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The aim of the current study is the loading of ceftazidime into the first generation of poly(propyleneimine) dendrimer (PPI-G1) to produce an effective drug delivery system against Pseudomonas aeruginosa. The mechanism of ceftazidime-PPI-G1 dendrimer complex formation is based on interaction between amine groups of dendrimers and carboxylic groups of ceftazidime. PPI-G1 was dissolved in dry tetrahydrofuran (THF), and ceftazidime was added to the solution to prepare the nanodrug. The series of tests, including size, zeta potential, drug release, stability and kinetic evaluation, as well as Scanning Electron Microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy, were performed for characterization of the ceftazidime-loaded PPI-G1. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the nanodrug were determined, with respect to Pseudomonas aeruginosa as the test microorganism. Ceftazidime-PPI-G1 complex was synthesized with the size of 156.6 nm and -10:2 mV zeta potential. The value of loaded ceftazidime was determined to be about 38.46 mol%. A gradual drug release was observed within three days; up to 92% of the loaded ceftazidime. The macrodilution assay demonstrated that PPI-G1 enhances the antibacterial activity of ceftazidime. A new drug delivery system was improved against P. aeruginosa with sustained release and enhanced antibacterial activity. [ABSTRACT FROM AUTHOR]

It is well known that all starlike trees, i.e. trees with exactly one vertex of degree at least three, are determined by their Laplacian spectrum. A double starlike tree is a tree with exactly two vertices of degree at least three. In 2009, the following question was posed: Are all the double starlike trees determined by their Laplacian spectra? In this direction, it was proved that one special double starlike treeis determined by its Laplacian spectrum, whereis a tree obtained by joiningpendant vertices to an end vertex of a path of orderand then joiningpendant vertices to another end of the path. Also, the banana treeis a tree obtained by joining a vertex to one arbitrary pendant vertex of each copy of-copies of. Recently, it is shown thatis determined by its Laplacian spectrum as well. In this paper, we study the Laplacian spectral characterization ofand. We show thatandare determined by their Laplacian spectra, for. [ABSTRACT FROM PUBLISHER]

Four-component reaction of cyclobutanone, dibenzylamine and (Nisocyanimino) triphenylphosphorane in the presence of aromatic carboxylic acids proceed smoothly at room temperature and under neutral conditions to afford N,N-dibenzyl-N-{1-[5-(3-aryl)-1,3,4-oxadiazol-2-yl]cyclobutyl}amine derivatives in high yields.

