Potential role of human umbilical cord stem cells-derived exosomes as novel molecular inhibitors of hepatocellular carcinoma growth.

Hepatocellular carcinoma (HCC) is one of the most critical cancers; thus, novel therapeutical regimens are of great need. In this study, we investigated the effects of umbilical cord mesenchymal stem cells (UC-MSCs) derived exosomes on HepG2 cell line, and the underlying mechanism to control HCC proliferation, to identify the potential clinical role of exosomes as a novel molecular therapeutic target. Proliferation, apoptosis, and angiogenesis effects were assessed together with the cell viability evaluation by MTT assay in HepG2 cells at 24/48 h. with or without UC-MSCs-derived exosomes. Gene expressions of TNF-α, caspase-3, VEGF, stromal cell-derived factor-1 (SDF-1), and CX chemokine receptor-4 (CXCR-4) were measured by quantitative real-time PCR technique. Expression of sirtuin-1 (SIRT-1) protein was detected by western blot. Treatment of HepG2 cells with UC-MSCs-derived exosomes for 24 and 48 h. demonstrated a significant reduction of cells survival compared to the control group (p < 0.05). The SIRT-1 protein, and VEGF, SDF-1, CXCR-4 expression levels were significantly lower, TNF-α and caspase-3 expression levels were significantly higher in exosomal-treated HepG2 cells for 24 and 48 h. than those in the control group. Moreover, our findings documented that the anti-proliferative, apoptotic, and anti-angiogenic effects were achieved in a time-dependent manner in which more effects were determined after 48 h supplementation compared to 24 h (p < 0.05). UC-MSCs-derived exosomes exert anticarcinogenic molecular effects on HepG2 cells through the involvement of SIRT-1, SDF-1, and CXCR-4. Hence, exosomes would be a potential novel therapy regimen against HCC. Large-scale studies are recommended to verify this conclusion.

Antibacterial and anti-corona virus (229E) activity of Nigella sativa oil combined with photodynamic therapy based on methylene blue in wound infection: in vitro and in vivo study.

Microbial skin infections, antibiotic resistance, and poor wound healing are major problems, and new treatments are needed. Our study targeted solving this problem with Nigella sativa (NS) oil and photodynamic therapy based on methylene blue (MB-PDT). Antibacterial activity and minimum inhibitory concentration (MIC) were determined via agar well diffusion assay and broth microdilution, respectively. Transmission electron microscopy (TEM) proved deformations in Staphylococcus aureus ATCC 6538. Gas chromatography-mass spectrometry identified useful compounds that were suggested to be responsible for the potency of the oil. NS oil was tested as an antivirus against low pathogenic coronavirus (229E). Therapies examined, MB-PDT, NS, and MB-PDT + NS oil, to accelerate wound healing. The antibacterial efficacy against S. aureus was promising, with a MIC of 12.5% and TEM showing injured cells treated with NS oil. This oil inhibited 229E virus up to 42.85% and 32.14%. All tested therapies were successful in accelerating wound healing. The most successful was combined therapy (MB-PDT + NS oil), with a faster healing time. The combined therapy (MB-PDT + NS oil) reduced bacterial counts, which may be a key factor in accelerating wound healing. Skin wound histology was investigated; blood hematology and biochemical analysis did not change significantly after the safe combination treatment. A combination treatment could facilitate healing in a simple and inexpensive way in the future. Based on the results of the in vitro and in vivo studies, it was determined that NS oil had antibacterial and anti-corona virus activity when used in conjunction with photodynamic treatment based on methylene blue to treat wound infections.

Developments of pyridodipyrimidine heterocycles and their biological activities.

The entitled review aimed to assemble and highlight the synthetic approaches and biological aspects of heterocycles with pyridodipyrimidine motifs. The recent synthetic approaches were categorized according to the accomplishments of the approaches under catalyst or catalyst-free conditions. The topic involved the synthesis of substituted tricyclic systems and spirocyclic systems. The present study offered an overview of the recent literature in addition to a scope of the preceding literature. The proposed mechanisms of the varied target products were discussed. Pyridodipyrimidine displayed potential and privileged cytotoxic, antioxidant, and antimicrobial performances. The competitions, challenges, and prospects are also deliberated.

