panax ginseng possessed the potential to improve male infertility parameters; promote spermatogenesis, recover the quality and motility of sperm and enhance testicular functions as it acted as a natural androgen supplement. The objective of this review is to offer a summary of the findings obtained from the current research data on the insult of bisphenol A (BPA) on male infertility and its supposed mode of action, as well as shed light on the potent ameliorative role of Panax ginseng extract, with a special focus on the mechanism behind its action. This review delivers a clear understanding of BPA mechanism of action on male infertility and the presumed risks deriving from its exposure. Also, this review provides evidence for the functional role of Panax ginseng extract in restoring male fertility., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, and bioenergetic functions. Mitochondria play a crucial role in metabolic reprogramming, which is a characteristic of cancer cells and allows them to ensure a steady supply of proteins, nucleotides, and lipids to enable rapid proliferation and development. Their dysregulated activities have been associated with the growth and metastasis of different kinds of human cancer, particularly ovarian carcinoma. In this review, we briefly demonstrated the modified mitochondrial function in cancer, including mutations in mitochondrial DNA (mtDNA), reactive oxygen species (ROS) production, dynamics, apoptosis of cells, autophagy, and calcium excess to maintain cancer genesis, progression, and metastasis. Furthermore, the mitochondrial dysfunction pathway for some genomic, proteomic, and metabolomics modifications in ovarian cancer has been studied. Additionally, ovarian cancer has been linked to targeted therapies and biomarkers found through various alteration processes underlying mitochondrial dysfunction, notably targeting (ROS), metabolites, rewind metabolic pathways, and chemo-resistant ovarian carcinoma cells., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The purpose of the current investigation was to produce cinammaldehyde-based chalcone derivatives ( 3a - k ) to evaluate their potential effectiveness as antioxidant and inhibitory agents versus human Caco-2 cancer cells. The findings obtained using the DPPH assay showed that compound 3e had the highest effective antioxidant activity with the best IC 50 value compared with the other compounds. Moreover, the cytotoxic findings revealed that compound 3e was the best compound for inhibiting Caco-2 development in contrast to all other produced derivatives, with the lowest IC 50 concentration (32.19 ± 3.92 µM), and it also had no detrimental effects on healthy human lung cells (wi38 cells). Exposure of Caco-2 cells with this IC 50 value of compound 3e resulted in a substantial rise in the number of early and late cells that are apoptotic with a significant comet nucleus when compared with control cells employing the annexin V/PI and comet evaluations, respectively. Furthermore, qRT-PCR and ELISA examinations indicated that compound 3e significantly altered the expression of genes and their relative proteins related to apoptosis in the treated Caco-2 cells, thus significantly inhibiting Caco-2 growth through activating Caspase-3 via an intrinsic apoptotic pathway. As a result, compound 3e could serve as an effective therapy for human colon cancer.

Background: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs., Methods: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days., Results: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-β, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain., Conclusion: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM., (© 2024. The Author(s).)

Tartrazine is a yellow colouring agent that is commonly used in foods; however, high dosages of Tartrazine affect fertility and create oxidative stress by generating free radicals. A plant species known as Stevia rebaudiana has natural antioxidants that show promise for protecting testicular tissue. Consequently, this study was intended to examine the ameliorative effect of the aqueous extract of S. rebaudiana (Stevia) on the fertility of male Wistar rats induced by the daily oral intake of Tartrazine. Utilizing gas chromatography-mass spectrometry, phytochemical identification was accomplished for Stevia extract. Study groups were separated into several groups: the first group (the control) got distilled water for up to 56 days; the Stevia group (1000 mg/kg), the Tartrazine group (300 mg/kg) and the Stevia and Tartrazine group (the group was given Tartrazine after 1 h of Stevia extract intake). Also, the oxidative damage in testicular tissues was assessed by measuring the levels of malondialdehyde (MDA) and antioxidants (catalase [CAT], superoxide dismutase [SOD] and glutathione reductase [GSH]). Further, histological alterations were examined. In addition, cyclic AMP-responsive element modulator (Crem) gene expression levels and their relative proteins were measured in the testicular tissues using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Sperm analysis and testosterone concentration were also performed. SPSS version 25 was used for the analysis of results while (p < .05) was regarded as significant. Compared with the control group, the results demonstrated that Tartrazine caused a significant reduction (p < .05) in the testosterone hormone level (0.70 ± 0.21) and the Crem protein quantity (1.21 ± 0.23) in the treated Tartrazine group. Also, it had a significant decrease (p < .05) in sperm motility, viability, count and antioxidant levels. Moreover, there was a significant increase (p < .05) in sperm abnormalities, MDA level (7.40 ± 1.10), kidney and liver function parameters, and DNA degradation in the treated Tartrazine group compared with the control group. On the contrary, the Stevia extract intake enhanced the testosterone (2.50 ± 0.60), antioxidants and Crem protein levels (2.33 ± 0.10) with an improvement in sperm quality in the Stevia and Tartrazine-treated group compared with the Tartrazine group. Stevia also caused a significant decrease (p < .05) in the MDA level (3.20 ± 0.20), and sperm abnormalities with an enhancement of the liver and kidney function parameters in the Stevia and Tartrazine-treated group compared to the Tartrazine group. Stevia administration has a protective effect on the testicular tissues and sperm quality against toxicity induced by Tartrazine exposure, so it will be a good antioxidant drug to be administered daily before daily administration of Tartrazine., (© 2023 John Wiley & Sons Ltd.)

