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Dypsis decaryi seeds need more phytochemical and biological attention specially on one of the most important life-threatening problems (cancer). Total ethanol extract of D. decaryi seeds (TEEDDS, Arecaceae) and its fixed oil fraction (FOF) were subjected to UPLC-HR-ESI-MS metabolic profiling and gas chromatography-mass spectrometry, respectively. Also, TEEDDS, FOF, and FOF silver nanoparticles (FOF-SNPs) were screened using 4 cell lines. FOF effects on expression of Bcl-2, Bax, P53, and epidermal growth factor receptor (EGFR) in human prostate carcinoma cell line (PC-3) were evaluated and supported by docking study. Metabolic profiling of TEEDDS resulted in identification of 18 compounds. While GC-MS of FOF displayed the presence of 12 fatty acids methyl esters. TEEDDS, staurosporine, FOF, and FOF-SNPs showed IC 50 = 3.55, 9.81, 16.88, and 0.01 µg/mL, respectively, against PC-3 (human prostate carcinoma cell line). FOF effects on the expression of Bcl-2, Bax, P53, and EGFR in PC-3 cell lines displayed IC 50 = 1.09, 220.6, 619.8, and 399.64 ng/mL, respectively. The FOF major constituent (E -13-octadecenoic acid) exhibited significant affinity and binding interactions that were comparable with that of the cocrystalized inhibitor. For the first time, in vitro antiproliferative activity against PC-3, HepG-2, HCT-116, and MCF-7 cells, and chemical profiles of TEEDDS and its FOF have been noteworthy studied. FOF and FOF-SNPs displayed the highest activities particularly on PC-3. Additionally, FOF showed significant activities on Bcl-2, Bax, P53, and EGFR, which was also supported by docking study. These results highlight that FOF and FOF-SNPs could have potent antiproliferative activity against PC-3 cell lines and may play an important role in antiproliferative drug development. [ABSTRACT FROM AUTHOR]

The diagnosis of osteomyelitis is invasive and expensive as the current standard technique is the bone biopsy. Our aim was to compare the degree of agreement and concordance between standard bone biopsy and other non-bone techniques. We performed an electronic search through 12 electronic databases to retrieve relevant studeis. Our criteria included any original article that reported the degree of agreement and/or the concordance between bone biopsy and other non-bone techniques in diagnosing osteomyelitis. We published our protocol in PROSPERO with a registration number, CRD42017080336. There were 29 studies included in the qualitative analysis, of which 15 studies were included in the meta-analysis. Samples from sinus tract had the highest concordance with bone biopsy samples, while swab samples were the least concordant with bone biopsy samples. Additionally, Staphylococcus aureus was the most common bacteria isolated and the most concordant from samples, compared to other types of causative agents. Sinus tract had a significantly very high degree of agreement with bone samples. S. aureus had the highest degree of agreement in bone smaples. Diagnosis of osteomyelitis using sinus tract swab is close in results' accuracy to bone biopsy. S. aureus was the most common extracted organism found in these samples and had the highest degree of agreement. [ABSTRACT FROM AUTHOR]

There is preliminary evidence for lavender as an anxiolytic agent through various routes of administration. Our goal is to elucidate the best route of administration for lavender as a treatment for anxiety. Thirteen electronic search engines were systematically scanned for relevant publications. The relevant articles were included after the title and abstract screening followed by the full-text screening. This study included randomized control trials reporting lavender for the treatment of anxiety. The protocol was registered in PROSPERO (CRD42017076711). Frequentist network meta-analysis and Bayesian meta-regression were conducted to report the best treatment modality and the effect of covariates on the effectiveness as an anxiolytic. Treatment arms were ordered according P-scores, where higher P-score indicates better treatment choice. Forty studies were eligible for qualitative analysis, and 32 were included in quantitative analysis. Lavender aromatherapy was the best approach for the treatment of anxiety among other lavender modalities at the first week recording [Standardized Mean Difference (SMD) = −0.57, 95% CI (−1.14–0.01), P-score = 0.72], in addition to achieve at the first time points [SMD = −0, 95% CI (−0.97 ̶ -0.16), P-score = 0.69], compared to placebo; however, lavender massage along with foot bath were found to be the most efficacious for anxiety treatment at the study endpoint [SMD = −1.10, 95% CI = (−7.41 ̶ 5.21), P-score = 0.65]. Furthermore, network meta-regression revealed that the duration of therapy influenced treatment, suggesting Silexan (oral lavender) 80 mg (first rank probability =.116) as the favorable option for anxiety in long-term treatment. Lavender aromatherapy is, clinically, superior in short-duration, while Silexan (oral lavender) 80 mg is preferable for long-term treatment of anxiety. [ABSTRACT FROM AUTHOR]

