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International Journal of Environmental... Jun 2022Pneumoconiosis remains one of the most serious global occupational diseases. However, effective treatments are lacking, and early detection is crucial for disease...
Pneumoconiosis remains one of the most serious global occupational diseases. However, effective treatments are lacking, and early detection is crucial for disease prevention. This study aimed to explore serum biomarkers of occupational coal workers' pneumoconiosis (CWP) by high-throughput metabolomics, combining with machine learning strategy for precision screening. A case-control study was conducted in Beijing, China, involving 150 pneumoconiosis patients with different stages and 120 healthy controls. Metabolomics found a total of 68 differential metabolites between the CWP group and the control group. Then, potential biomarkers of CWP were screened from these differential metabolites by three machine learning methods. The four most important differential metabolites were identified as benzamide, terazosin, propylparaben and N-methyl-2-pyrrolidone. However, after adjusting for the influence of confounding factors, including age, smoking, drinking and chronic diseases, only one metabolite, propylparaben, was significantly correlated with CWP. The more severe CWP was, the higher the content of propylparaben in serum. Moreover, the receiver operating characteristic curve (ROC) of propylparaben showed good sensitivity and specificity as a biomarker of CWP. Therefore, it was demonstrated that the serum metabolite profiles in CWP patients changed significantly and that the serum metabolites represented by propylparaben were good biomarkers of CWP.
Topics: Anthracosis; Biomarkers; Case-Control Studies; Coal; Coal Mining; Humans; Machine Learning; Metabolomics; Pneumoconiosis
PubMed: 35742299
DOI: 10.3390/ijerph19127051 -
International Journal of Molecular... Jul 2021While much of biomedical research since the middle of the twentieth century has focused on molecular pathways inside the cell, there is increasing evidence that...
While much of biomedical research since the middle of the twentieth century has focused on molecular pathways inside the cell, there is increasing evidence that extracellular signaling pathways are also critically important in health and disease. The neuromodulators norepinephrine (NE), serotonin (5-hydroxytryptamine, 5HT), dopamine (DA), acetylcholine (ACH), and melatonin (MT) are extracellular signaling molecules that are distributed throughout the brain and modulate many disease processes. The effects of these five neuromodulators on Alzheimer's disease (AD) are briefly examined in this paper, and it is hypothesized that each of the five molecules has a u-shaped (or Janus-faced) dose-response curve, wherein too little or too much signaling is pathological in AD and possibly other diseases. In particular it is suggested that NE is largely functionally opposed to 5HT, ACH, MT, and possibly DA in AD. In this scenario, physiological "balance" between the noradrenergic tone and that of the other three or four modulators is most healthy. If NE is largely functionally opposed to other prominent neuromodulators in AD, this may suggest novel combinations of pharmacological agents to counteract this disease. It is also suggested that the of cases of AD and possibly other diseases involve an excess of noradrenergic tone and a collective deficit of the other four modulators.
Topics: Adrenergic Agents; Adrenergic Neurons; Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain Chemistry; Cholinesterase Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Humans; Melatonin; Mice; Models, Neurological; Neurotransmitter Agents; Nootropic Agents; Norepinephrine; Phosphorylation; Protein Processing, Post-Translational; Rats; Receptors, Adrenergic, alpha-2; Selective Serotonin Reuptake Inhibitors; Signal Transduction; Synaptic Transmission; tau Proteins
PubMed: 34298984
DOI: 10.3390/ijms22147364 -
Toxicological Research Jul 2022Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study...
Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study attempted to investigate an alternative but better role of terazosin (alpha-adrenergic blocker) in APAP-induced acute liver injury in an animal model using New Zealand rabbits. APAP (1 g/kg of body weight) was given to New Zealand rabbits either with or without terazosin (0.5 mg/kg) and serum was collected after 4 h. Serum alanine transaminase (ALT), alkaline phosphatase (ALP) and ferritin level were determined to analyze the liver functioning of treated rabbits. Furthermore, total cholesterol (TC), total lipids (TL), high-density lipoproteins (HDL), low-density lipoprotein (LDL) and triglycerides (TG) levels were estimated to find any change in lipid profile of the treated animals. Moreover, the urea and creatinine levels assayed the actual renal functionality. To identify any modification in gene expression, qPCR of cytochrome P2E1 (CYP2E1) was performed. Terazosin in combination with APAP enhanced liver functioning by reducing the levels of liver injury markers viz. ALP and ALT, while lipid profile was also lowered by down regulation of TC, TL, LDL and TG with enhanced HDL levels. It caused significant down regulation of expression level of CYP2E1. It is concluded that terazosin has better effects induced on the recovery of normal liver functioning, by improving the liver profile, lipid profile and renal functioning both at tissue and molecular levels.
