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Heliyon May 2024Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms...
Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.
PubMed: 38807876
DOI: 10.1016/j.heliyon.2024.e31197 -
Caspian Journal of Internal Medicine 2024Flaxseed powder seems to improve bowel movements in these patients. Therefore, this study compares the effects of flaxseed powder and magnesium hydroxide on bowel...
BACKGROUND
Flaxseed powder seems to improve bowel movements in these patients. Therefore, this study compares the effects of flaxseed powder and magnesium hydroxide on bowel movements of acute myocardial infarction patients hospitalized in ICU.
METHODS
The population of the present parallel randomized controlled clinical trial included 70 acute myocardial infarction patients hospitalized in ICU who had no history of chronic constipation. The patients in the intervention group were given three sachets of flaxseed powder (each sachet was 3 g) twice a day for four days. The patients in the control group were given 20 cc of magnesium hydroxide syrup each morning. The Bristol scale was used to describe stool consistency.
RESULTS
The mean and standard deviation of the number of bowel movements within five days after intervention are 1.86 ± 1.08 and 1.6 ± 0.65 in the intervention and the control groups, respectively. The frequency of normal stool consistency of the first bowel movement is 94.3% for the intervention group and 85.7% for the control group, which shows no significant differences between the two groups in terms of stool consistency and bowel movement frequency (P=0.510). The bowel movements started on average after 35.2±97.97 hours in the flaxseed group and 24.771±2.677 hours in the magnesium hydroxide group (P=0.023).
CONCLUSION
The results showed that flaxseed powder increases bowel movement frequency and improves the patients' stool consistency, but the differences between the two groups are insignificant. Finally, the time to the first defecation was shorter in the magnesium hydroxide group.
PubMed: 38807721
DOI: 10.22088/cjim.15.2.234 -
Communications Biology May 2024SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations...
SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9 zebrafish. Spermidine oxidase (Smox) is increased in smg9 zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.
Topics: Animals; Zebrafish; Nonsense Mediated mRNA Decay; Aging, Premature; Zebrafish Proteins; RNA, Messenger; Oxidative Stress; Mutation
PubMed: 38806677
DOI: 10.1038/s42003-024-06356-6 -
Heliyon May 2024The early prediction of death is a challenge for medical staff. We evaluated the ability of the heart/breathing rate ratio (HBR) to predict mortality.
OBJECTIVES
The early prediction of death is a challenge for medical staff. We evaluated the ability of the heart/breathing rate ratio (HBR) to predict mortality.
METHODS
This was a single-center retrospective observational study of adult patients who had fever with or without respiratory symptoms, who survived at least 2 h after visiting the hospital, and whose lactate levels and vital signs were tested. We evaluated the distribution of mortality at different HBR levels and compared HBR with lactate.
RESULTS
A total of 18,872 fever clinic visits were screened, and 183 patients whose lactate levels were tested were recruited. Patients who had HBR values lower than 4·5 or higher than 5·5 had greater mortality than patients who had HBR values between 4·5 and 5·5 (21·3 % vs. 3·4 %, p = 0·003; 28·9 % vs. 3·4 %, p < 0·001, respectively). In patients whose HBR was <5, the AUROC for HBR for mortality was 0·762 (95 % CI: 0.643-0·880), and that for lactate was 0·701 (95 % CI: 0·564-0·837). In patients whose HBR was ≥5, the AUROC for HBR for mortality was 0·721 (95 % CI: 0·584-0·857), and that for lactate was 0·742 (95 % CI: 0·607-0·848).
CONCLUSIONS
HBR is helpful for stratifying mortality risk among critically ill patients in acute care clinics for infectious diseases.
PubMed: 38803872
DOI: 10.1016/j.heliyon.2024.e31187 -
Journal of Pain Research 2024Our pilot study shows that a modified moxibustion therapy called Ma's bamboo-based medicinal moxibustion can alleviate the symptoms of low back pain in lumbar disc... (Clinical Trial)
Clinical Trial
OBJECTIVE
Our pilot study shows that a modified moxibustion therapy called Ma's bamboo-based medicinal moxibustion can alleviate the symptoms of low back pain in lumbar disc herniation (LDH), and has the potential to treat LDH. The aim of this study is to evaluate the efficacy and safety of Ma's bamboo-based medicinal moxibustion for low back pain in LDH.
METHODS
A total of 312 LDH patients with low back pain were randomized to receive Ma's bamboo-based medicinal moxibustion (MBMM) or acupuncture (AT). The primary efficacy measure was the change of Visual Analogue Scale (VAS) on the 14th day compared with that at baseline. The secondary efficacy measures included VAS score, Oswestry disability index (ODI), modified Japanese Orthopaedic Association (M-JOA) score, and the content of β-endorphin (β-EP) and substance-P (SP). The safety measures included the occurrence of adverse events and the changes in laboratory indicators.
