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The Kobe Journal of Medical Sciences Jun 2024Intussusception is a common cause of intestinal obstruction in infants aged 6-18 months. However, intussusception in preterm neonates (IPN) is an exceedingly rare...
Intussusception is a common cause of intestinal obstruction in infants aged 6-18 months. However, intussusception in preterm neonates (IPN) is an exceedingly rare disorder. The etiology of IPN remains unclear, but common prenatal injuries, such as those causing intestinal hypoxia/hypoperfusion, dysmotility, and strictures, have been proposed as possible contributing factors. Diagnosis is often delayed because the symptoms closely resemble those of necrotizing enterocolitis (NEC). Given the divergent treatments for IPN and NEC, establishing an early and accurate diagnosis is crucial. IPN is predominantly located in the small intestine (91.6%), and ultrasonography proves useful in its diagnosis. We present a case of a very preterm infant who developed intussusception triggered by acquired cytomegalovirus (aCMV) infection, necessitating surgical treatment. The cause of intussusception in this case was diagnosed as aCMV enteritis because no organic lesions were observed in the advanced part of the intussusception. The presence of CMV was confirmed by CMV-DNA-PCR examination of the resected intestinal tract. Intestinal edema and decreased intestinal peristalsis due to aCMV enteritis are likely the primary causes of the intussusception.
Topics: Humans; Intussusception; Cytomegalovirus Infections; Infant, Newborn; Infant, Extremely Premature; Male; Female; Enteritis; Infant, Premature, Diseases
PubMed: 38936880
DOI: 10.24546/0100489974 -
European Journal of Histochemistry : EJH Jun 2024Cardiomyocyte apoptosis is a complex biological process involving the interaction of many factors and signaling pathways. In hypoxic environment, cardiomyocytes may...
Cardiomyocyte apoptosis is a complex biological process involving the interaction of many factors and signaling pathways. In hypoxic environment, cardiomyocytes may trigger apoptosis due to insufficient energy supply, increased production of oxygen free radicals, and disturbance of intracellular calcium ion balance. The present research aimed to investigate the role of microRNA-29b1 (miR-29b1) in hypoxia-treated cardiomyocytes and its potential mechanism involved. We established an in vitro ischemia model using AC16 and H9C2 cardiomyocytes through hypoxia treatment (1% O2, 48 h). Cell apoptosis was evaluated by flow cytometry using Annexin V FITC-PI staining assay. Moreover, we used Western blot and immunofluorescence analysis to determine the expression of Bcl-2, Bax caspase-3 and Cx43 proteins. We found that miR-29b1 protected AC16 and H9C2 cells from hypoxia-induced injury as evidence that miR-29b1 attenuated the effects of hypoxia treatment on AC16 and H9C2 cell apoptosis after hypoxia treatment. In conclusion, our findings suggest that miR-29b1 may have potential cardiovascular protective effects during ischemia-related myocardial injury.
Topics: Myocytes, Cardiac; Apoptosis; MicroRNAs; Animals; Rats; Cell Hypoxia; Cell Line; Connexin 43; Proto-Oncogene Proteins c-bcl-2
PubMed: 38934067
DOI: 10.4081/ejh.2024.4021 -
Frontiers in Immunology 2024Succinate, traditionally viewed as a mere intermediate of the tricarboxylic acid (TCA) cycle, has emerged as a critical mediator in inflammation. Disruptions within the... (Review)
Review
Succinate, traditionally viewed as a mere intermediate of the tricarboxylic acid (TCA) cycle, has emerged as a critical mediator in inflammation. Disruptions within the TCA cycle lead to an accumulation of succinate in the mitochondrial matrix. This excess succinate subsequently diffuses into the cytosol and is released into the extracellular space. Elevated cytosolic succinate levels stabilize hypoxia-inducible factor-1α by inhibiting prolyl hydroxylases, which enhances inflammatory responses. Notably, succinate also acts extracellularly as a signaling molecule by engaging succinate receptor 1 on immune cells, thus modulating their pro-inflammatory or anti-inflammatory activities. Alterations in succinate levels have been associated with various inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, obesity, and atherosclerosis. These associations are primarily due to exaggerated immune cell responses. Given its central role in inflammation, targeting succinate pathways offers promising therapeutic avenues for these diseases. This paper provides an extensive review of succinate's involvement in inflammatory processes and highlights potential targets for future research and therapeutic possibilities development.
Topics: Humans; Succinic Acid; Inflammation; Signal Transduction; Animals; Citric Acid Cycle; Receptors, G-Protein-Coupled
PubMed: 38933270
DOI: 10.3389/fimmu.2024.1404441 -
Frontiers in Medicine 2024The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in...
INTRODUCTION
The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in nature such as that associated with fetal growth restriction (FGR), is less well understood. Herein, we utilised a combination of clinically relevant MRI techniques to comprehensively characterize and differentiate the haemodynamic responses occurring during acute and chronic periods of fetal hypoxaemia.