PubMed: 35874506
DOI: 10.1007/s43188-021-00116-y -
PloS One 2023Combination therapy of α-receptor blockers (α-RBs) and traditional Chinese medicine external therapy can serve as a treatment of chronic prostatitis/chronic pelvic... (Meta-Analysis)
Meta-Analysis
Comparative analysis of efficacy of different combination therapies of α-receptor blockers and traditional Chinese medicine external therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome: Bayesian network meta-analysis.
BACKGROUND
Combination therapy of α-receptor blockers (α-RBs) and traditional Chinese medicine external therapy can serve as a treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). α-RBs includes tamsulosin, terazosin and so on and the traditional Chinese medicine external therapy includes needling, moxibustion, acupoint catgut embedding, acupoint application, auricular point sticking and hot medicated compress and so forth. Currently, there is no study in which Bayesian network meta-analysis is applied to making a comparative analysis of efficacy of different combination therapies of α-RBs and traditional Chinese medicine external therapy in the treatment of CP/CPPS. Therefore, based on Bayesian algorithm, a network meta-analysis was conducted by us to make a comparison between different combination therapies of α-RBs and traditional Chinese medicine external therapy.
METHODS
A document retrieval was conducted in the databases PubMed, Cochrane Library, Embase, Web of science, China National Knowledge Infrastructure, WanFang Data Dissertations of China database, VIP China Science and Technology Journal Database, SinoMed. Literatures were searched for published in biomedical journals concerning clinical study on α-RBs combined with various traditional Chinese medicine external therapies in the treatment of CP/CPPS from inception of database to July 2022. Newest version risks of bias assessment tool (RoB2) was used to assess the risks of bias of studies included in this analysis. Stata 16.0 software and R4.1.3 software were used to make a Bayesian network meta-analysis and charts.
RESULTS
19 literatures were included involving 1739 patients concerning 12 interventions which were used in the treatment of CP/CPPS. With respect to the total effective rate, α-RBs+ needling was most likely to be the optimal treatment. Concerning National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score, α-RBs+ moxibustion+ auricular point sticking was most likely to be optimal treatment, the therapy ranking second was α-RBs+ needling, and the therapy ranking third was α-RBs+ moxibustion. Pain score, voiding score and quality-of-life score are subdomains of the NIH-CPSI total score. With regard to pain score, α-RBs+ moxibustion was most likely to be optimal treatment. In reference to voiding and quality-of-life score, there was no statistically significant difference between the efficacy of various interventions.
CONCLUSIONS
α-RBs+ needling, α-RBs+ moxibustion and α-RBs+ moxibustion+ auricular point sticking provided relatively good efficacy in the treatment of CP/CPPS. In these treatments, attention should be paid on α-RBs+ needling and α-RBs+ moxibustion which ranked higher many times in the evaluation of various outcome indicators. However, there still were certain limitations in this study, so large-sample clinical randomized control trials with a rigor design following the evidence-based medicine standards need to be conducted to justify the results of this study.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier: [CRD42022341824].
Topics: Male; Humans; Medicine, Chinese Traditional; Prostatitis; Bayes Theorem; Network Meta-Analysis; Chronic Disease; Adrenergic alpha-Antagonists; Pelvic Pain; Acupuncture Therapy; Randomized Controlled Trials as Topic
PubMed: 37079509
DOI: 10.1371/journal.pone.0280821 -
Journal of Inflammation Research 2023Although Ge-Gen decoction (GGD) has beneficial effects on primary dysmenorrhea (PD), the underlying mechanisms remain poorly understood. Our previous proteomic data...
OBJECTIVE
Although Ge-Gen decoction (GGD) has beneficial effects on primary dysmenorrhea (PD), the underlying mechanisms remain poorly understood. Our previous proteomic data revealed decreased level of heat shock protein 90 (HSP90) in uterine tissues of rats with PD after GGD treatment. However, the potential role of HSP90 in the anti-PD effect of GGD and the underlying mechanisms remain unexplored. This study investigated the potential role and mechanism of HSP90 in the anti-PD effect of GGD using a PD rat model.
METHODS
Wistar female rats were used to investigate the potential role of HSP90 in the anti-PD effect of GGD. The rat PD model was established by injecting estradiol benzoate and oxytocin. GGD, Terazosin (an agonist of HSP90) or GGD combined with Terazosin were orally administered to the PD rats. The expression levels of protein and cytokines, including HSP90, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2) in the uterine tissue of rats in each group were detected by immunohistochemical assay or Western blot.
