A REVIEW OF TREATMENT, RISK FACTORS, AND INCIDENCE OF COLORECTAL CANCER

Colorectal cancer (CRC) is considered as the third most frequent cancer in the world and the incidence increases with increasing age. CRC accounts for nearly 9 % of all cancer incidence, with an estimated 1.4 million cases happening in 2012. The aim of this paper is to provide a review of incidence, risk factors, screening strategies, and treatment of colorectal cancer. We searched the studies in five English databases, including Web of Science, PubMed, Scopus, EMBASE, and Google Scholar with no limitation in publication time to find all papers regarding colorectal cancers. Papers with any language were included in the first step of search if they had an English abstract. We used the following words and terms including colorectal cancer, treatment, risk factor, diagnosis, chemotherapy, radiotherapy, surgery. Geographical variations and different time courses in the CRC incidence indicate that environmental factors and lifestyle are major factors in the development of this disease. The main preventable risk factors for CRC are nutrition, a high-fat diet, a low-fiber diet, obesity and physical inactivity, smoking and alcohol consumption, aspirin and nonsteroidal anti-inflammatory drugs, and some non-preventable risk factors such as age, gender, race, and diabetes mellitus. Colonoscopy remains the study of choice to diagnose colorectal cancer. Prior to any treatment, CT imaging of chest, abdomen and pelvis with contrast is needed for staging the patient’s CRC. The preferred option for localized colorectal cancer is surgery (etc, laparoscopic surgery, colostomy for rectal cancer); whereas the adjuvant chemotherapy is generally recommended for patients with lymph node metastases. Targeted treatment of colorectal cancer by monoclonal antibodies are important bioengineered proteins that can help the body's natural immune response to detect, attack, and kill cancer cells. Monoclonal antibodies may be used alone or in combination with other treatments such as chemotherapy. CRC accounts an important health problem worldwide that is estimated to increase because of the growth and aging of the population, and because of the adoption of at-risk manners and lifestyles, particularly in economically less developed countries. Screening has been confirmed to significantly decrease mortality and can prevent the onset of the disease. More international efforts are required to situate into practice targeted prevention approaches that might reduce the burden of CRC worldwide

Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p p Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results

Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats

Wilson’s disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a “thin film hydration method” was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats’ spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms

Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats

Wilson’s disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a “thin film hydration method” was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats’ spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms

Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction

The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib and the possibility of counteracting this adverse reaction by giving ascorbic acid intraperitoneally to male albino rats. Sixty adult male albino rats weighing 150–180 g were used. The rats were allocated into six equal groups. One group was a control, and the others were given azithromycin, etoricoxib, either alone or combination, with one group treated with ascorbic acid and the last group treated with the drug combination and ascorbic acid. Blood samples were collected for measuring AST, ALT, LDH, CK-MB, and troponin alongside antioxidant enzymes and histopathological examination for both liver and heart tissue. The results showed both hepatic and cardiac damage in azithromycin and etoricoxib groups represented by increasing levels of heaptoc enzymes (ALT, AST, LDH, CK-MB, and troponin) with declining antioxidant enzymes and elevation of malondialdehyde and the appearance of hepatic and cardiac toxicities. Upon administration, ascorbic acid ameliorated all the mentioned biochemical parameters. In conclusion, ascorbic acid has great antioxidant capacities and hepatic and cardiac ameliorative effects and can alleviate drug interaction toxicity

Moringa concanensis-Mediated Synthesis and Characterizations of Ciprofloxacin Encapsulated into Ag/TiO2/Fe2O3/CS Nanocomposite: A Therapeutic Solution against Multidrug Resistant E. coli Strains of Livestock Infectious Diseases