The research's goal is to create the surfaces of titanium dioxide nanoparticles (TiO 2 NPs) in a layer of folic acid (FA) that can effectively target human bladder cancer cells (T24). An efficient method for creating FA-coated TiO 2 NPs was used, and many tools have been used to analyze its physicochemical properties. The cytotoxic effects of FA-coated NPs on T24 cells and the mechanisms of apoptosis generation were examined employing a variety of methodologies. The prepared FA-coated TiO 2 NPs suspensions with a hydrodynamic diameter around 37 nm and a negative surface charge of -30 mV reduced T24 cell proliferation with stronger IC 50 value (21.8 ± 1.9 μg/ml) than TiO 2 NPs (47.8 ± 2.5 μg/ml). This toxicity resulted in apoptosis induction (16.63%) that was caused through enhanced reactive oxygen species formation and stopping the cell cycle over G2/M phase. Moreover, FA-TiO 2 NPs raised the expression levels of P53, P21, BCL2L4, and cleaved Caspase-3, while decreasing Bcl-2, Cyclin B, and CDK1 in treated cells. Overall, these findings revealed efficient targeting of the FA-TiO 2 NPs resulted in increasing cellular internalization caused increased apoptosis in T24 cells. As a result, FA-TiO 2 NPs might be a viable treatment for human bladder cancer., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

The goal of the current study was to prepare two new homologous series of N,N'-diarylurea and N,N'-diarylthiourea derivatives to investigate the therapeutic effects of these derivatives on the methodologies of inhibition directed on human MCF-7 cancer cells. The molecular structures of the prepared derivatives were successfully revealed through elemental analyses, 1 H-NMR, 13 C-NMR and FT-IR spectroscopy. The cytotoxic results showed that Diarylthiourea (compound 4 ) was the most effective in suppressing MCF-7 cell growth when compared to all other prepared derivatives, with the most effective IC 50 value (338.33 ± 1.52 µM) after an incubation period of 24 h and no cytotoxic effects on normal human lung cells (wi38 cells). Using the annexin V/PI and comet tests, respectively, treated MCF-7 cells with this IC 50 value of the Diarylthiourea 4 compound displayed a considerable increase in early and late apoptotic cells, as well as an intense comet nucleus in comparison to control cells. An arrest of the cell cycle in the S phase was observed via flow cytometry in MCF-7 cells treated with the Diarylthiourea 4 compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound 4 compared to control cells, suggesting that DNA damage induced by compound 4 may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea 4 compound inhibited the proliferation of MCF-7 cancer cells by arresting the S cell cycle and caspase-3 activation via an intrinsic apoptotic route. These results, however, need to be verified through in vivo studies utilizing an animal model.