METHODS
Prior to conception, carunclectomy surgery was performed on non-pregnant ewes to induce FGR. At 108-110 days (d) gestational age (GA), pregnant ewes bearing control ( = 12) and FGR ( = 9) fetuses underwent fetal catheterisation surgery. At 117-119 days GA, ewes underwent MRI sessions where phase-contrast (PC) and T oximetry were used to measure blood flow and oxygenation, respectively, throughout the fetal circulation during a normoxia and then an acute hypoxia state.
RESULTS
Fetal oxygen delivery (DO) was lower in FGR fetuses than controls during the normoxia state but cerebral DO remained similar between fetal groups. Acute hypoxia reduced both overall fetal and cerebral DO. FGR increased ductus venosus (DV) and foramen ovale (FO) blood flow during both the normoxia and acute hypoxia states. Pulmonary blood flow (PBF) was lower in FGR fetuses during the normoxia state but similar to controls during the acute hypoxia state when PBF in controls was decreased.
CONCLUSION
Despite a prevailing level of chronic hypoxaemia, the FGR fetus upregulates the preferential streaming of oxygen-rich blood via the DV-FO pathway to maintain cerebral DO. However, this upregulation is unable to maintain cerebral DO during further exposure to an acute episode of hypoxaemia. The haemodynamic alterations required at the level of the liver and lung to allow the DV-FO pathway to maintain cerebral DO, may have lasting consequences on hepatic function and pulmonary vascular regulation after birth.
PubMed: 38933113
DOI: 10.3389/fmed.2024.1340012 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Calcium pyrophosphate dehydrate (CPPD) crystals are found in the synovial fluid of patients with articular chondrocalcinosis or sometimes with osteoarthritis. In...
Calcium pyrophosphate dehydrate (CPPD) crystals are found in the synovial fluid of patients with articular chondrocalcinosis or sometimes with osteoarthritis. In inflammatory conditions, the synovial membrane (SM) is subjected to transient hypoxia, especially during movement. CPPD formation is supported by an increase in extracellular inorganic pyrophosphate (ePPi) levels, which are mainly controlled by the transporter Ank and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). We demonstrated previously that transforming growth factor (TGF)-β1 increased ePPi production by inducing Ank and Enpp1 expression in chondrocytes. As the TGF-β1 level raises in synovial fluid under hypoxic conditions, we investigated whether hypoxia may transform SM as a major source of ePPi production. Synovial fibroblasts and SM explants were exposed to 10 ng/mL of TGF-β1 in normoxic or hypoxic (5% O) culture conditions. Ank and Enpp1 expression were assessed by quantitative PCR, Western blot and immunohistochemistry. ePPi was quantified in culture supernatants. RNA silencing was used to define the respective roles of and in TGF-β1-induced ePPi generation. The molecular mechanisms involved in hypoxia were investigated using an promoter reporter plasmid for transactivation studies, as well as gene overexpression and RNA silencing, the respective role of hypoxia-induced factor (HIF)-1 and HIF-2. Our results showed that TGF-β1 increased Ank, Enpp1, and therefore ePPi production in synovial fibroblasts and SM explants. Ank was the major contributor in ePPi production compared to ENPP1. Hypoxia increased ePPi levels on its own and enhanced the stimulating effect of TGF-β1. Hypoxic conditions enhanced promoter transactivation in an HIF-1-dependent/HIF-2-independent fashion. We demonstrated that under hypoxia, SM is an important contributor to ePPi production in the joint through the induction of and . These findings are of interest as a rationale for the beneficial effect of anti-inflammatory drugs on SM in crystal depositions.
PubMed: 38931405
DOI: 10.3390/ph17060738 -
Pharmaceuticals (Basel, Switzerland) May 2024Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. (Hunter) Roxb. possesses bioactive compounds that have potential as...
Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. (Hunter) Roxb. possesses bioactive compounds that have potential as antifibrotic agents, while the mechanism of action in keloid has not yet been elucidated. The aim of this study was to investigate the interaction of gambir bioactive compounds with keloid target proteins using an epistatic and molecular simulation approach. The known bioactive compounds of gambir targets and keloid-related protein targets were screened using databases. The network was constructed and analyzed to obtain the core protein targets. The targets were enriched to describe the Gene Ontology (GO) and pathway related to the proteins. Eleven targets were defined as the main targets of gambir bioactive compounds related to keloid disease. Gambiriin C, Isogambirine, and Procyanidin B1 were identified as the most promising compounds with the highest binding energy to transforming growth factor beta 1 (TGFβ1), AKT serine/threonine kinase 1 (AKT1), and matrix metallopeptidase 1 (MMP1) as the target proteins. GO enrichment and pathway analysis found that gambir bioactive compounds may act on keloid-related target proteins to regulate cell proliferation, migration, transcription, and signal transduction activity via profibrotic cytokine and growth factor signaling pathways. This study provides a reference for potential targets, compounds, and pathways to explain the mechanism of gambir against keloid.
