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Background: Colorectal cancer (CRC), now the second most prevalent malignant tumor worldwide, is more prevalent in young adults. In recent decades, there has been progress in creating anti-colorectal cancer medications, including cytotoxic compounds. Objectives: Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of novel formulations in preventing colorectal cancer. Methods: During this study, we assessed a new kind of niosome called cyclo-Gly-L-DOPA (CG-Nio-CGLD) made from chitosan glutamate. We evaluated the anti-colorectal cancer properties of CG-Nio-CGLD utilizing CCK-8, invasion assay, MTT assay, flow cytometry, and cell cycle analysis. The transcription of genes associated with apoptosis was analyzed using quantitative real-time PCR. At the same time, the cytotoxicity of nanomaterials on both cancer and normal cell lines was assessed using MTT assays. Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of newly developed formulations in preventing colorectal cancer. Results: The Nio-CGLD and CG-Nio-CGLD were spherical mean diameters of 169.12 ± 1.87 and 179.26 ± 2.17 nm, respectively. Entrapment efficiency (EE%) measurements of the Nio-CGLD and CG-Nio-CGLD were 63.12 ± 0.51 and 76.43 ± 0.34%, respectively. In the CG-Nio-CGLD group, the percentages of early, late, necrotic, and viable CL40 cells were 341.93%, 23.27%, 9.32%, and 25.48%. The transcription of the genes PP53, cas3, and cas8 was noticeably higher in the treatment group compared to the control group (P > 0.001). Additionally, the treatment group had lower BCL2 and survivin gene expression levels than the control group (P < 0.01). Additionally, CG-Nio-CGLD formulations demonstrated a biocompatible nanoscale delivery mechanism and displayed little cytotoxicity toward the CCD 841 CoN reference cell line. Conclusion: These findings indicate that chitosan-based noisome encapsulation may enhance the effectiveness of CG-Nio-CGLD formulations in fighting cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), currently the second most widespread cancer globally, exhibits a higher incidence in young individuals. Advancements have been made in developing anti-colorectal cancer drugs, including cytotoxic chemicals, in the past few decades. There is a need for new and innovative medications to overcome the current challenges in cancer treatment. Recent research examined the efficacy of innovative formulations in the prevention of colorectal cancer. In this study, we evaluated the efficacy of a niosome formulation loaded with Enciprazine hydrochloride (Nio-USAN). We assessed the anti-colorectal cancer characteristics of Nio-USAN by employing several techniques including CCK-8, invasion test, MTT test, flow cytometry, and cell cycle assessment. Quantitative real-time PCR was utilized to assess the transcription of genes linked to apoptosis. The F1-Nio-USAN and F2-Nio-USAN have average sizes of 200 and 500 nm, respectively. The entrapment effectiveness (EE%) of the F1-Nio-USAN and F2-Nio-USAN was measured to be 85.32 ± 0.27 % and 87.12 ± 0.35 %, respectively. The F1-Nio-USAN group exhibited the following percentages of HT-29 cell states: 43 % early apoptosis, 21 % late apoptosis, 7 % necrotic, and 29 % viable. The levels of transcription for cas8, Bid, BAX, cas9, and cas3 were significantly elevated in the treatment groups as compared to the PBS control group (P