Effect of Hesperidin against Induced Colon Cancer in Rats: Impact of Smad4 and Activin A Signaling Pathway.

SCOPE: To evaluate the chemopreventive efficacy of hesperidin (Hsd) in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer (CRC) and demonstrate its role in mothers against decapentaplegic homolog 4(Smad4) and activin A signaling pathways. METHODS AND RESULTS: A CRC rat model was established by DMH exposure, and the animals were randomly divided into five groups: Control group, Hsd, DMH, DMH + Hsd, and DMH followed by Hsd. The resected colon was subjected to macroscopic, microscopic, molecular, histopathological, and immunohistochemical examination. Activin A, Smad4, malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), and superoxide dismutase (SOD) levels in tissues were also measured. The DMH group exhibited a significant increase in the gene and protein expression of activin A as well as MDA and NO levels in tissues. There was a significant reduction in the gene and protein expression of Smad4 as well as GSH and SOD levels in tissues. Administration of Hsd significantly upregulated Smad4 and activin A gene expressions in both the DMH + Hsd and DMH followed by Hsd groups. Moreover, Hsd improved the antioxidant status of the former two groups. CONCLUSION: This study demonstrated the chemopreventive effect of Hsd against CRC by modulating Smad4 and activin A signaling in vivo. Further studies are needed to demonstrate its clinical value and explore its possible role in advanced malignancy.

Effect of resveratrol and mesenchymal stem cell monotherapy and combined treatment in management of osteoporosis in ovariectomized rats: Role of SIRT1/FOXO3a and Wnt/ß-catenin pathways.

Osteoporosis is a skeletal disorder that is common in postmenopausal women. It is characterized by deteriorated bone mass and microarchitecture. In this study, we aimed to explore the effects and molecular mechanisms of resveratrol and mesenchymal stem cell (MSC) individual and combined treatment in management of osteoporosis in ovariectomized rats. Our results demonstrated that treatment of ovariectomized rats with resveratrol or MSCs improved bone mass and microstructure as indicated by increased bone mineral content and density. Moreover, resveratrol and MSCs stimulated osteogenesis as shown by increased levels of osteogenic markers such as runt-related transcription factor 2 (RUNX2). In addition, resveratrol and MSCs inhibited adipogenesis and osteoclastogenesis as indicated by the suppression of the adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ) and the osteoclastogenesis marker, receptor activator of nuclear factor-κB ligand (RANKL). Mechanistically, our results showed that management of osteoporosis in resveratrol or MSC treated rats was achieved by activating two signaling pathways, sirtuin 1 (SIRT1) and wingless-related MMTV integration site (Wnt). Finally, the combination of resveratrol and MSCs was more effective in increasing bone mass and improving osteoporosis than individual treatments.

Genetic polymorphism of lysyl oxidase, glutathione S-transferase M1, glutathione-S-transferase T1, and glutathione S-transferase P1 genes as risk factors for lung cancer in Egyptian patients.

Lung cancer is a lethal malignancy and is affected by genetic polymorphisms that contribute to an individual's susceptibility to developing the disease. Several studies on lung cancer showed conflicting results. The aim of this study is to investigate whether individual or combined modifying effects of LOX G/A, GSTM1 active/null, GSTT1 active/null and GSTP1 Ile/Val polymorphisms are related to the risk of lung cancer in relation to smoking in the Egyptian population. This study is a hospital-based case control study that included 200 patients and 200 control subjects. Genotyping of the 4 studied genes was determined by Multiplex PCR for GSTM1 and GSTT1 and Taq man SNP assay for GSTP1 and LOX genes. The LOX G/A and GSTP1 Ile/Val in both homozygous and heterozygous variants, and the GSTM1 and GSTT1 null genotype showed significant association with lung cancer. Combination between gene polymorphism and smoking increased the risk of developing cancer by 2.7 fold in the LOX GA+AA variant, 1.9 fold in the GSTM1 null variant, 4.8 fold in the GSTT1 null variant and 4.3 fold in the GSTP1 Ile/Val+Val/Val variant. The genetic combination (LOX GA+AA/GSTT1 active, LOX GG/GSTT1 null, LOX GA+AA/GSTT1 null, LOX GA+AA/GSTP1 Ile/Ile, LOX GG/GSTP1 Ile/Val+Val/Val and LOX GA+AA/GSTP1 Ile/Val+Val/Val) led to a higher lung cancer risk, compared to the reference group. The LOX GA/AA, GSTM1 null, GSTT1 null and GSTP1 Ile/Val, Val/Val genotypes contributed to increased lung cancer susceptibility. To the best of our knowledge, this is the first study of LOX genotyping in the Egyptian population. The combination of genotypes increased the risk of cancer, indicating the importance of gene-gene interaction and giving a targeted preventive approach.

