Elaboration of chitosan nanoparticles loaded with star anise extract as a therapeutic system for lung cancer: Physicochemical and biological evaluation.

The research study aimed to maximize the important medical role of star anise extract (SAE) through its loading on a widely available natural polymer (chitosan, Cs). Thus, SAE loaded chitosan nanoparticles (CsNPs) was prepared. The finding illustrated the formation of spherical particles of SAE loaded CsNPs as proved by transmission electron microscope (TEM). In addition, the average particle size of CsNPs and SAE loaded CsNPs are 131.8 ± 24.63 and 318.5 ± 73.94 nm, respectively. Scanning electron microscope (SEM) showed the presence of many spherical particles deposited on the surface of CsNPs owing to the deposition of SAE on the surface and encapsulated into pores of CsNPs. It also showed the presence of elements such as sodium, potassium, copper, magnesium, zinc, calcium, and iron, as well as the elements that accompanied with CsNPs: carbon, oxygen, nitrogen, and phosphorus. The extract was rich in bioactive components, such as anethole, shikimic acid, and different flavonoids, contributing to its medicinal qualities. The bioactive molecules in SAE were assessed by chromatographic analysis. Using the agar well diffusion test, the antibacterial qualities of CsNPs and SAE loaded CsNPs were evaluated against pathogenic bacteria linked to lung illnesses. The most significant inhibition zones showed that the SAE loaded CsNPs had the most antibacterial activity. The anticancer activity using MTT assay was used in the biological assessments to determine the cytotoxicity against the NCl-H460 lung cancer cell line. The results showed that CsNPs loaded with SAE considerably decreased cell viability in a dose-dependent manner, with the most significant anticancer impact by SAE loaded CsNPs. Furthermore, in vivo tests on lung cancer therapy revealed that when compared to other treatment groups, the SAE loaded CsNPs group showed the greatest reduction in tumor biomarkers and inflammation, as seen by decreased levels of Plasma malondialdehyde (MDA), tumor protein 53 (p53), Tumor necrosis factor-alpha (TNF- alpha), and fibronectin. Results concluded that these thorough characterizations, biological assessments, and antibacterial tests have confirmed the effective integration of SAE into CsNPs. Further, SAE loaded CsNPs could be a suitable option for various biomedical applications in tackling lung cancer and the inactivation of bacterial infection.

Unraveling the molecular significance of CYP1A2 (rs762551; c.-9-154 C>A) genetic variant on breast carcinoma susceptibility: Insights from case-control study and meta-analysis.

BACKGROUND: The human cytochrome P450 (CYP) superfamily encompasses different categories of isoenzymes that contribute to multiple metabolic processes involving drug detoxification, cellular signaling, and the proliferation of malignant tissues. Using genetic technology, customized bioinformatic analysis, and meta-analysis design, the main goal of this study was to identify the association between the CYP1A2*rs762551 variant and the susceptibility to breast carcinoma (BRCA). METHODS: The case-control study was conducted based on 104 BRCA women and 102 healthy controls. Using the TaqMan allelic discrimination assay, the CYP1A2 (rs762551; c.-9-154 C>A) variant was genotyped. Bioinformatic frameworks and logistic regression analysis were used to assess the involvement of this genetic variant in BRCA development. A meta-analysis design was accomplished based on our case-control study and other previously published records. Publication bias, heterogeneity between studies, and trial sequential analysis (TSA) were analyzed. RESULTS: The CYP1A2*rs762551 variant conferred protection against BRCA development under allelic (OR = 0.48, p-value < 0.001), dominant (OR = 0.34, p-value < 0.001), and recessive (OR = 0.44, p-value = 0.011) models. However, this intronic variant was correlated with a decreased risk of BRCA among late-onset menopause women compared to other cases. Bioinformatic analysis confirmed that this genetic variant has a functional impact on the progression of tumorgenesis. Moreover, this meta-analysis design included 12922 BRCA women and 15603 healthy controls. Our findings disclosed the contribution of the CYP1A2*rs762551 variant with protection against cancer development among Caucasian females under allelic (OR = 0.75, p-value = 0.025), and dominant (OR = 0.58, p-value = 0.015) models. CONCLUSIONS: This case-control study confirmed the contribution of the CYP1A2*rs762551 variant with decreased risk of BRCA development among Egyptian subjects. Moreover, BRCA women with late-onset menopause conferred protection against cancer progression compared to other subjects. Our findings identified that this meta-analysis design achieved protection against BRCA development among Caucasian women compared to other ethnicities.

Key genes and molecular mechanisms related to Paclitaxel Resistance.

