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1.
Biomolecules ; 14(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38927027

ABSTRACT

Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner-Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.


Subject(s)
Gastrointestinal Microbiome , Indoles , Renal Dialysis , Tryptophan , Humans , Tryptophan/metabolism , Indoles/metabolism , Male , Female , Middle Aged , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/microbiology , Feces/microbiology , Metabolic Networks and Pathways , Adult , Metagenome
2.
ACS Omega ; 9(22): 23984-23997, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38854515

ABSTRACT

The causative pathogen of COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), utilizes the receptor-binding domain (RBD) of the spike protein to bind to human receptor angiotensin-converting enzyme 2 (ACE2). Further cleavage of spike by human proteases furin, TMPRSS2, and/or cathepsin L facilitates viral entry into the host cells for replication, where the maturation of polyproteins by 3C-like protease (3CLpro) and papain-like protease (PLpro) yields functional nonstructural proteins (NSPs) such as RNA-dependent RNA polymerase (RdRp) to synthesize mRNA of structural proteins. By testing the tea polyphenol-related natural products through various assays, we found that the active antivirals prevented SARS-CoV-2 entry by blocking the RBD/ACE2 interaction and inhibiting the relevant human proteases, although some also inhibited the viral enzymes essential for replication. Due to their multitargeting properties, these compounds were often misinterpreted for their antiviral mechanisms. In this study, we provide a systematic protocol to check and clarify their anti-SARS-CoV-2 mechanisms, which should be applicable for all of the antivirals.

3.
Article in English | MEDLINE | ID: mdl-38852934

ABSTRACT

In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement. The proportions of riociguat- and PDE5i-treated patients achieving the primary end-point at REVEAL Lite 2 low, intermediate, and high baseline risk reflected the overall population. Proportions of riociguat-treated patients achieving the primary end-point were comparable between the COMPERA 2.0 intermediate-low risk (39%) and intermediate-high risk (43%) groups. Our findings show that patients in REPLACE achieved clinical improvement by switching from PDE5i to riociguat across all COMPERA 2.0 and most REVEAL Lite 2 baseline risk strata.

4.
Materials (Basel) ; 17(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38730876

ABSTRACT

Amorphous thin films can be applied to increase the anti-corrosion ability of critical components. Atomized FeCrNiMoCSiB powders were hot-pressed into a disc target for R. F. magnetron sputtering on a 316L substrate to upgrade its corrosion resistance. The XRD spectrum confirmed that the film deposited by R. F. magnetron sputtering was amorphous. The corrosion resistance of the amorphous film was evaluated in a 1 M HCl solution with potentiodynamic polarization tests, and the results were contrasted with those of a high-velocity oxy-fuel (HVOF) coating and 316L, IN 600, and C 276 alloys. The results indicated that the film hardness and elastic modulus, as measured using a nanoindenter, were 11.1 and 182 GPa, respectively. The principal stresses in two normal directions of the amorphous film were about 60 MPa and in tension. The corrosion resistance of the amorphous film was much greater than that of the other samples, which showed a broad passivation region, even in a 1 M HCl solution. Although the amorphous film showed high corrosion resistance, the original pinholes in the film were weak sites to initiate corrosion pits. After polarization tests, large, deep trenches were seen in the corroded 316L substrate; numerous fine patches in the IN 600 alloy and grain boundary corrosion in the C276 alloy were observed.

