Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(51)

Published: Nov. 6, 2019

Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, red blood cell membrane (mRBC)-camouflaged hollow MnO2 (HMnO2 ) catalytic nanosystem embedded with lactate oxidase (LOX) and glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion well synergistic metabolic therapy immunotherapy of tumor. Benefiting from long-circulation property mRBC, can gradually accumulate in site through enhanced permeability retention (EPR) effect. The extracellular consumes TME by catalyzing its oxidation reaction via LOX. Meanwhile, intracellular releases cut off source acid, achieve blockade adenosine triphosphate (ATP) supply. Both processes be sensitized O2 , which produced during decomposition endogenous H2 catalyzed PMLR nanosystem. results show that ceaselessly remove then lead an immunocompetent TME. Moreover, this regulation effectively effect anti-PDL1 without employment any immune agonists avoid autoimmunity.

Language: Английский

---

Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 24, 2022

Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.

Language: Английский

---

Nanotechnology intervention of the microbiome for cancer therapy

Nature Nanotechnology, Journal Year: 2019, Volume and Issue: 14(12), P. 1093 - 1103

Published: Dec. 1, 2019

Language: Английский

---

Social networks strongly predict the gut microbiota of wild mice

The ISME Journal, Journal Year: 2021, Volume and Issue: 15(9), P. 2601 - 2613

Published: March 17, 2021

Abstract The mammalian gut teems with microbes, yet how hosts acquire these symbionts remains poorly understood. Research in primates suggests that microbes can be picked up via social contact, but the role of interactions non-group-living species underexplored. Here, we use a passive tracking system to collect high resolution spatiotemporal activity data from wild mice (Apodemus sylvaticus). Social network analysis revealed association strength strongest predictor microbiota similarity among individuals, controlling for factors including spatial proximity and kinship, which had far smaller or nonsignificant effects. This effect was limited involving males (male-male male-female), implicating sex-dependent behaviours as driving processes. position also predicted richness, well-connected individuals having most diverse microbiotas. Overall, findings suggest contact provides key transmission pathway even relatively asocial mammals, strongly shapes adult microbiota. work underlines potential pick beneficial well pathogens interactions.

Language: Английский

---

Mitochondria: It is all about energy

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

---

Alterations of host-gut microbiome interactions in multiple sclerosis

EBioMedicine, Journal Year: 2022, Volume and Issue: 76, P. 103798 - 103798

Published: Jan. 27, 2022

Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between host system, metabolism diet have not been studied over time this disorder.We performed six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting patients 25 age, sex, race matched healthy control individuals. Gut composition function were characterized using 16S metagenomic shotgun sequencing. Flow cytometry was used to characterize blood cell populations cytokine profiles. Circulating metabolites profiled by untargeted UPLC-MS. A four-day food diary recorded capture habitual dietary pattern participants.Together with changes cells, analysis identified number microbiota decreased compared controls, positively or negatively correlated degree disability patients. demonstrated perturbations their metabolome, such as linoleate pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol methionine. Global correlations disrupted immune-microbiome relationship positive metabolome-microbiome correlation MS. Specific feature association potential network linking meat servings microbe B. thetaiotaomicron, increased Th17 greater abundance meat-associated metabolites. The metabolome profiles remained stable six months individuals.Our multi-system alterations microbiota, at global individual level. Multi-OMICS data integration deciphered important biological that links intakes metabolite, polysaccharides digesting bacteria, circulating proinflammatory marker.This work supported Washington University St. Louis Institute Clinical Translational Sciences, funded, part, Grant Number # UL1 TR000448 from National Institutes Health, Center for Advancing Sciences Award (Zhou Y, Piccio, L, Lovett-Racke Tarr PI); R01 NS10263304 Piccio L); Leon Harriet Felman Fund Human Research (Piccio L Cross AH). Cantoni C. Society Career Transition Fellowship (TA-180531003) donations Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. Italian Sclerosis research fellowship (FISM 2018/B/1) Post-Doctoral (FG-190734474). Anne Manny & Rosalyn Rosenthal-Dr. John Trotter Chair Neuroimmunology Barnes-Jewish Hospital Foundation. content is solely responsibility authors does necessarily represent official views Health.

Language: Английский

---

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 400 - 400

Published: Jan. 31, 2023

A novel syndrome called long-haul COVID or long is increasingly recognized in a significant percentage of individuals within few months after infection with SARS-CoV-2. This disorder characterized by wide range persisting, returning even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine systemic. Some overlapping symptomatologies exist between myalgic encephalomyelitis/chronic fatigue (ME/CFS). Very much like ME/CFS, infections herpes family viruses, immune dysregulation, the persistence inflammation have been reported as most common pattern for development COVID. review describes several factors determinants proposed, elaborating mainly on viral persistence, reactivation latent viruses such Epstein–Barr virus human herpesvirus 6 which are also associated pathology superantigen activation system, disturbance gut microbiome, multiple tissue damage autoimmunity. Based these factors, we propose diagnostic strategies measurement IgG IgM antibodies against SARS-CoV-2, EBV, HHV-6, superantigens, microbiota, biomarkers autoimmunity to better understand manage this multi-factorial continues affect millions people world.

Language: Английский

---

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: July 6, 2022

Abstract In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting gastrointestinal tract human health and disease. According to involvement microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, nutrient uptake), any alteration its composition diversity (i.e., dysbiosis) linked variety pathologies, including cancer. this bidirectional relationship, colonization with various bacterial species is correlated reduced or elevated risk certain cancers. Notably, gut microflora could potentially play direct indirect role tumor initiation progression by inducing chronic inflammation producing toxins metabolites. Therefore, identifying involved their mechanism action be beneficial preventing onset tumors controlling advancement. Likewise, community affects anti-cancer approaches’ therapeutic potential adverse effects immunotherapy chemotherapy). Hence, efficiency should evaluated context microbiome, underlining importance personalized medicine. review, we summarized evidence revealing microbiota's cancer mechanism. We also delineated how predict colon carcinoma development response current treatments improve clinical outcomes.

Language: Английский

---

Autoimmune pre-disease

Autoimmunity Reviews, Journal Year: 2022, Volume and Issue: 22(2), P. 103236 - 103236

Published: Nov. 25, 2022

Language: Английский

---

Gut microbiota and risk of five common cancers: A univariable and multivariable Mendelian randomization study

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(9), P. 10393 - 10405

Published: March 7, 2023

Previous studies have linked gut microbiota with cancer etiology, but the associations for specific are causal or owing to bias remain be elucidated.We performed a two-sample Mendelian randomization (MR) analysis assess effect of on risk. Five common cancers, including breast, endometrial, lung, ovarian, and prostate as well their subtypes (sample sizes ranging from 27,209 228,951) were included outcomes. Genetic information was obtained genome-wide association study (GWAS) comprising 18,340 participants. In univariable MR (UVMR) analysis, inverse variance weighted (IVW) method conducted primary method, robust adjusted profile scores, median, Egger used supplementary methods inference. Sensitivity analyses Cochran Q test, intercept leave-one-out verify robustness results. Multivariable (MVMR) evaluate direct effects risk cancers.UVMR detected higher abundance genus Sellimonas predicted estrogen receptor-positive breast (OR = 1.09, 95% CI 1.05-1.14, p 2.01 × 10-5 ), class Alphaproteobacteria associated lower 0.84, 0.75-0.93, 1.11 10-3 ). found little evidence in current study. MVMR further confirmed that exerted cancer, while driven by factors cancer.Our implies involvement development, which provides novel potential target screening prevention, might an implication future functional analysis.

Language: Английский

---