By combining docking and molecular dynamics simulations, we explored a library of 65 mostly axially chiral naphthylisoquinoline alkaloids and their analogues, with most different molecular architectures and structural analogues, for their activity against SARS-CoV-2. Although natural biaryls are often regarded without consideration of their axial chirality, they can bind to protein targets in an atroposelective manner. By combining docking results with steered molecular dynamics simulations, we identified one alkaloid, korupensamine A, that atropisomer-specifically inhibited the main protease (Mpro) activity of SARS-CoV-2 significantly in comparison to the reference covalent inhibitor GC376 (IC 50 = 2.52 ± 0.14 and 0.88 ± 0.15 μM, respectively) and reduced viral growth by five orders of magnitude in vitro (EC 50 = 4.23 ± 1.31 μM). To investigate the binding pathway and mode of interaction of korupensamine A within the active site of the protease, we utilized Gaussian accelerated molecular dynamics simulations, which reproduced the docking pose of korupensamine A inside the active site of the enzyme. The study presents naphthylisoquinoline alkaloids as a new class of potential anti-COVID-19 agents. [Display omitted] • Discovery of naphthylisoquinolines as a new class of potential anti-COVID-19 agents. • Screening of 65 axially chiral alkaloids for potential SARS CoV-2 Mpro inhibition. • Identification of korupensamine A as a new antiviral agent by computational methods. • Atropisomer-specific inhibition of SARS CoV-2 and its Mpro by korupensamine A. • Elucidation of the interaction of the korupensamine A Mpro complex using GaMD/MDS. [ABSTRACT FROM AUTHOR]

Quorum sensing (QS) inhibition is one of the potential methods to target bacterial infection. In this study, comprehensive molecular dynamics simulation (MDS) experiments were conducted on the LasR structure to understand its structural dynamic behavior either in its ligand-free form or in its ligand-bound form (i.e. agonist or antagonist). The results revealed that LasR structure is significantly unstable in its ligand-free and antagonist-bound forms and such structural instability led eventually to complete dissociation of the functioning LasR dimeric form. Accordingly, twenty-eight benzimidazole derivatives were designed, synthesized as potential LasR antagonists, and characterized in vitro as QS inhibitors. Compounds 3d and 7f disclosed the highest percentage inhibition in biofilm formation, pyocyanin, and rhamnolipids production in Pseudomonas aeruginosa (71.70%, 68.70%, 54.00%) and (68.90%, 68.00%, 51.80%), respectively. MDS experiments revealed that these compounds as inhibitors, particularly, 3d , 7f , 8a , and 9g induce LasR structure instability and complete dissociation of its functioning dimeric form similarly to the previously reported inhibitor bromophenethyl-2-nitrobenzamide (BPNB). Furthermore, gene expression assays as another mechanism targeting quorum sensing genes to prove the inhibitory activity of these compounds on virulence factors, revealed that a number of the synthesized compounds were able to downregulate lasR (e.g. 3d and 7f by 61.70% and 26.00%, respectively) and rhlR (e.g. 7f by 16.30%) expressions. The results presented here provide a functional model for LasR that could guide future design of LasR inhibitors. [Display omitted] • MDS was used on the LasR structure to understand its structural dynamic behavior. • Some benzimidazoles were synthesized and their MIC against P. aeruginosa were detected. • Compounds 3d and 7f revealed the highest percentage inhibition in virulence factors production. • MDS experiments confirmed that compounds 3d , 7f , 8a , and 9g act as LasR inhibitors. • Compounds 3d and 7f downregulated LasR expression by 61.7% and 26%, respectively. [ABSTRACT FROM AUTHOR]

