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Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. CC-90011 in vitro Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are elaborated. Overall, there is still significant room for development in macrophage-mediated immune modulation and macrophage-mediated drug delivery, which will further enhance current tumor therapies against various malignant solid tumors, including drug-resistant tumors and metastatic tumors.
Metronidazole has a substantial impact on the gut microbiome. However, the recovery of the microbiome after discontinuation of administration, and the metabolic consequences of such alterations have not been investigated to date.
To describe the impact of 14-day metronidazole administration, alone or in combination with a hydrolyzed protein diet, on fecal microbiome, metabolome, bile acids (BAs), and lactate production, and on serum metabolome in healthy dogs.
Twenty-four healthy pet dogs.
Prospective, nonrandomized controlled study. Dogs fed various commercial diets were divided in 3 groups control group (no intervention, G1); group receiving hydrolyzed protein diet, followed by metronidazole administration (G2); and group receiving metronidazole only (G3). Microbiome composition was evaluated with sequencing of 16S rRNA genes and quantitative polymerase chain reaction (qPCR)-based dysbiosis index. Untargeted metabolomics analysis of fecal and serum samples was performed, followed by targeted assays for fecal BAs and lactate.
No changes were observed in G1, or G2 during diet change. Metronidazole significantly changed microbiome composition in G2 and G3, including decreases in richness (P < .001) and in key bacteria such as Fusobacteria (q < 0.001) that did not fully resolve 4 weeks after metronidazole discontinuation. Fecal dysbiosis index was significantly increased (P < .001). Those changes were accompanied by increased fecal total lactate (P < .001), and decreased secondary BAs deoxycholic acid and lithocholic acid (P < .001).
Our results indicate a minimum 4-week effect of metronidazole on fecal microbiome and metabolome, supporting a cautious approach to prescription of metronidazole in dogs.
Our results indicate a minimum 4-week effect of metronidazole on fecal microbiome and metabolome, supporting a cautious approach to prescription of metronidazole in dogs.Best practice in dementia care is support in the home. Yet, crisis is common and can often result in hospital admission with adverse consequences. The objective of this mixed-methods case study research was to identify the critical factors for resolving crisis for a person with dementia living at home. The research was an in-depth investigation of what happens during crisis for people with dementia and how it is managed by a Home Treatment Crisis Team to resolution and outcome at 6 weeks and 6 months. The methods were; observation of crisis management for 15 patients with dementia (max three observations per patient, total 41), interviews with patients with dementia (n = 5), carers (n = 13) and professionals (n = 14, range one to six interviews per person, total 29), focus group (nine professionals), and extraction of demographics and medical history from medical records. Analysis focused on the identification of factors important for crisis resolution and avoidance of hospital admission. Critical factors for the Home Treatment Crisis Team to enable successful crisis resolution were immediate action to reduce risk of harm, expertise in dementia care and carer education, communication skills to establish trust and promote benefits of home treatment, shared decision-making, medication management, addressing the needs of carers independently of the person with dementia and, local availability of respite and other community services. The Home Treatment Crisis Team integrated the seven factors to deploy a biopsychosocial systems approach with embedded respect for personhood. This approach enabled crisis resolution for a person with dementia by creating a system of services, treatments, resources and relationships, 'Safe Dementia Space', in the community with avoidance of hospital admission in more than 80% of referrals. The identified critical factors for crisis resolution are important considerations in the design and delivery of home treatment services for people with dementia.Venous malformations (VMs) are common slow-flow vascular malformations, which affect almost anywhere of the body. From January 2010 to October 2019, 126 patients with VMs who had complete imaging and follow-up data were enrolled into this study, including 75 males. The initial treatment age ranged from 5 to 72 years. The role of imaging results on the choice of treatment measures and the application were summarized. In this study, we retrospectively analyzed the imaging examinations, treatment measures, and follow-up results of the patients with VMs in our clinic. In this series, imaging examinations included ultrasound, magnetic resonance imaging, computed tomography (CT) scan and enhanced scan, percutaneous sinus angiography and three-dimensional CT imaging, plain film, CT venography, CT angiography, and digital subtraction angiography. Treatment measures included surgical excision (n = 20), sclerotherapy (n = 86, including absolute ethanol [n = 75], polidocanol [n = 8], and pingyangmycin [n = 3]), and combination treatment with intralesional copper wire retention and sclerotherapy(n = 20). After treatment, most of the lesions shrunk obviously or disappeared, and the symptoms were largely relieved. Comprehensive and accurate imaging assessment of VMs is necessary for selecting appropriate treatment. Individual strategy and sequential treatment can achieve effective results and avoid potential complications.
Homepage: https://www.selleckchem.com/products/cc-90011.html
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