Paclitaxel is commonly used to treat breast, ovarian, lung, esophageal, gastric, pancreatic cancer, and neck cancer cells. Cancer recurrence is observed in patients treated with paclitaxel due to paclitaxel resistance emergence. Resistant mechanisms are observed in cancer cells treated with paclitaxel, docetaxel, and cabazitaxel including changes in the target molecule ß-tubulin of mitosis, molecular mechanisms that activate efflux drug out of the cells, and alterations in regulatory proteins of apoptosis. This review discusses new molecular mechanisms of taxane resistance, such as overexpression of genes like the multidrug resistance genes and EDIL3, ABCB1, MRP1, and TRAG-3/CSAG2 genes. Moreover, significant lncRNAs are detected in paclitaxel resistance, such as lncRNA H19 and cross-resistance between taxanes. This review contributed to discovering new treatment strategies for taxane resistance and increasing the responsiveness of cancer cells toward chemotherapeutic drugs.

The use of proteins and peptides-based therapy in managing and preventing pathogenic viruses.

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and ß) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review.

Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice.

Chemoresistance and chemotherapy-related ovarian damage are well-reported in breast cancer (BC) young patients. Herein, the inhibition of the mitochondrial fission was invested to explore its chemosensitizing role in Paclitaxel (PTX)-resistant cells, and its ability to restore the ovarian integrity in mice receiving PTX or cisplatin chemotherapy. To establish these aims, PTX-resistance was generated in BC cells, which were treated with PTX in combination with Drp1 deficiency, via mdivi-1, or Drp1-specific siRNA transfection. Furthermore, the alterations in the ovarian structure and the endocrine-related hormones were explored in mice receiving repetitive doses of PTX or cisplatin. We found that combining PTX with mdivi-1 improved cell responsiveness to PTX, induced apoptosis- and autophagy-mediated cell death, and relieved cellular oxidative stress. Additionally, the expression of PCNA1 and cyclin B1 genes were downregulated, meanwhile, p53, p21, and mitochondrial fusion proteins (Mfu1&Mfu2) were increased. The in vivo investigations in mice demonstrated that PTX induced gonadotoxic damage similar to cisplatin, whereas dual treatment of mice with PTX+ mdivi-1 failed to restore their normal follicular count and the circulating levels of E2 and AMH hormones. These results suggested that combining Drp1 inhibition with PTX resensitized breast cancer cells to PTX but failed to offer enough protection against chemotherapy-related gonadotoxicity.

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility.

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.

Magnetic biopolymers' nanocomposites from chitosan, lignin and phycosynthesized iron nanoparticles to remediate water from polluting oil.

Targeting the remediation of oil pollution in water, the construction of super magnetic adsorbent nanocomposites (NCs) was achieved using the nanoparticles of chitosan (Cht), lignin (Lg) and phycosynthesized iron nanoparticles (Fe MNPs) using Gelidium amansii extract. The syntheses and conjugations of nanomaterials were authenticated via infrared spectral analysis and the structural physiognomies of them were appraised via electron microscopy and zeta analysis. The Lg NPs, Cht NPs, Fe MNPs and their composites (Lg/Cht MNCs) had mean particles' sizes of 42.3, 76.4, 14.2 and 108.3 nm, and were charged with - 32.7, + 41.2, + 28.4 and +37.5 mV, respectively. The magnetometer revealed the high magnetic properties of both Fe MNPs and Lg/Cht MNCs; the maximum swelling of Lg/Cht NPs (46.3 %), and Lg/Cht MNPs (33.8 %) was detected after 175 min. The diesel oil adsorption experiments with Lg/Cht MNPs, using batch adsorption practices, revealed the powerful potentiality of magnetic NCs to remove oil pollution in water; the maximum adsorption capacity (qt) was achieved with the conditions of pH = 7.5, adsorption period = 90 min and adsorbent dose = 200 mg/L. The magnetic Lg/Cht MNCs exhibited excellent recovery/reusability attributes for five adsorption cycles; the qt differences were negligible after the entire oil-adsorption cycles, with oil removal of >90 %. The innovative fabricated Lg/Cht MNCs could provide an effectual, sustainable and eco-friendly approach for the removal of pollutant oil in water resources.

Correction: Almutairi et al. Application of Chitosan/Alginate Nanocomposite Incorporated with Phycosynthesized Iron Nanoparticles for Efficient Remediation of Chromium. Polymers 2021, 13, 2481.

The authors wish to make the following corrections to the published paper [...].

Application of Chitosan/Alginate Nanocomposite Incorporated with Phycosynthesized Iron Nanoparticles for Efficient Remediation of Chromium.