Environmental monitoring of Aichi virus and human bocavirus in samples from wastewater treatment plant, drain, and River Nile in Egypt.

Wastewater plays a major role in water pollution causing transmission of several viral pathogens, including Aichi virus (AiV) and human bocavirus (HBoV), associated with gastrointestinal illness in humans. In this study, we investigated the presence of AiV and HBoV in aquatic, sludge, sediment matrices collected from Abu-Rawash wastewater treatment plant (WWTP), El-Rahawy drain, Rosetta branch of the River Nile in Egypt by conventional polymerase chain reaction (PCR). AiV RNA was detected in 16.6% (2/12), 8.3% (1/12), 8.3% (1/12), 22% (16/72), 12.5% (3/24), 4% (1/24), and 0/24 (0%) of untreated raw sewage, treated sewage, sewage sludge, drainage water, drain sediment, river water, and river sediment, respectively. On the other hand, HBoV DNA was detected in 41.6% (5/12), 25% (3/12), 16.6% (2/12), 48.6% (35/72), 29% (7/24), 3/24 (12.5%), 4% (1/24) of untreated raw sewage, treated raw sewage, sewage sludge, drainage water, drain sediment, river water, and river sediment, respectively. This study provides data on the presence of these viruses in various types of water samples that are valuable to environmental risk assessment. In addition, the current study demonstrates the importance of environmental monitoring as an additional tool to investigate the epidemiology of AiV and HBoV circulating in a given community.

Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway.

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

Contribution of aorta glycosaminoglycans and PCSK9 to hyperlipidemia in experimental rabbits: the role of 10-dehdrogingerdione as effective modulator.

10-Dehydrogingerdione (10-DHGD) was previously reported to possess a hypolipidemic, anti-inflammatory and anti-oxidant properties in hyperlipidemic rabbit model. In this study, we investigated a possible new role for 10-DHGD in modulating atherogenic lipid profile by targeting proprotein convertase subtilisin kexin-9 (PCSK-9). Cholesterol (0.2% w/w)-fed rabbits received either atorvastatin (20 mg/kg) or 10-DHGD (10 mg/kg) for 12 weeks along with cholesterol feeding (HCD). Lipid profile, serum PCSK-9 and macrophage migration inhibitory factor (MIF), and aorta level of tumor necrosis factor-alpha (TNF-α) and glycosaminoglycans (GAGs) were measured. HCD-fed rabbits revealed an atherogenic lipid profile along with increased serum level of PCSK-9 (p < 0.001) and increased serum MIF and aortic TNF-α and GAGs (p < 0.001). 10-DHGD administration to HCD-fed rabbits prevented this atheogenicity by modulating the release of PCSK-9, inflammation extent (serum MIF and aortic TNF-α) and GAGs. These results provide new insights on the hypolipidemic potential of 10-DHGD. The effects of 10-DHGD was superior to that of atorvastatin in most studied parameters modulating atherogenicity. 10-DHGD is found to be able to suppress the release of PCSK-9, decrease aortic expression of GAGs in cholesterol-fed rabbits and halt the inflammation extent. These effects may provide new insights on the hypolipidemic potential of 10-DHGD.

Essential Role of IL-12 in Angiogenesis in Type 2 Diabetes.

