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PloS One 2024The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was... (Comparative Study)
Comparative Study
The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.
Topics: Animals; Dogs; Cytokines; Dog Diseases; Anal Sacs; Male; Microbiota; Female; RNA, Ribosomal, 16S; Dermatitis, Atopic; Case-Control Studies; Bacteria
PubMed: 38814946
DOI: 10.1371/journal.pone.0298361 -
World Journal of Stem Cells Mar 2024Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with...
BACKGROUND
Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with drainage procedure is effective as well. However, previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.
AIM
This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn's perianal fistula (CPF) closure rates after stem cell transplantation with and without anti-TNF therapy, and to identify the factors affecting CPF closure and recurrence.
METHODS
The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled. Clinical data were compared according to anti-TNF therapy and CPF closure.
RESULTS
A total of 65 patients were included. The median age of females was 26 years (range: 21-31) and that of males was 29 (44.6%). The mean follow-up duration was 65.88 ± 32.65 months, and complete closure was observed in 50 (76.9%) patients. The closure rates were similar after stem cell transplantation with and without anti-TNF therapy (66.7% 81.6% at 3 year, = 0.098). The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture ( = 0.027, 0.002, and 0.008, respectively). Clinical factors such as complexity, number of fistulas, presence of concurrent abscess, and medication were not significant for closure. The cumulative 1-, 2-, and 3-year closure rates were 66.2%, 73.8%, and 75.4%, respectively.
CONCLUSION
Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation. However, both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy. Fistulous tract length, proctitis, and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.
PubMed: 38577230
DOI: 10.4252/wjsc.v16.i3.257 -
Journal of Food and Drug Analysis Mar 2024Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver...
Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-β), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-β1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.
Topics: Animals; Dimethylnitrosamine; Liver Cirrhosis; Bivalvia; Inflammation; Dioxolanes
PubMed: 38526593
DOI: 10.38212/2224-6614.3491 -
Analytical Biochemistry Jun 2024Myoglobin (Myo), creatine kinase-MB (CKMB), and cardiac troponin I (cTnI) are crucial biomarkers for diagnosing acute myocardial infarction (AMI) The accurate and rapid...
Myoglobin (Myo), creatine kinase-MB (CKMB), and cardiac troponin I (cTnI) are crucial biomarkers for diagnosing acute myocardial infarction (AMI) The accurate and rapid detection of these three targets can greatly improve the prognosis of AMI patients. Herein, this study developed a microfluidic immunofluorescence method that can detect all three targets in 10-15 min. Ultrasonic atomization and spray technology are used to modify the surface of the injection-molded microfluidic chip (MFC), which effectively solves the problem of biological cross-linking and antibody immobilization on the MFC surface. In addition, it improves the hydrophilicity of the chip surface, thus enhancing fluid self-driving effect. The linear response towards Myo, CKMB and cTnI range from 5 ng/mL to 500 ng/mL, 1 ng/mL to 70 ng/mL, and 0.05 ng/mL to 30 ng/mL, respectively. The intra-batch precision is ≤ 10%, and the inter-batch precision is ≤ 15%. Furthermore, this method shows good consistency compared with the BECKMAN ACCESS2 chemiluminescent immunoanalyzer. The present work provides an AMI diagnostic method with high sensitivity, good repeatability, high accuracy and simple operation, which can satisfy the needs of clinical diagnosis, and shows promising application prospects.
Topics: Humans; Microfluidics; Myocardial Infarction; Creatine Kinase, MB Form; Prognosis; Troponin I; Biomarkers; Myoglobin; Sensitivity and Specificity
PubMed: 38453047
DOI: 10.1016/j.ab.2024.115502 -
Journal of Pharmaceutical and... May 2024Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to...
AIM
Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to systematically explore the specific mechanism of EB granules in the treatment of IS from the metabolic perspective.
METHODS
The model of transient middle cerebral artery occlusion (tMCAO) in mice was established by the suture-occluded method. The therapeutic effect of EB granules on tMCAO mice was evaluated by behavioral evaluation, brain water content determination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and levels of lactate dehydrogenase (LDH) and neuron specific enolase (NSE) in serum. In order to screen differential metabolites, non-targeted metabolomics technology was used to detect the metabolites in serum before and after administration. Univariate statistics, multivariate statistics and bioinformatics were used to analyze the changes of metabolites in serum of tMCAO mice. The possible related mechanism of EB granules in treating IS was screened by pathway enrichment analysis, and the preliminary verification was carried out at animal level by enzyme linked immunosorbent assay (ELISA) and western blot (WB).
