幽门螺杆菌感染引起非消化系统疾病的研究进展

幽门螺杆菌是一种革兰氏阴性微需氧型细菌, 可引起消化性溃疡、膜相关淋巴组织淋巴瘤和萎缩性胃炎, 是胃癌的主要诱因. 但近年来, 流行病学调查和动物实验数据提示, 该菌感染与一些非消化系统疾病, 如缺铁性贫血、特发性血小板减少性紫癜、菌血症、肺炎以及类风湿性关节炎等的发生密切相关. 本文就幽门螺杆菌感染引发非消化系统疾病的新进展进行系统剖析, 以期全面展现幽门螺杆菌感染的新领域.     

The Development of BTK Inhibitors: A Five-Year Update

Bruton’s tyrosine kinase (BTK) represented, in the past ten years, an important target for the development of new therapeutic agents that could be useful for cancer and autoimmune disorders. To date, five compounds, able to block BTK in an irreversible manner, have been launched in the market, whereas many reversible BTK inhibitors (BTKIs), with reduced side effects that are more useful for long-term administration in autoimmune disorders, are under clinical investigation. Despite the presence in the literature of many articles and reviews, studies on BTK function and BTKIs are of great interest for pharmaceutical companies as well as academia. This review is focused on compounds that have appeared in the literature from 2017 that are able to block BTK in an irreversible or reversible manner; also, new promising tunable irreversible inhibitors, as well as PROTAC molecules, have been reported. This summary could improve the knowledge of the chemical diversity of BTKIs and provide information for future studies, particularly from the medicinal chemistry point of view. Data reported here are collected from different databases (Scifinder, Web of Science, Scopus, Google Scholar, and Pubmed) using “BTK” and “BTK inhibitors” as keywords.     

Risks of Muscle Atrophy in Patients with Malignant Lymphoma after Autologous Stem Cell Transplantation

Objective: Muscle atrophy is associated with autologous stem cell transplantation (ASCT)-related outcomes in patients with malignant lymphoma (ML). However, the impact of ASCT on muscle mass remains unclear in patients with ML. The aims of this study were to investigate changes in muscle mass and risk profiles for muscle atrophy after ASCT. Method: We enrolled 40 patients with refractory ML (age 58 [20-74] years, female/male 16/24, body mass index (BMI) 21.1 kg/m² [17.1-29.6]). Psoas muscle mass was assessed using the psoas muscle index (PMI) before and after ASCT. Statistical analysis used: Independent factors associated with a severe decrease rate of change in PMI were evaluated by decision-tree analysis, respectively. Results: PMI was significantly decreased after ASCT (4.61 vs. 4.55 cm²/m²; P=0.0425). According to the decision-tree analysis, the regimen was selected as the initial split. The rates of change in PMI were −5.57% and −3.97% for patients administered MCEC and LEED, respectively. In patients who were administered LEED, the second branching factor was BMI. In patients with BMI < 20.3 kg/m², the rate of change in PMI was −7.16%. On the other hand, the rate of change in PMI was 4.05% for patients with BMI ≥ 20.3 kg/m². Conclusion: We demonstrated that muscle mass decreased after ASCT in patients with ML. Patients who received MCEC and patients with low BMI were at risk for a decrease in muscle mass.     

Molecular modelling studies on cinnoline-based BTK inhibitors using docking and structure-based 3D-QSAR

ABSTRACT

BTK inhibitors have been proved as an effective target for B-cell malignancies. Ibrutinib is the most advanced irreversible BTK inhibitor for treating mantle cell lymphoma/chronic lymphocytic leukaemia but with existing drug resistance and adverse effects. To design novel effective and safety reversible BTK inhibitors, 115 newly cinnoline analogues were selected to perform molecular docking and 3D-QSAR study because of the main scaffold similarity to Ibrutinib. Both established CoMFA and CoMSIA models obtained high predictive and satisfactory value. CoMFA/CoMSIA contour maps demonstrated that bulky substitutions are preferred at R₁ and R₃ positions, and introducing hydrophilic and negative electrostatic substitutions at R₁ positions is important for improving BTK inhibitory activities. These results will be useful to provide clues for rationally designing novel and high potency BTK inhibitors.     

Exploiting LIBS as a spectrochemical analytical technique in diagnosis of some types of human malignancies

In the present work we are presenting a detailed in vitro study of using laser-induced breakdown spectroscopy (LIBS) as a quick and simple method for spectrochemical analysis to identify and characterize some types of human malignancies. This has been performed via detection of the abundance of certain elements namely calcium and magnesium in malignant tissues with respect to the non-neoplastic ones. In order to improve the performance of the LIBS technique - in particular its sensitivity, reproducibility and limit of detection - the measurements have been performed under vacuum (10⁻² Torr) and the samples were frozen down to −196 °C in a specially designed vacuum chamber. Under such experimental arrangements a pronounced enhancement has been achieved in the signal to noise (S/N) ratio of different spectral lines. Significant discriminating results have been obtained in case of breast and colorectal cancers indicating the possibility of adopting LIBS in the early detection of the malignancy as well as the identification of the severity and the grade of the disease. The present work demonstrated that future in vivo measurements are also feasible and reliable using especial endoscopic systems for delivery of laser beam and collection of the emitted plasma light.     

