Therapeutic Effects of Crocin Nanoparticles Alone or in Combination with Doxorubicin against Hepatocellular Carcinoma In vitro.

OBJECTIVE: Crocin (CRO), the primary antioxidant in saffron, is known for its anticancer properties. However, its effectiveness in topical therapy is limited due to low bioavailability, poor absorption, and low physicochemical stability. This study aimed to prepare crocin nanoparticles (CRO-NPs) to enhance their pharmaceutical efficacy and evaluate the synergistic effects of Cro-NPs with doxorubicin (DOX) chemotherapy on two cell lines: human hepatocellular carcinoma cells (HepG2) and non-cancerous cells (WI38). METHODS: CRO-NPs were prepared using the emulsion diffusion technique and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Zeta potential, and Fourier transform infrared spectroscopy (FT-IR). Cell proliferation inhibition was assessed using the MTT assay for DOX, CRO, CRO-NPs, and DOX+CRO-NPs. Apoptosis and cell cycle were evaluated by flow cytometry, and changes in the expression of apoptotic gene (P53) and autophagic genes (ATG5 & LC3) were analyzed using real-time polymerase chain reaction. RESULTS: TEM and SEM revealed that CRO-NPs exhibited a relatively spherical shape with an average size of 9.3 nm, and zeta potential analysis indicated better stability of CRO-NPs compared to native CRO. Significantly higher antitumor effects of CRO-NPs were observed against HepG2 cells (IC50 = 1.1 mg/ml and 0.57 mg/ml) compared to native CRO (IC50 = 6.1 mg/ml and 3.2 mg/ml) after 24 and 48 hours, respectively. Annexin-V assay on HepG2 cells indicated increased apoptotic rates across all treatments, with the highest percentage observed in CRO-NPs, accompanied by cell cycle arrest at the G2/M phase. Furthermore, gene expression analysis showed upregulation of P53, ATG5, and LC3 genes in DOX/CRO-NPs co-treatment compared to individual treatments. In contrast, WI38 cells exhibited greater sensitivity to DOX toxicity but showed no adverse response to CRONPs. CONCLUSION: Although more in vivo studies in animal models are required to corroborate these results, our findings suggest that CRO-NPs can be a potential new anticancer agent for hepatocellular carcinoma. Moreover, they have a synergistic effect with DOX against HepG2 cells and mitigate the toxicity of DOX on normal WI38 cells.

Hepatoprotective effect of silymarin-chitosan nanocomposite against aluminum-induced oxidative stress, inflammation, and apoptosis.

Aluminum (Al) is abundant in the environment, and its toxicity is attributed to free radical formation and subsequent oxidative stress. While silymarin is a well-known antioxidant, its low water solubility and bioavailability limit its therapeutic effects. This study was designated to formulate silymarin chitosan nanoparticles (SM-CS-NPs) and evaluate its ameliorative effect against hepatotoxicity induced by aluminum chloride (AlCl3). SM-CS-NPs were prepared by ionotropic gelation method and characterized using different techniques. Rats were distributed into six groups (n=7/group), control, silymarin (SM; 15 mg/kg B.W), silymarin-chitosan nanoparticles (SM-CS-NPs; 15 mg/kg), aluminum chloride (AlCl3, 34 mg/kg), SM or SM-CS-NPs administrated orally one hour before the treatment with AlCl3 for 30 days, respectively. Results showed that supplementation of SM-CS-NPs or SM solo improved the antioxidant state and reduced oxidative stress. On the other hand, the pretreatment with SM-CS-NPs or SM followed by AlCl3 significantly restored liver functions (AST, ALT, ALP, LDH, total protein, albumin, globulin, and bilirubin) and modulated oxidative stress biomarkers (TBARS and H2O2), with improved cellular antioxidant defense (SOD, CAT, GPx, GR, GST, and GSH) and maintained normal liver histological structure compared to rats treated with AlCl3 alone. Furthermore, they alleviated the inflammation and apoptosis by downregulating the expression level of COX-2, caspase-3, and TNFα. This ameliorative effect was stronger with silymarin nanoform than in bulk-state silymarin. According to the findings, silymarin preparation in nanoform boosts its ameliorative and protective effects against AlCl3 hepatotoxicity.

