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1.
BMC Musculoskelet Disord ; 24(1): 50, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670364

RESUMO

BACKGROUND AND OBJECTIVES: Frozen shoulder (FS) is characterized by pain and significant loss of active and passive shoulder motion. Strengthening exercises are among the standard exercises used for FS. Neuromuscular exercise (NME) effectively improved pain and the range of motion in shoulder. However, no prior research has looked into the effects of NME compared to strengthening exercises in FS rehabilitation. The aim of the present study was to evaluate the effects of NME compared to strengthening exercises on pain and active range of motion (AROM) in individuals with idiopathic frozen shoulder. METHODS: Forty individuals with idiopathic frozen shoulder were randomly assigned to either the experimental group (NME with regular physical therapy, n = 20) or the control group (strengthening exercises with regular physical therapy, n = 20). In both groups, the interventions were performed once a day, 5 days a week for 8 weeks. Pain scores on the visual analogue scale (VAS) and AROM of the shoulder were assessed at baseline and after the 8-week treatment. The primary analysis was the group × time interaction. RESULTS: Two-by-two mixed analysis of variance (ANOVA) revealed a significant group × time interaction for VAS (F = 29.67; p < 0.01); AROM in flexion (F = 12.05; p < 0.01), internal rotation (F = 6.62; p < 0.05) and external rotation (F = 16.93; p < 0.01) in favor of the experimental group. The two-by-two mixed ANOVA revealed a significant main effect of time for VAS (F = 1648.47; p < 0.01); AROM in flexion (F = 591.70; p < 0.01), extension (F = 114.57; p < 0.01), abduction (F = 1602.04; p < 0.01), internal rotation (F = 664.14; p < 0.01) and external rotation (F = 1096.92; p < 0.01). No other significant differences were found. CONCLUSIONS: NME is superior to strengthening exercises in terms of pain and AROM of shoulder flexion, internal rotation and external rotation in individuals with idiopathic FS. NME could be used to treat individuals with FS. TRIAL REGISTRATION: Trial registration number: ChiCTR2100054453. Registration date: 17/12/2021.


Assuntos
Bursite , Terapia por Exercício , Humanos , Ombro , Dor , Amplitude de Movimento Articular , Bursite/terapia , Dor de Ombro/diagnóstico , Dor de Ombro/terapia , Resultado do Tratamento
2.
Brain Sci ; 13(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36672068

RESUMO

OBJECTIVE: Anxiety symptoms are persistent in Parkinson's disease (PD), but the underlying neural substrates are still unclear. In the current study, we aimed to explore the underlying neural mechanisms in PD patients with anxiety symptoms. METHODS: 42 PD-A patients, 41 PD patients without anxiety symptoms (PD-NA), and 40 healthy controls (HCs) were recruited in the present study. All the subjects performed 3.0T fMRI scans. The fractional amplitude of low-frequency fluctuation (fALFF) analysis was used to investigate the alterations in neural activity among the three groups. A Pearson correlation analysis was performed between the altered fALFF value of the PD-A group and anxiety scores. RESULTS: Compared with HCs, PD-A patients had higher fALFF values in the left cerebellum, cerebellum posterior lobe, bilateral temporal cortex, and brainstem and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, and left inferior parietal lobule. Moreover, between the two PD groups, PD-A patients showed higher fALFF values in the right precuneus and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, left inferior parietal lobule, and left occipital lobe. Furthermore, Pearson's correlation analysis demonstrated that the right precuneus and left caudate were correlated with the Hamilton Anxiety Rating Scale scores. CONCLUSION: Our study found that anxiety symptoms in PD patients may be related to alterations of neurological activities in multiple brain regions. Furthermore, these may be critical radiological biomarkers for PD-A patients. Therefore, these findings can improve our understanding of the pathophysiological mechanisms underlying PD-A.

3.
J Ethnopharmacol ; 306: 116158, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36638854

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear. AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases. MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored. RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia. CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.