PubMed: 38931330
DOI: 10.3390/ph17060662 -
Microorganisms Jun 2024Toxin-antitoxin (TA) systems are the major mechanism for persister formation in (). Previous studies found that HigBA2 (Rv2022c-Rv2021c), a predicted type II TA system...
Toxin-antitoxin (TA) systems are the major mechanism for persister formation in (). Previous studies found that HigBA2 (Rv2022c-Rv2021c), a predicted type II TA system of , could be activated for transcription in response to multiple stresses such as anti-tuberculosis drugs, nutrient starvation, endure hypoxia, acidic pH, etc. In this study, we determined the binding site of HigA2 (Rv2021c), which is located in the coding region of the upstream gene (), and the conserved recognition motif of HigA2 was characterized via oligonucleotide mutation. Eight binding sites of HigA2 were further found in the genome according to the conserved motif. RT-PCR showed that HigA2 can regulate the transcription level of all eight of these genes and three adjacent downstream genes. DNA pull-down experiments showed that twelve functional regulators sense external regulatory signals and may regulate the transcription of the HigBA2 system. Of these, Rv0903c, Rv0744c, Rv0474, Rv3124, Rv2603c, and Rv3583c may be involved in the regulation of external stress signals. In general, we identified the downstream target genes and possible upstream regulatory genes of HigA2, which paved the way for the illustration of the persistence establishment mechanism in .
PubMed: 38930627
DOI: 10.3390/microorganisms12061244 -
Journal of Clinical Medicine Jun 2024: () infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for...
: () infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for timely diagnosis, given potential diagnostic method limitations. A retrospective case series analysis was conducted on PCR-positive patients admitted to two Dutch secondary hospitals' ICUs between January 2023 and February 2024. Clinical presentations, treatments, outcomes, and mechanical ventilation data were assessed. : Seventeen ICU-admitted patients were identified, with a median age of 44 years, primarily due to hypoxia. Non-invasive ventilation was effective for most, while five required invasive mechanical ventilation. None of the patients required extracorporeal membrane oxygenation. No fatalities occurred. Post-PCR, treatment was adjusted to doxycycline or azithromycin; seven received steroid treatment. : Increased ICU admissions for infection were observed. Diverse clinical and radiological findings emphasize heightened clinical awareness. Early molecular diagnostics and tailored antibiotic regimens are crucial since beta-lactam antibiotics are ineffective. : This study highlights the escalating challenge of severe infections in ICUs, necessitating a multifaceted approach involving accurate diagnostics, vigilant monitoring, and adaptable treatment strategies for optimal patient outcomes.
PubMed: 38929972
DOI: 10.3390/jcm13123443 -
Journal of Personalized Medicine Jun 2024This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human...
Therapeutic Effects of Engineered Exosomes from RAW264.7 Cells Overexpressing hsa-let-7i-5p against Sepsis in Mice-A Comparative Study with Human Placenta-Derived Mesenchymal Stem Cell Exosomes.
This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.
PubMed: 38929840
DOI: 10.3390/jpm14060619 -
Journal of Personalized Medicine Jun 2024Overlap syndrome (OS), the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea, is frequently characterized by the presence of daytime...
BACKGROUND
Overlap syndrome (OS), the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea, is frequently characterized by the presence of daytime hypercapnia (pCO ≥ 45 mmHg). The aim of this study was to investigate potential differences in anthropometric, sleep and respiratory characteristics between hypercapnic and normocapnic patients with OS.
METHODS
Consecutive patients who underwent polysomnography, pulmonary function testing and arterial blood gases and had been diagnosed with OS were enrolled in the study.
RESULTS
According to pCO levels in wakefulness, the patients were divided into group A, consisting of OS patients without hypercapnia ( = 108) or group B, consisting of OS patients with hypercapnia ( = 55). The majority of included patients in both groups were males ( = 92 in group A vs. = 50 in group B). Group B had increased BMI ( = 0.001), neck ( = 0.017) and waist circumference ( = 0.013), higher scores in Epworth sleepiness scale (ESS) ( = 0.008), increased sleep efficiency ( = 0.033), oxygen desaturation index ( = 0.004) and time with oxyhemoglobin saturation <90% ( = 0.006) than group A. Also, Group B had decreased average and minimum oxyhemoglobin saturation during sleep ( < 0.001). Hypercapnic patients had lower FEV% ( = 0.003), FVC% ( = 0.004), pO and pCO ( < 0.001 for both) values compared with normocapnic patients. In binary regression analysis, which assessed various predictors on the likelihood of having hypercapnia, it was found that BMI (OR: 1.313, 95% CI: 1.048-1.646, = 0.018) and FVC (OR: 0.913, 95% CI: 0.845-0.986, = 0.020) were the major determinants of hypercapnia in OS patients.
CONCLUSIONS
Hypercapnic OS patients were more obese and sleepy and presented worse respiratory function in wakefulness and sleep hypoxia characteristics compared with normocapnic OS patients.
PubMed: 38929821
DOI: 10.3390/jpm14060600