Development of a novel elastomer with unique properties as fire and radiation resistance.

This study aims to create a novel, distinct form of elastomer with superior ability to resist fire, high resistance to radiation, and resistance to environmental conditions such as temperature and solvents. This type of natural-based elastomer was prepared using carboxymethyl cellulose CMC, polyacrylic acid PAA, crosslinked with tannic acid TA. Most techniques in elastomer manufacture technologies are unfriendly and participate in increasing carbon emissions. Gamma radiation was used as a clean tool for copolymerization and crosslinking the elastomer. The irradiation dose of 5 kGy with a rate of 3.32 kGy/h was enough to produce CMC/PAA/TA elastomer. The properties of the produced elastomer were investigated by Fourier-transformed infrared spectroscopy (FT-IR), X-ray diffraction, thermal gravimetric analysis (TGA), and limiting oxygen index (LOI). CMC/PAA/TA has high resistance to solvents such as acetone, benzene, HCl, and HNO3. The tensile strength is 3.376 MPa, the elongation percent is 501.689%, and the LOI value is 30%. The produced elastomer possessed excellent gamma radiation resistance. The elastomer was exposed later to 1864 kGy of gamma radiation without showing degradation and retained its properties, as confirmed by FTIR, TGA, and mechanical properties. After investigation, it can be inferred that the produced CMC/PAA/TA elastomer exhibited outstanding properties.

Virtues of routine suprahyoid release during tracheal resection and anastomosis in patients with post intubation stenosis.

Postintubation tracheal stenosis is the most common cause of benign tracheal stenosis. Surgical treatment is more challenging in long-segment stenosis. Suprahyoid release can increase tracheal length resected without anastomotic tension in patients with post-intubation tracheal stenosis. Its effect on swallowing has not been objectively studied and this article aims to explore its virtues and potential complications in a tertiary center for airway surgery. A prospective cohort study was conducted on forty consecutive patients from June 2020 till December 2023. Patients of both genders had tracheal resection anastomosis surgery with routine suprahyoid muscle release for resected tracheal segment of more than 2.5 cm in length aiming to decrease the anastomotic tension. Within two weeks postoperatively, a video naso-laryngoscope was done on all the patients to detect any vocal cord disorders, then they were examined by video fluoroscopy swallowing study VFSS to detect swallowing problems. Follow up was done for 6 months postoperatively. 40 patients were studied. Twenty-five patients (62.5%) were males. 21 patients (52.5%) had a cricotracheal resection. VFSS was performed on 38 patients (two patients excluded for serious morbidity). Six (15.7%) and four (10.5%) patients had residual semisolid and solid food in the vallecula and pyriform fossa respectively during swallowing. Five patients (13%) out of eight patients with abnormal VFSS had aspiration and dysphagia. Video nasolaryngoscopy was done pre- and post-operatively and showed that 7 patients (17.5%) had unilateral vocal cord paralysis, two of them had the same lesion preoperatively. Two patients developed postoperative anastomotic complications. All symptoms of dysphagia improved within 3 weeks of the procedure and improvement persisted for 6 months. Suprahyoid muscle release had a considerable reversible drawback on the process of swallowing. Its routine use in high-risk patients requiring long segment tracheal resections could be considered.

Comparison of the diversity of anaerobic-cultured gut bacterial communities on different culture media using 16S rDNA sequencing.