In the course of this investigation, a brand-new noisome-encapsulated 2,5-diketopiperazine (BHPPD) was developed, synthesized, and assessed. Utilizing CCK-8, invasion screens, MTT test, flow cytometry, and cell cycle analysis, we evaluated the anti-breast cancer properties of niosome-encapsulated BHPPD. Apoptosis-related gene expression and cytotoxicity was measured using quantitative real-time PCR and MTT assays. This meta-analysis showed a significant drug-binding affinity for intestinal protease. The spherical mean diameters of the free BHPPD, the F1 niosomal-BHPPD, and the F2 niosomal-BHPPD were all determined to be108.91 ± 4.2, 129.13 ± 7.2 nm, and 149.43 ± 3.2 nm, respectively. Also, it was found that the entrapment efficiency (EE%) of the F1 formulations of BHPPD that was niosome-encapsulated was 81.01 0.09% and that it was 70.22 0.13%, respectively. Early, late, necrotic, and viable MCF-7 cells were present in the cells with F1 formulation in proportions of 38.24%, 34.34%, 4.02%, and 23.40%, respectively. Compared to the control group, the treatment group's expression of the genes P57, Prkca, MDM4, Map2k6, and FADD was considerably greater (P < 0.001). Furthermore, compared to control cells, cells in the treatment group expressed less BCL2 and survival genes (P < 0.001). Moreover, formulations of BHPPD encapsulated in niosomes showed a biocompatible nanoscale delivery method and exhibited little cytotoxicity against the HEK-293 standard cell line. According to the findings, formulations of BHPPD with niosome-encapsulation might be viable for boosting anticancer activity. [ABSTRACT FROM AUTHOR]

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The main risk factors for CRC are family history of colon or rectal cancer, familial polyposis syndrome or hereditary nonpolyposis, and chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease). Recent studies show that the gastrointestinal microbiota play a significant role in colorectal carcinogenesis. In this review we present the microorganisms, whose influence on the development of CRC has been proven: Bacteroides fragilis , Clostridioides and Clostridium spp., Enterococcus faecalis, Escherichia coli , Fusobacterium nucleatum , Helicobacter pylori , Peptostreptococcus anaerobius , Streptococcus bovis group, and sulfate-reducing bacteria. Moreover, the carcinogenic mechanisms of action mediated by the above bacteria are laid out. [ABSTRACT FROM AUTHOR]

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a–g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a–g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes. [ABSTRACT FROM AUTHOR]

The study aimed to evaluation of immunohistochemical the Euphorbia Inarticulata Extract on Liver and Kidney Tissues in Hepatocellular Carcinoma Rats. Rats were grouped into six each of six as (1) control received one dose (1 ml 0.9% NaCl/ip) and two weeksafter 2 weeks later receivedgot olive oil (1 ml/sc) (once/week) for 16 weeks, in line with 1% DMSO/p.o. for 18 weeks. (2) 250mg Extract and (3) 400mg Extract groups were received as in the control group and received daily extract (250 mg/kg/P.o.) and (400 mg/kg/P.o.) in DMSO for 18 weeks, respectively. (4) DENA/CCl4 group received one dose of DENA (200 mg/kg/ip) in saline and two after 2 weeks weeks later received (3 ml/kg CCl4/sc) in olive oil (once/week) for 16 sixteen weeks, in line with 1% DMSO/p.o. for 18 weeks. DENA/CCl4 rat model group showed an induced strong positive reaction to Bax immunostaining in the cytoplasm of liver cells and glomeruli and renal tubules. The study suggests that the present model showed hepatic and renal apoptosis that is related to impairing their function and oral administration of E. inarticulata methanol extract, especially in higher dose (400 mg). [ABSTRACT FROM AUTHOR]

In ethnomedicine, plant parts and compounds are used traditionally to treat different diseases. Neem (Azadirachta indica A. Juss) is the most versatile and useful medicinal plant ever found. Its every part is rich in bioactive compounds, which have traditionally been used to treat different ailments including infectious diseases. Bioactive compounds such as nimbolide, azarirachtin, and gedunin of neem are reported to have a tremendous ability to regulate numerous biological processes in vitro and in vivo. The present review article aims to explore the importance of neem extracts and bioactive compounds in the regulation of different biological pathways. We have reviewed research articles up to March 2020 on the role of neem in antioxidant, anti-inflammatory, antiangiogenic, immunomodulatory, and apoptotic activities. Studies on the concerned fields demonstrate that the bioactive compounds and extracts of neem have a regulatory effect on several biological mechanisms. It has been unveiled that extensive research is carried out on limonoids such as nimbolide and azarirachtin. It is evidenced by different studies that neem extracts are the potential to scavenge free radicals and reduce ROS-mediated damage to cells. Neem can be used to normalize lipid peroxidation and minimize ROS-mediated cell death. Besides, neem extracts can significantly reduce the release of proinflammatory cytokines and elevate the count of CD4 + and CD8 + T-cells. This review indicates the pivotal roles of A. indica in the regulation of different biological pathways. However, future investigations on other bioactive compounds of neem may reveal different therapeutic potentials. [ABSTRACT FROM AUTHOR]

