Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting

Helicobacter pylori (H. pylori) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori, underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections

A Fusion Model Based on Dynamic Web Browsing Behavior Analysis for IoT Insider Threat Detection

With the wide application of Internet of things (IoT) devices in enterprises, the traditional boundary defense mechanisms are difficult to satisfy the demands of the insider threats detection. IoT insider threat detection can be more challenging, since internal employees are born with the ability to escape the deployed information security mechanism, such as firewalls and endpoint protection. In order to detect internal attacks more accurately, we can analyze users’ web browsing behaviors to identify abnormal users. The existing web browsing behavior anomaly detection methods ignore the dynamic change of the web browsing behavior of the target user and the behavior consistency of the target user in its peer group, which results in a complex modeling process, low system efficiency and low detection accuracy. Therefore, the paper respectively proposes the individual user behavior model and the peer-group behavior model to characterize the abnormal dynamic change of user browsing behavior and compare the mutual behavioral inconsistency among one peer-group. Furthermore, the fusion model is presented for insider threat detection which simultaneously considers individual behavioral abnormal dynamic changes and mutual behavioral dynamic inconsistency from peers. The experimental results show that the proposed fusion model can accurately detect insider threat based on the abnormal user web browsing behaviors in the enterprise networks

LSD1 as a Biomarker and the Outcome of Its Inhibitors in the Clinical Trial: The Therapy Opportunity in Tumor

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Hence, it is of inordinate significance to ascertain novel biomarkers to forecast the prognosis and therapy targets for tumors. This review characterized LSD1 as a biomarker in different tumors. LSD1 inhibitors in clinical trials were also discussed. The recent pattern advocates that LSD1 is engaged at sauce chromatin zones linking with complexes of multi-protein having an exact DNA-binding transcription factor, establishing LSD1 as a favorable epigenetic target, and also gives a large selection of therapeutic targets to treat different tumors. This review sturdily backing the oncogenic probable of LSD1 in different tumors indicated that LSD1 levels can be used to monitor and identify different tumors and can be a useful biomarker of progression and fair diagnosis in tumor patients. The clinical trials showed that inhibitors of LSD1 have growing evidence of clinical efficacy which is very encouraging and promising. However, for some of the inhibitors such as GSK2879552, though selective, potent, and effective, its disease control was poor as the rate of adverse events (AEs) was high in tumor patients causing clinical trial termination, and continuation could not be supported by the risk-benefit profile. Therefore, we propose that, to attain excellent clinical results of inhibitors of LSD1, much attention is required in designing appropriate dosing regimens, developing in-depth in vitro/in vivo mechanistic works of LSD1 inhibitors, and developing inhibitors of LSD1 that are reversible, safe, potent, and selective which may offer safer profiles

Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer

Nutlin-3 inhibits epithelial-mesenchymal transition by interfering with canonical transforming growth factor-beta 1-Smad-Snail/Slug axis

Enormous efforts have been made to explore small molecules that interfere with the TGF-beta signaling pathway, so as to inhibit EMT and the cancer metastasis, but few agents have been identified. In this study, we demonstrated that Nutlin-3 could abolish the down-regulation of E-cadherin induced by TGF-beta 1 in p53-deficient cancer cells. Further studies revealed that Nutlin-3 prohibited EMT by blocking the phosphorylation of Smad2/3, resulting in the decreased transcription of Snail/Slug. In addition, Nutlin-3 suppressed the motility of cancer cells, and potentiated the anti-proliferative activity of gefitinib and lapatinib. Collectively, Nutlin-3 could inhibit EMT and enhance the anti-cancer activity of EGFR inhibitors by interfering with the canonical TGF-beta 1-Smad-Snail/Slug axis, in a p53-independent manner

Multilayer Choline Phosphate Molecule Modified Surface with Enhanced Cell Adhesion but Resistance to Protein Adsorption

Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP–PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (di­methyl­amino)­ethyl meth­acrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering

Intelligent Drug Delivery System Based on Mesoporous Silica Nanoparticles Coated with an Ultra-pH-Sensitive Gatekeeper and Poly(ethylene glycol)

Mesoporous silica nanoparticles (MSNs) exhibit significant advantages for efficient drug/gene delivery but it is hard for simple MSNs to deliver the loaded drug to the target sites of disease. Considering that there are some well-known pH differences in the body, it is a useful strategy to modify the exterior surface of MSNs with stimuli-responsive gatekeepers to realize open–close transformation of their mesopores. In this work, multifunctional pH-sensitive MSNs were designed with mixed polymeric coatings, that is, poly­(ethylene glycol) (PEG) as a dispersity-enhancer and poly­(2-(pentamethyleneimino)­ethyl methacrylate) (PPEMA) as an ultra-pH-sensitive gatekeeper. Enhanced dispersity, high drug loading capacity, long-circulation time, pH-triggered targeting, and better cellular uptake of the multifunctional MSNs make them potential candidates for pH-sensitive drug delivery such as tumor therapy

Antibacterial and Biocompatible Cross-Linked Waterborne Polyurethanes Containing Gemini Quaternary Ammonium Salts

A cross-linked waterborne polyurethane (CPTMGPU) with long-term stability was developed from poly­(ethylene glycol) (PEG), polyoxytetramethylene glycol (PTMG), isophorone diisocyanate (IPDI), l-lysine, and its derivative diamine consisting of gemini quaternary ammonium salt (GQAS), using ethylene glycol diglycidyl ether (EGDE) as a cross-linker. Weight loss test, X-ray photoelectron spectroscopy (XPS) measurements, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were performed to prove the surface structure and stability of these CPTMGPU films. Furthermore, the GQAS-bearing CPTMGPUs show repeatable contact-active antibacterial efficacy against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria and do not show any inhibition effect against fibroblasts in vitro. After subcutaneous implantation in rats, the CPTMGPU films manifest good biocompatibility in vivo, despite the presence of a typical foreign body reaction toward surrounding tissues and mild systematic inflammation reaction that could be eliminated after a short implantation period, as demonstrated by histology and immunohistochemistry combined with interleukin (IL)-1β, IL-4, IL-6, IL-10, and TNF-α analysis though enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR). Therefore, these cross-linked waterborne polyurethanes hold great promise for antibacterial applications in vivo