5.
Plant Foods Hum Nutr ; 79(2): 374-380, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750193

ABSTRACT

Desmodium caudatum extracts (DCE) were investigated for their potential therapeutic effects on diabetic nephropathy (DN). In our study, the high-fat diet (HFD) / streptozotocin (STZ)-induced DN model in C57BL/6 mice was treated with 100 mg/kg, 200 mg/kg DCE. The results showed that DCE decreased biochemical parameters and proteinuria levels. The kidney sections staining indicated that DCE treatment recovered glomerular atrophy and alleviated lipid droplets in the glomerular. Additionally, DCE inhibited lipid and glycogen accumulation down-regulated the expression of sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) proteins. DCE also reduced collagenous fibrous tissue and the expression of transforming growth factor-ß1 (TGF-ß1) and alpha-smooth muscle actin (α-SMA) through Masson's trichrome staining and immunohistochemical analysis. We found that DCE alleviated hydroxyproline content, and epithelial-mesenchymal transition (EMT). Besides, the results shown that DCE enhanced the antioxidant enzymes to mitigate fibrosis by reducing oxidative stress. In conclusion, our study provided evidence of the protective effect of DCE which down-regulated hyperglycemia, hyperlipidemia and inhibition of TGF-ß1 and EMT pathway but elevated antioxidant, suggesting its therapeutic implication for DN.


Subject(s)
Diabetic Nephropathies , Diet, High-Fat , Mice, Inbred C57BL , Oxidative Stress , Plant Extracts , Sterol Regulatory Element Binding Protein 1 , Transforming Growth Factor beta1 , Animals , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Plant Extracts/pharmacology , Transforming Growth Factor beta1/metabolism , Male , Sterol Regulatory Element Binding Protein 1/metabolism , Mice , Oxidative Stress/drug effects , Diet, High-Fat/adverse effects , Diabetes Mellitus, Experimental/drug therapy , Antioxidants/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Fabaceae/chemistry , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Actins/metabolism , Fatty Acid Synthases/metabolism , Fibrosis
6.
Article in English | MEDLINE | ID: mdl-38598377

ABSTRACT

Blood pressure (BP) is predicted by this effort based on photoplethysmography (PPG) data to provide effective pre-warning of possible preeclampsia of pregnant women. Towards frequent BP measurement, a PPG sensor device is utilized in this study as a solution to offer continuous, cuffless blood pressure monitoring frequently for pregnant women. PPG data were collected using a flexible sensor patch from the wrist arteries of 194 subjects, which included 154 normal individuals and 40 pregnant women. Deep-learning models in 3 stages were built and trained to predict BP. The first stage involves developing a baseline deep-learning BP model using a dataset from common subjects. In the 2nd stage, this model was fine-tuned with data from pregnant women, using a 1-Dimensional Convolutional Neural Network (1D-CNN) with Convolutional Block Attention Module (CBAMs), followed by bi-directional Gated Recurrent Units (GRUs) layers and attention layers. The fine-tuned model results in a mean error (ME) of -1.40 ± 7.15 (standard deviation, SD) for systolic blood pressure (SBP) and -0.44 (ME) ± 5.06 (SD) for diastolic blood pressure (DBP). At the final stage is the personalization for individual pregnant women using transfer learning again, enhancing further the model accuracy to -0.17 (ME) ± 1.45 (SD) for SBP and 0.27 (ME) ± 0.64 (SD) for DBP showing a promising solution for continuous, non-invasive BP monitoring in precision by the proposed 3-stage of modeling, fine-tuning and personalization.

7.
Iran J Basic Med Sci ; 27(6): 706-716, 2024.
Article in English | MEDLINE | ID: mdl-38645497

ABSTRACT

Objectives: This study assessed the effects of electroacupuncture (EA) stimulation at different frequencies at the Dazhui and Baihui acupoints in the subacute phase after transient global cerebral ischemia (GCI). Materials and Methods: Rats were subjected to GCI for 25 min, followed by reperfusion for 7 days. EA at acupoints was performed at 10, 30, or 50 Hz, 1 day after reperfusion and then once daily for 6 consecutive days. Results: EA at acupoints at 10 and 50 Hz effectively down-regulated apoptosis in the hippocampal cornu ammonis 1(CA1) area and ameliorated memory deficits. Moreover, EA treatment at 10 and 50 Hz markedly increased phospho (p)-extracellular signal-regulated protein kinase 1/2 (ERK1/2), p-ERK1/2/neuronal nuclei (NeuN), p-cAMP response element-binding protein (CREB)/p-ERK1/2, B-cell lymphoma-2 (Bcl-2)/p-CREB, and X-linked inhibitor of apoptosis protein/NeuN expression levels and decreased Bcl-2 homologous antagonist/killer, second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI, cytochrome c, cleaved caspase-3, and apoptosis-inducing factor expression levels. Furthermore, 10-Hz EA treatment effectively increased p-p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK/NeuN, and p-CREB/p-p38 MAPK expression levels. Pretreatment with U0126 (ERK1/2 inhibitor) completely abrogated the effects of 10- and 50-Hz EA treatments on the aforementioned protein expression levels. Similarly, pretreatment with SB203580 (p38 MAPK inhibitor) completely abrogated the effects of 10-Hz treatment on the aforementioned protein expression levels. Conclusion: The effects of 10- and 50-Hz EA treatments on mitochondria-related apoptosis can be attributed to the activation of ERK1/2/p38 MAPK/CREB/Bcl-2- and ERK1/2/CREB/Bcl-2-mediated signaling, respectively, in the hippocampal CA1 area at 7 days after transient GCI.