RESULTS
EB granules could significantly improve behavior of tMCAO mice, reduce brain water content and cerebral infarction volume, improve morphology of brain tissue, reduce the levels of LDH and NSE in serum. A total of 232 differential metabolites were screened, which were mainly enriched in many biological processes such as sphingolipid metabolism. The differential metabolite S1P and its receptors S1PR1 and S1PR2 in sphingolipid metabolism were verified. The results showed that the level of S1P in brain tissue increased and the protein expression of S1PR1 decreased significantly after modeling, and reversed after administration, but there was no significant difference in the protein expression of S1PR2.
CONCLUSION
The therapeutic effects of EB granules may be related to affecting sphingolipid metabolism through regulating S1P/S1PR1.
Topics: Mice; Animals; Brain Ischemia; Erigeron; Ischemic Stroke; Infarction, Middle Cerebral Artery; Water; Sphingolipids
PubMed: 38422673
DOI: 10.1016/j.jpba.2024.116058 -
Frontiers in Pharmacology 2024Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that (APS) have...
Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that (APS) have anti-inflammatory properties, which make them a potential candidate for neuroprotection against central nervous system disease. Nevertheless, the extent of their effectiveness in treating epilepsy remains enigmatic. Therefore, our study aims to investigate the potential of APS to mitigate epileptogenesis and its comorbidities by exploring its underlying mechanism. Initially, we employed pentylenetetrazol-induced seizure mice to validate APS' effectiveness. Subsequently, we employed network pharmacology analysis to probe the possible targets and signaling pathways of APS in treating epilepsy. Ultimately, we verified the key targets and signaling pathways experimentally, predicting their mechanisms of action. APS have been observed to disturb the acquisition process of kindling, leading to reduced seizure scores and a lower incidence of complete kindling. Moreover, APS has been found to improve cognitive impairments and prevent hippocampal neuronal damage during the pentylenetetrazole (PTZ)-kindling process. Subsequent network pharmacology analysis revealed that APS potentially exerted their anti-epileptic effects by targeting cytokine and toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathways. Finally, experimental findings showed that APS efficiently inhibited the activation of astrocytes and reduced the release of pro-inflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, APS impeded the activation of the TLR4/NF-κB signaling cascade in a PTZ-induced kindling mouse model. The outcomes of our study suggest that APS exerts an impact on epileptogenesis and mitigates cognitive impairment by impeding neuroinflammatory processes. The mechanism underlying these observations may be attributed to the modulation of the TLR4/NF-κB signaling pathway, resulting in a reduction of the release of inflammatory mediators. These findings partially agree with the predictions derived from network pharmacology analyses. As such, APS represents a potentially innovative and encouraging adjunct therapeutic option for epileptogenesis and cognitive deficit.
PubMed: 38405667
DOI: 10.3389/fphar.2024.1336122 -
World Journal of Gastrointestinal... Jan 2024The incidence of colorectal cancer (CRC) is increasing annually. Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.
BACKGROUND
The incidence of colorectal cancer (CRC) is increasing annually. Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.
AIM
To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching (PSM).
METHODS
The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) were analyzed retrospectively. The control group included patients who underwent open surgery ( = 43), and those who underwent laparoscopic surgery formed the observation group ( = 57). The baseline information of both groups was equipoised using 1 × 1 PSM. Differences in the perioperative parameters, inflammatory response, immune function, degree of pain, and physical status between the groups were analyzed.
RESULTS
Thirty patients from both groups were successfully matched. After PSM, baseline data showed no statistically significant differences between the groups: (1) Perioperative parameters: The observation group had a longer surgery time, less intraoperative blood loss, earlier first ambulation and first anal exhaust times, and shorter gastric tube indwelling time than the control group; (2) Inflammatory response: 24 h after surgery, the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) between groups were higher than preoperatively. IL-6, CRP, and TNF-α levels in the observation group were lower than in the control group; (3) Immune function: At 24 h after surgery, counts of CD4-positive T-lymphocytes (CD4) and CD4/CD8-positive T-lymphocytes (CD8) in both groups were lower than those before surgery, whereas CD8 was higher than that before surgery. At 24 h after surgery, both CD4 counts and CD4/CD8 in the observation group were higher than those in the control group, whereas CD8 counts were lower; (4) Degree of pain: The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery; and (5) Physical status: One month after surgery, the Karnofsky performance score in the observation group was higher than that in the control group.
