Bacterial outer membrane vesicles in the fight against cancer.

ABSTRACT: Bacterial outer membrane vesicles (OMVs) are diminutive vesicles naturally released by Gram-negative bacteria. These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment. Therapeutic medicines may be delivered via OMVs directly to the tumor sites, thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity. Furthermore, the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells, which makes them a desirable tool for immunotherapy. They can also be genetically modified to carry specific antigens, immunomodulatory compounds, and small interfering RNAs, enhancing the immune response to cancerous cells and silencing genes associated with disease progression. Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects. This review highlights the crucial role of bacterial OMVs in cancer, emphasizing their potential as vectors for novel cancer targeted therapies. As researchers delve deeper into the complexities of these vesicles and their interactions with tumors, there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.

Effect of static magnetic field on gene expression of human umbilical cord mesenchymal stem cells by transcriptome analysis.

PURPOSE: Static magnetic fields (SMFs) induce various biological reactions and have been applied in the biological therapy of diseases, especially in combination with mesenchymal stem cells (MSCs) and tissue engineering. However, the underlying influence of SMFs on MSCs gene expression remains largely unclear. In this study, we aim to investigate the effects of SMFs on gene expression of human MSCs. MATERIALS AND METHODS: We exposed human MSCs to two different intensities (0.35 â€‹T and 1.0 â€‹T) of SMFs and observed the effects of SMFs on cell morphology. Subsequently, RNA-sequencing was performed to explore the gene expression changes. RESULTS: Compared with control group cells, no significant differences in cell morphology were observed under a phase contrast inverted microscope, but the transcriptome of SMF-exposed MSCs were significantly changed in both 0.35 â€‹T and 1.0 â€‹T groups and the differential expressed genes are involved in multiple pathways, such as ubiquitin mediated proteolysis, TNF signaling pathway, NF-kappa B signaling pathway, TGF-beta signaling pathway, metabolic pathways, and apoptosis, which regulate the biological functions of MSCs. CONCLUSIONS: SMFs stimulation could affect the gene expression of human MSCs and the biological effects vary by the different intensities of SMFs. These data offer the molecular foundation for future application of SMFs in stem cell technology as well as tissue engineering medicine.

A viable remedy for overcoming resistance to anti-PD-1 immunotherapy: Fecal microbiota transplantation.

Anti-PD-1 immunotherapy is a cancer therapy that focuses explicitly on the PD-1 receptor found on the surface of immune cells. This targeted therapeutic strategy is specifically designed to amplify the immune system's innate capacity to detect and subsequently eliminate cells that have become cancerous. Nevertheless, it should be noted that not all patients exhibit a favourable response to this particular therapeutic modality, necessitating the exploration of novel strategies to augment the effectiveness of immunotherapy. Previous studies have shown that fecal microbiota transplantation (FMT) can enhance the efficacy of anti-PD-1 immunotherapy in advanced melanoma patients. To investigate this intriguing possibility further, we turned to PubMed and conducted a comprehensive search for studies that analyzed the interplay between FMT and anti-PD-1 therapy in the context of tumor treatment. Our search criteria were centred around two key phrases: "fecal microbiota transplantation" and "anti-PD-1 therapy." The studies we uncovered all echo a similar sentiment. They pointed towards the potential of FMT to improve the effectiveness of immunotherapy. FMT may enhance the effectiveness of immunotherapy by altering the gut microbiota and boosting the patient's immunological response. Although promising, additional investigation is needed to improve the efficacy of FMT in the context of cancer therapy and attain a comprehensive understanding of the possible advantages and drawbacks associated with this therapeutic strategy.

Research progress of autoimmune diseases based on induced pluripotent stem cells.

Autoimmune diseases can damage specific or multiple organs and tissues, influence the quality of life, and even cause disability and death. A 'disease in a dish' can be developed based on patients-derived induced pluripotent stem cells (iPSCs) and iPSCs-derived disease-relevant cell types to provide a platform for pathogenesis research, phenotypical assays, cell therapy, and drug discovery. With rapid progress in molecular biology research methods including genome-sequencing technology, epigenetic analysis, '-omics' analysis and organoid technology, large amount of data represents an opportunity to help in gaining an in-depth understanding of pathological mechanisms and developing novel therapeutic strategies for these diseases. This paper aimed to review the iPSCs-based research on phenotype confirmation, mechanism exploration, drug discovery, and cell therapy for autoimmune diseases, especially multiple sclerosis, inflammatory bowel disease, and type 1 diabetes using iPSCs and iPSCs-derived cells.