8.
Heliyon ; 10(6): e27537, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38515682

ABSTRACT

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

9.
Arch Toxicol ; 98(5): 1415-1436, 2024 May.
Article in English | MEDLINE | ID: mdl-38436694

ABSTRACT

In vitro and in vivo models of lipopolysaccharide (LPS)-induced pulmonary injury, quercetin-3-glucuronide (Q3G) has been previously revealed the lung-protective potential via downregulation of inflammation, pyroptotic, and apoptotic cell death. However, the upstream signals mediating anti-pulmonary injury of Q3G have not yet been clarified. It has been reported that concerted dual activation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and autophagy may prove to be a better treatment strategy in pulmonary injury. In this study, the effect of Q3G on antioxidant and autophagy were further investigated. Noncytotoxic doses of Q3G abolished the LPS-caused cell injury, and reactive oxygen species (ROS) generation with inductions in Nrf2-antioxidant signaling. Moreover, Q3G treatment repressed Nrf2 ubiquitination, and enhanced the association of Keap1 and p62 in the LPS-treated cells. Q3G also showed potential in inducing autophagy, as demonstrated by formation of acidic vesicular organelles (AVOs) and upregulation of autophagy factors. Next, the autolysosomes formation and cell survival were decreased by Q3G under pre-treatment with a lysosome inhibitor, chloroquine (CQ). Furthermore, mechanistic assays indicated that anti-pulmonary injury effects of Q3G might be mediated via Nrf2 signaling, as confirmed by the transfection of Nrf2 siRNA. Finally, Q3G significantly alleviated the development of pulmonary injury in vivo, which may result from inhibiting the LPS-induced lung dysfunction and edema. These findings emphasize a toxicological perspective, providing new insights into the mechanisms of Q3G's protective effects on LPS-induced pulmonary injury and highlighting its role in dual activating Nrf2 and autophagy pathways.


Subject(s)
Acute Lung Injury , Lipopolysaccharides , Quercetin , Humans , Acute Lung Injury/chemically induced , Acute Lung Injury/prevention & control , Antioxidants/pharmacology , Autophagy , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Quercetin/analogs & derivatives
10.
Antimicrob Agents Chemother ; 68(4): e0095623, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38446062

ABSTRACT

Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. When introduced after viral adsorption, BPR3P0128 significantly decreased SARS-CoV-2 replication; however, it did not affect the early entry stage, as evidenced by a time-of-drug-addition assay. This suggests that BPR3P0128's primary action takes place during viral replication. We also found that BPR3P0128 effectively reduced the expression of proinflammatory cytokines in human lung epithelial Calu-3 cells infected with SARS-CoV-2. Molecular docking analysis showed that BPR3P0128 targets the RdRp channel, inhibiting substrate entry, which implies it operates differently-but complementary-with remdesivir. Utilizing an optimized cell-based minigenome RdRp reporter assay, we confirmed that BPR3P0128 exhibited potent inhibitory activity. However, an enzyme-based RdRp assay employing purified recombinant nsp12/nsp7/nsp8 failed to corroborate this inhibitory activity. This suggests that BPR3P0128 may inhibit activity by targeting host-related RdRp-associated factors. Moreover, we discovered that a combination of BPR3P0128 and remdesivir had a synergistic effect-a result likely due to both drugs interacting with separate domains of the RdRp. This novel synergy between the two drugs reinforces the potential clinical value of the BPR3P0128-remdesivir combination in combating various SARS-CoV-2 variants of concern.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19 , Pyrazoles , Quinolines , Humans , SARS-CoV-2/metabolism , RNA-Dependent RNA Polymerase/metabolism , Molecular Docking Simulation , COVID-19 Drug Treatment , Antiviral Agents/chemistry
11.
J Chin Med Assoc ; 87(4): 350-356, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38349136