Biopolymers and nanomaterials are ideal candidates for environmental remediation and heavy metal removal. As hexavalent chromium (Cr6+) is a hazardous toxic pollutant of water, this study innovatively aimed to synthesize nanopolymer composites and load them with phycosynthesized Fe nanoparticles for the full Cr6+ removal from aqueous solutions. The extraction of chitosan (Cht) from prawn shells and alginate (Alg) from brown seaweed (Sargassum linifolium) was achieved with standard characteristics. The tow biopolymers were combined and cross-linked (via microemulsion protocol) to generate nanoparticles from their composites (Cht/Alg NPs), which had a mean diameter of 311.2 nm and were negatively charged (-23.2 mV). The phycosynthesis of iron nanoparticles (Fe-NPs) was additionally attained using S. linifolium extract (SE), and the Fe-NPs had semispherical shapes with a 21.4 nm mean diameter. The conjugation of Cht/Alg NPs with SE-phycosynthesized Fe-NPs resulted in homogenous distribution and stabilization of metal NPs within the polymer nanocomposites. Both nanocomposites exhibited high efficiency as adsorbents for Cr6+ at diverse conditions (e.g., pH, adsorbent dose, contact time and initial ion concentration) using batch adsorption evaluation; the most effectual conditions for adsorption were a pH value of 5.0, adsorbent dose of 4 g/L, contact time of 210 min and initial Cr6+ concentration of 75 ppm. These factors could result in full removal of Cr6+ from batch experiments. The composited nanopolymers (Cht/Alg NPs) incorporated with SE-phycosynthesized Fe-NPs are strongly recommended for complete removal of Cr6+ from aqueous environments.

The Identification of a Novel Unsymmetrical Azine as an Apoptosis Inducer in Colorectal Cancer.

BACKGROUND: Defects in the physiological mechanisms of apoptosis are one of the pivotal factors implicated in carcinogenesis. Thus, the development of novel compounds that target various apoptotic pathways has provided promising anticancer therapeutic opportunities. OBJECTIVE: This study explores the cytotoxic effects of a novel unsymmetrical azine against specific cancer cell lines and investigates the mechanism of cytotoxicity. METHODS: Molecular modeling was used to test the binding affinity of four new unsymmetrical azines to a model of an apoptosis inhibitor protein (XIAP). The compound with the highest binding affinity, C4, was further tested on different cell lines. Real-time Polymerase Chain Reaction (PCR) and Transmission Electron Microscope (TEM) were used to study apoptosis induction biochemically and morphologically. RESULTS: In comparison to cisplatin as a control, the compound C4 exhibited notable cytotoxicity against all tested cancer cell lines, especially the human colorectal carcinoma cell line (HCT-116). Furthermore, C4-treated cells demonstrated marked overexpression of the pro-apoptotic proteins Bax and caspase-3 as well as the tumor suppressor p53. On the other hand, the expression of the anti-apoptotic protein Bcl-2 was inhibited. On TEM examination, C4-treated HCT-116 cells showed classical structural signs of apoptosis. CONCLUSION: This study identifies a novel azine (C4), which induces remarkable cytotoxicity against the colorectal carcinoma cell line, mediated through apoptosis induction. These novel insights suggest C4 as a promising therapeutic agent in colorectal cancer.

Augmented anticancer activity of curcumin loaded fungal chitosan nanoparticles.

Fungal chitosan (FCt) from Amylomyces rouxii, with 88.7% deacetylation degree and 112.4 kDa molecular weight, was utilized for nanoparticles (NPs) formation via ionic gelation. FCt-NPs were employed as carriers for curcumin (CUR) to augment its availability and anticancer bioactivity. The synthesis of CUR/FCt-NPs composite was succeeded as evidenced from their FTIR spectra. The scanning micrographs of synthesized CUR/FCt-NPs indicated their spherical shapes and well-distribution; they had average diameters of 115 ± 21 nm and positive zeta potentials of +33.8 mV. The NPs loading capacity for CUR was 21.6% and the encapsulation efficiency reached 83.8%. The CUR was vastly released in the beginning 5 h then gradually released up to 90 h, with higher release in pH 5.2 than in pH 7.0. The treatment of cancer cells, HCT-116 and A-549, with CUR/FCt NPs lead to time-dependent decrement of cells' viability; the dead cells were 67.6% from HCT-116 and 73.8% from A-546 after 96 h of exposure. Fluorescent imaging indicated that most cancer cells entered the apoptosis phase after treatment with 150 µM of CUR/FCt-NPs for 72 h. The efficiency of FCt-NPs was proved as carriers for loading CUR and augmenting its anticancer activity toward human cancer cells, using these natural and biosafe agents.