RESULTS
GGD ameliorated the writhing response, suppressed the protein levels of HSP90 and inflammation-associated proteins, including NLRP3, NF-κB, and COX-2 in uterine tissues of rats with PD. Terazosin attenuated the anti-PD effect of GGD and reversed the effects of GGD on the protein levels of NLRP3, NF-κB and COX-2 in uterine tissues.
CONCLUSION
GGD exerts an anti-PD effect and suppresses levels of HSP90 and some inflammation associated proteins in uterine tissues of rats.
PubMed: 37092132
DOI: 10.2147/JIR.S400545 -
Journal of Oncology 2022Chromaffin cell-centered pheochromocytoma (Pheo) is a rare tumour. Pheochromocytoma and how it affects the heart will be the topic of this article. Due to the comparable...
Chromaffin cell-centered pheochromocytoma (Pheo) is a rare tumour. Pheochromocytoma and how it affects the heart will be the topic of this article. Due to the comparable symptoms and indications of the sympathetic nervous system, a pheochromocytoma might be difficult to detect early. There are also other frequent differential diagnoses that might delay the detection of a pheochromocytoma. One of the most common side effects of pheochromocytoma is unmanageable hypertension. Hypertensive crisis (extreme increases in blood pressure) can develop, which is a life-threatening condition that leads to strokes or arrhythmia. Estimated to affect African Americans significantly, they frequently go undetected due to a lack of resources or accessibility of services. Because this tumour is difficult to identify and its symptoms often resemble those of other diseases, it is frequently overlooked. A pheochromocytoma's long-term consequences can include cardiac muscle deterioration, congestive heart failure (CHF), a higher diabetes risk and possibly death. Masked hypertension (MH) is more common in people with adrenal pheochromocytoma, which has been related to an increased risk of heart disease. With the use of ambulatory blood pressure monitoring, this research set out to find out how common mental health issues are among people with APs. There were 85 participants in all, 43 of whom had APs and 42 of whom had the same age, gender, BMI, smoking and diabetes as the AP patients. Measurements were made of the BP and AP in both the diseased and control groups. Retrospective data collection was used to gather biochemical, hormonal and radiological information on the patients. The Pearson-Boltzmann CNN method was then used to assess risk based on the diagnosis results. Furthermore, depending on the risk score, more nonselective blockers (e.g., prazosin, doxazosin, terazosin, and metyrosine) have been used to lower perioperative catecholamine levels, hence reducing illness risk. After a successful surgical excision of the tumour, the recommended therapy can usually be stopped quickly.
PubMed: 35186079
DOI: 10.1155/2022/3644212 -
Journal of Neurochemistry Mar 2023Noradrenergic neurotransmission is a critical mediator of stress responses. In turn, exposure to stress induces noradrenergic system adaptations, some of which are...
Noradrenergic neurotransmission is a critical mediator of stress responses. In turn, exposure to stress induces noradrenergic system adaptations, some of which are implicated in the etiology of stress-related disorders. Adrenergic receptors (ARs) in the ventral tegmental area (VTA) have been demonstrated to regulate phasic dopamine (DA) release in the forebrain, necessary for behavioral responses to conditional cues. However, the impact of stress on noradrenergic modulation of the VTA has not been previously explored. We demonstrate that ARs in the VTA regulate dopaminergic activity in the VTA-BLA (basolateral amygdala) circuit, a key system for processing stress-related stimuli; and that such control is altered by acute stress. We utilized fast-scan cyclic voltammetry to assess the effects of intra-VTA microinfusion of α -AR and α -AR antagonists (terazosin and RX-821002, respectively), on electrically evoked phasic DA release in the BLA in stress-naïve and stressed (unavoidable electric shocks - UES) anesthetized male Sprague-Dawley rats. In addition, we used western blotting to explore UES-induced alterations in AR protein level in the VTA. Intra-VTA terazosin or RX-821002 dose-dependently attenuated DA release in the BLA. Interestingly, UES decreased the effects of intra-VTA α -AR blockade on DA release (24 h but not 7 days after stress), while the effects of terazosin were unchanged. Despite changes in α -AR physiological function in the VTA, UES did not alter α -AR protein levels in either intracellular or membrane fractions. These findings demonstrate that NA-ergic modulation of the VTA-BLA circuit undergoes significant alterations in response to acute stress, with α -AR signaling indicated as a key target.