The gut microbiome is a dense and diverse community of different microorganisms that deeply influence human physiology and that have important interactions with pathogens. For the correct antibiotic treatment of infections, with its twin goals of effective inhibition of the pathogen and limitation of collateral damage to the microbiome, the identification of infectious organisms is key. Microbiological culturing is still the mainstay of pathogen identification, and anaerobic species are among the most demanding bacterial communities to culture. This study aimed to evaluate the impact of growth media on the culture of an-aerobic bacteria from human stool samples. Stool samples from eight human subjects were cultured each on a yeast extract cysteine blood agar (HCB) and a modified peptone-yeast extract-glucose (MPYG) plate and subjected to Illumina NGS analysis after DNA extraction and amplification. The results showed tight clustering of sequencing samples belonging to the same human subject. Various differences in bacterial richness and evenness could be observed between the two media, with HCB plates supporting the growth of a more diverse microbial community, and MPYG plates improving the growth rates of certain taxa. No statistical significance was observed between the groups. This study highlights the importance of choosing the appropriate growth media for anaerobic bacterial culture and adjusting culture conditions to target specific pathological conditions. HCB plates are suitable for standard microbiological diagnostics, while MPYG plates may be more appropriate for targeting specific conditions. This work emphasizes the role of next-generation sequencing in supporting future research in clinical microbiology.

Comprehensive overview of how to fade into succinate dehydrogenase dysregulation in cancer cells by naringenin-loaded chitosan nanoparticles.

Mitochondrial respiration complexes play a crucial function. As a result, dysfunction or change is intimately associated with many different diseases, among them cancer. The epigenetic, evolutionary, and metabolic effects of mitochondrial complex IΙ are the primary concerns of our review. Provides novel insight into the vital role of naringenin (NAR) as an intriguing flavonoid phytochemical in cancer treatment. NAR is a significant phytochemical that is a member of the flavanone group of polyphenols and is mostly present in citrus fruits, such as grapefruits, as well as other fruits and vegetables, like tomatoes and cherries, as well as foods produced from medicinal herbs. The evidence that is now available indicates that NAR, an herbal remedy, has significant pharmacological qualities and anti-cancer effects. Through a variety of mechanisms, including the induction of apoptosis, cell cycle arrest, restriction of angiogenesis, and modulation of several signaling pathways, NAR prevents the growth of cancer. However, the hydrophobic and crystalline structure of NAR is primarily responsible for its instability, limited oral bioavailability, and water solubility. Furthermore, there is no targeting and a high rate of breakdown in an acidic environment. These shortcomings are barriers to its efficient medical application. Improvement targeting NAR to mitochondrial complex ΙΙ by loading it on chitosan nanoparticles is a promising strategy.

Childhood and Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With t(8;14) and BCL2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge.

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as "DLBCL-NOS with MYC rearrangement" using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World Health Organization Classifications of Haematolymphoid Tumors (WHO-HAEM5). This report illustrates diagnostic challenges and treatment dilemmas that may be encountered, particularly for adolescent and young adults (AYA).

Hepatoprotective impact of Nigella sativa silver nanocomposite against genotoxicity, oxidative stress, and inflammation induced by thioacetamide.

Protection from liver damage and the repercussion of that harm is thought to be crucial for reducing the number of deaths each year. This work was developed to evaluate the possible role of silver nanocomposite prepared using Nigella sativa (N. sativa) aqueous extract against the hepatic damage brought on by thioacetamide (TAA), with particular attention to how they affect the NF-κß, TNF-α, IL-1ß, and COX-2 signaling pathways. There were seven groups of male Wistar rats used as follows: control, saline, N. sativa aqueous extract (NSAE; 200 mg/kg/d), N. sativa silver nanocomposite (NS-AgNC; 0.25 mg/kg/d), TAA (100 mg/kg; thrice weekly), NSAE + TTA, and NS-AgNC + TAA, respectively. The experiment continued for six weeks. The results showed that NS-AgNPs significantly enhanced liver functions (p<0.05) (albumin, ALP, LDH, AST, total protein, ALT, and globulin) and oxidant/antioxidant biomarkers (p<0.05) (H2O2, MDA, PCC, NO, SOD, CAT, GPx, GR, GST and, GSH), contrasted with TAA group. Moreover, a significant (p<0.05) downregulation of the gene expressions (COX-2, TNF-α, IL-1ß, and NF-κß) was also achieved by using silver nanocomposite therapy. These findings have been supported by histological analysis. Collectively, NS-AgNC exhibits more prominent and well-recognized protective impacts than NSAE in modulating the anti-inflammatory, genotoxicity and oxidative stress effects against TAA-induced liver injuries.