Recently, IL-12 emerged as a critical player in type 2 diabetes complications. We previously reported that ischemia-induced angiogenesis is compromised in type 2 diabetic mice. In this study, we determined that IL-12 disruption rescued angiogenesis and arteriogenesis in type 2 diabetic mice. To induce type 2 diabetes, wild-type (WT), p40IL-12-/- (p40-/-), and p35IL-12-/- (p35-/-) mice were fed a high-fat diet (HFD) for 12 weeks. Body weight, glucose test tolerance, and insulin test tolerance were assessed. After 12 weeks of an HFD, the femoral artery was ligated and blood flow recovery was measured every week for 4 weeks. WT, p40-/-, and p35-/- mice fed an HFD become obese after 12 weeks and exhibit glucose intolerance and insulin resistance. Blood flow recovery was fully restored in 2 to 3 weeks after femoral artery ligation in all groups of mice fed a normal diet. However, after 12 weeks of an HFD, blood flow recovery was compromised in WT mice, whereas it was fully recovered in p40-/- and p35-/- mice. The mechanism of blood flow recovery involves an increase in capillary/arteriole density, endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2 signaling, and a reduction in oxidative stress and inflammation. The disruption of IL-12 promotes angiogenesis and increases blood flow recovery in obese type 2 diabetic mice by an endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2/oxidative stress-inflammation-dependent mechanism.

Vanillin as a new modulator candidate for renal injury induced by cisplatin in experimental rats.

Cisplatin is commonly prescribed for the treatment of various solid tumors but its use is limited due to certain side effects and renal injury is a true example. Oxidative stress and inflammation may contribute to the cisplatin induced nephrotoxicity. Accordingly, we evaluated the effect of oral vanillin intake (100mg/kg body weight) daily for 4weeks to combat this hazard. The present results have demonstrated significant attenuation of oxidative stress and renal injury where reduced glutathione (GSH) showed significant increase along with malondialdehyde (MDA) decrease. Fibrotic markers like fibroblast growth factor-23 (FGF-23), transforming growth factor-ß1 (TGF-ß1), inflammatory mediators such as nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) showed also significant decrease in vanillin treated rats as compared with the control group. Renal function showed also significant improvement where urea and creatinine demonstrated significant decrease and the histopathological study presented a good support to the biochemical markers results. Our conclusion that vanillin is a potent antioxidant, anti-inflammatory and anti-fibrotic agent. Additionally, it is a good modulator candidate for the renal injury induced by cisplatin intake.

Mycosynthesis of selenium nanoparticles using Penicillium tardochrysogenum as a therapeutic agent and their combination with infrared irradiation against Ehrlich carcinoma.

Over the past years, the assessment of myco-fabricated selenium nanoparticles (SeNPs) properties, is still in its infancy. Herein, we have highly stable myco-synthesized SeNPs using molecularly identified soil-isolated fungus; Penicillium tardochrysogenum OR059437; (PeSeNPs) were clarified via TEM, EDX, UV-Vis spectrophotometer, FTIR and zeta potential. The therapeutic efficacy profile will be determined, these crystalline PeSeNPs were examined for antioxidant, antimicrobial, MIC, and anticancer potentials, indicating that, PeSeNPs have antioxidant activity of (IC50, 109.11 µg/mL) using DPPH free radical scavenging assay. Also, PeSeNPs possess antimicrobial potential against Penicillium italicum RCMB 001,018 (1) IMI 193,019, Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC 4330 and Porphyromonas gingivalis RCMB 022,001 (1) EMCC 1699; with I.Z. diameters and MIC; 16 ± 0.5 mm and MIC 500 µg/ml, 11.9 ± 0.6 mm, 500 µg/ml and 15.9±0.6 mm, 1000 µg/ml, respectively. Additionally, TEM micrographs were taken for P. italicum treated with PeSeNPs, demonstrating the destruction of hyphal membrane and internal organelles integrity, pores formation, and cell death. PeSeNP alone in vivo and combined with a near-infrared physiotherapy lamp with an energy intensity of 140 mW/cm2 showed a strong therapeutic effect against cancer cells. Thus, PeSeNPs represent anticancer agents and a suitable photothermal option for treating different kinds of cancer cells with lower toxicity and higher efficiency than normal cells. The combination therapy showed a very large and significant reduction in tumor volume, the tumor cells showed large necrosis, shrank, and disappeared. There was also improvement in liver ultrastructure, liver enzymes, and histology, as well as renal function, urea, and creatinine.