CONCLUSION
Laparoscopic radical resection of CRC has significant benefits, such as reducing postoperative pain and postoperative inflammatory response, avoiding excessive immune inhibition, and contributing to postoperative recovery.
PubMed: 38328309
DOI: 10.4240/wjgs.v16.i1.124 -
International Journal of Surgery Case... Mar 2024Recalcitrant esophagocutaneous fistula is a very uncommon complication after neck surgery. Management of this non-healing fistula has long been a topic of debate. This...
INTRODUCTION
Recalcitrant esophagocutaneous fistula is a very uncommon complication after neck surgery. Management of this non-healing fistula has long been a topic of debate. This report provides an approach for treating it.
PRESENTATION OF CASE
A 65-year-old woman presented nineteen years after branchial cleft cyst surgery with cyst recurrence associated with swelling. Sonography displayed a collection in the front of the left carotid artery in the suprasternal notch. On the CT, a similar finding was seen, a collection with gaseous density in front of the left sternocleidomastoid and a hypodense nodule on the right lobe of the thyroid. The pathology report describes an abscess with many macrophages and neutrophils, fat necrosis, microcalcification, and foreign body reaction around amorphous bodies. Again, surgical resection of the swelling area and tract was done and an esophago-cutaneous fistula was developed after surgery which did not heal after 6 months.
CLINICAL DISCUSSION
According to accelerating the healing time and complete closure of chronic wounds such as lower-extremity diabetic ulcers, persistent pneumothorax, anal fistula, and recalcitrant gastrocutaneous fistula by using platelet-rich plasma (PRP) and fibrin glue (FG); PRP-FG can be considered as a safe and effective treatment option for chronic wound healing. So, for treatment of this fistula, PRP-FG was used. PRP-FG was obtained from the patient's blood and injected into the fistula tract. The discharge was stopped after one week and the fistula was cured.
CONCLUSION
PRP-FG injection into the fistula tract provides a simple and non-invasive approach for the treatment of recalcitrant esophagocutaneous fistula.
PubMed: 38308979
DOI: 10.1016/j.ijscr.2024.109335 -
Medical Image Analysis Apr 2024This paper proposes an innovative approach to generate a generalized myocardial ischemia database by modeling the virtual electrophysiology of the heart and the 12-lead...
This paper proposes an innovative approach to generate a generalized myocardial ischemia database by modeling the virtual electrophysiology of the heart and the 12-lead electrocardiography projected by the in-silico model can serve as a ready-to-use database for automatic myocardial infarction/ischemia (MI) localization and classification. Although the virtual heart can be created by an established technique combining the cell model with personalized heart geometry to observe the spatial propagation of depolarization and repolarization waves, we developed a strategy based on the clinical pathophysiology of MI to generate a heterogeneous database with a generic heart while maintaining clinical relevance and reduced computational complexity. First, the virtual heart is simplified into 11 regions that match the types and locations, which can be diagnosed by 12-lead ECG; the major arteries were divided into 3-5 segments from the upstream to the downstream based on the general anatomy. Second, the stenosis or infarction of the major or minor coronary artery branches can cause different perfusion drops and infarct sizes. We simulated the ischemic sites in different branches of the arteries by meandering the infarction location to elaborate on possible ECG representations, which alters the infraction's size and changes the transmembrane potential (TMP) of the myocytes associated with different levels of perfusion drop. A total of 8190 different case combinations of cardiac potentials with ischemia and MI were simulated, and the corresponding ECGs were generated by forward calculations. Finally, we trained and validated our in-silico database with a sparse representation classification (SRC) and tested the transferability of the model on the real-world Physikalisch Technische Bundesanstalt (PTB) database. The overall accuracies for localizing the MI region on the PTB data achieved 0.86, which is only 2% drop compared to that derived from the simulated database (0.88). In summary, we have shown a proof-of-concept for transferring an in-silico model to real-world database to compensate for insufficient data.
Topics: Humans; Myocardial Perfusion Imaging; Myocardial Infarction; Ischemia; Myocardial Ischemia; Heart; Coronary Artery Disease
PubMed: 38244290
DOI: 10.1016/j.media.2024.103087 -
Journal of Pharmaceutical Analysis Dec 2023Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP)...
Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The knockout mice () and liver-specific overexpression of () mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, mice were defended against liver damage caused by APAP overdose by inhibiting the glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.
PubMed: 38223455
DOI: 10.1016/j.jpha.2023.08.004