Molecular characterization, expression analysis and function identification of Pf_IL-12p35, Pf_IL-23p19 and Pf_IL-12p40 genes in yellow catfish (Pelteobagrus fulvidraco).

The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf_IL-12p35a/b, Pf_IL-23p19 and Pf_IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf_IL-12p35a/b and Pf_IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf_IL-12p35a/b and Pf_IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf_IL-12p40a mRNA was induced in gill, and Pf_IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf_IL-12p35a and Pf_IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf_IL-12 and rPf_IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf_IL-12 and Pf_IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development.

Take the bull by the horns and tackle the potential downsides of the ketogenic diet.

The ketogenic diet (KD) is a distinctive dietary regimen known for its low-carbohydrate and high-fat composition. Recently, it has garnered considerable interest from the scientific community and the general population because of its claimed efficacy in facilitating weight reduction, improving the management of glucose levels, and raising overall energy levels. The core principle of the KD is the substantial decrease in carbohydrate consumption, which is subsequently substituted by ingesting nourishing fats. While the KD has promising advantages and is gaining popularity, it must be acknowledged that this dietary method may not be appropriate for all individuals. The dietary regimen may give rise to adverse effects, including constipation, halitosis, and imbalances in electrolyte levels, which may pose a potential risk if not adequately supervised. Hence, thorough and meticulous inquiry is needed to better comprehend the possible hazards and advantages linked to the KD over prolonged durations. By obtaining a more comprehensive perspective, we can enhance our ability to make well-informed judgments and suggestions as to implementation of this specific dietary regimen.

Vaginal microbiota transplantation is a truly opulent and promising edge: fully grasp its potential.

Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.

Biofluid biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.

Establishment of a pMCAO model in SD rats and screening for behavioral indicators suitable for long-term monitoring.

OBJECTIVE: This study aimed to establish a permanent middle cerebral artery occlusion (pMCAO) model in rats to simulate the pathological process of stroke patients with no reperfusion. And screen highly sensitive items that could be used to detect long-term behavioral abilities in rat of intraluminal suture models. METHOD: Established the pMCAO model then tested the rats for the bilateral asymmetry, modified neurological severity score, grid-walking, cylinder, rotating, and water maze test from week 1 to week 16. RESULTS: The infarct volume of the model rats was stable (26.72% ±1.86%). The sensorimotor test of bilateral asymmetry, grid-walking, cylinder, and mNSS test showed significant differences from week 1 to week 16 after injury. The water maze test at week 16 showed significant differences in spatial exploration and learning ability between the two groups. We confirmed that there was no significant difference between MRI and TTC staining in detecting the degree of brain injury, which facilitated the diversity of subsequent detection methods. We also confirmed that at multiple time points, grid, cylinder and water maze test were significantly positively correlated with rat brain infarct volume. CONCLUSION: They are suitable for the long-term observation of behaviors in the sequela stage of stroke in rat.

Quantitative Assessment of Breast Tumor: Comparison of Four Methods of Positioning Region of Interest for Synthetic Relaxometry and Diffusion Measurement.

