Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging.

BACKGROUND: Global and regional cerebral blood flow (CBF) changes in patients with unilateral internal carotid artery occlusion (ICAO) are unclear when the dual post-labeling delays (PLD) arterial spin labeling (ASL) magnetic resonance imaging (MRI) technique is used. Manual delineation of regions of interest for CBF measurement is time-consuming and laborious. AIM: To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique. METHODS: Twenty hospitalized patients with ICAO and sex- and age-matched controls were included in the study. Regional CBF was measured by Dr. Brain's ASL software. The present study evaluated differences in global, middle cerebral artery (MCA) territory, anterior cerebral artery territory, and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions (including the caudate nucleus, lentiform nucleus, insula ribbon, internal capsule, and M1-M6) and brain lobes (including frontal, parietal, temporal, and insular lobes) between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s. RESULTS: When comparing CBF between ICAO patients and controls, the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s; the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s, and it was lower in 9 brain regions at PLD 2.5 s; the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s. The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s. The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions, whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions. The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s, and in M6 at PLD 2.5 s. CONCLUSION: Unilateral ICAO results in hypoperfusion in the global and MCA territories, especially in the ASPECTS area. Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

Fasting: A Complex, Double-Edged Blade in the Battle Against Doxorubicin-Induced Cardiotoxicity.

In recent years, there has been a surge in the popularity of fasting as a method to enhance one's health and overall well-being. Fasting is a customary practice characterized by voluntary refraining from consuming food and beverages for a specified duration, ranging from a few hours to several days. The potential advantages of fasting, including enhanced insulin sensitivity, decreased inflammation, and better cellular repair mechanisms, have been well documented. However, the effects of fasting on cancer therapy have been the focus of recent scholarly investigations. Doxorubicin (Dox) is one of the most widely used chemotherapy medications for cancer treatment. Unfortunately, cardiotoxicity, which may lead to heart failure and other cardiovascular issues, has been linked to Dox usage. This study aims to comprehensively examine the possible advantages and disadvantages of fasting concerning Dox-induced cardiotoxicity. Researchers have investigated the potential benefits of fasting in lowering the risk of Dox-induced cardiac damage to solve this problem. Nevertheless, new studies indicate that prolonged alternate-day fasting may adversely affect the heart's capacity to manage the cardiotoxic properties of Dox. Though fasting may benefit overall health, it is essential to proceed cautiously and consider the potential risks in certain circumstances.

The Epstein-Barr virus small capsid protein BFRF3 disrupts the NF-кB signaling pathway by inhibiting p65 activity.

Epstein-Barr virus (EBV), a common gamma herpesvirus, establishes a life-long latent infection in the host to defend against innate immune recognition, which is closely related to a variety of malignant tumors, but its specific mechanism is unclear. BFRF3, an EBV-encoded small capsid protein, is mainly involved in the assembly of the viral capsid structure and the maintenance of its stability. Here, we showed that BFRF3 can inhibit TNF-α-mediated NF-кB promoter activation. Moreover, BFRF3 downregulates NF-кB-mediated promoter activation and transcription of inflammatory cytokines, including IL-6 and IL-8. Dual-luciferase reporter assay demonstrated that BFRF3 restrains NF-кB promoter activity at or below the p65 level, and coimmunoprecipitation analysis revealed that BFRF3 not only interacts with p65 but also binds to its critical truncated Rel homology domain (RHD) and transcriptional activation domain (TAD). However, BFRF3 does not affect the dimerization of p65-p50, but overexpression of BFRF3 reduces the nuclear accumulation of p65, and the phosphorylation of p65 (Ser536) is repressed during BFRF3 transfection and EBV lytic infection, which promotes the proliferation of EBV. Overall, our study suggested that BFRF3 may play a crucial role in antiviral immunity to defend against EBV infection by inhibiting NF-κB activity.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A novel major accidents evolution model and its application in Chinese industrial accident.

The accident mortality rate of major accidents (MAs) show that China is still in the bottleneck period of accident prevention and control. To further promote the MAs prevention and control, this paper presents a novel major accidents evolution model from the theoretical perspective of information processing (IP). Firstly, based on the safety science paradigm of accident prevention and the emergency management paradigm of accident control, a safety information processing (SIP) process is proposed. Secondly, established the SIP model for different stages of accident prevention and control, which involves danger information processing (DIP), potential hazard information processing (PHIP), risk information processing (RIP), and emergency information processing (EIP). Thirdly, revealed the SIP of various management subject and the failure principle of accident prevention and control, that is, MAs occur under the premise of continuous failures of DIP, PHIP, RIP, and EIP under the social-technical system. Finally, the DPRE-IP model is proposed from the whole evolution path of "danger-potential hazard-risk-accident". To demonstrate the viability of the model, this model is applied to the "6·13" Wenling major explosion accident. The results show that the proposed DPRE-IP model can provide new ideas for the formulation of accident prevention and control measures and accident analysis.

Road Traffic Sign Detection Method Based on RTS R-CNN Instance Segmentation Network.

With the rapid development of the autonomous driving industry, there is increasing research on related perception tasks. However, research on road surface traffic sign detection tasks is still limited. There are two main challenges to this task. First, when the target object's pixel ratio is small, the detection accuracy often decreases. Second, the existing publicly available road surface traffic sign datasets have limited image data. To address these issues, this paper proposes a new instance segmentation network, RTS R-CNN, for road surface traffic sign detection tasks based on Mask R-CNN. The network can accurately perceive road surface traffic signs and provide important information for the autonomous driving decision-making system. Specifically, CSPDarkNet53_ECA is proposed in the feature extraction stage to enhance the performance of deep convolutional networks by increasing inter-channel interactions. Second, to improve the network's detection accuracy for small target objects, GR-PAFPN is proposed in the feature fusion part, which uses a residual feature enhancement module (RFA) and atrous spatial pyramid pooling (ASPP) to optimize PAFPN and introduces a balanced feature pyramid module (BFP) to handle the imbalanced feature information at different resolutions. Finally, data augmentation is used to generate more data and prevent overfitting in specific scenarios. The proposed method has been tested on the open-source dataset Ceymo, achieving a Macro F1-score of 87.56%, which is 2.3% higher than the baseline method, while the inference speed reaches 23.5 FPS.

Bacteria associated with glioma: a next wave in cancer treatment.

Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today's mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.

Fecal microbiota transplantation holds the secret to youth.

Aging shows itself not just at the cellular level, with shortened telomeres and cell cycle arrest, but also at the organ and organismal level, with diminished brainpower, dry eyes, intestinal inflammation, muscular atrophy, wrinkles, etc. When the gut microbiota, often called the "virtual organ of the host," fails to function normally, it can lead to a cascade of health problems including, but not limited to, inflammatory bowel disease, obesity, metabolic liver disease, type II diabetes, cardiovascular disease, cancer, and even neurological disorders. An effective strategy for restoring healthy gut bacteria is fecal microbiota transplantation (FMT). It can reverse the effects of aging on the digestive system, the brain, and the vision by transplanting the functional bacteria found in the excrement of healthy individuals into the gut tracts of patients. This paves the way for future research into using the microbiome as a therapeutic target for disorders associated with aging.

Unexpected worsening of doxorubicin cardiotoxicity upon intermittent fasting.

Recently in Cell Metabolism, Ozcan et al. used preclinical and clinical data to suggest that alternate-day fasting may exacerbate the cardiotoxic effects of doxorubicin through the TFEB/GDF15 pathway, leading to myocardial atrophy and impaired cardiac function. The link between caloric intake, chemotherapy-induced cachexia, and cardiotoxicity warrants more clinical attention.