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Journal of Ethnopharmacology Jun 2024Morinda officinalis How. is a commonly used traditional Chinese herb with the pharmacological properties of tonifying liver and kidney, and enhancing bone and muscle....
ETHNOPHARMACOLOGICAL RELEVANCE
Morinda officinalis How. is a commonly used traditional Chinese herb with the pharmacological properties of tonifying liver and kidney, and enhancing bone and muscle. Iridoid glycosides are the predominant components of this plant, including monotropein, asperuloside, deacetylasperuloside and deacetylasperulosidic acid with their contents reaching more than 2%. Methotrexate (MTX) is the drug of choice for the treatment of rheumatoid arthritis (RA), but liver injury induced by MTX limits its wider use for RA. M. officinalis iridoid glycoside (MOIG) is reported as having anti-RA and hepatoprotective effects, but the exact efficacy on MTX-induced liver injury and the underlying molecular mechanism remain unclear.
AIM
To elucidate the mitigating effect of MOIG against liver injury in RA rats treated with MTX, and explore the possible mechanism.
MATERIALS AND METHODS
The effect and mechanism of MOIG were investigated in Wistar rats with collagen-induced arthritis (CIA) which were then treated with MTX, and MTX-induced hepatocyte injury in vitro. Network pharmacological and transcriptomic analyses were conducted to predict the possible mechanisms of MOIG in mitigating MTX-induced liver injury, and lipidomic analysis was performed to further verify the regulatory effects of MOIG on lipid metabolism. BRL-3A hepatocytes were used to evaluate the regulatory effects of MOIG against MTX-associated liver injury.
RESULTS
MOIG treatment enhanced the anti-RA effect of MTX, and mitigated oxidative damage, inflammation and apoptosis of liver tissues in CIA rats treated with MTX. Network pharmacological and transcriptomic analyses demonstrated that MOIG attenuated liver injury by regulating autophagy and lipid metabolism. The result of lipidomic analysis showed that MOIG reversed the disturbance of lipid metabolism of the liver tissue in CIA rats after MTX treatment. In addition, MOIG also inhibited the apoptosis, reduced the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (ALT) and alanine aminotransferase (AST), regulated oxidative stress, and increased the formation of autophagosome and translocation of LC3 in the nucleus and expression of autophagy regulatory genes Beclin-1, ATG5, LC3Ⅱ, ATG7 and ATG12 in hepatocytes subjected to MTX damage.
CONCLUSION
Our findings demonstrated that MOIG could ameliorate MTX-induced liver injury in the treatment of RA through increasing hepatocyte autophagy and improving lipid metabolism homeostasis.
PubMed: 38914148
DOI: 10.1016/j.jep.2024.118486 -
Heliyon Jun 2024To explore the relationship and difference between ventricular and lumbar cerebrospinal fluid(CSF), this study presents equations transforming their measures. By...
Exploring the correlation and difference between cerebrospinal fluid in the lateral ventricle and lumbar subarachnoid based on infants with intraventricular hemorrhage treated by the ommaya reservoir.
OBJECTIVE
To explore the relationship and difference between ventricular and lumbar cerebrospinal fluid(CSF), this study presents equations transforming their measures. By assessing the viability of substituting lumbar puncture, we aim to minimize the associated medical risks and trauma faced by infants with intraventricular hemorrhage(IVH) from anesthesia and lumbar puncture.
METHODS
We retrospectively analyzed CSF data from 27 infants diagnosed with IVH treated by Ommaya reservoir and lumbar puncture at our center, comprising 35 paired samples. Paired-sample and regression analyses were employed to determine test correlations, differences, and to derive transformation equations for the measurements.
RESULTS
Comparative analyses between the CSF from the lateral ventricle and the lumbar vertebrae revealed significant differences in the levels of chloride, glucose, protein, erythrocytes, total cells, and Pandy's test. Specifically:1. Levels of chloride, glucose, protein, and Pandy's test were higher in the lumbar vertebrae.2. Conversely, erythrocyte and total cell counts were higher in the lateral ventricle.There were no significant differences observed for lumbar lactate dehydrogenase(LDH), leukocytes, occult blood, clot, clarity, and color. Nevertheless, significant correlations were identified between various measures, including LDH, glucose, chloride, protein, erythrocyte, leukocyte, total cell count, Pandy's test, occult blood, clot, transparency, and color. Interestingly, the correlation strength and equation fit for each component are inversely proportional to its molecular weight.Notably, well-fitting regression equations were found for LDH, glucose, chloride, protein, leukocytes, erythrocytes, and total cells.
CONCLUSION
In infants with IVH and unobstructed CSF channels, a robust correlation was noted between ventricular CSF sourced via the Ommaya reservoir and lumbar CSF. This correlation tended to be inversely related to molecular weight, with smaller molecular weights showing lesser disparities. Ventricular CSF data could anticipate lumbar CSF trends, and using regression equations with Ommaya-obtained CSF, one can derive approximate values for lumbar CSF.
PubMed: 38912498
DOI: 10.1016/j.heliyon.2024.e32252 -
Clinical Medicine Insights. Oncology 2024There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma.
BACKGROUND
There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma.