Voice Prosthesis Coated with Sustained Release Varnish Containing Clotrimazole Shows Long-Term Protection against Candida albicans: An In Vitro Study

Fungal biofilm formation on voice prosthesis (VP) is a major health problem that requires repeated replacement of the prosthesis. Candida albicans is one of the pathogens that frequently inhabits the VP. We proposed that coating VPs with sustained-release varnish (SRV) containing clotrimazole (CTZ) might prevent fungal biofilm formation. The long-term antifungal activities of SRV-CTZ- versus SRV-placebo-coated VPs was tested daily by measuring the inhibition zone of C. albicans seeded on agar plates or by measuring the fungal viability of C. albicans in suspension. The extent of biofilm formation on coated VPs was analyzed by confocal microscopy and scanning electron microscopy. We observed that SRV-CTZ-coated VPs formed a significant bacterial inhibition zone around the VPs and prevented the growth of C. albicans in suspension during the entire testing period of 60 days. Fungal biofilms were formed on placebo-coated VPs, while no significant biofilms were observed on SRV-CTZ-coated VPs. HPLC analysis shows that CTZ is continuously released during the whole test period of 60 days at a concentration above the minimal fungistatic concentration. In conclusion, coating VPs with an SRV-CTZ film is a potential effective method for prevention of fungal infections and biofilm formation on VPs.     

血液肿瘤相关生物标志物的电化学传感检测

血液肿瘤是一类严重危害人类健康的血液系统恶性疾病,主要累及骨髓、血液及淋巴组织。血液肿瘤相关生物标志物的定量检测是实现疾病精细化病理分型以实施靶向治疗进而改善预后的关键。本文对血液肿瘤相关生物标志物的种类、目前国内外常用的检测方法进行概述,重点阐述电化学生物传感器在检测血液肿瘤相关生物标志物方面的最新进展,并对血液肿瘤相关生物标志物电化学传感技术的未来发展方向提出展望,拟为其深入研究与应用提供参考。     

The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite–methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients’ life. Therefore, novel targeted therapies based on the malignant cells’ common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose–methotrexate conjugate (Glu–MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu–MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu–MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients’ outcomes.     

Efficacy of physical exercise using the balance board game on physical and psychological function in patients with hematological malignancies confined to a bioclean room

Objective: This study aimed to define the efficacy and features of physical therapy (PT) using the Nintendo Wii Fit U (Nintendo Inc., Kyoto, Japan) in patients with hematological malignancies confined to a bioclean room. Method: A total of 33 patients with hematological malignancies confined to a bioclean room were enrolled in this study. This study was designed as a randomized crossover test between two weeklong interventions: PT program (Therapist PT) and Wii Fit U program (Wii PT). We compared the efficacy of Wii PT and Therapist PT with regard to physical and psychological function test scores. Results: Of the 33 patients, 22 were analyzed. The validity of the crossover design was demonstrated, as there were no significant differences in period and carryover effects between the two groups. Therapist PT resulted in significantly better improvements in fatigue scores and total mood disturbance (TMD) scores in the Profile of Mood States short-form Japanese version compared to Wii PT (fatigue score, -5.2±8.3 vs 2.7±8.2; TMD score, -22.5±32.8 vs -2.6±20.5; p<0.05). Physical function improved post-Wii PT and post-Therapist PT interventions (p<0.05), and there was no difference in treatment effect. Conclusion: Improvements in physical function were clearly observed following the use of Wii PT in patients confined to a bioclean room. However, compared to Therapist PT, Wii PT was less effective in improving the psychological function of patients.     

Recent Advancements in the Development of Anti-Breast Cancer Synthetic Small Molecules

Among all cancer types, breast cancer (BC) still stands as one of the most serious diseases responsible for a large number of cancer-associated deaths among women worldwide, and diagnosed cases are increasing year by year worldwide. For a very long time, hormonal therapy, surgery, chemotherapy, and radiotherapy were used for breast cancer treatment. However, these treatment approaches are becoming progressively futile because of multidrug resistance and serious side effects. Consequently, there is a pressing demand to develop more efficient and safer agents that can fight breast cancer belligerence and inhibit cancer cell proliferation, invasion and metastasis. Currently, there is an avalanche of newly designed and synthesized molecular entities targeting multiple types of breast cancer. This review highlights several important synthesized compounds with promising anti-BC activity that are categorized according to their chemical structures.