Anti-cancer medications that are delivered specifically to the tumor site possess greater efficacy with less negative effects on the body. So, the current research relies on a novel method for intercalating the anticancer medication methotrexate in poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugated with sodium hyaluronate. The graft copolymers were synthesized through persulfate-initiated grafting of acrylic acid onto a binary mixture of various amounts of chitosan and poly(3-hydroxybutyrate) (2/1, 1/1 and 1/2, w/w) using microwave irradiation. The graft copolymer was conjugated with sodium hyaluronate for targeted delivery of methotrexate drug specifically to colon cancer cell lines (Caco-2). The graft copolymers were characterized by many physical techniques. The maximum drug loading efficiency was observed in case of the graft copolymer/hyaluronate rich in chitosan content 69.7 ± 2.7 % (4.65 mg/g) with a sustained release about 98.6 ± 1.12 %, at pH 7.4. The findings of severe cytotoxicity having a value of the IC 50 of 11.7 μg/ml, a substantial proportion of apoptotic cells (67.88 %), and an elevated level of DNA breakage inside the treated Caco-2 cells verified the effective release of methotrexate from the loaded copolymer matrix. Besides, the high stability and biological activity of the released drug was exhibited through occurrence of greater increment of reactive oxygen species and effect on the extent of expression of genes connected to apoptosis and anti-oxidant enzymes within the treated cells. Ultimately, this system can be recommended as potent carrier for methotrexate administration to targeted cancerous cells in the colon., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predicting drug resistance., Objective: We studied the significance of PTEN rs701848 variants as significant predictors for trastuzumab resistance in HER2-positive metastatic BC patients. Therefore, considering their value in predicting clinical outcomes., Materials and Methods: This case-control study was conducted among female patients with HER2-positive metastatic breast cancer who underwent Trastuzumab therapy during the period from March 2017 to December 2020. PTEN rs701848 genotypes were analyzed in 160 HER2-positive metastatic breast cancer who received Trastuzumab therapy and clinically monitored for therapeutic response., Results: PTEN rs701848 is deemed a significant predictor of Trastuzumab resistance and an independent prognostic factor of progression-free survival (PPFS). In particular, the C allele is associated with increased risk for Trastuzumab resistance and shorter PFS as compared to the homozygous TT genotype., Conclusion: PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The current research relies on a one-pot green biosynthesis of silver nanoparticles (SNPs) with various ratios of silver (Ag) in the existence of N, N, N-trimethyl chitosan chloride (TMC) and carboxymethyl kappa-carrageenan (CMKC), to investigate the effectiveness of the synthesized silver nanocomposites (SNCs) as pH sensitive biodegradable carrier for orally intestinal delivery of 5-fluorouracil (5-FU) drug. FTIR, XRD, TEM and FE-SEM/EDX methods were utilized to demonstrate the structure of the prepared polyelectrolyte complex PEC (TMC/CMKC) and SNCs (TMC/CMKC/Ag). The results showed that the 5-FU encapsulation effectiveness inside all of the prepared SNCs samples was improved by increasing the concentration of Ag, reaching 92.16 ± 0.57 % with 3 % Ag. In vitro release behavior of 5-FU loaded SNC 3 % (TMC/CMKC/Ag 3 %), displayed slow and sustained release reaching 96.3 ± 0.81 % up to 24 h into pH 7.4 medium. The successful release of 5-FU from the loaded SNC 3 % was confirmed through occurrence of strong cytotoxicity, with an IC 50 value of 31.15 μg/ml, and high % of apoptotic cells (30.66 %) within the treated HCT116 cells. Besides, SNC 3 % showed good biodegradability and antimicrobial properties against different bacterial strains. Overall, SNC 3 % can be suggested as an effective system for both controlled drug delivery and antibacterial action., Competing Interests: Declaration of competing interest The authors declare no known conflicts of interest associated with this publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tissue iron overload is a life-threatening scenario in children with transfusion-dependent β-thalassemia major, miRNAs that are involved in iron hemostasis could serve as therapeutic targets for control of iron overload. We aimed to find out the association between three iron-related miRNAs "miR-let-7d, miR-122, and miR-200b" and excess iron in tissues, in transfusion-dependent β-thalassemia major patients. Circulating miRNA expressions are measured in peripheral blood (PB) samples using qPCR of transfusion-dependent (TDT) β-thalassemia patients (n = 140) and normalized to non-transfusion-dependent (NTDT) β-thalassemia (n = 45). Results revealed that plasma expression levels of miR-let-7d and miR-200b were significantly downregulated in TDT patients; however, miR-122 was upregulated. In terms of tissue iron load, aberrant expression of miRNAs was significantly associated with increased-iron accumulation in hepatic and cardiac tissues. We concluded that circulating miRNAs are strong candidates that associate iron hemostasis in transfusion-dependent β-thalassemia major patients. And by extension, targeting miR-let-7d, miR-122, and miR-200 might serve as novel sensitive, specific and non-invasive predictor biomarkers for cellular damage under condition of tissue iron excess., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO2 NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells., Methods: The prepared FA-SnO2 NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO2 NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO2 NPs treated SKOV3 cells were investigated using Annexin V/PI, AO/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO2 NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO2 NPs were studied in vivo using Wister rats., Results: The obtained FA-SnO2 NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO2 NPs, FA-SnO2 NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO2 NPs increased significantly the % of apoptotic cells in the sub- G1 and G2/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO2 NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells., Conclusion: Overall, the results suggested that an increase in cellular FA-SnO2 NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO2 NPs against living systems. So, FA-SnO2 NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: KHO volunteered as medical doctor in a healthcare centre for undocumented migrants in Bergen, Norway (2015-2017). DHR has no competing interests to declare.