METHODS
A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1).
RESULTS
One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%).
CONCLUSIONS
Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.
PubMed: 38911454
DOI: 10.1177/11795549241260572 -
Environmental Research Jun 2024In this study, g-CN/PANI was prepared by in situ oxidative polymerization. Graphite-phase carbon nitride (g-CN) with surface defects was deposited onto the surface of...
In this study, g-CN/PANI was prepared by in situ oxidative polymerization. Graphite-phase carbon nitride (g-CN) with surface defects was deposited onto the surface of conductive polyaniline (PANI) to form a p-n heterojunction. This construction aimed to create an efficient heterogeneous catalyst, increasing the surface defect level and active sites of the composites, and augmenting its capability to capture and transfer extracellular electrons under anaerobic conditions. This addresses the challenge of low efficiency in direct interspecies electron transfer between bacteria and archaea during anaerobic digestion for methane production. The results showed that the prepared g-CN/PANI increased the CH yield and CH production rate by 82% and 96%, respectively. Notably, the conductivity and XPS test results showed that the ratio of g-CN to PANI was 0.15, and the composites exhibited favorable conductivity, with a uniform distribution of pyrrolic nitrogen, pyridinic nitrogen, and graphitic nitrogen, each accounting for approximately 30%. Furthermore, g-CN/PANI effectively enhanced the metabolic efficiency of intermediate products such as acetate and butyrate. Analysis of the microbial community structure revealed that g-CN/PANI led to a significant increase in the abundance of hydrogenotrophic methanogen Methanolinea (from 48% to 64%) and enriched Clostridium (a rise of 1%) with direct interspecies electron transfer capability. Microbial community function analysis demonstrated that the addition of g-CN/PANI boosted the activities of key enzymes involved in anaerobic digestion, including phosphate transacetylase (PTA), phospho-butyryl transferase (PTB), and NAD-independent lactate dehydrogenase (NNLD), by 47%, 135%, and 153%, respectively. This acceleration in enzymatic activity promoted the metabolism of acetyl-CoA, butyryl-CoA, and pyruvate. Additionally, the function of ABC transporters was enhanced, thereby improving the efficiency of material and energy exchange among microorganisms.
PubMed: 38909948
DOI: 10.1016/j.envres.2024.119480 -
International Journal of Pharmaceutics Jun 2024The effect of three commonly used surfactants, poloxamer 188 (P188), polysorbate 20 and 80 (PS20 and PS80), on the stability of a model protein, lactate dehydrogenase...
The effect of three commonly used surfactants, poloxamer 188 (P188), polysorbate 20 and 80 (PS20 and PS80), on the stability of a model protein, lactate dehydrogenase (LDH), was compared in aqueous solutions. In the absence of a surfactant, protein solution revealed a gradual decrease in surface tension as a function of time. The addition of surfactant resulted in a rapid decrease in the surface tension. This suggested that the surface behavior was dictated by the surfactant. PS20 and PS80 were more effective than P188 in preventing LDH adsorption on the solution surface. The advantage of polysorbates over P188 was also evident from the higher LDH tetramer recovery after shaking (room temperature, 30 h), especially when the surfactants were used at concentrations ≤ 0.01 % w/v. However, PS20 and PS80 accelerated protein unfolding during quiescent storage at 40 °C. Based on circular dichroism results, polysorbates perturbed the tertiary structure of LDH but not the secondary structure, while P188 did not impact the protein structure and stability. Polysorbates were more effective in stabilizing LDH against mechanical stress (shaking), but their adverse effects on protein conformational stability need to be carefully evaluated.
PubMed: 38909927
DOI: 10.1016/j.ijpharm.2024.124374 -
ACS Applied Materials & Interfaces Jun 2024Herein we report the assessment of the effects of shockwave (SW) impacts on adult rat hippocampal progenitor cell (AHPC) neurospheres (NSs), which are used as in vitro...
Herein we report the assessment of the effects of shockwave (SW) impacts on adult rat hippocampal progenitor cell (AHPC) neurospheres (NSs), which are used as in vitro brain models, for enhancing our understanding of the mechanisms of traumatic brain injury (TBI). The assessment has been achieved by using culture dishes and a new microchip. The microchip allows the chemicals released from the brain models cultured inside the cell culture chamber under SW impacts to diffuse to the nanosensors in adjacent sensor chambers through built-in diffusion barriers, which are used to prevent the cells from entering the sensor chambers, thereby mitigating the biofouling issues of the sensor surface. Experiments showed the negative impact of the SW on the viability, proliferation, and differentiation of the cells within the NSs. A qPCR gene expression analysis was performed and appeared to confirm some of the immunocytochemistry (ICC) results. Finally, we demonstrated that the microchip can be used to monitor lactate dehydrogenase (LDH) released from the AHPC-NSs subjected to SW impacts. As expected, LDH levels changed when AHPC-NSs were injured by SW impacts, verifying this chip can be used for assessing the degrees of injuries to AHPC-NSs by monitoring LDH levels. Taken together, these results suggest the feasibility of using the chip to better understand the interactions between SW impacts and in vitro brain models, paving the way for potentially establishing in vitro TBI models on a chip.