ABSTRACT

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans.


Subject(s)
Calcitonin Gene-Related Peptide Receptor Antagonists , Migraine Disorders , Humans , Calcitonin Gene-Related Peptide Receptor Antagonists/therapeutic use , Calcitonin Gene-Related Peptide , Migraine Disorders/drug therapy , Antibodies, Monoclonal/therapeutic use , Tryptamines/therapeutic use
12.
J Chin Med Assoc ; 87(3): 273-279, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38252515

ABSTRACT

BACKGROUND: The long-term outcome on patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been ideal after standard medical treatment. However, good outcome for patients with CTEPH after interventions such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) has been reported recently. The aim of this study was to evaluate the impact of PEA or BPA on long-term outcomes for CTEPH patients in Han-Chinese population. METHODS: This was a multicenter, prospective case-control study. Patients with CTEPH were enrolled between January, 2018 and March, 2020. They were divided into two groups, including intervention (PEA or BPA) and conservative groups. The followed-up period was 26 months after treatment. The endpoints were all-cause mortality and CTEPH mortality. RESULTS: A total of 129 patients were enrolled and assigned to receive PEA/BPA (N = 73), or conservative therapy (N = 56). Overall, the 26-month survival rate of all-cause mortality was significantly higher in intervention group compared to that in conservative group (95.89% vs 80.36%; log-rank p = 0.0164). The similar trend was observed in the 26-month survival rate of CTEPH mortality (97.26% vs 85.71%; log-rank p = 0.0355). Regarding Cox proportional-hazard regression analysis, the hazard ratios (HRs) on patients with CTEPH receiving intervention in the outcome of all-cause mortality and CTEPH mortality were statistically significant (HR = 0.07 and p = 0.0141 in all-cause mortality; HR = 0.11 and p = 0.0461 in CTEPH mortality). CONCLUSION: This multicenter prospective case-control study demonstrated that intervention such as PEA and BPA increased the long-term survival rate for patient with CTEPH significantly. Intervention was an independent factor in long-term outcome for patients with CTEPH, including all-cause mortality and CTEPH mortality.


Subject(s)
Angioplasty, Balloon , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Hypertension, Pulmonary/surgery , Pulmonary Embolism/complications , Pulmonary Embolism/surgery , Case-Control Studies , Chronic Disease , Angioplasty, Balloon/adverse effects , Endarterectomy/adverse effects , Pulmonary Artery/surgery
13.
Cardiovasc Res ; 120(2): 203-214, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38252891

ABSTRACT

AIMS: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. METHODS AND RESULTS: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways. CONCLUSION: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.


Subject(s)
Exosomes , Hypertension, Pulmonary , Induced Pluripotent Stem Cells , Pulmonary Arterial Hypertension , Rats , Animals , Mice , Pulmonary Arterial Hypertension/metabolism , Induced Pluripotent Stem Cells/metabolism , Vascular Remodeling , Exosomes/metabolism , Fibroblasts/metabolism , Familial Primary Pulmonary Hypertension/metabolism , Pulmonary Artery , Monocrotaline/adverse effects , Monocrotaline/metabolism , Cell Proliferation , Disease Models, Animal , Core Binding Factor Alpha 1 Subunit/metabolism
14.
Plant Foods Hum Nutr ; 79(1): 182-188, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38270742