Topics: Rats; Animals; Male; Ventral Tegmental Area; Rats, Sprague-Dawley; Signal Transduction; Synaptic Transmission; Dopamine; Norepinephrine
PubMed: 36161462
DOI: 10.1111/jnc.15698 -
Pharmaceutics Jun 2020Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications...
Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (K) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and K values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology.
PubMed: 32560065
DOI: 10.3390/pharmaceutics12060554 -
Turkish Journal of Urology Mar 2021Transrectal ultrasound-guided prostate biopsy is the gold standard in the diagnosis of prostate cancer. Major and minor complications may develop at varying rates after...
OBJECTIVE
Transrectal ultrasound-guided prostate biopsy is the gold standard in the diagnosis of prostate cancer. Major and minor complications may develop at varying rates after prostate biopsies, one of which is voiding impairment. This study aimed to evaluate whether all alpha1-blockers were effective in preventing voiding impairment after a transrectal ultrasound-guided prostate biopsy and if so, was one superior to the others.
MATERIAL AND METHODS
This study included 240 patients who underwent a transrectal ultrasound-guided 12-core prostate biopsy and were prospectively randomized. Of the patients, 40 received 10 mg alfuzosin, 40 received 4 mg doxazosin, 40 received 8 mg silodosin, 40 received 0.4 mg tamsulosin, and 40 received 5 mg terazosin beginning on the day before the biopsy and for the following 30 days. The international prostate symptom score (IPSS), maximal flow rate, and post-void residual urine were recorded in all the patients before the procedure and on post-biopsy days 7 and 30. All he patients were followed up and questioned about voiding difficulty and acute urinary retention after the procedure.
RESULTS
In all the alpha1-blocker groups, the IPSS and post-void residuals were statistically significantly lower, and the maximal flow rate was statistically significantly greater on post-biopsy days 7 and 30 compared with the baseline values (p<0.05). No patient in any of the alpha1-blocker groups developed acute urinary retention after the biopsy.
CONCLUSION
To prevent voiding impairment and deterioration in the quality of life after a prostate biopsy, preemptive therapy with alpha1-blockers may have a protective role, especially in patients with large prostate volumes.
PubMed: 33819444
DOI: 10.5152/tud.2021.20509 -
European Journal of Pharmacology Apr 2024Abdominal aortic aneurysm (AAA), a vascular degenerative disease, is a potentially life-threatening condition characterised by the loss of vascular smooth muscle cells...
Abdominal aortic aneurysm (AAA), a vascular degenerative disease, is a potentially life-threatening condition characterised by the loss of vascular smooth muscle cells (VSMCs), degradation of extracellular matrix (ECM), inflammation, and oxidative stress. Despite the severity of AAA, effective drugs for treatment are scarce. At low doses, terazosin (TZ) exerts antiapoptotic and anti-inflammatory effects in several diseases, but its potential to protect against AAA remains unexplored. Herein, we investigated the effects of TZ in two AAA animal models: Angiotensin II (Ang II) infusion in Apoe mice and calcium chloride application in C57BL/6J mice. Mice were orally administered with TZ (100 or 1000 μg/kg/day). The in vivo results indicated that low-dose TZ alleviated AAA formation in both models. Low-dose TZ significantly reduced aortic pulse wave velocity without exerting an apparent antihypertensive effect in the Ang II-induced AAA model. Paternally expressed gene 3 (Peg3) was identified via RNA sequencing as a novel TZ target. PEG3 expression was significantly elevated in both mouse and human AAA tissues. TZ suppressed PEG3 expression and reduced the abundance of matrix metalloproteinases (MMP2/MMP9) in the tunica media. Functional experiments and molecular analyses revealed that TZ (10 nM) treatment and Peg3 knockdown effectively prevented Ang II-induced VSMC senescence and apoptosis in vitro. Thus, Peg3, a novel target of TZ, mediates inflammation-induced VSMC apoptosis and senescence. Low-dose TZ downregulates Peg3 expression to attenuate AAA formation and ECM degradation, suggesting a promising therapeutic strategy for AAA.
Topics: Mice; Humans; Animals; Muscle, Smooth, Vascular; Pulse Wave Analysis; Mice, Knockout; Mice, Inbred C57BL; Aortic Aneurysm, Abdominal; Apoptosis; Inflammation; Angiotensin II; Disease Models, Animal; Myocytes, Smooth Muscle; Kruppel-Like Transcription Factors; Prazosin
PubMed: 38331337
DOI: 10.1016/j.ejphar.2024.176397