The aim of the present study was to prepare curcumin nanoparticles (nanocurcumin) by a sol-oil method to improve curcumin absorption and bioavailability, and to investigate the therapeutic effects of the prepared nanoparticles on the inhibition mechanisms towards human Hep-2 cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, and zeta potential analysis. The prepared curcumin nanoparticles possessed a narrow particle size distribution with an average diameter of 28 nm. The inhibition effects on the growth of human Hep-2 cells were investigated using neutral red uptake and lactate dehydrogenase assays. The results indicated that the nanocurcumin has a selective effect in inhibiting Hep-2 cell growth in a dose- and time-dependent mode with the most effective IC 50 value (17 ± 0.31 μg ml -1 ) obtained after 48 h of incubation without any cytotoxic effects on normal cells. This IC 50 value of nanocurcumin revealed a significant increase of early and late apoptotic cells with an intense comet nucleus of Hep-2 cells as a marker of DNA damage. Flow cytometry analysis of the progression of apoptosis in nanocurcumin Hep-2 treated cells showed that arresting in the cell cycle in the G2/M phase with increasing apoptotic cells in the sub-G1 phase. At the same time, real-time PCR analysis indicated that the treatment of Hep-2 cells with nanocurcumin resulted in upregulation of P53, Bax, and Caspase-3, whereas there was downregulation of Bcl-XL. These findings gave insights into understanding that the inhibition mechanisms of nanocurcumin on the proliferation of Hep-2 cancer cells was through the G2/M cell cycle arrest and the induction of apoptosis was dependent on Caspase-3 and p53 activation. However, in vivo studies with an animal model are essential to validate these results., Competing Interests: The authors declare no known conflicts of interest associated with this publication., (This journal is © The Royal Society of Chemistry.)

This work deals with assessing the efficient performance of sodium caseinate (SC) as protein-based drug delivery system of niacin (NA) than carboxymethyl cellulose (CMC). In this respect the hydrogels from complexation of chitosan with sodium caseinate (SC/Ch) or sodium carboxymethyl cellulose (CMC/Ch) were prepared. The Synthesized NA free and loaded hydrogels were characterized by many techniques for examining the interaction, morphology, swelling, encapsulation efficiency (EE) and loading (L) % of niacin, as well as cytotoxicity study. The finding data showed the promising behavior of SC/Ch hydrogel than CMC/Ch hydrogel, toward the amount of loaded NA (95.6%) and in vitro slow sustained release up to 24 h. Whereas, the entrapment efficiency of the CMC/Ch to nicotinic acid was reached 85.6%, and it possessed highly initial burst release followed by a slower release up to 24 h. At pH 7.4 (simulated intestinal fluid) both hydrogels provided higher level of releasing profile to NA than pH 2.1 (gastric fluid). The NA release from hydrogels followed Fickian and non-Fickian diffusion mechanism according to pH 7.4 and 2.1, respectively. It is interesting to note that, the data obtained are higher than those obtained from literature reported hydrogel, e.g., poly (2-hydroxyethyl methacrylate). Neutral red uptake and lactate dehydrogenase assays confirmed both hydrogels have good biocompatibility and could be used as nontoxic drug delivery system. So, we recommended SC/Ch hydrogel as an effective controlled niacin drug delivery system with reducing systemic side effects and improved intestinal targeting efficiency., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of the present work was to investigate the preparation of polyelectrolyte hydrogel as potential drug carrier for antibacterial Ciprofloxacin drug (CFX), intended for controlled release formulation. Hydrogel of N-trimehtyl chitosan (TMC)/sodium carboxymethyl xanthan gum (CMXG) was prepared and ciprofloxacin was employed as a model drug to investigate the loading and release performance of the prepared hydrogel. FTIR, DSC, TGA and SEM analysis were