ABSTRACT

Hypertension is a global health problem and leads to cardiovascular disease and renal injury. Solanum muricatum Aiton leaf extract, rich in flavonoids, is known for its antioxidant capacity. However, the effects of Solanum muricatum Aiton leaf extract on hypertension combined with inflammatory complications were unknown. This study aimed to investigate the impact of Solanum muricatum Aiton leaf extract on hypertension in vivo and in vitro. In vivo, Solanum muricatum Aiton leaf extract led to decrease high blood pressure, improve heart, aorta, and kidney pathology, and enhance the antioxidative activity in spontaneously hypertensive rats (SHR). Our study demonstrated Solanum muricatum Aiton leaf extract inhibited angiotensin-converting enzyme (ACE), epithelial sodium channel (ENaC), sodium glucose co-transporters-1 (SGLT-1), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). In vitro, Solanum muricatum Aiton leaf extract improved the angiotensin II-induced reactive oxygen species (ROS) and mitochondrial membrane depolarization in NRK-52E cells. Besides, Solanum muricatum Aiton leaf extract could also decrease the expressions of ENaC, SGLT-1, and NF-κB in angiotensin II-treated NRK-52E cells. Solanum muricatum Aiton leaf can be suggested as a novel antihypertensive agent ameliorating hypertension via ACE inhibition, inflammation reduction, and ROS. PLE is a novel anti-hypertensive agent to ameliorate hypertension and its complications, including inflammation.


Subject(s)
Hypertension , Solanum , Rats , Animals , Solanum/metabolism , Antihypertensive Agents/pharmacology , Reactive Oxygen Species , NF-kappa B/metabolism , Angiotensin II , Antioxidants/pharmacology , Inflammation , Hypertension/drug therapy , Plant Extracts/pharmacology , Rats, Inbred SHR
15.
J Ultrasound Med ; 43(1): 161-169, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37873682

ABSTRACT

OBJECTIVES: This study compared ultrasound-guided nerve hydrodissection (HD) outcomes using two commonly used injectate volumes (10 and 5 mL) of normal saline to explore if there is a volume effect of HD for patients with moderate carpal tunnel syndrome (CTS). METHODS: Twenty-four participants were randomly assigned to treatment with HD using ultrasound-guidance and either 10 mL or 5 mL of normal saline (HD-10 and HD-5 groups respectively). Our primary outcome measures were the change scores of the two subscales of the Boston Carpal Tunnel Syndrome Questionnaire: The Symptom Severity Scale (SSS) and Functional Status Scale (FSS). We conducted a one-way repeated analysis of variance for 3 time points (4, 12, and 24 weeks) for both SSS and FSS, respectively, for change scores from time 0, and percentage change from time 0. RESULTS: All participants (n = 12 per group) completed the study. From 0 to 24 weeks the HD-10 group outperformed the HD-5 group for improvement in SSS (median ± IQR; -0.8 ± 0.4 versus -0.5 ± 0.5; P = .024) and FSS scores (mean ± SD; -0.8 ± 0.2 versus -0.5 ± 0.5; P = .011). The HD-10 group improvement in FSS subtest significantly exceeded the MCID percentage-change-based threshold of 27% (34%; P = .039). CONCLUSIONS: Despite the limitations of small study size, a largely inert injectate, and a single injection approach, these findings in favor of the 10 mL group suggest that the volume used for ultrasound-guided HD in moderate CTS matters, and a higher volume is more effective.