Synergistic effect of spermidine and ciprofloxacin against Alzheimer's disease in male rat via ferroptosis modulation.

Alzheimer's disease (AD) is a prevalent form of neurodegenerative disease with a complex pathophysiology that remains not fully understood, and the exact mechanism of neurodegeneration is uncertain. Ferroptosis has been linked to the progression of degenerative diseases observed in AD models. The present study is designed to investigate the protective effects of spermidine, a potent antioxidant and iron chelator, and its synergistic interactions with ciprofloxacin, another iron chelator, in modulating ferroptosis and mitigating AD progression in rats. This study investigated AD-related biomarkers like neurotoxic amyloid beta (Aß), arginase I, and serotonin. Spermidine demonstrated an anti-ferroptotic effect in the AD model, evident from the modulation of ferroptosis parameters such as hippocampus iron levels, reduced protein expression of transferrin receptor 1 (TFR1), and arachidonate 15-lipoxygenase (ALOX15). Additionally, the administration of spermidine led to a significant increase in protein expression of phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) and upregulation of Cystine/glutamate transporter (SLC7A11) gene expression. Moreover, spermidine notably decreased p53 protein levels, acrolein, and gene expression of spermidine/spermine N1-acetyltransferase 1 (SAT1). Overall, our findings suggest that spermidine and/or ciprofloxacin may offer potential benefits against AD by modulating ferroptosis. Furthermore, spermidine enhanced the antioxidant efficacy of ciprofloxacin and reduced its toxic effects.

Mechanistic role of quercetin as inhibitor for adenosine deaminase enzyme in rheumatoid arthritis: systematic review.

Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease's systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials.

The synergistic effect of nanocurcumin and donepezil on Alzheimer's via PI3K/AKT/GSK-3ß pathway modulating.

Alzheimer's disease (AD) hallmarks include amyloid-ßeta (Aß) and tau proteins aggregates, neurite degeneration, microglial activation with cognitive impairment. Phosphatidylinositol-3-kinase/protein kinase B/Glycogen synthase kinase-3-beta (PI3K/AKT/GSK-3) pathway is essential for neuroprotection, cell survival and proliferation by blocking apoptosis. This study aimed to assess protective role of nanocurcumin (NCMN) as strong antioxidant and anti-inflammatory agent with elucidating its synergistic effects with Donepezil as acetylcholinesterase inhibitor on AD in rats via modulating PI3K/AKT/GSK-3ß pathway. The experiment was performed on 70 male Wistar albino rats divided into seven groups (control, NCMN, Donepezil, AD-model, Donepezil co-treatment, NCMN only co-treatment, and NCMN+Donepezil combined treatment). Behavioral and biochemical investigations as cholinesterase activity, oxidative stress (malondialdehyde, reduced glutathione, nitric oxide, superoxidedismutase, and catalase), tumor necrosis factor-alpha, Tau, ß-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Phosphatase and tensin homolog (Pten), mitogen-activated protein kinase-1 (MAPK-1), Glycogen synthase kinase-3-beta (GSK-3ß) and toll-like receptor-4 were evaluated. Treatment with NCMN improved memory, locomotion, neuronal differentiation by activating PI3K/AKT/GSK-3ß pathway. These results were confirmed by histological studies in hippocampus.