4.
Neurobiol Dis ; 177: 105988, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603746

RESUMO

CXC chemokine receptor 2 (CXCR2) plays an important role in demyelinating diseases, but the detailed mechanisms were not yet clarified. In the present study, we mainly investigated the critical function and the potential molecular mechanisms of CXCR2 on oligodendrocyte precursor cell (OPC) differentiation and remyelination. The present study demonstrated that inhibiting CXCR2 significantly enhanced OPC differentiation and remyelination in primary cultured OPCs and ethidium bromide (EB)-intoxicated rats by facilitating the formation of myelin proteins, including PDGFRα, MBP, MAG, MOG, and Caspr. Further investigation identified phosphodiesterase 10A (PDE10A) as a main downstream protein of CXCR2, interacting with the receptor to regulate OPC differentiation, in that inhibition of CXCR2 reduced PDE10A expression while suppression of PDE10A did not affect CXCR2. Furthermore, inhibition of PDE10A promoted OPC differentiation, whereas overexpression of PDE10A down-regulated OPC differentiation. Our data also revealed that inhibition of CXCR2/PDE10A activated the cAMP/ERK1/2 signaling pathway, and up-regulated the expression of key transcription factors, including SOX10, OLIG2, MYRF, and ZFP24, that ultimately promoted remyelination and myelin protein biosynthesis. In conclusion, our findings suggested that inhibition of CXCR2 promoted OPC differentiation and enhanced remyelination by regulating PDE10A/cAMP/ERK1/2 signaling pathway. The present data also highlighted that CXCR2 may serve as a potential target for the treatment of demyelination diseases.

5.
Life (Basel) ; 13(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36676142

RESUMO

For the frequent occurrence of harmful algal blooms (HABs) in the Qinhuangdao coastal sea (QCS) of the Bohai Sea in summer, we tested the hypothesis that high-biodiversity HAB species exist in the area, and a series of censuses of HAB species were conducted in the QCS in the summers of 2014-2019. Through morphological identification, we found 100 algae species representing 42 genera in 3 phytoplankton phyla in this study, among which Bacillariophyta was the most dominant phylum. We also found that the population density of Dinoflagellata increased from 2016 to 2019. In total, 59 HAB species were annotated in this study, including 39 of Bacillariophyta, 18 of Dinoflagellata and 2 of Ochrophyta, of which 13 HAB species were reported in the Bohai Sea for the first time, and most HAB species were widely distributed in the QCS in summer. Notably, four dominant HAB species displayed unique temporal and spatial distribution characteristics, while their distribution ranges and population densities increased from 2014 to 2019. The distributions of five environmental factors were different in the QCS, while the temperature, salinity, and dissolved inorganic nitrogen might be the key environmental factors influencing the distribution of dominant HAB species in the summer. In conclusion, this study provides a detailed evaluation of phytoplankton diversity and interannual variation in the QCS. The existence of a high level of biodiversity of algal bloom species suggests the need for long-term monitoring in order to further study and prevent potential HABs.

6.
Sci Rep ; 13(1): 1353, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693886

RESUMO

As laser chaos has been proven to be a robust tool to solve the multi-armed bandit (MAB) problem, this study investigates the problem of multiuser dynamic channel assignment using laser chaos in cognitive radio networks with K-orthogonal channels and M secondary users. A novel dynamic channel assignment algorithm with laser chaos series for multiple users, named parallel processing learning with laser chaos (PPL-LC) algorithm, is proposed to efficiently address two main objectives: stable channel assignment and fuzzy stable channel assignment. The latter objective accounts for the realistic scenario where users have fuzzy preferences and do not necessarily pursue the best preference. The PPL-LC algorithm uses the randomness properties of laser chaos to learn the assignment of channels to multiple users without any limitations on the number of channels, which has not been considered in existing laser chaos algorithms. Moreover, the PPL-LC is equipped with parallel processing channel selections, resulting in higher throughput and stronger adaptability with environmental changes over time than comparison algorithms, such as distributed stable strategy learning and coordinated stable marriage MAB algorithms. Finally, numerical examples are presented to demonstrate the performance of the PPL-LC algorithm.