PubMed: 38905518
DOI: 10.1021/acsami.4c08026 -
PLoS Biology Jun 2024Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily...
Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.
Topics: Humans; Breast Neoplasms; Female; Cell Proliferation; Animals; Cell Line, Tumor; Histones; Mice; Gene Expression Regulation, Neoplastic; Up-Regulation; Neoplasm Metastasis; Potassium Channels, Tandem Pore Domain; Lactate Dehydrogenase 5; Mice, Nude; Neoplasm Invasiveness; Glycolysis; L-Lactate Dehydrogenase; Mice, Inbred BALB C; Prognosis; Cell Movement
PubMed: 38905316
DOI: 10.1371/journal.pbio.3002666 -
Molecular Medicine Reports Aug 2024Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the...
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p . The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes and H9C2 cells . BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R and in LPS‑stimulated macrophages , and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
Topics: Animals; MicroRNAs; Exosomes; Myocardial Reperfusion Injury; Rats; Macrophages; Male; Mesenchymal Stem Cells; STAT3 Transcription Factor; Janus Kinase 2; Signal Transduction; Rats, Sprague-Dawley; Disease Models, Animal; Myocytes, Cardiac; Cell Line
PubMed: 38904206
DOI: 10.3892/mmr.2024.13266 -
Cureus May 2024Thiamine is an essential water-soluble vitamin that must be obtained through diet. This vitamin is crucial for various biochemical reactions and is vital for aerobic...
Thiamine is an essential water-soluble vitamin that must be obtained through diet. This vitamin is crucial for various biochemical reactions and is vital for aerobic metabolism. When individuals are deficient in thiamine, which can be due to hypermetabolism (such as in inflammation, ischemia, or malnutrition, among other reasons), anaerobic metabolism may be utilized to maintain energy needs. Such chemical processes produce lactic acid. Excess lactic acid can cause various clinical signs and symptoms, though lactate dehydrogenase (LDH) can typically break down this compound. The following case presents a very unusual instance where a 51-year-old Caucasian woman presented with the chief complaint of ongoing and severe abdominal pain. After an extensive work-up ruling out numerous diagnoses and an eight-day hospital stay, it was believed that she may be suffering from hyperlactatemia secondary to thiamine deficiency, as she improved significantly after administration of this vitamin. It was thought that this was likely due to her previous systemic lupus erythematosus (SLE) diagnosis, vasculitis, chronic inflammation, and a hypermetabolic state, in addition to concurrent LDH malfunction.
PubMed: 38903294
DOI: 10.7759/cureus.60760 -
BioRxiv : the Preprint Server For... Apr 2024D-2-Hydroxyglutarate and L-2-Hydroxyglutarate (D-2HG/L-2HG) are typically metabolites of non-specific enzymatic reactions that are kept in check by the housekeeping...
D-2-Hydroxyglutarate and L-2-Hydroxyglutarate (D-2HG/L-2HG) are typically metabolites of non-specific enzymatic reactions that are kept in check by the housekeeping enzymes, D-2HG /L-2HG dehydrogenase (D-2HGDH/L-2HGDH). In certain disease states, such as D-2HG or L-2HG aciduria and cancers, accumulation of these biomarkers interferes with oxoglutarate-dependent enzymes that regulate bioenergetic metabolism, histone methylation, post-translational modification, protein expression and others. D-2HG has a complex role in tumorigenesis that drives metabolomics investigations. Meanwhile, L-2HG is produced by non-specific action of malate dehydrogenase and lactate dehydrogenase under acidic or hypoxic environments. Characterization of divergent effects of D-2HG/L-2HG on the activity of specific enzymes in diseased metabolism depends on their accurate quantification via mass spectrometry. Despite advancements in high-resolution quadrupole time-of-flight mass spectrometry (HR-QTOF-MS), challenges are typically encountered when attempting to resolve of isobaric and isomeric metabolites such as D-2HG/L-2HG for quantitative analysis. Herein, available D-2HG/L-2HG derivatization and liquid chromatography (LC) MS quantification methods were examined. The outcome led to the development of a robust, high-throughput HR-QTOF-LC/MS approach that permits concomitant quantification of the D-2HG and L-2HG enantiomers with the benefit to quantify the dysregulation of other intermediates within interconnecting pathways. Calibration curve was obtained over the linear range of 0.8-104 nmol/mL with r ≥ 0.995 for each enantiomer. The LC/MS-based assay had an overall precision with intra-day CV % ≤ 8.0 and inter-day CV % ≤ 6.3 across the quality control level for commercial standard and pooled biological samples; relative error % ≤ 2.7 for accuracy; and resolution, R = 1.6 between 2HG enantiomers (m/z 147.030), D-2HG and L-2HG (at retention time of 5.82 min and 4.75 min, respectively) following chiral derivatization with diacetyl-L-tartaric anhydride (DATAN). Our methodology was applied to disease relevant samples to illustrate the implications of proper enantioselective quantification of both D-2HG and L-2HG. The stability of the method allows scaling to large cohorts of clinical samples in the future.
PubMed: 38903117
DOI: 10.1101/2024.04.26.591335