Caffeine-folic acid-loaded-chitosan nanoparticles combined with methotrexate as a novel HepG2 immunotherapy targeting adenosine A2A receptor downstream cascade.

BACKGROUND: Methotrexate (MTX) is a common chemotherapeutic drug that inhibits DNA synthesis and induces apoptosis. Treatment with MTX increased CD73 expression, which leads to higher levels of extracellular adenosine. Adenosine levels are also high in the tumor microenvironment through Cancer cells metabolism. That promotes the survival of cancer cells and contributes to tumor immune evasion through the Adenosine 2a Receptor. A2A receptor antagonists are an emerging class of agents that treat cancers by enhancing immunotherapy, both as monotherapy and in combination with other therapeutic agents. Caffeine is an adenosine receptor antagonist. Herein, we demonstrate the ability of a novel well prepared and characterized nano formula CAF-FA-CS-NPs (D4) for A2aR blockade when combination with MTX to improve its antitumor efficacy by enhancing the immune system and eliminating immune suppression. METHODS: CAF-FA-CS-NPs (D4) were prepared and characterized for particle size, loading efficiency, and release profile. Molecular docking was used to validate the binding affinity of caffeine and folic acid to A2A receptor. The effects of the nano formula were evaluated on human liver cancer cells (HepG2), breast cancer cells (MCF-7), and MDA-MB-231, as well as normal human cells (WI-38). Different combination ratios of MTX and D4 were studied to identify the optimal combination for further genetic studies. RESULTS: Molecular docking results validated that caffeine and folic acid have binding affinity to A2A receptor. The CS-NPs were successfully prepared using ionic gelation method, with caffeine and folic acid being loaded and conjugated to the nanoparticles through electrostatic interactions. The CAF loading capacity in D4 was 77.9 ± 4.37% with an encapsulation efficiency of 98.5 ± 0.37. The particle size was optimized through ratio variations. The resulting nanoparticles were fully characterized. The results showed that (D4) had antioxidant activity and cytotoxicity against different cancer cells. The combination of D4 with MTX (IC50 D4 + 0.5 IC50 MTX) resulted in the downregulation of Bcl-2, FOXP3, CD39, and CD73 gene expression levels and upregulation of Bax and A2AR gene expression levels in HepG2 cells. CONCLUSIONS: This study suggests that CAF-FA-CS-NPs (D4) in combination with MTX may be a promising candidate for cancer immunotherapy, by inhibiting A2aR signaling and leading to improved immune activation and anti-tumor activity of MTX.

Biliary fistula and late recurrence of liver hydatid cyst: Role of cysto-biliary communication: A prospective multicenter study.

BACKGROUND: Hydatid cyst disease (HCD) is common in certain locations. Surgery is associated with postoperative biliary fistula (POBF) and recurrence. The primary aim of this study was to identify whether occult cysto-biliary communication (CBC) can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase (ALP) levels in predicting POBF and recurrent HCD. AIM: To identify whether occult CBC can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD. METHODS: From September 2010 to September 2016, a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty. Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence. RESULTS: There was a highly statistically significant association (P ≤ 0.001) between cystic fluid biochemical indices and the development of biliary complications (of 16 patients with POBF, 15 patients had high cyst fluid bilirubin and ALP levels), where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications. There was a highly statistically significant association (P ≤ 0.001) between biliary complications, biochemical indices, and the occurrence of recurrent HCD (of 30 patients with recurrent HCD, 15 patients had high cyst fluid bilirubin and ALP; all 16 patients who had POBF later developed recurrent HCD), where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts, respectively. CONCLUSION: Occult CBC can predict recurrent HCD. Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.

Gut Microbiota in Diagnosis, Therapy and Prognosis of Cholangiocarcinoma and Gallbladder Carcinoma-A Scoping Review.