Subject(s)
Carpal Tunnel Syndrome , Humans , Carpal Tunnel Syndrome/diagnostic imaging , Carpal Tunnel Syndrome/surgery , Single-Blind Method , Prospective Studies , Saline Solution , Ultrasonography , Median Nerve/diagnostic imaging
16.
J Environ Manage ; 351: 119919, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38157572

ABSTRACT

To replace the obsolete ponding system, palm oil mill effluent (POME) steam reforming (SR) over net-acidic LaNiO3 and net-basic LaCoO3 were proposed as the POME primary treatments, with promising H2-rich syngas production. Herein, the long-term evaluation of POME SR was scrutinized with both catalysts under the optimal conditions (600 °C, 0.09 mL POME/min, 0.3 g catalyst, & 74-105 µm catalyst particle size) to examine the catalyst microstructure changes, transient process stability, and final effluent evaluation. Extensive characterization proved the (i) adsorption of POME vapour on catalysts before SR, (ii) deposition of carbon and minerals on spent SR catalysts, and (iii) dominance of coking deactivation over sintering deactivation at 600 °C. Despite its longer run, spent LaCoO3 (50.54 wt%) had similar carbon deposition with spent LaNiO3 (50.44 wt%), concurring with its excellent coke resistance. Spent LaCoO3 (6.12 wt%; large protruding crystals) suffered a harsher mineral deposition than spent LaNiO3 (3.71 wt%; thin film coating), confirming that lower reactivity increased residence time of reactants. Transient syngas evolution of both SR catalysts was relatively steady up to 4 h but perturbed by coking deactivation thereafter. La2O2CO3 acted as an intermediate species that hastened the coke removal via reverse Boudouard reaction upon its decarbonation. La2O2CO3 decarbonation occurred continuously in LaCoO3 system but intermittently in LaNiO3 system. LaNiO3 system only lasted for 13 h as its compact ash blocked the gas flow. LaCoO3 system lasted longer (17 h) with its porous ash, but it eventually failed because KCl crystallites blocked its active sites. Relatively, LaCoO3 system offered greater net H2 production (72.78%) and POME treatment volume (30.77%) than LaNiO3 system. SR could attain appreciable POME degradation (>97% COD, BOD5, TSS, & colour intensity). Withal, SR-treated POME should be polished to further reduce its incompliant COD and BOD5.


Subject(s)
Calcium Compounds , Coke , Plant Oils , Titanium , Palm Oil , Plant Oils/chemistry , Steam , Lanthanum , Oxides , Carbon , Industrial Waste
17.
Cureus ; 15(10): e46494, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37927629

ABSTRACT

Introduction Gastric cancer is one of the leading causes of cancer-related death in the United States. Surgery remains integral to the curative management of non-metastatic gastric cancer. However, delays to the date of surgery for gastric cancer patients are commonplace. To investigate the impact of treatment delays on gastric cancer mortality, we conducted a multivariable analysis of over 36,000 patients. Materials & methods After querying the National Cancer Database and excluding patients who did not meet inclusion criteria, our sample included 36,598 patients with stage I-III gastric cancer. We ran multivariable logistic regressions by regressing 90-day mortality on wait time. Other co-variables included sex, race, age, area of residence, comorbidities, insurance, histology, tumor grade, tumor stage, resection margins, treatment facility type, and treatment with chemotherapy. Results Our results demonstrated that each day of increased waiting time is associated with a 0.5% decrease in 90-day mortality. Other statistically significant predictors of higher 90-day mortality risk included male sex, black or white race, living in a small metropolitan or non-metropolitan area, older age, more severe comorbidities, non-private insurance, non-gastric stromal tumor cancer, non-well differentiated tumors, worse clinical stage, residual cancer, treatment at non-academic center, and no adjuvant/neoadjuvant chemotherapy. Conclusion These findings demonstrate that patients with longer wait times until surgery do not experience worse outcomes. These results are reassuring and can be cited to alleviate patient concerns.

18.
Bioengineering (Basel) ; 10(11)2023 Oct 31.
Article in English | MEDLINE | ID: mdl-38002394

ABSTRACT

The buff-colored layer separating the plasma from red blood cells (RBCs) in centrifuged blood was named the "buffy coat" in the late 19th century. The division of platelets (PLTs) and leukocytes (WBCs) between the buffy coat, plasma, and RBC layers in centrifuged blood has not been described before. In this study, we centrifuged 8.5 mL anticoagulated blood samples at 1000× g for 1, 2, 3, 5, 10, and 20 min. We then divided each sample into ten layers and analyzed each layer for cellular composition and mean platelet volume (MPV). Our results show that even after 20 min of centrifugation, about 15% of platelets remain in the plasma layers and 65% in the RBC layers. We found that the platelet count achieved from aspiration of 1 mL volume was optimal, with aspiration beginning 1/2 mL below the buffy coat and extending 1/2 mL above the buffy coat rather than beginning at the buffy coat itself and aspirating only plasma. Using this method of aspiration, we found that the total platelet count means reached a maximum in the 1 mL around the buffy coat after only 5 min of centrifugation.

