Polyethylenimine-Enhanced Alumina Nanoscale Adjuvant for Cancer Vaccine

Aluminum oxide nanoparticles (Al2O3 NPs) have been shown to increase the efficiency of cell-mediated immune response. Specifically, CD8 and CD4 immune response is required for T cell activation by dendritic cells. These nanoparticles, when functionalized with peptides and other molecules, can be used as vaccine in cancer treatment. In this study, Al2O3 NPs were attached to E6/E7 proteins. HPV-induced cervical cancer expresses E6/E7 antigens. E6/E7 proteins were attached using surface modification of the Al2O3 NPs; different types of molecules were tested to see which adhered the highest amount of protein and produced the strongest cell response. Protein measurements were done using bicinchoninic acid assay (BCA assay) and spectrophotometry. CD8 and CD4 immune response was measured in vivo using flow cytometry. In vitro measurements of immune response were done using B3Z T cells. When coated on the nanoparticles and conjugated with E6E7 protein, the polymer polyethylenimine (PEI) proved to be most effective at strengthening the immune response in vaccinated mice. The NPs were characterized using transmission electron microscopy (TEM) and energy dispersive x-ray spectroscopy (EDX). Our findings in this study demonstrate the growing importance of applied physics in the fields of medicine and biology. Fabrication and characterization of nano-materials are important for improving vaccine delivery and ensuring effectiveness

Prevention of injury by resveratrol in a rat model of adenine-induced chronic kidney disease

Purpose: To investigate the preventive effect of resveratrol against renal pathological changes in a rat model of chronic kidney disease (CKD).Methods: CKD was induced by daily intragastric administration of adenine (200 mg/kg) for 1 month. The effect of 10, 15, and 20 mg/kg doses of resveratrol on the levels of parathyroid hormone, phosphorous, and fibroblast growth factor-23 (FGF-23) in rat urine samples after 2 months of adenine administration were analyzed using an auto-analyzer.Results: Resveratrol treatment significantly inhibited the adenine-mediated increase in serum parathyroid hormone, phosphorous and FGF-23 levels (p < 0.002). In rats treated with 10, 15 and 20 mg/kg doses of resveratrol after adenine, urine protein/creatinine ratio was reduced to 5, 675.6 ± 2453.7, 4, 789.8 ± 1,534.9, and 1, 965 ± 576.8 mg/g, respectively. In the untreated and normal control groups, the respective values were 7, 004 ± 1, 653.3 and 1, 627.5 ± 568.7 mg/g. Treatment with resveratrol after administration of adenine inhibited increases in creatinine, blood urea nitrogen, and uric acid levels in a dose-dependent manner (p < 0.002). Resveratrol treatment also inhibited adeninemediated increases in monocytes and inflammatory cells. Furthermore, resveratrol prevented renal tubule swelling and expansion induced by adenine administration.Conclusion: Resveratrol treatment prevent the renal pathological changes induced by adenine administration in a rat model of CKD by inhibiting FGF-23, parathyroid hormone, and phosphate. Thus, resveratrol may be of therapeutic importance for the treatment of CKD.Keyword: Parathyroid hormone, Phosphate, Creatinine, Monocytes, Chronic kidney disease, Fibroblast growth factor-2

Plug-and-Play Medical Dialogue System

Medical dialogue systems aim to provide accurate answers to patients, necessitating specific domain knowledge. Recent advancements in Large Language Models (LLMs) have demonstrated their exceptional capabilities in the medical Q&A domain, indicating a rich understanding of common sense. However, LLMs are insufficient for direct diagnosis due to the absence of diagnostic strategies. The conventional approach to address this challenge involves expensive fine-tuning of LLMs. Alternatively, a more appealing solution is the development of a plugin that empowers LLMs to perform medical conversation tasks. Drawing inspiration from in-context learning, we propose PlugMed, a Plug-and-Play Medical Dialogue System that facilitates appropriate dialogue actions by LLMs through two modules: the prompt generation (PG) module and the response ranking (RR) module. The PG module is designed to capture dialogue information from both global and local perspectives. It selects suitable prompts by assessing their similarity to the entire dialogue history and recent utterances grouped by patient symptoms, respectively. Additionally, the RR module incorporates fine-tuned SLMs as response filters and selects appropriate responses generated by LLMs. Moreover, we devise a novel evaluation method based on intent and medical entities matching to assess the efficacy of dialogue strategies in medical conversations more effectively. Experimental evaluations conducted on three unlabeled medical dialogue datasets, including both automatic and manual assessments, demonstrate that our model surpasses the strong fine-tuning baselines.Comment: 9 pages, 3 figures, Possible submission to Emnlp or AAA