7.
Fish Shellfish Immunol ; : 108565, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36702328

RESUMO

Prophenoloxidase (proPO) is essential in the prophenoloxidase-activating system (proPO-AS) which is important for defense against foreign infection in crustaceans. However, most studies have focused on expression in the presence of a single pathogenic bacterium, and very few have addressed the presence of environmental contaminants simultaneously, such as cadmium (Cd) and Aeromonas hydrophila. Our study aimed to investigate the function of proPO in the freshwater crab Sinopotamon henanense and the changes in its expression by Cd and infection of A. hydrophila. A novel proPO from the hemocytes of S. henanense (ShproPO) was found in this research, the full-length cDNA of ShproPO was 2620 bp of encoding a protein of 678 amino acids containing three typical hemocyanin domains. The ShproPO protein could be found in both the granular (GHc) and the semi-granular hemocytes (SGHc). The ShproPO mRNA was found to be abundantly expressed in hemocytes and could be influenced by A. hydrophila infection. These results indicate that ShproPO could be involved in the antibacterial process. Further research found that low concentrations of Cd could promote its expression after infection with A. hydrophila. Therefore, it was hypothesized that Cd disrupted the response of crabs to A. hydrophila infection. Subsequently, PO enzyme activity was found to be significantly reduced through in vivo RNA interference with ShproPO, and the results suggested that ShproPO is likely to be a key enzyme in the melanization response. Finally, ShproPO was found to significantly enhance the phagocytosis of A. hydrophila-infected hemocytes by in vitro recombination, confirming that ShproPO is involved in hemocyte-mediated melanization and phagocytosis. Our findings reveal completely new insight into the immunotoxicity of Cd and the immune function of ShproPO in S. henanense.

8.
Proc Natl Acad Sci U S A ; 120(4): e2209983120, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36669109

RESUMO

TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass transmembrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hemispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development.


Assuntos
Neocórtex , Animais , Camundongos , Humanos , Células Ependimogliais , Camundongos Knockout
9.
Plast Reconstr Surg ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700876

RESUMO

BACK GROUND: Capsular contracture was the most common complication of breast implantation surgery. Bacterial contamination was considered to play an important role in the occurrence of capsular contracture, and Gram-positive bacteria like Staphylococcus epidermidis were discovered in the clinical specimens. Lipoteichoic acid (LTA) was a component of Gram-positive bacteria cell wall, and was sufficient in the pathogenicity of the bacteria. We assumed that LTA could trigger the immunological response against the implant and cause capsular contracture. METHODS: We developed a rat model of capsular contracture by repeated injection of 10 µg/ml LTA. The histological changes of the capsule tissue were measured by HE, Sirius Red, Masson and Immunohistochemical staining. The expression of related cytokines was measured by qRT-PCR. The downstream pathway activation was shown by Western blot. We also applied Tocilizumab, an IL-6 receptor antagonist, to verify the role of IL-6 in this pathological process. RESULTS: We discovered that repeated LTA injection, at a low concentration, could induce the thickening of capsule tissue, the deposition of collagen fiber and the activation of myofibroblasts. IL-6/STAT3 signaling pathway was activated in this process, and the inhibition of IL-6 receptor could relieve the symptoms. B cells and T-helper cells, especially T-helper 1, could be related to this phenomenon. CONCLUSIONS: Our research corroborated that subclinical infection could trigger capsular contracture, and the immune system played an important role in this process. Our results provided a possible research direction for the mechanism of bacterial infection-induced immune response against breast implants.

10.
Int J Med Sci ; 20(1): 79-86, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36619220

RESUMO

Artificial intelligence (AI) has been widely used in various medical fields, such as image diagnosis, pathological classification, selection of treatment schemes, and prognosis analysis. Especially in the image-aided diagnosis of tumors, the cooperation of human-computer interactions has become mature. However, the ethics of the application of AI as an emerging technology in clinical decision-making have not been fully supported, so the clinical decision support system (CDSS) based on AI technology has not fully realized human-computer interactions in clinical practice as the image-aided diagnosis system. The CDSS was currently used and promoted worldwide including Watson for Oncology, Chinese society of clinical oncology-artificial intelligence (CSCO AI) and so on. This paper summarized the applications and clarified the principle of AI in CDSS, analyzed the difficulties of AI in oncology decisions, and provided a reference scheme for the application of AI in oncology decisions in the future.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Humanos , Inteligência Artificial , Oncologia/métodos , Tomada de Decisão Clínica/métodos , Prognóstico
11.
Exp Mol Med ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658227