Surfactant protein D, soluble intercellular adhesion molecule-1 and high-sensitivity C-reactive protein as biomarkers of chronic obstructive pulmonary disease.

OBJECTIVE: The aim of this study was to estimate the serum levels of surfactant protein D (SP-D), soluble intercellular adhesion molecule-1 (sICAM-1), and high-sensitivity C-reactive protein (hs-CRP) in patients with chronic obstructive pulmonary disease (COPD) and to assess the correlation of these indices with COPD severity. SUBJECTS AND METHODS: This analytic cross-sectional study was carried out on 64 COPD male patients, and 26 apparently healthy age-matched males as a control. Chest X-ray, spirometry and arterial blood gases were done for only COPD patients. Serum levels of SP-D, sICAM-1 and hs-CRP were determined by enzyme-linked immunosorbent assay in both patient and control groups. RESULTS: The serum levels of SP-D, sICAM-1 and hs-CRP were significantly higher in COPD patients than controls (p < 0.001 for each). Also, these biomarkers were significantly higher in stages III and IV compared to either stage I or II (p < 0.01 for each). SP-D was significantly positively correlated with sICAM-1 and hs-CRP (r = 515, p < 0.001; r = 501, p < 0.001, respectively) and negatively correlated with PaO2 (r = -0.651, p < 0.001) and all parameters of spirometry. CONCLUSION: SP-D, sICAM and hs-CRP were significantly higher in COPD patients in comparison with controls. Moreover, SP-D, sICAM-1, and hs-CRP were significantly negatively correlated with FEV1%. Accordingly, estimation of these biochemical indices may be used as biomarkers for assessment of COPD severity.

Bacterial nanocellulose production using Cantaloupe juice, statistical optimization and characterization.

The bacterial nanocellulose has been used in a wide range of biomedical applications including carriers for drug delivery, blood vessels, artificial skin and wound dressing. The total of ten morphologically different bacterial strains were screened for their potential to produce bacterial nanocellulose (BNC). Among these isolates, Bacillus sp. strain SEE-3 exhibited potent ability to produce the bacterial nanocellulose. The crystallinity, particle size and morphology of the purified biosynthesized nanocellulose were characterized. The cellulose nanofibers possess a negatively charged surface of - 14.7 mV. The SEM images of the bacterial nanocellulose confirms the formation of fiber-shaped particles with diameters of 20.12‒47.36 nm. The TEM images show needle-shaped particles with diameters of 30‒40 nm and lengths of 560‒1400 nm. X-ray diffraction show that the obtained bacterial nanocellulose has crystallinity degree value of 79.58%. FTIR spectra revealed the characteristic bands of the cellulose crystalline structure. The thermogravimetric analysis revealed high thermal stability. Optimization of the bacterial nanocellulose production was achieved using Plackett-Burman and face centered central composite designs. Using the desirability function, the optimum conditions for maximum bacterial nanocellulose production was determined theoretically and verified experimentally. Maximum BNC production (20.31 g/L) by Bacillus sp. strain SEE-3 was obtained using medium volume; 100 mL/250 mL conical flask, inoculum size; 5%, v/v, citric acid; 1.5 g/L, yeast extract; 5 g/L, temperature; 37 °C, Na2HPO4; 3 g/L, an initial pH level of 5, Cantaloupe juice concentration of 81.27 percent and peptone 11.22 g/L.

Comparative study of three plant-derived extracts as new management strategies against Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae).