RATIONALE AND OBJECTIVES: To compare the differences in apparent diffusion coefficient (ADC) and synthetic magnetic resonance (MR) measurements of four region of interest (ROI) placement methods for breast tumor and to investigate their diagnostic performance. METHODS: 110 (70 malignant, 40 benign) newly diagnosed breast tumors were evaluated. The patients underwent 3.0 T MR examinations including diffusion-weighted imaging and synthetic MR. Two radiologists independently measured ADCs, T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) using four ROI methods: round, square, freehand, and whole-tumor volume (WTV). The interclass correlation coefficient (ICC) was used to assess their measurement reliability. Diagnostic performance was evaluated using multivariate logistic regression analysis and the receiver operating characteristic (ROC) curves. RESULTS: The mean values of all ROI methods showed good or excellent interobserver reproducibility (0.79-0.99) and showed the best diagnostic performance compared to the minimum and maximum values. The square ROI exhibited superior performance in differentiating between benign from malignant breast lesions, followed by the freehand ROI. T2, PD, and ADC values were significantly lower in malignant breast lesions compared to benign ones for all ROI methods (p < 0.05). Multiparameters of T2 + ADC demonstrated the highest AUC values (0.82-0.95), surpassing the diagnostic efficacy of ADC or T2 alone (p < 0.05). CONCLUSION: ROI placement significantly influences ADC and synthetic MR values measured in breast tumors. Square ROI and mean values showed superior performance in differentiating benign and malignant breast lesions. The multiparameters of T2 + ADC surpassed the diagnostic efficacy of a single parameter.

Harnessing the power of goat milk-derived extracellular vesicles for medical breakthroughs: A review.

Research into goat milk-derived extracellular vesicles (GMVs) has grown in popularity in recent years owing to their potential uses in several sectors, including medicine. GMVs are tiny, lipid-bound structures that cells secrete and use to transport bioactive substances like proteins, lipids, and nucleic acids. They may be extracted from different body fluids, including blood, urine, and milk, and have been found to play crucial roles in cell-to-cell communication. GMVs are a promising field of study with applications in preventing and treating various disorders. Their immune-modulating properties, for instance, have been investigated, and they have shown promise in treating autoimmune illnesses and cancer. They may be loaded with therapeutic compounds and directed to particular cells or tissues, but they have also been studied for their potential use as drug-delivery vehicles. Goat milk extracellular vesicles are an intriguing study topic with many possible benefits. Although more study is required to thoroughly understand their functioning and prospective applications, they provide a promising path for creating novel medical treatments and technology.

Immune cells and RBCs derived from human induced pluripotent stem cells: method, progress, prospective challenges.

Blood has an important role in the healthcare system, particularly in blood transfusions and immunotherapy. However, the occurrence of outbreaks of infectious diseases worldwide and seasonal fluctuations, blood shortages are becoming a major challenge. Moreover, the narrow specificity of immune cells hinders the widespread application of immune cell therapy. To address this issue, researchers are actively developing strategies for differentiating induced pluripotent stem cells (iPSCs) into blood cells in vitro. The establishment of iPSCs from terminally differentiated cells such as fibroblasts and blood cells is a straightforward process. However, there is need for further refinement of the protocols for differentiating iPSCs into immune cells and red blood cells to ensure their clinical applicability. This review aims to provide a comprehensive overview of the strategies and challenges facing the generation of iPSC-derived immune cells and red blood cells.

Analgesic effects of Marasmius androsaceus mycelia ethanol extract and possible mechanisms in mice

Marasmius androsaceus is a medicinal fungus mainly used to treat various forms of pain in China. This study investigated the analgesic effects of an ethanol extract of M. androsaceus (MAE) and its potential molecular mechanisms. Oral administration of MAE (50, 200, and 1000 mg/kg) had significant analgesic effects in an acid-induced writhing test, a formalin test, and a hot-plate test, with effectiveness similar to tramadol (the positive control drug). The autonomic activity test showed that MAE had no harmful effects on the central nervous system in mice. MAE resulted in significantly enhanced levels of noradrenalin and 5-hydroxytryptamine in serum but suppressed both of these neurotransmitters in the hypothalamus after 30 s of hot-plate stimulation. Co-administration with nimodipine (10 mg/kg; a Ca2+ channel blocker) strongly enhanced the analgesic effect in the hot-plate test compared to MAE alone. Moreover, MAE down-regulated the expression of calmodulin-dependent protein kinase II (CaMKII) in the hypothalamus after a 30-s thermal stimulus. These results suggested that the analgesic ability of MAE is related to the regulation of metabolism by monoamine neurotransmitters and Ca2+/CaMKII-mediated signaling, which can potentially aid the development of peripheral neuropathic pain treatments obtained from M. androsaceus.