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Nutrients Jun 2024Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have...
Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have demonstrated that oral administration with probiotics may increase the immune response to lung infection via the gut-lung axis leading to the alleviation of the pulmonary disease. In this study, we evaluated the effects of oral administration of MIANGUAN2 (MIANGUAN2) on influenza infection in a mouse model. Our results showed that oral administration of MIANGUAN2 significantly improved weight loss, lung index, and lung pathology, and decreased lung viral load of influenza-infected mice. Additionally, MIANGUAN2-treated mice showed significantly lower levels of TNF-α, IL-1β, IFN-γ, and IL-12p70 and higher production of IL-4 in the lung. In accordance with this, the transcriptome analysis of the lung indicated that MIANGUAN2-treated mice had reduced expression of inflammation markers, such as TNF, apoptosis, and the NF-Kappa B pathway. Furthermore, the administration of MIANGUAN2 restored the SCFAs profiles through regulating the gut microbiota. SCFA-producing bacteria, such as p_Firmicutes, f_Lachnospiraceae, and f_Ruminococcaceae, were enriched in the MIANGUAN2-treated group compared with PBS-treated group. Consistently, the concentrations of SCFAs in the MIANGUAN2 group were significantly higher than those in the PBS-treated group. In addition, the concentrations of SCFAs were positively correlated with SCFA-producing bacteria, such as , while being negatively correlated with the virial titers and proinflammatory cytokines. In conclusion, this animal study suggests that MIANGUAN2 may alleviate the influenza infection by altering the gut microbiota composition and increasing the levels of gut microbiota-derived SCFAs.
Topics: Animals; Gastrointestinal Microbiome; Pediococcus pentosaceus; Fatty Acids, Volatile; Mice; Probiotics; Lung; Orthomyxoviridae Infections; Disease Models, Animal; Cytokines; Male
PubMed: 38931277
DOI: 10.3390/nu16121923 -
Microorganisms May 2024The use of proton pump inhibitors (PPIs) has increased considerably in many Western countries, and there is concern that numerous conditions and diseases associated with... (Review)
Review
The use of proton pump inhibitors (PPIs) has increased considerably in many Western countries, and there is concern that numerous conditions and diseases associated with PPI use may be adverse events. The main function of gastric acid is to defend the organism against orally ingested microorganisms, and there is also concern that alterations not only in the gastric microbiome but also the downstream intestinal microbiome may increase the risk of disease or alter the course of preexisting disease. The current study is a systematic review of the available evidence from experimental trials investigating the effects of PPIs on the gastrointestinal microbiota by next-generation sequencing. Thirteen studies were identified. The effects of PPIs were seen on alterations in diversity and richness in some of the studies, while a larger proportion of the studies detected alterations at various taxonomic levels. The general finding was that PPI use caused an increase in bacteria normally found in the oral microbiota in both the upper and lower GI tract. The most consistent taxonomic alterations seemed to be increases in oral flora along the axis Streptococcaceae and at genus level and various spp., as well as Veillonellaceae, and .
PubMed: 38930492
DOI: 10.3390/microorganisms12061110 -
Microorganisms May 2024Periodontitis is a destructive inflammatory response triggered by dysbiosis. LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the...
Periodontitis is a destructive inflammatory response triggered by dysbiosis. LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the effect of LA5 on alveolar bone loss in a periodontitis murine model and investigated its effect on the oral and gut microbiomes. and were inoculated in C57BL/6 mice (P+), with LA5 (L+). SHAM infected controls (P- and/or L- groups) were also evaluated. After 45 days, alveolar bone loss in the maxilla and oral and gut microbiomes were determined. The administration of LA5 controlled the microbial consortium-induced alveolar bone loss. Periodontopathogens infection resulted in shifts in the oral and gut microbiomes consistent with dysbiosis, and LA5 reshaped these changes. The oral microbiome of P+L- group showed the increased abundance of , , , and , which were attenuated by the administration of LA5 to the infected group (P+L+). The administration of LA5 to otherwise non-infected mice resulted in the increased abundance of the superphylum Patescibacteria and the family in the gut. These data indicate LA5 as a candidate probiotic for the control of periodontitis.
PubMed: 38930439
DOI: 10.3390/microorganisms12061057 -
Brain Sciences Jun 2024Both chronic and recurrent spinal pain alter sensorimotor integration (SMI), which is demonstrated using complex neurophysiological techniques. Currently, there is no...