Openings in the webs of steel beams are frequently required due to the installations, but the openings decrease the maximum capacity and efficiency of the beams to carry the loads. The use of corrugated webs, in various forms, instead of flat webs increases the efficiency of steel beams. In this study, flat webs were replaced with corrugated webs to increase the efficiency of steel beams with openings. Finite element simulations were conducted on 51 steel beams with flat and corrugated webs and different openings. The results of the numerical analyses of several beams with openings in flat webs were compared with previously published findings and found to be accurate in predicting the maximum load capacity and the corresponding deflection of the beams. The results showed that the same efficiency of beams with openings in flat webs can be obtained with corrugated webs of reduced thickness, which results in a reduction of approximately 40 % of steel material used. Rectangular corrugated webs are more efficient than the triangular and trapezoidal corrugated ones. The dimensions of the corrugated web have a greater effect than the spacing between openings, and circular openings have a lesser impact on the efficiency of the beam than rectangular openings. • The same efficiency of flat web beam can be obtained with corrugated web of reduced thickness. • Dimensions of corrugated web have a greater effect than the spacing between openings. • Circular openings have a lesser impact on efficiency of beam than rectangular openings. • Rectangular corrugated web is more efficient than triangular and trapezoidal corrugated ones. [ABSTRACT FROM AUTHOR]

The use of methotrexate (MTX), a classical immunosuppressant and anti-cancer agent, is associated with multiple organ toxicities, including the intestinal injury. Components of the renin-angiotensin system are expressed in the intestinal epithelium and mucosal immune cells where they provoke pro-inflammatory and pro-oxidant action. The present study was conducted to investigate the potential ability of perindopril (PER), an angiotensin-converting enzyme inhibitor (ACEI), to attenuate MTX-induced intestinal injury with emphasis on the role of the pro-inflammatory TLR4/NF-κB and c-Fos/c-Jun pathways alongside PPAR-γ and SIRT1 cytoprotective signals. The intestinal injury was induced by a single-dose injection of 20 mg/kg of MTX i.p at the end of the 5th day. PER was administrated once daily in a dose of 1 mg/kg, i.p, for five days before MTX and five days later. Herein, perindopril attenuated the intestinal injury as seen by lowering the histopathological aberrations and preserving the goblet cells in villi/crypts. These beneficial actions were associated with downregulating the expression of the pro-inflammatory angiotensin II, TNF-α, IL-1β, and IL-6 cytokines, alongside upregulating the anti-inflammatory angiotensin (1–7) and IL-10. At the molecular level, perindopril downregulated the TLR4/NF-κB and c-Fos/c-Jun pathways in inflamed intestine of rats. Moreover, it attenuated the pro-oxidant events by lowering intestinal MDA and boosting GSH, SOD, and GST antioxidants together with PPAR-γ and SIRT1 cytoprotective signals. The aforementioned findings were also highlighted using molecular docking and network pharmacology analysis. Perindopril demonstrated notable mitigation of MTX-induced intestinal injury through suppression of TLR4/NF-κB and c-Fos/c-Jun pathways alongside the augmentation of PPAR-γ/SIRT1 cytoprotective signals. [Display omitted] • Perindopril attenuates methotrexate (MTX)-induced intestinal injury. • It downregulates the Ang-II as well as TNF-α, IL-1β and IL-6 cytokines. • It downregulates TLR4/NF-κB and c-Fos/c-Jun signaling. • It counteracts oxidative stress and restores antioxidant status. • It upregulates PPAR-γ and SIRT1 cytoprotective signals. [ABSTRACT FROM AUTHOR]