RESULTS
In total, 304 patients were incorporated for the analysis of efficacy, including 96 males and 208 females, aged 21-65 years. There was no statistically significant difference in the change of VAS score between the two groups on the 14th day [mean difference (95% CI) = -2.31 (-2.48, -2.13) and -2.28 (-2.45, -2.11), respectively; = 0.819]. The VAS, ODI, and M-JOA scores changed after the intervention in both groups ( <0.001), with increased β-EP content ( = 0.014, = 0.032) and decreased SP content ( <0.001, = 0.048). The ODI score ( = 0.039) and M-JOA score ( = 0.032) of the MBMM group on the 28th day were lower than those of the AT group.
CONCLUSION
The efficacy of Ma's bamboo-based medicinal moxibustion therapy in relieving low back pain of LDH patients is comparable to that of acupuncture, and it has post-effect advantages in improving lumbar dysfunction and daily living ability, which can be used as a safe and effective alternative method for LDH treatment.
PubMed: 38803694
DOI: 10.2147/JPR.S457724 -
Frontiers in Neurology 2024Ventilator-Associated Pneumonia (VAP) severely impacts stroke patients' prognosis after endovascular treatment. Hence, this study created a nomogram to predict the...
BACKGROUND
Ventilator-Associated Pneumonia (VAP) severely impacts stroke patients' prognosis after endovascular treatment. Hence, this study created a nomogram to predict the occurrence of VAP after endovascular treatment.
METHODS
The individuals with acute ischemic stroke and large vessel occlusion (AIS-LVO) who received mechanical ventilation and endovascular therapy between July 2020 and August 2023 were included in this retrospective study. The predictive model and nomogram were generated by performing feature selection optimization using the LASSO regression model and multifactor logistic regression analysis and assessed the evaluation, verification and clinical application.
RESULTS
A total of 184 individuals (average age 61.85 ± 13.25 years, 73.37% male) were enrolled, and the rate of VAP occurrence was found to be 57.07%. Factors such as the Glasgow Coma Scale (GCS) score, duration of stay in the Intensive Care Unit (ICU), dysphagia, Fazekas scale 2 and admission diastolic blood pressure were found to be associated with the occurrence of VAP in the nomogram that demonstrating a strong discriminatory power with AUC of 0.862 (95% CI, 0.810-0.914), and a favorable clinical net benefit.
CONCLUSION
This nomogram, comprising GCS score, ICU duration, dysphagia, Fazekas scale 2 and admission diastolic blood pressure, can aid clinicians in predicting the identification of high-risk patients for VAP following endovascular treatment in large vessel occlusion stroke.
PubMed: 38803642
DOI: 10.3389/fneur.2024.1351458 -
Frontiers in Pharmacology 2024Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive... (Review)
Review
Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.
PubMed: 38803440
DOI: 10.3389/fphar.2024.1360179 -
Frontiers in Endocrinology 2024Hypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women's physical and mental health, and the...
OBJECTIVES
Hypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women's physical and mental health, and the impact of the latter on the offspring cannot not be ignored. Observational studies have investigated the correlation between uterine leiomyoma (UL) and the above conditions, but the relationship remains unclear. In this study, we employed two-sample Mendelian randomization (MR) analysis to assess the association between UL and hypertension, HDP, as well as blood pressure.
METHODS
We collected genetic association data of UL (35,474 cases), hypertension (129,909 cases), HDP (gestational hypertension with 8,502 cases, pre-eclampsia with 6,663 cases and eclampsia with 452cases), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both 757,601 participants) from published available genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) associated with UL phenotype were used as instrumental variables, and hypertension, three sub-types of HDP, SBP and DBP were used as outcomes. The inverse-variance weighted (IVW) method was employed as the primary method of causal inference. Heterogeneity was assessed using Cochran's Q test, and sensitivity analyses were conducted using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) tests to evaluate the pleiotropy of instrumental variables. PhenoScanner search was used to remove confounding SNP. Robustness and reliability of the results were assessed using methods such as the weighted median and weighted mode.
RESULTS
The IVW analysis revealed a positive correlation between genetically predicted UL and SBP [odds ratio (OR)= 1.67, 95% confidence interval (CI):1.24~2.25, = 0.0007], and no statistical association was found between UL and hypertension, HDP, or DBP. The MR-Egger regression suggested that the above causal relationships were not affected by horizontal pleiotropy. The weighted median method and weighted model produced similar results to the IVW.
CONCLUSION
Based on large-scale population GWAS data, our MR analysis suggested a causal relationship between UL and SBP. Therefore, women with UL, especially pregnant women, should pay attention to monitoring their blood pressure levels. For patients with hypertension who already have UL, interventions for UL may serve as potential therapeutic methods for managing blood pressure.
Topics: Humans; Female; Mendelian Randomization Analysis; Leiomyoma; Uterine Neoplasms; Blood Pressure; Pregnancy; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Hypertension; Hypertension, Pregnancy-Induced
PubMed: 38800482
DOI: 10.3389/fendo.2024.1373724 -
Cardiology Research and Practice 2024Cardiomyopathy encompasses a broad spectrum of diseases affecting myocardial tissue, characterized clinically by abnormalities in cardiac structure, heart failure,...