Finding innovative eco-friendly agents for pest control may be aided by investigating the plant-derived extracts' properties on economic pests. Therefore, the insecticidal, behavioral, biological and biochemical effects of Magnolia grandiflora (Magnoliaceae) leaf water and methanol extracts, Schinus terebinthifolius (Anacardiaceae) wood methanol extract, and Salix babylonica (Salicaceae) leaf methanol extract in comparison with a reference insecticide novaluron against S. littoralis were evaluated. The extracts were analyzed by High-Performance Liquid Chromatography (HPLC). The most abundant phenolic compounds were 4-hydroxybenzoic acid (7.16 mg/mL) and ferulic acid (6.34 mg/mL) in M. grandiflora leaf water extract; catechol (13.05 mg/mL), ferulic acid (11.87 mg/mL), and chlorogenic acid (10.33 mg/mL) in M. grandiflora leaf methanol extract; ferulic acid (14.81 mg/mL), caffeic acid (5.61 mg/mL), and gallic acid (5.07 mg/mL) In the S. terebinthifolius extract; cinnamic acid (11.36 mg/mL), and protocatechuic acid (10.33 mg/mL) In the methanol extract from S. babylonica extract. S. terebinthifolius extract had a highly toxic effect against second larvae after 96 h and eggs with LC50 values of 0.89 and 0.94 mg/L, respectively. Despite M. grandiflora extracts didn't show any toxicity against S. littoralis stages, they had an attractant effect on fourth- and second larvae, with feeding deterrence values of - 2.7% and - 6.7%, respectively, at 10 mg/L. S. terebinthifolius extract significantly reduced the percentage of pupation, adult emergence, hatchability, and fecundity, with values of 60.2%, 56.7%, 35.3%, and 105.4 eggs/female, respectively. Novaluron and S. terebinthifolius extract drastically inhibited the activities of α-amylase and total proteases to 1.16 and 0.52, and 1.47 and 0.65 ΔOD/mg protein/min, respectively. In the semi-field experiment, the residual toxicity of tested extracts on S. littoralis gradually decreased over time compared to novaluron. These findings indicate that extract from S. terebinthifolius is a promising insecticidal agent against S. littoralis.

Polycladia myrica-based delivery of selenium nanoparticles in combination with radiotherapy induces potent in vitro antiviral and in vivo anticancer activities against Ehrlich ascites tumor.

Background: Over the last few decades, nanotechnology has entered daily life through various applications, therefore, there has been a trend toward developing new approaches to green-mediated nanotechnology that encourage nanomaterial formation through biological methods such as plants or microorganisms. Algae have gained increasing attention from nanotechnology scientists and have paved the way for the emergence of "algae nanotechnology" as a promising field. Methods: Via using the aqueous extract of the brown alga Polycladia myrica, selenium nanoparticles were synthesized and characterized by using seven instruments: SEM, TEM, UV spectra, Zeta potential, EDX, X-ray diffraction, and FTIR. P. myrica selenium nanoparticles (PoSeNPs) were then examined for their antiviral activity against HSV-1 (Herpes simplex I) and anticancer against human colon cancer cell line (HCT-116) in vitro and in vivo alone and in combination with laser therapy of power 2 mW against Ehrlich carcinoma (EAC). Results: PoSeNPs ranging between 17.48 nm and 23.01 nm in size, and EDX revealed the selenium mass and its atoms as 0.46% ± 0.07% and 0.08% ± 0.01% respectively. Their anticancer potentiality in vitro was with maximum inhibitions of 80.57% and 73% and IC50 = 14.86 µg/mL and 50 mg/mL against HCT-116 and EAC cell lines respectively, while their in vivo alone and in combination with laser therapy of power 2 mW showed a potent therapy effect against Ehrlich ascites carcinoma (EAC). Conclusion: This study concluded that PoSeNPs do not have a toxic effect; they exhibit high effectiveness as a photothermal agent for cancer therapy, with promising applications in future biomedical fields. The combined therapy showed a significant decrease in tumor volume, massive tumor cell necrosis, shrinking, and disappearance. It also showed improvement in liver TEM, histology, kidney function: urea and creatinine, and liver enzymes: ALT, and AST.

Raspberry ketone improves non-alcoholic fatty liver disease induced in rats by modulating sphingosine kinase/sphingosine-1-phosphate and toll-like receptor 4 pathways.

