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Annual Review of Biochemistry Jun 2023The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by... (Review)
Review
The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.
Topics: Animals; Humans; Parkinson Disease; Polyamines; Neuroprotection; Parkinsonian Disorders; Spermidine; Mammals
PubMed: 37018845
DOI: 10.1146/annurev-biochem-071322-021330 -
Microbiome Jun 2023Intestinal inflammation has become a threatening concern in chicken production worldwide and is closely associated with Th17/Treg cell imbalance. Several studies...
BACKGROUND
Intestinal inflammation has become a threatening concern in chicken production worldwide and is closely associated with Th17/Treg cell imbalance. Several studies described that gut microbiota is significantly implicated in chicken growth by modulating intestinal immune homeostasis and immune cell differentiation. Whether reshaping gut microbiota by fecal microbiota transplantation (FMT) could improve chicken growth by balancing Th17/Treg cells is an interesting question.
RESULTS
Here, the chickens with significantly different body weight from three different breeds (Turpan cockfighting × White Leghorn chickens, white feather chickens, and yellow feather chickens) were used to compare Th17 and Treg cells. qPCR and IHC staining results indicated that Th17 cell-associated transcriptional factors Stat3 and rorγt and cytokines IL-6, IL-17A, and IL-21 were significantly (P < 0.05) higher in the jejunum of low body weight chickens, while Treg cell-associated transcriptional factor foxp3 and cytokines TGF-β and IL-10 were significantly (P < 0.05) lower in the jejunum of low body weight chickens, indicating imbalanced Th17/Treg cells were closely related to chicken growth performance. Transferring fecal microbiota from the healthy donor with better growth performance and abundant Lactobacillus in feces to 1-day-old chicks markedly increased growth performance (P < 0.001), significantly decreased Th17 cell-associated transcriptional factors and cytokines, and increased Treg cell-associated transcriptional factors and cytokines in the jejunum (P < 0.05). Furthermore, FMT increased the abundance of Lactobacillus (FMT vs Con; 84.98% vs 66.94%). Besides, the metabolites of tryptophan including serotonin, indole, and 5-methoxyindoleacetate were increased as well, which activated their receptor aryl-hydrocarbon-receptor (AhR) and expressed more CYP1A2 and IL-22 to maintain Th17/Treg cell balance and immune homeostasis.
CONCLUSION
These findings suggested that imbalanced Th17/Treg cells decreased chicken growth performance, while FMT-reshaped gut microbiota, i.e., higher Lactobacilli, increased chicken growth performance by balancing Th17/Treg cells. Video Abstract.
Topics: Animals; T-Lymphocytes, Regulatory; Chickens; Fecal Microbiota Transplantation; Th17 Cells; Jejunum; Cytokines; Body Weight
PubMed: 37344888
DOI: 10.1186/s40168-023-01569-z -
Journal of Neuroengineering and... Jul 2023Virtual reality (VR) is a promising solution for individuals with Parkinson's disease (PD) who experience symptoms that affect their daily activities and independence.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Virtual reality (VR) is a promising solution for individuals with Parkinson's disease (PD) who experience symptoms that affect their daily activities and independence. Through VR-based rehabilitation, patients can improve their motor skills in a safe and stress-free environment, making it an attractive alternative to traditional in-person rehabilitation during the COVID-19 pandemic. This study aimed to provide the most recent and convincing evidence on the rehabilitative effects of VR technology compared with conventional treatments.
METHODS
Two investigators systematically searched Embase, MEDLINE, CINAHL, PEDro, and the Cochrane Library from their inception until May 31, 2022, to identify randomized controlled trials (RCTs) comparing the effectiveness of VR training with that of conventional treatment for patients with PD. Studies were selected based on the patient, intervention, comparator, and outcome criteria and assessed for the risk of bias using the Cochrane tool. Meta-analysis was conducted by pooling mean differences with 95% confidence intervals.
RESULTS
A total of 14 RCTs, involving 524 participants, were included in the meta-analysis. The results indicated that VR-based rehabilitation significantly improved balance function, as measured using the Berg balance scale (BBS) and activities-specific balance confidence. However, no statistically significant differences in gait ability, activities of daily living, motor function, and quality of life were observed between the experimental and control groups. Subgroup analysis revealed that combination therapy affected heterogeneity in the BBS analysis. Meta-regression analysis demonstrated a significant positive relationship, indicating that more recent studies have shown greater improvements in balance function.