Male reproductive toxicity is becoming of growing significance due to clinical chemotherapy usage. Methotrexate (MTX) is an anti-folate used on a large scale for different tumors and autoimmune conditions. Despite its wide clinical use, MTX is associated with severe testicular intoxication. The exact underlying mechanism is unclear. Our study was conducted to explore the pathogenesis mechanism of MTX-induced testicular damage and the potential testicular protective effects of apocynin (APO) on testicular injury induced by single i.p. MTX (20 mg/kg). APO was administered orally (100 mg/kg) for ten days. As compared to rats given MTX alone, co-administration of MTX with APO demonstrated multiple beneficial effects evidenced by a marked increase in testosterone, FSH, and LH and significantly restored testes histopathological alterations. Mechanistically, APO restored antioxidant status through up-regulation of Nrf2, cytoglobin, PPAR-γ, SIRT1, AKT, and p-AKT, while effectively lowering Keap-1. Moreover, APO significantly attenuated inflammation by down-regulating NF-κB-p65, iNOS, and TLR4 expressions confirmed by in-silico evidence. Additionally, network pharmacology analysis, a bioinformatics approach, was used to decipher various cellular processes' molecular mechanisms. The current investigation proves the beneficial effects of APO in MTX-associated testicular damage through activation of cytoglobin, Keap-1/Nrf2/AKT, PPAR-γ, SIRT1, and suppressing of TLR4/NF-κB-p65 signal. Our data collectively encourage extending the investigation to the clinical setting to explore APO effects in MTX-treated patients. Illustrated diagram explores the molecular mechanism of APO against MTX-induced testicular damage. [Display omitted] • Apocynin abrogates MTX-induced testicular damage. • Apocynin regulates testicular Keap-1/Nrf2/AKT expression after MTX treatment. • Apocynin suppresses testicular iNOS/NF-κB/TLR4 expression. • In-silico and network pharmacology analysis confirmed biochemical and histological results. [ABSTRACT FROM AUTHOR]

Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid with a wide range of bioactivities. However, its therapeutic potential in GM-induced nephrotoxicity remains unclear. Rats received GM (100 mg/kg, i.p.) for 7 days either separately or in combination with oral DS (50 mg/kg). GM injection disrupted kidney function along with oxidant/antioxidant imbalance. Also, GM significantly decreased renal nuclear factor erythroid 2-related factor 2 (Nrf2), glutamyl cysteine synthetase (GCLC), heme oxygenase-1 (HO-1), superoxide dismutase3 (SOD-3), protein kinase B (AKT), and p-AKT expressions along with Kelch-like ECH-associated protein 1 (KEAP1) up-regulation. On the contrary, DS administration significantly attenuated GM-induced kidney dysfunction and restored kidney oxidant/antioxidant status. In addition, co-treatment with DS plus GM significantly enhanced Nrf2, GCLC, HO-1, SOD3, AKT, and p-AKT expressions along with KEAP1 down-regulation. Additionally, GM-treated rats exhibited a significant decrease in the expressions of renal peroxisome-proliferator activated receptor-gamma (PPAR-γ) and this reduction was alleviated by DS treatment. Furthermore, histopathological findings demonstrated that DS significantly reduced the GM-induced histological abrasions. Besides, an in-silico study was conducted to confirm our biochemical results. Interestingly, in-silico results strongly supported our biochemical investigation by studying the binding affinity of DS to KEAP1, AKT, and PPAR-γ proteins. DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways. • GM mediated oxidative stress injury in the kidney. • DS restored kidney function and oxidant/antioxidant balance. • DS modulated KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways. • In silico study validates AKT, KEAP1, and PPAR-γ as potential targets for DS therapy. [ABSTRACT FROM AUTHOR]

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (−)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases. Unlabelled Image [ABSTRACT FROM AUTHOR]

• The FE modeling can be used to calculate the shear capacity of RC beams. • The FE modeling can be used to predict the failure modes of RC beams. • By increasing the vertical circular opening diameter, the deflection decreases. • By increasing the vertical circular opening diameter, the ultimate load decreases. • The effect of opening diameter is greater than the effect of the number of openings. Transverse and vertical openings are usually created in beams made of reinforced concrete (RC) to accommodate the pipes and ducts used in utilities. The decrease in shear strength because of the openings causes problems in current RC beams. This study investigates the impact of various vertical circular web openings alongside the shear-area span of an RC beam on its shear performance. To this end, a model with three finite element (FE) dimensions was developed, primarily for investigating and analyzing the outcome of this case. Using the ANSYS-V15 FE program, 41 beams were analyzed. The findings of the eight investigational beams were compared with results from previously published works. The devised model was tested to ensure its accurate functioning, using outcomes already attained through experiments. The outcomes of the experimental test proved that the newly devised FE model could be used to calculate the RC beams' shear-load capacity and to accurately predict failure modes. The outcomes revealed that the effect of the vertical-opening diameter on the width of the beam section was greater than the effect of the length of the shear span. Therefore, we concluded that the influence of the opening diameter was greater than the effect of the number of openings. [ABSTRACT FROM AUTHOR]