Opinion Statement: Melanoma is defined as the most aggressive and deadly form of skin cancer. The treatment of melanoma depends on the disease stage, tumor location, and extent of its spread from its point of origin. Melanoma treatment has made significant advances, notably in the context of targeted and immunotherapies. Surgical resection is the main therapeutic option for earlystage melanoma, and it provides favourable outcomes. With disease metastasis, systemic treatments such as immunotherapy and targeted therapy become increasingly important. The identification of mutations that lead to melanoma has influenced treatment strategies. Targeted therapies focusing on these mutations offer improved response rates and fewer toxicities than conventional chemotherapy. Furthermore, developing immunotherapies, including checkpoint inhibitors and tumor-infiltrating lymphocyte (TIL) therapies, has demonstrated encouraging outcomes in effectively combating cancer cells. These therapeutic agents demonstrate superior effectiveness and a more tolerable side-effect profile, improving the quality of life for patients receiving treatment. The future of melanoma treatment may involve a multimodal approach consisting of a combination of surgery, targeted therapy, and immunotherapy adapted to each patient's profile. This approach may improve survival rates and health outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Proper and functional immune response requires a complex interaction between innate and adaptive immune cells, which dendritic cells (DCs) are the primary actors in this coordination as professional antigen-presenting cells. DCs are armed with numerous pattern recognition receptors (PRRs) such as nucleotide-binding and oligomerization domain-like receptors (NLRs) like NLRP3, which influence the development of their activation state upon sensation of ligands. NLRP3 is a crucial component of the immune system for protection against tumors and infectious agents, because its activation leads to the assembly of inflammasomes that cause the formation of active caspase-1 and stimulate the maturation and release of proinflammatory cytokines. But, when NLRP3 becomes overactivated, it plays a pathogenic role in the progression of several autoimmune disorders. So, NLRP3 activation is strictly regulated by diverse signaling pathways that are mentioned in detail in this review. Furthermore, the role of NLRP3 in all of the diverse immune cells' subsets is briefly mentioned in this study because NLRP3 plays a pivotal role in modulating other immune cells which are accompanied by DCs' responses and subsequently influence differentiation of T cells to diverse T helper subsets and even impact on cytotoxic CD8 + T cells' responses. This review sheds light on the functional and therapeutic role of NLRP3 in DCs and its contribution to the occurrence and progression of autoimmune disorders, prevention of diverse tumors' development, and recognition and annihilation of various infectious agents. Furthermore, we highlight NLRP3 targeting potential for improving DC-based immunotherapeutic approaches, to be used for the benefit of patients suffering from these disorders., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antigen recognition and presentation are highlighted as the first steps in developing specialized antigen responses. Dendritic cells (DCs) are outstanding professional antigen-presenting cells (APCs) responsible for priming cellular immunity in pathological states, including cancer. However, the diminished or repressed function of DCs is thought to be a substantial mechanism through which tumors escape from the immune system. In this regard, DCs obtained from breast cancer (BC) patients represent a notably weakened potency to encourage specific T-cell responses. Additionally, impaired DC-T-cell cross-talk in BC facilitates the immune evade of cancer cells and is connected with tumor advancement, immune tolerance, and adverse prognosis for patients. In this review we aim to highlight the available knowledge on DC-T-cell interactions in BC aggressiveness and show its therapeutic potential in BC treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Herein, a robust Pd(II)-based polyfunctional magnetic amphiphilic artificial metalloenzyme was prepared by anchoring a Pd(2,2'-dipyridylamine)Cl 2 bearing hydrophilic monomethyl ether poly(ethylene glycol) (mPEG) chains on the surface of amino-functionalized silica-coated magnetic nanoparticles. The 2,2'-dipyridylamine (dpa) has shown excellent complexation properties for Pd(II) and it could be easily anchored onto functionalized magnetic support by the bridging nitrogen atom. Moreover, the bridging nitrogen atom at the proximity of Pd(II) catalytic center could play an important role in dynamic suppramolecular interactions with substrates. The leaching, air and moisture resistant [Pd(dpa)Cl 2 ] complex endow the dynamic and robust structure to the designed artificial enzyme. Moreover, the water dispersibility of designed artificial metalloenzyme raised from mPEG chains and the magnetic nanoparticles core which could function as protein mimics endow it other necessary characters of artificial enzymes. The prepared artificial metalloenzyme displayed remarkable activity in Suzuki-Miyaura cross-coupling reaction employing low-palladium loading under mild conditions, with the exceptionally high turnover frequency, clean reaction profile, easy work-up procedure, good to excellent products yields and short reaction times. The designed air- and moisture-stable artificial metalloenzyme could recycle more than fifteen times with easy separation procedure in aqueous solution under aerobic conditions without any noticeable loss in activity.

Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330. Methods: Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. The MMP9, CXCR4, and VEGFR proteins were measured by western blotting. Results: The analysis of BACH1, miR-330-3p, and miR-330-5p expressions according to the COAD and READ projects showed that BACH1 was overexpressed, but miR-330-3p and miR330-5p were reduced in CRC tumors compared to normal controls. The miR-330 induction prevented proliferation of CRC cell by targeting BACH1 mRNA, which represses MMP9, C-X-C chemokine receptor type 4 (CXCR4), and vascular endothelial growth factor receptor (VEGFR) proteins expressions. Conclusion: Our results suggested that BACH1 is a potential target for miR-330 in CRC cells. The miR-330 induction inhibits CRC cells proliferation by suppressing BACH1 expression in posttranscriptional level. It was suggested that targeting of BACH1 via miRNA such as miR-330 could be a valid strategy in the field of CRC targeted therapy via modulating the oncogenic signaling pathway., (© 2020 The Authors.)

During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators high mobility group A2 (HMGA2) and BTB and CNC homology 1 (Bach-1) are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach-1 promote cancer development has been limited. We found that HMGA2 and Bach-1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach-1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach-1 knockdown additively decrease cell proliferation, migration, epithelial-to-mesenchymal transition, and colony formation, while promoting apoptotic cell death via upregulation of caspase-3 and caspase-9. First the first time, we show that HMGA2 and Bach-1 overexpression in tumors correlate positively and that the proteins cooperatively suppress a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity, and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer., (© 2019 Wiley Periodicals, Inc.)