RESUMO

Mitochondrial DNA (mtDNA) released through protein oligomers, such as voltage-dependent anion channel 1 (VDAC1), triggers innate immune activation and thus contributes to liver fibrosis. Here, we investigated the role of Parkin, an important regulator of mitochondria, and its regulation of VDAC1-mediated mtDNA release in liver fibrosis. The circulating mitochondrial DNA (mtDNA) and protein levels of liver Parkin and VDAC1 were upregulated in patients with liver fibrosis. A 4-week CCl4 challenge induced release of mtDNA, activation of STING signaling, a decline in autophagy, and apoptosis in mouse livers, and the knockout of Parkin aggravated these effects. In addition, Parkin reduced mtDNA release and prevented VDAC1 oligomerization in a manner dependent on its E3 activity in hepatocytes. We found that site-specific ubiquitination of VDAC1 at lysine 53 by Parkin interrupted VDAC1 oligomerization and prevented mtDNA release into the cytoplasm under stress. The ubiquitination-defective VDAC1 K53R mutant predominantly formed oligomers that resisted suppression by Parkin. Hepatocytes expressing VDAC1 K53R exhibited mtDNA release and thus activated the STING signaling pathway in hepatic stellate cells, and this effect could not be abolished by Parkin. We propose that the ubiquitination of VDAC1 at a specific site by Parkin confers protection against liver fibrosis by interrupting VDAC1 oligomerization and mtDNA release.

12.
J Bone Miner Res ; 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680558

RESUMO

Chronic high-altitude hypoxia induces irreversible abnormalities in various organisms. Emerging evidence indicates that hypobaric hypoxia markedly suppresses bone mass and bone strength. However, few effective means have been identified to prevent such bone deficits. Here, we assessed the potential of pulsed electromagnetic fields (PEMF) to noninvasively resist bone deterioration induced by hypobaric hypoxia. We observed that exogenous PEMF treatment at 15 Hz and 20 Gs improved the cancellous and cortical bone mass, bone microstructure, and skeletal mechano-properties in rats subjected to chronic exposure of hypobaric hypoxia simulating an altitude of 4,500 m for 6 weeks by primarily modulating osteoblasts and osteoblast-mediated bone-forming activity. Moreover, our results showed that while PEMF stimulated the functional activity of primary osteoblasts in hypoxic culture in vitro, it had negligible effects on osteoclasts and osteocytes exposed to hypoxia. Mechanistically, the primary cilium was found to function as the major electromagnetic sensor in osteoblasts exposed to hypoxia. The polycystins PC-1/PC-2 complex was identified as the primary calcium channel in the primary cilium of hypoxia-exposed osteoblastic cells responsible for the detection of external PEMF signals, and thereby translated these biophysical signals into intracellular biochemical events involving significant increase in the intracellular soluble adenylyl cyclase (sAC) expression and subsequent elevation of cAMP concentration. The second messenger cAMP inhibited the transcription of oxygen homeostasis-related hypoxia-inducible factor 1-alpha (HIF-1α), and thus enhanced osteoblast differentiation and improved bone phenotype. Overall, the present study not only advances our understanding of bone physiology at high altitudes, but more importantly, proposes effective means to ameliorate high altitude-induced bone loss in a non-invasive and cost-effective manner.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36608928

RESUMO

Gonadotropin-releasing hormone (GnRH) plays a key role in the control of the reproductive axis in vertebrates, however, little is known about its function in reproductive endocrine regulation in molluscs. In the present study, RNA-seq was used to construct transcriptomes of Ruditapes philippinarum testis and ovaries of control and GnRH suppressed individuals using RNA interference. GnRH suppression caused 112 and 169 enriched KEGG pathways in testis and ovary, with 92 pathways in common in both comparisons. The most enriched KEGG pathways occurred in the "Oxidative phosphorylation", "Dorso-ventral axis formation", "Thyroid hormone synthesis" and "Oxytocin signaling pathway" etc. A total of 1838 genes in testis and 358 genes in ovaries were detected differentially expressed in GnRH suppressed clams. Among the differentially expressed genes, a suit of genes related to regulation of steroid hormones synthesis and gonadal development, were found in both ovary and testis with RNAi of GnRH. These results suggest that GnRH may play an important role in reproductive function in bivalves. This study provides a preliminary basis for studying the function and regulatory mechanism of GnRH in bivalves.

14.
Carbohydr Polym ; 303: 120467, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36657846

RESUMO

Pectic polysaccharide has attracted increasing attention for their potential biological properties and applications in health industries. In this study, a low-molecular-weight pectic polysaccharide, POS4, was obtained from citrus peel. The structure of POS4 was preliminarily analyzed by gel-permeation chromatography, monosaccharide analysis, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Results showed that the molecular weight of POS4 was 4.76 kDa and it was a galacturonic acid enriched pectic polysaccharide. The anti-aging activity in vivo showed that POS4 could notably prolong the average lifespan of fruit flies by suppressing the generation of reactive oxygen species (ROS). Further studies demonstrated that POS4 could enhance intestinal homeostasis by modulating gut microbiota in a positive way and regulating autophagy associated genes. Taken together, we proposed that galacturonic acid enriched low molecular weight pectic polysaccharide have great potential in the development of healthy foods such as anti-aging health care products.