CONCLUSION
This study's findings suggest that VR-based rehabilitation is a promising intervention for improving balance function in patients for PD compared with conventional treatment, and recent research supports its efficacy. However, future research should focus on conducting long-term follow-up studies and developing standardized protocols to comprehensively establish this intervention's potential benefits.
Topics: Humans; Gait; Parkinson Disease; Virtual Reality
PubMed: 37475014
DOI: 10.1186/s12984-023-01219-3 -
Signal Transduction and Targeted Therapy Sep 2023The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves not only as a bicistronic message RNA to translate core protein (Cp) and DNA polymerase (Pol), but also as...
The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves not only as a bicistronic message RNA to translate core protein (Cp) and DNA polymerase (Pol), but also as the template for reverse transcriptional replication of viral DNA upon packaging into nucleocapsid. Although it is well known that pgRNA translates much more Cp than Pol, the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive. In this study, we systematically profiled HBV nucleocapsid- and pgRNA-associated cellular proteins by proteomic analysis and identified TIA-1-related protein (TIAR) as a novel cellular protein that binds pgRNA and promotes HBV DNA replication. Interestingly, loss- and gain-of-function genetic analyses showed that manipulation of TIAR expression did not alter the levels of HBV transcripts nor the secretion of HBsAg and HBeAg in human hepatoma cells supporting HBV replication. However, Ribo-seq and PRM-based mass spectrometry analyses demonstrated that TIAR increased the translation of Pol but decreased the translation of Cp from pgRNA. RNA immunoprecipitation (RIP) and pulldown assays further revealed that TIAR directly binds pgRNA at the 5' stem-loop (ε). Moreover, HBV replication or Cp expression induced the increased expression and redistribution of TIAR from the nucleus to the cytoplasm of hepatocytes. Our results thus imply that TIAR is a novel cellular factor that regulates HBV replication by binding to the 5' ε structure of pgRNA to tip the balance of Cp and Pol translation. Through induction of TIAR translocation from the nucleus to the cytoplasm, Cp indirectly regulates the Pol translation and balances Cp and Pol expression levels in infected hepatocytes to ensure efficient viral replication.
Topics: Humans; Cytoplasm; Hepatitis B virus; Proteomics; RNA
PubMed: 37699883
DOI: 10.1038/s41392-023-01573-7 -
Molecular Plant Feb 2024The growth-promoting hormones brassinosteroids (BRs) and their key signaling component BZR1 play a vital role in balancing normal growth and defense reactions. Here, we...
The growth-promoting hormones brassinosteroids (BRs) and their key signaling component BZR1 play a vital role in balancing normal growth and defense reactions. Here, we discovered that BRs and OsBZR1 upregulated sakuranetin accumulation and conferred basal defense against Magnaporthe oryzae infection under normal conditions. Resource shortages, including phosphate (Pi) deficiency, potentially disrupt this growth-defense balance. OsSPX1 and OsSPX2 have been reported to sense Pi concentration and interact with the Pi signal mediator OsPHR2, thus regulating Pi starvation responses. In this study, we discovered that OsSPX1/2 interacts with OsBZR1 in both Pi-sufficient and Pi-deficient conditions, inhibiting BR-responsive genes. When Pi is sufficient, OsSPX1/2 is captured by OsPHR2, enabling most of OsBZR1 to promote plant growth and maintain basal resistance. In response to Pi starvation, more OsSPX1/2 is released from OsPHR2 to inhibit OsBZR1 activity, resulting in slower growth. Collectively, our study reveals that the OsBZR1-SPX1/2 module balances the plant growth-immunity trade-off in response to Pi availability.
Topics: Plant Proteins; Oryza; Phosphates; Brassinosteroids; Gene Expression Regulation, Plant
PubMed: 38069474
DOI: 10.1016/j.molp.2023.12.003 -
Nutrients Jul 2023To clarify the effects of dietary inflammatory and pro-oxidative potential, we investigated the impact of the Dietary Inflammation Index (DII) and the Dietary Oxidative...
Association of Dietary Inflammatory Index and Dietary Oxidative Balance Score with All-Cause and Disease-Specific Mortality: Findings of 2003-2014 National Health and Nutrition Examination Survey.