OBJECTIVES: To investigate the therapeutic role of calorie-restricted diet (CR) and raspberry ketone (RK) in non-alcoholic fatty liver disease (NAFLD) and the implication of sphingosine kinase-1 (SphK1)/sphingosine-1-phosphate (S1P) and toll-like receptor 4 (TLR4) signalling. METHODS: NAFLD was induced by feeding rats high-fat-fructose-diet (HFFD) for 6 weeks. Rats were then randomly assigned to three groups (n = 6 each); NAFLD group continued on HFFD for another 8 weeks. CR group was switched to CR diet (25% calorie restriction) for 8 weeks and RK group was switched to normal diet and received RK (55 mg/kg/day; orally) for 8 weeks. Another six rats were used as normal control. KEY FINDINGS: HFFD induced a state of NAFLD indicated by increased fat deposition in liver tissue along with dyslipidemia, elevated liver enzymes, oxidative stress and inflammation. Either CR diet or RK reversed these changes and decreased HFFD-induced elevation of hepatic SphK1, S1P, S1PR1 and TLR4. Of notice, RK along with a normal calorie diet was even better than CR alone in most studied parameters. CONCLUSIONS: SphK1/S1P and TLR4 are interconnected and related to the establishment of HFFD-induced NAFLD and can be modulated by RK. Supplementation of RK without calorie restriction to patients with NAFLD unable to follow CR diet to achieve their treatment goals would be a promising therapeutic modality.

Synthesis of Tungsten Oxide, Iron Oxide, and Copper-Doped Iron Oxide Nanocomposites and Evaluation of Their Mixing Effects with Cyromazine against Spodoptera littoralis (Boisduval).

Nanotechnology research is emerging as a cutting-edge technology, and nanocomposites have played a significant role in pest control. Therefore, the present study focuses on the synthesis of tungsten oxide (WO3), iron oxide (magnetic nanoparticle, MNP), and copper-doped iron oxide (MNP-Cu) nanocomposites and explores the different effects of their binary combinations with the insecticide cyromazine against Spodoptera littoralis. The synthesized nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Raman spectroscopy. None of the tested nanomaterials showed any toxicity against the different stages of S. littoralis. Larval and pupal durations increased with increasing cyromazine and nanomaterial concentrations. The longest larval and pupal durations were recorded under treatment with the mixture of cyromazine (100 mg/L) + MNP-Cu (500 mg/L); the survival periods were 23.5 and 15.6 days, compared with 10.8 and 7.7 days in the control, respectively. The percentages of pupation and adult emergence were negatively affected by all treatments. Among the 500 mg/L nanomaterial combinations, only cyromazine (25 mg/L) and WO3 (500 mg/L) resulted in adult emergence (at a rate of 27.3%). Some abnormalities in the S. littoralis stages were observed following treatment with the tested materials. The glutathione S-transferase and alpha-esterase enzyme activities in S. littoralis were significantly increased after treatment with cyromazine, followed by cyromazine/MNP-Cu combinations. The quantitative polymerase chain reaction (Q-PCR) data showed that all treated insects had a higher immune response than the control. Finally, mixes of nanocomposites and cyromazine may be suggested as viable alternatives for S. littoralis management.

Insights into the recent progress in the medicinal chemistry of pyranopyrimidine analogs.

Heterocycles containing the pyranopyrimidine motif have attracted the interest of researchers in recent decades due to their ability to synthesize and explore at a large scale to explore the biological diversity. Therefore, this review highlights the biological characteristics and synthetic approaches adopted to prepare pyranopyrimidine analogs in the last five years. Several novel preparation procedures have been summarized to synthesize these compounds using ionic, basic, or nanocatalysts or catalyst-free conditions to obtain these compounds in good yields. Pyranopyrimidines could also be used as ligands in the preparation of metal complexes with increased biological potency. The different sections include the antimicrobial, antitubercular, antimalarial, antiviral "SARS-CoV-2 inhibitors", antidiabetic, antitumor, cytotoxic, antiinflammatory, antioxidant, anticoagulant, urease inhibitory activities, and tyrosine inhibitors. The results are discussed based on the structure-activity relationships (SARs) and the mechanism of action.