Both chronic and recurrent spinal pain alter sensorimotor integration (SMI), which is demonstrated using complex neurophysiological techniques. Currently, there is no patient-reported outcome measure that documents and/or assesses SMI in populations with spinal problems. The purpose of this study was to develop the Sensory-Motor Dysfunction Questionnaire (SMD-Q) and assess its test-retest reliability and internal consistency in individuals with recurrent spinal pain. The SMD-Q was developed based on the existing literature on motor control disturbances associated with disordered SMI. The initial SMD-Q drafts underwent review by two separate panels of subject matter experts and a focus group with subclinical spine pain. Their suggestions were incorporated into the questionnaire prior to reliability testing. The questionnaire was administered twice at a seven-day interval using Qualtrics. A total of 20 participants (14 females and 6 males; 20.95 ± 2.46 years of age) completed the study. Quadratic weighted kappa (K) was used to assess test-retest reliability and Cronbach's alpha (α) was used to assess internal consistency. Four items had a K < 0.40, seven had a 0.40 < K < 0.75, and one had a K > 0.75 (excellent agreement), with excellent internal consistency (α > 0.90). The pilot SMD-Q appears to reliably measure altered SMI, suggesting that revisions and testing with a larger sample are worth pursuing.
PubMed: 38928619
DOI: 10.3390/brainsci14060619 -
Brain Sciences Jun 2024Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening... (Review)
Review
BACKGROUND
Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs.
METHODS
This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.
RESULTS
The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol.
CONCLUSIONS
BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research.
PubMed: 38928583
DOI: 10.3390/brainsci14060583 -
International Journal of Molecular... Jun 2024While urinary polymerase chain reaction (PCR) testing is effective in organism identification in patients with complex urinary tract infections (cUTI), limited data...
While urinary polymerase chain reaction (PCR) testing is effective in organism identification in patients with complex urinary tract infections (cUTI), limited data exists on the clinical usefulness of this test. We serially surveyed physicians treating symptomatic patients with cUTI both at presentation and after PCR, and urine culture (UC) results were available to ascertain how the test results modified the therapy. A total of 96 unique surveys completed by 21 providers were included in the data analysis. The mean age for female and male patients was 69.4 ± 15.5 and 71.6 ± 12.7 years, respectively. The test positivity and line-item concordance for UC and PCR were consistent with prior reports. The PCR results modified or confirmed treatment in 59/96 (61.5%) and 25/96 (26.0%) of the cases, respectively, with 12/29 (41.4%) and 47/67 (70.1%) having negative and positive PCR results, respectively, resulting in treatment change (difference 28.7%, < 0.01). Of these, 55/59 (57.3%) were alterations in the antibiotic regimen. PCR use to modify treatment was similar across providers and not statistically different when stratified by patient age, gender, or prior empiric therapy. In 31/59 (52.5%) of the cases, the PCR results modified the treatment where UC would not; conversely, UC would have modified the treatment in 3/37 (8.1%) of the cases where PCR did not (difference 44.4%, < 0.01). We find that PCR test results are used by clinicians in managing cUTI, and use of this test provides an opportunity to improve antibiotic stewardship in this difficult-to-treat subset of patients.
Topics: Humans; Urinary Tract Infections; Female; Male; Aged; Polymerase Chain Reaction; Clinical Decision-Making; Middle Aged; Aged, 80 and over; Anti-Bacterial Agents; Urinalysis
PubMed: 38928323
DOI: 10.3390/ijms25126616 -
International Journal of Molecular... Jun 2024Mitochondrial quality control is essential in mitochondrial function. To examine the importance of Parkin-dependent mechanisms in mitochondrial quality control, we...
Mitochondrial quality control is essential in mitochondrial function. To examine the importance of Parkin-dependent mechanisms in mitochondrial quality control, we assessed the impact of modulating Parkin on proteome flux and mitochondrial function in a context of reduced mtDNA fidelity. To accomplish this, we crossed either the Parkin knockout mouse or ParkinW402A knock-in mouse lines to the Polg mitochondrial mutator line to generate homozygous double mutants. In vivo longitudinal isotopic metabolic labeling was followed by isolation of liver mitochondria and synaptic terminals from the brain, which are rich in mitochondria. Mass spectrometry and bioenergetics analysis were assessed. We demonstrate that slower mitochondrial protein turnover is associated with loss of mtDNA fidelity in liver mitochondria but not synaptic terminals, and bioenergetic function in both tissues is impaired. Pathway analysis revealed loss of mtDNA fidelity is associated with disturbances of key metabolic pathways, consistent with its association with metabolic disorders and neurodegeneration. Furthermore, we find that loss of Parkin leads to exacerbation of Polg-driven proteomic consequences, though it may be bioenergetically protective in tissues exhibiting rapid mitochondrial turnover. Finally, we provide evidence that, surprisingly, dis-autoinhibition of Parkin (ParkinW402A) functionally resembles Parkin knockout and fails to rescue deleterious Polg-driven effects. Our study accomplishes three main outcomes: (1) it supports recent studies suggesting that Parkin dependence is low in response to an increased mtDNA mutational load, (2) it provides evidence of a potential protective role of Parkin insufficiency, and (3) it draws into question the therapeutic attractiveness of enhancing Parkin function.