Phosphatidylinositol 3-kinases (PI3Ks) are crucial coordinators of intracellular signalling in response to the extracellular stimulators. Hyperactivation of PI3K signalling cascades is one among the most ordinary events in human cancers. Focusing on the PI3K pathway remains both a chance and a challenge for cancer therapy. The high recurrence of phosphoinositide 3-kinase (PI3K) pathway adjustments in cancer has led to a surge in the progression of PI3K inhibitors. Recent developments incorporate a re-assessment of the oncogenic mechanisms behind PI3K pathway modifications. Receptor tyrosine kinases upstream of PI3K, the p110a catalytic fractional unit of PI3K, the downstream kinase, AKT, and therefore the negative regulator, PTEN, are all often altered in cancer. In this review, we consider about the phosphoinositide 3-kinases family and mechanisms of PI3K-Akt stimulation in cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. BACH1, a basic leucine zipper transcription factor, has been shown to transcriptionally regulate expression of a range of genes that are associated with breast cancer metastasis. However, the exact role and the underlying molecular mechanism of BACH1 in prostate cancer remain unclear. This study aims to explore the expression of BACH1 in prostate cancer tissues and the effect of BACH1 suppression on prostate cancer cell behavior., Materials and Methods: In this study, we used quantitative real-time PCR (qRT-PCR) to measure BACH1 expression in prostate adenocarcinoma tissues and two metastasis-derived prostate cancer cell lines, DU145 and LNCaP. We also used immunohistochemical (IHC) staining to measure BACH1 protein expression in prostate adenocarcinoma and matched normal tissue samples. In the following BACH1 expression was silenced in DU145 cells using siRNA as well. Knockdown was confirmed by qRT-PCR and Western blotting. The cytotoxic effects of BACH1-siRNA on DU145 cells were determined using an MTT assay. The migration and invasive capacity of DU145 cells were examined by scratch wound healing assay and matrigel invasion assay, respectively. We also used qRT-PCR to study the effect of BACH1 silencing on the expression levels of metastasis-related genes., Results: We find that the expression of BACH1 mRNA and protein in prostate cancer tissues is significantly higher than in matched normal prostate tissues (p < .05). In addition, DU145 and LNCaP cells exhibited 4.25-fold and 3.45-fold higher levels of BACH1 compared to HFF cell line. BACH1-siRNA significantly reduced both mRNA and protein expression levels in DU145 cells. More importantly, we show that BACH1 promotes key features of metastasis, as BACH1-siRNA treatment significantly reduced cell invasion and migration by changing the expression levels of a number of metastasis-related genes in vitro., Conclusions: BACH1 is overexpressed in prostate cancer. Because this promotes invasion and migration, it may facilitate metastasis of prostate cancer. Thus, BACH1 is a potential therapeutic target for metastatic prostate cancer. BACH1 silencing therapy can be considered as a novel and effective adjuvant in prostate cancer targeted therapies.

Background: Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer., Methods: Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression., Results: The significant silencing of snail-1 reached 60pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate., Conclusion: These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Despite using lots of progression in hypersensitivity, it is not yet a cure. Current treatment for allergy focuses on two approaches, including treats only the symptoms of allergy by utilizing drugs and the other is desensitization therapy (immunotherapy), which involves administration of specific allergens. The main obstacle to hypersensitivity permanent treatment is the IgE producing subclass of B-lymphocytes which is the source of IgE- producing in hypersensitive patients. Removal of these lymphocytes causes noticeable reduction in the levels of IgE and allergic responses significantly. In this paper, we proposed a novel complementary approach, which we have called the "nano-liposomes-based target toxicity machine (NBTTM)", which controls hypersensitivity by removing the IgE producing B-lymphocytes. In this regard, our proposed nano-liposomes (pollen allergens/Aptamer/SCFV/MIP loaded lipid bilayer enclosing toxin interior) will be able to bind to any IgE markers in the lymphatic circulation. The nano-liposomes will bind to the IgE + atopic B cells and cause cell death by internalizing into B cells.