BACKGROUND
Cardiomyopathy encompasses a broad spectrum of diseases affecting myocardial tissue, characterized clinically by abnormalities in cardiac structure, heart failure, and/or arrhythmias. Clinically heterogeneous, major types include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RM), ischemic cardiomyopathy (ICM), among which DCM is more prevalent, while ICM exhibits higher incidence and mortality rates. Myocardial injury during cardiomyopathy progression may lead to myocardial fibrosis. Failure to intervene early and inhibit the process of myocardial fibrosis may culminate in heart failure. Cardiac fibroblasts constitute crucial cellular components determining the extent and quality of myocardial fibrosis, with various subpopulations exerting diverse roles in cardiomyopathy progression. Despite this, understanding of the cellular plasticity and transcriptional regulatory networks of cardiac fibroblasts in cardiomyopathy remains limited. Therefore, in this study, we conducted comprehensive single-cell analysis of cardiac fibroblasts in cardiomyopathy to explore differences in cellular plasticity and transcriptional regulatory networks among fibroblast subpopulations, with the aim of providing as many useful references as possible for the diagnosis, prognosis, and treatment of cardiomyopathy.
MATERIALS AND METHODS
Cells with mitochondrial gene expression comprising >20% of total expressed genes were excluded. Differential expression genes (DEGs) and stemness genes within cardiac fibroblast subpopulations were subjected to Gene Ontology (GO) analysis of biological processes (BP) and AUCell analysis. Monocle software was employed to analyze the pseudo-temporal trajectory of cardiac fibroblasts in cardiomyopathy. Additionally, the Python package SCENIC was utilized to assess enrichment of transcription factors and activity of regulators within cardiac fibroblast subpopulations in cardiomyopathy.
RESULTS
Following batch effect correction, 179,927 cells were clustered into 32 clusters, designated as T_NK cells, endothelial cells, myeloid cells, fibroblasts, pericytes, SMCs, CMs, proliferating cells, EndoCs, and EPCs. Among them, 8148 fibroblasts were further subdivided into 4 subpopulations, namely C0 THBS4+ Fibroblasts, C1 LINC01133+ Fibroblasts, C2 FGF7+ Fibroblasts, and C3 AGT + Fibroblasts. Results from GO_BP and AUCell analyses suggest that C3 AGT + Fibroblasts may be associated with immune response activation, protein transport, and myocardial contractile function, correlating with disease progression in cardiomyopathy. Transcription factor enrichment analysis indicates that FOS is the most significant TF in C3 AGT + Fibroblasts, also associated with the M1 module, possibly implicated in protein hydrolysis, intracellular DNA replication, and cell proliferation. Moreover, correlation analysis of transcriptional regulatory activity between fibroblast subpopulations reveals a more pronounced heterogeneity within C3 AGT + Fibroblasts in cardiomyopathy.
CONCLUSION
C3 AGT + Fibroblasts exhibit increased sensitivity towards adverse outcomes in cardiomyopathy, such as myocardial fibrosis and impaired cardiac contractile function, compared to other cardiac fibroblast subpopulations. The differential cellular plasticity and transcriptional regulatory activity between C3 AGT + Fibroblasts and other subgroups offer new perspectives for targeting fibroblast subpopulation activity to treat cardiomyopathy. Additionally, stemness genes EPAS1 and MYC, along with the regulator FOS, may play roles in modulating the biological processes of cardiac fibroblasts in cardiomyopathy.
PubMed: 38799173
DOI: 10.1155/2024/3131633 -
Life (Basel, Switzerland) Apr 2024The LPS-induced inflammation model is widely used for studying inflammatory processes due to its cost-effectiveness, reproducibility, and faithful representation of key...
The LPS-induced inflammation model is widely used for studying inflammatory processes due to its cost-effectiveness, reproducibility, and faithful representation of key hallmarks. While researchers often validate this model using clinical cytokine markers, a comprehensive understanding of gene regulatory mechanisms requires extending investigation beyond these hallmarks. Our study leveraged multiple whole-blood bulk RNA-seq datasets to rigorously compare the transcriptional profiles of the well-established LPS-induced inflammation model with those of several human diseases characterized by systemic inflammation. Beyond conventional inflammation-associated systems, we explored additional systems indirectly associated with inflammatory responses (i.e., ISR, RAAS, and UPR) using a customized core inflammatory gene list. Our cross-condition-validation approach spanned four distinct conditions: systemic lupus erythematosus (SLE) patients, dengue infection, candidemia infection, and staphylococcus aureus exposure. This analysis approach, utilizing the core gene list aimed to assess the model's suitability for understanding the gene regulatory mechanisms underlying inflammatory processes triggered by diverse factors. Our analysis resulted in elevated expressions of innate immune-associated genes, coinciding with suppressed expressions of adaptive immune-associated genes. Also, upregulation of genes associated with cellular stresses and mitochondrial innate immune responses underscored oxidative stress as a central driver of the corresponding inflammatory processes in both the LPS-induced and other inflammatory contexts.
PubMed: 38792580
DOI: 10.3390/life14050558