To clarify the effects of dietary inflammatory and pro-oxidative potential, we investigated the impact of the Dietary Inflammation Index (DII) and the Dietary Oxidative Balance Score (DOBS) on all-cause and disease-specific mortality. For DII and DOBS, 17,550 and 24,527 participants were included. Twenty-six and seventeen dietary factors were selected for scoring. Cox proportional hazards regression models were used. DII and DOBS were significantly associated with all-cause, CVD, and cancer mortality in this nationally representative sample of American adults. Compared with the lowest DII, the multivariable-adjusted hazard ratios (95% CI) of all-cause, CVD, and cancer mortality for the highest were 1.49 (1.23-1.80), 1.58 (1.08-2.33), and 1.56 (1.07-2.25). The highest quartile of DOBS was associated with the risk of all-cause death (HR 0.71, 95% CI 0.59-0.86). Pro-inflammatory and pro-oxidative diets were associated with increased risk for all-cause (HR 1.59, 95% CI 1.28-1.97), and CVD (HR 2.29, 95% CI 1.33-3.94) death compared to anti-inflammatory and antioxidant diets. Similar results were observed among the stratification analyses. Inflammation-reducing and oxidative-balancing diets are linked to lower all-cause and CVD mortality. Diets impact health by regulating inflammation and oxidative stress.
Topics: Adult; Humans; Nutrition Surveys; Cardiovascular Diseases; Prospective Studies; Diet; Inflammation; Neoplasms; Risk Factors
PubMed: 37513566
DOI: 10.3390/nu15143148 -
Frontiers in Microbiology 2023The global aging situation is severe, and the medical pressures associated with aging issues should not be underestimated. The need and feasibility of studying aging and... (Review)
Review
The global aging situation is severe, and the medical pressures associated with aging issues should not be underestimated. The need and feasibility of studying aging and intervening in aging have been confirmed. Aging is a complex natural physiological progression, which involves the irreversible deterioration of body cells, tissues, and organs with age, leading to enhanced risk of disease and ultimately death. The intestinal microbiota has a significant role in sustaining host dynamic balance, and the study of bidirectional communication networks such as the brain-gut axis provides important directions for human disease research. Moreover, the intestinal microbiota is intimately linked to aging. This review describes the intestinal microbiota changes in human aging and analyzes the causal controversy between gut microbiota changes and aging, which are believed to be mutually causal, mutually reinforcing, and inextricably linked. Finally, from an anti-aging perspective, this study summarizes how to achieve delayed aging by targeting the intestinal microbiota. Accordingly, the study aims to provide guidance for further research on the intestinal microbiota and aging.
PubMed: 38098677
DOI: 10.3389/fmicb.2023.1268142 -
Experimental & Molecular Medicine Jun 2023Sphingolipids, which are components of cellular membranes and organ tissues, can be synthesized or degraded to modulate cellular responses according to environmental... (Review)
Review
Sphingolipids, which are components of cellular membranes and organ tissues, can be synthesized or degraded to modulate cellular responses according to environmental cues, and the balance among the different sphingolipids is important for directing immune responses, regardless of whether they originate, as intra- or extracellular immune events. Recent progress in multiomics-based analyses and methodological approaches has revealed that human health and diseases are closely related to the homeostasis of sphingolipid metabolism, and disease-specific alterations in sphingolipids and related enzymes can be prognostic markers of human disease progression. Accumulating human clinical data from genome-wide association studies and preclinical data from disease models provide support for the notion that sphingolipids are the missing pieces that supplement our understanding of immune responses and diseases in which the functions of the involved proteins and nucleotides have been established. In this review, we analyze sphingolipid-related enzymes and reported human diseases to understand the important roles of sphingolipid metabolism. We discuss the defects and alterations in sphingolipid metabolism in human disease, along with functional roles in immune cells. We also introduce several methodological approaches and provide summaries of research on sphingolipid modulators in this review that should be helpful in studying the roles of sphingolipids in preclinical studies for the investigation of experimental and molecular medicines.
Topics: Humans; Sphingolipids; Genome-Wide Association Study; Cell Membrane; Homeostasis
PubMed: 37258585
DOI: 10.1038/s12276-023-01018-9