Association of CYP1B1 Polymorphisms with Breast Cancer: A Case-Control Study in the Han Population in Ningxia Hui Autonomous Region, P. R. China

Studies investigating possible associations between cytochrome P4501B1 (CYP1B1) polymorphisms and breast cancer risk have been inconsistent. We set out to ascertain whether there might be an association between polymorphisms in exon 2 (codon 119, G→T) and exon 3 (codon 432, G→C) of CYP1B1 and breast cancer in a Chinese Han population in the rural region of Ningxia. Using an allele-specific polymerase chain reaction method and direct DNA sequencing, the presence or absence of the two CYP1B1 polymorphisms was investigated. Genotype and allele frequencies were analyzed in breast cancer cases (n = 152) and healthy age-matched controls (n = 156). The odds ratio (OR) of 119G→T or 432G→C in breast cancer cases and controls was 3.3 (95% CI: 1.28 to 8.28) and 2.8 (95% CI: 1.04 to 7.51), respectively. In addition, the OR for people with both polymorphisms (119T and 432C) was 4.69 (95% CI: 1.97 to 11.19). Our results suggest that certain polymorphisms in the CYP1B1 gene might increase risk for breast cancer among Han Chinese, perhaps because they influence the efficiency of CYP1B1 bio-transformation of oestrogens or pro-carcinogens into DNA-reactive electrophiles that may act as cancer-initiating agents

The Novel Protein Cj0371 Inhibits Chemotaxis of Campylobacter jejuni

cj0371 is a novel gene that is associated with Campylobacter jejuni virulence, and an isogenic mutant of cj0371 showed hyper chemotaxis and motility. Chemotactic motility is an important virulence factor and is involved in C. jejuni pathogenesis. Campylobacter sp. has specific variations of the common chemotaxis components, including histidine autokinase CheA, coupling scaffold protein CheV, chemotaxis response regulator protein CheY and several chemoreceptor proteins. In this study, we used immunoprecipitation combined with LC-MS/MS analyses to screen six chemotaxis pathway proteins that potentially interact with the putative protein Cj0371. qRT-PCR was used to quantitatively analyze the expression of these chemotaxis genes and basic flagella genes. The results showed that the expression of cheV, cj1110c, and cj0262c was significantly up-regulated, and four flagella genes also had up-regulated expression in the cj0371 mutant. GST pull-down analyses found that Cj0371 interacted with the receiver domain of the CheV protein. Enzyme-coupled spectrophotometric assays showed that the ATPase activity of CheA was higher when Cj0371 was not present in the chemotaxis reaction medium. Therefore, we concludes that cj0371 has a negative influence on C. jejuni chemotaxis, which may occur by adjusting the receiver domain of CheV to influence chemotaxis. This paper provides a new component in the chemotaxis pathway of C. jejuni for the first time and highlight the complexity of this remarkable pathway

Modulation of the secondary Bjerknes force in multi-bubble systems

The behaviours of insonated bubble clusters are regulated by the secondary Bjerknes force between bubble pairs. While the force has been investigated extensively for two-bubble systems, the modulation of the force by nearby bubbles remains unclear. This problem is investigated in this paper by theoretical analyses and numerical simulations of a three bubble system. For weak oscillations, the third bubble is found to have strong effects when its radius is close to the resonant radius. The equilibrium distance between the bubble pair is reduced when the radius of the third bubble is smaller than the resonant threshold, and increased when it is larger. For strong oscillations of bubbles with radii of a few microns, the third bubble reduces the magnitude of the force, hence increasing the equilibrium distance. The modulation effects depend strongly on the relative sizes of the bubbles. Stronger effects can be produced when the third bubble is placed closer to the smaller bubble in the bubble pair. The findings highlight the need for a more accurate parametrization of the secondary Bjerknes force in the simulation and manipulation of bubble clusters