[Display omitted] • Vancomycin exhibited proximal tubular cell necrosis, oxidative stress and inflammation leading to renal impairment. • Scopoletin, a pharmacologically active coumarin, has been isolated from several plant species. • Scopoletin ameliorated vancomycin-induced renal injury via restoring the antioxidant defense system. • Scopoletin prompts its nephroprotection through streamlining both IkBα/p65 NF-κB and Nrf2 / HO-1signaling pathways. • HO-1, Keap1, NF-κB and p38MAPK are potential targets for therapeutic effect of scopoletin against vancomycin nephrotoxicity. Nephrotoxicity is an indication for the damage of kidney-specific detoxification and excretion mechanisms by exogenous or endogenous toxicants. Exposure to vancomycin predominantly results in renal damage and losing the control of body homeostasis. Vancomycin-treated rats (200 mg/kg/once daily, for seven consecutive days, i.p.) revealed significant increase in serum pivotal kidney function, oxidative stress, and inflammatory biomarkers. Histologically, vancomycin showed diffuse acute tubular necrosis, denudation of epithelium and infiltration of inflammatory cells in the lining tubular epithelium in cortical portion. In the existing study, the conservative consequences of scopoletin against vancomycin nephrotoxicity was investigated centering on its capacity to alleviate oxidative strain and inflammation through streamlining nuclear factor (erythroid-derived-2) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and prohibiting the nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (p38 MAPK) pathway. With respect to vancomycin group, scopoletin pretreatment (50 mg/kg/once daily, i.p.) efficiently reduced kidney function, oxidative stress biomarkers and inflammatory mediators. Moreover, histological and immunohistochemical examination of scopoletin-treated group showed remarkable improvement in histological structure and reduced vancomycin-induced renal expression of iNOS, NF-κB and p38 MAPK. In addition, scopoletin downregulated (Kelch Like ECH Associated Protein1) Keap1, P38MAPK and NF-κB expression levels while upregulated renal expression levels of regulatory protein (IκBα), Nrf2 and HO-1. Furthermore, molecular docking and network approach were constructed to study the prospect interaction between scopoletin and the targeted proteins that streamline oxidative stress and inflammatory pathways. The present investigations elucidated that scopoletin co-treatment with vancomycin may be a rational curative protocol for mitigation of vancomycin-induced renal intoxication. [ABSTRACT FROM AUTHOR]

This study aims to enhance progesterone (PG) oral bioavailability via its incorporation into hybrid colon-targeted pectin/NaCMC microspheres (MS) cross-linked with Zn2+ and Al3+. The MS were characterized for particle morphology, encapsulation efficiency, swelling behavior, drug release, mucoadhesivity and colon-specific degradability. Response-surface methodology was adopted to optimize the fabrication conditions. Enhancement of in vivo drug performance was evaluated through pharmacokinetic and pharmacodynamic studies. The optimized formulation was typically spherical with a mean diameter of 1031 µm and drug entrapment efficiency of 88.8%. This formulation exhibited pH-dependent swelling, negligible drug release in simulated gastric fluid and sustained-release pattern in simulated small intestinal fluid with a mean t 50% of 26.5 h. It also showed prolonged and preferential adhesion to rat colonic mucosa, as well as expedited degradation in presence of rat caecal contents. The MS significantly increased the area under the curve and mean residence time by 1.8 and 2.3-fold, respectively compared to the free drug. Orally administered MS showed ~10 times increase in myometrial thickness compared with the drug suspension and elicited uterine responses very similar to that obtained parenterally. These results confirm the ability of this new carrier system to improve the oral bioavailability of PG and attain adequate clinical efficacy. [ABSTRACT FROM AUTHOR]

Studying the structure-activity relationships (SAR) of oxadiazolylthiazole antibiotics unexpectedly led us to identify ethylenediamine- and propylenediamine-analogs as potential antimycotic novel lead structures. Replacement of the ethylenediamine moiety for the lead compound 7 with cis -diaminocyclohexyl group (compound 18) significantly enhanced the antifungal activity. In addition to the high safety margin of 18 against mammalian cells, it showed highly selective broad-spectrum activity against fungal cells without inhibiting the human normal microbiota. The antifungal activity of 18 was investigated against 20 drug-resistant clinically important fungi, including Candida species, Cryptococcus , and Aspergillus fumigatus strains. In addition to the low MIC values that mostly ranged between 0.125 and 2.0 μg/mL, compound 18 outperformed fluconazole in disrupting mature Candida biofilm. Image 1 • Replacement ethylenediamine motif with cis -diaminocyclohexane remarkably enhanced the antimycotic effect. • Stereochemistry of the two amines is critical as the trans -isomer is 64-times less active. • Compound 18 is effective vs. fluconazole-resistant albicans and non-albicans candida. • Compound 18 is more efficient in clearing cryptococcal infections than fluconazole. • Compound 18 is selective to fungal cells with antibiofilm activity. [ABSTRACT FROM AUTHOR]