Background: Despite therapeutics based on siRNA have an immense potential for the treatment of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery of this agent to the target site is one of the most controversial challenges. The helpful assistance by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based siRNA therapeutics is expected to become available in the near future., Methods: The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The studies were identified from seven databases (Scopus, Web of Science, Academic Search Premiere, CINAHL, Medline Ovid, Eric and Cochrane Library). Studies was selected based on titles, abstracts and full texts., Results: One hundred twenty nine papers were included in the review. These papers defined hurdles in RNAi delivery and also strategies to overcome these hurdles. This review discussed the existing hurdles for systemic administration of siRNA as therapeutic agents and highlights the various strategies to overcome these hurdles, including lipid-based nanoparticles and polymeric nanoparticles, and we also briefly reviewed chemical modification., Conclusion: Delivery of siRNA to the target site is the biggest challenge for its application in the clinic. The findings of this review confirmed by encapsulation siRNA in the nanoparticles can overcome these challenges. The rapid progress in nanotechnology has enabled the development of effective nanoparticles as the carrier for siRNA delivery. However, our data about siRNA-based therapeutics and also nanomedicine are still limited. More clinical data needs to be completely understood in the benefits and drawbacks of siRNA-based therapeutics. Prospective studies must pay attention to the in vivo safety profiles of the different delivery systems, including uninvited immune system stimulation and cytotoxicity. In essence, the development of nontoxic, biocompatible, and biodegradable delivery systems for medical application of RNAi-based therapeutics is needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Metastasis to distant organs is a hallmark of many tumor cells. BACH1 (BTB and CNC homology 1) is a transcriptional factor which promotes the migration and invasion of breast cancer cells. BACH1 expression and its target genes are intimately associated with the metastasis possibility of clinical samples, and BACH1 reduction leads to meaningful depletion in metastasis. The evaluation of BACH1 role in colon cancer remains elusive. This study seeks to further investigate the role of BACH1 in colon cancer cells., Methods: Quantitative RT-PCR (qRT-PCR) was used to detect BACH1 expression and other related metastatic genes following siRNA knockdown in colon cancer HT-29 cells. And the protein level assessed by Western blot. MTT assay was to measure the changed cell viability after BACH1 siRNA transfection. Scratch-wound motility assays measured capacity of tumor cell migration of HT-29 cells after BACH1 silencing., Results: The inhibitory effect of BACH1 was performed by siRNA knockdown using highly metastatic HT-29 colon cell lines. Quantitative RT-PCR and Western blot analysis revealed that the expression levels of BACH1 mRNA and protein in HT29 cells were significantly suppressed after transfection. Conversely, the BACH1 expression increased migration. Also the CXCR4 and MMP1 expression levels decreased following BACH1 knockdown in HT-29 cells., Conclusion: Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

BACH1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1) is a transcriptional factor and a member of cap 'n' collar (CNC) and basic region leucine zipper factor family. In contrast to other bZIP family members, BACH1 appeared as a comparatively specific transcription factor. It acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative. In regard to studies lately, although, BACH1 has been related to the regulation of oxidative stress and heme oxidation, it has never been linked to invasion and metastasis. Recent studies have showed that BACH1 is involved in bone metastasis of breast cancer by up-regulating vital metastatic genes like CXCR4 and MMP1. This newly discovered aspect of BACH1 gene provides new insight into cancer progression study and stands on its master regulator role in metastasis process, raising the possibility of considering it as a potential target for cancer therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: One of the major causes of cancer death internationally and the third most prevalent cancer in the world has been diagnosed with colorectal cancer. Although current routine treatments of cancer have been successful in some extent, mortality caused by adverse effects of these strategies is still raising. Medicinal plants are potential sources of anticancer compounds and can be exploited as a powerful complementary tool. This study aimed to investigate the cytotoxic effects of nettle extract on mouse colorectal cancer cells, HCT., Materials and Methods: In the present study, to evaluate the cytotoxicity of nettle extract, MTT assay and trypan blue were performed. Subsequently, DNA fragmentation and TUNEL test was carried out for determination of apoptosis. Real-time PCR test was used to quantify the expression of Caspase-3, Caspase-9, and Bcl-2 which is involved in apoptosis regulation. Finally, cell cycle analysis was conducted by using flow cytometry., Results: The results of MTT assay showed that the dichloromethane extract of U. dioica extract significantly destroyed cancer cells HCT-116. DNA fragmentation and TUNEL test demonstrated that Utrica extract elicited apoptotic response in the cancer cells. The messenger RNA (mRNA) expression levels of Caspase-3 and Caspase-9 markedly increased, while the Bcl-2 gene was conversely downregulated. Findings of flow cytometry confirmed that cell cycle arrest has occurred at the G2 phase., Conclusion: Taken together, our experiment showed that subjecting HCT-116 cells to dichloromethane extract of nettle (U. dioica), increases turnover of these cells. Thus, it may be a useful agent in the treatment of colorectal cancer.

The 1:1 imine intermediate generated by the addition of benzyl amine to cyclobutanone is trapped by (N-isocyanimino)triphenylphosphorane in the presence of an aromatic carboxylic acid leads to the formation of the corresponding iminophosphorane intermediate. Disubstituted 1,3,4-oxadiazole derivatives are formed via intramolecular aza-Wittig reaction of the iminophosphorane intermediate. The reactions were completed in neutral conditions at room temperature. The disubstituted 1,3,4-oxadiazole derivatives, were produced in excellent yields.