Cancers of the biliary tract are more common in Asia than in Europe, but are highly lethal due to delayed diagnosis and aggressive tumor biology. Since the biliary tract is in direct contact with the gut via the enterohepatic circulation, this suggests a potential role of gut microbiota, but to date, the role of gut microbiota in biliary tract cancers has not been elucidated. This scoping review compiles recent data on the associations between the gut microbiota and diagnosis, progression and prognosis of biliary tract cancer patients. Systematic review of the literature yielded 154 results, of which 12 studies and one systematic review were eligible for evaluation. The analyses of microbiota diversity indices were inconsistent across the included studies. In-depth analyses revealed differences between gut microbiota of biliary tract cancer patients and healthy controls, but without a clear tendency towards particular species in the studies. Additionally, most of the studies showed methodological flaws, for example non-controlling of factors that affect gut microbiota. At the current stage, there is a lack of evidence to support a general utility of gut microbiota diagnostics in biliary tract cancers. Therefore, no recommendation can be made at this time to include gut microbiota analyses in the management of biliary tract cancer patients.

Time-dependent changes in the glycolytic pathway in activated T cells are independent of tumor burden or anti-cancer chemotherapy.

Although activated adoptive T cells therapy (ATC) is an effective approach for cancer treatment, it is not clear how modulation of T cell activation impacts their biochemical signature which significantly impacts the cell function. This study is aimed to investigate the impact of polyclonal activation on the metabolic signature of T cells from tumor-bearing mice under different settings of treatment with chemotherapy. Thirty female Swiss albino mice were divided into 5 groups (n = 6/each), Gp1(PBS), groups Gp2 were inoculated intraperitoneal (i.p) with 1 × 106 cells/mouse Ehrlich ascites carcinoma (EAC), Gp3-Gp5 were treated with cisplatin (20 mg/mice) which were represented as EAC/CIS/1wk Or EAC/CIS/2wk 3 times every other day. Splenocytes were cultured in or presence of concanavalin-A (Con-A) and IL-2 for 24 h or 72 h, then cells were harvested, and processed to determine the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and glucose 6 phosphate dehydrogenase(G6PD) enzymes. The results showed that before culture, T cells harvested from EAC/PBS/1wk of mice or inoculated with EAC/CIS/1wk showed higher activity in HK, PFK, LDH, and G6PH as compared to naive T cells. After 24, and 72 h of culture and activation, the enzyme activities in T cells harvested from EAC/CIS/2wk mice or EAC/CIS/3wk mice decreased compared with their control. The late stage of the tumor without chemotherapy gives a low glycolic rate. In late activation, naive and early stages of the tumor with chemotherapy can give high glycolic metabolism. These results show great significance as an application of adoptive T-cell therapy.

Electrochemical, surface analysis, computational and anticorrosive studies of novel di-imine Schiff base on X65 steel surface.

The inhibitory effect of di-imine-SB namely ((N1Z, N4E)-N1, N4-bis (4 (dimethylamino) benzylidene) butane 1,4-diamine) on X65-steel in 1 M HCl has been investigated experimentally and theoretically. The electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), and weight loss outcomes display the anticorrosion properties of "di-imine- SB". The inhibitory efficiency exceeds 90% at the optimal concentration of 1 × 10-3 M "di-imine- SB". The metal surface was examined further using scanning electron microscope (SEM) and energy dispersive X-ray (EDX). The effectiveness of the di-imine-SB is returned into its adsorption on X65-steel surface and found in agreement with Langmuir adsorption isotherm. According to the standard Gibbs free energy of adsorption [Formula: see text], di-imine-SB adsorption tends to be chemical rather than physical, it increases the activation energy ([Formula: see text]) of metal dissolution reaction and makes it hard to occur. The PDP data suggested anodic and cathodic type of the di-imine-SB inhibitor. Meanwhile, increasing the resistance of X65-steel to 301 Ω cm2 after adding 1 mM of di-imine-SB confirms its protective effect. Whereas, the positive value of the fraction of electron transference (ΔN, 0.746), confirms the affinity of di-imine-SB to share electrons to the partially filed 3d-orbital of Fe forming strong protective film over X65-steel surface. Aided by Monte Carlo (MC) simulation, the calculated adsorption energy (Eads) suggests excessive adsorption affinity of di-imine-SB on metal surface over the corrosive chlorides and hydronium ions. A good correlation between the theoretical hypothesis and the experimental inhibition efficiency has been achieved. The comparative study showed the superior of the di-imine-SB as potential corrosion inhibitor compared with those reported before. Finally, global reactivity descriptors; electron affinity (A), ionization potential (I), electronegativity (χ), dipole moment (µ), global hardness ([Formula: see text]), electrophilicity index and, Fukui indices were also calculated and found well correlated to the reactivity of di-imine-SB.