Resume. In vitro experiments performed on human endothelial ceLL culture (HUVEC), nerve growth factor (NGF) angiotropic effects were studied. An intact ceLL culture it was shown that NGF exhibited angiogenic properties and stimulated the initial stage of angiogenesis -tubuLogenesis at a 10-9 M concentration, as evidenced by a statisticaLLy significant increase in the average totaL Length of microtubuLes compared with the control. Under conditions of oxidative stress, NGF neutraLizes the damaging effect of hydrogen peroxide in a high concentration (200 |±M) and not onLy shows an angioprotective effect, but aLso prevents the deveLopment of morphoLogicaL changes in nucLear chromatin, characteristic for apoptosis. Under these conditions NGF (10-9 M) reduces statisticaLLy significant by comparison with the controL the number of ceLLs with condensed and fragmented chromatin: 44 ± 9 and 78 ± 9 (р ≤ 0,05), respectiveLy. The obtained resuLts confirm the data about the NGF angiogenic activity and indicate that under conditions of the vesseLs endotheLiaL ceLLs damage by oxidative stress, it exhibits pronounced angioprotective and anti-apoptotic activity.

Granulocyte colony-stimulating factor (G-CSF) is used for heartfailure therapy and promotes myocardial regeneration byinducing mobilization of bone marrow stem cells to the injuredheart after myocardial infarction; however, this treatment hasone weakness in that its biological effect is transient. In ourprevious report, we generated 5 mutants harboring N-linkedglycosylation to improve its antiapoptotic activities. Amongthem, one mutant (Phe140Asn) had higher cell viability thanwild-type hG-CSF in rat cardiomyocytes, even after treatmentwith an apoptotic agent (H2O2). Cells treated with this mutantsignificantly upregulated the antiapoptotic proteins, andexperienced reductions in caspase 3 activity and PARPcleavage. Moreover, the total number of apoptotic cells wasdramatically lower in cultures treated with mutant hG-CSF.Taken together, these results suggest that the addition of anN-linked glycosylation was successful in improving theantiapoptotic activity of hG-CSF, and that this mutated productwill be a feasible therapy for patients who have experiencedheart failure.

Nowadays cancer is the second main cause of death in the world. The most known bacterial carcinogen is Helicobacter pylori. Pathogens that can have an impact on cancer development in the gastrointestinal tract are also found in the oral cavity. Some specific species have been identified that correlate strongly with oral cancer, such as Streptococcus sp., Peptostreptococcus sp., Prevotella sp., Fusobacterium sp., Porphyromonas gingivalis, and Capnocytophaga gingivalis. Many works have also shown that the oral periopathogens Fusobacterium nucleatum and Porphyromonas gingivalis play an important role in the development of colorectal and pancreatic cancer. Three mechanisms of action have been suggested in regard to the role of oral microbiota in the pathogenesis of cancer. The first is bacterial stimulation of chronic inflammation. Inflammatory mediators produced in this process cause or facilitate cell proliferation, mutagenesis, oncogene activation, and angiogenesis. The second mechanism attributed to bacteria that may influence the pathogenesis of cancers by affecting cell proliferation is the activation of NF-κB and inhibition of cellular apoptosis. In the third mechanism, bacteria produce some substances that act in a carcinogenic manner. This review presents potentially oncogenic oral bacteria and possible mechanisms of their action on the carcinogenesis of human cells.