Assuntos
Pectinas , Polissacarídeos , Pectinas/farmacologia , Pectinas/química , Peso Molecular , Polissacarídeos/farmacologia , Polissacarídeos/química
15.
Biology (Basel) ; 12(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36671793

RESUMO

Global cerebral ischemia can elicit rapid innate neuroprotective mechanisms that protect against delayed neuronal death. Brain-derived 17ß-estradiol (BDE2), an endogenous neuroprotectant, is synthesized from testosterone by the enzyme aromatase (Aro) and is upregulated by brain ischemia and inflammation. Our recent study revealed that G1, a specific G-protein-coupled estrogen receptor 1 (GPER) agonist, exerts anti-inflammatory and anti-apoptotic roles after global cerebral ischemia (GCI). Herein, we aimed to elucidate whether G1 modulates the early inflammatory process and the potential underlying mechanisms in the ovariectomized rat hippocampal CA1 region. G1 was found to markedly reduce pro-inflammatory (iNOS, MHCII, and CD68) and to enhance anti-inflammatory (CD206, Arginase 1, IL1RA, PPARγ, and BDNF) markers after 1 and 3 days of reperfusion after GCI. Intriguingly, the neuroprotection of G1 was blocked by the Aro inhibitor, letrozole. Conversely, the GPER antagonist, G36, inhibited Aro-BDE2 signaling and exacerbated neuronal damage. As a whole, this work demonstrates a novel anti-inflammatory role of GPER, involving a synergistic mediation with BDE2 during the early stage of GCI.

16.
J Affect Disord ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682696

RESUMO

BACKGROUND: Microglia-mediated neuroinflammation contributes to major depressive disorder (MDD). Targeting microglia is a promising strategy for treating MDD. Patchouli alcohol (PA), an active component of Pogostemon cablin, has anti-inflammatory and neuroprotective effects. PURPOSE: In this study, we investigate the microglia-mediated neurogenesis pathway in which PA ameliorates depressive-like behaviors in stress-induced animal model of depression. METHODS: C57BL/6J male mice were exposed to chronic mild stress (CMS) for 4 weeks, then administered PA intraperitoneally at 10, 20 or 40 mg/kg once per day for 3 weeks. The antidepressant effects of PA were evaluated in the sucrose preference test, forced swimming test, and tail suspension test. Microglial phenotypes and activation of the NLRP3 inflammation were analyzed using RT-PCR, western blotting and immunofluorescence staining. Effects of PA on neurogenesis were analyzed in vitro and in vivo using immunofluorescence staining. RESULTS: Behavioral assessments showed that PA alleviated depressive-like behaviors in CMS-exposed mice. CMS induced microglial activation and pro-inflammatory profiles, which were blocked by PA treatment. PA attenuated the activation of NLRP3 inflammasome, leading to decreases in the levels of caspase-1, ASC, IL-1ß, and IL-18 in the hippocampus of CMS-exposed mice. In primary microglia cultures, PA inhibited LPS-induced NLRP3 inflammasome activation. PA rescued inflammation-inhibited neurogenesis in vivo and in vitro. CONCLUSIONS: Our results suggest that PA inhibits the NLRP3 inflammasome and ameliorates microglia-mediated neurogenesis impairment, contributing to antidepressant effects. Thus, PA may be a novel treatment for inflammation-driven mental disorders.

17.
iScience ; 26(1): 105913, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36686391

RESUMO

The neural inhibitory gamma-aminobutyric acid (GABA) system in the regulation of anesthetic consciousness is heterogeneous, and the medial hypothalamus (MH), consisting of ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH), plays an important role in sleep and circadian rhythm. However, the role of MH GABAergic neurons (MHGABA) in anesthesia remains unclear. In this study, we used righting reflex, electroencephalogram (EEG), and arousal behavioral score to evaluate the sevoflurane anesthesia. Activation of MHGABA or DMHGABA neurons prolonged the anesthesia induction time, shortened the anesthesia emergence time, and induced EEG arousal and body movement during anesthesia; meanwhile, VMHGABA neurons activated only induced EEG changes during 1.5% sevoflurane anesthesia. Furthermore, inhibition of DMHGABA neurons significantly deepened sevoflurane anesthesia. Therefore, DMHGABA neurons exert a strong emergence-promoting effect on induction, maintenance, and arousal during sevoflurane general anesthesia, which helps to reveal the mechanism of anesthesia.