The drug delivery of candesartan cilexetil encounters an obstacle of low absolute oral bioavailability which is attributed mainly to its low aqueous solubility and efflux by intestinal P-glycoprotein (P-gp) transporters. However, the extent of P-gp contribution in the reduced oral bioavailability of candesartan cilexetil is not clear. In this study, a previously developed candesartan cilexetil–loaded self-nanoemulsifying drug delivery system (SNEDDS) was evaluated for its ability to increase the drug oral bioavailability via the inhibition of intestinal P-gp transporters. Despite the developed SNEDDS showing P-gp inhibition activity, P-gp–mediated efflux was found to have a minor role in the reduced oral bioavailability of candesartan cilexetil. On the other hand, the high surfactant concentration used in SNEDDS formulation represents a major challenge toward their widespread application especially for chronically administered drugs. The designed acute and subacute toxicity studies revealed that the degree of intestinal mucosal damage decreases as the treatment period increases. The latter observation was attributed to the reversibility of surfactant-induced mucosal damage. Thus, the developed SNEDDS could be considered as a promising delivery system for enhancing the oral bioavailability of chronically administered drugs. [ABSTRACT FROM AUTHOR]

Self-emulsifying drug delivery systems (SEDDS) have been widely employed to improve the oral bioavailability of poorly soluble drugs. In the past few years, SEDDS were extensively investigated to overcome various barriers encountered in the oral delivery of hydrophilic macromolecules ( e.g. , protein/peptide therapeutics and plasmid DNA (pDNA)), as well as in lowering the effect of food on drugs' bioavailability. However, the main mechanism(s) by which SEDDS could achieve such promising effects remains not fully understood. This review summarizes the recent progress in the use of SEDDS for protecting protein therapeutics and/or pDNA against enzymatic degradation and increasing the oral bioavailability of various drug substances regardless of the dietary condition. Understanding the underlying mechanism(s) of such promising applications will aid in the future development of rationally designed SEDDS. Entrapment of hydrophilic macromolecules in the oil phase of the formed emulsion is critical for protection of the loaded cargoes against enzymatic degradation and the enhancement of oral bioavailability. On the other hand, drug administration as a preconcentrated solution in the SEDDS preconcentrate allows the process of drug absorption to occur independently of the dietary condition, and thus reducing interindividual variability that results from concomitant food intake. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) is an effective chemotherapeutic drug that has been used successfully in treating various tumors. Although its higher antineoplastic agent activity, CDDP exhibited severe side effects that limit its use. CDDP-induced toxicity is attributed to oxidative stress and inflammation. Apocynin (APO) is a bioactive phytochemical with potent antioxidant and anti-inflammatory properties. However, pharmaceutical experts face significant hurdles due to the limited bioavailability and quick elimination of APO. Therefore, we synthesized a chitosan (CTS)-based nano delivery system using the ionic gelation method to enhance APO bioactivity. CTS-APO-NPs were characterized using different physical and chemical approaches, including FTIR, XRD, TGA, Zeta-sizer, SEM, and TEM. In addition, the protective effect of CTS-APO-NPs against CDDP-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity in rats was evaluated. CTS-APO-NPs restored serum biomarkers and antioxidants to their normal levels. Also, histopathological examination was used to assess the recovery of heart, kidney, and liver tissues. CTS-APO-NPs attenuated the oxidative stress mediated by Nrf2 activation while it dampened inflammation mediated by NF-κB suppression. CTS-APO-NPs is a potentially attractive target for more therapeutic trials. • CTS-APO enhanced the bioavailability of APO • APO is efficiently encapsulated into CTS-NPs and achieves a sustainable release profile. • CTS-APO-NPS exhibited a protective effect against CDDP-induced multiorgan toxicity that exceeded that of free APO. • CTS-APO-NPs attenuated the oxidative stress mediated by Nrf2 activation while it dampened inflammation mediated by NF-κB suppression. [ABSTRACT FROM AUTHOR]