Summary: It has been reported that all major chlamydial species can inhibit host cell apoptosis and the Chlamydia trachomatis antiapoptotic activity is correlated with inhibition of activation of the proapoptotic multidomain Bcl-2 proteins Bax and Bak and degradation of BH3-only domain Bcl-2 proteins such as Puma. The current study is to test whether the more invasive species can also suppress host apoptosis through inhibition of Bax and Bak activation. We compared the effects of the three invasive chlamydial species C. muridarum, C. caviae, C. psittaci with that of C. trachomatis on host cell Bax and Bak activation. We found that these chlamydial species not only failed to activate Bax and Bak but also significantly inhibited Bax and Bak activation, mitochondrial cytochrome c release and caspase 3 activation induced by staurosporine. These results have demonstrated that inhibition of host cell apoptosis pathways mediated by Bax and Bak activation is a common property of the major chlamydial species. [Copyright &y& Elsevier]

• Alginate lyase is covalently immobilized on Fe 3 O 4 nanoparticles. • Stability and moderate reusability of immobilized alginate lyase are enhanced. • Immobilized alginate lyase efficiently produces alginate oligosaccharides. • Alginate oligosaccharides show potent antioxidant effect in H 2 O 2 -stressed HUVECs. • Alginate oligosaccharides inhibit apoptosis in H 2 O 2 -stressed HUVECs. Alginate is a natural polysaccharide resource abundant in brown algae and it can be cleaved into alginate oligosaccharides by alginate lyase. Alginate lyases and the bioactive alginate oligosaccharides have been applied in diverse fields such as pharmaceutical therapy and nutraceutical supplementation. Immobilized enzymes greatly facilitate their industrial application owing to their reusability, stability, and tunability. In this study, magnetic Fe 3 O 4 nanoparticles were synthesized and used to immobilize an exolytic alginate lyase AlgL17 that was characterized previously. The immobilized AlgL17 demonstrated enhanced thermal and pH tolerance, extended storage stability, and moderate reusability. The mass spectrum indicated the specific activity of the immobilized AlgL17 to release alginate oligosaccharides (AOS) from alginate polysaccharide. The produced AOS exhibited their antioxidant and antiapoptotic activities in H 2 O 2 -stressed human umbilical vein endothelial cells by upregulation of reactive oxygen species scavenging activities and attenuation of the caspase-mediated apoptosis pathway. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most lethal diseases. In pancreatic cancer development and progression, genetic (gene mutations and activation of oncogenes) and environmental factors (smoking, alcohol consumption, type 2 diabetes mellitus, obesity) play an essential role. Recently, molecular studies revealed that dysbiosis of microbiota also has influence on cancer development. Research indicates that bacteria and viruses can lead to chronic inflammation, antiapoptotic changes, cell survival, and cell invasion. This review presents bacteria and viruses oncogenic for the pancreas. Possible mechanisms of carcinogenic action are also described., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nowadays cancer is the second main cause of death in the world. The most known bacterial carcinogen is Helicobacter pylori. Pathogens that can have an impact on cancer development in the gastrointestinal tract are also found in the oral cavity. Some specific species have been identified that correlate strongly with oral cancer, such as Streptococcus sp., Peptostreptococcus sp., Prevotella sp., Fusobacterium sp., Porphyromonas gingivalis, and Capnocytophaga gingivalis. Many works have also shown that the oral periopathogens Fusobacterium nucleatum and Porphyromonas gingivalis play an important role in the development of colorectal and pancreatic cancer. Three mechanisms of action have been suggested in regard to the role of oral microbiota in the pathogenesis of cancer. The first is bacterial stimulation of chronic inflammation. Inflammatory mediators produced in this process cause or facilitate cell proliferation, mutagenesis, oncogene activation, and angiogenesis. The second mechanism attributed to bacteria that may influence the pathogenesis of cancers by affecting cell proliferation is the activation of NF-κB and inhibition of cellular apoptosis. In the third mechanism, bacteria produce some substances that act in a carcinogenic manner. This review presents potentially oncogenic oral bacteria and possible mechanisms of their action on the carcinogenesis of human cells. [ABSTRACT FROM AUTHOR]