Background: Multidrug resistant MDR bacterial strains are causing fatal infections, such as mastitis. Thus, there is a need for the development of new target-oriented antimicrobials. Nanomaterials have many advantages over traditional antibiotics, including improved stability, controlled antibiotic release, targeted administration, enhanced bioavailability, and the use of antibiotic-loaded nanomaterials, such as the one herein reported for the first time, appear to be a promising strategy to combat antibiotic-resistant bacteria. The use of rationally designed metallic nanocomposites, rather than the use of single metallic nanoparticles (NPs), should further minimize the bacterial resistance. Aim: Green synthesis of a multimetallic/ternary nanocomposite formed of silver (Ag), titanium dioxide (TiO2), and iron(III) oxide (Fe2O3), conjugated to chitosan (CS), in which the large spectrum fluoroquinolone antibiotic ciprofloxacin (CIP) has been encapsulated. Methods: The metallic nanoparticles (NPs) Ag NPs, TiO2 NPs, and Fe2O3 NPs were synthesized by reduction of Moringa concanensis leaf aqueous extract. The ternary junction was obtained by wet chemical impregnation technique. CIP was encapsulated into the ternary nanocomposite Ag/TiO2/Fe2O3, followed by chitosan (CS) conjugation using the ionic gelation method. The resulting CS-based nanoparticulate drug delivery system (NDDS), i.e., CIP-Ag/TiO2/Fe2O3/CS, was characterized in vitro by gold standard physical techniques such as X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FTIR) spectroscopy. Pharmacological analyses (i.e., LC, EE, ex-vivo drug release behavior) were also assessed. Further, biological studies were carried out both ex vivo (i.e., by disk diffusion method (DDM), fluorescence-activated single cell sorting (FACS), MTT assay) and in vivo (i.e., antibacterial activity in a rabbit model, colony-forming unit (CFU) on blood agar, histopathological analysis using H&E staining). Results: The encapsulation efficiency (EE) and the loading capacity (LC) of the NDDS were as high as 94% ± 1.26 and 57% ± 3.5, respectively. XRD analysis confirmed the crystalline nature of the prepared formulation. FESEM revealed nanorods with an average diameter of 50–70 ± 12 nm. FTIR confirmed the Fe-O-Ti-CS linkages as well as the successful encapsulation of CIP into the NDDS. The zeta potential (ZP) of the NDDS was determined as 85.26 ± 0.12 mV. The antimicrobial potential of the NDDS was elicited by prominent ZIs against MDR E. coli (33 ± 1.40 mm) at the low MIC of 0.112 μg/mL. Morphological alterations (e.g., deformed shape and structural damages) of MDR pathogens were clearly visible overtime by FESEM after treatment with the NDDS at MIC value, which led to the cytolysis ultimately. FACS analysis confirmed late apoptotic of the MDR E. coli (80.85%) after 6 h incubation of the NDDS at MIC (p < 0.05 compared to untreated MDR E. coli used as negative control). The highest drug release (89% ± 0.57) was observed after 8 h using PBS medium at pH 7.4. The viability of bovine mammary gland epithelial cells (BMGE) treated with the NDDS remained superior to 90%, indicating a negligible cytotoxicity (p < 0.05). In the rabbit model, in which infection was caused by injecting MDR E. coli intraperitoneally (IP), no colonies were detected after 72 h of treatment. Importantly, the histopathological analysis showed no changes in the vital rabbit organs in the treated group compared to the untreated group. Conclusions: Taken together, the newly prepared CIP-Ag/TiO2/Fe2O3/CS nanoformulation appears safe, biocompatible, and therapeutically active to fight MDR E. coli strains-causing mastitis

Antibacterial Activity of Dental Composite with Ciprofloxacin Loaded Silver Nanoparticles

Resin composites have been widely used in dental restoration. However, polymerization shrinkage and resultant bacterial microleakage are major limitations that may lead to secondary caries. To overcome this, a new type of antibacterial resin composite containing ciprofloxacin-loaded silver nanoparticles (CIP-AgNPs) were synthesized. The chemical reduction approach successfully produced CIP-AgNPs, as demonstrated by FTIR, zeta potential, scanning electron microscopy, and ultraviolet-visible (UV-vis) spectroscopy. CIP-AgNPs were added to resin composites and the antibacterial activity of the dental composite discs were realized against Enterococcus faecalis, Streptococcus mutans, and the Saliva microcosm. The biocompatibility of modified resin composites was assessed and mechanical testing of modified dental composites was also performed. The results indicated that the antibacterial activity and compressive strength of resin composites containing CIP-AgNPs were enhanced compared to the control group. They were also biocompatible when compared to resin composites containing AgNPs. In short, these results established strong ground application for CIP-AgNP-modified dental composite resins

Preparation of Memantine-Loaded Chitosan Nanocrystals: In Vitro and Ex Vivo Toxicity Analysis