19.
Arthroplast Today ; 24: 101252, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38023649

ABSTRACT

Background: Leg length discrepancy (LLD) is a common complication after total hip arthroplasty (THA) leading to significant morbidity and dissatisfaction for patients. A popular system for robotic arm-assisted THA utilizes preoperative computed tomography (CT) scans for surgical planning. Accurate measurement of leg length is crucial for restoring appropriate patient anatomy during the procedure. This study investigates the interobserver and interlandmark reliability of 3 different pelvic landmarks for measuring preoperative LLD. Methods: We compiled preoperative pelvic CT scans from 99 robotic arm-assisted THAs for osteoarthritis. Radiologic leg length measurement was performed using the robotic arm-assisted THA application by 2 orthopaedic residents using reference lines bisecting the following pelvic landmarks: the anterior superior iliac spines, acetabular teardrops, and most inferior aspect of the ischial rami. Results: On multivariate analysis, there was no significant difference found (P value = .924) for leg length measurement based on the 3 different pelvic anatomical landmarks. Leg length measurements showed interobserver reliability with significant Pearson correlation coefficients (r = 1.0, 0.94, 0.96, respectively) and nonsignificant differences in LLD means between subjects on paired sample (P value = .158, .085, 0.125, respectively) as well as between landmarks on pairwise comparison. Conclusions: The 3 pelvic landmarks used in this study can be used interchangeably with the lesser trochanter as the femoral reference point to evaluate preoperative LLD on pelvic CT in patients undergoing robotic-arm assisted THA. This study is the first of its kind to evaluate the interobserver and interlandmark reliability of anatomical landmarks on pelvic CT scans and suggests interchangeability of 3 pelvic landmarks for comparing leg length differences.

20.
Ann Gastroenterol ; 36(6): 646-653, 2023.
Article in English | MEDLINE | ID: mdl-38023970

ABSTRACT

Background: The reported prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is 32%. We assessed the influence of NAFLD on IBD hospitalizations in the United States (US). Methods: We utilized the National Inpatient Sample database, from 2016-2019, to identify the total IBD hospitalizations in the US and we further subdivided them according to the presence or absence of NAFLD. Hospitalization characteristics, comorbidities and outcomes were compared. Statistical significance was set at P<0.05. Results: There were 1,272,260 IBD hospitalizations in the US, of which 5.04% involved NAFLD. For IBD hospitalizations with NAFLD, the mean age was 50-64 years, and the proportion of males was 46.97%. IBD hospitalizations with NAFLD had a lower proportion of African Americans (8.7% vs. 11.38%, P<0.001). Comorbidities such as hypertension (50.34% vs. 44.04%, P<0.001) and obesity (18.77% vs. 11.81%, P<0.001) were significantly higher in the NAFLD cohort. Overall, based on the Charlson Comorbidity Index, patients with NAFLD had a higher number of comorbidities (52.77% vs. 20.66%, P<0.001). Mortality was higher in the NAFLD compared to the non-NAFLD cohort (3.14% vs. 1.44%, P<0.001). Patients with NAFLD also incurred significantly higher hospital charges ($69,536 vs. $55,467, p<0.001) and had a longer mean length of stay (6.10 vs. 5.27 days, P<0.001) compared to the cohort without NAFLD. Complications and inpatient procedure requirements were also higher in the NAFLD cohort. Conclusion: Our study revealed greater mortality, morbidity, and healthcare resource utilization in patients with IBD who were hospitalized with a concomitant diagnosis of NAFLD.

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