18.
Infect Drug Resist ; 16: 115-124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36636374

RESUMO

Purpose: To summarize the clinical characteristics of progressive pneumonia caused by Chlamydia psittaci (C. psittaci) and to explore the effect of high-dose tigecycline on severe C psittaci. Patients and Methods: We retrospectively analyzed the clinical characteristics, treatment, and outcomes of three progressive pneumonia patients caused by C. psittaci in our hospital in the past three years. Results: All three patients showed high fever and progressive dyspnea, and all of them were finally diagnosed by bronchoalveolar lavage fluid (BALF) of metagenomic next-generation sequencing (mNGS). Case 1 rapidly developed into multilobar infiltration after raising a parrot with a normal appearance one week before. Respiratory failure occurred despite the use of moxifloxacin, requiring non-invasive ventilator-assisted ventilation. Case 2 developed discomfort one day after sightseeing in the forest park. Moxifloxacin was ineffective for her and she quickly developed respiratory failure, requiring invasive ventilator-assisted ventilation. Case 3 kept chickens and ducks at home. Respiratory failure and renal failure still occurred rapidly despite the use of doxycycline, requiring invasive ventilator-assisted ventilation and continuous renal replacement therapy (CRRT). After adjusting the antibiotic to high-dose tigecycline (100mg, I.V., q12h), all three patients were treated effectively and no side effects occurred. Conclusion: C. psittaci pneumonia is one of the causes of progressive pneumonia. High-dose tigecycline is safe and effective for the treatment of severe C. psittaci.

19.
JCI Insight ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692953

RESUMO

Loss of function mutations in CCM genes and gain of function mutation in the MAP3K3 gene encoding MEKK3 cause cerebral cavernous malformation (CCM). Deficiency of CCM proteins leads to the activation of MEKK3-KLF2/4 signaling, but it is not clear how this occurs. Here we demonstrate that deletion of the CCM3 interacting kinases STK24/25 in endothelial cells cause defects in vascular patterning during development as well as CCM lesion formation during postnatal life. While permanent deletion of STK24/25 in endothelial cells caused developmental defects of the vascular system, inducible postnatal deletion of STK24/25 impaired angiogenesis in the retina and brain. More importantly, deletion of STK24/25 in neonatal mice led to the development of severe CCM lesions. At the molecular level, a hybrid protein consisting of the STK kinase domain and the MEKK3 interacting domain of CCM2 rescued the vascular phenotype caused by the loss of ccm gene function in zebrafish. Our study suggests that CCM2/3 proteins act as adapters to allow recruitment of STK24/25 to limit the constitutive MEKK3 activity that contributes to vessel stability. Loss of STK24/25 causes MEKK3 activation leading to CCM lesion formation.

20.
Sci Signal ; 16(767): eabm0488, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626577

RESUMO

Escherichia coli are part of the normal intestinal microbiome, but some enterohemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) strains can cause potentially life-threatening gastroenteritis. Virulence factors underlying the ability of EHEC and EPEC to cause disease include those encoded in the locus of the enterocyte effacement (LEE) pathogenicity island. Here, we demonstrated that EsrL, a small RNA present in many E. coli strains, promoted pathogenicity, adhesion, and biofilm formation in EHEC and EPEC. PhoB, the response regulator of the two-component system that controls cellular responses to phosphate, directly repressed esrL expression under low-phosphate conditions. A phosphate-rich environment, similar to that of the human intestine, relieved PhoB-mediated repression of esrL. EsrL interacted with and stabilized the LEE-encoded regulator (ler) transcript, which encodes a transcription factor for LEE genes, leading to increased bacterial adhesion to cultured cells and colonization of the rabbit colon. EsrL also bound to and stabilized the fimC transcript, which encodes a chaperone that is required for the assembly of type 1 pili, resulting in enhanced cell adhesion in pathogenic E. coli and enhanced biofilm formation in pathogenic and nonpathogenic E. coli. Our findings demonstrate that EsrL stimulates the expression of virulence genes in both EHEC and EPEC under phosphate-rich conditions, thus promoting the pathogenicity of EHEC and EPEC in the nutrient-rich gut environment.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Animais , Humanos , Coelhos , Escherichia coli/genética , Escherichia coli/metabolismo , Virulência/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fosfatos/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica
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