used to characterize the TMC/CMXG hydrogel and its CFX loaded hydrogel. The results showed that the ciprofloxacin was successfully incorporated and released from the prepared hydrogel without the loss of structural integrity or the change in its functionality. The encapsulation efficiency of CFX within the prepared hydrogel was found to be increased with increasing the concentration of drug reaching about 93.8 ± 2.1% with concentration of CFX 250 µg/ml. It was shown also that the drug is entrapped within the gel without significant interaction as confirmed from FTIR spectra and DSC analysis. In vitro release study in phosphate buffer saline (PBS), indicated the steady rise in cumulative drug release with the highest release amount, reaching about 96.1 ± 1.8% up to 150 min, whereby the gel with high drug loading efficiency (3.52 ± 0.07%) displayed faster and higher release rate than that of gel containing a smaller amount of drug (0.44 ± 0.01%). The release kinetics of loaded drug followed zero-order kinetics. CFX drug loaded hydrogel showed high activity against the gram positive and gram negative bacterial strains due to the successful released of CFX from the CFX loaded hydrogel into the tested bacterial strains with the highest diameter of inhibition zone against Escherichia coli (67.0 ± 1.0) as compared to reference antibiotic, Gentamicin (28 ± 0.5). Cytotoxicity of the prepared hydrogel was examined in vitro using lung human normal cell lines and showed the highest cell viability (97 ± 0.5%) at concentration up to 50 µg/ml. Consequently, TMC/CMXG hydrogel can be proposed as new controlled release drug delivery system., (Copyright © 2018. Published by Elsevier Inc.)

Aim of the present study is to investigate synthesis of novel hydrogel as a potential protein carrier, intended for controlled release formulation. The hydrophilic bovine serum albumin (BSA) was chosen as a model protein to be encapsulated within xanthan gum (XG)/poly (N‑vinyl imidazole (PVI) hydrogel. Both XG/PVI hydrogel and XG/PVI/BSA matrix structures were elucidated via different analysis tools such as FTIR, XRD, FE-SEM and EDX. Both BSA loading and release profiles were determined. Cytotoxicity of XG/PVI hydrogel was investigated against normal cell line (VERO cells). The obtained results revealed that % Drug (BSA) loading (% DL) and Encapsulation Efficiency (% EE) increased with increasing both gelation time and loaded BSA concentration, while %DL and %EE decreased with increasing the polymer concentration. The maximum value of %DL and %EE was 59.50% and 99.17%, respectively. Results of in-vitro BSA release in PBS showed that increase in the polymer (XG and PVI) concentrations led to increase in BSA release. Kinetic studies of the in-vitro release of BSA from XG/PVI/BSA matrix followed non-Fickian and case II transport mechanism. Moreover, Cytotoxicity results showed good biocompatibility of this novel hydrogel. SDS-PAGE analysis confirmed that the structural integrity of BSA was not affected by the encapsulation or release conditions. Consequently, this novel hydrogel can be used as an efficient BSA carrier for protein delivery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The article probes the origins and content of the Framework of Engagement with Non-State Actors (FENSA) of the World Health Organization (WHO), approved on May 28, 2016, at the 69th World Health Assembly, which established different rules of collaboration to four categories of actors: nongovernmental organizations (NGOs), private sector entities, philanthropic foundations, and academic institutions. Applying the findings of International Legal Theory and based on extensive documentary research, we sought to determine whether FENSA is an appropriate accountability mechanism according to four functions of accountability: constitutional, democratic, epistemic, and populist. The article concludes that there is a risk of the prevalence of the populist function at the expense of the accountability potential that could result from the better use of the other three accountability functions.