The effect of accelerated pulsed high-fluence corneal cross-linking on corneal endothelium; a prospective specular microscopy study.

BACKGROUND: Corneal collagen cross-linking (CXL) is a procedure utilized for halting keratoconus progression with different approved protocols. The current study aimed to assess the corneal endothelial changes following the relatively new accelerated pulsed high-fluence protocol of epithelium-off corneal cross-linking for the treatment of mild to moderate keratoconus. METHODS: This prospective case series study enrolled 45 eyes of 27 patients with mild to moderate progressive keratoconus who underwent accelerated pulsed high-fluence CXL (pl-ACXL, 30 mW/ cm2 UVA at 365 nm wavelength, 8 min pulsed mode 1 s on / 1 s off with a total energy of 7.2 J/ cm2). The main outcome measures were corneal endothelial changes assessed by specular microscopy at 3 and 6 months postoperatively including endothelial cell density (ECD), coefficient of variation, percentage of hexagonal cells, average, minimum and maximum endothelial cell sizes. Demarcation line depth was assessed 1 month following surgery. RESULTS: The mean age of the studied sample was 24.89 ± 7.21. The mean preoperative ECD (2944.6 ± 247.41 cell/mm2) showed non-significant reduction at 3 and 6 months postoperatively (2931.03 ± 253.82 and 2924.7 ± 224.88 cell/mm2, respectively, P-value = 0.361). There were no significant changes in the mean coefficient of variation, percentage of hexagonal cells, average, minimum and maximum endothelial cell sizes at 3 and 6 months following pl-ACXL (P-value > 0.05). The mean demarcation line depth 1 month after pl-ACXL was 214 ± 17.43 µm. CONCLUSIONS: Corneal endothelial changes following accelerated pulsed high-fluence CXL were minimal with stability of endothelial cell count and non-significant morphological changes. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04160338 (13/11/2019).

Impairment of electron transport chain and induction of apoptosis by chrysin nanoparticles targeting succinate-ubiquinone oxidoreductase in pancreatic and lung cancer cells.

BACKGROUND: Flavonoids may help ameliorate the incidence of the major causes of tumor-related mortality, such as pancreatic ductal adenocarcinoma (PDAC) and lung cancer, which are predicted to steadily increase between 2020 to 2030. Here we compared the effect of chrysin and chrysin nanoparticles (CCNPs) with 5-fluorouracil (5-FLU) on the activity and expression of mitochondrial complex II (CII) to induce apoptosis in pancreatic (PANC-1) and lung (A549) cancer cells. METHODS: Chrysin nanoparticles (CCNPs) were synthesized and characterized, and the IC50 was evaluated in normal, PANC-1, and A549 cell lines using the MTT assay. The effect of chrysin and CCNPs on CΙΙ activity, superoxide dismutase activity, and mitochondria swelling were evaluated. Apoptosis was assessed using flow cytometry, and expression of the C and D subunits of SDH, sirtuin-3 (SIRT-3), and hypoxia-inducible factor (HIF-1α) was evaluated using RT-qPCR. RESULTS: The IC50 of CII subunit C and D binding to chrysin was determined and used to evaluate the effectiveness of treatment on the activity of SDH with ubiquinone oxidoreductase. Enzyme activity was significantly decreased (chrysin < CCNPs < 5-FLU and CCNPs < chrysin < 5-FLU, respectively), which was confirmed by the significant decrease of expression of SDH C and D, SIRT-3, and HIF-1α mRNA (CCNPs < chrysin < 5-FLU). There was also a significant increase in the apoptotic effects (CCNPs > chrysin > 5-FLU) in both PANC-1 and A549 cells and a significant increase in mitochondria swelling (CCNPs < chrysin < 5-FLU and CCNPs > chrysin > 5-FLU, respectively) than that in non-cancerous cells. CONCLUSION: Treatment with CCNPs improved the effect of chrysin on succinate-ubiquinone oxidoreductase activity and expression and therefore has the potential as a more efficient formulation than chemotherapy to prevent metastasis and angiogenesis by targeting HIF-1α in PDAC and lung cancer.