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unmet medical need, and is the leading cause of age-related dementia affecting millions of people worldwide. This work aims at developing small, high-drug loading capacity (DL) and -entrapment efficiency (EE) memantine hydrochloride (MEM)/chitosan nanocrystals (CS-NCs) to treat moderate to severe dementia associated with AD. MEM-loaded chitosan nanocrystals (MEM/CS-NCs, further abbreviated as MEM-NCs) were prepared by the ionic gelation method. Different formulations were prepared by varying the concentrations of CS and sodium tripolyphosphate (STPP). The prepared MEM-NCs formulations (n = 8) were evaluated for their particle size (PS), polydispersibility index (PDI), zeta potential (ZP), DL, EE and characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, in vitro (i.e., release behavior, cytotoxicity) and ex vivo studies (i.e., histopathology) studies were carried out. The results show that the DL was over 92% and the EE was higher than 73%, while the particles were relatively small with nanometric PS (152.63 ± 12.95 to 310.23 ± 10.49 nm), uniform with acceptable PDI (0.336 ± 0.05 to 0.534 ± 0.02), and stable with positive ZP (23.8 ± 0.4 mV to 54.0 ± 0.5 mV). The optimal formulation (MEM-NC3) was selected mainly based on the PS (152.63 ± 12.95 nm), DL (98.44 ± 3.31%), and EE (78.7 ± 3.11%). Interestingly, it does not elicit any cytotoxic and tissue damage when examining at goat nasal mucosa. The selected formulation was subjected to surface morphological studies such as transmission electron microscopy (TEM), which revealed that the NCs were spherical in shape and small (100 nm). Interestingly, the selected formulation was able to sustain the drug release for up to 24 h with an initial burst release (86.51 %). We conclude that the prepared MEM-NCs represent a promising drug formulation for further in vivo studies (in animal models and in a clinical setting) to prevent and treat AD

Efficacy of Prednisolone/Zn Metal Complex and Artemisinin Either Alone or in Combination on Lung Functions after Excessive Exposure to Electronic Cigarettes Aerosol with Assessment of Antibacterial Activity

The use of transition metal complexes as therapeutic compounds has become more and more pronounced. These complexes offer a great diversity of uses in their medicinal applications. Electronic cigarettes (ECs) are an electronic nicotine delivery system that contain aerosol (ECR). The ligation behavior of prednisolone, which is a synthetic steroid that is used to treat allergic diseases and asthma arthritis, and its Zn (II) metal complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FT-IR) spectra, electronic spectra, XRD, scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and transmission electron microscopy (TEM). The FT-IR spectral data revealed that PRD acts as a mono-dentate ligand via oxygen atoms of the carbonyl group. Electronic and FT-IR data revealed that the PRD/Zn (II) metal complexes have square planner geometry. Artemisinin (ART) is the active main constituent of Artemisia annua extract, and it has been demonstrated to exert an excellent antimalarial effect. The experiment was performed on 40 male mice that were divided into the following 7 groups: Control, EC group, PRD/Zn, ART, EC plus PRD/Zn, EC plus ART, and PRD plus combination of PRD/Zn and ART. Serum CRP, IL-6, and antioxidants biomarkers were determined. Pulmonary tissue histology was evaluated. When in combination with Zn administration, PRD showed potent protective effects against pulmonary biochemical alterations induced by ECR and suppressed severe oxidative stress and pulmonary structure alterations. Additionally, PRD/Zn combined with ART prevented any stress on the pulmonary tissues via antioxidant regulation, reducing inflammatory markers CRP and Il-6 and improving antioxidant enzymatic levels more than either PRD or ART alone. Therefore, PRD/Zn combined with ART produced a synergistic effect against any sort of oxidative stress and also improved the histological structure of the lung tissues. These findings are of great importance for saving pulmonary function, especially during pandemic diseases, such as during the COVID-19 pandemic

Punicalagin Protects against the Development of Methotrexate-Induced Hepatotoxicity in Mice via Activating Nrf2 Signaling and Decreasing Oxidative Stress, Inflammation, and Cell Death

Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a variety of health-promoting attributes, on MTX-induced hepatotoxicity in mice. PU (25 and 50 mg/kg/day) was given orally to the mice for 10 days, while a single dose of MTX (20 mg/kg) was injected intraperitoneally (i.p.) at day 7. The MTX-induced liver damage was demonstrated by remarkably higher transaminases (ALT and AST), ALP, and LDH, as well as significant histological alterations in hepatic tissues. MTX-injected mice also demonstrated increases in hepatic oxidative stress markers, including malondialdehyde (MDA) and nitric oxide (NO), with a concordant drop in glutathione (GSH) content and superoxide dismutase (SOD) and catalase (CAT) activities. PU significantly attenuated the MTX-induced serum transaminases, ALP and LDH elevations, and hepatic oxidative stress measures and boosted antioxidant defenses in the liver. Moreover, the liver of MTX-treated mice showed increases in NF-κB p65 expression, pro-inflammatory cytokine (IL-6 and TNF-α) levels, and pro-apoptotic protein (caspase-3 and Bax) expression, whereas Bcl-2 and Nrf2 expressions were reduced, which were all attenuated by PU treatment. Collectively, PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice. Thus, these findings suggest that PU may have great therapeutic potential for the prevention of MTX-induced hepatotoxicity, pending further exploration in upcoming studies