Topics: Animals; DNA Polymerase gamma; Ubiquitin-Protein Ligases; Mice; DNA, Mitochondrial; Mice, Knockout; Mutation; Proteomics; Proteome; Mitochondria; Mitochondria, Liver; Mitochondrial Proteins
PubMed: 38928146
DOI: 10.3390/ijms25126441 -
Genes May 2024Grain filling is critical for determining yield and quality, raising the question of whether central coordinators exist to facilitate the uptake and storage of various...
Grain filling is critical for determining yield and quality, raising the question of whether central coordinators exist to facilitate the uptake and storage of various substances from maternal to filial tissues. The duplicate NAC transcription factors ZmNAC128 and ZmNAC130 could potentially serve as central coordinators. By analyzing differentially expressed genes from mutants across different genetic backgrounds and growing years, we identified 243 highly and differentially expressed genes (hdEGs) as the core target genes. These 243 hdEGs were associated with storage metabolism and transporters. ZmNAC128 and ZmNAC130 play vital roles in storage metabolism, and this study revealed two additional starch metabolism-related genes, and , as their direct targets. A key finding of this study was the inclusion of 17 transporter genes within the 243 hdEGs, with significant alterations in the levels of more than 10 elements/substances in mutant kernels. Among them, six out of the nine upregulated transporter genes were linked to the transport of heavy metals and metalloids (HMMs), which was consistent with the enrichment of cadmium, lead, and arsenic observed in mutant kernels. Interestingly, the levels of Mg and Zn, minerals important to biofortification efforts, were reduced in mutant kernels. In addition to their direct involvement in sugar transport, ZmNAC128 and ZmNAC130 also activate the expression of the endosperm-preferential nitrogen and phosphate transporters and . This coordinated regulation limits the intake of HMMs, enhances biofortification, and facilitates the uptake and storage of essential nutrients.
Topics: Zea mays; Gene Expression Regulation, Plant; Plant Proteins; Transcription Factors; Seeds; Edible Grain; Nutrients
PubMed: 38927600
DOI: 10.3390/genes15060663 -
The Korean Journal of Physiology &... Jul 2024Mutations within the gene, which encodes the α-subunit 5 (Na1.5) of the voltage-gated Na channel, have been linked to three distinct cardiac arrhythmia disorders: long...
Mutations within the gene, which encodes the α-subunit 5 (Na1.5) of the voltage-gated Na channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the Na1.5 current (I) in HEK293 cells transfected with the wild-type and mutant with or without co-expression. The amplitude of I was not altered in mutant (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of with p.A385T/R504T revealed significant reduction of I and slower recovery from inactivation, consistent with the loss-of-function in Na channels. The dependent reduction of I was also observed in a single mutation p.R504T, but p.A385T co-expressed with showed no reduction. In contrast, the slower recovery from inactivation with was observed in A385T while not in R504T. The expression of is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of Na1.5, respectively.
PubMed: 38926839
DOI: 10.4196/kjpp.2024.28.4.313 -
Nature Cell Biology Jun 2024KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these...
KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain. Global chromatin profiling and chromatin immunoprecipitation followed by sequencing revealed altered H3K4me1, H3K27ac and H3K27me3 chromatin marks in knockout cells and demonstrated enhanced binding of the H3K27me3 lysine demethylase KDM6A, which significantly correlated with gene expression. We identified Mmp3 as being commonly upregulated via epigenetic mechanisms in both knockout models. Consistent with these findings, samples from patients with KMT2C-mutant TNBC have higher MMP3 levels. Downregulation or pharmacological inhibition of KDM6A diminished Mmp3 upregulation induced by the loss of histone-lysine N-methyltransferase 2 (KMT2) and prevented brain metastasis similar to direct downregulation of Mmp3. Taken together, we identified the KDM6A-matrix metalloproteinase 3 axis as a key mediator of KMT2C/D loss-driven metastasis in TNBC.
PubMed: 38926506
DOI: 10.1038/s41556-024-01446-3