The colon is a promising site for drug targeting owing to its long transit time and mild proteolytic activity. The aim of this study was to prepare new low methoxy amidated pectin/NaCMC microspheres cross-linked by a mixture of Zn 2+ and Al 3+ ions and test their potential for colonic targeting of progesterone. A 2 4 factorial design was carried out to optimize the preparation conditions. High drug entrapment efficiency (82–99%) was obtained and it increased with increasing drug concentration but decreased with increasing polymer concentration. Drug release rate was directly proportional to the microsphere drug content and inversely related to Al 3+ ion concentration. Drug release was minimal during the first 3 h but was significantly improved in the presence of 1% rat caecal contents, confirming the microsphere potential for colonic delivery. The microspheres achieved >2.3-fold enhancement of colonic progesterone permeability. These results confirm the viability of the produced microspheres as colon-targeted drug delivery vehicle. [ABSTRACT FROM AUTHOR]

Kidney diseases are major health problem and understanding the underlined mechanisms that lead to kidney diseases are critical research points with a marked potential impact on health. Cadmium (Cd) is a heavy metal that occurs naturally and can be found in contaminated food. Kidneys are the most susceptible organ to heavy metal intoxication as it is the main route of waste excretion. The harmful effects of Cd were previously well proved. Cd induces inflammatory responses, oxidative injury, mitochondrial dysfunction and disturbs Ca2+ homeostasis. The nuclear factor-kappa B (NF-κB) is a cellular transcription factor that regulates inflammation and controls the expression of many inflammatory cytokines. Therefore, great therapeutic benefits can be attained from NF-κB inhibition. In this review we focused on certain compounds including cytochalasin D, mangiferin, N -acetylcysteine, pyrrolidine dithiocarbamate, roflumilast, rosmarinic acid, sildenafil, sinapic acid, telmisartan and wogonin and certain plants as Astragalus Polysaccharide, Ginkgo Biloba and Thymus serrulatus that potently inhibit NF-κB and effectively counteracted Cd-associated renal intoxication. In conclusion, the proposed NF-κB involvement in Cd-renal intoxication clarified the underlined inflammation associated with Cd-nephropathy and the beneficial effects of NF-κB inhibitors that make them the potential to substantially optimize treatment protocols for Cd-renal intoxication. [Display omitted] • There is a close relationship between NF-κB and Cd-induced renal intoxication. • The renal harmful effects of Cd are mainly due to induction of inflammatory responses. • Potential promising effect of NF-κB inhibition against Cd-induced nephropathy • NF-κB inhibition that make them the potential to substantially optimize treatment protocols for Cd-renal intoxication [ABSTRACT FROM AUTHOR]

[Display omitted] • Sponges of the genus Echinoclathria are a source of cytotoxic sterols. • A new cytotoxic sterol, echinosterol with known one, thalassosterol were isolated. • Glucose-6-phosphate dehydrogenase inhibition and proliferation of cancer cells. • A comprehensive pharmacophore-based virtual screening was conducted. • Docking and molecular dynamic simulation studies. Chemical investigation of the methanol extract of the Red Sea sponge Echinoclathria sp., led to the isolation of two pure compounds, one new sterol, named as (echinosterol), compound (1), along with known first reported sterol, (thalassosterol), compound (2). Structure elucidation was achieved using different spectroscopic techniques. The in vitro cytotoxic activity of the isolated compounds was tested against three human cancer cell lines, MCF-7, HepG2, and HeLa. Both compounds displayed strong to moderate cytotoxicity with IC 50 values ranged from 3.23 to 28.1 µM. Subsequent pharmacophore-based virtual screening proposed glucose-6-phosphate dehydrogenase (G6PD) as the possible protein targets for both compounds, where they exhibited nanomolar inhibition (IC 50 14.59 ± 0.77 and 23.86 ± 1.25, and K i 15.3 ± 1.11 and 9.6 ± 1.2 µM, respectively) upon the in vitro testing. Docking and molecular dynamic simulation studies were further illustrated the binding modes of both compounds inside the enzyme's active site. [ABSTRACT FROM AUTHOR]