Tunable femtosecond laser suppresses the proliferation of breast cancer in vitro.

Worldwide, the most frequently diagnosed cancer is female breast cancer, and it poses a serious global health threat. Traditional cancer therapies are associated with various side effects, so developing better therapies for breast cancer is necessary, such as laser therapy which could be a promising treatment option. The aim of the current study was to investigate the femtosecond laser irradiation effect on breast cancer using T47D cell line as an in vitro model. Cells were seeded at a density of 5 × 104 cells/well in 96-well plates and incubated overnight. After that, the cells were exposed to femtosecond laser irradiation at various wavelengths falling in the UV, visible, and IR ranges for 3, 5, or 10 min and at a constant power of 100 mW. Cell viability was measured directly and 24 h after femtosecond laser irradiation using MTT assay. When using different femtosecond laser irradiation parameters, especially the 380 and 400 nm femtosecond laser irradiation, there was significant inhibition of breast cancer cell growth, either directly or 24 h after femtosecond laser exposure. Also, 420 and 440 nm significantly affected the viability of the cells. It was also observed that increasing exposure time enhances the observed effect, so 10 min exposure time was the best time of exposure. However, 700, 720, 750, and 780 nm did not significantly affect the cells viability with different exposure times. It was possible to conclude from the aforementioned results that femtosecond laser irradiation exerted a significant anticancer effect against T47D cells. Consequently, the femtosecond laser could be used successfully for breast cancer management.

Cord Blood Plasma and Placental Mesenchymal Stem Cells-Derived Exosomes Increase Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells While Maintaining Their Stemness.

BACKGROUND: Mesenchymal stem cells (MSCs) have been used for ex vivo expansion of umbilical cord blood (UCB) hematopoietic stem cells (HSCs) to maintain their primitive characters and long-term reconstitution abilities during transplantation. Therapeutic effects of MSCs mainly rely on paracrine mechanisms, including secretion of exosomes (Exos). The objective of this study was to examine the effect of cord blood plasma (CBP)-derived Exos (CBP Exos) and Placental MSCs-derived Exos (MSCs Exos) on the expansion of UCB HSCs to increase their numbers and keep their primitive characteristics. METHODS: CD34+ cells were isolated from UCB, cultured for 10 days, and the expanded HSCs were sub-cultured in semisolid methylcellulose media for primitive colony forming units (CFUs) assay. MSCs were cultured from placental chorionic plates. RESULTS: CBP Exos and MSCs Exos compared with the control group significantly increased the number of total nucleated cells (TNCs), invitro expansion of CD34+ cells, primitive subpopulations of CD34+38+ and CD34+38-Lin- cells (p < 0.001). The expanded cells showed a significantly higher number of total CFUs in the Exos groups (p < 0.01). CONCLUSION: CBP- and placental-derived exosomes are associated with significant ex vivo expansion of UCB HSCs, while maintaining their primitive characters and may eliminate the need for transplantation of an additional unit of UCB.